bluuebunny/crossref_metadata_2025 huggingface dataset:
Vertical interlock and the value of cash holdings
Authors: Chen Xin , Yang Chang
Published: December 2019

We test whether vertical interlock endangers cash resources that manifests in a lower value of cash in listed companies affiliated with business groups. Using a sample of 9,032 observations from 2007 to 2016 in the Chinese market, we find that investors tend to value cash holdings in companies with vertical interlock substantially less than in those without. The marginal effect of vertical interlock on the value of cash remains significantly negative after controlling for existing governance mechanisms, accounting conservatism and internal control quality, shedding light on agency problems between majority shareholders and minority shareholders within business groups of emerging markets.
Mandatory CSR disclosure, monitoring and investment efficiency: evidence from China
Authors: Liu Li , Tian Gary Gang
Published: December 2019

This study investigates the effect of mandatory corporate social responsibility (CSR) disclosure on firms’ investment efficiency in China. Using the CSR regulation that mandates a group of listed firms to disclose stand‐alone CSR reports after 2008 as a natural experiment, we find that firms subject to the mandatory CSR regulation have decreased investment inefficiency subsequent to the mandate, especially in cases of overinvestment. This effect is more pronounced for firms with a control‐ownership wedge, state‐owned enterprises (SOEs), and firms having lower institutional ownership. Further analyses find that the reduction of overinvestment is much more significant in industries with high pollution and that the reduction in investment is not due to the CSR spending siphoning off capital used in other projects. We argue that mandatory corporate social responsibility disclosure improves monitoring over firms in China, especially when firms are characterised as having severe agency problems.
Antipsychotic medication exposure, clozapine, and pneumonia: results from a self‐controlled study
Authors: Rohde C. , Siskind D. , de Leon J. , Nielsen J.
Published: December 2019

Objective

By using a self‐controlled design, we investigated whether antipsychotic medication exposure was associated with increased pneumonia risk and whether patients receiving clozapine were more likely to develop pneumonia than patients receiving other antipsychotic medications.

Methods

Through nationwide health registers, we identified all out‐patients with schizophrenia initiating antipsychotic treatment. First, we estimated whether antipsychotic‐naïve patients with schizophrenia increased their risk of pneumonia after initiation of either a first‐ or second‐generation antipsychotic medication using a one‐year mirror‐image model. Afterward, similar analyses were made for individual second‐generation antipsychotics. Lastly, the rate of pneumonia for patients initiated on clozapine was compared to patients commenced on other second‐generation antipsychotics.

Results

In total, 8355 antipsychotic‐naïve patients with schizophrenia were initiated on a first‐generation antipsychotic medication; 0.95% of the patients had developed pneumonia before exposure, compared to 0.68% after exposure (P = 0.057). Similar findings were made for the 8001 antipsychotic‐naïve patients with schizophrenia initiated on second‐generation antipsychotic medications, with 0.56% developing pneumonia before exposure compared to 0.55% after exposure (P = 1.00). Second‐generation antipsychotic medications did not increase the pneumonia risk, except for risperidone (increased by 0.32%; P = 0.007) and clozapine, which gave the largest absolute increase in pneumonia risk although not significant (increased by 0.64%; P = 0.10). The rate of pneumonia was higher after initiation of clozapine than for other second‐generation antipsychotic medications.

Conclusion

Most antipsychotic medications were not found to increase the risk of pneumonia. Clozapine exposure might be associated with increased risk of developing pneumonia.
Sometimes Less Is More: Censorship, News Falsification, and Disapproval in 1989 East Germany
Authors: Gläßel Christian , Paula Katrin
Published: December 2019

Does more media censorship imply more regime stability? We argue that censorship may cause mass disapproval for censoring regimes. In particular, we expect that censorship backfires when citizens can falsify media content through alternative sources of information. We empirically test our theoretical argument in an autocratic regime—the German Democratic Republic (GDR). Results demonstrate how exposed state censorship on the country's emigration crisis fueled outrage in the weeks before the 1989 revolution. Combining original weekly approval surveys on GDR state television and daily content data of West German news programs with a quasi‐experimental research design, we show that recipients disapproved of censorship if they were able to detect misinformation through conflicting reports on Western television. Our findings have important implications for the study of censoring systems in contemporary autocracies, external democracy promotion, and campaigns aimed at undermining trust in traditional journalism.
An Enumerative Review and a Meta‐Analysis of Primed Goal Effects on Organizational Behavior
Authors: Chen Xiao , Latham Gary P. , Piccolo Ronald F. , Itzchakov Guy
Published: December 2019

Drawing on results from 32 published and 20 unpublished laboratory and field experiments, we conducted an enumerative review of the primed goal effects on outcomes of organizational relevance including performance and the need for achievement. The enumerative review suggests that goal setting theory is as applicable for subconscious goals as it is for consciously set goals. A meta‐analysis of 23 studies revealed that priming an achievement goal, relative to a no‐prime control condition, significantly improves task/job performance (d = 0.44, k = 34) and the need for achievement (d = 0.69, k = 6). Three moderators of the primed goal effects on the observed outcomes were identified: (1) context‐specific vs. a general prime, (2) prime modality (i.e., visual vs. linguistic), and (3) experimental setting (i.e., field vs. laboratory). Significantly stronger primed goal effects were obtained for context‐specific primes, visual stimuli, and field experiments. Theoretical and managerial implications of and future directions for goal priming are discussed.
Regulating germline editing in assisted reproductive technology: An EU cross‐disciplinary perspective
Authors: Nordberg Ana , Minssen Timo , Feeney Oliver , de Miguel Beriain Iñigo , Galvagni Lucia , Wartiovaara Kirmo
Published: December 2019

Potential applications of genome editing in assisted reproductive technology (ART) raise a vast array of strong opinions, emotional reactions and divergent perceptions. Acknowledging the need for caution and respecting such reactions, we observe that at least some are based on either a misunderstanding of the science or misconceptions about the content and flexibility of the existing legal frameworks. Combining medical, legal and ethical expertise, we present and discuss regulatory responses at the national, European and international levels. The discussion has an EU starting point and is meant as a contribution to the general international regulatory debate. Overall, this paper concludes that gene editing technologies should not be regulated autonomously. Rather, potential uses should be regulated under general, existing frameworks and where applicable by reference to sufficiently equivalent technologies and techniques already subject to specific regulation. To be clear, we do not argue for the hasty introduction of gene editing as a reproductive treatment option in the immediate future. We call for caution with regard to overreaching moratoria and prohibitions that will also affect basic research. We recommend flexible regulations that allow for further responsible research into the potential development of the technology. We call for an open and inclusive debate and argue that scientific communication should claim a more prominent role to counter the danger of widespread misinformation. A high level of transparency and accuracy should guide scientific communication while simultaneously global‐scale responsibility and governance should be fostered by promoting cross‐disciplinary thinking and multi‐level stakeholder involvement in legal and regulatory processes.
That’s not fair! The effects of teacher justice and academic achievement on Self and Other’s resistant agency
Authors: Mameli Consuelo , Caricati Luca , Molinari Luisa
Published: December 2019

Background

Notwithstanding the emphasis on the idea that students should be actively and accountably engaged in their educational pathways, little research has investigated learners’ agentic behaviours that take the form of student resistance to adult authority.

Aims

This paper presents an experimental study aimed to assess whether, and to what extent, student Self and Other resistant agency depends on perceptions of teacher justice and student achievement.

Methods

Participants were asked to read one of four scenarios concerning a generic student asking for the possibility to retake a test she/he had previously failed, with an experimental design including two levels of teacher justice × 2 levels of academic achievement. Then, they answered two items regarding the likelihood of protest on the part of the student depicted in the scenario and enforced by themselves in having to deal with a similar situation.

Results

The multilevel analysis indicated a principal effect of justice and target, with resistant agency rated as more likely in the unjust condition and for the Other. The justice effect was further qualified by an interaction with the achievement level, with resistant agency higher in the unjust and low achievement condition. Finally, a three‐way interaction appeared, with Self resistant agency higher in the just and high achievement condition.

Conclusions

These results are discussed in terms of their implications for teacher practices, as they emphasize the importance just learning environments have in allowing students to express their opinions as well as dissent.
Self‐determined motivation and academic buoyancy as predictors of achievement in normative settings
Authors: Aydın Görkem , Michou Aikaterini
Published: December 2019

Background

Academic buoyancy (Martin & Marsh, 2006, Oxford Review of Education, 35, 353; 2008, Journal of School Psychology, 46, 53) is students’ competence to respond effectively to academic daily setbacks and is considered an optimal characteristic of students’ functioning related to achievement. From the self‐determination theory perspective (Ryan & Deci, 2017, American Psychologist, 55, 68), satisfaction of the need for autonomy, competence, and relatedness and autonomous forms of motivation relate to students’ optimal functioning in schooling.

Aims

We investigated (1) whether students’ end‐of‐course (T2) academic buoyancy in the normative environment of English preparatory programmes (EPP) is predicted by their beginning‐of‐course (T1) need satisfaction or frustration and autonomous or controlled motivation (i.e., high or low self‐determined motivation), and (2) whether students’ T2 academic buoyancy mediates the relation between students’ T1 self‐determined motivation and final (T3) academic achievement.

Sample

In T1 and T2, 267 students (Mage = 19.11, SD = 1.28) attending three EPPs in Ankara, Turkey, participated in the study.

Method

A prospective design was used, data were collected through self‐reports, and SEM was conducted to test the hypotheses.

Results

Students’ T1 need frustration negatively predicted T1 autonomous motivation and positively predicted T1 controlled motivation, which (respectively) positively and negatively predicted T2 academic buoyancy. T1 need satisfaction related positively to T2 academic buoyancy. Finally, T2 academic buoyancy mediated the relation between students’ need satisfaction and final achievement while controlled motivation was also negatively related to final achievement.

Conclusion

Students’ high need satisfaction and low need frustration as well as high autonomous and low controlled motivation could support students’ buoyancy and achievement in the normative settings of EPP.
Bringing the Falklands/Malvinas Home: Young People's Everyday Engagements with Geopolitics in Domestic Space
Authors: Benwell Matthew C. , Gasel Alejandro F. , Núñez Andres
Published: December 2019

This paper draws on recent research examining feminist and everyday geopolitics to focus on the relatively neglected domestic sphere as a space where geopolitical events like the Falklands/Malvinas war are learnt, (re)produced, remembered and contested by young people. It presents qualitative data drawn from interviews with young people from Argentina (Río Gallegos) and the Falkland Islands (Stanley), locations with intimate connections to the 1982 war. It argues that research in domestic environments that engages the familial relations, objects and practices that embody geopolitical pasts can help make sense of how young people (are able to) express geopolitical agency.
Younger Dryas and Holocene environmental change at the Atlantic fringe of Europe derived from lake‐sediment stable‐isotope records from western Ireland
Authors: Holmes Jonathan A. , Leuenberger Markus , Molloy Karen , O'Connell Michael
Published: December 2019

Western Ireland lies at the Atlantic fringe of Europe and is thus well positioned to record changes in climate linked to North Atlantic circulation. Lake‐sediment oxygen and carbon isotopes are sensitive to changes in the atmosphere, the lake catchment and the lake itself, and thus are valuable proxies for long‐term environmental change. Here we present Younger Dryas and Holocene stable‐isotope records from endogenic and biogenic carbonates from An Loch Mór, a karstic lake on Inis Oírr, Aran Islands, western Ireland. The bulk carbonate and ostracod‐derived stable‐isotope records are a complex response to regional climatic and local factors. Low oxygen‐isotope and high carbon‐isotope values in the Younger Dryas most likely reflect low air temperatures and dominance of bedrock‐derived carbon from the poorly vegetated catchment, but input of detrital carbonate cannot be ruled out. Holocene variations in oxygen‐isotope values are likely a response mainly to changes in the isotopic composition of rainfall, evaporative enrichment of lake water and, during the past millennium, incursion of seawater as a result of regional sea‐level rise. A reduction in carbon‐isotope values at the Younger Dryas/Early Holocene transition reflects increased input of soil‐derived carbon to the lake, modified by changes in aquatic productivity. During the past millennium a shift to less negative values is attributed mainly to increasing saline influence. Broad similarities with stable‐isotope records from other sites in western Ireland suggest regional climatic controls dominated by North Atlantic atmospheric circulation patterns, although abrupt events, that were possibly unique to An Loch Mór, point to local factors also being important.
Occlusal support predicts tooth loss in older Japanese people
Authors: Mihara Yusuke , Matsuda Ken‐ichi , Takahashi Toshihito , Hatta Kodai , Fukutake Motoyoshi , Sato Hitomi , Gondo Yasuyuki , Masui Yukie , Kamide Kei , Sugimoto Ken , Kabayama Mai , Ishizaki Tatsuro , Arai Yasumichi , Maeda Yoshinobu , Ikebe Kazunori
Published: December 2019

Objectives

Many older people lose their teeth. However, few studies have examined whether the number of remaining teeth or the amount of occlusal support is more important for tooth loss that occurs in older age after adjusting for systemic factors. The purpose of this study was to investigate comprehensively the factors related to tooth loss over a period of 6 years, including occlusal support in 70‐ and 80‐year‐old community‐dwelling Japanese people.

Methods

This cohort study included 296 participants in the 70‐year‐old group and 232 in the 80‐year‐old group. The number of teeth of all participants was recorded at baseline and after 6 years, and the participants were divided into two groups according to the number of teeth lost (0 or 4 or more). Occlusal support was classified into three groups based on posterior occlusal support. Mean probing pocket depth, tooth brushing habits, frequency of dental check‐ups, education level, economic status and systemic factors (carotid atherosclerosis, hypertension, diabetes mellitus, dyslipidemia, cognitive function and smoking habits) were evaluated. Multiple logistic regression analysis was performed to investigate the relationship of tooth loss with occlusal support and systemic factors.

Results

Logistic regression analysis revealed that mean probing pocket depth (odds ratio [OR] = 5.70, 95% confidence interval [CI] = 2.70‐12.04, P < .01) and posterior occlusal support (reference = Eichner class A; Eichner B1‐3, OR = 4.33, 95% CI = 1.54‐12.17, P < .01; Eichner B4 or C, OR = 6.16, 95% CI = 1.17‐32.44, P = .03) were associated significantly with the loss of four or more teeth.

Conclusions

This study revealed that age itself is not a predictor of multiple tooth loss in community‐dwelling older Japanese people. Deep mean probing pocket depth and a lack of posterior occlusal support were significantly associated with the loss of four or more teeth.
Obesity is common at diagnosis of childhood pituitary adenoma and may persist following successful treatment
Authors: Sethi Aashish , Didi Mohammed , Dharmaraj Poonam , Ramakrishnan Renuka , Senniappan Senthil , Das Urmi , Avula Shivaram , Sinha Ajay , Mallucci Conor , Weerasinghe Kamal , Daousi Christina , Gilkes Catherine , Thorp Nicola , Blair Joanne
Published: December 2019

Objective

There is a paucity of data describing long‐term outcomes of paediatric patients with pituitary adenoma. In this report, we describe clinical features, treatment and outcomes of a paediatric cohort.

Design

Retrospective cohort study.

Patients

Twenty‐four white Caucasian patients aged <16 years from a single tertiary care centre in the United Kingdom at diagnosis followed for (median, range) 3.3, 0.7‐8.4 years.

Measurements

Clinical and radiological data at diagnosis and follow‐up.

Results

Thirteen patients had prolactinomas (54.1%, age: 15.2 years, 13.2‐15.8 years; all females), including ten macroadenomas (11.0‐35.0 mm). Patients presented with menstrual disorders (91%), headache (46%), galactorrhoea (46%) and obesity (body mass index [BMI] SDS > 2): (38%). Ten patients with prolactinoma were treated with dopamine agonist alone, 3 also required surgery and 2 patients, cabergoline, surgery plus radiotherapy. Five patients had Cushing's disease (20.8%, age: 14.0, 4.0‐15.7 years; 2 female), including one macroadenoma (24 mm). Patients presented with obesity (100%), short stature (60%) and headache (40%). Transsphenoidal resection resulted in biochemical cure (09.00 cortisol < 50 nmol/L). Two patients relapsed 3‐ and 6 years following surgery, requiring radiotherapy. One patient also required bilateral adrenalectomy. Six patients had nonfunctioning pituitary adenoma (25.0%, age: 15.8, 12.5‐16.0 years; 2 female), including two macroadenomas (20.0‐53.0 mm). Patients presented with obesity (67%), visual field defects (50%) and headache (50%). Four required surgical resections; two recurred following surgery and required radiotherapy. On latest follow‐up; 13 (54.1%) patients were obese (BMI 3.09 SDS; range: 2.05‐3.73 SDS).

Conclusion

Obesity is common at diagnosis of pituitary adenoma in childhood and may persist despite successful treatment. Adenomas were larger, more resistant to treatment, and more likely to recur than in adult populations.
“Multiple sclerosis plus”: Does it influence the disease course?
Authors: de Seabra Mafalda Maria Laracho , Abreu Pedro Miguel Paredes , Soares Mendonça Maria Teresa , Reis Joaquim Jorge Correia Silva , Sá Maria José Pontes Marques , Guimarães Ferreira Almeida Joana Cruz
Published: December 2019

Objectives

To study the association between multiple sclerosis (MS) and other autoimmune diseases (AID).

Methods

From a cohort of 635 patients with MS, 66 patients with an history of AID were selected. Controls, matched 1:1, were chosen from the population of patients with MS without autoimmune comorbidities. Further analysis aimed to compare these groups.

Results

The prevalence of comorbid AID in our population was 10.4%. The mean age was 43 ± 13 years; 77% were women. A total of 15 different types of AID were identified, the predominant one was autoimmune thyroiditis (18/66; 27%). In 46% of patients, the AID was diagnosed before, and in 49%, it was diagnosed after the diagnosis of MS. The presence of family history of AID was not associated with the risk of developing AID. Our analysis found no association between the presence of AID and disease activity (new lesions, gadolinium enhancement, mean of annual relapse rate, initiation of a second‐line treatment), either when considering each variable individually or within a composite score. The median Extended Disability Status Scale and Multiple Sclerosis Severity Score was 1.5 (interquartile range [IQR] 3.0) and 1.0 (IQR 3.0), respectively, in the AID group, and 1.5 (IQR 3.0) and 2.0 (IQR 3.0), respectively, in the control group, and the difference was not statistically significant. The presence of a concomitant AID influenced therapeutic choice in nine patients.

Conclusions

The present study underlines the varied range of AID that might coexist with MS. This common ground does not seem to have a negative effect on the disease course.
Characterization of macrophages infiltrating peri‐implantitis lesions
Authors: Fretwurst Tobias , Garaicoa‐Pazmino Carlos , Nelson Katja , Giannobile William V. , Squarize Cristiane H. , Larsson Lena , Castilho Rogerio M.
Published: December 2019

Objectives

The mechanisms involved in the initiation and progression of peri‐implantitis lesions are poorly understood. It was the aim to determine the content and activation status of macrophages present in human peri‐implantitis lesions and compare the current findings with the macrophage polarization associated with periodontitis lesions.

Material and Methods

A total of 14 patients were studied in this investigation. Seven were soft tissue biopsies from dental implants affected by peri‐implantitis that required explantation. Seven biopsies were from chronic periodontal disease. Immunofluorescence stains were performed using biomarkers to identify macrophages (CD68+) undergoing M1 polarization (iNOS+) and M2 polarization (CD206+), along with Hoechst 33,342 to identify DNA content. All samples were stained and photographed, and double‐positive cells for CD68 and iNOS or CD68 and CD206 were quantified.

Results

All peri‐implantitis biopsies examined revealed a mixed population of macrophages undergoing M1 polarization and M2 polarization. Further analysis demonstrated the co‐expression of iNOS and CD206, which indicates the presence of a heterogenic immune response on peri‐implantitis lesions. Macrophage polarization in peri‐implantitis lesions presents a distinct pattern than in periodontitis. We observed a significant increase in the population of M1 macrophages on peri‐implantitis samples compared to periodontal disease samples.

Conclusion

Our results demonstrate that peri‐implantitis has higher numbers of macrophages displaying a distinct macrophage M1 polarization signature compared to periodontitis lesions. This pattern may explain, in part, the distinct nature of peri‐implantitis progression vs. periodontitis in humans.
Racial disparities after stoma construction in colorectal surgery
Authors: Sharp S. P. , Ata A. , Chismark A. D. , Canete J. J. , Valerian B. T. , Wexner S. D. , Lee E. C.
Published: December 2019

Aim

Racial disparities are under‐recognized among patients undergoing colorectal surgery. The purpose of this study was to determine the complication rates and surgical outcomes stratified by race and ethnicity among patients undergoing colorectal surgery with intestinal stoma creation.

Method

The ACS NSQIP database from 2013 to 2016 was used. Colon, rectum and small bowel cases requiring intestinal stoma creation were selected. Both African‐American and other groups of minority patients were compared with Caucasian patients using a complex multivariable analysis model. Primary outcomes of interest were complication rates, mortality and extended hospital length of stay.

Results

The study included 38 088 admissions. After multivariable analysis, African‐American patients still had a prolonged length of hospital stay and higher complication rates. Other minorities also had a prolonged length of hospital stay and higher complication rates.

Conclusions

Both African‐American and other groups of minority patients requiring an ostomy suffer significantly higher postoperative complication rates and a prolonged hospital length of stay, even after comorbidity adjustment. Access to care, socioeconomic status and comorbid disease management are all important factors for minority patients who undergo colorectal surgery requiring intestinal stoma construction.
Early clinical outcomes of a rapid colorectal cancer diagnosis pathway using faecal immunochemical testing in Nottingham
Authors: Chapman C. , Thomas C. , Morling J. , Tangri A. , Oliver S. , Simpson J. A. , Humes D. J. , Banerjea A.
Published: December 2019

Aim

We introduced primary care access to faecal immunochemical testing (FIT) as a stratification tool for symptomatic patients considered to be at risk of colorectal cancer (CRC) prior to urgent referral. We aimed to evaluate clinical and pathway outcomes during the first 6 months of this novel approach.

Method

FIT was recommended for all patients who consulted their general practitioner with lower gastrointestinal symptoms other than rectal bleeding and rectal mass. We undertook a retrospective audit of the results of FIT, related clinical outcomes and resource utilization on prospectively logged cases between November 2017 and May 2018.

Results

Of the 1862 FIT kits dispatched by post 91.4% were returned, with a median return time of 7 days (range 2–110 days); however, 1.3% of returned kits could not be analysed. FIT results ≥ 150.0 μg haemoglobin (Hb)/g faeces identified patients with a significantly higher risk of CRC (30.9% vs 1.4%, chi‐square 167.1, P < 0.0001). FIT results ≥ 10.0 μg Hb/g faeces identified patients with significantly higher risk of significant noncancer bowel pathology (24.1% vs 4.9%, chi‐square 73.6, P < 0.0001) and FIT results < 4.0 μg Hb/g faeces identified a group more likely to have non‐CRC pathology (5.1% vs 2.4%, chi‐square 3.9, P < 0.05). The CRC detection rate in 531 patients investigated after a FIT result of < 4.0 μg Hb/g faeces was 0.2%. In 899 investigated patients, a FIT result with a threshold of 4.0 μg Hb/g faeces had sensitivity 97.2% (85.5–99.9% CI), specificity 61.4% (58.1–64.7% CI), negative predictive value 99.8% (98.7–100.0% CI) and positive predictive value 9.5% (8.7–10.4% CI).

Conclusion

A symptomatic pathway incorporating FIT is feasible and appears more clinically effective than pathways based on age and symptoms alone.
Impact of severe‐to‐very severe chronic obstructive pulmonary disease on the prognosis of patients with non‐small cell lung cancer who received chemotherapy
Authors: Dong Weigang , Zhu Yaqian , Du Yan , Wang Lina , Feng Xue , Ma Shuping
Published: December 2019

Introduction

Chronic obstructive pulmonary disease (COPD) is associated with poor prognosis in non‐small cell lung cancer (NSCLC) patients. There are limited data about the impact of severe‐to‐very severe COPD on prognosis in patients with NSCLC receiving first‐line chemotherapy.

Objectives

To investigate whether severe‐to‐very severe COPD impacted survival of patients with NSCLC receiving first‐line chemotherapy.

Methods

A retrospective review was performed on 513 consecutive NSCLC patients receiving first‐line chemotherapy between February 2014 and May 2018. Prognostic impact of severe‐to‐very severe COPD was analysed using regression analyses.

Results

Totally 258 NSCLC patients (118 non‐COPD, 96 mild‐to‐moderate COPD and 44 severe‐to‐very severe COPD) were evaluated retrospectively. Kaplan‐Meier analysis showed that the median overall survival times in the severe‐to‐very severe COPD, mild‐to‐moderate COPD and non‐COPD groups were 14.0 months [95% confidence interval (CI): 11.0‐17.0], 18 months (95% CI: 14.8‐21.2) and 19 months (95% CI: 15.3‐22.7), respectively. The difference was significant between patients with severe‐to‐very severe COPD and those without COPD (χ2 = 6.8, P = 0.009) and between patients with severe‐to‐very severe COPD and those with mild‐to‐moderate COPD (χ2 = 4.0, P = 0.045). Multivariate analysis showed that survival time was significantly shorter in the severe‐to‐very severe COPD group than in the non‐COPD group (adjusted hazard ratio: 1.876, 95% CI: 1.161‐3.030, P = 0.01) and mild‐to‐moderate COPD group (adjusted hazard ratio: 1.782, 95% CI: 1.046‐3.034, P = 0.033).

Conclusion

Severe‐to‐very severe COPD may worsen the prognosis of NSCLC patients who received first‐line chemotherapy.
Blinatumomab vs historic standard‐of‐care treatment for minimal residual disease in adults with B‐cell precursor acute lymphoblastic leukaemia
Authors: Gökbuget Nicola , Dombret Hervé , Giebel Sebastian , Brüggemann Monika , Doubek Michael , Foa Robin , Hoelzer Dieter , Kim Christopher , Martinelli Giovanni , Parovichnikova Elena , Maria Ribera Josep , Schoonen Marieke , Tuglus Catherine , Zugmaier Gerhard , Bassan Renato
Published: December 2019

Objectives

Survival outcomes from a single‐arm phase 2 blinatumomab study in patients with minimal residual disease (MRD)‐positive B‐cell precursor (BCP)‐acute lymphoblastic leukaemia (ALL) were compared with those receiving standard of care (SOC) in a historic data set.

Methods

The primary analysis comprised adult Philadelphia chromosome (Ph)‐negative patients in first complete haematologic remission (MRD ≥ 10−3). Relapse‐free survival (RFS) and overall survival (OS) were compared between blinatumomab‐ and SOC‐treatment groups. Baseline differences between groups were adjusted by propensity scores.

Results

The primary analysis included 73 and 182 patients from the blinatumomab and historic data sets, respectively. When weighted by age to the blinatumomab‐treatment group, median RFS was 7.8 months and median OS was 25.9 months in the SOC‐treated group. In the blinatumomab study, median RFS was 35.2 months; median OS was not evaluable. Propensity score weighting achieved balance with seven baseline prognostic factors. With adjustment for haematopoietic stem cell transplantation (HSCT) status, a 50% reduction in risk of relapse or death was observed with blinatumomab vs SOC. Median RFS, unadjusted for HSCT status, was 35.2 months with blinatumomab and 8.3 months with SOC.

Conclusions

These analyses suggest that blinatumomab improves RFS, and possibly OS, in adults with MRD‐positive Ph‐negative BCP‐ALL vs SOC.
Biotic resistance to invasion is ubiquitous across ecosystems of the United States
Authors: Beaury Evelyn M. , Finn John T. , Corbin Jeffrey D. , Barr Valerie , Bradley Bethany A.
Published: December 2019

The biotic resistance hypothesis predicts that diverse native communities are more resistant to invasion. However, past studies vary in their support for this hypothesis due to an apparent contradiction between experimental studies, which support biotic resistance, and observational studies, which find that native and non‐native species richness are positively related at broad scales (small‐scale studies are more variable). Here, we present a novel analysis of the biotic resistance hypothesis using 24 456 observations of plant richness spanning four community types and seven ecoregions of the United States. Non‐native plant occurrence was negatively related to native plant richness across all community types and ecoregions, although the strength of biotic resistance varied across different ecological, anthropogenic and climatic contexts. Our results strongly support the biotic resistance hypothesis, thus reconciling differences between experimental and observational studies and providing evidence for the shared benefits between invasive species management and native biodiversity conservation.
Does rattling deter? The case of domestic dogs
Authors: Caine Nancy G. , Muñoz Rita , Mulholland Michele M.
Published: December 2019

Although the rattling of rattlesnakes (Crotalus and Sistrurus) is widely accepted as being aposematic, the hypothesis that rattling deters approach from the snake's potentially dangerous adversaries has not been well tested. In a controlled study using rattling recorded from captive rattlesnakes (C. oreganus helleri) and a variety of comparison sounds or no‐sound controls, domestic dogs (Canis familiaris) showed no hesitation to approach camouflaged speakers projecting the recorded rattles. The dogs were equally likely to approach speakers projecting rattling as they were to approach speakers playing control sounds, or speakers that were silent. Furthermore, the dogs spent no less time in front of the speakers projecting the rattles than they did in front of speakers projecting control sounds or no sound. The dogs' reactions may not be representative of other species with whom rattlesnakes come into contact, but the data suggest a need for some circumspection about the role of rattling in the rattlesnake's defensive repertoire. Our results also suggest that dogs may be vulnerable to envenomation because they fail to react to the sound of rattling with avoidance.
Evolution‐guided engineering of non‐heme iron enzymes involved in nogalamycin biosynthesis
Authors: Nji Wandi Benjamin , Siitonen Vilja , Dinis Pedro , Vukic Vladimir , Salminen Tiina A. , Metsä‐Ketelä Mikko
Published: December 2019

Microbes are competent chemists that are able to generate thousands of chemically complex natural products with potent biological activities. The key to the formation of this chemical diversity has been the rapid evolution of secondary metabolism. Many enzymes residing on these metabolic pathways have acquired atypical catalytic properties in comparison with their counterparts found in primary metabolism. The biosynthetic pathway of the anthracycline nogalamycin contains two such proteins, SnoK and SnoN, belonging to nonheme iron and 2‐oxoglutarate‐dependent mono‐oxygenases. In spite of structural similarity, the two proteins catalyze distinct chemical reactions; SnoK is a C2–C5″ carbocyclase, whereas SnoN catalyzes stereoinversion at the adjacent C4″ position. Here, we have identified four structural regions involved in the functional differentiation and generated 30 chimeric enzymes to probe catalysis. Our analyses indicate that the carbocyclase SnoK is the ancestral form of the enzyme from which SnoN has evolved to catalyze stereoinversion at the neighboring carbon. The critical step in the appearance of epimerization activity has likely been the insertion of three residues near the C‐terminus, which allow repositioning of the substrate in front of the iron center. The loss of the original carbocyclization activity has then occurred with changes in four amino acids near the iron center that prohibit alignment of the substrate for the formation of the C2–C5″ bond. Our study provides detailed insights into the evolutionary processes that have enabledStreptomycessoil bacteria to become the major source of antibiotics and antiproliferative agents.

Enzymes

EC number1.14.11.
Development of an in vitro screening assay for PIP5K1α lipid kinase and identification of potent inhibitors
Authors: Strätker Katja , Haidar Samer , Amesty Ángel , El‐Awaad Ehab , Götz Claudia , Estévez‐Braun Ana , Jose Joachim
Published: December 2019

The human phosphatidylinositol 4‐phosphate 5‐kinase type I α (hPIP5K1α) participates in the phosphoinositide‐3‐kinase/protein kinase B/mammalian target of rapamycin signaling pathway. Despite the evidence that hPIP5K1α plays a role in the development of prostate cancer (PCa), only one inhibitor is known to date. With the aim of identifying new inhibitors, a nonradiometric assay for measurement of the hPIP5K1α enzyme activity was developed. The assay is based on the separation of the fluorescently labeled substrate phosphatidylinositol‐4‐phosphate (PI(4)P) and the resulting product phosphatidylinositol‐4,5‐bisphosphate (PIP2) by capillary electrophoresis (CE). Furthermore, an inactive mutant K261A of hPIP5K1α was generated by site‐directed mutagenesis and used as a control. Michaelis–Menten analysis revealed a Km value of 21.6 µm and Vmax of 0.65 pmol·min−1 for the cosubstrate ATP. The average Z’ value was determined to be 0.86, indicating a high reliability of the assay. An in silico screening of an in‐house compound library was performed employing the crystal structure of zebrafish PIP5K1α. By applying this strategy, three compounds with a 2‐amino‐3‐cyano‐4H‐pyranobenzoquinone scaffold were identified and tested using the CE‐based assay. These compounds inhibited hPIP5K1α to > 90% at a concentration of 50 µm. Subsequently, the inhibitory activity of all compounds with a pyranobenzoquinone scaffold (29) was tested on hPIP5K1α. Compound 4‐(2‐amino‐3‐cyano‐6‐hydroxy‐5,8‐dioxo‐7‐undecyl‐5,8‐dihydro‐4H‐chromen‐4‐yl)benzoic acid appeared to be the most potent inhibitor of hPIP5K1α identified so far with an IC50 value of 1.55 µm, exhibiting a substrate‐competitive mode of action. The effects of this compound on cell viability and the induction of apoptosis were investigated in LNCaP, DU145, and PC3 PCa cells.
Measuring fish catch and consumption: Practical methods for small‐scale fisheries based on length as an alternative to weight‐based approaches
Authors: Garaway Caroline , Arthur Robert
Published: December 2019

Small‐scale fisheries are recognised as making important contributions to nutrition and economic development despite a lack of accurate quantitative information on catches and consumption. While direct measurement remains the most appropriate way of collecting such data, it is impractical at large scales. Instead, household surveys based upon informant recall of fish caught and/or consumed are frequently used. However, the accuracy of weight recall by informants (even over short recall periods) has not been established. Using data from household surveys, the accuracy and precision of catch and consumption estimates derived from: (a) asking informants to recall weights of fish caught and (b) asking respondents to recall lengths of fish caught and converting to weight were tested. Length‐based methods, using visual aids to assist recall, were more accurate, precise and correctable. These methods could be useful for catch estimation, especially where fish are processed, sold or consumed shortly after capture.
Local climate determines vulnerability to camouflage mismatch in snowshoe hares
Authors: Zimova Marketa , Sirén Alexej P. K. , Nowak Joshua J. , Bryan Alexander M. , Ivan Jacob S. , Morelli Toni Lyn , Suhrer Skyler L. , Whittington Jesse , Mills L. Scott
Published: December 2019

Aim

Phenological mismatches, when life‐events become mistimed with optimal environmental conditions, have become increasingly common under climate change. Population‐level susceptibility to mismatches depends on how phenology and phenotypic plasticity vary across a species’ distributional range. Here, we quantify the environmental drivers of colour moult phenology, phenotypic plasticity, and the extent of phenological mismatch in seasonal camouflage to assess vulnerability to mismatch in a common North American mammal.

Location

North America.

Time period

2010–2017.

Major taxa studied

Snowshoe hare (Lepus americanus).

Methods

We used > 5,500 by‐catch photographs of snowshoe hares from 448 remote camera trap sites at three independent study areas. To quantify moult phenology and phenotypic plasticity, we used multinomial logistic regression models that incorporated geospatial and high‐resolution climate data. We estimated occurrence of camouflage mismatch between hares’ coat colour and the presence and absence of snow over 7 years of monitoring.

Results

Spatial and temporal variation in moult phenology depended on local climate conditions more so than on latitude. First, hares in colder, snowier areas moulted earlier in the fall and later in the spring. Next, hares exhibited phenotypic plasticity in moult phenology in response to annual variation in temperature and snow duration, especially in the spring. Finally, the occurrence of camouflage mismatch varied in space and time; white hares on dark, snowless background occurred primarily during low‐snow years in regions characterized by shallow, short‐lasting snowpack.

Main conclusions

Long‐term climate and annual variation in snow and temperature determine coat colour moult phenology in snowshoe hares. In most areas, climate change leads to shorter snow seasons, but the occurrence of camouflage mismatch varies across the species’ range. Our results underscore the population‐specific susceptibility to climate change‐induced stressors and the necessity to understand this variation to prioritize the populations most vulnerable under global environmental change.
No Gastrointestinal Dysmotility in Transgenic Mouse Models of Migraine
Authors: Sprouse Blum Adam S. , Lavoie Brigitte , Haag Melody , Mawe Seamus M. , Tolner Else A. , van den Maagdenberg Arn M.J.M. , Chen Shih‐Pin , Eikermann‐Haerter Katharina , Ptáček Louis , Mawe Gary M. , Shapiro Robert E.
Published: December 2019

Objective

To determine whether transgenic mouse models of migraine exhibit upper gastrointestinal dysmotility comparable to those observed in migraine patients.

Background

There is considerable evidence supporting the comorbidity of gastrointestinal dysmotility and migraine. Gastrointestinal motility, however, has never been investigated in transgenic mouse models of migraine.

Methods

Three transgenic mouse strains that express pathogenic gene mutations linked to monogenic migraine‐relevant phenotypes were studied: CADASIL (Notch3‐Tg88), FASP (CSNK1D‐T44A), and FHM1 (CACNA1A‐S218L). Upper gastrointestinal motility was quantified by measuring gastric emptying and small intestinal transit in mutant and control animals. Gastrointestinal motility was measured at baseline and after pretreatment with 10 mg/kg nitroglycerin (NTG).

Results

No significant differences were observed for gastric emptying or small intestinal transit at baseline for any of the 3 transgenic strains when compared to appropriate controls or after pretreatment with NTG when compared to vehicle.

Conclusions

We detected no evidence of upper gastrointestinal dysmotility in mice that express mutations in genes linked to monogenic migraine‐relevant phenotypes. Future studies seeking to understand why humans with migraine experience delayed gastric emptying may benefit from pursuing other modifiers of gastrointestinal motility, such as epigenetic or microbiome‐related factors.
Acquired perforating dermatosis: clinicopathologic study of a 10‐year period at a tertiary teaching hospital
Authors: Garrido Pedro Miguel , Queirós Catarina , Borges‐Costa João , Soares‐Almeida Luís , Filipe Paulo
Published: December 2019

Background

Acquired perforating dermatosis (APD) comprises an uncommon group of skin disorders that develop in adulthood in association with systemic diseases. The aim of this study was to characterize clinicopathologic features and treatment outcomes in a series of patients diagnosed with APD.

Methods

Retrospective study of all patients diagnosed with an APD over a 10‐year period (2009–2018) at a tertiary teaching hospital in Lisbon, Portugal.

Results

Fifty‐seven patients with APD were identified. Thirty‐five patients presented lesions in multiple anatomic areas (61.4%), and the lower limbs were the most common location. Forty‐six patients reported pruritus (80.7%), which was classified as severe in 21 of them (36.8%). An underlying systemic disease was identified in 53 patients (93.0%). Diabetes mellitus (DM) and chronic kidney disease (CKD) were the most common associated systemic diseases, but psychiatric disorders, malignancies, and chronic infections were present in a significant number of patients. The combination of topical steroids with antihistamines was the most prescribed initial treatment, but only 37.8% of the patients had a complete response. Acitretin, systemic steroids, and phototherapy were the treatments associated with the best outcome.

Conclusion

Acquired perforating dermatosis can be associated with many systemic disorders that have pruritus as a common factor. Chronic viral infections and an occult malignancy should be sought, particularly in the absence of DM and CKD. The management of APD is challenging and is best achieved with the control of the underlying systemic diseases.
Intentional (Nation‐)States: A Group‐Agency Problem for the State’s Right to Exclude
Authors: Joseph Matthew R.
Published: December 2019

Most philosophical defences of the state’s right to exclude immigrants derive their strength from the normative importance of self‐determination. If nation‐states are taken to be the political institutions of a people, then the state’s right to exclude is the people’s right to exclude – and a denial of this right constitutes an abridgement of self‐determination. In this article, I argue that this view of self‐determination does not cohere with a group‐agency view of nation‐states. On the group‐agency view that I defend, a nation‐state is the kind of group‐agent that does not supervene on the intentionality of member/citizens. If we think that a nation‐state is an intentional group‐agent in its own right, then we should think that self‐determination resides with the institutions of the state rather than with the citizens. If nation‐states do not supervene on the intentionality of citizens, then it is unclear why citizens might have the right to control membership in the state as a feature of self‐determination.
Financial resources and decisions to avoid information about environmental perils
Authors: Losee Joy E. , Shepperd James A. , Webster Gregory D.
Published: December 2019

Environmental perils pose threats that require mitigation. Mitigation requires knowledge of the threat. Ironically, people may opt to avoid information about an environmental peril, especially if they lack resources to respond and the mitigation burden is high or costly. Three experiments (N = 845) examined how available resources and the resource burden of responding to an environmental peril affect the perceived of burden of taking action, and how perceiving burden, in turn, affects avoidance of information about the threat. Experiments 1a and 1b revealed that lower perceived likelihood of taking action and low income predicted a greater tendency to avoid hurricane risk information among Florida residents. Experiment 2 examined receptivity to information about home radon levels and manipulated the burden required to make repairs ($200 vs. $2,000). Having low income and learning repairs were costly corresponded with greater perceived burden of taking action, which predicted a lower likelihood to repair and greater information avoidance. These findings demonstrate that facing a high mitigation burden and lacking resources can lead to remaining uninformed about risks posed by environmental perils. Remaining uninformed is problematic because it may increase people's vulnerability to damage from these threats. However, these findings also identify a potential pathway for intervention. Reminding people of resources they may be unaware of will likely increase their likelihood of preparation and decrease information avoidance.