UK parents' attitudes towards meningococcal group B (MenB) vaccination: a qualitative analysis

OBJECTIVES: (1) To explore existing knowledge of, and attitudes, to group B meningococcal disease and serogroup B meningococcal (MenB) vaccine among parents of young children. (2) To seek views on their information needs. DESIGN: Cross-sectional qualitative study using individual and group interviews conducted in February and March 2015, prior to the introduction of MenB vaccine (Bexsero) into the UK childhood immunisation schedule. SETTING: Community centres, mother and toddler groups, parents’ homes and workplaces in London and Yorkshire. PARTICIPANTS: 60 parents of children under 2 years of age recruited via mother and baby groups and via an advert posted to a midwife-led Facebook group. RESULTS: Although recognising the severity of meningitis and septicaemia, parents’ knowledge of group B meningococcal disease and MenB vaccine was poor. While nervous about fever, most said they would take their child for MenB vaccination despite its link to fever. Most parents had liquid paracetamol at home. Many were willing to administer it after MenB vaccination as a preventive measure, although some had concerns. There were mixed views on the acceptability of four vaccinations at the 12-month booster visit; some preferred one visit, while others favoured spreading the vaccines over two visits. Parents were clear on the information they required before attending the immunisation appointment. CONCLUSIONS: The successful implementation of the MenB vaccination programme depends on its acceptance by parents. In view of parents’ recognition of the severity of meningitis and septicaemia, and successful introduction of other vaccines to prevent bacterial meningitis and septicaemia, the MenB vaccination programme is likely to be successful. However, the need for additional injections, the likelihood of post-immunisation fever and its management are issues about which parents will need information and reassurance from healthcare professionals. Public Health England has developed written information for parents, informed by these findings

Recognition and Assessment of Geomorphosites in Malta at the Il-Majjistral Nature and History Park

The Il-Majjistral Nature and History Park, located on the northwestern coast of the Island of Malta, is a protected area with natural, cultural and tourist interests. The Park, which was registered in 2008, is characterised by a landscape dominated by limestone and clay. Geomorphological features are highly controlled by the presence of faults and rock masses characterised by different physical and mechanical properties. Coastal cliffs, bays and sandy beaches are the most outstanding geomorphological features of the Park, creating a breathtaking landscape which is an attraction for a number of visitors. In the framework of an international research project, a study for the identification, selection and enhancement of the rich geomorphological heritage of the area has been carried out. In particular, a recognition and a quantitative assessment of geomorphosites on the basis of two different methodologies has been developed, and the results have been compared to establish the reliability of the methodologies. The results represent the first step and the necessary basic knowledge for possible enhancement of geomorphosites in Malta and the promotion of tourism activities at the Il-Majjistral Nature and History Park through the auspices of environmental agencies

Selecting Outcomes to Ensure Pragmatic Trials Are Relevant to People Living with Dementia

Outcome measures for embedded pragmatic clinical trials (ePCTs) should reflect the lived experience of people living with dementia (PLWD) and their caregivers, yet patient‐ and caregiver‐reported outcomes (PCROs) are rarely available in large clinical and administrative data sources. Although pragmatic methods may lead to use of existing administrative data rather than new data collected directly from PLWD, interventions are truly impactful only when they change outcomes prioritized by PLWD and their caregivers. The Patient‐ and Caregiver‐Reported Outcomes Core (PCRO Core) of the IMbedded Pragmatic Alzheimer's Disease (AD) and AD‐Related Dementias Clinical Trials (IMPACT) Collaboratory aims to promote optimal use of outcomes relevant to PLWD and their caregivers in pragmatic trials. The PCRO Core will address key scientific challenges limiting outcome measurement, such as gaps in existing measures, methodologic constraints, and burdensome data capture. PCRO Core investigators will create a searchable library of AD/AD‐related dementias (ADRD) clinical outcome measures, including measures in existing data sources with potential for AD/ADRD ePCTs, and will support best practices in measure development, including pragmatic adaptation of PCROs. Working together with other Cores and Teams within the IMPACT Collaboratory, the PCRO Core will support investigators to select from existing outcome measures, and to innovate in methods for measurement and data capture. In the future, the work of the IMPACT Collaboratory may galvanize broader embedded use of outcomes that matter to PLWD and their care partners in large health system

Duration of infectiousness and correlation with RT-PCR cycle threshold values in cases of COVID-19, England, January to May 2020.

Severe acute respiratory syndrome coronavirus 2 viral load in the upper respiratory tract peaks around symptom onset and infectious virus persists for 10 days in mild-to-moderate coronavirus disease (n = 324 samples analysed). RT-PCR cycle threshold (Ct) values correlate strongly with cultivable virus. Probability of culturing virus declines to 8% in samples with Ct > 35 and to 6% 10 days after onset; it is similar in asymptomatic and symptomatic persons. Asymptomatic persons represent a source of transmissible virus

Efeito das proporções de colmo e panículas sobre as porcentagens de fibra em detergente neutro de três híbridos de sorgo em cinco diferentes estádios de maturação.

Foram avaliados tres hibridos de sorgo de duplo proposito (BR 700, BR 701 e MASSA 03) para producao de silagem. Os hibridos foram cortados em cinco estadios de maturacao diferentes. Para avaliacao das proporcoes de colmos e paniculas utilizou-se delineamento estatistico em blocos ao acaso, em esquema fatorial 5x3x3, com tres repeticoes para cada tratamento. Nao foram observadas diferencas nas variaveis avaliadas entre os diferentes estadios de maturacao estudados, nem entre os hibridos avaliados. As porcentagens de fibra em detergente neutro (FDN) foram avaliadas nos materiais originais e respectivas silagens, nao sendo observado variacoes com o avanco do estadio de maturacao. para esta variavel utilizou-se delineamento estatistico inteiramente casualizado, em esquema fatorial 5x3x3x2. As medias foram comparadas pelo teste "SNK", com nivel de significancia de 5%

Avaliação agronômica de três híbridos de sorgo (BR 700, BR 701 e MASSA 03) colhidos em cinco diferentes estádios de maturação.

Foram avaliados tres hibridos de sorgo de duplo proposito (BR 700, BR 701 e MASSA 03) para producao de silagem. Os hibridos foram cortados em cinco estadios de maturacao diferentes. Foi utilizado delineamento estatistico em blocos ao acaso com tres repeticoes para cada tratamento. As medias foram comparadas pelo teste "SNK" (Student Newman Keuls), com nivel de significancia de 5%. os dados foram analisados pelo pacote estatistico SAEG (1997). Determinou-se a producao de materia seca/ha, altura das plantas e numero de plantas/ha. Nao foram observadas diferenças nas variaveis avaliadas entre os diferentes estadios de maturacao estudados, nem entre os hibridos avaliados dentro de uma mesma epoca

Teores de carboidratos solúveis e ácidos orgânicos de silagens de três genótipos de sorgo colhidos em cinco diferentes momentos de colheita.

Foram avaliados tres hibridos de sorgo de duplo proposito (BR 700, BR 701 e MASSA 03) para producao de silagem. Os hibridos foram cortados em cinco estadios de maturacao diferentes. O delineamento estatistico utilizado foi inteiramente casualizado, em esquema fatorial 5x3x3x2 para a analise de CHO's e de 5x3x3 para as analises realizadas apenas nas silagens (acidos organicos). As medias foram comparadas pelo teste "SNK", com nivel de significancia de 5%. No hibrido BR 700 observou-se reducao dos niveis de carboidratos soluveis entre as epocas dois e tres, no MASSA 03 a reducao ocorreu entre as epocas dois e tres, e quatro e cinco. Houve reducao significativa entre os teores de carboidratos soluveis doa materiais originais e das suas respectivas silagens. Os teores de acido acetico e butirico nao variaram com o avanco do estadio de maturacao. As porcentagens de acido latico reduziram entre a primeira e segunda epoca, no hibrido BR 700, e entre a segunda e terceira epoca nos outros dois, estabilizando a partir de entao

Soluble trivalent engagers redirect cytolytic T cell activity toward tumor endothelial marker 1.

Tumor endothelial marker 1 (TEM1) is an emerging cancer target with a unique dual expression profile. First, TEM1 is expressed in the stroma and neo-vasculature of many human carcinomas but is largely absent from healthy adult tissues. Second, TEM1 is expressed by tumor cells of mesenchymal origin, notably sarcoma. Here, we present two fully human anti-TEM1 single-chain variable fragment (scFv) reagents, namely, 1C1m and 7G22, that recognize distinct regions of the extracellular domain and possess substantially different affinities. In contrast to other, well-described anti-TEM1 binders, these fragments confer cytolytic activity when expressed as 2 <sup>nd</sup> generation chimeric antigen receptors (CARs). Moreover, both molecules selectively redirect human T cell effector functions toward TEM1 <sup>+</sup> tumor cells when incorporated into experimental soluble bispecific trivalent engagers that we term TriloBiTEs (tBs). Furthermore, systemic delivery of 1C1m-tB prevents the establishment of Ewing sarcoma tumors in a xenograft model. Our observations confirm TEM1 as a promising target for cancer immunotherapy and illustrate the prospective translational potential of certain scFv-based reagents

Pseudomonas aeruginosa toxin ExoU induces a PAF-dependent impairment of alveolar fibrin turnover secondary to enhanced activation of coagulation and increased expression of plasminogen activator inhibitor-1 in the course of mice pneumosepsis

<p>Abstract</p> <p>Background</p> <p>ExoU, a <it>Pseudomonas aeruginosa </it>cytotoxin with phospholipase A₂activity, was shown to induce vascular hyperpermeability and thrombus formation in a murine model of pneumosepsis. In this study, we investigated the toxin ability to induce alterations in pulmonary fibrinolysis and the contribution of the platelet activating factor (PAF) in the ExoU-induced overexpression of plasminogen activator inhibitor-1 (PAI-1).</p> <p>Methods</p> <p>Mice were intratracheally instilled with the ExoU producing PA103 <it>P. aeruginosa </it>or its mutant with deletion of the <it>exoU </it>gene. After 24 h, animal bronchoalveolar lavage fluids (BALF) were analyzed and lung sections were submitted to fibrin and PAI-1 immunohistochemical localization. Supernatants from A549 airway epithelial cells and THP-1 macrophage cultures infected with both bacterial strains were also analyzed at 24 h post-infection.</p> <p>Results</p> <p>In PA103-infected mice, but not in control animals or in mice infected with the bacterial mutant, extensive fibrin deposition was detected in lung parenchyma and microvasculature whereas mice BALF exhibited elevated tissue factor-dependent procoagulant activity and PAI-1 concentration. ExoU-triggered PAI-1 overexpression was confirmed by immunohistochemistry. In <it>in vitro </it>assays, PA103-infected A549 cells exhibited overexpression of PAI-1 mRNA. Increased concentration of PAI-1 protein was detected in both A549 and THP-1 culture supernatants. Mice treatment with a PAF antagonist prior to PA103 infection reduced significantly PAI-1 concentrations in mice BALF. Similarly, A549 cell treatment with an antibody against PAF receptor significantly reduced PAI-1 mRNA expression and PAI-1 concentrations in cell supernatants, respectively.</p> <p>Conclusion</p> <p>ExoU was shown to induce disturbed fibrin turnover, secondary to enhanced procoagulant and antifibrinolytic activity during <it>P. aeruginosa </it>pneumosepsis, by a PAF-dependent mechanism. Besides its possible pathophysiological relevance, <it>in vitro </it>detection of e<it>xoU </it>gene in bacterial clinical isolates warrants investigation as a predictor of outcome of patients with <it>P. aeruginosa </it>pneumonia/sepsis and as a marker to guide treatment strategies.</p

Lil ommi

Ġabra ta’ poeżiji u proża li tinkludi: Tifkiriet biss! ta’ Wallace Ph. Gulia – Elan vital ta’ Joe Saliba – B’tifkira ta’ għeluq il-ħamsin sena tal-mewt ta’ l-għażiż missieri Ċensu Busuttil ta’ E. D. Busuttil – Lil ommi ta’ V. Busuttil.peer-reviewe