Use of heterologous prime-boost COVID-19 vaccine schedules could facilitate mass COVID-19 immunisation. However, we have previously reported that heterologous schedules incorporating an adenoviral ...vectored vaccine (ChAdOx1 nCoV-19, AstraZeneca; hereafter referred to as ChAd) and an mRNA vaccine (BNT162b2, Pfizer–BioNTech; hereafter referred to as BNT) at a 4-week interval are more reactogenic than homologous schedules. Here, we report the safety and immunogenicity of heterologous schedules with the ChAd and BNT vaccines.
Com-COV is a participant-blinded, randomised, non-inferiority trial evaluating vaccine safety, reactogenicity, and immunogenicity. Adults aged 50 years and older with no or well controlled comorbidities and no previous SARS-CoV-2 infection by laboratory confirmation were eligible and were recruited at eight sites across the UK. The majority of eligible participants were enrolled into the general cohort (28-day or 84-day prime-boost intervals), who were randomly assigned (1:1:1:1:1:1:1:1) to receive ChAd/ChAd, ChAd/BNT, BNT/BNT, or BNT/ChAd, administered at either 28-day or 84-day prime-boost intervals. A small subset of eligible participants (n=100) were enrolled into an immunology cohort, who had additional blood tests to evaluate immune responses; these participants were randomly assigned (1:1:1:1) to the four schedules (28-day interval only). Participants were masked to the vaccine received but not to the prime-boost interval. The primary endpoint was the geometric mean ratio (GMR) of serum SARS-CoV-2 anti-spike IgG concentration (measured by ELISA) at 28 days after boost, when comparing ChAd/BNT with ChAd/ChAd, and BNT/ChAd with BNT/BNT. The heterologous schedules were considered non-inferior to the approved homologous schedules if the lower limit of the one-sided 97·5% CI of the GMR of these comparisons was greater than 0·63. The primary analysis was done in the per-protocol population, who were seronegative at baseline. Safety analyses were done among participants receiving at least one dose of a study vaccine. The trial is registered with ISRCTN, 69254139.
Between Feb 11 and Feb 26, 2021, 830 participants were enrolled and randomised, including 463 participants with a 28-day prime-boost interval, for whom results are reported here. The mean age of participants was 57·8 years (SD 4·7), with 212 (46%) female participants and 117 (25%) from ethnic minorities. At day 28 post boost, the geometric mean concentration of SARS-CoV-2 anti-spike IgG in ChAd/BNT recipients (12 906 ELU/mL) was non-inferior to that in ChAd/ChAd recipients (1392 ELU/mL), with a GMR of 9·2 (one-sided 97·5% CI 7·5 to ∞). In participants primed with BNT, we did not show non-inferiority of the heterologous schedule (BNT/ChAd, 7133 ELU/mL) against the homologous schedule (BNT/BNT, 14 080 ELU/mL), with a GMR of 0·51 (one-sided 97·5% CI 0·43 to ∞). Four serious adverse events occurred across all groups, none of which were considered to be related to immunisation.
Despite the BNT/ChAd regimen not meeting non-inferiority criteria, the SARS-CoV-2 anti-spike IgG concentrations of both heterologous schedules were higher than that of a licensed vaccine schedule (ChAd/ChAd) with proven efficacy against COVID-19 disease and hospitalisation. Along with the higher immunogenicity of ChAd/BNT compared with ChAD/ChAd, these data support flexibility in the use of heterologous prime-boost vaccination using ChAd and BNT COVID-19 vaccines.
UK Vaccine Task Force and National Institute for Health Research.
Priming COVID-19 vaccine schedules have been deployed at variable intervals globally, which might influence immune persistence and the relative importance of third-dose booster programmes. Here, we ...report exploratory analyses from the Com-COV trial, assessing the effect of 4-week versus 12-week priming intervals on reactogenicity and the persistence of immune response up to 6 months after homologous and heterologous priming schedules using the vaccines BNT162b2 (tozinameran, Pfizer/BioNTech) and ChAdOx1 nCoV-19 (AstraZeneca).
Com-COV was a participant-masked, randomised immunogenicity trial. For these exploratory analyses, we used the trial's general cohort, in which adults aged 50 years or older were randomly assigned to four homologous and four heterologous vaccine schedules using BNT162b2 and ChAdOx1 nCoV-19 with 4-week or 12-week priming intervals (eight groups in total). Immunogenicity analyses were done on the intention-to-treat (ITT) population, comprising participants with no evidence of SARS-CoV-2 infection at baseline or for the trial duration, to assess the effect of priming interval on humoral and cellular immune response 28 days and 6 months post-second dose, in addition to the effects on reactogenicity and safety. The Com-COV trial is registered with the ISRCTN registry, 69254139 (EudraCT 2020–005085–33).
Between Feb 11 and 26, 2021, 730 participants were randomly assigned in the general cohort, with 77–89 per group in the ITT analysis. At 28 days and 6 months post-second dose, the geometric mean concentration of anti-SARS-CoV-2 spike IgG was significantly higher in the 12-week interval groups than in the 4-week groups for homologous schedules. In heterologous schedule groups, we observed a significant difference between intervals only for the BNT162b2–ChAdOx1 nCoV-19 group at 28 days. Pseudotyped virus neutralisation titres were significantly higher in all 12-week interval groups versus 4-week groups, 28 days post-second dose, with geometric mean ratios of 1·4 (95% CI 1·1–1·8) for homologous BNT162b2, 1·5 (1·2–1·9) for ChAdOx1 nCoV-19–BNT162b2, 1·6 (1·3–2·1) for BNT162b2–ChAdOx1 nCoV-19, and 2·4 (1·7–3·2) for homologous ChAdOx1 nCoV-19. At 6 months post-second dose, anti-spike IgG geometric mean concentrations fell to 0·17–0·24 of the 28-day post-second dose value across all eight study groups, with only homologous BNT162b2 showing a slightly slower decay for the 12-week versus 4-week interval in the adjusted analysis. The rank order of schedules by humoral response was unaffected by interval, with homologous BNT162b2 remaining the most immunogenic by antibody response. T-cell responses were reduced in all 12-week priming intervals compared with their 4-week counterparts. 12-week schedules for homologous BNT162b2 and ChAdOx1 nCoV-19–BNT162b2 were up to 80% less reactogenic than 4-week schedules.
These data support flexibility in priming interval in all studied COVID-19 vaccine schedules. Longer priming intervals might result in lower reactogenicity in schedules with BNT162b2 as a second dose and higher humoral immunogenicity in homologous schedules, but overall lower T-cell responses across all schedules. Future vaccines using these novel platforms might benefit from schedules with long intervals.
UK Vaccine Taskforce and National Institute for Health and Care Research.
Solid waste management is one of the biggest challenges of the current era. The combustible fractions in the waste stream turn out to be a good energy source if converted into refuse-derived fuel. ...Researchers worldwide are successfully converting it into fuel. However, certain challenges are associated with its application in gasifiers, boilers, etc. to co-fire it with coal. These include high moisture content, low calorific value, and difficulty to transport and store. The present study proposed torrefaction as a pretreatment of the waste by heating it in the range of 200 °C–300 °C in the absence of oxygen at atmospheric pressure. The combustible fraction from the waste stream consisting of wood, textile, paper, carton, and plastics termed as mixed waste was collected and torrefied at 225 °C, 250 °C, 275 °C, and 300 °C for 15 and 30 min each. It was observed that the mass yield and energy yield decreased to 45% and 62.96% respectively, but the energy yield tended to increase by the ratio of 1.39. Proximate analysis showed that the moisture content and volatile matter decreased for torrefied samples, whereas the ash content and fixed carbon content increased. Similarly, the elemental analysis revealed that the carbon content increased around 23% compared to raw samples with torrefaction contrary to hydrogen and oxygen, which decreased. Moreover, the higher heating value (HHV) of the torrefied samples increased around 1.3 times as compared to the raw sample. This pretreatment can serve as an effective solution to the current challenges and enhance refuse-derived fuel's fuel properties.
The fast depletion of conventional fuel supplies has forced the world to find suitable substitutes to overcome the expected energy crisis. Fossil fuels also contribute to global warming because of ...their harmful emissions. Biofuels are sustainable and environment friendly. Biodiesel can be sourced from both edible and non-edible oils to replace fossil fuels. To avoid a shortage of food supply, it is preferred to produce biodiesel from non-edible oils. In this research, Litchi chinensis seed oil (LSO) is used as a feedstock to synthesize biodiesel employing transesterification using a microwave oven. The catalyst, potassium hydroxide (KOH), used in this research was extracted from potato waste. Sun-dried potato waste was converted into ash. The produced ash is then dissolved in distilled water, leading to a 34% yield of KOH. The transesterification achieves a 92.9% conversion rate under the conditions: 30% microwave power utilization, a catalyst loading of 15% (W/W), a stirring speed of 700 RPM, and a methanol concentration of 70% (V/V) with an 8-min reaction time. Response surface methodology (RSM), in comparison with artificial neural networks (ANNs), has been utilized for the optimization of biodiesel yield, giving efficient results with errors of 0.003% for RSM and 0.005% for ANN. Consequently, the study reports optimized biodiesel yields of 92.9% (experimental), 93.27% (RSM), and 92.40% (ANN). Physicochemical properties such as kinematic viscosity (4.4 mm 2 /s) at 40°C, density (875 kg/m 3 ) at 15°C, cetane number (53.2), calorific value (38.8 MJ/kg), flash point (175°C), oxidative stability (6.1 h), and cold flow properties were determined with respect to the ASTM and EN standards. The findings reveal that biofuels primarily support Sustainable Development Goals (SDGs) 7 and 13, with the prime focus on “affordable and clean energy” and “climate action,” respectively.
Pakistan is a developing country that faces severe energy crises due to the increased use of energy. The purpose of this study is energy transition by designing a strategy for the adoption of ...renewable energy policies in the entire energy system by using all renewable energy resources to forecast future energy needs and carbon emission mitigation potential. This research study aims to evaluate the renewable energy policies of Pakistan and to analyze the ways to secure energy sources in the future using LEAP. The study established a path for the transformation of the Pakistan energy system by considering the potential of renewable resources, the cost of the energy system, and the primary energy supply. The highest value of energy demand is noted for the 1st scenario, while the lowest emissions are noted for the 16th scenario for each renewable source (WIN16, SOL16, and BIO16). The lowest values of energy demand and emissions (192.1 TWh and 37.7 MMT, respectively) are shown using the green solution compared to other scenarios (hydro, nuclear, BAU), concluding that the green solution is the most suitable scenario. The analysis shows, that from a technological and economic perspective, it is possible to carry out transformation with the necessary steps to effectively achieve a renewable energy system. The findings of this study show that the green scenario in Pakistan which has the lowest operational and externality costs is the best choice for the future.
Introduction: Indigenous people in a far-flung mountainous area without basic facilities, mainly rely on medicinal plants to cope with various veterinary health problems. Objective: The present study ...was carried out to explore the traditional knowledge of ethnoveterinary practices in Kaghan Valley, district Mansehra, Western Himalayas-Pakistan. Method: Ethnoveterinary data were collected between February to October 2014 from nine villages of the Kaghan Valley by involving 80 local people include traditional healers using a semi-structured interview. Results: A sum of 41 plant taxa of ethnoveterinary medicinal plants was documented for treating livestock ailments. Out of which, herbaceous plants were recorded with high percentage (27 species, 65.8 %). Most of the species were used to treat gastrointestinal diseases (12 taxa), followed by health improvement (7 taxa). The widely used part of plants for livestock aliments was the whole plant (9 species) followed by leaves (7 species), and preparation were paste (18 species) followed by powder with 10 species. The highest used values were recorded for Arisaema costatum (0.82), Primula denticulata (0.76), and high relative frequency citations for Berberis lyceum and Dryopteris ramosa with 0.37 each. Among the plant species Skimmia laureola, Thymus linearis and Phytolacca latbenia were among the taxa with cent fidelity level. Conclusion: The flora used in traditional remedies of the valley was found mostly endemic due to excessive utilization. Thus, further chemical investigation, better utilization and conservation of indigenous use of the reported species should be considered for future work.
Background Urinary tract infections (UTIs) are common in patients with diabetes. The use of sodium-glucose cotransporter-2 inhibitors (SGLT2i) to achieve good glycemic control increases glucose ...levels in urine. This glycosuria further enhances the risk of UTIs. This study aimed to evaluate the frequency of UTIs in patients with type 2 diabetes receiving the SGLT2i dapagliflozin as an add-on therapy. Methods We conducted this cross-sectional study at the Endocrinology Department of Hayatabad Medical Complex in Peshawar from April 2020 to September 2020. A total of 400 patients with diabetes receiving either 5 mg or 10 mg of dapagliflozin as an add-on therapy for the treatment of type 2 diabetes were included in this study. We collected blood and urine samples from participants and measured glycosylated hemoglobin levels. Urine samples were cultured on cysteine lactose electrolyte deficient agar. We used IBM SPSS Statistics for Windows, version 25.0 (IBM Corp., Armonk, NY) to analyze our data. Results The prevalence of UTIs in diabetic patients receiving 5 mg or 10 mg of dapagliflozin was 5.3%. Women were more affected (76.2%) than men (p < 0.05). UTIs were more prevalent in patients older than 50 years (85.7%) than in any other age group. The dose strength of dapagliflozin was not associated with UTIs (p > 0.05). Conclusion This study examined UTIs in patients taking dapagliflozin for the treatment of type 2 diabetes. These infections were mild to moderate and were treated easily. None of these infections caused the patient to discontinue the treatment. Dapagliflozin is well-tolerated in patients with diabetes but should be used with appropriate caution and monitoring.
Introduccion: Los pueblos indigenas de zonas montanosas lejanas sin facilidades basicas dependen principalmente de las plantas medicinales para afrontar problemas de salud de tipo veterinario. ...Objetivo: Explorar el conocimiento tradicional en las practicas etnoveterinarias en el valle de Kaghan, distrito de Mansehra, Himalaya occidental-Pakistan. Metodos: Se recopilaron datos etnoveterinarios mediante una entrevista semiestructurada entre febrero y octubre de 2014 en nueve aldeas del valle de Kaghan, con la participacion de 80 habitantes locales, incluidos curanderos tradicionales. Resultados: Se documento un total de 41 taxones de plantas medicinales etnoveterinarias para el tratamiento de enfermedades del ganado. Se registro un alto porcentaje de plantas herbaceas (27 especies, 65.8 %). La mayoria de las especies utilizadas han sido para tratar enfermedades gastrointestinales (12 taxones), y mejora de la salud (7 taxones). Para el tratamiento de enfermedades del ganado, lo mas usual fue utilizar la planta entera (9 especies), seguida de las hojas (7 especies), con preparacion en pasta (18 especies) y en polvo (10 especies). Las especies registradas con mas uso fueron: Arisaema costatum (0.82), Primula denticulata (0.76) y Berberis lyceum y Dryopteris ramosa con la misma alta frecuencia relativa (0.37 cada una). Las especies Skimmia laureola, Thymus linearis y Phytolacca latbenia se reportaron entre los taxones con mayor nivel de fidelidad porcentual. Conclusion: La flora utilizada en los remedios tradicionales del valle de Kaghan fue mayoritariamente endemica. Se propone para trabajos futuros mayor investigacion quimica, y mayor utilizacion y conservacion en las especies de plantas reportadas por los indigenas. Palabras clave: conocimiento tradicional; dolencias del ganado; plantas medicinales; Valle de Kaghan. Introduction: Indigenous people in a far-flung mountainous area without basic facilities, mainly rely on medicinal plants to cope with various veterinary health problems. Objective: The present study was carried out to explore the traditional knowledge of ethnoveterinary practices in Kaghan Valley, district Mansehra, Western Himalayas-Pakistan. Method: Ethnoveterinary data were collected between February to October 2014 from nine villages of the Kaghan Valley by involving 80 local people include traditional healers using a semistructured interview. Results: A sum of 41 plant taxa of ethnoveterinary medicinal plants was documented for treating livestock ailments. Out of which, herbaceous plants were recorded with high percentage (27 species, 65.8 %). Most of the species were used to treat gastrointestinal diseases (12 taxa), followed by health improvement (7 taxa). The widely used part of plants for livestock aliments was the whole plant (9 species) followed by leaves (7 species), and preparation were paste (18 species) followed by powder with 10 species. The highest used values were recorded for Arisaema costatum (0.82), Primula denticulata (0.76), and high relative frequency citations for Berberis lyceum and Dryopteris ramosa with 0.37 each. Among the plant species Skimmia laureola, Thymus linearis and Phytolacca latbenia were among the taxa with cent fidelity level. Conclusion: The flora used in traditional remedies of the valley was found mostly endemic due to excessive utilization. Thus, further chemical investigation, better utilization and conservation of indigenous use of the reported species should be considered for future work. Key words: traditional knowledge; livestock ailments; medicinal plants; Kaghan Valley.
This study was conducted during 2015–2016. Extensive field work was conducted to collect and record huge amount of data on important environmental variables. Data was collected using reliable digital ...equipment with high precision and accuracy where possible. Material and samples collected for chemical analysis were based upon standardized methods used by prestigious labs across the globe. The results showed that July (Temperature 33.67 °C) is the warmest while December(19.1 °C) is the coldest month of the year in the study area. Air humidity ranges from 52.44% to23.22% between Union councils (UCs). Steepness of the slope or slope angle was found between 55.5 and 24°. Soil pH was between 7.39 and 6.55. Soil Nitrogen contents were found to be in a range of 0.0543% and 0.0320%. as far as soil organic matter is concerned it was recorded in a range of 0.77% and 0.48%. electric conductivity was between2.56 dS/m and 2.393 dS/m. Interaction among different environmental variables results in the establishment of different environmental complexes each with specific microclimate.
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