Guidance on protocol development for EFSA generic scientific assessments.

EFSA Strategy 2027 outlines the need for fit-for-purpose protocols for EFSA generic scientific assessments to aid in delivering trustworthy scientific advice. This EFSA Scientific Committee guidance document helps address this need by providing a harmonised and flexible framework for developing protocols for EFSA generic assessments. The guidance replaces the 'Draft framework for protocol development for EFSA's scientific assessments' published in 2020. The two main steps in protocol development are described. The first is problem formulation, which illustrates the objectives of the assessment. Here a new approach to translating the mandated Terms of Reference into scientifically answerable assessment questions and sub-questions is proposed: the 'APRIO' paradigm (Agent, Pathway, Receptor, Intervention and Output). Owing to its cross-cutting nature, this paradigm is considered adaptable and broadly applicable within and across the various EFSA domains and, if applied using the definitions given in this guidance, is expected to help harmonise the problem formulation process and outputs and foster consistency in protocol development. APRIO may also overcome the difficulty of implementing some existing frameworks across the multiple EFSA disciplines, e.g. the PICO/PECO approach (Population, Intervention/Exposure, Comparator, Outcome). Therefore, although not mandatory, APRIO is recommended. The second step in protocol development is the specification of the evidence needs and the methods that will be applied for answering the assessment questions and sub-questions, including uncertainty analysis. Five possible approaches to answering individual (sub-)questions are outlined: using evidence from scientific literature and study reports; using data from databases other than bibliographic; using expert judgement informally collected or elicited via semi-formal or formal expert knowledge elicitation processes; using mathematical/statistical models; and - not covered in this guidance - generating empirical evidence ex novo. The guidance is complemented by a standalone 'template' for EFSA protocols that guides the users step by step through the process of planning an EFSA scientific assessment.

Efficient trapping and destruction of SARS-CoV-2 using PECO-assisted Molekule air purifiers in the laboratory and real-world settings.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is transmitted human-to-human via aerosols and air-borne droplets. Therefore, capturing and destroying viruses from indoor premises are essential to reduce the probability of human exposure and virus transmission. While the heating, ventilation, and air conditioning (HVAC) systems help in reducing the indoor viral load, a targeted approach is required to effectively remove SARS-CoV-2 from indoor air to address human exposure concerns. The present study demonstrates efficient trapping and destruction of SARS-CoV-2 via nano-enabled filter technology using the UV-A-stimulated photoelectrochemical oxidation (PECO) process. Aerosols containing SARS-CoV-2 were generated by nebulization inside an air-controlled test chamber where an air purifier (Air Mini+) was placed. The study demonstrated the efficient removal of SARS-CoV-2 (99.98 %) from the test chamber in less than two minutes and PECO-assisted destruction (over 99%) on the filtration media in 1 h. Furthermore, in a real-world scenario, the Molekule Air-Pro air purifier removed SARS-CoV-2 (a negative RT-qPCR result post-running the filter device) from the circulating air in a COVID-19 testing facility. Overall, the ability of two FDA-approved class II medical devices, Molekule Air-Mini+ and Air-Pro air purifiers, to remove and destroy SARS-CoV-2 in indoor settings was successfully demonstrated. The study indicates that as the "tripledemic" of COVID-19, influenza, and respiratory syncytial virus (RSV) overwhelm the healthcare facilities in the USA, the use of a portable air filtration device will help contain the spread of the viruses in close door facilities, such as in schools and daycare facilities.

Hemodynamic responses to handgrip and metaboreflex activation are exaggerated in individuals with metabolic syndrome independent of resting blood pressure, waist circumference, and fasting blood glucose.

Introduction: Prior studies report conflicting evidence regarding exercise pressor and metaboreflex responses in individuals with metabolic syndrome (MetS). Purpose: To test the hypotheses that 1) exercise pressor and metaboreflex responses are exaggerated in MetS and 2) these differences may be explained by elevated resting blood pressure. Methods: Blood pressure and heart rate (HR) were evaluated in 26 participants (13 MetS) during 2 min of handgrip exercise followed by 3 min of post-exercise circulatory occlusion (PECO). Systolic (SBP), diastolic (DBP), and mean arterial pressure (MAP), along with HR and a cumulative blood pressure index (BPI), were compared between groups using independent samples t-tests, and analyses of covariance were used to adjust for differences in resting blood pressure, fasting blood glucose (FBG), and waist circumference (WC). Results: ΔSBP (∼78% and ∼54%), ΔMAP (∼67% and ∼55%), and BPI (∼16% and ∼20%) responses were significantly exaggerated in individuals with MetS during handgrip and PECO, respectively (all p ≤ 0.04). ΔDBP, ΔMAP, and BPI responses during handgrip remained significantly different between groups after independently covarying for resting blood pressure (p < 0.01), and after simultaneously covarying for resting blood pressure, FBG, and WC (p ≤ 0.03). Likewise, peak SBP, DBP, MAP, and BPI responses during PECO remained significantly different between groups after adjusting for resting blood pressure (p ≤ 0.03), with peak SBP, MAP, and BPI response remaining different between groups after adjusting for all three covariates simultaneously (p ≤ 0.04). Conclusion: These data suggest that exercise pressor and metaboreflex responses are significantly exaggerated in MetS independent of differences in resting blood pressure, FBG, or WC.

Photo-electrochemical oxidation flow system for stormwater herbicides removal: Operational conditions and energy consumption analysis.

Photoelectrochemical oxidation (PECO) is a promising advanced technology for treating micropollutants in stormwater. However, it is important to understand its operation prior to practical validation. In this study, we introduced a flow PECO system designed to evaluate its potential for full-scale applications in herbicides degradation, providing valuable insights for future large-scale implementations. The PECO flow reactor demonstrated the ability to treat a larger volume of stormwater (675 mL, approximately 10 times more than previous batch experiments) with effective removal rates of 92 % for diuron and 22 % for atrazine over 6 h of operation at 2 V. To address the large volume issue in stormwater treatment, a multiple module parallel application design is being considered to increase the treatment capacity of the PECO flow reactor. During the flow reactor operations, flow rate was found to have a notable impact on removal performance, particularly for diuron. At a flow rate of 610 mL min-1, approximately 90 % removal of diuron was achieved, while at 29 mL min-1, the removal efficiency decreased to 60 %. While light intensity had minimal effect on diuron degradation (all settings achieved over 90 % removal), it enhanced atrazine degradation from 9 % to 31 % with an increase in intensity from 63 mW cm-2 to 144 mW cm-2. Remarkably, the PECO flow system exhibited excellent removal performance (>90 % removal) for diuron even at extremely high initial pollutant concentrations (240 µg L-1), demonstrating its capacity to handle varying contaminant loads in stormwater. Energy consumption analysis revealed that flow rate as the primary factor influenced the specific energy consumption rate. Higher flow rate (e.g., 610 mL min-1) were preferable in flow reactor due to its well-balanced performance between removal and energy consumption. These findings confirm that the PECO flow system offers an efficient and promising approach for stormwater treatment applications.

Identification of Risk Factors for African Swine Fever: A Systematic Review.

African swine fever (ASF) is an internationally-spreading viral pig disease that severely damages agricultural pork production and trade economy as well as social welfare in disease-affected regions. A comprehensive understanding of ASF risk factors is imperative for efficient disease control. As the absence of effective ASF vaccines limits disease management options, the identification and minimisation of ASF-associated risk factors is critical to preventing ASF outbreaks. Here, we compile currently known potential ASF risk factors identified through a systematic literature review. We found 154 observation-based and 1239 potential ASF risk factors, which we were able to group into the following defined risk categories: 'ASF-virus', 'Biosecurity', 'Disease control', 'Environment', 'Husbandry', 'Movement', 'Network', 'Pig', 'Society' and 'Surveillance'. Throughout the epidemiological history of ASF there have been similar risk categories, such as 'Environment'-related risk factors, predominantly reported in the literature irrespective of the ASF situation at the time. While ASF risk factor reporting has markedly increased since 2010, the majority of identified risk factors overall have referred to domestic pigs. The reporting of risk factors for ASF in wild boar mostly commenced from 2016 onwards. The compendium of ASF risk factors presented herein defines our current knowledge of ASF risk factors, and critically informs ASF-related problem solving.

Photo-electrochemical oxidation herbicides removal in stormwater: Degradation mechanism and pathway investigation.

Although advanced oxidation processes (AOPs) such as photoelectrochemical oxidation (PECO), electrochemical oxidation (ECO) and photocatalytic oxidation (PCO), have shown potential for wastewater treatment, their application in urban stormwater has rarely been studied. This paper explored their major degradation mechanisms and possible degradation pathways of herbicides for stormwater applications (with treatment difficulty compared with wastewater). PECO and ECO showed excellent removal performance for diuron (100 %) and moderate for atrazine (around 35 %) under a relatively low potential (2 V). Superoxide radical (·O2-) has been found to be the dominant reactive species. Besides, there is evidence to indicate that hydroxyl radical (·OH) and free chlorine (·Cl) also support the degradation reactions. Up to 11 possible intermediate products have been identified during both diuron and atrazine degradation processes under PECO operation. Based on the proposed possible degradation pathways, the intermediates presented during PECO are species with further oxidation. As evidenced by the undetected species of more oxidized intermediates for ECO and PCO, some further degradation steps are missing, which demonstrate their lower oxidation capacity leading to incomplete decomposition of stormwater herbicides. Thus, PECO has a great potential to be developed into a passive stormwater degradation system due to its strong oxidation potential.

Recent advances on inactivation of waterborne pathogenic microorganisms by (photo) electrochemical oxidation processes: Design and application strategies.

Compared with other conventional water disinfection processes, (photo) electrochemical oxidation (P/ECO) processes have the characteristics of environmental friendliness, convenient installation and operation, easy control and high efficiency of inactivating waterborne pathogenic microorganisms (PMs), so that more and more research work has been focused on this topic, but there is still a huge gap between the research and practical application. Here, the research network of inactivating PMs by P/ECO processes has been comprehensively summarized, and the electrode/reactor/process design strategies based on strengthening direct and indirect oxidation, enhancing mass transfer efficiency and electron transfer efficiency, and improving the effective dose of electrogenerated oxidants are discussed. Furthermore, the factors affecting the inactivation of PMs and the issues regarding to stability and lifetime of the electrode are discussed respectively. Finally, the important research priorities and possible research challenges of P/ECO processes are put forward to make significant progress of this technology.

Stormwater herbicides removal with a solar-driven advanced oxidation process: A feasibility investigation.

The solar driven advanced oxidation process (AOP) has the potential to be developed as a passive stormwater post-treatment method. Despite its widespread studies in wastewater treatment, the applicability of the process for micropollutant removal in stormwater (which has very different chemical properties from wastewater) is still unknown. This paper investigated the feasibility of three different AOP processes for the degradation of two herbicides (diuron and atrazine) in pre-treated stormwater: (i) photoelectrochemical oxidation (PECO), (ii) electrochemical oxidation (ECO), and (iii) photocatalytic oxidation (PCO). The durability of different anode materials, the effects of catalyst loading, and solar photo- and thermal impacts under different applied voltages were studied. Boron-doped diamond (BDD) was found to be the most durable anode material compared to carbon fiber and titanium foil for long-term operation. Due to the very low electroconductivity of stormwater, a high voltage was required, causing severe oxidation of the carbon fiber material. PECO achieved the best degradation results compared to ECO and PCO, with over 90% degradation of both herbicides in 2 h under 5 V, following a first-order decay process (with a half-life value of 0.40 h for diuron and 0.58 h for atrazine). The voltage increase had a positive impact on the oxidation processes, with 5 V found to be the optimal applied voltage, while catalyst loading had a negligible effect. Interestingly, the solar thermal effect plays a dominant role in enhancing the performance of the PECO process, which indicates the potential of integrating a photovoltaic chamber with a PECO system to harness both the light and heat of solar energy for stormwater treatment.

Impact of a New Portable Air Purification Technology Device in the Pediatric Hospital Setting - A Pre-post Assessment Study.

Introduction We assessed whether portable photo-electrochemical oxidation (PECO) air purification in the pediatric hospital room setting could improve health outcomes for patients admitted with respiratory distress.  Methods We performed a prospective study evaluating the use of a portable air purifier with PECO technology. The historical control group comprised matched patients. Twenty-seven PECO-equipped portable air filtration devices were placed in the rooms. Clinical endpoints included length of stay in the hospital, length of stay in the intensive care unit (ICU), rates of intubation, non-invasive ventilation, and nebulizer use. Results The mean length of ICU stay was 0.7 days in the pre-intervention period and decreased to 0.4 days post-intervention. The mean length of overall hospitalization reduced by 0.3 days. The rate of non-invasive ventilation use was 77% in the pre-intervention period and decreased to 23% in the post-intervention period. The rate of nebulizer use was 59% in the pre-intervention period and 41% in the post-intervention period. The rate of intubation was 57.1% in the pre-intervention period and 43% in the post-intervention period.  Conclusion  Portable PECO air purification may reduce hospital length of stay, rates of intubation, and need for non-invasive intervention and nebulizers for pediatric patients admitted with respiratory distress.

Neurovascular and Clinical Outcomes of the Percutaneous Endoscopically Assisted Calcaneal Osteotomy (PECO) Technique to Correct Hindfoot Malalignment.

BACKGROUND:: Standard open calcaneal osteotomies to correct hindfoot malalignment have been associated with high complication rates, including nerve damage and wound infection. This has resulted in the development of minimally invasive techniques such as the percutaneous endoscopically assisted calcaneal osteotomy (PECO), which in cadaver studies has been shown to be potentially safer than open surgeries. The aim of this study was to demonstrate the safety and effectiveness of PECO in a clinical setting, with regard to neurovascular injury rates, infection, and short-term radiographic and functional outcomes. METHODS:: Forty-one (41) patients with planovalgus or cavovarus foot deformities underwent treatment using PECO. Outcomes were analyzed at 6 months and primarily included neurovascular outcomes and wound infection rates. Secondarily, radiographic and functional (visual analog scale for pain [VAS], 36-Item Short Form Medical Outcomes Survey [SF-36], and Foot Function Index [FFI] scores) outcomes were also assessed. RESULTS:: There were no reported cases of superficial wound infections, lateral calcaneal or sural nerve dysesthesia. Minor complications occurred in 6/41 feet. The mean postoperative hindfoot correction was 8.3 ± 2.2 mm (range: 6-15mm) compared to preoperative status. Compared to preoperative status, significant improvements ( P = .001 for all) were seen in the VAS, SF-36, and FFI at 6 months postoperatively. CONCLUSIONS:: PECO resulted in minimal complications with no lateral calcaneal or sural nerve dysesthesias and no wound complications. It also resulted in significant improvements in postoperative radiographic and functional outcomes from baseline to 6-months postoperatively, demonstrating its use as a safe and effective means of treating hindfoot malalignment. LEVEL OF EVIDENCE:: Level IV, retrospective case series.

Review of reviews on exposures to synthetic organic chemicals and children's neurodevelopment: Methodological and interpretation challenges.

Environmental epidemiology data are becoming increasingly important in public health decision making, which commonly incorporates a systematic review of multiple studies. This review addresses two fundamental questions: What is the quality of available reviews on associations between exposure to synthetic organic chemicals and neurodevelopmental outcomes? What is the value (e.g., quality and consistency) of the underlying literature? Published reviews on associations between synthetic organic environmental chemical exposures and neurodevelopmental outcomes in children were systematically evaluated. Seventy-four relevant reviews were identified, and these were evaluated with respect to four methodological characteristics: (1) systematic inclusion/exclusion criteria and reproducible methods for search and retrieval of studies; (2) structured evaluation of underlying data quality; (3) systematic assessment of consistency across specific exposure-outcome associations; and (4) evaluation of reporting/publication bias. None of the 74 reviews fully met the criteria for all four methodological characteristics. Only four reviews met two criteria, and six reviews fulfilled only one criterion. Perhaps more importantly, the higher quality reviews were not able to meet all of the criteria owing to the shortcomings of underlying studies, which lacked comparability in terms of specific research question of interest, overall design, exposure assessment, outcome ascertainment, and analytic methods. Thus, even the most thoughtful and rigorous review may be of limited value if the underlying literature includes investigations that address different hypotheses and are beset by methodological inconsistencies and limitations. Issues identified in this review of reviews illustrate considerable challenges that are facing assessments of epidemiological evidence.

A protocol for a systematic review to identify allergenic tree nuts and the molecules responsible for their allergenic properties.

Food regulations require that tree nuts and derived ingredients are included on food labels in order to help individuals with IgE-mediated allergies to avoid them. However, there is no consensus regarding which tree nut species should be included in this definition and specified on food labels. Allergen detection methods used for monitoring foods target allergen molecules, but it not clear which are the most relevant molecules to choose. A modified population-exposure-comparators-outcome (PECO) approach has been developed to systematically review the evidence regarding (1) which allergenic tree nuts should be included in food allergen labelling lists and (2) which are the clinically relevant allergens which should be used as analytical targets. A search strategy and criteria against which the evidence will be evaluated have been developed. The resulting evidence will be used to rank tree nuts with regards their ability to cause IgE-mediated allergies, and allergen molecules regarding their capacity to elicit an allergic reaction. The results of the systematic review will enable risk assessors and managers to identify tree nut species that should be included in food allergen labelling lists and ensure analytical methods for determination of allergens in foods are targeting appropriate molecules.

An Anatomic Study of the Percutaneous Endoscopically Assisted Calcaneal Osteotomy Technique to Correct Hindfoot Malalignment.

BACKGROUND: Open calcaneal osteotomy using traditional methods is associated with complications such as sural nerve injury and potential wound healing problems. We hypothesized that by using novel minimally invasive techniques, these potential risks could be mitigated. This anatomic cadaveric study serves to assess the safety of percutaneous endoscopically assisted calcaneal osteotomy (PECO) compared to a traditional open osteotomy technique. METHODS: Anatomic safety of PECO was assessed using 8 fresh-frozen cadaver below-knee specimens. Lateral calcaneal nerve (LCN) damage was primarily noted and then secondly compared to a potential open surgical incision approach. RESULTS: Only 1 of 11 LCN branches (n = 8 limbs) was transected using PECO, compared to up to 8 of 10 LCN branches (n = 6 limbs) that potentially would have been injured during open surgery. CONCLUSIONS: Percutaneous endoscopically assisted calcaneal osteotomy is a minimally invasive technique that had fewer nerve injuries in this cadaveric model than traditional open surgery. CLINICAL RELEVANCE: Percutaneous endoscopically assisted calcaneal osteotomy due to its less invasive nature may result in fewer neurovascular injuries relative to an open procedure.

<b>6. Recommendations and Results of Activities for the RMP from the Japan Pharmaceutical Manufacturers Association Data Science Expert Committee </b> / 薬剤疫学

MHLW released a guideline for Risk Management Plan (RMP) in April 2012, in order to manage the risk of pharmaceutical products from the development stage towards post marketing period. The guideline suggests to determine Safety Specification and to develop Pharmacovigilance Plan (PVP) and Risk Minimization Plan aligned to the ICH E2E guideline. However, in some of the RMPs, which had been published online (as of August 2014), conventional (Special) Drug Use Results Surveys are planned as a “universal” PVP regardless of the impact, severity and characteristics of the risks. Our JPMA taskforce (Data Science Expert Committee) summarized report and published in August 2014. In this report, we explained how to evaluate safety events based on evidence level for safety specification and how to develop PVP. Also, we would like to propose KAIZEN activities for RMP improvement as follows: <br>1. In order to clarify the research question, rationale and evidence for safety specification should be evaluated carefully. <br>2. It is essential to be considered in advance how to collect and analyze the safety data for detecting safety specification during clinical development. <br>3. Safety profiles should be discussed thoroughly on DSUR development among stakeholders in order to clarify safety specification at NDA. Research questions for each different risk and missing information should be established according to PECO, which will flow into appropriate PVP planning. <br>4. Continuous PDCA cycling is critical for RMP. The first survey or research will bring you next research question (s). <br>We expect all stakeholders, including clinical development specialists in industry, regulatory authorities, and academia, to have better understating of RMP principle and to manage and implement it more appropriately in a scientific manner.

Photoelectrocatalytic degradation of carbamazepine using Ti/TiO2 nanostructured electrodes deposited by means of a pulsed laser deposition process.

The objective of the present work is to evaluate the potential of photoelectrocatalytic oxidation (PECO) process using Ti/TiO2 for the degradation of carbamazepine (CBZ). Ti/TiO2 prepared by pulsed laser deposition (PLD) has been used as a photo-catalyst in a photoelectrocatalytic cell. The PLD TiO2 coatings were found to be of anatase structure consisting of nanocrystallites of approximately 15nm in diameter. Factorial and central and extreme composite design methodologies were successively employed to define the optimal operating conditions for CBZ degradation. Several factors such as current intensity, treatment time, pollutant concentration and cathode material were investigated. Using a 2(4) factorial matrix, the best performance for CBZ degradation (53.5%) was obtained at a current intensity of 0.1 A during 120min of treatment time and when the vitreous carbon (VC) was used at the cathode in the presence of 10mgL(-1) of CBZ. Treatment time and pollutant concentration were found to be very meaningful for CBZ removal. The PECO process applied under optimal conditions (at current intensity of 0.3A during 120min in the presence of 10mgL(-1) of CBZ with VC at the cathode) is able to oxidize around 73.5% ±2.8% of CBZ and to ensure 21.2%±7.7% of mineralization. During PECO process, CBZ was mainly transformed to acridine and anthranilic acid. Microtox biotests (Vibrio fisheri) showed that the treated - effluent was not toxic. The pseudo-second order kinetic model (k2=6×10(-4)Lmg(-1)min(-1)) described very well the oxidation of CBZ.

Functional imaging of cerebral perfusion.

The functional imaging of perfusion enables the study of its properties such as the vasoreactivity to circulating gases, the autoregulation and the neurovascular coupling. Downstream from arterial stenosis, this imaging can estimate the vascular reserve and the risk of ischemia in order to adapt the therapeutic strategy. This method reveals the hemodynamic disorders in patients suffering from Alzheimer's disease or with arteriovenous malformations revealed by epilepsy. Functional MRI of the vasoreactivity also helps to better interpret the functional MRI activation in practice and in clinical research.

The Difference between End-tidal and Arterial PCO2 in Anesthetized Patients / 대한마취과학회지

The relationship between end-tidal carbon dioxide tension(PECO2) as measured by infrared analysis(Datascope Accucap, U.S.A.) and arterial carbon dioxide tension(PaCO2) during general anesthesia was systemically examined in fifty relatively healthy patients(ASA class 1). Body temperature was measured to determine the variation in PaCO2 minus PECO2. The results were as follows: 1) The mean PEzCO2 was 26.2+/-0.7 torr. 2) The mean PaCO2 was 31.6+/-0.8 torr. 3) The average of PaCO2 minus PECO2 was 5.1+/-0.6 torr. 4) PaCO2 was directly related to PECO2. An equation was obtained by simple regression analysis to predict PaCO2. PaCO2=0.899. PECO2+7.57(r=0.715; p<0.01). 5) Body temperature (between 34.3 degrees C and 37.9 degrees C) was not related to PaCO2 minus PECO2 (r=0.1). I thought that measurement of PECO2 is very simple and a guideline of ventilation of the patients in anesthesis and ICU.