EffectS of non-nutritive sWeetened beverages on appetITe during aCtive weigHt loss (SWITCH): Protocol for a randomized, controlled trial assessing the effects of non-nutritive sweetened beverages compared to water during a 12-week weight loss period and a follow up weight maintenance period

Background Acute and medium-term intervention studies suggest that non-nutritive sweeteners (NNS) are beneficial for weight loss, however there is limited human data on the long-term effects of consuming NNS on weight loss, maintenance, and appetite. Further research is therefore required to elucidate the prolonged impact of NNS consumption on these outcome measures. Methods/design A randomized parallel groups design will be used to assess whether regular NNS beverage intake is equivalent to a water control in promoting weight loss over 12-weeks (weekly weight loss sessions; Phase I), then supporting weight maintenance over 40-weeks (monthly sessions; Phase II) and subsequently independent weight maintenance over 52-weeks (Phase III) in 432 participants. A subset of these participants (n = 116) will complete laboratory-based appetite probe days (15 sessions; 3 sessions each at baseline, at the start of phase I and the end of each phase). A separate subset (n = 50) will complete body composition scans (DXA) at baseline and at the end of each phase. All participants will regularly be weighed and will complete questionnaires and cognitive tasks to assess changes in body weight and appetitive behaviours. Measures of physical activity and biochemical markers will also be taken. Discussion The trial will assess the efficacy of NNS beverages compared to water during a behavioural weight loss and maintenance programme. We aim to understand whether the impact of NNS on weight, dietary adherence and well-being are beneficial or transient and effects on prolonged successful weight loss and weight maintenance through sustained changes in appetite and eating behaviour. Trial registration: Clinical Trials: NCT02591134; registered: 23.10.201

Coconut and sunflower oil ratios in ice cream influence subsequent food selection and intake

The effect of coconut oil (CO, containing mainly medium chain triglycerides - MCTs) and sunflower oil (SO, containing mainly long chain triglycerides - LCTs) used as fat source (10% fat ice cream) in different ratios (25% CO and 75% SO - 25CO:75SO, 50% CO and 50% SO - 50CO:50SO, 75% CO and 25% SO - 75CO:25SO) was investigated to assess differences in appetite and ad-libitum (evening and snack) food intake using a single blind design. 36 healthy female participants consumed a fixed portion (150 g) of ice cream 45 min before an ad-libitum dinner and snacks. Appetite sensations were tracked across the day. Participants ate significantly less fat after 75CO:25SO than 25CO:75SO (p = 0.007) and there was also a trend for lower fat intake in this condition as compared to 50CO:50SO (p = 0.068). High fat savoury snack intake significantly decreased after 75CO:25SO in comparison with both 25CO:75SO (p = 0.038) and 50CO:50SO (p = 0.008). Calorie intake from snacks was also found to be significantly lower after 25CO:75SO and 50CO:50SO than 75CO:25SO (p = 0.021 and 0.030 respectively). There was no effect of condition on appetite or desire ratings over the day. Eating a standard portion of ice cream containing different ratios of MCTs and LCTs can modestly influence acute food selection and intake, with MCTs manifesting their effect earlier and LCTs later due to differences in the absorption and metabolism of these lipids. However, the differences evident in the present study were small, and require further research before firm conclusions can be drawn

Short-term outcomes of pubertal suppression in a selected cohort of 12 to 15 year old young people with persistent gender dysphoria in the UK

BACKGROUND: In adolescents with severe and persistent gender dysphoria (GD), gonadotropin releasing hormone analogues (GnRHa) are used from early/middle puberty with the aim of delaying irreversible and unwanted pubertal body changes. Evidence of outcomes of pubertal suppression in GD is limited. METHODS: We undertook an uncontrolled prospective observational study of GnRHa as monotherapy in 44 12-15 year olds with persistent and severe GD. Prespecified analyses were limited to key outcomes: bone mineral content (BMC) and bone mineral density (BMD); Child Behaviour CheckList (CBCL) total t-score; Youth Self-Report (YSR) total t-score; CBCL and YSR self-harm indices; at 12, 24 and 36 months. Semistructured interviews were conducted on GnRHa. RESULTS: 44 patients had data at 12 months follow-up, 24 at 24 months and 14 at 36 months. All had normal karyotype and endocrinology consistent with birth-registered sex. All achieved suppression of gonadotropins by 6 months. At the end of the study one ceased GnRHa and 43 (98%) elected to start cross-sex hormones. There was no change from baseline in spine BMD at 12 months nor in hip BMD at 24 and 36 months, but at 24 months lumbar spine BMC and BMD were higher than at baseline (BMC +6.0 (95% CI: 4.0, 7.9); BMD +0.05 (0.03, 0.07)). There were no changes from baseline to 12 or 24 months in CBCL or YSR total t-scores or for CBCL or YSR self-harm indices, nor for CBCL total t-score or self-harm index at 36 months. Most participants reported positive or a mixture of positive and negative life changes on GnRHa. Anticipated adverse events were common. CONCLUSIONS: Overall patient experience of changes on GnRHa treatment was positive. We identified no changes in psychological function. Changes in BMD were consistent with suppression of growth. Larger and longer-term prospective studies using a range of designs are needed to more fully quantify the benefits and harms of pubertal suppression in GD

Is the effect of menu energy labelling on consumer behaviour equitable? A pooled analysis of twelve randomized control experiments

Menu energy labelling has been implemented as a public health policy to promote healthier dietary choices and reduce obesity. However, it is unclear whether the influence energy labelling has on consumer behaviour differs based on individuals’ demographics or characteristics and may therefore produce inequalities in diet. Data were analysed from 12 randomized control trials (N = 8508) evaluating the effect of food and drink energy labelling (vs. labelling absent) on total energy content of food and drink selections (predominantly hypothetical) in European and US adults. Analyses examined the moderating effects of participant age, sex, ethnicity/race, education, household income, body mass index, dieting status, food choice motives and current hunger on total energy content of selections. Energy labelling was associated with a small reduction (f2 = 0.004, −50 kcal, p < 0.001) in total energy selected compared to the absence of energy labelling. Participants who were female, younger, white, university educated, of a higher income status, dieting, motivated by health and weight control when making food choices, and less hungry, tended to select menu items of lower energy content. However, there was no evidence that the effect of energy labelling on the amount of energy selected was moderated by any of the participants' demographics or characteristics. Energy labelling was associated with a small reduction in energy content of food selections and this effect was similar across a range of participants’ demographics and characteristics. These preliminary findings suggest that energy labelling policies may not widen existing inequalities in diet

DOGS: Reaction-Driven de novo Design of Bioactive Compounds

We present a computational method for the reaction-based de novo design of drug-like molecules. The software DOGS (Design of Genuine Structures) features a ligand-based strategy for automated ‘in silico’ assembly of potentially novel bioactive compounds. The quality of the designed compounds is assessed by a graph kernel method measuring their similarity to known bioactive reference ligands in terms of structural and pharmacophoric features. We implemented a deterministic compound construction procedure that explicitly considers compound synthesizability, based on a compilation of 25'144 readily available synthetic building blocks and 58 established reaction principles. This enables the software to suggest a synthesis route for each designed compound. Two prospective case studies are presented together with details on the algorithm and its implementation. De novo designed ligand candidates for the human histamine H4 receptor and γ-secretase were synthesized as suggested by the software. The computational approach proved to be suitable for scaffold-hopping from known ligands to novel chemotypes, and for generating bioactive molecules with drug-like properties

The effects of low-calorie sweeteners on energy intake and body weight: a systematic review and meta-analyses of sustained intervention studies.

Previous meta-analyses of intervention studies have come to different conclusions about effects of consumption of low-calorie sweeteners (LCS) on body weight. The present review included 60 articles reporting 88 parallel-groups and cross-over studies ≥1 week in duration that reported either body weight (BW), BMI and/or energy intake (EI) outcomes. Studies were analysed according to whether they compared (1) LCS with sugar, (2) LCS with water or nothing, or (3) LCS capsules with placebo capsules. Results showed an effect in favour of LCS vs sugar for BW (29 parallel-groups studies, 2267 participants: BW change, -1.06 kg, 95% CI -1.50 to -0.62, I2 = 51%), BMI and EI. Effect on BW change increased with 'dose' of sugar replaced by LCS, whereas there were no differences in study outcome as a function of duration of the intervention or participant blinding. Overall, results showed no difference in effects of LCS vs water/nothing for BW (11 parallel-groups studies, 1068 participants: BW change, 0.10 kg, 95% CI -0.87 to 1.07, I2 = 82%), BMI and EI; and inconsistent effects for LCS consumed in capsules (BW change: -0.28 kg, 95% CI -0.80 to 0.25, I2 = 0%; BMI change: 0.20 kg/m2, 95% CI 0.04 to 0.36, I2 = 0%). Occurrence of adverse events was not affected by the consumption of LCS. The studies available did not permit robust analysis of effects by LCS type. In summary, outcomes were not clearly affected when the treatments differed in sweetness, nor when LCS were consumed in capsules without tasting; however, when treatments differed in energy value (LCS vs sugar), there were consistent effects in favour of LCS. The evidence from human intervention studies supports the use of LCS in weight management, constrained primarily by the amount of added sugar that LCS can displace in the diet

The LHCb upgrade I

The LHCb upgrade represents a major change of the experiment. The detectors have been almost completely renewed to allow running at an instantaneous luminosity five times larger than that of the previous running periods. Readout of all detectors into an all-software trigger is central to the new design, facilitating the reconstruction of events at the maximum LHC interaction rate, and their selection in real time. The experiment's tracking system has been completely upgraded with a new pixel vertex detector, a silicon tracker upstream of the dipole magnet and three scintillating fibre tracking stations downstream of the magnet. The whole photon detection system of the RICH detectors has been renewed and the readout electronics of the calorimeter and muon systems have been fully overhauled. The first stage of the all-software trigger is implemented on a GPU farm. The output of the trigger provides a combination of totally reconstructed physics objects, such as tracks and vertices, ready for final analysis, and of entire events which need further offline reprocessing. This scheme required a complete revision of the computing model and rewriting of the experiment's software

The influence of calorie and physical activity labelling on snack and beverage choices

Much research suggests nutrition labelling does not influence lower energy food choice. This study aimed to assess the impact of physical activity based and kilocalorie (Kcal) based labels on the energy content of snack food and beverage choices made.An independent-groups design, utilizing an online questionnaire platform tested 458 UK adults (87 men), aged 18-64 years (mean: 30 years) whose BMI ranged from 16 to 41 kg/m(2) (mean: 24 kg/m(2)). Participants were randomized to one of four label information conditions (no label, Kcal label, physical activity label [duration of walking required to burn the Kcal in the product], Kcal and physical activity label) and were asked to choose from higher and lower energy options for a series of items.Label condition significantly affected low vs. high-energy product selection of snack foods (p < 0.001) and beverages (p < 0.001). The physical activity label condition resulted in significantly lower energy snack and beverage choices than the Kcal label condition (p < 0.001). This effect was found across the full sample and persisted even when participants' dietary restraint, BMI, gender, socioeconomic status, habitual physical activity, calorie and numerical literacy were controlled.The provision of physical activity information appeared most effective in influencing the selection of lower Kcal snack food and beverage items, when compared with no information or Kcal information. These findings could inform the debate around potential legislative policies to facilitate healthier nutritional choices at a population level