Background Pregnant women with metabolic risk factors are at high risk of complications. We aimed to assess whether a Mediterranean-style diet reduces adverse pregnancy outcomes in high-risk women. Methods and findings We conducted a multicentre randomised trial in 5 maternity units (4 in London and 1 in Birmingham) between 12 September 2014 and 29 February 2016. We randomised inner-city pregnant women with metabolic risk factors (obesity, chronic hypertension, or hypertriglyceridaemia) to a Mediterranean-style diet with high intake of nuts, extra virgin olive oil, fruits, vegetables, nonrefined grains, and legumes; moderate to high consumption of fish; low to moderate intake of poultry and dairy products; low intake of red and processed meat; and avoidance of sugary drinks, fast food, and food rich in animal fat versus usual care. Participants received individualised dietary advice at 18, 20, and 28 weeks’ gestation. The primary endpoints were composite maternal (gestational diabetes or preeclampsia) and composite offspring (stillbirth, small for gestational age, or admission to neonatal care unit) outcomes prioritised by a Delphi survey. We used an intention-to-treat (ITT) analysis with multivariable models and identified the stratification variables and prognostic factors a priori. We screened 7,950 and randomised 1,252 women. Baseline data were available for 593 women in the intervention (93.3% follow-up, 553/593) and 612 in the control (95.6% follow-up, 585/612) groups. Over a quarter of randomised women were primigravida (330/1,205; 27%), 60% (729/1,205) were of Black or Asian ethnicity, and 69% (836/1,205) were obese. Women in the intervention arm consumed more nuts (70.1% versus 22.9%; adjusted odds ratio [aOR] 6.8, 95% confidence interval [CI] 4.3–10.6, p ≤ 0.001) and extra virgin olive oil (93.2% versus 49.0%; aOR 32.2, 95% CI 16.0–64.6, p ≤ 0.001) than controls; increased their intake of fish ( p < 0.001), white meat ( p < 0.001), and pulses ( p = 0.05); and reduced their intake of red meat ( p < 0.001), butter, margarine, and cream ( p < 0.001). There was no significant reduction in the composite maternal (22.8% versus 28.6%; aOR 0.76, 95% CI 0.56–1.03, p = 0.08) or composite offspring (17.3% versus 20.9%; aOR 0.79, 95% CI 0.58–1.08, p = 0.14) outcomes. There was an apparent reduction in the odds of gestational diabetes by 35% (aOR 0.65, 95% CI 0.47–0.91, p = 0.01) but not in other individual components of the composite outcomes. Mothers gained less gestational weight (mean 6.8 versus 8.3 kg; adjusted difference −1.2 Kg, 95% CI −2.2 to −0.2, p = 0.03) with intervention versus control. There was no difference in any of the other maternal and offsprin...

The UK weaning guidelines recommend the introduction of solid food at or around 6 months. The evidence suggests that knowledge of the guidelines is high, although only a small minority of parents wait until 6 months to wean. The aim of this study was to assess understanding of the UK weaning guidelines in a sample of UK parents and investigate the associations of this understanding with weaning timing, and in comparison to other influencing factors. This study conducted an online survey of UK parents. Eligible participants had weaned a child since the introduction of the current guidelines. Of 3607 participants, 86% accurately understood the guidelines. Eighty-seven per cent of health visitors were reported to have advised weaning at or around 6 months. Knowledge of the guidelines was associated with later weaning (independently of demographic factors) (P < 0.001) but did not ensure compliance: 80% of mothers who weaned before 24 weeks and 65% who weaned before 17 weeks were aware of the guidelines. Younger mothers (P < 0.001), those receiving benefits (P < 0.001), those educated only to 16 (P < 0.001) and minority ethnic groups (P < 0.001) had lower levels of awareness. Poor understanding of the guidelines was the most reliable predictor of early weaning (P = 0.021) together with young maternal age (P = 0.014). Following the baby-led weaning approach was the most reliable predictor of those weaning at 26 weeks, together with the Internet being the most influential source of advice. Understanding of the current weaning guidelines is high and is a key independent predictor of weaning age in this population.

(18)F-Fluoride bone plasma clearance can be estimated from a static scan and venous blood samples acquired 30-60 min after injection. The method enables K ( i ) to be estimated at multiple skeletal sites with a single injection of tracer.

Teriparatide increases skeletal mass, bone turnover markers, and bone strength, but local effects on bone tissue may vary between skeletal sites. We used positron emission tomography (PET) to study 18 F-fluoride plasma clearance (K i ) at the spine and standardized uptake values (SUVs) at the spine, pelvis, total hip, and femoral shaft in 18 postmenopausal women with osteoporosis. Subjects underwent a 1-hour dynamic scan of the lumbar spine and a 10-minute static scan of the pelvis and femurs at baseline and after 6 months of treatment with 20 mg/day teriparatide. Blood samples were taken to derive the arterial input function and lumbar spine K i values evaluated using a three-compartment model. SUVs were calculated for the spine, pelvis, total hip, and femoral shaft. After 6 months treatment with teriparatide, spine K i values increased by 24% (p ¼ .0003), while other model parameters were unchanged except for the fraction of tracer going to bone mineral (k 3 /[k 2 þ k 3 ]), which increased by 23% (p ¼ .0006). In contrast to K i , spine SUVs increased by only 3% (p ¼ .84). The discrepancy between changes in K i and SUVs was explained by a 20% decrease in 18 F À plasma concentration. SUVs increased by 37% at the femoral shaft (p ¼ .0019), 20% at the total hip (p ¼ .032), and 11% at the pelvis (p ¼ .070). Changes in bone turnover markers and BMD were consistent with previous trials. We conclude that the changes in bone formation rate during teriparatide treatment as measured by 18 F À PET differ at different skeletal sites, with larger increases in cortical bone than at trabecular sites. ß

SummaryThe tomato Mi-1 gene confers resistance against root-knot nematodes (Meloidogyne spp.) and a biotype of the potato aphid (Macrosiphum euphorbiae). Four mutagenized Mi-1/Mi-1 tomato populations were generated and screened for altered root-knot nematode resistance. Four independent mutants belonging to two phenotypic classes were isolated. One mutant was chosen for further analyzes; rme1 (for resistance to Meloidogyne) exhibited levels of infection comparable with those found on susceptible controls. Molecular and genetic data con®rmed that rme1 has a single recessive mutation in a locus different from Mi-1. Cross-sections through galls formed by feeding nematodes on rme1 roots were identical to sections from galls of susceptible tomato roots. In addition to nematode susceptibility, infestation of rme1 plants with the potato aphid showed that this mutation also abolished aphid resistance. To determine whether Rme1 functions in a general disease-resistance pathway, the response against Fusarium oxysporum f.sp. lycopersici race 2, mediated by the I-2 resistance gene, was studied. Both rme1 and the wild type plants were equally resistant to the fungal pathogen. These results indicate that Rme1 does not play a general role in disease resistance but may be speci®c for Mi-1-mediated resistance.

OBJECTIVES:Recurrent acute pancreatitis (RAP) is a complex inflammatory disorder that may progress to fibrosis and other irreversible features recognized as chronic pancreatitis (CP). Chymotrypsinogen C (CTRC) protects the pancreas by degrading prematurely activated trypsinogen. Rare mutations are associated with CP in Europe and Asia. We evaluated the occurrence of CTRC variants in subjects with RAP, CP, and controls from the North American Pancreatitis Study II cohort.METHODS:CP (n=694), RAP (n=448), and controls (n=1017) of European ancestry were evaluated. Subgroup analysis included CFTR and SPINK1 variants, alcohol, and smoking.RESULTS:We identified previously reported rare pathogenic CTRC A73T, R254W, and K247_R254del variants, intronic variants, and G60G (c.180 C>T; rs497078). Compared with controls (minor allele frequency (MAF)=10.8%), c.180T was associated with CP (MAF=16.8%, P<0.00001) but not RAP (MAF=11.9% P=NS). Trend test indicated co-dominant risk for CP (CT odds ratio (OR)=1.36, 95% confidence interval (CI)=1.13–1.64, P=0.0014; TT OR=3.98, 95% CI=2.10–7.56, P<0.0001). The T allele was significantly more frequent with concurrent pathogenic CFTR variants and/or SPINK1 N34S (combined 22.9% vs. 16.1%, OR 1.92, 95% C.I. 1.26–2.94, P=0.0023) and with alcoholic vs. non-alcoholic CP etiologies (20.8% vs. 12.4%, OR=1.9, 95% CI=1.30–2.79, P=0.0009). Alcohol and smoking generally occurred together, but the frequency of CTRC c.180 T in CP, but not RAP, was higher among never drinkers–ever smokers (22.2%) than ever drinker–never smokers (10.8%), suggesting that smoking rather than alcohol may be the driving factor in this association.CONCLUSIONS:The common CTRC variant c.180T acts as disease modifier that promotes progression from RAP to CP, especially in patients with CFTR or SPINK1 variants, alcohol, or smoking.

Background UK African and Caribbean (AfC) communities are disproportionately burdened by type 2 diabetes (T2D). Promoting healthy eating and physical activity through structured education is the cornerstone of T2D care, however cultural barriers may limit engagement in these communities. In addition, changes in lifestyle behaviour are shaped by normative influences within social groups and contextual factors need to be understood to facilitate healthful behaviour change. The Behaviour Change Wheel (BCW) and associated COM-B framework offer intervention designers a systematic approach to developing interventions. The aim of this study was to apply the BCW in the design of a culturally sensitive self-management support programme for T2D in UK AfC communities. Methods An intervention development study was conducted. Focus groups were held with 41 AfC patients with T2D to understand healthful weight-management, diet and physical activity behaviours. The COM-B framework and BCW were used to evaluate the qualitative data, identify appropriate behaviour change techniques and specify the intervention components. Results Participants were motivated to avoid diabetes-related consequences although did not always understand the negative impact of their current health behaviours on long-term diabetes outcomes. Barriers to healthful behaviour included gaps in knowledge related to diet, physical activity and weight management guidance. In addition, motivation and social opportunity barriers included an acceptance of larger body sizes, rejection of body mass index for weight guidance and cultural identity being strongly linked to consumption of traditional starches. There was a lack of social opportunity to perform moderate to vigorous physical activity, although walking and dance were culturally acceptable. The resulting Healthy Eating & Active Lifestyles for Diabetes (HEAL-D) intervention uses social support, social comparison, credible sources and demonstration as key behaviour change techniques. Conclusion Use of COM-B and the BCW highlighted the need for an intervention to address motivational and social opportunity barriers to engaging in healthful behaviours, as well as addressing key gaps in knowledge. This framework facilitated the linkage of theoretical behaviour constructs with evidence-based behaviour change techniques, which will enable us to evaluate operationalisation of our chosen BCTs and their impact on behaviour change in a future feasibility study. Electronic supplementary material The online version of this article (10.1186/s12889-019-7411-z) contains supplementary material, which is available to authorized users.

The functional imaging technique of 18 F-fluoride positron emission tomography ( 18 F-PET) allows the noninvasive quantitative assessment of regional bone formation at any skeletal site, including the spine and hip. The aim of this study was to determine if 18 F-PET can be used as an early biomarker of treatment efficacy at the hip. Twenty-seven treatment-naive postmenopausal women with osteopenia were randomized to receive teriparatide and calcium and vitamin D (TPT group, n ¼ 13) or calcium and vitamin D only (control group, n ¼ 14). Subjects in the TPT group were treated with 20 mg/day teriparatide for 12 weeks. 18 F-PET scans of the proximal femur, pelvis, and lumbar spine were performed at baseline and 12 weeks. The plasma clearance of 18 F-fluoride to bone, K i , a validated measurement of bone formation, was measured at four regions of the hip, lumbar spine, and pelvis. A significant increase in K i was observed at all regions of interest (ROIs), including the total hip (þ27%, p ¼ 0.002), femoral neck (þ25%, p ¼ 0.040), hip trabecular ROI (þ21%, p ¼ 0.017), and hip cortical ROI (þ51%, p ¼ 0.001) in the TPT group. Significant increases in K i in response to TPT were also observed at the lumbar spine (þ18%, p ¼ 0.001) and pelvis (þ42%, p ¼ 0.001). No significant changes in K i were observed for the control group. Changes in BMD and bone turnover markers were consistent with previous trials of teriparatide. In conclusion, this is the first study to our knowledge to demonstrate that 18 F-PET can be used as an imaging biomarker for determining treatment efficacy at the hip as early as 12 weeks after initiation of therapy. ß