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BackgroundThe influence of early exposure to allergenic foods on the subsequent development of food allergy remains uncertain.ObjectiveWe sought to determine the feasibility of the early introduction of multiple allergenic foods to exclusively breast-fed infants from 3 months of age and the effect on breastfeeding performance.MethodsWe performed a randomized controlled trial. The early introduction group (EIG) continued breastfeeding with sequential introduction of 6 allergenic foods: cow's milk, peanut, hard-boiled hen's egg, sesame, whitefish (cod), and wheat; the standard introduction group followed the UK infant feeding recommendations of exclusive breastfeeding for around 6 months with no introduction of allergenic foods before 6 months of age.ResultsOne thousand three hundred three infants were enrolled. By 5 months of age, the median frequency of consumption of all 6 foods was 2 to 3 times per week for every food in the EIG and no consumption for every food in the standard introduction group (P < .001 for every comparison). By 6 months of age, nonintroduction of the allergenic foods in the EIG was less than 5% for each of the 6 foods. Achievement of the stringent per-protocol consumption target for the EIG proved more difficult (42% of evaluable EIG participants). Breastfeeding rates in both groups significantly exceeded UK government data for equivalent mothers (P < .001 at 6 and at 9 months of age).ConclusionEarly introduction, before 6 months of age, of at least some amount of multiple allergenic foods appears achievable and did not affect breastfeeding. This has important implications for the evaluation of food allergy prevention strategies.

Abstract. Pagano S, Satta N, Werling D, Offord V, de Moerloose P, Charbonney E, Hochstrasser D, Roux-Lombard P, Vuilleumier N

Background: Domestic water hardness and chlorine have been suggested as important risk factors for atopic dermatitis (AD). Objective: We sought to examine the link between domestic water calcium carbonate (CaCO 3) and chlorine concentrations, skin barrier dysfunction (increased transepidermal water loss), and AD in infancy. Methods: We recruited 1303 three-month-old infants from the general population and gathered data on domestic water CaCO 3 (in milligrams per liter) and chlorine (Cl 2 ; in milligrams per liter) concentrations from local water suppliers. At enrollment, infants were examined for AD and screened for filaggrin (FLG) skin barrier gene mutation status. Transepidermal water loss was measured on unaffected forearm skin. Results: CaCO 3 and chlorine levels were strongly correlated. A hybrid variable of greater than and less than median levels of CaCO 3 and total chlorine was constructed: a baseline group of low CaCO 3 /low total chlorine (CaL/ClL), high CaCO 3 /low total chlorine (CaH/ClL), low CaCO 3 /high total chlorine (CaL/ClH) and high CaCO 3 /high total chlorine (CaH/ClH). Visible AD was more common in all 3 groups versus the baseline group: adjusted odds ratio (AOR) of 1.87 (95% CI, 1.25-2.80; P 5 .002) for the CaH/ClL group, AOR of 1.46 (95% CI, 0.97-2.21; P 5 .07) for the CaL/ClH, and AOR of 1.61 (95% CI, 1.09-2.38; P 5 .02) for the CaH/ClH group. The effect estimates were greater in children carrying FLG mutations, but formal interaction testing between water quality groups and filaggrin status was not statistically significant. Conclusions: High domestic water CaCO 3 levels are associated with an increased risk of AD in infancy. The influence of increased total chlorine levels remains uncertain. An intervention trial is required to see whether installation of a domestic device to decrease CaCO 3 levels around the time of birth can reduce this risk.

Nonwhite ethnicity: • In general a nonsignificant reduc on in food allergy in nonwhite EIG compared with nonwhite SIG Sensi zed: (IgE ≥0.1 kU/l to one or more foods) • EIG 19.2% versus SIG 34.2% developed any food allergy* Visible eczema: (moderate SCORAD 15 to <40) • EIG 22.6% versus SIG 46.7% developed any food allergy* • EIG 16.1% versus SIG 43.3% developed an egg allergy* Sensi zed: (IgE ≥0.1 kU/l to egg) • EIG 20.0% versus SIG 48.6% developed an egg allergy* *p<0.05 EIG: Early Introduc on Group SIG: Standard Introduc on Group Distribu on of enrollment (3 months of age) risk factors associated with a higher risk of developing a food allergy: Sensi za on (IgE ≥ 0.1 kU/l to one or more foods), visible eczema (any) at the clinic visit and nonwhite ethnicity (n=1170) Nonwhite Sensi zed

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the costs of phlebotomy. G.L. acknowledges the Davis Foundation for academic support. O.T. received a research fellowship from the Clemens von Pirquet Foundation (Geneva, Switzerland).

Genetic redundancy has evolved as a way for human cells to survive the loss of genes that are single copy and essential in other organisms, but also allows tumours to survive despite having highly rearranged genomes. In this study we CRISPR screen 1191 gene pairs, including paralogues and known and predicted synthetic lethal interactions to identify 105 gene combinations whose co-disruption results in a loss of cellular fitness. 27 pairs influence fitness across multiple cell lines including the paralogues FAM50A/FAM50B, two genes of unknown function. Silencing of FAM50B occurs across a range of tumour types and in this context disruption of FAM50A reduces cellular fitness whilst promoting micronucleus formation and extensive perturbation of transcriptional programmes. Our studies reveal the fitness effects of FAM50A/FAM50B in cancer cells.