cssi/SciSciGPT-SciSciNet huggingface dataset:
Combined Effects of Backbone and N-Substituents on Structure, Bonding, and Reactivity of Alkylated Iron(II)-NHCs.

Iron and N-heterocyclic carbenes (NHCs) have proven to be a successful pair in catalysis, with reactivity and selectivity being highly dependent on the nature of the NHC ligand backbone saturation and N-substituents. Four (NHC)Fe(1,3-dioxan-2-ylethyl)2 complexes have been isolated and spectroscopically characterized to correlate their reactivity to steric effects of the NHC from both the backbone saturation and N-substituents. Only in the extreme case of SIPr where NHC backbone and N-substituent steric effects are the largest is there a major structural perturbation observed crystallographically. The addition of only two hydrogen atoms is sufficient for a drastic change in product selectivity in the coupling of 1-iodo-3-phenylpropane with (2-(1,3-dioxan-2-yl)ethyl)magnesium bromide due to resulting structural perturbations to the precatalyst. Mossbauer spectroscopy and magnetic circular dichroism enabled the correlation of covalency and steric bulk in the SIPr case to its poor selectivity in alkyl–alkyl c...
Effects of Western Style Foods on Risk of Noncommunicable Diseases

Abstract The Western-style diet is known for its highly processed and refined foods with high contents of sugars, salt, fat, and protein from red meat. It has been identified as the major contributor to the development of type 2 diabetes and coronary heart disease. This chapter delineates the evidence behind the correlation between the Western-style diet and noncommunicable diseases.
Li+ Ion-Conducting Sulfonate-Based Neutral Metal–Organic Framework

Lithium ion-conducting metal–organic frameworks (MOFs) are rapidly gaining interest because of their potential application as ion-permeable, robust electrode separators in rechargeable batteries, arguably the most ubiquitous portable clean energy storage devices developed to date. A novel, water-stable 2D sheet-like neutral Cu(I)–sulfonate MOF featuring π-acidic naphthalenediimide (NDI) ligands that can simultaneously bind guest lithium ions with its carbonyl and uncoordinated sulfonate oxygen atoms and charge diffuse perchlorate anions through anion−π interaction has been constructed. While the pristine MOF pellets displayed poor intrinsic electrical conductivity (4.65 × 10–10 S/m) at room temperature due to inadequate charge carrier density and electron delocalization pathway, upon infiltration of LiClO4, its ionic conductivity surged almost million times to 2.3 × 10–4 S/m, and the activation energy for charge carrier transport dropped to a mere 0.167 eV. In contrast, the conductivity of Bu4NClO4-treate...
Chronic use of tramadol after acute pain episode: Cohort study

Abstract Objective To determine the risk of prolonged opioid use in patients receiving tramadol compared with other short acting opioids. Design Observational study of administrative claims data. Setting United States commercial and Medicare Advantage insurance claims (OptumLabs Data Warehouse) January 1, 2009 through June 30, 2018. Participants Opioid-naive patients undergoing elective surgery. Main outcome measure Risk of persistent opioid use after discharge for patients treated with tramadol alone compared with other short acting opioids, using three commonly used definitions of prolonged opioid use from the literature: additional opioid use (defined as at least one opioid fill 90-180 days after surgery); persistent opioid use (any span of opioid use starting in the 180 days after surgery and lasting ≥90 days); and CONSORT definition (an opioid use episode starting in the 180 days after surgery that spans ≥90 days and includes either ≥10 opioid fills or ≥120 days’ supply of opioids). Results Of 444 764 patients who met the inclusion criteria, 357 884 filled a discharge prescription for one or more opioids associated with one of 20 included operations. The most commonly prescribed post-surgery opioid was hydrocodone (53.0% of those filling a single opioid), followed by short acting oxycodone (37.5%) and tramadol (4.0%). The unadjusted risk of prolonged opioid use after surgery was 7.1% (n=31 431) with additional opioid use, 1.0% (n=4457) with persistent opioid use, and 0.5% (n=2027) meeting the CONSORT definition. Receipt of tramadol alone was associated with a 6% increase in the risk of additional opioid use relative to people receiving other short acting opioids (incidence rate ratio 95% confidence interval 1.00 to 1.13; risk difference 0.5 percentage points; P=0.049), 47% increase in the adjusted risk of persistent opioid use (1.25 to 1.69; 0.5 percentage points; P Conclusions People receiving tramadol alone after surgery had similar to somewhat higher risks of prolonged opioid use compared with those receiving other short acting opioids. Federal governing bodies should consider reclassifying tramadol, and providers should use as much caution when prescribing tramadol in the setting of acute pain as for other short acting opioids.
Why cities with high bicycling rates are safer for all road users

Abstract Introduction Despite bicycling being considered ten times more dangerous than driving, the evidence suggests that high-bicycling-mode-share cities are not only safer for bicyclists but for all road users. We look to understand what makes these cities safer. Are the safety differences related to ‘safety-in-numbers’ of bicyclists, or can they be better explained by built environment differences or the people that inhabit them? Methods Based on thirteen years of data from twelve large U.S. cities, we investigated over 17,000 fatalities and 77,000 severe injuries across nearly 8700 block groups via multilevel, longitudinal, negative binomial regression models. We hypothesize three pathways towards better road safety outcomes: i) travel behavior differences (e.g. ‘safety-in-numbers’ or shifts to ‘safer’ modes); ii) built environment differences (e.g. infrastructure that helps promote safer environments); and iii) socio-demographic/socio-economic differences (e.g. some cities may be populated by those with lower road safety risk). Results The results suggest that more bicyclists is not the reason these cities are safer for all road users. Better safety outcomes are instead associated with a greater prevalence of bike facilities – particularly protected and separated bike facilities – at the block group level and, more strongly so, across the overall city. Higher intersection density, which typically corresponds to more compact and lower-speed built environments, was strongly associated with better road safety outcomes for all road users. The variables representing gentrification also accounted for much of our explainable variation in safety outcomes. Conclusions This paper provides an evidence-based approach to building safer cities. While the policy implications of this work point to protected and separated bike infrastructure as part of the solution, we need to keep in mind that these approaches are complementary and should not be considered in isolation. Moreover, our results – particularly the safety disparities associated with gentrification – suggest equity issues and the need for future research.
Influence of length of incision and number of suture lines on the biomechanical properties of incisional gastropexy.

Objective To determine the effect of the length of incision and of the number of suture lines on the load to failure of incisional gastropexy in an ex vivo model. Study design Ex vivo study. Sample population Thirty-six hound-mix fresh canine cadavers. Methods Specimens were randomly divided into four groups of incisional gastropexies varying in length of incision (2 or 4 cm) and number of suture lines (one or two). Load to failure was measured. Number of suture bites on each side of the gastropexy and number of inadvertent full thickness gastric suture bites were recorded. Results Incisional gastropexies performed with one or two suture lines sustained loads to failure of 53.80 ± 12.10 N and 53.30 ± 10.60 N (P = .887), respectively. Loads to failure equal to 49.70 ± 10.80 N and 57.30 ± 10.60 N (P = .048) were measured on incisional gastropexies performed with 2- or 4-cm-suture lines, respectively. There was no interaction between the length of the incision and the number of suture lines (P = .634). Conclusion Length of incision but not number of suture lines influenced the biomechanical properties of gastropexies in this acute cadaveric model. Clinical significance According to this acute in vitro experiment, gastropexy can be performed with either one or two suture lines.
A murine neonatal model of necrotizing enterocolitis caused by anemia and red blood cell transfusions.

Necrotizing enterocolitis (NEC) is an idiopathic, inflammatory bowel necrosis of premature infants. Clinical studies have linked NEC with antecedent red blood cell (RBC) transfusions, but the underlying mechanisms are unclear. Here we report a neonatal murine model to investigate this association. C57BL/6 mouse pups rendered anemic by timed phlebotomy and then given RBC transfusions develop NEC-like intestinal injury with prominent necrosis, inflammation, and submucosal edema/separation of the lamina propria in the ileocecal region and colon within 12–24 h. The anemic intestine is infiltrated by inflammatory macrophages, which are activated in situ by RBC transfusions via a Toll-like receptor (TLR)-4-mediated mechanism and cause bowel injury. Chelation of RBC degradation products with haptoglobin, absence of TLR4, macrophage depletion, and inhibition of macrophage activation is protective. Intestinal injury worsens with increasing severity and the duration of anemia prior to transfusion, indicating a need for the re-evaluation of current transfusion guidelines for premature infants. The development of neonatal necrotising enterocolitis has been temporally associated with red blood cell transfusions in retrospective human studies. Here, the authors develop a neonatal mouse model of necrotising enterocolitis in anaemic mice receiving red blood cell transfusion that recapitulates features of the human condition.
STAT pathway activation limits the Ascl1-mediated chromatin remodeling required for neural regeneration from Muller glia in adult mouse retina.

Abstract Muller glia can serve as a source for retinal regeneration in some non-mammalian vertebrates. Recently we found that this process can be induced in mouse Muller glia after injury, by combining transgenic expression of the proneural transcription factor Ascl1 and the HDAC inhibitor TSA. However, new neurons are only generated from a subset of Muller glia in this model, and identifying factors that limit Ascl1-mediated MG reprogramming could potentially make this process more efficient, and potentially useful clinically. One factor that limits neurogenesis in some non-mammalian vertebrates is the STAT pathway activation that occurs in Muller glia in response to injury. In this report, we tested whether injury induced STAT activation hampers the ability of Ascl1 to reprogram Muller glia into retinal neurons. Using a STAT inhibitor, in combination with our previously described reprogramming paradigm, we found a large increase in the ability of Muller glia to generate neurons, similar to those we described previously. Single-cell RNA-seq showed that the progenitor-like cells derived from Ascl1-expressing Muller glia have a higher level of STAT signaling than those that become neurons. Using Ascl1 ChIP-seq and DNase-seq, we found that developmentally inappropriate Ascl1 binding sites (that were unique to the overexpression context) had enrichment for the STAT binding motif. This study provides evidence that STAT pathway activation reduces the efficiency of Ascl1-mediated reprogramming in Muller glia, potentially by directing Ascl1 to inappropriate targets.
Incidence of Venous Thromboembolism following Knee Arthroscopy: Effectiveness of a Risk-Based Stratified Chemoprophylaxis Protocol

The incidence of symptomatic venous thromboembolism (VTE) has been reported in up to 10.9% of patients undergoing knee arthroscopy without chemoprohylaxis. The purpose of this study was to evaluate the effectiveness of a chemoprophylaxis protocol in patients undergoing knee arthroscopy. A retrospective review of prospectively enrolled patients in a new institutional VTE prophylaxis protocol identified all patients undergoing knee arthroscopy during a 5-year period. This risk-based chemoprophylaxis protocol was instituted based on the Caprini model: patients at more than minimal risk were prescribed enoxaparin 40 mg daily for 3 weeks, while all others were instructed to take aspirin 325 mg twice daily. The primary outcome measure was incidence of VTE within 60 days postoperatively. Demographic characteristics and other risk factors for VTE were also recorded, as well as any postoperative complications. Among the 1,276 knee arthroscopies, there were 26 VTE events (2.0%), including 23 with deep vein thrombosis (DVT), two pulmonary emboli (PE), and one patient with both DVT and PE. There were no deaths or complications requiring hospitalization or reoperation. The VTE diagnosis occurred at, on average, 9 days postoperatively. Patients in the high-risk group treated with enoxaparin had a lower VTE incidence (1.49%) than those instructed to take aspirin (2.0%); p = 0.75. Those undergoing an anterior cruciate ligament (ACL) reconstruction had the highest VTE incidence (2.87%). This study found that a chemoprophylaxis protocol with preferential use of aspirin or low-molecular weight heparin based on risk factors reduced the VTE incidence below to 2.0%, which is lower than most historical controls.
Pulmonary Hypertension in Chronic Kidney Disease and End-Stage Renal Disease

Pulmonary hypertension (PH) is defined by an elevated mean pulmonary artery pressure >20 mm Hg. PH has emerged as an important comorbidity in both chronic kidney disease (CKD) and end-stage renal disease (ESRD) and is associated with increased mortality. Epidemiologic data suggest a high prevalence of PH especially with CKD stage III and higher. PH in most patients is “explained” by other comorbidities that are prevalent in these patients including left heart disease, lung disease, and sleep apnea and treatment should be directed at correcting these. However, after thorough workup, sometimes one is left with “unexplained” PH which could be attributed either to accumulation of uremic toxins, endothelial dysfunction, inflammation, microangiopathy, dialysis, or dialysis access-related issues. Interestingly, renal transplantation alleviates PH while presence of PH can impact graft function or survival. Select individuals with CKD-ESRD-PH could be considered for pulmonary vasodilators at PH specialized centers.
748 Myeloid cell infiltration correlates with prognosis and varies based on tumor location in cholangiocarcinoma

Background Cholangiocarcinoma (CC) is a rare malignancy with an increasing incidence and poor prognosis. Immunotherapy represents one potential treatment for CC, however identification of immunotherapeutic targets requires a thorough characterization of the tumor immune microenvironment (TIME). Mesothelin, a tumor associated antigen, is abundantly expressed in other malignancies, though its expression in CC has not been well characterized. We hypothesized that (1) the TIME of CC would vary by primary tumor location and between primary and metastatic lesions, (2) high tumor infiltration by CD8+ T cells and low infiltration by M2 macrophages would be associated with improved survival, and (3) most CC would express mesothelin. Methods 99 CC tumors from unique stage I-IV patients were included, of which 89 were primary tumors (24 intrahepatic (ICC), 65 extrahepatic (ECC - 30 hilar (H-ECC) and 35 distal (D-ECC))) and 10 were metastatic lesions. Tissue microarrays were constructed and immunohistochemistry (IHC) was performed for lymphoid and myeloid markers, as well as for PD-L1 and mesothelin. IHC+ cells were quantified by automated image analysis. Expression of mesothelin and PD-L1 by tumors cells were evaluated on a semiquantitative scale (0, +1, +2, or +3). Hypothesis testing was performed using Kruskal-Wallis test and survival analyses were performed with Univariate and Multivariate Cox Hazard Models. Results Most tumors were infiltrated by myeloid cells in addition to CD4+, CD8+, and FoxP3+ T-cells. Mesothelin was expressed (≥1+) in 68% of tumors (figure 1), while PD-L1 was expressed (≥1%) in only 16% of tumors. Higher densities of M1 macrophages (CD68+) were present in D-ECC relative to ICC and H-ECC (figure 2). M1 macropahges were also found in higher densities in metastatic tumors. Mesothelin and granzyme-B expression was significantly higher in D-ECC. Increasing density of myeloid cells (CD14+) and M2 macrophages (CD163+) was associated with worse survival (p= 0.02, 0.03, respectively) (figure 3). Intraepithelial and intratumoral T cell infiltration did not correlate with OS. Conclusions The TIME of CC varies significantly by primary tumor location and between primary and metastatic lesions. D-ECC has a favorable immune profile compared to ICC and H-ECC, with a better milieu for antigen presentation including increased mesothelin and less suppressive macrophages, which may support better response to checkpoint blockade. The data supported the hypothesis that higher densities of intra-tumoral M2 macrophages and myeloid cells correlated with worse OS, even after controlling for clinical variables, suggesting that these cell populations may represent promising immunotherapeutic targets in CC.
La globalización del sector agrícola y alimentario y las teorías del estado

The paper investigates the theoretical dislocation between the domestic oriented character of theories of the State and the transnational character of theories of socio-economic development. Employing the case of the food and agricultural sector, it is argued that the literature in this area has emphasized the transnational dimension of capital accumulation and the process of by-passing State authority at the national level. This situaion mandates a re-evaluation of State theories in regard to the international dimension of current processes of capital accumulation. Furthermore, the present analysis suggests patterns of "contradictory convergence" in which expansion at the transnational level of State action is demanded by transnational corporations and subordinate classes alike. This demand, however, is contradictory, as it finds its limits in the transnational bourgeoisie's desire to avoid State action. Politically, as a result of this situation the locus of emancipatory social action should be increasingly transferred to the international arena. La globalizacion del sector agricola y alimentario y las teorias del estado ?Resumen Este articulo indaga en el desfase teorico existente entre las teorias del Estado, con un caracter orientado hacia lo nacional, y el caracter transnacional de las teorias del desarrollo socio-economico. Con base en el caso del sector agricola y alimentario, se afirma que la literatura en esta area ha enfatizado la dimension transnacional de la acumulacion de capital y la evasion de la autoridad del Estado en el ambito nacional. Esta situacion requiere revaluar las teorias del Estado en atencion a la dimension internacional del presente proceso de acumilacion de capital. Mas aun, este analisis sugiere patrones de "convergencia contradictoria" en la cual, la expansion de la accion del Estado a nivel transnacional es exigido tanto por las corporaciones transnacionales como por las clases subordinadas. Esta exigencia, sin embargo, es contradictoria ya que se encuentra limitada por el interes de la burguesia transnacional de evadir la accion del Estado. Desde el punto de vista politico, como resultado de esta situacion, el espacio de la accion social emancipadora debe trasladarse, cada vez mas, a la escena internacional.
Yield and quality of A. hypochondriacus grain amaranth under drought and salinity at various phenological stages in southern Italy

Background Several studies have shown that grain amaranth (Amaranthus spp) is tolerant to abiotic stresses such as drought and salinity. Irrigation applied only during sensitive growth stages can stabilize yield and improve water use efficiency. Given the increasing frequency of salinity and drought stress in European Countries and the scarcity of information on grain amaranth responses to the combined salt and drought stress, an open field trial was carried out in Italy in order to evaluate the response of one accession of Amaranthus hypochondriacus to different irrigation strategies. Results Grain amaranth yield components were not negatively affected neither by different irrigation volumes nor by irrigation time. Some differences in seeds yield were caused by water quality; salinity has significantly reduced seed yield. The combined effect of irrigation time and irrigation volume significantly influenced seed yield. The quality of amaranth seeds has being preserved; no significant differences due to simple or combined stresses were found during the three years field experiment. Conclusion The overall results from this study suggest that Amaranth hypochondriacus can be cultivated in a more sustainable way compared to other protein crops, thus reducing water amounts and using saline water. It could be introduced to marginal European environments where traditional crops cannot be cultivated. This article is protected by copyright. All rights reserved.
Exploring the geometry of supersymmetric double field theory

The geometry of N=1 supersymmetric double field theory is revisited in superspace. In order to maintain the constraints on the torsion tensor, the local tangent space group of O(D) x O(D) must be expanded to include a tower of higher dimension generators. These include a generator in the irreducible hook representation of the Lorentz group, which gauges the shift symmetry (or ambiguity) of the spin connection. This gauging is possible even in the purely bosonic theory, where it leads to a Lorentz curvature whose only non-vanishing pieces are the physical ones: the generalized Einstein tensor and the generalized scalar curvature. A relation to the super-Maxwell$_\infty$ algebra is proposed. The superspace Bianchi identities are solved up through dimension two, and the component supersymmetry transformations and equations of motion are explicitly (re)derived.
Payment-For-Order-Flow Implications for Robinhood Users

The digital age has transformed financial exchanges from high-stress trading floors to automated processes ruled by algorithms and online brokerage firms. Payment-for-order-flow is a controversial practice, ironically instituted by Bernard Madoff (Farrell, 2008, pg.19) and approved by the New York Stock Exchange (NYSE) in 2009. Although the practice has expanded liquidity to the NYSE and has made markets more efficient, there are questionable aspects of payment-for-order-flow, spearheaded by online brokerage firms, that contribute to the potential exploitation of retail investors. This term paper highlights problems associated with payment-for-order-flow, assesses current policies regulating and allowing this practice, and explores policy alternatives. Additionally, it utilizes Robinhood Financial, an online brokerage firm, as a case study to characterize payment-for-order-flow and its broader implications for stakeholders in the United States. This term paper addresses implications of Financial Industry Regulatory Authority and Securities and Exchange Commission policies, the use of data by market makers, lack of transparency, and conflicts of interest that brokers face. The recommended policy alternative, in this paper, aims to respect individual autonomy over digital financial data yet allows for the market and economy to maximize benefits. The proposed policy will enable payment-for-order-flow to continue to exist but ensure that retail investors have the option to opt-out but continue to engage in the market. Additionally, the policy requires that brokerage firms immediately notify retail investors of any order routing decisions along with accompanying explanations for these decisions.
Stephen T. Warren: Human geneticist who advanced understanding of mutational mechanisms and developmental disorders.

The highly successful career of Stephen T. Warren was very well described in the PNAS Profile Series in 2015 (1). We write this remembrance of Steve’s life on behalf of his many friends and scientific colleagues. His death on June 6, 2021 came far too soon and he is sorely missed. Stephen T. Warren. Image credit: Karen Warren (photographer). Steve’s attraction to the field of genetics and his early scientific development came through his work with James Higgins at Michigan State University. It was a time when human genetics was transitioning from basic science to medical utility, with the application of laboratory testing to individual patients serving as the primary stimulus. Tay Sachs carrier screening was developed in Detroit out of the Henry Ford Hospital with Steve’s involvement even as an undergraduate. He recognized the importance of genetic testing to families through his early experience and elected to direct his career to original discovery, where he was very successful. Steve’s interest in syndromes with chromosomal breaks directed his initiative with two very different discovery outcomes. The first disorder he studied was a rare multiple chromosomal breakage disorder, Bloom syndrome. This research, as a graduate student with James Trosko at Michigan State University, seasoned him in somatic genetic methods. Bloom syndrome was eventually found to be caused by mutations in a single gene, a RecQ helicase, causing additional mutations at many sites, often involving chromosome breaks. This rare recessive disease was found to be caused by homozygous loss-of-function of this gene critical to DNA repair. During his postdoctoral training, Steve’s focus turned to a second chromosomal breakage syndrome, at the time termed marker X (fragile X) syndrome. The chromosome break could be elicited in lymphocytes … [↵][1]1To whom correspondence may be addressed. Email: nelson{at}bcm.edu. [1]: #xref-corresp-1-1
Retinal defocus in myopes wearing dual-focus zonal contact lenses.

PURPOSE To evaluate the refractive impact of dual-focus (DF) myopia control contact lenses (CLs) on accommodating young myopic adults. METHODS Phase 1: accommodative accuracy was assessed in 40 myopic participants. Phase 2: a subset of four subjects who demonstrated accurate accommodation and six who chronically underaccommodated were fitted with single vision (SV, Proclear 1 day) and centre-distance DF myopia control CLs (MiSight 1 day) with approximately +2.00 D of additional power in two surrounding annular zones. While binocularly viewing high contrast characters at 4.00, 1.00, 0.50, 0.33, 0.25 and 0.20 m, aberrometry data were captured across the central ±30° of the horizontal retina. Local refractive errors were pooled for each area of the pupil covered by the central distance or first annular defocus zone of the DF CLs. RESULTS In the "good" accommodator group fitted with SV CLs, accommodative lags were generally absent except at the closest viewing distance (mean errors: -0.09 ± 0.22 D, -0.12 ± 0.26 D, -0.05 ± 0.37 D and +0.38 ± 0.54 D for -2.00, -3.00, -4.00 and -5.00 D target vergences, respectively) but significantly larger in the "poor" accommodating participants (+0.81 ± 0.21 D, +0.97 ± 0.27 D, +1.18 ± 0.39 D, +1.47 ± 0.55 D). For most viewing distances, hyperopic defocus observed in the region of the pupil covered by the first annular zone was replaced with myopic defocus when fitted with the DF CLs. Myopic defocus created by the first annular region was present across the central 30° of the retina. CONCLUSIONS Some young adult myopes chronically experience high levels of hyperopic defocus when viewing near targets, which was replaced by myopic defocus in the annular part of the pupil covered by the treatment zones when fitted with a centre-distance myopia control DF CL.
Global Health Curricula in Ophthalmology Residency Programs in the United States

Objective The aim of the study is to investigate the design, content, and administration of global health curricula within ophthalmology residency programs in the United States (U.S.) and share the curriculum utilized in the Department of Ophthalmology at Boston University School of Medicine (BUSM). Design A survey designed through the Association of University Professors in Ophthalmology platform was emailed to residency program directors at 106 accredited ophthalmology residency programs. Setting BUSM Department of Ophthalmology, Boston, MA. Tertiary clinical care. Participants Twenty-eight ophthalmology residency program directors responded, which represent 26% of the total number of residency programs in the United States. Twenty-seven programs fully completed the survey, and one program partially completed the survey. Results Of the respondents, three programs do not include global health curricula. The most common curricular elements included are: lectures (n = 15, 60%); wet laboratories (n = 10, 40%); and journal clubs (n = 9, 36%). In terms of annual frequency, global health activities occur: twice a year (n = 12, 46%); less than once a year (n = 10, 39%); or every few months (n = 4, 15%). Fewer than half of programs (n = 10, 42%) incorporate local outreach at least once a year into their program. Twelve programs (48%) do not incorporate ethics-related topics, while the 13 remaining programs (52%) incorporate them at least once annually. The most common curricular topic is surgical techniques, with manual small incision cataract surgery (MSICS) being the most frequently emphasized (n = 17, 68%). Conclusion A robust global health curricula combined with a hands-on international component can contribute to a well-rounded training experience. Many ophthalmology residency programs value the importance of incorporating global health into their residents' training. The most common elements of global health curricula in U.S. ophthalmology residency programs included are teaching of surgical techniques for resource-limited settings and international electives. Further investigation into the impact of different components of a global health curriculum on both resident experience and international partnerships is warranted.
The Effect of Different Behavior in Tension than in Compression on the Mechanical Response of Polymeric Materials

High polymers exhibit different stress-strain behavior in tension than in compression. The effect of this characteristic is examined in terms of three-point bending tests on polyethylene and polypropylene. A model to predict the experimentally obtained force-deflection curves is presented and used to illustrate the importance of including both tension and compression stress-strain data when these differ.
Preclinical Evaluation of Targeted Cytotoxic Luteinizing Hormone-Releasing Hormone Analogue AN-152 in Androgen-Sensitive and Insensitive Prostate Cancers

Purpose and Experimental Design: To improve conventional chemotherapy, we developed cytotoxic analogues of luteinizing hormone-releasing hormone (LH-RH), which can be targeted to prostate cancers expressing LH-RH receptors. In view of pending clinical trials on cytotoxic LH-RH analogue AN-152, containing doxorubicin (DOX) linked to [D-Lys 6] -LH-RH, we investigated the effects of AN-152 on tumor growth of s.c. implanted androgen-sensitive LNCaP and MDA-PCa-2b prostate cancers, as well as androgen-independent C4-2 prostate cancers xenografted into the tibiae of nude mice. In the C4-2 study, serum prostate-specific antigen (PSA) levels were also measured. LH-RH receptors were analyzed by reverse transcription-PCR and ligand competition assay. We also evaluated whether AN-152 can affect mRNA expression of human epidermal growth factor receptor and HER-2 and -3 oncogenes Results: After 32 days of treatment with AN-152, the growth of LNCaP cancers in castrated nude mice was strongly inhibited by 83% versus intact controls ( P versus castrated controls ( P P versus controls) and was more effective ( P P Conclusions: Our findings suggest that cytotoxic analogue AN-152 could be considered for therapeutic trials in patients with advanced prostate carcinoma.
Popular Culture, Geopolitics, and Identity

Jason Dittmer's Pop Culture, Geopolitics, and Identity is arguably the most approachable text on geopolitics available today. The book explores relationships between popular culture and internation...
A Comparison of Three Types of Pulse Tube Refrigerators: New Methods for Reaching 60K

Pulse tube or thermoacoustic refrigerators require only one moving part—an oscillating piston or diaphragm at room temperature. Refrigeration occurs within a tube connected to the pressure wave generator when the thermal relaxation time between gas and tube is comparable to a half period. Three types have been discussed in the literature recently by Gifford, by Mikulin, and by Wheatley. A record low temperature of 60 K was achieved in our work using a single stage pulse tube similar to that of Mikulin. Previously 105 K was the lowest temperature achieved. Because of only one moving part, all three types have the potential for long life, but their efficiency and intrinsic limitations have never been investigated. This paper compares the three types with each other and with common refrigerators such as Joule-Thomson and Stirling refrigerators. An apparatus is described which can measure the intrinsic behavior of the different types from temperatures of about 30 K to 300 K. Overall cycle efficiency as well as sources of loss such as conduction and regenerator ineffectiveness are discussed and the advantages of various phase shifting techniques to increase refrigeration capacity are compared.
Computational modeling and verification of signaling pathways in cancer

We propose and analyze a rule-based model of the HMGB1 signaling pathway. The protein HMGB1 can activate a number of regulatory networks --- the p53, NFκ B, Ras and Rb pathways --- that control many physiological processes of the cell. HMGB1 has been recently shown to be implicated in cancer, inflammation and other diseases. In this paper, we focus on the NFκ B pathway and construct a crosstalk model of the HMGB1-p53-NFκ B-Ras-Rb network to investigate how these couplings influence proliferation and apoptosis (programmed cell death) of cancer cells. We first built a single-cell model of the HMGB1 network using the rule-based BioNetGen language. Then, we analyzed and verified qualitative properties of the model by means of simulation and statistical model checking. For model simulation, we used both ordinary differential equations and Gillespie's stochastic simulation algorithm. Statistical model checking enabled us to verify our model with respect to behavioral properties expressed in temporal logic. Our analysis showed that HMGB1-activated receptors can generate sustained oscillations of irregular amplitude for the NFκ B, Iκ B, A20 and p53 proteins. Also, knockout of A20 can destroy the Iκ B-NFκ B negative feedback loop, leading to the development of severe inflammation or cancer. Our model also predicted that the knockout or overexpression of the Iκ B kinase can influence the cancer cell's fate --- apoptosis or survival --- through the crosstalk of different pathways. Finally, our work shows that computational modeling and statistical model checking can be effectively combined in the study of biological signaling pathways.
8. Chemical Analysis by Laser Ablation

Publisher Summary The chapter discusses the use of laser ablation for chemical analysis. In forensics, health, environmental, nonproliferation, and many other disciplines, the chemical composition of a sample can be consequential. For the semiconductor industry, a trace amount of impurity may cost millions of dollars in lost processing. The billion-dollar effort to remediate contaminated environmental sites requires venerable chemical analysis. For nonproliferation, chemical analysis may foretell covert development of nuclear or chemical weapons. In health, chemical analysis can save lives. The chapter emphasizes on direct solid-phase analysis; when a pulsed laser beam is focused onto any solid sample, a portion of the material is instantaneously transformed into vapor phase constituents. Chemical analysis can be performed directly within the luminous laser-induced plasma at the sample surface, or by transporting the ablated mass to a secondary excitation source for analysis. The goal is to break (ablate) the sample into a fine vapor with a stoichiometric representation of the solid phase. Some of the technologies that have been investigated for direct solid-phase chemical analysis include the following: slurry nebulization; arc and spark sampling; electro-thermal vaporization; direct insertion into an analytical source using graphite cups; exploding films; and reduced pressure rf discharges.
In vivo study of the embryotoxic activity of leukocytes

Abstract The embryotoxic activity of polymorphonuclear leukocytes (PMNLs), macro-phages abd endometrial cells was studied in vivo. Rabbits were mated, both uterine horns were ligated at the cervical end, and different concentrations of intact or homogenized cells were injected in one horn while the other served as control. The fertility rate, size of implantations and number of cells in uterine flushings were assessed 10 days postcoitum. PMNLs, macrophages, and endometrial cells exhibited a potent antifertility effect, retarded post-implantation growth and attracted large numbers of white cells. A definite dose and effect relationship between the concentration of cells and the different parameters was demonstrated. Phagocytosis did not play a role in this system. The embryotoxic effect is not limited to uterine cells since it could also be demonstrated in liver, thyroid and red blood cells.
Mechanisms of Muscle Denervation in Aging: Insights from a Mouse Model of Amyotrophic Lateral Sclerosis

Muscle denervation at the neuromuscular junction (NMJ) is thought to be a contributing factor in age-related muscle weakness. Therefore, understanding the mechanisms that modulate NMJ innervation is a key to developing therapies to combat age-related muscle weakness affecting the elderly. Two mouse models, one lacking the Cu/Zn superoxide dismutase (SOD1) gene and another harboring the transgenic mutant human SOD1 gene, display progressive changes at the NMJ, including muscle endplate fragmentation, nerve terminal sprouting, and denervation. These changes at the NMJ share many of the common features observed in the NMJs of aged mice. In this review, research findings demonstrating the effects of PGC-1α, IGF-1, GDNF, MyoD, myogenin, and miR-206 on NMJ innervation patterns in the G93A SOD1 mice will be highlighted in the context of age-related muscle denervation.
B‐type Natriuretic Peptide and Amino‐terminal Pro‐B‐type Natriuretic Peptide in Pediatric Patients with Pulmonary Arterial Hypertension

Objectives. B-type natriuretic peptide (BNP) and the amino-terminal fragment (NTproBNP) correlate with clinical variables, but have not been simultaneously studied in a large number of pediatric patients with pulmonary arterial hypertension (PAH). The purpose of our investigation was to compare BNP and NTproBNP with clinical indicators of disease in a pediatric PAH population for which biomarkers are much needed. Design. We retrospectively compared BNP and NTproBNP levels with exercise capacity, echocardiographic data, and hemodynamics in PAH patients under 21 years old. Two hundred sixty-three blood samples from 88 pediatric PAH patients were obtained, with BNP and NTproBNP drawn at the same time. Results. There was a correlation between BNP and NTproBNP with mean pulmonary arterial pressure/mean systemic arterial pressure ratio (r = 0.40, P < .01; r = 0.45, P < .01; respectively), mean right atrial pressure (r = 0.48, P < .01; r = 0.48, P < .01), and tricuspid regurgitant velocity (r = 0.36, P < .01; r = 0.41, P < .01). BNP and NTproBNP are associated with 6-minute walk distance, mean pulmonary arterial pressure, mean pulmonary arterial pressure/ mean systemic arterial pressure ratio, mean right atrial pressure, pulmonary vascular resistance index, and tricuspid regurgitant velocity when investigated longitudinally. On the average, a 1-unit increase in log BNP or NTproBNP was associated with 4.5 units ¥ m 2 or 3.4 units ¥ m 2 increase in pulmonary vascular resistance index, respectively. There was a strong correlation between log BNP and log NTproBNP measurements (r = 0.87, P < .01). Conclusion. In pediatric PAH, BNP and NTProBNP are strongly correlated and predict changes in clinical variables and hemodynamics. In a cross-sectional analysis, NTproBNP correlated with echocardiographic and exercise data better than BNP; NTproBNP showed less within patient variability over time; therefore, NTproBNP can add additional information toward predicting these clinical measurements.
Cost-Utility Analysis of Mycophenolate Mofetil versus Azathioprine Based Regimens for Maintenance Therapy of Proliferative Lupus Nephritis

Background/Aims. We aimed to examine the cost-effectiveness of mycophenolate mofetil (MMF) and azathioprine (AZA) as maintenance therapy for patients with Class III and Class IV lupus nephritis (LN), from a United States (US) perspective. Methods. Using a Markov model, we conducted a cost-utility analysis from a societal perspective over a lifetime horizon. The modeled population comprised patients with proliferative LN who received maintenance therapy with MMF (2 gm/day) versus AZA (150 mg/day) for 3 years. Risk estimates of clinical events were based on a Cochrane meta-analysis while costs and utilities were retrieved from other published sources. Outcome measures included costs, quality-adjusted life-years (QALY), incremental cost-effectiveness ratios (ICER), and net monetary benefit. Results. The base-case model showed that, compared with AZA strategy, the ICER for MMF was $2,630,592/QALY at 3 years. Over the patients' lifetime, however, the ICER of MMF compared to AZA was $6,454/QALY. Overall, the ICER results from various sensitivity and subgroup analyses did not alter the conclusions of the model simulation. Conclusions. In the short term, an AZA-based regimen confers greater value than MMF for the maintenance therapy of proliferative LN. From a lifelong perspective, however, MMF is cost-effective compared to AZA.
Regional Anticoagulation with Sodium Citrate in Pediatric Patients on Intermittent Hemodialysis Therapy with Bleeding Risks

Heparin-free anticoagulation in hemodialysis (HD) is advocated for patients with clotting abnormalities and risk of bleeding. Objective: First publication on regional citrate anticoagulation (RCA) in children. RCA is free from systemic effects, guarantees excellent dialyzer life, but requires careful monitoring. Methods: We report on 3 patients treated by intermittent RCA HD (4 h each, high-flux dialyzer F40, Fresenius): (1) 17-year-old boy (renal transplant failure, access via cubital Cimino fistula) after hypertensive intra-cerebral hemorrhage (2 sessions); (2) 13-year-old girl (hemolytic uremic syndrome, access via jugular vein Shaldon catheter) after abdominal surgery and bleeding (8 sessions); and (3) 7-year-old boy (hyperoxaluria, access via PermCath® jugular vein catheter) after renal transplant biopsy (3 sessions). Sodium citrate 30% was infused into the extra corporeal circuit (blood flow 150 mL/min) before dialyzer (initial flow 30 mL/min) and calcium gluconate 10% for antidote into venous line near of catheter or fistula (initial flow 40 mL/min). Post-dialyzer extracorporeal serum Ca++ (aim 0.9) were measured for every 30 min. Serum Na+, K+, base excess (BE), blood flow, blood pressure, heart rate, and blood out-flow and in-flow pressure were also monitored. Results: For adequate RCA (mean extracorporeal serum Ca++ 0.24 ± 0.04 mmol/L), a mean citrate flow of 36.1 ± 5.9 mL/h and a mean calcium substitution rate of 40.8 ± 3.4 mL/h were needed. Intra-corporeal Ca++ was kept at 1.10 ± 0.07 mmol/L. Extracorporeal activated clotting time (ACT) was 194 ± 41 and intra-corporeal ACT 90 ± 12 sec. Serum Na+, K+, and BE during HD were 138 ± 2, 3.5 ± 0.3, and −0.6 ± 1.1 mmol/L, respectively. Mean arterial blood pressures of patients 1–3 were 117 ± 5, 103 ± 5, and 102 ± 6 mmHg. All patients were stable and without any bleeding during HD. The only adverse event was 1 episode of hypocalcemia (Ca++ < 0.6 mmol/L) cured by stopping dialysis. Conclusions: Local anticoagulation with sodium citrate during intermittent HD can be applied safely in children and adolescents.
Critical Role of Endogenous Akt/IAPs and MEK1/ERK Pathways in Counteracting Endoplasmic Reticulum Stress-induced Cell Death

Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of many diseases and in cancer therapy. Although the unfolded protein response is known to alleviate ER stress by reducing the accumulation of misfolded proteins, the exact survival elements and their downstream signaling pathways that directly counteract ER stress-stimulated apoptotic signaling remain elusive. Here, we have shown that endogenous Akt and ERK are rapidly activated and act as downstream effectors of phosphatidylinositol 3-kinase in thapsigargin- or tunicamycin-induced ER stress. Introduction of either dominant-negative Akt or MEK1 or the inhibitors LY294002 and U0126 sensitized cells to ER stress-induced cell death in different cell types. Reverse transcription-PCR analysis of gene expression during ER stress revealed that cIAP-2 and XIAP, members of the IAP family of potent caspase suppressors, were strongly induced. Transcription of cIAP-2 and XIAP was up-regulated by the phosphatidylinositol 3-kinase/Akt pathway as shown by its reversal by dominant-negative Akt or LY294002. Ablation of these IAPs by RNA interference sensitized cells to ER stress-induced death, which was reversed by the caspase inhibitor benzyloxycarbonyl-VAD-fluoromethyl ketone. The protective role of IAPs in ER stress coincided with Smac release from mitochondria to the cytosol. Furthermore, it was shown that mTOR was not required for Akt-mediated survival. These results represent the first demonstration that activation of endogenous Akt/IAPs and MEK/ERK plays a critical role in controlling cell survival by resisting ER stress-induced cell death signaling.
Water relations and productivity of alfalfa populations divergently selected for leaflet size

Abstract Several investigators have identified genetic variability for water-use efficiency (WUE=forage production/unit transpired water) in alfalfa (Medicago sativa L.). However, WUE as a component of drought resistance (drought avoidance by conserving water) has received limited emphasis in cultivar development. The objective of these studies was to evaluate the water relations and productivity of two alfalfa populations selected for large- or small-leaflet size. Forage yield, WUE, leaf transpiration, stem pressure potential and leaf temperature were determined under moisture regimes ranging from field capacity to midday plant wilting in a controlled environment. Plant WUE decreased as moisture stress increased for both populations in the controlled environment. The large-leaflet population produced an average of 11% more forage per unit of water used. Greater root mass was also observed for the large-leaflet population. Instantaneous transpiration per unit leaf area average 0.06 and 0.05 g m−2 s−1 (P