cssi/SciSciGPT-SciSciNet huggingface dataset:
44INIMMUNOTHERAPY: MYTH OR REALITY?

ABSTRACT An improved understanding of kidney cancer (KC) tumor biology has led to major advancements in the treatment of patients with metastatic disease. While agents that target the VEGF and mTOR pathways prolong survival, resistance develops for most patients within the first year of therapy. Agents that lead to durable remissions are of urgent need to patients living with this disease. For two decades, the clinical experience with high-dose bolus IL-2 has served as proof of principle that immunotherapy can produce durable responses in a small percentage of KC patients. Basic and translational investigation to elucidate the molecular mechanisms that govern the interaction between a tumor and its host immune response has helped to explain why immunotherapies too often fail to achieve satisfactory results. In KC, obstacles to effective immunotherapy may include the physiological down-modulation of the immune response through the expression of programmed death ligand-1 (PD-L1) on tumor cells and cytotoxic T-lymphocyte antigen-4 (CTLA-4) on activated T cells, which serve to restrict the cytolytic function of tumor-infiltrating T lymphocytes, the proliferation of regulatory (CD4+ CD25+) T cells (T-regs) in response to nonspecific cytokine administration, and the immunosuppressive effects of elevated circulating VEGF levels and myeloid-derived suppressor cells (MDSC). These insights have encouraged investigators to pursue agents that block T-cell regulation (e.g., PD-1 and CTLA-4 antibodies), inhibit tumor-induced immunosuppression (e.g. PD-L1 antibody) and more specifically activate T-cells (eg, CD-137 antibody, IL-21), and dendritic cells (e.g. AGS-003). Several of these approaches have shown encouraging efficacy in early trials both as single agents and in combination with standard therapies. However, for “targeted immunotherapy” to reach its full potential, significant work will need to be done to improve patient selection by refining proposed predictive biomarkers and overcome resistance mechanisms through the development of combination regimens. Disclosure: D.F. McDermott: BMS, Merck, Genentech - Scientific Advosry Board Partiicpation, compensated.
Hydraulic Modeling for Waste Stabilization Ponds

Treatment performance of waste stabilization ponds is a function of both the hydraulic transport and the biological and chemical transformation processes within the pond. Both the efficient hydraulic design of these ponds and the appropriate mathematical models for describing the hydraulic transport process are identified. A model consisting of a dispersed flow active zone and a fully-mixed return flow zone is developed and calibrated. Dye tracer studies and model simulations are utilized to illustrate the treatment efficiency of various pond geometries and inlet and outlet configurations. Recommendations are made for optimum design. For certain of the ponds analyzed, treatment efficiency predicted by the completely-mixed flow model compares well with that determined by analysis of dye tracer studies. The plug flow assumption seriously overestimates treatment efficiency.
The Effect of ACTH, Group Caging, and Adrenalectomy in Peromyscus leucopus with Emphasis on Suppression of Reproductive Function

SummarySham-adrenalectomized and adrenalectomized maturing white-footed mice (Peromyscus leucopus noveboracensis) of both sexes were injected subcutaneously with 4 units of ACTH daily for 10 days. Mice were adrenalectomized when 26–28 days old and each mouse was maintained thereafter on subcutaneous injections of 50 μg of cortisol acetate/day.In a second experiment, the effects of 5 units of ACTH daily for 10 days and of group caging (6–8 mice/cage) for 10 days were determined in intact mature P. leucopus 80–100 days old at the start of treatment.ACTH inhibited reproductive function in intact mature and maturing P. leucopus of both sexes, and in adrenalectomized maturing mice of both sexes maintained on cortisol. Group caging inhibited reproductive function in both sexes. In contrast to its effects on house mice, grouping reduced adrenal weight in both sexes. Grouping and ACTH inhibit reproductive function in male P. leucopus to a much greater extent than in house mice.ACTH produced no renal lesions in P....
Effect of gamma irradiation on flight time of Hypoderma lineatum (Diptera: Oestridae) males

When male Hypoderma lineatum (Villers) 10-day-old pupae were irradiated with 4,000 or 5,000 rad from 137Cs at 1,800 rad/min, the average flight time, the total flight time, and the proportion of flies that flew were reduced. A dose rate of 1,800 rad/min reduced flight time more than a dose rate of 430 rad/min given at the same age. Irradiation of 12-day-old pupae did not reduce flight time. All irradiated male flies were sterile.
The effect of prostaglandin E(2) and indomethacin on the placental vascular response to norepinephrine.

SummaryThe vascular response to norepinephrine is expressed in terms of a resistance ratio which is defined as the ratio of the vascular resistance seen 1.5 min after norepinephrine administration to that seen before norepinephrine administration. The injection of 1 μg/kg of norepinephrine to near-term sheep significantly increased the vascular resistance of the placenta to a ratio of 2.27 ± 0.52 (mean ± SEM; N = 7). Pretreatment with 20 jug of prostaglandin E2 per minute significantly decreased the placental response to norepinephrine to a resistance ratio of 1.47 ± 0.21 which was 65% of the untreated response (N = 7). Pretreatment with 10 mg/kg indomethacin significantly increased the placental response to norepinephrine from a resistance ratio of 2.25 ± 0.70 to 2.71 ± 0.84, which is 120% of the untreated value (N = 6). Prostaglandin E2 attenuated the placental vascular response to norepinephrine and indomethacin potentiated this response.
What is taught on firearm safety in undergraduate, graduate, and continuing medical education? A review of educational programs

OBJECTIVE: Because there have been no published formal reviews on teaching of firearm safety, we set out to systematically locate and review the literature on curricula that educated physicians and other health care providers, residents across specialties, and medical students on how to counsel on firearm safety. METHODS: We searched for all papers with outcomes that described firearm safety training programs for healthcare providers and trainees. Studies were identified through PubMed, Scopus, Google Scholar, PsychInfo, EMBASE, and MedEdPortal databases and electronically searched using combinations of words from general topic areas of firearms, learners, and education. RESULTS: We found four programs that met inclusion criteria. These targeted a narrow range of learners including medical students, pediatric residents, practicing pediatricians, and nurse practitioners. Teaching methods included lectures, case-based learning, group discussions, and audiotape training. There were two randomized controlled trials, one cohort design, and one posttest design. One of the randomized controlled trials was an office-based high quality multisite national study, although the focus of teaching was not on firearm safety alone. All studies used different outcomes, and only one study validated the outcome measures. There were no studies targeting psychiatrists or psychiatry residents. CONCLUSION: These results underscore a priority for developing firearm safety education programs in undergraduate, graduate, and continuing medical education settings. Language: en
Effect of hypertonic saline solution on left ventricular afterload in normovolumic dogs.

Abstract The effects of hypertonic saline solution (HSS) and hyperosmotic dextrose (HD; 2,400 mosm/L, 4 ml/kg of body weight) on left ventricular afterload were determined in normovolumic, chloralose-anesthetized, autonomically blocked dogs (n = 8). Solutions were infused IV over 3 minutes. Left ventricular afterload was assessed by use of a dual-tipped micromanometer catheter with an electromagnetic fluid-velocity sensor located in the ascending aorta, and the impedance spectrum was calculated after Fourier analysis of signal-averaged aortic pressure and flow signals. Hypertonic saline solution and HD decreased peripheral resistance, reflection coefficient at zero frequency, and frequency of the first zero crossing of the phase angle for 3 to 5 minutes after either fluid was administered. Characteristic impedance was not altered by HSS or HD. These impedance spectrum changes indicate transient vasodilatation and afterload reduction. We conclude that the vascular effect of an ionic hyperosmotic solution (HSS) is similar to that of a nonionic hyperosmotic solution (HD), and that HSS and HD transiently decrease afterload in normovolumic dogs. The duration of the afterload reduction after HSS administration appeared to be too short to be of great clinical benefit.
Determination of Calciom.Magnesium.Zinc and Iron in Bamboo by Flame Atomic Absorption Spectrometry

Objective The sample were treated with nocomplete digestion method.Methods:the samples of bamboo were digested in the mixed acid of HClO4-HNO3(1+3)under low temperature.Use Lanthanum of salt as releasing agents for calcium and magnesium.For determining Magnesium in bamboo the deuterium lamp was applied to deduct background absorption.Useing FAAS determining calcium、magnesium、zinc、iron elements in the bamboo.Results When the 0~1.95mg/ml Ca,Zn in 0~0.80 mg/ml,0~0.68mg/ml Fe,Mg concentrations in 0~0.95mg/ml area,elements of a good linear relationship between absorbance and concentration,the detection limits were :56μg/L,34μg/L.7μg/L,12μg/L.Conclusion The determination results indicted that the method was very handy and quickly.Every analytical of element result was satisfied.
Structural Reform and Growth: What Really Matters? Evidence from the Caribbean

Since the 1980's with the introduction of IMF/WB adjustment programs structural reforms have been a core part of the reform agenda in the Caribbean. The paper reviewed the package of structural reforms in trade liberalization, financial liberalization and tax policy, and gauges their impact on growth. The paper used a set of reform indices to gauge both short-run and long-run effects of structural reforms on growth, controlling for other possible growth determinants using panel dynamic OLS estimation. In addition, recognizing the importance of institutions to growth the empirical analysis also analyzed the impact of institutional quality on growth for a sample of small states including the Caribbean. We concluded that the benefits of structural reforms are only seen over the long-term and in reinvigorating growth the reform effort needs to be revived and include greater attention to strengthening institutional quality.
Organizing an Inter-Library Network: The State University of New York Approach

The State University of New York is a multicampus university which, in response to the fiscal and operational problems which are facing higher education, is developing a library network. Proposals to increase the cost efficiency and cost effectiveness of the libraries are made, and some of the unknown elements, including library output measurement, collection size formulae, and the balance of emphasis between the collection or archival and user service functions are discussed.
Cancer of the colon and rectum.

Carcinoma of the colon remains one of the most common visceral malignancies in the geriatric population. This article presents epidemiologic and personal risk factors influencing the development of colon cancer. Additionally, screening guidelines, clinical features, and new treatment modalities, with emphasis on the elderly patient, are discussed.
Nonoperative Care and Footwear for the Diabetic Foot and Ankle Patient

Initial treatment of the diabetic foot is largely regarded to be nonoperative. The goal of nonoperative care is to maintain a stable, plantigrade foot, supported by a shoe or brace, which avoids excessive focal pressure phenomenon to the foot or ankle, resulting from repetitive loading. This includes sensory neuropathic soft tissue ulceration, fractures, dislocations, and chronic Charcot deformities affecting the ankle, hindfoot, midfoot, and forefoot. Whatever initial nonoperative treatment is selected, patient education, routine visual inspection of feet, appropriate pressure-dissipating accommodative orthotics, along with shoe and total contact boot wear are the keystones which help maintain a functional foot during gait and avoid complications.
Optimized reagent dosage effect on rock dust to enhance rock dust dispersion and explosion mitigation in underground coal mines

Abstract Rock dust consisting of ultrafine calcium carbonate particles is required in underground coal mines to suppress the potential for coal dust explosions. When the dust is applied in a moist mining atmosphere or placed in the mine in wet form, caking of the rock dust particles occurs which negatively effects dispersion of the dust during an event thereby creating the potential for an explosion. An earlier investigation found that sodium oleate was effective in rendering the surfaces of rock dust particles hydrophobic thereby allowing the water to drain, eliminating the caking effect and enhancing their dispersive properties. However, subsequent research has shown that increasing the sodium oleate concentration above a specific value reverses the positive impact on dispersion by inducing particle agglomeration through hydrophobic particle-particle interactions. A detailed investigation found that monolayer adsorption of sodium oleate occurs most likely within the oleate concentration range of 0.1% and 0.15% by weight. A further increase in the oleate concentration resulted in a corresponding rise in the surface contact angle to a maximum of 126°. As a result, the inter-particle interactions become dominated by the attractive hydrophobic interaction force which results in spontaneous particle agglomeration upon contact between the rock dust particles. In addition, precipitated calcium oleate nucleated on top of the hydrophobic dust surface as nanoparticles and tended to agglomerate at high oleate concentrations. As a result, the benefits of hydrophobizing rock dust particles are limited to lower reagent dosages to maintain the desired dispersion characteristics.
I/O Aware Power Shifting

Power limits on future high-performance computing (HPC) systems will constrain applications. However, HPC applications do not consume constant power over their lifetimes. Thus, applications assigned a fixed power bound may be forced to slow down during high-power computation phases, but may not consume their full power allocation during low-power I/O phases. This paper explores algorithms that leverage application semantics -- phase frequency, duration and power needs -- to shift unused power from applications in I/O phases to applications in computation phases, thus improving system-wide performance. We design novel techniques that include explicit staggering of applications to improve power shifting. Compared to executing without power shifting, our algorithms can improve average performance by up to 8% or improve performance of a single, high-priority application by up to 32%.
A dynamic and cyclical model of bounded ethicality

Abstract We introduce a new model of bounded ethicality which helps explain three persistent puzzles of ethical behavior: when moral awareness is or is not present, when ethical behavior is more or less consistent with past behavior, and when blind spots obscure our ethical failures. The original conception of bounded ethicality ( Chugh, Banaji, & Bazerman, 2005 ) described the systematic psychological constraints on ethical behavior and has contributed to our field's understanding of the phenomena of everyday, “ordinary” unethical behavior. In this more detailed model, we delineate these systematic processes and mechanisms and show how concepts of automaticity, self-view, and self-threat play critical roles in our ethical decision-making. The model describes distinct, asymmetric patterns of (un)ethical behavior and pinpoints the contingency which determines which pattern is more likely to unfold, including when we will trend to more or less automaticity and more or less ethical behavior. Our model integrates and synthesizes many of the key models and findings in recent behavioral ethics research into a single, overarching model of ethical decision-making, offering an anchor for new questions and a new realm of study.
Rigor in Elementary Science Students' Discourse: The Role of Responsiveness and Supportive Conditions for Talk.

Teaching that is responsive to students’ ideas can create opportunities for rigorous sense-making talk by young learners. Yet we have few accounts of how thoughtful attempts at responsive teaching unfold across units of instruction in elementary science classrooms and have only begun to understand how responsiveness encourages rigor in conversations. In this study, the first author taught an electric circuits unit to four upper elementary science classes, exercising a responsive teaching stance. We found that rigorous episodes of whole-class talk were associated with the teacher's use of open-ended questions, follow-up prompts, references to activity or representations, prediscussion tasks, and asking students to comment on their peers’ ideas. Overall, higher rigor talk co-occurred with these conditions when used in combination. Despite being responsive to students’ emerging ideas, all four classes addressed the science ideas for the unit—an outcome we attribute to the use of an anchoring phenomenon and the teacher's awareness of the concepts required to construct evidence-based explanations for it. Finally, concerted attempts to teach in responsive ways—while also attending to rigor—surfaced pedagogical tensions that problematize efforts to create such discourse-rich environments and inform how this type of instruction might be enacted by others.
A Modern Devil Baby (1914)

Hull House, Chicago. There is a theory that woman first evolved and used the fairy story, that combination of wisdom and romance, in an effort to tame her mate and to make him a better father to her children.
Unintended Causal Pathways: Probing Experimental Mechanisms Through Mediation Analysis

We present the results of several experimental studies relevant to the general study of causal mechanisms, the specific study of audience costs, and the larger body of survey experiments. First, we show that in the context of audience cost experiments, a portion of the estimated treatment effect is related to the intended causal mechanism, national reputation, but this mechanism underlies a relatively small portion of the total causal effect, leaving much of the causal effect unexplained. Second, we show that the experimental treatment manipulates an unintended mechanism that also underlies part of the treatment effect. We conduct two tests to establish the relative independence of each mediator’s effect. Finally, we investigate the possibility that our findings represent question order effects rather than mediation effects, finding that priming does not substantially threaten our results. Our results and discussion advance our understanding of the challenge of studying causal mediation in survey experiments. We provide some recommendations for survey experimentation moving forward.
A common deletion in the haptoglobin gene associated with blood cholesterol levels among Chinese women.

Haptoglobin (HP) protein plays a critical role in binding and removing free hemoglobin from blood. A deletion in the HP gene affects the protein structure and function. A recent study developed a novel method to impute this variant and discovered significant association of this variant with low-density lipoprotein (LDL) and total cholesterol levels among European descendants. In the present study, we investigated this variant among 3608 Chinese women. Consistent with findings from Europeans, we found significant associations between the deletion with lower cholesterol levels; women homozygous for the deletion allele (HP1–HP1), had a lower level of total cholesterol (−4.24 mg dl–1, P=0.02) and LDL cholesterol (−3.43 mg dl–1, P=0.03) than those not carrying the deletion allele (HP2–HP2). Especially, women carrying the HP1S–HP1S, had an even lower level of total cholesterol (−5.59 mg dl–1, P=7.0 × 10–3) and LDL cholesterol (−4.68 mg dl–1, P=8.0 × 10–3) compared to those carrying HP2–HP2. These associations remained significant after an adjustment for an established cholesterol level-related variant, rs2000999. Our study extends the previous findings regarding the association of HP structure variant with blood cholesterol levels to East Asians and affirms the validity of the new methodology for assessing HP structure variation.
Curriculum-Based Handwriting Programs: A Systematic Review With Effect Sizes

Challenges with handwriting can have a negative impact on academic performance, and these challenges are commonly addressed by occupational therapy practitioners in school settings. This systematic review examined the efficacy of curriculum-based interventions to address children's handwriting difficulties in the classroom (preschool to second grade). We reviewed and computed effect sizes for 13 studies (11 Level II, 2 Level III) identified through a comprehensive database search. The evidence shows that curriculum-based handwriting interventions resulted in small- to medium-sized improvements in legibility, a commonly reported challenge in this age group. The evidence for whether these interventions improved speed is mixed, and the evidence for whether they improved fluency is insufficient. No clear support was found for one handwriting program over another. These results suggest that curriculum-based interventions can lead to improvements in handwriting legibility, but Level I research is needed to validate the efficacy of these curricula.
Humeanism without Humean Supervenience: A Projectivist Account of Laws and Possibilities

Acceptance of Humean Supervenience and thereductive Humean analyses that entail it leadsto a litany of inadequately explained conflictswith our intuitions regarding laws andpossibilities. However, the non-reductiveHumeanism developed here, on which law claimsare understood as normative rather than factstating, can accommodate those intuitions. Rational constraints on such norms provide aset of consistency relations that ground asemantics formulated in terms offactual-normative worlds, solving theFrege-Geach problem of construing unassertedcontexts. This set of factual-normative worldsincludes exactly the intuitive sets ofnomologically possible worlds associated witheach possible set of laws. The extension ofthe semantics to counterfactual and subjunctiveconditionals is sketched. Potential objectionsinvolving subjectivity, mind-dependence, andnon-factuality are discussed.
METHODS OF REGIONAL ECONOMIC ANALYSIS

Most of the models that have been employed in land use and transportation studies are intra-regional, examining economic relations within regions. Pittsburgh, Philadelphia, Boston, and San Francisco among others have been the subjects of investigations of this nature. This chapter discusses what some call the inter-regional models—models that have as their focus the relationship between the region under study and other regions in the nation. Interregional models often lack spatial content, treating the region as a single point in space. Instead of attempting to understand spatial associations—as is the case for intra-regional models—most inter-regional models are aimed at understanding and forecasting the process of regional growth. One of the earliest statistical models to be employed in regional research was the economic base model. Economic base studies have several uses. First, data collected for a base study are helpful simply for the information they convey. For instance, such data provide a view of the sources of employment, income, and weaknesses in the region's economy. Second, base studies are very often used as a means of forecasting local activity. They are applied in conjunction with other studies for land use and transportation planning, and for determining future levels of government activity.
Mechanisms and Significance of Bacterial Resistance to Human Cationic Antimicrobial Peptides

Cationic antimicrobial peptides (CAMPs) are essential compounds of the innate immunity system possessed by humans. CAMPs protect the host by exerting bactericidal activity, molecular signaling, modulating the immune response, and facilitating the communication between innate and acquired immunity. Over the millennia, bacteria have developed mechanisms to circumvent the antimicrobial activity of CAMPs, thereby promoting their survival during infection. In this chapter, we focus on the mechanisms used by various bacterial pathogens to resist the antibiotic-like action of CAMPs and the consequences of such resistance.
Mental Health Factors in the Utilization of Pediatric Primary Care

The relationship of mental health factors to use of pediatric medical care in a 12-month period is examined using cross-sectional and prospective data from a community-based cohort of children (aged 4–8 years at baseline) and their families. Results from this study demonstrate that mother's self-reported mental health is statistically significantly related to the number of pediatric visits. In the cross-sectional analysis, the effect of mothers's mental health on children with 5 or more pediatric visits is moderated by poverty and mothers with depressive symptoms are much more likely than those without such symptoms to have children who are very high service users (10 visits or more). In the longitudinal analysis, an inconsistent pattern of mothers' mental health problems over a 24-month period increases the likelihood of high use in the third year and the persistence of maternal mental health problems increases the likelihood of very high use.
The Fundamental Group

We turn now to the investigation of the structure of a topological space by means of paths or curves in the space. Recall that in Chapter 1 we decided that two closed paths in a space are homotopic provided that each of them can be “continuously deformed into the other.” In Figure 4.1, for example, paths C2 and C3 are homotopic to each other and C1 is homotopic to a constant path. Path C1 is not homotopic to either C2 or C3 since neither C2 nor C3 can be pulled across the hole that they enclose.
1.17 – Principles of Brain Scaling

Although mammalian brains come in many different sizes, they all conform to a single overall design. Scaling relationships between various parts of the brain – that is, the variation in size of one brain part compared with another as the overall brain size changes – are known to follow a very orderly pattern. These scaling relationships define the scalable architecture of the brain and place constraints on the possible computations performed by the brain regions.
Business Strategy from the Population Level

Much of the debate in the literature on business strategy revolves around the appropriate unit of analysis. For Michael Porter (1980) and others who take a “market power” position, the issue is how markets are structured and how a particular focal firm can take advantage of that structure. A second position, called the “resource-based view” (Wernerfelt 1984) begins with the firm, asks what its resources are, and then considers what product markets the firm could serve so as to most efficiently utilize the array of resources at its disposal. Both of these positions take for granted the ability of managers to control what firms are doing and how. This involves both the degree to which managers (presumptively top managers) control the organizations they are supposed to manage and the speed with which adjustment can be made. Finally, both take a single firm as the strategic referent, treating strategic analysis as something done uniquely by that firm.
Organelle Stress and mTOR in Aging-Associated Inflammation

Abstract Aging, defined as the time-dependent decline in organ and body functions, has been traditionally viewed as the result of tissue degenerative changes due to accumulation of unrepaired damage, cell death, and reduced cell renewal capacity. This rather “passive” model of aging is currently challenged by evidence that tissue adaptation/response to environmental, nutritional, and genotoxic stress actively contributes to the senescent phenotype. Such reactive response usually takes the form of a chronic, low-grade inflammatory process, as it occurs in several age-associated disorders like atherosclerosis, loss of bone and muscle mass, obesity and metabolic syndrome, and neurodegeneration. One key element of this emerging picture is the intricate connection between inflammatory components of aging ( inflammaging ) and metabolic aspects of senescence, such as obesity and diabetes, and the role played in both by deranged signaling through evolutionarily conserved nutrient-sensitive cascades [i.e. the insulin/insulin-like growth factor (IGF) cascade] that are known to regulate longevity and “health span” from model organs to mammals. This chapter focuses on the mammalian target of rapamycin (mTOR) and its downstream pathway as a central molecular platform that integrates diverse nutrient and stress-related cues and cross talks with intracellular organelles and the inflammatory response in the context of the aging body, thus representing a promising target for novel pharmacological strategies against age-related diseases.
Cervical Facet Joint Injection and Fatal Cerebritis: A Case Report (P06.262)

OBJECTIVE: To present a rare fatal complication of cervical facet joint injection (CFJI). BACKGROUND: Facet joint injections are used for the treatment of cervicogenic headache (CH). Limited knowledge is available regarding neurological complications of CFJI. To our knowledge, fatal complications are rare. We report a case of fatal neurological event in a patient who received a facet joint injection (FJI). DESIGN/METHODS: Case Report. RESULTS: 68 year old female with history of Rheumatoid arthritis and CH was transferred from a Pain Clinic to our hospital after developing acute onset loss of consciousness and weakness in all four extremities immediately after receiving a CFJI at C2-C3 level. The procedure was done under X-ray guidance and bone was felt upon needle insertion. Syringe was drawn and no blood or CSF was seen. 4 cc of 0.25% Marcaine, 1:200,000 Epinephrine and 40 mg of Depomedrol was given. She was hemodynamically stable but not responding to verbal and noxious stimuli. Brainstem reflexes were present. She was quadriplegic. Reflexes were normal in upper extremities and absent in lower extremities. Plantar responses were mute. CT scan of head showed hydrocephalus. CTA head and neck were normal. MRI of the brain showed T2 hyperintensity of bilateral thalami, cerebellum, occipital and temporal lobes without diffusion restriction suggesting cerebral edema due to encephalitis. Patient continued to get worse and repeat CT scan showed worsening hydrocephalus with herniation. An emergent bedside EVD was placed. Patient clinically continued to worsen with loss of brainstem reflexes and progressed to brain death in next 12 hours. CONCLUSIONS: We hypothesize that if drugs are injected in the cerebral vasculature, they alter the permeability of the blood–brain barrier by causing shrinkage of endothelial cells and enter into the cerebral interstitial tissue leading to direct neurotoxicity. Appropriate precautions and knowledge of rare complications of FJI needs to be considered while managing CH. Disclosure: Dr. Mir has nothing to disclose. Dr. Vaishnav has nothing to disclose. Dr. Downs has nothing to disclose. Dr. Remmel has received personal compensation for activities with Pfizer and Boehringer Ingelheim as a speaker.
Socioeconomic disadvantage, brain morphometry, and attentional bias to threat in middle childhood

Socioeconomic disadvantage is associated with higher rates of psychopathology as well as hippocampus, amygdala and prefrontal cortex structure. However, little is known about how variations in brain morphometry are associated with socio-emotional risks for mood disorders in children growing up in families experiencing low income. In the current study, using structural magnetic resonance imaging, we examined the relationship between socioeconomic disadvantage and gray matter volume in the hippocampus, amygdala, and ventrolateral prefrontal cortex in a sample of children (n = 34) in middle childhood. Using an affective dot probe paradigm, we examined the association between gray matter volume in these regions and attentional bias to threat, a risk marker for mood disorders including anxiety disorders. We found that lower income-to-needs ratio was associated with lower bilateral hippocampal and right amygdala volume, but not prefrontal cortex volumes. Moreover, lower attentional bias to threat was associated with greater left hippocampal volume. We provide evidence of a relationship between income-related variations in brain structure and attentional bias to threat, a risk for mood disorders. Therefore, these findings support an environment-morphometry-behavior relationship that contributes to the understanding of income-related mental health disparities in childhood.
Quantum Entropy and Accounting

In a previous paper we establish the equality between accounting numbers and information in a classical Arrow-Debreu economy. One of the conditions is complete market, that is, there exists an Arrow-Debreu security for every possible state realization. In this paper, we relax this condition and establish the equality between accounting numbers and information by exploring quantum information and measurement mathematics. In the revised domain expanded relationship, von Neumann entropy replaces Shannon entropy to capture the information effect.
Ubiquitin-dependent switch during assembly of the proteasomal ATPases mediated by Not4 ubiquitin ligase.

In the proteasome holoenzyme, the hexameric ATPases (Rpt1-Rpt6) enable degradation of ubiquitinated proteins by unfolding and translocating them into the proteolytic core particle. During early-stage proteasome assembly, individual Rpt proteins assemble into the hexameric “Rpt ring” through binding to their cognate chaperones: Nas2, Hsm3, Nas6, and Rpn14. Here, we show that Rpt ring assembly employs a specific ubiquitination-mediated control. An E3 ligase, Not4, selectively ubiquitinates Rpt5 during Rpt ring assembly. To access Rpt5, Not4 competes with Nas2 until the penultimate step and then with Hsm3 at the final step of Rpt ring completion. Using the known Rpt–chaperone cocrystal structures, we show that Not4-mediated ubiquitination sites in Rpt5 are obstructed by Nas2 and Hsm3. Thus, Not4 can distinguish a Rpt ring that matures without these chaperones, based on its accessibility to Rpt5. Rpt5 ubiquitination does not destabilize the ring but hinders incorporation of incoming subunits—Rpn1 ubiquitin receptor and Ubp6 deubiquitinase—thereby blocking progression of proteasome assembly and ubiquitin regeneration from proteasome substrates. Our findings reveal an assembly checkpoint where Not4 monitors chaperone actions during hexameric ATPase ring assembly, thereby ensuring the accuracy of proteasome holoenzyme maturation.
Identification and functional characterization of CD8+ T regulatory cells in type 1 diabetes patients

Type 1 diabetes is an autoimmune disease where autoreactive T lymphocytes destroy pancreatic beta cells. We previously reported a defect in CD4+ Tregs cell proliferation and reduced CD4+ Tregs PD-1 expression in patients. Another 'memory-like' regulatory subset, CD8+ Tregs, evaluated as CD8+CD25+FOXP3+, has recently raised interest for their effective suppressive activity. Different CD8+ T cell populations, their proliferation capacity and expression of PD-1 molecule were evaluated by flow-cytometer analysis in newly diagnosed, long-term Type 1 diabetes patients compared to healthy normal donors. Under basal conditions, CD8+ Tregs and CD8+ Teffs were seemingly represented among study groups while there was evidence of diminished expression of PD-1 in Teff subsets of long-term patients. After 3 days of PMA/ionomycin stimulation, patients CD8+ Tregs showed decreased percentage in respect to control group. CD8+ Teffs were instead increased in long-term diabetics versus controls. PD-1+CD8+ Tregs were represented at a much lower percentage in long-term diabetic patients, in respect to controls. Importantly, patients CD8+ Tregs and CD8+ Teffs presented a significant proliferation defect in respect to the control group. In conclusion, our study indicates that a defect of CD8+ Tregs is observed in diabetics. This subset could thus represent a novel target of immunotherapy in patients.
P83 Nutrition Education in Congregate and Home Delivered Meal Sites: What Do We Know?

Background By 2030, nearly 21% of the population will be 65 years and older. Those who reach 65 will live, on average, an additional 19 years. Adequate nutrition is essential to health and quality of life for older adults. Congregate and home-delivered meal programs are an ideal setting to provide nutrition education to promote successful aging. Objective This study described the content of nutrition education delivered at congregate and home-delivered meal programs and the extent to which education sessions were being evaluated for effectiveness. Study Design, Settings, Participants This cross-sectional study collected data through a novel, national, online survey for nutrition educators working with congregate and home-delivered meal programs. Survey participants were recruited via multiple listservs and contact information from agencies and organizations who work with congregate and home delivered meal participants (n = 236). Forty five states in the US were represented. Measurable Outcome/Analysis Descriptive statistics were conducted for the full sample and compared between dietetic (n = 116) and non-dietetic professionals (n = 120). Results Almost 70% of nutrition educators worked in the profession for 10+ years and more than half worked with older adults for 10+ years. The most common topics delivered at congregate and home-delivered meal programs were: food safety (62%), healthy eating (57%), and diabetes (56%); the most common delivery method was handouts (71%). Only 29% choose materials that focus specifically on behavior change. Nutrition educators were somewhat satisfied with available materials yet reported not knowing about, nor using, freely available, evaluated programs for older adults. Nutrition educators reported malnutrition as a major issue but that they lacked tools to screen for and address malnutrition. Dietetics professionals were more likely to conduct evaluations for their sessions (2.13 vs.1.67, 4-point scale) compared to non-dietetic professionals. Conclusion Nutrition educators working with congregate and home-delivered meal participants need training on how to conduct evaluations, especially non-dietetic professionals. Training is needed for addressing malnutrition and using screening tools. Resource-sharing hubs at both local and national levels are warranted. Funding None.
Meta-Analysis Reveals Reproducible Gut Microbiome Alterations in Response to a High-Fat Diet

Summary Multiple research groups have shown that diet impacts the gut microbiome; however, variability in experimental design and quantitative assessment have made it challenging to assess the degree to which similar diets have reproducible effects across studies. Through an unbiased subject-level meta-analysis framework, we re-analyzed 27 dietary studies including 1,101 samples from rodents and humans. We demonstrate that a high-fat diet (HFD) reproducibly changes gut microbial community structure. Finer taxonomic analysis revealed that the most reproducible signals of a HFD are Lactococcus species, which we experimentally demonstrate to be common dietary contaminants. Additionally, a machine-learning approach defined a signature that predicts the dietary intake of mice and demonstrated that phylogenetic and gene-centric transformations of this model can be translated to humans. Together, these results demonstrate the utility of microbiome meta-analyses in identifying robust and reproducible features for mechanistic studies in preclinical models.
Decreased Immunogenicity of Purified Topical Bovine Thrombin Preparations.

Abstract Abstract 4209 It has been reported that severe coagulopathy following exposure to topical bovine thrombin may be attributed to the impurities in bovine thrombin preparations. Prepared through the activation of bovine prothrombin by thromboplastin, a crude thrombin preparation was further purified using ion-exchange chromatography and membrane filtration steps to yield thrombin 4A and 4B preparations. The aim of this study was to compare the relative purity of these bovine thrombin preparations by virtue of the detection of bovine prothrombin-related antigens. Bovine prothrombin was administered to three individual rabbits on days 0, 21, 42, 91, 123 and 151 using standard immunologic method. Blood was drawn on 30, 50, 105, 137 and 165 days and the pooled antisera from three rabbits were purified to obtain IgG using protein G affinity columns. Utilizing western blotting, serial diluted bovine crude thrombin, 4A and 4B preparations were probed using the prothrombin IgGs from each time point to explore prothrombin-related antigens in these preparations. Compared with the IgG collected on day 30, the prothrombin IgGs collected from day 50 to 165 showed a time-dependent increased detecting ability for the prothrombin antigens in the bovine thrombin preparations. The lowest amount of crude thrombin, 4A and 4B preparations that prothrombin IgG could detect was 0.125U, 10U and 20U, respectively. The rank order of the number of immunoreactive bands in three bovine thrombin preparations probed by the prothrombin IgGs collected from any given time point was consistant and reproducible: crude thrombin > thrombin 4A > thrombin 4B. The results indicate that thrombin 4B represents the most purified thrombin preparation and relatively non-immunogenic form among three thrombin preparations studied. Disclosures: No relevant conflicts of interest to declare.
Ferroportin in Erythrocytes: Importance for Iron Homeostasis and its Role in Infection

Ferroportin (FPN), the only known vertebrate iron exporter, transports iron from intestinal, splenic, and hepatic cells into the blood to provide iron to other tissues and cells in vivo. Most of the circulating iron is consumed by erythroid cells to synthesize hemoglobin. Recently, we found that erythroid cells not only consume large amounts of iron, but also return significant amounts of iron to the blood. Erythroblast-specific Fpn knockout (Fpn KO) mice developed lower serum iron levels in conjunction with tissue iron overload and increased FPN expression in spleen and liver without changing hepcidin levels. Our results also showed that Fpn KO mice, which suffer from mild hemolytic anemia, were sensitive to phenylhydrazine-induced oxidative stress but were able to tolerate iron deficiency upon exposure to a low-iron diet and phlebotomy, supporting that the anemia of Fpn KO mice resulted from erythrocytic iron overload and resulting oxidative injury rather than a red blood cell (RBC) production defect. Moreover, we found that the mean corpuscular volume (MCV) values of gain-of-function FPN mutation patients were positively associated with serum transferrin saturations, whereas MCVs of loss-of-function FPN mutation patients were not, supporting that erythroblasts donate iron to blood through FPN in response to serum iron levels. Our results indicate that FPN of erythroid cells has an unexpectedly essential role in maintaining systemic iron homeostasis and protecting RBCs from oxidative stress, providing insight into the pathophysiology of FPN diseases. When malaria parasites invade red blood cells (RBCs), they consume copious amounts of hemoglobin, and severely disrupt iron regulation in humans. Anemia often accompanies malaria disease; however, iron supplementation therapy inexplicably exacerbates malarial infections. We recently found that the iron exporter ferroportin (FPN) was highly abundant in RBCs, and iron supplementation suppressed its activity. Conditional deletion of the Fpn gene in erythroid cells resulted in accumulation of excess intracellular iron, cellular damage, hemolysis, and increased fatality in malaria-infected mice. In humans, a prevalent FPN mutation,Q248H (glutamine to histidine at position 248), prevented hepcidin-induced degradation of FPN and protected against severe malaria disease. FPNQ248H appears to have been positively selected in African populations in response to the impact of malaria disease. Thus, FPN protects RBCs against oxidative stress and malaria infection. 1. Zhang DL, Wu J, Shah BN et al. Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk. Science. 2018;359 (6383):1520-1523. 2. Zhang DL, Ghosh MC, Ollivierre H, Li Y, Rouault TA. Ferroportin deficiency in erythroid cells causes serum iron deficiency and promotes hemolysis due to oxidative stress. Blood. 2018;132 (19):2078-2087. 3. Zhang DL, Rouault TA. How does hepcidin hinder ferroportin activity. Blood. 2018;131 (8):840-842. Disclosures No relevant conflicts of interest to declare.
De novo transcriptome of Phakopsora pachyrhizi uncovers putative effector repertoire during infection

Abstract Phakopsora pachyrhizi, which causes Asian soybean rust (ASR), secretes effector proteins to manipulate host immunity and promote disease. To date, only a small number of effectors have been identified from transcriptome studies. To obtain a more comprehensive understanding of P. pachyrhizi candidate secreted effector proteins (CSEPs), we sequenced the transcriptome using two next-generation sequencing technologies. Short-read Illumina RNA-Seq data was used for reducing base-calling errors for long-read PacBio Iso-Seq. After initial de novo assemblies for RNA-seq and error correction of transcripts for Iso-Seq followed by filtering, we obtained 8,528, 27,647, 26,895, and 17,141 non-plant, non-soybean transcripts at 3, 7, 10, and 14 days after inoculation, respectively. We identified a repertoire of CSEPs of which a majority was expressed during the later stages of infection, and many that could be bioinformatically associated with haustoria. This approach for identifying CSEPs improves our current understanding of the P. pachyrhizi effectorome, and these CSEPs are expected to be a valuable resource for future studies of P. pachyrhizi-soybean interactions.
Posttraumatic stress disorder in children and adolescents

Prior to the 1950s, there was little systematic investigation into the effects of traumatic events on children or adolescents. Excepting the early work of Anna Freud on the effects of war on children (see Freud & Burlington, 1943), little scientific interest was evident. This is not to suggest that children and adolescents were free of trauma; to the contrary, their lives were characterized by considerable turmoil that today would be described as “out of the range of usual human experience” (American Psychiatric Association, 1987, p. 250). However, consistent with the “adultmorphic” conception of children that was prevalent at the time, children were viewed as miniature adults capable of handling the multitude of stresses to which they were subjected (Ollendick & Hersen, 1989).