MassARRAY and SABER Analyses of SNPs in Embryo DNA Reveal the Abscission of Self-Fertilised Progeny during Fruit Development of Macadamia (Macadamia integrifolia Maiden & Betche).

Yield in many crops is affected by abscission during the early stages of fruitlet development. The reasons for fruitlet abscission are often unclear but they may include genetic factors because, in some crops, self-pollinated fruitlets are more likely to abscise than cross-pollinated fruitlets. Pollen parentage can also affect final fruit size and fruit quality. Here, we aimed to understand the effects of pollen parentage on fruitlet retention and nut quality in orchards of macadamia (Macadamia integrifolia Maiden & Betche). We identified the pollen parent of macadamia 'cultivar '816' embryos by analysing single nucleotide polymorphisms (SNPs) in their DNA using customised MassARRAY and Single Allele Base Extension Reaction (SABER) methods. This allowed us to determine the proportions of self-fertilised and cross-fertilised progeny during premature fruit drop at 6 weeks and 10 weeks after peak anthesis, as well as at nut maturity. We determined how pollen parentage affected nut-in-shell (NIS) mass, kernel mass, kernel recovery, and oil concentration. Macadamia trees retained cross-fertilised fruitlets rather than self-fertilised fruitlets. The percentage of progeny that were cross-fertilised increased from 6% at 6 weeks after peak anthesis to 97% at nut maturity, with each tree producing on average 22 self-fertilised nuts and 881 cross-fertilised nuts. Three of the four cross-pollen parents provided fruit with significantly higher NIS mass, kernel mass, or kernel recovery than the few remaining self-fertilised fruit. Fruit that were cross-fertilised by '842', 'A4', or 'A203' had 16-29% higher NIS mass and 24-44% higher kernel mass than self-fertilised fruit. Nuts that were cross-fertilised by 'A4' or 'A203' also had 5% or 6% higher kernel recovery, worth approximately $US460-540 more per ton for growers than self-fertilised nuts. The highly selective abscission of self-fertilised fruitlets and the lower nut quality of self-fertilised fruit highlight the critical importance of cross-pollination for macadamia productivity.

Pollen limitation and xenia effects in a cultivated mass-flowering tree, Macadamia integrifolia (Proteaceae).

BACKGROUND AND AIMS: Pollen limitation is most prevalent among bee-pollinated plants, self-incompatible plants and tropical plants. However, we have very little understanding of the extent to which pollen limitation affects fruit set in mass-flowering trees despite tree crops accounting for at least 600 million tons of the 9200 million tons of annual global food production. METHODS: We determined the extent of pollen limitation in a bee-pollinated, partially self-incompatible, subtropical tree by hand cross-pollinating the majority of flowers on mass-flowering macadamia (Macadamia integrifolia) trees that produce about 200 000-400 000 flowers. We measured tree yield and kernel quality and estimated final fruit set. We genotyped individual kernels by MassARRAY to determine levels of outcrossing in orchards and assess paternity effects on nut quality. KEY RESULTS: Macadamia trees were pollen-limited. Supplementary cross-pollination increased nut-in-shell yield, kernel yield and fruit set by as much as 97, 109 and 92 %, respectively. The extent of pollen limitation depended upon the proximity of experimental trees to trees of another cultivar because macadamia trees were highly outcrossing. Between 84 and 100 % of fruit arose from cross-pollination, even at 200 m (25 rows) from orchard blocks of another cultivar. Large variations in nut-in-shell mass, kernel mass, kernel recovery and kernel oil concentration were related to differences in fruit paternity, including between self-pollinated and cross-pollinated fruit, thus demonstrating pollen-parent effects on fruit quality (i.e. xenia). CONCLUSIONS: This study is the first to demonstrate pollen limitation in a mass-flowering tree. Improved pollination led to increased kernel yield of 0.31-0.59 tons ha-1, which equates currently to higher farm-gate income of approximately $US3720-$US7080 ha-1. The heavy reliance of macadamia flowers on cross-pollination and the strong xenia effects on kernel mass demonstrate the high value that pollination services can provide to food production.

Short distance pollen dispersal and low genetic diversity in a subcanopy tropical rainforest tree, Fontainea picrosperma (Euphorbiaceae).

Gene flow via pollen movement affects genetic variation in plant populations and is an important consideration in plant domestication. Fontainea picrosperma is a subcanopy rainforest tree that is of commercial interest because it is the source of tigilanol tiglate, a natural product used for the treatment of solid tumors. We identify patterns of pollen-mediated gene flow within natural populations of F. picrosperma and estimate genetic parameters and genetic structure between adult and juvenile groups using microsatellite markers. Our results show pollination events occur over much shorter distances than reported for tropical canopy species. At least 63% of seeds are sired by male trees located within 30 m of the mother. On average, 27% of the local male population contributed to successful reproduction of F. picrosperma with most fathers siring a single seed, however, the contributions to reproduction were uneven. Larger male trees with more flowers had greater reproductive success than those with less flowers (P < 0.05). There were comparatively low levels of genetic variation across the species (HE = 0.405 for adult trees and 0.379 for juveniles) and we found no loss of genetic diversity between adult and juvenile trees. Short distance pollen flow and low genetic diversity is theoretically a prelude to genetic impoverishment, however F. picrosperma has persisted through multiple significant climatic oscillations. Nevertheless, the remaining low genetic diversity is of concern for domestication programs which require maximal genetic diversity to facilitate efficient selective breeding and genetic improvement of this commercially significant species.

Nutritional quality of almond, canarium, cashew and pistachio and their oil photooxidative stability.

Daily consumption of nuts is recommended as a part of a healthy diet as they contain protein and are rich in beneficial fatty acids and essential nutrients. The nutritional qualities of nuts are affected by their fatty acid composition and other factors such as maturity. Oil oxidative stability is important to determine nut nutritional quality in terms of fatty acid composition over storage. Therefore, this study aimed to (a) assess the nutritional quality (photooxidative stability and nutrient composition) of almond, cashew, pistachio and canarium (a newly commercialised indigenous nut); and (b) explore differences in nutrient concentrations between immature and mature canarium nuts. A decrease in polyunsaturated fats after photooxidation in almond and pistachio was observed. Canarium oil did not change following photooxidation suggesting canarium may display a long shelf life when stored appropriately. Our study indicated that almond provided over 50% of the recommended daily intake for manganese whereas canarium intake provided 50% of the recommended daily intake for iron (for males). Pistachio was richer in potassium compared with other nuts and canarium was richer in boron, iron and zinc than other nut species. Mature canarium kernels were richer in boron, iron and zinc but contained less potassium than immature canarium. Therefore, the current study recommended to store kernels in dark to decrease oil photooxidation, and maturity of canarium kernels at the harvest time was important affecting nutrient concentrations of kernels.

Increased Population Risk of AIP-Related Acromegaly and Gigantism in Ireland.

The aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304* (or p.R304* ; NM_003977.3:c.910C>T, p.Arg304Ter) identified in Northern Ireland (NI) predisposes to acromegaly/gigantism; its population health impact remains unexplored. We measured R304* carrier frequency in 936 Mid Ulster, 1,000 Greater Belfast (both in NI) and 2,094 Republic of Ireland (ROI) volunteers and in 116 NI or ROI acromegaly/gigantism patients. Carrier frequencies were 0.0064 in Mid Ulster (95%CI = 0.0027-0.013; P = 0.0005 vs. ROI), 0.001 in Greater Belfast (0.00011-0.0047) and zero in ROI (0-0.0014). R304* prevalence was elevated in acromegaly/gigantism patients in NI (11/87, 12.6%, P < 0.05), but not in ROI (2/29, 6.8%) versus non-Irish patients (0-2.41%). Haploblock conservation supported a common ancestor for all the 18 identified Irish pedigrees (81 carriers, 30 affected). Time to most recent common ancestor (tMRCA) was 2550 (1,275-5,000) years. tMRCA-based simulations predicted 432 (90-5,175) current carriers, including 86 affected (18-1,035) for 20% penetrance. In conclusion, R304* is frequent in Mid Ulster, resulting in numerous acromegaly/gigantism cases. tMRCA is consistent with historical/folklore accounts of Irish giants. Forward simulations predict many undetected carriers; geographically targeted population screening improves asymptomatic carrier identification, complementing clinical testing of patients/relatives. We generated disease awareness locally, necessary for early diagnosis and improved outcomes of AIP-related disease.

Vitamin D and insulin resistance.

Vitamin D is a steroid hormone, which in active form binds to the vitamin D receptor. Expression of the vitamin D receptor in diverse cell types (pancreatic islet cells, myocytes, hepatocytes and adipocytes) raises the suspicion that vitamin D may be involved in multiple cellular processes, including the response to insulin. Insulin resistance is a characteristic feature of type 2 DM, and its attenuation may reduce the incidence of type 2 DM and cardiovascular disease. In observational studies, low serum 25-hydroxyvitamin D (25-OHD) concentrations are associated with an increased risk of type 2 DM. It has been suggested that increasing serum 25-OHD concentrations may have beneficial effects on glucose and insulin homeostasis. However, cross-sectional and interventional studies of vitamin D supplementation provide conflicting results and demonstrate no clear beneficial effect of vitamin D on insulin resistance. These studies are complicated by inclusion of different patient cohorts, different 25-OHD assays and different doses and preparations of vitamin D. Any possible association may be confounded by alterations in PTH, 1,25-dihydroxyvitamin D or tissue vitamin D concentrations. We identified 39 studies via MEDLINE and PUBMED. We review the evidence from 10 studies (seven observational and three interventional) examining vitamin D and type 2 DM incidence, and 29 studies (one prospective observational, 12 cross-sectional and 16 interventional trials) examining vitamin D and insulin resistance. Based on this data, it is not possible to state that vitamin D supplementation has any effect on type 2 DM incidence or on insulin resistance. Data from the multiple ongoing randomized controlled trials of vitamin D supplementation due to report over the next few years should help to clarify this area.

Resources or landmarks: which factors drive homing success in Tetragonula carbonaria foraging in natural and disturbed landscapes?

To date, no study has investigated how landscape structural (visual) alterations affect navigation and thus homing success in stingless bees. We addressed this question in the Australian stingless bee Tetragonula carbonaria by performing marking, release and re-capture experiments in landscapes differing in habitat homogeneity (i.e., the proportion of elongated ground features typically considered prominent visual landmarks). We investigated how landscape affected the proportion of bees and nectar foragers returning to their hives as well as the earliest time bees and foragers returned. Undisturbed landscapes with few landmarks (that are conspicuous to the human eye) and large proportions of vegetation cover (natural forests) were classified visually/structurally homogeneous, and disturbed landscapes with many landmarks and fragmented or no extensive vegetation cover (gardens and plantations) visually/structurally heterogeneous. We found that proportions of successfully returning nectar foragers and earliest times first bees and foragers returned did not differ between landscapes. However, most bees returned in the visually/structurally most (forest) and least (garden) homogeneous landscape, suggesting that they use other than elongated ground features for navigation and that return speed is primarily driven by resource availability in a landscape.

Phloroglucinols from anti-microbial deposit-resins of Australian stingless bees (Tetragonula carbonaria).

Stingless bees accumulate deposits of plant resins that are mixed with beeswax to produce propolis. Previous studies have reported anti-microbial constituents of stingless bee (Tetragonula carbonaria) propolis from East Australia, but several components remained to be characterized. In the search of natural products yet unreported for Australian propolis, four bee deposit-resins of T. carbonaria bees were analysed by gas and liquid chromatography mass spectrometry with accurate mass measurements. Ethanolic extracts of the deposit-resins were tested in vitro against Staphylococcus aureus ATCC 25983 and Pseudomonas aeruginosa ATCC 27853 by the agar diffusion method. Phloroglucinols, flavonoids and isoprenoids were identified in samples. The crude extracts showed strong anti-staphylococcal effects but were less active against the Gram-negative bacterium. The diagnostic data enabled the identification of markers that can be used for profiling other Australian propolis sources and to target the isolation of bioactive phloroglucinols in future studies against antibiotic resistant S. aureus strains.

Diversity matters: how bees benefit from different resin sources.

Biodiverse environments provide a variety of resources that can be exploited by consumers. While many studies revealed a positive correlation between biodiversity and consumer biomass and richness, only few studies have investigated how resource diversity affects single consumers. To better understand whether a single consumer species benefits from diverse resources, we tested how the protective function of a defensive plant resource (i.e. resin exploited by social bees) varied among different sources and target organisms (predators, parasites and pathogens). To assess synergistic effects, resins from different plant genera were tested separately and in combination. We found that resin diversity is beneficial for bees, with its functional properties depending on the target organisms, type and composition of resin. Different resins showed different effects, and mixtures were more effective than some of the single resins (functional complementarity). We conclude that resins of different plant species target different organisms and act synergistically where combined. Bees that rely on resin for protection benefit more when they have access to diverse resin sources. Loss of biodiversity may in turn destabilize consumer populations due to restricted access to a variety of resources.

Chemical constituents of kino extract from Corymbia torelliana.

Seven flavanones were identified from kino exudate of Corymbia torelliana by spectroscopic and spectrometric methods including UV, 1D and 2D NMR and UPLC-HR-MS. The study identified seven molecules, namely 3,4',5,7-tetrahydroxyflavanone (1), 3',4',5,7-tetrahydroxyflavanone (2), 4',5,7-trihydroxyflavanone (3), 3,4',5-trihydroxy-7-methoxyflavanone (4), (+)-(2S)-4',5,7-trihydroxy-6-methylflavanone (5), 4',5,7-trihydroxy-6,8-dimethylflavanone (6) and 4',5-dihydroxy-7-methoxyflavanone (7) from this eucalypt species. This is the first report of these natural products from C. torelliana kino exudate.

Understanding chemical pathways of brown centre formation in laboratory induced and conventionally dried nut-in-shell macadamia kernels.

World tree nut production has increased rapidly by around 50 % in the past decade; however, nut defects cause losses. For example, we know that brown centres are a major internal discolouration defect in macadamia nuts and are linked to the storage of nut-in-shell under improper conditions at high temperature and humidity. However, key chemical changes in brown centre kernels have not been described. In this study, we compared brown centres and white kernels from: 1) samples that were "induced" in the laboratory by storing at high moisture concentration; and 2) samples that were dried immediately after harvest using industry best practice methods recommended by the Australian Macadamia Society (AMS). We measured the moisture concentration, sugar concentration, fatty acid concentration, peroxide value, nutrient concentration and volatile compounds of induced and AMS samples. Our results showed that storing nut-in-shell macadamia under wet and hot conditions increased brown centres compared with samples immediately dried using the AMS regime, 10.33 % vs 1.44 %, respectively. Induced brown centres had significantly higher moisture concentrations than induced white centres. Volatile compounds including nonanoic acid, octanoic acid and 2,3 butanediol were identified and associated with brown centre formation in macadamia kernels and the initiation of lipid oxidation. Our results suggest sugar hydrolysis and the Maillard reaction are associated with brown centres both in laboratory induced samples and those formed using industry best practice drying methods. Our study suggests improper drying and storage at high temperature and high humidity are likely to result in brown centre formation. We recommend brown centre losses can be reduced by appropriate drying and storage practices.

Investigating the role of CFTR in human and mouse myometrium.

Background: Abnormal cystic fibrosis transmembrane conductance regulator (CFTR) function in cystic fibrosis (CF) has been linked to airway smooth muscle abnormalities including bronchial hyperresponsiveness. However, a role for CFTR in other types of smooth muscle, including myometrium, remains largely unexplored. As CF life expectancy and the number of pregnancies increases, there is a need for an understanding of the potential role of CFTR in myometrial function. Methods: We investigated the role of CFTR in human and mouse myometrium. We used immunofluorescence to identify CFTR expression, and carried out contractility studies on spontaneously contracting term pregnant and non-pregnant mouse myometrium and term pregnant human myometrial biopsies from caesarean sections. Results: CFTR was found to be expressed in term pregnant mouse myometrium. Inhibition of CFTR, with the selective inhibitor CFTRinh-172, significantly reduced contractility in pregnant mouse and human myometrium in a concentration-dependent manner (44.89 ± 11.02 term pregnant mouse, 9.23 ± 4.75 term-pregnant human; maximal effect at 60 µM expressed as a percentage of the pre-treatment control period). However, there was no effect of CFTRinh-172 in non-pregnant myometrium. Conclusion: These results demonstrate decreased myometrial function when CFTR is inhibited, which may have implications on pregnancy and labour outcome and therapeutic decisions for labour in CF patients.

Does aphasia impact on return to driving after stroke? A scoping review.

PURPOSE: Stroke can affect driving, an important activity of daily living. Little is known about whether aphasia (language impairment) impacts driving post-stroke. This scoping review explores impacts and perceived impacts of aphasia on driving performance, and the process of returning to driving post-stroke. MATERIALS AND METHODS: Scoping review using Arksey and O'Malley's framework, reported using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). Bibliographic databases were searched and international clinical practice guidelines were sourced online. Full-text articles were independently assessed by two reviewers. Results were tabulated and summarised using narrative synthesis. RESULTS: Forty-three literature sources and 17 clinical practice guidelines were identified. Six studies investigated return to driving with aphasia post-stroke; 37 sources from the broader literature contributed to objectives. It remains unclear whether aphasia impacts fitness-to-drive; however, people with aphasia face barriers in returning to driving due to: (1) uncertainty regarding the role of language in driving; (2) poor awareness and knowledge of aphasia, and (3) communication demands in the patient-journey and assessment. CONCLUSIONS: The current evidence base is limited, inconsistent, and lacking in quality and recency and there is a lack of guidelines to support clinical practice. People with aphasia face barriers in returning to driving; however, it is unclear if aphasia affects fitness-to-drive post-stroke. Implications for rehabilitationPeople with aphasia, their caregivers and clinicians have identified return to driving as a top 10 research priority.We do not know if aphasia affects fitness-to-drive post-stroke, but communication difficulties can make the process of returning to driving more difficult.Speech pathologists have an important role in ensuring that driving is discussed with people with aphasia post-stroke.Speech pathologists should support the multidisciplinary team to understand and meet the communication needs of people with aphasia throughout the driving evaluation process.

Mothers' experiences of a lifestyle intervention for weight reduction 12 months after gestational diabetes mellitus: Qualitative findings from the PAIGE2 study.

The standardised pooled prevalence of gestational diabetes mellitus (GDM) globally is approximately 14 %, a reflection of increasing rates of obesity in women of childbearing age. Lifestyle interventions to reduce GDM and subsequent type 2 diabetes (T2D) have been deemed a research priority but are challenging to perform and have variable success rates. The PAIGE2 study was a pragmatic lifestyle randomised controlled trial for women with GDM and body mass index ≥25 kg/m2, which began during pregnancy and continued for one year postnatally. The primary outcome was weight loss 12 months postnatally compared with mothers receiving standard maternity care. Qualitative results are presented from end of study focus groups conducted amongst intervention mothers to gather feedback and determine acceptability of the PAIGE2 intervention. In total, 19 mothers participated in five virtual focus groups. Content analysis explored general study experience, longer term changes to lifestyle and suggested improvements of intervention components including monthly phone calls, motivational text messages, Fitbit experience, Slimming World, and study contact timings. Overall, most mothers found the individual PAIGE2 intervention components enjoyable, although opinions differed as to which were the most effective. Several mothers claimed the intervention helped them make long-term changes to their behaviours. A common suggested improvement was the establishment of a local group where mothers could share their experiences. In conclusion, most mothers deemed the intervention acceptable, and felt that with minor enhancements, it could be utilised as an effective tool to support weight loss after pregnancy and reduce future risk of obesity and T2D.

'Sifting the significance from the data' - the impact of high-throughput genomic technologies on human genetics and health care.

This report is of a round-table discussion held in Cardiff in September 2009 for Cesagen, a research centre within the Genomics Network of the UK's Economic and Social Research Council. The meeting was arranged to explore ideas as to the likely future course of human genomics. The achievements of genomics research were reviewed, and the likely constraints on the pace of future progress were explored. New knowledge is transforming biology and our understanding of evolution and human disease. The difficulties we face now concern the interpretation rather than the generation of new sequence data. Our understanding of gene-environment interaction is held back by our current primitive tools for measuring environmental factors, and in addition, there may be fundamental constraints on what can be known about these complex interactions.

Maintaining high moisture content of macadamia nuts-in-shell during storage induces brown centres in raw kernels.

BACKGROUND: Kernel brown centres in macadamia are a defect causing internal discolouration of kernels. This study investigates the effect on the incidence of brown centres in raw kernel after maintaining high moisture content in macadamia nuts-in-shell stored at temperatures of 30°C, 35°C, 40°C and 45°C. RESULTS: Brown centres of raw kernel increased with nuts-in-shell storage time and temperature when high moisture content was maintained by sealing in polyethylene bags. Almost all kernels developed the defect when kept at high moisture content for 5 days at 45°C, and 44% developed brown centres after only 2 days of storage at high moisture content at 45°C. This contrasted with only 0.76% when stored for 2 days at 45°C but allowed to dry in open-mesh bags. At storage temperatures below 45°C, there were fewer brown centres, but there were still significant differences between those stored at high moisture content and those allowed to dry (P < 0.05). CONCLUSION: Maintenance of high moisture content during macadamia nuts-in-shell storage increases the incidence of brown centres in raw kernels and the defect increases with time and temperature. On-farm nuts-in-shell drying and storage practices should rapidly remove moisture to reduce losses. Ideally, nuts-in-shell should not be stored at high moisture content on-farm at temperatures over 30°C.

Hyperspectral Imaging of Adaxial and Abaxial Leaf Surfaces as a Predictor of Macadamia Crop Nutrition.

Tree crop yield is highly dependent on fertiliser inputs, which are often guided by the assessment of foliar nutrient levels. Traditional methods for nutrient analysis are time-consuming but hyperspectral imaging has potential for rapid nutrient assessment. Hyperspectral imaging has generally been performed using the adaxial surface of leaves although the predictive performance of spectral data has rarely been compared between adaxial and abaxial surfaces of tree leaves. We aimed to evaluate the capacity of laboratory-based hyperspectral imaging (400-1000 nm wavelengths) to predict the nutrient concentrations in macadamia leaves. We also aimed to compare the prediction accuracy from adaxial and abaxial leaf surfaces. We sampled leaves from 30 macadamia trees at 0, 6, 10 and 26 weeks after flowering and captured hyperspectral images of their adaxial and abaxial surfaces. Partial least squares regression (PLSR) models were developed to predict foliar nutrient concentrations. Coefficients of determination (R2P) and ratios of prediction to deviation (RPDs) were used to evaluate prediction accuracy. The models reliably predicted foliar nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), copper (Cu), manganese (Mn), sulphur (S) and zinc (Zn) concentrations. The best-fit models generally predicted nutrient concentrations from spectral data of the adaxial surface (e.g., N: R2P = 0.55, RPD = 1.52; P: R2P = 0.77, RPD = 2.11; K: R2P = 0.77, RPD = 2.12; Ca: R2P = 0.75, RPD = 2.04). Hyperspectral imaging showed great potential for predicting nutrient status. Rapid nutrient assessment through hyperspectral imaging could aid growers to increase orchard productivity by managing fertiliser inputs in a more-timely fashion.

Hyperspectral imaging for estimating leaf, flower, and fruit macronutrient concentrations and predicting strawberry yields.

Managing the nutritional status of strawberry plants is critical for optimizing yield. This study evaluated the potential of hyperspectral imaging (400-1,000 nm) to estimate nitrogen (N), phosphorus (P), potassium (K), and calcium (Ca) concentrations in strawberry leaves, flowers, unripe fruit, and ripe fruit and to predict plant yield. Partial least squares regression (PLSR) models were developed to estimate nutrient concentrations. The determination coefficient of prediction (R2P) and ratio of performance to deviation (RPD) were used to evaluate prediction accuracy, which often proved to be greater for leaves, flowers, and unripe fruit than for ripe fruit. The prediction accuracies for N concentration were R2P = 0.64, 0.60, 0.81, and 0.30, and RPD = 1.64, 1.59, 2.64, and 1.31, for leaves, flowers, unripe fruit, and ripe fruit, respectively. Prediction accuracies for Ca concentrations were R2P = 0.70, 0.62, 0.61, and 0.03, and RPD = 1.77, 1.63, 1.60, and 1.15, for the same respective plant parts. Yield and fruit mass only had significant linear relationships with the Difference Vegetation Index (R2 = 0.256 and 0.266, respectively) among the eleven vegetation indices tested. Hyperspectral imaging showed potential for estimating nutrient status in strawberry crops. This technology will assist growers to make rapid nutrient-management decisions, allowing for optimal yield and quality.

A pragmatic lifestyle intervention for overweight and obese women with gestational diabetes mellitus (PAIGE2): A parallel arm, multicenter randomized controlled trial study protocol.

Background: The global epidemic of type 2 diabetes (T2D) and obesity has been translated into pregnancy, with approximately 18% of women being diagnosed worldwide with Gestational Diabetes Mellitus (GDM). Whilst preventive strategies have proven effective in the non-pregnant context, attrition rates are high and there is an urgent need to develop a customized, pragmatic lifestyle intervention for women both during and after pregnancy. Diet and exercise modification, behavioral support, and Commercial Weight Management Organizations have been strongly recommended to aid postpartum weight reduction for mothers with previous GDM, subsequently reducing their risk of developing obesity and T2D. This study, informed by a previous pilot study, aims to determine the effectiveness of a pragmatic pregnancy and postpartum lifestyle modification program for overweight women with previous GDM (PAIGE2) to reduce body weight at 12 months postpartum. Methods/design: This paper summarizes the protocol for the PAIGE2 study, which has been developed based on results from a pilot study (PAIGE). A six center, two parallel arm, 12-month, randomized controlled trial will be conducted across Northern Ireland and the Republic of Ireland (3 centers each), involving 340 women with GDM and body mass index ≥25 kg/m2 recruited during pregnancy. The lifestyle intervention involves a one-hour virtual educational program (to take place at 32-36 weeks gestation). Postpartum, the intervention will include monthly phone calls, weekly motivational text messages, weekly step counts, and referral for three months to a Commercial Weight Management Organization (Slimming World). The control arm will receive usual care as offered by the local maternity hospital. The primary outcome is weight loss at 12 months postpartum. Study visits for anthropometric and clinical measurements, fasting blood samples, questionnaires pertaining to health, wellbeing and physical activity will take place at 6 weeks, 6- and 12-months postpartum. Focus groups will be conducted with intervention mothers' post-intervention to determine the acceptability of the study design including utility of a Commercial Weight Management Organization, feasibility of remote patient contact, family involvement and patient satisfaction. Discussion: The PAIGE2 study will address the gaps in previously conducted research and, if positive, has the potential to have major public health implications for the prevention of future GDM and subsequent T2D. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04579016?term=NCT04579016&draw=2&rank=1, identifier NCT04579016.