How have US clinicians planned for and responded to resource limitation during the coronavirus disease 2019 pandemic?This qualitative study included interviews with 61 clinicians across the United States. While institutions planned for an explicit and systematic approach to resource allocation in crisis settings, this approach did not address many challenges encountered by frontline clinicians, leaving them to struggle with what constituted acceptable standards of care and to make difficult allocation decisions.The findings of this study suggest that expanding the scope of institutional planning to address a broader spectrum of resource limitation may help to support clinicians, promote equity, and optimize care during the pandemic. This qualitative study describes the perspectives and experiences of clinicians involved in institutional planning for resource limitation and/or patient care during the coronavirus disease 2019 (COVID-19) pandemic. Little is known about how US clinicians have responded to resource limitation during the coronavirus disease 2019 (COVID-19) pandemic.To describe the perspectives and experiences of clinicians involved in institutional planning for resource limitation and/or patient care during the pandemic.This qualitative study used inductive thematic analysis of semistructured interviews conducted in April and May 2020 with a national group of clinicians  involved in institutional planning and/or clinical care during the COVID-19 pandemic across the United States.Emergent themes describing clinicians’ experience providing care in settings of resource limitation.The 61 participants  included in this study were practicing in 15 US states and were more heavily sampled from areas with the highest rates of COVID-19 infection at the time of interviews . Most participants were White individuals (39 [65%]), were attending physicians (45 [75%]), and were practicing in large academic centers . Three overlapping and interrelated themes emerged from qualitative analysis, as follows: (1) planning for crisis capacity, (2) adapting to resource limitation, and (3) multiple unprecedented barriers to care delivery. Clinician leaders worked within their institutions to plan a systematic approach for fair allocation of limited resources in crisis settings so that frontline clinicians would not have to make rationing decisions at the bedside. However, even before a declaration of crisis capacity, clinicians encountered varied and sometimes unanticipated forms of resource limitation that could compromise care, require that they make difficult allocation decisions, and contribute to moral distress. Furthermore, unprecedented challenges to caring for patients during the pandemic, including the need to limit in-person interactions, the rapid pace of change, and the dearth of scientific evidence, added to the challenges of caring for patients and communicating with families.The findings of this qualitative study highlighted the complexity of providing high-quality care for patients during the COVID-19 pandemic. Expanding the scope of institutional planning to address resource limitation challenges that can arise long before declarations of crisis capacity may help to support frontline clinicians, promote equity, and optimize care as the pandemic evolves. Early reports from frontline clinicians in global epicenters describing extreme shortages and bedside rationing of ventilators and intensive care unit (ICU) beds2 prompted a national conversation about how to respond to similar challenges in the United States.3 Hospitals and health care systems drew on frameworks developed by the Institute of Medicine (IOM) and other national organizations to guide care in resource-limited emergency settings.7Since the first US case of coronavirus disease 2019 (COVID-19) was diagnosed in mid-January 2020,8 Under crisis standards of care, a specialized triage team becomes responsible for rationing scarce resources and making decisions about which patients will and will not receive potentially life-saving treatments.Under the IOM’s framework, resource allocation is intentionally siloed from other aspects of clinical care to ensure a fair process and spare frontline clinicians from the responsibility of having to ration scarce resources at the bedside. The IOM recommends a phased adaptation to resource limitation. Institutions first shift from conventional to contingency capacity, in which resources are adapted, optimized, and redistributed to maintain a standard of care that is functionally equivalent to usual care. If resources become so limited that a functionally equivalent standard of care can no longer be sustained, institutions then shift to crisis capacity, and care is redirected to provide the greatest aggregate benefit to the population.10 and has been iteratively refined through ethical analysis8 and community deliberation,12 there have been few opportunities to test the framework in real-world clinical settings. Reports from past pandemics14 and from early global epicenters of the COVID-19 pandemic,15 press reports,17 and perspectives published in the scientific literature19 describe some of the challenges faced by frontline clinicians. However, there is little empirical work describing the experiences and perspectives of US clinicians pertaining to resource limitation and clinical care during the COVID-19 pandemic.21 To address this knowledge gap, we conducted a qualitative analysis of interviews with US clinicians during the pandemic.Although the IOM framework reflects lessons learned during earlier pandemicsCOREQ) reporting guideline  at our own institution (the University of Washington). We then expanded recruitment to include other groups of clinicians  and those practicing in other parts of the country. We used a snowballing recruitment strategy in which we asked participants to identify colleagues with relevant experience who might be interested in participating in the study. We did not exclude participants who had collegiate relationships with members of the research team. Interviews were conducted between April 9, 2020, and May 26, 2020. The University of Washington institutional review board approved this study and authorized verbal in lieu of written consent. Verbal consent was obtained from all participants. We report details of our methods using the Consolidated Criteria for Reporting Qualitative Research . All but 1 interview, which included 2 participants at their request, were conducted 1-on-1, and 2 interviews were spread over 2 sittings. A semistructured interview guide  independently reviewed and openly coded transcripts until reaching thematic saturation ,25 which occurred after reviewing 30 interview transcripts. One of us (C.R.B.) coded all remaining transcripts for concurrence. Throughout the analysis, the 2 investigators iteratively reviewed codes, collapsed codes into groups with related meanings and relationships, and developed larger thematic categories, returning frequently to the transcripts to ensure that emergent themes were well-grounded in the data.25 All coauthors  reviewed example quotations and themes and together developed the final thematic schema. We used Atlas.ti version 8 (Scientific Software Development GmbH) to organize and store text and codes.We conducted an inductive thematic analysis26 All but 1 participant completed the online survey. The mean (SD) age of participants was 46 (11) years, and most were White (39 [65%]), were attending physicians (45 [75%]), and were practicing in large academic hospitals . Participants were practicing in 15 states across the United States and had primary affiliations with 29 different hospitals or clinics, with greater sampling of clinicians practicing in states with the highest rates of COVID-19 infection at the time of the study .We approached a total of 97 clinicians by email, of whom 75 (77%) agreed to participate and 22 (23%) declined or did not respond to our inquiry. Among those who agreed to participate, we purposively sampled 61 clinicians to participate in interviews from April 9, 2020, to May 26, 2020 .26 All bThree overlapping and interrelated themes pertaining to resource limitation and clinical care during the COVID-19 pandemic emerged from qualitative analysis, as follows: (1) planning for crisis capacity, (2) adapting to resource limitation, and (3) multiple unprecedented barriers to care delivery. Exemplar quotations are referenced in parenthesis and listed in Institutional leaders who participated in planning for crisis capacity described the challenges of adapting and operationalizing existing guidelines as well as the substantial moral weight of the task. They were relieved when it became clear that these processes would likely not be needed at their institutions .Clinicians who were involved in institutional planning described strong institutional support for their work to develop protocols to guide care should their region reach crisis capacity (quotation 1). They believed that establishing protocols in advance would allow for a more carefully considered approach (quotation 2) and would be reassuring to staff (quotation 3).Their work involved developing actionable triage algorithms based on existing frameworks (quotation 4). Group deliberation focused on both big picture ethical questions (quotation 5) as well as more granular operational details (quotation 6). Several clinicians with whom we spoke were not formally involved in institutional planning efforts but had offered input and/or developed their own protocols when they identified gaps in planning or disagreed with institutional policies (quotations 7 and 8).To support fairness and avoid bias, the plan was for triage team members to receive very limited information about individual patients when making selection decisions (quotation 9). Some clinicians involved in planning were skeptical about the feasibility of making triage decisions in the absence of detailed clinical information (quotation 10). Others expressed uncertainty about whether and how triage protocols would address more ambiguous or dynamic types of resource limitation  (quotation 11). Clinicians could also be mindful of how their work might be viewed by other clinicians and the public (quotation 12) and were wary of sharing details about committee deliberations (quotation 13), plans (quotation 14), or team membership (quotation 15) with their colleagues and/or during the research interview.Clinicians who had been appointed to triage teams were usually respected leaders in intensive care, palliative care, or bioethics who were recognized for their ability to collaborate and communicate (quotation 16). Some of the intensivists and ethicists with whom we spoke saw the work of the triage team as an extension of their usual work (quotations 17 and 18), but many clinicians saw this experience as entirely new (quotation 19). Clinicians described being motivated to participate in the triage team out of a sense of duty and desire to contribute (quotation 20) but were also cognizant of the moral weight and emotional burden of the task before them (quotation 21).Clinicians involved in triage planning understood the processes they were developing to be intended exclusively for crisis settings (quotations 22 and 23) and saw the importance of optimizing resources under contingency capacity to avoid having to resort to crisis standards of care (quotation 24). While several clinicians described a period of intense planning early in the pandemic, by the time of our interviews, many were relieved to report that crisis standards of care were unlikely to be invoked at their institutions, and some had paused or disengaged from triage planning (quotations 25 and 26).Clinicians working during the pandemic were forced to grapple with multiple expected and unexpected forms of resource limitation that did not rise to the level of triggering crisis capacity. Nevertheless, these limitations could compromise care, require that they make difficult allocation decisions, and engender moral distress .Although none of the clinicians with whom we spoke reported a shift to crisis capacity at their institutions, they nevertheless described being faced with a range of expected and unexpected forms of resource limitation  (quotation 27) that could arise in a haphazard manner with little warning (quotation 28). Some expressed frustration that resource shortages they were seeing in practice were not acknowledged as such by hospital or regional leadership (quotations 29 and 30) or felt unsupported by colleagues at neighboring medical centers (quotation 31). When not available from their institutions, some clinicians resorted to obtaining health care equipment through personal contacts or even fabricated it themselves (quotations 32 and 33).Clinicians were strongly motivated to avoid situations in which they would have to categorically deny needed treatment to any patient (quotation 34) and went to great lengths to develop alternative treatment options (quotation 35). This might involve using unorthodox therapies or nontraditional approaches to care delivery that could be suboptimal or potentially harmful (quotations 36 and 37). For example, some nephrologists described triaging patients for hemodialysis based on immediate need (quotations 38 and 39), delaying dialysis until there was an emergent indication (quotation 40), and/or prescribing shorter treatment times. As 1 clinician explained, “everyone gets a little bit of bad care” (quotation 41). Rarely, clinicians were able to draw a clear line between acceptable and unacceptable care (quotation 42), but most focused on doing the best they could under the circumstances (quotation 43).The notion of rationing generally had negative connotations (quotation 44), and some clinicians even described erring on the side of providing more intensive interventions to avoid the appearance of rationing (quotation 45). With rare exceptions (quotation 46), clinicians did not explicitly speak of having had to ration health care resources (quotation 47). Nonetheless, some clinicians did describe situations in which they had to make difficult choices about which patients would and would not receive life-saving therapies, typically on the basis of age and/or comorbidity. This was often seen as part of the spectrum of normal clinical decision-making (quotations 48 and 49) and within their scope of practice (quotation 50). Some clinicians did describe struggling to understand what constituted acceptable practice vs rationing (quotations 51 and 52) and expressed misgivings about the approach to selecting patients for life-saving treatments during the pandemic (quotations 53 and 54).Many clinicians were fearful of having to ration resources (quotation 55). Even in lower acuity and outpatient settings, some struggled with whether it was acceptable to provide suboptimal care (quotation 56) and worried about the potential harms of disrupted care practices (quotation 57). A sense of responsibility for poor outcomes could take a substantial emotional toll (quotation 58). Some clinicians felt that explicit guidelines would be helpful in limiting this moral distress (quotation 59), while others felt personally responsible for poor outcomes regardless of whether they were adhering to institutional recommendations or requirements (quotation 60).Clinicians described multiple barriers to care delivery during the pandemic. These challenges compounded and were difficult to disentangle from the effects of resource limitation .Policies and practices were modified to limit physical interaction between staff, patients, and family members with the dual goals of reducing viral spread and conserving personal protective equipment. While necessary, policies to limit contact with patients were seen as being detrimental to care and to the experiences of both patients and clinicians (quotations 61 and 62). Decisions about something as routine as whether to perform a physical examination could expose tensions around the conflicting goals of conserving scarce resources, protecting oneself, and caring for patients (quotations 63 and 64). Visitor restrictions could complicate and disrupt the process of engaging family members in decision-making (quotations 65 and 66).The rapid pace of change and limited scientific understanding of COVID-19 (quotations 67 and 68) led to substantial uncertainty in day-to-day practice. A sense of desperation and a desire to do everything possible to save lives might lead to more aggressive treatment practices and/or greater willingness to try unproven therapies (quotation 69), reluctance to engage palliative care specialists (quotation 70), and delays in end-of-life decision-making (quotation 71).Many clinicians commented that families and patients were often quite understanding of care disruption (quotation 72), and that they were surprised at how accepting some families could be when care was compromised by the need to conserve resources and/or protect clinicians (quotations 73 and 74). However, some clinicians did describe contentious interactions with family members (quotation 75) and patients (quotation 76) who felt that care was being inappropriately withheld. Other clinicians described deliberately avoiding mention of resource limitation when talking with families (quotation 77).30 the clinicians we interviewed described how, even in the absence of formal declarations of crisis capacity, a variety of expected and unexpected forms of resource limitations severely compromised care and required that they make difficult allocation decisions at the bedside.Our thematic analysis of interviews with US clinicians who were directly involved in patient care and/or strategic planning during the COVID-19 pandemic highlights the real-world complexity of adaptation to resource limitation. Clinicians described patterns of institutional planning that mirrored the IOM’s phased approach, which assumes a common understanding about what constitutes usual standards of care with a plan for a coordinated regional response when these become untenable. However, consistent with prior anecdotal reports,31 and may not be supported by societal priorities for fairness in resource allocation.35Clinicians and clinical teams went to great lengths to develop alternative treatment options and to stretch existing resources to provide at least some care to all in need and avoid having to categorically deny treatment to any patient. However, this approach could mean providing care that fell far short of the IOM standard of functional equivalence to usual care. When substituting lower-quality or delayed treatments, clinicians and clinical teams were left to grapple with what constituted an acceptable standard of care, which could be a source of self-doubt and moral distress. While most clinicians did not feel that they had been in the position of having to ration scarce resources, some nevertheless described practices, such as selection by age or comorbidity, that may be subject to implicit biases7 represent an important step toward promoting fairness through transparent allocation processes.36 However, our results suggest that a narrow focus on crisis capacity may fail to address the full spectrum and complexity of challenges to providing high-quality care encountered by frontline clinicians during the COVID-19 pandemic .In this qualitative study, many clinicians described institutional planning for crisis capacity, but this did not always address real-world challenges to providing care when resources were limited. Expanding the scope of institutional planning beyond crisis capacity may be helpful in supporting clinicians and addressing moral distress, promoting equity, and optimizing care as the pandemic evolves.


Shortening of the hospital stay in patients admitted with the diagnosis of acute myocardial infarction (AMI) has been observed within the last decades. Our center is the only cardiac center in the region providing tertiary care facility and hence receives all AMI patients deemed suitable for invasive assessment and management and this leads to huge required demand. Our aim is to assess feasibility and safety of the early discharge of selected proportion of AMI patients.P = 0.04) and treated more with primary percutaneous coronary intervention (PPCI) (P = 0.04). They had favorable coronary anatomy , better hospital course, and higher left ventricular ejection fraction compared to non-early discharged patients . Follow-up of those early discharged patients were promising as majority of them were asymptomatic (95%) and did well post-discharge.Out of 557 of patients presented with AMI and treated with percutaneous coronary intervention (PCI), 310 (56%) were discharged early. Men patients and pilgrims were more prevalent among the early discharge group. Early discharged patients had significantly less comorbidities compared to the other group of patients. Moreover, they presented mainly with ST-elevation myocardial infarction (Our study demonstrated data that support safety of early discharge in a carefully selected group of AMI patients. Early but safe discharge may have a huge impact on increasing bed availability, reducing hospital costs, and improving patient’s satisfaction. Shortening of the hospital stay in patients admitted with the diagnosis of acute myocardial infarction (AMI) has been observed within the last decades –3.The current Guidelines of European Society of Cardiology for the management of acute myocardial infarction with ST-segment elevation, released in 2018, state that the selected patients may be considered (class of recommendation IIb) for early discharge (after approximately 72 h), if adequate follow-up is arranged . This isHajj is a great event and it is one of the five Islamic pillars. Millions of pilgrims from different countries of the world come to the Kingdom of Saudi Arabia for performing hajj. The overcrowding, hot climate, and huge physical stress expose the pilgrims to many health hazards. Cardiovascular disease has recently emerged as the leading cause of death during hajj , 11. ThiOur tertiary center is the only cardiac center in the region providing tertiary care facility including percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) and hence receives all AMI patients deemed suitable for invasive assessment and management and this leads to huge demand on cardiac services over the few weeks of hajj time. Reduced hospital stay has been proved to reduce the hospital burden and costs –15.The aim of our study is to assess feasibility and safety of the early discharge of selected proportion of AMI patients. This facilitates establishment and implementation of the successful and safe early discharge program to enhance bed’s efficiency, improve occupancy rate and serve more patients during hajj crowdedness.This is a prospective, single-center study reviewing the clinical details of all AMI referred to our center for early revascularization and discharged during the two hajj seasons 2018 and 2019. It is designed to be a part of the standards of patient’s care, to investigate and improve quality of AMI management and outcomes among a diverse population; general and cath consents were taken and has received approval of the ethics committee/institutional review board of our institution.As mentioned earlier, our center is the only cardiac center in Makkah with cath lab facilities, which provides invasive management of AMI, and we envisage capturing almost all AMI patients suitable for invasive management. Every year, our center receives about 1000 AMI patients; a quarter of them were admitted during the hot season in Makkah (2–3 weeks of hajj). Our study population included residence and hajj patients . They were referred either from other primary, secondary, and Al-Mashaer hospitals or presented directly through our emergency department, and underwent coronary angiogram and PCI with drug eluting stents.All patients admitted with established diagnosis of AMI  during the few weeks of hajj seasons 2018 and 2019.Patients presenting with AMI where coronary angiography was not done because of preference of the patient or due to any other reason and AMI patients admitted outside hajj seasons were not included as well.Demographics. Age, gender, and status (residence/hajj)Risk factors. Diabetes (DM), hypertension (HTN), smoking, dyslipidemia, presence of chronic kidney disease, old cerebrovascular accidents (CVA), chronic obstructive lung disease (COPD), ischemic heart disease (IHD), and previous PCI/CABGClinical data. Type of AMI are as follows:ST-elevation myocardial infarction (STEMI) treated either with PPCI or with non-PPCIIHistory of pulmonary edemaIILeft ventricular ejection fraction (LVEF) in echocardiographyNon-ST-elevation myocardial infarction (NSTEMI) with high-risk features , which necessitate early revasculrizationCoronary procedure description and angiography findings. Access site , presence of left main disease (LM), single vessel disease (SVD), two or three vessel coronary artery disease (CAD), infarct-related artery (IAR), thrombus aspiration, and use of tirofiban/AggrastatThe following data for each patient were collected:AMI treated with successful PCI (TIMI flow III in infarct-related artery)Age ≤ 75 yearsHemodynamic and rhythmic stabilityAbsence of comorbidities, which require continuation of hospitalizationAbsence of contraindication of dual anti-platelet treatmentSupposed cooperation, compliance, and adherence to medical treatment particularly DAPT Early discharge (24–72 h) was planned for selected patients who were fulfilled those criteria:Alive/death with dateRecurrent symptoms of ischemiaAny bleedingRecurrent hospital admissionFollow-up of early discharged patients with telephone communications within 15 days after discharge to check the safety of this strategy with collection of the following data:t test. Categorical data were given as a percentage and compared with a Chi-square test. A P value < 0.05 was considered statistically significant.Statistical analysis was performed by the use of the SPSS software package ; version 21.0. Continuous data were expressed as mean ± SD and compared using the Student Out of 1972 AMI consecutive patients, five hundred fifty seven were treated with PCI during their admission in our center within the two hajj seasons (2–3 weeks of hajj) of the 2 consecutive years 2018 and 2019, respectively. Patients were distributed in to two groups: group I, 310 (56%) who were fulfilled the given early discharge criteria and discharged, and group II, 247 (44%) who were discharged late (after 72 h). From the whole discharged AMI patients in the study period, 89 (16%) were discharged within 24 h and 221 (40%) were discharged within 48–72 h from admission. One hundred twenty patients (39%) were early discharged in the hajj season 2018 while 190 (61%) were early discharged in the hajj season 2019 . They also showed less prevalence of DM (161 (52%) vs 148 (60%)), HTN (181 (58%) vs 158 (64%)), history of ischemic heart disease (55 (17%) vs 53 (21%)), and previous coronary revasculrization (27 (9%) vs 34 (14%)) compared to group II patients  and 212 (68%) vs 87 (35%) and 146 (59%); P = 0.04). The early discharged patients had better hospital outcomes compared to the other group as they showed less prevalence of post myocardial infarction pulmonary edema (5 (2%) vs 15 (6%); P = 0.006) and higher LVEF . Otherwise, regarding the other treatment modalities, there were no detected significant differences between the two groups for the use of thrombolytic therapy and/or tirofiban post AMI treated with PCI.As shown in Table P = 0.003). Also, patients of group I with early discharge had favorable coronary artery disease anatomy as they showed less prevalence of both left main and three vessel disease in their coronary angiography compared to those of group II (7 (2%)and 55 (17%) vs 17 (7%) and 65 (26%); P = 0.01 and 0.02, respectively)  vs 171 (69%); Among 310 early discharged patients, only 187 (60%) could be contacted by phone (with help of many translators of different languages) for follow-up within 15 days from the discharge date. They were questioned and found that 177 (95%) patients were totally asymptomatic, 6 (3%) had nonspecific chest pain which did not require any hospitalization, 2 (1%) had minor bleeding (epistaxis resolved spontaneously), and 2 (1%) re-admitted with heart failure symptoms. Those two patients re-admitted with heart failure had been found to have low ejection fractions with ischemic mild to moderate mitral regurge in their pre-discharge echocardiography and their follow-up echocardiography showed the same findings; however, they had mild chest infection, which predisposed to aggravation of heart failure  vs 6 (2%), respectively) Fig. . No recoThe overview of most of literature investigating the issue of safety and feasibility of early discharge in AMI patients shows variable methodology and this explains that guidelines for early discharge are based just on limited data derived from randomized trials. The issue of early discharge was investigated in PRAGUE 5 study, which after pilot phase randomized 56 low-risk probands with STEMI, discharged even the next day after successful PCI. It was the first study in which mean length of hospital stay was shorter than 72 h . Most ofIt has been proven that substantial reduction in-hospital length of stay has been associated with reduction of in-hospital charge  with no Our center is the only cardiac center in the region providing tertiary care facilities and receives a huge number of AMI patients especially during the 2 to 3 weeks of hajj seasons, subsequently this puts a big burden for the required provided service and hospital costs. The primary aim of our study is to create and implement successful safe early discharge program to improve bed’s utilization efficiency and provide the best, safe, and maximum service for cardiac patients during over crowdedness of the hajj season. To the best of our knowledge, there are no similar studies conducted in our region concerned with this idea. We selected few weeks of each hajj season to conduct this study for many reasons: First, as previously mentioned, our cardiac center is the only center in the region of Makkah that has cath lab facilities and this required to provide tremendous tertiary care services to pilgrims and residents of Makkah during hajj season. Therefore, appropriate improvement of bed utilization is crucial with subsequent increase of hajj population in the successive years. Second, during this selected period, most of our AMI patients were pilgrims who had special ritual, religious emotions, and soul as most of them were doing their hajj for the first time having beliefs that longer hospital stay might reduce the opportunity to complete the hajj for which they were coming and persistently asking all the time for discharge. We believe that appropriate early post AMI discharge might grant their wishes provided it is totally safe. Third, during this short 2 weeks of hajj season additional two millions of population increase within Makkah city from pilgrimage and this requires a huge health service demand. Many facilities provided by the Ministry of Health and Hajj Committee during hajj seasons to provide a tremendous 24 h non-stop cardiac services included increasing manpower, raising number of working cath labs, improving working network, expanding all available services, and hence all that motivate the huge work and discharge of stable cases. We started implementation of early discharge program on hajj season 2018 and continued on 2019 to enlarge our sample size, which might help to gather more data and generalize our conclusion.Our results concluded that those early discharged patients had higher percentage of pilgrims who were in high need for early discharge to compete their hajj pillars with their groups and return back to the their home countries safely. They also showed to have low-risk AMI features including less prevalence of cardiovascular risk factors and comorbidities, which all might predict safe early discharge post revascularization. Early revascularization with PPCI with appropriate target for DBT  was recorded higher among those early discharged patients and this reflects higher quality of service provided by our center to AMI patients and could help in the process of early discharging them from the hospital. Clinical features and short-term outcome of AMI patients post event are crucial once decided the discharge process and these were followed carefully during our program implementation . Reassuringly, most of our early discharged patients had favorable coronary artery disease anatomy  and this encouraged their early discharge process.Follow-up data results were impressive as majority of our early discharged patients were totally asymptomatic (95%). Few percentages of those patients had non-serious symptoms and did not require any major intervention and this might reflect the early success of implementation of such program in our facility, which is considered the corner stone in the region.Finally, our current experience reflects many advantages: great compensation of the huge required hospitalization burden; provision of the best, safe, and maximum service for cardiac patients during over crisis periods; lower hospital cost; and improvement of patient’s satisfaction.Our study is limited to a single center and relatively small population number (short period selected only two hajj seasons) corresponds to the conclusions of mentioned studies. There are many factors explaining limitation of our follow-up data (as 40% of our early discharged patients lost their follow-up): language barrier, wrong written contact number in our records, non-attending calls, and higher percentage of those patients were pilgrims who returned back to their countries immediately after hajj without any follow-up here. We tried to support our results with some previous randomized studies with such recommended strategies and shorter length of hospital stay.Suggested plan to establish proper educational program with help of the health promotion department supported with different language materials, which will be provided to those patients during their hospitalization regarding to their disease process, medication compliance and proper short-/long-term follow-upProper recording of correct contact numbers of the patients organized by our admission office and bed management departmentsMotivation of the primary and secondary hospitals in the regions to conduct similar programs and possible organization of better follow-up protocolsWe hope to reduce these limitations in future seasons by the following suggestions:Our results provide preliminary data to support safety of early discharge in a carefully selected group of AMI patients while providing them dedicated telephone support and follow-up. Early but safe discharge may have huge impact on increasing patient’s satisfaction, bed availability  and reducing hospital costs. Furthermore, a larger multi-center study in the region has been encouraged to generalize our conclusion.


The present study analyzes the drug-target-disease network and may prove to be a useful tool in gene-phenotype connectivity for genistein in HBV-related liver cancer. Our data also pave the way for further research on Grb2 during the development of chronic HBV infection in liver cancer.Genistein is a type of isoflavone, which has been widely described as an antitumor agent in many cancers. The present study aimed to provide information on the mechanisms of genistein's activity and thus enable a wider range of targeted therapies in hepatitis B virus (HBV)-related liver cancer. We searched the DrugBank database for direct targets of genistein, which were then analyzed through the STRING  database to predict their secondary protein targets. Thirteen primary protein targets of genistein and 209 secondary protein targets-associated genes were identified. The data were integrated into the network of protein targets-associated genes and visualized with the Cytoscape software. We further carried out GO (Gene Ontology) analysis and KEGG (Kyoto Encyclopedia of Gene and Genome) pathway analysis using DAVID  tool. The top 14 KEGG pathways were further assessed, and 19 overlapping genes derived from pathways of hepatitis B and cancer were discovered. The overlapping targets were further mapped in the online tool UALCAN to evaluate the survival rate of hepatocellular carcinoma (HCC) patients. We found that the overexpression of Grb2 (growth factor receptor-binding protein 2) ( Worldwide, chronic infection due to hepatitis B virus (HBV) is recognized as a major reason for hepatocellular carcinoma (HCC), with a huge financial burden to the society  database, and generated 209 secondary protein targets-associated genes and constructed their protein–protein interaction (PPI) network with the Cytoscape software. Primary target genes and the genes associated with them were further analyzed using DAVID  online tools for KEGG (Kyoto Encyclopedia of Genes and Genomes) biochemical pathways, and finally, the top 14 KEGG pathways were picked out. Nineteen overlapping genes derived from hepatitis B and pathways in cancer on the top 14 KEGG pathways were identified. At last, the expression level and overall survival (OS) of these hub genes were analyzed with UALCAN, which is a tool to facilitate the study of survival associations and gene expression variations across tumors based on exhaustive evaluation of TCGA (The Cancer Genome Atlas) gene expression data  enrichment analysis and KEGG pathway enrichment analysis were carried out using an online tool DAVID, which is an online database and analytic tool that provides information about a large list of genes or proteins and their potential functions  between normal and tumor samples and assess the effect of clinicopathologic features and level of gene expression on patient survival , prolactin signaling pathway (19 genes), pathways in cancer (37 genes), hepatitis B (23 genes), focal adhesion (26 genes), erbB signaling pathway (18 genes), PI3K/AKT signaling pathway (33 genes), proteoglycans in cancer (25 genes), estrogen signaling pathway (18 genes), colorectal cancer (15 genes), FoxO signaling pathway (20 genes), AMPK signaling pathway (19 genes), mTOR signaling pathway (14 genes), and HIF-1 signaling pathway (17 genes) . Moreovehttp://ualcan.path.uab.edu). We found that expression of GRB2 (p < 0.0001) followed by AKT1 (p = 0.0015) and PIK3CA (p = 0.0088) was linked to worse OS for liver HCC patients (The expression level and prognostic details of 19 selected genes are accessible online (patients . The UALInvestigations carried out in the past decades have shown that genistein demonstrates synergistic activities combined with chemo-drugs (Spagnuolo et al., A system biochemistry approach integrating multiple web-based tools was applied, and associations of HBV-related HCC and biological molecules with drug targets were evaluated. We obtained 13 primary and 209 secondary target genes/proteins in DrugBank and STRING. Nineteen overlapping genes from 2 of 14 enriched KEGG pathways related to genistein-altered genes were selected. The overexpression of AKT1, PIK3CA, and GRB2 in HCC was linked to decline in OS as per UALCAN. Therefore, we hypothesized that those three genes might be potential targets by genistein during the development of chronic HBV infection into liver cancer.The PI3K/AKT signaling pathway has been found abnormally activated in HCC and affects cell behavior, including proliferation, survival, metabolism, and tumorigenesis (Chen et al., In conclusion, with the increase in number of studies on genistein by traditional experimental techniques, more and more genistein targets will undoubtedly be identified. However, there is ambiguity in determining whether the specific biological effects on genistein can be definitively assigned to the individual or simultaneous modulation of their newly established or identified targets. This analysis enabled the interpretation of the inherent mechanisms of HBV-related cancer and genistein's target identification and would ultimately aid in future studies with rational experimental likelihood for detection and validation of logical hypotheses about the role of genistein in HBV-related liver cancers in the future.


This talk explores the importance of a racially diverse graduate student interacting in an applied care setting with minority older adults in the Southeast relative to assessment of cognitive status and in the context of cultural mistrust and misdiagnosis. ~250 older adults (16% AA) in an applied care setting were administered a cognitive screener as part of a larger research battery. An independent samples t-test was conducted to assess differences in mean cognitive status. Non-Hispanic Whites (NHW) (M=76.8 years) were found to be more intact than AAs (M=73.27) on measures of cognitive status . Implications highlight that cognitive screeners have often been found to lack sensitivity in groups of marginalized older adults. Having an AA graduate student in these settings could be a way of mitigating the effects of culturally incompatible screening tools and bridging the gap between research and practice for AA older adults.


We combined Medicare claims and nursing home (NH) administrative data to determine the mortality and morbidity effect of Hurricane Irma on nursing home residents. We utilized the Centers for Medicare and Medicaid Services (CMS) Standard Analytical Files (SAFs) combined with the Minimum Data Set (MDS) to create an exposure cohort of NH residents residing in Florida facilities immediately prior to Hurricane Irma’s landfall on September 10, 2017. We created a control group of residents who resided in the same NHs over the same dates in 2015, a year when there were no hurricanes. Outcome variables included 30/90-day mortality and first hospitalizations post storm. Compared to the control, an additional 260 more NH deaths were identified at 30 days and 429 more deaths at 90 days. Long stay residents (≥100 days) were at particular risk for mortality compared to short stay residents (<100 days). Hospitalization was also markedly increased.


Digital transformation creates new opportunities and is an important driver of novel and often disruptive innovation and value creation. Entrepreneurs are using digital technologies to finance innovation Opportunities and management of digital methods of funding innovation and entrepreneurship New value creation and platform innovation through digital technologiesCorporate entrepreneurship and startups within established organizations to approach opportunities and challenges of digital transformationExploitation of missing regulation of digital entrepreneurship Opportunities of Digital EntrepreneurshipThe following list of topics is neither exclusive nor exhaustive. We have structured them along three dimensions (Recker and von Briel Competence and team needs of (corporate) digital entrepreneursDigital entrepreneurial cultureThe role of universities and entrepreneurial ecosystems for digital entrepreneurshipImpacts of digital technologies on entrepreneurial decision makingUse of Social media or crowdsourcing resources by entrepreneursOrganization, organizational learning, and performance of digital startupsManagement of digital business model innovationInternationalization of digital startupsAlignment of digital capabilities and business modelsBehavior of startups in digital platform ecosystems Development and management of new digital ecosystems by startupsIndustry-specific classification schemes of startups or business models Changes in startup investment processes due to digitalizationProcesses, Organization, and Challenges of Digital EntrepreneurshipImpacts of Digital EntrepreneurshipImpacts of digital entrepreneurship on regions and countries Investments in digital innovation and their economic or societal pay-offsThe dark side of new digital business models Influences of digital entrepreneurial and innovative activities on government policy or regulationhttp://www.editorialmanager.com/buis/). Please observe the instructions regarding the format and size of contributions to Business & Information Systems Engineering (BISE). Papers should adhere to the submission general BISE author guidelines .Please submit papers by 1 March 2021 at the latest via the journal’s online submission system (All papers will be reviewed anonymously (double-blind process) by at least two referees with regard to relevance, originality, and research quality. In addition to the editors of the journal, including those of this special focus, distinguished international scholars will be involved in the review process.https://www.fgf-ev.de/en/g-forum-conference-2020-karlsruhegermany/). In this paper development workshop, the special issue editors will provide feedback on early drafts or first paper versions. The submission to the G-Forum, however, is not a requirement for submitting to the special issue. Please Note: We are closely monitoring the current situation with regards to COVID-19 and the paper development workshop might therefore be canceled or moved to a digital setting.There will be a special issue paper development workshop at the 24th Annual Interdisciplinary Conference on Entrepreneurship, Innovation and SMEs (G-Forum) which will take place at KIT Karlsruhe, Germany, from 30 September to 2 October 2020 (Deadline for submission: 1 March 2021Notification of the author 1: 3 May 2021Completion revision 1: 2 July 2021Notification of the author 2: 17 August 2021Completion Revision 2: 21 September 2021


A questionnaire-based survey was conducted among members of the European Society for Gynaecological Endoscopy (ESGE), with the aim of increasing awareness of the diagnosis and surgical treatment of tubal disease as an alternative to in-vitro fertiliszation (IVF). Seventeen participants (34%) occasionally used a test for prediction of the ovarian reserve before surgery, and the most commonly used test was anti-mullerian hormone assay . Laparoscopy was the preferred method for staging tubal disease .Thirty-seven (76%) participants always performed salpingectomy or tubal occlusion before the first IVF attempt. Thirty (60%) of the gynaecological surgeons considered the outcome with tubal surgery and IVF to be similar in mild tubal disease, whereas for severe disease, 31/50 (62%) felt that surgery had worse outcome. Among other factors to be considered in choosing a strategy for treating infertility, 20/50 (40%) of respondents listed the stage of disease. The findings of this survey suggest that first-line treatment for women younger than 35 years old with minor tubal pathology, is tubal surgery. IVF appears to be offered if there are other infertility factors, if the patient is >38 years old and if moderate to severe tubal disease is present. Tubal disease is responsible for 30-40% of cases of female infertility. Pathology of the fallopian tubes may vary from peritubal adhesions and distorted tubal anatomy or damaged fimbriae to hydrosalpinx or tubal blockage . Pelvic st to March 31st , 2019, ESGE members were invited by the ESGE Central Office to complete a 22-item online questionnaire, accessible through the ESGE website. For some questions, more than one answer was acceptable. The invited gynaecological surgeons were not specifically infertility specialists, but they had experience in laparoscopic treatment of tubal-factor infertility. The participants received three reminders during this period. Fifty 50 gynaecological surgeons participated in the survey.A questionnaire survey was conducted to assess the approaches of members of the European Society for Gynaecological Endoscopy (ESGE). From March 1Forty-eight (96%) of the participants were specialists and two (4%) were trainees. Sixty per cent of the participants were aged 35 to 54 years; 25(50%) were experts who performed more than 90 laparoscopic procedures per year; and 19 (38%) had over 16 years of practice in endoscopic operations. Eighteen (36%) of the participants performed more than 30 laparoscopic tubal operations per year and 22 (44%) performed 10 to 30 per year. Seventeen of the participants (34%) worked in a university teaching hospital and 25 (50%) worked in a national health service hospital.According to 43 (86%) of the surveyed gynaecological surgeons, the best method for staging tubal disease was laparoscopy. Salpingectomy was the operation preferred by 30 (60%) participants, salpingoneostomy by nine (18%), tubal anastomosis by six (12%) and tubal occlusion by two (4%). Twenty-nine (58%) of the participants preferred bipolar energy for electrocoagulation during surgical treatment for tubal disease. When there is an incidental finding of hydrosalpinx 21(42%) of the gynaecological surgeons reported treatment in all cases; 18 (36%) reported treatment depending on the case; six (12%) reported no treatment; and 4 (8%) reported treatment only in case of bilateral disease. When hydrosalpinx was an incidental finding, 43 respondents (86%) preferred to inform the patient first and perform second-look surgical treatment only when there is indication, such as pain or infertility.In treatment of asymptomatic hydrosalpinx 23 (46%) gynaecological surgeons reported using no routine antibiotic treatment, 18 (36%) reported using occasional antibiotic treatment; and five (10%) reported using antibiotic treatment in all cases. When antibiotics were used for this condition, 20(40%) of the gynaecological surgeons seemed to prefer a combination of doxycycline, cephalosporin and penicillin, whilst 25 (50%) seemed to prefer doxycycline or cephalosporin only.Twenty-two (44%) participants reported using a test for predicting ovarian reserve in all cases before tubal surgery for infertility, and 40 (80%) felt the most precise and reliable test for predicting ovarian reserve is the serum anti-Mullerian hormone assay. Twenty-four (48%) reported salpingectomy as the best method for surgical treatment of hydrosalpinx in case of infertility, while 17 (34%) prefer laparoscopic tubal occlusion, six (12%)prefer salpingostomy, and three (6%) prefer hysteroscopic tubal occlusion, with permanent micro inserts to cause fibrosis and irreversible tubal occlusion, which develop within three months of insertion.Thirty-seven (76%) participants always performed surgical treatment of hydrosalpinx before the first IVF attempt, and 40 (80%) supported salpingectomy as being the best operative method regarding the outcome of a following IVF attempt. For women with mild tubal disease, good ovarian reserve and no other infertility factors, the prognosis of tubal surgery versus IVF is similar according to 30(60%) respondents. For women with moderate tubal disease 19(38%) participants felt that surgery and IVF had similar outcomes, and 17 (34%) felt that surgery had worse outcomes. In the treatment of severe tubal disease, 31 (62%) gynaecological surgeons stated that tubal surgery has worse outcomes than IVF. Twenty-two (44%) of participants reported that the combination of both methods imposes higher cost. Finally, according to 20 (40%) of the surveyed gynaecological surgeons, the stage of tubal disease is the first factor to take into account when considering strategies for treating infertility, whereas 30 (60%) felt that age and other infertility factors are most important.The results of this survey of 50 members of the ESGE on surgical treatment of tubal-factor infertility are comparable to the published literature on this subject. Thirty-eight (76%) participants favoured laparoscopy as the ideal method for the evaluation of tubal patency and the diagnosis of tubal disease, which is in line with reported practice . Almost Based on the survey responses, first-line treatment for women less than 35 years old with minor tubal pathology seems to be tubal surgery. IVF appears to be offered when there are other infertility factors, if the patient is >38 years old, and when moderate- to-severe tubal disease is present. According to the surveyed laparoscopic surgeons, tubal surgery and assisted reproductive technology in most of the cases are not competitive techniques, but usually tubal surgery is a prerequisite for the success of the IVF. Optimizing pregnancy rates and reducing the risks associated with IVF or surgical treatment should always be the main goal. The outcome of our survey is especially meaningful because of the high level of expertise in laparoscopic surgery and the high level of expertise in the laparoscopic treatment of hydrosalpinx among the participating gynaecological surgeons. On the other hand, the insufficient number of participants is a drawback, which points out the need for a future survey, better designed and with more gynaecologists with experience in laparoscopic treatment of tubal-factor infertility. Such a survey would minimize bias and produce clear answers and recommendations.


Family caregivers provide the majority of support for older adults and people with disabilities in the U.S. The onset of the COVID-19 pandemic forced radical changes in duties and relationships between family caregivers and care recipients. These changes can be attributed to fears of virus transmission as well as federal, state and local government mitigation strategies resulting in social distancing and quarantining limiting caregiving interactions. This qualitative investigation conducted 55 Zoom interviews over summer 2020 with family caregivers to explore their changing roles and duties during the pandemic. Researchers utilized a semi-structured interview guide to explore caregiver experiences with COVID-19. The average age of the caregiver participants was 59 and the average age of the care recipients for whom they provided care was 74. All participants provided unpaid care for family members. Interviews were conducted in English (n=40), Spanish (n=5), Somali (n=5) and Korean (n=5). Care recipients resided in a facility  (70%) with the caregiver (20%), and in a separate independent setting (10%). Data from each interview were coded into themes by two researchers. Themes that emerged from the analyses included concerns about care recipient mental and physical health deterioration, lack of communication from formal providers, change in relationships with other family members, and future concerns. Implications for additional research and practice are included.


Home-based medical care (HBMC) is emerging in China, but research understanding the efficiency and effectiveness of this new care model is rare. In this study, researchers interviewed 17 Chinese homebound adults aged 45 and older  who have received HBMC, and collected detailed information regarding their experiences and attitudes toward HBMC. Participants were recruited from healthcare institutions in Shanghai, Jinan, and Zhangqiu of China. The evaluation of patients’ experiences with HBMC yielded both positive and negative aspects. Positive experiences included 1) the delivery method was convenient for homebound patients; 2) health problems could be detected timely because doctors visited patients regularly; 3) home care providers had better bedside manners and professional skills than hospital-based providers; 4) the medical insurance covered the cost of home care services. Negative experiences related to the supply and quality of care, including 1) the scope of current HBMC services was too limited to meet the needs of homebound patients; 2) the visit time was too short; 3) healthcare providers’ professional skills varied greatly. Findings from this study suggest that the HBMC model benefited Chinese older adults, primarily homebound adults, in terms of convenience and affordability. There are opportunities to expand the scope of home care services and improve the quality of care. Policymakers may consider providing more resources and incentives to enhance HBMC in China. Educational programs may be created to train more HBMC providers and improve their professional skills.


Disease Models & Mechanisms (2019) 12, dmm040238 (doi:10.1242/dmm.040238).There was an error in The authors mistakenly used the wrong image for the FUS(1-359) vehicle panel in Both the online full-text and PDF versions have been updated and the authors apologise to readers for this error and any inconvenience it may have caused.


Pakistan is a developing country with high number of road traffic injuries. High magnitude of road traffic injuries highlights deficiencies in road traffic laws which are not at par with current safety requirements resultantly fail to address important risk factors such as distracted driving, non-use of seat belt and helmet. Purpose: - To assess effect of deficient traffic laws related of distracted driving, seat belt and helmet usage in term of estimate prevalence of different types of distractions and use of helmet by motorcycle riders and pillion riders and seat belts by the drivers and the passengers on National Highway in Pakistan that can lead to road crashes and increasing the injuries.Roadside survey was carried on N-5 National Highway to estimate number of distracted drivers, use of helmet by riders and pillion riders and use of seat belt by drivers and passengers.Three types of distraction were observed i.e. Mobile Phone distraction (24%); Equipment related distraction (1%) and eating related distraction (1%) amounting to 29% of drivers distracted ;car drivers (29%), other vehicle drivers (6%), motorcyclists (3%) and trailer drivers (3%). Likewise; 64% drivers were found without seat belt, LTV drivers (85%), car drivers (74%) and truck drivers (69%). Similarly; 97% passengers were found without seat belt, LTV passengers (100%), truck passenger (99%), cars passenger (97%), Oil tanker and trailer passenger (90%). Helmet violation was high with 87.4% motorcycle riders and 100% pillion riders were found without helmet. Lack of enforcement due to deficient traffic laws result in RTIs in Pakistan. There is need to improve legislation on different forms of distractions, use of seat belt among passengers and helmet use by pillion riders; so that enforcement efforts can be made to address risk factors effectively to meet Decade of Action 2011-2020 targets.Seat belt, Helmet, Distraction, Pakistan


Dear Editor,We would like to thank Dr Arjun Srirampur for his interest in our work. Below please notice our replies:1. All of our diabetic patients were operated upon due to proliferative diabetic retinopathy (PDR) complications such as non-clearing vitreous hemorrhage and traction retinal detachment but there was no case of rhegmatogenous retinal detachment; therefore no tamponade was used during surgery.2. None of our patients had uncontrolled IOP during the short follow-up period (two weeks) after surgery in both groups. The corneal epithelial defect (CED) was improved in all eyes except three; and in those three eyes, lateral tarsorrhaphy and application of a lubricant ointment resulted in healing of the CED less than one month after surgery.


Functional disability might be related to an increased risk of dementia or could represent a prodromal stage. We examined the occurrence of functional impairments over eight years follow-up and their association with dementia incidence in 1,666 participants aged 65+ from the English Longitudinal Study of Ageing. Growth models with distal outcome were used to examine whether different trajectories of functional abilities (activities of daily living (ADL); and instrumental activities of daily living (IADL)) between 2002/03 and 2010/11, were associated with dementia incidence four years later (2014/15). Participants with an increasing number of functional impairments (Class III), were more likely to be classified with subsequent dementia compared with those with no impairments (Class I). An increased risk was also observed for individuals with raised levels of impairments (Class II). We found IADLs more sensitive than ADLs, and this may imply a more comprehensive ascertainment during the prodromal stage of dementia.


In 2020, the Center of Innovation for Veteran Centered and Value Driven Care (COIN) continued its monitoring and evaluation of the Veterans Administration (VA) Medical Foster Home (MFH) programs expansion into rural areas. Veterans in MFHs are provided 24/7 care by VA trained and supervised community caregivers and primary care by VA Home Based Primary Care (HBPC) teams. One year after the three-year (2017-2019) expansion funds stopped, COIN continued monitoring remaining programs. Objectives were to understand factors critical for program expansion and sustainability and the impact of COVID-19. Phone interviews were conducted with sixteen coordinators from seventeen programs. A thematic analysis approach was used to address the evaluation objectives using transcript data. Findings showed factors important to program sustainability were: 1) Program fit (finding caregivers in the community); and 2) Local VA facility support . COVID prompted losing some caregivers and prevented others from joining. Program staffing was not impacted as many program activities ceased. Recreational therapists (RTs) were significant to maintaining Veterans well-being and reducing social isolation through virtual activities. COVID required coordinators transition their supervision of MFHs to new virtual environments and HBPC to increase telehealth to new levels. Local leadership became important to monitoring local conditions and providing support to programs. The evaluation: 1) Found factors important to program sustainability were also critical to keeping programs operational during the pandemic; and 2) Stimulated future research on the suitability of MFH programs to meet challenges to resurgences of COVID or other national emergencies.


The literature on the contribution of elastic fibre deposition to alcohol-related liver disease (ARLD) is limited. We studied: (1) 180 liver biopsies from ARLD patients; (2) 20 ARLD explant livers; (3) 213 liver biopsies with non-ARLD injury. Elastic fibres were assessed in terms of their distribution around hepatocytes [pericellular elastosis (PCE)] and within bridging fibrous septa  and scored using a semiquantitative system. We also investigated the composition of the elastic fibres  in 20 cases. PCE was associated with steatohepatitis in ARLD patients and with ARLD when compared to non-ARLD cases (p < 0.001). Oxytalan fibres were identified in PCE in ARLD biopsies and broken dense perisinusoidal mature elastic fibres in explanted livers. Septal elastosis increased from intermediate to advanced fibrosis stage. Early septal elastosis contained oxytalan fibres, whereas septal elastosis at more advanced stages contained mainly mature elastic fibres. PCE is a typical feature of steatohepatitis in ARLD and includes oxytalan fibres. Septal elastosis is a gradual process with a transition from oxytalan to mature elastic fibres usually present in explanted livers. There may be different dynamics in the assembly and reabsorption of pericellular and septal elastic fibres, and a potential role for stratification of patients with advanced stage ARLD. The spectrum of liver injury in alcohol-related liver disease (ARLD) ranges from simple steatosis to steatohepatitis and from minimal or no fibrosis to cirrhosis2. Elastic fibres are a component of the extracellular matrix (ECM) along with collagen, glycoproteins, glycosaminoglycans and proteoglycans3. The elastic fibres are composed of a core of elastin made of tropoelastin monomers encoded by ELN and a microfibrillar mantle composed of fibrillins, glycoproteins which in humans are present in three isoforms4. The relative proportion of tropoelastin and microfibrils divide elastic fibres into three main types: oxytalan, composed of microfibrils only with no elastin core; and elaunin and mature elastic fibres, both characterized by a central cross-linked core of elastin and a surrounding microfibrillar component. Elaunin fibres have a lower amount of elastin compared to mature elastic fibres5. Oxytalan fibres can be differentiated from both elaunin and mature elastic fibres by removing the oxidation step of histochemical elastic fibre staining methods such as the orcein stain or analogues9. Oxytalan fibres do not react with this modified protocol, whereas both elaunin and mature elastic fibres remain positive. Elastogenesis begins in the late stages of development and early after birth10 and is particularly active in those tissues in which elastic properties are essential for their function such as the aortic wall and lung parenchyma4. Elastogenesis is attenuated in normal adult tissues but reactivates in a wide spectrum of disease processes10 including wound healing12. Elastin has long been known to accumulate in fibrotic livers13. Little is known however about its role in the progression of ARLD and the literature on the contribution of elastic fibre deposition in ARLD injury is limited14. Porto et al.14 showed that in the early stage of alcoholic fibrosis there is deposition of oxytalan fibres in the space of Disse in the perivenular region. The internodular bridging fibrous septa of more advanced stages contained oxytalan and elaunin fibres. Our aim was to evaluate retrospectively a large series of liver biopsies from patients with ARLD focusing on the pattern, distribution and composition of elastic fibres.Worldwide alcohol-related mortality in 2016 was high at 38.8 per 100,000 people and half of cirrhosis related deaths were due, at least in part, to alcohol useOut of our initial cohort of 303 biopsies 180 fulfilled our selection criteria and were selected for our study.Seventy-three biopsies (40.6%) showed steatosis only (mild in 36 (49.3%), moderate in 28 (38.4%) and severe in 9 12.3%). Ninety-seven biopsies (53.9%) showed steatohepatitis. Ten (5.6%) biopsies were classified as NOS  of liver biopsies at the different disease stage were as follows: 0 (no fibrosis) = 4 (2.2%); 1 (early) = 84 (46.7%); 2 (intermediate) = 34 (18.9%); 3 (advanced stage cirrhotic transformation) = 13 (7.2%); 4 (advanced stage cirrhotic) = 45 (25%).For reference, examples of none and focal perihepatocytic elastic fibres, and PCE are demonstrated in Fig. The correlation between pericellular elastic fibres and overall disease pattern is detailed in Supplementary Table PCE was identified in 58 32.2%) of the 180 cases studied. PCE was present in 7 (9.6%) of the 73 biopsies with steatosis, 47 (48.5%) of the 97 biopsies with steatohepatitis, and 4 (40%) of the 10 biopsies classified as NOS. When biopsies were divided into two groups according to presence or absence of steatohepatitis, PCE was significantly associated with steatohepatitis  with end stage ARLD. All patients had been abstinent at the time of transplantation for at least 6 months.Most cases showed a combination of grades 2, 3 and 4 of septal elastic fibres. Grade 0 was not observed in any of these 20 cases and grade 1 was present in three cases only. PCE was not identified in most cirrhotic nodules in 18 cases. It was present very focally in occasional cirrhotic nodules after extensive examination at high magnification in 4 cases, and was easily identified at low magnification in a few (7 cases) or several (7 cases) cirrhotic nodules. The pericellular elastic fibres were often in the form of broken dense strands or in a more perisinusoidal distribution. Examples are shown in Supplementary Figure In two other cases PCE was more prominent affecting approximately half of the cirrhotic nodules in the sample examined. There was no evidence of active steatohepatitis.We next correlated our findings with the immunohistochemistry for elastin and the repeat Victoria blue stain with and without the oxidation step to explore the proportion of oxytalan, elaunin and mature elastic fibres. , in all ten biopsies showing grade 1 or grade 2 septal elastosis with the conventional Victoria blue an appreciable reduction in elastic fibre stain with the modified Victoria blue method suggested the presence of a significant proportion of oxytalan.Grade 3 or 4 septal elastosis, consisted of elastin positive septa without reduction in stain with the modified Victoria blue stain indicating that the septa were composed mostly of mature elastic fibres.PCE appears to be composed of a significant proportion of oxytalan in most of the biopsy specimens and of mature elastin in the explanted livers . Further studies are needed to better understand whether the elastification process can be used to stratify patients with advanced stage ARLD and correlate with clinical outcome.Our study was based on four cohorts of specimens; (i) a series of 303 core needle biopsy specimens from patients with known ARLD clinically; (ii) a series of 20 livers removed at transplantation for ARLD; (iii) a control group of 213 core needle biopsy specimens with a variety of liver conditions other than ARLD characterized after clinico-pathological correlation; (iv) a selection of representative cases from cohorts (i) and (ii) to investigate in more details the elastic fibres morphology and composition in terms of oxytalan, elaunin and elastin content.16: steatosis, steatohepatitis, and not otherwise specified (NOS).Our review of the first cohort of biopsies included the assessment of the overall pattern of liver injury, fibrosis stage, and pattern of elastic fibre deposition. The biopsies were divided into the following categoriesFibrosis staging was carried out using a semiquantitative scoring system (0 no fibrosis identified); 1 or early; 2 or intermediate (bridging fibrosis); 3 or advanced stage with features of cirrhotic transformation; and 4 or advanced stage cirrhotic.We assessed the presence of elastic fibres in a pericellular/perivenular distribution and within fibrous septa.Pericellular elastic fibres were classified as absent, focal  and after extensive search), or pericellular elastosis (PCE) (perihepatocytic elastic strands obvious at 10 × or 20 × magnification).We classified septal elastosis into the following grades: grade 0: bridging fibrous septa with no elastic fibres; grade 1: bridging fibrous septa with delicate fibres visible only at high magnification; grade 2: elastic fibres visible at low magnification and clearly distinguishable from the residual portal or liver capsule elastic fibres, grade 3: strong elastic bundles well visible at low magnification and of similar density, blending with or indistinguishable from the to the residual portal normal or liver capsule elastic fibres; and grade 4: slender, regressive type dense elastic bundles visible at low magnification. Pericellular and septal elastosis were further investigated, in terms of their composition on a subseries of 20 cases using 6 serial sections. The sections were stained in the following sequential order with (i) anti-Elastin [BA4] antibody IHC (ab9519), (ii) Victoria blue with no oxidation step (demonstrating only mature elastin fibres and Elaunin), (iii) Victoria blue with oxidation and decolourisation step , (iv) (spare unstained back-up section), (v) Picrosirius red and (vi) Haematoxylin and Eosin. Reduction in stain between the Victoria blue with and without oxidation step was assessed as follows: minimal and focal ; partial ; marked . Septal elastin immunohistochemical stain was regarded as diffuse when present in most or all septa and patchy when approximately half of the septa were negative. Pericellular elastin stain was considered as diffuse (most hepatic plates), patchy , focal (identified at high magnification after extensive search) or absent.Details on the biopsy selection, histological categories, fibrosis scoring system staining protocols, statistical analysis and elastic fibres assessment are provided as supporting information. All methods were carried out in accordance with relevant guidelines and regulations, experimental protocols were approved by the Royal Free Hospital Ethics Committee (07/Q0501/50) and informed consent was obtained as appropriate.Supplementary Information.


Loneliness and social isolation present emerging public health challenges for aging populations. To inform efforts against loneliness and social isolation, research is needed to evaluate impacts of these conditions on patterns of adverse aging outcomes. We used longitudinal, repeated measures data to isolate effects of loneliness and social isolation from effects of socioeconomic circumstances and psychological vulnerabilities, rule out reverse-causation, and test dose-response in associations with morbidity, disability, and mortality. We also explored the biological basis of relationships by testing associations with biological aging. We analyzed data from more than 12,000 adults aged 50-95 in the US Health and Retirement Study (HRS) who reported on symptoms of loneliness and social isolation at 2-3 time points during 2006-2014. We measured loneliness using the 3-item Revised UCLA Loneliness Scale and social isolation using a 6-item scale. We tested associations with chronic disease, disability, and biological aging in 2016 and with mortality through 2018. We found (1) associations of loneliness and social isolation with adverse aging outcomes are not fully explained by socioeconomic circumstances and psychological vulnerabilities; (2) the direction of relationships with disability indicates temporal precedence of loneliness and social isolation; (3) there is a dose-response in associations with loneliness; and (4) there is evidence of a biological mechanism explaining associations with loneliness and social isolation. Findings add to the emerging literature on health sequelae of loneliness and social isolation. Assessment of loneliness and social isolation in surveillance and intervention with older adults can enhance risk assessment for adverse aging outcomes.


Digital methods are a way to engage marginalized populations, such as sexual and gender minority (SGM) adults. No study to date has leveraged these methods to engage SGM caregivers of people with dementia. We used digital methods to access SGM caregivers of people with dementia in our study of psychosocial measures of caregiving for recruitment and data collection. Posts on social media and online registries targeted SGM caregivers. The study landing page received 2201 views; 285 caregivers completed the survey. Participants learned of the study most frequently from Facebook (45%). The sample was 84% white, with gay (52%), lesbian (32%), bisexual (11%), and other sexual orientations (5%) and transgender (17%) caregivers represented. While we exceeded goals for inclusion of Latinx (26%) and Native American (4%) caregivers, the number of African American SGM caregivers was lower than projected (7%). Digital methods are effective for engaging SGM caregivers of people with dementia.


Crops during their early growth stages are vulnerable to a wide range of environmental stressors; thus, earlier seed invigoration and seedling establishment are essential in crop production. As an alternative to synthetic chemical treatments, plasma technology could be one of the emerging technologies to enhance seed germination and seedling vigor by managing environmental stressors. Recent studies have shown its beneficial effects in various stress conditions, suggesting that plasma treatment can be used for early crop stress management. This paper reviewed the effects of different types of plasma treatments on plant responses in terms of the seed surface environment (seed scarification and pathogen inactivation) and physiological processes (an enhanced antioxidant system and activated defense response) during the early growth stages of plants. As a result, plasma treatment can enhance seed invigoration and seedling establishment by alleviating the adverse effects of environmental stressors such as drought, salinity, and pathogen infection. More information on plasma applications and their mechanisms against a broad range of stressors is required to establish a better plasma technology for early crop stress management. Rapid seed invigoration and seedling establishment during the early growth stages of crops are necessary to prevent crop yield loss due to unfavorable environments. Seed germination and early seedling growth are the most sensitive growth stages for a crop to a wide range of environmental stressors . Once thPlasma technology has been widely designated as an advanced oxidation process . It has However, no review has yet summarized plasma applications and their protective mechanisms against a broad range of stressors. The potential applications of plasma technology for early crop stress management are largely unknown. This review evaluated the effects of the different types of plasma treatments on plant responses in terms of the seed surface environment (seed scarification and pathogen inactivation) and physiological processes (an enhanced antioxidant system and activated defense response) during the early growth stages of plants. Recent information on plasma applications and their mechanisms against a broad range of stressors was reviewed from these two perspectives. Thus, this review proposes that plasma technology has potential uses for seed invigoration and seedling establishment under stressful conditions.The seed coat regulates seed germination through its thickness and permeability. Therefore, seeds with thick coats are incapable of water uptake rapidly unless it is scarified . In part6H5NH2) or cyclohexane (C6H12). However, RF discharge delayed the germination time of maize, radish, and some legumes such as soybeans, peas, and common beans when generated from carbon tetrafluoride (CF4) or octadecafluorodecalin (ODFD) otherwise known as perfluorodecalin (2H4)  .Dielectric barrier discharge (DBD) has been proven to be effective for seed germination and seedling vigor when generated under optimal conditions. DBD in air induced faster germination, leading to a better germination rate and early seedling growth of wheat, barley, and peas under laboratory conditions . A DBD wOther discharge plasmas, including corona, arc, glow, and microwave discharges, also have shown stimulating effects on seed invigoration of some crops although their maximum values differ depending on the treatment conditions of the plasma sources .These results suggest that plasma treatment can enhance the water absorption of seeds, thus leading to a better invigoration of crops. The beneficial effect of plasma treatment on seed invigoration is mainly associated with its power (W) and exposure time (min) , plasma treatments with DBD and arc discharge effectively inactivated its growth and thus reduced the fungal infection of rice by a maximum value of 51% under environmentally controlled conditions  radical into hydrogen peroxide (H2O2) and an ordinary molecular oxygen (O2). Finally, CAT in peroxisomes and PODs in the cytosol detoxify the hydrogen peroxide (H2O2) by catalyzing its reduction to water (H2O). Together with these enzymes, non-enzymatic antioxidants can provide cells with highly efficient machinery to detoxify the molecular species of active oxygen. After plasma treatment, the enhancement of these antioxidant systems has recently been reported in a few crops , catalase (CAT), and peroxidase (POD), in plant cells . The antCellular antioxidant systems are effectively enhanced by plasma treatments with a low power (W) and short exposure (min) see . SimilarDielectric barrier discharge has shown positive effects on the contents of the total phenolic compounds under laboratory conditions, although its effects depend on the types of feed gas. These results indicate that plasma treatments generated with a low power and short exposure time  can enhance cellular antioxidant systems  through H2O2-mediated signaling activating defense-related responses  and physiological processes  in seeds under stressful conditions such as drought, salinity, and pathogen infection (1) reduce infection with pathogenic microorganisms in germinating seeds or growing plants (2) regulate ROS homeostasis through the antioxidant machinery of plants (3) activate other defense-related responses in plant cells  and the seed surface, seed-borne pathogens, and cellular homeostasis, respectively. Although the plasma-induced effects are still poorly understood, their potential mechanisms for crop stress tolerance can be suggested based on the review of the literature on plasma-induced plant responses (Section 2). The ROS, RNS, and UV of plasma can change the physical and chemical properties of the seed surface before exposure to environmental stressors, thus enabling seeds to be more hydrophilic and permeable to water. Scanning electron microscopy studies have shown partial degradation of cellulose and formation of cracks on the surface of plasma-treated seeds . Additiog plants , 2) reguf plants , and 3) nt cells . Many stnt cells . AltogetSeed invigoration and seedling establishment under stressful conditions are highly variable depending on numerous factors, including biological  and environmental factors . There is little or no information for establishing crop stress management practices using plasma technology. To our knowledge, there are only a few studies under laboratory conditions on crop tolerance to disease , droughtPlasma applications have been widely used for seed scarification, pathogen inactivation, and antioxidant system activation with proven beneficial effects on seed invigoration and seedling establishment under laboratory and greenhouse conditions. Moreover, the optimal plasma exposure can enhance crop tolerance before stress events  by modulating the seed surface environment  and physiological processes  in seeds. This promising technology is potentially valuable for alleviating the adverse effects of environmental stressors on seed germination and seedling growth in crop production. However, information on plasma effects under stressful conditions is limited to a few crops under laboratory conditions. Further studies are necessary to fully understand the effectiveness of plasma applications to a broad range of stressors under field and greenhouse conditions. This review suggests that the power (W) and exposure time (min) are vital operating parameters of the plasma treatment that affect the phenomenon of the plasma. More experimental evidence is needed to adopt the use of the power (W) and the exposure time (min) as standardized values for the plasma treatment of various crops ” through the National Fusion Research Institute of Korea (NFRI) funded by government funds.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.


The Chinese Center of Disease Control and Prevention (CDC) executed an intensive investigation program. WHO named this novel strain of coronavirus as sever acute respiratory syndrome coronavirus 2 (SARS-CoV-2) aka coronavirus disease 2019 (COVID 19). The sufferer of this virus predominantly and typically shows the symptoms of acute respiratory infections ranging from barely noticeable cough and dyspnea to need of mechanical ventilation in excessively compromised individuals but it typically causes pneumonia thus producing pneumonia like symptoms.th leading cause of death in USA.According to World Health Organization (WHO) the ailments caused by viruses have always emerged in the past and posed masses to life threatening medical conditions. Considering the last two decades, a number of viral infections emerged as epidemic including severe acute respiratory syndrome coronavirus (SARS-CoV), H1N1 influenza, Middle East respiratory syndrome coronavirus (MERS-CoV) and when the timeline approaches the present days there is an outbreak of coronavirus once again with drastic dissemination all across the globe but this time it is the novel one, having a new strain and originating from China in the city of Wuhan with its 1MMAA: Concept, design and accountable for all work.SQ: Drafting and revision.KK: Critical analysis and final approval.


Purpose: To collect information on unintended drug exposure during pregnancy in early clinical drug development. Materials and methods: Questionnaire mailed in autumn 2015 to members of human pharmacology societies in Europe for anonymous responses via the online tool SurveyMonkey. Results: 53 of the ~ 700 addressees participated in the survey. 23 female trial participants and 11 female partners of male trial participants were exposed to investigational medicinal products during unintended pregnancies in a clinical trial. Most survey respondents confirmed adequate contraceptive methods by in/exclusion criteria and the use of pregnancy tests in female trial participants at screening and before the first dose. The last menstrual period was documented less frequently . A considerable proportion of respondents denied the routine use of compliance checks about the appropriate use of contraceptive methods, had no procedures in place if contraceptive methods failed, and did not train physicians in instructing trial participants about the appropriate use of contraceptive methods. Conclusion: The methods to avoid unintended pregnancies during participation in a clinical trial need improvement and should include (i) pregnancy tests, (ii) documentation of last menstrual period before the first dose, (iii) compliance checks of the appropriate use of contraceptive methods, and (iv) training of trial physicians. Procedures should be in place for what to do if contraceptive methods fail.  What is known about this subject Pregnancies in early clinical drug development must be avoided Appropriate methods to avoid unintended pregnancies are to be defined in the clinical trial protocol Guidance is provided in the ICH M3(R2) and the respective European Clinical Trial Facilitation Group recommendations (CTFG 2014) What this study adds This AGAH survey revealed that unintended pregnancies occur in early clinical drug development Regulatory recommendations are not fully implemented The methods to avoid unintended pregnancies during participation in a clinical trial need improvement A series of workshops related to early-phase clinical development has been hosted by the scientific society “Association for Applied Human Pharmacology” (AGAH e.V.) in Germany since 2012. In 2015, members from the pharmaceutical industry, contract research organizations, academia, ethics committees, and the German competent authority discussed unintended exposure to an investigational medicinal product (IMP) during pregnancy in clinical trials and its prevention [In early drug development, data on reproduction toxicity are in general not yet available. According to the ICH M3R2) Guidance [ Guidance“Men can be included in Phase I and II trials before the conduct of the male fertility study since an evaluation of the male reproductive organs is performed in the repeated-dose toxicity studies” “For women of childbearing potential (WOCBP) there is a high level of concern for the unintentional exposure of an embryo or foetus before information is available concerning the potential benefits versus potential risks” If reproduction toxicity studies are not available, and WOCBP are planned to be included in a clinical trial, the guideline recommends limiting the risk by taking precautions to prevent pregnancy by (i) pregnancy testing , (ii) use of highly effective methods of birth control, and (iii) trial entry only after a confirmed menstrual period. To enable trial participation of WOCBP, the ICH M3R2) Guidance [ GuidanceInformed consent should be based on known risks to the embryo/fetus related to reproduction toxicity. A general assessment of potential toxicity of pharmaceuticals with related structures or pharmacological effects should be provided If no relevant reproductive information is available, the potential for unidentified risks to the embryo or fetus should be communicated as well Subjects should be instructed to use adequate contraceptive measures during the period of drug exposure which could exceed the length of the trial Pregnancy tests are required during the trial to ensure compliance with the contraceptive measures planned in the trial protocol In Europe, the Clinical Trials Facilitation Group (CTFG) has issued further recommendations related to contraception and pregnancy testing in clinical trials . They arA survey was conducted (i) to collect information on unintended pregnancies during clinical trials in early drug development and (ii) to learn from current experience whether applied precautionary measures are in line with current guidances , 3 and aDefinitions used are: Drug exposure via parent (DEVP) Unintended drug exposure during pregnancy in a clinical trial The survey addressed specialists working in early-phase drug development in Germany, Belgium, France, and the United Kingdom. The questionnaire  compriseThe questions covered the following topics (see questions (Q) provided in Characteristics of survey participants  Number and cause of unintended pregnancies in female participants and female partners of male trial participants in clinical trials combined in one protocol (Q3 – Q8) Age of women becoming accidentally pregnant in a clinical trial (Q9) Preventive measures (Q10 – Q13) It cannot be excluded that different participants belonging to the same organization referred to the same trial protocol(s). In consequence, a qualitative rather than quantitative interpretation of results is indicated. Not all survey participants answered all questions. For the respective questions, the total number of responses is given . A total of 53 of ~ 700 addressees answered the questionnaire. The majority came from contract research organizations (19), the pharmaceutical industry (15), but also from academia (8), independent consultants (8), biotechnology (2), or regulatory authority (1). Participants were from Germany (47), The Netherlands (3), Belgium (1), Luxembourg (1), and South Africa (1). 15 survey participants reported that 23 female clinical trial participants were unintentionally exposed to IMP during pregnancy in a clinical trial they sponsored or conducted during the past 10 years. 33 survey participants denied the occurrence of such pregnancies. A total of 10 survey participants reported that 11 female partners of male clinical trial participants were unintentionally exposed to IMP during pregnancy in a clinical trial they sponsored or conducted during the past 10 years. 36 survey participants denied the occurrence of such pregnancies. These included (i) non-compliance with trial-specific contraceptive methods (9), (ii)  failure of contraceptive methods (3), and (iii) failure of the pregnancy test to detect pregnancy at screening or before first dose (1). The main outcome of this AGAH survey demonstrates that the occurrence of unintended pregnancies is a relevant issue in early drug development despite considerable effort to avoid them. Taking into account that 53 out of ~ 700 addressees responded, it may be assumed that the unintended exposure to IMPs in early pregnancy is higher than reported here. The number of participants is not a representative sample of all parties conducting clinical trials in Europe. Participants from the same organization may have referred to the same trials. To provide (i) data with respect to a topic with considerable lack of information, (ii) data on failure of/or compliance with contraceptive methods, (iii) data on training of physicians in instructing trial participants how to use the contraceptive methods as specified in the clinical trial protocol. Despite the advice provided in the ICH M3R2) guidance  guidance, 5, 6, 7If contraceptive methods fail in a clinical trial, the following procedures are useful in identifying the risk of having become or becoming pregnant and to estimate the usefulness of emergency contraception: Identification of exact kind and time point of contraceptive failure  Cycle history  Urine pregnancy test If possible, transvaginal ultrasound for determination of ovarian activity Blood sampling for determination of beta-human choriogonadotropin (β-HCG), estradiol, luteinizing hormone (LH), and progesterone There was agreement among participants of the workshop that good practices to avoid unintended pregnancies in early drug development comprise: Implementation of adequate contraceptive methods in the clinical trial protocol st dose, at appropriate time points thereafter, and upon completion of the clinical trial Pregnancy tests in female trial participants depending on the kinetics of the tested compound. At least screening before 1Written subject information concerning the adequate contraceptive methods to be used during the trial and the necessity avoiding DEVP as well as measures to be taken in case of possibly failed contraception before or during the trial Training of trial physicians on how to instruct trial participants about the appropriate use of adequate contraceptive methods as well as measures to be taken in case of possibly failed contraception  Routine compliance checks whether enrolled subjects are appropriately using the contraceptive methods as per protocol  Standard procedures in place regarding what to do if contraceptive methods failed  Decision on further measures to avoid unnecessary elective pregnancy terminations Compliance with measures indicated by the CTFG publication  Female clinical trial participants and female partners of male clinical trial participants must not become pregnant during early drug development; however, this AGAH survey shows that pregnancies did occur. According to the discussions during the workshop, the methods to mitigate the risk of unintended pregnancies need further improvement and should include (i) written information of the trial participants regarding contraceptive measures and the necessity of avoiding drug exposure via parent, (ii) repeated pregnancy tests, (iii) documentation of last menstrual period before the first dose, (iv) compliance checks of the appropriate use of contraceptive methods, (v) training of trial physicians. Procedures should be in place for what to do if contraceptive measures fail. Lessons learned from unintended pregnancies should result in appropriate modification of hitherto implemented procedures. This will mitigate the risk of DEVP in early-phase clinical trials. We thank Sam Welgemoed for her technical support . We thank all participants of the survey for their contributions. Survey: None. Open access provided by AGAH e.V. None. Supplemental material


Following these two introductory chapters, the monograph can then be divided into four main sections: (i) the technical overview of currently available commercial SGRT Systems (chapters 3–5), (ii) the commissioning of the systems described in part (i) (chapters 6–8), (iii) the clinical application of SGRT (chapters 9–19), and (iv) miscellaneous topics in surface image guidance (chapters 20–26). While the corresponding chapters in part (i) and (ii) can be read independently of each other, I personally would have found it more helpful if the technical overview of a particular surface image guidance technology would have been followed by the chapter on its commissioning. Having said that, each of the chapters in part (i) and (ii) strikes the right balance between technical detail and brevity, making them very useful both as a reference and an introduction to the technology and how to commission a given technology of surface image guidance. Part (iii) begins with an in depth look at the clinical application of this technology to breast cancer (chapters 9–11), while Chapters 12–14 consider Stereotactic Radiosurgery and Stereotactic Radiation Therapy in depth, including a very nice chapter on the risk analysis for SGRT‐based SRS/SRT. Part (iii) continues with a detailed description of respiratory motion management strategies employing surface image guidance in SBRT (chapter 15), including the use of surface image guidance for SBRT without respiratory gating (chapter 16). Chapters on the use of surface image guidance in the treatment of Head and Neck (chapter 17), extremities (chapter 18), and pediatric patients (chapter 19) conclude Part (iii). Chapters 20–26 round out the presentation with three perspectives on the clinical implementation of surface image guidance, one from the point of view of a physicist and two from the that of a radiation therapist (chapters 20–22); applications of surface image guidance to proton therapy (chapter 23); integration of surface image guidance into tomographic and bore type gantry systems (chapter 24); use of consumer grade cameras and alternate approaches to surface image guidance (chapter 25); and a final chapter discussing future directions for SGRT (chapter 26).In summary, this monograph presents a very readable account of the technical features of currently commercially available SGRT technologies, considers the commissioning of each in detail, and discusses in detail the clinical implementation and use of these systems for a number of important clinical sites, such as Breast, Stereotactic Body Radiation Therapy, Stereotactic Radiosurgery and Stereotactic Radiation Therapy, and Head and Neck. Regardless of career stage, professionals in either therapeutic medical physics or radiation oncology will find this monograph beneficial. The authors of this monograph balance technical detail with clinical information regarding the technology's implementation, and, hence, those interested in SGRT will find this monograph a valuable and welcome addition to their professional library. I have enjoyed reading through this monograph and found it a cogent reference and a thorough introduction to the topic.Wolfgang A. Tomé, Ph.D., FAAPM, FASTRO, is a Professor of Radiation Oncology and a Professor of Neurology at Albert Einstein College of Medicine  and the Chief of the Division of Therapeutic Medical Physics at Montefiore Medical Center .