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Vaccine Sep 2023Vaccine surveillance for children in England focuses on coverage at ages 1, 2, and 5 years. Previous studies exploring vaccine timeliness have used different arbitrary...
INTRODUCTION
Vaccine surveillance for children in England focuses on coverage at ages 1, 2, and 5 years. Previous studies exploring vaccine timeliness have used different arbitrary categories to define whether vaccines were received 'late' or 'on time'. This paper aims to provide more detailed and holistic information on timing and patterns of vaccine uptake across the childhood immunisation schedule in England.
METHODS
We included all children born in England between 2006 and 2014 and registered in the Clinical Practice Research Datalink (CPRD) Aurum, a primary care electronic health record. We described vaccine uptake for representative antigens (pertussis, pneumococcus, measles) by age in days and stratified by ethnicity, region and birth cohort. Alluvial diagrams were used to illustrate common journeys through the vaccination schedule, and we applied survival analysis using accelerated failure time models (AFT) to predict age of vaccine receipt based on timing of previous doses.
RESULTS
573,015 children were followed up until their fifth birthday, when they had 90.16 % coverage for two doses of measles, mumps, rubella (MMR) vaccine and 88.78% coverage for four doses of diphtheria, tetanus, pertussis (DTP) vaccine. Overall, the later the age at which a vaccine was due, the more delay in vaccination. Children of Black Ethnicity or from London showed deviating uptake patterns. If a child received their third DTP dose more than a year later than recommended, they would receive the next dose 2.7 times later than a child who was vaccinated on time. A smaller delay was found for children who did not receive first MMR dose on time.
DISCUSSION
We showed that the risk of vaccination delay increased with the age of the child and significant delay of previous doses. Primary care data can help to promptly identify children at higher risk of delayed vaccination.
Topics: Child; Humans; Infant; Measles-Mumps-Rubella Vaccine; Cohort Studies; Whooping Cough; Vaccination; Immunization Schedule; Measles; Mumps; Diphtheria-Tetanus-Pertussis Vaccine
PubMed: 37574342
DOI: 10.1016/j.vaccine.2023.08.002 -
International Journal of Infectious... Oct 2023SARS-CoV-2 remains a global health concern 3 years after its emergence. Safe and effective vaccines mitigate the pandemic impact, but the optimal schedule remains...
Vaccine-induced and hybrid immunity to SARS-CoV-2 after three or four doses of BNT162b2 - results from 22 months follow-up of a healthcare workers cohort, Israel, 2020-2022.
OBJECTIVES
SARS-CoV-2 remains a global health concern 3 years after its emergence. Safe and effective vaccines mitigate the pandemic impact, but the optimal schedule remains unclear, especially in a context where a high proportion of the population is infected.
METHODS
We periodically measured anti-spike SARS-CoV-2 immunoglobulin (Ig)G titers using a quantitative assay in an Israeli healthcare worker cohort who all received at least two BNT162b2 doses and either received further doses and/or were subsequently infected up to 22 months after dose two, and compared geometric mean concentrations according to number of doses received and infection status using analysis of variance.
RESULTS
Among the 993 included participants, infection after dose two led to higher geometric mean concentration IgG titers than a third dose (4285 vs 2845 arbitrary unit/ml 1-2 months after infection/vaccination, P = 0.03). In 16-18 months after dose two, those infected and those who received three or four vaccine doses all had IgG geometric mean concentration levels above 500 arbitrary unit/ml with no significant differences among groups (P = 0.6). IgG levels plateaued 16-22 months after dose two.
CONCLUSION
Three BNT162b2 doses provide long-term immunogenicity comparable to breakthrough infection after dose two. Dose four transiently increases IgG levels and may be especially important for providing additional protection to vulnerable individuals during periods of increased transmission risk.
Topics: Humans; Israel; SARS-CoV-2; BNT162 Vaccine; Follow-Up Studies; COVID-19; Vaccines; Health Personnel; Adaptive Immunity; Immunoglobulin G; Antibodies, Viral
PubMed: 37572957
DOI: 10.1016/j.ijid.2023.08.009 -
Heliyon Jul 2023Natural killer (NK) cells are innate immune cells that can remove viral-infected tumour cells without antigen priming. This characteristic offers NK cells an edge over...
Natural killer (NK) cells are innate immune cells that can remove viral-infected tumour cells without antigen priming. This characteristic offers NK cells an edge over other immune cells as a potential therapy for nasopharyngeal carcinoma (NPC). In this study, we report how cytotoxicity was evaluated in target NPC cell lines and patient-derived xenograft (PDX) cells with effector NK-92, a commercially available NK cell line, by using xCELLigence RTCA system (a real-time, label-free impedance-based monitoring platform). Cell viability, proliferation and cytotoxicity were examined by RTCA. Cell morphology, growth and cytotoxicity were also monitored by microscopy. RTCA and microscopy showed that both target and effector cells were able to proliferate normally and to maintain original morphology in co-culture medium as they were in their own respective culture medium. As target and effector (T:E) cell ratios increased, cell viability as measured by arbitrary cell index (CI) values in RTCA decreased in all cell lines and PDX cells. NPC PDX cells were more sensitive to the cytotoxicity effect of NK-92 cells, than the NPC cell lines. These data were substantiated by GFP-based microscopy. We have shown how the RTCA system can be used for a high throughput screening of the effects of NK cells in cancer studies to obtain data such as cell viability, proliferation and cytotoxicity.
PubMed: 37415945
DOI: 10.1016/j.heliyon.2023.e17480 -
Biology of Sport Jul 2023The aims of this scoping review were (i) to characterize the main methodological approaches to assessing individualized running speed thresholds in team sports players;... (Review)
Review
The aims of this scoping review were (i) to characterize the main methodological approaches to assessing individualized running speed thresholds in team sports players; (ii) to assess the use of traditional arbitrary (absolute) thresholds compared to individualized running speed thresholds in team sports players; (iii) to provide an evidence gap map (EGM) about the approaches and study designs employed in investigations in team sports and (iv) to provide directions for future research and practical applications for the strength and conditioning field. Methods studies were searched for in the following databases: (i) PubMed; (ii) Scopus; (iii) SPORTDiscus and (iv) Web of Science. The search was conducted on 15/07/2022. Risk of bias was assessed using the Risk of Bias Assessment Tool for Nonrandomized Studies (RoBANS). From 3,195 potentially relevant articles, 36 were eligible for inclusion in this review. Of the 36 included articles, 27 (75%) focused on the use of arbitrary and individualized running speed thresholds to describe the locomotor demands (e.g., high intensity running) of players. Thirty-four articles used individualized speed running thresholds based on physical fitness assessments (e.g., 40-m linear sprint) or physical performance (e.g., maximal acceleration). This scoping review supported the need for a greater focus to be placed on improving the methodological aspects of using individualized speed running thresholds in team sports. More than just creating alternatives to arbitrary thresholds, it is essential to increase the replicability of methodological conditions whilst ensuring that research comparing the most adequate measures and approaches to individualization takes into consideration the population and context of each study.
PubMed: 37398971
DOI: 10.5114/biolsport.2023.122480 -
Porcine Health Management Jun 2023Across the European Union (EU), efforts are being made to achieve modernisation and harmonisation of meat inspection (MI) code systems. Lung lesions were prioritised as...
BACKGROUND
Across the European Union (EU), efforts are being made to achieve modernisation and harmonisation of meat inspection (MI) code systems. Lung lesions were prioritised as important animal based measures at slaughter, but existing standardized protocols are difficult to implement for routine MI. This study aimed to compare the informative value and feasibility of simplified lung lesion scoring systems to inform future codes for routine post mortem MI.
RESULTS
Data on lung lesions in finisher pigs were collected at slaughter targeting 83 Irish pig farms, with 201 batches assessed, comprising 31,655 pairs of lungs. Lungs were scored for cranioventral pulmonary consolidations (CVPC) and pleurisy lesions using detailed scoring systems, which were considered the gold standard. Using the data collected, scenarios for possible simplified scoring systems to record CVPC (n = 4) and pleurisy (n = 4) lesions were defined. The measurable outcomes were the prevalence and (if possible) severity scoring at batch level for CVPC and pleurisy. An arbitrary threshold was set to the upper quartile (i.e., the top 25% of batches with high prevalence/severity of CVPC or pleurisy, n = 50). Each pair of measurable outcomes was compared by calculating Spearman rank correlations and assessing if batches above the threshold for one measurable outcome were also above it for their pairwise comparison. All scenarios showed perfect agreement (k = 1) when compared among themselves and the gold standard for the prevalence of CVPC. The agreement among severity outcomes and the gold standard showed moderate to perfect agreement (k = [0.66, 1]). The changes in ranking were negligible for all measurable outcomes of pleurisy for scenarios 1, 2 and 3 when compared with the gold standard (rs ≥ 0.98), but these changes amounted to 50% for scenario 4.
CONCLUSIONS
The best simplified CVPC scoring system is to simply count the number of lung lobes affected excluding the intermediate lobe, which provides the best trade-off between value of information and feasibility, by incorporating information on CVPC prevalence and severity. While for pleurisy evaluation, scenario 3 is recommended. This simplified scoring system provides information on the prevalence of cranial and moderate and severe dorsocaudal pleurisy. Further validation of the scoring systems at slaughter and by private veterinarians and farmers is needed.
PubMed: 37391833
DOI: 10.1186/s40813-023-00324-y -
JAMA Network Open Jun 2023In the ongoing COVID-19 pandemic, there remain unanswered questions regarding the nature and importance of the humoral immune response against other coronaviruses....
IMPORTANCE
In the ongoing COVID-19 pandemic, there remain unanswered questions regarding the nature and importance of the humoral immune response against other coronaviruses. Although coinfection of the Middle East respiratory syndrome coronavirus (MERS-CoV) with the SARS-CoV-2 has not been documented yet, several patients previously infected with MERS-CoV received the COVID-19 vaccine; data describing how preexisting MERS-CoV immunity may shape the response to SARS-CoV-2 following infection or vaccination are lacking.
OBJECTIVE
To characterize the cross-reactive and protective humoral responses in patients exposed to both MERS-CoV infection and SARS-CoV-2 vaccination.
DESIGN, SETTING, AND PARTICIPANTS
This cohort study involved a total of 18 sera samples collected from 14 patients with MERS-CoV infection before (n = 12) and after (n = 6) vaccination with 2 doses of COVID-19 mRNA vaccine (BNT162b2 or mRNA-1273). Of those patients, 4 had prevaccination and postvaccination samples. Antibody responses to SARS-CoV-2 and MERS-CoV were assessed as well as cross-reactive responses to other human coronaviruses.
MAIN OUTCOMES AND MEASURES
The main outcomes measured were binding antibody responses, neutralizing antibodies, and antibody-dependent cellular cytotoxicity (ADCC) activity. Binding antibodies targeting SARS-CoV-2 main antigens (spike [S], nucleocapsid, and receptor-binding domain) were detected using automated immunoassays. Cross-reactive antibodies with the S1 protein of SARS-CoV, MERS-CoV, and common human coronaviruses were analyzed using a bead-based assay. Neutralizing antibodies (NAbs) against MERS-CoV and SARS-CoV-2 as well as ADCC activity against SARS-CoV-2 were assessed.
RESULTS
A total of 18 samples were collected from 14 male patients with MERS-CoV infection (mean [SD] age, 43.8 [14.6] years). Median (IQR) duration between primary COVID-19 vaccination and sample collection was 146 (47-189) days. Prevaccination samples had high levels of anti-MERS S1 immunoglobin M (IgM) and IgG (reactivity index ranging from 0.80 to 54.7 for IgM and from 0.85 to 176.3 for IgG). Cross-reactive antibodies with SARS-CoV and SARS-CoV-2 were also detected in these samples. However, cross-reactivity against other coronaviruses was not detected by the microarray assay. Postvaccination samples showed significantly higher levels of total antibodies, IgG, and IgA targeting SARS-CoV-2 S protein compared with prevaccination samples (eg, mean total antibodies: 8955.0 AU/mL; 95% CI, -5025.0 to 22936.0 arbitrary units/mL; P = .002). In addition, significantly higher anti-SARS S1 IgG levels were detected following vaccination (mean reactivity index, 55.4; 95% CI, -9.1 to 120.0; P = .001), suggesting potential cross-reactivity with these coronaviruses. Also, anti-S NAbs were significantly boosted against SARS-CoV-2 (50.5% neutralization; 95% CI, 17.6% to 83.2% neutralization; P < .001) after vaccination. Furthermore, there was no significant increase in antibody-dependent cellular cytotoxicity against SARS-CoV-2 S protein postvaccination.
CONCLUSIONS AND RELEVANCE
This cohort study found a significant boost in cross-reactive NAbs in some patients exposed to MERS-CoV and SARS-CoV-2 antigens. These findings suggest that isolation of broadly reactive antibodies from these patients may help guide the development of a pancoronavirus vaccine by targeting cross-reactive epitopes between distinct strains of human coronaviruses.
Topics: Humans; Male; Adult; Middle East Respiratory Syndrome Coronavirus; COVID-19 Vaccines; SARS-CoV-2; BNT162 Vaccine; Cohort Studies; Pandemics; COVID-19; Severe acute respiratory syndrome-related coronavirus; Vaccination; Antibodies, Neutralizing; Immunoglobulin G; Immunoglobulin M
PubMed: 37389876
DOI: 10.1001/jamanetworkopen.2023.19222 -
Optics Express Jun 2023Atomic layer deposition (ALD), an emerging method of thin film fabrication, has recently witnessed a surge of applications in the optoelectronics field. However,...
Atomic layer deposition (ALD), an emerging method of thin film fabrication, has recently witnessed a surge of applications in the optoelectronics field. However, reliable processes capable of controlling film composition have yet to be developed. In this work, the effect of precursor partial pressure and steric hindrance on the surface activity was presented and analyzed in detail, which led to the development of a component tailoring process for ALD composition control in intralayer for the first time. Further, a homogeneous organic/inorganic hybrid film was successfully grown. The component unit of the hybrid film under the joint action of EG and O plasma could achieve arbitrary ratios by controlling the EG/O plasma surface reaction ratio via varied partial pressures. Film growth parameters (growth rate per cycle and mass gain per cycle) and physical properties (density, refractive index, residual stress, transmission, and surface morphology) could be modulated as desired. Moreover, the hybrid film with low residual stress was effectively used in the encapsulation of flexible organic light-emitting diodes (OLEDs). Such a component tailoring process is an important step forward in ALD technology, and allowing for in-situ control of thin film components at the atomic level in intralayer.
PubMed: 37381259
DOI: 10.1364/OE.488152 -
Materials (Basel, Switzerland) Jun 2023In this work, a dual-band transmissive polarization conversion metasurface (PCM), with omnidirectional polarization and low profile, is proposed. The periodic unit of...
In this work, a dual-band transmissive polarization conversion metasurface (PCM), with omnidirectional polarization and low profile, is proposed. The periodic unit of the PCM is composed of three metal layers separated by two substrates. The upper patch layer of the metasurface is the patch-receiving antenna, while the bottom layer is the patch-transmitting antenna. Both antennas are arranged in an orthogonal way so that the cross-polarization conversion can be realized. The equivalent circuit analysis, structure design, and experimental demonstration are conducted in detail, the polarization conversion rate (PCR) is greater than 90% within two frequency bands of 4.58-4.69 GHz and 5.33-5.41 GHz, and the PCR at two center operating frequencies of 4.64 GHz and 5.37 GHz is as high as 95%, with a thickness of only 0.062λL, where λL is the free space wavelength at the lowest operating frequency. The PCM can realize a cross-polarization conversion, when the incident linearly polarized wave at an arbitrary polarization azimuth, which indicates that it has the characteristics of omnidirectional polarization.
PubMed: 37374531
DOI: 10.3390/ma16124347 -
Clinical Rheumatology Oct 2023The study aims to increase the understanding regarding the role of regulatory T cells (Tregs) in lupus nephritis (LN) and ANCA-associated vasculitis (AAV) by comparing...
The study aims to increase the understanding regarding the role of regulatory T cells (Tregs) in lupus nephritis (LN) and ANCA-associated vasculitis (AAV) by comparing their localization in renal tissue and changes following immunosuppressive therapy. Kidney biopsies from 12 patients with LN and 7 patients with AAV were examined. Kidney biopsies had been performed both at active disease and following immunosuppressive treatment. Clinical data was collected at both biopsy occasions. Expression of Forkhead Box P 3 (Foxp3) in renal tissue was assessed by immunohistochemistry. An arbitrary scale was used to estimate the number of Foxp3+ cells. In LN, 8/12 (67%) had positive tissue staining for Foxp3 at baseline, most pronounced in inflammatory infiltrates, but also interstitially and in a peri-glomerular pattern. At second biopsies, after immunosuppressive treatment, 4/12 (33%) still had detectable Foxp3+ cells, found in persisting inflammatory infiltrates and some in the interstitium. Patients with a good clinical response to treatment had high grade of Foxp3+ cells in first biopsies. In AAV, only 2/7 (29%) had positive staining for Foxp3 at baseline, in inflammatory infiltrates and to a lesser extent in the interstitium, despite large areas of inflammatory infiltrates in all patients. At follow-up, 2/7 (29%) biopsies were positive for Foxp3. Our data show a higher presence of Foxp3+ cells in renal tissue from LN patients compared to AAV, suggesting that Tregs may be differently involved in the control of inflammatory mechanisms in these diseases. These findings could have further implication for therapeutic approaches aiming at restoring the immunological tolerance. Key Points • Foxp3+-cells are present in larger amount in renal tissue in lupus nephritis vs. ANCA-associated vasculitis. • Our data suggest that Foxp3+ regulatory T cells are involved in the control of inflammatory processes in lupus nephritis.
Topics: Humans; Lupus Nephritis; Kidney Glomerulus; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Biopsy; Forkhead Transcription Factors; Kidney
PubMed: 37368057
DOI: 10.1007/s10067-023-06676-8 -
3D Printing and Additive Manufacturing Jun 2023Metal additive manufacturing (AM) is known to produce internal defects that can impact performance. As the technology becomes more mainstream, there is a growing need to...
Metal additive manufacturing (AM) is known to produce internal defects that can impact performance. As the technology becomes more mainstream, there is a growing need to establish nondestructive inspection technologies that can assess and quantify build quality with high confidence. This article presents a complete, three-dimensional (3D) solution for automated defect recognition in AM parts using X-ray computed tomography (CT) scans. The algorithm uses a machine perception framework to automatically separate visually salient regions, that is, anomalous voxels, from the CT background. Compared with supervised approaches, the proposed concept relies solely on visual cues in 3D similar to those used by human operators in two-dimensional (2D) assuming no information about defect appearance, size, and/or shape. To ingest any arbitrary part geometry, a binary mask is generated using statistical measures that separate lighter, material voxels from darker, background voxels. Therefore, no additional part or scan information, such as CAD files, STL models, or laser scan vector data, is needed. Visual saliency is established using multiscale, symmetric, and separable 3D convolution kernels. Separability of the convolution kernels is paramount when processing CT scans with potentially billions of voxels because it allows for parallel processing and thus faster execution of the convolution operation in single dimensions. Based on the CT scan resolution, kernel sizes may be adjusted to identify defects of different sizes. All adjacent anomalous voxels are subsequently merged to form defect clusters, which in turn reveals additional information regarding defect size, morphology, and orientation to the user, information that may be linked to mechanical properties, such as fatigue response. The algorithm was implemented in MATLAB™ using hardware acceleration, that is, graphics processing unit support, and tested on CT scans of AM components available at the Center for Innovative Materials Processing through Direct Digital Deposition (CIMP-3D) at Penn State's Applied Research Laboratory. Initial results show adequate processing times of just a few minutes and very low false-positive rates, especially when addressing highly salient and larger defects. All developed analytic tools can be simplified to accommodate 2D images.
PubMed: 37346187
DOI: 10.1089/3dp.2021.0224