Patient-provider communication about gestational weight gain among nulliparous women: a qualitative study of the views of obstetricians and first-time pregnant women

BACKGROUND: In 2009 the Institute of Medicine updated its guidelines for weight gain during pregnancy, in part because women of childbearing age now weigh more pre-pregnancy and tend to gain more weight during pregnancy than women did when the previous set of guidelines were released in 1990. Women who begin pregnancy overweight or obese and women who gain weight outside IOM recommendations are at risk for poor maternal and fetal health outcomes. With these concerns in mind, we examined what obstetricians communicate about gestational weight gain to their pregnant patients and how nulliparous patients perceive weight-related counseling from their obstetricians. METHODS: We conducted one-on-one, semi-structured interviews with 19 nulliparous women and 7 obstetricians recruited from a single clinic at a large academic medical center in the United States. Interviews were transcribed verbatim and analyzed inductively using thematic analysis. RESULTS: We identified 4 major themes: 1) Discussions about the amount and pace of gestational weight gain: obstetricians reported variation in the frequency and timing of weight-related discussions with patients while most patients said that weight was not emphasized by their obstetricians; 2) The content of communication about nutrition and physical activity: obstetricians said they discuss nutrition and activity with all patients while most patients reported that their obstetrician either discussed these topics in general terms or not at all; 3) Communication about postpartum weight loss: obstetricians said that they do not typically address postpartum weight loss with patients during prenatal visits while patients had concerns about postpartum weight; and 4) Patient feelings about obstetrician advice: most patients said that their obstetrician does not tend to offer “unsolicited advice”, instead offering information in response to patient questions or concerns. Women were divided about whether they desired more advice from their obstetrician on weight gain, nutrition, and activity. CONCLUSIONS: Our analysis revealed discrepancies between obstetricians’ and patients’ perceptions of their weight-related clinical interactions. Our findings suggest that there is a missed opportunity to use prenatal visits as opportunities to discuss healthy eating and exercise during pregnancy, the postpartum period, and beyond. Additional research on the design, implementation, and testing of interventions to address prenatal nutrition and physical activity is warranted

Variation in parent-offspring kinship in socially monogamous systems with extra-pair reproduction and inbreeding

ACKNOWLEDGMENTS We thank the Tsawout and Tseycum First Nations bands for allowing access to Mandarte; everyone who contributed to long-term data collection; Lukas Keller and Ryan Germain for helpful discussions; and the European Research Council, UK Royal Society, National Sciences and Engineering Research Council of Canada and Swiss National Science Foundation for their invaluable support. DATA ARCHIVING Data are available from the Dryad Digital Repository: http://dx.doi.org/10.5061/dryad.4r383.Peer reviewedPublisher PD

Genomic and molecular analyses identify molecular subtypes of pancreatic cancer recurrence

Pancreatic cancer (PC) remains a highly lethal malignancy, and most patients with localized disease that undergo surgical resection still succumb to recurrent disease. Pattern of recurrence after pancreatectomy is heterogenous, with some studies illustrating that site of recurrence can be associated with prognosis.1 Another study suggested that tumors that develop local and distant recurrence can be regarded as a homogenous disease with similar outcomes.2 Here we investigate novel molecular determinants of recurrence pattern after pancreatectomy for PC

A third generation vaccine for human visceral leishmaniasis and post kala azar dermal leishmaniasis : First-in-human trial of ChAd63-KH

BACKGROUND: Visceral leishmaniasis (VL or kala azar) is the most serious form of human leishmaniasis, responsible for over 20,000 deaths annually, and post kala azar dermal leishmaniasis (PKDL) is a stigmatizing skin condition that often occurs in patients after successful treatment for VL. Lack of effective or appropriately targeted cell mediated immunity, including CD8+ T cell responses, underlies the progression of VL and progression to PKDL, and can limit the therapeutic efficacy of anti-leishmanial drugs. Hence, in addition to the need for prophylactic vaccines against leishmaniasis, the development of therapeutic vaccines for use alone or in combined immuno-chemotherapy has been identified as an unmet clinical need. Here, we report the first clinical trial of a third-generation leishmaniasis vaccine, developed intentionally to induce Leishmania-specific CD8+ T cells. METHODS: We conducted a first-in-human dose escalation Phase I trial in 20 healthy volunteers to assess the safety, tolerability and immunogenicity of a prime-only adenoviral vaccine for human VL and PKDL. ChAd63-KH is a replication defective simian adenovirus expressing a novel synthetic gene (KH) encoding two Leishmania proteins KMP-11 and HASPB. Uniquely, the latter was engineered to reflect repeat domain polymorphisms and arrangements identified from clinical isolates. We monitored innate immune responses by whole blood RNA-Seq and antigen specific CD8+ T cell responses by IFNγ ELISPOT and intracellular flow cytometry. FINDINGS: ChAd63-KH was safe at intramuscular doses of 1x1010 and 7.5x1010 vp. Whole blood transcriptomic profiling indicated that ChAd63-KH induced innate immune responses characterized by an interferon signature and the presence of activated dendritic cells. Broad and quantitatively robust CD8+ T cell responses were induced by vaccination in 100% (20/20) of vaccinated subjects. CONCLUSION: The results of this study support the further development of ChAd63-KH as a novel third generation vaccine for VL and PKDL. TRIAL REGISTRATION: This clinical trial (LEISH1) was registered at EudraCT (2012-005596-14) and ISRCTN (07766359)

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer

Background and aims: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress and novel therapeutic response in PC to develop a biomarker driven therapeutic strategy targeting DDR and replication stress in PC. Methods: We interrogated the transcriptome, genome, proteome and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient derived xenografts and human PC organoids. Results: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, co-segregates with response to platinum (P < 0.001) and PARP inhibitor therapy (P < 0.001) in vitro and in vivo. We generated a novel signature of replication stress with which predicts response to ATR (P < 0.018) and WEE1 inhibitor (P < 0.029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < 0.001) but not associated with DDR deficiency. Conclusions: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR proficient PC, and post-platinum therapy

The effectiveness of celebrities in conservation marketing

Celebrities are frequently used in conservation marketing as a tool to raise awareness, generate funding and effect behaviour change. The importance of evaluating effectiveness is widely recognised in both marketing and conservation but, to date, little research into the effectiveness of celebrity endorsement as a tool for conservation marketing has been published. Using a combination of interviews and an online choice survey instrument, we investigated the extent to which a sample of UK-based conservation organisations, and other charities, evaluate their own usage of celebrity endorsement, and then carried out an experimental evaluation of a hypothetical marketing campaign. This experiment compared participants' willingness-to-engage (WTE) with, and recall of, a conservation message presented in versions of an advert featuring one of three prominent UK celebrities (David Beckham, Chris Packham or HRH Prince William) or a non-celebrity control treatment (featuring Crawford Allan, a director of TRAFFIC USA). We find that the organisations we interviewed did not routinely evaluate their marketing campaigns featuring celebrities. Furthermore, our experiment provides evidence that celebrity endorsement can produce both positive and negative effects. Participants were more willing to engage when presented with an advert featuring one of the three celebrities than the non-celebrity control, and WTE varied according to the characteristics of the celebrity and the respondent. However, celebrities were less effective at generating campaign message recall than non-celebrities. These findings suggest that celebrity endorsement should be used carefully. Further work is required to fully understand the role celebrity endorsers can play in conservation but, drawing on best practice from the field of marketing, this study introduces an approach to evaluation which could be applied more widely to improve the effectiveness of conservation marketing

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

Understanding the top health issues facing Milwaukee County

Background: Health is determined by complex interactions among socioeconomic factors, health behavior, health care, and physical environment. Since 2012, the Milwaukee Health Care Partnership’s triennial Community Health Needs Assessment (CHNA) has reported the top health issues identified by residents and community leaders in Milwaukee County. The CHNA serves as the foundation from which hospitals, community health centers, and local health departments develop their community health improvement strategies. Purpose: To better understand the health of Milwaukee County and what influences it. Methods: The CHNA is informed by three key sources: Community Health Survey (a 14-minute, phone-based survey of Milwaukee County residents that addresses adult/child health risks, health behaviors, and community health needs); key informant interviews (conducted with health experts and community leaders to identify community health needs, contributing social factors, and organizations best suited to address those issues); and Health Compass Milwaukee (a compilation of publicly available data, including sources mentioned above, on a recently launched website). We utilized all three sources to create the CHNA to help understand the burdens, disparities, inequities, and determinants that contribute to health issues Results: The top 5 issues of greatest concern were chronic disease, mental health, substance use, violence, and access to health care. Among chronic disease conditions, heart disease was identified as the leading cause of death in Milwaukee County, with a premature death rate of 1228 per 100,000 lives, which is higher than the rest of Wisconsin. Among mental health outcomes, suicide rates in Wisconsin jumped 55.6% from 2000 to 2017 but remained relatively level in Milwaukee County. Regarding substance use in Milwaukee County, the opioid-related overdose death counts are concerning, with an increase from 144 in 2012 to 337 in 2017. In terms of violence against individuals that inflicts physical harm, Milwaukee County (945.1 violent crimes per 100,000 individuals) has a higher rate of violence than the rest of Wisconsin (282.9). On a positive note, regarding health care access, the Affordable Care Act spurred Milwaukee County’s uninsured rate to drop from 12.6% in 2013 to 7.2% in 2017. Conclusion: Health is complex. It is our hope that this assessment and website will help amplify providers and community conversations about the importance of cross-sector collaboration for health improvement

Inter-individual variation in DNA damage and base excision repair in young, healthy non-smokers: effects of dietary supplementation and genotype

Diets rich in fruits and vegetables are associated with lower risk of cancer which may be conferred in part by the antioxidant properties of these foods. However, antioxidant supplementation or increased consumption of antioxidant-rich foods has been reported to have inconsistent effects on DNA damage. The present work (the DART study) investigated the extent of inter-individual variation in DNA damage, the capacity for base excision repair (BER) and the responses of both variables to supplementation with an antioxidant supplement for 6 weeks. There was a wide inter-individual variation in endogenous lymphocyte DNA strand breaks (8-fold variation), in damage after a challenge with H2O2 (16-fold variation) and in DNA repair (41-fold variation) measured using the comet assay. When stratified into tertiles according to the pre-supplementation level of endogenous DNA damage, there was a statistically significant decrease in DNA damage after supplementation in the tertile with the highest pre-supplementation level of damage. There was no effect of supplementation on BER. Endogenous DNA damage level before supplementation was significantly different (P = 0·037) between the three genotypes for the Val16Ala single nucleotide polymorphism in manganese superoxide dismutase (rs4880) with individuals homozygous/wild type showing less damage than those carrying the alanine variant