bluuebunny/crossref_metadata_2025 huggingface dataset:
Association Between Extent of Stent-Graft Coverage and Thoracic Aortic Remodeling After Endovascular Repair of Type B Aortic Dissection
Authors: Xue Yan , Ge Yangyang , Ge Xiaohu , Miao Jianhang , Fan Weidong , Rong Dan , Liu Feng , Liu Xiaoping , Guo Wei
Published: February 2020

Purpose: To examine the association between the extent of stent-graft coverage and thoracic aortic expansion after thoracic endovascular aortic repair (TEVAR) for type B aortic dissection. Materials and Methods: A retrospective analysis was conducted of 201 patients (mean age 52.4±11.5 years; 178 men) with acute (135, 67.2%) or chronic (66, 32.8%) type B aortic dissection who underwent TEVAR at 4 medical centers. The mean stent-graft length was 157.1±33.3 mm. The percentage of stented descending aorta (PSDA) represented the extent of stent-graft coverage. After using restricted cubic smoothing spline plots to confirm the roughly linear relationship between PSDA and the risk of thoracic aortic expansion, patients were stratified into 2 groups on the median PSDA: the lower group (≤31.3%) and the higher group (>31.3%). Thoracic aortic expansion was defined as a ≥20% increase in the total thoracic aortic volume on the most recent postoperative computed tomography angiography scan compared with the preoperative measurement. The Kaplan-Meier method was used to estimate the cumulative freedom from thoracic aortic expansion after TEVAR; estimates are given with the 95% confidence interval (CI). A multivariable Cox proportional hazards model was used to analyze any independent association of the PSDA as a continuous or categorical variable with the risk of thoracic aortic expansion; results are presented as the hazard ratio (HR) and 95% CI. Results: No patients developed symptoms of spinal cord ischemia during hospitalization. Over a median 12.4 months of imaging follow-up, 34 (16.9%) patients developed thoracic aortic expansion. The estimate of freedom from thoracic aortic expansion at 12 months for the overall PSDA was 84.0% (95% CI 77.8% to 88.6%); between the groups, the freedom from thoracic aortic expansion estimate for the PSDA ≤31.3% group was significantly lower than in the higher group (p=0.032). Regression analysis showed no significant association between the risk of thoracic aortic expansion and the PSDA as a continuous variable (HR 0.97, 95% CI 0.91 to 1.03, p=0.288); however, analyzing the PSDA as a categorical variable indicated a significantly lower risk of thoracic aortic expansion for the PSDA >31.3% group (HR 0.46, 95% CI 0.22 to 0.95, p=0.036) after adjusting for a variety of demographic and anatomical characteristics. Conclusion: More extensive stent-graft coverage appears to improve thoracic aortic remodeling after TEVAR. However, the clinician should balance the benefit of extensive stent-graft coverage and its related risk of spinal cord ischemia.
The Relationships Between Sport Club Activities and University and Member Attachment
Authors: Lower-Hoppe Leeann M. , Beattie Mark A. , Wray Daniel E. , Bailey Richard L. , Newman Tarkington J. , Farrell Annemarie
Published: February 2020

Given the social purpose of sport clubs, an anticipated outcome of club participation is a sense of attachment to the university and campus community. However, the sport behaviors that contribute to club members’ social attachment are largely unknown. Therefore, this study sought to examine which sport club activities are related to university and member attachment. A survey was administered to 175 sport club members at a large public university in the United States. Using a multivariate analysis of variance, sport clubs with moderately low to high social inclusionary tactics reported significantly greater university attachment than clubs with low tactics. Additionally, clubs with high social inclusionary tactics reported significantly greater member attachment than clubs with low to moderately high tactics. No significant difference in attachment was found when accounting for clubs’ frequency of competition or travel. The findings support the use of formal socialization to enhance club members’ feelings of attachment.
Pathogenesis of non-hereditary brain arteriovenous malformation and therapeutic implications
Authors: Ota Takahiro , Komiyama Masaki
Published: February 2020

Brain arteriovenous malformations have a high risk of intracranial hemorrhage, which is a substantial cause of morbidity and mortality in patients with brain arteriovenous malformations. Although a variety of genetic factors leading to hereditary brain arteriovenous malformations have been extensively investigated, their pathogenesis is still not well elucidated, especially in sporadic brain arteriovenous malformations. The authors have reviewed the updated data of not only the genetic aspects of sporadic brain arteriovenous malformations, but also the architecture of microvasculature, the roles of the angiogenic factors, and the signaling pathways. This knowledge may allow us to infer the pathogenesis of sporadic brain arteriovenous malformations and develop pre-emptive treatments for them.
Information growth for sequential monitoring of clinical trials with a stepped wedge cluster randomized design and unknown intracluster correlation
Authors: Brown Siobhan P , Shoben Abigail B
Published: February 2020

Background/aims

In a stepped wedge study design, study clusters usually start with the baseline treatment and then cross over to the intervention at randomly determined times. Such designs are useful when the intervention must be delivered at the cluster level and are becoming increasingly common in practice. In these trials, if the outcome is death or serious morbidity, one may have an ethical imperative to monitor the trial and stop before maximum enrollment if the new therapy is proven to be beneficial. In addition, because formal monitoring allows for the stoppage of trials when a significant benefit for new therapy has been ruled out, their use can make a research program more efficient. However, use of the stepped wedge cluster randomized study design complicates the implementation of standard group sequential monitoring methods. Both the correlation of observations introduced by the clustered randomization and the timing of crossover from one treatment to the other impact the rate of information growth, an important component of an interim analysis.

Methods

We simulated cross-sectional stepped wedge study data in order to evaluate the impact of sequential monitoring on the Type I error and power when the true intracluster correlation is unknown. We studied the impact of varying intracluster correlations, treatment effects, methods of estimating the information growth, and boundary shapes.

Results

While misspecified information growth can impact both the Type I error and power of a study in some settings, we observed little inflation of the Type I error and only moderate reductions in power across a range of misspecified information growth patterns in our simulations.

Conclusion

Taking the study design into account and using either an estimate of the intracluster correlation from the ongoing study or other data in the same clusters should allow for easy implementation of group sequential methods in future stepped wedge designs.
Compliance of French academic clinical trials with the Clinical Trial Facilitation and Coordination Group recommendations on contraception and pregnancy testing requirements
Authors: Crepin Sabrina , Chiffoleau Anne , Gavard Marylaure , Olivier-Abbal Pascale , Roussillon Caroline , Ruault Sophie , Muller Charlotte , Peyro-Saint-Paul Laure , Ouk Thavarak , Franceschi Marie-Paule , Mouchel Catherine , Duranton Sophie , Petitpain Nadine , Coubret-Dumas Anne
Published: February 2020

Background/Aims

The Clinical Trials Coordination and Facilitation Group has issued recommendations on contraception and pregnancy testing to help sponsors meet regulatory expectations and harmonize practices to limit embryofetal risks in clinical trials. Our objective was to assess the compliance of French academic clinical trials with these recommendations and to describe the mitigation measures required by sponsors in their trials.

Methods

A cross-sectional study was performed on the French academic drug trials authorized by the national competent authority between January 2015 and June 2018. We included trials which tested systemic administration of drugs and enrolled men or women of childbearing potential.

Results

Data from 97 trials included were compiled. One-third of the trials (23.8%–43.3%, 95% confidence interval) complied with the Clinical Trial Facilitation and Coordination Group recommendations. No improvement over time or according to embryofetotoxic status or drug duration exposure was found. Contraception was required in 56.7% of trials and was more often required in case of potentially embryofetotoxic drugs (68.5% vs 41.9%, p = 0.013) or exposure over 1 month (71.7% vs 43.8%, p = 0.006). Pregnancy testing at inclusion was required in 59.1% of trials and additional testing in 17.2%. Pregnancy testing at inclusion was more often required in trials with drug exposure above 1 month (67.4% vs 45.8%, p = 0.035).

Conclusion

French academic sponsors barely met the recommendations on contraception and pregnancy testing potentially leading to potential embryofetal risks in case of pregnancy. They need to implement these recommendations quickly.
COMT gene variants and β-endorphin levels contribute to ethnic differences in experimental pain sensitivity
Authors: Xu Feng , Yin Jiangwen , Xiong Erfeng , Wang Ruixue , Zhai Jinwen , Xie Liping , Li Yan , Qin Xinlei , Wang Erqiang , Zhang Qingtong , Zuo Yansong , Fan Shiwen , Wang Sheng
Published: February 2020

This cross-sectional study investigated whether the catechol-O-methyltransferase (COMT) gene acts as a significant regulator of pain signaling pathways, regulates β-endorphin, and contributes to ethnic differences in pain sensitivity. One-hundred-sixty healthy subjects were enrolled in this study, with Han and Uyghur groups each consisting of 80 participants. Subjects went through six pain threshold experiments. From venous blood, COMT polymorphisms were genotyped, and serum β-endorphin levels were measured. Bivariate correlation analysis and multiple linear regression were used to identify the relationships among genotypes or β-endorphin levels and different types of pain thresholds. Han and Uyghur ethnic differences were determined in terms of acute-pressure pain-perception thresholds, blunt-pressure pain-perception thresholds, blunt-pressure pain-tolerance thresholds, electric pain-tolerance thresholds, β-endorphin levels, and distributions of rs4680 and rs4633 COMT polymorphisms. β-endorphin levels did not correlate with COMT rs4680 or rs4633 genotypes in both Han and Uyghur. Statistical predictors for a lower pain-threshold performance included being young, Uyghur, female, and having a low body mass index, low β-endorphin level, and the rs4680 GA or GG allele. There is the significant difference in pain sensitivity between healthy Han and Uyghur. COMT gene variants and β-endorphin levels contribute to ethnic differences in pain sensitivity.
Power and Culture: The Cultural Foundations of Brazilian Sociology
Authors: Lima Neto Fernando
Published: February 2020

In this article, I analyse how Brazilian sociology articulates the relationship between culture and power, which is one of the central problems of cultural sociology. I analyse two theoretical traditions, culturalism and institutionalism, which traverse different areas of Brazilian sociology. Broadly speaking, the approach of culturalism takes culture as a dimension that structures power relations (culture over power), while institutionalism considers that the structure lies in the institutionalised power relations that produce the cultural codes of political culture (power over culture). I conceive of political culture as an expression of an Ethos, and show how it is considered either as a cause or an effect of the historical nation building process. In Brazilian sociology, the notions of culture and power pose a permanent interpretational challenge for both classical and contemporary scholars. This makes the discussion about the relationship between culture and power a key element in understanding past and present historical processes in Brazil. I seek to understand the variations of meaning regarding these notions and their implications for Brazilian sociology. In this sense, this article is a cultural sociology of cultural sociology in Brazil, or, in other words, an analysis of the cultural foundations of Brazilian sociology.
Fatal adverse events associated with programmed cell death protein 1 or programmed cell death-ligand 1 monotherapy in cancer
Authors: Zhao Bin , Zhao Hong , Zhao Jiaxin
Published: February 2020

Background:

The introduction of antibodies targeting programmed cell death protein 1 (PD-1) and programmed cell death-ligand 1 (PD-L1) into clinical practice has had a revolutionary effect on cancer treatment. However, the incidence and risk of fatal adverse events (FAEs) following PD-1/PD-L1 inhibitor administration are controversial.

Methods:

We performed a systematic search for randomized controlled trials (RCTs) of PD-1/PD-L1 inhibitors (atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab) in Embase, PubMed, the Cochrane database, and abstracts presented at American Society of Clinical Oncology and European Society of Medical Oncology from inception to July 2018. FAEs were extracted from each study and pooled to calculate overall incidence and odds ratios (ORs).

Results:

In total, 20 RCTs involving 12,398 patients with solid tumors were included in this study. The overall incidence of FAEs with PD-1/PD-L1 inhibitors was 0.43% [95% confidence interval (CI), 0.25–0.66%]. However, the incidences of FAEs varied significantly by tumor type and median follow-up time. Compared with conventional agents, the application of PD-1/PD-L1 inhibitors significantly reduced the risk of FAEs (OR, 0.56; 95% CI, 0.35–0.89; p = 0.015). Moreover, trial sequential analysis confirmed that our results were solid and reliable; further studies were unlikely to alter this conclusion. FAEs occurred dispersed in major organ systems, with the most common mortalities appearing in the respiratory system (46.2%).

Conclusions:

Compared with conventional treatment, PD-1/PD-L1 blockade monotherapy is associated with a significantly reduced risk of mortality in patients with solid tumors.
Soviet federalism from below: The Soviet Republics of Odessa and the Russian Far East, 1917–1918
Authors: Penter Tanja , Sablin Ivan
Published: February 2020

In early 1918, the Bolshevik-dominated Third Congress of Soviets declared the formation of a new composite polity—the Soviet Russian Republic. The congress’s resolutions, however, simultaneously proclaimed a federation of national republics and a federation of soviets. The latter seemed to recognize regionalism and localism as organizing principles on par with nationalism and to legitimize the self-proclaimed Soviet republics across the former Russian Empire. The current article compared two such non-national Soviet republics, those in Odessa and the Russian Far East. The two republics had similar roots in the discourses and practices of the Russian Empire, such as economic and de facto administrative autonomy. They also took similar organizational forms, were run by coalitions, and opposed their own inclusion into larger national and regional formations in Ukraine and Siberia. At the same time, both of the Soviet governments functioned as ad hoc committees and adapted their institutional designs and practices to the concrete—and very different—social and international conditions in the two peripheries. The focus of the Odessa and Far Eastern authorities on specific problems and their embeddedness in the peculiar contexts reflected the very idea of federalism as governance based on decentralization and nuance but contradicted the party-based centralization and the exclusivity of the ethno-national federalism in the consolidated Soviet state.
The Wisdom of Christian Spiritual Formation
Authors: Wilhoit James C. , Howard Evan B.
Published: February 2020

This article is intended to serve as a reminder of the themes that have been present in Christian spiritual formation (CSF) through the centuries. In a WISDOM orientation we ground our approach to CSF in Scripture, in theology, and in “best practices,” yet we also seek to thoughtfully locate CSF within specific contexts. The WISDOM acronym reminds us that formation must involve: Wise planning, where the leaders prayerfully seek to implement what is needed in a specific situation; Intentionality, calling people to commit to walk differently from the ways of the world; Scripture, salvation, and Spirit, where the Salvation message and the Spirit-led mission of the whole of Scripture provides the framework for CSF; Discipleship, where the end of CSF is the imitation of Jesus Christ; Optimism, where we pursue our formation in an atmosphere of hope and expectation of change; and Means.
The Relationship Between Humeral Torsion and Arm Injury in Baseball Players: A Systematic Review and Meta-analysis
Authors: Helmkamp Joshua K. , Bullock Garrett S. , Rao Allison , Shanley Ellen , Thigpen Charles , Garrigues Grant E.
Published: February 2020

Context:

Humeral torsion (HT) has been linked to various injuries and benefits. However, the exact interplay between HT, shoulder range of motion (ROM), competition level differences, and injury risk is unclear.

Objective:

To determine the relationship between HT, ROM, and injury risk in baseball players. Secondarily, to determine HT based on competition level.

Data Sources:

PubMed, Embase, Web of Science, CINAHL, and Cochrane databases were searched from inception until November 4, 2018.

Study Selection:

Inclusion criteria consisted of (1) HT measurements and (2) arm injury or shoulder ROM.

Study Design:

Systematic review.

Level of Evidence:

Level 3.

Data Extraction:

Two reviewers recorded patient demographics, competition level, HT, shoulder ROM, and injury data.

Results:

A total of 32 studies were included. There was no difference between baseball players with shoulder and elbow injuries and noninjured players (side-to-side HT difference: mean difference [MD], 1.75 [95% CI, –1.83 to 2.18]; dominant arm: MD, 0.17 [95% CI, –1.83 to 2.18]). Meta-regression determined that for every 1° increase in shoulder internal rotation (IR), there was a subsequent increase of 0.65° in HT (95% CI, 0.28 to 1.02). HT did not explain external rotation (ER ROM: 0.19 [95% CI, –0.24 to 0.61]) or horizontal adduction (HA ROM: 0.18 [95% CI, –0.46 to 0.82]). There were no differences between HT at the high school, college, or professional levels.

Conclusion:

No relationship was found between HT and injury risk. However, HT explained 65% of IR ROM but did not explain ER ROM or HA ROM. There were no differences in HT pertaining to competition level. The majority of IR may be nonmodifiable. Treatment to restore and maintain clinical IR may be important, especially in players with naturally greater torsion. HT adaptation may occur prior to high school, which can assist in decisions regarding adolescent baseball participation.
Water knot: Case report of a rare complication during a urodynamic test
Authors: Blas Leandro , Roberti Javier , Lopez Francisco , Ameri Carlos Alberto
Published: February 2020

Intravesical catheter knotting is a rarely reported event that could lead to serious complications. We present a case that occurred during urodynamic test with two K30 tubes: a 56-year-old female with a double knot of two K30 (8.4 Fr) tubes. This case was resolved by removing the catheters with sustained traction. Because catheter knotting can be a serious complication, we recommend the use of a double-lumen catheter when possible and assessment of a safe insertion length.
Guideline-based flexible cystoscopy safely improves capacity, avoiding unnecessary intervention with cost savings
Authors: Habib A , Noel J , Batura D , Hellawell G
Published: February 2020

Introduction:

Flexible cystoscopy (FC) is a common and useful diagnostic tool. Because of its broader applications, availability and simplicity, there has been criticism of its overuse with accompanying financial burden to the health system and unnecessary invasive intervention to the patient. Therefore, we reviewed our local practice against current guidelines to evaluate compliance, enhance patient safety and capacity utilisation.

Patients and methodology:

Data were collected retrospectively on all patients having FC over two months. The indications and findings of FC were gathered from the hospital electronic patient record system.

Results:

A total of 413 FCs were carried out over the study period. The most common indications were cancer surveillance 116 (28%) and visible haematuria 76 (18.4%). A total of 152 (37%) FCs were performed for non-recommended indications. The most common conditions that deviated from guidelines were lower urinary tract symptoms (LUTS) (72, 17.4%), urinary tract infection (UTI) (41, 9.9%) and asymptomatic non-visible haematuria (35, 8.5%). In all non-visible haematuria cases, 65 (90%) of LUTS and 39 (95%) of UTI patients, FC was non-contributory. Adherence to guidelines would have yielded 37% of FC slots. Based on current UK National Tariffs, cost savings would have been £352,032 annually in this trust.

Conclusions:

FC is a frequent investigation within urology departments for which referral guidelines exist. Protocol-driven practice enables appropriate use, ensures patient safety and leads to efficient utilisation of capacity with substantial cost savings.

Level of evidence:

Not applicable for this multicentre audit.
Whistleblowing or leaking? Public opinion toward Assange, Manning, and Snowden
Authors: Touchton Michael R. , Klofstad Casey A. , West Jonathan P. , Uscinski Joseph E.
Published: February 2020

The release of classified documents through outlets like WikiLeaks has transformed American politics by shedding light on the innerworkings of governments, parties, and corporations. The high-profile criminal cases associated with such releases – those of Julian Assange, Chelsea Manning, and Edward Snowden – have highlighted important questions about journalism, government secrecy, and the public’s “right to know.” Scholars have focused on the journalistic and legalistic implications but have yet to explore how the public views those who release classified materials, and what factors affect those views. Using data from the 2018 Cooperative Congressional Election Study, we provide results from three embedded experiments testing the effects of two forms of framing on favorability ratings toward Assange, Manning, and Snowden. The first frame addresses partisanship (i.e., which party is injured by the release) and the second addresses how the action is framed (i.e., did the person “leak” or “blow the whistle”). The data show that both the party and leaking/whistleblowing frames significantly affect favorability in expected ways. The release of classified materials comes with both costs and benefits, but public opinion appears to be more sensitive to its implications for partisan competition.
Effect of Baseline Symptom Manifestations on Retention in Care and Treatment among HIV-Infected Patients in Nigeria
Authors: Adeola Juliet , Badejo Okikiolu Abimbola , Ahonkhai Aimalohi , Okonkwo Prosper , Aboh Akande Patrick , Evans Charlesnika Tyon , McHugh Megan , Pierce Leslie , Ahmed Isah , Jolayemi Toyin , Ladi Akinyemi Babatunde , Onwuatuelo Ifeyinwa , Murphy Robert , Kyriacou Demetrious , Musa Jonah , Agaba Patricia
Published: February 2020

Background:

Symptom management is an important component of HIV care. But symptom patterns and how they affect engagement with HIV care and treatment services have not been adequately explored in the era of increased HIV treatment scale-up. We investigated the relationship between symptom patterns among people living with HIV (PLHIV) and 12 months retention in care, within the context of other clinical and demographic characteristics.

Methods:

Retrospective cohort analysis of 5114 PLHIV receiving care within a large HIV treatment program in Nigeria. We assessed the prevalence and burden of baseline symptoms reported during routine clinic visits from January 2015 to December 2017. Multivariable regression was used to identify relationships between 12-month retention and symptom dimensions (prevalence and burden) while controlling for demographic and other clinical variables.

Results:

Increasing symptom burden was associated with higher likelihood of retention at 12 months (adjusted odds ratio [aOR] = 1.19 [95% confidence interval, CI: 1.09-1.29]; P < .001) as was the reporting of skin rashes/itching symptom (aOR = 2.59 [95% CI: 1.65-4.09]; P < .001). Likelihood of retention reduced with increasing World Health Organization (WHO) Clinical staging, with CD4 ≥500 cells/mL and self-reported heterosexual mode of HIV transmission. Conclusions: Symptom dimensions and standardized clinical/immunological measures both predicted retention in care, but effects differed in magnitude and direction. Standardized clinical/immunological measures in HIV care (eg, WHO clinical staging and CD4 count categories) can mask important differences in how PLHIVs experience symptoms and, therefore, their engagement with HIV care and treatment. Symptom management strategies are required alongside antiretroviral treatment to improve outcomes among PLHIV, including retention in care.
Heatmaps for Patterns of Association in log-Linear Models
Authors: Bucca Mauricio
Published: February 2020

Log-linear models offer a detailed characterization of the association between categorical variables, but the breadth of their outputs is difficult to grasp because of the large number of parameters these models entail. Revisiting seminal findings and data from sociological work on social mobility, the author illustrates the use of heatmaps as a visualization technique to convey the complex patterns of association captured by log-linear models. In particular, turning log odds ratios derived from a model’s predicted counts into heatmaps makes it possible to summarize large amounts of information and facilitates comparison across models’ outcomes.
Beauty and the Beast: The Ordinary City versus the Mediatised City—The Case of Cairo
Authors: Hendawy Mennatullah , Saeed Ahmed
Published: February 2020

Which city is made visible to those who use public versus private means of transportation? This question triggered an investigation of two alternate routes between two points in the mega urban city of Cairo, Egypt. Combining critical visual methodologies with ethnographic methods, this photo essay reveals the simultaneous existence of two cities as experienced by different publics: the ‘ordinary city’ of those who use public transport, and the ‘mediatised city’ of the elite who use private transport. Through comic-style photo editing, the essay demonstrates how the city is organised to include or exclude certain kinds of commuters using their chosen modes of transport, based on affordability and economic class.
Citizenship at the Margins: Exploring Participation as ‘Right to the City’ in Vizhinjam, Kerala
Authors: Ganga Aarathi
Published: February 2020

This article explores the nature of urban citizenship among fishers in Kerala, one of the state’s most marginalised communities, by analysing their participation in a centrally sponsored slum rehabilitation programme—Rajiv Awas Yojana (RAY)—in Vizhinjam, Thiruvananthapuram. The ‘right to participate’ is considered an integral part of the ‘right to the city’, and the inability of the fishing community to participate in the decision-making processes of urban development programmes that directly affect their lives reveals the exclusionary nature of their citizenship. In a state that is renowned for its achievements in human development and governance, the fishing community continues to be marginalised and lack collective power to influence policies. Participatory meetings in such contexts become tokenistic, and their transformative capacity is undermined. The inefficiency of participatory meetings organised under RAY also stems from the powerlessness of local governments to alter urban programmes designed by national governments.
Book review: Tejubehan, Salai Selvam, & V. Geetha (Trans.), Drawing from the City
Authors: Moharir Mitali
Published: February 2020

Tejubehan, Salai Selvam, & V. Geetha (Trans.), Drawing from the City. Chennai: Tara Books, 2017, 32 pp., ₹499. ISBN: 9789383145966.
A rational approach to the conversion of FEMA P-58 seismic repair costs to Europe
Authors: Silva Antonio , Castro Jose Miguel , Monteiro Ricardo
Published: February 2020

State-of-the-art seismic performance assessment of buildings requires a realistic estimation of the repair cost of structural and non-structural components. In this context, the US-based FEMA P-58 guidelines feature a procedure and repair cost database that have become a reference to many recent studies in the field. The number of cases in which it has been applied to Europe is however limited, and repair cost conversion factors have been generally adopted. Moreover, a rational methodology that covers multiple countries in a consistent manner is absent in the literature. This study attempts to address this gap, proposing an economy analysis–based repair cost conversion approach that will be useful for practical implementations of FEMA-P58 in Europe. The proposed conversion approach is validated with actual replacement costs monitored in the L’Aquila reconstruction process. While observing a good agreement between the real and estimated US-to-local repair cost ratios, limitations of the proposed methodology are also outlined and discussed, with a view to guide possible future research efforts to improve and consolidate the proposed conversion method.
Reduced–dose intensity therapy for pediatric lymphoblastic leukemia: long-term results of the Recife RELLA05 pilot study
Authors: Pedrosa Francisco , Coustan-Smith Elaine , Zhou Yinmei , Cheng Cheng , Pedrosa Arli , Lins Mecneide Mendes , Pedrosa Marcia , Lucena-Silva Norma , Ramos Alessandra Maria de Luna , Vinhas Ester , Rivera Gaston K. , Campana Dario , Ribeiro Raul C.
Published: February 2020

Treatment-related mortality is common among children with acute lymphoblastic leukemia (ALL) treated in poor-resource settings. We applied a simplified flow cytometric assay to identify patients with precursor B-cell ALL (B-ALL) at very low risk (VLR) of relapse and treated them with a reduced-intensity treatment plan (RELLA05). VLR criteria include favorable presenting features (age ≥ 1 and < 10 years), white blood cell count of <50 ×109/L, lack of extramedullary leukemia, and minimal residual disease level of <0.01% on remission induction day 19. Except for 2 doses of daunorubicin, treatment of patients with VLR B-ALL consisted of a combination of agents with relatively low myelotoxicity profiles, including corticosteroids, vincristine, L-asparaginase, methotrexate, and 6-mercaptopurine. Cyclophosphamide, systemic cytarabine, and central nervous system radiotherapy were not used. Of 454 patients with ALL treated at the Instituto de Medicina Integral Professor Fernando Figueira in Recife, Brazil, between December 2005 and June 2015, 101 were classified as having VLR B-ALL. There were no cases of death resulting from toxicity or treatment abandonment during remission induction. At a median follow-up of 6.6 years, there were 8 major adverse events: 6 relapses, 1 treatment-related death (from septicemia) during remission, and 1 secondary myeloid leukemia. The estimated 5-year event-free and overall survival rates were 92.0% ± 3.9% and 96.0% ± 2.8%, respectively. The 5-year cumulative risk of relapse was 4.24% ± 2.0%. The treatment was well tolerated. Episodes of neutropenia were of short duration. Patients with B-ALL selected by a combination of presenting features and degree of early response can be successfully treated with a mildly myelosuppressive chemotherapy regimen.
Propranolol inhibits molecular risk markers in HCT recipients: a phase 2 randomized controlled biomarker trial
Authors: Knight Jennifer M. , Rizzo J. Douglas , Hari Parameswaran , Pasquini Marcelo C. , Giles Karen E. , D’Souza Anita , Logan Brent R. , Hamadani Mehdi , Chhabra Saurabh , Dhakal Binod , Shah Nirav , Sriram Deepika , Horowitz Mary M. , Cole Steve W.
Published: February 2020

Preclinical research shows that stress-induced activation of the sympathetic nervous system can promote hematopoietic malignancies via β-adrenoreceptor–mediated molecular pathways. Hematopoietic cell transplant (HCT) recipients exposed to conditions of chronic stress show activation of a conserved transcriptional response to adversity (CTRA) gene expression profile, which in turn is associated with increased relapse and decreased disease-free survival. We conducted a randomized controlled phase 2 biomarker trial testing the impact of the nonselective β-antagonist propranolol on CTRA-related gene expression of 25 individuals receiving an autologous HCT for multiple myeloma. Propranolol was administered for 1 week prior to and 4 weeks following HCT. Blood was collected at baseline, day −2, and day +28. Intention-to-treat analyses controlling for demographic characteristics, high-risk disease (International Myeloma Working Group risk score), and tumor stage tested effects on a 53-gene CTRA indicator profile and measures of CTRA-related cellular processes in peripheral blood mononuclear cells. Twelve participants were randomized to the intervention and 13 to the control. Relative to the control group, propranolol-treated patients showed greater decreases from baseline to HCT day −2 and day +28 for both CTRA gene expression (P = .017) and bioinformatic measures of CD16− classical monocyte activation (P = .005). Propranolol-treated patients also showed relative upregulation of CD34+ cell–associated gene transcripts (P = .011) and relative downregulation of myeloid progenitor–containing CD33+ cell–associated gene transcripts (P = .001). Ancillary analyses identified nonsignificant trends toward accelerated engraftment and reduced posttransplant infections in propranolol-treated patients. Peri-HCT propranolol inhibits cellular and molecular pathways associated with adverse outcomes. Changes in these pathways make propranolol a potential candidate for adjunctive therapy in cancer-related HCT.
Genomic context and TP53 allele frequency define clinical outcomes in TP53-mutated myelodysplastic syndromes
Authors: Montalban-Bravo Guillermo , Kanagal-Shamanna Rashmi , Benton Christopher B. , Class Caleb A. , Chien Kelly S. , Sasaki Koji , Naqvi Kiran , Alvarado Yesid , Kadia Tapan M. , Ravandi Farhad , Daver Naval , Takahashi Koichi , Jabbour Elias , Borthakur Gautham , Pemmaraju Naveen , Konopleva Marina , Soltysiak Kelly A. , Pierce Sherry R. , Bueso-Ramos Carlos E. , Patel Keyur P. , Kantarjian Hagop , Garcia-Manero Guillermo
Published: February 2020

TP53 mutations are associated with adverse outcomes and shorter response to hypomethylating agents (HMAs) in myelodysplastic syndrome (MDS). Limited data have evaluated the impact of the type, number, and patterns of TP53 mutations in response outcomes and prognosis of MDS. We evaluated the clinicopathologic characteristics, outcomes, and response to therapy of 261 patients with MDS and TP53 mutations. Median age was 68 years (range, 18-80 years). A total of 217 patients (83%) had a complex karyotype. TP53 mutations were detected at a median variant allele frequency (VAF) of 0.39 (range, 0.01-0.94). TP53 deletion was associated with lower overall response rate (ORR) (odds ratio, 0.3; P = .021), and lower TP53 VAF correlated with higher ORR to HMAs. Increase in TP53 VAF at the time of transformation was observed in 13 patients (61%), and previously undetectable mutations were observed in 15 patients (65%). TP53 VAF was associated with worse prognosis (hazard ratio, 1.02 per 1% VAF increase; 95% confidence interval, 1.01-1.03; P < .001). Integration of TP53 VAF and karyotypic complexity identified prognostic subgroups within TP53-mutant MDS. We developed a multivariable model for overall survival that included the revised International Prognostic Scoring System (IPSS-R) categories and TP53 VAF. Total score for each patient was calculated as follows: VAF TP53 + 13 × IPSS-R blast score + 16 × IPSS-R cytogenetic score + 28 × IPSS-R hemoglobin score + 46 × IPSS-R platelet score. Use of this model identified 4 prognostic subgroups with median survival times of not reached, 42.2, 21.9, and 9.2 months. These data suggest that outcomes of patients with TP53-mutated MDS are heterogeneous and that transformation may be driven not only by TP53 but also by other factors.
Neuropeptide regulation of secretion and inflammation in human airway gland serous cells
Authors: McMahon Derek B. , Carey Ryan M. , Kohanski Michael A. , Tong Charles C.L. , Papagiannopoulos Peter , Adappa Nithin D. , Palmer James N. , Lee Robert J.
Published: February 2020

Airway submucosal gland serous cells are sites of expression of the cystic fibrosis transmembrane conductance regulator (CFTR) and are important for fluid secretion in conducting airways. To elucidate how neuropeptides regulate serous cells, we tested if human nasal turbinate serous cells secrete bicarbonate (HCO3−), important for mucus polymerisation and antimicrobial peptide function, during stimulation with cAMP-elevating vasoactive intestinal peptide (VIP) and if this requires CFTR. Serous cells stimulated with VIP exhibited a ∼15–20% cAMP-dependent decrease in cell volume and a ∼0.15 unit decrease in intracellular pH (pHi), reflecting activation of Cl−and HCO3−secretion, respectively. HCO3−secretion was directly dependent on CFTR and was absent in cells from CF patients. In contrast, neuropeptide Y (NPY) reduced VIP-evoked cAMP increases, CFTR activation, and Cl−/HCO3−secretion. Culture of primary serous cells in a model that maintained a serous phenotype confirmed the activating and inhibiting effects of VIP and NPY, respectively, on fluid and HCO3−secretion. Moreover, VIP enhanced antimicrobial peptide secretion and antimicrobial efficacy of secretions while NPY reduced antimicrobial efficacy. In contrast, NPY enhanced cytokine release while VIP reduced cytokine release through a mechanism requiring CFTR. As levels of VIP and NPY are up-regulated in diseases like allergy, asthma, and chronic rhinosinusitis, the balance of these two peptides in the airway may control mucus rheology and inflammatory responses in serous cells. Furthermore, the loss of CFTR conductance in serous cells may contribute to CF pathophysiology by increasing serous cells inflammatory responses in addition to directly impairing Cl−and HCO3−secretion.
Patient preferences for symptom-driven or regular preventer treatment in mild to moderate asthma: findings from the PRACTICAL study, a randomised clinical trial
Authors: Baggott Christina , Reddel Helen K. , Hardy Jo , Sparks Jenny , Holliday Mark , Corin Andrew , Montgomery Barney , Reid Jim , Sheahan Davitt , Hancox Robert J. , Weatherall Mark , Beasley Richard , Fingleton James
Published: February 2020

Symptom-driven low-dose inhaled corticosteroid–formoterol is safe and effective in mild asthma and has been recommended as one of the preferred treatment regimens at steps 1 and 2 in the 2019 update of the Global Initiative for Asthma. However, there are no data on patient preferences for this regimen.

A subgroup of participants in the PRACTICAL study (ACTRN12616000377437), a randomised controlled trial comparing symptom-driven budesonide–formoterol with maintenance budesonide plus as-needed terbutaline completed a survey on treatment preferences, satisfaction, beliefs and experience at their final study visit.

306 (75%) out of 407 eligible participants completed the survey. Regimen preference was strongly associated with randomised treatment, as were preferences for and beliefs about preventer inhaler use. Combination preventer and reliever as-needed therapy was preferred by 135 (90%, 95% CI 85.2–94.8%) out of 150 who were randomised to as-needed budesonide–formoterol, and by 63 (40%, 95% CI 32.7–48.1%) out of 156 who were randomised to maintenance budesonide. By contrast, twice-daily preventer inhaler with a reliever inhaler as required was preferred by 15 (10%) out of 150 of those randomised to as-needed budesonide–formoterol and 93 (60%) out of 156 of those randomised to maintenance budesonide. Satisfaction with all study inhalers was high. Of patients randomised to as-needed budesonide–formoterol 92% (n=138) were confident using it as a reliever at the end of the study.

Although most participants preferred the regimen to which they had been randomised, this association was much stronger for those randomised to budesonide–formoterol as needed, indicating that most patients preferred as-needed corticosteroid–formoterol therapy if they had experienced it.
PANEV: an R package for a pathway-based network visualization
Authors: Palombo Valentino , Milanesi Marco , Sferra Gabriella , Capomaccio Stefano , Sgorlon Sandy , D’Andrea Mariasilvia
Published: February 2020

Background

During the last decade, with the aim to solve the challenge of post-genomic and transcriptomic data mining, a plethora of tools have been developed to create, edit and analyze metabolic pathways. In particular, when a complex phenomenon is considered, the creation of a network of multiple interconnected pathways of interest could be useful to investigate the underlying biology and ultimately identify functional candidate genes affecting the trait under investigation.

Results

PANEV (PAthway NEtwork Visualizer) is an R package set for gene/pathway-based network visualization. Based on information available on KEGG, it visualizes genes within a network of multiple levels (from 1 to n) of interconnected upstream and downstream pathways. The network graph visualization helps to interpret functional profiles of a cluster of genes.

Conclusions

The suite has no species constraints and it is ready to analyze genomic or transcriptomic outcomes. Users need to supply the list of candidate genes, specify the target pathway(s) and the number of interconnected downstream and upstream pathways (levels) required for the investigation. The package is available at https://github.com/vpalombo/PANEV.
Motor, cognitive and mobility deficits in 1000 geriatric patients: protocol of a quantitative observational study before and after routine clinical geriatric treatment – the ComOn-study
Authors: Geritz Johanna , Maetzold Sara , Steffen Maren , Pilotto Andrea , Corrà Marta F. , Moscovich Mariana , Rizzetti Maria C. , Borroni Barbara , Padovani Alessandro , Alpes Annekathrin , Bang Corinna , Barcellos Igor , Baron Ralf , Bartsch Thorsten , Becktepe Jos S. , Berg Daniela , Bergeest Lu M. , Bergmann Philipp , Bouça-Machado Raquel , Drey Michael , Elshehabi Morad , Farahmandi Susan , Ferreira Joaquim J. , Franke Andre , Friederich Anja , Geisler Corinna , Hüllemann Philipp , Gierthmühlen Janne , Granert Oliver , Heinzel Sebastian , Heller Maren K. , Hobert Markus A. , Hofmann Marc , Jemlich Björn , Kerkmann Laura , Knüpfer Stephanie , Krause Katharina , Kress Maximilian , Krupp Sonja , Kudelka Jennifer , Kuhlenbäumer Gregor , Kurth Roland , Leypoldt Frank , Maetzler Corina , Maia Luis F. , Moewius Andreas , Neumann Patricia , Niemann Katharina , Ortlieb Christian T. , Paschen Steffen , Pham Minh H. , Puehler Thomas , Radloff Franziska , Riedel Christian , Rogalski Marten , Sablowsky Simone , Schanz Elena M. , Schebesta Linda , Schicketmüller Andreas , Studt Simone , Thieves Martina , Tönges Lars , Ullrich Sebastian , Urban Peter P. , Vila-Chã Nuno , Wiegard Anna , Warmerdam Elke , Warnecke Tobias , Weiss Michael , Welzel Julius , Hansen Clint , Maetzler Walter
Published: February 2020

Background

Motor and cognitive deficits and consequently mobility problems are common in geriatric patients. The currently available methods for diagnosis and for the evaluation of treatment in this vulnerable cohort are limited. The aims of the ComOn (COgnitive and Motor interactions in the Older populatioN) study are (i) to define quantitative markers with clinical relevance for motor and cognitive deficits, (ii) to investigate the interaction between both motor and cognitive deficits and (iii) to assess health status as well as treatment outcome of 1000 geriatric inpatients in hospitals of Kiel (Germany), Brescia (Italy), Porto (Portugal), Curitiba (Brazil) and Bochum (Germany).

Methods

This is a prospective, explorative observational multi-center study. In addition to the comprehensive geriatric assessment, quantitative measures of reduced mobility and motor and cognitive deficits are performed before and after a two week’s inpatient stay. Components of the assessment are mobile technology-based assessments of gait, balance and transfer performance, neuropsychological tests, frailty, sarcopenia, autonomic dysfunction and sensation, and questionnaires to assess behavioral deficits, activities of daily living, quality of life, fear of falling and dysphagia. Structural MRI and an unsupervised 24/7 home assessment of mobility are performed in a subgroup of participants. The study will also investigate the minimal clinically relevant change of the investigated parameters.

Discussion

This study will help form a better understanding of symptoms and their complex interactions and treatment effects in a large geriatric cohort.
Increased plasma concentration of cell-free DNA precedes disease recurrence in children with high-risk neuroblastoma
Authors: Su Yan , Wang Lijun , Jiang Chiyi , Yue Zhixia , Fan Hongjun , Hong Huimin , Duan Chao , Jin Mei , Zhang Dawei , Qiu Lihua , Cheng Xianfeng , Xu Zhong , Ma Xiaoli
Published: February 2020

Background

Neuroblastoma is the most common extracranial solid tumor of childhood. The high rate of recurrence is associated with a low survival rate for patients with high-risk neuroblastoma. There is thus an urgent need to identify effective predictive biomarkers of disease recurrence.

Methods

A total of 116 patients with high-risk neuroblastoma were recruited at Beijing Children’s Hospital between February 2015 and December 2017. All patients received multidisciplinary treatment, were evaluated for the therapeutic response, and then initiated on maintenance treatment. Blood samples were collected at the beginning of maintenance treatment, every 3 months thereafter, and at the time of disease recurrence. Plasma levels of cell-free DNA (cfDNA) were quantified by qPCR. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the ability of plasma cfDNA concentration to predict recurrence.

Results

Of the 116 patients, 36 (31.0%) developed recurrence during maintenance treatment. The median time to recurrence was 19.00, 9.00, and 8.00 months for patients who had achieved complete response (n = 6), partial response (n = 25), and stable disease (n = 5), respectively, after multidisciplinary treatment. The median plasma cfDNA concentration at the time of recurrence was significantly higher than the concentration in recurrence-free patients throughout maintenance treatment (29.34 ng/mL vs 10.32 ng/mL). Patients recorded a plasma cfDNA level ≥ 29 ng/mL an average of 0.55 months before diagnosis of disease recurrence. ROC analysis of the power of plasma cfDNA to distinguish between patients with or without recurrence yielded an area under the curve of 0.825, with optimal sensitivity and specificity of 80.6 and 71.3%, respectively, at a cfDNA level of 12.93 ng/mL.

Conclusions

High plasma cfDNA concentration is a potential molecular marker to signal disease recurrence in patients with high-risk neuroblastoma.