Reliable quality of life assessment is important for identification of health problems, evaluation of health interventions and planning of optimal health policies and care packages. Due to lack of a psychometrically robust measurement tool for quality of life appraisal among the Iranian older population, this study was aimed to investigate psychometric properties of the Persian version of the World Health Organization quality of life-old module (WHOQOL-OLD-P) for use on the Iranian and other Persian-speaking aged populations.The standard translate/back-translate procedure was applied to convert the English version of the WHOQOL-OLD into Persian. The face and content validities were assessed by a panel of experts including 15 specialists in geriatrics and allied fields. The Cronbach’s alpha and intra-class correlation (ICC) coefficients were estimated to assess internal validity and reliability of the translated version. Factorial structure of the WHOQOL-OLD-P was also tested using confirmatory factor analyses in a sample of 400 Persian-speaking older adults (aged 60 years of old and above) residing in the city of Yazd, the capital city of Yazd province, center of Iran.The internal consistency and reliability indices of the WHOQOL-OLD-P were in the vicinity of acceptable range . The confirmatory factor analysis outputs confirmed the six-factor solution of the WHOQOL-OLD-P .The study findings support validity and reliability of the WHOQOL-OLD-P for use on Iranian and possibly other Persian-speaking older populations. Further cross-cultural and comparative multinational studies are recommended to provide more vigorous evidence about feasibility and acceptability of the translated tool in diverse and multicultural Persian-speaking communities. Quality of life (QOL) assessment is considered by health scholars as an important requirement for evidence based health care decision making and policy formulation for ageing population of the world. Therefore, QOL assessment is a part of routine health care packages in many countries to ensure effectiveness of health care or innovative interventions that targeted aged populations , 2.The ratio of aged to overall population of Iran as a transitional country is rapidly increasing and based on the 2016 demographic census’s results aged people constituted about 9.3% of the country’s population .QOL according to the World Health Organization (WHO)‘s definition is the self-perception of individuals’ current standpoint position in life with respect to what goals, expectations, standards, priorities, culture and value system they might have in their living ambience . Thus, tApplication of a reliable and explicit tool to measure QOL of elder people is an imperative prerequisite in health systems and also for conduction of robust research projects . HoweverThe WHOQOL-OLD as an explicit measurement instrument for QOL assessment was introduced by the WHO  and has Preeminent advantage of the WHOQOL-OLD relative to other QOL assessment tools is its development through an extensive international cooperation  that makMain aim of this study was to translate and psychometrically appraise properties of the Persian version of the WHOQOL-OLD to provide a robust measurement instrument for application in akin studies of QOL on aged Persian-speaking populations in the Middle East region and other neighborhood countries. Thus, cross-cultural and international comparisons of the findings from studies in different populations will be applicable.The study sample consisted of 400 older adults  aged 60 years old and above who were registered in the two primary health care center in the city of Yazd, the capital city of Yazd province, center of Iran. The sample size was decided based on the recommended sample size (8 people per each of the instrument’s items)  which is somehow consistent with the findings of other psychometric studies of the WHOQOL-OLD module on other socio-cultural contexts , 19, 36.The calculated ICC measure of reliability over time for both the total WHOQOL-OLD-P and its subscales’ scores were in the vicinity of acceptable range  and simiThe identified 6-factor solution that best fitted the study data was congruent with the reported priori factor structure of the original scale  and in tRegarding the obtained results in this validation study, it can be concluded that the WHOQOL-OLD-P’s application is feasible since no problem encountered in the data collection stage and a relatively limited time frame (6–8 min for older adults with academic education and 10–13 min for the rest of interviewees) was required to complete the scale on every individual participant.The study sample in this research consisted of elder people with at least one to three diagnosed simultaneous chronic diseases who had been registered in the two primary health care centers in the city of Yazd, the capital city of Yazd province, central part of Iran. The purposively selected health care centers and therefore, non-probabilistic sample that was selected for inclusion might be limited representativeness of the study participants and restraint extrapolation and generalizability of the findings. Comparison of the within-subjects perceived QOL measures and association of the factors such as religion, age, gender, level of education and overall health status with the estimated QOL values were not speculated in this study. Therefore; interim data collection and analysis in future corresponding studies could add further detail and explanation about precipitating factors of QOL.Iran is a multi-cultural, multi-religious and multi-ethnic country and the study findings might not be generalizable to elder people residing in the country’s other provinces and geographical areas due to socio-cultural diversities.There is also possibility of the reporting bias based on the respondents’ willingness and ability to provide accurate responses especially concerning the length of the WHOQOL-OLD-P, although the concern was attempted to be mitigated by emphasis on the anonymity of the participants and allocation of proper time for interview.Elder people who suffer from multiple chronic diseases are more likely to develop depression and therefore; tend to report lower quality of life . Such anMultidimensional nature of QOL and the effects posed by certain underlying factors warrant further research to examine how these circumstances might relate to self-reported quality of life among older people. QOL assessment by use of measures that actually highlight specific domains e.g. physical, emotional and social functioning or over emphasis on health-related aspect of daily life experiences may also cause bias especially in measurement of elder population’s QOL . Aged peIntroduction of a valid and reliable instrument for measurement of quality of life among Iranian and other Persian-speaking elder adults was the primary objective of this study. Taking into account all above mentioned limitations, the WHOQOL-OLD-P application could be recommended as an explicit instrument for measurement of perceived QOL as a proxy measure of aged people’s overall health in the Iranian and other Persian-speaking elder populations across the world. The WHOQOL-OLD-P application could enhance reliability of QOL assessment by a wide range of healthcare providers (HCPs)  in primary health care centers, secondary and tertiary care providing settings . The instrument can be utilized in routine care provision activities or in assessment of influences a specific health condition or morbidity and also subsequent restorative therapeutic intervention might have on perceived overall QOL among the aged people. Other social care providing organizations could also use the WHOQOL-OLD-P for estimation of impacts their policies, services or targeted interventions might have on elder people within the Persian-speaking countries.The WHOQOL-OLD module was translated into Persian in this study and psychometrically tested for possible application in the research and practice settings within the Iranian context. The translated version indicated robust internal consistency, reliability and construct validity. Due to growing number of aged population in Iran presence of sound data collection tool for QOL assessment will add to the accuracy of scientific knowledge and intervention modalities that target elder people’s quality of life in different socio-cultural and practice settings. The WHOQOL-OLD–P utilization in future studies will also make comparison of cross-region and cross-border health status of elder people attainable and desirable.


This paper highlights some peculiar characteristics of the economic crisis induced by the spread of COVID-19. It suggests two intertwined policy measures in order to tackle the emergency phase of the crisis and to support the economy in the subsequent recovery phase. The proposed short-term policy measures offer policy responses in the event of a second wave of coronavirus infections in the coming months. In the aftermath of the emergency phase, the current proposal puts forward the implementation of a massive EU-wide recovery plan addressing the long-lasting technological and environmental challenges of these years, which will be financed by European institutions through the issuance of European Pandemic Recovery Bonds.


Despite its origins in the study of race in America in Gunnar Myrdal’s American Dilemma, research on cumulative dis/advantage (CDA) and the life course has paid little attention to the significance of racism in the overall production and patterning of CDA. Building on recent work that has reviewed the life-course implications of the inscribing of racist interests in social policy, this paper explores the life-course implications of race bias in another domain, specifically the domain of medical diagnosis, where algorithm formulas have been shown to disadvantage black patients based on economic and other parameters. Even with training, experimental evidence comparing human and AI diagnostics have demonstrated that despite improvements, residual racism is evident in differential diagnoses. We consider the life-course implications of this and similar race-based differentials in organizational decision-making as a component in systems of cumulating dis/advantage.


Farkas certificates for lower and upper bounds on minimal and maximal reachability probabilities in Markov decision processes (MDP), which we derive using an MDP-variant of Farkas’ Lemma. The set of all such certificates is shown to form a polytope whose points correspond to witnessing subsystems of the model and the property. Using this correspondence we can translate the problem of finding minimal witnesses to the problem of finding vertices with a maximal number of zeros. While computing such vertices is computationally hard in general, we derive new heuristics from our formulations that exhibit competitive performance compared to state-of-the-art techniques. As an argument that asymptotically better algorithms cannot be hoped for, we show that the decision version of finding minimal witnesses is This paper introduces


We read with great interest the pilot single arm trial by Matsumoto et al , which eThe authors begin by explaining that difficulties with accessing CBT are due to the expense, number, and uneven urban distribution of therapists, and feel that telemental health has resolved these issues. We would comment that whilst distribution will have been addressed, the use of video conferencing alone would likely be insufficient to address the expense and the paucity of therapists. Therefore, this represents an apparent limitation on the scalability of such interventions. Varying the level of interaction with the therapist through the use of computer-assisted CBT  has already been described with positive results both in terms of outcomes and cost-effectiveness in a population of primary care patients undergoing treatment for depression . Future The equivalence of face-to-face CBT and ICBT in a meta-analysis of 1418 patients  further Although the single-arm nature of the trial limits the applicability of the conclusions, the authors describe a preference (83% of participants) for video conferencing over face-to-face CBT. More information as to the rationale belying this preference would help inform future intervention strategies. Furthermore, previous experience and perceptions toward face-to-face CBT before an intervention could also help further elucidate the validity of participants’ preference toward video conferencing. One potential explanation could be that the method of participant recruitment and selection could introduce a bias of intrinsic preference of trial subjects toward seeking video-based CBT, given that one recruitment strategy employed by the authors was web-based advertising.Although a need for further clarification exists, the authors are to be commended on their unique contribution to the field, and it is with great excitement that we anticipate future works to further describe the potential benefits of ICBT and its applications.


A 30-year-old male presents to emergency medical services profoundly combative with a Richmond Agitation–Sedation Scale of +4 after reported use of intravenous methamphetamines. A preliminary diagnosis of excited delirium syndrome is made based on the history obtained and the decision is made to chemically sedate the patient. While preparing for sedation, you wonder which pharmacological agent will produce the fastest and safest sedation in this patient population. A 30-year-old male presents to emergency medical services (EMS) profoundly combative with a Richmond Agitation–Sedation Scale of +4 after reported use of intravenous methamphetamines. A preliminary diagnosis of excited delirium syndrome (ExDS) is made based on the history obtained and the decision is made to chemically sedate the patient. While preparing for sedation, you wonder which pharmacological agent will produce the fastest and safest sedation in this patient population.In patients presenting with ExDS in the pre-hospital environment, is the use of benzodiazepines, antipsychotics or ketamine superior in producing rapid and uncomplicated sedation?United States of America National Library of Medicine (up to September 2019):) AND Cumulative Index to Nursing and Allied Health Literature (up to September 2019):TX  AND TX Literature was considered relevant if it described a piece of primary research in the pre-hospital setting, with a focus on the pharmacological management of ExDS. Literature was excluded if the research was undertaken in a hospital-based setting, or if it was non-interventional in nature.United States of America National Library of Medicine:90 results, of which nine were considered relevant.Cumulative Index to Nursing and Allied Health Literature:145 results, of which eight were considered relevant. None in addition to those identified previously.See Despite the challenges which patients suffering from ExDS will present to practitioners, literature examining the management of these patients in the pre-hospital environment is exclusively from the United States or founded in the setting of an emergency department with regional variations in the optimal sedative recommended for use in this patient population. Although the pre-hospital and emergency department settings share a number of features, the pre-hospital environment is an unpredictable, profoundly resource-poor setting without consistent access to anaesthesia and advanced medical therapies potentially required for management of deteriorating patients with ExDS. This is of particular importance when considering not simply the efficacy, but the safety of pharmacological management of patients presenting with ExDS.There is insufficient evidence to recommend one pharmacological agent in the management of ExDS within the pre-hospital environment generally, and no evidence specific to specialist paramedic practice in the United Kingdom. Although ketamine is associated with the most rapid onset of adequate sedation in patients with ExDS, it is also associated with the highest rate of adverse events and its use is frequently reported to result in the requirement for endotracheal intubation. However, it is unclear whether the requirement for intubation is driven by clinical need or provider discomfort, given the number of intubations performed by single providers within multiple studies. Antipsychotic agents such as haloperidol and droperidol appear to have a superior safety profile when compared against ketamine and midazolam, although they are associated with a protracted time to adequate sedation, which is of particular relevance in the setting of an ExDS patient and in the setting of the resource-poor pre-hospital environment.The choice of pharmacological agent for sedation of the patient with ExDS will depend on the local legality of paramedic-led administration of scheduled medications, availability, clinician comfort and available resources to manage unexpected complications. Further high-quality controlled trials of benzodiazepines, antipsychotics and ketamine are required before any recommendation for widespread use of any agent can be made.None declared.None.


To this end, this project compares the socioeconomic status (SES) gradient in formal and informal care across Europe and over time. A particular effort is made to include macro-level indicators of LTC systems in cross-level analyses across countries. The first paper presented in this symposium by the UK team studied SES-inequality in care receipt across European nations with different care systems; the second paper presented by the German team studied the same question but now among caregivers, the third paper provides the analyses for caregivers in Japan, and the fourth paper by the Dutch team studies SES-inequalities in care use within the Netherlands over time (1995-2015). The symposium will start off with a short description of the IN-CARE project (2019-2022). Tine Rostgaard agreed to be our discussant.Ageing societies and recent reforms to long-term care (LTC) in many European countries are likely to make informal care by kin and nonkin increasingly critical for fulfilling the care needs of older people. To date, it is unknown whether informal care falls disproportionately on disadvantaged populations. The IN-CARE project (a collaboration of Dutch, UK and German research teams;


The aim of this study was to assess differences in the effect of traumatic brain injury (TBI) on the onset of Alzheimer’s disease (AD) and other dementias between veteran and non-veteran respondents of the Health and Retirement Study as well as to measure the sensitivity of these differences to the introduction of controls for groups of demographic, medical co-morbidity and polygenic risk scores reflecting AD hallmarks. Using the Fine-Gray proportional hazards model we found that TBI was a strong predictor of dementia in community dwelling residents age 65+: for AD associated risk was 181%  sample-wide and 142%  in veteran males. Effect magnitude decreased with the addition of risk-related control variables but remained associated with significantly increased risk. Large differences in risk were observed between veteran and non-veteran males for AD, vascular dementia, senile dementia, and dementia with Lewy Bodies


About 41 million people die of chronic non-communicable diseases (CNCDs) each year, accounting for 71% of all global deaths. The high prevalence of CNCDs is particularly problematic for sub-Saharan Africa (SSA) since CNCDs are already a major cause of mortality in the sub-region. While the case fatality rate of COVID-19 is quite low, it is worth noting that people with underlying CNCDs constitute the majority of those who die from this virus. Underpinned by the chronic care model (CCM), we present a commentary on the implications of COVID-19 for the management of CNCDs in SSA. We realized that despite the World Health Organisation’s guidelines for countries to maintain essential services while putting necessary measures in place to prevent and control the spread of COVID-19, myriad of health systems and community-level factors militate against effective management of the CNCDs in SSA. This results in disruptions in management of the conditions as well as possible long-term effects such as the deterioration of the health status of CNCD patients and even deaths. Without immediate interventions to salvage the status quo, SSA countries may not be able to achieve the Sustainable Development Goal 3.4 target of reducing by one-third, premature mortality from CNCDs by the year 2030. We recommend that financial constraints could be ameliorated through short- and long-term loan facilities from the International Monetary Fund and the World Bank to augment national efforts at strengthening health systems while combating COVID-19. We also recommend increased community engagement and public education by COVID-19 response teams to enhance community support for persons living with CNCDs and to reduce social stigmatization Coronaviruses constitute a large family of viruses which cause ailments ranging from the common cold to more severe diseases among humans such as the Severe Acute Respiratory Syndrome (SARS) in 2002 and Middle East Respiratory Syndrome (MERS) in 2012 . The higThis paper is underpinned by the chronic care model (CCM), which was developed by the MacColl Institute for Healthcare Innovation at Group Health Cooperative in 1992 . The CCMHealth systems: the health system forms the backbone of the management of CNCDs in SSA. To ensure effective management which improves the health outcomes of people living with CNCDs, the CCM admonishes a resilient health system that provides safe and high-quality care through a dedicated and motivated team of health professionals who are well-positioned to support improvement strategies and encourage open and systematic handling of errors through the provision of quality care [ity care . The heaThe increasing prevalence and mortality from COVID-19 with its rapidly increasing demand on health systems makes it almost impossible for the health systems of SSA countries to keep providing the CNCD management services as expected . This isAside from the fact that the existing inadequate number of beds in health facilities are being occupied by COVID-19 patients, the majority of the already inadequate health professionals previously designated to care for patients with CNCDs are redirected to focus on COVID-19 related activities such as attending to patients in isolation/intensive care and contact tracing. Besides, laboratories, which conduct specimen testing for CNCD patients have now focused on taking specimen for COVID-19 suspected cases as well as carrying out the test at the expense of CNCDs. Patients with CNCDs, thus, have limited access to these facilities. Moreover, infrastructure initially designated as special clinics for managing CNCDs patients are now being used as holding centres where suspected COVID-19 cases are quarantined. The meagre financial resources of health facilities have also been diverted towards the management of COVID-19 in terms of purchasing personal protective equipment (PPE) such as masks and hand gloves to the detriment of CNCDs. The diversion of health system resources towards the management of COVID-19 at the expense of CNCDs comes at the backdrop of the WHO´s recommendation and operational planning guidelines, which entreat countries to maintain the status quo regarding the provision of already existing health services to mitigate the risk of health system collapse and aggravation of patients´ health. Health systems in SSA are, however, unable to maintain the status quo due to their logistical, financial, and human resource challenges.In several SSA countries, people are encouraged to avoid presentation to hospitals unless it is absolutely necessary. Due to the existing inadequacy of health professionals and limited PPEs, the aim is to reduce the burden of CNCDs on the health systems of SSA countries as they are already overwhelmed by the COVID-19 pandemic, and to reduce the risk of contamination of patients with CNCDs attending routine visits at hospitals. In most SSA countries, patients with CNCDs themselves, for the fear of contracting virus, avoid going to the hospitals for their reviews. Individuals developing CNCDs and needing care for the first time also avoid going to the hospitals for diagnosis and subsequent management of their conditions. The implication of the myriad of health systems challenges, precipitated by the COVID-19 pandemic entail delays in seeking prompt care by CNCD patients, the disruption of CNCD management timelines, and the deterioration of the health status of persons living with CNCDs leading to needless deaths.Community: community as a tenet of the CCM entails self-management, resources mobilization and advocacy for policies that improve CNCD care [NCD care . Self-maNCD care . Self-maNCD care . HoweverNCD care . The impThe CCM also identifies coping strategies by patients with CNCDs as a major factor that helps in the management of the conditions . Coping Despite the WHO guidelines to all countries across the world to maintain essential services including those related to the management of CNCDs while putting necessary measures in place to prevent and control the spread of COVID-19, myriad of health systems and community-level factors militate against effective management of the CNCDs in SSA resulting in the disruptions in management of the conditions as well as possible long-term effects such as the deterioration of the health status of CNCD patients and even deaths. Without immediate interventions to salvage the status quo, SSA countries may not be able to achieve the SDG 3.4 target of reducing by one-third, premature mortality from CNCDs by the year 2030.Recommendations: to mitigate the immediate and long-term irreversible negative effects of COVID-19 on the management of CNCDs in SSA, the following recommendations have been proffered: 1) Financial constraints could be ameliorated through short- and long-term loan facilities from the International Monetary Fund and the World Bank to augment national efforts at strengthening health systems in SSA to enable them to continue being resilient to manage CNCDs even as they strive to end the COVID-19 pandemic. 2) More health professionals should be employed and deployed to continue providing care for other patients including those with CNCDs while the rest focus on effectively responding to COVID-19. 3) In countries where the recruitment and deployment of more health professionals becomes challenging due to the existing financial constraints, alternative measures for the follow-up of patients with CNCDs could be implemented. These include the use of telemedicine to check-up on patients´ progress and self-management practices. Also, courier services and drones could be used to deliver CNCD medications and urgently required documents where necessary. 4) Health professionals should be adequately provided with PPEs to improve their protection against COVID-19 infections. When this is done, they would encourage patients with CNCDs to come for reviews knowing they have minimal risk of exposure to the infection. 5) Health infrastructures in SSA should be expanded and equipped with donor support to accommodate Covid-19 patients and at the same time CNCDs patients. 6) There should be increased community engagement through their leadership and public education by COVID-19 response teams of the various SSA countries to enhance community support for persons living with CNCDs and to reduce social stigmatization.The authors declare no competing interests.


This thematic review includes short reviews on GH deficiency and insensitivity in children and adults from basic science to clinical significance. We are proud to present this thematic review on growth hormone (GH) deficiency and insensitivity in children and adults. It contains short reviews made by eminent experts in the field that together comprises a comprehensive assessment of the field from basic science to clinical significance.The activity of the GH-IGF-I axis is regulated by the amount and secretory pattern of the GH, the endocrine and paracrine/autocrine production of IGF-I and the interaction of GH and IGF-I at the tissue specific level. Additionally, GH and IGF-1 have both unique and overlapping actions related to growth and metabolism. Therefore, overall effects of the GH-IGF-axis on growth and metabolism is dependent on the amount of GH and IGF-I at the tissue level as well as the responsiveness/sensitivity of the GH and IGF-I receptors.Through clinical observation and experience, clinicians have observed variable responses to GH treatment in children. For example, the same GH exposure can produce a highly variable magnitude of growth. Similarly in adults, GH replacement in patients with hypopituitarism and severe GH deficiency can produce a response that is highly variable. In adults the efficacy of GH replacement varies from changes in body composition and lipid profile to improvement in well-being and quality of life. Additionally, it is also unpredictable to which of these endpoints an individual subject seems to respond most.The aim of this thematic issue was therefore to shed light on the clinical aspects related to GH deficiency and insensitivity in both children and adults. This issue also includes human models of extreme GH insensitivity induced by inactivating changes in the GH receptor as well as at the post receptor level. The careful phenotyping as well as the molecular discoveries in these patients have extended the findings on the physiology of the GH-IGF-I axis and some of the individual sensitivities attributed to either GH or IGF-I. These observations have also been useful in better understanding the consequences of long-standing GH deficiency in children and adults. In addition to human studies, animal models of GH deficiency and insensitivity have also improved our understanding on the impact of GH and/or IGF-1 on tissue specific metabolism and in the end its impact on health- and life-span. Related to this is the findings in adults with GH deficiency that showed reduced survival in the unreplaced state. The causal relationship with GH deficiency has been debated and is further reviewed and discussed in this thematic issue.The clinical challenges in the diagnosis of GH deficiency and various degree of insensitivity are further discussed together with strategies to improve outcome among these patients. With a perfect mix between basic, translational and clinical topics related to GH deficiency and insensitivity, we hope that the readers of this issue will enjoy and appreciate the science behind the short reviews. We also hope that the reader will improve their understanding of the molecular mechanism(s) of GH/IGF-1 action, the clinical consequences and the treatment strategies to improve each patient’s outcome from childhood to adulthood.


The official installation of the European Reference Networks in 2017 formed the foundation to improve quality and safety and access to highly specialized health care across the EU for patients affected by rare or low prevalence and complex conditions. The European Reference Network on Rare Endocrine Conditions (Endo-ERN) covers specific expertise from birth to senescence with a specific governance structure characterized by both a pediatric and an adult chair, and equal responsibilities for patient representatives and health care providers. The introduction on the scope and mission of Endo describes the complexity of the Endo-ERN mission and will thrive toward the ultimate aim and mission of the network of reducing health care inequalities across Europe. Specific knowledge and medical expertise of the existing rare endocrine condition is urgently needed, and therefore, raising awareness for Rare Disease Day from the Endo-ERN perspective is imperative. The EU directive 2011/24 of patient’s rights in cross border health care that was accepted by the European parliament in 2011 formed the foundation for the development of European Reference Networks (ERNs) [The European Reference Network on Rare Endocrine Conditions (Endo-ERN) was initiated by clinical committee members of both European endocrine societies: the European Society of Pediatric Endocrinology (ESPE) and the European Society of (adult) Endocrinology (ESE) that identified and nominated a pediatric and an adult chair as well as steering committee members who developed and decided upon the coordination and governance. On the landscape for rare endocrine conditions Endo-ERN was divided into eight organ- and physiology-based main thematic disease groups  which were included in five Work Packages .Endo-ERN, at present, is the largest ERN, representing 86 HCPs from 26 countries. Patient involvement is crucial to all ERNs, and Endo-ERN already integrated patient representation during the construction phase of the network, with equal responsibilities for patient representatives and HCPs . Each MTThis special and unique supplemental issue of ‘Endocrine’ has been compiled by Endo-ERN experts and encompasses a large array of specific features of rare endocrine conditions, covering specific activities carried out in the different work packages and main thematic groups of the network, and range from mini-reviews of a specific condition to manuscripts describing original novel data, including data on the use of virtual consultations, and on the educational and research needs from the patient’s perspective, representing all work packages and main thematic groups. With this, we are confident that the complexity of the Endo-ERN mission is well described and we will thrive towards the ultimate aim of reducing health care inequalities across Europe.Written and compiled in the midst of the Covid-19 pandemic, raising awareness for Rare Disease Day from the Endo-ERN perspective is quite necessary. As we will see from the manuscripts, the specific knowledge and medical expertise of the existing rare condition was mandatory for battling corona infections in our patients. Furthermore, during the pandemic, the anxiety of chronically ill patients increased and their medical attention could often not be met. With the more specific medical but also societal approaches to Covid-19, it is time to turn again to all medical necessities of our European fellow citizen, so no one is “forgotten”.


International Journal of Cardiology 30384-3; DOI: 10.1016/j.ijcard.2020.04.013). Eight Italian high-volume centres of Paediatric Cardiology were involved in this observational, retrospective data collection and analysis. In this dataset, clinical and procedural characteristics of 1423 newborns submitted to 1551 interventional cardiac catheterization procedures were analyzed. Primary outcomes were considered procedure and in-hospital mortality as well as major adverse event and procedural failure rates. Secondary outcomes were considered minor adverse events and need for blood transfusion. Targets of this data analysis were: 1) to evaluate the overall major risk factors of interventional cardiac catheterization; 2) to identify the most hazardous interventional procedures; 3) to assess possible trends of individual procedures as well as their outcome over time; 4) to find possible relationships between the volume activity of any centre and the procedure and follow-up outcome. In particular, this Data in Brief companion paper aims to report the specific statistic highlights of the multivariable analysis (binary logistic regression) used to assess the impact of any potential risk factors on the type of procedure over a short-term follow-up.A comprehensive description of morbidity and mortality as well as risk factors of interventional cardiac catheterization performed in neonatal age was reported in our paper recently published on the  Specifications table•Interventional cardiac catheterization is an increasing approach to treat newborns with critical congenital heart disease. No data about risk stratification of interventional procedures in this subset of patients are so far reported in literature. Our dataset aims to evaluate the intrinsic risk of trans-catheter interventional approach as well as the potential risk factors involved in any individual procedure performed at this age.•The nationwide cohort dataset recently published in the related research article provides specific information on morbidity and mortality of newborns submitted to interventional cardiac catheterization. The Authors showed that the morbidity  is significantly related to the complexity of the intended procedure while the in-hospital mortality significantly depends on the clinical characteristics and hemodynamic stability of the patient. These data may be useful to cardiologists involved in the management of newborns affected by congenital heart disease to clearly understand patient's risk profile of any interventional procedure.•The safety and effectiveness data of trans-catheter approach reported in this Data in Brief paper and its related research article may hopefully promote further developments in trans-catheter treatment of neonates with critical congenital heart disease. “Ad hoc”-planned future researches aiming to specifically compare percutaneous and surgical approaches in this subset of patients will give further useful information to set the future guide-lines of management of critical, neonatal-onset cardiac malformations.•Defining careful risk profile of newborns in whom an interventional cardiac catheterization is planned allows to improve pre-procedure counselling with parents and care-givers as well as gives further insights about the short-term prognosis of these frail patients. These data will hopefully improve timing and type of interventional approach  in this frail subset of patients.1-the -the -the -the -the -A) and the most performed procedures (B) on the primary outcomesthe -A) and, accordingly, the rate of composite outcome (B)the This dataset  gives relevant details and explanations about the enrolled population/procedures (catheterizations/procedures and adverse events) and statistical analysis techniques . These data are expressed as figures and tables as well as in form of RAW DATA in the SUPPPLEMENTARY FILE section:2In the related research article Multi-variable analysis was performed with a binary logistic regression The data reported in the The data were then divided for any centre in order to evaluate, by linear regression test, the impact of the volume of activity of any individual centre on the composite outcome. The same statistical analysis was also made by separating the higher-risk procedures (risk category 4) from the lower ones (risk category 3)


The implementation of physical activity policies has been slow and uneven. As a remedy, the World Health Organization has recommended that national policy implementation should be supported with practical tools and guidance. The Physical Activity Environment Policy Index (PA-EPI) is a tool that allows the extent of policy implementation to be assessed. It comprises a list of good practice policy indicators. These are categorized into eight policy domains targeting aspects of the physical activity environment and seven infrastructure support domains for strengthening physical activity policy systems. This protocol provides researchers with guidance on how to use this tool.Guided by a protocol developed by the International Network for Food and Obesity / Non-communicable Diseases (NCDs) Research, Monitoring and Action Support (INFORMAS), the PA-EPI protocol. The INFORMAS protocol was modified based on the research teams experience carrying out the first study utilising the PA-EPI tool.A multi-step process is recommended. This process relies upon the identification of two groups of partners: national policymakers and independent stakeholders tasked with the promotion of physical activity directly and/or indirectly. During the early steps of the process the desk-based research is undertaken to identify information about and evidence of physical activity policy implementation- the PA-EPI Evidence Document. This mapped information is presented to the national policymakers to verify that it is valid and comprehensive. Subsequently, the evidence of implementation is presented to the stakeholders who, using a 5-point Likert scale (1-little or none to 5 high), individually rate the extent of policy implementation in practice. These individual ratings are aggregated and a implementation scorecard is generated displaying the extent of implementation of each of the good practice indicators Stakeholder then engage in an expert workshop to review implementation scores, and identify key policy implementation recommendations which are presented to government.The process of conducting a policy implementation assessment using the PA-EPI requires the cooperation of several stakeholders as part of a national coalition. It is envisioned that PA-EPI assessments will enable international cross comparison. This will promote learning from international best practice.


Sepsis is one of the most common reasons for admission to the intensive care unit, and its incidence continues to increase. However, the precise mechanism of sepsis has not yet been fully elucidated. Outer membrane vesicles (OMVs) present in the outer membrane of bacteria have been speculated to be one of the causes of sepsis. Direct hemoperfusion with polymyxin B-immobilized fiber (PMX-DHP) can be used as a means to remove OMVs. This study evaluated whether the use of PMX-DHP affects bacterial distribution.A total of 30 critically ill patients with severe septic shock were enrolled from intensive care unit of Haeundae Paik hospital. Plasma and urine samples were collected before and after the use of PMX-DHP. Sequencing-based metagenome analysis of the microbiome was performed, and changes in the distribution of various bacteria before and after the use of PMX-DHP were identified.Bradyrhizobium . Figure 3 shows the changes in the distribution of bacteria in urine before and after the use of PMX-DHP. No bacteria showed a statistically significant difference in distribution before and after the use of PMX-DHP in this distribution.A total of 30 patients were enrolled. Figure 1 shows the changes in the distribution of bacteria in plasma before and after the use of PMX-DHP. The only strain that showed a statistically significant difference in the pre-mean and post-mean values in this distribution was Figure 1Distribution of bacteria in plasma before and after the use of PMX-DHPFigure 2Changes in the distribution of Bradyrhizobium in plasmaFigure 3Distribution of bacteria in urine before and after the use of PMX-DHPBradyrhizobium was the only strain that showed a statistically significant decrease in the amount of outer membrane vesicles (OMVs) in plasma through hemoperfusion using PMX-DHP.All Authors: No reported disclosures


Nature Communications 10.1038/s41467-023-38565-8, published online 23 May 2023Correction to: The original version of this Article contained an error in the order of names in the author list, which incorrectly listed the second author Chenxin Yu in the last position. This has now been corrected and the numbering of author affiliations has been updated accordingly in both the PDF and HTML versions of the Article.


Emphasising the importance of patient-centred outcome reporting to guide decision-making in this cohort of patients. This can only be achieved with the availability of high-quality patient-reported outcome data. Previous reviews have highlighted several limitations regarding studies reporting patient-reported outcomes in LRRC, including variability in the patient-reported outcome measures (PROMs) being used, and in the timing of PROM assessments, with the evidence being low in quality overall.6 The results identified several issues related to the quality of reporting of PROMs in LRRC, most importantly that none of the PROMs currently being used to report outcomes in LRRC have been validated for use in this group of patients. Methods for handling missing PROM data and defining the patient-reported outcome of interest are also poorly reported. However, the person completing the PROM and method of data collection, and conclusions and discussion of the clinical relevance of the patient-reported outcome data, were well reported.This systematic review focused on assessing the methodological quality of studies reporting PROMs in LRRC to identify the PROMs being used and to assess their psychometric properties using the COSMIN Risk of Bias checklist.The lack of disease-specific PROMs which have been validated for use in LRRC, is the most important issue to address to improve the quality of reporting PROMs in LRRC. Several approaches could be employed, including developing new disease-specific PROMs for patients with LRRC or undertaking content validity studies of the PROMs which are currently being used in LRRC.


AlZahrani  The authors regret that the funding information was incorrectly shown in the Acknowledgements section of the original manuscript. The corrected funding acknowledgement is as shown below.The authors extend their appreciation to the Deanship of Scientific Research at Northern Border University, Arar, KSA for funding this research work through the project number NBU-FFR-2023-0020.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


T-lymphocytes or T-cells) were able to transfer protection against infectious agents, allowing for the definition of cell-mediated immunity (CMI)  . Since tT-cells has been a topic of interest for immunologists for decades and the study of these cells has contributed to major observations on the immune system  is a chronic contagious disease caused by the bovine leukemia virus (BLV), which compromises lymphocyte activities and leads to immune response dysfunction. Most of studies on the pathogenesis of EBL have been focused on the analysis of B and chanisms . Howeverchanisms  raise quRainard et al. provide a broad review of reports on the adaptive immune response mechanisms in the mammary gland (MG) of ruminants, with an emphasis on cell-mediated immunity. Mammary gland is armed of physical and cellular defenses compatible with the production, storage, and secretion of milk, which differ from mechanisms found in other organs exposed to invaders. The immunological functions of mammary gland also varies greatly among mammals and this particularity limits extrapolations from one species to another  paved the way for a better understanding of multiple processes of immune response including host response to infections and cancer, as well as immunotolerance . AlthougT-cell exhaustion, which is caused by the expression of immune checkpoint molecules that limit cell-mediated protective immunity  non-antibiotic approaches covering the most critical period of the cow's life.The immune checkpoint blockade has revolutionized the therapeutic landscape in oncology. Its success in cancer therapy implies that targeting similar pathways may prove beneficial in preventing and treating infectious diseases. Indeed, persistent infections are sustained by immunity . In thisAs a whole, this Research Topic proposes alternatives to some drawbacks involving the study of cell-mediated immunity in ruminants and highlights the better understanding of this arm of immune response as a fundamental step for the development of improved vaccines and therapies for these species.Research Topic conception by RPM. Research Topic editing and editorial writing by RPM and FNS. Both authors contributed to the article and approved the submitted version.


Objectives: Candidemia has become one of the leading causes of healthcare-associated bloodstream infection, particularly in the intensive care unit. The management of candidemia remains challenging. We reassessed the protective effectiveness of a comprehensive care bundle on the management of candidemia and the effects of compliance with each element on the outcomes of patients. Methods: This network meta-analysis was conducted using the frequentist method. The participants included adult patients both infected with candidemia and who received bundle care. The primary outcome was the all-cause mortality among the patients included. Results: Studies in which a care bundle was created for patients with candidemia were identified, and 5 eligible studies with 5,808 participants were enrolled for further analysis. The random-effects model of the overall odds ratio (OR) revealed a significant reduction in the risk of all-cause mortality compared with that of the controls , as well as a reduction in the risk of developing persistent candidemia compared with the controls . In addition, no single element reached a protective effectiveness to improve the clinical outcome. Conclusions: This meta-analysis demonstrated that the combination of core elements in the care bundle resulted in protective effects, in that the all-cause mortality rates and incidence rates were effectively reduced among patients with persistent candidemia.


This presentation will talk about co-production findings from three completed studies to develop and evaluate a culturally appropriate Japanese version of the New Forest Parent Training Programme (NFPP), named Well Parent Japan (WPJ). Dr Shimabukuro will also present an on-going prospective study aiming to provide support for Japanese mothers and teachers of children with ADHD in a school setting. Dr. Shimabukuro will share the experiences worked with different stakeholders at the different stage of the study and highlight the benefits of co-production in the research and how WPJ was shaped. This presentation will also discuss difficulties and challenges when evidence-based parent training intervention is transferred from research to practice.None Declared


A simple, robust and computationally inexpensive method of generating statistical representations of X-ray free-electron laser (XFEL) radiation is presented. Many coherent imaging applications that utilize ultrafast X-ray free-electron laser (XFEL) radiation pulses are highly sensitive to fluctuations in the shot-to-shot statistical properties of the source. Understanding and modelling these fluctuations are key to successful experiment planning and necessary to maximize the potential of XFEL facilities. Current models of XFEL radiation and their shot-to-shot statistics are based on theoretical descriptions of the source and are limited in their ability to capture the shot-to-shot intensity fluctuations observed experimentally. The lack of accurate temporal statistics in simulations that utilize these models is a significant barrier to optimizing and interpreting data from XFEL coherent diffraction experiments. Presented here is a phenomenological model of XFEL radiation that is capable of capturing the shot-to-shot statistics observed experimentally using a simple time-dependent approximation of the pulse wavefront. The model is applied to reproduce non-stationary shot-to-shot intensity fluctuations observed at the European XFEL, whilst accurately representing the single-shot properties predicted by FEL theory. Compared with previous models, this approach provides a simple, robust and computationally inexpensive method of generating statistical representations of XFEL radiation. The results from our model demonstrate the ease and effectiveness of our approach in replicating the temporal characteristics of the XFEL wavefield over a range of key experimental timescales.2.et al., 2020et al., 2019et al., 2020et al., 2022et al., 2022et al., 2022et al., 2019The European XFEL is the world’s first high-repetition-rate XFEL facility   = 1 denoting fluctuations in pulse intensity that are perfectly correlated, g(2) = 0 denoting no correlation and g(2) = −1 denoting anti-correlation. The shot-to-shot correlation of the pulse trains whose intensities are presented in Fig. 1Intensity distributions with time-dependent shot-to-shot statistics have previously been recorded during operation on the SPB/SFX instrument , where r is the transverse position vector: r = . We write this wavefield as the superposition of two functions describing the transverse and longitudinal properties of the pulse wavefield, ψ⊥ and f(t). We assume the transverse properties to be a slowly varying function of time (microseconds) in comparison to the longitudinal components (femtoseconds), and subsequently treat each function independently. The pulse wavefield at a time t within a pulse train can be written as the Fourier integralWe construct a numerical representation of the source wavefield that is the product of two components: (i) a stationary Gaussian approximation of the fluctuations in the SASE pulse spectra  are the radius of curvature and spatial wavevector in the transverse plane, respectively, which both vary with time. We define the time-constant amplitude factor with respect to the peak intensity of the pulse, I0, 0 and σz are, respectively, the beam widths at the waist and in a transverse plane located a distance z downstream of the waist.In modelling the transverse characteristics of the pulse wavefront, we make the assumption that shot-to-shot fluctuations in the source phase are the primary origin of fluctuations in the observed pulse intensities. This assumption implies both a constant pulse amplitude and a time-dependent beam phase. The evolution of the XFEL source intensity along the axis of propagation is determined by the gradient and curvature of the source wavefront phase XFEL wavefields are highly paraxial. Estimates of statistics of the time-dependent components of the pulse wavefield x, Δy) relative to the mean centre of mass calculated over all pulses within a pulse train. These displacements correspond to horizontal and vertical deflections of the pulse intensity,Shot-to-shot phase tilts of the source plane wavefield lead to displacements in the time-dependent centre of mass . The single-shot properties of each pulse were assumed to be Gaussian and of the form given in equation (3)et al.  ] ]. Using these probability distributions, the temporal properties of the beam phase were determined iteratively. Fig. 6Probability distributions were obtained by fitting a covariance ellipse enclosing 95% of the recorded data in the state space of each pulse property at sequential time points Each pulse within a pulse train was propagated independently through the SPB/SFX beamline model to a detection plane 3.644 m downstream of the instrument focus, matching the parameters of the intensity measurements described in Section 2i.e.g(2), is a linear function of the mean pulse intensity and thus shares the same highly correlated statistics. Such an autocorrelation function depicts the decay in the correlation between the first pulse in a pulse train and sequential pulses, which is of primary interest for time-resolved imaging experiments The intensity statistics of the experimental and simulated pulse trains are highly correlated, yielding an average Pearson correlation coefficient The Pearson correlation between the experimental and simulated intensity statistics is time dependent and provides an indication of the conditions under which the geometric phase approximation of our model is suitable. Fig. 9b) illustrates that poorly correlated pulses are, on average, more truncated by the mirror aperture than highly correlated pulses. For a Gaussian beam truncated along one dimension, the true (prior to truncation) and recorded centres of mass deviate by a percentage beam width approximately equal to the percentage of intensity outside the mirror aperture. Consequently, the error in the calculated pointing angle increases linearly with pulse intensity losses  provides an indication of beamline instabilities that are not currently captured by the SPB/SFX model. These instabilities, such as thermal deformation of mirror surfaces and positional jitter of photon transport optics, may result in a nonlinear relationship between the beam pointing angle and the observed centre of mass. While our results suggest that these phenomena are not the primary contribution to wavefront fluctuations on the megahertz timescale, these effects, which can arise over long-duration operations, may be significant contributors to the intensity statistics between pulse trains (Petrov et al., 2022The overlap between the centres of mass of highly correlated and uncorrelated pulses in Fig. 95.Our phenomenological model of radiation at the European XFEL describes shot-to-shot fluctuations that are time dependent, and it requires no prior knowledge of the properties and operation of the accelerator and undulator. The mean intensity profile of our model is consistent with predictions based on FEL theory and, when paired with probabilistic models derived from experimental measurements, can be perturbed to replicate shot-to-shot wavefront statistics that these previous models do not describe. This model is a highly generalized approach to simulating XFEL radiation that can provide descriptions of the statistics of large ensembles of pulse wavefields under a broad range of operational conditions. The accuracy of these measurements is limited only by suitable estimates of the expected values of pulse width and divergence, and the quality of intensity data recorded. Our model provides a method of generating statistically accurate descriptions of the experimental pulse wavefield, in a manner that is robust to instrument operation and is suitable for users of XFEL facilities who may wish to carry out simulations of wavefront properties during an experiment.et al., 2020et al., 2022et al., 2022et al., 2021et al., 2017et al., 2015et al., 2016et al., 2017et al., 2011When paired with efficient wavefront propagation simulations (Chubar & Celestre, 2019et al., 2010tth pulses. In the case where pulse intensity or wavefront information can be recorded simultaneously during diffraction experiments, the development of filtering and classification algorithms (Rose et al., 2018Alongside the capacity to reproduce intensity distributions observed experimentally, our model provides new information on the shot-to-shot statistical properties of radiation at the European XFEL. In circumstances where the observed fluctuations in beam size and position are time dependent, our model predicts that the shot-to-shot coherence of the European XFEL is non-stationary. This implication of non-stationary spatial coherence between XFEL pulses has significant consequences in both imaging and wavefront characterization experiments, and is not captured in current descriptions of radiation at the facility (Geloni et al., 2020et al., 2020et al., 2021et al., 2019et al., 2014Regarding the characterization and remediation of the pulse wavefront, non-stationary shot-to-shot coherence has significant implications in a broad range of applications. Measurements of coherence from intensity correlations, for example via the Siegert relation (Ferreira et al., 2022et al., 2021Applications of our simplified representation of the XFEL source could prove highly beneficial as a photon diagnostic for the accelerator by providing a simple relationship between the stability of the observed intensities and the wavefront phase. This ‘top down’ approach may provide a route to optimizing operational parameters and could take advantage of machine-learning techniques in some cases to extract key factors of operation that determine FEL performance (Patel et al., 2022et al., 2020Finally, we expect that the residual disparity between the simulated and experimental shot-to-shot intensity fluctuations can be addressed in future applications by improving the experimental conditions under which fluctuations in the beam size and position are recorded. Specifically, it should be possible to achieve this by recording the shot-to-shot intensity distributions prior to photon transport. By further modifying the experimental setup used on the SPB/SFX beamline, our phenomenological model can be readily extended to represent shot-to-shot statistics of other pulse properties, including pulse energy, duration and spectra. This could be achieved using currently available photon diagnostics (Grünert We note that our model is intended to complement solutions based on theoretical descriptions of the SASE radiation process. For applications that are highly sensitive to pulse spectra, this model should be used in conjunction with these methods to describe highly nonlinear modes of operation.6.We have presented a phenomenological model of shot-to-shot wavefront statistics at the European XFEL. Our model maps the shot-to-shot statistics of intensity fluctuations observed experimentally to a geometric representation of the source phase. Unlike alternative models of XFEL radiation, our approach is robust with respect to non-fundamental practical effects caused by instrument operation, while requiring no prior knowledge of their physical origins. Using wavefront propagation simulations, we have demonstrated the capacity of our model to represent pulse wavefronts that reflect the time-dependent intensity statistics observed at the European XFEL.


The COVID-19 pandemic disrupted specialist training across Australia and New Zealand particularly in the area of assessments. Large-scale face-to-face exams were especially vulnerable to disruptions including lockdowns, travel and density restriction and required the Royal Australian and New Zealand College of Psychiatrists (RANZCP) to introduce alternatives.Following several small-scale Objective Structured Clinical Exams (OSCEs) in late 2020 and 2021 (both AV and multi-site), the RANZCP introduced an Alternative Assessment Pathway (AAP) after an exam cancellation in November 2021.To discuss the introduction of an Alternative Assessment Pathway at the RANZCP and share progress regarding the broader changes to assessment models under consideration.The AAP was co-designed with trainees and Specialist International Medical Graduates and introduced in December 2021 as an interim measure to assess clinical competence in the absence of an OSCE. It comprises a portfolio review of completed end-of-rotation forms and, if required, a case-based discussion held via Zoom.The AAP has been held over two rounds (December 2021 and March 2022) with 97% and 90% pass rates respectively (data correct as at 6 October 2022). An evaluation into the pathway is currently underway.In July 2022, the RANZCP introduced the Clinical Competency Assessment as a continuation of the AAP (with some modifications) for the remainder of 2022 and 2023.While the pandemic has become a catalyst for change, the RANZCP has been considering broader changes to the theory and practice of its assessments for some time. The presentation will provide an overview of its short-term clinical assessment model and share progress regarding change to the long-term assessment strategy.None Declared


Introduction: COVID-19 is a disease that causes flu-like symptoms and difficulty breathing. Emerging in 2019, the COVID-19 pandemic has affected the entire world through restrictions and lockdowns. Multiple studies have compared the effects of COVID-19 on different types of head trauma, with each one producing different results. The goal of this study was to use state and hospital data to determine whether the COVID-19 pandemic had a significant impact on surgeries for traumatic brain injury (TBI).Methods: Public state data on COVID-19 incidence, sourced from the Virginia Department of Health, was compared to hospital data of 352 patients receiving surgeries for TBI from a single major level-one trauma hospital in Northern Virginia. We used data from the three years before COVID-19 and the two years during the pandemic, using t-tests and Pearson correlation to analyze the data. This is a retrospective case review study on the number and age of patients receiving TBI surgery from March 2017 through February 2022 at Inova Fairfax Hospital in Northern Virginia to determine the impact of the COVID-19 pandemic on these factors.Results: When comparing the data, there was a 60% reduction in cases of operative TBI during the peak months of COVID-19 compared to the same months in previous years (p<0.005). Comparing data on the number of Virginia and Northern Virginia COVID-19 cases and data on the age of individuals undergoing TBI surgery four weeks later showed a statistically significant negative correlation (p<0.05) in which the average age of individuals undergoing TBI surgery was lower in the four-week block following a four-week block of increased COVID-19 incidence.Conclusion: Our findings indicate a correlation between the period of decreased activity from COVID-19 restrictions in Virginia and a decline in both the number of TBI surgeries and the age of individuals undergoing these surgeries. A coronavirus emerged in December 2019 from the city of Wuhan, China . The COVTraumatic brain injury (TBI) is widespread, being one of the leading causes of death globally ,7. It isSeveral studies have shown an overall decrease in the incidence of TBI during the COVID-19 pandemic compared to prior years -19, wherTo determine the effects of the COVID-19 pandemic and its subsequent lockdown on the incidence of TBI surgeries performed in Northern Virginia, we compared hospital data from Inova Fairfax Hospital on patients receiving surgery for TBI to publicly available Virginia State data on new COVID-19 infections. We determined the number of TBI surgeries performed and the average age of the TBI surgery patients by month at our institution in the three years before the COVID-19 pandemic  and the two years following its start (March to February of 2020-2021 and 2021-2022). We chose to analyze the first two years following the outbreak of COVID-19 as this period of time represents the most significant impact of COVID-19 on the population, and we selected the three years prior for comparison to minimize the effects of annual variations. We compared the number of TBI surgeries performed at Inova Fairfax Hospital during the first two years of COVID-19 to the three years prior. We also compared the number of TBI surgeries performed at our institution during the four months of increased lockdown restrictions (March to June 2020) to the same four months of the previous three years. We compared the age of patients receiving surgery for TBI during the first two years of the COVID-19 lockdown to the three years prior. We also compared the age of patients receiving surgery for TBI during the four months of increased lockdown restrictions (March to June 2020) to the same four months of the previous three years. All of these comparisons were performed using t-test statistics.We further determined if there was a correlation between the number of new COVID-19 cases in Virginia and Northern Virginia with the incidence of performed TBI surgeries four weeks later, or if there was a correlation between the number of new COVID-19 cases in Virginia and Northern Virginia with the average age of patients receiving surgery for TBI four weeks later during the first two years of the COVID-19 pandemic. Our correlation was between the average incidence of COVID-19 and TBI injury data of the following four weeks because we assumed that it would be time for people to be aware of an increase in COVID-19 infections and change their behaviors. For this comparison, we used publicly available data from the State of Virginia on the incidence of new COVID-19 infections in the State of Virginia and the Northern Virginia area organized by four-week periods from April 2020 to February 2021. The data from Inova Fairfax Hospital on the number of TBI surgeries and the average age of TBI surgery patients were also organized by four-week periods from April 2020 to February 2021. We used Pearson correlation statistics for this analysis. Statistics were completed using Minitab Statistical Software  on a Hewlett-Packard personal computer . Values of p<0.05 were considered statistically significant.A comparison of the average number of performed TBI surgeries per month during the first two years of the COVID-19 pandemic to the average number of performed TBI surgeries per month during every month of the three years prior can be seen in Figure A similar result was seen when assessing the average age of patients receiving TBI surgery, but this comparison did not reach statistical significance. Figure Figure There was a statistically significant negative correlation when evaluating the mean age of patients receiving TBI surgery. Figure Our analysis revealed that during the peak four-month period of COVID-19 lockdown restrictions, there was a marked decline in TBI surgeries compared to the averages of the same four months over the preceding three years. We believe that this decrease in TBI surgeries performed during lockdown restrictions might be a byproduct of fewer opportunities for people to engage in activities that may be associated with TBI such as driving. A study done in Normandy, France, found decreased ICU admissions for TBI during the COVID-19 pandemic, linking it to a 74% decrease in motor vehicle accidents across France, but this study also found an increase in TBI surgery . HoweverOther studies showed more variance from our findings. A meta-analysis of 13 studies found a higher mortality rate from TBI during the pandemic but only in low- and middle-income countries . The autOur analysis indicated a notable shift toward an older demographic, with the average age of patients undergoing TBI surgery during the heightened COVID-19 lockdown months being 73.9, compared to an average of 66.9 in the same period over the previous three years. We believe this trend to be related to fall-induced TBIs common among elderly patients. While elderly patients continued to be susceptible to TBI-prone falls which frequently occur at home, during the four months of increased lockdown restrictions, patients of younger age groups were less susceptible to TBI-prone activities, such as operating motor vehicles, than they were during the three years prior. A study done in the Netherlands found a similar trend of increased age among TBI patients while lockdown restrictions were in place, linking it to a decrease in commuting among younger populations that might pose the risk of TBI . FurtherDuring the two years following the start of the COVID-19 pandemic, as the incidence of new COVID-19 cases in Virginia and Northern Virginia increased, we found that the average age of patients receiving TBI surgery decreased. We believe that this negative correlation might be a result of increased domestic abuse, especially among children. A study done on the rise of abusive head trauma (AHT) supports this idea, reporting an increase in AHT among children at their institution during the pandemic and linking it to the increased exposure of children to their parents .Another study that agrees with our overall findings observed a decrease in the mean number of TBI cases during the pandemic, linking it to a decrease in traffic accidents . HoweverAnother study done in Vento, Italy, observed an overall decrease in the incidence of TBI (approximately 49% less than expected TBI rates) in the year following the start of the COVID-19 pandemic . This isA primary limitation of our study is its retrospective design. Retrospective analyses, while valuable, might not account for all potential confounders as effectively as prospective studies. This may affect the generalizability and causative interpretations of our results. Another limitation of this study is that it does not compare the several years prior to the COVID-19 pandemic with each other to see if there was a preexisting, long-term, negative trend in TBI surgeries performed. An overall yearly decrease in operative TBI may inappropriately suggest this trend to be a result of the COVID-19 pandemic as the trend continues through the years analyzed following the emergence of COVID-19. Another limitation of this study is that it uses data from only one hospital in one country while attempting to draw conclusions about a global pandemic. As we have discussed above, other regions of the world have reported results different from our findings suggesting limitations in generalizability. It’s also essential to note that our study centered primarily on operative TBIs. Thus, while our findings shed light on this subset of TBI cases, extrapolating these conclusions to encompass the entire TBI spectrum during the pandemic would require a more expansive analysis.With our study, we found an overall decrease in TBI surgeries performed and an increase in the average age of patients receiving TBI surgery during the four months of increased COVID-19 restrictions (March to June 2020). Our findings represent an example of how policy decisions and peoples’ behaviors in reaction to environmental pressures can affect unrelated health conditions such as head trauma. This is important for us to keep in mind when making policies and addressing the concerns of the overall population. This also suggests that changes in society occurring during the COVID-19 lockdown that could be continued after the pandemic, such as an increase in working from home, may have the effect of decreasing severe TBI.


Micromachines retracts article [The journal  article  due to d article  will be Micromachines. This retraction was approved by the Editor-in-Chief of the journal The author agreed to this retraction.


Editorial on the Research TopicData driven and model based computational futures in cardiovascular practiceWith the turn of the millenium medicine has been witness to a tidal change in practices around real world evidence, and research, whose opportunity arose from the growing availability of computing resources, and the associated ever increasing ability to collect and store data. The value and perils of this new normal have become evident during the COVID-19  medicine, with a special focus on two apparently alternative approaches: machine learning, and physiological models.Enthusiasm about the promises of machine learning applications in the biomedical field is evergrowing, pushed by the amazing list of state-of-the-art works established by data-driven computational approaches in recent years , 3. NeveInterest in hypothesis driven computational model approaches has been growing, and in some notable cases  to provide proximal flow control.Reid et al. present the application of virtual imaging technology for diagnosis and planning of the aortic valve sparing procedure demonstrating that obtained information could be successfully applied to pre-operative surgical planning.The manuscripts we could map to machine learning applications to cardiovascular medicine appeared comparatively competitive on the technological solutions but somewhat less mature in terms of governance and technological solutions available to access the clinical settings.Cheng et al. present work to develop a reliable prediction tool of composite outcomes of postoperative complications using a minimum of easily accessible clinical parameters.Jiang et al. present the use of machine learning techniques to identify atrial fibrillation recurrence following Cox-Maze IV procedures.Baskaran et al. present an exploration of the generalisability of currently available predictors of major adverse cardiovascular events to under-represented populations.Cabrero-Holgueras and Pastrana present work to adapt the linear algebra operations of deep learning layers to packed homomorphic encryption demonstrating a speed-up in processing of convolutional layers compared to the existing proposals of privacy-preserving deep learning over encrypted medical data.Very interestingly with regards to making machine learning real-world ready, lowering barriers to data access, We believe this special theme will offer the readers a timely and strategic overview of the state-of-the-art in computational methods applied to cardiovascular medicine, offering a realistic and grounded insight into adjacent possibles they will soon be faced with in research and clinical practice.


The authors regret that the affiliations for Ji-Youn Kim and Hye-Ryeon Yu were incorrectly shown in the original manuscript. The corrected list of affiliations is as shown here.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.


Molecules entitled “Role of Computer Aided Drug Design in Drug Development” to present the most recent progress in this field. This Issue includes nine articles in total (two reviews and seven research articles), covering the research field of biomarker and ligand–protein interaction prediction, drug repurposing, ligand binding site identification and largescale virtual screening.The introduction of computational techniques to pharmaceutical chemistry and molecular biology in the 20th century has changed the way people develop drugs. The computer-aided drug design method utilizes the 3D structures of potential drug targets  that are involved in the process of disease and the assembly of potential candidates to design novel molecules or modify existing agonists/antagonists against the target specifically ,2. As thAs previously mentioned, computer-aided drug design is an interdisciplinary field that involves a variety of techniques. The two review articles in this Special Issue provide us with a detailed introduction to commonly used methods and tools in drug design. Hasan et al.  not onlyFour out of seven research articles in this Special Issue present case studies of virtual screening and drug design using structure- and ligand-based computational methods. Rayevsky et al.  virtuallThe impressive progress of machine learning and artificial intelligence in the past decade is reshaping the field of rational drug design. Another three works in this Special Issue show how data-driven techniques accelerate drug discovery. Li et al.  developeBesides, Liu et al.’s work  providesTo summarize, this Special Issue covers most of the computer-aided drug design techniques. It provides the readers with an overview of not only the application of structure- and ligand-based methods for drug discovery but also the development of machine learning methods for the prediction of biomarkers and potential ligands. We sincerely hope the articles in this Special Issue will draw researchers’ attention to the field of rational drug design and prompt the development of novel computational methods for drug discovery.


Retraction Note: Journal of Autism and Developmental Disorders (2021) 52:2627–264310.1007/s10803-021-05120-7The Publisher and the Editors-in-Chief are retracting this article. After publication concerns were raised with respect to the methodology used in this article. Post-publication review by a number of experts in the field has confirmed the following:Misrepresentation of the incidence of autism and insufficient attention given to various other factors that might account for apparent changes in ratesUse of unrepresentative dataNo valid justification for the mechanisms proposed for preventionArbitrary and insufficiently justified use of the birth cohort 1931 as an origin for the time trendUse of higher estimates and assumptions that inflated costs, together with failure to consider discrete events that occurred in referent years, including changes in definitions, alternative surveillance methods, and alternative explanations which may have contributed to changes in diagnosis.In addition, the Conflict of Interest statement does not accurately reflect the non-financial interests of the authors.The Editors-in Chief therefore no longer has confidence in the conclusions presented. Mark Blaxill, Toby Rogers and Cynthia Nevison disagree with this retraction.


In liver transplantation, a side-to-side anastomosis is one of the commonly performed techniques of the inferior vena cava reconstruction. The authors report a case of an application of an endoscopic vascular linear stapler for a side-to-side caval anastomosis during deceased-donor liver transplantation. The back table procedure was performed in a standard fashion for a side-to-side anastomosis. The linear vascular stapler was introduced during the temporary clamping of the recipient’s inferior vena cava and the anastomosis was created without problems. Suturing of the resulting defect completed the anastomosis. The use of the stapler resulted in a shortening of the anastomosis time. The staple line after the reperfusion of the graft was completely sealed. The patient’s postoperative course was uncomplicated and post-operative ultrasound and computed tomography confirmed the patency of the anastomosis. This case demonstrates a novel approach to a side-to-side caval reconstruction during liver transplantation that enables a shortening of the implantation time and may improve the quality of anastomoses. Since the first orthotopic liver transplantation was performed in 1963 by Starzl et al.  that preA 43-year-old male with hepatitis C virus (HCV)-related liver cirrhosis underwent elective deceased-donor orthotopic liver transplantation at the Department of General, Transplant and Liver Surgery of the Medical University of Warsaw. At the time of transplantation, his Model for End-Stage Liver Disease (MELD) and Child–Pugh scores were 19 and 9, respectively. A hepatectomy with preservation of the recipient’s IVC was performed. The whole-liver graft procurement from the brain-dead donor and preparation for piggy-back transplantation was performed as described previously . The livA one-centimeter incision was made in the distal part of the recipient’s IVC and a corresponding venotomy was performed in the IVC of the liver graft A,B. Two No post-reperfusion syndrome was observed. The biliary ducts were anastomosed end-to-end with two running 6-0 polydioxanone sutures. The postoperative period was uneventful. An ultrasound examination on postoperative day (POD) one and POD 5 showed patent vascular anastomoses with typical flow characteristics. There was no stricture observed in the cavo-caval anastomosis and the maximal blood flow velocity (Vmax) equaled 73 cm/s. On POD 7, the patient’s laboratory results revealed normalization of the liver function . Follow-A modified cavo-caval side-to-side anastomosis with a linear stapler and partial restoration of the IVC blood flow during orthotopic liver transplantation was presented. The authors chose the simplest possible technique of performing a stapled side-to-side cavo-cavostomy with a single linear cartridge application and closure of the resulting defect with a continuous suture. The authors believe this type of anastomosis most closely mimics the sutured piggy-back anastomosis and offers at least the same quality and safety of the resulting reconstruction . The impThe piggy-back technique reduces the risk of acute kidney injury (AKI) after transplantation compared to the caval-replacement technique due to the preservation of the IVC blood flow . This beLiu et al. in 2006 published an experimental study on an EndoGIA linear stapler for IVC anastomosis in dogs . The allStapled IVC anastomosis is a useful technique in voluminous liver grafts or cases of large caudate lobes when access to the proximal part of the IVC may be cumbersome. The placement of an EndoGIA stapler and suturing of the defect in the IVCs is performed from the caudal approach, which requires only minimal retraction of the liver to expose the infrahepatic IVCs. Moreover, sutured anastomoses in bulky grafts may be prone to excessive tension on the suture line, resulting in minimal lacerations in the vessel wall. This frequently leads to oozing from the anastomotic line after the restoration of blood flow through the liver and the IVC. Another possible problem with sutured anastomosis under tension may be its shortening and an increased risk of outflow obstruction. However, it has to be noted that the limitations of sutured modified piggy-back anastomosis also pertain to the stapled piggy-back technique. Anatomic limitations, abnormalities of the IVC, or severe adhesions between the liver and the retrohepatic IVC preclude safe preservation of the IVC during hepatectomy . VoluminThe stapled side-to-side cavo-caval anastomosis during orthotopic liver transplantation may offer some benefits, including shortening of the graft ischemia period, improved feasibility of anastomosis in large liver grafts or inconvenient caudate anatomy and better quality of the anastomotic line. However, some disadvantages and risks are possible, including less control of the anastomotic line, the lack of a way to adjust during the placement of staples, the risk of leaving loose staples in the venous lumen and the possible increased rigidity at the apex of the anastomosis. Well-designed randomized studies are needed to assess the clinical significance of the expected advantages and disadvantages of such an approach.Stapled cavo-caval anastomosis is a promising modification of the piggy-back liver transplantation technique. Other devices for vascular anastomosis may become future alternatives, including non-penetrating single staples  or even


The glomerular filtration rate was obtained through an equation devised by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), which was derived from pooled data from clinical studies in the United States.The prevalence of CKD among apparently healthy people was analyzed among the participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).One point to emphasize is that ELSA-Brasil researchers did not correct the glomerular filtration rate for race in the manner proposed by the CKD-EPI consortium.Although the U.S. Preventive Services Task Force concluded that the "evidence is insufficient to assess the balance of benefits and harms of routine screening for CKD in asymptomatic adults,"


Correction: Biotechnology for Biofuels and Bioproducts (2023) 16:122 10.1186/s13068-023-02361-9Erysipelotrichaceae bacterium). However, ChPPK is the focus of research in this article and not EbPPK. The authors apologize for not being aware of the previous publication and have now cited the previous publication reporting the sequence [Following publication of the original article , it camesequence  in the asequence  in the Rsequence  previousThe authors also state that the correction does not affect the discussion or conclusions and that they sincerely apologize for the unintentional errors.The original article has been corrected.


Health system response to the co-incidence of epidemics and disasters: the importance of lessons learned during the COVID-19 pandemic” was selected and notified by the journal “Frontiers in Public Health” to publish research papers that investigated and reported the different aspects of the health system response to the co-incidence of the COVID-19 pandemic and disasters across the world.The COVID-19 epidemic started in the Chinese city of Wuhan in December 2019 . In the Moslehi et al.). People's risk perception regarding the COVID-19 pandemic was investigated by Chinese researchers. They indicated that the older population, as a vulnerable group, had the highest risk perception score regarding the COVID-19 epidemic in China . Several authors investigated and analyzed the status of healthcare providers at the time of COVID-19. For example, the insufficient preparedness of nurses to respond to the COVID-19 crisis in Iran was extracted and reported (Moradian and Mahmoudi). In Germany, the self-images of ICU clinicians for crisis management during the COVID-19 epidemic were explored and reported as important perceptions that should be notified by policymakers . NGOs, as one of the important relief providers, can supply emergency relief resources with the support of the government through media publicity and policymaking encouragement in China (Lu and Wang). Regarding post-disaster recovery, resilient communities could cope with the effects of the COVID-19 epidemic better than vulnerable communities, which have insufficient communications and information . The surge capacity of healthcare facilities was an important issue at the time of the COVID-19 epidemic. Accordingly, the Arizona Department of Health Services has designed and implanted a surge line since the COVID-19 pandemic. This line was successful in facilitating patient transfer and benefiting marginalized populations . Medical performance evaluation and COVID-19 vaccination optimization were also investigated by Chinese authors, who published their research in this Research Topic .A total of 11 papers related to this Research Topic were accepted and published in the journal. None of the submitted papers addressed the co-incidence of the COVID-19 epidemic and natural disasters but considered the COVID-19 epidemic as a disaster and reported its various health aspects. For instance, regarding the social health aspect of COVID-19, social vulnerability indicators were developed to highlight the incidence of the COVID-19 epidemic in socially vulnerable regions in Iran (Although the impacts of disasters and epidemics on health systems have been reported by several studies, little is known about how to reduce the dual risk of disasters and epidemics. The COVID-19 epidemic provided a unique opportunity for identifying the emergent challenges and establishing innovative risk reduction and preparedness strategies to respond to similar crises in the future. The health sector has the main responsibility for people's health, and thus, plays special roles during the co-incidence of epidemics and disasters. Applying the lessons learned during the COVID-19 epidemic and establishing resilient health facilities and prepared healthcare staff can reduce deaths, injuries, and health system destruction after epidemics and disasters. Otherwise, all the adverse challenges and issues that the world experienced during the COVID-19 pandemic will probably repeat in any similar pandemic in the future. Thus, health systems need scientific collaborations and policymaking efforts at regional and international levels. The documentation and publication of effective lessons learned by health systems in the areas of prevention and treatment and disaster and emergency management should be considered as important measures and the first steps in future planning and policymaking.SS: Writing—original draft, Writing—review and editing. LM: Writing—review and editing. MY: Writing—review and editing. MZ: Writing—review and editing.


Correction: Journal of Pharmaceutical Policy and Practice (2023) 16:158 10.1186/s40545-023-00652-yFollowing publication of the original article , it was dry ice. This unusual requirement necessitated training of physicians and pharmacists in the safe handling of dry ice and the support of the Swiss military pharmacy for logistics and distribution.This was achieved by shipping the vaccine vials in trays secured within thermal containers cooled with The original article has been updated.


The COVID-19 pandemic has radically changed our lives in every way. Since the beginning of the pandemic, more than 760 million cases and nearly 7 million deaths related to the COVID-19 disease have recorded worldwide . These p-Suicide risk related to isolation and financial stress;-The greater risk of domestic violence in the home environment;-The removal of young people from community relations within the school and other social fields;-Burnout within the healthcare community;-Difficulties in the surveillance and treatment of mental illnesses;-Reduced access to care for patients suffering from chronic alcohol and/or drug abuse;-The risk of stigma surrounding COVID-19-positive patients.According to the WHO , in the first year of the pandemic, there was a noted increase in the prevalence of mental disorders such as anxiety and depression, equal to approximately 25% . In the Although today, after approximately 3 years, we are witnessing a post-emergency period with a gradual recovery of all activities, scientific interest in the COVID-19 pandemic and its respective effects on mental health remain the subject of numerous studies, especially with respect to the long-term psychological effects of the disease. A recently published study by Xie et al. revealed an increase in the risk of mental illness in subjects who survived the acute phase of the COVID-19 pandemic . In 2023The evidence that has been offered leads us to further investigate the impact of the COVID-19 pandemic on our psychological states, both in the short and long terms . The pur