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Abstract Neutralizing antibody titer has been a surrogate endpoint for guiding COVID-19 vaccine approval and use, although the pandemic’s evolution and the introduction of variant-adapted vaccine boosters raise questions as to this surrogate’s contemporary performance. For 985 recipients of an mRNA second bivalent or monovalent booster containing various Spike inserts [Prototype (Ancestral), Beta, Delta, and/or Omicron BA.1 or BA.4/5] in the COVAIL trial (NCT05289037), titers against 5 strains were assessed as correlates of risk of symptomatic COVID-19 (“COVID-19”) and as correlates of relative (Pfizer-BioNTech Omicron vs. Prototype) booster protection against COVID-19 over 6 months of follow-up during the BA.2-BA.5 Omicron-dominant period. Consistently across the Moderna and Pfizer-BioNTech vaccine platforms and across all variant Spike inserts assessed, both peak and exposure-proximal (“predicted-at-exposure”) titers correlated with lower Omicron COVID-19 risk in individuals previously infected with SARS-CoV-2, albeit significantly less so in naïve individuals [e.g., exposure-proximal hazard ratio per 10-fold increase in BA.1 titer 0.74 (95% CI 0.59, 0.94) for naïve vs. 0.41 (95% CI 0.23, 0.64) for non-naïve; interaction p = 0.013]. Neutralizing antibody titer was a strong inverse correlate of Omicron COVID-19 in non-naïve individuals and a weaker correlate in naïve individuals, posing questions about how prior infection alters the neutralization correlate.

Tham T Le,1 Benjamin Emmanuel,1 Rohit Katial,2 Trung N Tran,1 Justin Joseph Kwiatek,1 David S Cohen,1 Shoshana R Daniel,3 Yunhui Cao,1 Vivian H Shih,1 Maria Gil Melcón,4 Gilles Devouassoux,5 Girolamo Pelaia6 On behalf of the RANS Study Investigators1BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 2Center for Clinical Immunology, National Jewish Health & University of Colorado School of Medicine, Denver, CO, USA; 3Market Access Consulting, Fortrea Inc., Durham, NC, USA; 4Otorhinolaryngology and Head and Neck Surgery Department, University Hospital of Salamanca, Salamanca, Spain; 5Department of Pulmonology, Hospices Civils de Lyon (HCL), Hôpital de la Croix-Rousse, Lyon, and F-CRIN INSERM Network CRISALIS, Toulouse, France; 6Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, ItalyCorrespondence: Girolamo Pelaia, University “Magna Graecia” of Catanzaro, Viale Europa, 88100 Catanzaro, Italy, Tel +39 961 3647171, Fax +39 961 3647193, Email pelaia@unicz.itPurpose: Real-world evidence of benralizumab effectiveness on nasal polyps (NP) and asthma outcomes in patients with severe eosinophilic asthma (SEA) and comorbid chronic rhinosinusitis with NP are limited. The objective of this study was to assess NP and asthma outcomes in benralizumab-treated patients with SEA and comorbid NP in a real-world setting.Patients and Methods: RANS was a retrospective, multi-country observational study (ClinicalTrials.gov: NCT05180357) using medical chart reviews of adults with SEA and comorbid NP. Total NP Score (NPS), SinoNasal Outcome Test-22 (SNOT-22) total score, annualized exacerbation rate (AER), and 6-item Asthma Control Questionnaire (ACQ-6) and Asthma Control Test (ACT) scores during the 12 months pre-index (baseline) and post-index (follow-up) were measured. Clinically meaningful improvement from baseline following treatment, in terms of total NPS (≥ 1-point reduction), SNOT-22 total (≥ 8.9-point reduction), ACQ-6 (≥ 0.5-point reduction) or ACT (≥ 3-point increase) scores, were reported.Results: A total of 233 patients were included. Baseline mean (standard deviation [SD]) NPS and SNOT-22 total scores were 3.8 (2.4) and 47.5 (22.6), respectively. The mean change (95% confidence interval [CI]) from baseline was – 1.2 (– 1.7, – 0.6) for NPS, and – 19.8 (– 23.6, – 15.9) for SNOT-22. The AER (95% CI) was 1.2 (0.96, 1.41) at baseline and 0.2 (0.13, 0.28) at follow-up. Mean (SD) ACQ-6 and ACT scores were 1.6 (1.3) and 15.0 (5.2) at baseline and 0.8 (1.0) and 22.0 (3.9) at follow-up, respectively. The proportion of patients who achieved clinically meaningful improvements in NPS, SNOT-22 total, ACQ-6, and ACT scores was 49.1%, 67.6%, 56.6%, and 81.1%, respectively.Conclusion: In this real-world study, improvements in NP and asthma outcomes in patients with SEA and comorbid NP were observed during the 12 months following benralizumab initiation.Keywords: exacerbations, comorbidity, biologics, patient-reported outcomes, SinoNasal Outcome Test-22, Nasal Polyps Score

Abstract Diesel oil contamination is a threat to environment and human health. Many technologies have been developed to address this issue; however, they are costly to be deployed in real-world oil remediation. Adsorption remains to be one of the most economical methods to remove oil from water. Here, we used banana peel biochar (BPBC) immobilized in teabags as an adsorbent for the removal of diesel oil in water. We investigated the adsorption behavior of BPBC under different conditions, examining the influence of adsorbent loading, pH, salinity, and contact time on its efficiency for removing diesel oil in water. Our results show that the sorption capacity of BPBC is significantly affected by the amount of adsorbent used. Lower biochar loadings enhance the sorption capacity due to greater surface area accessibility, while higher loadings lead to decreased efficiency due to pore blockage and reduced surface exposure. Interestingly, the pH of the solution was found to have minimal impact on the sorption process. This is attributed to diesel oil’s hydrophobic and non-polar nature, which leads to its interaction with BPBC being predominantly governed by hydrophobic forces instead of pH-sensitive electrostatic interactions. Salinity emerged as a crucial factor in the adsorption process. An increase in salinity enhances the sorption capacity, likely due to the “salting-out” effect, where higher salt concentrations decrease the solubility of diesel oil, promoting its adsorption onto the biochar surface. Furthermore, the study highlights the importance of contact time, with longer exposure resulting in increased sorption capacity. This trend is explained by the adsorption kinetics, initially characterized by rapid adsorption, followed by a slower, progressive occupation of the biochar’s adsorption sites. The kinetic analysis of the process suggests that the pseudo-second-order model is more suitable, indicating a chemisorption mechanism. The Harkins–Jura isotherm model was identified as the best fit for explaining the isotherm behavior, owing to its capacity to account for the heterogeneous nature of the biochar surface and the formation of multiple adsorbate layers. The optimum conditions for maximum diesel oil removal are as follows: BPBC loading of 0.50 g, a solution pH of 5.00, a salinity concentration of 12,656.57 mg/L, and a contact time of 240 min. Under these conditions, BPBC exhibited an adsorption capacity of 19.04 g/g. In summary, our research establishes BPBC, particularly when contained within teabags, as an efficient and practical adsorbent for diesel oil removal in water. Its effectiveness, superior to other biochar, is mainly due to its porosity and hydrophobic properties. These findings not only enhance our understanding of BPBC’s adsorption capabilities but also underscore its potential for environmental remediation. Graphical Abstract

Andrew N Menzies-Gow,1,2 Trung N Tran,3 Brooklyn Stanley,4 Victoria Ann Carter,4 Josef S Smolen,5 Arnaud Bourdin,6 J Mark Fitzgerald7 ,† Tim Raine,8 Jatin Chapaneri,2 Benjamin Emmanuel,3 David J Jackson,9,10 David B Price4,11 1Royal Brompton and Harefield Hospitals, Guys & St Thomas’ NHS Foundation Trust, London, UK; 2AstraZeneca, Cambridge, UK; 3AstraZeneca, Gaithersburg, MD, USA; 4Observational and Pragmatic Research Institute, Singapore; 5Medical University of Vienna, Vienna, Austria; 6Université de Montpellier, CHU Montpellier, PhyMedExp, INSERM, CNRS, Montpellier, France; 7The University of British Columbia, Vancouver, British Columbia, Canada; 8Cambridge University Hospitals NHS Foundation Trust, Addenbrooke’s Hospital, Cambridge, UK; 9Guy’s Severe Asthma Centre, Guy’s & St Thomas’ NHS Trust, London, UK; 10School of Immunology & Microbial Sciences, King’s College London, London, UK; 11Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK†J. Mark Fitzgerald passed away on January 18, 2022Correspondence: David B Price, Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building-Foresterhill, Aberdeen, AB25 2ZD, UK, Tel +65 3105 1489, Email dprice@opri.sgPurpose: Associations between systemic glucocorticoid (SGC) exposure and risk for adverse outcomes have spurred a move toward steroid-sparing treatment strategies. Real-world changes in SGC exposure over time, after the introduction of steroid-sparing treatment strategies, reveal areas of successful risk mitigation as well as unmet needs.Patients and Methods: A population-based ecological study was performed from the Optimum Patient Care Research Database to describe SGC prescribing trends of steroid-sparing treatment strategies in primary care practices before and after licensure of biologics in the United Kingdom from 1990 to 2019. Each analysis year included patients aged ≥ 5 years who were registered for ≥ 1 year with a participating primary care practice. The primary analysis was SGC exposure, defined as total cumulative SGC dose per patient per year, for asthma, severe asthma, chronic obstructive pulmonary disease (COPD), nasal polyps, Crohn’s disease, rheumatoid arthritis, ulcerative colitis, and systemic lupus erythematosus. Secondary outcomes were percentages of patients prescribed SGCs and number of SGC prescriptions per patient per year.Results: The number of patients who met study inclusion criteria ranged from 219,862 (1990) to 1,261,550 (2019). At the population level, patients with asthma or COPD accounted for 67.7% to 73.2% of patients per year with an SGC prescription. Over three decades, decreases in SGC total yearly dose ≥ 1000 mg have been achieved in multiple conditions. Patients with COPD prescribed SGCs increased from 5.8% (1990) to 34.8% (2017). SGC prescribing trends for severe asthma, Crohn’s disease, and ulcerative colitis show decreased prescribing trends after the introduction of biologics.Conclusion: Decreases in total yearly SGC doses have been shown in multiple conditions; however, for conditions such as severe asthma and COPD, an unmet need remains for increased awareness of SGC burden and the adoption or development of SGC-sparing alternatives to reduce overuse.Keywords: glucocorticoids, practice patterns, drug prescriptions, biological products, drug utilization

This study focused on designing a WASH Index for assessing the status of WASH in Primary Healthcare Facilities (PHCs) especially for low- and middle-income countries. To assess the effectiveness of the WASH Index in evaluating the WASH in PHCs, PHCs were selected from 70 Local Government Areas (LGA) across 3 Southwestern States in Nigeria. The WASH index comprises of the five Joint Monitoring Programme service ladders as outlined in the World Health Organization Global Baseline Report for monitoring basic WASH services in health care facilities: water, sanitation, hygiene, waste management and environmental cleaning. The 5 service elements (termed as components) assessed were based on 10 indicators and 30 sub-indicators. The results of the WASH Index of the PHCs were compared statistically on LGA and State basis with emphasis on the status of WASH facilities. The study concludes that the result would further provide baseline information on the status of WASH in PHCs in the selected States in the quest to achieve the Sustainable Development Goals (SDGs). This study recommends that the WASH Index could be adopted an assessment tool for evaluating WASH in PHCs in other to ensure communication of results to policy makers and other relevant stakeholders, for effective monitoring healthcare facilities.

Summary: Background: The development of a universal influenza virus vaccine, to protect against both seasonal and pandemic influenza A viruses, is a long-standing public health goal. The conserved stalk domain of haemagglutinin (HA) is a promising vaccine target. However, the stalk is immunosubdominant. As such, innovative approaches are required to elicit robust immunity against this domain. In a previously reported observer-blind, randomised placebo-controlled phase I trial (NCT03300050), immunisation regimens using chimeric HA (cHA)-based immunogens formulated as inactivated influenza vaccines (IIV) −/+ AS03 adjuvant, or live attenuated influenza vaccines (LAIV), elicited durable HA stalk-specific antibodies with broad reactivity. In this study, we sought to determine if these vaccines could also boost T cell responses against HA stalk, and nucleoprotein (NP). Methods: We measured interferon-γ (IFN-γ) responses by Enzyme-Linked ImmunoSpot (ELISpot) assay at baseline, seven days post-prime, pre-boost and seven days post-boost following heterologous prime:boost regimens of LAIV and/or adjuvanted/unadjuvanted IIV-cHA vaccines. Findings: Our findings demonstrate that immunisation with adjuvanted cHA-based IIVs boost HA stalk-specific and NP-specific T cell responses in humans. To date, it has been unclear if HA stalk-specific T cells can be boosted in humans by HA-stalk focused universal vaccines. Therefore, our study will provide valuable insights for the design of future studies to determine the precise role of HA stalk-specific T cells in broad protection. Interpretation: Considering that cHA-based vaccines also elicit stalk-specific antibodies, these data support the further clinical advancement of cHA-based universal influenza vaccine candidates. Funding: This study was funded in part by the Bill and Melinda Gates Foundation (BMGF).

Abstract Background Fewer than 1 in 20 people on the African continent in need of palliative care receive it. Malawi is a low-income country in sub-Saharan Africa that has yet to achieve advanced palliative care integration accompanied by unrestricted access to pain and symptom relieving palliative medicines. This paper studied the impact of Malawi’s Waterloo Coalition Initiative (WCI) – a local project promoting palliative care integration through service development, staff training, and increased service access. Methods Interdisciplinary health professionals at 13 hospitals in southern Malawi were provided robust palliative care training over a 10-month period. We used a cross-sectional evaluation to measure palliative care integration based on 11 consensus-based indicators over a one-year period. Results 92% of hospitals made significant progress in all 11 indicators. Specifically, there was a 69% increase in the number of dedicated palliative care rooms/clinics, a total of 253 staff trained across all hospitals (a 220% increase in the region), substantive increases in the number of patients receiving or assessed for palliative care, and the number of hospitals that maintained access to morphine or other opioid analgesics while increasing the proportion of referrals to hospice or other palliative care programs. Conclusion Palliative care is a component of universal health coverage and Sustainable Development Goal 3. The WCI has made tremendous strides in establishing and integrating palliative care services in Malawi with notable progress across 11 project indicators, demonstrating that increased palliative care access is possible in severely resource-constrained settings through sustained models of partnership at the local level.

Background: The study of how people interact with their work environment is known as ergonomics. Medical laboratory practitioners are exposed to work-related musculoskeletal disorders, resulting in a reduction in the quality of health care services rendered. The practicability of ergonomic principles can reduce the risk of these work-related disorders. Despite growing knowledge of ergonomics, its awareness in the health sector in Nigeria is poorly reported. Objectives: This study aimed to assess ergonomic awareness levels and the effects of its lack of implementation among medical laboratory practitioners in tertiary hospitals in Plateau State, Nigeria. Materials and Methods: A total of 154 medical laboratory practitioners, comprising laboratory physicians, scientists, technicians, laboratory assistants, and administrative staff from four hospitals in Jos, Nigeria were recruited into the study via a simple random sampling technique. Data were obtained using a self-constructed questionnaire and analyzed using SPSS version 26.0, with P < 0.05 considered statistically significant. Results: The awareness rate among the participants was 66.9%. Ergonomics awareness was significantly associated with gender (P = 0.006), professional cadre (P = 0.02), and duration of service (P = 0.001). A significant relationship was found between the implementation of good body posture and awareness (P = 0.005). The prevalence of work-related musculoskeletal pain was found to be 83.1%. Conclusion: A positive correlation was found between ergonomic awareness and the implementation of good body posture. The high prevalence of work-related musculoskeletal pain underscores the urgent need for interventions to enhance ergonomic knowledge and practices in the health care sector.

This article deals with the investigation of iron losses in toroidally wound laminated magnetic cores excited with wide-bandgap-device-based power electronic converters. The study aims to analyze the impact of selected pulsewidth modulation voltages on the iron losses, through an extensive experimental measurement campaign. In particular, four toroidal specimens made of different magnetic materials are supplied by pulsewidth-modulated voltage waveforms with switching frequencies ranging from 1 to 350 kHz and different deadtimes. Test campaigns have been conducted with the dual objectives of critically reviewing an engineering method proposed in the prior literature for predicting iron losses under distorted voltage waveforms. Additionally, the aim is to extend this estimation model to accommodate the highest frequencies currently employed in high-speed ac motor drives equipped with wide-bandgap semiconductor power converters.

Public Private Partnership (PPP) initiatives are often promoted as a mechanism for achieving win-win outcomes. However, recent studies highlight the realisation as a hurdle due to gaps in public and private sector competencies. PPP studies have typically focused on specific competency areas and have typically overlooked assessing the interrelationships among various competency dimensions, although these interconnections reflect how competencies function in real-world projects. Therefore, this study sets the pace in the development and modelling of a holistic competency requirement model for the public and private sectors in PPP schemes. A comprehensive literature review coupled with expert validation through piloting identified and categorised the competencies while Structural Equation Modelling (PLS-SEM) was adopted in model development. Findings indicated that public and private sector competencies for win-win optimisation should capture functional requirements, which are PPP scheme and type dependent, organisational requirements which highlight the institutional build of the project parties and relational/behavioural competency requirements that capture the traits and alliancing attributes. The study recommends the strategic alignment of public and private sector roles, skills, and capabilities before initiating infrastructure development to cultivate an environment conducive to achieving win-win outcomes in PPPs. This study challenges the conventional isolated approaches to PPP competencies with an integrated approach that deepens the understanding of successful infrastructure development in PPP.

Gary Tse,1,2 Benjamin Emmanuel,3 Cono Ariti,1 Mona Bafadhel,4 Alberto Papi,5 Victoria Carter,1 Jiandong Zhou,1 Derek Skinner,1 Xiao Xu,3 Hana Müllerová,6 David Price1,7 1Observational and Pragmatic Research Institute, Singapore, Singapore; 2School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, People’s Republic of China; 3AstraZeneca, Gaithersburg, MD, USA; 4Department of Immunobiology, School of Immunology and Microbial Sciences, Faculty of Life Sciences and Medicine, King’s College London, London, UK; 5Respiratory Medicine, Department of Translational Medicine, University of Ferrara, Ferrara, Italy; 6AstraZeneca, Cambridge, UK; 7Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, &num;06-76, Midview City, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgBackground: Oral corticosteroids (OCS) are often prescribed for chronic obstructive pulmonary disease (COPD) exacerbations.Methods: This observational, individually matched historical cohort study used electronic medical records (1987– 2019) from the UK Clinical Practice Research Datalink linked to English Hospital Episode Statistics (HES) to evaluate adverse outcomes in patients with COPD who used OCS (OCS cohort) and those not exposed to OCS (non-OCS cohort). Risk of 17 adverse outcomes was estimated using proportional hazard regression.Results: Of 323,722 patients, 106,775 (33.0%) had COPD-related OCS prescriptions. Of the 106,775 patients in the overall cohort, 58,955 had HES linkage and were eligible for inclusion in the OCS cohort. The individual matching process identified 53,299 pairs of patients to form the OCS and non-OCS cohorts. Median follow-up post-index was 6.9 years (OCS cohort) and 5.4 years (non-OCS cohort). Adjusted risk of multiple adverse outcomes was higher for the OCS cohort versus the non-OCS cohort, including osteoporosis with/without fractures (adjusted hazard ratio [aHR] 1.80; 95% confidence interval [CI] 1.70– 1.92), type 2 diabetes mellitus (aHR 1.44; 95% CI 1.37– 1.51), cardiovascular/cerebrovascular disease (aHR 1.26; 95% CI 1.21– 1.30), and all-cause mortality (aHR 1.04; 95% CI 1.02– 1.07). In the OCS cohort, risk of most adverse outcomes increased with increasing categorized cumulative OCS dose. For example, risk of cardiovascular/cerebrovascular disease was 34% higher in the 1.0–< 2.5 g group versus the < 0.5 g group (HR 1.34; 95% CI 1.26– 1.42).Conclusion: Any OCS use was associated with higher risk of adverse outcomes in patients with COPD, with risk generally increasing with greater cumulative OCS dose.Plain Language Summary: Many patients with chronic obstructive pulmonary disease (COPD) have occasions when their symptoms suddenly worsen, called flare-ups or exacerbations. To treat flare-ups, doctors might prescribe a course of steroid tablets (oral corticosteroids or OCS for short). Doctors might also prescribe “rescue packs” containing OCS and antibiotics, to keep at home and start taking when needed.While OCS may speed up recovery from flare-ups, repeated use may have negative health effects. We studied effects of OCS use in patients with COPD, using anonymized electronic patient medical records in England. These databases are made available following a high-quality research proposal to research and ethics committees.Of 323,722 patients with COPD, around one-third received OCS for flare-ups. We studied 17 outcomes including important medical diagnoses and death. We grouped patients into 53,299 pairs so that every patient who used OCS matched a similar patient (eg, the same age and sex) who never used OCS. The patients were followed for an average of 6.9 years (used OCS) and 5.4 years (never used OCS).Most diagnoses, including diabetes, osteoporosis, cardiovascular/cerebrovascular disease, and death, were more likely in patients who used OCS than those who never used OCS. Patients using larger amounts of OCS over time were generally more likely to experience diagnoses or die.These results show risks of using OCS, even occasionally, in patients with COPD. Flare-up prevention is important, for example with appropriate daily “maintenance” medication, vaccinations for infections, and quitting smoking, thereby reducing health effects from OCS use for flare-ups. Keywords: chronic obstructive pulmonary disease, cohort study, COPD, corticosteroids, observational, primary care

Abstract Immune responses to SARS-CoV-2 primarily target the receptor binding domain of the spike protein, which continually mutates to escape acquired immunity. Other regions in the spike S2 subunit, such as the stem helix and the segment encompassing residues 815-823 adjacent to the fusion peptide, are highly conserved across sarbecoviruses and are recognized by broadly reactive antibodies, providing hope that vaccines targeting these epitopes could offer protection against both current and emergent viruses. Here we employ computational modeling to design scaffolded immunogens that display the spike 815-823 peptide and the stem helix epitopes without the distracting and immunodominant receptor binding domain. These engineered proteins bind with high affinity and specificity to the mature and germline versions of previously identified broadly protective human antibodies. Epitope scaffolds interact with both sera and isolated monoclonal antibodies with broadly reactivity from individuals with pre-existing SARS-CoV-2 immunity. When used as immunogens, epitope scaffolds elicit sera with broad betacoronavirus reactivity and protect as “boosts” against live virus challenge in mice, illustrating their potential as components of a future pancoronavirus vaccine.

Abstract Background Hypertension is a major risk factor for cardiovascular diseases. Insights and foresights on trends of hypertension prevalence are crucial to informing health policymaking. We examined and projected the patterns of hypertension prevalence among sexes. Methods Using annual hypertension prevalence (18 + years) data sourced from WHO Global Health Observatory data repository from 1975 to 2015, Prophet models were developed to forecast the 2040 prevalence of hypertension in males, females, and both sexes. We used k-means clustering and self-organising maps to determine the clusters of hypertension prevalence concerning both sexes among 176 countries. Results Worldwide, Croatia is estimated to have the highest prevalence of hypertension in males by 2040, while that of females is in Niger. Among the world’s most populated countries, Pakistan and India are likely to increase by 7.7% and 4.0% respectively in both sexes. South-East Asia is projected to experience the largest hypertension prevalence in males, whereas Africa is estimated to have the highest prevalence of hypertension in females. Low-income countries are projected to have the highest prevalence of hypertension in both sexes. By 2040, the prevalence of hypertension worldwide is expected to be higher in the male population than in female. Globally, the prevalence of hypertension is projected to decrease from 22.1% in 2015 to 20.3% (20.2 – 20.4%) in 2040. We also identified three patterns of hypertension prevalence in 2040, cluster one countries are estimated to have the highest prevalence of hypertension in males (29.6%, 22.2 – 41.1%) and females (29.6%, 19.4 – 38.7%). Conclusion These findings emphasise the need for new and effective approaches toward the prevention and control of hypertension in Africa, South-East Asia, and Low-income countries.

Summary: Background: Although immunomodulators have established benefit against the new coronavirus disease (COVID-19) in general, it is uncertain whether such agents improve outcomes without increasing the risk of secondary infections in the specific subgroup of previously immunocompromised patients. We assessed the effect of immunomodulators on outcomes of immunocompromised patients hospitalized for COVID-19. Methods: The protocol was prospectively registered with PROSPERO (CRD42022335397). MEDLINE, Cochrane Central Register of Controlled Trials and references of relevant articles were searched up to 01-06-2022. Authors of potentially eligible randomized controlled trials were contacted to provide data on immunocompromised patients randomized to immunomodulators vs control (i.e., placebo or standard-of-care). Findings: Eleven randomized controlled trials involving 397 immunocompromised patients hospitalized for COVID-19 were included. Ten trials had low risk of bias. There was no difference between immunocompromised patients randomized to immunomodulators vs control regarding mortality [30/182 (16.5%) vs 41/215 (19.1%); RR 0.93, 95% CI 0.61–1.41; p = 0.74], secondary infections (RR 1.00, 95% CI 0.64–1.58; p = 0.99) and change in World Health Organization ordinal scale from baseline to day 15 (weighed mean difference 0.27, 95% CI -0.09–0.63; p = 0.15). In subgroup analyses including only patients with hematologic malignancy, only trials with low risk of bias, only trials administering IL-6 inhibitors, or only trials administering immunosuppressants, there was no difference between comparators regarding mortality. Interpretation: Immunomodulators, compared to control, were not associated with harmful or beneficial outcomes, including mortality, secondary infections, and change in ordinal scale, when administered to immunocompromised patients hospitalized for COVID-19. Funding: Hellenic Foundation for Research and Innovation.

Abstract Background Adjuvanted inactivated influenza vaccine (aIIV) and high-dose inactivated influenza vaccine (HD-IIV) are U.S.-licensed for adults aged ≥ 65 years. This study compared serum hemagglutination inhibition (HAI) antibody titers for the A(H3N2) and A(H1N1)pdm09 and B strains after trivalent aIIV3 and trivalent HD-IIV3 in an older adult population. Results The immunogenicity population included 342 participants who received aIIV3 and 338 participants who received HD-IIV3. The proportion of participants that seroconverted to A(H3N2) vaccine strains after allV3 (112 participants [32.8%]) was inferior to the proportion of participants that seroconverted after HD-IIV3 (130 participants [38.5%]) at day 29 after vaccination (difference, − 5.8%; 95%CI, − 12.9% to 1.4%). There were no significant differences between the vaccine groups in percent seroconversion to A(H1N1)pdm09 or B vaccine strains, in percent seropositivity for any of the strains, or in post-vaccination GMT for the A(H1N1)pdm09 strain. The GMTs for the post-vaccination A(H3N2) and B strains were higher after HD-IIV than after aIIV3. Conclusions Overall immune responses were similar after aIIV3 and HD-IIV3. For the primary outcome, the aIIV3 seroconversion rate for H3N2 did not meet noninferiority criteria compared with HD-IIV3, but the HD-IIV3 seroconversion rate was not statistically superior to the aIIV3 seroconversion rate. Trial registration ClinicalTrials.gov Identifier: NCT03183908.

BackgroundThere is limited evidence to assess if interventions implemented during pregnancy proactively mitigate parental vaccine hesitancy and promote timely vaccination among children after birth. This study protocol describes the evaluation of an ADaptivE PrenaTal (ADEPT) intervention to increase childhood vaccinations that is implemented with first-time pregnant individuals (PIs).MethodsWithin the framework of a type 1 effectiveness-implementation hybrid study design, a cluster-randomized trial (CRT) will determine the effectiveness of ADEPT at increasing childhood vaccinations, and a nested explanatory mixed methods (NMM) study will assess changes in parental vaccine hesitancy. Study practices will be randomized to deliver ADEPT in addition to standard of care or standard of care alone. Providers at intervention sites will participate in a 4-part training program on childhood vaccines and effective communication. During a routine prenatal visit, providers will discuss vaccines recommended for the PI during pregnancy and for the child after birth, following which PIs will be screened for vaccination intention. Vaccine-hesitant PIs will be offered adaptive components of the intervention, which include an educational website and phone call with a vaccine navigator to discuss concerns. They will also be offered enrollment into the NMM study, where their vaccination intention will be assessed post-intervention. After PIs give birth, their child's vaccination outcomes at 2 months will be extracted from the state immunization registry. The primary study outcome is the difference in timely childhood vaccination at 2 months between the intervention and control arms. The secondary outcome is reduction in vaccine hesitancy assessed among PIs in the NMM study as the pre-post intervention change in vaccination intention.DiscussionThe study findings are expected to contribute evidence on the effectiveness of prenatal interventions to proactively mitigate parental vaccine hesitancy and promote timely vaccinations after the child's birth.Trial registrationThe study protocol is registered in ClinicalTrials.gov (NCT05795855).

Senna alata, a flowering shrub, is widely cultivated in the Philippines for its anti-fungal properties. Despite this, its chloroplast genome is not yet established. We assembled and annotated the complete chloroplast genome of accession from the germplasm collection of the Institute of Crop Science, University of the Philippines, Los Baños, using Illumina sequencing data. The complete cp genome was 159,176-bp long characterized by a large single copy of 88,769 bp, short single-copy of 18,301 bp and a pair of inverted repeat regions of 26,053 bp each. The overall GC content of the chloroplast genome was 36.4%. The plastome comprised 37 tRNA genes, 8 rRNA genes and 78 mRNA genes. Phylogenetic analysis showed that S. alata is closely related to S. siamea.

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

Stephanie Chen,1 Marc Miravitlles,2 Chin Kook Rhee,3 Ian D Pavord,4 Rupert Jones,5 Victoria Carter,6 Benjamin Emmanuel,1 Marianna Alacqua,7 David B Price6,8 1BioPharmaceuticals Medical, Respiratory & Immunology, AstraZeneca, Gaithersburg, MD, USA; 2Pneumology Department, Hospital Universitari Vall d’Hebron, Vall d’Hebron Institut de Recerca (VHIR), Vall d’Hebron Barcelona Hospital Campus, CIBER de Enfermedades Respiratorias (CIBERES), Barcelona, Spain; 3College of Medicine, Seoul St Mary’s Hospital, the Catholic University of Korea, Seoul, South Korea; 4Oxford Respiratory NIHR BRC, Nuffield Department of Medicine, University of Oxford, Oxford, UK; 5Faculty of Health, University of Plymouth, Plymouth, UK; 6Observational and Pragmatic Research Institute, Singapore, Singapore; 7BioPharmaceuticals Medical, Respiratory & Immunology, AstraZeneca, Cambridge, UK; 8Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UKCorrespondence: David B Price, Observational and Pragmatic Research Institute, 22 Sin Ming Lane, #06-76, Midview City, Singapore, 573969, Singapore, Tel +65 3105 1489, Email dprice@opri.sgBackground: Some patients with chronic obstructive pulmonary disease (COPD) experience frequent exacerbations despite maximal inhaled therapy (“triple therapy”), possibly leading to high health care resource utilization (HCRU).Aim: Describe characteristics, future HCRU, and mortality of patients with COPD who experience frequent exacerbations despite triple therapy; characterize individuals who may be candidates for biologic therapies.Methods: This descriptive observational study used primary care data of patients aged ≥ 40 years in the United Kingdom receiving maintenance therapy for COPD who had ≥ 1 year of data prior to index date and ≥ 1 year of follow-up data. We described these patients’ clinical and demographic characteristics, including blood eosinophil counts (BEC), pattern of exacerbations, hospitalizations, and corticosteroid exposure, as well as future exacerbations, hospitalizations, and death.Results: Of 43,753 patients with maintenance-treated COPD, 6480 experienced exacerbations despite ≥ 3 months of triple therapy. Of these, 5669 had available BEC: 1287 (22.7%) had BEC ≥ 250 cells/μL and ≥ 3 exacerbations in the year prior to the index date; 471 (36.6%) received ≥ 4 acute courses of oral corticosteroids. Patients with a pattern of high disease burden continued to have high disease burden: 51.1% experienced ≥ 3 exacerbations and 2.6% experienced ≥ 3 hospitalizations. Patients who experienced exacerbations despite triple therapy had a significantly higher risk of COPD-related death than other maintenance-treated patients (5.8% vs 2.1%).Conclusion: Nearly one-quarter of patients receiving triple therapy for COPD who experienced frequent exacerbations had elevated BEC and ≥ 3 exacerbations, suggesting a potential mechanism of persistent eosinophilic inflammation that could be a target for eosinophil-depleting biologic therapy.Keywords: chronic obstructive pulmonary disease, disease burden, eosinophils, exacerbations, health care resource utilization

In this study, the solutions of the Schrodinger equation (SE) with modified Hylleraas potential in arbitrary dimensions was obtained using the asymptotic iteration method (AIM) to obtain the energy and wave functions, respectively. The energy equation was used to obtain the thermal properties of this system. The effect of the potential parameters and dimensions on the energy spectra and thermal properties was scrutinized thoroughly. It was found that the aforementioned affects the thermal properties and energy spectra, respectively. In addition, we also computed the numerical energy spectra of the MHP for the first time and discussed it in detail. The results of our study can be applied to molecular physics, chemical physics, etc.

IntroductionHemagglutination inhibition (HAI) antibody titers to seasonal influenza strains are important surrogates for vaccine-elicited protection. However, HAI assays can be variable across labs, with low sensitivity across diverse viruses due to lack of standardization. Performing qualification of these assays on a strain specific level enables the precise and accurate quantification of HAI titers. Influenza A (H3N2) continues to be a predominant circulating subtype in most countries in Europe and North America since 1968 and is thus a focus of influenza vaccine research.MethodsAs a part of the National Institutes of Health (NIH)-funded Collaborative Influenza Vaccine Innovation Centers (CIVICs) program, we report on the identification of a robust assay design, rigorous statistical analysis, and complete qualification of an HAI assay using A/Texas/71/2017 as a representative H3N2 strain and guinea pig red blood cells and neuraminidase (NA) inhibitor oseltamivir to prevent NA-mediated agglutination.ResultsThis qualified HAI assay is precise (calculated by the geometric coefficient of variation (GCV)) for intermediate precision and intra-operator variability, accurate calculated by relative error, perfectly linear (slope of -1, R-Square 1), robust (

An innovative remote sensing device for the detection and monitoring of sewage levels in underground onsite septic tank is developed. The overflow of underground onsite sewage septic tanks located around buildings for the collection and disposal of wastewater is hazardous to the environment releasing infectious pollutants and obnoxious contaminants. The inability to accurately determine the level of the sewage in the underground septic tank most times causes overflow of sewage into the environment without the knowledge of the users of the facility. A smart onsite sewage septic tank level monitoring device is developed enabling the users of the facility to promptly detect when it malfunctions to plan ahead for the evacuation in order to prevent the overflow. The device implements ultrasonic sensor to detect and monitor level of the wastewater in the septic tank and a Global System for Mobile Communications (GSM) module to send short message service (SMS) to the enrolled users’ mobile phone numbers and the sewage evacuation agents. A test run conducted showed response time within 30 s. The developed device is suitable for low income countries of Africa.

PURPOSEThe burden of cancer disproportionately affects low- and middle-income countries. Low 5-year survival figures for children with cancer in low-income countries are due to late presentation at diagnosis, treatment abandonment, absence of sophisticated multidisciplinary care, and lack of adequate resources. The reasons for late presentation are partly due to limited awareness of cancer symptoms, high treatment costs, and facility-level barriers to timely access to treatment. Given the systemic challenges, the regional need for palliative oncology care for children care is high. Despite the enormity of the need for palliative oncology for children with cancer in Africa, its level of development remains poor. This paper presents the evidence on the status of palliative oncology care for children in sub-Saharan Africa.METHODSThis review provides an overview of the current status of palliative oncology care for children in sub-Saharan Africa, using the WHO building blocks for health systems strengthening as reference points, before proposing a forward-looking prioritized agenda for its development.RESULTSWe noted that survival rates for children with cancer remain much poorer in Africa compared with developed countries and palliative oncology care resources are scant. Our results also show low coverage for palliative oncology care services for children, lack of a critical mass of health workers with the skills to deliver the care, a lack of robust documentation of the burden of cancer, widespread lack of access to essential controlled medicines, limited funding from government and limited coverage for palliative oncology care in most cancer control plans.CONCLUSIONThis review highlights priority areas for action that align to the WHO health system building blocks for strengthening health systems.

ABSTRACT The first encounter with influenza virus biases later immune responses. This “immune imprinting,” formerly from infection within a few years of birth, is in the United States now largely from immunization with a quadrivalent, split vaccine (IIV4 [quadrivalent inactivated influenza vaccine]). In a pilot study of IIV4 imprinting, we used single-cell cultures, next-generation sequencing, and plasma antibody proteomics to characterize the primary antibody responses to influenza in two infants during their first 2 years of seasonal influenza vaccination. One infant, who received only a single vaccination in year 1, contracted an influenza B virus (IBV) infection between the 2 years, allowing us to compare imprinting by infection and vaccination. That infant had a shift in hemagglutinin (HA)-reactive B cell specificity from largely influenza A virus (IAV) specific in year 1 to IBV specific in year 2, both before and after the year 2 vaccination. HA-reactive B cells from the other infant maintained a more evenly distributed specificity. In year 2, class-switched HA-specific B cell IGHV somatic hypermutation (SHM) levels reached the average levels seen in adults. The HA-reactive plasma antibody repertoires of both infants comprised a relatively small number of antibody clonotypes, with one or two very abundant clonotypes. Thus, after the year 2 boost, both infants had overall B cell profiles that resembled those of adult controls. IMPORTANCE Influenza virus is a moving target for the immune system. Variants emerge that escape protection from antibodies elicited by a previously circulating variant (“antigenic drift”). The immune system usually responds to a drifted influenza virus by mutating existing antibodies rather than by producing entirely new ones. Thus, immune memory of the earliest influenza virus exposure has a major influence on later responses to infection or vaccination (“immune imprinting”). In the many studies of influenza immunity in adult subjects, imprinting has been from an early infection, since only in the past 2 decades have infants received influenza immunizations. The work reported in this paper is a pilot study of imprinting by the flu vaccine in two infants, who received the vaccine before experiencing an influenza virus infection. The results suggest that a quadrivalent (four-subtype) vaccine may provide an immune imprint less dominated by one subtype than does a monovalent infection.

John Busby,1 David Price,2– 4 Riyad Al-Lehebi,5 Sinthia Bosnic-Anticevich,6– 8 Job FM van Boven,9 Benjamin Emmanuel,10 J Mark FitzGerald,11 Mina Gaga,12 Susanne Hansen,13,14 Mark Hew,15,16 Takashi Iwanaga,17 Désirée Larenas Linnemann,18 Bassam Mahboub,19,20 Patrick Mitchell,21 Daniela Morrone,22 Jonathan Pham,15,23 Celeste Porsbjerg,14 Nicolas Roche,24,25 Eileen Wang,26,27 Neva Eleangovan,2,3 Liam G Heaney28 1Centre for Public Health, Queen’s University Belfast, Belfast, Northern Ireland; 2Optimum Patient Care, Cambridge, UK; 3Observational and Pragmatic Research Institute, Singapore, Singapore; 4Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK; 5Department of Pulmonology, King Fahad Medical City, Riyadh, Saudi Arabia; 6Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia; 7Woolcock Institute of Medical Research, The University of Sydney, Sydney, Australia; 8Central Sydney Local Area Health District, Sydney, Australia; 9Department of Clinical Pharmacy & Pharmacology, Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, Groningen, the Netherlands; 10BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA; 11Department of Medicine, The University of British Columbia, Vancouver, Canada; 12 7th Respiratory Medicine Department and Asthma Centre, Athens Chest Hospital, Athens, Greece; 13Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark; 14Respiratory Research Unit, Bispebjerg University Hospital, Copenhagen, Denmark; 15Allergy, Asthma & Clinical Immunology Service, Alfred Health, Melbourne, Australia; 16Public Health and Preventive Medicine, Monash University, Melbourne, Australia; 17Center for General Medical Education and Clinical Training, Kindai University Hospital, Osakasayama, Japan; 18Directora Centro de Excelencia en Asma y Alergia, Hospital Médica Sur, Ciudad de México, Mexico; 19College of Medicine, University of Sharjah, Sharjah, United Arab Emirates; 20Rashid Hospital, Dubai Health Authority, Dubai, United Arab Emirates; 21Cumming School of Medicine, University of Calgary, Calgary, Alberta, Canada; 22Personalized Medicine, Asthma and Allergy, Humanitas Clinical and Research Center, IRCCS, Rozzano, Italy; 23Allergy and Lung Health Unit, Centre for Epidemiology and Biostatistics, Melbourne School of Population & Global Health, The University of Melbourne, Melbourne, Australia; 24Respiratory Medicine, Cochin Hospital, APHP.Centre, Paris, France; 25University of Paris, Cochin Institute (UMR1016), Paris, France; 26Division of Allergy & Clinical Immunology, Department of Medicine, National Jewish Health, Denver, CO, USA; 27Division of Allergy & Clinical Immunology, Department of Internal Medicine, University of Colorado School of Medicine, Aurora, CO, USA; 28Wellcome-Wolfson Centre for Experimental Medicine, Queen’s University Belfast, Belfast, Northern IrelandCorrespondence: David PriceCentre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Polwarth Building, Foresterhill, Aberdeen, AB25 2ZD, UKTel +65 6962 3627Email dprice@opri.sgIntroduction: Asthma morbidity and health-care utilization are known to exhibit a steep socioeconomic gradient. Further investigation into the modulators of this effect is required to identify potentially modifiable factors.Methods: We identified a cohort of patients with asthma from the Optimum Patient Care Research Database (OPCRD). We compared demographics, clinical variables, and health-care utilization by quintile of the UK 2011 Indices of Multiple Deprivation based on the location of the patients’ general practice. Multivariable analyses were conducted using generalized linear models adjusting for year, age, and sex. We conducted subgroup analyses and interaction tests to investigate the impact of deprivation by age, sex, ethnicity, and treatment step.Results: Our analysis included 127,040 patients with asthma. Patients from the most deprived socio-economic status (SES) quintile were more likely to report uncontrolled disease (OR: 1.54, 95% CI: 1.16, 2.05) and to have an exacerbation during follow-up (OR: 1.27, 95% CI: 1.13, 1.42) than the least deprived quintile. They had higher blood eosinophils (ratio: 1.03; 95% CI: 1.00, 1.06) and decreased peak flow (ratio: 0.95, 95% CI: 0.94, 0.97) when compared to those in the least deprived quintile. The effect of deprivation on asthma control was greater among those aged over 75 years (OR = 1.81, 95% CI: 1.20, 2.73) compared to those aged less than 35 years (OR: 1.22, 95% CI: 0.85, 1.74; pinteraction=0.019). Similarly, socioeconomic disparities in exacerbations were larger among those from ethnic minority groups (OR: 1.94, 95% CI: 1.40, 2.68) than white patients (OR: 1.24, 95% CI: 1.10, 1.39; pinteraction=0.012).Conclusion: We found worse disease control and increased exacerbation rates among patients with asthma from more deprived areas. There was evidence that the magnitude of socioeconomic disparities was elevated among older patients and those from ethnic minority groups. The drivers of these differences require further exploration.Keywords: asthma, socioeconomic status, disparities

Abstract Background E-Learning solutions are increasingly being advocated to augment existing traditional teaching and learning efforts in health training institutions. Unfortunately, these emerging technologies rarely focus on health sciences education within the context of public universities, hence the need for this study. This project evaluated experiences of healthcare trainees with a pilot e-Learning project (SMART e-Learning project) initiated in one of Ghana’s public universities in 2017. The study used a mixed methods cross-sectional approach among 363 healthcare trainees. Data collection was between 17th October, 2019 to 3rd December, 2019. Data was analysed descriptively and test for variable differences done using Pearson Chi-square and Fisher’s Exact for categorical variables. Wilcoxon Mann-Whitney test was used to test for differences in the Likert scale items. Additionally, rotated varimax factor analysis was performed for the health trainees’ rated satisfaction factors. Results Out of 446 respondents who consented to participate in the study, 363 responses were complete and valid, representing a response rate of 81 %. Most frequently used e-learning facilities by healthcare trainees were: writing interim assessments (IAs) (82 %) while the least used function was live chating with faculty (5 %). Challenges associated with the e-learning pilot project were: limited workspace in the pilot computer laboratory (33 %), slow internet/intranet speed (29 %) and limited capacity of teaching and ICT staff to support users (28 %). Conclusions There is the need to engage relevant stakeholders at the University, ministries of health and education through policy dialogues to develop statutory e-Learning guidelines for health educational institutions of higher learning to complement existing traditional teaching and learning approaches.

Green fuel represents one of the most promising means of sustainably replacing liquid fuels, and freshwater macrophytes has become one of the auspicious substrates for biofuel production due to high cellulose and hemicellulose contents. In this study, the use of Spirogyra porticalis and Nymphaea alba Linn for biodiesel, bioethanol and biogas production was investigated with other feedstocks (rice husk and biochar) using dry and wet extraction methods. Spirogyra porticalis and Nymphaea alba Linn were harvested from a freshwater lake in Ndufu Echara in Ikwo Local Government, Ebonyi State, Nigeria and thoroughly washed. Biodiesel, bioethanol and biogas production by an alkali-catalysed transesterification using mechanical and chemical methods, acid and base simultaneous saccharification and fermentation, and anaerobic digestion was carried out, respectively. Results showed that freshwater macrophytes produced more biodiesel compared to rice husk and biochar. S. porticalis and Nymphaea L. yielded higher biodiesel using chemical and mechanical methods, respectively. Quality evaluation of the diesel oil according to ASTM standard revealed that chemical method was the most proficient for biodiesel production because of its proximity to ASTM D6751 standard. For bioethanol, acid hydrolysis (1M HCl) produced more bioethanol than the base (1M NaOH) with Nymphaea L. yielding 60% ethanol. However, the macrophytes did not generate biogas after 30-d of anaerobic digestion compared to other feedstocks. Further analysis revealed sample acidification and inhibitions on the anaerobes responsible for anaerobic digestion (p

The objective of this study was to identify factors at the individual, provider, and systems levels that serve as challenges or opportunities for increasing adolescent vaccination—including Human Papillomavirus (HPV) vaccination—in rural communities in the southern United States (US). As part of a broader study to increase HPV vaccine uptake in the southern US, we conducted in-depth interviews with vaccination stakeholders representing public health and education agencies in North Carolina (NC) and South Carolina (SC). Fourteen key stakeholders were recruited using purposive sampling to obtain insights into challenges and solutions to rural-urban disparities in HPV vaccination coverage. Stakeholders were also queried about their experiences and attitudes toward school-based vaccination promotion programs and campaigns. We used a rapid qualitative approach to analyze the data. Stakeholders identified factors at the individual, provider, and systems levels that serve as challenges to vaccination in rural communities. Similar to previous studies, stakeholders mentioned challenges with healthcare access and vaccine-related misconceptions that pose barriers to HPV vaccination for rural residents. Systems-level challenges identified included limited access to high-speed internet in rural areas that may impact providers’ ability to interface with state-level digital systems such as the vaccination registry. Stakeholders identified a number of opportunities to increase HPV vaccination coverage, including through school-based health promotion programs. Stakeholders strongly supported school-based programs and approaches to strengthen confidence and demand for HPV vaccination and to help address persistent social determinants and system level factors that pose challenges to HPV vaccination coverage in many rural areas.

Abstract Background Increasing arbovirus infections have been a global burden in recent decades. Many countries have experienced the periodic emergence of arbovirus diseases. However, information on the prevalence of arboviruses is largely unknown or infrequently updated because of the lack of surveillance studies, especially in Africa. Methods A surveillance study was conducted in Gabon, Central Africa, on arboviruses, which are a major public health concern in Africa, including: West Nile virus (WNV), dengue virus (DENV), Zika virus (ZIKV), yellow fever virus (YFV), chikungunya virus (CHIKV), and Rift Valley fever virus (RVFV). Serological and molecular assays were performed to investigate past infection history and the current status of infection, using serum samples collected from healthy individuals and febrile patients, respectively. Results The overall seroprevalence during 2014˗2017 was estimated to be 25.3% for WNV, 20.4% for DENV, 40.3% for ZIKV, 60.7% for YFV, 61.2% for CHIKV, and 14.3% for RVFV. No significant differences were found in the seroprevalence of any of the viruses between the male and female populations. However, a focus on the mean age in each arbovirus-seropositive individual showed a significantly younger age in WNV- and DENV-seropositive individuals than in CHIKV-seropositive individuals, indicating that WNV and DENV caused a relatively recent epidemic in the region, whereas CHIKV had actively circulated before. Of note, this indication was supported by the detection of both WNV and DENV genomes in serum samples collected from febrile patients after 2016. Conclusions This study revealed the recent re-emergence of WNV and DENV in Gabon as well as the latest seroprevalence state of the major arboviruses, which indicated the different potential risks of virus infections and virus-specific circulation patterns. This information will be helpful for public health organizations and will enable a rapid response towards these arbovirus infections, thereby preventing future spread in the country.

Background and objectives: HPV vaccination coverage is lower than that of other adolescent vaccines in the southern US. This study sought to characterize caregiver attitudes associated with adolescent HPV vaccination in the southern US and to inform interventions to promote HPV vaccination. Methods: From December 2019 – January 2020, caregivers of adolescents (ages 9–17 years) living in thirteen southern US states were recruited from a nationally-representative online survey panel. Caregivers (N = 1,105) completed a cross-sectional survey that assessed general adolescent vaccine attitudes as well as those associated with the HPV vaccine and HPV vaccination decision-making. The primary study outcome was adolescents’ receipt of at least one dose of the HPV vaccine. Results: Caregivers with vaccinated adolescents had greater positive attitudes towards adolescent vaccines compared to caregivers of unvaccinated adolescents. Top three areas of concern among caregivers were related to vaccine ingredients, perceptions that adolescents receive too many vaccines, and worry about vaccine side effects. In multivariable regression models, positive attitudes towards the HPV vaccine and HPV vaccination decision-making strongly associated with HPV vaccination in addition to general adolescent vaccination attitudes. Caregivers’ reported discomfort with discussing the topic of sex was predictive of lower vaccination uptake for older adolescents. Conclusions: Public health messaging in the southern US should be tailored to reduce concerns about vaccine safety and to communicate the importance of timely HPV vaccination. Campaigns that deliver information specific to the HPV vaccine and to support vaccination decision-making may be more effective than those delivering only general adolescent vaccination information at promoting on-time HPV vaccination.

Abstract Background High consumption of red and processed meat is commonly associated with increased cancer risk, particularly colorectal cancer. Antibodies against the red meat-derived carbohydrate N-glycolylneuraminic acid (Neu5Gc) exacerbate cancer in “human-like” mice. Human anti-Neu5Gc IgG and red meat are both independently proposed to increase cancer risk, yet how diet affects these antibodies is largely unknown. Methods We used world global data to demonstrate that colorectal cancer incidence and mortality are associated with increased national meat consumption. In a well-defined large cohort, we used glycomics to measure daily Neu5Gc intake from red meat and dairy, and investigated serum as well as affinity-purified anti-Neu5Gc antibodies. Based on 24-h dietary records, daily Neu5Gc intake was calculated for 19,621 subjects aged ≥ 18 years of the NutriNet-Santé study. Serum and affinity-purified anti-Neu5Gc antibodies were evaluated by ELISA and glycan microarrays in representative 120 individuals, each with at least eighteen 24-h dietary records (aged 45–60, Q1–Q4; aged > 60, Q1 and Q4; 10 men/women per quartile). Results We found that high-Neu5Gc diet, gender, and age affect the specificity, levels, and repertoires of anti-Neu5Gc IgG immune responses, but not their affinity. Men consumed more Neu5Gc than women, mostly from red meat (p = 0.0015), and exhibited higher overall serum anti-Neu5Gc IgG levels by ELISA (3.94 ng/μl versus 2.22 ng/μl, respectively; p = 0.039). Detailed glycan microarray analysis against 56 different glycans revealed high Neu5Gc-specificity with increased anti-Neu5Gc IgG and altered repertoires, associated with higher consumption of Neu5Gc from red meat and cow dairy. Affinity purification of serum anti-Neu5Gc antibodies revealed increased levels and biased array repertoire patterns, without an increase in antibody affinity, in individuals consuming higher Neu5Gc levels. Furthermore, in a high-meat diet, antibody diversity patterns on glycan microarrays shifted towards Neu5Gcα3-linked glycans, increasing the α3/α6-glycans ratio score. Conclusions We found a clear link between the levels and repertoire of serum anti-Neu5Gc IgG and Neu5Gc intake from red meat and dairy. These precise rational methodologies allowed to develop a Gcemic index to simplify the assessment of Neu5Gc in foods that could potentially be adapted for dietary recommendations to reduce cancer risk.

The present study investigated the gross and histological description of the rabbit testes with the histomorphometrical indices of the testes. Four male intact New Zealand white rabbits were procured with average weight of 1.35 ±0.13kg and were housed in individual cages at the animal house of the Faculty of Veterinary Medicine, University of Ibadan. Gross pictures and measurements of the testes were recorded while the testes tissues were processed for histology and histometric assessment of seminiferous tubules. Results showed that gross measurement of the right testis were about 2.88cm in length and 0.61cm in breadth. The measurement of the left testis were about 2.65cm and 0.65cm. The average histomorphometrical readings for the seminiferous tubular diameter and seminiferous epithelial height were 265.84µm and 204.09µm respectively. The histological slides revealed normal testicular architecture in the rabbits.

The quadrivalent HPV vaccine (4vHPV) was originally recommended as a three-dose series (0/2/6 months), though delays in completing the series frequently occur. We previously found delayed dosing in girls resulted in similar or higher antibody titers compared to on-time dosing. Archived sera from 262 healthy females aged 9–18 recruited from pediatric clinics were tested to determine if delayed dosing intervals affected antibody avidity. Avidity index (AI; ratio of IgG Ab bound in the treated and untreated sample) was determined pre- and post-dose 3 4vHPV for each participant using a modified multiplex ELISA. Data were grouped by dosing intervals: (1) on-time dose 2 and 3, (2) delayed dose 2 and on-time dose 3, (3) on-time dose 2 and delayed dose 3, (4) delayed dose 2 and 3. Overall, mean AI was highest for HPV16 and lowest for HPV6. As expected, AI did not differ between groups 1 & 3 or groups 2 & 4 pre-dose 3, however, for most types mean AI was significantly higher both pre- and post-dose 3 for groups with delayed dose 2. For all types, mean AI was higher post-dose 3 in all delayed dosing groups compared to group 1. One month post-dose 3, there was a positive but weak correlation between AIs and antibody titer for HPV 6 (ρ = 0.25, p = .0001), HPV 11 (ρ = 0.14, p = .0370), HPV 16 (ρ = 0.11, p = .0934), and HPV 18 (ρ = 0.37, p < .0001). Our findings suggest longer intervals between doses result in higher antibody avidity, providing further evidence that delayed dosing of 4vHPV does not hinder the immune response.

Determination of physicochemical characteristics of soil and water adjoining dumpsites is important to ascertain the fitness of drinkable water and their public health implications. Following the paucity of information on this area of study, physicochemical characteristics of water and soil in electronic waste dump site, Alaba, Lagos, Nigeria. Six samples from the dumpsite made up of three soil and water respectively were collected and extracted using USEPA methods. One soil and water sample far from the dumpsite served as control. Physicochemical parameters of water and soil samples were determined using standard methods. Results show that pH of the water samples ranged from 4.81 to 7.30. SW1 had highest pH (slightly alkaline) while SW3 had lowest pH and was acidic. The electrical conductivity of SW1, SW2 and SW3 ranged from 61 µS to 1421 µS respectively. Water temperature was between 29.53 and 29.57oC. Total dissolved solid of the water ranged from 32.33 to 722 mg/L. Sulphate ranged from 238 mg/L to 314 mg/L. Phosphate ranged from 41.92 to 60 mg/L. Dissolved oxygen ranged from 0.93 to 2.4 mg/L. Similarly, soil pH ranged from 6.57 to 7.44. Soil temperature ranged from 28.43 to 30.7. Soil organic carbon ranged from 13.75% to 20.25% while the soil organic matter ranged from 17.88% to 26.32%. Soil particle distribution ranged from 58.56 – 87.52% sand, 3.22 – 13.79% clay and 8.84 – 27.65% slit. Some physicochemical characteristics of soil and water in sampled location did not follow the WHO standard. This study has informed the state of water available for consumption as well as the state of soil contamination. Proper care is required to checkmate this location to avoid future contaminations.

Additive manufacturing has been well established in many sectors, including the medical industry. For load-bearing bone implants, titanium and its alloys, such as Ti6Al4V, are widely used due to their high strength to weight ratio and osseointegrative properties. However, bone resorption and loosening of implants is related to the significantly higher stiffness of dense Ti6Al4V, leading to stress shielding. With the aging of population, there is an increasing need for orthopedic implants with a high success rate and a long implant life span. Besides that the treatment of non-healing segmental bone defects, where the self-repairing properties of bone tissue are not sufficient, is still a challenge. In both fields of application, patient-specific titanium implants combined with functionally graded porosity designed according to locally expected loads unlock new possibilities. Many studies underline the huge potential of the new design freedom to generate open porous structures and more personalized implants with enhanced mechanical properties that also integrate well with surrounding tissues. Integration of functionally graded open porosity into implants allows for the implant to more closely mimic the mechanical properties of human bone and its internal architecture. The results of this work represent the basis for developing complex porous titanium structures with various pore sizes and shapes to tailor structural mechanical properties and biological responses. Therefore, 3D porous structures with various pore sizes and shapes were designed and manufactured in Ti6Al4V using laser powder bed fusion (PBF-LB/M). Based on these structures, the correlation of pore size and shape with cell ingrowth, morphology, metabolic activity, and early markers for bone formation (ALP activity) was investigated in static cell cultures using the osteosarcoma cell line Saos-2. Mechanical properties, such as stiffness and compression strength, were investigated with compression testing. The present study concludes that cell morphology, metabolic activity, and ALP activity are widely independent of pore shape and size within the tested range of 400–700 µm pore size. Furthermore, the mechanical properties of the evaluated structures were in the range of cortical and trabecular bone. This opens the possibility to design mechanical properties with gradient porosity without decisively affecting biological responses.

Evaluation of surgical skills during minimally invasive surgeries is needed when recruiting new surgeons. Although surgeons’ differentiation by skill level is highly complex, performance in specific clinical tasks such as pegboard transfer and knot tying could be determined using wearable EMG and accelerometer sensors. A wireless wearable platform has made it feasible to collect movement and muscle activation signals for quick skill evaluation during surgical tasks. However, it is challenging since the placement of multiple wireless wearable sensors may interfere with their performance in the assessment. This study utilizes machine learning techniques to identify optimal muscles and features critical for accurate skill evaluation. This study enrolled a total of twenty-six surgeons of different skill levels: novice (n = 11), intermediaries (n = 12), and experts (n = 3). Twelve wireless wearable sensors consisting of surface EMGs and accelerometers were placed bilaterally on bicep brachii, tricep brachii, anterior deltoid, flexor carpi ulnaris (FCU), extensor carpi ulnaris (ECU), and thenar eminence (TE) muscles to assess muscle activations and movement variability profiles. We found features related to movement complexity such as approximate entropy, sample entropy, and multiscale entropy played a critical role in skill level identification. We found that skill level was classified with highest accuracy by i) ECU for Random Forest Classifier (RFC), ii) deltoid for Support Vector Machines (SVM) and iii) biceps for Naïve Bayes Classifier with classification accuracies 61%, 57% and 47%. We found RFC classifier performed best with highest classification accuracy when muscles are combined i) ECU and deltoid (58%), ii) ECU and biceps (53%), and iii) ECU, biceps and deltoid (52%). Our findings suggest that quick surgical skill evaluation is possible using wearables sensors, and features from ECU, deltoid, and biceps muscles contribute an important role in surgical skill evaluation.

Background Cancer is associated with trauma and stress which impacts the physical, psychological, and spiritual/existential well-being of patients. Psychological/behavioral healing may help alleviate this distress and the associated health-related suffering. Psycho-Social-Spiritual healing outcome measures are thus needed to stimulate service development. The NIH Healing Experiences in All Life Stressors (NIH-HEALS), is a novel 35-item measure of psycho-social-spiritual healing, developed in USA and is yet to be validated and adapted for use in African countries. Objectives This study aimed to assess the face and content validity of the NIH-HEALS in the population of cancer patients in Uganda and to culturally adapt this measure. Methods Cross-sectional study using cognitive interviewing alongside standard piloting. We recruited adult (18 years and above) patients with advanced cancer from Hospice Africa Uganda. Interviews were conducted in two phases, using the think aloud technique and concurrent probing and were audio recorded. Phase 1 was used to identify initial concerns around clarity of the statements, and phase 2 further explored whether the issues of clarity had been addressed, alongside the standard cognitive interview parameters. The transcripts were imported into NVivo-12 analyzed using the content analysis technique and categorized using Tourengeau’s information processing model. Results We recruited thirty-five (35) patients: phase one (n = 5) two (n = 30). The median completion time was 20 minutes. Problems identified included comprehension of some statements, words, and phrases, suggestions to include local examples, highlighting of potentially sensitive statements that lean towards difficult conversations, and some cultural differences in the construction of the “Trust and Acceptance” construct, our sample showed less emphasis on family/friend relations. This feedback was used to adapt the NIH-HEALS for the local context. Conclusion The NIH-HEALS has sufficient face and content validity properties to be used among palliative cancer patients in Uganda. We propose some changes to inform the adaptation of this measure for the local context.

Introduction: Coccidioidomycosis is a fungal infection endemic in the southwestern United States (US). Primary pulmonary coccidioidomycosis (PPC) is a leading cause of community-acquired pneumonia (CAP) in this region, although its diagnosis is often delayed, leading to lag in antifungal treatment and subsequent morbidity. The impact of early empiric antifungal therapy as part of treatment for CAP in endemic areas on clinical outcomes is unknown. Methods: Phase IV randomized, double-blind, placebo-controlled trial in individuals aged 18 years or older with CAP who met all eligibility criteria in Coccidioides endemic regions in the US. Eligible participants with CAP were randomized to receive either fluconazole (400 mg daily) or matching placebo for 42 days and were subsequently monitored for clinical resolution of their illness. Objectives: The primary objective was to assess the clinical response of early empiric antifungal therapy with fluconazole through Day 22 in subjects with PPC who were adherent to the study intervention. Secondary objectives included: assessments of the impact of early empiric antifungal therapy with fluconazole through Day 22 and 43 in subjects with PPC regardless of adherence, comparisons of the clinical response and its individual components over time by treatment group in subjects with PPC, assessments of days lost from work or school, hospitalization, and all-cause mortality. Discussion: This trial was halted early due to slow enrollment (72 participants in one year, 33 received fluconazole and 39 received placebo). Of those enrolled, eight (11%) met the study definition of PPC. The study design and challenges are discussed.

BackgroundDeficits in global oral health care are paramount, and complications of odontogenic infections constitute a considerable global health problem, particularly in low-income countries. A high mortality rate has been observed for patients who have been admitted with complicated odontogenic infections to our facilities in Tonkolili District, Sierra Leone, although exact data have not been published yet. Data regarding who in this region is at risk and why are lacking. ObjectiveThe Dental Abscess Study (DELAY) aims to prospectively investigate morbidity and mortality from complicated dental abscesses and to analyze patients’ characteristics and microbial findings to examine predisposing factors for poor outcomes. In particular, the incidence and the clinical and microbial characteristics of complicated odontogenic infections, as well as the sociodemographic data and comorbidities of affected patients, will be studied to develop improved management algorithms based on circumstance-specific factors. MethodsPatients who present with complicated dental infections requiring hospital admission in Masanga Hospital or Lion Heart Medical Centre will be consecutively selected for possible inclusion in the study (starting on September 4, 2021) over a study period of 1 year, and individual routine follow-ups will be conducted at least 3 months after discharge. The results of standardized questionnaires will be obtained, and clinical measurements as well as medical photos will be taken. Standard laboratory tests (eg, full blood count and HIV status tests) will be performed, and pus specimens will be examined. Local treatment guidelines will be adhered to, and data on medical and surgical treatment as well as data on outcomes will be collected. The study results will be reported according to the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) criteria. Routine follow-ups will take place at 1 and 3 months postdischarge. ResultsThe DELAY protocol was endorsed by the Masanga Medical Research Unit’s Scientific Review Committee on June 16, 2021, and ethical approval was granted on July 5, 2021, by the Sierra Leone National Ethics Committee. The funding of the budgeted study costs was approved by Dental Health International Netherlands in August 2021. The projected start date of data collection was September 4, 2021, and the study period will most likely last for 1 year. As such, data collection is expected to be complete in November 2022. ConclusionsThe aim of our prospective observational cohort study is to gain more knowledge about complicated odontogenic infections in Tonkolili District, Sierra Leone, to further improve treatment strategies. International Registered Report Identifier (IRRID)DERR1-10.2196/33677

OBJECTIVES:. We sought to validate prognostic scores in coronavirus disease 2019 including National Early Warning Score, Modified Early Warning Score, and age-based modifications, and define their performance characteristics. DESIGN:. We analyzed prospectively collected data from the Adaptive COVID-19 Treatment Trial. National Early Warning Score was collected daily during the trial, Modified Early Warning Score was calculated, and age applied to both scores. We assessed prognostic value for the end points of recovery, mechanical ventilation, and death for score at enrollment, average, and slope of score over the first 48 hours. SETTING:. A multisite international inpatient trial. PATIENTS:. A total of 1,062 adult nonpregnant inpatients with severe coronavirus disease 2019 pneumonia. INTERVENTIONS:. Adaptive COVID-19 Treatment Trial 1 randomized participants to receive remdesivir or placebo. The prognostic value of predictive scores was evaluated in both groups separately to assess for differential performance in the setting of remdesivir treatment. MEASUREMENTS AND MAIN RESULTS:. For mortality, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.60–0.68), and improved with addition of age (c-index, 0.66–0.74). For recovery, baseline National Early Warning Score and Modified Early Warning Score demonstrated somewhat better prognostic ability (c-index, 0.65–0.69); however, National Early Warning Score+age and Modified Early Warning Score+age further improved performance (c-index, 0.68–0.71). For deterioration, baseline National Early Warning Score and Modified Early Warning Score were weakly to moderately prognostic (c-index, 0.59–0.69) and improved with addition of age (c-index, 0.63–0.70). All prognostic performance improvements due to addition of age were significant (p < 0.05). CONCLUSIONS:. In the Adaptive COVID-19 Treatment Trial 1 cohort, National Early Warning Score and Modified Early Warning Score demonstrated moderate prognostic performance in patients with severe coronavirus disease 2019, with improvement in predictive ability for National Early Warning Score+age and Modified Early Warning Score+age. Area under receiver operating curve for National Early Warning Score and Modified Early Warning Score improved in patients receiving remdesivir versus placebo early in the pandemic for recovery and mortality. Although these scores are simple and readily obtainable in myriad settings, in our data set, they were insufficiently predictive to completely replace clinical judgment in coronavirus disease 2019 and may serve best as an adjunct to triage, disposition, and resourcing decisions.

Nanocrystalline diamond (NCD) thin films grown by chemical vapour deposition have an intrinsic surface roughness, which hinders the development and performance of the films’ various applications. Traditional methods of diamond polishing are not effective on NCD thin films. Films either shatter due to the combination of wafer bow and high mechanical pressures or produce uneven surfaces, which has led to the adaptation of the chemical mechanical polishing (CMP) technique for NCD films. This process is poorly understood and in need of optimisation. To compare the effect of slurry composition and pH upon polishing rates, a series of NCD thin films have been polished for three hours using a Logitech Ltd. Tribo CMP System in conjunction with a polyester/polyurethane polishing cloth and six different slurries. The reduction in surface roughness was measured hourly using an atomic force microscope. The final surface chemistry was examined using X-ray photoelectron spectroscopy and a scanning electron microscope. It was found that of all the various properties of the slurries, including pH and composition, the particle size was the determining factor for the polishing rate. The smaller particles polishing at a greater rate than the larger ones.

Abstract Background Sub-Saharan Africa (SSA) countries are faced with the challenge of educating a critical mass of occupational therapists (OTs) and physiotherapists (PTs) to meet the growing demand for health and rehabilitation services. The World Federation of Occupational Therapy (WFOT) and World Confederation of Physical Therapy (WCPT) have argued for the need of graduate-level training for OTs and PTs for decades. However, very few studies have been conducted to determine the availability of OT and PT training programs and practitioners in SSA countries. Methods Initial data were collected and compiled from an extensive literature search conducted using MEDLINE and PubMed to examine the availability of OT and PT education and training programs in SSA countries. Additional data were collected, compiled, and collated from academic institutions, ministries of health, health professions associations, and licensing authorities in SSA countries. Secondary data were also collected from the websites of organizations such as the World Bank, World Health Organization (WHO), WFOT, and WCPT. Results This investigation revealed that there are limited number of OT and PT training programs and that these training programs in Anglophone SSA countries are offered at or below the bachelor’s level. More than half of the countries do not have OT or PT training programs. The number of qualified OTs and PTs appears to be insufficient to meet the demand for rehabilitation services. Nigeria and South Africa are the only countries offering post-entry-level masters and doctoral-level training programs in physiotherapy and occupational therapy. Conclusions Higher learning institutions in SSA countries need to collaborate and partner with other regional and foreign universities to elevate the educational training and increase the supply of PTs and OTs in the region.

PURPOSE:Ocular somatosensory-autonomic reflexes play critical roles in maintaining homeostasis of the eye. The purpose of this study was to investigate the pupil response to nociceptive corneal stimuli. METHODS:A Waterloo-Belmonte pneumatic esthesiometer was used to determine detection thresholds and randomly deliver mechanical and chemical stimuli from levels of detection threshold to twice the threshold in 50% steps to the central cornea of 15 healthy subjects. For each stimulus, imaging of the stimulated/unstimulated eye was performed using two modified/calibrated Logitech c920 digital cameras for 4 seconds each, pre/post stimulus capture. The data were processed with a custom segmentation algorithm to help identify the pupils and pupil diameter was measured using ImageJ software. Pupil dilation response differences between the ipsi- and contralateral eye was analyzed using dependent t-tests. The effect of stimulus intensity, modality and sex of subjects were analyzed using repeated measures. RESULTS:In mechanical and chemical stimulation experiments, there was no difference in pupil responses between the stimulated eye and the unstimulated eye, (all dependent T-test p > 0.05). On average, pupil diameter increased from baseline as the corneal stimulus intensity increased. This happened regardless of whether mechanical or chemical stimulation occurred (ANOVA p < 0.05). At 200% threshold, pupil diameter was greater than at all stimulus intensities (Tukey HSD, all p < 0.05). Based on stimulus intensity, females had greater pupil diameters than males at levels of 150% threshold and 200% threshold (ANOVA p < 0.05, all Tukey HSD p < 0.05). CONCLUSION:This study serves as a basis for the characterization of the local stimulus-response neural circuitry relating nociceptive stimuli to autonomic responses and in combination with our work on completely separate autonomic circuits of bulbar conjunctival vessel dilation and reflex tearing suggests that the monotonic measurements of redness, tearing and pupils provide accurate, separable responses that reflect painful stimulus intensity.

# Background Trauma is a leading cause for major limb loss (MLL) during war. As societies transition into peace other factors become important. The voluntary sector plays a diminishing role in service delivery as countries transition towards peace. # Methods We undertook a retrospective review of 141 inpatient case notes at two hospitals in Northern Uganda to study the etiology of MLL. Focus group discussions, a literature search and key informant interviews were undertaken to ascertain patients' experience and the state of current services. # Results The most common indication for amputation was malignancy (36%), followed by gangrene and complications from diabetes. Trauma was the 5^th^ most common cause. The mean (standard deviation, SD) age of this cohort was 43 (22.2) years and the mean (SD) distance from their homes to the closest rehabilitation service unit was 91 (75) km. Less than 1% of patients were formally referred to rehabilitation services. Patients described experiences of stigma and marginalization impacting relationship and/or employability. Rehabilitation services were limited/unaffordable and inaccessible. Unpreparedness of government agencies in taking over rehabilitation services was evident. # Conclusions Non-communicable diseases account for the majority of MLL in this region now. These new cohorts of patients join an existing large pool of war-related amputees. Chronic dependence on the voluntary sector has rendered a state of unpreparedness amongst the local health providers.

There has been an increasing interest in the search for colour indicators of natural origin for titrimetric analysis. This is due to some challenges associated with the currently used synthetic ones. This study evaluates and validates the acid-base indicator property of plumbagin isolated from Plumbago zeylanica Linn. Plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone) was isolated from the roots of Plumbago zeylanica Linn using silica gel chromatography and characterized using spectroscopic methods in comparison with those reported in the literature. Its acid-base indicator property was evaluated alongside phenolphthalein and methyl orange, after it was found to exhibit a sharp change in colour at various pH ranges. The plumbagin indicator was successfully used to assay ibuprofen powder and tablets (400 mg) using the British Pharmacopoeia (2013) method. Data obtained were analyzed statistically by Student’s t-test and one-way ANOVA in GraphPad Prism (version 5.01, 2010). Analysis of the use of the plumbagin indicator in acid-base titrations between strong acids and strong bases and between weak acids and strong bases has been evaluated and validated according to the ICH guidelines. Plumbagin use in ibuprofen powder and tablets has also been verified. Plumbagin has been validated for use as an indicator suitable for different acid-base titrations and the analysis of ibuprofen.

Antimicrobial resistance (AMR) is a threat to the prevention and treatment of the increasing range of infectious diseases. There is therefore the need for renewed efforts into antimicrobial discovery and development to combat the menace. The antimicrobial activity of plumbagin isolated from roots of Plumbago zeylanica against selected organisms was evaluated for resistance modulation antimicrobial assay, time-kill kinetics assay, and inhibition of biofilm formation. The minimum inhibitory concentrations (MICs) of plumbagin and standard drugs were determined via the broth microdilution method to be 0.5 to 8 μg/mL and 0.25–128 μg/mL, respectively. In the resistance modulation study, MICs of the standard drugs were redetermined in the presence of subinhibitory concentration of plumbagin (4 μg/mL), and plumbagin was found to either potentiate or reduce the activities of these standard drugs with the highest potentiation recorded up to 12-folds for ketoconazole against Candida albicans. Plumbagin was found to be bacteriostatic and fungistatic from the time-kill kinetics study. Plumbagin demonstrated strong inhibition of biofilm formation activity at concentrations of 128, 64, and 32 μg/mL against the test microorganisms compared with ciprofloxacin. Plumbagin has been proved through this study to be a suitable lead compound in antimicrobial resistance drug development.