bluuebunny/crossref_metadata_2025 huggingface dataset:
‘To be understood as to understand’: A readability analysis of public library acceptable use policies
Authors: Robinson Elaine , McMenemy David
Published: August 2019

Acceptable Use Policies (AUPs) are documents stating the limitations users must agree to when first accessing information and communications technologies (ICTs) in organisations, such as employers, educational institutions and public libraries. AUPs lay out the parameters of acceptable use expected of someone accessing the ICT services provided, and should state in clear and understandable terms what behaviours will attract sanctions, both legal and in terms of restricting future access. Utilising a range of standard readability tests used to measure how understandable documents are, the paper investigates how readable the AUPs presented to public library patrons in the UK are in practice. Of the 206 AUPs in use across the local government departments who manage public library services 200 were obtained and subjected to a range of readability testing procedures. Four readability tests were used for analysis: the Flesch Reading Ease, the Coleman-Liau Index, the Gunning Fog Index and the SMOG Grade. Results for all four readability tests administered on all AUPs raise significant questions. For the Flesch Reading Ease score only 5.5% of AUPs scored at the standard readability level or higher (60+), and 8% scored at a very high level of difficulty akin to a piece of scientific writing. Similarly, for SMOG, only 7.5% of the 200 AUPs scored at the recommended level of 10. Likewise, very few AUPs scored at levels recommended for a general audience with either the Gunning Fog Index (11.5%) or the Coleman-Liau Index (2%). With such variability in readability, the fitness for purpose of the average AUP as a contract patrons must agree to can be called into question. This paper presents the first ever analysis of the readability of library AUPs in the literature. Recommendations are made as to how public library services may improve this aspect of practice.
Near infrared spectroscopic measurement of strain in rocks
Authors: Butcher Emily , Gibson Andrew , Benson Philip M , Koor Nick , Swift Gareth
Published: August 2019

The measurement of strain is a fundamental and widely studied parameter in engineering, rock mechanics, construction and materials testing. Contact sensors often used in these fields require contact with the target surface throughout the duration of a strain event. Non-contact methods typically require that that the measurement surface is prepared and often coated prior to testing. This paper considers the potential application of near infrared spectroscopy as a non-contact technique for the measurement of strain on natural surfaces. Excellent correlation was found between surface measurements of visible-NIR spectra and longitudinal strain taken during indirect Brazilian Disc Test for samples of sandstone, marble and basalt.
Sensitivity in ethical decision-making: The experiences of nurse managers
Authors: Roshanzadeh Mostafa , Vanaki Zohreh , Sadooghiasl Afsaneh
Published: August 2019

Background

In order to achieve the goals of the healthcare system, nursing managers are required to comply with ethical principles in decision-making. In complex and challenging healthcare settings, it is shown that the managers’ mere awareness of ethics does not suffice and managers need to be sensitive toward making ethical decisions.

Aim

To explore nursing managers and their sensitivity toward ethical decision-making by analyzing their related experiences.

Method

The current study has been conducted in Iran in 2017 through a qualitative content analysis approach. Nineteen nurse managers were selected purposefully from different hospitals in Tehran. Data were collected using semi-structured, in-depth, face-to-face interviews, and after transcription, they were analyzed according to the Graneheim and Lundman method.

Ethical considerations

The research was approved by the ethics committee of Tarbiat Modares University, Tehran, Iran. Participants were informed about the purpose of the study and submitted written informed consents regarding their participation. The principle of autonomy, confidentiality, and anonymity was taken into account in data collection.

Results

Fifteen subcategories, three categories (assertiveness, commitment, and insight), and one theme of excellent decision-making were the results of data analysis.

Discussion

Findings showed that nursing managers’ sensitivity to ethical decision-making allows them to make the best decision by insight, commitment, and assertiveness. Making a morally excellent decision ensures that ethical principles are followed in the healthcare system.

Conclusion

Considering that most managers are committed to making ethical decisions, it is required to develop the scope of their insights even further using a professional management and ethical principles training program. Also, by addressing some of the ethical barriers at personal and organizational levels, the assertiveness in managers can be improved, which in turn can facilitate their ethical decision-making.
Sarecycline Review
Authors: Haidari Wasim , Bruinsma Raquel , Cardenas-de la Garza Jesus Alberto , Feldman Steven R.
Published: August 2019

Objective: Sarecycline is a new oral tetracycline antibiotic recently approved by the US Food and Drug Administration. The aim of this article was to evaluate the data from published clinical trials of sarecycline in the treatment of acne, review the drug’s pharmacology, and understand how this new medication may apply to clinical practice. Data Sources: A systematic literature review was performed using the terms sarecycline (Seysara), P005672, and WC-3035 in the MEDLINE and EMBASE databases. ClinicalTrials.gov was searched to identify ongoing or nonpublished studies. Study Selection and Data Extraction: Articles in English between January 2000 and April 2019 relating to clinical trials, pharmacology, safety, and microbiological profile were evaluated. Data Synthesis: In a phase 3 clinical trial (SC1401), absolute change from baseline in facial inflammatory lesion count at week 12 was −15.3 for the sarecycline arm and −10.1 for placebo ( P < 0.01). In another phase 3 clinical trial (SC1402), the absolute change in this category was −15.7 for sarecycline and −10.7 for placebo ( P < 0.01). Mean percentage change in facial inflammatory lesion count was higher in the sarecycline group than in the placebo group in both studies ( P < 0.01). Relevance to Patient Care and Clinical Practice: The 1.5-mg/kg sarecycline dose has efficacy in reducing inflammatory lesions, is well tolerated, and has more targeted antimicrobial activity, which may help reduce the risk of developing antibiotic resistance. Conclusions: This novel, once-daily treatment may represent a useful treatment for patients with moderate to severe acne.
Vibroacoustic characteristics and sound attenuation analyses of a duct–membrane system coupled with strip masses
Authors: Liu Yang , Du Jingtao
Published: August 2019

In this paper, the vibroacoustic characteristics and noise reduction behavior of a duct–membrane system with attached strip masses are investigated analytically. Fully coupled structural–acoustic interactions between membrane–mass dynamics and duct sound propagation are constructed using the energy formulation and Rayleigh–Ritz procedure. Results from the current model are compared to those calculated by finite element analysis to verify the accuracy and effectiveness of the proposed model. Effective dynamic density and average vibrational velocity of the membrane are explicitly demonstrated at the peak/valley frequencies of transmission loss. The transmission loss peak frequency for such a model can be tuned by the variation of mass position and its weight, in which the first peak is mainly dependent on the mass properties, while the second one is more sensitive to the mass position. An extension to noise reduction analysis of a three-dimensional duct–membrane coupling system is also conducted. Significant enhancement of duct silencing performance has been obtained for the first time by making use of strip mass attachment.
Comparison of four inflation techniques on endotracheal tube cuff pressure using a feline airway simulator
Authors: White Donna M , Makara Mariano , Martinez-Taboada Fernando
Published: August 2019

Objectives

The aim of this study was to compare four inflation techniques on endotracheal tube cuff (ETC) pressure using a feline airway simulator.

Methods

Ten participants used four different endotracheal cuff inflation techniques to inflate the cuff of a low-pressure, high-volume endotracheal tube within a feline airway simulator. The simulator replicated an average-sized feline trachea, intubated with a 4.5 mm endotracheal tube, connected to a circle breathing system and pressure-controlled ventilation with oxygen and medical air. Participants inflated the ETC: by pilot balloon palpation (P); by instilling the minimum occlusive volume (MOV) required for loss of airway leaks during mechanical ventilation; until a passive release of pressure with use of a loss-of-resistance syringe (LOR); and with use of a syringe with a digital pressure reader (D) specifically designed for endotracheal cuff inflation. Intracuff pressure was measured by a manometer obscured to participants. The ideal pressure was considered to be between 20 and 30 cmH2O. Data were analysed by Shapiro–Wilk, Kruskal–Wallis and χ2 tests, as appropriate.

Results

Participants were eight veterinarians and two veterinary nurses with additional training in anaesthesia. Measured median intracuff pressures for P, MOV, LOR and D, respectively, were 25 cmH2O (range 4–74 cmH2O), 41 cmH2O (range 4–70 cmH2O), 31 cmH2O (range 18–64 cmH2O) and 22 cmH2O (range 20–30 cmH2O). D performed significantly better ( P <0.001) than all other techniques, with no difference between the other techniques.

Conclusions and relevance

Use of D for cuff inflation achieved optimal cuff pressures. There may be high operator-dependent variability in the cuff pressures achieved with the use of P, MOV or LOR inflation techniques. As such, a cuff manometer is recommended when using any of these techniques.
Snuff box radial artery access for arteriovenous fistula intervention
Authors: Hull Jeffrey , Workman Stephanie , Heath Jean Isabell
Published: August 2019

Purpose:

The aim of this article is to retrospectively compare snuff box radial artery access with direct fistula access for radiocephalic fistula intervention.

Materials and Methods:

Review of 68 consecutive radiocephalic interventions between April 2013 and April 2017 was performed. The snuff box radial access was performed under ultrasound guidance with the hand in a neutral position (thumb up). The snuff box radial artery was entered distal to the extensor pollicis longus, over the trapezium bone. Hand held pressure was applied for hemostasis. The procedure times, success, and complications of snuff box radial artery access procedures were reviewed.

Results:

Snuff box radial artery access was used in 25% (17/68) of radiocephalic fistula interventions. All access procedures were successful. Snuff box radial artery access was only used in cases involving the proximal fistula. Lesions treated from snuff box radial artery access approach included 19% (10/54) of fistula stenosis, 50% (1/2) thrombosis, 63% (5/8) immature fistulae, 100% (1/1) steal syndrome, and none of the (0/5) symptomatic outflow occlusions. The mean procedure times for snuff box radial artery access and direct fistula access were not significant at 29.1 ± 16.3 min (range = 10–81) and 26.8 ± 14.0 min (range = 5–70), respectively (p < 0.57). Minor hematoma occurred in 12% (2/17) snuff box radial artery access and 2% (1/51) direct fistula access. There were no major complications.

Conclusion:

Snuff box radial access was used successfully for radiocephalic fistula intervention with procedure times similar to direct fistula access without major complications.
Effortful control and attention as predictors of cognition in children born preterm
Authors: Nobre Fabíola DA , Gaspardo Claudia M , Linhares Maria Beatriz Martins
Published: August 2019

Background:

Preterm childbirth increases the risk of developmental problems. The aim of the present study was to examine the effects of temperament and attention on the cognition of school-age children who were born preterm, controlling for socioeconomic variables.

Material and Methods:

The sample was composed of 50 six-year-old children who were born preterm with very low birth weight. The children were evaluated using the Wechsler Intelligence Scale for Children (WISC-III) and the Cancellation Attention Test. The mothers were interviewed using the Children’s Behavior Questionnaire (CBQ). Statistical multiple linear regression analyses were performed.

Results:

70% of the children presented average or above-average full intellectual quotient (IQ). In the attention total score, 74% of the children were also within the average range or above. High verbal IQ associated with high maternal schooling explained 73% variability of the full IQ. High attention and maternal schooling, associated with children’s temperament with more effortful control, explained 35% variability of the verbal IQ. High attention, associated with high maternal schooling and socioeconomic level, explained 37% variability of the performance IQ. The neonatal clinical variables (gestational age, birth weight, 5th-minute Apgar, and length of stay in neonatal intensive care unit (NICU) and hospital) were not predictors of cognitive outcomes.

Conclusion:

The majority of the children who were born preterm presented average or above-average cognitive and attentional performances at school age, demonstrating potential resources for learning. Taken together, attention and temperament, associated with maternal schooling and socioeconomic status, were predictors of cognitive outcomes of children born preterm at school age.
Experimental study on bolted and anchored beam-to-column joints of prefabricated concrete frames
Authors: Zhang Xizhi , Hao Jiashu , Duan Dongchao , Xu Shengbo , Zhang Shaohua , Yu Houxin
Published: August 2019

A new type of beam-to-column joint used in prefabricated concrete frames was proposed in this study. In this joint, the longitudinal bars at the top of the beam are anchored to the column using straight thread sleeves, and the bars at the bottom are welded to the steel fastener that is bolted to the column. Cyclic loading tests of three specimens, namely, two beam–column joints of this type and a cast-in-place beam–column joint, were conducted to study the seismic behavior and feasibility of this type of joint. The difference between the two prefabricated joints is the shape of the holes on the end plate. Failure modes of the specimens were observed and analyzed. The hysteretic curves, bearing capacities, stiffness degeneration, ductility, and energy-dissipating capacities of the specimens were compared and studied. Test results indicated that all beam–column joints exhibited beam hinge failure. No slippage was observed between the concrete and horizontal plates of the steel fasteners used in the new type of joint. The bearing capacity and initial stiffness of both prefabricated specimens compared with the cast-in-place ones were increased. The steel fastener could increase the distance between the plastic hinge and the side surface of the column while enlarging the length of the plastic hinge. The trend of energy dissipation and stiffness degeneration of the specimens were similar, and the ductility coefficient ranged from 2.7 to 4.91. The displacement angles of the joints exceeded 1/50 before the failure of the specimens. The mechanical behavior of both prefabricated joints was similar, but the joint with U-shaped holes on the end plate was convenient to create.
Patient and public involvement in health research: A Nordic perspective
Authors: Sand Anne-Sofie , Grimsgaard Sameline , Pettersen Ingvild
Published: August 2019

Patient and public involvement (PPI) in health research is of increasing interest internationally, as well as being a means to enhance the quality and relevance of research. PPI was one of the main themes and parallel sessions at The Nordic Health Research and Innovation Networks in Oslo in 2017. In this short comment/debate article, we outline some of the experiences from the event. Importantly, there are many common challenges. More collaboration across the borders could ensure a broader range of experience in the field and provide better ways of developing and evaluating PPI in health research.
‘He Has Problems; He Is Not the Problem . . .’ A Qualitative Study of Non-Custodial Staff Providing Services for Young Offenders Assessed for Foetal Alcohol Spectrum Disorder in an Australian Youth Detention Centre
Authors: Hamilton Sharynne L. , Reibel Tracy , Watkins Rochelle , Mutch Raewyn C. , Kippin Natalie R. , Freeman Jacinta , Passmore Hayley M. , Safe Bernadette , O’Donnell Melissa , Bower Carol
Published: August 2019

Little is known about the challenges non-custodial youth detention centre staff face supporting young people with foetal alcohol spectrum disorder (FASD). We undertook qualitative inquiry to identify and describe the perspectives of non-custodial staff detention staff regarding the value of an FASD prevalence study. Data were collected using semi-structured interviews and focus groups and analysed using thematic network analysis. Staff held few concerns about the prevalence study and its impact on participating young people; however, they identified barriers related to study processes, and practices and culture within their workplace, which hindered gaining maximum benefit from the research and its findings.
Stereotactic Ablative Radiotherapy for Prostate Cancer—The Treatment Results of 500 Patients and Analysis of Failures
Authors: Miszczyk Leszek , Namysł-Kaletka Agnieszka , Napieralska Aleksandra , Kraszkiewicz Małgorzata , Miszczyk Marcin , Woźniak Grzegorz , Stąpór-Fudzińska Małgorzata , Głowacki Grzegorz , Tukiendorf Andrzej
Published: August 2019

Objective:

Stereotactic ablative radiotherapy is a very promising approach for the treatment of patients with prostate cancer. The aim of this study was to evaluate the clinical tolerance, effectiveness, patterns of failure, and attempt to define predictive factors based on our experience.

Methods:

The cohort consists of 264 low-risk and 236 intermediate-risk consecutive patients treated at one institution. Prostate-specific antigen (PSA), adverse effects, and androgen deprivation therapy (ADT) usage were noted.

Results:

Median follow-up was 31.3 months. Over 90% of the patients reported no gastrointestinal toxicity. There were 4 occurrences of G3+ sequelae. 75% patients had no genitourinary toxicity at first month, and up to 90% during the rest of follow-up, with only 1 case of G3 adverse event. The toxicity was more pronounced in patients with higher PSA concentrations. Prior to stereotactic ablative radiotherapy, the mean PSA was 7.59 and 277 patients used ADT. The PSA decreased for up to 20 months before reaching a plateau. The decline was slower, and PSA levels were higher in patients without ADT. A total of 15 treatment failures occured in a median time of 19.9 months. Higher PSA concentrations were connected with higher failure rates, even in the first month and prior to reaching Phoenix criterion.

Conclusion:

CyberKnife-based stereotactic ablative radiotherapy of low-risk and intermediate-risk prostate cancer patients is an effective and well-tolerated modality of treatment. PSA is the most important predictive factor. The evolution of PSA concentration in a particular subgroup of patients suggests that ADT in intermediate-risk cases could improve long-term results.
Necrotizing Fasciitis: Low-Dose Radiotherapy as a Potential Adjunct Treatment
Authors: Dhawan Gaurav , Kapoor Rachna , Dhamija Asha , Singh Ravinder , Monga Bharat , Calabrese Edward J.
Published: August 2019

Necrotizing fasciitis (NF) is a rapidly spreading bacterial infection causing extensive tissue necrosis and destruction. Despite appropriate therapy, the disease results in significant morbidity/mortality and substantial treatment costs. Several studies published in the early 1900s demonstrated the effective use of low-dose X-ray radiotherapy (RT) for the treatment of many diverse inflammatory conditions and diseases (eg, gas gangrene, sinus infections, arthritis, tendonitis, and serious inflammatory lung conditions). The mechanism by which therapeutic RT doses produce positive patient outcomes is related at least in part to its capacity to induce tissue-based anti-inflammatory responses. This action is due to the polarization of macrophages to an anti-inflammatory or M2 phenotype via optimized low-dose RT. Low-dose RT has the potential to significantly reduce debilitating surgeries and aggressive treatments required for NF, providing a 3-prong benefit in terms of patient mortality, length of hospitalization stays, and cost of health care (both short term and long term). Low cost and easy availability of low-dose RT makes it a potentially useful option for patients of every age-group. In addition, low-dose RT may be a particularly useful option in countries treating many patients who are unable to afford surgeries, antibiotics, and hyperbaric oxygen.
Childhood constipation
Authors: Rahim Syukri
Published: August 2019

Constipation is a common problem in childhood. It is often under-reported and families may delay seeking help due to fear of embarrassment and a negative response from healthcare professionals. Healthcare professionals may also underestimate the impact of constipation on the child and their family and this may subsequently contribute to poor clinical outcomes. Although it is rarely life-threatening, many children and young people experience psychological, social and educational consequences that require prolonged support. Signs and symptoms of childhood constipation are often poorly recognised. Delayed diagnosis, suboptimal therapy and lack of understanding of the condition often contribute to the ongoing symptoms and multiple medical consultations.
Trajectories of Marital Satisfaction in Diverse Newlywed Couples
Authors: Williamson Hannah C. , Lavner Justin A.
Published: August 2019

Couples’ marital satisfaction is thought to decline over the newlywed years, but recent research indicates that the majority of spouses have high, stable trajectories during this period, and significant declines occur only among initially dissatisfied spouses. These findings are drawn from predominantly White, middle-class samples, however, which may overestimate marital stability compared to samples with higher levels of sociodemographic risk. Accordingly, the current study tested the generalizability of newlyweds’ marital stability by examining satisfaction trajectories among 431 ethnically diverse newlywed couples living in low-income neighborhoods. Consistent with previous work, most spouses had high levels of satisfaction, substantial declines were limited to spouses with lower initial levels of satisfaction, and divorce significantly differed between groups. Wives with higher levels of sociodemographic risk started marriage less satisfied and declined more in satisfaction. Overall, these findings reveal risky and resilient relationships among disadvantaged couples, with considerable stability during the newlywed years.
Case-Based Insights: Arab Muslim Mothers’ Experiences of Managing a Child Newly Diagnosed With Type 1 Diabetes Mellitus
Authors: Rossiter Rachel Cathrine , Cooper Jennifer Louise , Marjei Suhad Issa , Brownie Sharon
Published: August 2019

Mothers frequently fulfill the role of primary caregiver for children diagnosed with type 1 diabetes mellitus (T1DM). A T1DM diagnosis has a significant impact on the child and the wider family unit. The objective is to develop understanding of mothers’ experiences caring for children diagnosed with T1DM in the cultural context of the Middle East to facilitate enhanced health service provision and support. This study used a qualitative design. Data were collected in individual semistructured interviews. Participants were mothers of Arabic descent and Muslim belief who had a child diagnosed with T1DM within the last 12 months. All mothers were registered at the health service where this research was conducted and resident in the United Arab Emirates at the time of this study. COREQ guidelines informed reporting of the research and findings. Participating mothers described initial reactions of shock and disbelief, followed by transition to near ordinary and near normal ( 85% normal) family functioning. Family, culture, and faith emerged as critical supports in the whirlwind daily challenge of balancing the multiple demands and competing needs of the newly diagnosed child and the broader family. This study is the first of its kind from countries comprising the Gulf Cooperation Council. The findings provide insight into the challenges and support needs of mothers caring for children newly diagnosed with T1DM in an Arab Muslim context. The findings also provide a basis for enhancing health service support and suggest themes to inform further research.
Risk Factors, Etiology, and Clinical Outcome of Ischemic Stroke in Young Adults Admitted in a Tertiary Care Hospital in India
Authors: Karri Madhavi , Ramasamy Balakrishnan
Published: August 2019

Background: Ischemic stroke in young adults is becoming a rising concern with the increase in vulnerability to traditional risk factors and changing lifestyles.

Aim: An overview of risk factors, classification, and clinical outcome of ischemic stroke in young adults (19 to 45 years) has been presented.

Methods: Data fulfilling the study criteria from the stroke registry between June 2014 and June 2017 were collected, and a detailed proforma was taken that included history, clinical examination, and routine investigations. Selective investigations such as prothrombotic workup and 24-hour Holter monitoring were performed. Stroke was subclassified using the Trial of Org 10172 in Acute Stroke Treatment criteria. National Institute of Health Stroke Scale (NIHSS) scores at baseline and the modified Rankin score (mRS) scoring after 3 months of patients’ admission were calculated.

Results: Out of 223 identified cases of ischemic stroke in young adults, 186 (83.4%) were taken for analysis, constituting 7.3% of the total stroke population of 3,059. Among the cases taken for analysis, 137 were males and 49 were females. A total of 150 patients were among the age group of 36 to 45 years. Dyslipidemia, smoking, and alcohol consumption were prevalent in the study group. Atherosclerotic strokes were predominant in the study population. NIHSS scores at admission had a significant impact on mRS scores after 3 months. In this study, only 4% reported the recurrence of stroke, whereas mortality was about 0.02%.

Conclusions: Workup required for ischemic stroke in young adults has always been a diagnostic challenge for physicians who treat the stroke patients, and this must be optimized in all health care centers. Despite extensive workup, 23.66% participants were found to be cryptogenic in this study. The clinical outcome was good in this study with less mortality observed.
Bronchial thermoplasty decreases airway remodelling by blocking epithelium-derived heat shock protein-60 secretion and protein arginine methyltransferase-1 in fibroblasts
Authors: Sun Qingzhu , Fang Lei , Roth Michael , Tang Xuemei , Papakonstantinou Eleni , Zhai Weiqi , Louis Renaud , Heinen Vincent , Schleich Florence N. , Lu Shemin , Savic Spasenjia , Tamm Michael , Stolz Daiana
Published: August 2019

Bronchial thermoplasty (BT) is to date the only therapy that provides a lasting reduction in airway wall remodelling. However, the mechanism of action of BT is not well understood. This study aimed to characterise the changes of remodelling regulating signalling pathways by BT in asthma.

Bronchoalveolar lavage fluid (BALF) was obtained from eight patients with severe asthma before and after BT. Primary bronchial epithelial cells were isolated from 23 patients before (n=66) and after (n=62) BT. Epithelial cell culture supernatant (Epi.S) was collected and applied to primary fibroblasts.

Epithelial cells obtained from asthma patients after BT proliferated significantly faster compared with epithelial cells obtained before BT. In airway fibroblasts, BALF or Epi.S obtained before BT increased CCAAT enhancer-binding protein-β (C/EBPβ) expression, thereby downregulating microRNA-19a. This upregulated extracellular signal-regulated kinase-1/2 (ERK1/2) expression, protein arginine methyltransferase-1 (PRMT1) expression, cell proliferation and mitochondrial mass. BALF or Epi.S obtained after BT reduced the expression of C/EBPβ, ERK1/2, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), PRMT1 and mitochondrial mass in airway fibroblasts. Proteome and transcriptome analyses indicated that epithelial cell-derived heat shock protein-60 (HSP60) is the main mediator of BT effects on fibroblasts. Further analysis suggested that HSP60 regulated PRMT1 expression, which was responsible for the increased mitochondrial mass and α-smooth muscle actin expression by asthmatic fibroblasts. These effects were ablated after BT. These results imply that BT reduces fibroblast remodelling through modifying the function of epithelial cells, especially by reducing HSP60 secretion and subsequent signalling pathways that regulate PRMT1 expression.

We therefore hypothesise that BT decreases airway remodelling by blocking epithelium-derived HSP60 secretion and PRMT1 in fibroblasts.
Efficacy and safety of inhaled α1-antitrypsin in patients with severe α1-antitrypsin deficiency and frequent exacerbations of COPD
Authors: Stolk Jan , Tov Naveh , Chapman Kenneth R. , Fernandez Pablo , MacNee William , Hopkinson Nicholas S. , Piitulainen Eeva , Seersholm Niels , Vogelmeier Claus F. , Bals Robert , McElvaney Gerry , Stockley Robert A.
Published: August 2019

Patients with inherited α1-antitrypsin (AAT) deficiency (ZZ-AATD) and severe chronic obstructive pulmonary disease (COPD) frequently experience exacerbations. We postulated that inhalation of nebulised AAT would be an effective treatment.

We randomly assigned 168 patients to receive twice-daily inhalations of 80 mg AAT solution or placebo for 50 weeks. Patients used an electronic diary to capture exacerbations. The primary endpoint was time from randomisation to the first event-based exacerbation. Secondary endpoints included change in the nature of the exacerbation as defined by the Anthonisen criteria. Safety was also assessed.

Time to first moderate or severe exacerbation was a median of 112 days (interquartile range (IQR) 40–211 days) for AAT and 140 days (IQR 72–142 days) for placebo (p=0.0952). The mean yearly rate of all exacerbations was 3.12 in the AAT-treated group and 2.67 in the placebo group (p=0.31). More patients receiving AAT reported treatment-related treatment-emergent adverse events compared to placebo (57.5%versus46.9%, respectively) and they were more likely to withdraw from the study. After the first year of the study, when modifications to the handling of the nebuliser were introduced, the rate of safety events in the AAT-treated group dropped to that of the placebo group.

We conclude that in AATD patients with severe COPD and frequent exacerbations, AAT inhalation for 50 weeks showed no effect on time to first exacerbation but may have changed the pattern of the episodes.
ERS/EAACI statement on severe exacerbations in asthma in adults: facts, priorities and key research questions
Authors: Bourdin Arnaud , Bjermer Leif , Brightling Christopher , Brusselle Guy G. , Chanez Pascal , Chung Kian Fan , Custovic Adnan , Diamant Zuzana , Diver Sarah , Djukanovic Ratko , Hamerlijnck Dominique , Horváth Ildikó , Johnston Sebastian L. , Kanniess Frank , Papadopoulos Nikos , Papi Alberto , Russell Richard J. , Ryan Dermot , Samitas Konstantinos , Tonia Thomy , Zervas Eleftherios , Gaga Mina
Published: August 2019

Despite the use of effective medications to control asthma, severe exacerbations in asthma are still a major health risk and require urgent action on the part of the patient and physician to prevent serious outcomes such as hospitalisation or death. Moreover, severe exacerbations are associated with substantial healthcare costs and psychological burden, including anxiety and fear for patients and their families. The European Academy of Allergy and Clinical Immunology (EAACI) and the European Respiratory Society (ERS) set up a task force to search for a clear definition of severe exacerbations, and to also define research questions and priorities. The statement includes comments from patients who were members of the task force.
Let‐7 as biomarker, prognostic indicator, and therapy for precision medicine in cancer
Authors: Chirshev Evgeny , Oberg Kerby C. , Ioffe Yevgeniya J. , Unternaehrer Juli J.
Published: August 2019

Abnormal regulation and expression of microRNAs (miRNAs) has been documented in various diseases including cancer. The miRNA let‐7 (MIRLET7) family controls developmental timing and differentiation. Let‐7 loss contributes to carcinogenesis via an increase in its target oncogenes and stemness factors. Let‐7 targets include genes regulating the cell cycle, cell signaling, and maintenance of differentiation. It is categorized as a tumor suppressor because it reduces cancer aggressiveness, chemoresistance, and radioresistance. However, in rare situations let‐7 acts as an oncogene, increasing cancer migration, invasion, chemoresistance, and expression of genes associated with progression and metastasis. Here, we review let‐7 function as tumor suppressor and oncogene, considering let‐7 as a potential diagnostic and prognostic marker, and a therapeutic target for cancer treatment. We explain the complex regulation and function of different let‐7 family members, pointing to abnormal processes involved in carcinogenesis. Let‐7 is a promising option to complement conventional cancer therapy, but requires a tumor specific delivery method to avoid toxicity. While let‐7 therapy is not yet established, we make the case that assessing its tumor presence is crucial when choosing therapy. Clinical data demonstrate that let‐7 can be used as a biomarker for rational precision medicine decisions, resulting in improved patient survival.
From ‘Vermeer Illuminated’ to ‘The Girl in the Spotlight’: approaches and methodologies for the scientific (re-)examination of Vermeer’s Girl with a Pearl Earring
Authors: Vandivere Abbie , Wadum Jørgen , van den Berg Klaas Jan , van Loon Annelies ,   The Girl in the Spotlight research team
Published: August 2019

Girl with a Pearl Earring by Johannes Vermeer (c. 1665) is the most beloved painting in the collection of the Mauritshuis in The Hague, The Netherlands. The Girl was last examined during a 1994 restoration treatment, within the project Vermeer Illuminated. Conservators and scientists investigated the material composition and condition of the painting using the analytical and scientific means that were available at the time: technical photography (visible light, ultraviolet fluorescence, and infrared), X-radiography, and stereomicroscopy. To understand the build-up of the paint layers, they investigated paint samples, often mounted as cross-sections. Their results were published in the book Vermeer Illuminated (1994), and as a chapter in Vermeer Studies (1998). This paper reviews the results published in the 1990s and considers them in light of a recent research project, where new findings were made possible by advances in non-invasive imaging, chemical analysis and data science. The project The Girl in the Spotlight is a Mauritshuis initiative, and involves a team of internationally recognised specialists working within the collaborative framework of the Netherlands Institute for Conservation+Art+Science+ (NICAS), with some scientists from other institutions. In 2018, the painting was examined in front of museum visitors at the Mauritshuis. The complementary imaging techniques employed included: technical photography, multispectral infrared reflectography, reflectance and fluorescence imaging spectroscopy (hyperspectral imaging), fibre optic reflectance spectroscopy, multiscale scanning optical coherence tomography, 3D scanning, 3D digital microscopy, macroscopic X-ray fluorescence and macroscopic X-ray powder diffraction. Furthermore, the samples mounted in 1994 were re-examined, and new forms of microscopic, organic and inorganic analysis were carried out to identify the pigments and binding media. Advances in computation and data science allow the results of these techniques to be co-registered and compared, and new results to be generated. These complementary research methods have allowed the Girl in the Spotlight team to: visualise and identify materials at and beneath the surface of the painting, scan the surface topography, and examine the surface at an extremely high magnification. Ultimately, they reveal the steps Vermeer took to create the iconic image of the Girl using layers of paint and subtle optical effects. They also provide information about how the painting originally looked, and the changes that have occurred over time.
Has There Been a Shift in Use of Subacute Rehabilitation Instead of Hospice Referral Since Immunotherapy Has Become Available?
Authors: Yeh Jonathan C. , Knight Louise S. , Kane Joyce , Doberman Danielle J. , Gupta Arjun , Smith Thomas J.
Published: August 2019

PURPOSE:

Immunotherapy has rapidly become the mainstream treatment of multiple cancer types. Since the first drug approval in 2011, we have noted a decline in referrals from inpatient oncology to hospice and an increase in referrals to subacute rehabilitation (SAR) facilities, possibly with the aim of getting strong enough for immunotherapy and other promising drugs. This study explores outcomes after discharge to SAR, including rates of cancer-directed therapy after SAR, overall survival, and hospice use.

METHODS:

We performed an electronic chart review of patients discharged from our inpatient oncology units to SAR facilities from 2009 to 2017. Demographics, admission statistics, and post-discharge outcomes were gathered from discharge summaries and targeted chart searches.

RESULTS:

Three hundred fifty-eight patients were referred to SAR 413 times. One hundred seventy-four patients (49%) returned to the oncology clinic before readmission or death, and only 117 (33%) ever received additional cancer-directed treatment (chemotherapy, radiation, or immunotherapy). Among all discharges, 28% led to readmissions within 30 days. Seventy-four patients (21%) were deceased within 30 days, only 31% of whom were referred to hospice. Palliative care involvement resulted in more frequent do not resuscitate code status, documented goals of care discussions, and electronic advance directives.

CONCLUSION:

A growing number of oncology inpatients are being discharged to SAR, but two thirds do not receive additional cancer therapy at any point, including a substantial fraction who are readmitted or deceased within 1 month. These data can help guide decision making and hospital discharge planning that aligns with patients’ goals of care. More clinical data are needed to predict who is most likely to benefit from SAR and proceed to further cancer therapy.
FOXO1 Negates the Cooperative Action of FOXL2C134W and SMAD3 in CYP19 Expression in HGrC1 Cells by Sequestering SMAD3
Authors: Belli Martina , Secchi Christian , Stupack Dwayne , Shimasaki Shunichi
Published: August 2019

Adult granulosa cell tumor (aGCT) is a rare type of ovarian cancer characterized by estrogen excess. Interestingly, only the single somatic mutation FOXL2C134W was found across virtually all aGCTs. We previously reported that FOXL2C134W stimulates CYP19 transcription synergistically with SMAD3, leading to elevated estradiol synthesis in a human granulosa cell line (HGrC1). This finding suggested a key role for FOXL2C134W in causing the typical estrogen overload in patients with aGCTs. We have now investigated the effect of FOXO1, a tumor suppressor, on CYP19 activation by FOXL2C134W in the presence of SMAD3. Intriguingly, FOXO1 antagonized the positive, synergistic effect of FOXL2C134W and SMAD3 on CYP19 transcription. Similar to FOXL2C134W, FOXO1 binds SMAD3 but not the proximal FOXL2C134W binding site (−199 bp) of the CYP19 promoter identified in our earlier studies. The results of a competitive binding assay suggested a possible underlying mechanism in which FOXO1 sequesters SMAD3 away from FOXL2C134W, thereby negating the cooperative action of FOXL2C134W and SMAD3 in inducing CYP19 expression. To our knowledge, this study is the first to demonstrate the ability of FOXO1 to restore an altered CYP19 expression by FOXL2C134W and SMAD3 and provides insight as to why FOXO1 deficiency promotes GCT development in mice.
Versions of the Natural
Authors: Kay Sarah , Zeeman Nicolette
Published: August 2019

This volume explores new ways of understanding medieval and early modern conceptualizations of nature in light of current developments in critical animal studies, ecocriticism, new materialism, as well as our expanding knowledge of premodern philosophy, medicine, and encyclopedism. The articles engage numerous disciplines, including philosophy, history of science, history of ideas, and Anglo-Saxon, French, and English literary studies; their approaches represent a broad range of Anglophone and Continental European academic traditions. Collectively, the volume brings to light tensions and contradictions in premodern ideas of “nature” and “the natural.” The “versions of the natural” that emerge are more ecological and less anthropocentric than in much previous work in this area, their emphases correspondingly more philosophical, scientific, even secular, than religious or theological. All contributions combine the detailed study of specific texts and problems with wider historical, theoretical, or philosophical inquiry.
Slow Moving Debt Crises
Authors: Lorenzoni Guido , Werning Iván
Published: August 2019

We study slow moving debt crises: self-fulfilling equilibria in which high interest rates, due to the fear of a future default, lead to a gradual but faster accumulation of debt, ultimately validating investors’ fear. We show that slow moving crises arise in a variety of settings, both when fiscal policy follows a given rule and when it is chosen by an optimizing government. A key assumption, in all these settings, is that the borrowing government cannot commit to issue a fixed amount of bonds in a given period. We discuss how multiplicity is avoided for low debt levels, for sufficiently responsive fiscal policy rules, and for long enough debt maturities. When the equilibrium is unique, debt dynamics are characterized by a tipping point, below which debt falls and stabilizes and above which debt and default rates grow. (JEL E43, E62, H50, H63)
Consumers as Tax Auditors
Authors: Naritomi Joana
Published: August 2019

To investigate the enforcement value of third-party information on potentially collusive taxpayers, I study an anti-tax evasion program that rewards consumers for ensuring that firms report sales and establishes a verification system to aid whistle-blowing consumers in São Paulo, Brazil (Nota Fiscal Paulista). Firms reported sales increased by at least 21 percent over 4 years. The results are consistent with fixed costs of concealing collusion, increased detection probability from whistle-blower threats, and with behavioral biases associated with lotteries amplifying the enforcement value of the program. Although firms increased reported expenses, tax revenue net of rewards increased by 9.3 percent. (JEL D22, H25, H26, L25, O14, O17)
Brands in Motion: How Frictions Shape Multinational Production
Authors: Head Keith , Mayer Thierry
Published: August 2019

Following the 2016 Leave vote in the referendum on UK membership in the EU and the election of Donald Trump, trade agreements have entered a period of great instability. To predict the impact of possible disruptions to existing arrangements requires counterfactual analysis that takes into account the complex set of factors influencing the production and marketing strategies of multinational corporations. We estimate a model of multinational decision-making in the car industry. This model predicts the production reallocation and consumer surplus consequences of changes in tariffs and non-tariff barriers induced by US-led protectionism, Brexit, transpacific, and transatlantic integration agreements. (JEL F13, F23, L21, L62, M31)
How Efficient Is Dynamic Competition? The Case of Price as Investment
Authors: Besanko David , Doraszelski Ulrich , Kryukov Yaroslav
Published: August 2019

We study industries where the price that a firm sets serves as an investment into lower cost or higher demand. We assess the welfare implications of the ensuing competition for the market using analytical and numerical approaches to compare the equilibria of a learning-by-doing model to the first-best planner solution. We show that dynamic competition leads to low deadweight loss. This cannot be attributed to similarity between the equilibria and the planner solution. Instead, we show how learning-by-doing causes the various contributions to deadweight loss to either be small or partly offset each other. (JEL D21, D25, D43, D83, L13)
Pre-Event Trends in the Panel Event-Study Design
Authors: Freyaldenhoven Simon , Hansen Christian , Shapiro Jesse M.
Published: August 2019

We consider a linear panel event-study design in which unobserved confounds may be related both to the outcome and to the policy variable of interest. We provide sufficient conditions to identify the causal effect of the policy by exploiting covariates related to the policy only through the confounds. Our model implies a set of moment equations that are linear in parameters. The effect of the policy can be estimated by 2SLS, and causal inference is valid even when endogeneity leads to pre-event trends (“pre-trends”) in the outcome. Alternative approaches perform poorly in our simulations. (JEL C23, C26)
Current outcomes and treatment of tetralogy of Fallot
Authors: van der Ven Jelle P.G. , van den Bosch Eva , Bogers Ad J.C.C. , Helbing Willem A.
Published: August 2019

Tetralogy of Fallot (ToF) is the most common type of cyanotic congenital heart disease. Since the first surgical repair in 1954, treatment has continuously improved. The treatment strategies currently used in the treatment of ToF result in excellent long-term survival (30 year survival ranges from 68.5% to 90.5%). However, residual problems such as right ventricular outflow tract obstruction, pulmonary regurgitation, and (ventricular) arrhythmia are common and often require re-interventions. Right ventricular dysfunction can be seen following longstanding pulmonary regurgitation and/or stenosis. Performing pulmonary valve replacement or relief of pulmonary stenosis before irreversible right ventricular dysfunction occurs is important, but determining the optimal timing of pulmonary valve replacement is challenging for several reasons. The biological mechanisms underlying dysfunction of the right ventricle as seen in longstanding pulmonary regurgitation are poorly understood. Different methods of assessing the right ventricle are used to predict impending dysfunction. The atrioventricular, ventriculo-arterial and interventricular interactions of the right ventricle play an important role in right ventricle performance, but are not fully elucidated. In this review we present a brief overview of the history of ToF, describe the treatment strategies currently used, and outline the long-term survival, residual lesions, and re-interventions following repair. We discuss important remaining challenges and present the current state of the art regarding these challenges.