cssi/SciSciGPT-SciSciNet huggingface dataset:
Senile and Pre-Senile Dementia: A Clinical Overview

Age related brain dysfunction, in particular senile dementia explored at this symposium, is one of the country’s most serious health problems. This is true not only in terms of the human suffering experienced by patients and their families but also in terms of its enormous social and economic impact.
Pressure Transmission Ratios

Pressure transmission ratios are designed to study objectively the relative transmission of pressure to the bladder and the urethra during stress. Characteristically the stress is continuous coughing during the measurement of the cough urethral closure pressure profile. The magnitude of the pressure transmitted to these two organs is determined in Fig. 23.1 by measuring the amount of pressure transmitted to the bladder (b) in a particular cough compared to that transmitted to a particular part of the urethra (u) during withdrawal of the urethral pressure transducer catheter. The pressure transmitted is measured as the bladder pressure increment and the urethral pressure increment above the urethral pressure profile curve caused by withdrawal of the urethral pressure transducer through the urethra during repetitive coughing.
Photoluminescence–Voltage (PL–V) Hysteresis of Perovskite Solar Cells

This article investigates the effect of an external electric field on the photoluminescence (PL) of a methylammonium lead iodide (MAPbI3) film in a working solar cell architecture. Our study reveals hysteretic PL intensity responses when changing the voltage scanning direction, namely, PL–V hysteresis. The external electric field is found to have multiple effects on the photoexcited states of PSCs. First, an external electric field instantaneously changes the drift velocity of photogenerated charge carriers. Second, it drives ion migration and thus generates an induced electric field which screens the external field. Third, the ion migration driven by the external electric field also changes the distribution and density of charge traps that are responsible for nonradiative recombination. The first effect leads to instant PL change which is not responsible for PL–V hysteresis, while the other two effects are closely related to the slow kinetics of ion migration and lead to the PL–V hysteresis in perovskite...
The Norman Yoke—Canon Law

If John Adams feared the revival of the feudal law in British North America as one bow of the Norman Yoke, he feared the canon law, the other bow, even more. From Adams’s his perspective, as feudalism destroyed the political structure of Anglo-Saxon society, reducing the people to serfdom, establishing an Anglican diocese in America would spell the end of true Protestantism in America as William the Conqueror imposed Roman reform on the Saxon Church, ending the distinctive Saxon tradition of Christianity.
Collet-Sicard Syndrome Attributable to Extramedullary Plasmacytoma of the Jugular Foramen.

Background Collet-Sicard syndrome is a rare manifestation of skull base disease involving the jugular and hypoglossal foramina. We report the first case of Collet-Sicard attributable to extramedullary plasmacytoma—multiple myeloma (EP-MM) and the second case of EP-MM precipitating a jugular foramen syndrome (JFS)-spectrum disorder. Case Description A 59-year-old woman presented with 4 months of left aural fullness and pulsatile tenderness, positional vertigo, hoarseness, and dysphagia. Examination identified left tongue weakness and nonspecific sensory abnormalities of the ear, pharynx, and throat localizing to cranial nerves IX–XII. Imaging revealed a 3.4 × 1.4 × 2.8 cm lytic lesion extending from the left jugular foramen into the posterior fossa, for which she was referred to neurosurgery and otolaryngology for consideration of resection. A second, much smaller (1.1-cm) lytic lesion in the left posterior occipital bone was incidentally discovered by the surgeon during preoperative consultation. A stereotactic biopsy of the occipital lesion was subsequently recommended, which identified plasma cell neoplasm. Serum studies and skeletal survey were consistent with MM, and a definitive pathologic diagnosis of MM with cranial EP was confirmed by bone marrow biopsy. Conclusion Tumors of the jugular foramen present with a diverse array of lower cranial nerve deficits, including Collet-Sicard syndrome, a rare subset of JFS-spectrum diseases. Paragangliomas are the most common jugular foramen neoplasms, followed by schwannomas and meningiomas; however, many other rare entities have been reported as masqueraders, and diligent work-up with consideration for preliminary biopsy is recommended, particularly in the presence of additional lesions, equivocal imaging findings, or cases arousing high suspicion.
S-NPP VIIRS day-night band calibration and status update

The Visible Infrared Imaging Radiometer Suite (VIIRS) Day-Night Band (DNB) onboard the Suomi-National Polar Orbiting Partnership (S-NPP) satellite measures broadband visible radiances providing imagery of clouds and other Earth features over illumination levels spanning 7 orders of magnitude, ranging from quarter moon to full sunlight (3e-5 to 200 W/m2/sr). Due to its original purpose to provide imagery rather than radiometric products as well as this extensive radiance range, the DNB calibration requirements are less restrictive as compared to the other 21 VIIRS bands. Over time the importance of the DNB data product imagery has engendered efforts to improve the calibration stability of the DNB over its mission. This paper discusses The Aerospace Corporation's support of the DNB calibration over the S-NPP mission.
Enhanced Recovery after Colorectal Surgery: Can We Afford Not to Use It?

Background Enhanced recovery pathways (ERPs) aim to reduce length of stay without adversely affecting short-term outcomes. High pharmaceutical costs associated with ERP regimens, however, remain a significant barrier to widespread implementation. We hypothesized that ERP would reduce hospital costs after elective colorectal resections, despite the use of more expensive pharmaceutical agents. Study Design An ERP was implemented in January 2016 at our institution. We collected data on consecutive colorectal resections for 1 year before adoption of ERP (traditional, n = 160) and compared them with consecutive resections after universal adoption of ERP (n = 146). Short-term surgical outcomes, total direct costs, and direct hospital pharmacy costs were compared between patients who received the ERP and those who did not. Results After implementation of the ERP, median length of stay decreased from 5.0 to 3.0 days (p Conclusions Implementation of an ERP for patients undergoing elective colorectal resection substantially reduced length of stay, total hospital cost, and direct pharmacy cost without increasing complications or readmission rates. Enhanced recovery pathway after colorectal resection has both clinical and financial benefits. Widespread implementation has the potential for a dramatic impact on healthcare costs.
Straightlining: Overview of Measurement, Comparison of Indicators, and Effects in Mail–Web Mixed-Mode Surveys:

Straightlining occurs when survey respondents give identical (or nearly identical) answers to items in a battery of questions using the same response scale, which may reduce data quality. Despite i...
An evaluation of mosquito repellents and essential plant oils as deterrents of Asian citrus psyllid

Abstract A study was conducted to evaluate mosquito repellents against Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Liviidae) and to expand our knowledge of the potential of essential plant oils as deterrents of ACP infestations. The psyllid vectors a bacterium, ‘Candidatus Liberibacter asiaticus,’ presumed causal agent of a serious disease of citrus, huanglongbing (also known as citrus greening disease). Twenty-two candidate deterrents were tested as 20% solutions in methanol using a laboratory assay. Adults were free to enter and settle in one of three vials containing orange jasmine flush, one vial treated with a candidate deterrent, one vial treated with water or one treated with methanol. Seven mosquito repellents (CisPMD, DEET, DHS220, Icaridin, IR-3535, S-220, and TransPMD) and four essential oils (citronella, lavender, lemon eucalyptus, and a commercial mixture of oils from orange, clove, cinnamon, eucalyptus and rosemary) reduced ACP infestations on flush in the vials. Following a 24-h assay period, an average of 75% (range 58–88%) fewer psyllids were found in vials treated with these deterrents as compared to the combined number found in the control vials. Greenhouse evaluations were conducted on phytotoxicity of 5 or 25% solutions of eight deterrents and on ACP colonization of citrus seedlings sprayed with these deterrents. Few ACP colonized seedlings sprayed with 25% solutions, but this was attributed to phytotoxicity. Infestations were reduced on seedlings treated with 5% solutions, but these reductions also were largely attributed to phytotoxicity. Although unsprayed seedlings were in close proximity, adults found these plants and laid relatively large numbers of eggs. While some of the mosquito repellents and essential plant oils deterred infestations, none was completely effective and 5–25% solutions were too phytotoxic to be feasible as direct plant sprays. These results indicated the deterrents as tested hold little potential as a major tactic for reducing ACP infestations in citrus. Alternative application approaches to avoid phytotoxicity could be explored, and individual constituents of the more promising essential plant oils could be investigated.
Suture Embolism of the Left Superior Lobar Pulmonary Artery

Endogenous pulmonary thromboemboli are a common cause of noncardiac sudden natural death. Embolism of exogenous material is a rare but potential finding in autopsies following surgeries, medical procedures, penetrating trauma, and nonparenteral drug abuse. This report describes the first case of a suture embolism of the left superior lobar pulmonary artery following complicated abdominal surgery.
Maternity and Paternity in the Developmental Context: Contribution to Integration and Differentiation as a Procreative Person

The antecedents of adult parental attitudes, and particularly the relationship of the procreative drive to sexual and aggressive drives and cultural influences, are discussed.
The Future of African Customary Law: Traditional Institutions and Governance in Modern African Democracies

In most African countries, constitutionally established authorities exercise the power of government alongside traditional authorities. Executive, legislative, and judicial functions are generally attributed by most modern African constitutions to presidents and prime ministers, parliaments, and modern judiciaries.However, almost invariably the same functions, whether or not formally defined and characterized in the same terms or exercised in the same manner, are also performed by traditional institutions and their leaders. Chiefs administer land and people, contribute to the creation of rules that regulate the lives of those under their jurisdiction, and are called on to solve disputes among their subjects.The relationship between traditional leadership and inherited western-style governance institutions often generates tensions. In Ghana, for example, local governance is an area where traditional leadership and the constitutional government sometimes “lock horns.” Traditional leaders often feel left out when the government takes decisions affecting their people and land without their consent or involvement. Chieftaincy is further plagued with its own internal problems, including issues of relevance, succession, patriarchy, jurisdiction, corruption and intra-tribal conflict. Challenges confronting the institution of chieftaincy have continued from the colonial era into recent times. The role of chieftaincy within post-colonial African countries continues to incite lively debates, as the case of Ghana exemplifies.This chapter examines traditional leadership within the context of the emerging constitutional democracy in Ghana. After examining the history, challenges, and opportunities for the “institution” of traditional leadership within a modern democracy, the chapter considers the effect of the current constitutional guarantee for chieftaincy and evaluates its practical workability and structural efficiency under the current governance system. The chapter further examines the dabbling of traditional leaders in the political process in spite of the proscription of the institution from mainstream politics and, in this context, analyzes the policy rationale for attempting to detach chieftaincy from partisan politics. It then analyzes the implications of the dual allegiance of the citizenry to chiefs and the government. In this context the chapter further touches on the compatibility of the institution of chieftaincy with constitutional principles such as equality, accountability, natural justice, good governance, and respect for fundamental human rights. Finally, the chapter considers the future of the institution against the background of the many issues and challenges considered.
Mechanisms of Ischemia in in Situ Vascular Occlusive Disease

This chapter describes the mechanisms of ischemia in in situ vascular occlusive disease. Cerebral blood flow below critical levels is the most important factor responsible for brain damage in patients with ischemic stroke. In patients with in situ vascular occlusive disease, stroke is most commonly caused by atherosclerosis. Two basic mechanisms can explain the vast majority of episodes of focal cerebral ischemia due to in situ vascular disease: vascular thrombosis or other condition resulting in narrowed vessel lumen and limitation of flow, and thrombus fragmentation at a vessel resulting in embolic occlusion of a distal vessel. In most patients, a thorough general physical and neurological exam can determine the presence of vascular risk factors, evidence of atherosclerosis in other organs, the vascular territory involved, and the nature of the occlusion. Lacunar syndromes reflect ischemia caused by occlusion of small vessels secondary to lipohyalinosis. Diagnostic studies demonstrate the presence of narrowing of the vessel lumen. Tests used for this purpose are ultrasound studies, magnetic resonance angiography, and catheter-requiring arteriography.
Embedded Merge & Split: Visual Adjustment of Data Grouping

Data grouping is among the most frequently used operations in data visualization. It is the process through which relevant information is gathered, simplified, and expressed in summary form. Many popular visualization tools support automatic grouping of data (e.g., dividing up a numerical variable into bins). Although grouping plays a pivotal role in supporting data exploration, further adjustment and customization of auto-generated grouping criteria is non-trivial. Such adjustments are currently performed either programmatically or through menus and dialogues which require specific parameter adjustments over several steps. In response, we introduce Embedded Merge & Split (EMS), a new interaction technique for direct adjustment of data grouping criteria. We demonstrate how the EMS technique can be designed to directly manipulate width and position in bar charts and histograms, as a means for adjustment of data grouping criteria. We also offer a set of design guidelines for supporting EMS. Finally, we present the results of two user studies, providing initial evidence that EMS can significantly reduce interaction time compared to WIMP-based technique and was subjectively preferred by participants.
What Is the Optimal Sedative Regimen in Severe Traumatic Brain Injury Patients

Sedatives play an important role in the management of severe traumatic brain injury (TBI) patients. Unfortunately, no ideal sedative is available for use in this critically ill patient subset. Therefore, selection of one agent over another is based on differential effects of the available agents on cerebral and systemic hemodynamics, as well as their comparative pharmacokinetic properties and side effect profiles. Despite a large number of undesirable side effects, including possible neurotoxicity, propofol remains the agent of choice for short-term sedation in TBI patients because of its rapid onset and offset. Benzodiazepines also play a role in the sedation of TBI patients, with midazolam being the most commonly used due to its short-acting properties. Nonetheless, concerns with the delirium development and prolonged effects with increasing duration of benzodiazepine use undoubtedly diminish their utility in severe TBI patients. Opiate narcotics including morphine, fentanyl, sufentanil, and remifentanil continue to be important analgosedative agents in TBI patients. Barbiturate use in TBI patients is primarily limited to pentobarbital for the treatment of refractory intracranial hypertension. The anesthetic induction agents, etomidate and ketamine, have limited roles in TBI patients because of their side effects, although there is renewed interest in ketamine as a possible neuroprotective agent based on its unique sedative mechanism of action. Dexmedetomidine is the newest sedative in clinical use and has been proposed as a viable agent for select TBI patients. However, before usurping the dominant role of propofol as the sedative of choice in TBI patients, randomized comparative clinical trials are needed. Monitoring of pain, sedation, and delirium is challenging in the TBI patient although there are tools available for evaluation of pain and sedation in the unresponsive patient. While recommended for other critically ill patients, the risk of daily sedation interruption is of great concern in TBI patients, in particular, those patients with elevated intracranial pressure. Consideration of pharmacokinetic alterations in severe TBI patients is yet another challenge in optimally dosing sedatives in severe TBI patients.
Variability for Sennoside A and B concentrations in eight Senna species

Abstract Some Senna species are important medicinal plants used worldwide and may show variation for sennoside concentrations. The USDA, ARS, PGRCU (United States Department of Agriculture, Agricultural Research Service, Plant Genetic Resources Conservation Unit) curates several Senna species including candlebush [S. alata (L.) Roxb.], Alexandrian senna [S. alexandrina Mill.], S. angulata (Vogel) H.S. Irwin & Barneby, S. covesii (A. Gray) H.S. Irwin & Barneby, S. hirsuta var. hirta H.S. Irwin & Barneby, S. hirsuta var. leptocarpa (Benth.) H.S. Irwin & Barneby, S. occidentalis (L.) Link, and S. uniflora (Mill.) H.S. Irwin & Barneby. The natural products including sennoside A and B are the primary laxative ingredients in many medicinal products. However, it is unknown if sennoside A and B are found in many of these Senna species and at what concentrations. The objective of this study was to evaluate sennoside A and B content from leaves of 14 and pods of four accessions including eight Senna species over two years and locations. Sample analysis was performed by HPLC (high performance liquid chromatography) on an Agilent 1100 with an auto-sampler and diode array detector. Significant accession and location x accession effects were observed for sennoside A and B. Mean separations revealed that leaves from S. alata produced significantly more sennoside A (8.55 mg/g) than all other species. However, immature pods from S. alexandrina produced the significantly highest sennoside B (16.19 mg/g) content. While this is a preliminary analysis, it provides evidence for higher levels of sennoside A and B in S. alata and S. alexandrina than in S. angulata, S. covesii, S. hirsuta var. hirta, S. hirsuta var. leptocarpa, S. occidentalis, and S. uniflora. These results show that both S. alata and S. alexandrina produced the highest sennoside concentrations. However, additional studies are required to verify sennoside content in other Senna species and organs including Senna pods.
Skills Needed by New Accounting Graduates in a Rapidly Changing Technological Environment

Current research indicates that newly-hired accounting graduates may lack some of the skills necessary to be successful in their chosen profession. This paper examines recent research to determine what skills are needed by accounting graduates. A number of papers suggest that accounting graduates may not have the soft skills, such as analytical thinking skills and communication skills, necessary to succeed. This may be due in part to differences between Millennial students and students of prior generations This paper concludes by examining specific skills needed by accounting graduates and who should be responsible for providing those skills—universities, employers, or both.
Pain symptomology, functional impact, and treatment of people with Neurofibromatosis type 1.

Introduction Neurofibromatosis type 1 (NF1) is a neurogenetic disorder affecting 1 in 3000 people worldwide, where individuals are prone to develop benign and malignant tumors. In addition, many people with NF1 complain of pain that limits their daily functioning. Due to the complexity of the disorder, there are few options for treating pain symptoms besides surgery and medications. Moreover, the spectrum of pain symptomatology and treatment, as well as the mechanisms underlying NF1-associated pain, has been understudied. Methodology To address this knowledge gap, we conducted a survey of 255 adults with NF1, leveraging the Washington University NF1 Patient Registry Initiative (NPRI) database. Demographic and pain data were collected using a Qualtrics survey. Results All participants had at least one surgical procedure, with 55% reporting having at least one surgery within the last year and 17% being currently prescribed opioid medication. A positive relationship was shown (p<0.001) between those prescribed prescription pain medication, and their pain severity and interference. Moreover, there was a significant relationship (p=0.049) between the usage of complementary treatments and pain severity and interference. Conclusion The current study demonstrates that individuals with NF1 report a higher incidence of pain severity and interference than observed in NF1 previous studies, with pain symptoms not localized to any specific region of the body. The consideration for alternative treatments and careful monitoring of current treatments that are more conservative or have less potential adverse side effects may improve pain management and reduce the risk of developing medication dependence.
Misused Theories Behind Trump’s Economic Policies

The fundamental economic problem in America and most of Europe, too, is the Great Western Slowdown and the ensuing symptoms: weak investment, generally falling rates of return on investment, enlarged markups, declining job satisfaction, and near-disappearance of exhilarating growth. This fifty-year decline is not addressed by our politicians—least of all by President Donald Trump. Recent economic policies, not just Trump’s, have relied on and misused Keynesian theory. Through a survey of 14 OECD countries, I analyze the effectiveness of fiscal and monetary stimulus on a country’s speed of recovery from the Global Recession of 2008. The results support my position that today’s politicians need to focus not on stimulating demand but nourishing economic dynamism.
The Interaction of Acoustic and Electromagnetic Waves (“Son et Lumière”) with Plasmas in a Magnetic Field

In this chapter I will be concerned with the nature of the single-particle and collective excitations of plasmas in solids and their interactions with acoustic (A) waves and electromagnetic (E) waves in a magnetic field under conditions ħω > ΔC and ħω > Δp, where ΔC = ħ/Δt is the uncertainty in the energy of the excitation and Δp = ħ/Δx is the uncertainty in the momentum of the excitation. Under these conditions the interactions can be treated semiclassically in terms of elementary processes in which (1) a phonon or photon of frequency ω and wave vector q is absorbed (or emitted) and an electron undergoes a transition from an initial state of energy C and wave vector k to a final (unoccupied) state of energy C’ = C + ħω and wave vector k’ = k + ħq in the same Landau subband (a Landau transition) or in another Landau subband (a cyclotron transition); or (2) a phonon or photon is absorbed (or emitted) and a quantum of collective excitation of frequency Ω = ω and wave vector Q = q is created or annihilated. The investigation of the interactions of A and E waves with plasmas provides useful information about the nature of the single-particle and collective excitations of the plasma as well as about the energy band structure of semiconductors and the Fermi surface of metals.
Magnetohydrodynamic simulations of binary neutron star mergers in general relativity: Effects of magnetic field orientation on jet launching.

Binary neutron star mergers can be sources of gravitational waves coincident with electromagnetic counterpart emission across the spectrum. To solidify their role as multimessenger sources, we present fully 3D, general relativistic, magnetohydrodynamic simulations of highly spinning binary neutrons stars initially on quasicircular orbits that merge and undergo delayed collapse to a black hole. The binaries consist of two identical stars modeled as $\mathrm{\ensuremath{\Gamma}}=2$ polytropes with spin ${\ensuremath{\chi}}_{\mathrm{NS}}=0.36$ aligned along the direction of the total orbital angular momentum $L$. Each star is initially threaded by a dynamical unimportant interior dipole magnetic field. The field is extended into the exterior where a nearly force-free magnetosphere resembles that of a pulsar. The magnetic dipole moment $\ensuremath{\mu}$ is either aligned or perpendicular to $L$ and has the same initial magnitude for each orientation. For comparison, we also impose symmetry across the orbital plane in one case where $\ensuremath{\mu}$ in both stars is aligned along $L$. We find that the lifetime of the transient hypermassive neutron star remnant, the jet launching time, and the ejecta (which can give rise to a detectable kilonova) are very sensitive to the magnetic field orientation. By contrast, the physical properties of the black $\mathrm{hole}+\text{disk remnant}$, such as the mass and spin of the black hole, the accretion rate, and the electromagnetic (Poynting) luminosity, are roughly independent of the initial magnetic field orientation. In addition, we find imposing symmetry across the orbital plane does not play a significant role in the final outcome of the mergers. Our results suggest that, as in the black hole-neutron star merger scenario, an incipient jet emerges only when the seed magnetic field has a sufficiently large-scale poloidal component aligned to the initial orbital angular momentum. The lifetime [$\mathrm{\ensuremath{\Delta}}t\ensuremath{\gtrsim}140({M}_{\mathrm{NS}}/1.625\text{ }\text{ }{M}_{\ensuremath{\bigodot}})\text{ }\text{ }\mathrm{ms}$] and Poynting luminosities [${L}_{\mathrm{EM}}\ensuremath{\simeq}{10}^{52}\text{ }\text{ }\mathrm{erg}/\mathrm{s}$] of the jet, when it forms, are consistent with typical short gamma-ray bursts, as well as with the Blandford-Znajek mechanism for launching jets.
Appraising Otolaryngology–Head and Neck Surgery Clinical Practice Guidelines for Effective Dissemination and Implementation Design:

ObjectivesDissemination and implementation (D&I) science analyzes interventional strategies that aid in spreading scientific knowledge, adopting evidence into practice, and identifying barriers to ...
Birth Mothers’ Experiences of Privacy Turbulence in Relation to Closed Adoption Information

Adoption information, including original birth certificates (OBCs) and (non)identifying information, is kept secret from birth mothers who place their children in closed adoptions. Through the lens...
Influence of immunomodulatory drugs on the gut microbiota.

Immunomodulatory medications are a mainstay of treatment for autoimmune diseases and malignancies. In addition to their direct effects on immune cells, these medications also impact the gut microbiota. Drug-induced shifts in commensal microbes can lead to indirect but important changes in the immune response. We performed a comprehensive literature search focusing on immunotherapy/microbe interactions. Immunotherapies were categorized into 5 subtypes based on their mechanisms of action: cell trafficking inhibitors, immune checkpoint inhibitors, immunomodulators, antiproliferative drugs, and inflammatory cytokine inhibitors. Although no consistent relationships were observed between types of immunotherapy and microbiota, most immunotherapies were associated with shifts in specific colonizing bacterial taxa. The relationships between colonizing microbes and drug efficacy were not well-studied for autoimmune diseases. In contrast, the efficacy of immune checkpoint inhibitors for cancer was tied to the baseline composition of the gut microbiota. There was a paucity of high-quality data; existing data were generated using heterogeneous sampling and analytic techniques, and most studies involved small numbers of participants. Further work is needed to elucidate the extent and clinical significance of immunotherapy effects on the human microbiome
Energy transduction versus design characteristics of a magnetoelastic peristalsis pump

This Conference Presentation, “Energy transduction versus design characteristics of a magnetoelastic peristalsis pump,” was recorded for the Smart Structures + Nondestructive Evaluation 2021 Digital Forum.
Covers and the Poetics of Communication

Do covers still have a place in our digital age? The physical book has proved more resilient than champions of electronic texts once predicted, but the overall trend is plain: with each passing yea...
Immunogenicity in humans of a transdermal multipeptide melanoma vaccine administered with or without a TLR7 agonist.

Background Experimental cancer vaccines are traditionally administered by injection in subcutaneous tissue or muscle, commonly with adjuvants that create chronic inflammatory depots. Injection of melanoma-derived peptides induces T cell responses; however, the depots that form following injection may inhibit optimization of the immune response. In skin, epidermal Langerhans cells (LC) are a dominant source of professional antigen presenting cells. We hypothesized that: (1) applying melanoma-derived peptides topically, in proximity to LC, could be immunogenic and safe, with low vaccine-site toxicity and (2) topical toll-like receptor 7 (TLR7) agonist would increase immunogenicity of the peptide vaccine. Methods Twelve melanoma peptides plus a tetanus helper peptide were combined with granulocyte macrophage colony stimulating factor (GM-CSF) and were administered topically on days 1, 8, and 15, to 28 patients randomized to one of four adjuvant preparations: (1) incomplete Freund’s adjuvant (IFA); (2) IFA plus a TLR7 agonist (imiquimod) administered on days 0, 7, 14; (3) dimethyl sulfoxide (DMSO) or (4) DMSO+ imiquimod administered on day 0, 7, 14. Every 3 weeks thereafter (x 6), the peptides were combined with GM-CSF and were injected into the dermis and subcutis in an emulsion with IFA. Toxicities were recorded and immune responses assayed by ELIspot. Results CD8+ T cell responses to transdermal vaccination in DMSO occurred in 83% of participants in group 3 and 86% in group 4, and responses to vaccination in IFA were observed in 29% of participants in group 1 and 14% in group 2. Overall, 61% of participants had CD4+ T cell immune responses to the tetanus peptide, with large, durable responses in groups 3 and 4. Five of seven participants in group 4 had a severe rash, one that was dose limiting. Ten-year overall survival was 67% and disease-free survival was 44%. Conclusions These data provide proof of principle for immunogenicity in humans of transdermal immunization using peptides in DMSO. Further study is warranted into the pharmacokinetics and immunobiology of TLR agonists as vaccine adjuvants during transcutaneous application. Overall survival is high, supporting further investigation of this immunization approach.
Dynamic historical data borrowing using weighted average

In many clinical trials, especially trials in rare diseases or a certain population like paediatric, it is of great interest to incorporate historical data to increase power of evaluating the treatment effect of an experimental drug. In practice, historical data and current data may not be congruent, and borrowing historical data is often associated with bias and Type‐1 error rate inflation. It remains a challenge for historical data borrowing methods to control Type‐1 error rate inflation at an adequate level and maintain sufficient power at the same time. To address this issue, dynamic historical borrowing methods can borrow historical data more when historical data are similar to current data and less otherwise. This paper proposed to use a weighted average of historical and current control data, with the weight being set as an approximation to the optimal weight that minimizes the mean‐squared errors in the treatment effect estimation. Comparing to selected existing methods, the proposed method showed reduced bias, robust gain in power and better control in Type‐1 error rate inflation through simulation studies. The proposed method enables the utilization of all possible historical data in the public domain and is readily used by skipping the need for external expert input in some existing approaches.
Fear is associated with attrition of first-time whole blood donors: A longitudinal examination of donor confidence and attitude as potential mediators.

BACKGROUND Elevated fear and anxiety regarding donation-related stimuli (e.g., needles, pain, blood, fainting) has been associated with reduced blood donor recruitment and retention. The present longitudinal study tests the notion that this inverse relationship may be accounted for by lower donation confidence and more negative donation attitudes among fearful first-time donors. STUDY DESIGN AND METHODS In a sample of 1479 first-time whole blood donors [67.9% female; mean age = 19.3 (standard deviation (SD) = 2.5) years], path analyses were conducted to examine relationships among donor ratings of fear of blood draw and donation anxiety obtained approximately 1 week after donation, donation confidence and attitudes assessed approximately 6 weeks later, and donation attempts over the 14 months following the original donation. RESULTS Path analyses indicated that both fear of blood draws and donation anxiety were associated with fewer attempted donations, and that these effects were indirectly mediated by a combination of lower donor confidence and more negative donation attitudes. CONCLUSION Because retention of new blood donors is essential to maintain a healthy blood supply, the results of the present study suggest that first-time donors should be assessed for fear and anxiety so that appropriate strategies can be provided to address their concerns, bolster their confidence and attitudes, and ultimately promote their long-term retention.
Normative and mechanistic model of an adaptive circuit for efficient encoding and feature extraction

Abstract One major question in neuroscience is how to relate connectomes to neural activity, circuit function, and learning. We offer an answer in the peripheral olfactory circuit of the Drosophila larva, composed of olfactory receptor neurons (ORNs) connected through feedback loops with interconnected inhibitory local neurons (LNs). We combine structural and activity data and, using a holistic normative framework based on similarity-matching, we propose a biologically plausible mechanistic model of the circuit. Our model predicts the ORN → LN synaptic weights found in the connectome and demonstrate that they reflect correlations in ORN activity patterns. Additionally, our model explains the relation between ORN → LN and LN – LN synaptic weight and the arising of different LN types. This global synaptic organization can autonomously arise through Hebbian plasticity, and thus allows the circuit to adapt to different environments in an unsupervised manner. Functionally, we propose LNs extract redundant input correlations and dampen them in ORNs, thus partially whitening and normalizing the stimulus representations in ORNs. Our work proposes a comprehensive framework to combine structure, activity, function, and learning, and uncovers a general and potent circuit motif that can learn and extract significant input features and render stimulus representations more efficient. Significance The brain represents information with patterns of neural activity. At the periphery, due to the properties of the external world and of encoding neurons, these patterns contain correlations, which are detrimental for stimulus discrimination. We study the peripheral olfactory neural circuit of the Drosophila larva, that preprocesses neural representations before relaying them to higher brain areas. A comprehensive understanding of this preprocessing is, however, lacking. Here, we propose a mechanistic and normative framework describing the function of the circuit and predict the circuit’s synaptic organization based on the circuit’s input neural activity. We show how the circuit can autonomously adapt to different environments, extracts stimulus features, and decorrelate and normalize input representations, which facilitates odor discrimination downstream.
Evaluation of Atlas Based Segmentation in Accelerated Partial Breast Irradiated Patients.

Purpose/Objective(s) Accelerated partial breast irradiation (APBI) provides a convenient treatment option for patients with early-stage breast cancer, reducing treatment duration and the volume of breast treated. Automated contouring tools can decrease contouring time and improve consistency in contours of organs at risk (OARs). The purpose of this study was to evaluate the efficacy of atlas-based contours created by a commercially available software compared with manually contoured left breast, right breast, and heart OARs. Materials/Methods Thirty-one patients treated with APBI were randomly selected to generate an OAR atlas. The manually contoured left breast, right breast, heart, left lung, right lung, and spinal cord were included to construct the atlas using commercially available software. Since the atlas-based contour for lungs and spinal cord are well established at our clinic, our evaluation focused on the left/right breast and heart OARs. Using a specific workflow for partial breast irradiation, atlas-based OAR contours were automatically generated upon uploading of the image set. For left and right breast contours, this workflow automatically contracted breast contours 5mm away from skin surface. A twenty-one patient dataset was used to test the atlas. Dice Similarity Coefficient (DSC) and the mean Hausdorff distance (MSHD) were used for quantitative comparison to contoured breast and heart OARs. In addition to quantitative analysis, atlas-based segmentation was evaluated qualitatively by two staff radiation oncologists. They evaluated the contours using a four scaled score, defined as no change, minor change, major change, or not acceptable. Results The median and range DSC for the left breast, right breast and the heart were 0.85 ± 0.06 (0.71-0.94), 0.85 ± 0.06 (0.77-0.94), and 0.93 ± 0.03 (0.83-0.97), respectively. The average MSHD were 0.39 cm for the left breast, 0.36 cm for the right breast, and 0.20 cm for the heart. Qualitatively, among 21 test cases, each contour was assigned to whichever was the lower score from the two radiation oncologists. No atlas-based contours were rated not clinically acceptable by the radiation oncologists, consistent with all DSC > 0.7. 71% of atlas-based left breast contours were rated minor change, 81% for the right breast, and 76% for the heart, also consistent with the DSC values observed above. Conclusion Atlas-based segmentation used for patients receiving APBI is clinically useful with minor contour editing required from physicians. Our results from using a commercially available software program can be readily applied to other centers and may be tested for patients undergoing whole breast irradiation.
Emergency department psychiatric holds are linked to increased emergency department violence

Summary Background Violence towards professionals within the emergency department (ED) occurs at a concerning rate. We hypothesized that increased violence may be associated with the number of patients on mental health holds (MHHs) boarding in the ED. Objectives This study investigates factors that may be associated with assault in the ED. Methods This was an exploratory, retrospective study of pre-existing data from assault code activations, involuntary MHHs, and ED metrics at a level 2 trauma center and regional referral center, from May 2016 through April 2017. Results Of the 297 assault code activations in the hospital, 57 (19.2%) occurred in the ED. For ED MHHs, there were 524 holds written during the study period. Assault code activations were associated with an increased number of patients on MHHs (P = 0.04). Even when controlling for overall ED volume, activations were more likely to occur when there were more than 3 patients on MHHs (OR = 4.44, 95% CI: 1.49 - 19.07) and more likely to occur later in the month compared to the beginning of the month (OR = 2.39, 95% CI: 1.11 - 5.36). There was a diurnal pattern of activations, with more occurring between the hours of 12:00–23:59 (P = 0.03). Conclusions The number MHHs in the ED was associated with an increase in ED violence. While a causal association cannot be established at this time, further investigation and discussion on the topic is warranted. System-wide efforts to improve acute psychiatric care, and therefore reduce the number of patients on MHHs boarding in the ED, could potentially reduce ED workplace violence.
Membrane Stabilization by Drugs: Tranquilizers, Steroids, and Anesthetics

Publisher Summary Anesthesia or stabilization of the nerve membrane is caused by alcohols, steroids, local anesthetics, phenothiazine tranquilizers, antihistamines, and various detergents. This chapter extends the idea of membrane stabilization to many types of cell membranes and subcellular membranes rather than confine the term just to the neurolemma. It also examines some of the physicochemical factors that may be important in determining the degree of membrane stabilization and presents a comparison of the many types of in vitro effects of membrane stabilizers along with a juxtaposition of the in vitro effects of local anesthetics and the phenothiazine tranquilizers on membrane-bound organelles. There is an extremely close analogy, both qualitative and quantitative, between neuron stabilization and erythrocyte stabilization against hypotonic hemolysis. A definite correlation exists between the anesthetic potency of steroids and the erythrocyte stabilization by a very diverse group of steroid compounds over a 100-fold range of concentrations. A second analogous action of stabilizers on nerve and nonneural membranes is to be found in their mode of toxicity at high concentrations. At high concentrations the majority if not all the neuron stabilizers cause a depolarization of the neurolemma; this is presumably related to the fact that practically all these compounds are surface-active and cause membrane emulsification at high drug concentration.
Gatekeepers: How Procurement Personnel Guard Against Hybrid Accountability

Though much attention has been given to the relationship between contractor and vendor in regard to governmental accountability, little attention has been paid to the internal struggles that surface in regard to accountability in the procurement process. These informal horizontal relationships often circumvent vertical accountability controls most often thought to ensure equitable vendor selection. Similarly, though much attention has been paid to political influence in contracting, hierarchal organizational structures, and measures of performance, the contract officer-program manager relation has not been explored. Specifically, the informal tension that often forms between the program manager and contract officer has not been examined in regard to such accountability. This paper examines the relationship between the program officer and the contract officer in order to describe how hybrid public administration can affect the contracting process.
The Declining Significance of Traditional Borders (and the Appearance of New Borders) in an Age of High Technology

Publisher Summary This chapter focuses on the weakening significance of traditional borders and appearance of new borders in high technology era. The significance of traditional borders in drawing clean clear lines separating individuals and groups from each other and from their environments is weakening. New forms and borders whose meaning is unclear or contested are appearing at an accelerated rate. Developments in communications and surveillance technology are particularly important in undermining the physical, geographical, spatial, and juridical borders that have defined the self, communities, homes, cities, regions, and nation-states as entities that are believed to be distinct. The meaning and importance of distinctions such as between urban and rural, and center and periphery, are changing. International borders and face-to-face interaction are not as central as they have been. The chapter explains four broad areas where boundaries are changing and discusses the social implications of these changes. The borders involve physical space, the senses, time, and the individual's body and self.
Minimum Time Control with Trajectory Reassignment for Multi Degree-of-Freedom Systems Part II

Multilink manipulators and autonomous mobile systems are modeled as multi degree-of-freedom systems. These systems operate in environments where minimum time motion is required. A solution is given for the minimum time motion of these systems with real-time mid-stream trajectory reassignment. The method is developed for multi-link manipulators with actuator dynamics and the use of a global linearization and decoupling transformation feedback. The solution is based upon a time optimal position control for static endpoints and extended as the only known solution to arbitrary midstream trajectory reassignment. The nominal trajectory inputs are concatenated with the reassignment inputs to allow further reassignment. A companion paper shows examples of nominal and trajectory reassignments moves for nonlinear one and two degree-of-freedom systems.
A Stochastic Programming Model with Decision Dependent Uncertainty Realizations for Technology Portfolio Management

Technology development involves research and development (R&D) projects aimed to design, test and improve a technology, or the process of building a technology. Technology development is often an essential part of the operational strategy of an organization, during which deployment or implementation decisions are made. In most cases, organizations have several potential technologies with different characteristics that they can choose to invest in and develop using available resources. Selection of projects and allocation of the resources to the selected projects are important decisions with huge economic implications for an organization.