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BACKGROUND: Rotator cuff weakness is considered an important risk factor for shoulder injuries in volleyball. OBJECTIVE: To evaluate association of shoulder preseason strength status with shoulder injury occurrence in subsequent season. METHODS: Volleyball players (N= 181; 99 men) from Slovenian 1st and 2nd national league volunteered to participate in this prospective cohort study. Preseason isokinetic testing of the shoulder was conducted at 60∘/s in the concentric mode of contraction over a RoM of 60∘ with five repetitions of internal (IR) and external (ER) rotation. During the subsequent season the players reported shoulders injuries through a weekly questionnaire. RESULTS: During the season we have registered 14 (7.7%) shoulder injuries (10 in men). All injuries affected the dominant shoulder. There was significant preseason weakness of ER and lower ER/IR strength ratio in players with shoulder injury. Normal strength ratio ER/IR was a significant protective factor (Exp (B) = 0.217, 95% C.I. 0.058–0.811) for shoulder injury occurrence when controlled for sex and previous injury. CONCLUSIONS: The inclusion of systematic strengthening of the external rotators of the shoulder is necessary, especially for male volleyball players, as part of preventive measures for the prevention of shoulder injuries.

Background Plasma cell vulvitis (PCV) is an inflammatory vulvar dermatosis that is not well characterized. Diagnosis is often delayed, and the condition can be refractory to treatment. To date, there are no systematic reviews on this topic. Objective This study aimed to provide a systematic review of PCV, including epidemiologic, clinical, and histopathologic findings, as well as associated comorbidities and treatment options. Methods A primary literature search was conducted using the PubMed, Ovid Medline, Cochrane, and CINAHL databases. Results Fifty-three publications with 196 patients (mean age: 55.3 ± 14.5 years) were included. The majority of studies were case reports and case series. Common symptoms included burning/stinging (52%), dyspareunia (44%), and pruritus (41%). Common findings included erythema (84%), glistening/shiny appearance (29%), well-demarcated lesions (25%), and erosions (22%). Common anatomic sites were the labia minora (45%), introitus (31%), and periurethral (19%). Fifty-three percent of patients had a solitary lesion. Common histologic findings were a predominant plasma cell infiltrate (88%), presence of other inflammatory cells (55%), hemosiderin/siderophages (46%), and epidermal atrophy (43%). Topical corticosteroids (64%) and tacrolimus ointment (13%) were the most frequent treatment modalities. In most reports, previous treatments were tried, and there was a diagnostic delay. Conclusion PCV is likely underrecognized and should be considered in patients with erythema of the mucous and modified mucous membranes, symptoms of burning or stinging, and a predominant plasma cell infiltrate on histopathology. First-line therapy should begin with high-potency topical corticosteroids, with the most evidence for clobetasol 0.05% or tacrolimus 0.1% ointment. Prospective studies are needed to further characterize this condition and to develop treatment guidelines.

Breastmilk is considered the optimal nutrition for newborns. US Black women continue to have the lowest breastfeeding initiation and duration rates. This Perspective examines factors associated with breastfeeding disparities and inequities among Black women through the lens of critical race theory and the social-ecological model. Recommendations to increase breastfeeding rates in this population include increased communication and educational strategies by health care professionals, education to recognize implicit bias and systemic racism in our health care system, early prenatal and ongoing postpartum breastfeeding support, increased community support, and breastfeeding groups developed by and for Black women. In addition, equity policies such as paid maternity leave and work policies that support milk expression would provide needed institutional support for women in the workplace.

Children with Clostridioides difficile infection (CDI) can experience recurrent or severe disease. Recurrent CDI occurs in 20%-30% of children with an initial CDI episode. A careful clinical evaluation is important to distinguish recurrent CDI from other disorders that cause recurring gastrointestinal symptoms. Multiple treatment options exist for recurrent CDI, but the optimal therapeutic approach remains undefined. Severe or fulminant CDI can result in poor outcomes and significant morbidity in children. Since there is not a validated definition for severe CDI in children, physicians must use their clinical judgment to identify patients with severe CDI to institute appropriate therapy. In this review, we describe the diagnostic and management challenges in caring for children with recurrent and severe CDI.

As the global population ages, hospital administrators will need to employ a sufficient number of OR nurses to meet the demands of increasing surgical volumes. However, ORs can be intimidating working environments and undergraduate nursing programs lack formal didactic courses in perioperative nursing, leaving little to entice newly graduated nurses to the perioperative specialty. It is important for nurse leaders to employ interventions for recruiting and retaining OR nurses, particularly in specialty service lines, including cardiovascular surgery. A Periop 202 course for open-heart procedures was developed and woven into a cardiovascular OR (CVOR) orientation program for newly graduated nurses and experienced nurses who were new to the CVOR. The program aimed to increase new CVOR nurses' competencies and knowledge of protocols and guidelines for open-heart procedures and their self-efficacy to function on the CVOR team. Knowledge questionnaire and learning scale results showed increased postintervention knowledge and self-efficacy among program participants.

Youth with type 2 diabetes might have suboptimal peak bone mass, but it is unknown whether similar effects are evident in youth with prediabetes. Results from this study suggest that diabetes-related effects on peak bone mass likely occur before disease onset, and involve the muscle-bone unit. Type 2 diabetes might adversely influence bone health around the age of peak bone mass, but it is unknown whether diabetes-related effects on areal bone mineral density (aBMD) are evident in youth with prediabetes. We compared age-related trends in aBMD and associations between lean body mass (LBM) and aBMD between children and adolescents with prediabetes vs. normal glucose regulation. Cross-sectional analysis of data from the National Health and Nutrition Examination Survey (2005–2006) in youth ages 12–20 years (49% female, 34% black) with prediabetes (n = 267) and normal glucose regulation (n = 1664). Whole body aBMD and LBM were assessed via DXA. LBM index (LBMI) and Z-scores for aBMD and LBMI were computed. Unadjusted between-group comparisons revealed greater mean weight and LBMI Z-scores in youth with prediabetes vs. normal glucose regulation, but similar bone Z-scores between the two groups. While accounting for differences in BMI Z-score, there was a significant interaction between prediabetes status and age with respect to whole body aBMD Z-score (P

Treatment of patients with severe burn injuries is complex, relying on attentive fluid resuscitation, successful management of concomitant injuries, prompt wound assessment and closure, early rehabilitation, and compassionate psychosocial care. The goal of fluid resuscitation is to maintain organ perfusion at the lowest possible physiologic cost. This requires careful, hourly titration of the infusion rate to meet individual patient needs, and no more; the risks of over-resuscitation, such as compartment syndromes, are numerous and life-threatening. Recognizing runaway resuscitations and understanding how to employ adjuncts to crystalloid resuscitation are paramount to preventing morbidity and mortality. This article provides an update on fluid resuscitation techniques in burn patients, to include choosing the initial fluid infusion rate, using alternate endpoints of resuscitation, and responding to the difficult resuscitation.

Misidentification delusions are false, fixed beliefs that assign an incorrect identity to a previously familiar or unfamiliar person or place. Such delusions are common in several neuropsychiatric disorders and place a particular burden on individuals with Major Neurocognitive Disorder and their caregivers. No standard pharmacologic or non-pharmacologic treatment approaches have been shown to be consistently effective in addressing this problem. We describe two caregiver-care recipient dyads in which an innovative non-pharmacologic, digital intervention reduced delusional misidentification, improved care recipient behavior, and decreased caregiver burden.

Development of greenways represent a planning strategy that seeks to reconcile both nature conservation and human uses. It is crucial for maintaining landscape connectivity in an increasingly anthropized world. Such strategy encompasses complex socio-ecological variables and its success greatly depends on the integration of different types of knowledge and active support from the local communities and stakeholders. This demands participatory planning processes within multidisciplinary platforms that promote a close collaboration between experts and lay people. The goal of this paper is to describe and analyse a participatory planning approach for the early-stage design of a greenway network for municipalities in South Brazil. The majority of southern Brazilian municipalities contain a very high rate of small farms which are under intensive agricultural production, and consequently, harming the natural landscapes. Actions to effectively tackle this problem are scarcely observed. The procedures encompassed by the approach were determined by the context constraints and potentials that make it applicable in the reality at stake. The approach is focusing on the early-stage design of a greenway network plan and comprises two phases with each a multi-stakeholder workshop for the local landscape analysis and the plan co-design by experts and local actors. The application of the approach in a municipality in southern Brazil has enabled local actors to use key concepts of connectivity planning and foster a critical reflection on local issues, and allowed the incorporation of local knowledge into the solution developed by participants. This resulted in a plan tailored to the local reality.

Zusammenfassung Hintergrund Der Beginn und Frühwarnzeichen von Krankheitsepisoden der bipolaren Störung werden von Betroffenen häufig erst spät erkannt. Je früher eine Krankheitsepisode behandelt wird, desto prognostisch günstiger ist der Verlauf. Die Symptomüberwachung per Smartphone-Applikation (App) könnte eine innovative Möglichkeit darstellen, um Frühwarnzeichen zu erkennen und schneller mit den richtigen Strategien darauf zu reagieren. Das Ziel dieser Studie war es zu evaluieren, ob PatientInnen mit bipolarer Erkrankung und deren Angehörige eine technische Unterstützung durch eine App als sinnvoll und praktikabel in der Früherkennung sowie in der Behandlung erachten. Methoden In der vorliegenden Studie wurden 51 PatientInnen mit bipolarer Störung und 28 Angehörige befragt. Es wurde ermittelt, ob die ProbandInnen Frühwarnzeichen in Form von Verhaltensänderungen derzeit subjektiv ausreichend und rechtzeitig wahrnehmen können. Zudem wurde erhoben, ob die StudienprobandInnen ein Smartphone als Behandlungsunterstützung nutzen würden. Ergebnisse Obwohl sich 94,1% der befragten PatientInnen und 78.6% der Angehörigen gut über die Erkrankung informiert fühlten, waren 13,7% beziehungsweise 35,7% mit den derzeitigen Behandlungsmöglichkeiten nicht zufrieden. Frühwarnzeichen jeder depressiven Entwicklung wurden von 25,5% der PatientInnen wahrgenommen (Angehörige 10,7%). Jede (hypo)manische Entwicklung wurde lediglich von 11,8% der PatientInnen wahrgenommen (Angehörige 7,1%). 88,2% der PatientInnen und 85,7% ihrer Angehörigen bemerkten zu Beginn einer Depression und 70,6% beziehungsweise 67,9% zu Beginn einer (hypo)manischen Episode wiederkehrend dieselben Symptome (insbesondere Veränderungen der körperlichen Aktivität, des Kommunikationsverhaltens und des Schlaf-Wach-Rhythmus). 84,3% der PatientInnen und 89,3% der Angehörigen gaben an, dass sie eine technische Unterstützung, welche auf Veränderungen in Stimmungs- und Aktivitätslage aufmerksam macht, als sinnvoll erachten und dass sie eine Smartphone-App für die Behandlung nutzen würden. Diskussion Die derzeitigen Möglichkeiten zur Wahrnehmung von Frühwarnzeichen einer depressiven oder (hypo)manischen Episode bei bipolarer Störung sind klinisch unzureichend. Bei Betroffenen und Angehörigen besteht der Wunsch nach innovativen, technischen Unterstützungen. Die rechtzeitige Früherkennung von Krankheitssymptomen, die sich oft in Veränderungen von Verhaltens- oder Aktivitätsmustern äußert, ist für den Verlauf essentiell. Apps könnten hierbei durch objektive, kontinuierliche und individuelle Datenerhebung in der Zukunft für die klinische Behandlung und die Forschung genutzt werden.

BACKGROUND Obstructive sleep apnea is associated with increased risk of sudden cardiac death.OBJECTIVE The purpose of this study was to elucidate changes in ventricular repolarization and electromechanical interaction during obstructive respiratory events simulated by intermittent negative upper airway pressure (INAP) in pigs. We also investigated the effect of a reduced repolarization reserve in drug-induced long QT (LQT) following INAP-induced changes in ventricular repolarization.METHODS In sedated spontaneously breathing pigs, 75 seconds of INAP was applied by a negative pressure device connected to the endotracheal tube. Ventricular electromechanical coupling was determined by the electromechanical window (EMW) before (preINAP), during (INAP), and after INAP (post-INAP). Incidence rates of premature ventricular contractions (PVCs) were measured respectively. A drug-induced LQT was modeled by treating the pigs with the hERG1 Mocker dofetilide (DOE).RESULTS Whereas QT interval increased during and decreased after INAP (pre-INAP: 273 +/- 5 ms; INAP 281 +/- 6 ms; post-INAP 254 +/- 9 ms), EMW shortened progressively throughout INAP and post-INAP periods (pre-INAP 81 +/- 4 ms; post-INAP 44 +/- 7 ms). DOF shortened EMW at baseline. Throughout INAP, EMW decreased in a comparable fashion as before DOF (pre-INAP/+DOF 61 +/- 7 ms; post-INAP/+DOF 14 +/- 9 ms) but resulted in shorter absolute EMW levels. Short EMW levels were associated with increased occurrence of PVCs (pre-INAP 7 +/- 2 ms vs post-INAP 26 +/- 6 ms; P = .02), which were potentiated in DOF pigs (pre-INAP/+DOF 5 +/- 2 ms vs post-INAP/+DOF 40 +/- 8 ms; P = .006). Administration of atenolol prevented post-INAP EMW shortening and decreased occurrence of PVCs.CONCLUSION Transient dissociation of ventricular electromechanical coupling during simulated obstructive respiratory events creates a dynamic ventricular arrhythmogenic substrate, which is sympathetically mediated and aggravated by drug-induced LQT.

Systemic sclerosis is a connective tissue disease that presents with significant gastrointestinal involvement, commonly in the esophagus. Dysphagia is a common clinical manifestation of systemic sclerosis and is strongly related to esophageal dysmotility. However, there are multiple other contributing factors in each step in the physiology of swallowing that may contribute to development of severe dysphagia. The oral phase of swallowing may be disrupted by poor mastication due to microstomia and poor dentition, as well as by xerostomia. In the pharyngeal phase of swallowing, pharyngeal muscle weakness due to concurrent myositis or cricopharyngeal muscle tightening due to acid reflux can cause disturbance. The esophageal phase of swallowing is most commonly disturbed by decreased peristalsis and esophageal dysmotility. However, it can also be affected by obstruction from chronic reflux changes, pill-induced esophagitis, or Candida esophagitis. Other contributing factors to dysphagia include difficulties in food preparation and gastroparesis. Understanding the anatomy and physiology of swallowing and evaluating systemic sclerosis patients presenting with dysphagia for disturbances in each step can allow for development of better treatment plans to improve dysphagia and overall quality of life.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) results in a loss of humoral immunity and subsequent risk for severe infections. Thus, re-vaccination is required but may fail due to incomplete immune reconstitution. We retrospectively analyzed predictors of immune response to primary vaccination applied according to the EBMT (European Blood and Marrow Transplantation Group) recommendations. Serologic response to vaccination against diphtheria (D), tetanus (T), Bordetella pertussis (aP) and Haemophilus influenzae (Hib) (administrated as combined DTaP-Hib-IPV vaccination) was studied in 84 alloHSCT patients transplanted between 2008 and 2015 (age at alloHSCT: 18.6-70.6 years). All patients with a relapse-free survival of ≥9 months, at least 3 consecutive vaccinations and absence of intravenous immunoglobulin administration within 3 months before and after vaccination met the primary inclusion criteria. Additionally, immunological response to a pneumococcal conjugate vaccine was analyzed in a subgroup of 67 patients. Patients' characteristics at the time of first vaccination were recorded. Responses were measured as vaccine-specific antibody titers. Regarding DTaP-Hib-IPV vaccination, 89.3% (n = 75) of all patients achieved protective titers to at least 3 of the 4 vaccine components and were thus considered responders. 10.7% (n = 9) of the patients were classified as non-responders with positive immune response to less than 3 components. Highest response was observed for Hib (97.4%), tetanus (95.2%) and pneumococcal vaccination (83.6%) while only 68.3% responded to vaccination against Bordetella pertussis. Significant risk factors for failure of vaccination response included low B cell counts (p 0.001; cut-off: 0.05 B cells/nl) and low IgG levels (p = 0.026; mean IgG of responders 816 mg/dl vs. 475 mg/dl of non-responders). Further, a trend was observed that prior cGvHD impairs vaccination response as 88.9% of the non-responders but only 54.7% of the responders had prior cGvHD (p = 0.073). The results demonstrate, that the currently proposed vaccination strategy leads to seroprotection in the majority of alloHSCT patients.

Contains fulltext : 235298.pdf (Publisher’s version ) (Open Access) Importance: Cardiovascular disease (CVD) is common in patients treated for breast cancer, especially in patients treated with systemic treatment and radiotherapy and in those with preexisting CVD risk factors. Coronary artery calcium (CAC), a strong independent CVD risk factor, can be automatically quantified on radiotherapy planning computed tomography (CT) scans and may help identify patients at increased CVD risk. Objective: To evaluate the association of CAC with CVD and coronary artery disease (CAD) in patients with breast cancer. Design, Setting, and Participants: In this multicenter cohort study of 15915 patients with breast cancer receiving radiotherapy between 2005 and 2016 who were followed until December 31, 2018, age, calendar year, and treatment-adjusted Cox proportional hazard models were used to evaluate the association of CAC with CVD and CAD. Exposures: Overall CAC scores were automatically extracted from planning CT scans using a deep learning algorithm. Patients were classified into Agatston risk categories (0, 1-10, 11-100, 101-399, >400 units). Main Outcomes and Measures: Occurrence of fatal and nonfatal CVD and CAD were obtained from national registries. Results: Of the 15915 participants included in this study, the mean (SD) age at CT scan was 59.0 (11.2; range, 22-95) years, and 15879 (99.8%) were women. Seventy percent (n = 11179) had no CAC. Coronary artery calcium scores of 1 to 10, 11 to 100, 101 to 400, and greater than 400 were present in 10.0% (n = 1584), 11.5% (n = 1825), 5.2% (n = 830), and 3.1% (n = 497) respectively. After a median follow-up of 51.2 months, CVD risks increased from 5.2% in patients with no CAC to 28.2% in patients with CAC scores higher than 400. After adjustment, CVD risk increased with higher CAC score (hazard ratio [HR]CAC = 1-10 = 1.1; 95% CI, 0.9-1.4; HRCAC = 11-100 = 1.8; 95% CI, 1.5-2.1; HRCAC = 101-400 = 2.1; 95% CI, 1.7-2.6; and HRCAC>400 = 3.4; 95% CI, 2.8-4.2). Coronary artery calcium was particularly strongly associated with CAD (HRCAC>400 = 7.8; 95% CI, 5.5-11.2). The association between CAC and CVD was strongest in patients treated with anthracyclines (HRCAC>400 = 5.8; 95% CI, 3.0-11.4) and patients who received a radiation boost (HRCAC>400 = 6.1; 95% CI, 3.8-9.7). Conclusions and Relevance: This cohort study found that coronary artery calcium on breast cancer radiotherapy planning CT scan results was associated with CVD, especially CAD. Automated CAC scoring on radiotherapy planning CT scans may be used as a fast and low-cost tool to identify patients with breast cancer at increased risk of CVD, allowing implementing CVD risk-mitigating strategies with the aim to reduce the risk of CVD burden after breast cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03206333.

Large progress has been made in the last decades to reduce the carbon footprint of ammonia, which is an essential commodity of the food, chemical and energy industry. Apart from alternative routes for green feedstock production, such as hydrogen via electrolysis and nitrogen via solar thermochemical methods, alternatives are explored to replace the Haber-Bosch process. The present article reviews four promising mild condition ammonia production methods: solid state synthesis, molten salt synthesis, thermochemical looping and photocatalytic routes. Contrary to the Haber-Bosch method, which requires high pressures of 200–400 bar, they operate at low-pressures, furthermore such routes open the possibility for direct ammonia production from H2O and N2 without the intermediate hydrogen production step. These advantages allow easier renewable energy integration; however, R&D activities are needed for scaling-up. An analysis is given on renewable energy integration with focus on solar resources both in the form of electricity and heat.

Les patients atteints de pneumopathie grave dans le cadre de COVID-19 sont à haut risque de complications thrombotiques, en rapport avec une coagulopathie induite par le SARS-CoV-2, ce qui aggrave leur pronostic. Les mécanismes physiopathologiques de cette coagulopathie incluent une dysfonction endothéliale en partie expliquée par un état hyper-inflammatoire et l’activation de la coagulation qui en découle. Les bilans standards d’hémostase ne semblent pas suffisants pour évaluer ce sur-risque thrombotique et la thromboprophylaxie de ces patients doit probablement être renforcée.

This article describes the innovative nurse retentionist role that a large academic medical health system in the southeastern United States implemented to improve nurse retention. The program leveraged 5 key strategies to drive results. Example outcomes during the first 2 years include a 27% increase in clinical ladder participation, a 43% clinical ladder advancement, and an 187% increase in ambulatory nurse recognition. Internal promotions increased 31%. Participation in nursing career development increased 294%. Extern program increased 420%, and 77 nurse residents were retained that initially considered resignation. Nurse turnover dropped to 11.8% with the retention of 254 nurses.

In a notoriously obscure passage in Metaphysics 7.1 Aristotle claims that substance is primary in time. The only concrete literal interpretation suggested so far of this controversial claim is in terms of existing before and after in time. I argue that this interpretation faces serious problems. I then present a novel literal interpretation, in terms of being an appropriate subject of temporal predications, that is immune to these problems and strongly supported by philosophical and contextual considerations.

After the introduction of Persistent Memory in the form of Intel’s Optane DC Persistent Memory on the market in 2019, it has found its way into manifold applications and systems. As Google and other cloud infrastructure providers are starting to incorporate Persistent Memory into their portfolio, it is only logical that cloud applications have to exploit its inherent properties. Persistent Memory can serve as a DRAM substitute, but guarantees persistence at the cost of compromised read/write performance compared to standard DRAM. These properties particularly affect the performance of index structures, since they are subject to frequent updates and queries. However, adapting each and every index structure to exploit the properties of Persistent Memory is tedious. Hence, we require a general technique that hides this access gap, e.g., by using DRAM caching strategies. To exploit Persistent Memory properties for analytical index structures, we proposeselective caching. It is based on a mixture of dynamic and static caching of tree nodes in DRAM to reach near-DRAM access speeds for index structures. In this paper, we evaluate selective caching on the OLAP-optimized main-memory index structure Elf, because its memory layout allows for an easy caching. Our experiments show that if configured well, selective caching with a suitable replacement strategy can keep pace with pure DRAM storage of Elf while guaranteeing persistence. These results are also reflected when selective caching is used for parallel workloads.

Successful exams require a balance of easy, medium, and difficult questions. Question difficulty is generally either estimated by an expert or determined after an exam is taken. The latter provides no utility for the generation of new questions and the former is expensive both in terms of time and cost. Additionally, it is not known whether expert prediction is indeed a good proxy for estimating question difficulty. In this paper, we analyse and compare two ontology-based measures for difficulty prediction of multiple choice questions, as well as comparing each measure with expert prediction (by 15 experts) against the exam performance of 12 residents over a corpus of 231 medical case-based questions that are in multiple choice format. We find one ontology-based measure (relation strength indicativeness) to be of comparable performance (accuracy = 47%) to expert prediction (average accuracy = 49%).

The clinical differentiation of face and scalp lesions (FSLs) is challenging even for trained dermatologists. Studies comparing the diagnostic performance of a convolutional neural network (CNN) with dermatologists in FSL are lacking.A market-approved CNN (Moleanalyzer-Pro, FotoFinder Systems) was used for binary classifications of 100 dermoscopic images of FSL. The same lesions were used in a two-level reader study including 64 dermatologists (level I: dermoscopy only; level II: dermoscopy, clinical close-up images, textual information). Primary endpoints were the CNN's sensitivity and specificity in comparison with the dermatologists' management decisions in level II. Generalizability of the CNN results was tested by using four additional external data sets.The CNN's sensitivity, specificity and ROC AUC were 96.2% [87.0%-98.9%], 68.8% [54.7%-80.1%] and 0.929 [0.880-0.978], respectively. In level II, the dermatologists' management decisions showed a mean sensitivity of 84.2% [82.2%-86.2%] and specificity of 69.4% [66.0%-72.8%]. When fixing the CNN's specificity at the dermatologists' mean specificity (69.4%), the CNN's sensitivity (96.2% [87.0%-98.9%]) was significantly higher than that of dermatologists (84.2% [82.2%-86.2%]; p 0.001). Dermatologists of all training levels were outperformed by the CNN (all p 0.001). In confirmation, the CNN's accuracy (83.0%) was significantly higher than dermatologists' accuracies in level II management decisions (all p 0.001). The CNN's performance was largely confirmed in three additional external data sets but particularly showed a reduced specificity in one Australian data set including FSL on severely sun-damaged skin.When applied as an assistant system, the CNN's higher sensitivity at an equivalent specificity may result in an improved early detection of face and scalp skin cancers.

Despite increasing interest in how artificial intelligence (AI) can augment and improve healthcare delivery, the development of new AI models continues to outpace adoption in existing healthcare processes. Integration is difficult because current approaches separate the development of AI models from the complex healthcare environments in which they are intended to function, resulting in models developed without a clear and compelling use case and not tested or scalable in a clinical setting. We propose that current approaches and traditional research methods do not support successful AI implementation in healthcare and outline a repeatable mixed-methods approach, along with several examples, that facilitates uptake of AI technologies into human-driven healthcare processes. Unlike traditional research, these methods do not seek to control for variation, but rather understand it to learn how a technology will function in practice coupled with user-centered design techniques. This approach, leveraging design thinking and quality improvement methods, aims to increase the adoption of AI in healthcare and prompt further study to understand which methods are most successful for AI implementations.

PurposeTo investigate the dosimetric impact of breathing motion on robustly optimized proton therapy treatment plans for left-sided breast cancer patients with an indication for locoregional irradiation.Materials and methodsClinical Target Volumes (CTVs) (left-sided breast, level 1 to 4 axillary lymph nodes, interpectoral and internal mammary lymph node regions) and organs at risk were delineated on 4 D-CTs of ten female patients. After treatment planning to a prescribed dose of 40.05 Gy(RBE) in 15 fractions on the time-averaged CT, the dose was calculated on all ten phases of the breathing cycle. Robustness to setup (5 mm) and range errors (3%) was evaluated for those ten phases. Correlations were evaluated between the phases of the breathing cycle and the D98% of the CTV and the D-mean of the heart.ResultsCorrelations coefficients were between -0.12 and 0.29. At the most extreme values of the 28 robustness scenarios, the clinical goals were met for all but two patients. The mean heart dose was 0.41 Gy(RBE) with a standard deviation of 0.31 Gy(RBE) of proton therapy plans.ConclusionThe effect of breathing motion on the robustness of proton therapy treatment plans for this patient group is minor and not of clinical significance. Based on this patient group, a deep-inspiration breath hold seems to be unnecessary to improve robustness for these patients.

Psychologists housed in two family medicine residency clinics located in underserved communities quickly transitioned their mode of psychotherapy from in-person to completely virtual at the beginning of the COVID-19 pandemic. We share numerous successes and advantages of a telehealth model in serving our community and describe challenges we have encountered.

Background Thromboprophylaxis of COVID-19 patients is a highly debated issue. We aimed to compare the occurrence of thrombotic/ischemic events in COVID-19 patients with acute respiratory distress syndrome (ARDS) treated with either prophylactic or therapeutic dosage of heparin. All patients referred for COVID-19 ARDS in two intensive care units (ICUs) from two centers of a French tertiary hospital were included in our cohort study. Patients were compared according to their anticoagulant treatment to evaluate the risk/benefit of prophylactic anticoagulation versus therapeutic anticoagulation. Medical history, symptoms, biological data and imaging were prospectively collected. Results One hundred and seventy-nine patients (73% men) were analyzed: 108 in prophylactic group and 71 in therapeutic group. Median age and SAPS II were 62 [IQR 51; 70] years and 47 [IQR 37; 63] points. ICU mortality rate was 17.3%. Fifty-seven patients developed clinically relevant thrombotic complications during their ICU stay, less frequently in therapeutic group (adjusted OR 0.38 [0.14–0.94], p = 0.04). The occurrences of pulmonary embolism (PE), deep vein thrombosis (DVT) and ischemic stroke were significantly lower in the therapeutic group (respective adjusted OR for PE: 0.19 [0.03–0.81]; DVT: 0.13 [0.01–0.89], stroke: 0.06 [0–0.68], all p Conclusion Increasing the anticoagulation of severe COVID-19 patients to a therapeutic level might decrease thrombotic complications without increasing their bleeding risk.

forma são planejados os cuidados preventivos para lesão por pressão em pacientes internados nas unidades de terapia intensiva (UTI). Métodos: Trata-se de uma revisão integrativa da literatura nacional, em um recorte temporal de cinco anos. Foram selecionados 11 artigos com a combinação dos descritores: “Lesão por pressão, “Unidade de Terapia Intensiva”, “Cuidados de Enfermagem”. A busca pelos artigos foi realizada nas bases de dados BVS, Lilacs, PubMed e Ibecs. Resultados: após um processo de seis etapas de filtragem de buscas, foram selecionados 11 artigos para a construção da revisão integrativa, possibilitando os autores elucidar estudos que puderam contribuir para o ajuste dos vieses da prática profissional de enfermagem. Conclusão: Com esse estudo pôde-se concluir que mediante a revisão de literatura bibliografica, os desafios são amplos em prevenir a lesão por pressão no ambiente de terapia intensiva, visto que necessitamos de qualificação profissional, desenvolvimento de competências, gerenciamento do tempo, gerenciamento de recursos humanos, adesão ao planejamento da assistência.

Background Reaching an appropriate physical activity level (PAL) in adolescence is an important public health problem. This study aimed to evaluate factors associated with PAL and changes in PAL in late adolescence. Material and Methods The sample involved 411 adolescents (201 girls) who were 16 years of age at study baseline; the participants completed a structured validated questionnaire at baseline (the beginning of the third grade of high school) and again at follow-up (the end of the fourth grade; when they were 18 years of age). Variables were obtained at both testing waves and included the following predictors: sociodemographic indices (sex, socioeconomic status, parental education), sports factors (participation in individual and team sports, competitive sports achievement, experience in sports), and PAL (the primary outcome), which was measured using the Physical Activity Questionnaire for Adolescents . Results A significant decrease in PAL between baseline and follow-up testing was evidenced (t-test = 6.17, p < 0.001). A logistic regression model calculated with a dichotomized outcome (normal PAL vs. low PAL), and sex as a covariate, showed a significant influence of participation in team sports and maternal education on PAL, both at baseline (OR = 1.56, 95% CI: 1.11–1.87; OR = 1.38, 95% CI: 1.02–1.90) and at follow-up (OR = 1.45, 95% CI: 1.01–1.90; OR = 1.35, 95% CI: 1.08–1.70, for team sports and maternal education, respectively). Conclusions The study confirmed certain associations between the studied variables and PAL, but there was no significant influence of the observed indicators on changes in PAL in late adolescence. Further studies evaluating other predictors of changes in PAL are warranted. Med Pr. 2020;71(6):637–47

Background In recent studies, convolutional neural networks (CNNs) outperformed dermatologists in distinguishing dermoscopic images of melanoma and nevi. In these studies, dermatologists and artificial intelligence were considered as opponents. However, the combination of classifiers frequently yields superior results, both in machine learning and among humans. In this study, we investigated the potential benefit of combining human and artificial intelligence for skin cancer classification. Methods Using 11,444 dermoscopic images, which were divided into five diagnostic categories, novel deep learning techniques were used to train a single CNN. Then, both 112 dermatologists of 13 German university hospitals and the trained CNN independently classified a set of 300 biopsy-verified skin lesions into those five classes. Taking into account the certainty of the decisions, the two independently determined diagnoses were combined to a new classifier with the help of a gradient boosting method. The primary end-point of the study was the correct classification of the images into five designated categories, whereas the secondary end-point was the correct classification of lesions as either benign or malignant (binary classification). Findings Regarding the multiclass task, the combination of man and machine achieved an accuracy of 82.95%. This was 1.36% higher than the best of the two individual classifiers (81.59% achieved by the CNN). Owing to the class imbalance in the binary problem, sensitivity, but not accuracy, was examined and demonstrated to be superior (89%) to the best individual classifier (CNN with 86.1%). The specificity in the combined classifier decreased from 89.2% to 84%. However, at an equal sensitivity of 89%, the CNN achieved a specificity of only 81.5% Interpretation Our findings indicate that the combination of human and artificial intelligence achieves superior results over the independent results of both of these systems.

The past 25 years have seen many attempts to introduce defeasible-reasoning capabilities into a description logic setting. Many, if not most, of these attempts are based on preferential extensions of description logics, with a significant number of these, in turn, following the so-called KLM approach to defeasible reasoning initially advocated for propositional logic by Kraus, Lehmann, and Magidor. Each of these attempts has its own aim of investigating particular constructions and variants of the (KLM-style) preferential approach. Here our aim is to provide a comprehensive study of the formal foundations of preferential defeasible reasoning for description logics in the KLM tradition. We start by investigating a notion of defeasible subsumption in the spirit of defeasible conditionals as studied by Kraus, Lehmann, and Magidor in the propositional case. In particular, we consider a natural and intuitive semantics for defeasible subsumption, and we investigate KLM-style syntactic properties for both preferential and rational subsumption. Our contribution includes two representation results linking our semantic constructions to the set of preferential and rational properties considered. Besides showing that our semantics is appropriate, these results pave the way for more effective decision procedures for defeasible reasoning in description logics. Indeed, we also analyse the problem of non-monotonic reasoning in description logics at the level of entailment and present an algorithm for the computation of rational closure of a defeasible knowledge base. Importantly, our algorithm relies completely on classical entailment and shows that the computational complexity of reasoning over defeasible knowledge bases is no worse than that of reasoning in the underlying classical DL ALC .

Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). So far, viral targets of cellular immunity and factors determining successful mounting of T cell responses are poorly defined. We therefore analyzed cellular responses to membrane, nucleocapsid, and spike proteins in individuals suffering from moderate or severe infection and in individuals who recovered from mild disease. We demonstrate that the CoV-2-specific CD4+ T helper cell response is directed against all 3 proteins with comparable magnitude, ex vivo proliferation, and portions of responding patients. However, individuals who died were more likely to have not mounted a cellular response to the proteins. Higher patient age and comorbidity index correlated with increased frequencies of CoV-2-specific CD4+ T cells, harboring higher portions of IL-2-secreting, but lower portions of IFN-γ-secreting, cells. Diminished frequencies of membrane protein-reactive IFN-γ+ T cells were particularly associated with higher acute physiology and chronic health evaluation II scores in patients admitted to intensive care. CoV-2-specific T cells exhibited elevated PD-1 expression in patients with active disease as compared with those individuals who recovered from previous mild disease. In summary, our data suggest a link between individual patient predisposition with respect to age and comorbidity and impairment of CoV-2-specific Th1-type cellular immunity, thereby supporting a concept of altered T cell function in at-risk patients.

Background The role of inpatient rehabilitation after total knee arthroplasty (TKA) remains uncertain, with evidence suggesting no better functional outcomes for those who discharge to rehabilitation to those who discharge home. The aim of this study is to develop and implement a pre-operative predictive tool, ARISE (Arthroplasty Rehabilitation Initial Screening Evaluation), that incorporated psychological, functional, and socio-demographic factors to determine discharge destination. Methods One week prior to TKA, the ARISE tool was administered to 100 patients, in addition to an EQ-5D-5L survey and other demographic data being recorded. The primary outcome was discharge destination. An enhanced recovery pathway, which included an anesthetic protocol designed to optimize early mobilization, was utilized. Univariable and multivariable logistic regression analysis was performed to determine the likelihood of discharge destination. Results Patients in the rehabilitation group were, on average, 4.5 years older than the home group (P = .036). After multivariable regression, ARISE questions were predictive of discharge destination related to beliefs around the superiority of inpatient rehabilitation (odds ratio = 9.9 [2.6-37.9]) and post-discharge level of support (odds ratio = 6.3 [1.5-26.8]). No question around self-reported physical function was predictive. Conclusion Pre-operative patient beliefs regarding rehabilitation and future home support are highly predictive of discharge destination after primary TKA. Pre-operative patient-reported functional status and demographic variables, with the exception of increasing age, were not shown to be predictive. Predicting those that are most likely to discharge to rehabilitation allows for early, targeted interventions to optimize resources and increase likelihood of home discharge.

Concentrated solar thermal technology is considered a very promising renewable energy technology due to its capability of producing heat and electricity and of its straightforward coupling to thermal storage devices. Conventionally, this approach is mostly used for power generation. When coupled with the right conversion process, it can be also used to produce methanol. Indeed methanol is a good alternative fuel for high compression ratio engines. Its high burning velocity and the large expansion occurring during combustion leads to higher efficiency compared to operation with conventional fuels. This study is focused on the system level modeling of methanol production using hydrogen and carbon monoxide produced with cerium oxide solar thermochemical cycle which is expected to be CO2 free. A techno-economic assessment of the overall process is done for the first time. The thermochemical redox cycle is operated in a solar receiver-reactor with concentrated solar heat to produce hydrogen and carbon monoxide as the main constituents of synthesis gas. Afterwards, the synthesis gas is turned into methanol whereas the methanol production process is CO2 free. The production pathway was modeled and simulations were carried out using process simulation software for MW-scale methanol production plant. The methanol production from synthesis gas utilizes plug-flow reactor. Optimum parameters of reactors are calculated. The solar methanol production plant is designed for the location Almeria, Spain. To assess the plant, economic analysis has been carried out. The results of the simulation show that it is possible to produce 27.81 million liter methanol with a 350 MWth solar tower plant. It is found out that to operate this plant at base case scenario, 880685 m2 of mirror's facets are needed with a solar tower height of 220 m. In this scenario a production cost of 1.14 €/l Methanol is predicted.

Apart from being a major feedstock for chemical production, hydrogen is also a very promising energy carrier for the future energy. Currently hydrogen is predominantly produced via fossil routes, but as green energy sources are gaining a larger role in the energy mix, novel and green production routes are emerging. The most abundant renewable hydrogen sources are water and biomass, which allow several possible processing routes, such as electrolysis, thermochemical cycles and gasification. By introducing heat to the process the required electricity demand can be reduced (high temperature electrolysis) or practically eliminated (thermochemical cycles). Each renewable hydrogen production route has its own strength and weaknesses; the choice of the most suitable method is always dependent on the economical potentials and the location. The aim of this paper is to evaluate the different high temperature, renewable hydrogen production technologies.

Solar thermochemical water splitting was successfully demonstrated with monolithic receiver-reactors in field at 50 kW scale. Since monolithic receiver-reactors are limited in size, several of the reactors will have to be combined in receiver-reactor arrays for large-scale plants. In this study, the yearly performance of solar thermochemical plants for hydrogen production implementing receiver-reactor arrays is investigated. Thereto, a transient receiver-reactor model is used in combination with realistic hourly flux profiles from dedicated MW high temperature solar concentrator systems. The batched operation of receiver-reactors leads to particular requirements of the array. Therefore, an array efficiency is introduced and different control strategies for the solar field are analyzed for performance optimization. Advanced strategies have the potential to substantially (~46%) improve the overall performance compared to the base case. Further design and operational optimization approaches are discussed, which allow approaching the theoretical array performance limit.

Background General practitioners play a vital and increasing part in the perioperative care of patients undergoing total knee replacement (TKR). Rising obesity rates, sports-related injuries and an ageing population are likely to result in a sharp increase in TKR procedures within the next decade, combined with higher cost concerns. Rehabilitation practices that show economic efficiency and produce superior patient outcomes are a major focus of current research. Objective The aim of this article is to provide an evidence-based summary of current rapid recovery protocols following TKR surgery. Discussion Rapid recovery protocols have been shown to be effective at reducing length of stay, postoperative pain and complications without compromising patient safety. These rapid recovery protocols include same-day mobilisation; blood preservation protocols; self-directed pedalling-based rehabilitation; and individualised targeted discharge to self-directed, outpatient therapist-directed or inpatient therapist-directed rehabilitation. Low-cost self-directed rehabilitation should be considered usual care, with inpatient rehabilitation reserved for the minority of at-risk patients.

The COVID-19 pandemic exposed numerous deficiencies of the U.S. primary care infrastructure. The system is overstretched with little to no surge capacity to deal with crisis situations, its reach restrained due to overreliance on brick and mortar clinics, and its behavior overwhelmingly more reactive than preventive. As delivery systems reorganize on the fly to fight COVID-19, many are turning to tools like telemedicine, pre-visit planning, and centralized population health programs. We propose how these rapid transformations happening across the country, born out of necessity, present a silver lining opportunity to fix primary care. We describe how integrating telemedicine, patient-generated data, and preventive care into a retooled intake and care optimization process is achievable through an approach powered by humans and augmentable with artificial intelligence. Primary care must retool to meet the challenge of COVID-19 and emerge in the post-crisis world better equipped to care for a wounded nation. Our collective willingness to invest in primary care teams, relaxation of rules around telemedicine reimbursement and patient-generated data sharing, workforce training, and movement to value-based payments are necessary to achieve this vision.

Pridopidine is an investigational drug in late stage development for the treatment of Huntington disease and originally postulated to act as dopamine stabilizer by modulating dopamine-dependent motor behavior. However, preclinical studies show pridopidine has highest affinity to sigma-1 receptors. Importantly, mediated by sigma-1 receptors, pridopidine has neuroprotective properties and enhances neuronal plasticity. The aim of our study was to determine the in-vivo the target engagement (receptor occupancy) of pridopidine at clinically relevant doses in healthy volunteers and Huntington disease patients. We used sigma-1 receptor-specific (S)-(-)-[18F]Fluspidine and dopamine D2/D3 receptor-specific [18F]Fallypride PET imaging to quantify the sigma-1 and dopamine D2/D3 receptor occupancy of pridopidine. Eleven male healthy volunteers (pridopidine 0.5 to 90 mg in six dose groups) and three male Huntington disease patients (pridopidine 90 mg) were studied twice before and 2h following single oral doses of pridopidine using S-(-)-[18F]Fluspidine PET (300 MBq, 0-90min p.i.). Distribution volume VT was quantified using kinetic modeling (One-tissue compartment model; metabolite correction). Four male healthy volunteers were studied twice using [18F]Fallpride PET (200 MBq, 0-210min p.i.) before and 2h after a single oral dose of pridopidine (90 mg). Binding potential BPND was assessed by the simplified reference model. Volume-of-interest analyses were performed. For each subject/tracer, the receptor occupancy was calculated by the Lassen plot analysis. In healthy volunteers, there was high sigma-1 receptor occupancy (87 to 91%) across all brain regions at doses ranging from 22.5 to 90 mg. The sigma-1 receptor occupancy was 43% at 1 mg pridopidine. In Huntington disease patients, very similar to healthy volunteers, at 90 mg pridopidine, there was high sigma-1 receptor occupancy (87±7%, n.s.). In contrast, in healthy volunteers, there was only negligible dopamine D2/D3 receptor occupancy (3±2%) at 90 mg pridopidine. We established a sigmoid-shaped dose/sigma-1 receptor occupancy relation (Hill equation) with Hill coefficient larger than 1 in healthy volunteers, suggesting a positive cooperative binding nature of the sigma-1 receptor. Using PET, we report for the first time in the living human brain that after a single dose of 90 mg, pridopidine acts as a selective sigma-1 receptor ligand showing near to complete sigma-1 receptor occupancy (~90%) but only minimal (~3%) dopamine D2/D3 receptor occupancy. Our findings provide significant clarification about pridopidine’s mechanism of action and support further use of the 45 mg bidaily dose to achieve full and selective targeting of the sigma-1 receptor in future clinical trials in Huntington disease and amyotrophic lateral sclerosis.

Introduction: Despite program efforts to encourage use of clean cookstoves and fuels to mitigate climate change, many communities continue to use wood-fueled open fires. Objectives: Describe experiences of participants with mixed use of cooking and fuel technologies (e.g. open fires and chimney stoves using wood and liquefied petroleum gas (LPG) stoves) in rural Lambayeque, Peru in 2018. Material and methods: Fifteen participants were interviewed using a qualitative exploratory research design. Data was collected through semi-structured interviews and analyzed using thematic content analysis. Results: Four categories emerged: decisions about acquiring cooking fuels are primarily based on cost; plastic trash is used to light wood-burning stoves; decisions to use gas over wood are based on quick food cooking time; and benefits and health problems are recognized, but mixed use of fuels persist. Conclusion: Use of both traditional wood cookstoves and plastic trash to ignite fires were used frequently because both are free or cheap. The environmental impact of cutting down trees isn't considered important, but interviewees did notice detriments to their wellbeing. Although gas stoves are used and benefits were mentioned, use of traditional stoves persists. We recommend that policy makers in Peru begin to address barriers to full adoption of new clean cooking technologies and consider governmental subsidies to meet families' spending priorities. Introducción: A pesar de los esfuerzos del programa para alentar el uso de estufas y combustibles limpios para mitigar el cambio climático, muchas comunidades continúan utilizando fuegos abiertos a leña. Objetivo: Describa las experiencias de los participantes con el uso mixto de la cocina y las tecnologías de combustible (por ejemplo, fuegos abiertos y estufas de chimenea que usan estufas de leña y gas licuado de petróleo (GLP)) en la zona rural de Lambayeque, Perú, en 2018. Material y métodos: Quince participantes fueron entrevistados utilizando un diseño de investigación exploratoria cualitativa. Los datos se recopilaron a través de entrevistas semiestructuradas y se analizaron mediante análisis de contenido temático. Resultados: Surgieron cuatro categorías: las decisiones sobre la adquisición de combustibles para cocinar se basan principalmente en el costo; la basura plástica se usa para encender estufas de leña; las decisiones de usar gas sobre la madera se basan en el tiempo de cocción de comida rápida; y se reconocen los beneficios y los problemas de salud, pero persiste el uso mixto de combustibles. Conclusión: El uso de estufas de leña tradicionales y basura plástica para encender incendios se usaba con frecuencia porque ambos son gratuitos o baratos. El impacto ambiental de la tala de árboles no se considera importante, pero los entrevistados notaron daños en su bienestar. Aunque se usan estufas de gas y se mencionaron los beneficios, el uso de estufas tradicionales persiste. Recomendamos que los encargados de formular políticas en Perú comiencen a abordar las barreras para la adopción total de nuevas tecnologías de cocina limpia y consideren los subsidios gubernamentales para cumplir con las prioridades de gasto de las familias.

Background and Purpose: Inhibition of the G-protein gated ACh-activated inward rectifier potassium current, I-K,I-ACh may be an effective atrial selective treatment strategy for atrial fibrillation (AF). Therefore, the anti-arrhythmic and electrophysiological properties of a novel putatively potent and highly specificI(K,ACh)inhibitor, XAF-1407 (3-methyl-1-[5-phenyl-4-[4-(2-pyrrolidin-1-ylethoxymethyl)-1-piperidyl]thieno[2,3-d]pyrimidin-6-yl]azetidin-3-ol), were characterised for the first time in vitro and investigated in horses with persistent AF.Experimental Approach: The pharmacological ion channel profile of XAF-1407 was investigated using cell lines expressing relevant ion channels. In addition, eleven horses were implanted with implantable cardioverter defibrillators enabling atrial tachypacing into self-sustained AF. The electrophysiological effects of XAF-1407 were investigated after serial cardioversions over a period of 1 month. Cardioversion success, drug-induced changes of atrial tissue refractoriness, and ventricular electrophysiology were assessed at baseline (day 0) and days 3, 5, 11, 17, and 29 after AF induction.Key Results: XAF-1407 potently and selectively inhibited K(ir)3.1/3.4 and K(ir)3.4/3.4, underlying theI(K,ACh)current. XAF-1407 treatment in horses prolonged atrial effective refractory period as well as decreased atrial fibrillatory rate significantly (similar to 20%) and successfully cardioverted AF, although with a decreasing efficacy over time. XAF-1407 shortened atrioventricular-nodal refractoriness, without effect on QRS duration. QTc prolongation (4%) within 15 min of drug infusion was observed, however, without any evidence of ventricular arrhythmia.Conclusion and Implications: XAF-1407 efficiently cardioverted sustained tachypacing-induced AF of short duration in horses without notable side effects. This supportsI(K,ACh)inhibition as a potentially safe treatment of paroxysmal AF in horses, suggesting potential clinical value for other species including humans.

Aims Impaired myocardial sympathetic innervation assessed by 123Iodine-Metaiodobenzylguanidine (123I-MIBG) scintigraphy is associated with cardiac events. Since regional disparities of structural abnormalities are common in inherited arrhythmia syndromes (iAS), a chamber-specific innervation assessment of the right (RV) and left ventricle (LV) could provide important insights for a patient-individual therapy. Aim of this study was to evaluate chamber-specific patterns of autonomic innervation by Single-photon emission computed tomography/computed tomography (SPECT/CT) in patients with iAS with respect to clinical outcome regarding cardiac events. Methods and results We assessed ventricular sympathetic innervation (LV, RV and planar heart/mediastinum-ratios, and washout-rates) by 123I-MIBG-SPECT/CT in 48 patients (arrhythmogenic right ventricular cardiomyopathy [ARVC], n = 26; laminopathy, n = 8; idiopathic ventricular fibrillation [iVF], n = 14) in relation to a composite clinical endpoint (ventricular arrhythmia; cardiac death; cardiac hospitalization). RV tracer uptake was lower in patients with ARVC than in laminopathy and iVF patients (1.7 ± 0.4 vs. 2.1 ± 0.7 and 2.1 ± 0.5, respectively). Over a median follow-up of 2.2 years, the combined endpoint was met in 18 patients (n = 12 ventricular tachyarrhythmias, n = 5 hospitalizations, n = 1 death). LV, but not RV H/M ratio was associated with the combined endpoint (hazard-ratio 2.82 [1.30–6.10], p Conclusion We demonstrated that chamber-specific 123MIBG-SPECT/CT imaging is feasible and that reduced LV sympathetic innervation was associated with worse outcome in iAS. These findings provide novel insights into the potential role of regional autonomic nervous system heterogeneity for the evolution of life-threatening cardiac events in iAS.

Gerhard Sattler,1 Martina Kerscher,2 Ernst Magnus Noah,3 Welf Prager,4 Tanja C Fischer,5 Patricia Ogilvie,6 Matthias Hofmann,7 Hanna Dersch,7 Gemma Odena8 1Rosenparkklinik GmbH, Darmstadt, Germany; 2Division of Biochemistry and Molecular Biology, Cosmetic Science, University of Hamburg, Hamburg, Germany; 3Department of Plastic, Reconstructive, Aesthetic and Hand Surgery, Kassel, Germany; 4Prager & Partner Dermatologische Praxis, Hamburg, Germany; 5Haut- Und Lasercentrum Berlin-Potsdam, Potsdam, Germany; 6SkinConcept, Munich, Germany; 7Merz Pharmaceuticals GmbH, Frankfurt Am Main, Germany; 8Merz North America, Inc., Raleigh, NC, USACorrespondence: Gerhard Sattler Email gerhard.sattler@rosenparkklinik.deBackground: Facial aging is characterized by increased prominence of nasolabial folds (NLFs), marionette lines, and thinning of the lips. Cross-linked hyaluronic acid injection is a very effective method for the temporary correction of these areas.Objective: To confirm the clinical performance and the safety of Etermis 3 (ET3) and/or Etermis 4 (ET4) in the treatment of moderate and severe wrinkles/folds, as well as lip volume enhancement.Methods: Subjects were treated in at least two facial areas (NLFs, marionette lines, lips). ET3 was used in facial moderate wrinkles while ET4 was used in severe facial skin volume loss. An optional touch-up 1 month after treatment was possible. A blinded investigator assessed improvement on Merz Aesthetic Scales (MAS). Subjects were followed-up for 12 months after the last treatment.Results: In total, 154 healthy subjects were enrolled. The proportion of subjects achieving ≥ 1 score improvement in MAS after treatment was above 60% for ET4 (Month 6/7: NLFs 94.9% and marionette lines 81.4%, p≤ 0.0004; Month 3/4: lips 63.0%, p=0.39) and ET3 (Month 6/7: marionette lines 79.4%, p=0.0005; Month 3/4: lips 65.5%, p=0.31). Facial improvement was still visible at Month 12/13 for ET4 (NLFs ≥ 76.6%, marionette lines ≥ 61%, lips ≥ 36%) and ET3 (marionette lines ≥ 50% and lips ≥ 21.9%). No treatment-related serious AEs occurred. The most frequent AEs were injection-site reactions.Conclusion: Etermis 3 and Etermis 4 demonstrated good clinical performance and safety for NLFs and marionette lines volume enhancement for up to 12 months. Both products can also be used safely to treat lips for volume augmentation.Keywords: hyaluronic acid, wrinkles, facial volume enhancement

In response to the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), researchers are expeditiously searching for antiviral treatments able to alleviate the symptoms of infection, which can be life-threatening. Here, we provide a general overview of what is currently known about the structure and characteristic features of SARS-CoV-2, some of which could potentially be exploited for the purposes of antiviral therapy and vaccine development. This minireview also covers selected and noteworthy antiviral agents/supportive therapy out of hundreds of drugs that are being repurposed or tested as potential treatments for COVID-19, the disease caused by SARS-CoV-2.