cssi/SciSciGPT-SciSciNet huggingface dataset:
The effect of cytochalasin B on the endosteal lining cells of mammalian bone. A scanning electron microscopic study.

The lining osteoblasts of the rat tibial endosteum were treated for various times (between 1 and 60 min) and increasing doses (3.87–38.7 μg/ml) with the macrolide fungal metabolite cytochalasin B (CB). Dimethylsulfoxide (DMSO) served as the vehicle for CB and was administered to control tissues. An in vitro incubation system and scanning electron microscopy (SEM) were used to evaluate the effects of CB. The drug initiated cell rounding (contraction), nuclear protrusion, bleb formation, and the subsequent clustering of blebs and microvilli into aggregates. All CB-induced aberrations of the surface structure were readily reversible when tissues were washed with CB-free media. DMSO had no significant effect on cell surface morphology. The reversible structural changes brought about by CB are explained in terms of alterations of the subplasmalemmal cortical microfilament system of osteoblasts. The potential use of CB in evaluating the bone cell cytoskeleton and its relationship to the physiology of the cellular functional membrane (endosteum) of bone is discussed.
Stereotactic Radiosurgery for Psychiatric and Pain Disorders

Since its inception, stereotactic radiosurgery has been utilized to treat functional disorders of the brain. These have included psychiatric conditions such as intractable obsessive-compulsive disorder. It has also been employed to treat medically refractory pain disorders of which trigeminal neuralgia is the most commonly treated pain condition. Radiosurgery offers a minimally invasive option for treating functional disorders while avoiding the need for costly neural stimulators or lifelong medical therapy. In treating patients with functional disorders, high radiosurgical doses are employed. As such, a thorough understanding of the target anatomy is required along with a high degree of accuracy and precision in the radiosurgical delivery. Advanced neuro-imaging will shed light on the underlying changes effectuated by radiosurgery and likely lead to refinements in the radiosurgical technique for indications of psychiatric and pain disorders.
Preparing for the Delivery of a Neonate With Neural Tube Defect

NOTE: To learn to perform a procedure, there are both cognitive and procedural steps that should be followed. These steps are explained and demonstrated in this month’s Video Corner and are summarized for quick reference in the list below. The video depicts one of the methods of handling a neonate with a prenatal diagnosis of neural tube defect (NTD).⇓ Figure 1. Click here to view the video. (Reproduced with permission of Akshaya Vachharajani, MD, and The Saigh Foundation Pediatric Simulation Center, St Louis Children’s Hospital and Washington University School of Medicine. Copyright 2012.) These points may be discussed before attending the birth of an infant with prenatal diagnosis of neural tube defect (NTD):
An Agent-Based Model for Addressing the Impact of a Disaster on Access to Primary Care Services.

OBJECTIVE: Hurricane Sandy in the Rockaways, Queens, forced residents to evacuate and primary care providers to close or curtail operations. A large deficit in primary care access was apparent in the immediate aftermath of the storm. Our objective was to build a computational model to aid responders in planning to situate primary care services in a disaster-affected area. METHODS: Using an agent-based modeling platform, HAZEL, we simulated the Rockaways population, its evacuation behavior, and primary care providers' availability in the aftermath of Hurricane Sandy. Data sources for this model included post-storm and community health surveys from New York City, a survey of the Rockaways primary care providers, and research literature. The model then tested geospatially specific interventions to address storm-related access deficits. RESULTS: The model revealed that areas of high primary care access deficit were concentrated in the eastern part of the Rockaways. Placing mobile health clinics in the most populous census tracts reduced the access deficit significantly, whereas increasing providers' capacity by 50% reduced the deficit to a lesser degree. CONCLUSIONS: An agent-based model may be a useful tool to have in place so that policy makers can conduct scenario-based analyses to plan interventions optimally in the event of a disaster. (Disaster Med Public Health Preparedness. 2016;page 1 of 8). Language: en
La cascada de justicia y el impacto de los juicios de derechos humanos en América Latina

Desde la decada de 1980 los Estados se han abocado cada vez mas a abordar las violaciones a los derechos humanos ocurridas en el pasado mediante la utilizacion de variados mecanismos de justicia de transicion que incluyen a los juicios internos e internacionales sobre derechos humanos. A mediados de esa decada, los estudiosos de las transiciones a la democracia llegaron en general a la conclusion que los juicios por violaciones a los derechos humanos ocurridas en el pasado eran politicamente insostenibles y podian socavar las nuevas democracias. Mas recientemente, algunos especialistas en relaciones internacionales se han hecho eco de las afirmaciones pesimistas de aquellos primeros "escepticos de los juicios" y han anadido dudas sobre el impacto de los juicios. Sin embargo, hay pocos estudios empiricos que abarquen varios paises y que tengan la meta de poner a prueba estas afirmaciones, en parte por falta de una base de datos sobre este tipo de juicios.
Existing and new applications of micropellet injection (MPI) in magnetic fusion

The intense heat and energetic particle fluxes expected in ITER and future magnetic fusion reactors pose prohibitive problems to the design, selection and maintenance of the first wall and divertor. Micropellet injection (MPI) technologies can offer some innovative solutions to the material and extreme heat challenges. Basic physics of micropellet motion, ablation and interactions with high-temperature plasmas and energetic particles are presented first. We then discuss MPI technology options and applications. In addition to plasma diagnostic applications, controlled injection of micropellets of different sizes, velocities and injection frequencies will offer several possibilities: (1) better assessment of the core plasma cooling due to dust produced in situ; (2) better understanding of the plasma–material interaction physics near the wall; (3) new methods for plasma fuelling and impurity control; and (4) techniques for edge cooling with minimal impact on the plasma core. Dedicated small-scale laboratory experiments will complement major fusion experiments in development and applications of MPI.
Epidemiological characteristics of human brucellosis,Puyang city,2006-2014

Objective To analyze the epidemiological characteristics of human brucellosis in Puyang city,so as provide measures for its prevention and control. Methods Descriptive epidemiological method was used to analyze the three-dimensional distribution of cases,sources and routes of infection. Results A total of 128 cases were reported from 2006to2014,with the annual incidence rate from 0.08/105 to 1.48/105,which was rising year by year.Human brucellosis could occur year-round;The incidence mainly concentrated from March to August,and the total reported cases were 85,accounting for 66.41%;The peaks were from April to May,with 37 cases reported,accounting for 28.91%.Human brucellosis cases were reported in all counties;The highest percentage was Taiqian county(50.00%,64/128),followed by Puyang county(16.41%,21/128).103 cases were males,25 cases were females,and the male-female ratio was 4.12;The 31-60 years oldgroup accounted for 74.22%(95/128);The occupations were mainly farmers,accounting for 90.63%(116/128).Among 76 cases in 2013 and 2014investigated,the main symptoms were fever,weakness,hyperhidrosis,bone and arthrosis pain and muscles pain;all of them had contact history with livestock(mainly sheep)and/or animal products;38cases were infected by farming the grazing livestock and delivering cubs,accounting for 50.00%,mainly distributed in Puyang county,Nanle county,and Fan county;31cases of patients were infected for buying and trafficking livestock,fur and feather,slaughering livestock and peeling lambskin,accounting for 40.79%,mainly distributed in Taiqian county;7cases of patients were infected for playing in the sheepfold and eating mutton hotpot,accounting for 9.21%,mainly distributed in Puyang county. Conclusion The infection of human brucellosis in Puyang city shows an increasing trend,widening scope and diversification of infection routes.
Overconfident Agent's Incentive Mechanisms Based on the Combined Long-term and Short-term Performance

The current research on overconfident agent's incentive mechanisms is based on net profit and current period performance. However,net profit is only the matching result of whole income and whole expenditure according to accrual basis. Since net profit doesn't include the cost of equity capital,it cannot reflect an enterprise's value creation. Current period performance,also named short-term performance,lies primarily on an agent's short-term effort. In fact,an agent's effort includes not only short-term effort but also long-term effort,such as research development and market development. The contribution of long-term effort may not be able to improve the current period performance. On the contrary,it decreases the current period performance because of investment. It can influence an agent's short-term game behavior. This paper uses value creation as performance measurement standard and designs overconfident agent's incentive model by combining long-term and short-term performance according to current period performance and future performance. This paper uses principal and agent's overconfidence degree and risk preference,tests the incentive effect of compensation contract for agent based on combined long-term and short-term performance,and reveals agent's effort and requirement for surplus share proportion. Important findings are drawn from this study. Firstly,the higher an agent's degree of overconfidence for unfavorable factors,the smaller the required surplus share proportion is,and the lower the working effort level is. Contrary findings can be found for favorable factors. Secondly,the higher the principal's degree of overconfidence degree for unfavorable factors,the bigger the surplus share proportion an agent can receive and the greater an agent's effort is. Contrary findings can be found for favorable factors. Thirdly,the stronger an agent's risk preference,the higher the distribution proportion of long-term and short-term effort is,and the lower an agent's effort is. The stronger a principal's risk preference,the bigger the surplus share proportion of long-term and short-term performance is and the greater an agent's effort is. Fourthly,agents in monopoly industries make less effort than ones in competitive industries. The greater the proportion of monopoly earnings is,the less effort agents make. Therefore,it is necessary to introduce competitive mechanism in monopoly industries or transform monopoly industries to competitive industries in order to motivate agents' enthusiasm.
Foot Reconstruction in Diabetes Mellitus and Peripheral Vascular Insufficiency

The great majority of diabetic patients have diabetic foot symptoms. Significant recent advances in reconstructive surgery, as well as improvements in the management of both diabetes mellitus and peripheral vascular disease, make these patients eligible for plastic and reconstructive surgery. Many diabetic patients who would previously have had below-the-knee amputations are now having their complex foot wounds reconstructed. In addition to the metabolic consequences of the disease and the increased susceptibility to infection and wound healing complications, infrapopliteal arterial occlusive disease, peripheral neuropathy, and hemorrheologic changes are addressed in this article.
Chain Binomial Models

We look next at both the deterministic and stochastic versions of the chain binomial model. Although this model was originally designed as an educational device, it has proven to be a useful representation for analysing small epidemics, such as those within a single family or a school.
Trust & Self-Organising Socio-technical Systems

We present our theory on trust and its components and dimensions, and apply it to trust in complex dynamic socio-technical systems and to their self-organising emergent results. Specifically, we apply our theory to ICT-based systems, where a “Social Order” is no longer fully “spontaneous” due to the invisible hand impinging on individual and selfish-decisions. In such contexts, a social order is rather based on programmed interactions, algorithmic procedures and big data. Since trust cannot be fully programmable and predictable, how can we build it in this complex and dynamic system? Some of our research questions sound: is it necessary that folks “understand” the underlying mechanisms they are relying on? What kind of information about forecasts or future projections should be provided and adjusted? What kind of role do simulation, serious games play on learning to understand and expect? Will there be algorithms working on the micro-processes and producing the emergent organisation, and if yes, how effective and reliable will they be? There are at least two different levels of trust in complex systems and in their functioning processes: trust in the emergent order and trust in the micro-layer rules. Are the systems rules and resulting equilibriums fair, equity inspired, in relation to the interests of the involved groups/subjects? A complex and cognitive model of trust is needed for this analysis.
High-Resolution Non-Hydrostatic Modeling of Frontal Features in the Mouth of the Columbia River

Airborne data measured during the recent RIVET II field experiment has revealed that horizontally distributed thermal fingers regularly occur at the Mouth of Columbia River (MCR) during strong ebb tidal flows. The high-resolution, non-hydrostatic coastal model, NHWAVE, predicts salinity anomalies on the water surface which are believed to be associated with the thermal fingers. Model results indicate that large amplitude recirculation are generated in the water column between an oblique internal hydraulic jump and the North Jetty. Simulation results indicate that the billows of higher density fluid have sufficiently large amplitudes to interrupt the water surface, causing the prominent features of stripes on the surface. The current field is modulated by the frontal structures, as indicated by the vorticity field calculated from both the numerical model and data measured by an interferometric synthetic aperture radar.
Safety and Pharmacodynamics of the PDE4 Inhibitor Roflumilast in Advanced B-cell Malignancies

Purpose: In this study, we aimed to validate our extensive preclinical data on phosphodiesterase 4 (PDE4) as actionable target in B-cell malignancies. Our specific objectives were to determine the safety, pharmacokinetics, and pharmacodynamics (PI3K/AKT activity), as well as to capture any potential antitumor activity of the PDE4 inhibitor roflumilast in combination with prednisone in patients with advanced B-cell malignancies.Experimental Design: Single-center, exploratory phase Ib open-label, nonrandomized study. Roflumilast (500 mcg PO) was given daily for 21 days with prednisone on days 8 to 14. Additional 21-day cycles were started if patients tolerated cycle 1 and had at least stable disease.Results: Ten patients, median age 65 years with an average of three prior therapies, were enrolled. The median number of cycles administered was 4 (range, 1-13). Treatment was well tolerated; the most common ≥grade 2 treatment-related adverse events were fatigue, anorexia (≥25%), and transient ≥ grade 2 neutropenia (30%). Treatment with roflumilast as a single agent significantly suppressed PI3K activity in the 77% of patients evaluated; on average, patients with PI3K/AKT suppression stayed in trial for 156 days (49-315) versus 91 days (28-139 days) for those without this biomarker response. Six of the nine evaluable patients (66%) had partial response or stable disease. The median number of days in trial was 105 days (range, 28-315).Conclusions: Repurposing the PDE4 inhibitor roflumilast for treatment of B-cell malignancies is safe, suppresses the oncogenic PI3K/AKT kinases, and may be clinically active. Clin Cancer Res; 23(5); 1186-92. ©2016 AACR.
Chapter 6 Dancing for the Nation: The Voloshky Ukrainian Dance Ensemble, The Duquesne University Tamburitzans, and the Gandy Dancers

In this chapter, the author traces the development of three different dance companies which are based in the United States: Voloshky Ukrainian Dance Ensemble, the Duquesne University Tamburitzans, and the Gandy Dancers of Los Angeles. Each of these groups performs Ukrainian ethno-identity dances, but each has a different ethnic composition and different motives for performing the dances— for nation, for profit, for fun, respectively. Shay then gives a brief history of the Ukraine, describing the historical elements that parallel Irish history: the fraught relations with Russia, a great Famine in the 1930s, and continuing conflict with the Russians. (The conflict that was ongoing in 2016 occurred after the writing of this chapter.) He describes Ukrainian dance, both in the field dances and the spectacularized ethno-identity staged dances.
Generalized Inter-Cloud Structured Data Sharing

In this paper, we discuss the issue of collaborative data sharing among a number of parties to provide rich online services to their clients. We assume that each party hosts its data in a private cloud infrastructure but they collectively agree to certain well-defined set of accesses and access restrictions to one another's databases. We show how these can be used to derive access rules that become the basis of access control and query planning. In this paper we focus entirely on relational database sharing, and present efficient and near optimal heuristic algorithms for access rule derivation and query planning in spite of the NP-hardness and high complexity of the underlying problems.
Observation and characterization of microvascular vasomotion using erythrocyte mediated ICG angiography (EM-ICG-A)

A clinical method for characterizing the state of micro-vasculature vasomotion is demonstrated, based on observing in capillaries the dynamics of autologously re-injected erythrocytes containing ICG dye. Since a manifestation of vasomotion is transient erythrocyte pausing, vasomotion state within a field of capillaries is characterized by an histogram plot of the number of paused erythrocytes as a function of pause duration during a fixed period of observation, then the ratio of long-pausing to short-pausing erythrocytes was calculated. The method was first applied to the posterior pole retinal vasculatures of anesthetized-monkey eyes, and normal vasomotion state during air-breathing was compared to the state induced by O2-breathing, known to cause mild arteriolar vasoconstriction in the mature eye. Subsequently, the effects of other antagonists to normal arteriolarvasotonia state (long-standing experimentally-induced ocular hypertension and branch-vein occlusion, as well as tissue edema) were similarly characterized and the results compared to those obtained during baseline air-breathing. The feasibility of applying the histogram characterization of vasomotion state to human eyes and skin was also preliminarily explored.
Blood Pressure and Hispanic/Latino Cognitive Function: Hispanic Community Health Study/Study of Latinos Results.

Background Hispanics/Latinos are at increased risk for cardiovascular disease and cognitive decline and dementias. High blood pressure (BP) has been implicated in both stroke and dementias. Associations between BP and cognition among diverse Latinos are still unpublished. Objective We examined associations between cognition and four BP based measures among diverse Hispanics/Latinos. We hypothesized that higher BP, particularly systolic pressure, and increased arterial stiffness (i.e., pulse pressure), would be associated with lower cognitive function. Methods We used baseline (2008-2011) Hispanic Community Health Study/Study of Latinos (HCHS/SOL; n = 9,019; ages 45-74 years) data to examine cognition in relation to BP measures. Results In age, sex, and education adjusted models, systolic, pulse, and mean arterial pressure were consistently negatively associated with executive function, psychomotor speed and sustained attention, verbal episodic learning and memory, speech fluency, and mental status measures. These associations were attenuated but remained statistically significant in fully adjusted models. Conclusion Among middle-aged and older diverse Hispanics/Latinos, we found modest but consistent associations between indicators of arterial stiffness, and compromised blood flow and lower cognitive function. Clinical management and public health interventions to raise awareness and enhance BP management beginning in midlife could reduce disparities and improve population health by reducing cognitive decline burdens.
Mixed-domain biological motion tracking for underwater human-robot interaction

We present a novel algorithm for an autonomous underwater robot to visually detect and follow its companion human diver. Using both spatial-domain and frequency-domain features pertaining to human swimming patterns, we devise an algorithm to visually detect the position and swimming direction of the diver. Our algorithm is unique in the way that it allows detection of arbitrary motion directions, in addition to keeping track of a diver's position through the image sequence over time. A Hidden Markov Model (HMM)-based approach prunes the search-space of all potential trajectories relying on image intensities in the spatial-domain. A diver's motion signature is subsequently detected in a sequence of non-overlapping image subwindows exhibiting human swimming patterns. The pruning step ensures efficient computation by avoiding exponentially large search-spaces, whereas the frequency-domain detection allows us to detect the diver's position and motion direction accurately. Experimental validation of the proposed approach is presented on datasets collected from open-water and closed-water environments.
Chondrosarcoma of the Epiglottis: A Case Report and Literature Review

Summary Background Laryngeal chondrosarcoma (LCS) is an exceedingly rare malignancy and least frequently reported in the epiglottis. Methods and Results We report a case of a 71-year-old male smoker who presented with sore throat, dysphagia, and odynophagia for 3 months. Computed tomography scan revealed an inhomogeneously enhancing necrotic mass emanating from the right epiglottis and traveling along the aryepiglottic fold. The mass was removed via endoscopic en bloc laser resection. Histopathological examination of the biopsied specimen confirmed low-grade LCS of the epiglottis. Conclusion Differentiating low-grade LCS from laryngeal chondroma is a challenging task with an increased risk of potential misdiagnosis. This case study reinforces the need for a histopathological examination in forming the basis for ongoing management and follow-up observations. Timely surgery remains the optimal, primary means of treatment notwithstanding the rarity of LCS.
Coordinated delivery and function of bacterial MARTX toxin effectors.

Summary Bacteria often coordinate virulence factors to fine-tune the host response during infection. These coordinated events can include toxins counteracting or amplifying effects of another toxin or though regulating the stability of virulence factors to remove their function once it is no longer needed. Multifunctional autoprocessing repeats-in toxin (MARTX) toxins are effector delivery toxins that form a pore into the plasma membrane of a eukaryotic cell to deliver multiple effector proteins into the cytosol of the target cell. The function of these proteins includes manipulating actin cytoskeletal dynamics, regulating signal transduction pathways, and inhibiting host secretory pathways. Investigations into the molecular mechanisms of these effector domains are providing insight into how the function of some effectors overlap and regulate one another during infection. Coordinated crosstalk of effector function suggests that MARTX toxins are not simply a sum of all their parts. Instead, modulation of cell function by effector domains may depend on which other effector domain are co-delivered. Future studies will elucidate how these effectors interact with each other to modulate the bacterial host interaction.
Alteration of brain network topology in HIV-associated neurocognitive disorder: A novel functional connectivity perspective.

HIV is capable of invading the brain soon after seroconversion. This ultimately can lead to deficits in multiple cognitive domains commonly referred to as HIV-associated neurocognitive disorders (HAND). Clinical diagnosis of such deficits requires detailed neuropsychological assessment but clinical signs may be difficult to detect during asymptomatic injury of the central nervous system (CNS). Therefore neuroimaging biomarkers are of particular interest in HAND. In this study, we constructed brain connectivity profiles of 40 subjects (20 HIV positive subjects and 20 age-matched seronegative controls) using two different methods: a non-linear mutual connectivity analysis approach and a conventional method based on Pearson's correlation. These profiles were then summarized using graph-theoretic methods characterizing their topological network properties. Standard clinical and laboratory assessments were performed and a battery of neuropsychological (NP) tests was administered for all participating subjects. Based on NP testing, 14 of the seropositive subjects exhibited mild neurologic impairment. Subsequently, we analyzed associations between the network derived measures and neuropsychological assessment scores as well as common clinical laboratory plasma markers (CD4 cell count, HIV RNA) after adjusting for age and gender. Mutual connectivity analysis derived graph-theoretic measures, Modularity and Small Worldness, were significantly (p < 0.05, FDR adjusted) associated with the Executive as well as Overall z-score of NP performance. In contrast, network measures derived from conventional correlation-based connectivity did not yield any significant results. Thus, changes in connectivity can be captured using advanced time-series analysis techniques. The demonstrated associations between imaging-derived graph-theoretic properties of brain networks with neuropsychological performance, provides opportunities to further investigate the evolution of HAND in larger, longitudinal studies. Our analysis approach, involving non-linear time-series analysis in conjunction with graph theory, is promising and it may prove to be useful not only in HAND but also in other neurodegenerative disorders.
Influence of sublattice bias on superfluid to Mott insulator transitions

We model the superfluid to Mott insulator transition for a Bose gas on a lattice with two inequivalent sublattices. Using the Gutzwiller ansatz, we produce phase diagrams and provide an understanding of the interplay between superfluidity on each sublattice. We explore how the Mott lobes split and describe the experimental signatures.
An Integrated Heater Equalizer for Lithium-Ion Batteries of Electric Vehicles

In this paper, an automotive onboard heater equalizer is proposed to heat low-temperature batteries and balance cell voltages without the requirement of external power supplies. The proposed integrated topology only needs one MOSFET for one cell, resulting in a compact size and low cost, which can be easily applied to electric vehicles. In particular, all MOSFETs are driven by one high-frequency pulsewidth modulation signal and the batteries can be heated internally by the ohmic and electrochemical losses and warmed externally by the switching and conduction losses of MOSFETs, leading to a high heating speed and efficiency. Further, a thermoelectric model for the internal and external combined heating is developed to provide guidance for the optimized design of the proposed heater. In addition, the proposed topology can realize passive balancing of series-connected battery strings at a higher switching frequency and a smaller duty cycle. Experimental results show that the proposed heater, by generating a periodic ramped discharge current with an rms value of 1.8 C at a switching frequency of 150 kHz, can heat the lithium-ion batteries from −20 to 0 °C within 1.9 min, consuming about 5% of the cell energy.
Mathematical models of tumor cell proliferation: A review of the literature

ABSTRACTIntroduction: A defining hallmark of cancer is aberrant cell proliferation. Efforts to understand the generative properties of cancer cells span all biological scales: from genetic deviatio...
[Ethics committees in security-relevant research according to the recommendations of Leopoldina and the German Research Foundation].

Die im Grundgesetz geschutzte Wissenschaftsfreiheit ist eine Grundvoraussetzung fur den Fortschritt und Wohlstand der Gesellschaft. Freie Forschung ist aber auch mit Risiken verbunden, die daraus resultieren, dass an sich nutzliche Forschungsergebnisse und -methoden missbraucht werden konnen, etwa als Kriegswaffen bzw. als Mittel krimineller oder terroristischer Aktivitaten. Nach Ansicht der Nationalen Akademie der Wissenschaften Leopoldina und der Deutschen Forschungsgemeinschaft (DFG) kann eine sinnvolle Kontrolle dieser Risiken nicht durch weitere Gesetze, sondern nur durch eine entsprechende Bewusstseinsbildung und die Instrumente der Selbstverwaltung in der wissenschaftlichen Gemeinschaft erfolgen. Um dies zu konkretisieren, haben beide Organisationen im Jahr 2014 die gemeinsamen „Empfehlungen zum Umgang mit sicherheitsrelevanter Forschung“ veroffentlicht und zu deren wirkungsvoller und nachhaltiger Umsetzung den „Gemeinsamen Ausschuss zum Umgang mit sicherheitsrelevanter Forschung“ gegrundet. In Deutschland existieren bereits zahlreiche Kommissionen mit unterschiedlichen Bezeichnungen, die sich mit ethischen Fragestellungen in der Wissenschaft befassen. Neben den zahlreichsten hauptsachlich fur die medizinische Forschung am Menschen zustandigen „medizinischen Ethikkommissionen“ und solchen, die zur Wahrung des Tierschutzes die Behorden bei der Entscheidung uber die Genehmigung von Tierversuchen unterstutzen, gibt es seit einigen Jahren, den Empfehlungen des Gemeinsamen Ausschusses von DFG und Leopoldina folgend, eine steigende Zahl sogenannter Kommissionen fur Ethik sicherheitsrelevanter Forschung, die Forschende vor Ort bei entsprechenden Fragestellungen beraten.
Early Infectious Disease Consultation Is Associated With Lower Mortality in Patients With Severe Sepsis or Septic Shock Who Complete the 3-Hour Sepsis Treatment Bundle

Objective Severe sepsis and septic shock (SS/SS) treatment bundles reduce mortality, and early infectious diseases (ID) consultation also improves patient outcomes. We retrospectively examined whether early ID consultation further improves outcomes in Emergency Department (ED) patients with SS/SS who complete the sepsis bundle. Method We included 248 adult ED patients with SS/SS who completed the 3-hour bundle. Patients with ID consultation within 12 hours of ED triage (n = 111; early ID) were compared with patients who received standard care (n = 137) for in-hospital mortality, 30-day readmission, length of hospital stay (LOS), and antibiotic management. A competing risk survival analysis model compared risks of in-hospital mortality and discharge alive between groups. Results In-hospital mortality was lower in the early ID group unadjusted (24.3% vs 38.0%, P = .02) and adjusted for covariates (odds ratio, 0.47; 95% confidence interval (CI), 0.25-0.89; P = .02). There was no significant difference in 30-day readmission (22.6% vs 23.5%, P = .89) or median LOS (10.2 vs 12.1 days, P = .15) among patients who survived. A trend toward shorter time to antibiotic de-escalation in the early ID group (log-rank test P = .07) was observed. Early ID consultation was protective of in-hospital mortality (adjusted subdistribution hazard ratio (asHR), 0.60; 95% CI 0.36-1.00, P = .0497) and predictive of discharge alive (asHR 1.58, 95% CI, 1.11-2.23; P-value .01) after adjustment. Conclusions Among patients receiving the SS/SS bundle, early ID consultation was associated with a 40% risk reduction for in-hospital mortality. The impact of team-based care and de-escalation on SS/SS outcomes warrants further study.
Amplification of HER-2/neu (erbB2) gene expression in gallbladder (GBC) and in bile duct cancer (BDC) (biliary tract cancer, BTC)

4011 Background: GBC and BDC (BTC) are uncommon in the United States, but are endemic in parts of South America and Asia. BTC are aggressive tumors with poor survival rates. Chemotherapy RR is <30%...
The Challenge of Aging

□ In summary, our study of the medical aspects of aging has led to the following recommendations: a complete history and physical examination on a periodic basis throughout the individual's life; a...
Comparison of personal and shared frameshift neoantigen vaccines in a mouse mammary cancer model

It is widely hoped that personal cancer vaccines will extend the number of patients benefiting from checkpoint and other immunotherapies. However, it is clear creating such vaccines will be challenging. It requires obtaining and sequencing tumor DNA/RNA, predicting potentially immunogenic neoepitopes and manufacturing a one-use vaccine. This process takes time and considerable cost. Importantly, most mutations will not produce an immunogenic peptide and many patient’s tumors do not contain enough DNA mutations to make a vaccine. We have discovered that frameshift peptides (FSP) created from errors in the production of RNA rather than from DNA mutations are potentially a rich source of neoantigens for cancer vaccines. These errors are predictable, enabling the production of a FSP microarray. Previously we found that these microarrays can identify both personal and shared neoantigens. Here, we compared the performance of personal cancer vaccines (PCVs) with that of a shared antigen vaccine, termed Frameshift Antigen Shared Therapeutic (FAST) vaccine, using the 4 T1 breast cancer model. Sera from 4 T1-tumor bearing mice were assayed on the peptide microarray containing 200 Fs neoantigens, for the PCV, the top 10 candidates were select and personal vaccines constructed and administrated to the respective mice. For the FAST, we selected the top 10 candidates with higher prevalence among all the mice challenged. Seven to 12 days challenged mice were immunized, combined or not with immune checkpoint inhibitor (ICI) (αPD-L1 and αCTLA-4). Primary and secondary tumor clearance and growth were evaluated as well as cellular and humoral immune response against the vaccine targets by IFN-γ ELISPOT and ELISA. Lastly, we analyzed the immune response of the FAST-vaccinated mice by flow cytometry in comparison to the control group. We found that PCVs and FAST vaccines both reduced primary tumor incidence and growth as well as lung metastases when delivered as monotherapies or in combination with ICI. Additionally, the FAST vaccine induces a robust and effective T-cell response. These results suggest that FSPs produced from RNA-based errors are potent neoantigens that could enable production of off-the-shelf shared antigen vaccines for solid tumors with efficacy comparable to that of PCVs.
A Case Series of Devastating Intracranial Hemorrhage During Venovenous Extracorporeal Membrane Oxygenation for COVID-19.

Objective Anticoagulation may be a challenge in coronavirus disease 2019 (COVID-19) extracorporeal membrane oxygenation due to endothelial injury and dysregulation of coagulation, which may increase the risk of thrombotic and bleeding complications. This report was created to describe the authors’ single institutional experience, with emphasis on the high rate of intracranial hemorrhage for the first 10 patients with COVID-19 placed on venovenous extracorporeal membrane oxygenation (VV ECMO). Design Case series, retrospective analysis. Setting Single institution. Participants Ten patients. Interventions None. Measurements and Main Results Patient characteristics, mortality, stroke rate, and length of stay data were collected in all patients. In addition, laboratory values of D-dimer and C-reactive protein and standard measurements of prothrombin and activated partial thromboplastin time were collected on all patients. Ten patients, each confirmed with COVID-19 via reverse transcription-polymerase chain reaction, were supported on VV ECMO for acute respiratory distress syndrome (ARDS) for a mean duration of 9.4 ± 7 days. Four of 10 patients had hemorrhagic strokes, 3 of which resulted in death. At 30 days after initiation of VV ECMO, a total of 7 survivors included 6 patients discharged from the hospital and 1 patient who remained in the intensive care unit. Conclusions In this small study of 10 patients, intracranial hemorrhage was a common complication, resulting in a high rate of death. The authors urge caution in the anticoagulation management of VV ECMO for patients with severe ARDS and COVID-19 patients. Close monitoring of all hematologic parameters is recommended during ECMO support while awaiting larger, multicenter studies to examine the best practice.
EUS assessment for intermediate risk of choledocholithiasis after a negative magnetic resonance cholangiopancreatography

Background and Aims: Guidelines recommend either EUS or magnetic resonance cholangiopancreatography (MRCP) for intermediate risk of choledocholithiasis. There is a lack of evidence that supports proceeding with EUS if the MRCP is negative and if clinical suspicion still exists. Methods: This is a retrospective study of all patients who underwent EUS to assess for choledocholithiasis at a tertiary care referral center from July 2013 to October 2019. Results: A total of 593 patients underwent EUS for evaluation for choledocholithiasis. Of the 593 patients, 35.2% (209/593) had an MRCP. 73.2% (153/209) had a negative MRCP while 26.8% (56/209) had a positive MRCP. Of the group of patients who underwent EUS with a negative MRCP, 15% (23/153) were positive for choledocholithiasis on EUS. Of these, 91% (21/23) were also positive for sludge or stones on endoscopic retrograde cholangiopancreatography and thus 14% (21/153) of the EUS were “true positives.” There were no clinical or laboratory factors predictive of choledocholithiasis on univariate analysis in the EUS plus negative MRCP group. When further analyzing the MRCP negative group into MRCP-/EUS+ and MRCP-/EUS-subgroups, a total bilirubin >3 mg/dL predicted a bile duct stone (55% vs. 32%, P = 0.05). Conclusion: The diagnostic yield of EUS for suspected choledocholithiasis in the setting of a negative MRCP is 14% in our cohort. EUS should be considered in patients with intermediate risk of choledocholithiasis with a negative MRCP if the clinical suspicion is still present, and especially if the total bilirubin is above 3 mg/dL.
Determination of parameters affecting aerodynamic performance in S833 airfoil

This study presents the investigation of the factors affecting the performance of the airfoil, which is supposed to be used in a low power wind turbine. Airfoil surface roughness, angle of attack and wind speed parameters and interactions between these parameters affect performance. The conditions that the airfoil will be exposed to in the field of use can be modeled in the wind tunnel beforehand, and its performance in working conditions can be predicted. For this purpose, the airfoil model prepared using a three-dimensional printer can be tested in the wind tunnel, and the most effective parameter on performance can be determined. With the factorial design method used differently from the literature, performance analysis can be performed without the need for long mathematical calculations and analyzes. As a result, the most effective parameter on the performance is found as the surface roughness from the experimental design model created according to the selected factor levels. The second important parameter is the angle of attack-surface roughness binary factor interaction.
Anisotropic Micropolar Fluids Subject to a Uniform Microtorque: The Unstable Case

We study a three-dimensional, incompressible, viscous, micropolar fluid with anisotropic microstructure on a periodic domain. Subject to a uniform microtorque, this system admits a unique nontrivial equilibrium. We prove that this equilibrium is nonlinearly unstable. Our proof relies on a nonlinear bootstrap instability argument which uses control of higher-order norms to identify the instability at the $$L^2$$ level.
Decanal Leadership in Law Schools and the Abraham L. Freedman Fellowship Program

Temple University School of Law offered the Abraham L. Freedman Fellowship Program for four decades beginning in the 1970s, assisting to establish post-J.D. teaching fellowships as a well-recognized path into legal academia. Over the two-year fellowship, Freedman Fellows taught multiple legal writing courses and one doctrinal course, collaborated with faculty teaching doctrinal courses, attended faculty meetings, and received guidance in preparing a scholarly article and interviewing for teaching positions, ultimately obtaining an LL.M. degree. Freedman Fellows generally obtained faculty positions at law schools nationwide, and a significant number of Freedman Fellows later assumed decanal leadership roles. This Essay explores the contributions of the Freedman Fellow Program’s foundational training to the leadership required of deans and associate deans at law schools, adding to the important but limited scholarship on routes to legal academic leadership. The Essay first generally describes the functions of decanal leadership at law schools. The Essay then describes the particular responsibilities of deans and associate deans for academic affairs, research, and strategic initiatives at law schools. The Essay next sets forth the origin, purpose, and structure of the Freedman Fellow Program. The Essay thereafter details the significant representation of former Freedman Fellows as deans and associate deans at law schools and explores possible connections between participation in the Freedman Fellow Program and decanal leadership. The Essay concludes by noting lessons from the Freedman Fellow Program for other law schools that seek to launch candidates into academic careers that might include educational leadership.
The Murine Neuronal Receptor NgR1 Is Dispensable for Reovirus Pathogenesis

ABSTRACT Engagement of host receptors is essential for viruses to enter target cells and initiate infection. Expression patterns of receptors in turn dictate host and tissue tropism and disease pathogenesis during infection. Mammalian orthoreovirus (reovirus) displays serotype-dependent patterns of tropism in the murine central nervous system (CNS) that are dictated by viral attachment protein σ1. However, the receptor that mediates reovirus CNS tropism is unknown. Two proteinaceous receptors have been identified for reovirus, junctional adhesion molecule-A (JAM-A) and Nogo 66 receptor 1 (NgR1). Engagement of JAM-A is required for reovirus hematogenous dissemination but is dispensable for neural spread. To determine whether NgR1 functions in reovirus neuropathogenesis, we compared virus replication and disease following inoculation of wild-type (WT) and NgR1-/- mice. Genetic ablation of NgR1 did not alter replication of neurotropic reovirus strain T3SA- in the intestine and transmission to the brain following peroral inoculation. Viral titers in neural tissues following intramuscular inoculation, which provides access to neural dissemination routes, also were comparable in WT and NgR1-/- mice, suggesting that NgR1 is dispensable for reovirus neural spread to the CNS. The absence of both NgR1 and JAM-A also did not alter replication, neural tropism, and virulence of T3SA- following direct intracranial inoculation. In agreement with these findings, we found that the human but not the murine homolog of NgR1 functions as a receptor and confers efficient reovirus binding and infection of nonsusceptible cells in vitro. These results eliminate functions for JAM-A and NgR1 in shaping CNS tropism in mice and suggest that other receptors, yet to be identified, support this function. IMPORTANCE The CNS presents a range of barriers to pathogen invasion. Yet neurotropic viruses have evolved strategies to breach these barriers and establish infection by engagement of host factors that allow navigation to the CNS and neural cell entry. Human NgR1 was identified as a reovirus receptor in an RNA interference screen and is expressed in CNS neurons in a pattern overlapping with reovirus tropism. Using mice genetically lacking NgR1 expression, and following different routes of inoculation, we discovered that murine NgR1 is dispensable for reovirus dissemination to the CNS, tropism and replication in the brain, and resultant disease. Concordant with these results, expression of human but not murine NgR1 confers reovirus binding and infection of nonsusceptible cells in vitro. These results point to species-specific use of alternate receptors by reovirus. A detailed understanding of species- and tissue-specific factors that dictate viral tropism will inform development of interventions and targeted gene delivery and therapeutic viral vectors.
The Religious and the Political: Religion, state and Japanese exceptionalism: nihonjinron

Introduction: Japanese uniqueness In this volume I have deliberately and self-consciously referred to the work of Max Weber in virtually every chapter as a starting point from which to launch a study of politics and religion within a comparative perspective. In the case of Japan we cannot employ the same strategy, because he had little to say about Japanese society. However, he concluded The religion of China (1951: 248) with the observation that the ‘Chinese in all probability would be quite capable, probably more capable than the Japanese, of assimilating capitalism which has technically and economically been fully developed in the modern cultural area’. For Weber, China and Japan were different in one crucial respect. Whereas in China the literati had been the dominant status group, in the case of Japan he observed that the samurai had despised ‘the pen-pushers’ of the imperial bureaucracy (Weber, 1951: 120). Japan obviously presents a challenge to Weber’s views regarding the social conditions that contributed to the rise of capitalism, given the impressive success of Japan as an industrial society. Weber commented on the organization of religion, specifically Buddhism, in Japan in The religion of India , and we might speculate therefore about what Weber might have written about Japan had he written The religion of Japan . First, there is a well-established tradition of folk religion in Japan that was local and closely related to agricultural production and seasons. Mountains have been an important part of Japanese religion and symbols of national specificity. Weber noted (1958: 281) that the religiosity of the ordinary people ‘approximated general Asiatic and ancient conditions insofar as Shinto, Confucian, Taoist and Buddhist deities and redeemers were called upon according to function and occasion’. Second, Buddhism was closely connected to the Japanese system of power, and noble families were interrelated to the hierarchy of monastic authority.