Left sided non-recurrent laryngeal nerves (NRLN) are very rarely observed during surgery in the head and neck region. Arising directly from the cervical aspect of the vagus nerve, the NRLN lies in a vulnerable position distant from its normal location. NRLNs are normally associated with embryological branchial arch aberrations and subsequent vascular anomalies. The anomalous course of the NRLN makes it more susceptible to injury during surgery in the neck region. Knowledge of this anatomical variant will reduce the potential for injury and resultant vocal cord paralysis. During microsurgical dissection of the carotid sheath for the implantation of a vagus nerve stimulator in a 19-year-old female patient with refractory epilepsy, a moderate-sized branch of the main vagus nerve trunk was identified postero-medially within the carotid sheath. Intra-operative stimulation of this nerve resulted in a compound muscle evoked potential from the left vocal cord. Thus, this branch was confirmed to be a left-sided NRLN. The patient had no associated vascular anomalies. This is first reported case of a left-sided NRLN found during VNS insertion. Awareness of the possibility of an NRLN is imperative to prevent iatrogenic injury. A medial location of the vagus nerve within the carotid sheath should alert the surgeon to the possible presence of an NRLN. The absence of fourth branchial arch remnant anomalies is not a guarantee as to the absence of a left-sided NRLN. The addition of intra-operative nerve monitoring for vagus nerve stimulator (VNS) implantation procedures should be strongly considered to help avoid iatrogenic injury. Left sided non-recurrent laryngeal nerves (NRLN) are very rarely observed during surgery in the head and neck region. In “non-anomalous” cases, the right recurrent laryngeal nerve (RLN) arises from the right vagus nerve anterior to the first part of the subclavian artery, it then hooks around the right subclavian artery and ascends towards the tracheo-oesophageal groove before entering the larynx . On the The anomalous course of the NRLN makes it more susceptible to injury during surgery in the neck region. Knowledge of both the normal anatomy and anatomical variants of the recurrent laryngeal nerve should serve to reduce iatrogenic injury to the nerve. We report a case of a left NRLN discovered during vagus nerve stimulator implantation (VNS).A 19-year-old female patient with drug-resistant epilepsy, who was not considered a suitable candidate for resective epilepsy surgery, was offered vagal nerve stimulation for seizure control.Surgery was performed under general anaesthesia after the administration of intravenous antibiotics and under strict aseptic protocol. The patient was placed supine with the head in the midline and a slightly extended position. A horizontal neck incision was made at the level of the mid larynx, halfway between the clavicle and mastoid process. The sternocleidomastoid muscle was dissected along its anterior aspect and retracted posteriorly. A combination of sharp and blunt dissection was used to expose a 4-cm long segment of the carotid sheath. The fibrous connective tissue of the sheath was opened with atraumatic forceps by splitting the fibres of the sheath medially and laterally to reveal the contents of the carotid sheath. Further dissection was performed under microscopic visualisation. .® Eclipse, Minneapolis, MN, USA) to the vagus trunk and to the medial branch. The vocal cord responses were recorded by a commercially available EMG embedded endotracheal tube device used to detect vocal cord responses . Stimulation of the common trunk and medial branch both elicited a compound muscle evoked potential from the left vocal cord. A similar latency period of 6 ms was detected following stimulation of both the trunk and the medial branch; however, the amplitude of the compound muscle potential was approximately half when the vagal trunk was stimulated as opposed to the medial branch stimulation.During dissection of the carotid sheath, a moderate-sized branch of the main vagus nerve trunk was identified postero-medially within the carotid sheath . Vessel The VNS coils of the VNS Stimulator  were placed around the main vagal trunk, away from the branching point. . The lead wire was passed subcutaneously to an infraclavicular subcutaneous pocket. Then, the lead was attached to the implantable pulse generator. There were no cardiac responses to intra-operative test stimulation. The wound was closed in anatomical layers. The patient had no intra-operative nor post-operative complications. A routine chest X-ray was performed as part of the pre-operative workup, and this did not demonstrate evidence of situs invertus or a right-sided aortic arch. Additional investigations for vascular anomalies were not performed.The patient was seen for regular follow-up visits. During follow up, a structured questionnaire designed to elicit any laryngopharyngeal symptoms was administered. The patient presented no evidence of vagal nerve dysfunction. At six-month follow up, she had responded well to the VNS, with a reduction in seizure frequency and severity.To our knowledge, this is the first reported case of an NRLN in the setting of VNS implantation and one of the few cases in which the course of the NRLN is described both within the carotid sheath and once exiting the sheath. According to our knowledge, it is also the first reported case to demonstrate the benefit of standard intra-operative nerve monitoring (IONM) in the setting of VNS implantation in delineating anatomical variations in this region and the potential of IONM to assist in avoiding iatrogenic injury.Embryologically, the recurrent laryngeal nerves (RLNs), also frequently referred to as the “inferior laryngeal nerves”, are derived from the VI branchial arch and have a horizontal course. Subsequently, the V and distal portion of the VI branchial arches regress bilaterally, and the RLNs remain anchored to structures that develop from the IV branchial arch: the aortic arch on the left and the subclavian artery on the right ,5. As thThe NRLN is a rare anomaly in which the NRLN branches off the cervical vagal trunk to enter the larynx directly from within the carotid sheath, without first descending to the thoracic level. It has been reported in only 0.3–0.8%  of the pThree types of NRLN have previously been distinguished : type 1 Most descriptions of the NRLN describe the path of the nerve once it exits the carotid sheath, as this is of most relevance to thyroid and parathyroid surgery. Very little is described regarding NRLN anatomy within the carotid sheath. Gurleyik  describeGenerally speaking, the non-recurrence of the right laryngeal nerve results from a vascular anomaly during embryonic development of the aortic arches, with the resultant absence of the innominate artery and the formation of an aberrant right subclavian artery, the so-called arteria lusoria, which arises directly from the aorta left of the midline and crosses the oesophagus. For non-recurrence of the left-sided laryngeal nerve, a triad of fourth branchial arch remnant anomalies are required: a right-sided aortic arch with an associated situs inversus; a right-sided ligamentum arteriosum, and a left subclavian artery with a lusoria course . HoweverAs far as we are aware, this is the first reported case of an NRLN in the setting of VNS therapy. Despite the widespread use of intra-operative nerve monitoring (IONM) in head and neck endocrine surgery ,15, IONMAwareness of the possibility of an NRLN within the carotid sheath during VNS implantation or any other surgery involving dissection of the carotid sheath is imperative to prevent iatrogenic injury to the vagus nerve and its branches. A medial location of the vagus nerve within the carotid sheath should alert the surgeon to the possible presence of an NRLN. The absence of fourth branchial arch remnant anomalies is not a guarantee as to the absence of a left-sided NRLN. The addition of IONM for VNS implantation procedures should be strongly considered to help avoid iatrogenic injury.


Cognitive decline usually coexists with motor impairment in PD. Multitask settings provide appropriate measures to evaluate the complex interaction between motor and cognitive impairments. The main objective was to analyze which concurrent task, i. e., motor or hybrid motor-cognitive, in combination with a cognitive task better differentiates between PD patients with mild and moderate levels of disease.  Thirty-seven individuals  with idiopathic PD performed dual and triple tasks combining a cognitive task (phonemic fluency) with motor  and/or cognitive-motor hybrid (tracking) tasks. Mild and moderate disability PD groups were specified considering the Hoehn and Yahr scale. Mixed ANOVA analyses for each of the concurrent task were carried out to test differences between the single and dual or triple condition performances comparing the low and high PD disability groups. Supplementary mixed ANCOVA analysis was performed considering the cognitive status as the covariate.  The only significant differences between disability PD groups were found for performances in the cognitive-motor hybrid (tracking) task, both in dual and triple conditions. Our results showed a better performance for the mild rather than for the moderate disability group in the single condition task and a significant decline of the mild disability group in the dual and triple condition when compared to the levels of those shown by the moderate disability group. The group-condition interaction remained significant when the cognitive status was statistically controlled.  The hybrid of motor-cognitive task combining with a cognitive task  successfully differentiated between mild and moderate PD patients in the context of dual and triple multitask sets even when the cognitive status was statistically controlled. Our results highlight the importance of jointly measuring the complex interplay between motor and cognitive skills in PD. Parkinson's disease (PD) is mainly characterized by the progressive impairment of motor abilities . HoweverThe interaction between the motor and cognitive components seems to determine the functional capacity and should be considered simultaneously in the evaluation of the progression of PD . Thus, vThe concurrent-task paradigm (multitask setting) constitutes an appropriate paradigm to evaluate the reciprocal influences between the motor and cognitive components because reciprocal costs can easily be estimated considering how the performance in both motor and cognitive tasks is hindered in concurrent condition regarding its performances in the single condition. The analysis of the relationships between cognitive and motor impairments in PD should be useful to assess the progression of symptoms, optimize the effectiveness of interventions, and finally, improve the patient's quality of life . The conAs far as we know, no study has been conducted to analyze the influence of the triple condition in patients with PD, but considering what has been reported for healthy older adults , a decliSome studies carried out on healthy older adults have pointed out that the multitasking costs  were higher in motor-cognitive than in motor-motor task sets –15. EvidOur aim was to elucidate which concurrent task  in combination with a cognitive task is better to differentiate between PD patients with mild and moderate levels of disease . Three tIn light of dual task taxonomy by McIsaac et al. , higher Thirty-seven individuals  with idiopathic PD were recruited for this baseline analysis. All patients with PD had been clinically diagnosed with idiopathic PD by a neurologist and were tested in the practical ON levodopa state, after ingesting antiparkinsonian medication (they reported that levodopa had taken its full effect). Subjects were recruited from Parkinson associations. They were invited to participate if they were between the ages of 50 and 85 years, were on levodopa treatment, experienced motor response fluctuations, and were able to ambulate independently. Five patients were excluded because they did not complete all the tasks.Participants were classified as mild disability (stages I and II of the disease) and moderate disability (stages III and IV) according to the Hoehn and Yahr scale . This scAll patients gave their written informed consent to participate in this study according to the Declaration of Helsinki. The protocol of this study was approved by the Research Ethics Committee of the Faculty of Education and Sport Sciences and then assigned code number 12-2205-17.This variable was assessed using the Walk protocol with Wiva® sensors , a set oThe cognitive status of the participants was measured with the Montreal Cognitive Assessment (MoCA) . The MoCTasks that mainly involve a mechanical or repetitive physical movement by the patient are representative of pure motor tasks. It applies, therefore, to any work that necessarily involves a movement of the body. Due to the characteristics of the patients, the selected motor task was pedaling, which consisted of indoor cycling , 38 for The cognitive task chosen for the development of the study was a phonemic verbal fluency task. Verbal fluency tasks are often included in neuropsychological assessment to indicate cognitive impairment in persons with neurodegenerative diseases such as PD . The tasThe task administered consists of using a pencil to draw a line through circles arranged in a path around a sheet of A3 paper containing 319 circles . After aThe same measures were recorded in the phonemic fluency (number of correct words), tracking (number of circles crossed) and pedaling  in the simple, dual and triple conditions. The phonemic fluency was measured by the number of correct words starting with the designated letter produced in 60 seconds. In the tracking task, the number of circles crossed with the pencil within the 60 seconds was recorded. In the pedaling task, the number of pedal strokes was recorded after the 60 seconds.The tasks were performed by each patient individually, in a spacious and comfortable location and always supervised by the evaluators. The patients sat in a chair without armrests with a height of 47 cm and with the backrest fixed to the wall. In front of the patients was a desk 72 cm high. Tasks were administered to the participants seven days a week and always in the morning. The protocol was carried out within two weeks, and all measurements for each patient were taken on the same day.All the tasks and conditions were applicable to the sample participants . Tasks wt-tests were conducted by comparing mild and moderate disability groups for age (years), years of education, MoCA score, and gait: spatiotemporal parameters, phonemic fluency , tracking , and pedaling . Mixed ANOVA analyses were performed to test group differences (mild and moderate disability) between single and dual conditions for phonemic fluency, tracking, and pedaling tasks in the following combinations: phonemic fluency-tracking and phonemic fluency-pedaling, considering the MoCA total score as the covariate. Similarly, mixed ANOVA analyses were also performed to test group differences between single and triple conditions for each of the following tasks: phonemic fluency, tracking, and pedaling, also controlling for MoCA total score. The estimated marginal means represented in the figures correspond to the average scores for each level of combination of the factors considered , adjusted for the covariate of the cognitive status. Multiple-comparison post hoc Bonferroni correction was used to evaluate pairwise significant comparisons. The alpha value was established at .05 for all analyses, and the partial eta squared value (ηp2) is reported as an estimate of effect size in the mixed ANCOVAs.A descriptive analysis was carried out through measurements of central tendency (mean) and dispersion (standard deviation) to describe the sample, thus stratifying the description according to the stage in which the sample is located. Student's Comparisons between groups with mild and moderate disability are shown in Mixed ANOVA analyses comparing group differences between single and dual conditions see  revealedThe significant differences in condition disappeared in the mixed ANCOVA when the MoCA score was included as covariate, whereas the main effects for the disability group factor in tracking, and pedaling tasks, and the significant interaction between the task condition and the disability group for tracking, remained significant see . Post hoSimilar to those results described above for dual conditions, comparisons between single and triple conditions revealed that see : (a) theSimilar to those results found for the comparisons between dual and simple conditions, the significant differences in experimental conditions disappeared in mixed ANCOVA when the MoCA score was included as a covariate see . Only thOur results showed significantly worse performance in the more disabled PD group for the pure motor  and hybrid (tracking) tasks regardless the experimental condition . However, disabled groups showed similar performance in the cognitive task (fluency), regardless of the experimental condition. In line with previous studies , 24, ourSimilar dual costs  in both disability groups were observed in fluency (when combined with tracking), pedaling (when combined with fluency), and tracking tasks (when combined with fluency), but not for the fluency task when combined with pedaling. As expected , the comIn line with what it was hypothesized, the tracking measure when performed with the fluency task was the only combination sensitive to the differences in condition between the disability PD groups. Unlike what was observed in pedaling when combined with fluency, the tracking task was sensitive to detect significantly better performance in the mild than in the moderate disability group for the single condition and to show a significant decrease in performance in the dual condition for the mild disability group that reaches levels similar to those shown by the moderate disability group. Thus, the tracking task was the only one able to detect differences between PD disability groups in concurrent-task paradigms.On the other hand, motor  and, particularly, cognitive (fluency) task failed in discrimination between disability groups in multitask setting. Thus, although pedaling performance was significantly poor in mild than in moderate disability group even when cognitive status was statistically controlled, differences were similar in single and dual conditions. Regarding fluency task, disability group differences were neutralized when cognitive status covariates were considered.Only the hybrid task demonstrated the ability to differentiate between disability groups in multitask setting. We suggest that the subtle interplay between difficulty, novelty, and cognitive-motor demands should be critical in determining the sensibility to the motor, cognitive, and interaction of cognitive-motor impairments in PD.The interaction between group and condition in the tracking task was robust and remained significant when the cognitive status was statistically controlled, suggesting that its specific motor-cognitive hybrid nature is responsible for capturing the differences between disability groups by condition. However, contrary to what has been reported in healthy older subjects  and to tOur results highlight the importance of jointly measuring the complex interplay between motor and cognitive skills in PD , 5, not Some limitations of this study should be overcome in the future. First, the sample size must be enlarged and control of physical activity or specific motoric interventions should be considered because it could affect differently the progression of motor symptoms in each of the disability groups. Likewise, the inclusion of a healthy control group is considered of interest in order to study dual performance differences with PD patients in concurrent tasks. To add the motor-hybrid task pairing would be useful in order to have a complete picture of the motor-cognitive task combination possibilities. Finally, the substitution of the phonemic fluency task for the action fluency modality should be relevant because it has shown higher sensibility to progression in PD.(1) Hybrid motor-cognitive task differentiated between mild and moderate PD patients. (2) Mild group performance worsened in dual condition to match that of the moderate group. (3) Between-group differences in the hybrid task were not neutralized by cognitive status


Cardiovascular disease is a leading cause of death and a serious economic burden to patients and society. An estimated 18 million people die of cardiovascular disease  annually . This isCutting Edge Methodologies in Experimental Cardiovascular Research presents a collection of nine experimental and review articles covering a broad area of experimental cardiovascular research ranging from studies on the preclinical cell  and animal models  to mathematical modeling . Two articles represent typical methodological studies demonstrating novel or improved protocols. In the first, Woulfe et al. present a method for the isolation of myofibrils (a basic unit of a muscle) from rat primary cardiomyocytes. Experiments with these isolated myofibrils provide insight into muscle mechanics in the absence of non-motor proteins. This advancement enables the study of specific aspects of the function of the cardiomyocyte contractile apparatus that are not possible when using intact cells. Myofibrils are traditionally obtained from a small section of cardiac muscle and their isolation from cultured cardiomyocytes opens new opportunities for the in vitro manipulation of cultured cells prior to the isolation of myofibrils. In the second methodological study, Stellato et al. present a new approach to identifying and isolating murine cardiac fibroblasts using simple two-color flow cytometry. They showed that the defined combination of cell surface antigens  allowed the identification of collagen-producing fibroblasts in freshly isolated hearts of wild-type, non-transgenic mice . This method is breaking new ground for employing flow cytometry-based approaches to study cardiac fibroblasts in mouse models without the need for specific reporter mouse strain. In an experimental study, Burja et al. used an in vitro model of atherosclerosis to show the anti-inflammatory effects of olive leaf extracts in human coronary artery endothelial cells activated by serum amyloid A. The proof-of-concept provided by this early preclinical study demonstrates how promising candidates (here olive oil) may be employed for future therapeutic use. The next step in this bench-to-bedside approach is to validate any beneficial effects of these potential therapeutic agents in a living organism.This Research Topic on Oppi et al. describes commonly used mouse models of atherosclerosis. Because atherosclerosis can be induced in several atherosclerosis-prone genetic mouse strains by different mechanisms, the paper provides a road map for researchers to choose the most appropriate model for a specific scientific question . In another review article on animal models, Błyszczuk focused on myocarditis and its consequence of dilated cardiomyopathy. This review presents the pathogenesis of myocarditis with possible clinical scenarios for the patients as well as the most commonly used experimental mouse models (Błyszczuk). This Research Topic also contains two experimental studies on animal models. In the first, Bacmeister et al. identified key methodological factors in the murine pressure-volume analysis under β-adrenergic stimulation. The authors emphasized the importance of establishing measurement protocols for both accuracy and the reproducibility of experimental data. In the second, Daskalopoulos et al. describe problems of data irreproducibility in animal models. As an example, the authors presented experimental results following treatment with a homologous peptide fragment of Wnt3a/5a UM206 in a mouse model of myocardial infarction. The authors go on to describe the inherent weaknesses associated with a single animal study due to the high number of uncontrollable variables . In laboratory practice, large scale, multicenter animal studies are often not possible for ethical and economic reasons. These data underscore the difficulty of assessing animal studies where the complexity of living organisms and the variability of housing conditions can affect outcomes.Currently, experimental animal models of human disease represent the most advanced platform for preclinical research. A review paper by in vitro and in silico models. Zuppinger presents an overview of cardiovascular 3D cell culture technologies and discusses the advantages and drawbacks of various cardiac organoid cultures. The generation of human-induced pluripotent stem cell (iPSC)-derived cardiomyocytes have been proposed as models of human cardiac tissue, while advanced cell culture models coupled with human genetics are highly desirable in both experimental research and in regenerative medicine. However, these models have a number of limitations and must be considered premature as a replacement for animal studies. Although certain aspects of cardiovascular physiology and pathophysiology can be reliably mirrored by such in vitro models, it seems that the complete rejection of animal-based research is currently not possible. Mathematical modeling represents another option in cardiovascular research. Through the use of clinical data, Faes et al. built a mathematical model of coronary circulation to address the effects of the fractional flow reserve on the degree of coronary arterial stenosis. The successful implementation of a mathematical model to diagnostic procedures could reduce costs, save time, and minimize risk along with the social and economical burden for the patient.An alternative to animal studies is offered by in silico approaches to address more complex scientific questions in the future. On a global scale, such advances would contribute to the faster translation of bench findings into clinical applications. This collection of Research Topic articles offers important insights into recent methodological advances in cardiovascular research that will help in the development of innovative treatment strategies.Novel technologies and continued improvements to established protocols need to be shared across the scientific community to enhance experimental research and ensure that it is time- and cost- effective. The rapid development of machine learning, deep learning, and artificial intelligence may broaden the application of PB, KB, and GK wrote manuscript. All authors contributed to the article and approved the submitted version.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


To provide an overview of recent studies of coronary computed tomography angiography (CCTA) and how it has helped to improve clinical outcomes for patients presenting with chest pain.Randomised controlled trials have uniformly demonstrated that the use of CCTA is associated with improvements in patient diagnosis, management and treatments as well as the avoidance of unnecessary invasive coronary angiography. These changes have been associated with consistent reductions in long-term rates of fatal or non-fatal myocardial infarction.Major beneficial effects in clinical management and patient outcomes are seen with the use of coronary computed tomography angiography. CCTA might be considered to be the first test of choice for the investigation of coronary heart disease. Cardiovascular disease and coronary artery disease are the primary causes of morbidity and mortality in developed countries –3. In thCoronary computed tomography angiography is being increasingly utilised in clinical practice for evaluating coronary anatomy for obstructive disease and plaque. Computed tomography was first introduced by Sir Godfrey Hounsfield in the 1970 and the first commercial scanner was available at 1972. In the early 1980s, an important advance helps to demonstrate the potential for CT technology to image the moving heart. This was the introduction of the electron beam computed tomography (EBCT) by Douglas Boyd. This technology decreased scan times and improved temporal resolution. For the first time, it was possible to view cardiac contractions and to visualise small structures such as calcium deposits within the walls of the coronary artery. A limitation of EBCT is the spatial resolution due to the slice width of 1.5 mm. An additional major advance in computed tomography imaging came in the early 1990s with the introduction of multidector computed tomography (MDCT) that could rotate 360°. With these advances, spatial resolution improved due to multidetection technology and temporal resolution compromise was reduced since the X-ray beam was able to rotate continuously around the patient as they moved through the scanner . Early mAccording to the current European Society of Cardiology guidelines and American College of Cardiology and American Heart Association appropriate-use criteria, CCTA is a level IIa recommendation as an alternative to a stress test for ruling out stable coronary artery disease in patients with low to intermediate pre-test probability , 5. In cPatients attending the emergency department and outpatient department with chest pain account for almost half of all admissions . The iniExercise treadmill test has been the cornerstone method for evaluating patients with stable chest pain for several decades. Depending on the results, the patient would often receive either medical therapy or be referred for invasive angiography. Although this test is cheap and cost-effective, its sensitivity and specificity remain low , and it is even lower in women , 19 and The sensitivity and specificity of functional imaging tests have been reviewed extensively in multiple systematic reviews and meta-analyses . ExercisWith the 64-slice detector computed tomography becoming the minimum standard, the improved temporal and spatial resolution allowed for a high degree of image quality assessment of coronary arteries with CCTA. The extent and severity of angiographic coronary artery disease are amongst the most important prognostic factors and remain vital determinants for revascularisation decision making . SeveralIn addition to precisely detecting obstructive coronary artery disease , CCTA prThe FACTOR-64 trial  has beenSeveral studies have demonstrated improved outcomes when CCTA is added to standard care in patients with stable chest pain . RecentlAlthough in the first 12 months, there was an increase in the invasive angiograms and coronary revascularisation performed in the CCTA group, there was no difference between the two groups in terms of invasive angiography or coronary revascularisation by 5 years of follow-up . HoweverThe benefits of preventative medical therapy are well described in major randomised controlled trials. Nevertheless, it should be remembered that many trials  treated a general and broad population of patients at risk of cardiovascular disease. Most of these trial participants did not have cardiovascular disease and they had no chance of benefiting from the intervention. In SCOT-HEART, we identified a population with the disease before treatment initiation, which potentially led to greater proportionate benefits. Similarly, in the JUPITER trial, patients were risk stratified according to elevated high-sensitive c-reactive protein, enabling the identification of a high-risk population who then received a more marked benefit from rosuvastatin , P < 0.001) than has been seen in previous primary prevention trials .The findings from the SCOT-HEART trial are supported by two other recent studies reviewing patients with stable angina. The CAPP   showed that, although there was no difference in the overall primary outcome, CCTA predicted subsequent cardiovascular events better than functional testing , 44. In  observational Danish registry  [In addition to these individual studies, a meta-analysis of randomised controlled trials published in 2016 comparing CCTA with standard care identified an incidence rate ratio for myocardial infarction of 0.69 following CCTA  : aresultto 0.82) , demonstThere have been several studies assessing the value of CCTA in the emergency department using a surrogate of early and safe discharge . The larA meta-analysis by Gongora et al.  showed tRecent studies as well as large meta-analyses have demonstrated that the use of CCTA is associated with important reductions in coronary heart disease death or non-fatal myocardial infarction . It also


Case Presentation. We present a 60-year-old female with a history of metastatic melanoma who presented with bilateral and symmetric polyarthralgia and clubbing. A plain film radiograph demonstrated periosteal thickening involving the metacarpals and proximal phalanges as well as the distal radius and ulna, consistent with HOA. The patient was treated with nonsteroidal anti-inflammatory agents for supported care.  Hypertrophic osteoarthropathy (HOA) is a rare finding in the setting of metastatic melanoma. A majority of cases of secondary HOA involve lung malignancies. Evaluation of presenting symptoms such as polyarthralgia and clubbing followed by review of imaging studies are diagnostic steps for HOA.  HOA may be a secondary manifestation of metastatic melanoma. Recognition and supportive care of this condition may lead to improved quality of life for patients. Hypertrophic osteoarthropathy (HOA) is characterized by digital clubbing, periostosis, and arthralgia of extremities. This condition is secondary to abnormal proliferation of osseous and soft tissue. There are two forms of HOA: a primary genetic form, which accounts for approximately 3% of cases, and a secondary form, mainly attributed to paraneoplastic syndrome from non-small cell lung cancer and to a lesser degree, from pulmonary diseases such as sarcoidosis, pulmonary tuberculosis, and cystic fibrosis , 2. The We present the case of a 60-year-old female with a medical history of B-RAF wild-type metastatic melanoma with metastasis to the liver and lung, presenting with swelling over the fingers and toes. The patient reported the presence of edema for years and was told it was related to an autoimmune condition given a previously positive ANA result. The patient stated that the swelling was also associated with symmetric polyarthralgia of the upper and lower extremities. She denied any alleviating or aggravating factors. On physical exam, clubbing was present on bilateral distal phalanges . AdditioPlain film radiography of the upper extremities demonstrated periosteal thickening involving the metacarpals and proximal phalanges as well as the distal radius and ulna, consistent with hypertrophic osteoarthropathy . Given pThe proposed pathophysiology of HOA involves the release of platelet-derived and vascular endothelium-derived growth factors. The exact mechanism of disease in HOA is uncertain. This diagnosis should be considered in the setting of clubbing with imaging findings supportive of periosteal thickening. In the setting of HOA with no underlying cause, a plain film radiograph of the chest should be indicated to rule out pulmonary etiology .There are no specific or reliable lab tests available for the diagnosis of HOA. A plain radiograph is the most telling diagnostic modality for HOA. The presence of periosteal thickening is the most specific radiographic finding associated with HOA. This finding may be generalized to include more than one specific region of the bone or localized to a specific site of the bone , 5.Treatment of the underlying disease process is key for secondary HOA. Supportive care with nonsteroidal anti-inflammatory agents as well as bisphosphonates may provide relief. VEGF inhibitors have also been proposed as therapeutic options for alleviating pain symptoms in secondary HOA .This case exhibits the importance of both, a thorough clinical history and physical examination. This diagnosis should be considered in patients presenting with polyarthralgia and appropriate imaging findings. Early diagnosis of this condition combined with appropriate management and therapy may result in improved quality of life for affected patients.


An 83-year-old woman was referred to our hospital under a diagnosis of acute aortic dissection. Contrast-enhanced computed tomography revealed no intimal flap in the mid-ascending aorta, and the intimal flap was found from the distal ascending aorta to the aortic arch. Operative findings showed that the intima of the mid-ascending aorta was circumferentially dissected and was inverted into the aortic arch. An emergent replacement of the ascending aorta was successfully performed; however, she died of a global intestinal ischemia on the fourth operative day. We experienced a case of circumferential type A aortic dissection with intimo–intimal intussusception.Circumferential dissection with intimo–intimal intussusception is a rare condition in the aortic dissection. Initial report by Hufnagel and ConradAn 83-year-old woman suffered from nausea and posterior headache with a history of hypertension, peripheral artery disease, and hemodialysis for 16 years. An emergent magnetic resonance imaging revealed a small infarction in the right cerebellum, and the cardiologist pointed out blood pressure difference between the right upper arm (88/55 mmHg) and the right lower leg (152/76 mmHg). Contrast-enhanced computed tomography (CT) was performed on suspicion of aortic dissection and revealed that the intimal flap was recognized in the distal ascending aorta through the aortic arch but was not found in the mid-ascending aorta  can detect the real-time motion of the intimal flap, degree of the intussusception, degree of the interference with coronary ostium and the aortic valve, and function of the left ventricle. TEE is useful to assist physicians in determining the exact diagnosis and the optimal treatment strategies.To diagnose in an acute setting, multiple modalities were used. proposed the typical finding of this phenomenon. They describe the intraluminal wind sock-like appearance filled with contrast material and surrounded by a contrast column, curvilinear intimal flap in the aortic root, absence of a flap in the dilated mid-ascending aorta, and dissection with intimo–intimal intussusception. Nowadays, multidetector-row CT and electrocardiogram-gated CT are helpful to make a clear image and understand this rare mechanism. Although the diagnosis of aortic dissection had been made by previous hospital in our case, we could not decide the type of dissection because the intimal flap did not exist in the mid-ascending aorta as a typical aortic dissection. The increasing pericardial effusion presumably because of the rupture of the ascending aorta forced us to rush into the operating room. During the operation, we became aware of this condition, and CT findings were recognized as intussusception retrospectively. The blood pressure of the lower leg was higher than that of the right arm in our patient. The intimal flap is seen in complex fashion in sagittal view of the CT (Regarding CT, Karabulut et al.The operation comprises the retrieve and reduction of the intussuscepted intima. From the view of entry exclusion, the ascending aortic replacement is appropriate when the intimal tear exists in the ascending aorta. The aortic root reconstruction or arch procedure may be required according to the existence of another tear, degree of the aortic valve dysfunction, and suffocation of the coronary ostium or arch vessels.Our patient died from mesenteric ischemia. The CT showed no residual dissection, patent celiac and superior mesenteric artery, and highly atherosclerotic change of another vessel. It was possible that a nonocclusive mesenteric ischemia occurred considering the age of the patient and long history of hemodialysis. Dehydration by continuous renal replacement therapy was done slowly; we could not prevent the ischemia. The precise cause of ischemia was unclear because autopsy was not permitted.Making an exact diagnosis of intimo–intimal intussusception in the aortic dissection before operation is difficult. The combination of less invasive modalities, such as CT and echocardiography, helps us reach an accurate diagnosis and perform an optimal operation.We report a case of circumferential dissection with intimo–intimal intussusception in type A aortic dissection.


Previous studies conducted on nurses’ knowledge regarding endotracheal tube cuff pressure revealed that there were differences in intensive care nurses’ knowledge, leading to varying practices.This study aimed to evaluate how an educational intervention based on the existing evidence-based guidelines, using both passive and active implementation strategies, could improve the knowledge of nurses regarding managing endotracheal tube cuff pressures in Malawian intensive care units.Six functional ICUs (four public and two private) in Malawi.t-test) were utilised.The study followed a quasi-experimental, pre- and post-test design using an educational intervention. Intensive care nurses of six functional intensive care units in Malawi were randomly assigned to two intervention groups. Both groups received a half-day educational session, a printed version of the evidence-based guidelines, a printed and laminated summary of the guidelines and a related algorithm. Additionally, Intervention 2 group received four monitoring visits. Pre- and post-test questionnaires were conducted between February and August 2016. Descriptive and inferential data analyses .An improvement in knowledge was observed on the nursing care practices for the management of endotracheal tube cuff pressure for both groups following the educational intervention, although only the results comparing Intervention 2 group participants indicate that the level of knowledge was significant (Implementation of a formal training and mentorship programme for Malawian intensive care nurses would be of great benefit to enhance the knowledge and skills managing endotracheal tube cuff pressure. Follow-up studies would also assist in understanding how guidelines could be implemented most effectively to achieve better knowledge outcomes. Furthermore, three quarters of these six ICUs did not have evidence-based guidelines accessible to the intensive care nurses, guiding them in the management of ETT cuff pressure in mechanically ventilated adult patients. However, no study regarding the management of ETT cuff pressure in ICUs had been conducted in Malawi. In addition, the first author observed that the non-availability of guidelines for the management of ETT cuff pressure in some ICUs often led to inadequate knowledge of ETT cuff pressure practices. These observations highlighted the need for evaluating how an educational intervention based on the existing evidence-based guidelines, using passive versus active implementation strategies, could improve the knowledge of nurses regarding managing ETT cuff pressures in Malawian ICUs.This study aimed to evaluate how an educational intervention based on the existing evidence-based guidelines, using both passive and active implementation strategies, could improve the knowledge of nurses regarding managing ETT cuff pressures in Malawian ICUs.2O and 30 cmH2O as evidenced by the literature.Endotracheal tube cuff pressure is the amount of pressure inside the cuff created by inflating it in order to create a seal to the entry of pharyngeal contents into the trachea and enhance positive pressure ventilation  is the primary method of supporting organ function by using an artificial (machine) respirator in patients treated in ICUs. Non-invasive mechanical ventilation is where the ventilator support is provided without the use of an ETT, whereas invasive mechanical ventilation refers to the use of an ETT  in Malawi. The average bed capacity of the hospitals was 4, except for one public ICU that had a bed capacity of 6. In both set-ups, there were more nurses trained on the job than those who had undergone formal intensive care nursing specialisation training.An independent observer divided the four public ICUs and the two private ICUs into two intervention groups so that each group contained one private and two public ICUs, using simple randomisation. Firstly, the names of one private and two public hospitals were randomly picked from two bowls containing the names of private and public hospitals, respectively. The names of the first set of hospitals were then placed in an envelope and the second set of hospitals was put in another envelope. These envelopes were then placed in a basket, and the first envelope chosen by the same independent observer would be the intervention group receiving the full educational intervention, using both active (monitoring visits) and passive implementation strategies.For both the pre- and post-test questionnaires, the targeted population comprised the nurses working in the ICUs for the duration of the study. The total number of nurses working in the six ICUs during the study was 61. The small population made it unnecessary to calculate a minimum sample size, as the research plan was to include as many population as possible. Because of the small number of nurses available in Malawi, convenience sampling was used to include as many as nurses as possible during the study. In total, 48 nurses were included in the pre-test questionnaire and 52 participants were included in the post-test questionnaire see .An educational intervention was developed based on the existing evidence-based guidelines for the management of ETT cuff pressure in mechanically ventilated adult patients Jordan . These gA PowerPoint presentation was developed that was used for a half-day orientation to the concepts of the evidence-based guidelines. The PowerPoint presentation included a definition of mechanical ventilation, indications for mechanical ventilation, complications of mechanical ventilation, the management of ETT cuff pressure, the complications of ETT cuff pressure and the prevention of ETT cuff pressure complications. A summary of the evidence-based guidelines and an algorithm for the management of ETT cuff pressure in mechanically ventilated adult patients were printed and laminated. The monitoring visits involved one-on-one sessions between the first author and the ICU nurses regarding the importance of adhering to the evidence-based guidelines, how the nurses were coping with the implementation of the guidelines and the problems faced in implementation of these. Any uncertainties linked to the guidelines were clarified during these sessions. The educational intervention was reviewed regarding its relevance by the second author who is an experienced ICU nurse.Intervention 1 group (which served as the control group) received only a half-day educational session using printed and laminated evidence-based guidelines, a summary of these, a related algorithm, a PowerPoint presentation and no monitoring visits (only passive implementation strategies). Intervention 2 group received the full educational intervention using both active (monitoring visits) and passive implementation strategies.For the pre- and post-test questionnaires, structured questionnaires were used, adapted with permission from Jordan  by the fData from the pre-test questionnaire were collected in February–March 2016 using a hand-delivered self-administered questionnaire. A detailed explanation was given to each participant regarding the objectives of the study prior to their signing a consent form agreeing to participate. The participants were assured that the study would not pose risks to themselves or to the patients. Participants were requested not to discuss the questions with their colleagues for the answers to truly reflect their knowledge. Questionnaires were collected immediately after completion and secured in an opaque envelope to ensure confidentiality of information. Because of the busy schedules and the nurses’ shifts in the ICUs, the first author had to visit each ICU several times to complete data collection during the nurses’ day shifts. Data from the staff on night shifts were collected just after handover to the day shift at the end of the night shift or just after handover from the day shift at the beginning of the night shift.n1.1 and n2.1), the educational intervention was implemented. Both groups were given the half-day educational session using a PowerPoint presentation so that both groups would be at the same level of knowledge pertaining to the guideline at the beginning of the implementation of the educational intervention  using the same data collection procedure as the pre-test questionnaire.After the pre-test questionnaire was completed by both groups (2 and t tests) was used to analyse the knowledge questions where the χ2 test was based on sample frequencies (two or more per sample) and was conducted as a further investigation of the differences between the two intervention groups, and the t test was based on sample mean values  which allowed for looking at the means only instead of distribution of the scores. This facilitated an examination of the level of significance of the nurses’ knowledge improvement, the t distribution and degree of freedom and the determination of the probability of difference between the two intervention groups. Significance was at p < 0.05.Data were analysed using descriptive and inferential statistics. The first author was assisted by the third author, a senior statistician consultant, using visual basic applications in Excel. Means, frequencies and standard deviations were used for the descriptive analysis, whilst inferential statistics  at the Nelson Mandela University and from the National Health Sciences Research Ethics Committee in Malawi (ethics number: 15/3/139). Approval was obtained from each of the six hospitals involved in the study. Consent was requested from all the participants and participation was voluntary. The questionnaires did not include any confidential data.Sixty-one questionnaires were delivered, which were completed by 48 participants (for the pre-test questionnaire) and 52 participants (for the post-test questionnaire), amounting to the response rates of 79% and 85%, respectively. The pre-test questionnaire yielded a Cronbach’s alpha of 0.50 for the knowledge score, whilst the post-test questionnaire resulted in a score of 0.47. An acceptable reliability interval score of 0.47, was considered sufficiently close to the required score of 0.50. However, the obtained score was at a lower range of the acceptable reliability interval.Most of the nurses who completed both the pre- and post-test questionnaire in both intervention groups were women. Most participants were between 25 and 39 years old. Not even a quarter of the nurses were specialised in intensive care nursing. Most nurses were from public hospitals and almost half of the participants had worked in the ICU for only a period of 1–4 years. Questionnaire responses with respect to the practices related to the management of ETT cuff pressure were statistically treated as knowledge questions and are outlined in Statistics for the knowledge scores calculated for each respondent as the percentage of correct responses to the questionnaire items listed in As indicated in Management of ETT cuff pressure is an essential aspect of nursing care of intubated patients, and the importance of complications related to undesirable cuff pressure cannot be overemphasised  and monitoring visits (active implementation strategy). Active approaches, including monitoring or site visits, have been proven particularly effective in the implementation of guidelines but should preferably be part of a multifaceted approach to effectively improve knowledge amongst practitioners  in the study, but participation was voluntary; thus, a bigger sample could not be achieved. Furthermore, the participants’ pre- and post-test data could not be matched as participants responded anonymously.The demographic differences between the pre- and post-tests within both groups were because of the different samples for these groups. However, the participants within each intervention group were the same for the pre- and post-test questionnaires. Randomised sampling could have been used to avoid this but was not possible because of the already small sample. An attempt was made to include all the participants  and monitoring visits (active strategy), significantly improved their knowledge. The implementation of a formal training programme and mentorship programme for nurses working in the ICU in Malawi would be of great benefit to empower nurses with adequate knowledge, skills and appropriate attitudes for the management of the ETT cuff pressure. Follow-up studies would also assist in understanding how guidelines could be implemented effectively to achieve better knowledge outcomes amongst nurses concerning nursing care practices as well as patient outcomes in the ICU context.


The current article aims to present a numerical analysis of MHD Williamson nanofluid flow maintained to flow through porous medium bounded by a non-linearly stretching flat surface. The second law of thermodynamics was applied to analyze the fluid flow, heat and mass transport as well as the aspects of entropy generation using Buongiorno model. Thermophoresis and Brownian diffusion is considered which appears due to the concentration and random motion of nanoparticles in base fluid, respectively. Uniform magnetic effect is induced but the assumption of tiny magnetic Reynolds number results in zero magnetic induction. The governing equations (PDEs) are transformed into ordinary differential equations (ODEs) using appropriately adjusted transformations. The numerical method is used for solving the so-formulated highly nonlinear problem. The graphical presentation of results highlights that the heat flux receives enhancement for augmented Brownian diffusion. The Bejan number is found to be increasing with a larger Weissenberg number. The tabulated results for skin-friction, Nusselt number and Sherwood number are given. A decent agreement is noted in the results when compared with previously published literature on Williamson nanofluids. Based on their properties, over the years, the fluids have been categorized into sub-categories. The most recent class of fluids is called nanofluids, which was introduced by Choi  in earlyThe fluid flow caused by a stretching surface has manifold applications in various industrial and engineering setups that involve nanofluids in their production procedures. For example, melt-spinning, glass fiber manufacturing, cooling process of metallic plates, manufacturing of rubber bands, and plastic sheets are the well known applications of nanofluids that involve stretching surfaces. Skiadis  attempteEntropy generation in mathematical models that are related with industrial and engineering applications of nanofluids, is one of the trending aspect these days and over the years it has received an utmost consideration in the research community. Several fluid models are available in the literature to explain the phenomena of entropy generation in fluid flow systems. Though the primary source of entropy generation lies in the unreversibility in the presence of low Reynolds number but the existence of larger Reynolds is yet another undeniable fact and it has association with hydrodynamics in the context of entropy generation. Numerous research articles have been reported in recent years discussing the flow profiles as well as the entropy generation in the prescribed models. For example, Afridi and Qasim  proposedPseudo-plastic materials have extensive demand in the industry for their special properties. The wide use of such materials ranges in photographic films, melts and solutions of polymers with larger molecular weights, suspensions, expulsion of sheets, etc. Various models were proposed in the literature to discuss such kind of fluid flow but the complex nature of rheological systems limits the sufficiency of the Navier stokes equations. Models, such as those by Carreau, Cross, Ellis, and the power law model were reported in the literature to discuss the characteristics of such Pseudo-plastic materials. However, models such as the Powell–Eyring model and the Williamson model are worthy to cover the deficiency in the original Navier Stokes equations. Williamson  reportedx-axis. Numerical simulation of the problem gives graphical results that are plotted accordingly. Various interesting aspects of fluid flow, heat, and mass transport mechanism, the wall drag intensity and the entropy generation were analyzed on the basis of numerical data. The results are compared with previous literature on Williamson nanofluids.Inspired by the above literature, we targeted the aspects of binary chemical reaction, Arrhenius activation energy and the entropy generation in magnetohydrodynamic Darcy flow of Williamson nanofluid. The Brownian diffusion due to random motion of nanoparticles and the Thermophoresis phenomena are present due to the saturation of metallic nanoparticles. The medium is maintained over an infinite nonlinearly stretching surface along the x-axis given the velocity component u whereas no-displacement is taken alongside y-axis given the velocity component v. The sheet spreads nonlinearly along the positive x-axis with velocity b is taken to be positive. Thermophoresis and Brownian diffusion is considered which appears due to the concentration of nanoparticles in base fluid as well as the random motion of the nanoparticles, respectively. A physical diagram of the flow model can be seen in Here we consider an incompressible, viscous and chemically reactive MHD Williamson nano-fluid flow maintained to flow through porous medium bounded by a non-linearly stretching surface in two dimensions ,(1)∂u∂t et al.  define,By virtue of transformations, the final ODEs are given below,Here The governing Entropy equation for the modeled problem can be formulated as followed,  are defined as follows,The nonlinear problems (8–12) and (15) subject to the given boundary conditions formulate two-point BVPs. The system is solved through numerical shooting technique, transforming the BVPs into initial value problems (IVPs) first. The following procedure is adopted in this transformation.The governing equations are, therefore, written as follows,Such that,Following the same procedure as above, the entropy equation is given as follows,The physical quantities, i.e., Skin-friction, Nusselt and Sherwood numbers used in the numerical scheme are given below,A careful selection of initial guesses is made to repeatedly solve the given IVPs using fourth order RK-method. Secant method is implemented to adjust the values of aforementioned three quantities for better approximation. A convergence criteria based on the difference of previous to current iteration is employed. For a difference equal or less than Velocity field, temperature distribution, concentration of nanoparticles, and entropy generation rate are described physically here in this section. A numerical scheme is applied to achieve the final solutions that are sufficient to depict the behavior of flow profiles. In The stream functions for the given flow model are plotted in We analyzed the velocity field for three parameters i.e., Weissenberg number, Inertial force parameter and porosity factor. One can see that the velocity field is decaying in the whole domain i.e.,  for the above mentioned three parameters. The inverse relation of these parameters with momentum equation is justified. For Weissenberg number we justify our graphical explanation given in From Here in this subsection we discuss the variations noted in concentration of the nanoparticles for various values of Brownian diffusion parameter, Thermophoresis parameter, Schmidt number, Chemical reaction, and Arrhenius activation energy parameter. The results are plotted graphically in The graphs plotted in An enhancement in the drag force for augmented values of Magnetic parameter is noticed whereas a decrement can be seen for the Weissenberg number. The resistive Lorentz force active normal to the fluid flow is responsible for this behavior.The Brownian diffusion results in decay of heat transfer rate whereas, the variation in Prandtl number results in enhancement of the heat transfer rate.The mass flux rate enhances for augmented values of chemical reaction but decays for the Arrhenius activation energy parameter.For the stream functions, we see that smooth curves are produced for linear case whereas, in nonlinear case the curves spread more from the origin.Greater values of Weissenberg numbers are linked with more relaxation time which creates more resistance period for fluid motion.The more stronger inertial force results in more thermal distribution and the associated boundary layer thickness receives increment.In the whole domain i.e., , the concentration of nanoparticles shows reduction for higher values of Schmidt factor is treated as a non-dimensional number relating mass diffusivity with momentum diffusivity yielding a fluid flow display. These two terms are physically called the mass transport layer and hydrodynamic thickness layer. For an enhancement in the Schmidt number, mass diffusion drops down which results in a decrement in the concentration field.We considered an incompressible, viscous MHD Williamson nanofluid flow maintained to flow through porous medium bounded by a non-linearly stretching surface in two dimensions (


Background: The present study investigated the role of temperament and attachment security in predicting individual differences in the five factor personality traits among adults. As previous studies suggested the potential moderating role of attachment in the association between temperament and personality traits, the present study sought to examine an interactionist model combining attachment and temperament in explaining individual differences in personality traits. Methods: A sample of 1871 participants (1151 women and 719 men) completed self-report measures of adult attachment style (the Relationships Questionnaire—RQ), temperament dimension (the Fisher Temperament Inventory—FTI), and personality domain (the Five Factor Model—FFM). Results: Partial correlational analyses revealed associations between attachment security and each of the five domains of the FFM, and few associations between some temperament dimensions and several domains of the FFM. Moderated regression analyses showed that attachment security moderated the associations between temperament dimensions and the Agreeableness domain of the FFM. Among secure individuals, those with higher scores on the Curious/Energetic, Cautious/Social Norm Compliant and Prosocial/Empathetic scales exhibited higher Agreeableness scores, whereas among insecure individuals, those with higher scores on the Analytic/Tough-minded scale exhibited lower scores on the Agreeableness scale. Conclusion: Overall, the current study provides evidence in support of the substantive role of social-environmental factors (Adult Attachment) as a moderating element bridging temperament-related personality elements and a number of their FFM manifestations. There is a considerable body of literature investigating the determinants of personality traits in adults, which include both environmental and genetic factors ,2. A betThe Five Factor Model (FFM)  of persoExamination of the etiological factors involved in the development of individual differences in personality highlights the importance of heritability , as wellTemperament has been regarded as a direct precursor of personality , with soRecently, Fisher and colleagues  investigApart from the substantial role that temperament plays in the etiology of individual differences in the FFM, parental behavior, and especially the role of attachment to parental figures, has been suggested to be an important factor as well. Attachment theory emphasizes that early experiences with caregivers are crucial to the development of internal working models (IWMs), models that influence how individuals relate to significant others and cultivate interpersonal interactions throughout the life course . DevelopEmpirical studies have demonstrated the link between temperament and attachment to personality traits. However, very few studies have tested both the biological and environmental precursors of the FFM personality traits in one model. Among the few attempts was Hagekull and Bohlin’s  study, iThe aim of the present study was to investigate the role of temperament and attachment security in predicting individual differences in personality traits. Furthermore, given previous findings suggesting the potential moderating role of attachment in the association between temperament and personality traits, the present study additionally examined the moderating effect of attachment.n = 1233) were undergraduate students in the Max Stern Academic College in the northern part of Israel. The rest of the participants were junior and high school students (n = 106) as well as individuals aged 30 and above (n = 532). The study was approved by the institutional review boards (IRBs) of the Max Stern Academic College of Emek Yezreel . “All procedures performed in the study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards”. Informed consent was obtained from all individual participants included in the study.In the current study, there were 1871 participants (mean age 29.32 ± 9.98), of which 1151 were women (61.6%) and 719 were men (38.5%). The majority of participants  is a 10-item measure of the Big Five  personality traits . It measAdult attachment style was assessed using the Relationship Questionnaire (RQ) . The RQ Fisher’s personality type was assessed using the Fisher Temperament Inventory (FTI) . The 56-Our study was approved by the Yezreel Valley College ethics committee . Study participants were recruited by third-year B.A. students, who participated in a social science research seminar on personality during the years 2015–2018. After providing their written consent to participate in the study, participants completed four online questionnaires covering basic demographics details, as well as three personality questionnaires regarding temperament, character, and lexical personality dimensions as outlined above.Personality domains, measured by the TIPI, served as the dependent variables. The independent variables were: attachment security and temperament. Attachment security was measured by the RQ scales. The highest of the four attachment prototype ratings was then used to classify participants into an attachment category. The temperament dimensions were measured by the FTI scales. t-tests were conducted to test for sex differences in the dependent variables  Additionally, bivariate correlations were conducted between participant age and the dependent variables. Next, partial correlation analyses (controlling for sex and age) were conducted in order to investigate the association between temperament dimensions and attachment security (dummy coded with “secure attachment” as the reference group) with individual differences in personality domains. Bonferroni corrections for multiple comparisons were used. Finally, we tested for the moderating role of attachment security in the association between temperament dimensions and personality domains using moderated regression analyses. In order to avoid problems of multicollinearity, the predictor variables were centered before calculating the interaction terms [First, independent samples on terms . In the on terms .All analyses were performed using SPSS version 25.Sex differences. We checked for sex differences in personality. Significant sex differences on each personality domain were found , however, the association was not significant for insecure individuals .A significant interaction was revealed in a multiple regression analysis with Agreeableness as the dependent variable and with the inclusion of an interaction term between attachment security and the Curious/Energetic scale. Simple slope analyses  revealedb = 0.01, t = 3.22, p = 0.001); however, the association was not significant for insecure individuals . Therefore, a significant relationship between scores on the Cautious/Social Norm Compliant scale and Agreeableness was found only among secure individuals: higher Cautious/Social Norm Compliant scores were associated with higher scores in Agreeableness.A multiple regression analysis with Agreeableness as the dependent variable and with the inclusion of the interaction between attachment security and the Cautious/Social Norm Compliant scale interaction, revealed a significant interaction. Simple slope analyses revealed that scores on the Cautious/Social Norm Compliant scale were positively associated with Agreeableness for secure individuals , however, the association was not significant for secure individuals .A significant interaction was revealed in a multiple regression analysis with Agreeableness as the dependent variable and with the inclusion of an interaction term between attachment security and the Analytic/Tough-minded scale. Simple slope analyses revealed that the Analytic/Tough-minded scale was negatively associated with Agreeableness for insecure individuals , however, the association was not significant for insecure individuals .Finally, a significant interaction was revealed in a multiple regression analysis with Agreeableness as the dependent variable and with the inclusion of an interaction term between attachment security and the Prosocial/Empathetic scale. Simple slope analyses revealed that the Prosocial/Empathetic scale was positively associated with Agreeableness for secure individuals (A multiple regression model with Conscientiousness as the dependent variable and with the inclusion of interactions between attachment security and each of the temperament dimensions, revealed that the addition of the interaction terms did not account for a significant amount of additional variance in Conscientiousness.A multiple regression model with Neuroticism as the dependent variable and with the inclusion of interactions between attachment security and each of the temperament dimensions, revealed that the addition of the interaction terms did not account for a significant amount of additional variance in Neuroticism.A multiple regression model with Openness as the dependent variable and with the inclusion of interactions between attachment security and each of the temperament dimensions, revealed that the addition of the interaction terms did not account for a significant amount of additional variance in Openness.Previous studies have demonstrated the role of parental behavior, as well as biological factors, in predicting individual differences in personality traits. The present study provided support based on a very large sample for these findings by showing that attachment security and temperament dimensions were associated with personality traits. Specifically, the current study found that attachment security accounted for individual differences across all personality domains of the FFM. Attachment security was positively associated with Extraversion, Agreeableness, Conscientiousness and Openness, and negatively associated with Neuroticism. These results agree with previous studies showing that secure attachment was positively associated with extraversion, agreeableness, and negatively associated with neuroticism . These fThe literature on temperament characterizes it as a stable trait, representing particular dispositions that influence behavior throughout the life span . FurtherIn light of the inconsistencies that characterize the literature on the role of temperament and attachment in predicting individual differences in personality traits, the present study further examined the potential moderating role of attachment in the association between temperament and personality traits through an interactive model. We found that attachment security moderated the association between temperament dimensions and the Agreeableness domain of the FFM. Among secure individuals, those with higher scores on the Curious/Energetic, Cautious/Social Norm Compliant and Prosocial/Empathetic scales also exhibited higher Agreeableness scores. Furthermore, attachment security moderated the association between the Analytic/Tough-minded scale and the Agreeableness domain of the FFM. Among insecure individuals, those with higher scores on the Analytic/Tough-minded scale exhibited lower scores on the Agreeableness scale. The moderating role of attachment security has been previously suggested in developmental studies. For example, Lickenbrock and colleagues  have shoThe present study has some limitations. First, we found low-to-moderate Cronbach’s alphas for the TIPI scales. This is a common finding when using short measures . HoweverTo summarize, the present data are consistent with previous findings, especially developmental studies, suggesting an interplay between biological factors and parental behavior in predicting personality traits. The implications of the present study relate to both normative and psychopathological development. The etiology of psychiatric disorders includes temperament, attachment, and personality , among o


In the recent years, the progress of international trade and travel has led to an increased risk of emerging infections. Around 75 percent of the pathogens causing these infections are of animal origin. Point-of-care tests (POCT) and point-of-need tests (PONT) have been established in order to directly provide accurate and rapid diagnostics at field level, the patient bed-side or at the site of outbreaks. These assays can help physicians and decision makers to take the right action without delay. Typically, POCT and PONT rely on genomic identification of pathogens or track their immunological fingerprint. Recently, protocols for metagenomic diagnostics in the field have been developed. In this review, we give an overview of the latest developments in portable diagnostic methods. In addition, four mobile platforms for the implementation of these techniques at point-of-care and point-of-need are described. These approaches can provide reliable diagnostics and surveillance, especially in low resource settings as well as at the level of one health. Many different microorganisms such as bacteria, viruses, fungi, or parasites exist in the environment. Most of them are important to maintain the ecosystem on earth, however, some of them are pathogenic and cause infectious diseases in both humans and animals. Infectious diseases are one of the major reasons for death especially in the low- and middle-income regions of the world . While globalization and international travel progresses, the risk of emerging diseases is increasing. Due to global flight connections, people, goods, or traded animals can reach almost every location in the world within one or two days. Unfortunately, this time frame is shorter than the incubation periods of several important zoonotic and animal diseases with an emerging potential defined by the World Organization for Animal Health . As a consequence of rapid testing, disease control as well as change in treatment and care was achieved particularly, in regions where stable electricity supply, highly trained personal, or specialized devices are not available . Most POImmunoassays are based on binding of an antibody and an antigen to each other. The simplest and most used equipment-free assays are lateral flow immunoassays (LFIAs) as they are performed in a small disposable cartridge . LFIAs dPaper-based micro fluid devices (µPAD) are yet another development of the lateral flow technique. Here, the sample is guided by hydrophobic channels . This deA critical drawback of this technology is the sensitivity and specificity, as lateral flow assays (LFA) highly depend on the labelling and binding affinity of the tested biomolecules . A high Nucleic acid amplification methods have the advantage of being highly sensitive as opposed to immunological assays due to the amplification step. DNA is amplified using cycling methods such as polymerase chain reaction (PCR) or isothermal amplification. In contrast to the PCR, isothermal amplification assays have the advantage of employing a constant reaction temperature for the amplification. This offers more utility in the field due to the use of portable heat sources and shorter run time in comparison to the cycle driven PCR . MoreoveThe implementation of equipment-free nucleic acid amplification at POC and PON is extremely challenging. Although there are equipment-free LAMP assays, they still need a heating source ,27. NeveNucleic acid lateral flow (immuno-) assays (NALFAs/NALFIAs) provided a simple and inexpensive read-out of the different amplification methods . These aThe bottleneck of the molecular diagnostics is the nucleic acid extraction as high quality DNA is needed for both DNA amplification assays and sequencing. Moreover, the sensitivity of diagnostic method is questioned if the right extraction method is not implemented. Despite many breakthroughs and full automation of the DNA and RNA extraction, very few studies have tried to set up a field-applicable extraction procedure. The most common extraction procedure relies on the binding of the nucleic acid to a silica gel membrane after a lysis step using a cocktail of chaotropic salts and proteinases . In suchMetagenomic diagnostics is the identification of pathogens after sequencing of genomic material collected from suspected cases . This apThe molecular detection through PCR or isothermal amplification of a pathogen requires a known target nucleic acid sequence. Thus, in an outbreak of unknown cause, selection of the right molecular assay upon the clinical signs is challenging and a novel pathogen or variants of known infectious agent may remain undetected . MetagenSequencing methods require heavy and complex devices. However, the introduction of nanopore sequencing to the market by Nanopore Technologies allowed third-generation sequencing at PON due to small portable sequencing devices . The greImmunoassays are an inexpensive, robust, and simple way to detect antibodies. Since different types of antibodies can be detectable after several days and up to several years in the blood , immunoaThe need for on-site diagnostic facilities was demonstrated during the West African Ebola outbreak as health systems of the affected countries were overloaded or not existing. Mobile laboratories were developed to enable diagnosis during outbreak situations. Their great advantage was their capacity to perform several diagnostic tests just as a central laboratory while being in the field at the site of an outbreak.To overcome the problem of the long distances to the central diagnostic laboratories during the hemorrhagic fever outbreak in West-Africa, the European Mobile Lab Project established a moving laboratory unit in Nigeria, consisting of 27 boxes, each approximately 20 kg to 30 kg in weight. These boxes contained more than 400 equipment items needed to set up a fully-functional BSL3 or BSL4 diagnostic laboratory in a tent or in a local house. Minimum requirements were at least 28 square meters of space and a car for constant energy supply. European Mobile Labs enabled sample inactivation and preservation, molecular diagnostics using real-time PCR, antigen/antibody tests via ELISA and immunofluorescence assay as well as direct visualization of blood parasites using microscopy .Originally developed for the field-applicable detection of avian influenza, the mobile suitcase laboratory was implemented in Guinea during the time of the West African Ebola outbreak. This PON diagnostics solution consists of two trolley cases, a solar panel, a power pack, and an optional glove box. One of the trolley cases was employed for nucleic acid extraction applying a reverse purification magnetic beads-based method. The second trolley case contained all instruments for the detection of the extracted nucleic acid via RPA or nanopore sequencing. The devices were placed on foam covered by a PVC top layer to be protected from shocks and to facilitate disinfection. The glove box can be used for sample disinfection and nucleic acid extraction in the case of BSL3 and BSL4 pathogens. All materials, kits, and reagents needed for nucleic acid extraction, isothermal amplification, and sequencing were stored in the suitcases. Due to the compact design, the mobile suitcase laboratory was easy to operate even in challenging surroundings ,57.Another example for a mobile lab solution is the lab in a caravan. Based on the experiences made during the Ebola outbreak in West Africa in 2016, the Zika in Brazil Real Time Analysis (ZEBRA) project implemented two labs in caravan. These complete BSL 3 laboratories were set up in a trailer and used to collect and sequence samples of the Zika virus (ZIKV) using the nanopore sequencing technology along parts of the Brazilian east coast . The Praesens Foundation developed a mobile laboratory implemented in a small truck . The mob2, bacterial culture and quantification was accomplished by surface plasmon resonance and protein microarrays [The miniaturization and automatization of various laboratory workflows in one small apparatus were achieved through the lab-on-chip or microfluidics technologies. Bacterial concentration and recovery were conducted by combining ceramic membrane and tangential flow filtration . In a siroarrays . The advroarrays  and moleroarrays  and LAMProarrays ) in the roarrays . The labIn the case of an emerging or new disease like coronavirus disease 2019 (COVID-19), the first step to identifying the causative agent is isolation and/or nucleic acid sequencing . Upon idIn the last three decades, more than 30 new infectious diseases have emerged, most of them zoonotic . To prevPOCT and PONT are valuable tools for the diagnostics directly in the field and at the site of an outbreak. The big advantage of POC and PON diagnostics is the identification of pathogens directly at the site of the diseased person or animal with small turn-around times. So, the persons responsible for treatment can react more quickly according to the result. The use of POCT and PONT at airports, harbors, and quarantine stations can prevent the global spread of many infectious diseases due to international travel and trade. Furthermore, the sample volume needed for the tests is often smaller than in conventional laboratory tests. In addition, the use of POCT and PONT can lead to more adherence and optimization of the treatment regimen at the clinical site. Routine use of POCT and PONT can support the building of broad and comprehensive diagnostic infrastructure, especially in low resource settings, as the tests are mostly equipment-free and only small investments in local facilities are necessary . The tests can be shipped easily to the location where they are needed and can overcome the pitfalls of low or demolished diagnostic infrastructures, especially in limited resource settings. These abilities make POCT and PONT an important instrument for the prevention of disease spread.Unfortunately, current POCT and PONT are often designed for the detection of a single pathogen and do not have the diagnostic capabilities of laboratory tests. A platform suitable for the investigation of multiple pathogens is needed in order to identify the causative pathogen of an outbreak. Tests based on nucleic acid amplification can easily be adjusted to several pathogens. Once the outbreak causing pathogen is detected, a target-specific rapid test kit can be deployed to recognize the diseased individuals. Implemented in mobile laboratories POCT and PONT are a valuable tool not only for diagnostics in an outbreak situation but also for surveillance. This eases the implementation of functional diagnostics in a region with low infrastructure and helps to build up diagnostic capacity.


The 2019 NIJ Report to Congress on the needs of the forensic science community [1] highlighted the staffing deficit of forensic scientists by more than 900 positions. The Report emphasized the impact of the opioid crisis and the evolution of synthetic opioids on the demands for forensic laboratories. The resource drain attributable to the opioid crisis has filtered into all other areas of investigation as laboratories divert limited resources from other uses to meet the high demand in drug chemistry and toxicology from opioid abuse. We introduce the forensic laboratory workforce calculator, a tool that any forensic laboratory may use to evaluate their current personnel allocation and estimate any under- or over-staffing to meet current or estimated caseloads. The forensic laboratory workforce calculator is available free to any laboratory through the Forensic Technology Center of Excellence website. HoweverThe societal cost from the delays in casework investigation has a devastating impact on the U.S. economy. The Council of Economic Advisors estimates that the cost to the U.S. economy from the opioid crisis may exceed $600 billion dollars per year . This soForensic laboratories exhibit similar output capabilities as demonstrated in the provision of all goods and services. There are economies of scale associated with the examination of forensic evidence, which makes the allocation of the 900 plus shortage of full-time equivalent employment (FTE) a complex issue. Fortunately, economic theory and econometric analysis permit the estimation of those needs at the individual laboratory level.In this manuscript, we introduce the forensic laboratory workforce calculator, a tool that any forensic laboratory may use to evaluate their current personnel allocation and estimate any under- or over-staffing to meet current or estimated caseloads. The underlying model takes advantage of twelve years of data from Project FORESIGHT ,15 and a2The data underlying the construction of the workforce calculator comes from Project FORESIGHT ,15. ProjProject FORESIGHT collects data on two levels of detail. Level I data represents the minimum detail on caseload, FTE, and expenditures required for economic analysis. Level II data expands upon the caseload detail with information on items examined internally and outsourced, samples examined internally, tests performed, reports written, turnaround time, and backlogs.Level I submission includes the data highlighted in the following three figures. The two budgetary questions regarding direct charges for utilities and telecommunications ensure that all costs are included in the overhead charges in the expenditure worksheets. Many jurisdictions satisfy their obligations in these areas outside the direct budgets of the laboratories. In those cases, the FORESIGHT cost calculations assess an estimated cost for these necessities. Additionally, laboratories indicate any extraordinary situations to aid in the evaluation and interpretation of the performance by the laboratory.3Examination of the mission statements of forensic laboratories reveals some common themes. Synthesizing these mission statements into a unified objective statement suggests that laboratories attempt to analyze evidence correctly and process as many cases as budgets permit .3 The caThis decomposition of the ratio of cases processed to total expenditures reveals that a laboratory’s performance may be explained by four ratio relationships. The two numerator ratios indicate that case processing occurs at a higher rate when the laboratory demonstrates greater throughput per person or when more expenditures are allocated towards personnel. This latter ratio reflects more immediate results versus investment in capital expenditures for higher long-term results. Additionally, increases in either denominator ratio will reduce cases processed for a given level of expenditures. This comes through greater sampling intensity or higher compensation levels in the laboratory relative to other laboratories.These four ratios enable a laboratory to interpret their laboratory performance compared to other FORESIGHT laboratories. For three of the ratios, average compensation, sampling intensity, and percent personnel expenditures, a comparison of the laboratory’s performance relative to the benchmark FORESIGHT summary statistics provides a simple interpretation of the underlying forces behind the laboratory’s CASE/TOTEXP. 4For each of these three figures, the solid line represents the results of a simple linear regression of the ratio relative to caseload. While 4The relationship between productivity and caseload highlighted in The American Society of Crime Laboratory Directors (ASCLD) recognizes high performing laboratories each year with the Maximus Award. The award recognizes laboratories that have performed at a 90% efficiency level or higher, based upon a weighted average of performance across areas of investigation. The Project FORESIGHT data collection separates activity into 21 areas of investigation. Although there are 21 categories, it is the rare laboratory that conducts evidence analysis in all areas. Individual laboratories have a jurisdictional mandate for which areas of investigation the laboratory provides analysis. The vast majority of forensic laboratories analyze data in six to twelve of these areas of investigation. Because of this variation in activity across laboratories, the efficiency metric considers each activity of the laboratory, determines the fully allocated expenditures for its caseload, and compares that expenditure to the estimation of the efficient frontier  Program and population data from the U.S. Bureau of the Census.Project FORESIGHT data included over one thousand submissions across investigative areas with the data categories highlighted in i). The independent variables include  dummy variables for type of jurisdiction (metropolitan or state), population or natural logarithm of population, state violent crime rate, state property crime rate, and interactions between the dummy variables and the other independent variables.For each area of investigation, we observed the scatter plots of the productivity metric, similar to In other areas of investigation, the scatter plot suggested that perfect economies of scale had yet to be reached. We considered two alternative specifications for the relationship between productivity and caseload, logarithmic and double logarithmic. In the logarithmic specification, we treated the natural logarithm of caseload as an independent variable.In the double logarithmic specification, we use the natural logarithm of productivity as the dependent variable and the natural logarithm of caseload as an independent variable.i), as used with the quadratic regression, were employed.For each of these specifications the series of other independent variables , and interaction variables between these independent variables.Laboratories testing the beta calculator were encouraged to share results with the Forensic Technology Center of Excellence (FTCoE) and Project FORESIGHT. Along with the results of the calculator, laboratories offered suggestions for the improvement of the workforce calculator. In addition to testing laboratories, we presented the beta calculator at a Western United States laboratory directors meeting and solicited suggestions for the updated calculator. Several of these suggestions guided the updates in the workforce calculator.First, the sample laboratories used in the construction of the beta calculator resulted in some restrictions on personnel estimations because of statistical restrictions from in-sample caseloads. To overcome the statistical limitations, a greater number of large caseload laboratories was solicited to provide a wider range of estimates. Fortunately, the fiscal year 2018 and fiscal year 2019 Project FORESIGHT submissions expanded the caseload range to permit broader applicability of the model.Second, several laboratory directors suggested that improved output would result if the personnel shortfall/surplus was broken down into operational staffing needs versus staffing needs for administration & support. This distinction is a featured output in the updated calculator.Third, several laboratories encouraged an explicit note of the change in staffing suggested by the model. While such a change in FTE is a simple calculation, it was argued that having the explicit change noted through an independent source might offer greater assistance to local arguments for increased staffing.The final change added to the model referenced the accompanying support for the capital budget. Several laboratory directors feared that a call for additional personnel lines would result in a directive to shift budgets from capital to personnel. Since the model estimation included an assumption that efficiency included the corresponding capital investments, the annual capital budget requirement to support caseload activity was added to the calculator output.The enhanced workforce calculator output incorporates the suggestions from the various test laboratories in their use of the beta workforce calculator. 1.Type jurisdiction 2.State violent crime rate3.State property crime rateA laboratory chooses from three drop down menus:Next, the laboratory completes the population data for their state, jurisdiction, and the largest city within the jurisdiction. Additionally for each area of investigation, the laboratory enters the anticipated annual caseload in the relevant shaded areas. The laboratory optionally includes their current staffing. The output fields (non-shaded boxes) automatically populate as the laboratory enters caseloads and corresponding current FTE.4.State populations (2015–2019) and Uniform Crime Reporting Program data (2018 & 2019).5.City populations sorted by state (2015–2019).6.County populations separated by state (2015–2019).To assist in the input process, there are additional worksheets with U.S. Census Bureau data:7.The Project FORESIGHT definitions for each area of investigation.An additional worksheet includes some definitions:10.13039/501100007185Total FTE, Operational Staff FTE, and Administration & Support FTE are generated once the laboratory provides the detail on caseload. If the laboratory enters the current FTE column, the final output column, Additional Staffing Needed, will populate.For the example laboratory, their current 57.24 FTE falls short by 12.39 FTE as the staffing required for optimal performance. The final output indicates the minimum annual capital investment to support that level of performance.Although this sample laboratory represents a fictitious example for demonstration of the tool, consider the output from several trial laboratories. Twenty-eight laboratories shared results from their test of the updated calculator. Note that the FTE shortfall or surplus is relatively small in most areas of investigation, but the cumulative effect is substantial for many laboratories. The example regional laboratory has small deviations, both positive and negative across areas of investigation with the exception of firearms & ballistics with a need for over 4.5 FTE. The regional laboratory with a larger city within the region has modest differences from the efficient allocation of personnel and suggests a surplus employment of 1.05 FTE. The metropolitan laboratory shows a large shortfall of personnel, primarily in Crime Scene Investigation. The statewide laboratory also has modest deviations with the exception of a large shortfall in DNA Casework personnel. Finally, the medical examiner/coroner example laboratory appears slightly overstaffed in the toxicology areas, but dramatically understaffed in forensic pathology.Beyond these example laboratories, we found that the average shortfall for laboratories that tested the calculator was 7.43 FTE.7The forensic laboratory workforce calculator begins to address the forensic science macro-level shortfall identified by the 2019 NIJ Report to Congress on the needs of the forensic community [Additionally, the transition to the National Incident-Based Reporting System (NIBRS) may provide more information about the forensic laboratory staffing needs. Future versions of the forensic laboratory workforce calculator will require re-estimation to include NIBRS.8All laboratories are encouraged to visit the Forensic Technology Center of Excellence site and try the Workforce Calculator . The calThe authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.