bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of the introduction of novel hormonal agents on metastatic castration-resistant prostate cancer treatment choice
Authors: Lahcene Halima , Aprikian Armen G , Vanhuyse Marie , Hu Jason , Bladou Franck , Cury Fabio , Kassouf Wassim , Perreault Sylvie , Dragomir Alice
Published: April 2019

Background

Docetaxel-based chemotherapy has been the cornerstone of the management of symptomatic metastatic castration-resistant prostate cancer (mCRPC) since 2004. This study aimed to describe how real-world clinical practice was changed with the public funding of novel hormonal agents (abiraterone and enzalutamide) in Quebec.

Methods

We conducted a retrospective cohort study in two McGill University hospitals. Hospital-based cancer registries were used to select mCRPC patients in medical oncology departments from January 2010 to June 2014. Two groups according to mCRPC diagnosis year were built, with 2012 chosen as the cut-off year, corresponding to the year abiraterone was approved for public reimbursement in second-line in Quebec. Kaplan–Meier analysis was used to estimate time to first docetaxel prescription since mCRPC diagnosis before and after 2012. Cox regression was used to identify predictive factors of docetaxel and novel hormonal agent use.

Results

In our cohort, 308 patients diagnosed with mCRPC were selected with 162 patients in the pre-2012 group and 146 patients in the post-2012 group. The median age at mCRPC was 74.0 years old. At 12 months from diagnosis, 69% of patients received a prescription for docetaxel in the pre-2012 group comparatively to 53% in the post-2012 group. Factors that decreased the likelihood of docetaxel utilization were: age older than 80 at mCRPC diagnosis (HR: 0.5; 95%CI: 0.3–0.7), mCRPC diagnosis after 2012 (HR: 0.6; 95%CI: 0.4–0.8), and asymptomatic disease at mCRPC diagnosis (HR: 0.5; 95%CI: 0.3–0.7).

Conclusion

The introduction of novel hormonal agents reduced first-line and overall docetaxel utilization and delayed time to its initiation.
Infection of Previously Closed Urachus Mimicking Malignancy: A Case Report and Literature Review of Radiological Findings to the Diagnosis
Authors: Lam Siu W , Linsen Philip VM , Elgersma Otto E
Published: April 2019

The urachus is a vestigial structure of the allantois and cloaca. It involutes as fetal development progresses to become a fibrous cord, which courses between the umbilicus and bladder dome within the retropubic space. Infection occasionally occurs in patients with congenital patent urachus. Here, we report a patient with infection of a previously closed urachal tract presenting as an abdominal mass. This has rarely been described in the literature. Current knowledge on imaging findings to the diagnosis is discussed.
Application of an Intensive Rehabilitation Program After Very Late Recovery of Consciousness: A Single-Case Neurorehabilitation and Neuroimaging Study
Authors: Errante Antonino , Saviola Donatella , Fasano Fabrizio , Basagni Benedetta , Alinovi Serena , Bosetti Sara , Chiari Margherita , Minardi Rita , Pinardi Chiara , Crisi Girolamo , Fogassi Leonardo , De Tanti Antonio
Published: April 2019

Late recovery of consciousness in vegetative state is considered as an exceptional outcome and has been reported prevalently in patients who suffered a traumatic brain injury. In these patients, the benefits of prolonging the rehabilitation, aimed at the recovery of autonomy in basic everyday activities, has been demonstrated. Here, we describe the application of an intensive multi-professional rehabilitation program carried out on a young female patient, with exceptionally late recovery of consciousness, specifically, after 7 years of vegetative state due to severe brain hemorrhage. Neuropsychological and functional assessment was conducted before and after the end of the rehabilitation program. In addition, functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI)-based probabilistic tractography were performed. Two follow-up neuropsychological and functional assessments were also conducted 6 and 29 months after the conclusion of the program. Functional results showed an improvement, maintained over time, in walking with assistance, cognitive efficiency, visual acuity and visual field, dysarthria, and execution of activities of daily living. Moreover, functional and structural magnetic resonance imaging (MRI) data documented the existence of preserved neural networks involved in sensory, motor, and linguistic tasks, which in all likelihood support the recovery process. This report suggests the possibility of undertaking an intensive rehabilitation program in patients who remain for long periods in altered states of consciousness, in spite of early negative prognosis.
Gender and cultural understandings in medical nonindicated interventions: A critical discussion of attitudes toward nontherapeutic male circumcision and hymen (re)construction
Authors: Coene Gily , Saharso Sawitri
Published: April 2019

Hymen (re)construction and nontherapeutic male circumcision are medical nonindicated interventions that give rise to specific ethical concerns. In Europe, hymen (re)construction is generally more contested among medical professionals than male circumcision. Yet, from a standard biomedical framework, guided by the principles of autonomy, beneficence, nonmaleficence, and justice, circumcision of boys is, as this article explains, more problematic than hymen (re-) construction. While there is a growing debate on the acceptability of infant circumcision, in the case of competent minors and adults the surgery is not questioned. In the case of hymenoplasty, usually requested by a competent patient, it is recommended to only perform the operation after extensive counseling and if there are compelling conditions. The article further explores why attitudes of medical professionals toward both surgeries diverge and seeks to explain how this is largely informed by gendered and socio-cultural understandings. The article further raises critical questions on medical paternalism and the role of counseling.
“I would prefer not to”: Assessing competence to consent in a case of refusal of cancer treatment
Authors: Castellana Gustavo B , Schraiber Lilia B , de Oliveira Talita R , de Barros Daniel M
Published: April 2019

Background

Based on an actual case in which a psychiatrist was called in to assess a patient’s capacity to refuse treatment, the aim of this study is to discuss how to manage this ethical and clinical issue and the dilemmas faced by the medical team. Case presentation: The case involved a 45-year-old female patient diagnosed with breast cancer who refused treatment. Since the mastology team had doubts about the patient’s mental state and given that she refused to consent to surgery, a forensic psychiatric consult was requested.

Conclusion

The forensic psychiatry team concluded that the patient’s decision-making capacity was preserved. The team suggested some actions to help the specialists deal with the ethical conflict. A reflection is proposed about the role of psychiatrists when an ethical dilemma involving decision-making capacity emerges in clinical situations, elucidating their work not only as physicians who determine diagnoses and conducts, but also as agents of transformation in the doctor–patient relationship.
Introducing clinical ethics consultation service in Malaysia: A SWOT analysis
Authors: Khoo Erwin Jiayuan , Chua Siew Houy , Thong Meow-Keong , Zilfalil Bin Alwi , Lantos John
Published: April 2019

Clinical ethics consultation service remains undeveloped in developing countries. It is recognised that its introduction poses challenges. Malaysia, a multicultural society with diverse religions, values and perceptions further complicate the introduction of formal clinical ethics consultation service. Clinicians attending a national congress workshop completed a Strengths–Weaknesses–Opportunities–Threats analysis. The aim was to gain insight into clinician’s expectations and promote initiatives leading to the introduction of clinical ethics consultation service. Clinicians agree that clinical ethics consultation service can improve quality of care, reduce healthcare costs and advocate for patients and providers. The analysis highlighted constraints in sufficient critical mass of relevant expertise and restricted opportunities for training. The opportunities lie in education, curriculum development and availability of dedicated proponents. Cultural barriers, limited resources, lack of awareness, differences in opinions, fear of litigation and destructive influence of social media are seen as threats to the introduction of clinical ethics consultation service. This study illustrates the value of involving stakeholders when introducing clinical ethics consultation service formally. The issues identified will inform the strategic directions for the delivery of clinical ethics consultation service at a national level.
Not just a phase: Exploring the role of program stage on well-being and motivation in doctoral students
Authors: Sverdlik Anna , Hall Nathan C
Published: April 2019

Doctoral students’ well-being and motivation are important factors that are both shaped by, and shape students’ academic experiences in their programs. Existing literature consistently highlights the concerning well-being and maladaptive motivational patterns in doctoral students, but no research to date attempted to explore some of the structural features associated with these wellness and achievement factors in a large-scale study. The present study examined whether doctoral program phase (i.e. coursework, comprehensive examination, or dissertation phase had an effect on 3004 doctoral students’ well-being levels (stress, depression, program satisfaction, and illness symptoms) and motivation (self-determined motivation and self-efficacy). Results revealed doctoral students to report the highest well-being and internal motivation during the coursework phase, while the comprehensive examination phase was found to be the most challenging for most students as indicated by the lowest wellness and motivation scores. A discussion of the present results and their theoretical and practical implications ensues.
Persistence and career criminality: Enjoying crime!
Authors: Mercan Boran Ali
Published: April 2019

Despite its existence as a common-sense category and criminological analytic, the notion of the ‘persistent criminal’ remains theoretically underdeveloped. While there is a notion that particular individuals ‘commit’ to a life of crime, criminology is yet to properly articulate why this is and how it comes to be. Drawing on psychoanalytically inflected discourse theory, this article demonstrates that the clinical categories of psychoanalysis such as subject, lack, identification and jouissance (enjoyment) are useful in understanding persistence and career criminality. The imagined possibility of inhabiting a ‘fantasmatic’ lifestyle becomes unconsciously reinforced by the joyful sensations that accompany aspects of their criminal lifestyle: criminal cultural consumerism, peer group respect and appearing attractive to women. Without being conscious and rationalistic, these processes nevertheless inform self-perception and behaviour at a deep level of being. This article provides a novel explanation for why persistent criminals remain dedicated to their illicit lifestyles.
Toward a Positive Psychology of Immigrants
Authors: Cobb Cory L. , Branscombe Nyla R. , Meca Alan , Schwartz Seth J. , Xie Dong , Zea Maria Cecilia , Molina Ludwin E. , Martinez Charles R.
Published: April 2019

The vast majority of immigration-focused research in psychology is rooted in deficit models that center on negative health outcomes (e.g., depression, acculturative stress, anxiety, substance use), resulting in a widely held assumption that immigrants are at greater risk for pathology and poor well-being compared with native-born individuals. Moreover, current political discourse often portrays immigrants as more prone to crime compared with native-born individuals. From a positive-psychology perspective, we argue that, despite numerous migration-related challenges, many immigrant populations report positive patterns of psychological health. We also provide evidence that immigrants are, in fact, less prone to crime than their native-born counterparts. We conclude by discussing several contributing factors that account for positive immigrant well-being across the range of destination countries. Ultimately, the field should address questions regarding (a) immigrants’ strategies for coping with the challenges involved in adapting to new homelands and (b) asset-based factors that help immigrants to thrive during difficult life challenges.
String-based flapping mechanism and modularized trailing edge control system for insect-type FWMAV
Authors: Gong DuHyun , Lee DaWoon , Shin SangJoon , Kim SangYong
Published: April 2019

This paper presents the design process and experimental results of a brand new flapping and trailing edge control mechanism for a flapping wing micro air vehicle. The flapping mechanism, whose main components are fabricated from string, is suggested and optimized further by a modified pattern search method. The trailing edge control mechanisms for pitching and rolling moments are designed to be attached onto the present flapping mechanism in a modularized fashion. Prototypes of both mechanisms are fabricated and experimentally tested in order to examine the feasibility of the designs. It is expected that the present flapping mechanism will generate enough lift for the total weight of the vehicle. The present control mechanism is found to be able to supply sufficient control moment.
Rotor performance enhancement through blade surging
Authors: Bensebaa T , Jardin T , Prothin S , Doue N
Published: April 2019

This short paper introduces a new concept of rotor where the blades undergo a periodic surging motion in the rotor disk plane. It is shown that the unsteady actuation induces aerodynamic phenomenon that can enhance both rotor thrust and efficiency, depending on the amplitude and frequency of actuation. In particular, the increase in aerodynamic performance is found to correlate with the development of a large scale leading edge vortex. Accordingly, the optimal frequency is found to correlate with the formation time of this vortex.
No differences in effectiveness and safety between pipeline embolization device and stent-assisted coiling for the treatment of communicating segment internal carotid artery aneurysms
Authors: Enriquez-Marulanda Alejandro , Salem Mohamed M , Ascanio Luis C , Maragkos Georgios A , Gupta Raghav , Moore Justin M , Thomas Ajith J , Ogilvy Christopher S , Alturki Abdulrahman Y
Published: April 2019

Background

Aneurysms arising from the communicating segment (C7) of the internal carotid artery (ICA) are one of the most frequent locations of intracranial aneurysms. Stent-assisted coiling (SAC) and flow diversion therapies are both endovascular strategies used for the treatment of ICA aneurysms occurring at the C7 segment.

Objective

The aim of this study is to compare both methods' angiographic and functional outcomes, and procedural complications. To our knowledge, this is the first study to compare both modalities for aneurysms at this location.

Methods

A retrospective review was performed of our prospectively collected database from 2008 until 2017 for patients treated with SAC and from 2013 until 2017 for patients treated with pipeline embolization devices (PEDs).

Results

We identified 35 patients for this cohort with 38 aneurysms; 17 treated with SAC and 21 with PED. Mean age was 59 years, and 30 patients were female (86%). Complete occlusion at last follow-up occurred in 70.6% of patients in the SAC group and in 81% in the PED group ( p = 0.45). Posterior communicating artery patency at last follow-up did not differ significantly between the two groups (94.1% vs 85.7%; p = 0.40). Good functional outcome at last follow-up (mRS 0–2) was achieved in 100% and 88.2% of patients, respectively. Additionally, there was no significant difference between the two groups for retreatment rates, procedural hemorrhagic, or thromboembolic complications.

Conclusion

SAC and PED are two equally efficacious modalities for endovascular treatment of ICA aneurysms arising at the communicating segment of the ICA.
Experiences of School Counselor Mothers: A Phenomenological Investigation
Authors: Hermann Mary A. , Walsh Robyn L. , Underwood Jennifer W.
Published: April 2019

Researchers have identified some of the benefits and challenges working mothers experience. This phenomenological study extends this line of research to school counselor mothers. Themes highlighted include benefits of combining school counselor and motherhood roles, instances of role incompatibility, and strategies for managing multiple roles. We also provide suggestions for advocacy efforts to further support working mothers and to address the challenges specific to school counselor mothers.
King George’s Medical University: Inculcating a Service Mindset
Authors: Mehra Payal
Published: April 2019

The case narrates the dilemma faced by Dr Ravi Kant, the Vice Chancellor (VC) of King George’s Medical University, and the steps he took to resolve the same. The widely reputed public hospital had, under the leadership of Dr Ravi Kant, successfully introduced a series of communication interventions in the hospital in 2015. The aim of these interventions was to sensitize the doctors on the importance of empathy, patient-centred care, and its outcomes in line with the recent directives of the Medical Council of India. However, no tangible benefits of these interventions were visible, just yet. Doctor–patient clashes were far more frequent. Many times, the university almost came to a standstill because of flash strikes by the junior doctors and even doctors in residence. The VC was often confronted with disgruntled patients, irritated patient attendants, an angry media and missives from the state government. The key issues highlighted in this case are: How to make the doctors more responsive to the needs of the patient? What additional measures should be initiated to inculcate values of medical ethics and empathy within the doctors? What more could be added to the medical curriculum to bring about a greater change in perspective? Finally, how to develop a service mindset?
Brick or Click? Channel Choice Disruptions in Travel Industry
Authors: Jasrotia Sahil Singh , Mishra H. G. , Koul Surabhi
Published: April 2019

In the current era of digital infusion, customer behaviour is highly fluctuating. This has resulted retailers to be in a confused situation. The current need of the situation is to understand this change in customer behaviour and strategise accordingly. The purpose of the current study is to investigate the drivers of the channel choice, in relevance to travel industry. The study presents a conceptual model that reflects the antecedents to customer channel choice in travel industry. The article is based on a qualitative research analysis using semi-structured interviews to systematically collect and analyse the data. A sample of 25 retailers and 27 customers were selected and interviewed. A grounded theory approach has been adopted to generate a conceptual model. The article identifies several antecedents to channel choice in travel industry. Factors such as customer awareness, urgency of purchase, promotions and facilities have been highlighted and elaborated through the three-staged coding process. The other antecedents of the channel choice that have been highlighted through the verbatim are catchment area, family influences and affordability. In travel industry, channel structures have been well-studied. These studies dominantly focus on the players of the channel or the role of the middleman. The current study is unique in the way it explores the channel choice of customers after understanding both the extremes of the channel, that is, retailers and the customers. Also the methodology used is unique in its own way.
Impact of Anterior Cruciate Ligament Reconstruction on NCAA FBS Football Players: Return to Play and Performance Vary by Position
Authors: Wise Patrick Martin , Gallo Robert A.
Published: April 2019

Background:

Anterior cruciate ligament (ACL) injuries are devastating for college football players. Although the change in functional performance of National Collegiate Athletic Association (NCAA) football players after reconstruction has been shown to be negligible, studies have failed to analyze the statistical performance of these players upon their return.

Purpose/Hypothesis:

The purpose of this study was to quantify the impact of ACL reconstruction on the statistical performance of collegiate football players. We hypothesized that statistical performance would vary by position and that running backs, wide receivers, and defensive backs, compared with preinjury and controls, would experience the largest decline in performance after returning from ACL reconstruction.

Study Design:

Descriptive epidemiology study.

Methods:

NCAA Football Bowl Subdivision (FBS) football players who experienced ACL tears between the years 2010 and 2015 were identified. The rates of return to play after surgery were determined for each position. Preinjury and postoperative performance statistics of each running back, receiver, defensive lineman, linebacker, and defensive back who met inclusion criteria were compared. A t-test analysis was used to compare the performance changes experienced by these players versus the performance changes of matched controls.

Results:

A total of 349 players were identified. Only 63.64% of eligible offensive linemen returned to play. Upon return, running backs experienced significant performance decreases compared with controls in carries (mean ± SD, –2.4 ± 2.7 vs 2.8 ± 1.6; P = .003), yards (–12.3 ± 15.5 vs 13.8 ± 7.8; P = .006), and receptions (–0.22 ± 0.32 vs 0.32 ± 0.23; P = .011) per game. Receivers displayed significant performance decreases compared with controls in number of touchdowns (–0.019 ± 0.110 vs 0.18 ± 0.06; P = .004), receptions (–0.11 ± 0.79 vs 1.2 ± 0.4; P = .004), and yards (–3.2 ± 10.6 vs 18.6 ± 5.4; P = .0009) per game. Linebackers demonstrated less improvement than controls in tackles for loss (0.007 ± 0.115 vs 0.31 ± 0.11; P = .0003) and sacks (0.001 ± 0.061 vs 0.10 ± 0.06; P = .026).

Conclusion:

Although offensive linemen were the least likely to return to play, running backs and receivers returned to play at a lower level of performance. The performance of defensive players was less affected by ACL reconstruction.
Evolution of the kidney–cancer connection
Authors: Perazella Mark A , Workeneh Biruh , Chen Sheldon
Published: April 2019

Over the past decade, Onco-Nephrology has emerged as an important sub-field of not only nephrology and oncology but also hematology, urology, critical care medicine, clinical pharmacology, and palliative care medicine. This nexus reflects the unique connection that exists for kidney disease and cancer in all of clinical medicine. As noted, Onco-Nephrology combines the knowledge and skills of a number of specialty groups that span all areas of medicine. In this issue of the Journal of Onco-Nephrology, a series of papers addressing the various forms of kidney disease that develop in patients with cancer and its therapy is presented as part of the Onco-Nephrology Highlights section. These papers are based on the Onco-Nephrology Symposium that took place at MD Anderson Cancer Center in 2018. We hope you find these six papers educational and practical as you evaluate and treat patients with cancer and kidney disease in your clinical practice.
Neurosteroid Levels in the Orbital Frontal Cortex of Subjects With PTSD and Controls: A Preliminary Report
Authors: Cruz Dianne A. , Glantz Leisa A. , McGaughey Kara D. , Parke Gillian , Shampine Lawrence J. , Kilts Jason D. , Naylor Jennifer C. , Marx Christine E. , Williamson Douglas E.
Published: April 2019

Background

Neurosteroids mediate stress signaling and have been implicated in the pathogenesis of post-traumatic stress disorder (PTSD) in both preclinical and clinical studies. Compared to controls, subjects with PTSD exhibit altered neurosteroid levels in peripheral blood and cerebrospinal fluid as well as hypoactivity in the medial orbital frontal cortex (mOFC). Therefore, the aim of this study was to compare neurosteroid levels in the mOFC of subjects with PTSD ( n = 18) and controls ( n = 35).

Methods

Gray matter was dissected from fresh-frozen mOFC, and levels of the neurosteroids pregnenolone, allopregnanolone, pregnanolone, epiallopregnanolone, epipregnanolone, tetrahydrodeoxycorticosterone, and androsterone were determined by gas chromatography-tandem mass spectrometry.

Results

Analyses of unadjusted levels revealed that males with PTSD had significantly decreased levels of allopregnanolone ( p = 0.03) compared to control males, and females with PTSD had significantly increased levels of pregnenolone ( p = 0.03) relative to control females. After controlling for age, postmortem interval, and smoking status, results showed that males with PTSD had significantly decreased levels of androsterone ( t46 = 2.37, p = 0.02) compared to control males and females with PTSD had significantly increased levels of pregnanolone ( t46 = −2.25, p = 0.03) relative to control females.

Conclusions

To our knowledge, this is the first report of neurosteroid levels in postmortem brain tissue of subjects with PTSD. Although replication is required in other brain regions and a larger cohort of subjects, the results suggest a dysregulation of allopregnanolone and androsterone in males with PTSD and pregnanolone in females with PTSD in the mOFC.
ORP4L: Can Targeting an MCS Component Provide Tools for Eradication of Leukemia?
Authors: Olkkonen Vesa M.
Published: April 2019

The study commented here reports that the OSBP homologue ORP4L is aberrantly induced in CD34+CD38− leukemia stem cells (LSCs) of patients with acute myeloid leukemia and acts as an accessory factor for phospholipase C β3 (PLCβ3), a PLC isoform with a dominant role in these cells. Our mechanistic data suggest that ORP4L extracts and presents PI4,5P2 for catalysis by PLCβ3, thus controlling Ca2+ oscillations, bioenergetics, and survival of the cells. A small molecular compound LYZ-81 is described as a specific inhibitor of ORP4L, which can be employed to eradicate LSCs in vitro and in vivo in NOD/SCID mice. Our observations identify ORP4L as a potential target for new leukemia therapies.
Comparative risks of chronic inhaled corticosteroids and macrolides for bronchiectasis
Authors: Henkle Emily , Curtis Jeffrey R. , Chen Lang , Chan Benjamin , Aksamit Timothy R. , Daley Charles L. , Griffith David E. , Winthrop Kevin L.
Published: April 2019

Introduction

Non-cystic fibrosis (CF) bronchiectasis (“bronchiectasis”) is a chronic airway disease for which little data exist to inform treatment decisions. We sought to compare the risks of respiratory infections in chronic users of inhaled corticosteroids (ICSs)versusmacrolide monotherapy.

Methods

We identified a cohort of US Medicare enrollees with a bronchiectasis diagnosis (International Classification of Diseases, Ninth Revision, Clinical Modification code 494.0 or 494.1) between 2006 and 2014, excluding CF. We defined chronic new use as the first ≥28-day prescription of ICS therapy or macrolide monotherapy. We compared the characteristics of the exposure cohorts using standardised mean differences (SMDs) and computed a propensity score (PS) to account for treatment differences. The risks of acute exacerbation, hospitalised respiratory infection, all-cause hospitalisation and mortality were compared using PS decile-adjusted Cox regression models.

Results

We identified 83 589 new users of ICSs and 6500 new users of macrolides from 285 043 included Medicare enrollees with bronchiectasis. The crude incidence of hospitalised respiratory infection was 12.6 (ICS therapy) and 10.3 (macrolide monotherapy) per 100 patient-years. The PS-adjusted HRs comparing ICS with macrolide new users were 1.39 (95% CI 1.23–1.57) for hospitalised respiratory infection, 1.56 (95% 1.49–1.64) for acute exacerbation and 1.09 (95% 0.95–1.25) for mortality.

Interpretation

Among patients with bronchiectasis, the use of ICSs was associated with an increased risk of hospitalised respiratory infections compared with macrolide monotherapy.
Moving target: shifting the focus to pulmonary sarcoidosis as an autoimmune spectrum disorder
Authors: Kaiser Ylva , Eklund Anders , Grunewald Johan
Published: April 2019

Despite more than a century of research, the causative agent(s) in sarcoidosis, a heterogeneous granulomatous disorder mainly affecting the lungs, remain(s) elusive. Following identification of genetic factors underlying different clinical phenotypes, increased understanding of CD4+T-cell immunology, which is believed to be central to sarcoid pathogenesis, as well as the role of B-cells and other cells bridging innate and adaptive immunity, contributes to novel insights into the mechanistic pathways influencing disease resolution or chronicity. Hopefully, new perspectives and state-of-the-art technology will help to shed light on the still-elusive enigma of sarcoid aetiology. This perspective article highlights a number of recent advances in the search for antigenic targets in sarcoidosis, as well as the main arguments for sarcoidosis as a spectrum of autoimmune conditions, either as a result of an external (microbial) trigger and/or due to defective control mechanisms regulating the balance between T-cell activation and inhibition.
Dual mechanism of action of T2 inhibitor therapies in virally induced exacerbations of asthma: evidence for a beneficial counter-regulation
Authors: Efthimiou John , Poll Chris , Barnes Peter J.
Published: April 2019

Biological agents such as omalizumab and monoclonal antibodies (mAbs) that inhibit type 2 (T2) immunity significantly reduce exacerbations, which are mainly due to viral infections, when added to inhaled corticosteroids in patients with severe asthma. The mechanisms for the therapeutic benefit of T2 inhibitors in reducing virally induced exacerbations, however, remain to be fully elucidated. Pre-clinical and clinical evidence supports the existence of a close counter-regulation of the high-affinity IgE receptor and interferon (IFN) pathways, and a potential dual mechanism of action and therapeutic benefit for omalizumab and other T2 inhibitors that inhibit IgE activity, which may enhance the prevention and treatment of virally induced asthma exacerbations. Similar evidence regarding some novel T2 inhibitor therapies, including mAbs and small-molecule inhibitors, suggests that such a dual mechanism of action with enhancement of IFN production working through non-IgE pathways might also exist. The specific mechanisms for this dual effect could be related to the close counter-regulation between T2 and T1 immune pathways, and potential key underlying mechanisms are discussed. Further basic research and better understanding of these underlying counter-regulatory mechanisms could provide novel therapeutic targets for the prevention and treatment of virally induced asthma exacerbations, as well as T2- and non-T2-driven asthma. Future clinical research should examine the effects of T2 inhibitors on IFN responses and other T1 immune pathways, in addition to any effects on the frequency and severity of viral and other infections and related exacerbations in patients with asthma as a priority.
Significance of Ground Motion Scaling Parameters on Amplitude of Scale Factors and Seismic Response of Short- and Long-Period Structures
Authors: Cavdar Esengul , Ozdemir Gokhan , Bayhan Beyhan
Published: April 2019

In this study, an ensemble of ground motions is selected and scaled in order to perform code-compliant bidirectional Nonlinear Response History Analysis for the design purpose of both short- and long-period structures. The followed scaling method provides both the requirements of the Turkish Earthquake Code regarding the scaling of ground motions and compatibility of response spectra of selected ground motion pairs with the target spectrum. The effects of four parameters, involved in the followed scaling method, on both the amplitude of scale factors and seismic response of structures are investigated. These parameters are the number of ground motion records, period range, number of periods used in the related period range, and distribution of weight factors at the selected periods. In the analyses, ground motion excitations were applied to both fixed-base and seismically isolated structure models representative of short- and long-period structures, respectively. Results revealed that both the amplitudes of scale factors and seismic response of short-period structures are more prone to variation of investigated parameters compared to those of long-period structures.
Optimal EDPs for Post-Earthquake Damage Assessment of Extended Pile-Shaft–Supported Bridges Subjected to Transverse Spreading
Authors: Wang Xiaowei , Shafieezadeh Abdollah , Ye Aijun
Published: April 2019

During earthquakes, extended pile-shaft–supported bridges in laterally spreading ground can undergo inelastic deformations, especially in their embedded portions. Following earthquakes, it is critical to assess damage to these difficult-to-inspect portions and determine whether vehicles can safely pass bridges. This paper aims to identify optimal aboveground engineering demand parameters (EDPs) that are readily measurable after earthquakes and have high-quality probabilistic associations with post-earthquake load-carrying capacity of bridges as well as underground difficult-to-inspect EDPs. For this purpose, an experimentally validated bridge-soil-foundation model considering liquefaction-induced lateral spreading is adopted and subjected to ground-motion time histories in the transverse direction. Subsequently, pushdown analyses are performed to assess the post-earthquake vertical load-carrying capacity of bridges. Metrics such as efficiency, practicality, and measurability are established and examined for EDPs. Results show that residual column drift ratio is the optimal EDP for load-carrying capacity assessments, whereas maximum column drift ratio best predicts pile demands. Furthermore, developed probabilistic relationships between residual and maximum column drift ratios will assist in preliminary post-earthquake evaluation of bridges for damage assessment and posting decisions.
Sleep-Related Breathing Disorders in Young Adults With Prader-Willi Syndrome: A Placebo-Controlled, Crossover GH Trial
Authors: Donze Stephany H , de Weerd Al W , van den Bossche Renilde A S , Joosten Koen F M , Hokken-Koelega Anita C S
Published: April 2019

Context

Sleep-related breathing disorders (SRBD) are common in people with Prader-Willi syndrome (PWS). Young adults with PWS benefit from GH continuation after attaining adult height by maintaining the improved body composition obtained during childhood. There are, no studies about the effects of GH on SRBD in young adults with PWS who were treated with GH during childhood.

Objective

Investigate the effects of GH vs placebo on SRBD in young adults with PWS who were treated with GH during childhood and had attained adult height.

Design

Two-year, randomized, double-blind, placebo-controlled, crossover study in 27 young adults with PWS, stratified for sex and body mass index.

Setting

Dutch PWS Reference Center.

Intervention

Crossover intervention with GH (0.67 mg/m2/d) and placebo, both over one year.

Main Outcome Measures

Apnea hypopnea index (AHI), obstructive apnea index (OAI), central apnea index (CAI), measured by polysomnography.

Results

Compared with placebo, GH did not increase AHI, CAI, or OAI (P > 0.35). The effect of GH vs placebo was neither different between men and women, nor between patients with a deletion or maternal uniparental disomy/imprinting center defect. After two years, there was no difference in AHI, CAI, or OAI compared with baseline (P > 0.18). Two patients (7%) fulfilled the criteria of obstructive sleep apnea regardless of GH or placebo.

Conclusions

GH compared with placebo does not cause a substantial increase in AHI, CAI, or OAI in adults with PWS who were treated with GH during childhood and have attained adult height. Our findings are reassuring and prove that GH can be administered safely.
Using Pupillary Pain Index to Assess Nociception in Sedated Critically Ill Patients
Authors: Vinclair Marc , Schilte Clotilde , Roudaud Florian , Lavolaine Julien , Francony Gilles , Bouzat Pierre , Bosson Jean-Luc , Payen Jean-Francois
Published: April 2019

BACKGROUND:

Pupillary reflex dilation is a reliable indicator of response to noxious stimulation. In a proof of concept study, we investigated the performance of pupillary pain index, a new score derived from pupillary reflex dilation measurements, to predict nociceptive response to endotracheal suctioning in sedated critically ill patients.

METHODS:

Twenty brain-injured and 20 non–brain-injured patients were studied within 48 hours of admission (T1) in the intensive care unit and at 48–72 hours later (T2). Video-based pupillometer was used to determine pupillary reflex dilation during tetanic stimulation. The tetanic stimulation (100 Hz) was applied to the skin area innervated by the ulnar nerve and was stepwise increased from 10 to 60 mA until pupil size had increased by 13% compared to baseline. The maximum intensity value allowed the determination of a pupillary pain index score ranging from 1 (no nociception) to 9 (high nociception). The Behavioral Pain Scale response to endotracheal suctioning was measured thereafter.

RESULTS:

Behavioral Pain Scale responses to endotracheal suctioning and pupillary pain index scores were positively correlated at T1 and T2 (both P < .01). After adjustments for repeated measurements and group of patients, the area under the receiver operating characteristic curve of pupillary pain index to predict Behavioral Pain Scale response to endotracheal suctioning was of 0.862 (95% CI, 0.714–0.954). In the combined set of patients, a pupillary pain index score of ≤4 could predict no nociceptive response to endotracheal suctioning with a sensitivity of 88% (95% CI, 68%–97%) and a specificity of 79% (95% CI, 66%–88%). By contrast with endotracheal suctioning, tetanic stimulation had no effect on intracranial pressure in the brain-injured group.

CONCLUSIONS:

These results are a proof of concept. The nociceptive response to endotracheal suctioning could be accurately predicted using the determination of pupillary pain index score in sedated critically ill patients whether they have brain injury or not.
The Aesthetics of Scholarship
Authors: Matteini Michele
Published: April 2019

In the late 1770s Weng Fanggang (1733–1818) initiated what would become a defining feature of High Qing cultural and social life: ceremonies in honor of Su Shi's birthday. These elaborate, collective rituals took place yearly in Weng's Beijing residence and centered on a number of authentic “traces” (ji) of Su Shi that Weng had rediscovered over time. What was the significance of these rituals and how did they relate to the broader late-eighteenth-century interest in the past's material traces? This essay follows Weng Fanggang's quest for Su Shi across the empire and reconstructs the ways three such traces—a calligraphy, a poetry anthology, and a portrait—were continually transformed to accommodate Weng's act of devotion to Su Shi. The active participation of Chosŏn scholars in Weng's endeavors extended the cult of Su Shi beyond the borders of the Qing empire, outlining the existence of a transnational community of scholars who identified themselves in shared cultural symbols.
Sampling-Based Approximation Schemes for Capacitated Stochastic Inventory Control Models
Authors: Cheung Wang Chi , Simchi-Levi David
Published: April 2019

We study the classical multiperiod capacitated stochastic inventory control problems in a data-driven setting. Instead of assuming full knowledge of the demand distributions, we assume that the demand distributions can only be accessed through drawing random samples. Such data-driven models are ubiquitous in practice, where the cumulative distribution functions of the underlying random demand are either unavailable or too complex to work with. We consider the sample average approximation (SAA) method for the problem and establish an upper bound on the number of samples needed for the SAA method to achieve a near-optimal expected cost, under any level of required accuracy and prespecified confidence probability. The sample bound is polynomial in the number of time periods as well as the confidence and accuracy parameters. Moreover, the bound is independent of the underlying demand distributions. However, the SAA requires solving the SAA problem, which is #P-hard. Thus, motivated by the SAA analysis, we propose a polynomial time approximation scheme that also uses polynomially many samples. Finally, we establish a lower bound on the number of samples required to solve this data-driven newsvendor problem to near-optimality.
Recurso estilísticos en la producción narrativa de las novelas Bartleby y compañía y El mal de Montano de Enrique Vila-Matas
Authors: Gutiérrez Muñoz Óscar
Published: April 2019

In this paper we attempt to analyze the stylistic resources used by the Spanish writer Enrique Vila-Matas in the construction of his novels Bartleby & Co., and El mal de Montano. We focus on the use of certain aspects of intertextual mechanisms, displayed in the development of the fable, which gave rise to these novels. Thus, we reflect on the construction of the characters, as well as on their relationship to both the archive and literary tradition.
El ventall de la societat del seu temps segons Ramon Llull
Authors: Ensenyat Pujol Gabriel
Published: April 2019

The tripartite scheme based on the three orders (oratores, bellatores and laboratores), which characterized the society in the early Middle Ages, was already obsolete in the 13th century, since by this time the social structure had become much more complex. Furthermore, the presence of new social groups, such as the merchants and the bourgeois, raised a debate about its “raison d’être”. Therefore a person such as Ramon Llull, who knew very well the world where he lived, described a more representative image of the society of his time. Moreover, the interest of his analysis goes even further, since the Blessed took sides for some groups, such us the merchants –whose activity had been condemned until that moment– or the farmers, usually reviled. He even incorporates in his analysis some groups of people, such as the pilgrims or the painters, missing in any other work of the time.
Los inmigrantes europeos en las novelas de Ricardo Piglia. Lecturas paralelas de las novelas Respiración artificial y La ciudad ausente
Authors: Cselik Ágnes
Published: April 2019

En las novelas La ciudad ausente y Respiración artificial de Ricardo Piglia la mayoría de los personajes son inmigrantes europeos que desempeñan un papel clave. Italianos, alemanes, rusos y húngaros, intelectuales, artistas, obreros, y conspiradores que, con su simple  presencia,  con su historia personal y nacional, con sus tradiciones,  su lengua y cultura se encajan en la sociedad argentina, opinan y reflexionan sobre el presente y pasado histórico de su país de origen y a la par conversan y reaccionan sobre el presente y el pasado de su país de residencia dando un enfoque peculiar: argentino y europeo al mismo tiempo.
Una escritura que se olvida de las fronteras: visión supranacional y desterritorialización de la trama en los relatos del uruguayo Daniel Mella
Authors: Riccardi Giuseppe Gatti
Published: April 2019

Dentro de la producción literaria de las promociones hispanoamericanas más recientes, el objeto de nuestro estudio reside en reflexionar sobre esa vertiente que pone de relieve un proceso de superación de los fenómenos de localización de la escritura y de los contenidos narrados. Nuestro análisis de centra, en particular, en la producción artística (y literaria) de un país como Uruguay, en el que durante los últimos treinta años se han ido consolidando escrituras deslocalizadas e historias desterritorializadas. El objetivo de nuestro estudio (apoyado en la teoría de especialistas como Fernando Aínsa o Néstor García Canclini) reside en aplicar a la narrativa de Daniel Mella (Montevideo, 1975) esta capacidad del escritor ecléctico para franquear los límites fronterizos y salir de la tentación de una escritura localizada.
Para analizar este proceso, que conlleva la ausencia de un referente patriótico inmediato e implica la desaparición de todo “centro”, se estudiará la recopilación de cuentos Lava, en la que el cosmopolitismo topográfico del escritor se funda no tanto en una narrativa escrita desde una posición de nomadismo espacial del artista, sino en una escritura que configura para sus personajes una ausencia de fronteras en cuanto a la ubicación de sus hazañas ficcionales, y plantea también una nueva dimensión de alejamiento del centro, de tipo anímico-emocional.
Componentes lingüísticos de la chilenidad: lexicología
Authors: Branza Mircea-Doru
Published: April 2019

Las diferentes variedades diatópicas del español se caracterizan no sólo por diferentes fenómenos de  variación fonética y morfo-sintáctica, sino, sobre todo, por una rica variación léxica. En el caso de la variedad chilena, sus rasgos característicos son, por lo general, de índole léxica y se deben a contactos lingüísticos específicos de dicha área geográfica, ausentes o menos frecuentes en otras áreas: el contacto con el quechua, aimara, mapuche (o mapudungún), alemán, gitano o con la variedad argentina del español. La existencia de tales préstamos  en la variedad chilena del español se explica por la evolución histórico-cultural de la República de Chile.
Americanidad en la música barroca andina (Bolivia, Ecuador, Perú): sincretismo e identidades
Authors: Sarfson Gleizer Susana , Madrid Gómez Rodrigo
Published: April 2019

Cuando las ciudades virreinales del otrora imperio incaico buscaban consolidar una identidad, los elementos culturales de la metrópoli se entrelazaron con la tradición antigua, de manera que el sincretismo da un carácter singular a las manifestaciones culturales andinas del siglo XVIII. En este trabajo se reflexiona acerca de rasgos culturales propios, cuyas raíces se remiten tanto a los modelos españoles como a los propios de los pueblos originarios, que sustancian creaciones musicales que se enmarcan en la estética del barroco pero con elementos distintivos del mundo andino. Así, por ejemplo, advocaciones marianas cuya imagen se identifica con una ñusta, van acompañadas de música propia, que presentamos junto con otros ejemplos de sincretismo musical y cultural, a partir de una labor investigadora realizada en archivos de Bolivia, Ecuador y Perú.
El profesor y el decadente. Dos reacciones al positivismo en la generación del 900 en el Uruguay: José Enrique Rodó y Julio Herrera y Reissig
Authors: Nagy Marcel
Published: April 2019

Como en todo el continente latinoamericano, a finales del siglo 19 las nuevas generaciones intelectuales del Uruguay buscaban una salida del pensamiento de las décadas anteriores, marcadas por la influencia del positivismo. José Enrique Rodó y Julio Herrera y Reissig representan con sus obras maestras Ariel y Tratado de la imbecilidad del país, respectivamente, dos polos aparentemente opuestos. En el presente artículo se presentarán estas dos reacciones a la crisis del positivismo resaltando las diferencias y similitudes entre los dos intelectuales uruguayos tal vez los más destacados del cambio de siglo, que en sus obras, y pese a las diferencias estilísticas y de metodología, plantean un afán civilizador que difiere menos de lo que sugiere su primera lectura.