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Stroke is the second leading cause of death and the third leading cause of disability worldwide and its burden is increasing rapidly in low-income and middle-income countries, many of which are unable to face the challenges it imposes. In this Health Policy paper on primary stroke prevention, we provide an overview of the current situation regarding primary prevention services, estimate the cost of stroke and stroke prevention, and identify deficiencies in existing guidelines and gaps in primary prevention. We also offer a set of pragmatic solutions for implementation of primary stroke prevention, with an emphasis on the role of governments and population-wide strategies, including task-shifting and sharing and health system re-engineering. Implementation of primary stroke prevention involves patients, health professionals, funders, policy makers, implementation partners, and the entire population along the life course.

We characterized the profile of Crohn’s disease (CD) or ulcerative colitis (UC) biologic-naive patients (starting a new therapy with vedolizumab or TNFα-antagonists), their baseline disease activity predictors, and their perception of the quality of life (HRQoL). The VEDOIBD-Study is a real-world study on the effectiveness of vedolizumab vs other biologics as induction and maintenance therapy for CD and UC. A total of 627 CD and 546 UC patients were enrolled from IBD-experienced centers across Germany. In both biologic-naive vedolizumab (n=397) and anti-TNF (n=359) patients, CD and UC disease severity and HRQoL predictors were analyzed with logistic regression. The results were reported as odds ratio (OR) and 95% confidence interval (CI). When compared to biologic-naive anti-TNF patients, a first biological therapy with vedolizumab was considered for older CD patients, with a less complicated though longer disease course, and with a history of comorbidities. No differences in (unmet) needs were observed among patients with UC. The presence of extra-intestinal manifestations in biologic-naive anti-TNF patients with CD (OR (95% CI): 3.83 (1.69–8.68)) and, in both biologic-naive groups of patients with UC, stool frequency (2.00 (1.25–3.19); 1.82 (1.10–3.02), respectively) and rectal bleeding (2.24 (1.20–4.18); 1.92 (1.19–3.11), respectively) emerged as the most important predictors of disease severity, which in turn were also significantly associated with a worse HRQoL. This study highlights the existence of unmet medical needs of patients with CD or UC, for whom a new biological therapy is planned as part of the VEDOIBD-Study, which considerably impacts their HRQoL.

Highlights •MR continues to be a challenge encountered in clinical practice. If left untreated, the effects are far reaching with LV volume overload, pulmonary hypertension, and potentially progression into severe heart failure. Many patients are not routinely offered surgery because of comorbidities and perceived surgical risk. •The Mitral Butterfly is a novel device offering minimally invasive repair of a prolapsing valve with a simple, single-step deployment. This catheter-based device is composed of a nitinol frame and a polymer matrix covering the entire prolapsing segment of the insufficient valve. Unlike other chordal repair techniques, there is no need for myocardial fixation. •Device performance in a 90-day chronic animal study and in silico analysis substantiated the underlying device concept. •Progress continues to be made in developing a safe and effective transcatheter alternative for MV repair.

Background Improving stroke services is critical for reducing the global stroke burden. The World Stroke Organization–World Health Organization– Lancet Neurology Commission on Stroke conducted a survey of the status of stroke services in low and middle-income countries (LMICs) compared to high-income countries. Methods Using a validated World Stroke Organization comprehensive questionnaire, we collected and compared data on stroke services along four pillars of the stroke quadrangle (surveillance, prevention, acute stroke, and rehabilitation) in 84 countries across World Health Organization regions and economic strata. The World Health Organization also conducted a survey of non-communicable diseases in 194 countries in 2019. Results Fewer surveillance activities (including presence of registries, presence of recent risk factors surveys, and participation in research) were reported in low-income countries than high-income countries. The overall global score for prevention was 40.2%. Stroke units were present in 91% of high-income countries in contrast to 18% of low-income countries (p Conclusions There is an urgent need to improve access to stroke units and services globally especially in LMICs. Countries with less stroke services can adapt strategies from those with better services. This could include establishment of a framework for regular monitoring of stroke burden and services, implementation of integrated prevention activities and essential acute stroke care services, and provision of interdisciplinary care for stroke rehabilitation.

A 40-year-old male double yellow-headed Amazon parrot (Amazona ochrocephala oratrix) was evaluated for a history of chronic recurrent subcutaneous emphysema. Whole-body radiographs and computed tomography imaging revealed significant subcutaneous emphysema in the right cervical area that was suggestive of a chronic ruptured cervical air sac. Surgical exploration of the right cervical area revealed a 4cm defect in the right cervical air sac. The defect was sutured in a double-layer closure first of the thickened air sac tissue, followed by the subcutaneous layer with 5-0 polydioxanone. Following closure of the skin, the remaining air was aspirated from the subcutaneous space. The patient healed without complication, and on last follow-up approximately 5 months postsurgery, there was no sign of recurrence of subcutaneous emphysema, demonstrating successful primary closure of the chronic ruptured cervical air sac. Surgical management of a chronic air sac rupture was successful in resolving recurrent subcutaneous emphysema in an Amazon parrot. The clinical findings, diagnostic approach, anesthesia, surgical technique, and postoperative outcome are described in this clinical report and can aid clinicians presented with cases of chronic, recurrent subcutaneous emphysema that are refractory to other treatments.

We demonstrate optical frequency comb generation in hybrid high-Q optical microresonators fabricated using direct wafer bonding of photonic Damascene silicon nitride wafer with thin-film lithium niobate-on-insulator (LNOI). The devices enable direct phase control via Pockels effect.

Safety assessment of biological drugs has its challenges due to the multiple new different modalities, for example, antibody-drug conjugates, bispecifics, nanobodies, fusion proteins and advanced therapy medicinal products (ATMPs), their different pharmacokinetic and pharmacodynamic properties, and their ability to trigger immunogenicity and toxicity. In the public and in the pharmaceutical industry, there is a strong and general desire to reduce the number of animals used in research and development of drugs and in particular reducing the use of nonhuman primates. Important discussions and activities are ongoing investigating the smarter designs of early research and dose range finding studies, reuse of animals, and replacing animal experiments with in vitro studies. Other important challenges include absence of a relevant species and design of studies and developing genetically modified animals for special investigative toxicology studies. Then, the learnings and challenges from the development of the first ATMPs are available providing valuable insights in the development path for these new potentially transformative treatments. Finally, development of strategies for assessment of immunogenicity and prediction of translation of immunogenicity and associated findings to the clinic. On this, the eighth meeting for the European BioSafe members, these challenges served as the basis for the presentations and discussions during the meeting. This article serves as the workshop report reviewing the presentations and discussions at the meeting.

Zusammenfassung Einleitung Der Einfluss einer SARS-CoV-2-Infektion auf chronisch entzündliche Darmerkrankungen (CED) ist bislang nicht gut charakterisiert, und es ist unklar, ob diese eine Anpassung der immunsuppressiven Therapie erfordert. Methodik Für die retrospektive Dokumentation klinischer Parameter und Veränderungen einer immunsuppressiven Therapie von mit SARS-CoV-2 infizierten CED-Patienten wurde ein nationales Melderegister etabliert. Ergebnisse Insgesamt wurden nur 3 von 185 CED-Patienten (1,6 %) wegen abdomineller Symptome auf eine SARS-CoV-2-Infektion getestet. Im COVID-19-Krankheitsverlauf entwickelten 43,5 % Durchfall, abdominelle Schmerzen oder Hämatochezie (Hospitalisierungsrisiko mit vs. ohne abdominelle Symptome: 20,0 % vs. 10,6 %, p Diskussion Bei mit SARS-CoV-2 infizierten CED-Patienten traten häufig neue abdominelle Symptome bei Infektion auf. Diese führten aber nur selten zur SARS-CoV-2-Testung. Eine hohe CED-Aktivität zum Zeitpunkt des SARS-CoV-2-Nachweises war mit einem erhöhten Hospitalisierungsrisiko assoziiert.

We demonstrate optical frequency comb generation in hybrid high-Q optical microresonators fabricated using direct wafer bonding of photonic Damascene silicon nitride wafer with thin-film lithium niobate-on-insulator (LNOI). The devices enable direct phase control via Pockels effect.

Background Globally, violence disproportionately affects young people, leading to injury, hospitalisation, death, social dysfunction, and poor mental wellbeing. Moreover, it has far-reaching economic consequences for whole nations, due to loss of productivity. Research suggests that attaining a higher level of education promotes factors that insulate youths from poverty and violence. Purpose In this study, we investigated the outcomes, the cost, and the cost-effectiveness of a non-formal education program with an additional psychosocial component. The short-term outcome measure was an increase in educational attainment, a crucial step for youth empowerment. The program analysed was the Alternative Learning System (ALS) offered by the Balay Rehabiliation Centre in Bagong Silang, an urban slum in Manila, which targeted out of school youth. Methods The cost-effectiveness analysis of ALS compared to a ‘do nothing approach’ was performed from the perspective of the service provider. The study sample comprised 239 learners who were enrolled in the ALS during 2015–2018. For the ‘do nothing’ comparator, a counterfactual scenario was hypothesised. The average cost of the intervention per enrolled learner, and the incremental cost effectiveness ratio (ICER) for passing the Accreditation and Evaluation (A&E) exam at elementary or secondary level, were calculated. Results The ALS intervention studied resulted in 41% (n = 97) of the learners passing the examination over a period of four years (from 2015–2018). The estimated total cost of the intervention was $371,110, corresponding to $1550 per enrolled learner. The incremental cost-effectiveness ratio for a pass in the exam was found to be $3830. Compared to other, international, alternative learning interventions, the ALS intervention as used in Bagong Silang was found to be more cost-effective. Conclusion From the service provider perspective, the ALS for out-of-school young people was found to be a valuable investment to benefit poor young people living in slums in Manila.

Summary Background Psychosocial factors significantly influence patient care in many fields of medicine, among these in the field of endocrinology. Easily applicable validated assessment tools for such psychosocial factors are lacking. Visual instruments may facilitate doctor-patient communication. This study describes the development and validation of a multidimensional visual tool for the self-assessment of health. Methods An expert panel performed the multistep development of the psychosomatic assessment health disc (PAHD). Assessment of face validity was performed by means of a focus group of medical doctors (n = 6) and patient interviews (n = 24). For determining test-retest reliability, internal consistency and construct validity, patients of an endocrine outpatient clinic in Graz, Austria, completed the PAHD and the following questionnaires: short-form 36 health survey, work ability index, Pittsburgh sleep quality index and the social life scales of the life satisfaction questionnaire. Results A numeric six-item analogue scale was developed in the form of a disc. It addresses the following aspects of health: physical well-being, social life, sexuality, mental well-being, sleep, working ability/performance. For the validation process, 177 patients (57.1% females) participated in the study. Correlation coefficients of the six items with other questionnaires ranged between r = 0.51 (social life) and r = 0.72 (sleep). Test-retest reliability was assessed among 98 patients and was ≥ 0.74 for all 6 items, while Cronbach’s alpha was 0.78. Conclusion The psychometric properties of the PAHD support its use in clinical encounters with patients suffering from endocrine disorders. Further validation studies may be required to extend its application to other fields of medicine.

Background Physicians are exposed to workplace factors that may result in acute or chronic stress resulting in burnout. This may impact the productivity and result in suboptimal patient care practices. Methods We surveyed pediatric cardiology attending physicians at our institution to assess their perception of burnout and work-life balance using the Maslach Burnout Inventory and the Areas of Work-Life Survey. Results Forty-five out of the 50 pediatric cardiology attendings responded to the survey. They were divided into 4 groups: Interventional/Electrophysiology [n = 3], Cardiac Intensive Care/Inpatient [n = 8], Non-Invasive Imaging [n = 6], and Outpatient [n = 28]. The Maslach Burnout Inventory demonstrated group-specific scores in the areas of emotional exhaustion, depersonalization, and personal accomplishment that were all significantly better than the general population. However, group-specific Areas of Work-Life Survey results demonstrated concerning findings with respect to the perception of work-life balance. Conclusions Although the Maslach Burnout Inventory did not demonstrate significant burnout among the attending physicians, the Areas of Work-Life Survey results demonstrated reduced work engagement, which can impact patient care and lead to burnout in the future. Based on these results, we plan to implement strategies to help increase work engagement and improve overall organizational effectiveness.

Aims: Cardiac repair has steered clinical attention and remains an unmet need, because available regenerative therapies lack robust mechanistic evidence. Pressure-controlled intermittent coronary sinus occlusion (PICSO), known to induce angiogenetic and vasoactive molecules as well as to reduce regional ischemia, may activate endogenous regenerative processes in failing myocardium. We aimed to investigate the effects of PICSO in patients with advanced heart failure undergoing cardiac resynchronization therapy. Methods and results: Eight out of 32 patients were treated with PICSO, and the remainder served as controls. After electrode testing including left ventricular leads, PICSO was performed for 20 min. To test immediate molecular responses, in both patient groups, coronary venous blood samples were taken at baseline and after 20 min, the time required for the intervention. Sera were tested for microRNAs and growth factors. To test the ability of up-regulated soluble factors on cell proliferation and expression of transcription factors [e.g. Kruppel-like factor 4 (KLF-4)], sera were co-cultured with human cardiomyocytes and fibroblasts. As compared with controls, significant differential expression (differences between pre-values and post-values in relation to both patient cohorts) of microRNA patterns associated with cardiac development was observed with PICSO. Importantly, miR-143 (P

Background Prospective, observational real world studies on the effectiveness and safety of ustekinumab (UST) in Crohn’s disease (CD) are required in addition to RCTs, usually confined to selected patients, which may not represent special treatment patterns and everyday clinical practice. The aim of the present 3-year RUN-CD study was to investigate the induction phase effectiveness of UST vs. other biologics (OB) in CD in terms of clinical and steroid-free remission at week 16. To the best of our knowledge, RUN-CD is currently the largest prospective real world evidence (RWE) study with UST in CD using propensity score adjustment. Methods Between 2017–2020, 901 CD-patients starting a new therapy with UST or OB, were enrolled in 44 IBD-experienced centers across Germany. After exclusion of missing outcomes, the final sample consisted of 657 patients. Clinical remission (HBI ≤ 4), and steroid-free remission (HBI ≤ 4 and no systemic use of steroids or budesonide during the last 8 weeks) were considered as outcomes at week 16. To reduce the effect of confounders, propensity score (PS) adjustment with inverse probability of treatment weighting (IPTW) was implemented. A weighted logistic regression was used, and the results were reported as odds ratio (OR) and 95% confidence interval (CI). Results 339 UST (naïve: 34) and 318 OB CD-patients were included (ADA: 50.3%, IFX: 37.4%, VDZ: 12.3%) (naïve: 203). PS removed systematic differences between both groups (30.8% smokers, 15.1% perianal disease, 36.2% surgical resection, 40.5% EIM). The effectiveness of UST for clinical and steroid-free remission was comparable to that of OB at week 16. Besides, in bio-naïve patients, clinical remission was numerically, though not significantly, higher in UST vs OB (Table 1). Similar results were observed in the bio-experienced UST vs. OB groups [remission: 59.3% vs 55.4%; OR: 1.17 (0.73–1.90)]. For both the remission rates were higher in the bio-naïve than in the bio-experienced groups (p Conclusion In this prospective RUN-CD study, with propensity score weighted groups, UST showed similar induction effectiveness in comparison with OB therapies. Remarkably higher remission rates were observed in this RWE study than in prior RCTs. An additional favorable safety profile supports consideration of UST as a first-line targeted therapy for CD.

OBJECTIVE The current study aimed to identify how sex influences neurobiological responses to food cues, particularly those related to hedonic eating, and how this relates to obesity propensity, using functional magnetic resonance imaging (fMRI). METHODS Adult men and women who were either obesity resistant (OR) or obesity prone (OP) underwent fMRI while viewing visual food cues (hedonic foods, neutral foods, and nonfood objects) in both fasted and fed states. RESULTS When fasted, a significant sex effect on the response to hedonic vs. neutral foods was observed, with greater responses in women than men in the nucleus accumbens (P = 0.0002) and insula (P = 0.010). Sex-based differences were not observed in the fed state. No significant group effects (OP vs. OR) or group-by-sex interactions were observed in fasted or fed states. CONCLUSIONS Greater fasted responses to hedonic food cues in reward-related brain regions were observed in women compared with men, suggesting that women may be more sensitive to the reward value of hedonic foods than men when fasted. This may indicate sex-dependent neurophysiology underlying eating behaviors.

Objectives This review discusses challenges to stability, analytics and manufacturing of protein coformulations. Furthermore, general considerations to be taken into account for the pharmaceutical development of coformulated protein drug products are highlighted. Key findings Coformulation of two or more active substances in one single dosage form has recently seen increasing use offering several advantages, such as increased efficacy and/or the overall reduction of adverse event incidents in patients. Most marketed coformulated drug products are composed of small molecules. As proteins are not only comparatively large but also complex molecules, the maintenance of their physicochemical integrity within a formulation throughout pharmaceutical processing, storage, transport, handling and patient administration to ensure proper pharmacokinetics and pharmacodynamics in vivo already represents various challenges for single-entity products. Thus, nowadays, only sparse biologics-based coformulations can be found, as additional complexity during development is given for these products. Summary The complexity of the dosage form and the protein molecules results into additional challenges to formulation, manufacture, storage, transport, handling and patient administration, stability and analytics during the pharmaceutical development of protein coformulations. Various points have to be considered during different stages of development in order to obtain a safe and efficacious product.

This protocol describes thedifferentiation of iPSCs with stably integrated doxycycline-inducible Ngn2 (such as i3Ns).

Introduction: Limited access to stroke specialist expertise produces disparities in inpatient stroke treatment. The impact of telestroke on the remote delivery of guideline-based inpatient stroke care is yet to be comprehensively studied. The TELECAST trial (NCT03672890) prospectively examined the impact of a 24-7 telestroke specialist service dedicated to inpatient acute stroke care spanning admission to discharge. Methods: AHA stroke guidelines were used to derive outcome metrics in the following acute stroke inpatient care categories: diagnostic stroke evaluation (DSE), secondary stroke prevention (SSP), health screening and evaluation (HSE), and stroke education (SE). Adherence to AHA guidelines for stroke inpatients pre-telestroke (July 1, 2016-June 30, 2018) and post-telestroke intervention (July 1, 2018-June 30, 2019) were studied. The primary outcome was a composite score of all guideline-based stroke care. Secondary outcomes consisted of subcategory composite scores in DSE, SSP, HSE, and SE. Chi-squared tests were utilized to assess primary and secondary outcomes. Statistical analysis was performed using STATA 15.0. Results: Following institution of a comprehensive inpatient telestroke service, overall adherence to guideline-based metrics improved (composite score: 85% vs 94%, p Conclusion: The implementation of a 24-7 inpatient telestroke service improved adherence to AHA guidelines for inpatient acute stroke care. Dedicated inpatient telestroke specialist coverage may improve inpatient stroke care and reduce stroke recurrence in hospitals without access to stroke specialists.

We demonstrate the integration of a Si3N4 Damascene photonic platform with thin-film lithium niobate on insulator (LNOI) via direct wafer bonding. This process enables fabrication of hybrid X(2)-X(3) microresonators with Q " 106, as well as integrated travelling wave EO modulators.

The hygiene hypothesis suggests that a reduction in microbial exposure contributes to an impaired immune response later in life and increases the incidence of immune-mediated diseases such as inflammatory bowel diseases (IBD). Thumb sucking and nail biting are two early habits that modulate the oral microbiota composition and antigen load. We hypothesized a lower risk of Crohn’s disease (CD) and ulcerative colitis (UC) in adults with prior thumb sucking and nail biting. 918 IBD cases and their 918 siblings without IBD were asked to fill out a survey containing 32 questions on environmental factors in childhood and early adulthood. Prevalence of thumb sucking and/or nail biting at the usually well-remembered time of (1) school enrollment and (2) coming-of-age ceremonies was the predefined combined risk factor of this study. 65% of the patients were female and 57% suffered from CD. About 49% of IBD patients but only 44% of their siblings reported thumb sucking/nail biting at the time of school enrollment or coming-of-age (p = .007). Sensitivity analysis revealed that this difference was observed in patients with CD (50% versus 41%; RR= 1.22; 95% CI 1.09–1.37, p = .001) but not in patients with UC (49% versus 48%; RR= 1.02; 95% CI 0.90–1.17; p = .83). Contrary to our expectation and challenging the hygiene hypothesis, we found that common oral habits are not protective against IBD. Instead, nail biting at the time of school enrollment and coming-of-age was a statistically significant risk factor for CD in our cohort. Key summary Evidence available before this study: The hygiene hypothesis suggests that a reduction in microbial exposure due to improved health activities has contributed to an immunological imbalance in the intestine and an increased incidence of allergic and autoimmune diseases. A population-based birth cohort study has demonstrated that thumb-sucking and nail biting in children lead to a reduction of the risk of atopic sensitization, asthma, and hay fever. Added value of this study: Contrary to the hypothesis, thumb sucking and nail biting were not associated with a reduced risk of IBD. Instead, thumb sucking and/or nail biting at the usually well-remembered points in time of school enrollment and of religious or secular coming-of-age ceremonies was associated with a higher risk of Crohn’s disease but not of ulcerative colitis. Our data did not support the hygiene hypothesis, one pathogenic concept in the context of IBD.

Background Air embolism is an extremely rare complication that can follow gastrointestinal endoscopy. The most accepted treatment of cerebral air embolism (CAE) is hyperbaric oxygen (HBO). Limited evidence suggests that lidocaine may have a neuroprotective effect. The exact mechanism does not appear to be well elucidated. Methods We conducted a literature search using multiple combinations of keywords from PubMed and Ovid Medline databases according to the PRISMA guidelines. We included articles with cases of air embolism caused by an esophagogastroduodenoscopy (EGD). We excluded cases related to other procedures e.g. colonoscopy, endoscopic retrograde cholangiopancreatography, cholangioscopy, Kasai procedure, bronchoscopy, laparoscopy or thoracoscopy. We were able to identify 30 cases of CAE associated with EGD. We included our experience in treating one patient with CAE after elective EGD. Results Given the results of our literature search and this patient's characteristics, we chose to treat our patient with HBO and lidocaine infusion. Our case series consists of 31 patients of post EGD CAE, the mean age was 63.7 ± 11.14 years, 38.7% of the patients were women (n = 12). 38.7% of the cases underwent esophageal dilatation (n = 12), while 19.35% had EGD biopsy (n = 6), 9.6% had variceal ligation (n = 3), and 3.22% had variceal banding (n = 1). In 20 out of 31 cases, echocardiography has been documented, 20% of those patients (n = 4) had patent foramen ovale. HBO was used in treatment of 48% of cases (n = 15), among the included patients, 61% survived (n = 19). Our patient showed significant neurological improvement. Conclusions Despite the rare incidence of CAE during or after EGD, physicians should be aware of this potential complication. In patients who develop sudden acute neurological symptoms, early diagnosis and intervention may prevent devastating neurological injury and death. The most accepted emergent treatment for CAE includes HBO, consideration of lidocaine, and work-up of source of the air embolism.

We recently reported the existence of fluctuations in neural signals that may permit neurons to code multiple simultaneous stimuli sequentially across time. This required deploying a novel statistical approach to permit investigation of neural activity at the scale of individual trials. Here we present tests using synthetic data to assess the sensitivity and specificity of this analysis. We fabricated datasets to match each of several potential response patterns derived from single-stimulus response distributions. In particular, we simulated dual stimulus trial spike counts that reflected fluctuating mixtures of the single stimulus spike counts, stable intermediate averages, single stimulus winner-take-all, or response distributions that were outside the range defined by the single stimulus responses (such as summation or suppression). We then assessed how well the analysis recovered the correct response pattern as a function of the number of simulated trials and the difference between the simulated responses to each "stimulus" alone. We found excellent recovery of the mixture, intermediate, and outside categories (>97% percent correct), and good recovery of the single/winner-take-all category (>90% correct) when the number of trials was >20 and the single-stimulus response rates were 50Hz and 20Hz respectively. Both larger numbers of trials and greater separation between the single stimulus firing rates improved categorization accuracy. These results provide a benchmark, and guidelines for data collection, for use of this method to investigate coding of multiple items at the individual-trial time scale., Accepted for publication in Neurons, Behavior, Data analysis, and Theory

Introduction Acute neuromuscular respiratory failure is a source of morbidity and mortality in neurological diseases, including acute inflammatory demyelinating polyneuropathy (AIDP), also known as Guillain-Barré syndrome. It is important for health care providers to recognize this condition and provide early ventilatory support. In this simulation, learners must assess and treat a standardized patient with acute respiratory complications related to AIDP. Methods This is a single-session simulation that can be run in a standard simulation center using a live standardized patient. The simulation scenario is followed by a facilitated debriefing session. Details about the simulation scenario, critical action checklist, environment preparation, actors/roles, and debriefing session are outlined. Results A total of 14 neurology residents participated in this simulation. A postsimulation survey revealed that participants thought the simulation achieved its stated objectives, was useful, and would impact their future practice. Discussion We designed this simulation to assess a learner's ability to identify acute neuromuscular respiratory weakness in a patient with AIDP and initiate treatment with ventilatory support. This simulation can easily be incorporated into an existing curriculum for neurology residents or for trainees in other specialties.

Transparent conductive films are used in a wide variety of devices. While solar cell top electrodes as well as tablet and mobile phone screens require high optical transparency and low sheet resistance (>80% and

Objective: The Mitral Butterfly is a novel transcatheter mitral stent device. A polymer matrix spreads from nitinol wings along the annulus of the mitral valve towards a swing arm covering a prolap...

An important performance criterion for blood pumps is blood damage due to the non-physiological loads on the blood cells. Especially for miniature pumps that are inserted into blood vessels in catheter devices and – due to their small diameters - operate at high rotational speeds, hemolysis is an important design issue. The Assistocor heart catheter pump is a left ventricular assist device which is inserted into the Aorta and has an outer diameter of 6.8 mm, it operates at rotational speeds up to 40000 rpm. In-vitro tests with animal blood and different pump prototypes of the Assistocor heart pump showed that hemolysis values stayed below the recommended values for five out of nine of the tested prototypes and are comparable with results from literature, indicating that the design process is adequate to keep the damage of blood cells within acceptable limits despite the high rotational speeds.

A one-year-old female spayed miniature schnauzer was referred to the Kansas State University Veterinary Health Center Ophthalmology Service for evaluation of chronic purulent discharge and conjunctival hyperaemia of the right eye. Two months before presentation, the dog was treated by its primary veterinarian for grass awn foreign bodies in the periocular area. Three visible grass awns were removed, and an associated superficial corneal ulcer healed without complication. However, ocular discharge and conjunctival hyperaemia persisted. Due to the patient’s history and the focal pattern of conjunctival hyperaemia, diagnostic imaging (ultrasound) was recommended to screen for retained plant foreign material. The dog was anaesthetised, and a hyperechoic linear structure was identified in the dorsolateral periocular space on ultrasound examination. The plant material was successfully extracted during a brief conjunctival exploration, and the previously reported clinical signs subsequently resolved over the course of one week.

van der Waals solids have been recognized as highly photosensitive materials that compete conventional Si and compound semiconductor based devices. While 2-dimensional nanosheets of single and multiple layers and 1-dimensional nanowires of molybdenum and tungsten chalcogenides have been studied, their nanostructured derivatives with complex morphologies are not explored yet. Here, we report on the electrical and photosensitive properties of WS2 nanowire-nanoflake hybrid materials we developed lately. We probe individual hybrid nanostructured particles along the structure using focused ion beam deposited Pt contacts. Further, we use conductive atomic force microscopy to analyze electrical behavior across the nanostructure in the transverse direction. The electrical measurements are complemented by in situ laser beam illumination to explore the photoresponse of the nanohybrids in the visible optical spectrum. Photodetectors with responsivity up to ∼0.4 AW-1 are demonstrated outperforming graphene as well as most of the other transition metal dichalcogenide based devices.

Background and Aims: Azathioprine [AZA] is recommended for maintenance of steroid-free remission in inflammatory bowel disease IBD. The aim of this study has been to establish the incidence and severity of AZA-induced pancreatitis, an idiosyncratic and major side effect, and to identify specific risk factors. Methods: We studied 510 IBD patients [338 Crohn’s disease, 157 ulcerative colitis, 15 indeterminate colitis] with initiation of AZA treatment in a prospective multicentre registry study. Acute pancreatitis was diagnosed in accordance with international guidelines. Results: AZA was continued by 324 [63.5%] and stopped by 186 [36.5%] patients. The most common cause of discontinuation was nausea [12.2%]. AZA-induced pancreatitis occurred in 37 patients [7.3%]. Of these: 43% were hospitalised with a median inpatient time period of 5 days; 10% had peripancreatic fluid collections; 24% had vomiting; and 14% had fever. No patient had to undergo nonsurgical or surgical interventions. Smoking was the strongest risk factor for AZA-induced acute pancreatitis [p < 0.0002] in univariate and multivariate analyses. Conclusions: AZA-induced acute pancreatitis is a common adverse event in IBD patients, but in this study had a mild course in all patients. Smoking is the most important risk factor.

Treating hyperglycemia in previously non-diabetic individuals with exogenous insulin immediately after kidney transplantation reduced the odds of developing Posttransplantation Diabetes Mellitus (PTDM) in our previous proof-of-concept clinical trial. We hypothesized that insulin-pump therapy with maximal insulin dosage during the afternoon would improve glycemic control compared to basal insulin and standard-of-care. In a multi-center, randomized, controlled trial testing insulin isophane for PTDM prevention, we added a third study arm applying continuous subcutaneous insulin lispro infusion (CSII) treatment. CSII was initiated in 24 patients aged 55±12 years, without diabetes history, receiving tacrolimus. The mean daily insulin lispro dose was 9.2±5.2 IU. 2.3±1.1% of the total insulin dose were administered between 00:00 and 6:00, 19.5±11.6% between 6:00 and 12:00, 62.3±15.6% between 12:00 and 18:00 and 15.9±9.1% between 18:00 and 24:00. Additional bolus injections were necessary in five patients. Mild hypoglycemia (52–60 mg/dL) occurred in two patients. During the first post-operative week glucose control in CSII patients was overall superior compared to standard-of-care as well as once-daily insulin isophane for fasting and post-supper glucose. We present an algorithm for CSII treatment in kidney transplant recipients, demonstrating similar safety and superior short-term efficacy compared to standard-of-care and once-daily insulin isophane.

A 63-year-old patient presented with dyspnea and chest distress. A computerized tomography and echocardiogram showed a cardiac mass in the right ventricle, which caused obstruction of the right ventricular outflow tract. Coronary angiography revealed a dense meshwork of the abnomorly capillary vessels originating from right coronary artery. The mass was completely excised under cardiopulmonary bypass. The mass attached right ventricle lateral wall and posterior triscupid leaflet. Histology was typical myomatous tissue.

Clinical heart failure prevention and contemporary therapy often involve breaking the vicious cycle of global haemodynamic consequences of myocardial decay. The lack of effective regenerative therapies results in a primary focus on preventing further deterioration of cardiac performance. The cellular transplantation hypothesis has been evaluated in many different preclinical models and a handful of important clinical trials. The primary expectation that cellular transplants will be embedded into failing myocardium and fuse with existing functioning cells appears unlikely. A multitude of cellular formulas, access routes and clinical surrogate endpoints for evaluation add to the complexity of cellular therapies. Several recent large clinical trials have provided insights into both the regenerative potential and clinical improvement from non-regenerative mechanisms. Initiating endogenous repair seems to be another meaningful alternative to recover structural integrity in myocardial injury. This option may be achieved using a transcoronary sinus catheter intervention, implying the understanding of basic principles in biology. With intermittent reduction of outflow in cardiac veins (PICSO), vascular cells appear to be activated and restart a programme similar to pathways in the developing heart. Structural regeneration may be possible without requiring exogenous agents, or a combination of both approaches may become clinical reality in the next decade.

Background Azathioprine is recommended as first-line immunosuppressant in patients with steroid-dependent inflammatory bowel diseases (IBDs). However, data on steroid withdrawal after induction therapy in IBD patients are sparse. Methods In this post-hoc analysis of a prospective multicenter study, we analyzed the proportion and clinical characteristics of 324 azathioprine-tolerant patients as to whether they could terminate the glucocorticoid therapy after initiation of treatment with azathioprine. Results Systemic steroid therapy was required in 190 patients (58.6 %) at baseline and in 40 patients (12.3 %) at the end of the follow-up period (p Conclusion The majority of patients with thiopurine-naive IBDs that needed systemic steroids at baseline were able to discontinue steroids after 3 – 6 months of azathioprine therapy. These data support the continued high value of azathioprine in the immunosuppressive therapy of IBD.

Background The VEDOibd I study is an investigator initiated, ongoing, non-interventional trial on biologics in IBD-patients (Crohn′s disease (CD) and ulcerative colitis (UC)) in Germany with consecutive recruitment and prospective documentation of effectiveness in induction and maintenance therapy of biologics, especially vedolizumab (VEDO). The aim of this analysis was to compare steroid-free remission rates in CD- and UC-patients after a 14-week-long induction phase of VEDO (bio-naïve and bio-experienced) vs. other biologics (infliximab (IFX), adalimumab (ADA), Golimumab (GLM), Ustekinumab (UST)) in bio-naïve patients. Methods From 10/2017 to 07/2019 750 IBD-patients (CD: 414; UC: 336) from 45 gastroenterology practices and hospitals with IBD-experience from all over Germany were recruited in the VEDOibd I study of whom 232 CD- and 184 UC-patients completed induction phase (week 14) in this interim analysis. At week 14 we compared clinical response (CD: reduction of Harvey Bradshaw Index [HBI] from baseline to week 14 by >3 points or HBI < 4 in week 14; UC: reduction of partial Mayo score [pMayo] from baseline to week 14 by >3 points or a reduction of at least 30% compared with baseline) and steroid-free remission rates (CD: HBI < 4 and no systemic use of steroids or budesonide at week 14; UC: pMayo ≤1 plus a bleeding subscore = 0 and no systemic use of steroids or budesonide at week 14) in patients with VEDO vs. other biologics. Results Ninety-two CD- and 111 UC-patients started a first-time VEDO therapy; of these 40 CD- (43%) and 57 UC-patients (51%) were bio-naïve. Furthermore 140 CD-patients (IFX 48.6%; ADA 47.1%; UST 4.3%) and 73 UC-patients (IFX 58.9%; ADA 24.7%; GLM 16.4%) started treatment with another biologic than VEDO and all of these were bio-naïve. Baseline characteristics were well balanced between both naïve groups (VEDO/other biologics; p > 0.05): males [%]: CD 38/41, UC 37/51; age [years]: CD 46 ± 15/42 ± 15, UC 43 ± 19/39 ± 15; disease duration [years]: CD 15 ± 11/9 ± 11, UC 9 ± 9/6 ± 7; extraintestinal manifestations [%]: CD 23/20, UC 7/15. Response/steroid-free remission rates after induction phase in biologic-naïve patients with VEDO and other biologics were 74.4%/57.5% vs. 78.4%/64.3% in CD (p>0.05) and 60.0%/21.1% vs. 56.0%/13.7% in UC (p>0.05), respectively. Conclusion In this real-world setting we could show that in CD the effectiveness of VEDO vs. other biologics was very similar in bio-naïve patients and that in UC patients, VEDO treatment tended to be numerically superior to other biologics with respect to response and steroid-free remission rates. Further follow-up data of this interim-analysis including the whole planned study population of 1.200 IBD-patients will be shown in the near future.

In the 1950s, the Tennessee State Highway Department planned Interstate-40 segments through Overton Park in Memphis and a central city black community in Nashville. Although slow to develop, freeway revolts emerged in both cities by the mid-1960s. Citizen activists in each city battled local municipal regimes and downtown business allies, Tennessee state road engineers, and bureaucrats in several federal transportation agencies. In Memphis, the anti-freeway organization Citizens to Preserve Overton Park, led by relentless activist and park preservationist Anona Stoner, outwitted opponents for years with appeals, demands for reviews or modifications, and eventually litigation that ended up, successfully, in the U.S. Supreme Court. In Nashville, the Interstate-40 Steering Committee, a group of black professionals led by Fisk University professor Flournoy Coles, cobbled together an opposition movement at the last moment. Their legal argument that the I-40 expressway through the North Nashville black community represented racial discrimination against an entire community seemed logical in Nashville but failed in the Supreme Court. The goal of this article, then, is to reflect on the impact of the Interstates on American cities, as well as to analyze how and why one anti-freeway movement succeeded and another failed.

Cardiac regeneration remains a clinical target regardless of numerous therapeutic concepts. We formulated a hypothesis claiming that periodic coronary venous pressure elevation (PICSO; Pressure controlled Intermittent Coronary Sinus Occlusion) initiates embedded, but dormant developmental processes in adult jeopardized hearts. Hemodynamics in the primitive beating heart tube is sensed transducing “mechanical” epigenetic information during normal cardiac development. In analogy mechanotransduction via shear stress and pulsatile stretch induced by periodic elevation of blood pressure in cardiac veins reconnects this dormant developmental signal, setting regenerative impulses in the adult heart. Significant increase of hemeoxygenase-1 gene expression (p < 0.001) and vascular endothelial growth factor (VEGF) (p < 0.002) as well as production of VEGRF2 in experimental infarction underscores the resurgence of developmental stimuli by PICSO. Molecular findings correspond with risk reduction (p < 0.0001) in patients with acute coronary syndromes as well as observations in heart failure patients showing substantial risk reduction up to 5 years endorsing our hypothesis and preclinical experience that PICSO via hemodynamic power activates regenerative processes also in adult human hearts. These results emphasize that our proposed hypothesis “embryonic recall” claiming revival of an imbedded albeit dormant “epigenetic” process is able not only to sculpture myocardium in the embryo, but also to redesign structure in the adult and failing heart.

The past year has been an exciting one for the stroke field. In 2017 and early 2018, we saw the results of clinical trials demonstrating the benefits of mechanical thrombectomy in selected patients with large vessel occlusion up to 24 hours after stroke,1,2 data suggesting a benefit in stroke prevention by closing patent foramen ovale in some patients,3 and the publication of new American Heart Association (AHA)/American Stroke Association (ASA) guidelines on acute stroke4 and the definition and management of high blood pressure.5 These critical advances have the potential to improve public health by reducing the incidence, mortality, and morbidity of stroke. All of the consequences of this critical work, however, can only reach their full potential through public awareness and education: prevention and treatment can only succeed if they reach the public and our patients. While the AHA has focused on fighting stroke since the 1950s, the American Stroke Association (ASA) was created as a division of the AHA 20 years ago to amplify its efforts to educate the public and healthcare providers about stroke prevention, treatment, and rehabilitation. The ASA is, in essence, the public-facing arm of the AHA’s stroke efforts. The mission of the ASA is to accelerate the implementation of science into practice by providing a link between the high quality, crucial research published in Stroke and similar journals, and the public. Essential to this link is a clear, consistent message that is directed at the level of public understanding. For example, the ASA likes to say “stroke is preventable, treatable, and beatable,” which provides a simple way to combine into a single statement its three core messages around prevention, acute treatment and intervention, and rehabilitation and recovery after stroke. One of the year’s main events for the ASA is …

Introduction: Circulating Tumor Cells (CTCs) have clinical utility for cancer prognosis and monitoring disease. The goal of this study was to compare CTC enumeration by the FDA-approved CellSearch technology to a new technology, the nCyte Dx system by Axon Dx, LLC. Methods: Duplicate peripheral blood samples from 24 patients with advanced prostate cancer were collected in CellSave tubes as standard of care and submitted for CTC quantification using the CellSearch system at ARUP Laboratories. Following CellSearch testing, a paired sample was sent from ARUP to Axon Dx for nCyte Dx analyses. For every pair of samples, the blood was collected at the same time, but the sample tested by Axon Dx was aged 24 to 72 hours beyond the sample tested with CellSearch. CellSearch identifies CTCs by immunomagnetic capture of EpCAM-postive cells, while nCyte Dx does not incorporate specific CTC enrichment. With nCyte Dx, all PBMCs are isolated via density-based separation in a CPT tube and stained with Axon’s immunofluorescent cocktail (nPac). The cells are drawn down onto semi-porous membranes and placed onto microscope slides. Slides are imaged with the nCyte, a rapid fluorescent scanning instrument, and Axon’s advanced cell finding and analysis software (nAble) facilitates automated CTC detection. Due to the high-quality optical properties of the nCyte, the detected material can be characterized and categorized based on morphology and cellular structure. Results: CellSearch-derived CTC counts were compared with the enumeration results from the nCyte Dx system. Results were reported per 7.5mL blood for both methods. Bland-Altman analysis demonstrates that CellSearch and nCyte Dx results agreed in 22 of the 24 patient sample sets tested within a 95% confidence interval (CI). For both discrepant samples, the CellSearch count was found to be higher. The nCyte Dx method generally detected more CTCs than CellSearch in the lower enumeration range ( Summary and Conclusions: A comparison of CTC enumeration results using the CellSearch and nCyte Dx platforms was performed using duplicate blood samples from 24 prostate cancer patients. The results reveal high similarity between the two technologies, with 22 of 24 patients (92%) having enumeration results that agreed within a 95% CI. While both technologies deliver similar results, there are notable advantages of the nCyte Dx system over CellSearch, including a lack of bias toward EpCAM positive material. Additionally, the superior image quality of nCyte Dx may limit subjectivity in CTC identification and offer the ability to characterize CTC heterogeneity. Citation Format: Josefa Andrade, Ramsey Mohl, Stephanie Thomas, John Kearney, Phillip Bernard, Hillary S. Sloane. Comparison of the nCyte Dx and CellSearch systems for CTC enumeration [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2285.

A tanulmany a kockazatnak es a kockazatok felmeresenek az eves beszamolok (penzugyi kimutatasok) konyvvizsgalatban betoltott szerepevel foglalkozik. A modern konyvvizsgalat – belső es kulső korlatainal fogva – nem letezhet a vizsgalt vallalkozas uzleti kockazatainak felmerese nelkul. Olyannyira igaz ez, hogy a szakma alapvető szabalyait lefektető nemzeti es nemzetkozi standardok is kotelező jelleggel előirjak az ugyfelek uzleti kockazatainak megismereset. Mindez nem oncelu tevekenyseg, hanem eppen ez jelenti a konyvvizsgalat kiindulo magjat: a kockazatbecsles – a tervezes reszekent – az audit vegrehajtasanak alapja, es egyben vezerfonala. A szerző előszor bemutatja a konyvvizsgalat es a kockazat kapcsolatanak alapvonasait, azt, hogy mikent jelenik meg egyaltalan a kockazat problemaja a konyvvizsgalatban. Ezt kovetően a kulonfele kockazatalapu megkozeliteseket targyalja, majd nehany főbb elem kiragadasaval abrazolja a kockazatkoncepcio beagyazodasat a szakmai szabalyozasba. Vegul – mintegy az elmelet tesztjekent – bemutatja a kockazatmodell gyakorlati alkalmazasanak nehany aspektusat. ______ The study examines the role of risk and the assessment of risks in the external audit of financial statements. A modern audit – due to its internal and external limitations – cannot exist without the assessment of the business risk of the entity being audited. This is not a l’art pour l’art activity but rather the very core of the audit. It is – as part of the planning of the audit – a guideline to the whole auditing process. This study has three main sections. The first one explains the connection between audit and risk, the second discusses the different risk based approaches to auditing and the embeddedness of the risk concept into professional regulation. Finally – as a test of theory – some practical aspects of the risk model are discussed through the lens of former empirical research carried out mostly in the US. The conclusion of the study is that though risk based models of auditing have many weaknesses they still result in the most effective and efficient high quality audits.

The emerging hydrogen economy has created a demand for the development of improved hydrogen sensors operating at room temperature. In this work, we present hydrogen detectors based on metal decorat ...

Background and Purpose— Stroke is a leading cause of disability, cognitive impairment, and death in the United States and accounts for 1.7% of national health expenditures. Because the population is aging and the risk of stroke more than doubles for each successive decade after the age of 55 years, these costs are anticipated to rise dramatically. The objective of this report was to project future annual costs of care for stroke from 2012 to 2030 and discuss potential cost reduction strategies. Methods and Results— The American Heart Association/American Stroke Association developed methodology to project the future costs of stroke-related care. Estimates excluded costs associated with other cardiovascular diseases (hypertension, coronary heart disease, and congestive heart failure). By 2030, 3.88% of the US population >18 years of age is projected to have had a stroke. Between 2012 and 2030, real (2010$) total direct annual stroke-related medical costs are expected to increase from $71.55 billion to $184.13 billion. Real indirect annual costs (attributable to lost productivity) are projected to rise from $33.65 billion to $56.54 billion over the same period. Overall, total annual costs of stroke are projected to increase to $240.67 billion by 2030, an increase of 129%. Conclusions— These projections suggest that the annual costs of stroke will increase substantially over the next 2 decades. Greater emphasis on implementing effective preventive, acute care, and rehabilitative services will have both medical and societal benefits. (Stroke. 2013;44:2361-2375.)

Introduction: The present investigation was based on a survey in 2005, in which the authors found pulmonary function abnormalities in survivors of childhood cancer, who were treated with anticancer therapy. Aim: The purpose of the present study was to follow-up childhood cancer survivors and detect late pulmonary toxicity. Patients and methods: Lung function test was performed with spirometry in 26 survivors participated in this study (10 females and 16 males; mean age, 19.4 years at the time of the second follow-up evaluation). The average time periods from treatment until the first and second follow-up evaluation were 4.5 and 10 years, respectively. Results: The authors found 14 patients with pathological pulmonary function tests results at the time of the first follow-up evaluation, from which 7 patients had obstructive, 5 patients had mixed and 2 patients had restrictive abnormalities. However, there were only 6 patients who had abnormal pulmonary function at the time of the second follow-up evaluation (2 patients with obstructive and 4 patients with restrictive pulmonary function tests (p