bluuebunny/crossref_metadata_2025 huggingface dataset:
Surfactant protein D alleviates eosinophil‐mediated airway inflammation and remodeling in patients with aspirin‐exacerbated respiratory disease
Authors: Choi Y. , Lee D.‐H. , Trinh H. K. T. , Ban G.‐Y. , Park H.‐K. , Shin Y. S. , Kim S.‐H. , Park H.‐S.
Published: April 2018

Background

Surfactant protein D (SPD) is a member of the collectin family that lines the airway epithelial cells with host defense. However, the role of SPD in the pathogenesis of aspirin‐exacerbated respiratory disease (AERD) is still unclear.

Methods

The serum SPD level was measured in patients with AERD (n = 336), those with aspirin‐tolerant asthma (ATA, n = 442), and healthy controls (HC, n = 104). Polymorphisms of SFTPD in the study subjects were analyzed. The effect of LTE4 on SPD production through eosinophil infiltration was investigated in BALB/c mice. The protective function of SPD against eosinophils inducing inflammation and remodeling was assessed in vitro/vivo. The potential efficacy of nintedanib against airway remodeling through the production of SPD was evaluated.

Results

The serum SPD level was significantly lower (P < .001) in AERD compared with ATA patients, and negatively correlated with fall in FEV1 (%) after lysine‐aspirin bronchoprovocation test and/or the urinary LTE4 level. In addition, polymorphism of SFTPD at rs721917 was significantly different in the study subjects (odds ratio, 2.124; 95% confidence intervals, 1.310‐3.446; P = .002). LTE4‐exposed mice showed an increased eosinophil count with a decreased SPD level in bronchoalveolar lavage fluid. Eosinophils increased α‐smooth muscle actin expression in airway epithelial cells, which was attenuated by SPD treatment. Furthermore, nintedanib protected the airway epithelial cells against eosinophils by enhancing the production of SPD.

Conclusion

The decreased level of SPD in AERD was associated with airway inflammation/remodeling under the eosinophilic condition, suggesting that modulation of SPD may provide a potential benefit in AERD.
Unlock the Volume: Towards a Politics of Capacity
Authors: Peters Kimberley , Turner Jennifer
Published: April 2018

In recent years “volume” has become a key analytic idea, and tool, for re‐imagining and making sense of historical and contemporary socio‐cultural and geopolitical phenomena. This paper argues that this important work could be pushed in new directions by thinking seriously of how volume might otherwise be interpreted spatially, ascapacity. Accordingly, in this paper, we address what we call a “politics of capacity”. To do so, we draw specifically on debates in carceral geography and, in particular, the pressures on the prison system to illustrate our argument. Drawing on notions of “operational capacities” and “capacity building” in the prison setting, we outline a manifesto for volumetric thinking that moves beyond expressions of power that cut through height, depth and angles, to an understanding of how power is conveyed through maximum and minimum capacities; density and mass; and capacity‐building techniques.
Prediction models for the risk of spontaneous preterm birth based on maternal characteristics: a systematic review and independent external validation
Authors: Meertens Linda J.E. , van Montfort Pim , Scheepers Hubertina C.J. , van Kuijk Sander M.J. , Aardenburg Robert , Langenveld Josje , van Dooren Ivo M.A. , Zwaan Iris M. , Spaanderman Marc E.A. , Smits Luc J.M.
Published: April 2018

Introduction

Prediction models may contribute to personalized risk‐based management of women at high risk of spontaneous preterm delivery. Although prediction models are published frequently, often with promising results, external validation generally is lacking. We performed a systematic review of prediction models for the risk of spontaneous preterm birth based on routine clinical parameters. Additionally, we externally validated and evaluated the clinical potential of the models.

Material and methods

Prediction models based on routinely collected maternal parameters obtainable during first 16 weeks of gestation were eligible for selection. Risk of bias was assessed according to the CHARMS guidelines. We validated the selected models in a Dutch multicenter prospective cohort study comprising 2614 unselected pregnant women. Information on predictors was obtained by a web‐based questionnaire. Predictive performance of the models was quantified by the area under the receiver operating characteristic curve (AUC) and calibration plots for the outcomes spontaneous preterm birth <37 weeks and <34 weeks of gestation. Clinical value was evaluated by means of decision curve analysis and calculating classification accuracy for different risk thresholds.

Results

Four studies describing five prediction models fulfilled the eligibility criteria. Risk of bias assessment revealed a moderate to high risk of bias in three studies. The AUC of the models ranged from 0.54 to 0.67 and from 0.56 to 0.70 for the outcomes spontaneous preterm birth <37 weeks and <34 weeks of gestation, respectively. A subanalysis showed that the models discriminated poorly (AUC 0.51–0.56) for nulliparous women. Although we recalibrated the models, two models retained evidence of overfitting. The decision curve analysis showed low clinical benefit for the best performing models.

Conclusions

This review revealed several reporting and methodological shortcomings of published prediction models for spontaneous preterm birth. Our external validation study indicated that none of the models had the ability to predict spontaneous preterm birth adequately in our population. Further improvement of prediction models, using recent knowledge about both model development and potential risk factors, is necessary to provide an added value in personalized risk assessment of spontaneous preterm birth.
Early echocardiography does not predict subsequent treatment of symptomatic patent ductus arteriosus in extremely preterm infants
Authors: Pereira Sujith S. , Kempley Stephen T. , Shah Divyen K. , Morris Joan K. , Sinha Ajay K.
Published: April 2018

Aim

To determine whether early echocardiographic ductal parameters identified infants who subsequently received medical or surgical treatment of the patent ductus arteriosus (PDA).

Methods

Infants <29 weeks had PDA size in 2D and colour, flow velocity and patterns obtained on days 1 and 3. Infants were followed up to identify those subsequently receiving treatment for symptomatic PDA by clinicians who were unaware of scan results. Receiver operator characteristics curves and logistic regression were performed.

Results

Sixty infants were studied. Mean (SD) gestation and birthweight were 25.8 (1.5) weeks and 817 (190) grams, respectively. Twenty‐four (40%) infants received medical treatment, and nine (15%) infants received surgical ligation of PDA at a median age of 12 and 37 days, respectively. PDA size on days 1 and 3, change in ductal size between days 1 and 3, flow pattern/velocity did not predict whether infants subsequently received medical or surgical management of PDA. Using logistic regression, gestation (p = 0.006) was the only factor that predicted whether infants would subsequently receive medical or surgical treatment for PDA in this cohort.

Conclusion

Echocardiographic ductal parameters on day 1 or 3 did not identify infants who received PDA treatment. Gestation was the most powerful predictor for receiving medical or surgical treatment of PDA.
Breast carcinoma in pregnancy with spheroid‐like placental metastases—a case report
Authors: Froehlich Karolin , Stensheim Hanne , Markert Udo R. , Turowski Gitta
Published: April 2018

Breast cancer is one of the most common malignancies diagnosed in pregnancy. Although the tumor is often detected at an advanced stage, placental metastases are rare. Here, we describe the case of a woman with breast cancer recurrence during pregnancy and subsequent metastases. The focus of this study is the large amount of placenta metastases, which have been analyzed immunohistochemically. Staining with trophoblast markers (placenta alkaline phosphatase, beta human chorionic gonadotropin and human placental lactogen) showed the strict localization of metastases in the intervillous space without invasion into fetal tissue. They have a large spheroidal shape and are free of blood vessels. Staining with Ki‐67 revealed an outer proliferative shell and inner necrotic core. At week 28, a healthy newborn was born by elective cesarean section. A few weeks later, after surgery and FEC60 (fluorouracil, epirubicin, cyclophosphamide) cycles, the patient died. Breast cancer metastases in the placenta are rarely described. The special immunological environment in pregnancy may influence phenotype, growth, and behavior of tumor and metastases.
Recurrent coronary disease in HIV‐infected patients: role of drug–drug interactions
Authors: Bravo Iria , Álvarez Hortensia , Mariño Ana , Clotet Bonaventura , Moltó José
Published: April 2018

Cardiovascular disease represents a leading comorbidity in HIV populations. Different factors may contribute to the recurrence of cardiovascular events in HIV‐infected patients. Here, we describe two patients with HIV infection and an acute coronary syndrome who developed in‐stent thrombosis after a percutaneous revascularization procedure. Also, we discuss the potential role of drug interactions between antiretroviral and antiplatelet treatments as a contributing factor for recurrent coronary disease in HIV‐infected patients.
Patterns of antidepressant use during pregnancy: a nationwide population‐based cohort study
Authors: Bénard‐Laribière Anne , Pambrun Elodie , Sutter‐Dallay Anne‐Laure , Gautier Sophie , Hurault‐Delarue Caroline , Damase‐Michel Christine , Lacroix Isabelle , Bégaud Bernard , Pariente Antoine
Published: April 2018

Aims

We explored the patterns of antidepressant use during pregnancy.

Methods

A cohort of women who started a pregnancy in 2014 was identified using data from the French reimbursement healthcare system (covering approximately 99% of the population). Antidepressant usage (initiated before or during pregnancy) was assessed. Explored changes in antidepressant treatment were: associations, switches, discontinuation and resumption of antidepressants during pregnancy.

Results

The cohort included 766 508 pregnancies (755 519 women). Antidepressant use during pregnancy was 25.7 per 1000 [95% CI: 25.3–26.0]. New use concerned 3.9 per 1000 [95% CI: 3.7–4.0]; the most initiated class during pregnancy was selective serotonin reuptake inhibitors (SSRIs), while the most prescribed individual drug in second and third trimesters was amitriptyline, a tricyclic. Most changes were observed before pregnancy and during the first trimester: 63% of ongoing treatments in the year before pregnancy were discontinued before conception; 68% of treatments maintained after conception were discontinued during the first trimester; switches or antidepressant associations mostly occurred during the periconceptional period or during the first trimester. Regardless of initial antidepressant, switches to sertraline were the most frequent. Associations mainly consisted of a prescription of tri‐/tetracyclic or mirtazapine/mianserin in addition to an SSRI. Discontinuation during pregnancy led to treatment resumption in 22% of pregnancies.

Conclusions

These results suggest that pregnancy was planned or the treatment especially adapted in accordance with existing recommendations in a large proportion of women under antidepressants or in whom such treatments have been initiated after starting a pregnancy.
Optimization of a drug transporter probe cocktail: potential screening tool for transporter‐mediated drug–drug interactions
Authors: Stopfer Peter , Giessmann Thomas , Hohl Kathrin , Hutzel Sabine , Schmidt Sven , Gansser Dietmar , Ishiguro Naoki , Taub Mitchell E. , Sharma Ashish , Ebner Thomas , Müller Fabian
Published: April 2018

Aims

Previous pharmacokinetic characterization of a transporter probe cocktail containing digoxin (P‐gp), furosemide (OAT1, OAT3), metformin (OCT2, MATE1, MATE2‐K) and rosuvastatin (OATP1B1, OATP1B3, BCRP) in healthy subjects showed increases in rosuvastatin systemic exposure compared to rosuvastatin alone. In this trial, the doses of metformin and furosemide as putative perpetrators were reduced to eliminate their drug–drug interaction (DDI) with rosuvastatin.

Methods

In a randomized, open‐label, single‐centre, five‐treatment, five‐period crossover trial, 30 healthy male subjects received as reference treatments separately 0.25 mg digoxin, 1 mg furosemide, 10 mg metformin and 10 mg rosuvastatin, and as test treatment all four drugs administered together as a cocktail. Primary pharmacokinetic endpoints were AUC0‐tz (area under the plasma concentration–time curve from time zero to the last quantifiable concentration) and Cmax (maximum plasma concentration) of each probe drug.

Results

Geometric mean ratios and 90% confidence intervals of test (cocktail) to reference (single drug) for AUC0‐tz were 96.4% (88.2–105.3%) for digoxin, 102.6% (93.8–112.3%) for furosemide, 97.5% (93.5–101.6%) for metformin and 105.0% (96.4–114.4%) for rosuvastatin, indicating lack of interaction. The same analysis for Cmax and for pharmacokinetic parameters of urinary excretion of all cocktail components also indicated no DDI.

Conclusions

Digoxin (0.25 mg), furosemide (1 mg), metformin (10 mg) and rosuvastatin (10 mg) exhibit no mutual pharmacokinetic interactions and are well tolerated administered as a cocktail. The cocktail is thus optimized and has the potential to be used as a screening tool for clinical investigation of transporter‐mediated DDI.
A Whole‐Body Physiologically Based Pharmacokinetic Model for Colistin and Colistin Methanesulfonate in Rat
Authors: Bouchene Salim , Marchand Sandrine , Couet William , Friberg Lena E. , Gobin Patrice , Lamarche Isabelle , Grégoire Nicolas , Björkman Sven , Karlsson Mats O.
Published: April 2018

Colistin is a polymyxin antibiotic used to treat patients infected with multidrug‐resistant Gram‐negative bacteria (MDR‐GNB). The objective of this work was to develop a whole‐body physiologically based pharmacokinetic (WB‐PBPK) model to predict tissue distribution of colistin in rat. The distribution of a drug in a tissue is commonly characterized by its tissue‐to‐plasma partition coefficient, Kp. Colistin and its prodrug, colistin methanesulfonate (CMS) Kp priors, were measured experimentally from rat tissue homogenates or predicted in silico. The PK parameters of both compounds were estimated fitting in vivo their plasma concentration–time profiles from six rats receiving an i.v. bolus of CMS. The variability in the data was quantified by applying a nonlinear mixed effect (NLME) modelling approach. A WB‐PBPK model was developed assuming a well‐stirred and perfusion‐limited distribution in tissue compartments. Prior information on tissue distribution of colistin and CMS was investigated following three scenarios: Kp was estimated using in silico Kp priors (I) or Kp was estimated using experimental Kp priors (II) or Kp was fixed to the experimental values (III). The WB‐PBPK model best described colistin and CMS plasma concentration–time profiles in scenario II. Colistin‐predicted concentrations in kidneys in scenario II were higher than in other tissues, which was consistent with its large experimental Kp prior. This might be explained by a high affinity of colistin for renal parenchyma and active reabsorption into the proximal tubular cells. In contrast, renal accumulation of colistin was not predicted in scenario I. Colistin and CMS clearance estimates were in agreement with published values. The developed model suggests using experimental priors over in silico Kp priors for kidneys to provide a better prediction of colistin renal distribution. Such models might serve in drug development for interspecies scaling and investigate the impact of disease state on colistin disposition.
The role of defensive symbionts in host–parasite coevolution
Authors: Vorburger Christoph , Perlman Steve J.
Published: April 2018

Understanding the coevolution of hosts and parasites is a long‐standing goal of evolutionary biology. There is a well‐developed theoretical framework to describe the evolution of host–parasite interactions under the assumption of direct, two‐species interactions, which can result in arms race dynamics or sustained genotype fluctuations driven by negative frequency dependence (Red Queen dynamics). However, many hosts rely on symbionts for defence against parasites. Whilst the ubiquity of defensive symbionts and their potential importance for disease control are increasingly recognized, there is still a gap in our understanding of how symbionts mediate or possibly take part in host–parasite coevolution. Herein we address this question by synthesizing information already available from theoretical and empirical studies. First, we briefly introduce current hypotheses on how defensive mutualisms evolved from more parasitic relationships and highlight exciting new experimental evidence showing that this can occur very rapidly. We go on to show that defensive symbionts influence virtually all important determinants of coevolutionary dynamics, namely the variation in host resistance available to selection by parasites, the specificity of host resistance, and the trade‐off structure between host resistance and other components of fitness. In light of these findings, we turn to the limited theory and experiments available for such three‐species interactions to assess the role of defensive symbionts in host–parasite coevolution. Specifically, we discuss under which conditions the defensive symbiont may take over from the host the reciprocal adaptation with parasites and undergo its own selection dynamics, thereby altering or relaxing selection on the hosts' own immune defences. Finally, we address potential effects of defensive symbionts on the evolution of parasite virulence. This is an important problem for which there is no single, clear‐cut prediction. The selection on parasite virulence resulting from the presence of defensive symbionts in their hosts will depend on the underlying mechanism of defence. We identify the evolutionary predictions for different functional categories of symbiont‐conferred resistance and we evaluate the empirical literature for supporting evidence. We end this review with outstanding questions and promising avenues for future research to improve our understanding of symbiont‐mediated coevolution between hosts and parasites.
Associations Among Mothers’ Depression, Emotional and Learning‐Material Support to Their Child, and Children's Cognitive Functioning: A 16‐Year Longitudinal Study
Authors: Wu Victoria , East Patricia , Delker Erin , Blanco Estela , Caballero Gabriela , Delva Jorge , Lozoff Betsy , Gahagan Sheila
Published: April 2018

This study examined the associations among maternal depression, mothers’ emotional and material investment in their child, and children's cognitive functioning. Middle‐class Chilean mothers and children (N = 875; 52% males) were studied when children were 1, 5, 10, and 16 years (1991–2007). Results indicated that highly depressed mothers provided less emotional and material support to their child across all ages, which related to children's lower IQ. Children with lower mental abilities at age 1 received less learning‐material support at age 5, which led to mothers’ higher depression at child age 10. Mothers’ low support was more strongly linked to maternal depression as children got older. Findings elucidate the dynamic and enduring effects of depression on mothers’ parenting and children's development.
Peanut gastrointestinal delivery oral immunotherapy in adolescents: Results of the build‐up phase of a randomized, double‐blind, placebo‐controlled trial (PITA study)
Authors: Fauquert J.‐L. , Michaud E. , Pereira B. , Bernard L. , Gourdon‐Dubois N. , Rouzaire P.‐O. , Rochette E. , Merlin E. , Evrard B. ,   the PITA Group
Published: April 2018

Background

Oral immunotherapy to peanut is effective in desensitizing patients but has significant side effects including anaphylaxis and gastrointestinal symptoms. In most protocols, peanut is administered in a vehicle food.

Objective

In an exclusively adolescent population, we tested a new approach using sealed capsules of peanut (gastrointestinal delivery oral immunotherapy or GIDOIT) to bypass the upper gastrointestinal tract. The primary aim was to assess the efficacy of the oral build‐up phase of GIDOIT and the secondary aim to analyse its safety.

Methods

Adolescents with a history of a clinical allergic reaction after peanut ingestion were included in a 2‐armed, parallel‐design, individually randomized, double‐blind, placebo‐controlled, multicentre trial after a positive double‐blind placebo‐controlled oral food challenge (DBPCFC1). A central randomization centre used computer‐generated tables to allocate treatments. Peanut (or placebo) capsules were ingested daily over a period of 24 weeks with increments every 2 weeks from 2 to 400 mg of peanut protein (pp). Primary outcome was tolerance of 400 mg of pp at DBPCFC2.

Results

Thirty patients were included between September 2013 and May 2014. At DBPCFC2, unresponsiveness to 400 mg of pp was achieved in 17/21 peanut group patients (2 withdrawn patients) and 1/9 in the placebo group (Intention‐to‐treat analysis, P < .001, absolute difference = 0.7, 95%IC 0.43 0.96). Oropharyngeal symptoms were equally frequent in both groups. No dysphagia or other signs of eosinophilic oesophagitis occurred. Digestive adverse events (AE) were more frequent in the treated group (P = .02), but mild and without compliance issues. Only one severe advent event led to withdrawal in a patient who ingested twice the investigated treatment. Peanut‐specific humoral immune responses were modulated.

Conclusion

The GIDOIT protocol demonstrated clinical and immunological efficacy and had an acceptable level of safety with weak oropharyngeal symptoms, no dysphagia, mild digestive events and few severe systemic AE.
The rheumatic disease-associated FAM167A-BLK locus encodes DIORA-1, a novel disordered protein expressed highly in bronchial epithelium and alveolar macrophages
Authors: Mentlein L , Thorlacius G E , Meneghel L , Aqrawi L A , Ramírez Sepúlveda J I , Grunewald J , Espinosa A , Wahren-Herlenius M
Published: April 2018

Triggering of autoimmunity that leads to rheumatic disease has been suggested to depend upon gene–environment interactions occurring in epithelial barriers and associated immune cells. Genetic studies have identified associations of the FAM167A-BLK locus with rheumatoid arthritis, systemic lupus erythematosus (SLE) and Sjögren's syndrome. While BLK (B lymphocyte kinase) has a well-established role in B cells, family with sequence similarity to 167 member A (FAM167A) and its gene family remain uncharacterized. To begin to understand the role of FAM167A in rheumatic disease pathogenesis, we explored this gene family and cloned and investigated the gene products. Expression of quantitative trait locus analysis was performed in immune cells. FAM167A and FAM167B were cloned from human peripheral blood mononuclear cells (PBMC). Gene conservation and protein properties were analysed by online tools, mRNA expression measured in mouse organs by quantitative polymerase chain reaction (qPCR) and protein expression investigated in human tissues by immunohistochemistry. We found that autoimmune risk genotypes within the FAM167A-BLK locus lead to increased expression of FAM167A. The FAM167 gene family includes two members, FAM167A and FAM167B, which are not homologous to any other annotated gene but are evolutionarily conserved. The encoded proteins, which we denote ‘disordered autoimmunity’ (DIORA)-1 and DIORA-2, respectively, are characterized by a high content of intrinsic disorder. Notably, DIORA-1 has its highest expression in the lung, detectable in both bronchial epithelium and alveolar macrophages with an endosomal localization pattern. In summary, the FAM167A gene is associated with several rheumatic diseases and encodes a novel disordered protein, DIORA-1, which is expressed highly in the lung, consistent with a potential role in disease pathogenesis.
Needs and preferences of parents of adolescents with multiple and complex needs in residential care
Authors: Van den Steene Helena , van West Dirk , Glazemakers Inge
Published: April 2018

The perspective of parents whose children are in residential care, has received only minor attention in the literature, despite evidence pointing out the value of parental involvement in care delivery for their child. Drawing upon in‐depth interviews with 12 parents of adolescent girls with multiple and complex needs in residential child welfare, this exploratory study describes parents' own needs and preferences with regard to care delivery. Parents wish: (a) to have a true partnership between parents and professionals (involvement), (b) to feel respected by professionals (respect), (c) to have the information and mandate necessary for decision‐making (agency), and (d) to receive consideration and (emotional) support, besides advice on how to handle the challenges their family faces (support). Their plea draws attention to an aspect of the dimension of “parent–caregiver partnership” in family‐centred residential care that deserves more emphasis. Indeed, being attentive to the needs of parents can contribute to the optimization of services for the most vulnerable families.
“It Was Love in All the Buildings They Tore Down”: How Caregiving Grandmothers Create and Experience a Sense of Community in Chicago Public Housing
Authors: Pittman LaShawnDa , Oakley Deirdre
Published: April 2018

About 16,000 families residing in Chicago's public housing have been relocated over the last two decades through the U.S. Department of Housing and Urban Development's Housing Opportunities for People Everywhere (HOPE VI) redevelopment initiative. We situate this paper within a larger conversation about the presence and utilization of community ties within public housing despite the territorial stigmatization of traditional public housing. Utilizing in–depth interviews with 20 Black caregiving grandmothers relocated from Chicago public housing we explore how women charged with performing the lion's share of the kinwork needed to ensure family stability experienced and created a sense of community while living in public housing. We show that by providing (1) safety nets for multiple generations, (2) social support and connections to neighborhood institutions, as well as (3) opportunities for Black activist mothering, these women, often at the heart of vertical lineages, created a sense of community amidst the problems in their communities.
The Gentrifier's Dilemma: Narrative Strategies and Self–Justifications of Incoming Residents in Bedford–Stuyvesant, Brooklyn
Authors: Donnelly Kathleen
Published: April 2018

This paper examines how gentrifiers negotiate tensions between the narratives of liberal progressivism they espouse and their role in neighborhood change. Through in–depth interviews with recent residents in a gentrifying neighborhood in Brooklyn, this paper identifies patterns in rhetorical strategies and narrative techniques employed by interviewees to manage points of conflict. It finds that gentrifiers express ambivalence and feelings of guilt surrounding their presence in the neighborhood and that they manage this ambivalence through three main strategies: (1) reframing the outcomes of gentrification in positive terms, (2) distinguishing their behaviors and attitudes from the stereotypical “bad” gentrifier, and (3) displacing their responsibility for the process of gentrification onto another group of actors, such as the government or real estate developers. These results provide a framework for understanding how individuals justify their complicity in other processes which they see as morally questionable, such as unethical consumerism.
Memory Politics: Growth Coalitions, Urban Pasts, and the Creation of “Historic” Philadelphia
Authors: Hunter Marcus Anthony , Loughran Kevin , Fine Gary Alan
Published: April 2018

Facing economic changes and disinvestment, powerful actors in post–World War II American cities attempted to define the city as a space of public culture to confront demographic shifts, suburban growth, and the breakdown of community. Some civic actors, especially in older Eastern cities, looked to a nostalgic and heroic past where a theme of American identity became salient as a result of the Cold War and rapid cultural and economic changes in the postwar era. To achieve urban growth, elites argued for urban redevelopment policies based on historical themes and imagery. We examine the sociopolitical history of Philadelphia's Independence Hall redevelopment project (1948–1959) and the development of the adjacent Society Hill neighborhood (1959–1964). We offer the framework of memory politics—political contests over the use of shared community history—to examine how growth coalitions implement plans for economic growth, tourism, and civic allegiance. Philadelphia, particularly during the postwar era, exemplifies how heritage, politics, and place dynamically collide and direct urban development.
A retrospective study on the crestal bone loss associated with different implant surfaces in chronic periodontitis patients under maintenance
Authors: Gallego Luis , Sicilia Alberto , Sicilia Pelayo , Mallo Carmen , Cuesta Susana , Sanz Mariano
Published: April 2018

Objective

To analyze retrospectively interproximal crestal bone loss (CBL) on external‐hex “non‐identical” (NI) dental implants with different surface topography, when placed in the same intra‐oral location in patients with a history of chronic periodontitis following maintenance care.

Material and methods

The patient population consisted of 206 consecutive patients with a history of chronic periodontitis who underwent implant surgery between 2007 and 2010; 755 NI implants with different implant surfaces were placed at posterior mandibular sites: 72 machined, 145 acid‐etched/machined (hybrid), and 538 anodized. Crestal bone loss measurements were carried out analyzing the calibrated digital X‐rays taken at 1‐year intervals as part of the maintenance program, being the time of this retrospective examination from 1 to 3 years.

Results

At 3 years (51 patients), the mean CBL was 1.36/1.35 mm at implant/patient level (range: 0–6 mm). A higher CBL was observed at anodized surface implants, when compared to machined and hybrid implants, being the mean CBL 1.48, 0.96, and 0.77 mm, respectively (p = .005). CBL between 2 and 3.9 mm was found in 10.6% of the implants at 3 years (95% CI: 6%–15%), ≥4 mm in 5% (95% CI: 2%–8%). Anodized surface implants had CBL >2 mm at 2 years of 9% (95% CI: 6%–12%) and at 3 years of 18% (95% CI: 12%–24%), which were 2.5 times higher than hybrid implants with 3.6% (95% CI: 0.8%–4%) and 7.4% (95% CI: 0%–17%), respectively.

Conclusions

A higher CBL was observed in the anodized surface implants group, when compared to the hybrid implants group in patients with a history of chronic periodontitis followed during 1–3 years.
Effects of inspiratory muscle training in COPD patients: A systematic review and meta‐analysis
Authors: Beaumont Marc , Forget Patrice , Couturaud Francis , Reychler Gregory
Published: April 2018

Objectives

In chronic obstructive pulmonary disease (COPD), quality of life and exercise capacity are altered in relationship to dyspnea. Benefits of inspiratory muscle training (IMT) on quality of life, dyspnea, and exercise capacity were demonstrated, but when it is associated to pulmonary rehabilitation (PR), its efficacy on dyspnea is not demonstrated. The aim of this systematic review with meta‐analysis was to verify the effect of IMT using threshold devices in COPD patients on dyspnea, quality of life, exercise capacity, and inspiratory muscles strength, and the added effect on dyspnea of IMT associated with PR (vs. PR alone).

Study selection

This systematic review and meta‐analysis was conducted on the databases from PubMed, Science direct, Cochrane library, Web of science, and Pascal. Following key words were used: inspiratory, respiratory, ventilatory, muscle, and training. The searching period extended to December 2017. Two reviewers independently assessed studies quality.

Results

Forty‐three studies were included in the systematic review and thirty‐seven studies in the meta‐analysis. Overall treatment group consisted of six hundred forty two patients. Dyspnea (Baseline Dyspnea Index) is decreased after IMT. Quality of life (Saint George's Respiratory Questionnaire), exercise capacity (6 min walk test) and Maximal inspiratory pressure were increased after IMT. During PR, no added effect of IMT on dyspnea was found.

Conclusion

IMT using threshold devices improves inspiratory muscle strength, exercise capacity and quality of life, decreases dyspnea. However, there is no added effect of IMT on dyspnea during PR (compared with PR alone).
Hand‐assisted laparoscopic retroperitoneal donor nephrectomy: A single‐institution experience of over 500 cases—Operative technique and clinical outcomes
Authors: Kumar Sanjaya , Witt Russell G. , Tullius Stefan G. , Malek Sayeed K.
Published: April 2018

Objective

Although there are several variations of laparoscopic living‐donor nephrectomies, there is no consensus as to the best technique. Our objective was to describe our technique and assess the outcomes of our approach to hand‐assisted laparoscopic retroperitoneal donor nephrectomies.

Methods

From July 2001 to October 2015, 507 consecutive hand‐assisted laparoscopic retroperitoneal donor nephrectomies were performed. Their clinical information was retrospectively reviewed including warm ischemia time, skin incision to kidney ready time, estimated blood loss, adverse intraoperative events, and postoperative complications.

Results

Mean incision time to kidney removal was 135 minutes (55‐260), mean warm ischemia time was 125 seconds (30‐390), and mean blood loss was 83 mL (20‐500). Average length of stay was 3 days (1‐6). There were no significant differences between left and right kidney donors based on demographics, length of hospital stay, or warm ischemia time. There were no conversions to open surgery. Complications occurred in 4.9% of patients (25/507), including 4 cases of perioperative bleeding.

Conclusions

This is a single‐center series describing the safety and efficacy of the hand‐assisted laparoscopic retroperitoneal donor nephrectomy for both right and left sides. It does not require intraperitoneal manipulation and allows for safe extraction of either kidney with minimal warm ischemia time.
Macroeconomic Effects of 21st Century Trade and Investment Agreements: The Case of the Trans‐Pacific Partnership
Authors: Capaldo Jeronim , Izurieta Alex
Published: April 2018

Following United States withdrawal, the Trans‐Pacific Partnership agreement (TPP) is likely to be replaced or complemented by a series of bilateral deals between the US and TPP partners. In this case, TPP will shape trade, finance and public policy globally even without formal US participation. Proponents of TPP emphasize its prospective economic benefits, with economic growth increasing due to rising trade volumes and investment. Widely cited projections suggest modest GDP gains after 10 years, varying from less than half a percentage point in the USA to 13 per cent in Vietnam. However, these projections assume full employment and constant income distribution in all countries, excluding some of the major risks of trade liberalization. This article provides alternative projections of the TPP's economic effects using the United Nations Global Policy Model, which allows for changes in employment and income distribution. Using this model, the authors obtain very different results. They find that the benefits to economic growth are even smaller than those projected with full‐employment models, and are negative for Japan and the USA. More importantly, they find that the TPP will likely lead to losses in employment and increases in inequality.
LGBT Advocacy and Transnational Funding in Singapore and Malaysia
Authors: Ng Eve
Published: April 2018

LGBT advocacy is an emergent site attracting transnational funding from an expanded set of donor types that now include private corporations, national governments, NGOs, intergovernmental organizations and public–private partnerships. This article discusses LGBT advocacy as involving an expanded range of issues that go beyond a traditional focus on HIV/AIDS prevention. The geographical focus is on Singapore and Malaysia, two Southeast Asian countries where homosexuality is officially illegal. Alongside the global politics of LGBT rights, previous critiques about external funding and North/South asymmetries in transnational aid raise questions about its effectiveness for transformative socio‐political change, and its political and theoretical implications. Three case studies are examined: Pink Dot Singapore, and the PT Foundation and Kuala Lumpur activist workshops in Malaysia. The data demonstrate the capacity for transnational support to contribute to grassroots activism and coalitional politics. However, significant observable outcomes are currently limited, partly because most of the grants are modest, and Singapore and Malaysia's high‐ and middle‐income status excludes them from various funding bodies. Furthermore, domestic resistance to transnational funding has emerged, constituting more widespread discourses in which anti‐LGBT sentiment is framed in terms of opposing Western encroachments and the dominance of the global North.
Exenatide effects on gastric emptying rate and the glucose rate of appearance in plasma: A quantitative assessment using an integrative systems pharmacology model
Authors: Voronova Veronika , Zhudenkov Kirill , Penland Robert C. , Boulton David W. , Helmlinger Gabriel , Peskov Kirill
Published: April 2018

This study aimed to quantify the effect of the immediate release (IR) of exenatide, a short‐acting glucagon‐like peptide‐1 (GLP‐1) receptor agonist (GLP‐1RA), on gastric emptying rate (GER) and the glucose rate of appearance (GluRA), and evaluate the influence of drug characteristics and food‐related factors on postprandial plasma glucose (PPG) stabilization under GLP‐1RA treatment. A quantitative systems pharmacology (QSP) approach was used, and the proposed model was based on data from published sources including: (1) GLP‐1 and exenatide plasma concentration‐time profiles; (2) GER estimates under placebo, GLP‐1 or exenatide IR dosing; and (3) GluRA measurements upon food intake. According to the model's predictions, the recommended twice‐daily 5‐ and 10‐μg exenatide IR treatment is associated with GluRA flattening after morning and evening meals (48%‐49%), whereas the midday GluRA peak is affected to a lesser degree (5%‐30%) due to lower plasma drug concentrations. This effect was dose‐dependent and influenced by food carbohydrate content, but not by the lag time between exenatide injection and meal ingestion. Hence, GER inhibition by exenatide IR represents an important additional mechanism of its effect on PPG.
On the relationship between intermediate input imports and export quality in China
Authors: Xu Jiayun , Mao Qilin
Published: April 2018

This paper studies the connection between intermediate input imports and firms’ export quality using firm‐level data from 2000 to 2007. Our regression results show that intermediate input imports promote manufacturing firms’ export quality through ‘variety effects’ and ‘innovation effects’, though the effects are significantly different among firms with different characteristics, and the magnitude of these effects differs across import sources and the quality of imported intermediate inputs themselves. Moreover, we find that a good institutional environment is conducive to the strengthening of the positive influence of intermediate input imports on export quality. Furthermore, the dynamic decomposition demonstrates that the reallocation effect is the key force through which imported inputs boost industrial aggregate quality growth. Taken together, these results suggest that product upgrading facilitated by quality embedded in imported intermediate inputs, a good institutional environment and market share reallocation help Chinese firms to improve the quality of their export products.
Effect of ethylenediaminetetraacetic acid and hyaluronic acid on the viability and cytokine expression of periodontal ligament fibroblasts
Authors: França Monique Costa Moreira , da Silva Tânia Mara , Silva Gleyce Oliveira , Valera Márcia Carneiro , Camargo Carlos Henrique Ribeiro
Published: April 2018

Background/Aims

Dental root cell proliferation following tooth avulsion has not been well researched. Understanding the effects of dry time and dentin treatment influences on cell proliferation is essential to provide evidence‐based guidelines for tooth replantation. The study evaluated the viability of periodontal ligament fibroblasts (PLF) in contact with roots, submitted to surface treatments with ethylenediaminetetraacetic acid (EDTA) and hyaluronic acid (HA) at different times, including to quantify inflammatory cytokines interleukin (IL)‐6, IL‐8, IL‐1β and TNF‐α expressed by PLF. The adhesion of fibroblasts to treated root surfaces was also evaluated.

Material and Methods

One hundred and eight cementum discs from bovine teeth were randomly divided into groups according to time periods of being dry (n = 12) as follows: (i) fresh discs that were not kept dry, (WD); (ii) dry for 1 hour (1 hd); and (iii) dry for 24 hours (24 hd). The discs were subdivided into 3 subgroups (n = 12) according to surface treatments: (iv) no treatment, (v) treatment with EDTA, (vi) treatment with HA. The discs were placed in 96‐well plates, and PLF were seeded and kept in contact with the discs for 48 hours. Cell viability on the surface of the discs was assessed by XTT, and PLF adhesion was evaluated using scanning electron microscopy (SEM). Quantification of cytokines was performed using enzyme‐linked immunosorbent assay (ELISA). Data were submitted to ANOVA and Tukey's test (α = .05).

Results

Surface treatment had a statistically significant effect on the cell viability in groups WD (P = .03), 1 hd (P = .01) and 24 hd (P = .048). PLF in contact with dried root surfaces expressed more cytokines without treatment with IL‐6 decreasing the expression when treated with HA for 24 hours. SEM also showed adhesion of PLF to the surface of all discs at all time periods.

Conclusion

EDTA + HA is an alternative treatment for cases of avulsed teeth as it promoted adhesion and increased viability of PLF.
Malignant lymphoma in the HIV‐positive patient
Authors: Meister Anne , Hentrich Marcus , Wyen Christoph , Hübel Kai
Published: April 2018

The introduction of combination antiretroviral therapy (cART) drastically improved performance status, immune function, and life expectancy of HIV‐infected individuals. In addition, incidence of opportunistic infections and of AIDS‐defining malignancies declined. Nevertheless, aggressive non‐Hodgkin’s lymphoma still remains the leading cause of AIDS‐related deaths. The availability of cART, however, significantly improved the therapeutic options for HIV‐positive patients with lymphomas. Diffuse large B‐cell lymphoma, Burkitt’s lymphoma, or Hodgkin lymphoma has increasingly become curable diseases. In light of these favorable developments in the treatment of HIV and HIV‐associated lymphomas, reduction in treatment‐associated toxicities and further improvement of outcome of patients with advanced immune suppression are major requirements for future clinical trials. This review summarizes the current treatment landscape and gives an overview on future needs in HIV‐positive patients with lymphoma.
Hume's distinction between impressions and ideas
Authors: Rickless Samuel C.
Published: April 2018

An important part of Hume's philosophy is grounded in a fundamental distinction between two kinds of perceptions: impressions and ideas. Existing views of the distinction are that the former are livelier than the latter, that the former are causally prior to the latter, that the latter are copies of the former, that the former but not the latter are perceptions of an objective realm, and that the former are feelings whereas the latter are thoughts. I argue that all of these views of the distinction are problematic and should be replaced by the Reflection view, according to which (simple) ideas are, while impressions are not, the direct products of reflection on other perceptions.
Long‐term efficacy of add‐on lacosamide treatment in children and adolescents with refractory epilepsies: A single‐center observational study
Authors: Rosati Anna , Ilvento Lucrezia , Rizzi Riccardo , Doccini Viola , Leo Maria Carmela , Pugi Alessandra , De Masi Salvatore , Guerrini Renzo
Published: April 2018

Objective

To assess long‐term efficacy and tolerability of lacosamide (LCM) as adjunctive treatment through a retrospective study in children and adolescents with refractory epilepsies.

Methods

All patients consecutively treated with LCM as add‐on for refractory focal and generalized epilepsy and followed at the Neuroscience Center of Excellence of the Meyer Children's Hospital of Florence between January 2011 and September 2015 were included in the study. Responder rate, relapse‐free survival, and retention rate were calculated. Tolerability was assessed by reporting adverse events.

Results

A total of 88 individuals (41 female) aged 4 months to 18 years (median 10.5 years; mean ± SD 10.6 ± 4.8 years) received add‐on LCM treatment for refractory epilepsy. Thirty‐four patients (38.6%) were responders with a median time to relapse of 48 months. Nine (26.4%) of the 34 responders were seizure‐free. For all 88 patients, the probability of remaining on LCM without additional therapy was 74.4% at 6 months, 47.7% at 12 months, 27.9% at 24 months, 18.0% at 48 months, and 8.2% at 72 months of follow‐up. No statistically significant differences in relapse and retention time were observed with regard to epilepsy and seizure types, duration and course of epilepsy, number and type of antiepileptic drugs (AEDs; sodium channel blockers vs others) used in add‐on. The most frequent adverse events were dermatological (4/11) and behavioral (3/11).

Significance

This study documents a real‐world progressive and significant loss of LCM efficacy over time in a pediatric population. Further prospective studies on larger populations are required to confirm the remarkable loss of LCM efficacy over time.