Effectiveness of a behavioural intervention to prevent excessive weight gain during infancy (The Baby Milk Trial): study protocol for a randomised controlled trial.

BACKGROUND: Infancy is a period of rapid growth and habit formation and hence could be a critical period for obesity prevention. Excess weight gain during infancy is associated with later obesity and formula-fed babies are more likely to gain excess weight compared to breastfed babies. The primary trial outcome is a change in the weight standard deviation score from birth to 1 year. METHODS/DESIGN: We will recruit 650 to 700 parents who introduce formula-milk feeds within 14 weeks of their baby's birth to a single (assessor) blind, parallel group, individually randomised controlled trial. The focus of the intervention is the caregiver (usually the mother), and the focus of the primary outcome is the infant. The intervention group will receive the behavioural intervention, which aims to reduce formula-milk intake, promote responsive feeding and healthy weaning, and prevent excessive weight gain during infancy. The intervention is based on Social Cognitive Theory and action planning ('implementation intentions'). It consists of three components: (1) a motivational component to strengthen parents' motivation to follow the Baby Milk feeding guidelines, (2) an action planning component to help translate motivation into action, and (3) a coping planning component to help parents deal with difficult situations. It will be delivered by trained facilitators (research nurses) over 6 months through three face-to-face contacts, two telephone contacts and written materials. The control group will have the same number of contacts with facilitators, and general issues about feeding will be discussed. Anthropometric outcomes will be measured by trained research staff, blind to group allocation, at baseline, 6 months and 12 months following standard operating procedures. Validated questionnaires will assess milk intake, temperament, appetite, sleep, maternal quality of life and maternal psychological factors. A 4-day food diary will be completed at 8 months. DISCUSSION: The results of the trial will help to inform infant feeding guidelines and to understand the links between infant feeding, behaviour, appetite and growth. TRIAL REGISTRATION: ISRTCN20814693 . Registration date 13 January 2011.The work was undertaken under the auspices of the Centre for Diet and Activity Research (CEDAR), a UKCRC Public Health Research Centre of Excellence which is funded by the British Heart Foundation, Cancer Research UK, Economic and Social Research Council, Medical Research Council, the National Institute for Health Research, and the Wellcome Trust. The Baby Milk trial is funded by the National Prevention Research Initiative (http://www.npri.org.uk Grant no. MR/J000361/1). The Funding Partners relevant to this award are (in alphabetical order): Alzheimer’s Research Trust; Alzheimer’s Society; Biotechnology and Biological Sciences Research Council; British Heart Foundation; Cancer Research UK; Chief Scientist Office, Scottish Government Health Directorate; Department of Health; Diabetes UK; Economic and Social Research Council; Health and Social Care Research and Development Division of the Public Health Agency (HSC R&D Division); Medical Research Council; The Stroke Association; Wellcome Trust; Welsh Assembly Government; and World Cancer Research Fund. Lakshman Rajalakshmi was funded by a MRC Population Health Fellowship (Grant no. G070165).This is the final version of the article. It first appeared from BioMed Central via http://dx.doi.org/10.1186/s13063-015-0941-

Randomised controlled trial of a theory-based behavioural intervention to reduce formula milk intake

Objective: To assess the efficacy of a theory-based behavioural intervention to prevent rapidweight gain in formula-milk fed infants.  Design: In this single (assessor) blind, randomised controlled trial, 669 healthy full-terminfants receiving formula-milk within 14 weeks of birth were individually-randomised tointervention (n=340) or attention-matched control (n=329) groups. The intervention aimed toreduce formula-milk intakes, and promote responsive feeding and growth monitoring toprevent rapid weight gain (>+ 0.67 standard deviation scores [SDS]). It was delivered tomothers by trained facilitators up to infant age 6 months through 3 face-to-face contacts, 2telephone contacts, and written materials.  Results: Retention was 93% (622) at 6 months, 88% (586) at 12 months, and 94% attended >4/5 sessions. The intervention strengthened maternal attitudes to following infant feedingrecommendations, reduced reported milk intakes at ages 3 (-14%; intervention vs controlinfants), 4 (-12%), 5 (-9%), and 6 (-7%) months, slowed initial infant weight gain frombaseline to 6 months (mean change 0.32 vs 0.42 SDS, baseline-adjusted difference(intervention vs control) -0.08 [95% CI; -0.17, -0.004] SDS), but had no effect on the primaryoutcome of weight gain to 12 months (baseline-adjusted difference -0.04 [-0.17, 0.10] SDS).By 12 months, 40.3% of infants in the intervention group and 45.9% in the control groupshowed rapid weight gain (OR: 0.84 [95% CI; 0.59, 1.17]).  Conclusions: Despite reducing milk intakes and initial weight gain, the intervention did notalter the high prevalence of rapid weight gain to age 12 months suggesting the need forsustained intervention

Radio Spectra of Luminous, Heavily Obscured WISE-NVSS Selected Quasars

We present radio spectra spanning $0.1 - 10$ GHz for the sample of heavily obscured luminous quasars with extremely red mid-infrared-optical colors and compact radio emission. The spectra are constructed from targeted 10 GHz observations and archival radio survey data, which together yield $6-11$ flux density measurements for each object. Our suite of Python tools for modeling the radio spectra is publicly available on Github. Our primary result is that most (61%) of the sample have peaked or curved radio spectra and many (36%) could be classified as Gigahertz Peaked Spectrum (GPS) sources. This indicates compact emission regions likely arising from recently triggered radio jets. Assuming synchrotron self-absorption (SSA) generates the peaks, we infer compact source sizes ($3 - 100$ pc) with strong magnetic fields ($6 - 100$ mG) and young ages ($30 - 10^4$ years). Conversely, free-free absorption (FFA) could also create peaks due to the high column densities associated with the deeply embedded nature of the sample. However, we find no correlations between the existence or frequency of the peaks and any parameters of the MIR emission. The high-frequency spectral indices are steep ($\alpha \approx -1$) and correlate, weakly, with the ratio of MIR photon energy density to magnetic energy density, suggesting that the spectral steepening could arise from inverse Compton scattering off the intense MIR photon field. This study provides a foundation for combining multi-frequency and mixed-resolution radio survey data for understanding the impact of young radio jets on the ISM and star formation rates of their host galaxies.Comment: 48 pages, 17 figures, published in Astrophysical Journa

Protocol for the ADDITION-Plus study: a randomised controlled trial of an individually-tailored behaviour change intervention among people with recently diagnosed type 2 diabetes under intensive UK general practice care.

BACKGROUND: The increasing prevalence of type 2 diabetes poses both clinical and public health challenges. Cost-effective approaches to prevent progression of the disease in primary care are needed. Evidence suggests that intensive multifactorial interventions including medication and behaviour change can significantly reduce cardiovascular morbidity and mortality among patients with established type 2 diabetes, and that patient education in self-management can improve short-term outcomes. However, existing studies cannot isolate the effects of behavioural interventions promoting self-care from other aspects of intensive primary care management. The ADDITION-Plus trial was designed to address these issues among recently diagnosed patients in primary care over one year. METHODS/DESIGN: ADDITION-Plus is an explanatory randomised controlled trial of a facilitator-led, theory-based behaviour change intervention tailored to individuals with recently diagnosed type 2 diabetes. 34 practices in the East Anglia region participated. 478 patients with diabetes were individually randomised to receive (i) intensive treatment alone (n = 239), or (ii) intensive treatment plus the facilitator-led individual behaviour change intervention (n = 239). Facilitators taught patients key skills to facilitate change and maintenance of key behaviours (physical activity, dietary change, medication adherence and smoking), including goal setting, action planning, self-monitoring and building habits. The intervention was delivered over one year at the participant's surgery and included a one-hour introductory meeting followed by six 30-minute meetings and four brief telephone calls. Primary endpoints are physical activity energy expenditure (assessed by individually calibrated heart rate monitoring and movement sensing), change in objectively measured dietary intake (plasma vitamin C), medication adherence (plasma drug levels), and smoking status (plasma cotinine levels) at one year. We will undertake an intention-to-treat analysis of the effect of the intervention on these measures, an assessment of cost-effectiveness, and analyse predictors of behaviour change in the cohort. DISCUSSION: The ADDITION-Plus trial will establish the medium-term effectiveness and cost-effectiveness of adding an externally facilitated intervention tailored to support change in multiple behaviours among intensively-treated individuals with recently diagnosed type 2 diabetes in primary care. Results will inform policy recommendations concerning the management of patients early in the course of diabetes. Findings will also improve understanding of the factors influencing change in multiple behaviours, and their association with health outcomes.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Quasars That Have Transitioned from Radio-quiet to Radio-loud on Decadal Timescales Revealed by VLASS and FIRST

We have performed a search over 3440 deg² of Epoch 1 (2017–2019) of the Very Large Array Sky Survey to identify unobscured quasars in the optical (0.2 2500%) but roughly steady fluxes over a few months at 3 GHz are inconsistent with extrinsic variability due to propagation effects, thus favoring an intrinsic origin. We conclude that our sources are powerful quasars hosting compact/young jets. This challenges the generally accepted idea that "radio-loudness" is a property of the quasar/AGN population that remains fixed on human timescales. Our study suggests that frequent episodes of short-lived AGN jets that do not necessarily grow to large scales may be common at high redshift. We speculate that intermittent but powerful jets on subgalactic scales could interact with the interstellar medium, possibly driving feedback capable of influencing galaxy evolution

The Canadian Perinatal Network: A National Network Focused on Threatened Preterm Birth at 22 to 28 Weeks\u27 Gestation

Objective: The Canadian Perinatal Network (CPN) maintains an ongoing national database focused on threatened very preterm birth. The objective of the network is to facilitate between-hospital comparisons and other research that will lead to reductions in the burden of illness associated with very preterm birth. Methods: Women were included in the database if they were admitted to a participating tertiary perinatal unit at 22+0 to 28+6 weeks\u27 gestation with one or more conditions most commonly responsible for very preterm birth, including spontaneous preterm labour with contractions, incompetent cervix, prolapsing membranes, preterm prelabour rupture of membranes, gestational hypertension, intrauterine growth restriction, or antepartum hemorrhage. Data were collected by review of maternal and infant charts, entered directly into standardized electronic data forms and uploaded to the CPN via a secure network. Results: Between 2005 and 2009, the CPN enrolled 2524 women from 14 hospitals including those with preterm labour and contractions (27.4%), short cervix without contractions (16.3%), prolapsing membranes (9.4%), antepartum hemorrhage (26.0%), and preterm prelabour rupture of membranes (23 0%) The mean gestational age at enrolment was 25.9 ± 1.9 weeks and the mean gestation age at delivery was 29.9 ± 5.1 weeks; 57.0% delivered at \u3c 29 weeks and 75.4% at \u3c 34 weeks. Complication rates were high and included serious maternal complications (26 7%), stillbirth (8.2%), neonatal death (16.3%), neonatal intensive care unit admission (60 7%), and serious neonatal morbidity (35 0%). Conclusion: This national dataset contains detailed information about women at risk of very preterm birth. It is available to clinicians and researchers who are working with one or more CPN collaborators and who are interested in studies relating processes of care to maternal or perinatal outcomes

A mutation in the viral sensor 2'-5'-oligoadenylate synthetase 2 causes failure of lactation

We identified a non-synonymous mutation in Oas2 (I405N), a sensor of viral double-stranded RNA, from an ENU-mutagenesis screen designed to discover new genes involved in mammary development. The mutation caused post-partum failure of lactation in healthy mice with otherwise normally developed mammary glands, characterized by greatly reduced milk protein synthesis coupled with epithelial cell death, inhibition of proliferation and a robust interferon response. Expression of mutant but not wild type Oas2 in cultured HC-11 or T47D mammary cells recapitulated the phenotypic and transcriptional effects observed in the mouse. The mutation activates the OAS2 pathway, demonstrated by a 34-fold increase in RNase L activity, and its effects were dependent on expression of RNase L and IRF7, proximal and distal pathway members. This is the first report of a viral recognition pathway regulating lactation.This work was supported by grants from the Congress Directed Medical Research Program (BC995364 and DAMD17-01-1-0241), Cure Cancer Australia Foundation, NHMRC Australia (projects 1047149, Fellowships 1058356, 481310, 1043400), the Australian Research Council Discovery Project (DP110102288), Princeton University, NIH grant 1R01GM110161-01 (AK), Sidney Kimmel Foundation for Cancer Research (AK), Burroughs Wellcome Foundation (AK), Banque Nationale de Paris-Paribas Australia and New Zealand, Mostyn Family Foundation, Cue Clothing Co., Estee Lauder Australia, RT Hall Trust and Fellowships (ECF-13-08 and ECF-16-022) from the National Breast Cancer Foundatio

Failure of Decidualization and Maternal Immune Tolerance Underlies Uterovascular Resistance in Intra Uterine Growth Restriction

Failure of uterine vascular transformation is associated with pregnancy complications including Intra Uterine Growth Restriction (IUGR). The decidua and its immune cell populations play a key role in the earliest stages of this process. Here we investigate the hypothesis that abnormal decidualization and failure of maternal immune tolerance in the second trimester may underlie the uteroplacental pathology of IUGR. Placental bed biopsies were obtained from women undergoing elective caesarian delivery of a healthy term pregnancy, an IUGR pregnancy or a pregnancy complicated by both IUGR and preeclampsia. Decidual tissues were also collected from second trimester terminations from women with either normal or high uterine artery Doppler pulsatile index (PI). Immunohistochemical image analysis and flow cytometry were used to quantify vascular remodeling, decidual leukocytes and decidual status in cases vs. controls. Biopsies from pregnancies complicated by severe IUGR with a high uterine artery pulsatile index (PI) displayed a lack of: myometrial vascular transformation, interstitial, and endovascular extravillous trophoblast (EVT) invasion, and a lower number of maternal leukocytes. Apoptotic mural EVT were observed in association with mature dendritic cells and T cells in the IUGR samples. Second trimester pregnancies with high uterine artery PI displayed a higher incidence of small for gestational age fetuses; a skewed decidual immunology with higher numbers of; CD8 T cells, mature CD83 dendritic cells and lymphatic vessels that were packed with decidual leukocytes. The decidual stromal cells (DSCs) failed to differentiate into the large secretory DSC in these cases, remaining small and cuboidal and expressing lower levels of the nuclear progesterone receptor isoform B, and DSC markers Insulin Growth Factor Binding protein-1 (IGFBP-1) and CD10 as compared to controls. This study shows that defective progesterone mediated decidualization and a hostile maternal immune response against the invading endovascular EVT contribute to the failure of uterovascular remodeling in IUGR pregnancies

Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine

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