A survey of school’s preparedness for managing anaphylaxis in pupils with food allergy

Allergic diseases are on the increase and can affect the child's well-being. The aim of this survey was to assess regional schools' preparedness in dealing with anaphylaxis following the publication of national and international guidelines for schools in 2014. The survey was developed in 2015 and distributed to schools in Cumbria, North West England, UK between 2015 and 2016. Only 47% of the respondents (95% CI, 39-57%) felt confident to manage anaphylaxis. Schools without allergic pupils were significantly less likely to have a standard management protocol in place for emergencies compared to those with allergic pupils (p < 0.001). The majority of the schools indicated that further training was needed (81% (95% CI, 74-88%).Conclusion: At the time of the survey, schools' preparedness in the region, did not meet safety standards recommended by national and international organisations. Although schools have shown eagerness in accessing training in the management of anaphylaxis, tailored training for schools is not yet widely available. There is now an urgent need to design feasible training strategies that create a safe environment for allergic pupils across all UK schools.What is Known:• One quarter of the severe allergic reactions take place for the first time while at school with some of them being fatal.• School staff is ill-prepared in the management of anaphylaxis. Access to formal training is not widely available.What is New:• School staff remains unconfident in managing the severe allergic child.Training in the management of anaphylaxis is scarce, and when available, it does not offer the required depth to cover the holistic needs of allergic pupils.• Schools would welcome generic adrenaline autoinjectors and a national policy with central funding which would describe step by step the necessary measures for the management of anaphylaxis

School allergy training promotes internal policy review and enhances staff's preparedness in managing pupils with food allergy

Abstract: Background: Recently non‐statutory allergy management guidance for schools has been produced in the United Kingdom; however, there has been limited progress in implementing this. The aim of this study was to evaluate the effect of face‐to‐face training on self‐reported school staff preparedness in managing the severely allergic child and whether it would stimulate schools' allergy policy review. Methods: A preparedness survey was conducted prior and 2 months post‐intervention to assess the effect of training on self‐reported preparedness and perceived confidence to manage children with food allergies. Results: A sample of 18 primary schools that consented to participate were selected. Of the trained schools, 89% of the head teachers felt confident in dealing with an allergy emergency compared to 39% prior training (p = 0.016). Post‐intervention all but one had arranged/were considering introducing allergy awareness sessions to help pupils manage their allergies (45% pre‐training vs. post‐training 93%, p = 0.003). Preventative measures for accidental exposure to food allergens (i.e., no food sharing policy) were adopted by all (pre‐training 61% vs. post‐training 100%, p = 0.03). Conclusion: A face‐to‐face school allergy training programme enhances self‐reported staff preparedness and promotes internal allergy policy review in managing the needs of these children, hence addressing the current gap between recommendations and practice in schools

Monopolin subunit Csm1 associates with MIND complex to establish monopolar attachment of sister kinetochores at meiosis I

Sexually reproducing organisms halve their cellular ploidy during gametogenesis by undergoing a specialized form of cell division known as meiosis. During meiosis, a single round of DNA replication is followed by two rounds of nuclear divisions (referred to as meiosis I and II). While sister kinetochores bind to microtubules emanating from opposite spindle poles during mitosis, they bind to microtubules originating from the same spindle pole during meiosis I. This phenomenon is referred to as mono-orientation and is essential for setting up the reductional mode of chromosome segregation during meiosis I. In budding yeast, mono-orientation depends on a four component protein complex referred to as monopolin which consists of two nucleolar proteins Csm1 and Lrs4, meiosis-specific protein Mam1 of unknown function and casein kinase Hrr25. Monopolin complex binds to kinetochores during meiosis I and prevents bipolar attachments. Although monopolin associates with kinetochores during meiosis I, its binding site(s) on the kinetochore is not known and its mechanism of action has not been established. By carrying out an imaging-based screen we have found that the MIND complex, a component of the central kinetochore, is required for monopolin association with kinetochores during meiosis. Furthermore, we demonstrate that interaction of monopolin subunit Csm1 with the N-terminal domain of MIND complex subunit Dsn1, is essential for both the association of monopolin with kinetochores and for monopolar attachment of sister kinetochores during meiosis I. As such this provides the first functional evidence for a monopolin-binding site at the kinetochore

Diagnosing, managing and preventing anaphylaxis:Systematic review

Background This systematic review used the GRADE approach to compile evidence to inform the European Academy of Allergy and Clinical Immunology's (EAACI) anaphylaxis guideline. Methods We searched five bibliographic databases from 1946 to 20 April 2020 for studies about the diagnosis, management and prevention of anaphylaxis. We included 50 studies with 18 449 participants: 29 randomized controlled trials, seven controlled clinical trials, seven consecutive case series and seven case-control studies. Findings were summarized narratively because studies were too heterogeneous to conduct meta-analysis. Results It is unclear whether the NIAID/FAAN criteria or Brighton case definition are valid for immediately diagnosing anaphylaxis due to the very low certainty of evidence. There was also insufficient evidence about the impact of most anaphylaxis management and prevention strategies. Adrenaline is regularly used for first-line emergency management of anaphylaxis but little robust research has assessed its effectiveness. Newer models of adrenaline autoinjectors may slightly increase the proportion of people correctly using the devices and reduce time to administration. Face-to-face training for laypeople may slightly improve anaphylaxis knowledge and competence in using autoinjectors. We searched for but found little or no comparative effectiveness evidence about strategies such as fluid replacement, oxygen, glucocorticosteroids, methylxanthines, bronchodilators, management plans, food labels, drug labels and similar. Conclusions Anaphylaxis is a potentially life-threatening condition but, due to practical and ethical challenges, there is a paucity of robust evidence about how to diagnose and manage it

H1N1 Antibody Persistence 1 Year After Immunization With an Adjuvanted or Whole-Virion Pandemic Vaccine and Immunogenicity and Reactogenicity of Subsequent Seasonal Influenza Vaccine: A Multicenter Follow-on Study

Background. We investigated antibody persistence in children 1 year after 2 doses of either an AS03B-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV). Methods. Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination. Results. Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03B-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%–100%) vs 32.4% (95% CI, 21.5%–44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%–99.4%) vs 65.9% (95% CI, 55.3%–75.5%) in those 3–12 years old at immunization, respectively (P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03B-adjuvanted vaccine. Conclusions. This study provides serological evidence that 2 doses of AS03B-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

The immunological mechanisms underlying the development of immune tolerance in childhood

The increasing prevalence of allergic disease is linked to changes in the development of immune tolerance in early childhood. Better understanding of immune tolerance mechanisms that underpin these changes and the identification of strategies to prevent the development of allergy are required. Here the potential of maternal vitamin D supplementation in pregnancy to modify immune function at birth was investigated. The effects of familial risk of atopy on immune function at birth was also considered. Vitamin D might be an important factor in the development of the immune system in early life and in the development of allergy. Interventional studies focusing on vitamin D supplementation during pregnancy suggest supplementation will prevent the development of allergy. Here, the opportunity was taken as part of a larger vitamin D supplementation in pregnancy study (MAVIDOS) to investigate the effects of the infant’s vitamin D level at birth on various features of immune function at this same time. Parameters measured included total T, B and NK cells, T memory cells, T regulatory cells, iNKT cells and dendritic cells in cord blood mononuclear cells (CBMC) as well as the cytokine response to lipopolysaccharide (LPS) or phytohaemagglutinin (PHA). The key findings were a positive association between neonatal 25(OH)D3 and total naive CD4+ T cells and CD4+ and non-CD4+ CCR9+ putative gut homing T cells; PHA-stimulated TNFα and TNFβ levels were both inversely related to neonatal 25(OH)D3. In a parallel study, the effects of familial risk - high risk (HR) with two first degree relatives with allergic disease versus low risk (LR) with no first-degree relatives with allergic disease – on the innate immune response at birth was considered. This was part of a larger ongoing birth cohort to study the development of immune tolerance in early life. A comparison of the response of CBMC from HR versus LR newborns to various activators of pattern recognition receptors (Toll like receptors, NOD-like receptors and inflammasome) formed a critical first step to the longer-term analysis plans for this cohort. Statistically significant cytokine responses were found for IL10 for NOD1, NLRP3 and NLRP3/LPS; IL-13 responses for TLR4, TLR2/6, TLR7/8 and NOD1 and IL-6 for TLR7/8. In each occasion, the responses were higher in the LR than the HR group. The novel findings presented in this thesis will inform the proposed longer term follow up of the children born onto these two studies with the goal of alleviating the burden of allergic diseases