Find Me the Evidence: Connecting the Practitioner With the Evidence on Bereavement Care

This is an Accepted Manuscript of an article published by Taylor & Francis in DEATH STUDIES on January 15 2015, available online: http://wwww.tandfonline.com/10.1080/07481187.2014.992498 Author version under embargo for 12 months from publication, in accordance with the publisher's policy.This study reports on the development and application of a Bereavement Search Filter with a known level of retrieval performance to support access to the underlying knowledge base for bereavement care

Social Interactions as a Source of Information about E-Cigarettes: A Study of U.S. Adult Smokers

The novelty of e-cigarettes and ambiguity about their effects may foster informal sharing of information, such as through social interactions. We aimed to describe smokers’ social interactions about e-cigarettes and their recommendations that others use e-cigarettes. Data were collected from 2149 adult smokers in North Carolina and California who participated in a study of the impact of pictorial cigarette pack warnings. In the previous month, almost half of participants (45%) reported talking to at least one person about e-cigarettes and nearly a third of participants (27%) recommended e-cigarettes to someone else. Smokers recommended e-cigarettes to cut back on smoking (57%), to quit smoking (48%), for health reasons (36%), and for fun (27%). In adjusted analyses, more frequent e-cigarette use, positive views about typical e-cigarette users, and attempting to quit smoking in the past month were associated with recommending e-cigarettes for health reasons (all p < 0.05). Social interactions appear to be a popular method of information-sharing about e-cigarettes among smokers. Health communication campaigns may help to fill in the gaps of smokers’ understanding of e-cigarettes and their long-term effects

Quantification of Progesterone and 17-β Estradiol in Mouse Serum by Liquid Chromatography-Tandem Mass Spectrometry

Quantification of progesterone and 17-β estradiol in mouse serum by liquid chromatography-tandem mass spectrometry Authors: Benjamin Kennard, Allison Cobble, Amy Gravitte, Keleigh Galloway, Jen Kintner, Jennifer Hall, Stacy Brown Introduction: In the United States, Chlamydia trachomatis is a commonly appearing sexually transmitted infection1. It affects the U.S. healthcare system to a tune of about $500 million dollars annually2. In women, it generally appears asymptomatic and can lead to severe secondary complications such as pelvic inflammatory diseases or infertility1. Female sex hormones, estrogen and progesterone, are being identified to have a role in chlamydial infection. Specifically, this study aims to create quantification methods to detect levels of estrogen and progesterone in mice, infected with Chlamydia muridarum, plasma samples. Methods: Progesterone samples were prepared using solid-liquid extraction (SLE+) cartridges with ethyl acetate as the elution solvent. Estradiol samples were prepared using liquid-liquid extraction (LLE) with methyl tert-butyl ether and subsequent derivatization with DMIS. Following sample preparation, hormones were quantified in samples using LC-MS/MS with a gradient elution of 1 mM ammonium fluoride in water and acetonitrile. The separation was achieved using a UCT C18 column (100 x 21.mm, 1.8 μm particle size) maintained at 50oC. The mass spectrometer was set up to isolate molecular ions for progesterone (m/z 315.0910) and derivatized estradiol (m/z 431.1835). Quantification was facilitated by the use of deuterium-labeled internal standards and their corresponding molecular ions in the mass spectrometer (d9-progesterone; m/z 324.1230 and d5-estradiol; m/z 436.2922). Results: Several aspects of the assay presented have been optimized for maximum analyte recovery and analytical sensitivity, including column choice, mobile phase, derivatizing agents for estradiol, and extraction protocols for progesterone. The LC-MS/MS method was investigated for precision and accuracy over three separate days. The dynamic range of the progesterone assay was 5 – 100 ng/mL, with a limit of detection of 1 ng/mL. Likewise, the estradiol assay was linear in the range of 5 – 100 ng/mL, with a limit of detection of 0.5 ng/mL. The average precision, represented by % RSD was 0.74 – 8.5% and 6.3 – 13.4% for progesterone and estradiol, respectively. The accuracy of the method, represented by % error was 1.6 – 14.4% and 4.0 – 10.5% for progesterone and estradiol, respectively. Successful validation was defined as \u3c 15% RSD and error (\u3c 20% at the limit of quantification), per current FDA Guidelines. Conclusions: The developed LC-MS/MS method is specific for progesterone and estradiol, and the extraction is suitable for preparation of mouse serum samples. This assay could be successfully applied to hormone quantification in mouse samples to support the investigation of the link between chlamydia infection and hormone levels in female animals. References 1. Chlamydia - 2017 Sexually Transmitted Diseases Surveillance. https://www.cdc.gov/std/stats17/chlamydia.htm. Accessed October 23, 2018. 2. Owusu-Edusei K, Chesson HW, Gift TL, et al. The Estimated Direct Medical Cost of Selected Sexually Transmitted Infections in the United States, 2008. Sex Transm Dis. 2013;40(3):197-201. doi:10.1097/OLQ.0b013e318285c6d

“My First Thought was Croutons”: Perceptions of Cigarettes and Cigarette Smoke Constituents Among Adult Smokers and Nonsmokers

Understanding what people think about harmful and potentially harmful constituents in cigarettes and cigarette smoke has new urgency given legislation requiring US Food and Drug Administration (FDA) to disclose constituent information. Our study sought to obtain qualitative information on what people think about these constituents and the language they use to talk about them

A Search for Exozodiacal Clouds with Kepler

Planets embedded within dust disks may drive the formation of large scale clumpy dust structures by trapping dust into resonant orbits. Detection and subsequent modeling of the dust structures would help constrain the mass and orbit of the planet and the disk architecture, give clues to the history of the planetary system, and provide a statistical estimate of disk asymmetry for future exoEarth-imaging missions. Here we present the first search for these resonant structures in the inner regions of planetary systems by analyzing the light curves of hot Jupiter planetary candidates identified by the Kepler mission. We detect only one candidate disk structure associated with KOI 838.01 at the 3-sigma confidence level, but subsequent radial velocity measurements reveal that KOI 838.01 is a grazing eclipsing binary and the candidate disk structure is a false positive. Using our null result, we place an upper limit on the frequency of dense exozodi structures created by hot Jupiters. We find that at the 90% confidence level, less than 21% of Kepler hot Jupiters create resonant dust clumps that lead and trail the planet by ~90 degrees with optical depths >~5*10^-6, which corresponds to the resonant structure expected for a lone hot Jupiter perturbing a dynamically cold dust disk 50 times as dense as the zodiacal cloud.Comment: 22 pages, 6 figures, Accepted for publication in Ap

Brand switching and toxic chemicals in cigarette smoke: A national study

US law requires disclosure of quantities of toxic chemicals (constituents) in cigarette smoke by brand and sub-brand. This information may drive smokers to switch to cigarettes with lower chemical quantities, under the misperception that doing so can reduce health risk. We sought to understand past brand-switching behavior and whether learning about specific chemicals in cigarette smoke increases susceptibility to brand switching

SARS-CoV-2 infection in the first trimester and the risk of early miscarriage: a UK population-based prospective cohort study of 3041 pregnancies conceived during the pandemic

STUDY QUESTION: Does maternal infection with severe acute respiratory syndrome coronavirus (SARS-CoV-2) in the first trimester affect the risk of miscarriage before 13 week's gestation? SUMMARY ANSWER: Pregnant women with self-reported diagnosis of SARS-CoV-2 in the first trimester had a higher risk of early miscarriage. WHAT IS KNOWN ALREADY: Viral infections during pregnancy have a broad spectrum of placental and neonatal pathology. Data on the effects of the SARS-CoV-2 infection in pregnancy are still emerging. Two systematic reviews and meta-analyses reported an increased risk of preterm birth, caesarean delivery, maternal morbidity and stillbirth. Data on the impact of first trimester infection on early pregnancy outcomes are scarce. This is the first study, to our knowledge, to investigate the rates of early pregnancy loss during the SARS-CoV-2 outbreak among women with self-reported infection. STUDY DESIGN, SIZE, DURATION: This was a nationwide prospective cohort study of pregnant women in the community recruited using social media between 21st May and 31st December, 2020. We recruited 3545 women who conceived during the SARS-CoV-2 pandemic who were less than 13 week's gestation at the time of recruitment. PARTICIPANTS/MATERIALS, SETTING, METHODS: The COVID-19 Contraception and Pregnancy Study (CAP-COVID) was an on-line survey study collecting longitudinal data from pregnant women in the UK aged 18 years or older. Women who were pregnant during the pandemic were asked to complete on-line surveys at the end of each trimester. We collected data on current and past pregnancy complications, their medical history and whether they or anyone in their household had symptoms or been diagnosed with SARS-CoV-2 infection during each trimester of their pregnancy. RT-PCR-based SARS-CoV-2 RNA detection from respiratory samples (e.g., nasopharynx) is the standard practice for diagnosis of SARS-CoV-2 in the UK. We compared rate of self-reported miscarriage in three groups: 'presumed infected' i.e those who reported a diagnosis with SARS-CoV-2 infection in the first trimester; 'uncertain' i.e those who did not report a diagnosis but had symptoms/household contacts with symptoms/diagnosis; and 'presumed uninfected' i.e., those who did not report any symptoms/diagnosis and had no household contacts with symptoms/diagnosis of SARS-CoV-2. MAIN RESULTS AND THE ROLE OF CHANCE: A total of 3545 women registered for the CAP-COVID study at less than 13 weeks gestation and were eligible for this analysis. Data for the primary outcome were available from 3041 women (86%). In the overall sample, the rate of self-reported miscarriage was 7.8% (238/3041 [95% CI, 7-9]). The median gestational age at miscarriage was 9 weeks (interquartile range 8-11). Seventy-seven women were in the 'presumed infected' group (77/3041, 2.5% [95% CI 2 - 3]), 295/3041 were in the uncertain group (9.7%, [95% CI 9-11]) and the rest in the 'presumed uninfected' (87.8%, 2669/3041, [95% CI 87-89]). The rate of early miscarriage was 14% in the 'presumed infected' group, 5% in the 'uncertain' and 8% in the 'presumed uninfected' (11/77 [95% CI 6-22] versus15/295, [95% CI 3-8] versus 212/2669 [95% CI 7-9], p = 0.02). After adjusting for age, BMI, ethnicity, smoking status, gestational age at registration and the number of previous miscarriages, the risk of early miscarriage appears to be higher in the 'presumed infected' group (relative rate 1.7, 95% CI 1.0-3.0, p = 0.06). LIMITATIONS, REASONS FOR CAUTION: We relied on self-reported data on early pregnancy loss and SARS-CoV-2 infection without any means of checking validity. Some women in the 'presumed uninfected' and 'uncertain' groups may have had asymptomatic infections. The number of 'presumed infected' in our study was low and therefore the study was relatively underpowered. WIDER IMPLICATIONS OF THE FINDINGS: This was a national study from the UK, where infection rates were one of the highest in the world. Based on the evidence presented here, women who are infected with SARS-CoV-2 in their first trimester may be at an increased risk of a miscarriage. However, the overall rate of miscarriage in our study population was 8%. This is reassuring and suggests that if there is an effect of SARS-CoV-2 on the risk of miscarriage, this may be limited to those with symptoms substantial enough to lead to a diagnostic test. Further studies are warranted to evaluate a causal association between SARS-CoV-2 infection in early pregnancy and miscarriage risk. Although we did not see an overall increase in the risk of miscarriage, the observed comparative increase in the presumed infected group reinforces the message that pregnant women should continue to exercise social distancing measures and good hygiene throughout their pregnancy to limit their risk of infection. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by a grant from the Elizabeth Garrett Anderson Hospital Charity, (G13-559194). The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report. JAH is supported by an NIHR Advanced Fellowship. ALD is supported by the National Institute for Health Research University College London Hospitals Biomedical Research Centre. All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: support to JAH and ALD as above; no financial relationships with any organisations that might have an interest in the submitted work in the previous 3 years; no other relationships or activities that could appear to have influenced the submitted work. TRIAL REGISTRATION NUMBER: n/a

mTORC2 signaling drives the development and progression of pancreatic cancer

mTOR signaling controls several critical cellular functions and is deregulated in many cancers, including pancreatic cancer. To date, most efforts have focused on inhibiting the mTORC1 complex. However, clinical trials of mTORC1 inhibitors in pancreatic cancer have failed, raising questions about this therapeutic approach. We employed a genetic approach to delete the obligate mTORC2 subunit Rictor and identified the critical times during which tumorigenesis requires mTORC2 signaling. Rictor deletion resulted in profoundly delayed tumorigenesis. Whereas previous studies showed most pancreatic tumors were insensitive to rapamycin, treatment with a dual mTORC1/2 inhibitor strongly suppressed tumorigenesis. In late-stage tumor-bearing mice, combined mTORC1/2 and PI3K inhibition significantly increased survival. Thus, targeting mTOR may be a potential therapeutic strategy in pancreatic cancer

IQN path ASBL report from the first European cfDNA consensus meeting:expert opinion on the minimal requirements for clinical ctDNA testing

Liquid biopsy testing is a new laboratory-based method that detects tumour mutations in circulating free DNA (cfDNA) derived from minimally invasive blood sampling techniques. Recognising the significance for clinical testing, in 2017, IQN Path provided external quality assessment for liquid biopsy testing. Representatives of those participating laboratories were invited to attend a workshop to discuss the findings and how to achieve quality implementation of cfDNA testing in the clinical setting, the discussion and outcomes of this consensus meeting are described below. Predictive molecular profiling using tumour tissue in order to select cancer patients eligible for targeted therapy is now routine in diagnostic pathology. If insufficient tumour tissue material is available, in some circumstances, recent European Medicines Agency (EMA) guidance recommends mutation testing with plasma cfDNA. Clinical applications of cfDNA include treatment selection based on clinically relevant mutations derived from pre-treatment samples and the detection of resistant mutations upon progression of the disease. In order to identify tumour-related mutations in amongst other nucleic acid material found in plasma samples, highly sensitive laboratory methods are needed. In the workshop, we discussed the variable approaches taken with regard to cfDNA extraction methods, the tests, and considered the impact of false-negative test results. We explored the lack of standardisation of complex testing procedures ranging from plasma collection, transport, processing and storage, cfDNA extraction, and mutation analysis, to interpretation and reporting of results. We will also address the current status of clinical validation and clinical utility, and its use in current diagnosis. This workshop revealed a need for guidelines on with standardised procedures for clinical cfDNA testing and reporting, and a requirement for cfDNA-based external quality assessment programs