cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract NS 2: Antiphospholipid Associated Hypercoagulability and Subclinical White Matter Lesions in Patent Foramen Ovale Related Stroke - Searching for Footprints of Paradoxical Embolism

Background: Patent foramen ovale (PFO) related stroke has been reported to have higher frequency of hypercoagulable state and “non-specific” subclinical white matter lesions on MRI. While it is interesting to hypothesize that paradoxical embolic events may trigger subclinical infarcts in the setting of prothrombotic state, the associations are unclear. We examined antiphospholipid antibody status, one of the hypercoagulable conditions, with respect to white matter lesions (WMLs) in PFO related stroke to better understand this relationship. Methods: 79 consecutive prospectively recruited non-migrainous PFO-related stroke patients (adjudicated by two vascular neurologists) underwent FLAIR sequence MRI and anticardiolipin antibody IgG, IgM and lupus anticoagulant measurement. Subclinical (or clinically “silent”) white matter lesions (WMLs) were inspected by investigators blind to clinical information using two scales (Fazekas and Scheltens) to insure inter-rater reliability and accuracy. Results: Patients with elevated anticardiolipin titer (n=6; 7.6%; 50% men) had similar age (mean = 53 vs 48) to those with normal titers (n= 73; 92.4%). Of the patients with positive anticardiolipin antibody, mean IgG was 27 GPL (range 21.4-38.6; normal range 0-15); mean IgM was 32.7 MPL (range 22.2-36.6; normal range 0-15), and none had lupus anticoagulant. WMLs were found in both periventricular regions (PV-WML) and in deep white matter (D-WML). Overall, global WML burden is statistically significantly increased in PFO stroke patients with positive anticardiolipin antibody compared to those with negative titers (Fazekas scale - 2.333 vs 1.35 , p Conclusions: In non-migraineur PFO-related stroke patients with antiphospholipid-associated hypercoagulability, there is greater global WMLs burden than those without any hypercoagulable states. Antiphospholipid antibody positivity may contribute to global burden of WMLs in patients with PFO related stroke, independent of conventional risk factors for WML. WMLs found on MRI FLAIR maybe “footprints” of subclinical embolic events which can potentially be used to follow disease progression and triage more aggressive stroke prevention strategy in this patient population. Further study with a larger disease cohort and other hypercoagulable states are needed to validate these preliminary findings.
Immunosuppressive Therapy for Ulcerative Colitis, Ileitis, and Granulomatous Colitis

In spite of the lack of conclusive evidence that inflammatory bowel diseases are autoimmune in nature, it is apparent from the data presented that immunosuppressive therapy deserves a role in the treatment of these disorders. Most patients responded satisfactorily in that they had a diminution of symptoms, were able to function more effectively, and required significantly less corticosteroids. The rationale for the use of these agents is examined, and experience of the authors and others is evaluated.
Attaching and Treating Freeze-Dried Tissue Sections On Slides for Enzymatic Assay

Jacob Lundy (above) is with the Biomedical Department, Biophysics Laboratory, Research Laboratories, Edgewood Arsenal, Maryland. The late William C. FitzWilliam was with the Department of Gynecology-Obstetrics, The Johns Hopkins Medical School, Baltimore. In order to minimize the loss of labile tissue components by diffusion, solubil ization, or chemical reaction, some workers avoid the use of the common histological solvents, including water, in handling freeze-dried tissue sections. Thus, freeze-dried paraffin sections are sometimes mounted wi thout f lotat ion, the dry sections being pressed on the slides wi th the finger. The reaction is then performed on the section w i th out first removing the paraffin. Using undeparaffinized sections, trypsin digestions were performed by Jackson. Ruyter and Neumann determined alkaline phosphatase activity histochemically through the celloidinparaffin matrix of free-floating sections, and Goetsch and Reynolds demonstrated acid-phosphatase reactions in acetone-fixed paraffin sections wi thout removal of paraffin. In this laboratory, freeze-dried, mounted paraffin sections are employed in assays of sensitive enzymes. In order to improve preservation of enzyme activity, both f lotation and deparaffinizat ion were avoided, prior to the reaction. Enzyme reactions successfully performed on freeze-dried sections by this method were: NAD diaphorase (using reduced nicot inamide adenine dinucleotide), 6-phosphogluconic acid dehydrogenase (Fig. 1), glucose-6phosphate dehydrogenase, and alkaline phosphatase. The commonly-used gelatin and egg albumen adhesives were often ineffective in retaining dry, pressed sections on slides. To overcome this problem, a rubber cement, previously used in this
On the choice of penalty term in generalized FPE criterion

In variable selection, many existing selection criteria are closely related to the generalized final prediction error (FPE) criterion. In the linear regression context, the FPE criterion amounts to minimizing C(k, λ) = RSS(k)+λkσ2 over k, where k is the number of parameters in the model, RSS(k) is the residual sum of squares and σ2 is some estimate of the error variance. Different values of λ give different selection criteria. This article presents some useful results on the choice of λ. Some insights are obtained. Application to the study of the multifold cross validation criterion is also discussed.
Tools of Teaching-Research

Vrunda Prabhu remarked at the end of Unit 2 that Teaching-Research, just like mathematics is not a spectator sport. Unit 3 develops that view in an effort to encourage colleagues, teachers of mathematics in schools and colleges to pick up the mantle of this unusually creative bisociative approach to teaching and research. Involvement in teaching-research is not particularly difficult especially taking into account again the comment of William J. Harrington, describing his work of a teacher-as-researcher in Laura R. Van Zoest (2006)
Zika virus epidemic: an update

ABSTRACTIntroduction: Zika Virus (ZIKV), previously the cause of only rare and sporadic human infections, is now considered a Public Health Emergency of International Concern. Over the past two years, ZIKV has become a pandemic encompassing much of the Americas. ZIKV is now proven to cause microcephaly and ophthalmic anomalies in the newborn. Hydrops fetalis, developmental delay, and other anomalies are increasingly being attributed to ZIKV infection in fetuses and neonates. Sequelae of congenital infection and rapid spread of ZIKV throughout the Americas has catapulted Zika virus concerns to the forefront of the medical community.Areas covered: This review seeks to consolidate ZIKV epidemiology, diagnostic testing methods, CDC screening recommendations, and preventive strategies including potential vaccines.Expert commentary: Many unknowns still exist regarding ZIKV infections and its long-term effects in neonates. In addition, further studies need to evaluate if genomic differences that have occurred fr...
Uncertainty and the Policy Analyst

The paper reviews JNK's examination of the scope and method of political economy, suggests that Friedman's re-examination of JNK's pronouncements on methodology resulted in two problems (a) the ove...
Stable functional networks exhibit consistent timing in the human brain

Despite many advances in the study of large-scale human functional networks, the question of timing, stability, and direction of communication between cortical regions has not been fully addressed. At the cellular level, neuronal communication occurs through axons and dendrites, and the time required for such communication is well defined and preserved. At larger spatial scales, however, the relationship between timing, direction, and communication between brain regions is less clear. Here, we use a measure of effective connectivity to identify connections between brain regions that exhibit communication with consistent timing. We hypothesized that if two brain regions are communicating, then knowledge of the activity in one region should allow an external observer to better predict activity in the other region, and that such communication involves a consistent time delay. We examine this question using intracranial electroencephalography captured from nine human participants with medically refractory epilepsy. We use a coupling measure based on time-lagged mutual information to identify effective connections between brain regions that exhibit a statistically significant increase in average mutual information at a consistent time delay. These identified connections result in sparse, directed functional networks that are stable over minutes, hours, and days. Notably, the time delays associated with these connections are also highly preserved over multiple time scales. We characterize the anatomic locations of these connections, and find that the propagation of activity exhibits a preferred posterior to anterior temporal lobe direction, consistent across participants. Moreover, networks constructed from connections that reliably exhibit consistent timing between anatomic regions demonstrate features of a small-world architecture, with many reliable connections between anatomically neighbouring regions and few long range connections. Together, our results demonstrate that cortical regions exhibit functional relationships with well-defined and consistent timing, and the stability of these relationships over multiple time scales suggests that these stable pathways may be reliably and repeatedly used for large-scale cortical communication.
Nutrition Literacy among Cancer Survivors: Feasibility Results from the Healthy Eating and Living Against Breast Cancer (HEAL-BCa) Study: a Pilot Randomized Controlled Trial.

Knowledge of nutrition among breast cancer patients is insufficient, despite their motivation to seek valid information about healthy food choices. This study examines the feasibility of nutrition education workshops for cancer survivors, to inform the design of a multi-center intervention. Fifty-nine female English-speaking breast cancer patients, who had completed treatment, were enrolled. Participants were randomized to the intervention or control group. The intervention group attended six nutrition education sessions, and the control group received brochures. Measurements were done at baseline and 3-month follow-up and included the Assessment Instrument for Breast Cancer (NLit-BCa), fruit/vegetable and general health literacy screeners. Height and weight were measured. Changes in nutrition literacy, health literacy, and food intake from baseline to follow-up (within-group change) were calculated for both groups (effect sizes were reported as Cohen’s d). Participants were mostly white, with a mean age of 58 years, BMI of 31.6 kg/m2, and had college degrees. Follow-up rates were high (89% = control and 77% = intervention group). At baseline, participants scored high for most NLit-BCa assessment components except food portions in both groups. At the 3-month follow-up, effect sizes (d) on the NLit-BCa ranged from −0.5 to 0.16. The study met its recruitment goals within 6 months. Focus groups indicated that (a) attending six sessions was acceptable, (b) patients found social/emotional support, (c) improvements should include information for special diets and booster sessions. This pilot study suggests that the intervention was acceptable and that scaling up of this intervention is feasible and could provide benefit to breast cancer survivors.
Musculoskeletal symptoms in chronic myeloid leukemia patients after stopping tyrosine kinase inhibitors.

e18547Background: TKIs have revolutionized outcomes for CML patients (pts) but are not without cost or side effects. For pts with a prolonged response to treatment, discontinuing (d/c) treatment is appealing and has been investigated in a number of trials. In pts in whom treatment was stopped, musculoskeletal (MSK) symptoms were reported that were shown in some cases to resolve with resuming TKIs. Methods: Records of pts with chronic phase CML who stopped TKIs were reviewed. Results: We report 8 pts with chronic phase CML whose TKI was stopped following a prolonged molecular remission. 5 pts were receiving imatinib and 3 dasatinib. 5 pts were experiencing intolerable side effects of TKIs and agreed to a trial of d/c; 2 pts requested d/c; a third pt was planning for pregnancy. The median duration of therapy with TKI before d/c was 10 years. 6/8 pts developed MSK complaints with arthralgias and joint stiffness after cessation. Involved joints included the cervical spine, shoulders, elbows, small joints of t...
Abstract 5802: Efficacy of PI3Kβ inhibitor AZD8186 in PTEN-deficient triple-negative breast cancer

Background: Phosphatase and tensin homologue (PTEN) loss is a frequently disrupted tumor suppressor in cancer. PTEN serves as a negative regulator of the phosphatidylinositol 3-kinase (PI3K)/AKT/mTOR pathway to promote balanced cell proliferation, survival and differentiation. Consequently, loss of PTEN function increases cell proliferation, decreases cell death and contributes to tumor initiation. PTEN loss occurs across a variety of cancer subtypes, and these PTEN deficient tumors are dependent on PI3Kβ activity. As a result, therapeutic approaches that focus on the inhibition of PI3Kβ isoform in PTEN-null cells are of interest. We evaluate the efficacy of PI3Kβ inhibitors focused on triple negative breast cancers with loss of PTEN function. Methods: We studied the effects of p110β inhibitor AZD8186 in a panel of ten TNBC cell lines, which included four PTEN-mutant cell lines. Three of four cell lines were confirmed to have PTEN loss on western blot. In vitro, cell proliferation assays were performed to determine the half maximal inhibitory concentration (IC50) after 3 days of treatment and to test the effects in combination with chemotherapy. We confirmed the sensitivity of the PTEN-null cell lines to AZD8186 with colony formation assays. Western blot analysis was performed to assess PTEN expression and PI3K pathway activation in MDA-MB-436 and MDA-MB-468 cell lines, and to evaluate effects of AZD8186 on PI3K signaling. Results: Cell lines with PTEN loss were significantly more sensitive to AZD8186 in vitro (p= 0.008). AZD8186 inhibited PI3K signaling. Western blot revealed decreased activation of pAKT, pGSK3β, pPRAS40 and pS6. Activation of other pathways were evaluated with no activation of the MAPK/ERK or MEK pathways appreciated. AZD8186 treatment resulted in increased apoptosis but did not have a significant effect on cell-cycle progression in PTEN-deficient cell lines. AZD8186 was not synergistic with eribulin, paclitaxel or carboplatin; combinations with novel targeted therapies in vitro and in vivo are ongoing. Conclusion: AZD8186 had single agent efficacy in PTEN-deficient triple negative breast cancer cell lines in vitro. Further study is needed to identify rationale combinations and in vivo efficacy. Citation Format: Nicci Owusu-Brackett, Ming Zhao, Argun Akcakanat, Kurt W. Evans, Erkan Yuca, Funda Meric-Bernstam. Efficacy of PI3Kβ inhibitor AZD8186 in PTEN-deficient triple-negative breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 5802.
Preclinical translation of exosomes derived from mesenchymal stem/stromal cells

Exosomes are nanovesicles secreted by virtually all cells. Exosomes mediate the horizontal transfer of various macromolecules previously believed to be cell-autonomous in nature, including nonsecretory proteins, various classes of RNA, metabolites, and lipid membrane-associated factors. Exosomes derived from mesenchymal stem/stromal cells (MSCs) appear to be particularly beneficial for enhancing recovery in various models of disease. To date, there have been more than 200 preclinical studies of exosome-based therapies in a number of different animal models. Despite a growing number of studies reporting the therapeutic properties of MSC-derived exosomes, their underlying mechanism of action, pharmacokinetics, and scalable manufacturing remain largely outstanding questions. Here, we review the global trends associated with preclinical development of MSC-derived exosome-based therapies, including immunogenicity, source of exosomes, isolation methods, biodistribution, and disease categories tested to date. Although the in vivo data assessing the therapeutic properties of MSC-exosomes published to date are promising, several outstanding questions remain to be answered that warrant further preclinical investigation.
eLearning course for improving civil registration and vital statistics systems

The World Bank Group (WBG), in partnership with the Global Civil Registration and Vital Statistics (CRVS) Group, the Korea Ministry of Economy and Finance, and the WBG Open Learning Campus, launched the first comprehensive CRVS eLearning course in May 2017. The development of this course demonstrates the commitment and collaboration of development partners and governments working closely together in building the capacity of national institutions to improve CRVS systems in low- and middle-income countries. As of December 2018, over 2300 learners from 137 countries have enrolled in the course. This paper discusses how the course has been developed, disseminated, and evaluated thus far. It also presents the challenges faced and how the course has improved based on feedback from course participants.
Discreet Inequality: How Party Agendas Embrace Privileged Interests:

A growing literature documents that public policy in modern democracies fails to represent the preferences of traditionally marginalized subconstituencies. By dissecting party agendas, I show that ...
210Po and 210Pb distributions during a phytoplankton bloom in the North Atlantic: Implications for POC export

Abstract During the North Atlantic Bloom Experiment (NABE) of the Joint Global Ocean Flux Study (JGOFS), water column sampling for particulate and dissolved 210Po and 210Pb was performed four times (26 April and 4, 20, 30 May 1989) during a month-long Lagrangian time-series occupation of the NABE site, as well as one-time samplings at stations during transit to and from the site. There are few prior studies documenting short-term changes in 210Po and 210Pb profiles over the course of a phytoplankton bloom, and we interpret the profiles in terms of the classical “steady-state” (SS) approach used in most studies, as well as by using a non-steady state approach suggested by the temporal evolution of the profiles. Changes in 210Po profiles during a bloom are expectable as this radionuclide is scavenged and exported. During NABE, 210Pb profiles also displayed non-steady state, with significant increases in upper water column inventory occurring midway through the experiment. Export of 210Po from the upper 150 m using the classic “steady-state” model shows increases from 0.5 ± 8.5 dpm m−2 d−1 to 68.2 ± 4.2 dpm m−2 d−1 over the ~one-month occupation. Application of a non-steady state model, including changes in both 210Pb and 210Po profiles, gives higher 210Po export fluxes. Detailed depth profiles of particulate organic carbon (>0.8 μm) and particulate 210Po (>0.4 μm) are available from the 20 and 30 May samplings and show maxima in POC/Po at ~37 m. Applying the POC/210Po ratios at 150 m to the “steady state” 210Po fluxes yields POC export from the upper 150 m of 8.2 ± 1.5 mmol C m− 2 d−1 on 20 May and 6.0 ± 1.6 mmol C m−2 d−1 on 30 May. The non-steady state model applied to the interval 20 to 30 May yields POC export of 24.3 mmol C m−2 d−1. The non-steady state (NSS) 210Po-derived POC fluxes are comparable to, but somewhat less than, those estimated previously from 234Th/238U disequilibrium for the same time interval (37.3 and 45.0 mmol m−2 d−1, depending on the POC/Th ratio used). In comparison, POC fluxes measured with a floating sediment trap deployed at 150 m from 20 to 30 May were 11.6 mmol m−2 d−1. These results suggest that non-steady state Po-derived POC fluxes during the NABE agree well with those derived from 234Th/238U disequilibrium and agree with sediment trap fluxes within a factor of ~2. However, unlike the 234Th-POC flux proxy, non-steady stage changes in profiles of 210Pb, the precursor of 210Po, must be considered.
Addressing Neurocognitive Disorders, Dementias, and Alzheimer’s Disease in Colonias of the Lower Rio Grande Valley: Establishing a Research Foundation Using Promotores

Several Texas communities along the Mexican border, including the Lower Rio Grande Valley (LRGV), are home to low-income Hispanic populations, many of whom live in underserved communities known as colonias. These areas have high incidences of neurocognitive disorders, dementia, and Alzheimer's disease (AD); health care strategies that are culturally and linguistically appropriate for the area are needed. We aim to build capacity to reduce risk, facilitate treatment, and provide caregiver support for affected individuals. However, gaining trust of communities and presenting information about research studies in a way that is culturally appropriate is critical for engagement of underserved communities. This brief report examines our work with local community health workers.(CHWs), promotores in Spanish, to establish contact with, engage, mobilize, and educate the Hispanic communities of the LGRV. Lessons from the succesful experience of training promotores in autism spectrum disorder in the LRGV highlight the importance of specifically addressing outreach in health fairs, clinic vists and referral as well as adequate selection, training, management, and support of the promotores as critical aspects. To initiate and sustain recruitment of older adults and care partners in research studies of AD and other dementias in the RGV, we have incorporated these aspects as components of the promotores training and engagement model, which has been developed and implemented by researchers and their colleagues at the School of Medicine at the University of Texas Rio Grande Valley.
Corn-soybean rotation, tillage, and foliar fungicides: Impacts on yield and soil fungi

Abstract Fungal diseases can have a detrimental impact on soybean and corn yield. Foliar fungicides are used to manage fungal diseases and minimize yield loss, along with cultural practices like tillage and crop rotation. Prophylactic foliar fungicide use does not consistently increase yield for corn and soybean, especially when disease pressures are low. Also, there are concerns about the impact of fungicides on non-target organisms, including fungi living in the soil. We tested the effects of tillage, crop rotation, and foliar fungicide use on corn grain and soybean seed yield over three growing seasons. For both crops, rotation was key to achieving high yields, although there was an interaction of tillage × crop rotation for soybean and crop rotation × fungicide for corn. For soybean seed yield, both foliar fungicide treatments showed a small yield increase over untreated plots. Additionally, we assessed bulk soil fungal communities in a subset of treatments (crop rotation and fungicide treatments in no-till plots), using ITS sequencing and PLFA-FAME. We observed distinct fungal communities in the continuously cropped treatments, while annually rotated communities were very similar. There was also greater overall microbial biomass and a higher relative abundance of arbuscular mycorrhizae fungi associated with continuous corn. There were no differences in soil fungal communities or microbial biomass associated with foliar fungicide treatments. Based on our findings, we recommend that farmers use integrated pest management strategies to manage fungal diseases, which may include fungicide applications, if they are justified by economic disease thresholds or prediction tools.
Finanzinformierte Bürger_Innen, Bürgerbestimmtes FinanzsystemEin Essay Aus Anlass Des International Handbook of Financial Literacy (Finance-Informed Citizens, Citizen-Informed Finance: An Essay Occasioned by the International Handbook of Financial Literacy (German Edition))

German Abstract: Uberall in der Welt sieht der dominante Diskurs „Finanzbildung“ als notwendig und ausreichend an, um das Wohl Einzelner und der Gesellschaft zu verbessern. In diesem Essay wird argumentiert, dass Finanzbildung weder notwendig noch ausreichend ist und dass die Forderung der Finanzbildung ein abwegiger Ansatz ist, um unzureichende Finanzierung von Renten, Uberschuldung, Finanzkrisen und andere soziale Missstande in den Griff zu bekommen, wie es Regierungen und Padagog_innen von dieser Masnahme erhofft haben. Stattdessen wird hier angeregt, das Ziel von Finanzbildung darin zu sehen, finanzinformierte Burger_innen heranzuziehen, die die Fahigkeit zum burgerschaftlichen Engagement besitzen, das eine von den Burger_innen bestimmte Wirtschaftspolitik und Finanzregulierung hervorbringen kann. English Abstract: Throughout the world, the dominant discourse treats “financial literacy” as both necessary and sufficient to improve the well-being of individuals and society. This essay argues that financial literacy is neither, and that promoting financial literacy is a perverse way to address the inadequate retirement funding, overindebtedness, financial crises, and other social ills that have inspired governments and educators to pursue it. In its place, this essay suggests that the aim of financial education ought to be to foster finance-informed citizens, who have the capacity for civic engagement that can create citizen-informed economic policies and financial regulation.
Promoting Bandlike Transport in Well-Defined and Highly Conducting Polymer Thin Films upon Controlling Dopant Oxidation Levels and Polaron Effects

To close the technological gap between laboratory-based conducting polymers and commercially available inorganic semiconductors, it is imperative to develop synthesis approaches that allow for the ...
Ciudadanía y mujer en la segunda serie de los Episodios nacionales: del absolutismo a la nación liberal

En este articulo se examinan los personajes de Solita Gil de la Cuadra y Genara Baraona a la luz del concepto de ciudadania femenina que se construye en la Espana del siglo XIX. Aunque las expectativas de genero sexual limitaron la participacion de las mujeres en la vida publica, algunas de ellas se las ingeniaron para desempenar cargos oficiales de los que legalmente estaban excluidas. Estas contradicciones entre el discurso oficial y las practicas sociales se observan en la conversion de subditas en ciudadanas que experimentan Solita y Genara tras el fin del absolutismo fernandino.
Fast-track two-stage hepatectomy by concurrent portal vein embolization at first-stage hepatectomy in hybrid interventional radiology / operating suite.

Abstract Objectives In two-stage hepatectomy for bilateral liver metastases, patient dropout between stages is a major issue. We recently proposed a novel approach of fast-track two-staged hepatectomy (FT-TSH), in which patients undergo concurrent first-stage hepatectomy (FSH) with portal vein embolization (PVE) in a hybrid interventional radiology surgical suite. However, its efficacy remains unclear. Methods Patients with bilateral liver metastases scheduled for FT-TSH at MD Anderson Cancer Center between October 2017 and December 2020 were included on a prospective registry. The effectiveness and feasibility were evaluated. Results Nineteen patients were scheduled for FT-TSH. Primary site of tumor was colon/rectum in 18 patients and ovary in one patient. Median number of tumors was 10 and median size of largest tumor before surgery was 2.4 cm. Two (11%) patients did not undergo PVE and seventeen patients (89%) completed FSH + PVE. None of the patients had a major complication (Clavien-Dindo grade ≥ III) after FSH + PVE. Median kinetic growth rate after FSH + PVE was 2.9%/week (range 0.8–5.6). Twelve patients (71%) among the seventeen who underwent FSH + PVE proceeded to second-stage hepatectomy, and ten patients (59%) finally completed second-stage hepatectomy. Median interval between stages was 5.6 weeks (4.0–20.1). One patient (10%) had a major morbidity after SSH, and there was no 90-day mortality. Conclusions FT-TSH is safe and allows for short intervals between hepatectomy stages while achieving favorable liver hypertrophy. Further investigation is needed to evaluate the true efficacy of FT-TSH.
Patent Law: An Open-Source Casebook (Chapter 1: The Patent and Its Claims)

Less than a handful of casebooks are truly open source, in the sense of being fully modifiable. Patent Law: An Open-Source Casebook is the first patent law casebook that provides adopting professors, students, and others the ability to fully modify its contents. This chapter of the casebook covers the patent document, including patent claims, focusing on the substantive rules of claim construction and definiteness.
Flash nanoprecipitation for the production of endosomolytic polymersomes for cytosolic drug delivery

The delivery of biomacromolecular drugs to cytosolic targets has been a long-standing engineering challenge due to the presence of multiple biological barriers including cellular and endosomal membranes. Although many promising carriers designed to facilitate endosomal escape have been developed, the clinical translation of these carriers is often limited by complex production processes that are not amenable to scaled-up manufacturing. In this study, we employed flash nanoprecipitation (FNP) for the rapid, scalable, and reproducible assembly of nanocarriers composed of the pH-responsive, endosomolytic diblock copolymer poly[(ethylene glycol)x-block-[((2-diethylamino) ethyl methacrylate)0.6-co-(butyl methacrylate)0.4]y (PEG-b-DEAEMA-co-BMA). We found that varying the second block molecular weight, while holding the first block molecular weight constant, significantly influenced nanoparticle self-assembly and hence nanocarrier properties and function – including drug encapsulation, endosomolytic capacity, cytotoxicity, and in vitro activity of a cytosolically-active drug cargo, a cyclic dinucleotide (CDN) stimulator of interferon genes (STING) agonist. We found that while increasing second block molecular weight enhanced the capacity of nanocarriers to induce endosomal destabilization, larger second block molecular weights also lead to increased cytotoxicity, increased particle size and heterogeneity, increased the encapsulation efficiency of small (<0.5 kDa) hydrophilic drugs, decreased the encapsulation efficiency of large (10 kDa) hydrophilic biomacromolecules, and decreased long-term particle stability. Collectively, these results demonstrate the utility of FNP for the rapid and scalable production of uniform PEG-b-DEAEMA-co-BMA nanocarriers and implicate an optimal hydrophilic mass fraction for balancing desirable nanoparticle properties with cytosolic cargo delivery efficiency.
Factors Affecting the Generation and Contraceptive Effectiveness of Immune Responses to Sperm

In recent years it has been demonstrated that anti-sperm immunity is often associated with infertility in men and women, and a number of immunogenic sperm-specific antigens have been identified and characterized. It is now possible to mass produce these antigens by genetic engineering technology for use in contraceptive vaccine trials. However, knowledge of the complexities of the immune system and the manipulation of immune responses especially in the reproductive tissues lags considerably behind these more precise technological advances. Male and female reproductive tissues are naturally potential immunologic targets protected by immunologic barriers, immunosuppressive factors and possibly other immunoregulatory mechanisms. This area remains a largely unexplored research frontier and it is likely that considerable research on fundamental questions of reproductive immunology shall have to be performed before an effective contraceptive vaccine can be developed. In this chapter, I review certain classical immunologic considerations in the development of vaccines, focusing on immunological peculiarities of reproductive tissues and their antigens that require special consideration.
Postpartum Contraception for Adolescents

Adolescent mothers are more likely to experience a repeat pregnancy prior to the age of 20 than other adolescent women are to become pregnant a single time. American teens who have delivered have a 12–44 % risk of pregnancy within the first 12 months after birth. This high rate of repeat pregnancy is associated with poor maternal and fetal outcomes, lack of continuing education, unemployment, and poverty. The postpartum period is one of many physical, social, and emotional changes. Many of the concerns specific to the immediate and later postpartum periods can impact contraceptive use. This chapter focuses specifically on these issues and addresses method-specific considerations related to contraceptive use by adolescents in the early and later postpartum periods. We evaluate the success of various strategies to reduce rapid-repeat adolescent pregnancy and review the data supporting the use of long-acting reversible contraceptives for this population.
The Effect of Transducer Placement on the Echocardiographic Pattern of Mitral Valve Prolapse

Specific patterns of mitral valve prolapse have been identified with echocardiography. The variability of presentation of these patterns within a single patient has been noted in our laboratory. In an attempt to clarify this variability, echocardiographic studies were carried out in 100 presumably normal females aged 18 to 35. Echocardiograms of the mitral valve were performed from the second, third, fourth, and fifth intercostal spaces and orientation of the transducer in each of these interspaces was noted. Subjects with no evidence of mitral valve prolapse show a flat or posterior systolic segment from the second intercostal space with caudal transducer direction. Perpendicular placement of the transducer in the third intercostal space shows a gradual anterior migration of the mitral valve during systole. Cephalad direction of the transducer from the fourth intercostal space or below shows a markedly anterior systolic segment of the mitral valve. This pattern is apparently related to descent of the mitral annulus towards the apex during ventricular contraction and the component of this motion registered along the path of the sound beam. The posterior motion of the mitral valve seen in mitral valve prolapse can be reliably recorded only when the transducer is perpendicular to the chest wall as caudal direction of the transducer gives false positive records and cephalad direction of the transducer gives false negative records.
On the Economic Distortions of Smoothing Aggregate VolatilityWith Monetary Policy

Monetary policy is a blunt instrument with which to smooth aggregate volatility. I demonstrate that there is actually very little correlation between how much real state income responds to monetary policy and to shocks that prompt aggregate smoothing by the Federal Reserve. This mismatch turns out to be strong enough to imply that while monetary policy might have reduced the variance of aggregate output in the US over the last three decades, it has actually increased the variance of output in a majority of states. Moreover, policy rules that minimize aggregate variance are not equal in the severity of distortions they create in the volatility of state income. Optimal rules that place more weight on price variance typically create the largest distortions while those that place weight on aggregate income volatility create the smallest. In the end, monetary policy has the potential to create large distortions, but need not do so.
Team Trust in Online Education: Assessing and Comparing Team-Member Trust in Online Teams versus Face-to-Face Teams

Trust is a key factor in enabling effective team performance and, in online teams, needs to be built quickly and early. As universities expand their online offerings students are increasingly working in online teams. Understanding how trust development may differ in online teams versus face-to-face can have implications for online education development. This study compared trust levels in online and face-to-face teams at the beginning of the semester and at the end of the semester after the teams worked together on a series of tasks. The findings indicate that online teams do develop trust in their teammates, and actually have higher trust levels on a variety of trust dimensions. Resume La confiance, un facteur cle permettant a une equipe d’etre performante et efficace, doit etre bâtie rapidement et le plus tot possible lorsqu’il s’agit d’equipes en ligne. En raison du nombre sans cesse croissant de cours a distance offerts par les universites, les etudiants sont appeles a travailler, de plus en plus souvent, en equipes en ligne. Comprendre en quoi l’etablissement de la confiance peut differer selon qu’il s’agisse d’equipes en ligne ou d’equipes travaillant en face-a-face, peut avoir des repercussions au niveau de l’elaboration de l’enseignement en ligne. Cette etude compare les niveaux de confiance existant au sein d’equipes en ligne et d’equipes travaillant en face-a-face au debut du trimestre et a la fin du trimestre, alors que les equipes ont travaille ensemble a la realisation d’une serie de tâches. Les donnees indiquent que les equipes en ligne developpent de la confiance envers leurs coequipiers et qu’elles ont, en effet, un niveau de confiance plus eleve au niveau de certaines dimensions de la confiance.
Abstract 4392: Tumor suppressor miR-339-5p regulates PD-L1 expression in lung cancer

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA The PD1/PD-L1 (programmed death 1/programmed death 1 ligand 1) pathway is a central mechanism by which tumors escape host immunity. PD1 is a B7 receptor and is expressed by immune effector cells, including T cells, B cells, and natural killer cells. The predominant ligand for the PD1 receptor is PD-L1. Tumor expression of PD-L1 is thought to promote T-cell tolerance by binding PD1 on activated T cells and suppressing their capacity to secrete stimulatory cytokines. Tumor expression of PD-L1 has also been shown to directly inhibit T-cell-mediated lysis by inactivating tumor-reactive cytotoxic T lymphocytes. Targeting immune checkpoints that promote immune suppression such as PD1/PD-L1 has proven effective for suppressing tumor growth. Thus an important area of focus is on clarifying the mechanisms of cellular sensitivity and resistance to PD1/PD-L1 blockade and identifying biomarkers of response and survival with such therapy. MicroRNAs (miRNAs) are small RNAs that regulate virtually all processes in the cell, including immune response. However, there are very few studies linking miRNAs regulation to immune modulators. In this study, we aimed to identify miRNAs that regulate the immunoregulator PD-L1 in lung cancer. By using three different prediction programs (targetscan; MirWalk; miRNAbodymap), we identified a list of twenty miRNAs that potentially regulate PD-L1. We then selected the miRNAs that inversely correlated with PD-L1 expression in 532 patients with non-small lung cancer (NSCLC) from The Cancer Genome Atlas data (TCGA). Next, we overexpressed these miRNAs in NSCLC cells and analyzed the expression of PD-L1 by quantitative PCR and western blotting. Among the miRNAs selected, enforced overexpression of miR-339-5p decreased the expression of PD-L1 mRNA and protein compared with scrambled control. To investigate whether miR-339-5p interacts directly with the putative target gene PD-L1, we co-transfected 3′ UTR luciferase reporter vectors with miR-339-5p precursors and used luciferase assays to confirm that miR-339-5p regulates PD-L1 expression. Specifically, luciferase activity was reduced in cells transfected with miR-339-5p, PD-L1 3′ UTR constructs compared with scrambled. Mutation of miR-339-5p interaction sites rescued the luciferase activity, thus confirming that miR-339-5p directly interacts with the PD-L1 3´ UTRs. Taken together, these findings suggest that miR-339-5p is a new regulator of PD-L1 expression in NSCLC and may possibly be used as immunotherapy or as biomarker in future clinical approaches. Citation Format: Rachel Heymach, Lixia Diao, Lauren Averett Byers, Monique Nilsson, Jing Wang, Maria A. Cortez. Tumor suppressor miR-339-5p regulates PD-L1 expression in lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4392. doi:10.1158/1538-7445.AM2014-4392
NONGRAFTED AND GRAFTED OSTEOTOMIES OF PROXIMAL SESAMOID BONES OF THE HORSE

A radiographic study of healing patterns of nongrafted and grafted basilar osteotomies of proximal sesamoid bones in 14 horses was performed. Osteotomies were created in one proximal sesamoid bone of each fromt leg. One was treated by an autogenous rib graft, and the other was left nongrafted. Wedge-shaped cortical bone, corticocancellous bone with multiple drill holes, and chips of cancellous hbone were used as autogenous grafts. Presurgical, surgical, and postsurgical radiographic examinations were performed. The longest follow-up period was 40 weeks. High detail radiography of 3-mm bone sections and microangiography were also perofromed. Radiographic interpretation of lack of bone healing was erroneous in approximately one-half of the cases. Lack of an external bridging callus was incorrectly interpreted as lack of bony union. If noted, periosteal new bone formation failed to develop into a pattern of bridging callus. Radiographs did not permiit detection of the osteotomy line entering the articular surface or displacement of distal fragments. From angiography obtained ten weeks after surgery, the pattern of blood supply was similar in nontreated and grafted sesamoid bones. Microangiography showed rich vascularization of the cancellous graft and callus, reflecting good healing activity, whitle vascularization of the osteotomy site was absent in the nontreated osteotomies.
Skills Needed in the 21st Century Workplace: A Comparison of Feedback from Undergraduate Business Alumni and Employers with a National Study

The purpose of this research was to determine what skills alumni from Richard Stockton College of New Jersey (RSC) and regional employers think are important for the workplace. The results of the RSC study were compared to results from the report, College Learning for the New Global Century, sponsored by the Association of American Colleges and Universities.Managing time, speaking/oral communications skills, and having strong interpersonal skills were in the top five skills identified by both employers and alumni of The Richard Stockton College. A statistically significant greater percentage of employers who participated in the study commissioned by the Association of American Colleges and Universities identified knowledge of global issues as being an essential learning outcome compared with the employers and alumni surveyed in the RSC study who identified knowledge of global issues as being a very important or important skill for the workplace. The lower priority given to global issues and international perspectives by employers and alumni in this study may have been due to the location of their workplaces. Respondents to the surveys were located primarily in the central and southern areas of New Jersey where industries and corporations had a regional rather than an international focus. Faculty in the School of Business should consider incorporating those skills identified as important or very important by the majority of alumni and employers into the curriculum as well as emphasizing global issues in their courses.
A nationwide assessment of outcomes after bile duct reconstruction

Background Bile duct reconstruction (BDR) is used to manage benign and malignant neoplasms, congenital anomalies, bile duct injuries and other non-malignant diseases. BDR outcomes overall, by year, and by indication were compared.
Postoperative antibiotics are not associated with decreased wound complications among patients undergoing appendectomy for complicated appendicitis.

Abstract Background The objective of this study was to determine the role of postoperative antibiotics in reducing complications in patients undergoing appendectomy for complicated appendicitis. Methods We performed a 5-year retrospective cohort study of adult patients who underwent appendectomy for acute appendicitis. Patients with complicated appendicitis (perforated or gangrenous) were analyzed on the basis of whether they received postoperative antibiotics. Main outcome measures were wound complications, length of stay (LOS), and readmission to hospital. Results Of 410 patients with complicated appendicitis, postoperative antibiotics were administered to 274 patients (66.8%). On univariate and multivariate analyses, postoperative antibiotics were not associated with decreased wound complications or readmission, but independently predicted an increased LOS ( P = .01). Conclusions Among patients with complicated appendicitis, postoperative antibiotics were not associated with a decrease in wound complications but did result in an increased hospital LOS.
Investigation of Argon Gas as a Potential Shock Attenuator in Z-IFE Chambers Using ALEGRA

The Z-IFE (inertial fusion energy) plant is a unique, inertial confined, fusion energy concept in which high yield targets will be ignited to fusion, yielding brief energy bursts in the 3 to 20-gigajoule range. The fusion reaction yields an energetic burst that consists principally of neutrons, X rays, and charged particles. The X rays rapidly attenuate in matter, causing the material to expand rapidly, thus generating a strong shock wave. This shock wave must be mitigated if the Z-IFE chamber is to last for a period of 30 to 50 years. ALEGRA simulations were conducted for a hypothetical Z-IFE chamber filled with argon gas and ionized by an X ray source. The calculations employed a set of sophisticated models, including Saha ionization, XSN and CDF opacities, bremsstrahlung radiation, linearized diffusion of X ray photons for a blackbody, fully-coupled magnetohydrodynamic models, electron thermal conduction, Spitzer thermal conductivity with cold material interpolation, and Mie-Gruneisen EOS. In order to obtain confidence in the results, a laser experiment from UCSD was simulated. In the experiment, laser photons were used to ionize argon gas. The simulations showed that ALEGRA quite successfully calculated the measured temperature, level of ionization, and spatial evolution of the argon plasma.
Introducing Tarzan, a Peer-to-Peer Anonymizing Network Layer

We introduce Tarzan, a peer-to-peer anonymous network layer that provides generic IP forwarding. Unlike prior anonymizing layers, Tarzan is flexible, transparent, decentralized, and highly scalable.Tarzan achieves these properties by building anonymous IP tunnels between an open-ended set of peers. Tarzan can provide anonymity to existing applications, such as web browsing and file sharing, without change to those applications. Performance tests show that Tarzan imposes minimal overhead over a corresponding non-anonymous overlay route.
Comparison of Recovering and Non-Alcoholic Alcoholism Counselors: A survey

A survey of alcoholism counselors from a state and a national sample was conducted as a preliminary study to be used in the planning of a larger survey. The survey attempted to gather qualitative and quantitative data with which to test observations made about the recovering counselor in the alcoholism literature. Recovering counselors were contrasted with non-alcoholic counselors in terms of demographic characteristics and attitudes toward alcoholism counseling as a profession and the issue of relapse in recovering counselors. The results found that despite significant differences in demographic characteristics, recovering and nonalcoholic counselors tended to have very similar attitudes toward issues involving alcoholism treatment and relapse.