Antiplatelet therapy is the key point in the treatment of cardiovascular and cerebrovascular diseases. Effective and safe antiplatelet therapy can avoid the risk of thrombosis or bleeding again. Herbal and Western medicine combined with antiplatelet therapy for ischemic cardiovascular events is a common phenomenon in clinical application, and more and more animal experiments, in vitro cell experiments, and randomized controlled clinical studies have also clarified the efficacy and interaction mechanism of the combination and safety. Herbal and Western medicine combined with antiplatelet therapy has made some progress in improving aspirin resistance and clopidogrel resistance, enhancing antiplatelet and antithrombotic effect, and reducing gastrointestinal adverse reactions caused by antiplatelet drugs. Both of them play the role of antiplatelet and antithrombotic by reducing platelet adhesion, inhibiting platelet activation and aggregation, and inhibiting platelet release, and the combination of drugs is safe. This article elaborates and analyzes the application progress and prospect of Chinese and Western medicine combined with antiplatelet therapy, in order to provide more theoretical support for future research. According to the data of “Chinese Cardiovascular Health and Disease Report” , it is ePanax notoginseng and red ginseng decoction can improve the bioavailability of aspirin in vivo [With the increasing use of antiplatelet drugs such as aspirin or clopidogrel in combination with herbal or Chinese patent medicine, the study on the pharmacokinetics of the absorption, distribution, metabolism, and excretion characteristics of various active ingredients in drugs in vivo is also increasing . Based o in vivo , 7.Salvia miltiorrhiza capsule on clopidogrel pharmacodynamics and pharmacokinetics in the human body and the influence of 20 healthy subjects who selected oral dose of clopidogrel and Salvia miltiorrhiza capsules and clopidogrel together, and the results found that clopidogrel in the combination group and its active metabolites of pharmacokinetic parameters changed, Salvia miltiorrhiza capsule induction of the metabolism of clopidogrel occurred, and the antiplatelet effect of clopidogrel was weakened. At the same time, in vitro study results showed that the two active components (cryptotanshinone and tanshinone IIA) in Salvia miltiorrhiza capsule could change the pharmacokinetic parameters of clopidogrel by enhancing the activity of CYP3A4 enzyme and inducing its protein expression, thus exploring the pharmacokinetic and pharmacodynamics mechanism in human body. Xiao et al. [The study of pharmacokinetics of antiplatelet therapy combined with herbal and Western medicine is of great significance to guide rational drug use in clinic. At present, it is generally believed that herbal affects the in vivo process of Western medicine mainly by inducing or inhibiting the activity of drug metabolism enzymes and/or transporters . Zhou 99 researco et al.  found thThis information is of great significance to the further application of the integration of herbal and Western medicine in clinical practice. The pharmacokinetics of the combination of herbal and Western medicine is worth further clinical verification due to the complexity of the composition of herbal and the difference of varieties.In the treatment of cardiovascular and cerebrovascular diseases, commonly used antiplatelet drugs include cyclooxygenase inhibitors such as aspirin, adenosine diphosphate (ADP) P2Y12 receptor blockers such as clopidogrel and platelet membrane glycoprotein IIb/IIIa (GP IIb/IIIa) receptor antagonists such as tirofiban. Antiplatelet drugs can inhibit platelet aggregation and antithrombotic effect by acting on a certain target and pathway. However, in clinical practice, some patients may express platelet resistance events after taking antiplatelet drugs. Platelet resistance refers to patients with reduced or no response to antiplatelet drugs, resulting in ischemic cardiovascular and cerebrovascular events, including aspirin resistance and clopidogrel resistance . Studies2 (TXA2) and prostaglandin I2 (PGI2), reduce platelet adhesion and aggregation, and then inhibit thrombosis. Wu [Panax notoginseng saponins. Modern pharmacology has proved that Xuesaitong capsule can block calcium channel, inhibit platelet aggregation, and increase cerebral blood flow [Modern pharmacological experiments of Xuefu Zhuyu  decoctioosis. Wu  observedood flow . Throughood flow  found thood flow  observedood flow  observedood flow , through2 (TXB2) levels and enhance the antiplatelet and antithrombotic effect. Zhang and Zhu [Antiplatelet drugs can inhibit platelet adhesion, activation and aggregation, and reduce cardiovascular and cerebrovascular events. The study found that traditional Chinese medicine combined with antiplatelet drugs can enhance the antiplatelet and antithrombotic effect and reduce the incidence of thrombotic events, which has a good clinical prospect . Zhu et  and Zhu  observed and Zhu  observed and Zhu  carried 2 and also inhibits the synthesis of PGI2, leading to original ulcer bleeding [Panax quinquefolium (PQS) combined with DAPT on gastric mucosal injury in rats with acute myocardial infarction and found that PQS combined with DAPT can enhance the defense and repair function of gastric mucosal barrier, reduce gastrointestinal erosion and bleeding, and reduce the score of dyspepsia, and its mechanism is related to the upregulated expression of cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), prostaglandin I2 (PGI2), and VEGF in gastric tissue. Yu et al. [2/PGI2. Bai et al. [Sedum notoginseng on gastric hemorrhage model mice established by intragastric administration of aspirin and found that Sedum notoginseng can increase the number of platelet and platelet membrane GP IIb/IIIa receptors, promote platelet activation, and have hemostatic effect on gastric hemorrhage caused by aspirin. Other traditional Chinese medicines for promoting blood circulation and removing blood stasis have also been proved to protect gastric mucosal damage caused by antiplatelet drugs [Clinically, the gastrointestinal adverse reactions caused by antiplatelet drugs are very common, such as nausea, vomiting, epigastric discomfort, or pain. Long-term use of antiplatelet drugs is easy to cause gastric mucosal damage, causing gastric ulcer and gastric bleeding . Recent bleeding . Clopidobleeding . Kou et bleeding  observedu et al.  found thi et al.  observedet drugs . For exaet drugs .The combination of herbal and Western medicine has significant advantages in improving antiplatelet drug resistance, enhancing antiplatelet and antithrombotic effect, and reducing adverse reactions of antiplatelet drugs, which is the embodiment of the theory of treating the same disease with different methods and treating different diseases with the same method.Intact vascular endothelium can inhibit platelet adhesion, so when vascular endothelium is damaged, platelets are activated, leading to the activation of membrane glycoprotein receptor on the surface of platelets. The activated membrane glycoprotein receptor combines with a series of substances, such as von Willebrand factor, fibronectin, and collagen, causing platelets adhere to each other. After platelets adhere to endothelial cells, the morphology of platelets changes. Under the induction of aggregation agents such as ADP, thrombin, platelet activating factor (PAF), collagen, and histamine, a series of biochemical reactions occur, which aggravate the adhesion and aggregation of platelets and eventually lead to thrombosis. Therefore, the protection of vascular endothelial cells and inhibition of the binding of aggregator and receptor are two ways to reduce platelet adhesion.Panax notoginseng saponins combined with DAPT treatment, it can raise the PI3K/Akt pathway of endothelial cells, reduce the apoptosis of endothelial cells, and inhibit the platelet adhesion induced by endothelial injury. Lu et al. [Panax notoginseng saponins combined with DAPT have protective effects on ox-LDL induced apoptosis of human umbilical vein endothelial cells and can improve endothelial platelet adhesion. Zhou et al. [2 under the condition of myocardial ischemia, increase the secretion of vascular protective factor NO, and improve vascular endothelial function, which has good clinical efficacy. In a clinical trial involving patients with ACS [Ge et al.  observedu et al.  found thu et al.  found thwith ACS , in addi2+ concentration is the key to platelet activation. Reducing the concentration of free Ca2+ can inhibit platelet activation. Study [Intracellular Can. Study  found th2 (PGH2) under the action of COX-1 and COX-2, and the latter synthesizes and releases TXA2, PGI2, and PGE2 under the action of corresponding enzymes. TXA2 has a short biological half-life and can be metabolized rapidly to TXB2, which can promote vasoconstriction and platelet aggregation; the metabolite of PGI2 is 6-keto-PGF1α, which can promote local vasodilation and inhibit platelet aggregation. Therefore, the imbalance of TXA2/PGI2 is one of the important causes of platelet aggregation and thrombosis. Hong [2 in the combination group were significantly lower. Zou et al. [2 level of Trichosanthes kirilowii combined with the aspirin group was significantly lower, and compared with the aspirin group, TXB2/6-keto- PGF1α of the combined medium and high-dose groups could be significantly improved and tended to be normal, indicating that the combined therapy can better inhibit platelet activation and aggregation. Kou et al. [2 pathway in platelets and the upregulation of the COX/PGI2 pathway and activating the fibrinolytic system.After platelet activation, free AA is transformed into prostaglandin His. Hong  exploredu et al.  found thu et al.  found thcAMP and cGMP in platelets are the inhibitory second messengers of various aggregation agents and platelet-specific receptors, which can inhibit platelet aggregation by increasing the concentration of cAMP and cGMP in platelets. Fan et al.  studied 2, TXB2, phospholipase Cβ3, phospholipase Cγ2, the activity of COX-1 and TXA2 synthase, and the phosphorylation of proteins. At the same time, these factors in turn promote platelet aggregation [After stimulation, platelets activate and release P-selectin (CD62P), serotonin, and AA, which can in turn lead to the release of TXAregation . TherefoPaeonia lactiflora, artificial borneol, Panax ginseng, and other kinds of Chinese medicine, and multiple traditional Chinese medicine combinations play the role of multitarget therapy [He et al.  found th therapy . Zhang e therapy  studied Salvia miltiorrhiza dropping pills to clopidogrel-resistant patients and found that compound Danshen dripping pills could further inhibit platelet function, and no bleeding complications such as gastrointestinal bleeding and cerebral hemorrhage occurred, and no liver and kidney function damage was found after treatment. It provides a certain basis for the safety of compound Danshen dripping pills in clinical application. Liu et al. [The combined use of herbal and Western medicine for antiplatelet treatment of cardiovascular events has definite efficacy, but whether the combined use will cause bleeding, aggravation of gastrointestinal damage, and other safety issues have also attracted attention. Therefore, more and more studies have proved the safety of the combined use. Compound Danshen dripping pills are widely used in the treatment of coronary heart disease. Chen et al.  applied u et al.  found thIn recent years, Chinese and Western medicine combined with antiplatelet therapy has made some progress in improving aspirin resistance and clopidogrel resistance, enhancing antiplatelet and antithrombotic effect, and reducing gastrointestinal adverse reactions caused by antiplatelet drugs. Both of them play the role of antiplatelet and antithrombotic by reducing platelet adhesion, inhibiting platelet activation and aggregation, and inhibiting platelet release and the combination of drugs is safe.Different from the characteristics of modern antiplatelet drugs acting on a single target and single pathway, antiplatelet therapy of traditional Chinese medicine has the characteristics of multicomponent, multitarget, and multilink. Animal experiments and in vitro cell experiments have explored the interaction mechanism of Chinese and Western medicine combined with antiplatelet from many aspects. At the same time, a number of randomized controlled clinical trials , 51 arou


The shortage of medicines represents a complex global phenomenon that triggers patient care and safety issues. The study was undertaken to explore the impact of medicines shortages on patients in Pakistan. The study also identified barriers which hinder the solutions of medicines shortages issue.A qualitative study design was adopted and the data was collected in stages between July and September 2019using an in-depth interview approach. The purposive and convenient sampling strategy was used to recruit the study participants. Sample size was limited by using the saturation point criteria. All interviews were audio-recorded, transcribed verbatim, and analyzed using thematic analysis.A total of 35 stakeholders including 13 physicians, 12 pharmacists and 10 patients participated in the study. The findings of the study were classified into five key themes and seven subthemes. The five themes included, ‘impact of medicine shortages on patients’, ‘patients’ practices in response to medicine shortages’, ‘influence of medicines shortages on medical practice or pharmaceutical business’, ‘barriers to solutions for medicines shortages’, and ‘suggestions to assuage the impact of medicine shortages.’This study showed that the medicine shortages had significant clinical and financial impact on patients. Patients’ opted for a number of risk-prone practices to avoid treatment disruption during shortages. An array of pharmaceutical market, medicines quality and patient related factors refrain physicians to switch from brand name medicine to generics and lead to ineffective management of medicines shortages. Promotion of generic prescription, implementation of punitive policies and proper patient consultation was advised to assuage the impact of medicine shortages on patients.The adverse clinical, economic and humanistic impact affirmed in this study demand the introduction of risk-management strategies for medicines shortages in hospital and community settings in accordance with the international standards. Promotion of effective patient counselling by the healthcare professionals to deter risk-prone practices associated with medicines shortages is mandatory.The online version contains supplementary material available at 10.1186/s12913-021-06812-7. Access to affordable essential medicines is a fundamental human right and Target 3.8 of the Sustainable Development Goals . NeverthConsidering the complexity and kaleidoscopic nature of the problem, the International Pharmaceutical Federation has advocated country-specific investigations to assess various aspects of medicines shortages in-order to effectively curb them . HoweverNot an exception, Pakistan has long struggled with inadequate access to essential medicines , 24. AppThis study was conducted in the district of Bahawalpur, Punjab, Pakistan. Bahawalpur is the 12th largest city of Pakistan with an approximate population of 3,333,467 people . To cateA qualitative methodological approach was applied to explore the views of patients, pharmacists and physicians regarding impact of medicines shortages on patients. In-depth interview approach was selected to achieve the study objectives because this approach is suitable to explore untouched issues and effectively translate the interviewees’ viewpoints and experiences . The ConPurposive sampling accompanied by convenience sampling was used to engage participants . In the The interview schema , and were recorded on an audio tape. The senior authors frequently debriefed the interviewing author (AS), to ensure the standardized administration of the interview guide, and thereby enriching the quality and trustworthiness of the data. The sample size was determined by applying the saturation point criteria . A totalThe data from HCPs and patients were separately subjected to thematic analysis . The audA total of 43 participants  were invited to participate in the study. Of these, seven refused due to their busy schedule, while 35 agreed to participate in the study. In all, we conducted interviews with 13 physicians and 12 pharmacists and 10 patients. Among 13 physicians, nine were male and four were female. Pharmacists were distributed equally in each gender category . Of the total 10 patients, six were male and four were female, and half had secondary level of education. The average duration of interviews with physicians, pharmacists and patients was 24 min (SD = 3.2), 28 min (SD = 3.7) and 22 min (SD = 3.4), respectively. Physicians and pharmacists had an average experience of 7.9 years and 3.8 years, respectively. The respondents’ characteristics are given in Table The analysis of the data extracted from interviews yielded five key themes and seven subthemes. The themes covered ‘impact of medicine shortages on patients’, ‘patients’ practices in response to medicine shortages’, ‘influence of medicines shortages on medical practice and pharmaceutical business’, ‘barriers to solutions of medicines shortages issue’, and ‘suggestions to assuage the impact of medicine shortages’. The summary of the findings is provided in Fig. Almost all the study participants had health related concerns about the patients. According to them, medicines shortages adversely impact patients. From a clinical point of view, most HCPs (23 out of 25 HCPs) highlighted compromised treatment (20 out of 25 HCPs), medication safety issues (18 out of 25 HCPs) and risk of mortality (14 out of 25 HCPs) as the consequences of medicine shortages. According to them, medicine unavailability contributed to treatment delays, disease proliferation and complications, and treatment failure. Further, they elaborated that shortages can place patient at increased risk of medication safety, such as wrong therapeutic alternatives, medication errors and adverse drug reactions. Likewise, patients reported compromised patient care and treatment delays (7 out of 10 respondents), adverse events (8 out of 10 respondents) and high risk of mortality (9 out of 10 respondents) when questioned about whether they had experienced any consequences because of medicines shortages. In addition to the clinical impact, both HCPs (21 out of 25 respondents) and patients (9 out of 10 respondents) implied that shortage cause financial burden on patients, and humanistic impact in the form of confusion and wastage of time.The overlapping theme (Theme 1), respective subthemes and categories, together with illustrative quotes are presented in Table When asked whom they consult in order to avoid disruption of their treatment during medicines shortages, five patients reported seeking physician consultation. The majority of the patients (8 out of 10 patients) preferred non-pharmacist pharmacy workers for consultation, and only (4 out of 10 patients) reported having consulted a pharmacist amid shortages. Patients asserted that they prefer non-pharmacist pharmacy workers because of their good knowledge and way of medication related counseling. Other practices opted by a plethora of patients included self-decision about alternative brands (8 out of 10 patients), exploring the internet (6 out of 10 patients), asking for family or friend advice (5 out of 10 patients) and forgoing treatment (3 out of 10 patients). The patient specific theme (Theme 2), respective subthemes and categories, together with illustrative quotes are presented in Table When physicians were asked if they had encountered challenges in the event of medicines shortages, nine out of 13 physicians reported personal dissatisfaction and loss of their credibility among patients. From an economical point of view, the majority of HCPs (20 out of 25 HCPs) indicated that shortages of medicines often lead to financial losses for providers and pharmaceutical business. They were of the view that financial losses due to consistent short medicines sometimes compel them to switch to alternative brand to avoid same loss in future. However, this may impact patient management due to differences in efficacy and lack of patient’s psychological acceptance or dissatisfaction.According to the healthcare professionals, an array of barriers contributed to ineffective solution of medicines shortages problem, thereby negatively influencing the desired patient outcomes. Major reasons that refrained physicians from switching to alternative generics during shortages included excessive advertisement and promotional campaigns of short brands (25 out of 25 HCPs) and availability of inferior quality alternatives (24 out of 25 HCPs). Further, stakeholders indicated that it was challenging for them to minimize the impact of shortages by switching to alternate brand because of patient psychological acceptance and rigid perception about efficacy of a particular short brand. With regard to hospitals, many healthcare professionals (15 out of 25 HCPs) reported difficulties in correctly selecting and procuring important medicines and the consequent inexorable shortage of high demand medicines due to poor collaboration and communication between physicians and pharmacists.Stakeholders reported a number of potential ways to assuage the impact of medicine shortages. Among these, the key suggestion for addressing medicines shortages was enactment of generic prescription in the country or prescription of medicines by international nonproprietary name (INN) (24 out of 25 HCPs), and check and balance on pharmaceutical promotion to avoid incentives driven irrational prescription of short brand (22 out of 25 HCPs). Upon further exploration, the participants indicated the physician as having the responsibility to offset the issue through educating patients about the efficacy of alternative brands (18 out of 25 HCPs), and staying up-to-date on the unavailability of any brands in the market (13 out of 25 HCPs). With regard to management of shortages in hospitals, collaborative efforts of physicians and pharmacists to better procure, select cost-effective alternative brands and optimize selected alternative therapy were stressed by more than half of the respondents (14 out of 25 respondents).All healthcare professionals’ specific themes , respective subthemes and categories, together with illustrative quotes are presented in Table The consequences of medicines shortages are challenging, especially for the patients and healthcare system of LMICs, including Pakistan , 41, 43.The participants in this study reported many clinical implications of medicines shortages. According to them, the impact on patients could be altered dosage regimen, disease proliferation and complications, medication errors, adverse drug events and high risk of mortality due to inappropriate alternatives, and substandard and counterfeit medicines. Correspondingly, all patients interviewed in this study confirmed that they had experienced these consequences owing to shortages. These were fully supported by published scoping reviews sought to assess the impact of medicines shortages on patient outcomes , 15. BeyIn addition to clinical consequences, the study participants reported medicines shortages being a problem for patients in terms of increased treatment costs and out-of-pocket expenses. These findings highlighted more pronounced clinical impact of medicines shortages on patients due to increased likelihood of abandoned treatment, as up to 25% of Pakistani people live below the poverty line and cannot bear out-of-pocket expenses , 46. SimAnother important theme that arose from the data was patients’ practices in response to medicines shortages. A plethora of patients reported that they preferred consultation with non-pharmacist pharmacy workers followed by consultation with physicians and pharmacists, to prevent harm and interruption of their treatment. The reason for their inclination towards non-pharmacist pharmacy workers may be due to ease of access to dispensers, high consultation fees of physicians, and lack of awareness about pharmacists driven by their limited availability in hospital and community settings , 52. HowIn this study, several barriers contributing to the ineffective solution of medicines shortages and relevant suggestions were also reported by the healthcare professionals. According to them, major reasons that refrain physicians from switching to alternative generics during shortages were excessive advertisement and promotional campaigns of those brands which were short in supply. In several instances these brands were of inferior quality. These barriers are attributable to lax regulatory infrastructure, the unavailability of national guidelines for the prescription of generics, and the questionable quality of generics owing to the lack of bioavailability or bio-equivalence studies , 55, 56., thereby remedying shortages. With regard to hospitals, healthcare professionals suggested improved collaboration and communication between physicians and pharmacists. This was reportedly because of the need to better procure, and select the alternative therapy. The importance of this suggestion can be gauged by the fact that pharmacists around the world are utilizing their problem-solving skills and collaborating with prescribers and nurses in hospitals during COVID-19 pandemic. They preserve medicines prone to shortage by identifying possible alternatives, optimizing selected therapy and reducing wastage of important medicines [In this regard, the study participants recommended generic prescribing, regulatory check and balance on promotional agreements between pharmaceutical companies and physicians, and selection of better alternative in collaboration with pharmacists. These suggestions were also strongly advocated in previous studies from Pakistan, Malaysia and Taiwan , 55–58. edicines –67. Howeedicines , 68–70.This study successfully filled out the gap particularly concerning patient experiences regarding medicines shortages, and views of physicians and pharmacists on the impact of medicines shortages in Pakistan. However, there are a few limitations in this study. First, the participants in the study were all from one city. Second, some important stakeholders, for example, nurses, manufacturers, health regulators and distributors were not included in this study. Third, the findings of this preliminary study, though have provided solid foundation for future research, might have understated or overstated the impact of medicines shortages due to biasness. However, to generate more reliable evidence, it is strongly advised that future studies should involve all stakeholders from different cities and perform broad quantitative surveys to visibly estimate the impact of medicines shortages on patients.This study revealed that access to medicines in Pakistan continues to be problematic with adverse clinical, economic and humanistic effects on patients. Patients opt for a number of risk-prone practices to avoid treatment disruption during shortages. An array of pharmaceutical market, medicines quality and patient related factors refrain physicians from switching brand to available generic medicines, which in turns leads to ineffective resolution of medicines shortages. Promotion of generic prescription, active involvement of pharmacists in healthcare delivery system, implementation of effective policies and proper patient consultation are advised in this context.In addition to the implications of this study for the literature, insights about various aspects can be gleaned from the findings and may help concerned stakeholders to justify legislative change and interventions.Taken as a whole, the adverse consequences of medicines shortages urgently require the introduction of risk-assessment and risk-management strategies in hospital and community settings in accordance with the international standards. Moreover, a harmonized impact scoring system is mandatory to streamline the efforts targeted at medicines shortages issue. To deter risk-prone patient practices, patients should be deftly counseled by the prescribers and made aware of the generics, management approaches they should follow, and to whom they should communicate during shortages.In order to minimize the influence of medicines shortages resulting from excessive promotional campaigns on solution to medicines shortages, strict enforcement of punitive polices and logical implementation of generic prescribing policy could be considered on priority basis.The study findings strongly advocate future large scale quantitative studies to measure the extent and overall harm of medicines shortages in order to inform decision makers and address the problemsAdditional file 1. COREQ checklist.Additional file 2. Interview schema of physicians, pharmacists and patients.


Growing concerns about the circular economy and sustainable waste management for civil applications of non-hazardous mineral industrial waste have increased in recent years. Therefore, this study presents a trend analysis of industrial waste generation and treatment during the years of 2010–2020, and focused on promotion policies and regulatory measures for mandatory renewable resources from industrial sources in Taiwan, including reclaimed asphalt pavement (RAP) material, water-quenched blast furnace slag, and ilmenite chlorination furnace slag. According to the official database of the online reported statistics during the period of 2010–2020, approximately three million metric tons per year of renewable resources were totally reused in civil engineering or related cement products, reflecting a balanced supply chain in the domestic market. Among these, water-quenched blast furnace slag accounted for about 90% (about 2.7 million metric tons) in Taiwan. Currently, the legislative framework of sustainable waste management in Taiwan is based on the Waste Management Act and the Resource Recycling Act, but there are some problems with them. In order to effectively reduce environmental loadings and conserve natural resources to mitigate climate change, some recommendations are addressed from different points of view. Situated to the east of mainland China, and as an export-dependent economy of 23.4 million people, Taiwan has shown rapid industrial development over the past few decades and now occupies a strategic position in global supply chains, such as those of microchips and information and communication technology (ICT) products. However, the enormous economic development in Taiwan has resulted in a greater complexity of industrial waste management during this period. Before the Taiwan government revised the Waste Management Act in 1999, businesses either had to dispose of their waste on their own or commission government departments. At that time, industrial waste was often abandoned illegally and/or exported to other Asian countries due to incompetent government administrations, insufficient capacity of waste treatment facilities, and the high cost of hazardous waste treatment , the TaiIn order to significantly reduce environmental loading and effectively reuse available materials from waste resources for the targets of zero waste ,14,15 anAs reviewed above, it was seldom found in combination with a description of the current status and regulatory measures of renewable resources from industrial waste in Taiwan’s engineering applications. Therefore, this paper firstly analyzed the trends of industrial waste generation and treatment during the period of 2010–2020; furthermore, an updated status of the announced renewable resources that can be reused in civil engineering was also discussed in the study. Finally, regulatory promotion of renewable resource reused in civil engineering was addressed to echo a case study in the establishment of Environmental Science and Technology Parks (ESTP).The main purposes of this study were to analyze the updated status of industrial waste and announced renewable resources , and further address regulatory measures for promoting them in civil engineering applications. Therefore, a statistical database, recycling and reuse, and regulatory measures relevant to the announced renewable resources are briefly summarized below.Activity (statistics and status) of industrial waste generation and treatment:The updated data on the statistics and status of industrial waste generation and treatment in Taiwan were obtained from the official yearbook  and websActivity (statistics and status) of renewable resources reused in civil engineering:In order to highlight the recycling and reuse of renewable resource in Taiwan, the updated data on the statistics and status of the announced items  reused in civil engineering were also accessed on the official website .Regulatory measures for the renewable resources and the establishment of ESTP:Information about the regulatory measures for the announced renewable resources was accessed on the relevant website . In addiBased on the Waste Management Act in Taiwan, there are two categories of industrial waste , which refer to waste generated from industry activities, but excludes waste generated by the employees of those industries themselves. Herein, the industry activities include agricultural, industrial and mining plants and sites, construction enterprises, medical/hospital/clinic organizations, public and private waste management  organizations, joint industrial waste treatment organizations, laboratories of schools or agency groups, and other enterprises designated by the central competent authority. General (non-hazardous) industrial waste is composed of movable solid, liquid substances, or objects other than hazardous industrial waste. In contrast, hazardous industrial waste is legally identified by its toxic characteristics and hazardous substances due to their negative impacts on human health and the environment when it is not managed properly. The central competent authority as referred to in the act means the EPA. It should be noted that radioactive waste management is in accordance with the relevant atomic energy regulations, such as the Ionization Radiation Protection Act.2) sludge. Currently, this sludge is reused as raw cement material in Taiwan [In July 1999, the act was revised to promulgate a legal framework for industrial waste management, thus formulating the “National Industrial Waste Management Program”, the “Industrial Waste Control Center”, and the online reporting system that has tracked the complete life cycle of industrial wastes since 2001 from the generation source to the final disposal. On the other hand, the Resource Recycling Act was newly enacted to further promote recycling and reuse of so-called renewable resource, which are produced or derived from general industrial waste. Currently, there are three renewable resources announced by the central industry authorities, reclaimed asphalt pavement material, quenched blast furnace slag, and ilmenite chlorination furnace slag. n Taiwan .As described above, industrial waste management in Taiwan started with the implementation of the Waste Management Act, which has been revised several times. According to the official definition of industrial waste treatment, the term “treatment” refers to three methods, immediate treatment , final disposal , and reuse. The term “reuse” is defined as “the reuse of industrial waste produced by an enterprise as raw material, materials, fuel, land reclamation fill, or other reuse methods recognized by the central industry competent authority via self-use, sale, transfer, or commissioning, and in compliance with the related regulations”. Under the authorization of the Resource Recycling Act, a so-called “renewable resource” is defined as “the announced substances that have lost their original usefulness, are economically and technologically feasible to recycle, and may be recycled or reused” . Herein,2)-making, and rotary kiln in the thermal reuse treatment of steelmaking dust. Currently, slags from water-quenched blast furnace steelmaking and ilmenite chlorination furnace TiO2-making have been listed as “renewable resources” by the central industry competent authority . In Taiwan, water-quenched blast slag powder (after being ground) is blended with cement to replace general cement and is widely applied in various kinds of construction projects. On the other hand, RAP comes from oil-based tar (a fossil resource). RAP materials were derived from frequent milling and overlay activities for roads, and thus are produced in considerable amounts annually. In Taiwan, experience has indicated that the recycling of bitumen binder in RAP is a circular economy approach from technical, economical, and environmental viewpoints [In fact, there are many different slags from manufacturing industries in Taiwan, including electric arc furnace steelmaking, induction furnace steelmaking, cupola furnace steelmaking, water-quenched blast furnace steelmaking, basic oxygen furnace (BOF) steelmaking, ilmenite chlorination furnace titanium dioxide  and the Resource Recycling Act . The cenIn Taiwan, industrial waste management started with the promulgation of the Waste Management Act in 1974, which has been revised several times to comply with the domestic industrial structure and international trends. When established in 1987, the EPA began to put emphasis on industrial waste minimization (or cleaner production) and also set up a permit system concerning waste generation sources and waste treatment organizations. In recent years, the waste management concept has shifted to source reduction approaches, such as circular economy, sustainable materials management (SMM) and cradle-to-cradle (C2C). In order to promote industrial waste recycling and reuse, the regulatory measures and incentives have been incorporated into the act, which will be briefly described below.1.-The product is determined to be of no economic or market value by the EPA, and is intended to be disposed of illegally or harmful to the environment and human health.-The product is not lawfully stored or used, and is intended to be disposed of illegally or causing pollution.-The recycled/reused product is not used in accordance with this act, and is intended to be disposed of illegally or causing pollution.Any product from industry activities shall be determined as waste when it is under any of the following circumstances:2.Industrial waste management, with the exception of that subject to recycling/reuse methods, shall be performed in accordance with the methods of self-treatment, joint treatment and commissioned treatment.3.Industrial waste reuse shall be processed in accordance with the regulations promulgated by the central industry competent authorities or central competent authority. As listed in 4.The expenses incurred by the enterprise to waste management should be partially exempted from tax. Furthermore, the enterprises that are in compliance with relevant waste management regulations and with excellent performance in the waste reduction, recycling, and reuse shall be rewarded by the EPA and the central industry competent authority.The disposal of industrial waste, with the exception of that subject to reuse methods, shall be performed in accordance with the following methods:1.To promote the recycling and reuse of renewable resources, the public organizations shall preferentially procure the government-certified environment-friendly products, domestic renewable resource, or recycled products in which contain a certain proportion of renewable resource. Therefore, the EPA requested relevant government agencies to consider the possibility of using products made from recyclable and reusable waste materials in their public construction projects. Through the efforts of these government agencies, the usage of such products in public construction has been increased gradually. As listed in 2.The EPA shall regularly hold the awards for excellence in recycling/reusing technological developments and their actual achievements. The business or enterprise engaged in renewable resource recycling and reusing shall be granted tax incentives (tax deduction) for the cost of investment in research, facilities, tools, and equipment. In this regard, the “Award Ceremony for Excellent Performance of Industrial Waste and Resource Recycling and Reuse” has been held annually. In addition, the EPA held symposiums and exhibitions annually to further share the successful recycling experience with the general public and the industrial sector.3.To promote the recycling and reuse of renewable resources, acquire advanced technologies and talents, and encourage innovative research and development (R&D) technologies by the domestic industry, the EPA in collaboration with the local governments established the environmental science and technology parks , which wIn order to conserve natural resources, reduce waste generation, promote recycling and reuse of materials, and mitigate environmental loading, the Resource Recycling Act was passed on 21 January 2002. The act stipulates that businesses or enterprises must be in accordance with the management regulations when recycling or reusing the designated renewable resources designated by the central industry authority. The current promotion (assistance and incentive) measures for recycling or reusing renewable resources in industry were briefly addressed as follows:Since the 1992 United Nations Conference on Environment and Development (UNCED) held in Rio de Janeiro (Brazil), sustainable development and recycling-oriented societies have become global trends. Thereafter, one of the significant policies was to establish ecological industrial zones by the developed countries for incorporating industrial development into the natural ecological system. In 2001, the EPA started planning the establishment of Environmental Science and Technology Parks (ESTP) for jointly cooperating with local governments. The three main development axes of ESTP are “high-level resource recycling technology”, “high-level environmental protection technology” and “ecological industries”. The ESTP proposal was approved by the Executive Yuan (the Cabinet) on 9 September 2002, and was revised on 11 March 2004. The total budget for the ESTP planning and construction has reached 6.2 billion NT$ (about 0.22 billion US$). In order to successfully develop the ESTP, the EPA and local governments cooperated to construct so-called sustainable ecological communities. In this regard, the EPA was responsible for providing financial incentives to attract enterprises which needed to be reviewed by the examination mechanism and administrative measures. In addition, the EPA also provided tenants and research institutes with rewards for investing in technology development and industrial production of environment-friendly products. By contrast, the local governments were responsible for providing sufficient and suitable land, and administrative services for establishment, recruitment and operations.By the end of 2011, the EPA had established four ESTP zones in Taiwan, as shown in With the implementation of renewable resources recycling and reuse in Taiwan under the authorization of the Resource Recycling Act in 2002, reclaimed asphalt pavement material, water-quenched blast furnace slag, and ilmenite chlorination furnace slag have been listed as “mandatory” recyclables by the EPA for the production of recycled aggregate materials in concrete and construction applications. During the period of 2010–2020, there were approximately three million metric tons of renewable resources reused annually in civil engineering or related cement products, reflecting a balanced supply chain in the domestic market. Currently, these announced renewable resources are completely reused in civil engineering or related products like cement material. This approach, not only reduces the amount of industrial waste disposal, but also recycles the valuable resources. More significantly, this sustainable waste management approach also raised green productivity and drove supply chain sustainability to develop a circular economy.-Combining the Waste Management Act and the Resource Recycling Act into a new act, which will incorporate the 5R  principles towards the ultimate goal of zero waste through total recycling.-Promulgating the specific regulations for high-tech industries  to conduct an industrial symbiosis through industrial waste recycling and cleaner production.-Adding several mineral waste sources  to the lists of renewable resources like electric arc furnace slag, induced current furnace slag, coal ash, and scrap masonry material, which can be reused as available materials in civil engineering.-Providing sufficient economic and financial (tax) incentives in the accounting/cost system of enterprises or businesses based on the performances of sustainable goals (SDGs) or corporate social responsibility (CSR).Currently, the legislative framework of sustainable waste management in Taiwan is based on the Waste Management Act and the Resource Recycling Act. However, there are some problems between them, including unclear definitions , waste generation sources and central competent authorities. In the near future, major sources of industrial waste in Taiwan will be generated from the high-tech industries due to the global supply chains. To further enhance the recycling and reuse of WEEE and mineral industrial waste, the following measures were recommended:


While the recreational use of cannabis has well-established dose-dependent effects on neurocognitive and psychomotor functioning, there is little consensus on the degree and duration of impairment typically seen with medical marijuana use. Compared to recreational cannabis users, medical cannabis patients have distinct characteristics that may modify the presence and extent of impairment. The goal of this review was to determine the duration of acute neurocognitive impairment associated with medical cannabis use, and to identify differences between medical cannabis patients and recreational users. These findings are used to gain insight on how medical professionals can best advise medical cannabis patients with regards to automobile driving or safety-sensitive tasks at work. A systematic electronic search for English language randomized controlled trials (RCTs), clinical trials and systematic reviews  between 2000 and 2019 was conducted through Ovid MEDLINE and EMBASE electronic databases using MeSH terms. Articles were limited to medical cannabis patients using cannabis for chronic non-cancer pain or spasticity. After screening titles and abstracts, 37 relevant studies were subjected to full-text review. Overall, seven controlled trials met the inclusion/exclusion criteria and were included in the qualitative synthesis: six RCTs and one observational clinical trial. Neurocognitive testing varied significantly between all studies, including the specific tests administered and the timing of assessments post-cannabis consumption. In general, cognitive performance declined mostly in a THC dose-dependent manner, with steady resolution of impairment in the hours following THC administration. Doses of THC were lower than those typically reported in recreational cannabis studies. In all the studies, there was no difference between any of the THC groups and placebo on any neurocognitive measure after 4 h of recovery. Variability in the dose-dependent relationship raises the consideration that there are other important factors contributing to the duration of neurocognitive impairment besides the dose of THC ingested. These modifiable and non-modifiable factors are individually discussed. The legalization and decriminalization of cannabis in multiple countries and states has contributed to a wealth of research on the potential therapeutic benefits of cannabis-based medicines –5. In 201) agonists acutely impair psychomotor and neurocognitive domains including attention, manual dexterity, coordination, and reaction time, as CB1 receptors are neuroanatomically expressed in regions responsible for cognitive and motor control  and the second metabolite “11-nor-9-carboxy-tetrahydrocannabinol” (THC-COOH) . The latThere is evidence that medical cannabis patients who use THC regularly develop tolerance to many of the impairing effects of THC . ToleranDetermining the duration of potential THC impairment, and what THC dose a medical cannabis patient should take to minimize neurocognitive impairment, proves to be challenging. There are some unique considerations when studying impairment in medical cannabis patients, defined here as someone who uses cannabis under the guidance of a medical practitioner, compared to recreational cannabis users. Medical cannabis patients often use THC to manage symptoms for a variety of conditions including chronic pain, insomnia, PTSD, autoimmune conditions, and neurological disorders, that induce a certain level of neurocognitive impairment by themselves. By treating these symptoms, their neurocognitive and psychomotor functioning may actually improve. Medical cannabis patients also have different patterns of use, including a more consistent and standardized dosing schedule, along with different expectations and goals . They ofThe aim of the present scoping review was to identify and summarize studies that investigate the duration and degree of acute neurocognitive impairment with medical cannabis use, and to compare this literature with the body of research on neurocognitive impairment in recreational cannabis users –35. Impa* OR dronabinol OR marijuana OR tetrahydrocannabinol OR THC OR Sativex) AND (chronic non? cancer pain OR Chronic Pain/OR muscle spasticity/OR spasticity) AND (impair* OR cognition OR intoxication OR reaction time OR coordination OR neurocognitive OR psychomotor). This search strategy was developed with the assistance of a medical librarian, and was conducted as we have previously reported on prior studies of drug-associated psychological effects , clinical trials and systematic reviews  between 2000 and 2019 was conducted through Ovid MEDLINE and EMBASE electronic databases using the following MeSH terms: , the THC concentrations assessed, the THC dosing intervals, the neurocognitive tests utilized, the timing of the neurocognitive testing intervals and the results of these neurocognitive tests for each THC dose and timing interval. The data drawn from the included studies was interpreted and summarized to make a preliminary recommendation on the duration of neurocognitive and motor impairments in medical cannabis users.We identified 454 potentially eligible publications from the search strategy and twenty other potential articles from other resources. After screening titles and abstracts, 37 relevant studies were subjected to full-text review. One review article analyzed contained three additional RCTs which were independently reviewed for a total of 40 relevant studies reviewed. 32 studies were excluded for the following reasons: they measured subacute impairment of THC (days to weeks after ingestion), they did not have formal neurocognitive testing, there was no formal medical THC intervention completed, the study was not interventional, or they did not study adults living with chronic, non-cancer pain and/or spasticity. Eight studies met our final criteria, five systematic reviews and three RCT's. From the systematic reviews, three RCT's were extracted for analysis. One newly published observational clinical trial discovered through expert recommendation was added that was not found in our original search. Overall, seven controlled trials met the inclusion/exclusion criteria and were included in the qualitative synthesis: six RCTs and one observational clinical trial. A flow diagram of our search strategy summarizes our methodology .Study characteristics for the six RCTs and one observational trial are summarized in Route of cannabis administration varied: two studies required patients to smoke cannabis, three used vaporized cannabis, one allowed for smoking or vaporizing, and one study used sublingual THC, CBD, or THC: CBD spray. All three vaporization studies utilized the Foltin Puff Procedure, where participants are verbally signaled to “hold the vaporizer bag with one hand and put the vaporizer bag mouthpiece in their mouth” (30 s), “get ready” (5 s), “inhale” (5 s), “hold vapor in lungs” (10 s), “exhale and wait” before repeating the puff cycle (40 s) , 43, 44.Four of the seven studies required participants to abstain from non-study cannabis use for at least 30 days prior to the start of the study , 40, 44.There were a variety of testing protocols, with significant variability on the timing of THC or placebo administration and when the neurocognitive testing was completed. Some studies performed a single THC administration , 41, 45,Neurocognitive testing varied significantly between all studies, including the specific tests administered and the timing of assessments post-cannabis consumption. Two of the three studies using the Trails Making Test to assess visual attention and processing speed with switching tasks did not find significant differences between THC groups compared to placebo except for at two timepoints , 43. In Of the three studies using the Paced Auditory Serial Attention Test for auditory processing speed and working memory , 41, 43,Results were mixed between the three studies using the Grooved Pegboard Test (GPT) , 43, 44 All three studies that administered the Hopkins Verbal Learning Test and Delayed Learning Test to assess learning, immediate and delayed recall found THC dose-dependent impairment on learning and recall compared to placebo , 43, 44.Two of the three studies administering the Wechsler Adult Intelligence Scale Digit Symbol Test to assess concentration and graphomotor speed found no significant dose-effect differences throughout the duration of the study , 43 withOne study used the Adult Memory and Information Processing Battery in addition to Trails Making Test, although the authors did not report their results . The finIn summary, there is evidence that cognitive performance declined mostly in a THC dose-dependently manner, with steady resolution of impairment in the hours following THC administration. There is some variability in this dose-dependent relationship, bringing forward the consideration that there are other important factors contributing to the duration of neurocognitive impairment besides the dose of THC ingested. For example, one study found no neurocognitive impairment, and even higher neurocognitive test scores in the THC group compared to the normative data set , 43, 45.This scoping review provides evidence that cognitive performance in medical cannabis patients acutely declines after THC use, with steady resolution of impairment in the hours following THC administration. The degree of impairment is predominantly dose-dependent; higher doses of THC are generally more impairing than the lower doses. The duration of neurocognitive impairment varied between studies, partly due the heterogeneity in study designs. Nonetheless, there was no difference on any neurocognitive test between placebo and the active THC groups at 4-h of recovery, irrespective of the THC dose inhaled –45. ImpoSeveral observations from this review draw important comparisons with the recreational cannabis literature. As we have already discussed in detail the results of the scoping review and the seven studies in the Summary of Findings above, the focus on the present Discussion is to highlight and discuss important considerations when reviewing the current literature in addition to a variety of modifiable and non-modifiable factors that were found to influence the duration and degree of neurocognitive impairment in medical cannabis patients see .There are several non-modifiable factors, intrinsic to the patient, that influence both the degree and duration of impairment . These iGenetic and metabolic profiles or predispositions influence how an individual responds to cannabis, and thus the side effects experienced. Genetics, such as variations in the COMT/AKT genotype , 47, indIt is important to consider personal or family mental health history when assessing factors of impairment. Experienced or known pre-dispositions to some mental health conditions may increase the risk of impairment for some individuals  51, 52), 5251, 5Studies that assess the therapeutic effects of THC based on ability to manage symptoms, predominantly pain or spasticity, should acknowledge that these symptoms may contribute to impairment . PatientAs represented in The degree and duration of neurocognitive impairment is dose-dependent, with higher THC doses being more impairing than lower doses. The dose of THC used among the medical cannabis studies reviewed were substantially lower compared to typical recreational studies . RecreatRather than using data from studies with medical cannabis users and with doses typically used by medical cannabis patients, Health Canada's “Cannabis Impairment” report based its conclusions on data from studies of recreational cannabis, where doses are substantially higher. The report notes: “(s)ome effects of cannabis use, for example drowsiness, can last up to 24 h, well after other effects may have faded…(T)here is no standard waiting time to drive after using cannabis. If you are using cannabis, do not drive.” . If theyThis review of the literature found no reports of neurocognitive deficits with THC use 4-h after inhalation using modest THC-dosing strategies. We would recommend using lower-THC doses, (as were seen in the studies in this review), for daily symptom management, as higher doses may prolong the duration of impairment.The addition of other cannabinoids, such as CBD, may have an impact on the severity of neurocognitive impairment  69). On. On69). Medical cannabis patients often utilize other impairing substances to manage their conditions. The interaction of these substances with THC may further the duration and severity of neurocognitive impairment . For exaOne of the important differences between the medical cannabis patient and those who use recreational cannabis is the pattern of THC use . Medical cannabis patients typically manage symptoms using THC on a daily basis, which can lead to pharmacological tolerance, including tolerance to possible side effects  73–77).–77.73–77Some of the studies evaluated in this review enrolled participants with a previous history of cannabis use , 45, whiFindings from this review were constrained by the limitations of the current literature. Due to the heterogeneity of the study populations, study designs and protocols, and variability in the objective testing measures between studies, we were unable to complete a meta-analysis. The lack of cognitive and motor test standardization and the inconsistent methods between studies, including the type and time of testing post-THC ingestion, precluded statistical pooling of the data. There were no standardized medical cannabis products used across studies, with each study exploring varying concentrations of THC and CBD in either smoked, vaporized, or sublingual formulations, including cannabis-based medicines such as THC:CBD oromucosal spray . CombiniAn additional limitation in the literature was lack of research assessing oral THC products, including cannabis oils. Due to the known pharmacokinetic differences between ingested and inhaled THC and given that many medical cannabis patients use oral formulations, it will be important for future studies to incorporate these products in their trials. An important confounder in studies on impairment are the participants underlying medical conditions . Patients baseline cognitive functioning was only described and controlled for in three of the six studies , 40, 43,Finally, the literature on this topic is limited by the relatively small sample sizes of included studies. Small sample sizes may overestimate treatment effects or be insufficiently powered to detect a true difference, although some studies stated they were sufficiently powered to detect differences. Future trials would provide more robust information if they had larger sample sizes and captured data on a wider range of medical cannabis patients. Nevertheless, the trends that emerged among these medical cannabis impairment studies compared to the recreational data supports that medical cannabis patients do not have the same duration or degree of neurocognitive impairment as recreational users.This review suggests that the duration of neurocognitive impairment following inhalation or sublingual absorption of THC containing products is 4 h or less in medical cannabis patients. The results of this review are consistent with the College of Family Physicians of Canada's 2014 statement that medical cannabis patients should err on the side of caution, and delay safety sensitive activities for 3–4 h if cannabis (THC) is inhaled, 6–8 h if ingested orally, and 8 h if any euphoria is experienced . There aThe original contributions presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding author.LE was primarily responsible for the review of published abstracts, with additional support from LL, and wrote the first draft. CM supervised the project and provided the overall intellectual leadership. All other authors contributed to revising the manuscript with additional intellectual input.CM has received support for industry sponsored continuing medical education from Canopy, Medreleaf, Doja, Compass Cannabis Clinics. She has been on the scientific advisory board of Emerald Health Therapeutics, Shoppers Drug Mart, Strainprint and Resolve. She is the Medical Director of Greenleaf medical clinic, Vitality and Translational Life Sciences. She is on the Board of Directors for The Green Organic Dutchman. WP is the founder and CEO of Translational Life Sciences, an early stage science company focused on cannabinoid therapeutics. He has also been on the scientific advisory board of Medipure Pharmaceuticals and Vitality Biopharma, and in the past has been on the board of directors for Abbatis bioceuticals and on the advisory board of Vinergy Resources. AB has been a scientific advisor to Emerald Health Therapeutics, Cannevert Therapeutics, Global Cannabis Applications Corp, Medipure Pharmaceuticals, Vitality Biopharma and Hai Beverages. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Here we examine the influence of prenatal maternal physiology and phenotype on condition-dependent signals of their offspring in adulthood. Specifically, we explore how prenatal maternal testosterone, corticosterone, and ornament color and size correlate with female and male offspring survival to adulthood and ornament quality in the lizard Sceloporus undulatus. Offspring of females with more saturated badges and high prenatal corticosterone were less likely to survive to maturity. Badge saturation and area were negatively correlated between mothers and their male offspring, and uncorrelated to those in female offspring. Maternal prenatal corticosterone was correlated negatively with badge saturation of male offspring in adulthood. Our results indicate that maternal ornamentation and prenatal concentrations of a stress-relevant hormone can lead to compounding fitness costs by reducing offspring survival to maturity and impairing expression of a signal of quality in surviving males. This mechanism may occur in concert with social costs of ornamentation in mothers. Intergenerational effects of female ornamentation and prenatal stress may be interdependent drivers of balancing selection and intralocus sexual conflict over signaling traits.Colorful traits  that signal quality have well-established relationships with individual condition and physiology. Furthermore, ornaments expressed in females may have indirect fitness effects in offspring  Intergenerational associations between ornaments in offspring and maternal hormones and/or maternal inheritance might have important fitness consequences and could represent alternative ways in which female ornamentation can be evolutionarily relevant.Many animal species employ visually conspicuous traits in communication and signaling , 2. The in ovo or in utero to circulating maternal hormones that cross the amniotic barrier such as androgens , and predicted that: 1) high maternal CORT would reduce offspring survival to sexual maturity while low maternal CORT and high maternal T would improve offspring ornament quality (color saturation and badge area) due to known intraindividual relationships between these hormones and traits , and 2) We collected gravid females from the St. Francis National Forest and private lands in Lee County, Arkansas (AR), USA (n = 9), and from the Edgar Evins State Park and Land Between the Lakes National Recreation Area, Tennessee (TN), USA (n = 3). Immediately after capture, we collected blood samples from the post-orbital sinus  which weMaternal T and CORT were quantified using enzyme immunoassays . Protocols for plasma steroid extraction and immunoassays are detailed in the We took ventral photographs of each offspring (at maturity) and their mothers (prior to laying) using uniform camera settings and lighting conditions, and with a metric ruler in view as a scale for badge measurements Figure 1Badge color was measured on the blue portion of each lizard’s left throat badge using an Ocean Optics Jaz UV/VIS spectrometer. Saturation was calculated as light reflectance at the range of peak wavelength reflectance ± 50 nm, divided by total light reflectance between 300 and 700 nm , 40. Fenlme4  and were thus removed from the model. All other VIFs < 2.9.or area (for the model with the corresponding trait in offspring), maternal T, and maternal CORT. In addition, we included interaction terms between maternal badge traits and hormones (T or CORT), but none were significant and were thus removed from the models . Maternal identity nested within site of origin was included as a random effect.Intergenerational correlations for badge saturation and badge area were analyzed for male and female offspring separately. Thus, four LMM were built (for the two badge traits and the two offspring sexes), each with the following predictors: maternal badge saturation 2 distribution. Significant differences between models would indicate that maternal identity explained a significant proportion of variation in offspring traits, providing evidence for heritability.To investigate heritability of badge traits we used univariate LMM for each badge trait (color saturation and area) of mothers and offspring, along with site and maternal identity as random effects. These were compared to identical models without the maternal identity effect using likelihood ratio tests based on a χOf 120 hatchlings, 42 survived to 321 days of age. Across all clutches, greatest mortality occurred before hatchlings reached 126 days (18 weeks)  and survival , 16. In Negative effects of experimentally elevated maternal CORT on offspring survival have been previously documented in this species . Our resOrnament quality in mothers (badge color saturation and area) was negatively associated with those of male, but not female, offspring S1. BadgS. undulatus. Social interactions mediated by this condition-signaling trait – such as competition for food or dominance hierarchy formation within housing groups – could explain differences in survival to adulthood  can be found below: ScholarSphere; The animal study was reviewed and approved by The Pennsylvania State University’s Institutional Animal Care and Use Committee (IACUC).Designed the study: BA and TL. Collected and analyzed the data: BA, JA, RE, and TL. Prepared the manuscript: BA, JA, RE, and TL. All authors contributed to the article and approved the submitted version.Funding was provided in part by the National Science Foundation (IOS- 1456655 to TL).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Despite the growing interest in developing and using mobile health  and digital technologies in mental health, little is known about the scope and nature of virtual community inclusion.The overarching goal of this study was to understand and conceptualize virtual community inclusion of individuals with serious mental illness (SMI). Specific objectives of this study were as follows: (1) mapping the prevalence, trends, and experiences related to mHealth and digital technology use among individuals with SMI; (2) comparing patterns of technology use by individuals with and those without SMI; and (3) examining whether use of mHealth and digital technologies predicts recovery among individuals with SMI.A web-based survey of technology use and virtual participation was developed and distributed among adults with and those without SMI via social media, national email discussion lists, nonprofit organizations, and advocacy groups.A total of 381 adults aged 18 years or older participated in the survey, of whom 199 (52%) identified as having a SMI. Participants with SMI reported significantly greater access to technology and significantly fewer days of face-to-face participation in community activities than those without SMI. Among participants with SMI, greater technology use was positively associated with positive emotions and significantly predicted recovery.This study is the first to explore, map, and conceptualize virtual community inclusion among adults with SMI. Our findings indicate a gap in the literature and research on community inclusion and participation, and emphasize the need for virtual community inclusion, particularly during the COVID-19 pandemic and its future implications. The COVID-19 pandemic has emphasized the necessity of mobile health  and the use of digital technology more generally in managing chronic health conditions . RecentlA pioneering survey conducted in the United States among individuals who self-identified with schizophrenia  indicateRecently, studies that developed and examined mHealth interventions for individuals with SMI have confirmed the feasibility and acceptability of these emerging interventions ,15-18. TCommunity participation is a multidimensional concept defined as “active involvement in activities that are intrinsically social, and either occur outside of the home or are part of a non-domestic role, such as work, social (outside of the household), and other community roles” -25. CommUse of digital technologies and mHealth interventions may be particularly valuable in the current global pandemic. The COVID-19 crisis has posed significant challenges for the delivery of mental health services . PolicieThis study addresses these gaps by exploring patterns of digital participation among individuals with and those without SMI. Our specific objectives were (1) mapping the prevalence, trends, and experiences related to mHealth and digital technology use among individuals with SMI; (2) comparing the usage patterns of individuals with and those without SMI; and (3) examining whether the use of mHealth and digital technologies predicts recovery among individuals with SMI.A web-based survey of technology use and participation was developed for dissemination in Israel on the basis of the National Alliance on Mental Illness (NAMI) mHealth survey . The oriSurvey questions focused on access to digital devices , frequency of use, purposes of use , emotional experience while using digital technologies (negative or positive emotions), and helpfulness of activities using the devices in managing mental health (only for respondents with SMI). Survey questions were translated to Hebrew and adapted from the 2014 NAMI mHealth survey ); and extent of participation , defined as the number of unique participation areas  with at least 1 day of participation reported. For this analysis, Cronbach α=.93.This variable was assessed using the community participation measure , a self-The survey was distributed in Israel between February 2018 and May 2019 among adult individuals (over the age of 18 years) who identified as having SMI (the study group) and those without SMI (a comparison group), based on a screening question. SMI was defined on the basis of the Substance Abuse and Mental Health Services Administration criteria , which aBefore large-scale dissemination, we conducted a field-test of the final version of the survey with 4 individuals with SMI who commented on the questions and wording and further refinement. Survey participants were recruited via a snowball approach using Facebook groups and national email discussion lists (“Listservs”) of consumers and service providers as well as via nonprofit organizations and advocacy groups of and for people with SMI. We also provided an option of a paper-and-pencil version of the survey for individuals with SMI who were interested in participating via a face-to-face meeting with the research assistant.P value of <.05 was set as the significance level.The study was approved by both the University of Haifa Institutional Review Board and Israel Ministry of Health. SPSS  was used to present descriptive statistics and calculate correlations and means differences. A The sample includes 381 respondents, of whom 199 (52%) reported having at least 1 SMI, with 16 (8%) having reported more than 1 SMI. The most common condition was schizophrenia , followed by affective disorders , personality disorders , and posttraumatic stress disorder . Most respondents with SMI  reported an additional nonmental health chronic condition, mostly diabetes  or an orthopedic condition , compared to those without SMI, who reported no such condition.More women  than men were included in the survey, although the distribution was more balanced among those with SMI . The mos379t=3.62; P<.001). Women reported significantly greater negative emotions  when using digital technologies compared to men . Compared to men, women also reported significantly more total days of community participation in terms of both amount  and extent of participation .Overall, men reported having significantly greater access to technology  than did women . Respondents with SMI also reported significantly greater negative  and positive emotions  when using digital technologies compared to those without SMI . Finally, respondents with SMI reported significantly fewer days of participation in community activities  compared to those without SMI .Respondents with SMI reported significantly greater access to technology  than those without SMI . Greater experience of emotions while using technology, both negative  and positive , and greater amount of community participation  significantly predicted recovery. Greater positive emotions and more days of community participation were positively related to recovery, while greater negative emotions were negatively related to recovery.Multiple linear regression analysis was conducted to predict recovery among the respondents with SMI (n=199) based on their access to digital devices, emotional experience with technology use (negative and positive), and the amount and extent of their community participation. A significant regression model was obtained .Regression analyses were conducted to assess the contribution of technology use (for illness management) and emotions experienced while using the technology to recovery among respondents with SMI (n=199). First, we assessed the direct association between technology use for illness management  and positive emotions .Second, 2 regression analyses were carried out with technology use for illness management as the independent variable; 1 model included negative emotions and the other included positive emotions as the dependent variables , path a.β weight was obtained between negative emotions and recovery when controlling for technology use . A positive and significant β weight was obtained between positive emotions and recovery when controlling for technology use . A positive and significant β weight was obtained when predicting recovery with technology use as the predictor and controlling for negative emotions . No such result was obtained when predicting recovery with technology use as the predictor and controlling for positive emotions   , path c.This study is the first to explore and conceptualize digital community inclusion among individuals with SMI. Our study focused on digital participation of adults with SMI in Israel. We compared the mHealth and digital technology use  of adults with and those without SMI and explored whether and how participation factors predict recovery among adults with SMI. The main findings included higher rates of digital participation among individuals with SMI compared to those without SMI. In addition, greater positive emotions were noted when digital participation in the community, digital technology use, and more days of face-to-face community participation were positively related to recovery among adults with SMI. Positive emotions during digital community participation mediated the relationship between technology use (for illness management) and recovery. The findings emphasize the important role of digital participation on community inclusion of adults with SMI.Previous studies that compared digital technology use among individuals with and those without SMI have yielded contradictory findings. On one hand, lower rates of technology access and use were observed among individuals with SMI than among those from the general population ,48. On tsocial , productive , and leisure  [In addition to exploring mHealth and digital technology use among adults with SMI, this study examined whether digital community participation predicted recovery. The theoretical framework of community participation traditionally refers to face-to-face or actual participation and is defined as the empowered, self-determined choice and action among individuals to be active in valued roles in the communities of their choice . Accorditaurant) . Engagintaurant) -57.However, it seems that the life domains of community participation have referred to the physical environment, while participation in the digital environment has been excluded, although the digital environment has become an integral part of our life ,59 and eMoreover, recent studies have not conceptually included digital participation as part of community participation. This study has addressed this concept and theoretical gaps by exploring the predictive factors to recovery while taking into account both digital and face-to-face, in-person participation. As reported by Hendryx et al , involveFurthermore, emotional experience of technology use were found to mediate the relationship between technology use and recovery, while positive emotions completely mediated this relationship. Studies on human-computer interactions emphasize the important role of emotions in technology adoption ,68. EmotThe study has several limitations. First, because the survey was conducted on the internet, sampling may be biased by recruiting adults who are likely to be more technologically savvy. However, we recruited adults with SMI not only through web-based groups but also in face-to-face meetings with individuals with SMI who were interested in participating, and they completed a paper-and-pencil version of the survey. This strategy enabled us to recruit a more heterogeneous sample in terms of access to technology. Second, the majority of survey respondents were young adults with only few over the age of 65 years, which could also explain the relatively high use of technology. Therefore, the results for older adults with SMI must be interpreted with caution, and future studies should target a subgroup of older adults with SMI.Lastly, although we acknowledge that poverty plays a crucial role in access to technology ,72, partThis study demonstrated the potential of digital community inclusion to recovery and well-being among individuals with SMI. Our findings indicate higher rates of access and use of mHealth and digital technologies among individuals with SMI than among the general population. Furthermore, our findings show that digital participation could promote recovery among adults with SMI. Accordingly, this study emphasizes the need to update and expand the definition and conceptualization of community participation, and include aspects of digital participation needs of individuals with SMI.Our findings suggest that policy makers, service users, and researchers should use existing digital technologies and design novel mHealth interventions to support the recovery process of adults with SMI. In particular, the current COVID-19 crisis poses an opportunity for mental health care systems to adopt digital technologies for service provision. In this sense, this study, conducted before the current COVID-19 pandemic, contributes to the understating that digital participation of adults with SMI is valuable to their recovery not only in crisis but also in routine. Furthermore, it is important to support the participation of individuals with SMI in the virtual environment in a manner that facilitates a positive emotional experience. Positive emotional experience while using digital technologies is a key factor in their engagement in the web-based environment and consequently in their recovery.


Epidemics and disease outbreaks often overwhelm existing health care systems and infrastructure, making them ill prepared to respond to these crises. In the 1990s, the health infrastructure of many African countries in Sub-Saharan Africa (SSA) was overwhelmed by the HIV/AIDS pandemic. In 2007, the World Health Organization (WHO) recommended six core components or “building blocks” that included leadership and governance as essential ingredients of a functional health system that could efficiently deliver equitable services.4To contribute to bridging the gap of transformative leadership in health care, the Afya Bora Consortium Fellowship (ABC) was developed to train health care leaders for global health at ministries of health, academic institutions as well as governmental and non-governmental organizations to promote evidence- based health care and public health services in SSA.Fellows participate in a highly interdisciplinary one year training that includes: week-long face-face modules on key skills needed by global health leaders, including Leadership, Communications and Media, Global Health Policy and Governance, Monitoring and Evaluation, Human Resource and Budget Management, Qualitative methods, Effective Grant Writing, Implementation Science and Health Systems Research. Fellows receive up to nine months of mentored practical leadership experience at a local institutions  in the partner countries. In addition, during their experiential attachment period, fellows use distance learning modules to strengthen their understanding of Research & Analytic Methods, Responsible Conduct of Research and Practice, HIV as a Global Health Challenge, and Program Management.6Each fellow is mentored by at least two people, a working group member and a mentor from the respective attachment site for the experiential placement. In each country, attachment sites were selected based on the strength and capacity to mentor and provide experiential training to fellows. Fellows undertake a project which may have a research or a practice focus. Fellows' progress is routinely documented by an established structured M&E framework.7With the lessons learned from the COVID 19 pandemic experience, ABC is transitioning most of the modules to virtual training to allow fellows to continue learning despite international travel restrictions. The Fellowship has set up a strong alumni platform to encourage networking and long-term collaboration in research, training and leadership in global health.Global health-focused authors have repeatedly called for inter-professional training in Global Health to enrich interdisciplinary perspectives and embed teamwork approaches to overcome healthcare challenges.


The present paper studies the flow and heat transfer of the hybrid nanofluids flows induced by a permeable power-law stretching/shrinking surface modulated orthogonal surface shear. The governing partial differential equations were converted into non-linear ordinary differential equations by using proper similarity transformations. These equations were then solved applying a numerical technique, namely bvp4c solver in MATLAB. Results of the flow field, temperature distribution, reduced skin friction coefficient and reduced Nusselt number were deduced. It was found that increasing mass flux parameter slows down the velocity and, hence, decreases the temperature. Furthermore, on enlarging the stretching parameter, the velocity and temperature increases and decreases, respectively. In addition, that the radiation parameter can effectively control the thermal boundary layer. Finally, the temperature decreases when the values of the temperature parameter increases. We apply similarity transformation in order to transform the governing model into a system of ODEs . Numerical solutions for particular values of involved parameters are in very good agreement with previous calculations. The most important and interesting result of this paper is that for both the cases of shrinking and stretching sheet flows exhibit dual solutions in some intervals of the shrinking and stretching parameter. In spite of numerous published papers on the flow and heat transfer over a permeable stretching/shrinking surface in nanofluids and hybrid nanofluids, none of the researchers studied the present problem. Therefore, we believe that the results of the present paper are new, and have many industrial applications. Devi and Devi [During the last few years, hybrid nanofluids appeared as an extension of nanofluids and are believed to improve their thermophysical and rheological characteristics and also heat transfer attributes. Suresh et al.  supervis Huminic . Mabood and Devi  predicteand Devi  used botand Devi  and Takaand Devi  engaged and Devi  was publand Devi , Waini eand Devi ,11, Khasand Devi , Zainal and Devi , to mentand Devi , Shafiq and Devi ,16,17, Sand Devi , Khan etand Devi , Khan [2and Devi  and Makiand Devi , Mabood The boundary layer flows driven by stretching/shrinking sheets have been investigated by a lot of people due to their many applications. The heat transfer and flow characteristics generated by stretching/shrinking surfaces appear widely in engineering application processes (see Fisher ). TherefThis paper extends the zero-pressure-gradient boundary-layer solutions for power-law stretching/shrinking sheet studied by Banks  to incluBased on these hypotheses and using hybrid nanofluid model suggested by Takabi and Salehi , the gov Weidman ; Devi an Weidman ):(1)∂ u Here Furthermore, d Salehi .(6)μhnf=2O3 particles and fk and sk represents the thermal conductivities of the base fluid and the hybrid nano-sized particles, respectively, Here According to Weidman , the nexThus,Substituting the similarity variables (7) into Equations (1)–(3), the following ordinary differential equations are obtained:From a physical point of view we are interested in the skin friction coefficients Using (7) and (13), we getWe can observe that for a normal fluid  and (18) is given by –(11) and the conditions (12) at the boundaries are numerically solved for the value of the Prandtl number fixed to e et al. ). This id Cannon  or Corted Cannon , and thef′(0) and g′(0), the reduced local Nusselt Graphs that display the influence of the governing parameters on the reduced skin friction coefficients Finally, For the potential stretching and shrinking flows there exist two solutions (first/upper branch and second/lower branch), when some of the governing parameters lie in specific intervals.We can control the separation of the boundary layer by using lower magnitude of The increment of the copper or alumina nano-sized particles solid volume concentration has a large influence on the critical value The increase of concentration The increase in The increase in concentration Our main conclusions are the following: