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Infectious bronchitis virus (IBV) is an avian pathogen from the Coronavirus family causing major health issues in poultry flocks worldwide. Because of its negative impact on health, performance, and bird welfare, commercial poultry are routinely vaccinated by administering live attenuated virus. However, field strains are capable of rapid adaptation and may evade vaccine-induced immunity. We set out to describe dynamics within and between lineages and assess potential escape from vaccine-induced immunity. We investigated a large nucleotide sequence database of over 1700 partial sequences of the S1 spike protein gene collected from clinical samples of Dutch chickens submitted to the laboratory of Royal GD between 2011 and 2020. Relative frequencies of the two major lineages GI-13 (793B) and GI-19 (QX) did not change in the investigated period, but we found a succession of distinct GI-19 sublineages. Analysis of dN/dS ratio over all sequences demonstrated episodic diversifying selection acting on multiple sites, some of which overlap predicted N-glycosylation motifs. We assessed several measures that would indicate divergence from vaccine strains, both in the overall database and in the two major lineages. However, the frequency of vaccine-homologous lineages did not decrease, no increase in genetic variation with time was detected, and the sequences did not grow more divergent from vaccine sequences in the examined time window. Concluding, our results show sublineage turnover within the GI-19 lineage and we demonstrate episodic diversifying selection acting on the partial sequence, but we cannot confirm nor rule out escape from vaccine-induced immunity. RESEARCH HIGHLIGHTS Succession of GI-19 IBV variants in broiler populations. IBV lineages overrepresented in either broiler, or layer production chickens. Ongoing episodic selection at the IBV S1 spike protein gene sequence. Several positively selected codons coincident with N-glycosylation motifs.

The monocytic/macrophage system is essential for skeletal muscle homeostasis, but its dysregulation contributes to the pathogenesis of muscle degenerative disorders. Despite our increasing knowledge of the role of macrophages in degenerative disease, it still remains unclear how macrophages contribute to muscle fibrosis. Here, we used single-cell transcriptomics to determine the molecular attributes of dystrophic and healthy muscle macrophages. We identified six novel clusters. Unexpectedly, none corresponded to traditional definitions of M1 or M2 macrophage activation. Rather, the predominant macrophage signature in dystrophic muscle was characterized by high expression of fibrotic factors, galectin-3 and spp1. Spatial transcriptomics and computational inferences of intercellular communication indicated that spp1 regulates stromal progenitor and macrophage interactions during muscular dystrophy. Galectin-3+macrophages were chronically activated in dystrophic muscle and adoptive transfer assays showed that the galectin-3+phenotype was the dominant molecular program induced within the dystrophic milieu. Histological examination of human muscle biopsies revealed that galectin-3+macrophages were also elevated in multiple myopathies. These studies advance our understanding of macrophages in muscular dystrophy by defining the transcriptional programs induced in muscle macrophages, and reveal spp1 as a major regulator of macrophage and stromal progenitor interactions.

CCR Translation for the Article from A New Immunostain Algorithm Classifies Diffuse Large B-Cell Lymphoma into Molecular Subtypes with High Accuracy

Purpose: Hans and coworkers previously developed an immunohistochemical algorithm with ∼80% concordance with the gene expression profiling (GEP) classification of diffuse large B-cell lymphoma (DLBCL) into the germinal center B-cell–like (GCB) and activated B-cell–like (ABC) subtypes. Since then, new antibodies specific to germinal center B-cells have been developed, which might improve the performance of an immunostain algorithm.Experimental Design: We studied 84 cases of cyclophosphamide-doxorubicin-vincristine-prednisone (CHOP)–treated DLBCL (47 GCB, 37 ABC) with GCET1, CD10, BCL6, MUM1, FOXP1, BCL2, MTA3, and cyclin D2 immunostains, and compared different combinations of the immunostaining results with the GEP classification. A perturbation analysis was also applied to eliminate the possible effects of interobserver or intraobserver variations. A separate set of 63 DLBCL cases treated with rituximab plus CHOP (37 GCB, 26 ABC) was used to validate the new algorithm.Results: A new algorithm using GCET1, CD10, BCL6, MUM1, and FOXP1 was derived that closely approximated the GEP classification with 93% concordance. Perturbation analysis indicated that the algorithm was robust within the range of observer variance. The new algorithm predicted 3-year overall survival of the validation set [GCB (87%) versus ABC (44%); P < 0.001], simulating the predictive power of the GEP classification. For a group of seven primary mediastinal large B-cell lymphoma, the new algorithm is a better prognostic classifier (all “GCB”) than the Hans' algorithm (two GCB, five non-GCB).Conclusion: Our new algorithm is significantly more accurate than the Hans' algorithm and will facilitate risk stratification of DLBCL patients and future DLBCL research using archival materials. (Clin Cancer Res 2009;15(17):5494–502)

Objectives: Three experiments tested the utility of minimal versus extended voir dire questions in predicting mock jurors’ verdicts and damage awards, and whether the biasing impact of their preexisting attitudes on case judgments could be reduced by judicial rehabilitation. Hypotheses: We hypothesized that extended voir dire questions would be more predictive of case judgments than minimal voir dire questions. We hypothesized that judicial rehabilitation would not reduce this impact of preexisting attitudes on case judgments. Method: Across three experiments, each focusing on a different civil case (insurance bad faith, wrongful birth, medical malpractice misdiagnosis), online participants (N=2,041; 62% female; 77% White, 9% African American, 6% Asian/Pacific Islander, 6% Hispanic or Latino/a; Mage=40) were paid Mturk workers. They were randomly assigned to experience (a) no voir dire, minimal voir dire focusing on previous legal experience and self-identification of biases, or extended voir dire focusing on specific attitudes about civil litigation, parties, and laws, before judging the case and (b) no judicial rehabilitation, or judicial rehabilitation. Participants read a civil case, made case judgments, and completed bias awareness measures. Results: Demographic information and minimal voir dire questions did not predict case judgments, but the majority of extended voir dire responses predicted verdicts and damage awards. Judicial rehabilitation did not reduce the biasing impact of their preexisting attitudes on case judgments—but did result in mock jurors reporting that they were less biased, despite judicial rehabilitation not actually reducing their bias. Conclusions: Attorneys need the opportunity during voir dire to ask jurors about specific attitudes that might bias their decisions because relying on jurors’ self-identification of their own biases has little utility. Further, although judicial rehabilitation might make jurors think that they are less biased, it may not actually reduce the impact of their preexisting attitudes on their case decisions. Public interest statement: Contrary to popular belief, juror biases are not likely to be cured by judicial rehabilitation, and might backfire by creating the illusion in jurors that they are unbiased. Although very few mock jurors were able to self-identify things that might bias them when asked general questions in voir dire, they were willing to admit specific attitudes that biased their verdicts and damage awards when asked. Thus, we suggest reducing bias on juries by allowing attorneys to ask specific, detailed voir dire questionnaires crafted by the parties to streamline the jury selection process and remove jurors for cause or via peremptory challenges, rather than relying on “quick fixes”, such as general questions that ask jurors to self-identify their own bias or judicial rehabilitation.

Men with castration-resistant prostate cancer (CRPC) face poor prognosis and increased risk of treatment-incurred adverse effects resulting in one of the highest mortalities among patient population globally. Immune cells act as double-edged sword depending on the tumor microenvironment, which leads to increased infiltration of pro-tumor (M2) macrophages. Development of new immunomodulatory therapeutic agents capable of targeting the tumor microenvironment, and hence orchestrating the transformation of pro-tumor M2 macrophages to anti-tumor M1, would substantially improve treatment outcomes of CRPC patients. We report, herein, Mangiferin functionalized gold nanoparticulate agent (MGF-AuNPs) and its immunomodulatory characteristics in treating prostate cancer. We provide evidence of immunomodulatory intervention of MGF-AuNPs in prostate cancers through observations of enhanced levels of anti-tumor cytokines (IL-12 and TNF-α) with concomitant reductions in the levels of pro-tumor cytokines (IL-10 and IL-6). In the MGF-AuNPs treated groups, IL-12 was elevated to ten-fold while TNF-α was elevated to about 50-fold, while IL-10 and IL-6 were reduced by two-fold. Ability of MGF-AuNPs to target splenic macrophages is invoked via targeting of NF-kB signaling pathway. Finally, therapeutic efficacy of MGF-AuNPs, in treating prostate cancer in vivo in tumor bearing mice, is described taking into consideration various immunomodulatory interventions triggered by this green nanotechnology-based nanomedicine agent.

Atherosclerosis is a major cause of abdominal aortic aneurysm (AAA) and up to 80% of AAA patients have atherosclerosis. Therefore it is critical to understand the relationship and interactions between atherosclerosis and AAA to treat atherosclerotic aneurysm patients more effectively. In this paper, we develop a mathematical model to mimic the progression of atherosclerotic aneurysms by including both the multi-layer structured arterial wall and the pathophysiology of atherosclerotic aneurysms. The model is given by a system of partial differential equations with free boundaries. Our results reveal a 2D biomarker, the cholesterol ratio and DDR1 level, assessing the risk of atherosclerotic aneurysms. The efficacy of different treatment plans is also explored via our model and suggests that the dosage of anti-cholesterol drugs is significant to slow down the progression of atherosclerotic aneurysms while the additional anti-DDR1 injection can further reduce the risk.

Objective: There are no drugs to prevent the growth of abdominal aortic aneurysm (AAA), responsible for ~200,000 deaths in the world each year. There is a growing interest in natural anti-inflammatory compounds using nanotechnology-based drug-delivery. Mangiferin (MGF) is one such phytochemical isolated from Mangifera indica. Conjugation of MGF on gold nanoparticles (MGF-AuNPs) enhances bioavailability, through cellular penetration, presenting new opportunities toward the design of innovative nanomedicine agents. Recently, we have demonstrated the unique applications of MGF-AuNPs as an immunomodulatory therapeutic agent in the treatment of metastatic breast and prostate cancers. Here, we investigated whether MGF-AuNPs prevent the development of AAA. Approach and Results: Apoe –/– mice were subjected to angiotensin (AngII; 1μg/min/kg)-induced AAA. MGF-AuNPs (~7 mg/30g mouse) or starch (S)-AuNPs were administered daily, a week prior to AngII and continued for 28 days (n=6-12 per group). The incidences of AAA were significantly attenuated with MGF-AuNPs than AngII group (P Apoe –/– mice than AngII group. Mechanistically, Notch1, its ligands (Jag1, Dll4) and downstream targets (HeyL, NFκB2, pStat3), were significantly reduced by MGF-AuNPs in the aorta (P Conclusion: Our studies provide compelling pre-clinical evidence of protective effects of MGF-AuNPs on AAA development through inactivation of Notch1 signaling, thus present realistic potential toward clinical translation of this nanoceutical for use as a non-invasive effective treatment for AAA.

Therapeutic drug monitoring van anti-epileptica kan dienen als een waardevol hulpmiddel in het optimaliseren en individualiseren van de behandeling van epilepsie. Ongelukkigerwijs wordt Therapeutic drug monitoring vaak suboptimaal uitgevoerd door beperkingen in het bepalen van de dalspiegel. Deze bijdrage geeft een beschrijving van Volumetric Absorptive Micro Sampling, een nieuwe thuis-bloedafnamemethode, die dit probleem zou kunnen oplossen.

Background Therapeutic drug monitoring (TDM) of antiepileptic drugs (AEDs) can serve as a valuable tool in optimising and individualising epilepsy treatment, especially in vulnerable groups such as pregnant women, the elderly and children. Unfortunately, TDM is often performed suboptimally due to limitations in blood collection. Therefore, we investigated volumetric absorptive micro sampling (VAMS) – a new home-sampling technique. We aimed to evaluate VAMS to determine and quantify the different AEDs and concentrations of 16 different AEDs in whole blood collected by VAMS. Methods Patient blood samples (n = 138) were collected via venepunctures at the Academic Centre for Epileptology Kempenhaeghe. AED concentrations were determined, and these concentrations were used to compare the VAMS method (whole blood) with the conventional method (serum). In addition, the recovery was examined as well as the impact of haematocrit. Finally, AED-spiked blood was used to test the stability of the AEDs inside the micro-sampler devices over a period of time and whether temperature had an effect on the stability. Results VAMS allows for an accurate detection of 16 different AEDs within 2 days after sampling. Deviation in recovery was less than 10% and high correlations were found between VAMS and conventional sampling. Moreover, haematocrit does not have an effect with values between 0.3 and 0.5 (L/L). Finally, although storage temperature of VAMS does affect some AEDs, most are unaffected. Conclusions VAMS enables an accurate detection of a wide variety of AEDs within 2 days after sampling.

Clinical and experimental studies show that angiotensin II (AngII) promotes vascular pathology via activation of AngII type 1 receptors (AT1Rs). We recently reported that NP‐6A4, a selective peptide agonist for AngII type 2 receptor (AT2R), exerts protective effects on human vascular cells subjected to serum starvation or doxorubicin exposure. In this study, we investigated whether NP‐6A4–induced AT2R activation could mitigate AngII‐induced abdominal aortic aneurism (AAA) using AngII‐treated Apoe−/− mice. Male Apoe−/− mice were infused with AngII (1 µg/kg/min) by implanting osmotic pumps subcutaneously for 28 days. A subset of mice was pre‐treated subcutaneously with NP‐6A4 (2.5 mg/kg/day) or vehicle for 14 days prior to AngII, and treatments were continued for 28 days. NP‐6A4 significantly reduced aortic stiffness of the abdominal aorta induced by AngII as determined by ultrasound functional analyses and histochemical analyses. NP‐6A4 also increased nitric oxide bioavailability in aortic tissues and suppressed AngII‐induced increases in monocyte chemotactic protein‐1, osteopontin and proteolytic activity of the aorta. However, NP‐6A4 did not affect maximal intraluminal aortic diameter or AAA incidences significantly. These data suggest that the effects of AT2R agonist on vascular pathologies are selective, affecting the aortic stiffness and proteolytic activity without affecting the size of AAA.

Morbid obesity (BMI35 kg/m2 with comorbid conditions) is present in 25 - 35% of acute decompensated heart failure (AHF) patients. Prevalence of HF increases with duration of morbid obesity from 30% at 15 years to over 90% at 30 years. There is a need to develop pragmatic therapies that address the unique physical and mental challenges faced by obese AHF patients. Siddha is 5,000 year old Tamil Medicine using yoga and mind-body methods towards higher consciousness. Hunger gratitude Experience (HUGE) is intuitive Siddha fasting method which may improve in-hospital AHF outcomes independent of weight reduction.We present 5 cases of morbidly obese patients with cardiorenal syndrome (CRS) that began intermittent fasting either during their AHF hospitalization or in the outpatient setting for refractory symptoms despite hospitalization. Initiation of fasting correlated with reduction of respiratory distress and edema as well as improvements in psychological wellbeing and functional capacity.Siddha fasting mediates hemodynamic and anti-inflammatory effects through natural ketosis and psychological benefits through empowerment in AHF. Potential role of fasting in reducing myocardial workload, coronary steal, angina, volume overload, and CRS needs further study in cardiac patients.

Background Platelet adhesion to the subendothelial collagen fibrils is one of the first steps in hemostasis. Understanding how structural perturbations in the collagen fibril affect platelet adhesion can provide novel insights into disruption of hemostasis in various diseases. We have recently identified the presence of abnormal collagen fibrils with compromised D-periodic banding in the extracellular matrix remodeling present in abdominal aortic aneurysms (AAA). Objective In this study, we employed multimodal microscopy approaches to characterize how collagen fibril structure impacts platelet adhesion in clinical AAA tissues. Methods Ultrastructural atomic force microscopy (AFM) analysis was performed on tissue sections after staining with fluorescently labeled collagen hybridizing peptide (CHP) to recognize degraded collagen. Second harmonic generation (SHG) microscopy was used on CHP-stained sections to identify regions of intact versus degraded collagen. Finally, platelet adhesion was identified via SHG and indirect immunofluorescence on the same tissue sections. Results Our results indicate that ultrastructural features characterizing collagen fibril abnormalities coincide with CHP staining. SHG signal was absent from CHP-positive regions. Additionally, platelet binding was primarily localized to regions with SHG signal. Abnormal collagen fibrils present in AAA (in SHG negative regions) were thus found to inhibit platelet adhesion compared to normal fibrils. Conclusions Our investigations reveal how the collagen fibril structure in the vessel wall can serve as another regulator of platelet-collagen adhesion. These results can be broadly applied to understand the role of collagen fibril structure in regulating thrombosis or bleeding disorders.

Aufgrund akut einsetzender Atemnot stellt sich ein 67-jahriger Patient vor. Er ist in der Praxis mit einem Lungenemphysem und einer COPD bekannt. Seine Medikation nimmt er regelmasig ein. Er berichtet, dass er in den letzten Tagen mehr Hustenanfalle gehabt habe als sonst.

Objective— Abdominal aortic aneurysm is caused by the accumulation of inflammatory cells in the aortic wall. Our recent studies demonstrated that inhibition of Notch signaling attenuates abdominal aortic aneurysm formation by shifting the macrophage balance towards anti-inflammatory (M2) phenotype. Using IL12p40 −/− (interleukin 12 p40) mice, we investigated the effects of M2-predominant macrophages on the development of abdominal aortic aneurysm. Approach and Results— Male (8–10 week-old) wild-type and IL12p40 −/− mice (n=15) on C57BL/6 background were infused with Ang II (angiotensin II, 1000 ng/kg per minute) by implanting osmotic pumps subcutaneously for 28 days. In the IL12p40 −/− mice, Ang II significantly increased the maximal intraluminal diameter (9/15) as determined by transabdominal ultrasound imaging. In addition, IL12p40-deletion significantly increased aortic stiffness in response to Ang II as measured by pulse wave velocity and atomic force microscopy. Histologically, IL12p40 −/− mice exhibited increased maximal external diameter of aorta and aortic lesions associated with collagen deposition and increased elastin fragmentation compared with wild-type mice infused with Ang II. Mechanistically, IL12p40 deficiency by siRNA (small interfering RNA) augmented the Tgfβ2 -mediated Mmp2 expression in wild-type bone marrow–derived macrophages without affecting the expression of Mmp9 . No such effects of IL12p40 deficiency on MMP2/MMP9 was observed in human aortic smooth muscle cells or fibroblasts. Depletion of macrophages in IL12p40 −/− mice by clodronate liposomes significantly decreased the maximal external diameter of aorta and aortic stiffness in response to Ang II as determined by imaging and atomic force microscopy. Conclusions— IL12p40 depletion promotes the development of abdominal aortic aneurysm, in part, by facilitating recruitment of M2-like macrophages and potentiating aortic stiffness and fibrosis mediated by Tgfβ2 .

The emergency department (ED) is one of the crucial parts of the hospital infrastructure during all phases of the pandemic. The ED plays an important part in detecting an increasing number of new contagious diseases, which could potentially lead to an epidemic or pandemic.During a pandemic, the ED's main task is to detect infected individuals. These patients then need to be isolated and an adequate treatment is required. The ED must be prepared in order to perform well in such a situation. One major part for readiness is communication in an open manner to all partners within the department, as well as with emergency medical services and other departments of the hospital.The ED must be restructured to withstand the rising number of infected patients. These patients must be separated from other critically ill patients. Strategies for a diagnostic workup depending on the kind of infection have to be put in place. Pathways for the outpatient and inpatient management must be defined to avoid overcrowding in the ED. Depending on the number of patients, escalation and de-escalation strategies have to be set up within the hospital.Over the whole course of the pandemic, all staff members are the key resources for the ED and the entire hospital. The ED can only cope with a pandemic situation if staff are working together as a whole. This implies several important steps to get the staff prepared: Recurring, open conversations about fears, problems, and successes are critical for staff morale. Training must be continually provided, and protection strategies implemented. In the chronic phase of the pandemic the focus should shift more towards strategies on how to create possibilities for recuperation, domestic support measures, and mental health care for staff.

Enhanced mineralocorticoid receptor (MR) signaling is critical to the development of endothelial dysfunction and arterial stiffening. However, there is a lack of knowledge about the role of MR-induced adipose tissue inflammation in the genesis of vascular dysfunction in women. In this study, we hypothesize that MR activation in myeloid cells contributes to angiotensin II (Ang II)-induced aortic stiffening and endothelial dysfunction in femalesviaincreased pro-inflammatory (M1) macrophage polarization. Female mice lacking MR in myeloid cells (MyMRKO) were infused with Ang II (500 ng/kg/min) for 4 weeks. This was followed by determinations of aortic stiffness and vasomotor responses, as well as measurements of markers of inflammation and macrophage infiltration/polarization in different adipose tissue compartments. MyMRKO mice were protected against Ang II-induced aortic endothelial stiffening, as assessedviaatomic force microscopy in aortic explants, and vasorelaxation dysfunction, as measured by aortic wire myography. In alignment, MyMRKO mice were protected against Ang II-induced macrophage infiltration and M1 polarization in visceral adipose tissue (VAT) and thoracic perivascular adipose tissue (tPVAT). Collectively, this study demonstrates a critical role of MR activation in myeloid cells in the pathogenesis of vascular dysfunction in females associated with pro-inflammatory macrophage polarization in VAT and tPVAT. Our data have potential clinical implications for the prevention and management of cardiovascular disease in women, who are disproportionally at higher risk for poor outcomes.

This paper identifies multiple challenges that courts face to achieving fairness in the selection of juries in civil cases. Achieving representative cross-sections of the community in jury venires, and ensuring that our civil juries reflect the community as well, are essential components contributing to the fairness and legitimacy of our civil justice system. Although legal rules and practices attempt to maximize fair and representative juries, the courts encounter substantial difficulty in achieving this important goal. Problems arise in summoning citizens for jury service, in questioning them during voir dire, and in exercising peremptory and for-cause challenges. Systematic empirical research on representativeness and new psychological studies on implicit and unconscious bias raise questions about the efficacy of current jury selection procedures. This paper identifies these problems and the challenges they present for producing representative and fair juries.

Zusammenfassung Hintergrund Das neue, pandemische Coronavirus SARS-CoV-2 und die damit einhergehende Erkrankung COVID-19 (Coronavirus Disease 2019) stellt die medizinischen Versorgungssysteme vor große Herausforderungen. Die vorliegende Arbeit fasst die Strategie, Organisation und Maßnahmen der COVID-Taskforce des Universitätsklinikums Freiburg zusammen und berichtet über Erfahrungen und Behandlungsergebnisse von der Versorgung der ersten 115 COVID-19-Patienten. Methoden Retrospektive, narrative Prozessbeschreibung und -analyse des Zeitraums Ende Januar bis Anfang April 2020, durchgeführt unter Mitwirken der beteiligten Departments, Kliniken und Institute des Universitätsklinikums Freiburg. Ergänzend erfolgte eine retrospektive Beobachtungsstudie mit deskriptiver statistischer Auswertung der epidemiologischen und klinischen Daten aller bis 31. März 2020 hospitalisierten COVID-19-Patienten. Ergebnisse Durch eine interdisziplinär zusammengesetzte Taskforce Coronavirus wurden Maßnahmen in den Bereichen ambulante Testung und Beratung, Separierung der Patientenströme sowie Eskalation der Versorgungskapazitäten auf Normal- und Intensivstationen im Sinne eines dynamischen Stufenmodells angeregt und umgesetzt. Die Versorgung der ersten 115 Patienten gelang somit ohne Entstehung von Engpässen. Diskussion Durch Zusammenwirken sämtlicher Disziplinen und Abteilungen des Universitätsklinikums Freiburg konnte eine adäquate Versorgung von COVID-19-Patienten sichergestellt und die Handlungsfähigkeit des Klinikums in der aktuellen Ausbruchsituation erhalten werden.

Abdominal aortic aneurysm (AAA) is a localized pathological dilation of the aorta exceeding the normal diameter (∼20 mm) by more than 50% of its original size (≥30 mm), accounting for approximately 150000–200000 deaths worldwide per year. We previously reported that Notch inhibition does not decrease the size of pre-established AAA at late stage of the disease. Here, we examined whether a potent pharmacologic inhibitor of Notch signaling (DAPT (N-[N-(3,5-Difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester)), regresses an actively growing AAA. In a mouse model of an aneurysm (Apoe−/− mice; n=44); DAPT (n=17) or vehicle (n=17) was randomly administered at day 14 of angiotensin II (AngII; 1 µg/min/kg), three times a week and mice were killed on day 42. Progressive increase in aortic stiffness and maximal intraluminal diameter (MILD) was observed in the AngII + vehicle group, which was significantly prevented by DAPT (P

An abdominal aortic aneurysm (AAA) is defined as a localized dilation of the abdominal aorta that exceeds the maximal intraluminal diameter (MILD) by 1.5 times of its original size. Clinical and experimental studies have shown that small aneurysms may rupture, while a subpopulation of large aneurysms may remain stable. Thus, in addition to the measurement of intraluminal diameter of the aorta, knowledge of structural traits of the vessel wall may provide important information to assess the stability of the AAA. Aortic stiffening has recently emerged as a reliable tool to determine early changes in the vascular wall. Pulse propagation velocity (PPV) along with the distensibility and radial strain are highly useful ultrasound-based methods relevant for assessing aortic stiffness. The primary purpose of this protocol is to provide a comprehensive technique for the use of ultrasound imaging system to acquire images and analyze the structural and functional properties of the aorta as determined by MILD, PPV, distensibility and radial strain.

In civil litigation voir dire (jury selection) has a fundamental impact on jury composition, and by extension, is inextricably entangled with constitutional, statutory, and precedential guarantees regarding an impartial jury of the parties' peers. However, despite its deep influence on jury composition, and by extension trial outcomes, the rules for jury selection vary wildly by jurisdiction, ranging from almost no questioning of jurors at all to extensive questioning that dives into details of the underlying cases. Indeed, selection can take a week in some states and 20 minutes in others. This article involves a first of its kind empirical study that analyzes results from a national sample of over 2,000 mock jurors. The study measures the impact of jury selection across three distinct civil case presentations based on actual cases. It measures existing jury biases, explores how those biases impact juror decisions, considers whether existing methods common to voir dire sufficiently identify those biases, and analyzes whether existing methods for "curing" such biases are effective. It concludes that a) existing biases, many of which are prevalent in the existing jury population, fundamentally impact juror decision making - sometimes in ways that are inappropriate, b) these biases can harm both sides of civil litigation but they skew in favor of civil defendants, c) these biases will often go unidentified under existing rules so that an impartial jury is not assured, d) this problem is not cured by existing interventions, and e) jurors are largely blind to the role bias plays in their decision making. The article concludes with best practices that could be useful to attorneys, legislators, and judges.

Objectives: Three experiments tested the utility of minimal versus extended voir dire questions in predicting mock jurors’ verdicts and damage awards, and whether the biasing impact of their preexisting attitudes on case judgments could be reduced by judicial rehabilitation. Hypotheses: We hypothesized that extended voir dire questions would be more predictive of case judgments than minimal voir dire questions. We hypothesized that judicial rehabilitation would not reduce this impact of preexisting attitudes on case judgments. Method: Across three experiments, each focusing on a different civil case (insurance bad faith, wrongful birth, medical malpractice misdiagnosis), online participants (N=2,041; 62% female; 77% White, 9% African American, 6% Asian/Pacific Islander, 6% Hispanic or Latino/a; Mage=40) were paid Mturk workers. They were randomly assigned to experience (a) no voir dire, minimal voir dire focusing on previous legal experience and self-identification of biases, or extended voir dire focusing on specific attitudes about civil litigation, parties, and laws, before judging the case and (b) no judicial rehabilitation, or judicial rehabilitation. Participants read a civil case, made case judgments, and completed bias awareness measures. Results: Demographic information and minimal voir dire questions did not predict case judgments, but the majority of extended voir dire responses predicted verdicts and damage awards. Judicial rehabilitation did not reduce the biasing impact of their preexisting attitudes on case judgments—but did result in mock jurors reporting that they were less biased, despite judicial rehabilitation not actually reducing their bias. Conclusions: Attorneys need the opportunity during voir dire to ask jurors about specific attitudes that might bias their decisions because relying on jurors’ self-identification of their own biases has little utility. Further, although judicial rehabilitation might make jurors think that they are less biased, it may not actually reduce the impact of their preexisting attitudes on their case decisions. Public interest statement: Contrary to popular belief, juror biases are not likely to be cured by judicial rehabilitation, and might backfire by creating the illusion in jurors that they are unbiased. Although very few mock jurors were able to self-identify things that might bias them when asked general questions in voir dire, they were willing to admit specific attitudes that biased their verdicts and damage awards when asked. Thus, we suggest reducing bias on juries by allowing attorneys to ask specific, detailed voir dire questionnaires crafted by the parties to streamline the jury selection process and remove jurors for cause or via peremptory challenges, rather than relying on “quick fixes”, such as general questions that ask jurors to self-identify their own bias or judicial rehabilitation.

Diabetes mellitus ist eine komplexe Erkrankung mit zunehmender Pravalenz. Oft bleibt eine diabetische Stoffwechsellage unerkannt. Bei der Versorgung entsprechender Patienten in Notfallsituationen muss differenzialdiagnostisch nicht nur an die hypo- und hyperglykamischen Komplikationen eines bekannten Diabetes und seine Langzeitfolgen gedacht werden, sondern auch an die evtl. untypische Diabeteserstmanifestation. Daruber hinaus sind Diabetespatienten durch kardiovaskulare, chirurgische und infektiologische Komplikationen bedroht. Besondere Risikogruppen sind Kinder, Schwangere oder geriatrische Patienten mit ihrer in Notfallsituationen oft unspezifischen Symptomatik. Die Versorgungskette sollte aus ambulanter hausarztlicher Betreuung, Rettungsdiensten und der Behandlung in Notfallzentren bestehen. Eine enge Vernetzung ist notwendig, um sektorenubergreifende und patientenzentrierte Strategien zu gewahrleisten. Die klinische Notfallmedizin sollte hier Schnittstellenfunktion haben.

IntroductionThe word transplant" conjures up diverse images, whether it is a team of doctors crowded around an operating table during an organ transplant, or rows of small tomato plants recently inserted into newly tilled earth. For comparative law scholars, the term signals something completely different. Decades ago, the Scotsman Alan Watson (1974) generated the concept of a legal transplant, which continues to be a major focus of comparative law scholarship (Graziadei 2006; Riles 2006). According to Watson, a legal transplant is the common phenomenon of one country adopting, in whole or in part, another country's established law, legal procedure, legal institution, or legal system. Some see this as the single most important phenomenon in the development of law, for example: "the growth of law is principally to be explained by the transplantation of legal rules" (Ewald 1995:489). The notion has been employed to explain the dissemination of legal procedures (Brake and Katzenstein 2013), plea bargaining (Langer 2004), and a host of other legal phenomena across the globe. This essay employs the concept of legal transplant as a vehicle to describe the global spread of trial by jury.The concept of a legal transplant has been ubiquitous in the field of comparative law, but also contentious. Scholars differ in their views of the extent to which culture and society affect the transfer of laws and legal procedures (for a review of the debate, see Goldbach 2015:92-95). Even the "transplant" terminology is contested (Graziadei 2006:443). Some scholars of comparative law maintain that the word is at the very least misleading because it suggests that an organ, plant, or legal procedure transplant might function exactly the same in its new body, garden, or country as it did in the previous one (Legrand 1997; Merryman et al. 1994). From this perspective, the idea of legal "translating" more correctly captures the ways in which legal systems import, borrow, or export their laws, procedures, constitutions, or institutions to other legal systems (Berkowitz, Pistor, and Richard 2003; Langer 2004). These scholars believe translation is a more apt metaphor because it allows one to distinguish between two countries' laws that may be textually identical but function in completely different manners.I am an outsider to the field of comparative law. I am trained as a social psychologist, running experiments, analyzing surveys, and interviewing participants. But like many others in the interdisciplinary Law and Society Association, my research focus on juries and lay participation has lured me into fields well beyond my initial training, in this case, the domain of comparative law. From my outsider's perspective, I find the concepts of transplanting and translating to be thought-provoking metaphors for the movement of the jury in global legal systems: its introduction and its flourishing, as well as its abolition and its decline, around the world.My essay about the jury as a legal transplant presumes the importance of society on legal movements, and has two emphases. First, I try to understand the societal, political, and legal circumstances and actions that have led to the adoption, expansion, and decline of lay citizen participation in law (Hans 2007, 2008; Thaman 2007; Thomas 2016). Trial by jury is a frequent topic in popular culture. It is regularly featured in movies, television shows, books, and other popular media, particularly in the United States (Abramson 2000:498-500; Hans 2013:392-94; Marder 2007; Papke et al. 2007). Further, research on how the jury functions as a decision making body is voluminous (Baldwin and McConville 1979; Devine 2012; Diamond and Rose 2005; Goodman-Delahunty and Tait 2006; Kovera 2017; Vidmar and Hans 2007). Much jury research is focused on how a jury or another lay fact-finding body functions within a single country at a particular point in time. There is a relatively modest amount of work that engages generally in historical and international comparisons and that specifically contrasts different forms of lay participation (Hans et al. …

Background Dermal neural lesions arise in various circumstances and may be difficult to classify. Methods We describe the clinical, histopathologic and immunophenotypic features of a series of terminally-differentiated neural lesions not described previously, to our knowledge. Results Four cases from men aged 58–66 years were included. Some lesions reportedly bled, but no inciting trauma or prior biopsies were reported. None recurred after biopsy, with follow-up ranging from 19 to 113 months. All lesions were papular, with vertically-oriented S100-positive spindled cells and nerve fibers in the papillary dermis. Slight epidermal hyperplasia, dilated superficial thin-walled vessels and minimal to mild inflammation were seen in each. Fibers were uniformly fine in three cases, with slightly thicker central fibers in the fourth. Three had parakeratotic scale. None were associated with dermal fibrosis or adnexal proliferation. Neurofilament stained axons in each. EMA was negative in all cases. CD34, melan-A and HMB45 were negative when performed. Conclusions We report a small series of benign neural lesions and propose the name “superficial papular neuroma” for this distinct entity. Awareness is important to understand the clinical significance of these lesions and avoid misinterpretation that could lead to overtreatment, unnecessary work-up and increased cost.

Abdominal aortic aneurysm (AAA) is characterized by transmural infiltration of myeloid cells at the vascular injury site. Previously, we reported preventive effects of Notch deficiency on the development of AAA by reduction of infiltrating myeloid cells. In this study, we examined if Notch inhibition attenuates the progression of pre-established AAA and potential implications. Pharmacological Notch inhibitor (N-[N-(3,5-difluorophenacetyl)-L-alanyl]-(S)-phenylglycine t-butyl ester; DAPT) was administered subcutaneously three times a week starting at day 28 of angiotensin II (AngII) infusion. Progressive increase in pulse wave velocity (PWV), maximal intra-luminal diameter (MILD) and maximal external aortic diameter (MEAD) were observed at day 56 of the AngII. DAPT prevented such increase in MILD, PWV and MEAD (P Apoe−/− mice had significant reduction in inflammatory response and elastin fragmentation. Naked collagen microfibrils and weaker banded structure observed in the aortae of Apoe−/− mice in response to AngII, were substantially diminished by DAPT. A significant decrease in the proteolytic activity in the aneurysmal tissues and vascular smooth muscle cells (vSMCs) was observed with DAPT (P 2 = 0.61). Collectively, we propose inhibition of Notch signaling as a potential therapeutic target for AAA progression.

This chapter reviews theoretical arguments and empirical research pertaining to the symbolic and other significance of the criminal jury trial and to the ways in which it may be related to crime control. The jury is both the symbol and the actual presence of the public in court. The symbolic and real involvement of citizens in the legal system, it is argued, helps to provide legitimacy for the system and its verdicts. One finding that tends to support assertions about the educative and legitimizing effects of the jury is that jurors themselves report holding the institution in very high regard after they have served as jurors. Procedural justice research suggests that people's obedience to law is linked to the extent to which they see the legal system as legitimate. Jury service—direct observation and participation as decisionmakers in the legal system —enhances appreciation for the rule of law.

Naïve macrophages (Mφ) polarize in response to various environmental cues to a spectrum of cells that have distinct biological functions. The extreme ends of the spectrum are classified as M1 and M2 macrophages. Previously, we demonstrated that Notch1 deficiency promotes Tgf-β2 dependent M2-polarization in a mouse model of abdominal aortic aneurysm. The present studies aimed to characterize the unique set of genes regulated by Notch1 signaling in macrophage polarization. Bone marrow derived macrophages isolated from WT or Notch1+/− mice (n = 12) were differentiated to Mφ, M1 or M2-phenotypes by 24 h exposure to vehicle, LPS/IFN-γ or IL4/IL13 respectively and total RNA was subjected to RNA-Sequencing (n = 3). Bioinformatics analyses demonstrated that Notch1 haploinsufficiency downregulated the expression of 262 genes at baseline level, 307 genes with LPS/IFN-γ and 254 genes with IL4/IL13 treatment. Among these, the most unique genes downregulated by Notch1 haploinsufficiency included fibromodulin (Fmod), caspase-4, Has1, Col1a1, Alpl and Igf. Pathway analysis demonstrated that extracellular matrix, macrophage polarization and osteogenesis were the major pathways affected by Notch1 haploinsufficiency. Gain and loss-of-function studies established a strong correlation between Notch1 haploinsufficiency and Fmod in regulating Tgf-β signaling. Collectively, our studies suggest that Notch1 haploinsufficiency increases M2 polarization through these newly identified genes.

This chapter examines the procedural roles of professional judges, lay judges, and lay jurors in criminal adjudication. It considers the relationships between each actor and other participants in the criminal process, using examples from specific jurisdictions within three identified adjudicatory frameworks. It also discusses competing trends in the roles of each actor in systems across the world, focusing on increased reliance on professional judges in some countries and introduction of new lay judge and jury systems in others. The likely impact of these shifts is explored by comparing patterns in judge versus jury decision-making. The chapter concludes by highlighting reasons for global trends observed in the allocation of decision-making in criminal adjudication to particular actors, noting the desire for greater accountability in systems shifting toward more judicial control as well as the attraction of democratizing decision-making in systems embracing trial by jury.

BACKGROUND: Dengue incidence is rising globally which was estimated 100 million per year, whereas in Indonesia was estimated 7.5 million per year. Dengue clinical course varies from mild dengue fever (DF) to dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS). Patients, clinicians and care facilities would benefit if reliable predictors can determine at admission which cases with clinically suspected dengue will progress to DHF or DSS. METHODS: From 2009 through 2013, a cohort of 494 children admitted with clinically suspected dengue at a tertiary care hospital in Jakarta, Indonesia, was followed until discharge. We evaluated the clinical course and disease outcome of admitted patients and estimated the burden of dengue cases hospitalized over time. RESULTS: Of all 494 children, 185 (37%) were classified at admission as DF, 158 (32%) as DHF and 151 (31%) as DSS. Of DF patients, 52 (28%) progressed to DHF or DSS, 10 (5%) had other viral diseases. Of DHF patients, 9(6%) progressed to DSS. Of 33 routinely collected parameters at admission, duration of fever ≤4 days was the only significant predictor of disease progression (P = 0.01). Five cases (3%) admitted with DSS died. Between 2009 and 2013, annual dengue admissions declined, while distribution of disease severity remained stable. CONCLUSIONS: Almost a third of children admitted to tertiary care with clinically suspected DF progress to DHF or DSS. Among routinely collected parameters at admission, only fever duration was significantly associated with clinical progression, emphasizing unpredictability of dengue disease course from parameters currently routinely collected.

The introduction to the special issue describes the goals of the conference on Juries and Mixed Tribunals across the Globe, and identifies themes that emerged as jury scholars from all over the world examined different forms of lay participation in legal decision-making. The introduction focuses on common challenges that different systems of lay participation face, including the selection of impartial fact finders and the presentation of complex cases to lay citizens. The introduction and special issue articles also highlight new developments and innovative practices to address these challenges, including some tools, like decision trees, that remain highly controversial. The introduction closes by emphasizing the enduring political importance of citizen participation in law. La introducción a este número especial describe los objetivos de la conferencia sobre jurados y tribunales mixtos en el mundo, e identifica los temas que surgieron cuando académicos de todo el mundo especializados en jurados analizaron diferentes formas de participación de legos en la toma de decisiones jurídicas. La introducción se centra en los desafíos comunes a los que se enfrentan los diferentes sistemas de participación de legos, incluyendo la selección de jurados imparciales y la presentación de casos complejos a ciudadanos profanos en la materia. La introducción y el número especial también destacan nuevos desarrollos y prácticas innovadoras para afrontar estos retos, incluyendo algunas herramientas, como los árboles de decisiones, que todavía son muy controvertidas. La introducción finaliza, haciendo hincapié en la importancia política duradera de la participación ciudadana en el derecho. DOWNLOAD THIS PAPER FROM: http://ssrn.com/abstract=2785708

This article introduces a scientific exchange over the status of procedural justice theory and its applicability to policing reform. The introduction notes the long history of sociolegal research on procedural justice and its emergence as a source of ideas for criminal justice reforms and police training programs. The article contrasts the positions taken by Nagin & Telep (2017) and Tyler (2017) . Nagin & Telep assert that it is premature to apply procedural justice principles without more definitive causal studies in policing. In contrast, Tyler draws on experimental research and other causal studies from different domains to argue that the work is sufficient to proceed with policy reforms.

This chapter presents and analyzes the current state of law and research on the capital jury. First, it presents the legal framework for capital jury selection and research on the “death-qualified” jury, whose members are eligible to serve in a capital case. It also discusses research showing that the death-qualification process skews the composition of the capital jury so that it fails to represent the community and is more conviction-prone. Next, the chapter considers the contemporary death penalty in the United States, noting the challenge that comes from declining support for capital punishment and the need to select representative capital juries. The chapter concludes by discussing the implications of the current trends in support for the death penalty and research on capital juries.

Introduction: Our previous studies demonstrated that loss of Notch1 signaling reduces the incidence of abdominal aortic aneurysm (AAA) by preventing the influx of pro-inflammatory M1 macrophages and that Notch1 deficiency promotes M2-polarization. In the present study, we determined if inhibition of Notch signaling could reverse the pre-existing pro-inflammatory M1 macrophages to anti-inflammatory M2 phenotype. Methods and Results: Raw cells (264.7 murine macrophage cell line) were treated with various concentrations of LPS (5, 10, 100 ng/ml) and IFN-γ (10 ng/ml) for 3h to polarize naïve macrophages into M1-phenotype. After washing, these cells were treated with either vehicle or DAPT (10 ng/ml or 25 ng/ml); a potent Notch inhibitor for 6, 12, 24 or 48h and later used for gene expression studies or functional assays. LPS pretreatment significantly increased the gene expression of M1-genes; Il6 , Il12, Cd38, Fpr2 and iNOS , whereas the expression of M2 genes; Egr2 and c-Myc was significantly decreased. Replacement of LPS with vehicle alone lowered the expression of Il6 and Il12 within 6-12h, but remained significantly higher than basal levels. Expression of iNOS , Cd38 and Fpr2 remained unchanged in response to vehicle in the LPS-pretreated macrophages. DAPT treatment further reduced the gene expression of Il6 and Il12 significantly and iNOS moderately as compared to vehicle-treated macrophages. Interestingly, Notch inhibition increased the expression of Egr2 and c-Myc genes at 24 and 48h. Similar trends with regard to M1 and M2 genes were observed in bone marrow derived macrophages from Apoe -/- and WT mice treated with LPS followed by vehicle or DAPT. Phagocytosis assay showed increased uptake of zymosan bioparticles in the macrophages treated with LPS. Replacement of LPS with vehicle for 24h did not affect the phagocytosis significantly. DAPT treatment decreased phagocytic activity of these macrophages as compared to vehicle-treated macrophages. Conclusions: Our data suggest that Notch inhibition reverses the M1-polarized macrophages towards M2-like macrophages. These novel insights in the functions of Notch signaling may have potential implications in chronic inflammatory diseases including AAA and atherosclerosis.

Introduction: Abdominal aortic aneurysm (AAA) is caused by the immune and inflammatory cell accumulation of the aortic wall, leading to enhanced inflammation and aneurysm formation. Our recent studies demonstrate that inhibition of Notch signaling attenuates AAA formation by shifting the macrophage balance towards anti-inflammatory (M2) phenotype. Using IL12p40 knockout (KO) mice, we investigated the direct effects of M2-like macrophages in the development of AAA. Methods and Results: Male (8-10 week-old) wild-type (WT) and IL12p40-KO mice (n=10) on C57BL/6 background were infused with angiotensin-II (AngII, 1,000 ng/kg/min) by implanting osmotic pumps subcutaneously for 28 days. Comparable increase in mean, systolic and diastolic arterial blood pressure was observed between WT and IL12p40-KO mice in response to AngII. Unexpectedly, AngII significantly increased the AAA-associated mortality (2/10) and luminal expansion (7/10) in IL12p40-KO mice as determined by transabdominal ultrasound. In addition, IL12p40-deficiency significantly increased aortic stiffness in the abdominal aortas in response to AngII than WT as measured by pulse wave velocity (PWV) and atomic force microscopy (AFM). Macroscopic and histological examination also showed that IL12p40-KO mice exhibited severe abdominal aortic lesion formation and increased maximal aortic width compared to WT mice. Increased elastin fragmentation and collagen deposition was detected in aorta of AngII-infused IL12p40-KO mice compared to AngII-infused WT mice. Further, there was no significant change in the total cholesterol, triglycerides and HDL-cholesterol levels in the serum of WT and IL12p40-KO mice treated with AngII. Importantly, bone marrow derived macrophages (BMDM) from IL12p40-KO mice showed increased mRNA expression of M2-markers (TGF-β1 and IL10) and decreased expression of M1-markers (iNOS and TNF-α) at basal level compared to WT BMDM. Conclusions: IL12p40 deficiency may promote the development of AAA, in part, by facilitating recruitment of M2-like macrophages and potentiating aortic-stiffness and fibrosis mediated by TGF-β1 and IL10. In summary, optimal M1/M2 balance rather than predominance of M2-phenotype may be prerequisite to prevent AAA formation.

12 Journal of Empirical Legal Studies, 70-99 (2015)This article addresses the effect of judge versus jury decision making through analysis of a database of all capital sentencing phase hearing trials in the State of Delaware from 1977– 2007. Over the three decades of the study, Delaware shifted responsibility for death penalty sentencing from the jury to the judge. Currently, Delaware is one of the handful of states that gives the judge the final decision-making authority in capital trials. Controlling for a number of legally relevant and other predictor variables, we find that the shift to judge sentencing significantly increased the number of death sentences. Statutory aggravating factors, stranger homicides, and the victim’s gender also increased the likelihood of a death sentence, as did the county of the homicide. We reflect on the implications of these results for debates about the constitutionality of judge sentencing in capital cases.