Characteristics and serotype distribution of childhood cases of invasive pneumococcal disease following pneumococcal conjugate vaccination in England and Wales, 2006-14

Background The 7-valent (PCV7) and 13-valent (PCV13) pneumococcal conjugate vaccines are highly effective in preventing invasive pneumococcal disease (IPD) caused by vaccine serotypes. Vaccine failure (vaccine-type IPD after age-appropriate immunisation) is rare. Little is known about the risk, clinical characteristics or outcomes of PCV13 compared to PCV7 vaccine failure. Methods Public Health England conducts IPD surveillance and provides a national reference service for serotyping pneumococcal isolates in England and Wales. We compared the epidemiology, rates, risk factors, serotype distribution, clinical characteristics, and outcomes of IPD in children with PCV13 and PCV7 vaccine failure. Results A total of 163 episodes of PCV failure were confirmed in 161 children over eight years (04 September 2006 to 03 September 2014) in ten birth cohorts. After three vaccine doses, PCV7 and PCV13 failure rates were 0.19/100,000 (95% CI, 0.10-0.33; 57 cases) and 0.66/100,000 (95% CI, 0.44-0.99; 104 cases) vaccinated person-years, respectively. Children with PCV13 failure were more likely to be healthy (87/105 [82.9%] vs. 37/56 [66.1%]; P=0.02), present with bacteremic lower respiratory tract infection (61/105 [58.1%] vs. 11/56 [19.6%]; P<0.001) and develop empyema (41/61 [67.2%] vs. 1/11 [9.1%]; P<0.001) compared to PCV7 failures. Serotypes 3 (n=38, 36.2%) and 19A (n=30, 28.6%) were responsible for most PCV13 failures. Five children died (3.1%; 95% CI, 1.0-7.1%), including four with co-morbidities. Conclusions PCV failure is rare and, compared to PCV7 serotypes, the additional PCV13 serotypes are more likely to cause bacteremic lower respiratory tract infection and empyema in healthy vaccinated children

The Productivity of Wh- Prompts when Children Testify

This is the author accepted manuscript. The final version is available from Wiley via http://dx.doi.org/10.1002/acp.3204Wh- prompts (what, how, why, who, when, where) vary widely in their specificity and accuracy, but differences among them have largely been ignored in research examining the productivity of different question-types in child testimony. We examined 120 6- to 12-year-olds’ criminal court testimony in child sexual abuse cases to compare the productivity of various wh- prompts. We distinguished among what/how prompts, most notably: what/how-happen prompts focusing generally on events, what/how-dynamic prompts focusing on actions or unfolding processes/events, what/how-causality prompts focusing on causes and reasons, and what/how-static prompts focusing on non-action contextual information regarding location, objects, and time. Consistent with predictions, what/how-happen prompts were the most productive, and both what/how-dynamic prompts and wh- prompts about causality were more productive than other wh- prompts. Prosecutors asked proportionally more what/how-dynamic prompts and fewer what/how-static prompts than defense attorneys. Future research and interviewer training may benefit from finer discrimination among wh- prompts.This research was supported in part by NICHD Grant HD047290 to Thomas D. Lyon and an ESRC studentship to Samantha J. Andrews

Vaccination of Infants with Meningococcal Group B Vaccine (4CMenB) in England.

BACKGROUND: In September 2015, the United Kingdom introduced the multicomponent meningococcal group B vaccine (4CMenB, Bexsero) into its publicly funded national immunization program at a reduced two-dose priming schedule for infants, with a 12-month booster. METHODS: Using data from enhanced national surveillance of invasive meningococcal disease in England, we evaluated the effect of vaccination on the incidence of meningococcal group B disease during the first 3 years of the program. The effect of vaccination was assessed by comparing the observed incidence of disease with the expected incidence based on the incidence during the 4-year prevaccination period in equivalent cohorts and with the use of disease trends in cohorts of children younger than 5 years of age who were not eligible to receive the vaccine. Vaccine effectiveness was estimated with the use of the indirect screening method. RESULTS: 4CMenB uptake in England remained consistently high; data from the first 3 months of 2018 showed that 92.5% of children had completed the primary immunizations by their first birthday and 87.9% had received all three doses by 2 years. From September 2015 through August 2018, the incidence of meningococcal group B disease in England (average annual birth cohort, approximately 650,000 infants) was significantly lower in vaccine-eligible cohorts than the expected incidence (63 observed cases as compared with 253 expected cases; incidence rate ratio, 0.25; 95% confidence interval [CI], 0.19 to 0.36), with a 75% reduction in age groups that were fully eligible for vaccination. The adjusted vaccine effectiveness against meningococcal group B disease was 52.7% (95% CI, -33.5 to 83.2) with a two-dose priming schedule for infants and 59.1% (95% CI, -31.1 to 87.2) with a two-dose priming schedule plus a booster at 1 year). Over the 3-year period, there were 169 cases of meningococcal group B disease in the vaccine-eligible cohorts, and an estimated 277 cases (95% CI, 236 to 323) were prevented. CONCLUSIONS: The 4CMenB program was associated with continued positive effect against meningococcal group B disease in children in England, and protection after three doses of the vaccine was sustained for at least 2 years. (Funded by Public Health England.)

The fetal mouse is a sensitive genotoxicity model that exposes lentiviral-associated mutagenesis resulting in liver oncogenesis

This article is available open access through the publisher’s website at the link below. Copyright @ 2013 The American Society of Gene & Cell Therapy.Genotoxicity models are extremely important to assess retroviral vector biosafety before gene therapy. We have developed an in utero model that demonstrates that hepatocellular carcinoma (HCC) development is restricted to mice receiving nonprimate (np) lentiviral vectors (LV) and does not occur when a primate (p) LV is used regardless of woodchuck post-translation regulatory element (WPRE) mutations to prevent truncated X gene expression. Analysis of 839 npLV and 244 pLV integrations in the liver genomes of vector-treated mice revealed clear differences between vector insertions in gene dense regions and highly expressed genes, suggestive of vector preference for insertion or clonal outgrowth. In npLV-associated clonal tumors, 56% of insertions occurred in oncogenes or genes associated with oncogenesis or tumor suppression and surprisingly, most genes examined (11/12) had reduced expression as compared with control livers and tumors. Two examples of vector-inserted genes were the Park 7 oncogene and Uvrag tumor suppressor gene. Both these genes and their known interactive partners had differential expression profiles. Interactive partners were assigned to networks specific to liver disease and HCC via ingenuity pathway analysis. The fetal mouse model not only exposes the genotoxic potential of vectors intended for gene therapy but can also reveal genes associated with liver oncogenesis.Imperial College London, the Wellcome Trust, and Brunel University

Protection against symptomatic infection with delta (B.1.617.2) and omicron (B.1.1.529) BA.1 and BA.2 SARS-CoV-2 variants after previous infection and vaccination in adolescents in England, August, 2021-March, 2022: a national, observational, test-negative, case-control study.

BACKGROUND: Little is known about protection against SARS-CoV-2 infection following previous infection with specific individual SARS-CoV-2 variants, COVID-19 vaccination, and a combination of previous infection and vaccination (hybrid immunity) in adolescents. We aimed to estimate protection against symptomatic PCR-confirmed infection with the delta (B.1.617.2) and omicron (B.1.1.529) variants in adolescents with previous infection, mRNA vaccination, and hybrid immunity. METHODS: We conducted an observational, test-negative, case-control study using national SARS-CoV-2 testing and COVID-19 mRNA vaccination data in England. Symptomatic adolescents aged 12-17 years who were unvaccinated or had received primary BNT162b2 immunisation at symptom onset and had a community SARS-CoV-2 PCR test were included. Vaccination and previous SARS-CoV-2 infection status in adolescents with PCR-confirmed COVID-19 (cases) were compared with vaccination and previous infection status in adolescents who had a negative SARS-CoV-2 PCR test (controls). Vaccination data were collected from the National Immunisation Management System, and were linked to PCR testing data. The primary outcome was protection against SARS-CoV-2 delta and omicron infection (defined as 1 - odds of vaccination or previous infection in cases divided by odds of vaccination or previous infection in controls). FINDINGS: Between Aug 9, 2021, and March 31, 2022, 1 161 704 SARS-CoV-2 PCR tests were linked to COVID-19 vaccination status, including 390 467 positive tests with the delta variant and 212 433 positive tests with the omicron variants BA.1 and BA.2. In unvaccinated adolescents, previous SARS-CoV-2 infection with wildtype, alpha (B.1.1.7), or delta strains provided greater protection against subsequent delta infection (>86·1%) than against subsequent omicron infection (<52·4%); previous delta or omicron infection provided similar protection against omicron reinfection (52·4% [95% CI 50·9-53·8] vs 59·3% [46·7-69·0]). In adolescents with no previous infection, vaccination provided lower protection against omicron infection than against delta infection, with omicron protection peaking at 64·5% (95% CI 63·6-65·4) at 2-14 weeks after dose two and 62·9% (60·5-65·1) at 2-14 weeks after dose three, with waning protection after each dose. Adolescents with hybrid immunity from previous infection and vaccination had the highest protection, irrespective of the SARS-CoV-2 strain in the primary infection. The highest protection against omicron infection was observed in adolescents with vaccination and previous omicron infection, reaching 96·4% (95% CI 84·4-99·1) at 15-24 weeks after vaccine dose two. INTERPRETATION: Previous infection with any SARS-CoV-2 variant provided some protection against symptomatic reinfection, and vaccination added to this protection. Vaccination provides low-to-moderate protection against symptomatic omicron infection, with waning protection after each dose, while hybrid immunity provided the most robust protection. Although more data are needed to investigate longer-term protection and protection against infection with new variants, these data question the need for additional booster vaccine doses for adolescents in populations with already high protection against SARS-CoV-2 infection. FUNDING: None

Characteristics of Invasive Pneumococcal Disease Caused by Emerging Serotypes After the Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in England: A Prospective Observational Cohort Study, 2014-2018.

BACKGROUND: England is experiencing a rapid increase in invasive pneumococcal disease (IPD) caused by serotypes 8, 12F, and 9N; their clinical characteristics and outcomes have not been described. METHODS: Public Health England conducts national IPD surveillance. Cases due to emerging serotypes were compared with those included in the 13-valent pneumococcal conjugate vaccine (PCV13) and the remaining non-PCV13 serotypes. RESULTS: There were 21 592 IPD cases during 2014-15 to 2017-18, including 20 108 (93.1%) with serotyped isolates and 17 450 (86.8%) with completed questionnaires. PCV13 serotypes were responsible for 20.1% (n = 4033), while serotype 8 (3881/20 108 [19.3%]), 12F (2365/20 108 [11.8%]), and 9N (1 296/20 108 [6.4%]) were together responsible for 37.5% of cases. Invasive pneumonia was the most common presentation (11 424/16 346 [69.9%]) and, overall, 67.0% (n = 11 033) had an underlying comorbidity. The median age (interquartile range) at IPD due to serotypes 8 (59 [45-72] years) and 12F (56 [41-70] years) was lower than serotype 9N (67 [53-80] years), PCV13 serotypes (68 [52-81] years), and remaining non-PCV13 serotypes (70 [53-82] years). Serotype 9N IPD cases also had higher comorbidity prevalence (748/1087 [68.8%]) compared to serotype 8 (1901/3228 [58.9%]) or 12F (1042/1994 [52.3%]), and higher case fatality (212/1128 [18.8%]) compared to 8.6% (291/3365) or 10.0% (209/2086), respectively. CONCLUSIONS: Serotypes 8 and 12F were more likely to cause IPD in younger, healthier individuals and less likely to be fatal, while serotype 9N affected older adults with comorbidities and had higher case fatality

Hit Improves Aerobic Capacity Without a Detrimental Decline in Blood Glucose in People with Type 1 Diabetes.

AIMS: To investigate whether 1) six weeks of high-intensity interval training (HIT) induces similar improvements in cardio-metabolic health markers as moderate-intensity continuous training (MICT) in people with type 1 diabetes, and 2) whether HIT abolishes acute reductions in plasma glucose observed following MICT sessions. METHODS: Fourteen sedentary individuals with type 1 diabetes (n=7 per group) completed six weeks of HIT or MICT 3 times per week. Pre- and post-training measurements were made of 24h interstitial glucose profiles (using continuous glucose monitors (CGMS)) and cardio-metabolic health markers (V˙O2peak, blood lipid profile and aortic pulse wave velocity; aPWV). Capillary blood glucose concentrations were assessed before and after exercise sessions throughout the training programme to investigate changes in blood glucose during exercise in the fed state. RESULTS: Six weeks of HIT or MICT increased V˙O2peak by 14% and 15%, respectively (P0.05). In the fed state, the mean change in capillary blood glucose concentration during the HIT sessions was -0.2±0.5 mmol/L, whereas blood glucose change was -5.5±0.4 mmol/L during MICT. CONCLUSIONS: Six weeks of HIT improved V˙O2peak and aortic PWV to a similar extent as MICT. The finding that blood glucose remained stable during HIT in the fed state, but consistently fell during MICT, suggests that HIT may be the preferred training mode for some people with type 1 diabetes

Fasted High-Intensity Interval and Moderate-Intensity Exercise do not Lead to Detrimental 24-Hour Blood Glucose Profiles.

Aims: To compare the effect of a bout of high-intensity interval training (HIT) with a bout of moderate-intensity continuous training (MICT) on glucose concentrations over the subsequent 24h period. METHODS: Fourteen people with type 1 diabetes (duration of type 1 diabetes 8.2±1.4 years), all on basal-bolus regimen, completed a randomised, counterbalanced, crossover study. Continuous glucose monitoring was used to assess glycaemic control following a single bout of HIT (6 x 1min intervals) and 30 mins of moderate-intensity continuous training (MICT) on separate days, compared to a non-exercise control day (CON). Exercise was undertaken following an overnight fast with omission of short-acting insulin. Capillary blood glucose samples were recorded pre and post-exercise to assess the acute changes in glycaemia during HIT and MICT. RESULTS: There was no difference in the incidence of or percentage time spent in hypoglycaemia, hyperglycaemia or target glucose range over the 24h and nocturnal period (24:00-06:00h) between CON, HIT and MICT (P>0.05). Blood glucose concentrations were not significantly (P=0.49) different from pre to post-exercise with HIT (+0.39±0.42 mmol/L) or MICT (-0.39±0.66 mmol/L), with no difference between exercise modes (P=1.00). CONCLUSIONS: HIT or 30 mins of MICT can be carried out after an overnight fast with no increased risk of hypoglycaemia or hyperglycaemia, and provided the pre-exercise glucose concentration is 7-14 mmol/L, no additional carbohydrate ingestion is necessary to undertake these exercises. As HIT is a time-efficient form of exercise, the efficacy and safety of long-term HIT should now be explored

Parental cultural models and resources for understanding mathematical achievement in culturally diverse school settings

This paper proposes that the theoretical concept of cultural models can offer useful insights into parental involvement in their child’s mathematical achievement and the resources they use to go about gaining information in culturally diverse learning settings. This examination takes place within a cultural-developmental framework and draws on the notion of cultural models to explicate parental understandings of their child’s mathematics achievement and what resources are used to make sense of this. Three parental resources are scrutinized: (a) the teacher, (b) examination test results, and (c) constructions of child development. The interviews with 22 parents revealed some ambiguity around the interpretation of these resources by the parent, which was often the result of incongruent cultural models held between the home and the school. The resources mentioned are often perceived as being unambiguous but show themselves instead to be highly interpretive because of the diversity of cultural models in existence in culturally diverse settings. Parents who are in minority or marginalized positions tend to have difficulties in interpreting cultural models held by school, thereby disempowering them to be parentally involved in the way the school would like