bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased Tissue Factor Pathway Inhibitor (TFPI) and Coagulation in Patients with Insulin-dependent Diabetes mellitus
Authors: Leurs Paul B , van Oerle Rene , Wolffenbuttel Bruce H R , Hamulyak Karly
Published: July 2018

Recently, we found an increase in tissue factor pathway inhibitor (TFPI) activity in patients with insulin-dependent diabetes mellitus (IDDM). This increase in TFPI activity could be the result of increased thrombin formation and/or altered binding of TFPI to glycosaminoglycans. We studied TFPI activity (chromogenic assay) in relation to prothrombin F1+2 fragments and endogenous thrombin potential (ETP), in 46 IDDM patients, and 18 age and sex-matched healthy controls. Prothrombin, antithrombin and thrombomodulin were also determined. In IDDM patients, TFPI activity and F1+2 levels were significantly higher, while ETP, prothrombin antigen levels, and antithrombin activity were lower as compared to the controls. In IDDM patients with microalbuminuria, a manifestation of generalized angiopathy, TFPI activity, F1+2 and thrombomodulin levels were higher than in patients with only retinopathy or patients without complications. No correlation between TFPI activity, F1+2 levels and thrombomodulin was found, while TFPI activity was negatively correlated with ETP (r = -0.27). Microalbuminuria was significantly correlated with TFPI activity (r = 0.46), F1+2 (r = 0.56), and thrombomodulin (r = 0.52). In TFPI-depleted plasma, ETP increased, indicating that ETP is affected by TFPI. In conclusion, the increase in TFPI activity in IDDM patients may not be considered to be a reaction on a procoagulant state. It is hypothesized that vascular damage, leading to alterations in glycosaminoglycans, is in part responsible for the changes in TFPI activity, F1+2 levels and ETP.
Ventilation-Perfusion Lung Scanning and the Diagnosis of Pulmonary Embolism: Improvement of Observer Agreement by the Use of a Lung Segment Reference Chart
Authors: Lensing Anthonie W A , van Beek Edwin J R , Demers Christine , Tiel-van Buul Monique M C , Yakemchuk Valerie , van Dongen Annemarie , Coates Geoffrey , Ginsberg Jeffrey S , Hirsh Jack , ten Cate Jan Wouter , Büller Harry R
Published: July 2018

Objective. To test the hypothesis that the systematic use of a lung segment reference chart can improve the inter- and intra-observer agreement for the interpretation of ventilation-perfusion lung scans.

Design. A randomized trial.

Study population. Ventilation-perfusion lung scans were obtained in a series of 220 consecutive patients with clinically suspected pulmonary embolism.

Intervention. Ventilation-perfusion scans were randomly allocated to one of two series each consisting of 110 ventilation-perfusion lung scans. The first series of lung scans was interpreted according to the routine diagnostic approach, and the second series was interpreted with the mandatory use of a lung segment reference chart on which observed ventilation and perfusion defects were drawn. The two nuclear medicine physicians agreed a priori on the diagnostic criteria of the classification scheme.

Measurements. Lung scans were classified as normal, non-high probability, or high probability for pulmonary embolism. The extent of disagreement between the nuclear medicine physicians (inter-observer disagreement) and the lack of internal consistency of each nuclear medicine physician (intra-observer disagreement) was assessed by the percentage disagreement and by kappa statistic.

Results. Inter-observer disagreement which was 20% in the first series, decreased significantly in the second series to 7%; P = 0.003. Intra-observer disagreement for the first series was 10% and 22% for the nuclear medicine physicians, respectively. Intra-observer disagreement for the second series of lung scans decreased significantly for one nuclear medicine physician (intra-observer disagreement, 0%; P <0.01), whereas intra-observer disagreement was reduced to 10% for the other nuclear medicine physician (P = 0.09).

Conclusion. Inter- and intra-observer disagreement were significantly reduced when two nuclear medicine specialists interpreted ventilation-perfusion lung scans according to the routine diagnostic approach plus the use of a lung segment reference chart. The use of the lung segment reference chart for the interpretation of lung scans is likely to improve the management of patients with clinically suspected pulmonary embolism.
Activation of Coagulation and Fibrinolysis Following OKT3 Administration to Renal Transplant Recipients: Association with Distinct Mediators
Authors: Raasveld Maarten H M , Hack C Erik , ten Berge Ineke J M
Published: July 2018

Treatment with OKT3 induces cytokine release and activates the complement system. Since both phenomena may affect coagulation and fibrinolysis we studied these systems in 8 renal transplant recipients during OKT3 treatment. In 8 of 9 patients a similar pattern was observed: plasma thrombin-antithrombin-III-complex, tissue-type plasminogen-activator and plasmin-α2-antiplasmin-complex levels were increased as compared to pretreatment levels (p <0.05) at 15 min after the first OKT3 dose and reached peak values at 1 h. No significant changes were observed upon subsequent OKT3 administrations or in a control group of 8 patients. In one patient upon the first OKT3 administration only complement activation, and no cytokine release was observed, whereas plasma thrombin-antithrombin-III-complex, tissue-type plasminogen-activator and plasmin-α2-antiplasmin-complex levels increased only at 15 min.

In conclusion, we demonstrate a biphasic activation of coagulation and fibrinolysis upon the first OKT3 dose; the initial phase seems to be associated with complement activation, the later phase with cytokine release.
Immunoglobulin Fractions Isolated from Patients with Antiphospholipid Antibodies Prevent the Inactivation of Factor Va by Activated Protein C on Human Endothelial Cells
Authors: Borrell Montserrat , Sala Nuria , de Castellarnau Conxita , Lopez Silvia , Gari Merce , Fontcuberta Jordi
Published: July 2018

We studied the effect of purified immunoglobulins (Ig) from 21 patients with antiphospholipid antibodies (aPL) on factor Va degradation by activated protein C (aPC) on cultured human umbilical vein endothelial cells (HUVEC). Sera from patients were tested on an ELISA aPL assay to determine the isotype with aPL activity. HUVEC were incubated with purified IgG or IgM fraction from controls or patients. Activated PC and factor Va were then added and factor Va degradation was measured after several reaction times. 13 of 14 IgM and 8 of 10 IgG from patients showed an inhibitory effect on factor Va degradation by aPC when compared with control Ig. We also observed the same inhibitory effect with patients’ Ig on studying the degradation of factor Va by aPC in a purified system containing aPC, protein S and phospholipids. These results suggest that aPL antibodies disturb the anticoagulant activity of aPC, which may contribute to the thrombotic tendency of these patients.
A Rapid Monoclonal Antibody-Based Enzyme Immunoassay (EIA) for the Quantitative Determination of Soluble Fibrin in Plasma
Authors: Nieuwenhuizen W , Hoegee-De Nobel E , Laterveer R
Published: July 2018

Soluble fibrin is considered as a molecular marker for intravascular fibrin formation, and impending thrombotic events. Most of the existing assays are less suitable for routine clinical applications and their specificity may be limited.

We have developed a sandwich-type EIA with a fibrin-specific MoAb described by us before (Proc Natl Acad Sci 1989; 86: 8951) as the capture antibody. An other MoAb (G8; Thromb Haemostas 1988; 60: 415) with an epitope in the carboxyl-terminal sections of the fibrin α-chains, was labeled with peroxidase and used as the tagging antibody. The EIA is calibrated against plasma spiked with known concentrations of soluble fibrin. The time-to-result of the EIA is only 1.5 h. Concentrations as low as 0.5 µg soluble fibrin/ml plasma are readily measurable. Heparin has no effect on the results. Fibrinogen and fibrin(ogen) degradation products are not detected. The values of fibrinopeptide A and soluble fibrin values found with the “COA-SET soluble fibrin” assay correlated well with the soluble fibrin values found with our EIA i.e. r = 0.998 and 0.984, respectively. The run-to-run variabilities were 7.9% and 6.6% for samples with low and high soluble fibrin concentrations, respectively. The within-run variabilities were 2.5, 1.8, 4.0 and 4.6% for samples with 1, 0.5, 0.25 and 0.125 µg soluble fibrin/ml, respectively.

The sensitivity, specificity, accuracy and short time-to-result make our EIA suitable for routine clinical applications and the monitoring of the effectivity of heparinization.
Typ-2-Diabetes und Migranten: Menschen aus verschiedenen Sprach- und Kulturräumen
Authors: Berger Faize
Published: July 2018

Migrants are more likely, earlier and more severely affected by type 2 diabetes than the native population. Prevalence, incidence and mortality in this population group, whose proportion of the total population continues to grow, are increased by a factor of 2 – even stronger depending on ethnicity, country of origin, gender and socio-economic conditions. This makes it necessary to pay special attention to this group.
Numerical analysis of the influence of water/air medium on the muzzle flow field characteristics of machine gun
Authors: Zhang Xinwei , Yu Yonggang
Published: July 2018

The mathematical and physical model for underwater sealed gun is established to investigate the flow field distribution characteristics for gun muzzle in different mediums. The muzzle flow field for the 12.7 mm gun which is sealed launched underwater is numerically simulated by combining User-Defined Functions (UDF) and dynamic grid technique. The predicted results show that, the muzzle flow field for gun launched underwater is significantly different with that for in air. Unlike that the initial air forming bottle shock wave at the muzzle for gun launched in air, it hits the gas-liquid interface with forming series cylindrical compressed wave in the area before the projectile for gun sealed launched underwater. As the gunpowder gas sprays out, Mach disk appears at 60μs after the projectile shot into water. Meanwhile, the shape of shock waves is fusiform and then turns into a peach heart gradually. However, the bow shock for gun launched in air, which is affected by the projectile base with its structure being bowl-shaped, fails to develop into the Mach disk at even 160μs. Compared with gun launched in air, the muzzle shock wave area for gun launched underwater is obviously smaller.
Interstitial flow promotes macrophage polarization toward an M2 phenotype
Authors: Li Ran , Serrano Jean Carlos , Xing Hao , Lee Tara A. , Azizgolshani Hesham , Zaman Muhammad , Kamm Roger D.
Published: July 2018

Tumor tissues are characterized by an elevated interstitial fluid flow from the tumor to the surrounding stroma. Macrophages in the tumor microenvironment are key contributors to tumor progression. While it is well established that chemical stimuli within the tumor tissues can alter macrophage behaviors, the effects of mechanical stimuli, especially the flow of interstitial fluid in the tumor microenvironment, on macrophage phenotypes have not been explored. Here, we used three-dimensional biomimetic models to reveal that macrophages can sense and respond to pathophysiological levels of interstitial fluid flow reported in tumors (∼3 µm/s). Specifically, interstitial flow (IF) polarizes macrophages toward an M2-like phenotype via integrin/Src-mediated mechanotransduction pathways involving STAT3/6. Consistent with this flow-induced M2 polarization, macrophages treated with IF migrate faster and have an enhanced ability to promote cancer cell migration. Moreover, IF directs macrophages to migrate against the flow. Since IF emanates from the tumor to the surrounding stromal tissues, our results suggest that IF could not only induce M2 polarization of macrophages but also recruit these M2 macrophages toward the tumor masses, contributing to cancer cell invasion and tumor progression. Collectively, our study reveals that IF could be a critical regulator of tumor immune environment.
Genomic analysis reveals multiple mismatches between biological and management units in yellowfin tuna (Thunnus albacares)
Authors: Mullins Rachel B , McKeown Niall J , Sauer Warwick H H , Shaw Paul W
Published: July 2018

The South African (SAF) yellowfin tuna (Thunnus albacares) fishery represents a potential example of misalignment between management units and biological processes. The SAF fishery spans an operational stock with a boundary at 20°E, either side of which fish are considered part of Atlantic or Indian Ocean regional stocks. However, the actual recruitment of fish from Atlantic and Indian Ocean spawning populations into SAF waters is unknown. To address this knowledge gap, genomic analysis (11 101 SNPs) was performed on samples from Atlantic and Indian Ocean spawning sites, including SAF sites spanning the current stock boundary. Outlier loci conferred high discriminatory power to assignment tests and revealed that all SAF fish were assigned to the Indian Ocean population and that no Atlantic Ocean fish appeared in the SAF samples. Additionally, several Indian Ocean migrants were detected at the Atlantic spawning site demonstrating asymmetric dispersal and the occurrence of a mixed-stock fishery in Atlantic waters. This study highlights both the spatial inaccuracy of current stock designations and a misunderstanding of interactions between the underlying biological units, which must be addressed in light of local and global declines of the species. Specifically, the entire SAF fishery must be managed as part of the Indian Ocean stock.
Celiac Disease: Against the Grain in Gastroenterology
Authors: Zhu Julie , Mulder Chris J J , Dieleman Levinus A
Published: July 2018

The incidence of celiac disease has risen quickly and has a worldwide distribution in Europe, North and South America, Asia, the Middle East and Africa. This is attributed in part to increased availability in screening but also to the fast-rising gluten consumption and perhaps unknown environmental factors. In daily practice, this means that more subclinical cases and very young and elderly patients are diagnosed. The pathogenesis of celiac disease is a T-cell driven process initiated by gluten, leading to increased intestinal permeability and villous atrophy. The process requires HLA genotypes DQ2, DQ8 or both. Additional non-HLA alleles have been identified in genome-wide association studies. Serological testing, followed by duodenal biopsies, are still required to confirm the diagnosis. Advances are in the making for novel biomarkers to monitor disease and for pharmacological support of celiac disease. Medical costs and patient-perceived disease burden remain high in celiac disease, which point to the need for ongoing research in drug development to improve quality of daily life. Drugs undergoing phase I and phase II clinical trials include intraluminal therapies and vaccines to restore immune tolerance. These therapies aim to reduce symptoms and mucosal injuries as adjunct therapies to a gluten-free diet.
The Israeli Raid Against the PLO Headquarters in Tunis—1985
Authors: Pobjie Erin , Declercq Fanny , Van Steenberghe Raphaël
Published: July 2018

This chapter examines the Israeli raid against the Palestine Liberation Organisation (PLO) headquarters in Tunis in 1985. It first sets out the facts and context of the raid, the positions of the main protagonists (Israel and Tunisia) and the reactions of third States and international organizations. The chapter then analyses the legal issues raised by the incident under international law as it stood at the time, and its impact on the jus ad bellum. The 1985 raid was an early example of a claimed right to exercise self-defence in response to attacks committed by non-state actors without those attacks being attributable to the state on whose territory the action in self-defence takes place. However, it is argued that this incident left unsettled whether or not such a right was accepted at the time.
Changes in the sensitivity of solar p-mode frequency shifts to activity over three solar cycles
Authors: Howe R , Chaplin W J , Davies G R , Elsworth Y , Basu S , Broomhall A-M
Published: July 2018

Low-degree solar p-mode observations from the long-lived Birmingham Solar-Oscillations Network (BiSON) stretch back further than any other single helioseismic data set. Results from BiSON have suggested that the response of the mode frequency to solar activity levels may be different in different cycles. In order to check whether such changes can also be seen at higher degrees, we compare the response of medium-degree solar p modes to activity levels across three solar cycles using data from Big Bear Solar Observatory, Global Oscillation Network Group, Michelson Doppler Imager, and Helioseismic and Magnetic Imager, by examining the shifts in the mode frequencies and their sensitivity to solar activity levels. We compare these shifts and sensitivities with those from radial modes from BiSON. We find that the medium-degree data show small but significant systematic differences between the cycles, with solar Cycle 24 showing a frequency shift about 10 per cent larger than Cycle 23 for the same change in activity as determined by the 10.7 cm radio flux. This may support the idea that there have been changes in the magnetic properties of the shallow subsurface layers of the Sun that have the strongest influence on the frequency shifts.
A Stronger Role for the European Supervisory Authorities in the EU27
Authors: Busch Danny
Published: July 2018

The chapter addresses two topics that are crucial to achieving more supervisory convergence in the European Union 27 (EU-27): (1) a more pan-European governance or decision-making structure of the European Supervisory Authorities (ESAs); and (2) more direct supervisory powers to the ESAs, particularly (but not exclusively) to the European Securities and Markets Authority (ESMA). These topics are analysed and discussed within the framework of the Commission's public consultation on the functioning of the ESAs; the Commission proposal of 29 June 2017 for a Regulation on a pan-European Personal Pension Product; the Commission's FinTech consultation of 23 March 2017; and the Commission proposal of 13 June 2017 to amend the European Market Infrastructure Regulation and the ESMA, which aims to introduce a more pan-European approach to central counterparties supervision.
OTC Derivatives Clearing, Brexit, and the CMU
Authors: Ferrarini Guido , Trasciatti Davide
Published: July 2018

This chapter contributes to the debate on the future of European over-the-counter (OTC) clearing and relevant infrastructures in light of the Capital Markets Union and its re-configuration after Brexit. It begins by introducing some basic notions about clearing dynamics. It then analyses the available divorce options between the EU and the UK once Article 50 has been triggered, and their impact on clearing particularly in light of the European Market Infrastructure Regulation's equivalence regime. Next, it examines the worst-case scenario that would materialize if UK central counterparties (CCPs) were excluded from the single market, and considers possible network strategies that CCPs could adopt to remedy the consequences of Brexit.
Private Placements in the Capital Markets Union
Authors: Graaf Frank GB
Published: July 2018

This chapter looks at recent initiatives in the context of the European Commission's flagship plans for a Capital Markets Union (CMU) designed to encourage a pan-European private placement market. In reality, private placements are mainly available as a funding tool for medium-sized and larger companies. Nonetheless, private placements are regarded by CMU's policymakers as an alternative source of long-term funding, which is simple enough for smaller corporates and small and medium-sized enterprises (SME), and with benefits that they might find attractive. The Commission's initial intention in the design of a CMU was to enable a greater use by SMEs of private placements.
Relief from Prudential Requirements to Support the Capital Markets Union
Authors: Joosen Bart , Lieverse Kitty
Published: July 2018

This chapter examines the regulatory impediments to financing by European banks of corporate borrowers and the means to improve the financing capability of banks. In this context, it not only looks at banks, but also considers the position of another type of a highly regulated funder: European insurance companies. The working assumption is that capital requirements, and risk weights for credit risks in particular, have an impact on the capability of banks to lend. Quite simply, a higher risk weight of an exposure increases the capital a bank needs to maintain in connection with such exposure. As a result, increases in capital requirements will potentially constrain the lending capability of a bank.
Securitization in the Capital Markets Union
Authors: Kastelein Gerard
Published: July 2018

On 30 May 2017, the European Parliament, Council, and Commission reached a political agreement on the package of regulatory reforms of the European securitisation market. The package is aimed at facilitating the development of a securitisation market in Europe. The package represents the latest development of a negotiation process that started back in September 2015. The application date is expected to be 1 January 2019. Meanwhile, market participants have expressed uncertainties as to its effectiveness. This chapter considers the risk that the package will have a negative effect on the European securitisation market, resulting in further contraction. The primary focus of the chapter is on the rules on long-term securitisations as opposed to the short-term securitisations (asset-backed commercial paper).
A Global Perspective on Securitized Debt
Authors: Schwarcz Steven L
Published: July 2018

Securitisation represents a significant worldwide source of capital market financing. European investors commonly invest in asset-backed securities issued in U.S. securitisation transactions, and vice versa One of the key goals of the European Commission's proposed Capital Markets Union (CMU) is to further facilitate securitisation as a source of capital market financing as a viable alternative to bank-based finance for companies operating in the EU. To that end, this chapter explains securitisation and attempts to put its rise, its decline after the global financial crisis, and its recent CMU-inspired revival into a global perspective. It examines not only securitisation's relationship to the financial crisis but also post-crisis comparative regulatory approaches in the EU and the United States.
The Body as Musical Instrument
Authors: Tanaka Atau , Donnarumma Marco
Published: July 2018

This chapter explores the possibility of thinking of the human body as musical instrument. It builds on the philosophy of phenomenology to discuss body schemata that might be considered “instrumental” and discusses the diversity of bodies proposed by body theory to consider the incorporation of digital technology. Concepts of embodied interaction from the scientific field of human–computer interaction are discussed with an eye toward musical application. The history of gestural musical instruments is presented, from the Theremin to instruments from the STEIM studio. The text then focuses on the use of physiological signals to create music, from historical works of Lucier and Rosenboom to recent performances by the authors. The body as musical instrument is discussed in a dynamic of coadaptation between performer and instrument in different configurations of body and technology.
Efferent Innervation to the Cochlea
Authors: Elgoyhen Ana Belén , Wedemeyer Carolina , Di Guilmi Mariano N.
Published: July 2018

The auditory system consists of ascending and descending neuronal pathways. The best studied is the ascending pathway, whereby sounds that are transduced in the cochlea into electrical signals are sent to the brain via the auditory nerve. Before reaching the auditory cortex, auditory ascending information has several central relays: the cochlear nucleus and superior olivary complex in the brainstem, the lateral lemniscal nuclei and inferior colliculus in the midbrain, and the medial geniculate body in the thalamus. The function(s) of the descending corticofugal pathway is less well understood. It plays important roles in shaping or even creating the response properties of central auditory neurons and in the plasticity of the auditory system, such as reorganizing cochleotopic and computational maps. Corticofugal projections are present at different relays of the auditory system. This review focuses on the physiology and plasticity of the medial efferent olivocochlear system.
Latino Public Policy Opinions
Authors: Sanchez Gabriel R. , Garcia F. Chris , Juárez Melina
Published: July 2018

Latinos are playing a growing role in public policy debates not only surrounding immigration, but across several domestic policy domains. This has led to an increased interest in the attitudes of the Latino population toward public policy. This chapter focuses on four specific aspects related to Latino public opinion. First, we briefly discuss the vital role that public opinion plays in American politics today. We then examine Latino attitudes toward important policy areas. Next, we discuss issues involved in the accurate measuring of Latino public opinion. And finally, we suggest some future directions in the study of Latino public opinion.
Reflections on the Ideology of Reasons
Authors: Hawthorne John , Magidor Ofra
Published: July 2018

In this chapter we offer a series of reflections on the ideology of reasons. Among the normative reasons for an agent X to phi, it is common to distinguish between those reasons that the agent possesses and those which she does not. After some background (5.1), we argue (5.2) that possession of a reason requires knowledge. In 5.3, we argue, first, that the normative reason construction is factive, and second, that possession ascriptions can be factored into a normative reason construction and a possession claim. In 5.4, we compare two prominent views concerning the nature of normative reasons: those of Kearns and Star and of John Broome. While both views have significant merit, we argue that they also face some non-trivial challenges, and discuss a range of considerations that can help to adjudicate between these two conceptions.
Abductions and Disappearances in Bangladeshi Policing
Authors: Uddin Md. Kamal
Published: July 2018

This article is about policing practice in Bangladesh, with special focus on the involvement of the Bangladeshi law enforcement agencies in abductions and disappearances. Recently, Bangladeshi policing has been criticized for abductions and forced disappearances. The empirical analysis of this article focuses on the key factors and dynamics of abductions and disappearances in Bangladeshi policing. This article also investigates how and why the law enforcement agencies in Bangladesh are engaged in abductions and disappearances based on interviews of different stakeholders. The empirical parts of the article employ qualitative techniques of data analysis in order to process the body of evidence collected during the fieldwork. The key argument of this article is that the acute politicization of the law enforcement agencies and misuse of entrusted power implementing the political agenda of the ruling elite contribute to human rights violations in policing practice in Bangladesh.
Cognitive decline and alcohol consumption adjusting for functional status over a 3-year period in French speaking community living older adults
Authors: Vasiliadis Helen-Maria , Payette Marie-Christine , Berbiche Djamal , Grenier Sébastien , Hudon Carol
Published: July 2018

Background

The effect of alcohol consumption on cognitive decline is not clear. We aimed to study the association between alcohol consumption and cognitive functioning controlling for functional heath status.

Methods

A total of 1610 older adults with a score ≥26 on the Mini-Mental State Examination (MMSE) were followed to assess the change in scores at the 3-year follow-up. Information on alcohol consumption as well as socio-demographic, lifestyle, psychosocial and clinical factors, as well as health service use were assessed at baseline and 3-year follow-up interviews. Linear mixed models with repeated measures were used stratifying by functional status.

Results

Close to 73% reported consuming alcohol in the past 6 months, of which 11% were heavy drinkers (≥11 and ≥16 drinks for women and men). A significant decrease in MMSE scores was observed in low functioning non-drinkers (−1.48; 95% CI: −2.06, −0.89) and light to moderate drinkers (−0.99; 95% CI: −1.54, −0.44) and high functioning non-drinkers (−0.51; 95% CI: −0.91, −0.10).

Conclusions

Alcohol consumption did not contribute to cognitive decline. Cognitive decline was greater in individuals reporting low functional status. Research should focus on the interaction between changing patterns of alcohol consumption and social participation in individuals with low and high functioning status.
Toronto Addis Ababa Academic Collaboration: A Relational, Partnership Model for Building Educational Capacity Between a High- and Low-Income University
Authors: Wondimagegn Dawit , Pain Clare , Baheretibeb Yonas , Hodges Brian , Wakma Melaku , Rose Marci , Sherif Abdulaziz , Piliotis Gena , Tsegaye Admasu , Whitehead Cynthia
Published: July 2018

Educational partnerships between academic health sciences centers in high- and low-resource settings are often formed as attempts to address health care disparities. In this Perspective, the authors describe the Toronto Addis Ababa Academic Collaboration (TAAAC), an educational partnership between the University of Toronto and Addis Ababa University. The TAAAC model was designed to help address an urgent need for increased university faculty to teach in the massive expansion of universities in Ethiopia. As TAAAC has developed and expanded, faculty at both institutions have recognized that the need to understand contextual factors and to have clarity about funding, ownership, expertise, and control are essential elements of these types of collaborative initiatives. In describing the TAAAC model, the authors aim to contribute to wider conversations and deeper theoretical understandings about these issues.
Effect of an Enhanced Recovery After Surgery Program on Opioid Use and Patient-Reported Outcomes
Authors: Meyer Larissa A. , Lasala Javier , Iniesta Maria D. , Nick Alpa M. , Munsell Mark F. , Shi Qiuling , Wang Xin Shelley , Cain Katherine E. , Lu Karen H. , Ramirez Pedro T.
Published: July 2018

OBJECTIVE:

To investigate the effect of an enhanced recovery after surgery (ERAS) program on perioperative outcomes with an emphasis on opioid consumption and patient-reported outcomes in the immediate and extended postoperative periods.

METHODS:

We initiated our ERAS program as part of a quality improvement initiative in November 2014. We compared clinical outcomes among a cohort of 607 women undergoing open gynecologic surgery before or after implementation of ERAS. For 293 patients, patient-reported outcomes were compared using the MD Anderson Symptom Inventory-Ovarian Cancer.

RESULTS:

Median age was 58 years (range 18–85 years). Median length of stay decreased by 25% for patients in the ERAS pathway (P<.001). Overall, patients in the ERAS group had a 72% reduction in median opioid consumption and 16% were opioid-free during admission up to postoperative day 3 (P<.001). There was no difference in pain scores (P=.80). Patients on ERAS reported less fatigue (P=.01), interference with walking (P=.003), and total interference (composite score of physical and affective measures) during hospitalization (P=.008). After discharge, those on the ERAS pathway demonstrated a significantly shorter median time to return to no or mild fatigue (10 vs 30 days, P=.03), mild or no interference with walking (5 vs 13 days, P=.003), and mild to no total interference (3 vs 13 days, P=.02). There were no significant differences in complications, rates of readmission, or reoperation between the pre- and post-ERAS groups.

CONCLUSION:

Implementation of an ERAS program was associated with significantly decreased opioid use after surgery and improvement in key patient-reported outcomes associated with functional recovery after surgery without compromising pain scores.
Human Papillomavirus Genotypes From Vaginal and Vulvar Intraepithelial Neoplasia in Females 15–26 Years of Age
Authors: Garland Suzanne M. , Joura Elmar A. , Ault Kevin A. , Bosch F. Xavier , Brown Darron R. , Castellsagué Xavier , Ferenczy Alex , Ferris Daron G. , Giuliano Anna R. , Hernandez-Avila Mauricio , Huh Warner K. , Iversen Ole-Erik , Kjaer Susanne K. , Kurman Robert J. , Luna Joaquin , Monsonego Joseph , Muñoz Nubia , Paavonen Jorma , Pitisuttihum Punnee , Ronnett Brigitte M. , Steben Marc , Stoler Mark H. , Wheeler Cosette M. , Wiley Dorothy J. , Perez Gonzalo , Saah Alfred J. , Luxembourg Alain , Li Se , DiNubile Mark J. , Wagner Monika , Velicer Christine
Published: July 2018

OBJECTIVE:

To estimate the proportion of vulvar and vaginal low-grade and high-grade squamous intraepithelial lesions (LSILs and HSILs) in females 15–26 years of age attributable to 14 human papillomavirus (HPV) genotypes (6, 11, 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59).

METHODS:

A post hoc analysis of prospectively diagnosed vulvar and vaginal LSILs and HSILs among females 15–26 years of age enrolled in the placebo arms of two phase 3, randomized HPV vaccine trials assessed 14 prespecified HPV genotypes associated with cervical cancers or anogenital warts using a type-specific multiplex polymerase chain reaction assay. The frequency of lesions associated with specific HPV genotypes was estimated by proportional and other attribution methods.

RESULTS:

During approximately 4 years of follow-up in 8,798 females, 40 vulvar LSILs and 46 vulvar HSILs were diagnosed in 68 females, and 118 vaginal LSILs and 33 vaginal HSILs were diagnosed in 107 females. Females developing vulvar (41.2%) or vaginal (49.5%) lesions also had cervical lesions, whereas 6.5% of females with cervical lesions had vaginal or vulvar lesions. At least 1 of the 14 HPV genotypes was detected in females with vulvar LSIL (72.5%), vulvar HSIL (91.3%), vaginal LSIL (61.9%), and vaginal HSIL (72.7%). Considering only HPV-positive lesions, the nine most common genotypes causing cervical cancer and anogenital warts (6, 11, 16, 18, 31, 33, 45, 52, and 58) were found in 89.4% of vulvar LSILs, 100% of vulvar HSILs, 56.0% of vaginal LSILs, and 78.3% of vaginal HSILs.

CONCLUSION:

Most vulvar and vaginal lesions were attributable to at least 1 of the 14 HPV genotypes analyzed. Effective immunization programs could potentially prevent substantial numbers of HPV-related vulvar and vaginal LSILs and HSILs.

CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov,

NCT00092521 and NCT00092534.
C1q/TNF-Related Protein 9 Inhibits THP-1 Macrophage Foam Cell Formation by Enhancing Autophagy
Authors: Zhang Lu , Liu Qi , Zhang Hui , Wang Xue-Dong , Chen Shu-Yuan , Yang Yang , Lv Hang , Hou Jing-Bo , Yu Bo
Published: July 2018

During the pathogenesis of early atherosclerosis, lipid-loaded macrophages are involved in plaque development and progression. As a novel adipokine, C1q/tumor necrosis factor–related protein-9 (CTRP9) has beneficial effects in cardiovascular disease. However, previous reports have not studied whether the formation of macrophage foam cell induced by oxidized low-density lipoprotein (ox-LDL) is affected by CTRP9. According to our study, in ox-LDL–induced THP-1 macrophages, CTRP9 could reduce the quantity of lipid droplets, lower the level of cholesteryl ester (CE), promote cholesterol efflux, as well as increase the expression level of the cholesterol transport receptors ATP-binding membrane cassette transporter A1 (ABCA1) and G1 (ABCG1). In addition, the protein of LC3 II is elevated and that of p62 is decreased in CTRP9-treated foam cells by enhancing autophagy. However, using 3-methyladenine (3-MA) abolished the role of CTRP9 by inhibiting autophagy. Mechanistically, the autophagy-promoting effects of CTRP9 on foam cells was reversed by an AMPK inhibitor, Compound C, which inhibited the signaling pathway of adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR). These results show that CTRP9 protects against atherosclerosis by promoting cholesterol efflux to reduce the formation of foam cell in virtue of inducing autophagy in an AMPK/mTOR signaling pathway–dependent manner.
Physical activity and weight gain after smoking cessation in postmenopausal women
Authors: Luo Juhua , Manson JoAnn E. , Hendryx Michael , Shadyab Aladdin H. , Johnson Karen C. , Dinh Paul C. , Going Scott B. , Chlebowski Rowan , Stefanick Marcia L. , Margolis Karen L.
Published: July 2018

Objective:

Weight gain frequently occurs after smoking cessation. The objective of this study was to examine whether weight gain after smoking cessation was attenuated by physical activity (PA) in postmenopausal women.

Methods:

A total of 4,717 baseline smokers from the Women's Health Initiative were followed for 3 years. One thousand two hundred eighty-two women quit smoking, and 3,435 continued smoking. Weight was measured at baseline and at the year 3 visit. PA was assessed at both times by self-report, summarized as metabolic equivalent task-hours per week. Multiple linear regression models were used to assess the association between PA and postcessation weight gain, adjusting for potential confounding factors.

Results:

Compared with continuing smokers, quitters gained an average of 3.5 kg (SD = 5.6) between the baseline and year 3 visit. Quitters with decreased PA had the highest amount of weight gain (3.88 kg, 95% CI: 3.22-4.54); quitters with increased PA (≥15 metabolic equivalent task-hours /week) had the lowest weight gain (2.55 kg, 95% CI: 1.59-3.52). Increased PA had a stronger beneficial association for postcessation weight gain for women with obesity compared to normal weight women. Quitters who had low PA at baseline and high PA at year 3 and were also enrolled in a dietary modification intervention had nonsignificant weight gain (1.88 kg, 95% CI: −0.21-3.96) compared with continuing smokers.

Conclusions:

Our data demonstrate that even a modest increase in PA (equivalent to current recommendations) can attenuate weight gain after quitting smoking among postmenopausal women, especially in combination with improved diet.
Carboplatin and Pembrolizumab Chemoimmunotherapy Achieves Remission in Recurrent, Metastatic Sebaceous Carcinoma
Authors: Kodali Saranya , Tipirneni Eswar , Gibson Pamela C. , Cook Deborah , Verschraegen Claire , Lane Katherine A.
Published: July 2018

A 72-year-old Caucasian woman who had recurrent sebaceous carcinoma of the right orbit with bilateral cervical lymph node involvement 24 months after orbital exenteration was treated with carboplatin (area under the curve of 5) and pembrolizumab (2 mg/kg) for 6 cycles, followed by maintenance pembrolizumab. She obtained a complete pathological remission and remains free of local, regional, and systemic disease at 15 months.
Physical Therapy Student Choices When Engaging With Traditional or Technological Teaching Resources
Authors: van Kessel Gisela , Gill Robyn , Milanese Steve
Published: July 2018

Introduction.

Student engagement with both face-to-face and online sessions is becoming increasingly important as a metric of teaching success. Understanding engagement needs to move beyond positioning the student as a generic learner and explore the variations in person and context that will enable a transformative approach to blended learning arrangements. This article investigates physical therapy students' perceptions regarding resources they choose to engage with to support their learning.

Methods.

One hundred and fifteen (59% female); average age 21.7 years; 7.8% international students in the Bachelor of Physiotherapy and Master of Physiotherapy programs at the University of South Australia. A questionnaire with open-ended questions was administered in class and provided data on students' preferences and perceptions regarding resources that support their learning. Students' attendance, online resource usage, and grade point average were collected and used to explore themes emerging from the data.

Results.

Students with higher grades described their own behaviors that assisted their learning while students with lower grades focused on external barriers that limited their learning. Participants chose to attend class because this enabled them to ask questions, access explanations and demonstrations, increase concentration, pick up nonverbal communication, and access teacher support. Participants chose to use online activities because this supported them to work at their own pace, or at an optimal time, or concentrate more.

Discussion.

Participants reported making choices based on perceptions that a particular behavior would contribute to the immediate process of learning or assessment outcomes, rather than long-term goals such as being able to provide the best patient care. Classroom delivery is successful for students who attribute social interaction as a key aspect to their effective learning while online delivery formats meet the needs of students who engage better in private contexts.

Conclusion.

Engagement success may increase if face-to-face sessions have flexible access, while online activities include opportunities for interaction and support.
Current treatment paradigm and landscape for the management of chronic idiopathic constipation in adults: Focus on plecanatide
Authors: Martinez de Andino Nicole
Published: July 2018

Background and purpose:

Chronic idiopathic constipation (CIC) is a prevalent disorder affecting productivity, quality of life, and health care resource utilization. Nurse practitioners (NPs) play a critical function in managing patients presenting with CIC, with roles including evaluation, diagnosis, treatment decisions, and patient education. For adults with inadequate response or tolerability issues using over-the-counter treatments, three prescription agents (plecanatide, linaclotide, and lubiprostone) are available in the United States to treat CIC, of which plecanatide was mostly recently approved. This review provides NPs with a current overview and summary of plecanatide in the current treatment landscape for CIC.

Methods:

PubMed was searched for the literature regarding clinical practice guidelines and published trial data for lubiprostone, linaclotide, and plecanatide in CIC.

Conclusions:

Efficacy and safety comparisons between prescription agents are limited beacause of the differences in trial duration and primary end points (all different). Generally, plecanatide and linaclotide demonstrated similar efficacy, with plecanatide demonstrating lower rates of adverse events.

Implications for practice:

The success of CIC treatment can be affected by patient adherence to the regimen, which is dependent on the efficacy and tolerability of treatment. Plecanatide is a promising option for patients whose CIC symptoms are not adequately controlled using their current treatment approach.
Classic and Hypertrophic Vulvar Lichen Planus
Authors: Day Tania , Weigner Julie , Scurry James
Published: July 2018

Objectives

Three types of lichen planus (LP) occur on the vulva: erosive, classic, and hypertrophic. The latter 2 occur on keratinized skin and little is known about their clinicopathologic appearance.

Materials and Methods

Vulvar biopsies of keratinized skin reported as LP or “lichenoid” between 2011 and 2017 were reviewed. Inclusion required age of older than 18 years, a lichenoid tissue reaction, and insufficient abnormal dermal collagen to diagnose lichen sclerosus. Clinical and histopathologic data were collected and cases were categorized as hypertrophic, classic, or nonspecific lichenoid dermatosis. Descriptive statistics were performed and groups were compared with the Fisher exact test.

Results

Sixty-three cases met criteria for inclusion. Twenty-nine (46%) cases were categorized as hypertrophic LP, 21 (33%) as classic LP, and 13 (21%) as nonspecific lichenoid dermatosis. There were no significant differences in age, primary symptom, biopsy location, or duration of disease between the 3 groups. When compared with classic and nonspecific disease, hypertrophic LP was less likely to have comorbid dermatoses and more likely to be red, diffuse, have scale crust, and contain plasma cells in the infiltrate. Nonspecific disease had similar clinical features to classic LP but was less likely than the other 2 categories to have a dense lymphocytic infiltrate and exocytosis.

Conclusions

Vulvar LP on keratinized skin has a diversity of appearances and presents a clinicopathologic challenge. Further research is required to understand the natural history of hypertrophic LP and the underlying diagnosis of nonspecific lichenoid cases.
Disease activity, steroid use and extraintestinal manifestation are associated with increased disability in patients with inflammatory bowel disease using the inflammatory bowel disease disability index: a cross-sectional multicentre cohort study
Authors: Lo Bobby , Julsgaard Mette , Vester-Andersen Marianne Kajbæk , Vind Ida , Burisch Johan
Published: July 2018

Background

The inflammatory bowel disease disability index (IBD-DI) was developed recently. The aim was to translate the IBD-DI into Danish and validate it for future clinical studies and practice, and to assess the level of disability among IBD patients.

Patients and methods

The IBD-DI was translated using a transcultural adaptation method. Between January and December 2017, patients from three outpatient clinics in three different regions in Denmark were given the final version of the IBD-DI for self-completion. Validation was carried out according to guidelines. Disability level was assessed among the entire cohort and in various subgroups.

Results

A total of 200 patients were included in the study, including 112 Crohn’s disease (CD) and 88 ulcerative colitis (UC) patients. The response rate was 90%. The IBD-DI showed excellent reliability and validity. CD patients showed worse disability levels than UC patients [mean (SD): CD: 37.3 (20.2) vs. UC: 21.7 (16.4); P=0.04]. In both CD and UC, significantly increased disability levels were found between patients with active disease, use of steroid and extraintestinal manifestation (P<0.05).

Conclusion

A valid and reliable version of the IBD-DI is now available in Danish for future studies. Several clinical factors are shown to affect the levels of disability among patients with CD and UC. The disability levels are significantly increased in patients with active disease, treated with systemic steroids, and extraintestinal manifestations are present in both CD and UC. Further testing of the Danish IBD-DI is needed to assess its responsiveness and interpretability.