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Borderline personality disorder (BPD) and persistent depressive disorder (PDD) are related to interpersonal dysfunction which might become particularly apparent in situations of social exclusion (SE). While emotional responses to SE have been widely explored, behavioral data in clinical samples are lacking. In this cross-diagnostic study, we applied a variant of the Cyberball paradigm to investigate the dynamic behavioral response to partial SE in BPD and PDD. BPD patients (n = 36), PDD patients (n = 34) and age and gender matched healthy controls (HC) (total n = 70) played experimental (i.e. partial SE Cyberball) and control (i.e. inclusion only) conditions in randomized order. While all groups tended to increase ball tosses towards the excluder in response to SE, this behavioral turn was significantly lower in PDD (p = .03, d = -.30) and trendwise in BPD patients (p = .06, d = -.28). Thus, an altered immediate response to partial SE was observed in BPD and PDD, in addition to the emotional reactions. This study supports the hypothesis of a behavioral coping with SE in BPD and PDD that might be problematic in the long run and provides an experimental paradigm for future research on interpersonal dysfunction.

Purpose The paper provides evidence-based managerial advice for preparing the organizations to find successful pathways through crises by priming the managerial decision-making towards either entrepreneurial thinking or resource conservation, and hence cascading the inventive or rigid state of mind through all management levels. Design/methodology/approach The general review is based on summarizing the peer-reviewed academic studies of organizational decision-making and acting in crisis situations, illustrated using the turnaround cases of Corticeira Amorim (reinventing itself when faced with emerging technological threats) and Kiddiegarten School (adjusting to the pandemic shock of social/human nature) Findings This study reveals that a set of dimensions in the crisis situation’s cognitive framing determines the firm’s response to adversity, freezing it in a rigid state or unfreezing it to stimulate an organization-wide entrepreneurial search for turnaround strategies. If managers sense having a lack of time to deal with adversity, or a lack of predictability, they become paralyzed with threat-rigidity mechanisms, stubbornly pursuing the established methods of doing business, which often were the cause of crisis in the first place. Hence, in situations requiring an immediate response, the dual threats of urgency and unpredictability become cognitive blinders, preventing organizations from pursuing new opportunities, exposing firms to the risk of being too slow, eroding their competitive advantage and, ultimately, going out of business. Originality/value Integrating the insights of three decades prior research of the topic of managerial decision making in crisis situations, this study proposes the novel leadership framework allowing to stimulate entrepreneurial behavior in adverse contexts.

Substance use is common among those with heart failure (HF) and is associated with worse clinical outcomes. Alcohol, tobacco, cannabis, and cocaine are commonly abused substances that can contribute to the development and worsening of HF. Heavy alcohol consumption can lead to dilated cardiomyopathy, whereas moderate intake may decrease incident HF. Tobacco increases the risk of HF through coronary artery disease and coronary artery disease–independent mechanisms. Continued smoking worsens outcomes for those with HF and cessation is associated with an improved risk of major adverse cardiac events. Cannabis has complex interactions on the cardiovascular system depending on the method of consumption, amount consumed, and content of cannabinoids. Delta-9-tetrahydrocannabinol can increase sympathetic tone, cause vascular dysfunction, and may increase the risk of myocardial infarction. Cannabidiol is cardioprotective in preclinical studies and is a potential therapeutic target. Cocaine increases sympathetic tone and is a potent proarrhythmogenic agent. It increases the risk of myocardial infarction and can also lead to a dilated cardiomyopathy. The use of beta-blockers in those with HF and cocaine use is likely safe and effective. Future studies are needed to further elucidate the impact of these substances both on the development of HF and their effects on those who have HF.

Ziel Die Chemosaturation mittels perkutaner hepatischer Perfusion mit Melphalan (CS-PHP) ist ein palliatives Therapieverfahren für Patienten mit nicht kurativ behandelbaren Lebertumoren. Die CS-PHP erlaubt eine selektive intrahepatische Anreicherung von hochdosiertem Melphalan bei minimaler systemischer Toxizität durch venöse Hämofiltration. Ziel dieser Studie war es, das Ansprechen und Überleben sowie die Sicherheit der CS-PHP-Prozedur bei Patienten mit leberdominant metastasiertem Aderhautmelanom zu evaluieren. Material und Methoden Gesamtansprechrate (overall response rate, ORR) und Krankheitskontrollrate (disease control rate, DCR) wurden anhand von Response Evaluation Criteria In Solid Tumors (RECIST1.1) ermittelt. Medianes Gesamtüberleben (mOS), medianes progressionsfreies Überleben (mPFS) und hepatisches mPFS (mhPFS) wurden mittels Kaplan-Meier-Schätzer ermittelt. Nebenwirkungen wurden entsprechend der einheitlichen Terminologie-Kriterien für Nebenwirkungen (CTCAE) v5 klassifiziert. Ergebnisse 30 Patienten wurden zwischen Oktober 2014 und Januar 2019 mit 70 Chemosaturationen behandelt. Die ORR betrug 42,3 % und die DCR 80,8 %. Das mOS betrug 12 (95 %-Konfidenzintervall (KI) 7–15) Monate, das mPFS 6 (95 %-KI 4–10) und das mhPFS ebenfalls 6 (95 %-KI 4–13) Monate. Signifikante, aber transiente hämatotoxische Nebenwirkungen waren häufig (87 % Grad-3/4-Thrombozytopenie), hepatische Toxizität bis Leberversagen (n = 1/70) sowie kardiovaskuläre Komplikationen (ischämischer Insult, n = 1/70) waren selten. Schlussfolgerung Das palliative Therapiekonzept der Chemosaturation ist bei Patienten mit hepatisch metastasiertem Aderhautmelanom effektiv. Die interventionelle Prozedur ist sicher, seltene, aber schwerwiegende kardiovaskuläre und hepatische Komplikationen erfordern eine sorgfältige Patientenselektion und intensive Aufmerksamkeit.

Background The first wave of COVID-19 in South Africa peaked in July, 2020, and a larger second wave peaked in January, 2021, in which the SARS-CoV-2 501Y.V2 (Beta) lineage predominated. We aimed to compare in-hospital mortality and other patient characteristics between the first and second waves. Methods In this prospective cohort study, we analysed data from the DATCOV national active surveillance system for COVID-19 admissions to hospital from March 5, 2020, to March 27, 2021. The system contained data from all hospitals in South Africa that have admitted a patient with COVID-19. We used incidence risk for admission to hospital and determined cutoff dates to define five wave periods: pre-wave 1, wave 1, post-wave 1, wave 2, and post-wave 2. We compared the characteristics of patients with COVID-19 who were admitted to hospital in wave 1 and wave 2, and risk factors for in-hospital mortality accounting for wave period using random-effect multivariable logistic regression. Findings Peak rates of COVID-19 cases, admissions, and in-hospital deaths in the second wave exceeded rates in the first wave: COVID-19 cases, 240·4 cases per 100 000 people vs 136·0 cases per 100 000 people; admissions, 27·9 admissions per 100 000 people vs 16·1 admissions per 100 000 people; deaths, 8·3 deaths per 100 000 people vs 3·6 deaths per 100 000 people. The weekly average growth rate in hospital admissions was 20% in wave 1 and 43% in wave 2 (ratio of growth rate in wave 2 compared with wave 1 was 1·19, 95% CI 1·18–1·20). Compared with the first wave, individuals admitted to hospital in the second wave were more likely to be age 40–64 years (adjusted odds ratio [aOR] 1·22, 95% CI 1·14–1·31), and older than 65 years (aOR 1·38, 1·25–1·52), compared with younger than 40 years; of Mixed race (aOR 1·21, 1·06–1·38) compared with White race; and admitted in the public sector (aOR 1·65, 1·41–1·92); and less likely to be Black (aOR 0·53, 0·47–0·60) and Indian (aOR 0·77, 0·66–0·91), compared with White; and have a comorbid condition (aOR 0·60, 0·55–0·67). For multivariable analysis, after adjusting for weekly COVID-19 hospital admissions, there was a 31% increased risk of in-hospital mortality in the second wave (aOR 1·31, 95% CI 1·28–1·35). In-hospital case-fatality risk increased from 17·7% in weeks of low admission (8000 admissions; aOR 1·24, 1·17–1·32). Interpretation In South Africa, the second wave was associated with higher incidence of COVID-19, more rapid increase in admissions to hospital, and increased in-hospital mortality. Although some of the increased mortality can be explained by admissions in the second wave being more likely in older individuals, in the public sector, and by the increased health system pressure, a residual increase in mortality of patients admitted to hospital could be related to the new Beta lineage. Funding DATCOV as a national surveillance system is funded by the National Institute for Communicable Diseases and the South African National Government.

This study aimed to establish the effects that travel motives and life domains have on visitors’ quality-of-life. Based on the setting, a convenience sampling technique was used in which fieldworkers administered the questionnaire to visitors at Comic Con Africa 2019. Data from 433 (N) completed questionnaires were captured regarding their travel motives, life domains, life domains overall, and quality-of-life affect, and analysed. A structural equation modelling analysis indicated a positive linear relationship between the visitors’ travel motives, life domains measured, life domains overall, and quality-of-life; all of which attained good composite reliabilities. The findings indicate that travel motives have an influence on visitors’ life domains, positive and negative, relevant to their perceived importance. Overall, a visit to this pop culture event had a positive effect on visitors’ quality-of-life. Based on the visitor demographics, social media marketing should be aimed at niche lifestyle aspects that are most enticing to visitor’s pop culture life. The approach would most likely appeal to the markets’ higher-order needs, which could increase visitor numbers and help improve their quality-of-life overall. This research opened the door to the new pop culture life domain, and contributes to the literature and methodology in tourism, life domains and quality-of-life.

Summary Background The interaction between COVID-19, non-communicable diseases, and chronic infectious diseases such as HIV and tuberculosis is unclear, particularly in low-income and middle-income countries in Africa. South Africa has a national HIV prevalence of 19% among people aged 15–49 years and a tuberculosis prevalence of 0·7% in people of all ages. Using a nationally representative hospital surveillance system in South Africa, we aimed to investigate the factors associated with in-hospital mortality among patients with COVID-19. Methods In this cohort study, we used data submitted to DATCOV, a national active hospital surveillance system for COVID-19 hospital admissions, for patients admitted to hospital with laboratory-confirmed SARS-CoV-2 infection between March 5, 2020, and March 27, 2021. Age, sex, race or ethnicity, and comorbidities (hypertension, diabetes, chronic cardiac disease, chronic pulmonary disease and asthma, chronic renal disease, malignancy in the past 5 years, HIV, and past and current tuberculosis) were considered as risk factors for COVID-19-related in-hospital mortality. COVID-19 in-hospital mortality, the main outcome, was defined as a death related to COVID-19 that occurred during the hospital stay and excluded deaths that occurred because of other causes or after discharge from hospital; therefore, only patients with a known in-hospital outcome (died or discharged alive) were included. Chained equation multiple imputation was used to account for missing data and random-effects multivariable logistic regression models were used to assess the role of HIV status and underlying comorbidities on COVID-19 in-hospital mortality. Findings Among the 219 265 individuals admitted to hospital with laboratory-confirmed SARS-CoV-2 infection and known in-hospital outcome data, 51 037 (23·3%) died. Most commonly observed comorbidities among individuals with available data were hypertension in 61 098 (37·4%) of 163 350, diabetes in 43 885 (27·4%) of 159 932, and HIV in 13 793 (9·1%) of 151 779. Tuberculosis was reported in 5282 (3·6%) of 146 381 individuals. Increasing age was the strongest predictor of COVID-19 in-hospital mortality. Other factors associated were HIV infection (adjusted odds ratio 1·34, 95% CI 1·27–1·43), past tuberculosis (1·26, 1·15–1·38), current tuberculosis (1·42, 1·22–1·64), and both past and current tuberculosis (1·48, 1·32–1·67) compared with never tuberculosis, as well as other described risk factors for COVID-19, such as male sex; non-White race; underlying hypertension, diabetes, chronic cardiac disease, chronic renal disease, and malignancy in the past 5 years; and treatment in the public health sector. After adjusting for other factors, people with HIV not on antiretroviral therapy (ART; adjusted odds ratio 1·45, 95% CI 1·22–1·72) were more likely to die in hospital than were people with HIV on ART. Among people with HIV, the prevalence of other comorbidities was 29·2% compared with 30·8% among HIV-uninfected individuals. Increasing number of comorbidities was associated with increased COVID-19 in-hospital mortality risk in both people with HIV and HIV-uninfected individuals. Interpretation Individuals identified as being at high risk of COVID-19 in-hospital mortality (older individuals and those with chronic comorbidities and people with HIV, particularly those not on ART) would benefit from COVID-19 prevention programmes such as vaccine prioritisation as well as early referral and treatment. Funding South African National Government.

ZusammenfassungDesorientierung kann ein frühes Merkmal eines Delirs sein. Für die Überwachung eines Delirs testet die im deutschsprachigen Raum weit verbreitete „Confusion Assessment Method for Intensive Care Unit“ (CAM-ICU) die Orientierung nicht, da intubierte Intensivpatienten sich nicht verbal äußern können. Die Mehrheit der Patienten auf deutschen Intensivstationen ist aber nicht beatmet, sie könnten hinsichtlich ihrer Orientiertheit befragt werden. Die vorliegende Studie untersuchte, ob sich durch das Kriterium „Desorientierung“ bei extubierten Patienten im Vergleich zur CAM-ICU divergierende Befunde ergeben und ob sich die Sensitivität der CAM-ICU durch Kombination mit dem Merkmal „Desorientierung“ („CAM-IMC“) erhöhen lassen. Insgesamt 86 gepaarte Untersuchungen fanden bei 50 extubierten Patienten statt. Ein Delir fand sich bei 19,8 % (n = 17) aller Untersuchungen. Die CAM-ICU hatte eine Sensitivität von 71 % (95%-KI: 44–90 %) und eine Spezifität von 100 % (95–100 %). Für „Desorientierung“ als alleiniges Delir-Merkmal fand sich eine Sensitivität von 77 % (50–93 %) und eine Spezifität von 93 % (89–100 %). Die CAM-IMC erreichte eine Sensitivität von 88 % (64–99 %) bei einer Spezifität von 100 % (95–100 %). Die „Receiver-Operating-Characteristics(ROC)-Analyse“ fand mit einer „area under the curve“ (AUC) von 0,941 (95%-KI: 0,851–1,000) für die CAM-IMC den höchsten Wert im Vergleich zu den anderen Delir-Tests (CAM-ICU, AUC 0,853 [0,720–0,986]; Desorientierung, AUC 0,868 [0,745–0,991]). Diese Arbeit unterstreicht die Wertigkeit des Merkmals „Desorientierung“ für Delir-Tests bei verbal kommunikationsfähigen Patienten und erklärt einige diskrepante Beurteilungen schwierig einzuschätzender Patienten in der täglichen Praxis. Die CAM-IMC scheint als Delir-Test für extubierte Patienten günstigere Eigenschaften als die CAM-ICU zu haben und sollte eingehender überprüft werden.

Purpose of Review In this scoping review, we aimed to (1) provide an overview of chronic sleep reduction by systematically reviewing the existing literature (limited to systematic reviews and meta-analyses), (2) investigate the evidence of the effects of short sleep duration on daytime functioning, and (3) identify research gaps in this field. Recent Findings The results showed that (1) clear definitions of chronicity of sleep reduction are lacking—none of the included reviews/meta-analyses provided a full definition—and (2) short sleep duration appeared to be related to obesity and diabetes, whereas relations with cardiovascular disease (CVD), cognitive functioning, emotional problems, general health, and mortality, showed either small effects and appeared to be complex (e.g., for CVD and cognitive functioning), or studies were scarce or completely lacking (e.g., mortality in children/adolescents and emotional problems in adults). Summary Although short or insufficient sleep is highly prevalent and is associated with impaired mental and physical wellbeing, as well as pervasive negative consequences for daytime functioning, the concepts of “chronicity” and “chronic sleep reduction” have not been clearly defined and its effects on health are therefore still largely unknown. Moreover, there are large research gaps concerning studies on the relations between short sleep and health consequences. Further studies are recommended to define and operationalize chronicity of sleep reduction and develop measurements that adequately represent the complexity of the concept.

BMC public health 21(1), 1295 (2021). doi:10.1186/s12889-021-11206-9, Published by BioMed Central, London

PurposeThe way that disasters are managed, or indeed mis-managed, is often represented diagrammatically as a “disaster cycle”. The cyclical aspects of the disaster (risk) management concept, comprised of numerous operational phases, have, in recent years, been criticised for conceptualising and representing disasters in an overly simplistic way that typically starts with a disaster “event” – and subsequently leads onto yet another disaster. Such cyclical thinking has been proven to not be very useful for the complexities associated with understanding disasters and their risks. This paper aims to present an alternative conceptualisation of the Disaster Risk Management phases, in a way that can better factor in the underlying root causes that create differential levels of vulnerability.Design/methodology/approachThis is a conceptual paper developed, through a review of the literature and discussions between the authors, as a counterpoint to the pervasive “disaster cycle”.FindingsThe “Disaster Risk Management (DRM) Helix” is presented as an alternative way of conceptualising the DRM phases. The helictical conceptualisation of DRM phases presented in this paper is intentionally presented to start a discussion (rather than as an end point) on how best to move away from the constraints of the “disaster cycle”.Originality/valueIt is envisaged that the helictical conceptualisation of DRM can be suitably malleable to include important factors such as temporal considerations and the underlying root causes that create differential levels of vulnerability. It is, thus, the intention that the DRM Helix can provide a catalyst for exciting discussions and future adaptations of the diagram that can better capture the dynamic (non-cyclical) nature of disasters and their root causes.

Randomized clinical trials are the foundation of evidence-based medicine and central to practice guidelines and patient care decisions. Nonetheless, randomized trials in heart failure (HF) populations have become increasingly difficult to conduct and are frequently associated with slow patient enrollment, highly selected populations, extensive data collection, and high costs. The traditional model for HF trials has become particularly difficult to execute in the United States, where challenges to site-based research have frequently led to modest U.S. representation in global trials. In this context, the TRANSFORM-HF (Torsemide Comparison with Furosemide for Management of Heart Failure) trial aims to overcome traditional trial challenges and compare the effects of torsemide versus furosemide among patients with HF in the United States. Loop diuretic agents are regularly used by most patients with HF and practice guidelines recommend optimal use of diuretic agents as key to a successful treatment strategy. Long-time clinical experience has contributed to dominant use of furosemide for loop diuretic therapy, although preclinical and small clinical studies suggest potential advantages of torsemide. However, due to the lack of appropriately powered clinical outcome studies, there is insufficient evidence to conclude that torsemide should be routinely recommended over furosemide. Given this gap in knowledge and the fundamental role of loop diuretic agents in HF care, the TRANSFORM-HF trial was designed as a prospective, randomized, event-driven, pragmatic, comparative-effectiveness study to definitively compare the effect of a treatment strategy of torsemide versus furosemide on long-term mortality, hospitalization, and patient-reported outcomes among patients with HF. (TRANSFORM-HF: ToRsemide compArisoN With furoSemide FORManagement of Heart Failure [TRANSFORM-HF]; NCT03296813 )

Genomic classification has improved risk assignment of pediatric, but not adult B-lineage acute lymphoblastic leukemia (B-ALL). The international UKALLXII/ECOG-ACRIN E2993 (#NCT00002514) trial accrued 1229 adolescent/adult patients with BCR-ABL1− B-ALL (aged 14 to 65 years). Although 93% of patients achieved remission, 41% relapsed at a median of 13 months (range, 28 days to 12 years). Five-year overall survival (OS) was 42% (95% confidence interval, 39, 44). Transcriptome sequencing, gene expression profiling, cytogenetics, and fusion polymerase chain reaction enabled genomic subtyping of 282 patient samples, of which 264 were eligible for trial, accounting for 64.5% of E2993 patients. Among patients with outcome data, 29.5% with favorable outcomes (5-year OS 65% to 80%) were deemed standard risk (DUX4-rearranged [9.2%], ETV6-RUNX1/-like [2.3%], TCF3-PBX1 [6.9%], PAX5 P80R [4.1%], high-hyperdiploid [6.9%]); 50.2% had high-risk genotypes with 5-year OS of 0% to 27% (Ph-like [21.2%], KMT2A-AFF1 [12%], low-hypodiploid/near-haploid [14.3%], BCL2/MYC-rearranged [2.8%]); 20.3% had intermediate-risk genotypes with 5-year OS of 33% to 45% (PAX5alt [12.4%], ZNF384/-like [5.1%], MEF2D-rearranged [2.8%]). IKZF1 alterations occurred in 86% of Ph-like, and TP53 mutations in patients who were low-hypodiploid (54%) and BCL2/MYC-rearranged (33%) but were not independently associated with outcome. Of patients considered high risk based on presenting age and white blood cell count, 40% harbored subtype-defining genetic alterations associated with standard- or intermediate-risk outcomes. We identified distinct immunophenotypic features for DUX4-rearranged, PAX5 P80R, ZNF384-R/-like, and Ph-like genotypes. These data in a large adult B-ALL cohort treated with a non–risk-adapted approach on a single trial show the prognostic importance of genomic analyses, which may translate into future therapeutic benefits.

Die Mortalitat von Patienten mit isoliert auftretenden angeborenen Zwerchfellhernien liegt in spezialisierten Zentren bei 20–40%. Wesentliche, das Outcome beeinflussende Faktoren, sind die bestehende Lungenhypoplasie, eine daraus resultierende pulmonale Hypertonie, sowie das Vorliegen weiterer Fehlbildungen. Begleitfehlbildungen wie angeborene Herzfehler treten bei ca. 18% aller Neonaten mit Zwerchfellhernie auf. Schwere angeborene Herzfehler wie das hypoplastische Linksherz Syndrom zeigen sich in ca. 8% der Falle. In einer retrospektiven Analyse des Patientenkollektivs unserer Klinik zwischen 01/2012 und 12/2018 wurde das pra- und postnatale Management, sowie das Outcome von Neugeborenen mit der Kombination aus angeborenen Herzfehlern und Zwerchfellhernien untersucht. Im Studienzeitraum wurden in unserer Klinik 156 Neugeborene mit Zwerchfellhernie behandelt. Bei 10 Patienten (6,4%) lag zusatzlich ein schwerer, bei 11 Patienten (7,1%) ein moderater Herzfehler vor. 6/21 Patienten verstarben im Verlauf des Krankenhausaufenthaltes, davon 3 am ersten Lebenstag. Es zeigte sich eine deutlich geringere Mortalitat bei Patienten mit Zwerchfellhernie und moderatem Herzfehler im Vergleich zu schwerem Herzfehler (9 vs. 50%). Besonders hoch lag die Mortalitat bei Kindern mit einem univentrikularen Herzen. Trotz einer deutlich reduzierten Prognose bei der Kombination aus angeborenem Herzfehler und Zwerchfellhernie muss nicht generell mit einer infausten Prognose gerechnet werden. In spezialisierten Zentren kann ein kurativer Ansatz erfolgen. The mortality of patients with isolated congenital diaphragmatic hernia (CDH) in specialized centers is 20–40%. The main factors influencing the outcome are the underlying pulmonary hypoplasia, the resulting pulmonary hypertension and the presence of other malformations. Concomitant malformations such as congenital heart defects occur in around 18% of all neonates with a diaphragmatic hernia. Serious congenital heart defects such as hypoplastic left heart syndrome occur in approximately 8% of cases. In a retrospective analysis of the patient collective of our hospital between 01/2012 and 12/2018, the prenatal and postnatal management as well as the outcome of newborns with a combination of congenital heart defects and diaphragmatic hernias were examined. During the study period, 156 newborns with diaphragmatic hernias were treated at our institution. In 10 patients (6.4%) there was also a severe, and in 11 patients (7.1%) a moderate heart defect. 6/21 patients died during their hospital stay, 3 of them on the first day of life. There was a significantly lower mortality in patients with diaphragmatic hernia and moderate heart defects compared to severe heart defects (9 vs. 50%). The mortality in children with a univentricular heart was particularly high. Despite a significantly reduced prognosis for the combination of congenital heart defects and diaphragmatic hernia, generally a poor prognosis does not have to be expected. A curative approach can be achieved in specialized centers.

Purpose To evaluate the feasibility and effect of an approach to adrenal venous sampling (AVS) analysis by combining established selective cortisol and aldosterone indices with the acquisition of a collimated C-arm CT(CACTColl). Methods Overall, 107 consecutive patients (45f,62 m; 54 ± 10 years) undergoing 111 AVS procedures without hormonal stimulation from 7/13 to 2/20 in a single institution were retrospectively analysed. Hormone levels were measured in sequential samples of the suspected adrenal veins and right iliac vein, and selectivity indices (SI) computed. Stand-alone SICortisol and/or SIAldosterone ≥ 2.0 as well as SICortisol and/or SIAldosterone ≥ 1.1 combined with positive right-sided CACTColl of the adrenals (n = 80; opacified right adrenal vein) were defined as a successful AVS procedure. Radiation exposure of CACT was measured via dose area product (DAP) and weighed against an age-/weight-matched cohort (n = 66). Results Preliminary success rates (SICortisol and/or SIAldosterone ≥ 2.0) were 99.1% (left) and 72.1% (right). These could be significantly increased to a 90.1% success rate on the right, by combining an adjusted SI of 1.1 with a positive CACTColl proving the correct sampling position. Sensitivity for stand-alone collimated CACT (CACTColl) was 0.93, with 74/80 acquired CACTColl confirming selective cannulation by adrenal vein enhancement. Mean DAPColl_CACT measured 2414 ± 958 μGyxm2, while mean DAPFull-FOV_CACT in the matched cohort measured 8766 ± 1956 μGyxm2 (p Conclusion Collimated CACT in AVS procedures is feasible and leads to a significant increase in success rates of (right-sided) selective cannulation and may in combination with adapted hormone indices, offer a successful alternative to previously published AVS analysis algorithms with lower radiation exposure compared to a full-FOV CACT.

Multiple medications are proven to reduce morbidity and mortality in patients with heart failure with reduced ejection fraction (HFrEF), but data regarding personalized approaches to optimize medication dosing remain limited. Current treatment guidelines recommend up-titration to target or maximally tolerated doses of these medications, yet use and dosing remain suboptimal in clinical practice. Body surface area (BSA) is a readily available clinical metric, used for dosing many medications, closely associated with blood pressure, renal function, and vascular congestion, and may influence efficacy, safety, and tolerability of HFrEF medications. In this review, we examine the rationale, strengths/weaknesses, and potential utility of BSA as a means of optimizing HFrEF medication use and dosing.

There has been a worldwide effort to accelerate the development of safe and effective vaccines for severe acute respiratory syndrome coronavirus-2. When vaccines become licensed and available broadly to the public, the final hurdle is equitable distribution and access for all who are recommended for vaccination. Frameworks and existing systems for allocation, distribution, vaccination, and monitoring for safety and effectiveness are assets of the current immunization delivery system that should be leveraged to ensure the equitable distribution and broad uptake of licensed vaccines. The system should be strengthened to address gaps in access to immunization services and to modernize the public health infrastructure. We offer five recommendations as guideposts to ensure that policies and practices at the federal, state, local, and tribal levels support equity, transparency, accountability, availability, and access to coronavirus disease 2019 vaccines.

The low adoption of climate-smart agriculture (CSA) technologies by farmers in developing regions where agrarian livelihoods are threatened by climate-related disasters remains a concerning enigma....

PurposePatients with peripheral arterial disease (PAD) or critical limb ischemia (CLI) require revascularization. Traditionally, endovascular therapy (EVT) is performed with iodinated contrast agent (ICM), which can provoke potential deterioration in renal function. CO2 is a safe negative contrast agent to guide vascular procedures, but interpretation of CO2 angiography is challenging. Changes in blood flow following iodine-aided EVT are assessable with 2D-perfusion angiography (2D-PA). The aim of this study was to evaluate 2D-PA as a tool to monitor blood flow changes during CO2-aided EVT.Material and Methods2D-PA was performed before and after ten EVTs (nine stents; one endoprosthesis; 10/2012–02/2020) in nine patients (six men; 65 ± 10y) with Fontaine stage IIb (n = 8) and IV (n = 1). A reference ROI (ROIINFLOW) was placed in the artery before the targeted obstruction and a target ROI (ROIOUTFLOW) distally. Corresponding ROIs were used pre- and post-EVT. Time to peak (TTP), peak density (PD) and area under the curve (AUC) were computed. The reference/target ROI ratios (TTPOUTFLOW/TTPINFLOW; PDOUTFLOW/PDINFLOW; AUCOUTFLOW/AUCINFLOW) were calculated.Results2D-PA was technically feasible in all cases. A significant increase of 82% in PDOUTFLOW/PDINFLOW(0.44 ± 0.4 to 0.8 ± 0.63;p = 0.002) and of 132% in AUCOUTFLOW/AUCINFLOW(0.34 ± 0.22 to 0.79 ± 0.59;p = 0.002) was seen. A trend for a decrease in TTPOUTFLOW/TTPINFLOWwas observed (− 24%; 5.57 ± 3.66 s–4.25 ± 1.64 s;p = 0.6).ConclusionThe presented 2D-PA technique facilitates the assessment of arterial flow in CO2-aided EVTs and has the potential to simplify the assessment of immediate treatment response.

Purpose The aim of this retrospective study was to evaluate the feasibility of a motion correction 3D reconstruction prototype technique for C-arm computed tomography (CACT). Material and Methods We included 65 consecutive CACTs acquired during transarterial chemoembolization of 54 patients (47 m,7f; 67 ± 11.3 years). All original raw datasets (CACTOrg) underwent reconstruction with and without volume punching of high-contrast objects using a 3D image reconstruction software to compensate for motion (CACTMC_bone;CACTMC_no bone). Subsequently, the effect on image quality (IQ) was evaluated using objective (image sharpness metric) and subjective criteria. Subjective criteria were defined by vessel geometry, overall IQ, delineation of tumor feeders, the presence of foreign material-induced artifacts and need for additional imaging, assessed by two independent readers on a 3-(vessel geometry and overall IQ) or 2-point scale, respectively. Friedman rank-sum test and post hoc analysis in form of pairwise Wilcoxon signed-rank test were computed and inter-observer agreement analyzed using kappa test. Results Objective IQ as defined by an image sharpness metric, increased from 273.5 ± 28 (CACTOrg) to 328.5 ± 55.1 (CACTMC_bone) and 331 ± 57.8 (CACTMC_no bone; all p MC_no bone in all categories (e.g., vessel geometry: CACTOrg: κ = 0.51, CACTMC_bone: κ = 0.42, CACTMC_no bone: κ = 0.69). Conclusion The application of a motion correction algorithm was feasible for all data sets and led to an increase in both objective and subjective IQ parameters. Level of Evidence 3

Background Patients with substantially impaired kidney function and peripheral arterial disease (PAD) underwent comparative CO2-based depiction of the pelvic arteries (PAs). Purpose To evaluate the feasibility and diagnostic performance of CO2-based C-arm computed tomography (CACT) and compare its depiction of PAs with CO2-digital subtraction angiography (DSA). Material and Methods Fifteen patients (10 men, mean age 70 ± 11 years) with PAD received CO2-DSA and CO2-CACT of the PAs, depicted from the aorta to femoral arteries. These were divided into nine segments (135 in total) and graded by two independent readers for image quality (IQ; 1 = sufficient, 2 = minimal impairments, 3 = insufficient, 4 = outside field of view) and subsequent stenosis grading (SG; grade 1: normal to grade 4: occlusion), under exclusion of all segments with insufficient IQ. Inter-observer and inter-modality agreement calculation and subsequent consensus reading were performed and correlated to a standard of reference (StOR), representing a modality consensus. Results Of 135 segments, 117 showed sufficient IQ, excluding 18 segments (10 CACT, 8 DSA). Inter-observer agreement for IQ and consecutive SG demonstrated good to excellent agreement: IQDSA: κ = 0.83, IQCACT: κ = 0.76; StenosisDSA: κ = 0.71, StenosisCACT: κ = 0.84. Inter-modality agreement for SG lay at κ = 0.76 and κ = 0.65, respectively. More stenoses could be detected by CACT, and analysis of pooled consensus values of SG in CACTcons versus StOR showed an excellent agreement (κ = 0.96) that proved considerably higher than the moderate agreement between consensus values in DSAcons versus StOR (κ = 0.43). Conclusion CO2-CACT proved feasible, and has the potential to optimize angiographic work-up of PAD in patients with contraindications for other contrast media.

Local elected officials play a leadership role in setting plan directions and can jeopardize implementation if they are not committed to plan goals. In this research, we apply topic modeling, seman...

Postconditioning attenuates inflammation and fibrosis in myocardial infarction (MI). The aim of this study was to investigate whether postconditioning with the cytosine-phosphate-guanine (CpG)-containing Toll-like receptor-9 (TLR9) ligand 1668-thioate (CpG) can modulate inflammation and remodeling in reperfused murine MI. Thirty minutes of left descending coronary artery (LAD) occlusion was conducted in 12-wk-old C57BL/6 mice. Mice were treated with CpG intraperitoneally 5 min before reperfusion. The control group received PBS; the sham group did not undergo ischemia. M-mode echocardiography (3, 7, and 28 days) and Millar left ventricular (LV) catheterization were performed (7 and 28 days) before the hearts were excised and harvested for immunohistochemical (6 h, 24 h, 3 days, 7 days, and 28 days), gene expression (6 h, 24 h, and 3 days; Taqman RT-qPCR), protein, and FACS analysis (24 h and 3 days). Mice treated with CpG showed significantly better LV function after 7 and 28 days of reperfusion. Protein and mRNA expressions of proinflammatory and anti-inflammatory cytokines were significantly induced after CpG treatment. Histology revealed fewer macrophages in CpG mice after 24 h, confirmed by FACS analysis with a decrease in both classically M1- and alternative M2a-monocytes. CpG treatment reduced apoptosis and cardiomyocyte loss and was associated with induction of adaptive mechanisms, e.g., of heme-oxigenase-1 and β-/α-myosin heavy chain (MHC) ratio. Profibrotic markers collagen type Iα (Col-Ια) and Col-III induction was abrogated in CpG mice, accompanied by fewer myofibroblasts. This led to the formation of a smaller scar. Differential matrix metalloproteinase (MMP)/tissue inhibitor of metalloproteinase (TIMP) expression contributed to attenuated remodeling in CpG, resulting in preserved cardiac function in a Toll-like receptor 1- and TLR9-dependent manner. Our study suggests a cardioprotective mechanism of CpG postconditioning, involving Toll-like receptor-driven modulation of inflammation. This is followed by attenuated remodeling and preserved LV function.NEW & NOTEWORTHY Cytosine-phosphate-guanine (CpG) postconditioning seems to mediate inflammation via Toll-like receptor-1 and Toll-like receptor-9 signaling. Enhanced cytokine and chemokine expressions are partly attenuated by IL-10 and matrix metalloproteinase-8 (MMP8) induction, being associated with lower macrophage infiltration and M1-monocyte differentiation. Furthermore, switch from α- to β-MHC and balanced MMP/TIMP expression led to lesser cardiomyocyte apoptosis, smaller scar size, and preserved cardiac function. Data of pharmacological postconditioning have been widely disappointing to date. Our study suggests a new pathway promoting myocardial postconditioning via Toll-like receptor activation.

Key points Ipsilateral-projecting corticobulbar pathways, originating primarily from secondary motor areas, innervate the proximal and even distal portions, although they branch more extensively at the spinal cord. It is currently unclear to what extent these ipsilateral secondary motor areas and subsequent cortical projections may contribute to hand function following stroke-induced damage to one hemisphere. In the present study, we provide both structural and functional evidence indicating that individuals increasingly rely on ipsilateral secondary motor areas, although at the detriment of hand function. Increased activity in ipsilateral secondary motor areas was associated with increased involuntary coupling between shoulder abduction and finger flexion, most probably as a result of the low resolution of these pathways, making it increasingly difficult to open the hand. These findings suggest that, although ipsilateral secondary motor areas may support proximal movements, they do not have the capacity to support distal hand function, particularly for hand opening. Abstract Recent findings have shown connections of ipsilateral cortico-reticulospinal tract (CRST), predominantly originating from secondary motor areas to not only proximal, but also distal muscles of the arm. Following a unilateral stroke, CRST from the ipsilateral side remains intact and thus has been proposed as a possible backup system for post-stroke rehabilitation even for the hand. We argue that, although CRST from ipsilateral secondary motor areas can provide control for proximal joints, it is insufficient to control either hand or coordinated shoulder and hand movements as a result of its extensive spinal branching compared to contralateral corticospinal tract. To address this issue, we combined magnetic resonance imaging, high-density EEG, and robotics in 17 individuals with severe chronic hemiparetic stroke and 12 age-matched controls. We tested for changes in structural morphometry of the sensorimotor cortex and found that individuals with stroke demonstrated higher grey matter density in secondary motor areas ipsilateral to the paretic arm compared to controls. We then measured cortical activity when participants were attempting to generate hand opening either supported on a table or when lifting against a shoulder abduction load. The addition of shoulder abduction during hand opening increased reliance on ipsilateral secondary motor areas in stroke, but not controls. Crucially, the increased use of ipsilateral secondary motor areas was associated with decreased hand opening ability when lifting the arm as a result of involuntary coupling between the shoulder and wrist/finger flexors. Taken together, this evidence implicates a compensatory role for ipsilateral (i.e. contralesional) secondary motor areas post-stroke, although with no apparent capacity to support hand function.

Effective interventions have demonstrated the ability to improve motor function by reengaging ipsilesional resources, which appears to be critical and feasible for hand function recovery even in individuals with severe chronic stroke. However, previous studies focus on changes in brain activity related to motor execution. How changes in motor preparation may facilitate these changes at motor execution is still unclear. To address this question, 8 individuals with severe chronic hemiparetic stroke participated in a device-assisted intervention for seven weeks. We then quantified changes in both coupling between regions during motor preparation and changes in topographical cortical activity at motor execution for both hand opening in isolation and together with the shoulder using high-density EEG. We hypothesized that intervention-induced changes in cortico-cortico interactions during motor preparation would lead to changes in activity at motor execution specifically towards an increased reliance on the ipsilesional hemisphere. In agreement with this hypothesis, we found that, following the intervention, individuals displayed a reduction in coupling from ipsilesional M1 to contralesional M1 within gamma frequencies during motor preparation for hand opening. This was followed by a reduction in activity in the contralesional primary sensorimotor cortex during motor execution. Similarly, during lifting and opening, a shift to negative coupling within ipsilesional M1 from gamma to beta frequencies was accompanied by an increase in ipsilesional primary sensorimotor cortex activity following the intervention. Together, these results show that intervention-induced changes in coupling within or between motor regions during motor preparation may affect cortical activity at execution.

Hereditary angioedema (HAE) is becoming much more genetically complex than was initially considered. Thus, the role of HAE genetics is expanding beyond research laboratories, and the genotyping of subjects suffering from HAE has become diagnostically indispensable in clinical practice. The synthesis and interpretation of the clinical and biochemical analyses to facilitate appropriate genetic test selection has thus also become significantly more complex. With this in mind, an international multidisciplinary group of 14 experts in HAE genetics and disease management was convened in October 2018. The objective was to develop clear, actionable, evidence- and consensus-based statements aiming to facilitate the communication between physicians treating patients with HAE and clinical geneticists, and thus promote the effective use of genetics in the management of the disease. Eleven consensus statements were generated, encompassing considerations regarding the clinical indications for genotyping patients with angioedema, the methods of detection of HAE-causative variants, the variant pathogenicity curation, the genotyping of patients with HAE in the clinic, and genetic counseling. These statements are intended both to guide clinicians and to serve as a framework for future educational and further genetic testing developments as the field continues to evolve rapidly.

The coronaviruses belong to the family Coronaviridae in the order Nidovirales. CoVs are found globally and infect a variety of animals, causing illnesses that range from gastrointestinal tract infections, encephalitis and demyelination; and can be fatal. Humans coronaviruses (hCoVs) have traditionally been associated with self-limiting upper respiratory tract infections and gastrointestinal tract infections. In recent years, however, it has become increasingly evident that the hCoVs can cause more severe lower respiratory tract infections such as bronchitis, pneumonia and even acute respiratory distress syndrome (ARDS), and can lead to death. Seven CoVs are known to infect humans, with the four “common cold” CoVs circulating globally on a yearly basis. The remaining three are more pathogenic and have resulted in outbreaks with high mortality rates. This review focussed on the three pathogenic CoVs.

Study design Expert Consensus Study. Objectives This expert panel was created to establish best practice guidelines to identify and treat patients with poor bone health prior to elective spinal reconstruction. Summary of background data Currently, no guidelines exist for the management of osteoporosis and osteopenia in patients undergoing spinal reconstructive surgery. Untreated osteoporosis in spine reconstruction surgery is associated with higher complications and worse outcomes. Methods A multidisciplinary panel with 20 experts was assembled including orthopedic and neurological surgeons, endocrinologists, and rheumatologists. Surveys and discussions regarding the current literature were held according to Delphi method until a final set of guidelines was created with over 70% consensus. Results Panelists agreed that bone health should be considered in every patient prior to elective spinal reconstruction. All patients above 65 and those under 65 with particular risk factors (chronic glucocorticoid use, high fracture risk or previous fracture, limited mobility, and eight other key factors) should have a formal bone health evaluation prior to undergoing surgery. DXA scans of the hip are preferable due to their wide availability. Opportunistic CT Hounsfield Units of the vertebrae can be useful in identifying poor bone health. In the absence of contraindications, anabolic agents are considered first line therapy due to their bone building properties as compared to antiresorptive medications. Medications should be administered preoperatively for at least 2 months and postoperatively for minimum 8 months. Conclusions Based on the consensus of a multidisciplinary panel of experts, we propose best practice guidelines for assessment and treatment of poor bone health prior to elective spinal reconstructive surgery. Patients above age 65 and those with particular risk factors under 65 should undergo formal bone health evaluation. We also established guidelines on perioperative optimization, utility of various diagnostic modalities, and the optimal medical management of bone health in this population.Level of Evidence: 5.

Survivors of central nervous system injury commonly present with spastic hypertonia. The affected muscles are hyperexcitable and can display involuntary static muscle tone and an exaggerated stretch reflex. These symptoms affect posture and disrupt activities of daily living. Symptoms are typically measured using subjective manual tests such as the Modified Ashworth Scale; however, more quantitative measures are necessary to evaluate potential treatments. The hands are one of the most common targets for intervention, but few investigators attempt to quantify symptoms of spastic hypertonia affecting the fingers. We present the isometric force pillow (IFP) to quantify involuntary grip force. This lightweight, computerized tool provides a holistic measure of finger flexion force and can be used in various orientations for clinical testing and to measure the impact of assistive devices.

Background: The global spread of SARS-CoV-2 is a serious public health issue. Large-scale surveillance screenings are crucial but can exceed diagnostic test capacities. We optimized test conditions and implemented high throughput pool testing of respiratory swabs into SARS-CoV-2 diagnostics. Methods: In preparation for pool testing, we determined the optimal pooling strategy and pool size, and evaluated aspects of pre-analytics including method and timepoint of sample collection during course of infection. In addition, we measured the impact of vortexing prior to sample processing, compared pipette- and swab-pooling method as well as the sensitivity of three different PCR assays. Findings: Using optimized strategies for pooling, we systematically pooled 16,164 samples in a period of 18 weeks resulting in a reduction of 14,170 PCR reactions. In a low prevalence setting, we defined a preferable pool size of ten in a two-stage hierarchical pool testing strategy. Vortexing of the swab increased cellular yield by a factor of 2·34, and sampling at or shortly after symptom onset by oropharyngeal or combined nasal/oropharyngeal swabs was associated with higher viral loads. By comparing different pooling strategies, pipette-pooling was more efficient compared to swab-pooling. Interpretation: For implementing pooling strategies into high throughput diagnostics, we recommend to apply a pipette-pooling method, using pool sizes of ten samples, performing sensitivity validation of the PCR assays used, and vortexing swabs prior to analyses. Our data shows, that pool testing for SARS-CoV-2 detection is feasible and highly effective in a low prevalence setting. Funding: No external funding was received. Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All samples and clinical data were collected on the wards or outpatient departments of the University Hospital of Cologne. No identifying data were used for the patient’s characterization. According to §15 subparagraph 3 (Professional Code for Physicians in Germany) ethical principles of WMA Declaration of Helsinki were respected, and no ethics committee approval and informed consent were necessary for this study.

To evaluate mosaic perfusion patterns and vascular lesions in patients with chronic thromboembolic pulmonary hypertension (CTEPH) using C-Arm computed tomography (CACT) compared to computed tomography pulmonary angiography (CTPA). We included 41 patients (18 female; mean age 59.9 ± 18.3 years) with confirmed CTEPH who underwent CACT and CTPA within 21 days (average 5.3 ± 5.2). Two readers (R1; R2) independently evaluated datasets from both imaging techniques for mosaic perfusion patterns and presence of CTEPH-typical vascular lesions. The number of pulmonary arterial segments with typical findings was evaluated and the percentage of affected segments was calculated and categorized: cons vs. CTPAcons) was calculated using the ICC. Inter-observer agreement was excellent for central vascular lesions (ICC > 0.87) and the percentage of affected segments (ICC > 0.76) and good for the perceptibility of mosaic perfusion (ICC > 0.6) and attribution of the pattern of mosaic perfusion (ICC > 0.6) for both readers on CACT and CTPA. Inter-modality agreement was excellent for the perceptibility of mosaic perfusion (ICC = 1), the present perfusion pattern (ICC = 1) and central vascular lesions (ICC = 1). However, inter-modality agreement for the percentage of affected segments was fair (ICC = 0.50), with a greater proportion of identified affected segments on CACTcons. CACT demonstrates a high agreement with CTPA regarding the detection of mosaic perfusion. CACT detects a higher number of peripheral vascular lesions compared to CTPA.

Median arcuate ligament syndrome (MALS) is the chronic symptomatic compression of the celiac artery by the median arcuate ligament. A known potential sequela of MALS is celiac artery aneurysm, which could predispose the diseased artery to dissection. However, the presence of celiac artery dissection and MALS is yet to be reported. Here, we present a case of MALS with a coincident celiac artery aneurysm and dissection.

Several studies have shown high prevalence rates of sleep problems among medical students, including insufficient sleep duration, poor sleep quality, and excessive daytime sleepiness. This review aims to systematically summarize the existing literature on sleep problems among medical students and consequently estimate the prevalence of these disturbances. The MEDLINE, EMBASE, ScienceDirect, and ProQuest Medical databases, the Google Scholar engine, and reference lists of retrieved articles were systematically searched and evaluated for quality. Forty–three studies involving a total of 18,619 students from 13 countries were included in the analyses. Results showed that the mean pooled sleep duration (K = 16, N = 10,512) was 6.3 h per night for medical students, [95% confidence interval (CI) 6.0–6.6]. The results also indicated that 55% [95% CI 48.0%–62.0%] of students reported poor sleep quality (K = 33, N = 15,462) according to the Pittsburgh Sleep Quality Index (PSQI); the mean pooled score of 6.3. Excessive daytime sleepiness (K = 18, N = 5688) was reported by 31.0% [95% CI 24.4%–37.7%] of students according to the Epworth Sleepiness Scale (ESS). Age and gender were not significant moderators for sleep quality or excessive daytime sleepiness. Some differences were obtained between countries, suggesting that cultural values, local conditions, and environment all have an impact on sleep practices and attitudes. Sleep problems are highly prevalent among medical students and are therefore a severe problem. Prevention and intervention programs targeting these are therefore highly recommended for future studies.

Objective The flexion and extension synergies were quantified at the paretic elbow, forearm, wrist, and finger joints within the same group of participants for the first time. Differences in synergy expression at each of the four joints were examined, as were the ways these differences varied across the joints. Methods Twelve post-stroke individuals with chronic moderate-to-severe hemiparesis and six age-matched controls participated. Participants generated isometric shoulder abduction (SABD) and shoulder adduction (SADD) at four submaximal levels to progressively elicit the flexion and extension synergies, respectively. Isometric joint torques and EMG were recorded from shoulder, elbow, forearm (radio-ulnar), wrist, and finger joints and muscles. Results SABD elicited strong wrist and finger flexion torque that increased with shoulder torque level. SADD produced primarily wrist and finger flexion torque, but magnitudes at the wrist were less than during SABD. Findings contrasted with those at the elbow and forearm, where torques and EMG generated due to SABD and SADD were opposite in direction. Conclusions Flexion and extension synergy expression are more similar at the hand than at the shoulder and elbow. Specific bulbospinal pathways that may underlie flexion and extension synergy expression are discussed. Significance Whole-limb behavior must be considered when examining paretic hand function in moderately-to-severely impaired individuals.

Because of a remarkably high theoretical energy density, the lithium–sulfur (Li–S) battery has attracted significant attention as a candidate for next-generation batteries. While employing solid el...

A standard technique for generating a burst of hard x rays (above 30 keV) is to use ultra high intensity lasers incident on a target. The strong laser field causes rapid electron oscillations which then generate hard x rays via bremsstrahlung. We have demonstrated a new technique for optimizing the conversion efficiency of laser light to hard x rays at moderate Iλ2 (mid 1013 W/cm2.µm2) assuming that the two plasmon decay plasma instability is the predominant acceleration mechanism. In this scheme, electrons are not directly accelerated by the laser field but by electron plasma waves. Experiments at the National Ignition Facility show the effect of a pre-pulse on the hard x ray spectrum and conversion efficiency. Different experimental configurations are investigated to optimize the conversion efficiency using various pre-pulse levels as well as different target designs (gold vs. silver, varying target thickness, presence of an ablator layer of CH). The conversion efficiency of laser energy into photon above 30 keV for a 100 ps short pulse scales as ∼ I1.23 for laser intensity ranging from 1 × 1016 to 1 × 1017 W/cm2 at 3ω for high Z target. A 1-ns-long pre-pulse pre-seeding an 88-ps Gaussian laser pulse coupled with a CH-coated thin Au target led the highest conversion efficiency above 30 keV of ∼ 3 × 10 − 4 .

(1) Background: To comparatively analyze the uptake of hepatocellular carcinoma (HCC) on pre-therapeutic imaging modalities, the arterial phase multi-detector computed tomography (MDCT), the parenchymal phase C-arm computed tomography (CACT), the Technetium99m-macroaggregates of human serum albumin single-photon emission computed tomography/computed tomography (SPECT/CT), and the correlation to the post-therapeutic Yttrium90 positron emission tomography/computed tomography (PET/CT) in patients with selective internal radiation therapy (SIRT). (2) Methods: Between September 2013 and December 2016, 104 SIRT procedures were performed at our institution in 74 patients with HCC not suitable for curative surgery or ablation. Twenty-two patients underwent an identical sequence of pre-therapeutic MDCT, CACT, SPECT/CT, and post-therapeutic PET/CT with a standardized diagnostic and therapeutic protocol. In these 22 patients, 25 SIRT procedures were evaluated. The uptake of the HCC was assessed using tumor-background ratio (TBR). Therefore, regions of interest were placed on the tumor and the adjacent liver tissue on MDCT (TBRMDCT), CACT (TBRCACT), SPECT/CT (TBRSPECT/CT), and PET/CT (TBRPET/CT). Comparisons were made with the Friedman test and the Nemenyi post-hoc test. Correlations were analyzed using Spearman’s Rho and the Benjamini–Hochberg method. The level of significance was p &lt, 0.05. (3) Results: TBR on MDCT (1.4 ± 0.3) was significantly smaller than on CACT (1.9 ± 0.6) and both were significantly smaller compared to SPECT/CT (4.6 ± 2.0) (pFriedman-Test &lt, 0.001, pTBRMDCT/TBRCACT = 0.012, pTBRMDCT/TBRSPECT/CT &lt, 0.001, pTBRCACT/TBRSPECT/CT &lt, 0.001). There was no significant correlation of TBR on MDCT with PET/CT (rTBRMDCT/TBRPET/CT = 0.116, p = 0.534). In contrast, TBR on CACT correlated to TBR on SPECT/CT (rTBRCACT/TBRSPECT/CT = 0.489, p = 0.004) and tended to correlate to TBR on PET/CT (rTBRCACT/TBRPET/CT =0.365, p = 0.043). TBR on SPECT/CT correlated to TBR on PET/CT (rTBRSPECT/CT/TBRPET/CT= 0.706, p &lt, 0.001) (4) Conclusion: The uptake assessment on CACT was in agreement with SPECT/CT and might be consistent with PET/CT. In contrast, MDCT was not comparable to CACT and SPECT/CT, and had no correlation with PET/CT due to the different application techniques. This emphasizes the value of the CACT, which has the potential to improve the dosimetric assessment of the tumor and liver uptake for SIRT.

ObjectiveSuccessive improvements in high density surface electromyography and decomposition techniques have facilitated an increasing yield in decomposed motor unit (MU) spike times. Though these advancements enhance the generalizability of findings and promote the application of MU discharge characteristics to inform the neural control of motor output, limitations remain. Specifically, 1) common approaches for generating smooth estimates of MU discharge rates introduce artifacts in quantification, which may bias findings, and 2) discharge characteristics of large MU populations are often difficult to visualize.ApproachIn the present study, we propose support vector regression (SVR) as an improved approach for generating continuous estimates of discharge rate and compare the fit characteristics of SVR to traditionally used methods, including Hanning window filtering and polynomial regression. Furthermore, we introduce ensembles as a method to visualize the discharge characteristics of large MU populations. We define ensembles as the average discharge profile of a subpopulation of MUs, composed of a time normalized ensemble average of all units within this subpopulation. Analysis was conducted with MUs decomposed from the tibialis anterior (N = 2128), medial gastrocnemius (N = 2673), and soleus (N = 1190) during isometric plantarflexion and dorsiflexion contractions.Main ResultCompared to traditional approaches, we found SVR to alleviate commonly observed inaccuracies and produce significantly less absolute fit error in the initial phase of MU discharge and throughout the entire duration of discharge. Additionally, we found the visualization of MU populations as ensembles to intuitively represent population discharge characteristics with appropriate accuracy for visualization.SignificanceThe results and methods outlined here provide an improved method for generating smooth estimates of MU discharge rate with SVR and present a unique approach to visualizing MU populations with ensembles. In combination, the use of SVR and generation of ensembles represent an efficient method for rendering population discharge characteristics.

Background: Neural impairments that follow hemiparetic stroke may negatively affect passive muscle properties, further limiting recovery. However, factors such as hypertonia, spasticity, and botulinum neurotoxin (BoNT), a common clinical intervention, confound our understanding of muscle properties in chronic stroke.Objective: To determine if muscle passive biomechanical properties are different following prolonged, stroke-induced, altered muscle activation and disuse.Methods: Torques about the metacarpophalangeal and wrist joints were measured in different joint postures in both limbs of participants with hemiparetic stroke. First, we evaluated 27 participants with no history of BoNT; hand impairments ranged from mild to severe. Subsequently, seven participants with a history of BoNT injections were evaluated. To mitigate muscle hypertonia, torques were quantified after an extensive stretching protocol and under conditions that encouraged participants to sleep. EMGs were monitored throughout data collection.Results: Among participants who never received BoNT, no significant differences in passive torques between limbs were observed. Among participants who previously received BoNT injections, passive flexion torques about their paretic wrist and finger joints were larger than their non-paretic limb (average interlimb differences = +42.0 ± 7.6SEM Ncm, +26.9 ± 3.9SEM Ncm, respectively), and the range of motion for passive finger extension was significantly smaller (average interlimb difference = −36.3° ± 4.5°SEM; degrees).Conclusion: Our results suggest that neural impairments that follow chronic, hemiparetic stroke do not lead to passive mechanical changes within the wrist and finger muscles. Rather, consistent with animal studies, the data points to potential adverse effects of BoNT on passive muscle properties post-stroke, which warrant further consideration.

Tasks of daily life require the independent use of the arms and hands. Individuals with hemiparetic cerebral palsy (HCP) often experience difficulty with fine motor tasks demonstrating mirrored movements between the arms. In this study, bilateral muscle activations were quantified during single arm isometric maximum efforts and submaximal reaching tasks. The magnitude and direction of mirrored activation was examined in 14 individuals with HCP and 9 age-matched controls. Participants generated maximum voluntary torques (MVTs) in five different directions and completed ballistic reaches while producing up to 80% of shoulder abduction MVT. Electromyography (EMG) signals were recorded from six upper extremity muscles bilaterally. Participants with HCP demonstrated more mirrored activation when volitionally contracting the non-paretic (NP) arm than the paretic arm (F = 83.543, p < 0.001) in isometric efforts. Increased EMG activation during reach acceleration resulted in a larger increase in rest arm co-activation when reaching with the NP arm compared to the paretic arm in the HCP group (t = 8.425, p < 0.001). Mirrored activation is more pronounced when driving the NP arm and scales with effort level. This directionality of mirroring is indicative of the use of ipsilaterally terminating projections of the corticospinal tract (CST) originating in the non-lesioned hemisphere. Peripheral measures of muscle activation provide insight into the descending pathways available for control of the upper extremity after early unilateral brain injury.

In May 2021, the Alpha variant (B.1.1.7) of SARS-CoV-2 was found in 91% of the SARS-CoV-2 cases in Germany. Not much is known about the symptoms, courses of disease, and infectiousness in pediatric patients with the Alpha variant. Objective: The aim of this retrospective analysis was to gain information on the infection with the Alpha variant in children and adolescents. Methods: Between 12 January 2021 and 3 June 2021, all nucleic acid amplification tests (NAATs) of children who received a swab for SARS-CoV-2 were included. Data were collected on standardized questionnaires. The analysis of data was anonymized and retrospective. Results: We investigated 3544 NAATs, 95 children were tested positive (2.7%) for SARS-CoV-2. For the sub-analysis, 65 children were analyzed. In 59 children, the Alpha variant was found (90.8%), and 54.2% (n = 32/59) were symptomatic. The most common symptoms were fever, cough, and rhinitis. The median Ct value was 24.0 (min 17.0, max 32.7). Conclusions: We can underline early findings that children are still less effected by SARS-CoV-2 infection with the spread of the Alpha variant. We found no evidence that children infected with the Alpha variant showed more severe symptoms or suffered from a more severe clinical course than those infected with the wild type.

Study Design: Retrospective cohort study. Objectives: The current evidence regarding how level of lumbar pedicle subtraction osteotomy (PSO) influences correction of sagittal alignment is limited. This study sought to investigate the relationship of lumbar level and segmental angular change (SAC) of PSO with the magnitude of global sagittal alignment correction. Methods: This study retrospectively evaluated 53 consecutive patients with adult spinal deformity who underwent lumbar PSO at a single institution. Radiographs were evaluated to quantify the effect of PSO on lumbar lordosis (LL), thoracic kyphosis (TK), sacral slope (SS), pelvic tilt (PT), pelvic incidence (PI), T1-spinopelvic inclination (T1SPI), T1-pelvic alignment (TPA), and sagittal vertical axis (SVA). Results: Significant correlations were found between PSO SAC and the postoperative increase in LL ( r = 0.316, P = .021) and PT ( r = 0.352, P = .010), and a decrease in TPA ( r = −0.324, P = .018). PSO level significantly correlated with change in T1SPI ( r = −0.305, P = .026) and SVA ( r = −0.406, P = .002), with more caudal PSO corresponding to a greater correction in sagittal balance. On multivariate analysis, more caudal PSO level independently predicted a greater reduction in T1SPI (β = −3.138, P = .009) and SVA (β = −29.030, P = .001), while larger PSO SAC (β = −0.375, P = .045) and a greater number of fusion levels (β = −1.427, P = .036) predicted a greater reduction in TPA. Conclusion: This study identified a gain of approximately 3 degrees and 3 cm of correction for each level of PSO more caudal to L1. Additionally, a larger PSO SAC predicted greater improvement in TPA. While further investigation of these relationships is warranted, these findings may help guide preoperative PSO level selection.

Monitoring the burden and spread of infection with the new coronavirus SARS-CoV-2, whether within small communities or in large geographical settings, is of paramount importance for public health purposes. Serology, which detects the host antibody response to the infection, is the most appropriate tool for this task, since virus-derived markers are most reliably detected during the acute phase of infection. Here we show that our ELISA protocol, which is based on antibody binding to the Receptor Binding Domain (RBD) of the S1 subunit of the viral Spike protein expressed as a novel fusion protein, detects antibody responses to SARS-CoV-2 infection and COVID-19 vaccination.We also show that our ELISA is accurate and versatile. It compares favorably with commercial assays widely used in clinical practice to determine exposure to SARS-CoV-2. Moreover, our protocol accommodates use of various blood- and non-blood-derived biospecimens, such as breast milk, as well as dried blood obtained with microsampling cartridges that are appropriate for remote collection. As a result, our RBD-based ELISA protocols are well suited for seroepidemiology and other large-scale studies requiring parsimonious sample collection outside of healthcare settings.

The identification and isolation of highly infectious SARS-CoV-2-infected individuals is an important public health strategy. Rapid antigen detection tests (RADT) are promising tools for large-scale screenings due to timely results and feasibility for on-site testing. Nonetheless, the diagnostic performance of RADT in detecting infectious individuals is not yet fully determined. In this study, RT-qPCR and virus culture of RT-qPCR-positive samples were used to evaluate and compare the performance of the Standard Q COVID-19 Ag test in detecting SARS-CoV-2-infected and possibly infectious individuals. To this end, two combined oro- and nasopharyngeal swabs were collected at a routine SARS-CoV-2 diagnostic center. A total of 2,028 samples were tested, and 118 virus cultures were inoculated. SARS-CoV-2 infection was detected in 210 samples by RT-qPCR, representing a positive rate of 10.36%. The Standard Q COVID-19 Ag test yielded a positive result in 92 (4.54%) samples resulting in an overall sensitivity and specificity of 42.86 and 99.89%, respectively. For adjusted CT values of

Background While the leading symptoms during coronavirus disease 2019 (COVID-19) are acute and the majority of patients fully recover, a significant fraction of patients now increasingly experience long-term health consequences. However, most data available focus on health-related events after severe infection and hospitalisation. We present a longitudinal, prospective analysis of health consequences in patients who initially presented with no or minor symptoms of severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infection. Hence, we focus on mild COVID-19 in non-hospitalised patients. Methods 958 Patients with confirmed SARS-CoV-2 infection were observed from April 6th to December 2nd 2020 for long-term symptoms and SARS-CoV-2 antibodies. We identified anosmia, ageusia, fatigue or shortness of breath as most common, persisting symptoms at month 4 and 7 and summarised presence of such long-term health consequences as post-COVID syndrome (PCS). Predictors of long-term symptoms were assessed using an uni- and multivariable logistic regression model. Findings We observed 442 and 353 patients over four and seven months after symptom onset, respectively. Four months post SARS-CoV-2 infection, 8•6% (38/442) of patients presented with shortness of breath, 12•4% (55/442) with anosmia, 11•1% (49/442) with ageusia and 9•7% (43/442) with fatigue. At least one of these characteristic symptoms was present in 27•8% (123/442) and 34•8% (123/353) at month 4 and 7 post-infection, respectively. A lower baseline level of SARS-CoV-2 IgG, anosmia and diarrhoea during acute COVID-19 were associated with higher risk to develop long-term symptoms. Interpretation The on-going presence of either shortness of breath, anosmia, ageusia or fatigue as long-lasting symptoms even in non-hospitalised patients was observed at four and seven months post-infection and summarised as post-COVID syndrome (PCS). The continued assessment of patients with PCS will become a major task to define and mitigate the socioeconomic and medical long-term effects of COVID-19. Funding COVIM:„NaFoUniMedCovid19"(FKZ: 01KX2021)