The state of integrated disease surveillance globally: synthesis report of a mixed methods study.

OBJECTIVES: Disease surveillance is an essential public health function needed to prevent, detect, monitor and respond to health threats. Integrated disease surveillance (IDS) enhances its utility and has been advocated for decades by the World Health Organization. This study sought to examine the state of IDS implementation worldwide. STUDY DESIGN: The study used a concurrent mixed methods approach consisting of a systematic scoping review of the literature on IDS, a survey of International Association of National Public Health Institutes (IANPHI) members and qualitative deep dive case studies in seven countries. METHODS: This report collates, analyses and synthesises the findings from the three components. The scoping review consisted of a review of summarised evidence on IDS. Eight reviews and five primary studies were included. The cross-sectional survey was conducted of 110 IANPHI members representing ninety-five countries. Qualitative case studies were conducted in Malawi, Mozambique, Uganda, Pakistan, Canada, Sweden, and England, which involved thirty-four focus group discussions and forty-eight key informant interviews. RESULTS: In the different countries, IDS is conceptualised differently and there are differing levels of maturity of IDS functions. Although the role of National Public Health Institutes has not been well defined in the IDS, they play a significant role in IDS in many countries. Fragmentation between sectors and resourcing (human and financial) issues were common. Good governance measures such as appropriate legislative and regulatory frameworks and roles and responsibilities for IDS were often unclear. The COVID-19 pandemic has strengthened some surveillance systems, often through leveraging existing respiratory surveillance systems. In some instances, improvements were seen only for COVID-19 related data but these changes were not sustained. Evaluation of IDS was also reported to be weak. CONCLUSIONS: Integration should be driven by a clear purpose and contextualised. Political commitment, clear governance, and resourcing are needed. Technology and the establishment of technical communities of practice may help. However, the complexity and cost of integration should not be under-estimated, and further economic and impact evaluations of IDS are needed.

Direct Observation of the Pressure-Induced Structural Variation in Gold Nanoclusters and the Correlated Optical Response.

The ability to gradually modify the atomic structures of nanomaterials and directly identify such structural variation is important in nanoscience research. Here, we present the first example of a high-pressure single-crystal X-ray diffraction analysis of atomically precise metal nanoclusters. The pressure-dependent, subangstrom structural evolution of an ultrasmall gold nanoparticle, Au25S18, has been directly identified. We found that a 0.1 Å decrease of the Au-Au bond length could induce a blue-shift of 30 nm in the photoluminescence spectra of gold nanoclusters. From theoretical calculations, the origins of the blue-shift and enhanced photoluminescence under pressure are investigated, which are ascribed to molecular orbital symmetry and conformational locking, respectively. The combination of the high-pressure in situ X-ray results with both theoretical and experimental optical spectra provides a direct and generalizable avenue to unveil the underlying structure-property relations for nanoclusters and nanoparticles which cannot be obtained through traditional physical chemistry measurements.

Ukraine refugee crisis: evolving needs and challenges.

This case report examines the initial experience of Poland in responding to the refugee crisis triggered by the war in Ukraine. In the first 2 months of the crisis, more than 3 million Ukrainian refugees fled to Poland. The large influx of refugees rapidly overwhelmed local services and led to a complex humanitarian emergency. The initial priorities were to address basic human needs, such as shelter, infectious disease concerns and healthcare access, but evolved to include mental health, non-communicable diseases and protection needs. This necessitated a 'whole of society' response involving multiple agencies and civil society. Emerging lessons learned include the need for ongoing needs assessments, robust disease monitoring and surveillance, as well as flexible multisectoral responses that are culturally sensitive. Finally, Poland's efforts to integrate refugees may help mitigate some of the adverse consequences of the conflict-related migration.

Prostaglandin E2-Mediated Impairment of Innate Immune Response to A(H1N1)pdm09 Infection in Diet-Induced Obese Mice Could Be Restored by Paracetamol.

BACKGROUND: Obesity is associated with increased severity of influenza infection. However, the underlying mechanism is largely unknown. METHODS: We employed a mouse model with diet-induced obesity (DIO) to study the innate immune responses induced by influenza virus. RESULTS: The lungs of DIO mice were heavily affected by obesity-associated chronic systemic inflammation with a significant increase in inflammatory cytokines/chemokines. Concurrently, lipid immune mediator prostaglandin E2 (PGE2) was also significantly elevated in DIO mice. However, the DIO mice mounted a blunted and delayed upregulation of mRNA and protein concentrations of interferon-ß and inflammatory cytokines/chemokines upon A(H1N1)pdm09 virus (H1N1/415742Md) challenge compared with those of lean mice. PGE2 concentrations were significantly higher in the lungs of DIO mice compared to that of lean mice postchallenge. Treatment with paracetamol in challenged DIO mice significantly enhanced the expression of interferon-α/ß and cytokine genes at days 1 and 3 postinfection compared with that of untreated DIO mice. Furthermore, paracetamol treatment alone started 3 days before virus challenge and continued until 6 days postchallenge ameliorated the severity of a lethal H1N1/415742Md infection in DIO mice with improved survival. CONCLUSIONS: Impaired innate response to influenza in DIO mice is associated with elevated PGE2, which could be restored to some degree by paracetamol treatment.

Triple combination of FDA-approved drugs including flufenamic acid, clarithromycin and zanamivir improves survival of severe influenza in mice.

Seasonal influenza virus remains a common cause of mortality despite the use of neuraminidase inhibitors. This study evaluated the efficacy of a triple combination of zanamivir, clarithromycin and flufenamic acid (FFA) in the treatment of influenza virus A(H1N1) infection. An in vitro cell protection assay and a multiple-cycle growth assay showed that the antiviral activity of zanamivir was enhanced when combined with clarithromycin or FFA. A mouse challenge model was used here for the evaluation of the in vivo efficacy of the triple combination treatment. We found that mice receiving the triple combination of FFA, zanamivir, and clarithromycin had a significantly better survival rate than those receiving the double combination of zanamivir and clarithromycin (88% versus 44%, P = 0.0083) or zanamivir monotherapy (88% versus 26%, P = 0.0002). Mice in the FFA-zanamivir-clarithromycin triple combination group also exhibited significantly less body weight loss than those in the zanamivir-clarithromycin double combination group. There was no significant difference in the lung viral titers among the different groups from day 2 to day 6 postinfection. However, the levels of IL-1ß, TNF-α and RANTES in the FFA-zanamivir-clarithromycin triple combination group were significantly lower than those in the zanamivir-clarithromycin double combination group, zanamivir monotherapy group, or solvent group on day 2 postinfection. Our findings showed that the FFA-zanamivir-clarithromycin triple combination improved the inflammatory markers and survival of severe influenza A(H1N1) infection in mice.

Prevalence of depressive symptoms and its associated factors in older adults: a cross-sectional study in Kathmandu, Nepal.

OBJECTIVE: Globally, depression is one of the most prevalent and burdensome conditions in older adults. However, there are few population-based studies of depression in older adults in developing countries. In this paper, we examine the prevalence of depressive symptoms and explore possible contributory risk factors in older adults living in Nepal. METHODS: A cross-sectional study was conducted in two semi-urban communities in Kathmandu, Nepal. Depression was assessed using the 15-item Geriatric Depression Scale in 303 participants, aged 60 years and over. Multivariate logistic regression was then used to assess associations between potential risk factors and depression. RESULTS: More than half of the participants (n = 175, 60.6%) had significant depressive symptomatology, with 27.7% having scores suggesting mild depression. Illiteracy (aOR = 2.01, 95% CI: 1.08-3.75), physical immobility (aOR = 5.62, 95% CI: 1.76-17.99), the presence of physical health problems (aOR = 1.97, 95% CI: 1.03-3.77), not having any time spent with family members (aOR = 3.55, 95% CI: 1.29-9.76) and not being considered in family decision-making (aOR = 4.02, 95% CI: 2.01-8.04) were significantly associated with depression in older adults. CONCLUSION: The prevalence of depression was significant in older adults. There are clear associations of depression with demographic, social support and physical well-being factors in this population. Strategies that increase awareness in the community along with the health and social care interventions are needed to address the likely drivers of depression in older adults.

Avian influenza virus A H7N9 infects multiple mononuclear cell types in peripheral blood and induces dysregulated cytokine responses and apoptosis in infected monocytes.

Most patients with avian influenza A H7N9 virus (H7N9) infection suffer from severe illness, accompanied by dysregulated cytokine/chemokine response, delayed viral clearance and impaired neutralizing antibody response. Here, we evaluated the role of peripheral blood mononuclear cells (PBMCs) in the pathogenesis of H7N9 infection using an ex vivo infection model. H7N9 infected a significantly higher percentage of PBMCs (23.9 %) than those of avian influenza A H5N1 virus (H5N1) (12.3 %) and pandemic H1N1 virus (pH1N1) (5.5 %) (P<0.01). H7N9 infected significantly more B and T lymphocytes than H5N1. When compared with pH1N1, H7N9-infected PBMCs had significantly higher mRNA levels of proinflammatory cytokines and type I interferons (IFNs) at 6 h post-infection (p.i.), but significantly lower levels of IFN-γ and IP-10 at 12 h p.i. Among the PBMCs, CD14+ monocytes were most permissive to H7N9 infection. The percentage of infected CD14+ monocytes was significantly higher for H7N9 than that of pH1N1, but not significantly different from that of H5N1. H7N9-infected monocytes showed higher expression of MIP-1α, MIP-1ß and RANTES than that of pH1N1 at 6 h p.i. H7N9- but not pH1N1-infected monocytes died rapidly via apoptosis. Furthermore, pH1N1- but not H7N9-infected monocytes showed increased expression of the monocyte activation and differentiation markers. Unlike pH1N1, H7N9 showed similar PBMC/monocyte cytokine/chemokine expression profile, monocyte cell death and expression of activation/differentiation markers to H5N1. Besides proinflammatory cytokine activation leading to a cytokine storm, impaired IFN-γ production, rapid monocytic death and lack of monocyte differentiation may affect the ability of H7N9-infected innate immune cells to recruit protective adaptive immunity.

Accuracy of diagnosis and classification of COPD in primary and specialist nurse-led respiratory care in Rotherham, UK: a cross-sectional study.

BACKGROUND: Studies have suggested that chronic obstructive pulmonary disease (COPD) is commonly misdiagnosed and misclassified in primary care, but less is known about the quality of diagnosis in specialist respiratory care. AIMS: To measure the accuracy of COPD diagnosis and classification of airway obstruction in primary care and at a specialist respiratory centre, and to explore associations between misdiagnosis and misclassification and a range of explanatory factors. METHODS: Data were obtained for 1,205 referrals to a specialist respiratory centre between 2007 and 2010. Standard analysis methods were used. RESULTS: The majority of patients were referred for pulmonary rehabilitation (676/1,205, 56%). Of 1,044 patients with a primary care diagnosis of COPD, 211 (20%) had spirometry inconsistent with COPD. In comparison, of 993 specialist centre diagnoses, 65 (6.5%) had inconsistent spirometry. There was poor agreement between the airflow obstruction grade recorded on the referral and that based on spirometry (kappa=0.26, n=448), whereas agreement between the respiratory centre assessment of airflow obstruction and spirometry was good (kappa=0.88, n=1,016). Referral by practice nurse was associated with accuracy of airflow obstruction classification in primary care (OR 1.85, 95% CI 1.33 to 2.57). Males were more likely than females to have an accurate specialist care classification of airway obstruction (OR 1.40, 95% CI 1.01 to 1.93). Grade of airway obstruction changed between referral and assessment in 56% of cases. CONCLUSIONS: In primary care, a proportion of patients diagnosed with COPD do not have COPD, and misclassification of grade of airflow obstruction is common. Misdiagnosis and misclassification is less common in the specialist care setting of BreathingSpace.

MicroRNAs: relevant tools for a colorectal surgeon?

Colorectal cancer is the third most common malignancy and cause of cancer-related deaths worldwide. Approximately half of the patients diagnosed with colorectal cancer ultimately die of the condition. Death from colorectal cancer can be prevented by early detection, but unfortunately presentation is often late, with a worse prognosis. Screening by fecal occult blood testing reduces disease-specific mortality, but there is a need for sensitive and specific noninvasive biomarkers to facilitate detecting the disease, staging it, and predicting the best therapeutic options. MicroRNAs (miRNAs) are short noncoding RNA sequences that have a crucial role in the regulation of gene expression. They have significant regulatory functions in basic cellular processes, such as cell differentiation, proliferation, and apoptosis. Evidence suggests that miRNAs may function as both tumor suppressors and oncogenes. The main mechanism for changes in the function of miRNAs in cancer cells is due to aberrant gene expression. Accurate discrimination of miRNA profiles between tumor and normal mucosa in colorectal cancer allows definition of specific expression patterns of miRNAs, giving good potential as diagnostic and therapeutic targets. MiRNAs expressed in colorectal cancers are also abundantly present and stable in stool and plasma samples. Their extraction from these three sources is feasible and reproducible. The ease and reliability of determining miRNA profiles in plasma or stool makes them potential molecular markers for colorectal cancer screening. This review summarizes the role miRNAs have in colorectal cancer, highlighting particularly the potential diagnostic, prognostic, and therapeutic implications in the future treatment of the disease.

Emergency management in health: key issues and challenges in the UK.

BACKGROUND: Emergency planning in the UK has grown considerably in recent years, galvanised by the threat of terrorism. However, deficiencies in NHS emergency planning were identified and the evidence-base that underpins it is questionable. Inconsistencies in terminologies and concepts also exist. Different models of emergency management exist internationally but the optimal system is unknown. This study examines the evidence-base and evidence requirements for emergency planning in the UK health context. METHODS: The study involved semi-structured interviews with key stakeholders and opinion leaders. Purposive sampling was used to obtain a breadth of views from various agencies involved in emergency planning and response. Interviews were then analysed using a grounded approach using standard framework analysis techniques. RESULTS: We conducted 17 key informant interviews. Interviewees identified greater gaps in operational than technical aspects of emergency planning. Social and behavioural knowledge gaps were highlighted with regards to how individuals and organisations deal with risk and behave in emergencies. Evidence-based approaches to public engagement and for developing community resilience to disasters are lacking. Other gaps included how knowledge was developed and used. Conflicting views with regards to the optimal configuration and operation of the emergency management system were voiced. CONCLUSIONS: Four thematic categories for future research emerged:(i) Knowledge-base for emergency management: Further exploration is needed of how knowledge is acquired, valued, disseminated, adopted and retained.(ii) Social and behavioural issues: Greater understanding of how individuals approach risk and behave in emergencies is required.(iii) Organisational issues in emergencies: Several conflicting organisational issues were identified; value of planning versus plans, flexible versus standardized procedures, top-down versus bottom-up engagement, generic versus specific planning, and reactive versus proactive approaches to emergencies.(iv) Emergency management system: More study is required of system-wide issues relating to system configuration and operation, public engagement, and how emergency planning is assessed.

Where is the evidence for emergency planning: a scoping review.

BACKGROUND: Recent terrorist attacks and natural disasters have led to an increased awareness of the importance of emergency planning. However, the extent to which emergency planners can access or use evidence remains unclear. The aim of this study was to identify, analyse and assess the location, source and quality of emergency planning publications in the academic and UK grey literature. METHODS: We conducted a scoping review, using as data sources for academic literature Embase, Medline, Medline in Process, Psychinfo, Biosis, Science Citation Index, Cinahl, Cochrane library and Clinicaltrials.gov. For grey literature identification we used databases at the Health Protection Agency, NHS Evidence, British Association of Immediate Care Schemes, Emergency Planning College and the Health and Safety Executive, and the websites of UK Department of Health Emergency Planning Division and UK Resilience.Aggregative synthesis was used to analyse papers and documents against a framework based on a modified FEMA Emergency Planning cycle. RESULTS: Of 2736 titles identified from the academic literature, 1603 were relevant. 45% were from North America, 27% were commentaries or editorials and 22% were event reports.Of 192 documents from the grey literature, 97 were relevant. 76% of these were event reports.The majority of documents addressed emergency planning and response. Very few documents related to hazard analysis, mitigation or capability assessment. CONCLUSIONS: Although a large body of literature exists, its validity and generalisability is unclear There is little evidence that this potential evidence base has been exploited through synthesis to inform policy and practice. The type and structure of evidence that would be of most value of emergency planners and policymakers has yet to be identified.

The impact of telehealth support for patients with diabetes or chronic obstructive pulmonary disease on unscheduled secondary care utilisation: a service evaluation.

BACKGROUND: Telehealth has been promoted as an adjunct to managing patients with long-term conditions. It has been used in various settings and for different disease groups. However, robust evidence for the efficacy of telehealth is currently lacking. OBJECTIVES: To evaluate the impact of a telehealth service on emergency admissions and emergency department (ED) attendances. METHODS: We evaluated a telehealth service providing supported self-management to patients that was implemented in Nottingham City. Two groups of patients ('graduates' of the Nottingham telehealth service and service 'decliners') were compared for two periods; 2009 (pre-service implementation) and 2011. Eighty-nine pairs of graduates and decliners were identified who were matched for age and sex. The number and cost of emergency admissions and ED attendances for these patients were then collated and analysed. RESULTS: Graduates had significantly fewer emergency admissions and ED attendances compared with decliners in 2011. However, differences of a similar magnitude in emergency admissions and ED attendances were found in 2009. Telehealth service users were likely to be qualitatively different from decliners, reflecting a degree of self-selection. This suggests that decliners were more likely to have a confounding reason for not engaging with telehealth, such as greater disease severity. CONCLUSIONS: This service review found no evidence that the Nottingham telehealth service has had a significant impact on secondary care utilisation in the short term. Longer term follow up is needed to establish conclusively whether telehealth initiatives like the Nottingham telehealth service does lead to tangible patient benefits and provide value for money.

Evaluation of internal standards for inductively coupled plasma-mass spectrometric analysis of arsenic in soils.

Arsenic (As) is a common contaminant in soils, and analysis of soils by inductively coupled plasma-mass spectrometry (ICP-MS) is often used to detect As in soil extracts. Internal standards (ISs) are part of ICP-MS analyses to enhance precision and accuracy by compensating for instrument variability; however, an improper choice of IS can result in negative analytical bias. The goal of this study was to develop a protocol for evaluating ISs commonly used in ICP-MS. Three soils of varying clay content and total As were extracted with a dilute electrolyte [0.005 mol L-1 Mg(NO3 )2 ] and an acid digest. Arsenic concentrations were quantified by ICP-MS using typical ISs: 6 Li, 45 Sc, 69 Ga, 89 Y, 103 Rh, 115 In, 159  Tb, and 209 Bi. Standard addition was used as a benchmark for As quantification. The most consistent IS was 115 In. Elevated, naturally occurring concentrations were detected for several of the ISs, particularly in the total digests, emphasizing the necessity for screening soils prior to analysis.

Age-associated SARS-CoV-2 breakthrough infection and changes in immune response in a mouse model.

Older individuals are at higher risk of SARS-CoV-2 infection and severe outcomes, but the underlying mechanisms are incompletely understood. In addition, how age modulates SARS-CoV-2 re-infection and vaccine breakthrough infections remain largely unexplored. Here, we investigated age-associated SARS-CoV-2 pathogenesis, immune responses, and the occurrence of re-infection and vaccine breakthrough infection utilizing a wild-type C57BL/6N mouse model. We demonstrated that interferon and adaptive antibody response upon SARS-CoV-2 challenge are significantly impaired in aged mice compared to young mice, which results in more effective virus replications and severe disease manifestations in the respiratory tract. Aged mice also showed increased susceptibility to re-infection due to insufficient immune protection acquired during the primary infection. Importantly, two-dose COVID-19 mRNA vaccination conferred limited adaptive immune response among the aged mice, making them susceptible to SARS-CoV-2 infection. Collectively, our findings call for tailored and optimized treatments and prevention strategies against SARS-CoV-2 among older individuals.

Corrigendum: Co-stimulation with TLR7 agonist imiquimod and inactivated Influenza virus particles promotes mouse B cell activation, differentiation, and accelerated antigen specific antibody production.

[This corrects the article DOI: 10.3389/fimmu.2018.02370.].

The genetic legacy of religious diversity and intolerance: paternal lineages of Christians, Jews, and Muslims in the Iberian Peninsula.

Most studies of European genetic diversity have focused on large-scale variation and interpretations based on events in prehistory, but migrations and invasions in historical times could also have had profound effects on the genetic landscape. The Iberian Peninsula provides a suitable region for examination of the demographic impact of such recent events, because its complex recent history has involved the long-term residence of two very different populations with distinct geographical origins and their own particular cultural and religious characteristics-North African Muslims and Sephardic Jews. To address this issue, we analyzed Y chromosome haplotypes, which provide the necessary phylogeographic resolution, in 1140 males from the Iberian Peninsula and Balearic Islands. Admixture analysis based on binary and Y-STR haplotypes indicates a high mean proportion of ancestry from North African (10.6%) and Sephardic Jewish (19.8%) sources. Despite alternative possible sources for lineages ascribed a Sephardic Jewish origin, these proportions attest to a high level of religious conversion (whether voluntary or enforced), driven by historical episodes of social and religious intolerance, that ultimately led to the integration of descendants. In agreement with the historical record, analysis of haplotype sharing and diversity within specific haplogroups suggests that the Sephardic Jewish component is the more ancient. The geographical distribution of North African ancestry in the peninsula does not reflect the initial colonization and subsequent withdrawal and is likely to result from later enforced population movement-more marked in some regions than in others-plus the effects of genetic drift.

Global public health training in the UK: preparing for the future.

BACKGROUND: Many major public health issues today are not confined by national boundaries. However, the global public health workforce appears unprepared to confront the challenges posed by globalization. We therefore sought to investigate whether the current UK public health training programme adequately prepares its graduates to operate in a globalized world. METHODS: We used mixed methods involving an online cross-sectional survey of UK public health trainees on the international content of the Faculty of Public Health's written examination, a qualitative review of the Faculty's 2007 training curriculum and a questionnaire survey of all training deaneries in the UK. RESULTS: We found that global health issues are not addressed by the current training curriculum or in the written examination despite trainee interest for this. Many of the deaneries were also unreceptive to international placements. CONCLUSIONS: Despite the recognized educational legitimacy of global health placements and the favourable UK policy context, the opportunities and international content of public health training remain limited. In order to retain its position as a leader in the field of public health, the UK needs to adapt its training programme to better reflect today's challenges.