Resources and services needed by educators to work with autistic students in mainstream primary schools : the Maltese perspective

Maltese governments have invested considerably in education and inclusion in society. In this article, the resources and services needed by the senior management team (SMT), teachers, and learning support educators (LSEs) when working with autistic students in mainstream primary schools in Malta are discussed. This is done in light of research showing that resources and services in inclusive schools can ease the challenges of IE and make it a positive experience. Data was collected through qualitative questionnaires and semi-structured interviews. All primary school educators in one college [i] were invited to participate. 172 educators accepted the invitation and filled out a questionnaire. Of the 172 participants, 19 agreed to participate in a semi-structured interview. The findings show that in the Maltese education system several services already exist for autistic students. However, such services have certain deficiencies that must be addressed. Moreover, the findings show that certain resources and other services are lacking.peer-reviewe

The burden of tuberculosis in crisis-affected populations: a systematic review.

Crises caused by armed conflict, forced population displacement, or natural disasters result in high rates of excess morbidity and mortality from infectious diseases. Many of these crises occur in areas with a substantial tuberculosis burden. We did a systematic review to summarise what is known about the burden of tuberculosis in crisis settings. We also analysed surveillance data from camps included in UN High Commissioner for Refugees (UNHCR) surveillance, and investigated the association between conflict intensity and tuberculosis notification rates at the national level with WHO data. We identified 51 reports of tuberculosis burden in populations experiencing displacement, armed conflict, or natural disaster. Notification rates and prevalence were mostly elevated; where incidence or prevalence ratios could be compared with reference populations, these ratios were 2 or higher for 11 of 15 reports. Case-fatality ratios were mostly below 10% and, with exceptions, drug-resistance levels were comparable to those of reference populations. A pattern of excess risk was noted in UNHCR-managed camp data where the rate of smear testing seemed to be consistent with functional tuberculosis programmes. National-level data suggested that conflict was associated with decreases in the notification rate of tuberculosis. More studies with strict case definitions are needed in crisis settings, especially in the acute phase, in internally displaced populations and in urban settings. Findings suggest the need for early establishment of tuberculosis services, especially in displaced populations from high-burden areas and for continued innovation and prioritisation of tuberculosis control in crisis settings

Deregulation of the phosphatase, PP2A is a common event in breast cancer, predicting sensitivity to FTY720

We would like to thank Professor Andrew Hanby, Professor Valerie Speirs and Dr Thomas A Hughes for the breast cancer cell lines used in this study. This research was supported by the Faculty of Medicine and Surgery, University of Malta.Background: The most commonly used biomarkers to predict the response of breast cancer patients to therapy are the oestrogen receptor (ER), progesterone receptor (PgR), and human epidermal growth factor receptor 2 (HER2). Patients positive for these biomarkers are eligible for specific therapies such as endocrine treatment in the event of ER and PgR positivity, and the monoclonal antibody, trastuzumab, in the case of HER2-positive patients. Patients who are negative for these three biomarkers, the so-called triple negatives, however, derive little benefit from such therapies and are associated with a worse prognosis. Deregulation of the protein serine/threonine phosphatase type 2A (PP2A) and its regulatory subunits is a common event in breast cancer, providing a possible target for therapy. Methods: The data portal, cBioPortal for Cancer Genomics was used to investigate the incidence of conditions that are associated with low phosphatase activity. Four (4) adherent human breast cancer cell lines, MDA-MB-468, MDA-MB-436, Hs578T and BT-20 were cultured to assess their viability when exposed to various dosages of rapamycin or FTY720. In addition, RNA was extracted and cDNA was synthesised to amplify the coding sequence of PPP2CA. Amplification was followed by high-resolution melting to identify variations. Results and conclusion: The sequence of PPP2CA was found to be conserved across a diverse panel of solid tumour and haematological cell lines, suggesting that low expression of PPP2CA and differential binding of inhibitory PPP2CA regulators are the main mechanisms of PP2A deregulation. Interestingly, the cBioPortal for Cancer Genomics shows that PP2A is deregulated in 59.6% of basal breast tumours. Viability assays performed to determine the sensitivity of a panel of breast cancer cell lines to FTY720, a PP2A activator, indicated that cell lines associated with ER loss are sensitive to lower doses of FTY720. The subset of patients with suppressed PP2A activity is potentially eligible for treatment using therapies which target the PI3K/AKT/mTOR pathway, such as phosphatase activators.peer-reviewe

SARS-CoV-2 infection and transmission in educational settings : cross-sectional analysis of clusters and outbreaks in England

BACKGROUND: Understanding severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and transmission in educational settings is crucial for ensuring the safety of staff and children during the COVID-19 pandemic. We estimated the rate of SARS-CoV-2 infection and outbreaks among staff and students in educational settings during the summer half-term (June-July, 2020) in England. METHODS: In this prospective, cross-sectional analysis, Public Health England initiated enhanced national surveillance in educational settings in England that had reopened after the first national lockdown, from June 1 to July 17, 2020. Educational settings were categorised as early years settings (<5-year-olds), primary schools (5-11-year-olds; only years 1 and 6 allowed to return), secondary schools (11-18-year-olds; only years 10 and 12), or mixed-age settings (spanning a combination of the above). Further education colleges were excluded. Data were recorded in HPZone, an online national database for events that require public health management. RT-PCR-confirmed SARS-CoV-2 event rates and case rates were calculated for staff and students, and direction of transmission was inferred on the basis of symptom onset and testing dates. Events were classified as single cases, coprimary cases (at least two confirmed cases within 48 h, typically within the same household), and outbreaks (at least two epidemiologically linked cases, with sequential cases diagnosed within 14 days in the same educational setting). All events were followed up for 28 days after educational settings closed for the summer holidays. Negative binomial regression was used to correlate educational setting events with regional population, population density, and community incidence. FINDINGS: A median of 38 000 early years settings (IQR 35 500-41 500), 15 600 primary schools (13 450-17 300), and 4000 secondary schools (3700-4200) were open each day, with a median daily attendance of 928 000 students (630 000-1 230 000) overall. There were 113 single cases of SARS-CoV-2 infection, nine coprimary cases, and 55 outbreaks. The risk of an outbreak increased by 72% (95% CI 28-130) for every five cases per 100 000 population increase in community incidence (p<0·0001). Staff had higher incidence than students (27 cases [95% CI 23-32] per 100 000 per day among staff compared with 18 cases [14-24] in early years students, 6·0 cases [4·3-8·2] in primary schools students, and 6·8 cases [2·7-14] in secondary school students]), and most cases linked to outbreaks were in staff members (154 [73%] staff vs 56 [27%] children of 210 total cases). Probable direction of transmission was staff to staff in 26 outbreaks, staff to student in eight outbreaks, student to staff in 16 outbreaks, and student to student in five outbreaks. The median number of secondary cases in outbreaks was one (IQR 1-2) for student index cases and one (1-5) for staff index cases. INTERPRETATION: SARS-CoV-2 infections and outbreaks were uncommon in educational settings during the summer half-term in England. The strong association with regional COVID-19 incidence emphasises the importance of controlling community transmission to protect educational settings. Interventions should focus on reducing transmission in and among staff. FUNDING: Public Health England

What have we learnt from measles outbreaks in 3 English cities? A qualitative exploration of factors influencing vaccination uptake in Romanian and Roma Romanian communities

Abstract Background: Since 2016, large scale measles outbreaks have heavily affected countries across Europe. In England, laboratory confirmed measles cases increased almost four-fold between 2017 and 2018, from 259 to 966 cases. Several of the 2017-18 measles outbreaks in England particularly affected Romanian and Roma Romanian communities, with the first outbreaks in these communities occurring in Birmingham, Leeds and Liverpool. This study explored factors influencing vaccination behaviours amongst Romanian and Roma Romanian communities in these three cities. Methods: Across Birmingham, Leeds and Liverpool, we conducted semi-structured interviews with 33 key providers to explore their experience in delivering vaccinations and managing the outbreak response. We also interviewed 9 Romanian women in one of the cities to explore their vaccination attitudes and behaviours. To categorise factors affecting vaccination we applied the 5As Taxonomy for Determinants of Vaccine Uptake (Access, Affordability, Awareness, Acceptance and Activation) during data analysis. Findings: Factors related to access and acceptance, such as language and literacy, ease of registering with a general practice, and trust in health services, were reported as the main barriers to vaccination amongst the communities. Concerns around vaccination safety and importance were reported but these appeared to be less dominant contributing factors to vaccination uptake. The active decline of vaccinations amongst interviewed community members was linked to distrust in healthcare services, which were partly rooted in negative experiences of healthcare in Romania and the UK. Conclusion: Access and acceptance, dominant barriers to vaccination, can be improved through the building of trust with communities. To establish trust providers must find ways to connect with and develop a greater understanding of the communities they serve. To achieve this, cultural and linguistic barriers need to be addressed. Better provider-service user relationships are crucial to reducing vaccination inequalities and tackling broader disparities in health service access.</jats:p

Responding to measles outbreaks in underserved Roma and Romanian populations in England: the critical role of community understanding and engagement.

Since 2016, the European Region has experienced large-scale measles outbreaks. Several measles outbreaks in England during 2017/18 specifically affected Romanian and Romanian Roma communities. In this qualitative interview study, we looked at the effectiveness of outbreak responses and efforts to promote vaccination uptake amongst these underserved communities in three English cities: Birmingham, Leeds and Liverpool. Semi-structured in-depth interviews were conducted with 33 providers involved in vaccination delivery and outbreak management in these cities. Interviews were analysed thematically and factors that influenced the effectiveness of responses were categorised into five themes: (1) the ability to identify the communities, (2) provider knowledge and understanding of the communities, (3) the co-ordination of response efforts and partnership working, (4) links to communities and approaches to community engagement and (5) resource constraints. We found that effective partnership working and community engagement were key to the prevention and management of vaccine-preventable disease outbreaks in the communities. Effective engagement was found to be compromised by cuts to public health spending and services for underserved communities. To increase uptake in under-vaccinated communities, local knowledge and engagement are vital to build trust and relationships. Local partners must work proactively to identify, understand and build connections with communities

Promoting influenza vaccine for children

This autumn influenza vaccine will again be offered to all 2- and 3-year-olds in general practice. In addition, all children in clinical risk groups aged 6 months and above should be offered the vaccine. Children in primary school years from reception class to year 4 will also be offered the vaccine as part of the on-going extension of influenza vaccination to healthy children. Since the start of the paediatric programme, transmission of influenza has reduced across all age groups in those parts of the country vaccinating all children of primary school age. Children under 5 years of age have the highest rate of hospital admissions for influenza. However, many parents do not think that influenza is a serious illness and it is the vaccine they are most likely to decline. Health professionals are the most trusted source of advice and information about vaccination, so staff in general practice have a crucial role to play in recommending this vaccine to parents. Health professionals are the most trusted source of advice and information about vaccination, so practice nurses have a crucial role to play in recommending the influenza vaccine to parents and increasing uptake </jats:p

Triazole Substitution of a Labile Amide Bond Stabilizes Pantothenamides and Improves Their Antiplasmodial Potency

The biosynthesis of coenzyme A (CoA) from pantothenate and the utilization of CoA in essential biochemical pathways represent promising antimalarial drug targets. Pantothenamides, amide derivatives of pantothenate, have potential as antimalarials, but a serum enzyme called pantetheinase degrades pantothenamides, rendering them inactive in vivo. In this study, we characterize a series of 19 compounds that mimic pantothenamides with a stable triazole group instead of the labile amide. Two of these pantothenamides are active against the intraerythrocytic stage parasite with 50% inhibitory concentrations (IC50s) of ∼50 nM, and three others have submicromolar IC50s. We show that the compounds target CoA biosynthesis and/or utilization. We investigated one of the compounds for its ability to interact with the Plasmodium falciparum pantothenate kinase, the first enzyme involved in the conversion of pantothenate to CoA, and show that the compound inhibits the phosphorylation of [14C]pantothenate by the P. falciparum pantothenate kinase, but the inhibition does not correlate with antiplasmodial activity. Furthermore, the compounds are not toxic to human cells and, importantly, are not degraded by pantetheinase

A novel heteromeric pantothenate kinase complex in apicomplexan parasites

Coenzyme A is synthesised from pantothenate via five enzyme-mediated steps. The first step is catalysed by pantothenate kinase (PanK). All PanKs characterised to date form homodimers. Many organisms express multiple PanKs. In some cases, these PanKs are not functionally redundant, and some appear to be non-functional. Here, we investigate the PanKs in two pathogenic apicomplexan parasites, Plasmodium falciparum and Toxoplasma gondii. Each of these organisms express two PanK homologues (PanK1 and PanK2). We demonstrate that PfPanK1 and PfPanK2 associate, forming a single, functional PanK complex that includes the multi-functional protein, Pf14-3-3I. Similarly, we demonstrate that TgPanK1 and TgPanK2 form a single complex that possesses PanK activity. Both TgPanK1 and TgPanK2 are essential for T. gondii proliferation, specifically due to their PanK activity. Our study constitutes the first examples of heteromeric PanK complexes in nature and provides an explanation for the presence of multiple PanKs within certain organisms. Author summary: Apicomplexans are a phylum of obligate intracellular parasites that cause diseases in humans and other animals, inflicting considerable burdens on human societies. During their intracellular stage, these parasites must scavenge vitamins from their host organisms in order to survive and proliferate. One such vitamin is pantothenate (vitamin B5), which parasites convert in a universal five-step pathway to the essential metabolite coenzyme A (CoA). The first reaction in the CoA biosynthesis pathway is catalyzed by the enzyme pantothenate kinase (PanK). The genomes of humans and many other organisms, including apicomplexans, encode multiple PanK homologues, although in all studied examples, the functional PanK enzyme exists as a homodimer. In this study, we demonstrate that the two PanK homologues encoded in the genomes of the apicomplexans Plasmodium falciparum and Toxoplasma gondii, PanK1 and PanK2, exist as functional heteromeric complexes. We provide evidence that both PanK homologues contribute to the PanK activity in these parasites, and that both PanK1 and PanK2 are essential for the proliferation of T. gondii parasites specifically for their PanK activity. Our data describe the first known instances of heteromeric PanK complexes in nature and may explain why some organisms that express multiple PanKs seemingly harbor non-functional isoforms.ETT, VMH and CS were supported by Research Training Program scholarships from the Australian Government. CS was also funded by an NHMRC Overseas Biomedical Fellowship (1016357). This work was, in part, supported by a Project Grant (APP1129843) from the National Health and Medical Research Council to KJS and a Discovery Grant (DP150102883) from the Australian Research Council to Gv

Summer music and arts festivals as hot spots for measles transmission: experience from England and Wales, June to October 2016.

We report 52 cases of measles linked to music and arts festivals in England and Wales, between mid-June and mid-October 2016. Nearly half were aged 15 to 19 years. Several individuals who acquired measles at one festival subsequently attended another festival while infectious, resulting in multiple interlinked outbreaks. Transmission within festivals resulted in a geographical spread of cases nationally as well as internationally, which presents particular challenges for measles control