bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Lean Management Practices and Sustainably‐Oriented Innovation on Sustainability Performance of Small and Medium‐Sized Enterprises: Empirical Evidence from the UK
Authors: Dey Prasanta Kumar , Malesios Chrisovalantis , De Debashree , Chowdhury Soumyadeb , Abdelaziz Fouad Ben
Published: November 2019

While lean management practices (LMP) help small and medium‐sized enterprises (SMEs) to be efficient, sustainability‐oriented innovation (SOI) facilitates adopting environmental and social practices. Although prior research looks into the effect of LMP on the economic performance (EP) of SMEs, less is known about the effect of LMP on sustainability (economic, environmental and social) performance. Studies on the effect of SOI on sustainability and economic performance are also scant. Additionally, examining the mediating effect of corporate social responsibility (CSR) practices (environmental and social practices) on both LMP and SOI achieving sustainability performance (SP) is rare. This research bridges these knowledge gaps by answering the question of how LMP, SOI, CSR practices, sustainability and economic performance are correlated. Through hypothesis testing using structural equation modelling, this study reveals the impact of LMP, SOI, CSR (environmental and social) practices on sustainability and economic performance. The study uses data from 119 SMEs within manufacturing industries in the Midlands, UK. The analysis reveals that LMP and SOI facilitate achieving both sustainability and economic performance, and SOI mediates LMP to achieve sustainability performance. Additionally, although CSR practices mediate LMP to achieve sustainability performance, they only borderline mediate SOI to achieve sustainability performance.
Frequent intoxication and alcohol tolerance in adolescence: associations with psychiatric disorders in young adulthood
Authors: Sarala Marian , Miettunen Jouko , Koskela Jari , Mustonen Antti , Rose Richard J. , Hurtig Tuula , Veijola Juha , Niemelä Solja
Published: November 2019

Aims

To assess the associations of intoxication frequency and number of drinks needed to become intoxicated in mid‐adolescence with onset of psychiatric disorders in early adulthood.

Design, Setting and Participants

Prospective cohort study in Northern Finland, with people from the Northern Finland Birth Cohort 1986 who self‐reported adolescent alcohol use: 6548 subjects (69.4% of the original sample). Data on alcohol use were collected using questionnaires at ages 15–16 years.

Measurements

Outcomes were any non‐organic psychosis, mood disorder, anxiety disorder, any substance use disorder (SUD) and all the studied psychiatric disorders in early adulthood gathered from nation‐wide health care, pension and insurance registers. Number of drinks needed to become intoxicated was categorized into three classes: (1) no alcohol use or intoxication, and (2) low and (3) high alcohol tolerance (more than seven/nine drinks for females/males) groups. Similarly, intoxication frequency was divided into three classes: (1) never, (2) one to two times and (3) three or more times during the past 30 days. Information regarding gender, family type, other drug use, psychopathology using Youth Self‐Report (YSR) total score and parental psychiatric disorders were used as covariates.

Findings

In the multivariable analyses, both low [odds ratio (OR) = 3.0, 95% confidence interval (CI) = 1.3–6.7, P‐value = 0.009] and high (OR = 4.4, 95% CI = 1.8–11.1, P‐value = 0.001) alcohol tolerance were associated with increased risk of SUD. More frequent intoxication was associated with increased frequency of SUD (OR = 3.9, 95% CI = 2.0–7.3, P‐value < 0.001) and mood disorder (OR = 1.6, 95% CI = 1.1–2.3, P‐value = 0.008). The latter was attenuated after adjusting with concurrent psychopathology (YSR) and other drug use.

Conclusions

Both higher alcohol tolerance and frequent intoxication in adolescence appear to be associated with increased risk of future substance use disorder.
Association study of the single‐nucleotide polymorphisms −3971G/A and +276G/T in the adiponectin gene with type 2 diabetes in a North Indian Punjabi population
Authors: Bains Veena , Kaur Harjit , Badaruddoza
Published: November 2019

Objective

To investigate the role of ADIPOQ gene variants (−3971G/A rs822396 and +276G/T rs1501299) with type 2 diabetes risk in a North Indian Punjabi population.

Methods

Adiponectin is one of the most abundant circulating adipocytokines in the human body that plays an important role in the metabolic processes and positively regulates energy homeostasis and insulin secretion. Several studies have provided the evidence of adiponectin gene polymorphisms association with type 2 diabetes mellitus (T2DM) in different ethnic populations. A total of 616 subjects including 316 T2DM patients and 300 normal healthy controls from Punjab were genotyped for ADIPOQ polymorphisms (rs822396 and rs1501299) by using a polymerase chain reaction–based restriction fragment length polymorphism (PCR‐RFLP) technique. Anthropometric, physiometric, and biochemical measurements were taken from each participant.

Results

Genotypic frequencies were significantly different in T2DM subjects and healthy controls for both polymorphisms (rs822396 and rs1501299). The risk genotype GG of −3971A/G and TT of +276G/T conferred an approximately twofold risk towards the development of T2DM and were found to be significantly higher in T2DM cases than control subjects (p = 0.006 and p = 0.019, respectively, after the Bonferroni correction). The recessive model of the ADIPOQ polymorphism rs822396 was significantly shown to confer a 3.63‐fold risk towards type 2 diabetes after adjusting for confounding factors and Bonferroni correction [odds ratio (OR): 3.63 (1.20–10.96), p = 0.022]. rs1501299 gave a 3.82‐fold risk towards development of T2DM but was not statistically significant after Bonferroni correction [OR: 3.82 (1.16–12.55), p = 0.027]. Meta‐analysis also illustrated the overall effect of the minor allele of rs822396 (−3971A/G) polymorphism, providing a greater risk for the T2DM development.

Conclusion

Thus, we concluded on the basis of observed results that the ADIPOQ gene polymorphisms rs822396 and rs1501299 plays an important role in the development of type 2 diabetes in North Indian Punjabi population.
Muslim mothers mainly saw circumcision in terms of religion or tradition but wanted it to be carried out medical professionals
Authors: Altunkol Adem , Abat Deniz , Topuz Ayşe Nur , Alma Ergün , Gürbüz Zafer Gökhan , Verit Ayhan
Published: November 2019

Aim

This study assessed the relationship between the education level of Muslim Turkish mothers whose sons had been circumcised and their views on circumcision.

Methods

Interviews based on 20 close‐ended questions were carried out in the Çukurova region of southern Turkey between June 2015 and September 2016. The participants were 1497 Muslim Turkish mothers whose sons had been circumcised and who were recruited using convenience sampling in schools, hospitals and public spaces.

Results

Most (82%) of the mothers saw circumcision as a religious and traditional requirement, 64% mentioned the health benefits and 48% mentioned cosmetic appearance. The majority (80%) were performed by health organisations, with two‐thirds (66%) expressing this preference. Most circumcisions were at school age (38%), which was about 6 years of age plus at the time of the study, and there were no complications in 79% of cases. Higher education levels were associated with views that circumcision was an important surgical procedure, it decreased the risk of urinary tract infections, it should be performed in hospitals and the foreskin did not prevent sexual intercourse.

Conclusion

Circumcision was mainly seen as a religious and traditional ritual, and more highly educated Turkish Muslim mothers were better informed about the health aspects.
Hypnotics with novel modes of action
Authors: Hoyer Daniel , Allen Andrew , Jacobson Laura H.
Published: November 2019

Insomnia and, more generally, lack of sleep are on the rise. Traditionally treated by classical hypnotics, such as benzodiazepines and Z drugs, which both act on the GABAA receptor, and other modalities, including nondrug therapies, such as cognitive behavioural therapy, there is a range of new hypnotics which are being developed or have recently received market approval. Suvorexant and the like target the orexin/hypocretin system: they should have less side effects in terms of drug–drug interactions with e.g. alcohol, less memory impairment and dependence potential compared to classical hypnotics.
In silico screening and surface plasma resonance‐based verification of programmed death 1‐targeted peptides
Authors: Zhang Pengli , Li Chengping , Ji Xiaoyue , Gao Mingjie , Lyu Sifan , Dai Xiaojun , Du Jiangfeng
Published: November 2019

Programmed death 1 (PD‐1) is a key immune checkpoint molecule. When it binds to programmed death‐ligand 1 (PD‐L1), it can negatively regulate the immune response. Therefore, blockade of the PD‐1/PD‐L1 interaction could unleash the power of immune system. Though successes achieved by anti‐PD‐1/PD‐L1 antibody drugs in clinical for various cancers, many intrinsic limitations of the high molecular weight drugs require alternatives such as peptide drugs and chemical compounds. In this study, we described a novel in silico approach which was used to screen peptides from PDB database and aimed to identify peptides that have potential to bind the PD‐L1 binding area of PD‐1 molecule. Based on the docking poses, eight peptides were synthesized and measured for their binding abilities by surface plasma resonance technique. The KD values of the synthesized peptides ranged from 10.0 to 133.0 μM. Furthermore, the binding mechanism between PD‐1 and the peptides was studied. In conclusion, we established a fast and reliable screening method for peptide discovery, which could be applied for identifying peptide inhibitors of various targets. The synthesized peptides could be served as starting points for designing PD‐1 drug for cancer immunotherapy.
Relationship between changes in motor capacity and objectively measured motor performance in ambulatory children with spastic cerebral palsy
Authors: Halma Elisabeth , Bussmann Johannes Bernardus Josephus , van den Berg‐Emons Hendrika Johanna Gerarda , Sneekes Emanuel Maria , Pangalila Robert , Schasfoort Fabienne Carmen ,   On behalf of the SPACE BOP study group
Published: November 2019

Background

Different interventions are offered to children with cerebral palsy (CP) to improve the activity domain of the international classification of functioning (ICF). In therapy settings, the focus is mostly on motor capacity, but the ultimate goal is to improve motor performance. We therefore examined if changes in motor capacity outcomes are accompanied by changes in objectively measured motor performance after a 3‐month intensive treatment period in ambulatory children with CP.

Methods

A secondary analysis on prospective clinical trial data was performed using multivariate linear regression. Sixty‐five children (37 boys and 28 girls) with spastic CP, mean age 7 years and 3 months, Gross Motor Function Classification System (GMFCS) levels I–III were involved in a distinct 3‐month intensive treatment period. Motor capacity (Gross Motor Function Measure [GMFM], functional muscle strength [FMS], and walking speed [WS]) and motor performance (using three Actigraph‐GT3X+‐derived outcome measures) were measured at baseline, 12 and 24 weeks.

Results

No significant associations were found for any of the change scores (∆12) between motor capacity and motor performance after a 12‐week intensive treatment period. After 24 weeks, ∆24FMS (p = .042) and ∆24WS (p = .036) were significantly associated with changes in motor performance outcome measure percentage of time spent sedentary (∆24%sedentary). In this model, 16% of variance of ∆24%sedentary was explained by changes in motor capacity (p = .030).

Conclusions

Changes in motor capacity are mostly not accompanied by changes in objectively measured motor performance after an intensive treatment period for ambulatory children with CP. These findings should be taken into account during goal setting and are important to manage expectations of both short‐ and longer term effects of treatment programmes.
Our experience of a paediatrician‐led clinic for the medical management of children with obstructive sleep‐disordered breathing
Authors: Kubba Haytham , Rowe Katherine , Pinczower Gideon , Sloane Robert , Waterham Michelle , Weiss Emma , Harwood Rachel
Published: November 2019

Background

Obstructive sleep‐disordered breathing (OSDB) is very common in children. Adenotonsillectomy is usually curative, but there is emerging evidence that topical nasal steroids can also be effective for some children and may avoid the need for surgery. The number of children referred for assessment of OSDB is increasing and in some departments, waiting times are long. We established a paediatrician‐led clinic for assessment and initial medical management of OSDB and in this study we report the proportion of children who avoided the need for surgery.

Method

Referral letters to the otolaryngology department were screened and those with suspected OSDB and no significant co‐morbidities were diverted to the paediatrician‐led clinic. We recorded data for a consecutive series of children seen in this clinic with suspected OSDB over a 3‐month period. Parents completed a 5‐item subset of questions from the OSA‐11 questionnaire before and after treatment with 6 weeks of topical nasal steroids.

Results

In the 3‐month study period, 103 children were seen, with a mean age of 6 (range 1‐16). Six (5.8%) had improved spontaneously before clinic attendance. Of the 97 children who were still symptomatic, 17 (17.5%) were referred directly for surgery on the basis of the severity of their symptoms, or because of other coexisting conditions that required surgical treatment (such as recurrent tonsillitis or otitis media). Three declined intranasal steroids. Seventy‐seven had a trial of intranasal steroids, of whom 34 (35%) reported enough improvement to avoid surgery, and 29 (28%) failed to improve and were referred for surgery. Fourteen (14%) failed to attend after the trial of steroids: of these, 5 (5%) were contactable by phone and confirmed improvement after topical steroids. OSA‐5 scores were significantly improved following intranasal steroids.

Discussion

A paediatrician‐led clinic can be an effective way to ease the workload of an over‐stretched otolaryngology service, and judicious use of topical nasal steroids can help around 40% of children with OSDB avoid surgery.
Plaque stage folliculotropic mycosis fungoides: histopathologic features and prognostic factors in a series of 40 patients
Authors: van Santen Suzanne , Jansen Patty M. , Quint Koen D. , Vermeer Maarten H. , Willemze Rein
Published: November 2019

Background

Folliculotropic mycosis fungoides (FMF) is a distinct variant of mycosis fungoides. Recent studies recognized indolent and aggressive subgroups of FMF, but there is controversy how patients presenting with plaques should be classified. The present study describes the histopathologic features of 40 FMF plaques. The aim of the study was to identify risk factors for disease progression and poor outcome in this group.

Methods

Clinical, histopathological, and immunophenotypical data from 40 patients with plaque stage FMF were reviewed and analysed for risk factors for disease progression and survival.

Results

After a median follow‐up of 80 months, disease progression occurred in 20 of 40 patients. Percentage of atypical cells, cell size, percentage of Ki‐67+ cells, and co‐existent interfollicular epidermotropism, but not the extent of perifollicular infiltrates, were associated with disease progression and reduced survival, while extensive follicular mucinosis was associated with increased survival.

Conclusions

This study underlines that FMF patients presenting with plaques represent a heterogeneous group and that a subgroup of these patients may have an indolent clinical course. It further shows that histological examination is a valuable tool to differentiate between indolent and aggressive disease.
Localization value of subclinical seizures on scalp video‐EEG in epilepsy presurgical evaluation
Authors: Wang Shan , Wang Z. Irene , Tang Yingying , Alexopoulos Andreas V. , Chen Cong , Katagiri Masaya , Aung Thandar , Najm Imad M. , Ding Meiping , Wang Shuang , Chauvel Patrick
Published: November 2019

Objective

To evaluate the localization value and prognostic significance of subclinical seizures (SCSs) on scalp video‐electroencephalography monitoring (VEEG) in comparison to clinical seizures (CSs) in patients who had epilepsy surgery.

Methods

We included 123 consecutive patients who had SCSs and CSs during scalp‐VEEG evaluation. All patients had subsequent epilepsy surgery and at least 1‐year follow‐up. Concordance between SCSs and CSs was summarized into five categories: complete, partial, overlapping, no concordance, or indeterminate. Using the same scheme, we analyzed the relationship between resection and SCS/CS localizations. The concordance measures, along with demographic, electroclinical, and other presurgical evaluation data, were evaluated for their associations with postoperative seizure outcome.

Results

Sixty‐nine patients (56.1%) had seizure‐free outcome at 1‐year follow‐up. In 68 patients (55.3%), the localizations of SCSs and CSs were completely concordant. Multivariate logistic analysis showed that complete SCS/CS concordance was independently associated with seizure‐free outcome at 1‐year (P = .020) and 2‐year follow‐up (P = .040). In the temporal lobe epilepsy (TLE) seizure‐free group, SCS localization was completely contained within the resection in 44.4% and CS localization was completely contained within the resection in 41.7%; in the extratemporal lobe epilepsy (ETLE) seizure‐free group, SCS localization was completely contained within the resection in 54.5% and CS localization was completely contained within the resection in 57.6%.

Significance

Complete concordance between CS and SCS localization is a positive prognostic factor for 1‐year and 2‐year postoperative seizure‐free outcome. Localization value of SCSs on scalp VEEG is similar to that of CSs for TLE and ETLE. Although SCSs cannot replace CSs, localization information from SCSs should not be ignored.
Urbanization drives cross‐taxon declines in abundance and diversity at multiple spatial scales
Authors: Piano Elena , Souffreau Caroline , Merckx Thomas , Baardsen Lisa F. , Backeljau Thierry , Bonte Dries , Brans Kristien I. , Cours Marie , Dahirel Maxime , Debortoli Nicolas , Decaestecker Ellen , De Wolf Katrien , Engelen Jessie M. T. , Fontaneto Diego , Gianuca Andros T. , Govaert Lynn , Hanashiro Fabio T. T. , Higuti Janet , Lens Luc , Martens Koen , Matheve Hans , Matthysen Erik , Pinseel Eveline , Sablon Rose , Schön Isa , Stoks Robby , Van Doninck Karine , Van Dyck Hans , Vanormelingen Pieter , Van Wichelen Jeroen , Vyverman Wim , De Meester Luc , Hendrickx Frederik
Published: November 2019

The increasing urbanization process is hypothesized to drastically alter (semi‐)natural environments with a concomitant major decline in species abundance and diversity. Yet, studies on this effect of urbanization, and the spatial scale at which it acts, are at present inconclusive due to the large heterogeneity in taxonomic groups and spatial scales at which this relationship has been investigated among studies. Comprehensive studies analysing this relationship across multiple animal groups and at multiple spatial scales are rare, hampering the assessment of how biodiversity generally responds to urbanization. We studied aquatic (cladocerans), limno‐terrestrial (bdelloid rotifers) and terrestrial (butterflies, ground beetles, ground‐ and web spiders, macro‐moths, orthopterans and snails) invertebrate groups using a hierarchical spatial design, wherein three local‐scale (200 m × 200 m) urbanization levels were repeatedly sampled across three landscape‐scale (3 km × 3 km) urbanization levels. We tested for local and landscape urbanization effects on abundance and species richness of each group, whereby total richness was partitioned into the average richness of local communities and the richness due to variation among local communities. Abundances of the terrestrial active dispersers declined in response to local urbanization, with reductions up to 85% for butterflies, while passive dispersers did not show any clear trend. Species richness also declined with increasing levels of urbanization, but responses were highly heterogeneous among the different groups with respect to the richness component and the spatial scale at which urbanization impacts richness. Depending on the group, species richness declined due to biotic homogenization and/or local species loss. This resulted in an overall decrease in total richness across groups in urban areas. These results provide strong support to the general negative impact of urbanization on abundance and species richness within habitat patches and highlight the importance of considering multiple spatial scales and taxa to assess the impacts of urbanization on biodiversity.
A Limited Central Bank
Authors: Plosser Charles I.
Published: November 2019

The President of the Philadelphia Federal Reserve Bank from 2006–2015 discusses the Fed's essential role as preserver of the currency's purchasing power and how the institution might be improved to better fulfill that role. To that end, the author proposes the imposition of four limits on the central bank that, by restricting its discretion, can be expected to improve outcomes and accountability.

First, limit the Fed's monetary policy goals to a narrow mandate in which price stability is the sole, or at least the primary, objective;

Second, limit the types of assets that the Fed can hold on its balance sheet to Treasury securities;

Third, limit the Fed's discretion in monetary policymaking by requiring a systematic, rule‐like approach; and

Fourth, limit the boundaries of its lender‐of‐last‐resort credit extension.

These changes, by creating a more limited central bank, would help preserve the central bank's independence, thereby improving the effectiveness of monetary policy. They would also make it easier for the public to hold the Fed accountable for its policy decisions.
The Fed's Communications: Suggestions for Improvement
Authors: Levy Mickey D.
Published: November 2019

The chief economist of Berenberg Capital Markets proposes three broad ways of improving the Fed's communications: (1) establish a more systematic approach to achieving its dual mandate; (2) clarify the proper role of monetary policy in achieving those objectives by distinguishing what is within the scope of monetary policy from what is clearly beyond it; and (3) articulate the Fed's goals and role in achieving macro‐prudential risk management and financial stability.

With these three ends in view, the author begins by urging FOMC members to refrain from making public comments immediately following government data releases and, when making public speeches and statements, to relate their comments on the economy to the Fed's dual mandate. The author also suggests three modifications of the Fed's official Policy Statement following FOMC meetings. First, each statement should start with an assessment of monetary policy and its consistency with achieving the Fed's statutory mandate, rather than the Fed's assessments of the economy and its subsectors with which such statements now begin. Second, the Fed should communicate separate explicit risk assessments of inflation and of the prospects for employment and the economy. (The Fed's current practice of sometimes dropping the risk assessments from statements and replacing them with nuanced language—for example, on changes in inflation and inflationary expectations—can be a source of confusion.) Third, all statements should discuss as clearly as possible the Fed's strategy for its balance sheet and unwind policy.

The Fed's quarterly Summary of Economic Projections (SEPs) should be redesigned to include FOMC estimates of forecast uncertainties and what they imply for monetary policy, and such alternative forecasts should be presented in place of the current central tendency and range of forecasts. The redesigned SEPs should be (1) based on a rigorous Fed assessment of expected monetary policy under different situations and contingency planning, and (2) as transparent as possible about the Fed's economic and inflation outlooks, the uncertainties in forecasting, and the conditionality of monetary policy. An illustration is provided of the alternative SEPs that would replace the current “dot plots” and include the Fed's forecasts of nominal GDP, calculated confidence intervals around the FOMC's median forecasts, and three separate forecasts of the Fed's perceived appropriate Fed funds rate.

Finally, the author views the “optimal solution” as a more systematic approach in which the Fed publishes a single forecast based on a model consistent with its dual mandate that shows how the appropriate Fed funds rate path would be expected to vary under different economic and inflation outcomes. Such an approach, by thus mapping likely monetary policy responses to alternative plausible economic and inflation outcomes, would increase the Fed's accountability as well as its transparency.
Dividend Consistency: Rewards, Learning, and Expectations
Authors: Michayluk David , Walker Scott , Neuhauser Karyn
Published: November 2019

The fact that many companies have a long track record of consistent dividend increases suggests that managers believe there is some benefit to establishing and maintaining such a pattern. Many companies, for example, follow a perennial policy of increasing the dividend in a particular quarter, maintaining it at the same level for the next three quarters, and then increasing it in the same quarter of the following year. But does the capital market reward companies for maintaining a consistent dividend policy? Do companies with a history of repeated dividend increases earn long‐term positive abnormal returns; and if so, how long do the returns persist?

The authors find that companies earned significantly positive abnormal returns following each of the first five annual dividend increases, over and above the positive announcement‐month returns. Nevertheless, the reward decreases as the track record of dividend increases becomes longer. After the first dividend increase, companies enjoy significantly positive returns for the next two years. Companies that increase the dividend in the same quarter of the following year also enjoy significant positive returns, but returns that are smaller (and less statistically significant) than in the case of first‐time dividend increases. And as the dividend‐increase track record further lengthens, the size and statistical significance of the abnormal returns continues to shrink; and after the sixth dividend increase, the abnormal returns in the next twelve months are statistically indistinguishable from zero.

In sum, although there is some support for maintaining a consistent dividend policy, the market response diminishes over time, and investors do not earn abnormal returns by buying stocks whose annual dividend has already been increased six or more times.
Reading with the eyes and under the skin: Comprehending conflicting digital texts
Authors: Mason Lucia , Zaccoletti Sonia , Scrimin Sara , Tornatora Maria Caterina , Florit Elena , Goetz Thomas
Published: November 2019

This study investigated the contribution of both physiological and behavioural process data to the comprehension of conflicting digital texts. We measured skin conductance level (SCL) as an index of arousal and the first‐pass and look‐back fixation times as indices of visual behaviour while reading. Forty‐eight seventh graders read four webpages on genetically modified food, and their comprehension of the texts was measured using a short essay. Results showed that the type of webpage did not differentiate the process data. Statistical procedures for the comparison of a series of regression models revealed that SCL and first‐pass fixation time negatively predicted multiple‐text comprehension while also considering the control variables. The more the students were aroused while reading and the longer the processing time during the first encounter with the reading material, the poorer their comprehension of the conflicting texts. However, the interaction of prior knowledge and arousal positively predicted multiple‐text comprehension. A slope analysis revealed that when participants had high prior knowledge and high arousal during reading, their postreading comprehension performance increased.
Up‐regulation of DDIT4 predicts poor prognosis in acute myeloid leukaemia
Authors: Cheng Zhiheng , Dai Yifeng , Pang Yifan , Jiao Yang , Liu Yan , Cui Longzhen , Quan Liang , Qian Tingting , Zeng Tiansheng , Si Chaozeng , Huang Wenhui , Chen Jinghong , Pang Ying , Ye Xu , Shi Jinlong , Fu Lin
Published: November 2019

The mammalian target of rapamycin (mTOR) inhibitor, DNA damage inducible transcript 4 (DDIT4), has inducible expression in response to various cellular stresses. In multiple malignancies, studies have shown that DDIT4 participates in tumorigenesis and impacts patient survival. We aimed to study the prognostic value of DDIT4 in acute myeloid leukaemia (AML), which is currently unclear. Firstly, The Cancer Genome Atlas was screened for AML patients with complete clinical characteristics and DDIT4 expression data. A total of 155 patients were included and stratified according to the treatment modality and the median DDIT4 expression levels. High DDIT4 expressers had shorter overall survival (OS) and event‐free survival (EFS) than the low expressers among the chemotherapy‐only group (all P < .001); EFS and OS were similar in the high and low DDIT4 expressers of the allogeneic haematopoietic stem cell transplantation (allo‐HSCT) group. Furthermore, in the DDIT4high group, patients treated with allo‐HSCT had longer EFS and OS than those who received chemotherapy alone (all P < .01). In the DDIT4low group, OS and EFS were similar in different treatment groups. Secondly, we analysed two other cytogenetically normal AML (CN‐AML) cohorts derived from the Gene Expression Omnibus database, which confirmed that high DDIT4 expression was associated with poorer survival. Gene Ontology (GO) enrichment analysis showed that the genes related to DDIT4 expression were mainly concentrated in the acute and chronic myeloid leukaemia signalling pathways. Collectively, our study indicates that high DDIT4 expression may serve as a poor prognostic factor for AML, but its prognostic effects could be outweighed by allo‐HSCT.
Inhibition of DNM1L and mitochondrial fission attenuates inflammatory response in fibroblast‐like synoviocytes of rheumatoid arthritis
Authors: Wang Xiaoyan , Chen Zhufeng , Fan Xuemei , Li Wei , Qu Jiaqi , Dong Chuan , Wang Zhixue , Ji Zhenwei , Li Yang
Published: November 2019

Mitochondrial fission and fusion are important for mitochondrial function, and dynamin 1‐like protein (DNM1L) is a key regulator of mitochondrial fission. We investigated the effect of mitochondrial fission on mitochondrial function and inflammation in fibroblast‐like synoviocytes (FLSs) during rheumatoid arthritis (RA). DNM1L expression was determined in synovial tissues (STs) from RA and non‐RA patients. FLSs were isolated from STs and treated with a DNM1L inhibitor (mdivi‐1, mitochondrial division inhibitor 1) or transfected with DNM1L‐specific siRNA. Mitochondrial morphology, DNM1L expression, cell viability, mitochondrial membrane potential, reactive oxygen species (ROS), apoptosis, inflammatory cytokine expression and autophagy were examined. The impact of mdivi‐1 treatment on development and severity of collagen‐induced arthritis (CIA) was determined in mice. Up‐regulated DNM1L expression was associated with reduced mitochondrial length in STs from patients with RA and increased RA severity. Inhibition of DNM1L in FLSs triggered mitochondrial depolarization, mitochondrial elongation, decreased cell viability, production of ROS, IL‐8 and COX‐2, and increased apoptosis. DNM1L deficiency inhibited IL‐1β–mediated AKT/IKK activation, NF‐κBp65 nuclear translocation and LC3B‐related autophagy, but enhanced NFKBIA expression. Treatment of CIA mice with mdivi‐1 decreased disease severity by modulating inflammatory cytokine and ROS production. Our major results are that up‐regulated DNM1L and mitochondrial fission promoted survival, LC3B‐related autophagy and ROS production in FLSs, factors that lead to inflammation by regulating AKT/IKK/NFKBIA/NF‐κB signalling. Thus, inhibition of DNM1L may be a new strategy for treatment of RA.
Fibroblast growth factor‐2/platelet‐derived growth factor enhances atherosclerotic plaque stability
Authors: Mao Yang , Liu Xiao Qiong , Song Yu , Zhai Chun Gang , Xu Xing Li , Zhang Lei , Zhang Yun
Published: November 2019

Increased immature neovessels contribute to plaque growth and instability. Here, we investigated a method to establish functional and stable neovessel networks to increase plaque stability. Rabbits underwent aortic balloon injury and were divided into six groups: sham, vector and lentiviral transfection with vascular endothelial growth factor‐A (VEGF)‐A, fibroblast growth factor (FGF)‐2, platelet‐derived growth factor (PDGF)‐BB and FGF‐2 + PDGF‐BB. Lentivirus was percutaneously injected into the media‐adventitia of the abdominal aorta by intravascular ultrasound guidance, and plaque‐rupture rate, plaque‐vulnerability index and plaque neovessel density at the injection site were evaluated. Confocal microscopy, Prussian Blue assay, Evans Blue, immunofluorescence and transmission electron microscopy were used to assess neovessel function and pericyte coverage. To evaluate the effect of FGF‐2/PDGF‐BB on pericyte migration, we used the mesenchymal progenitor cell line 10T1/2 as an in vitro model. VEGF‐A‐ and FGF‐2‐overexpression increased the number of immature neovessels, which caused intraplaque haemorrhage and inflammatory cell infiltration, eventually resulting in the plaque vulnerability; however, FGF‐2/PDGF‐BB induced mature and functional neovessels, through increased neovessel pericyte coverage. Additionally, in vitro analysis of 10T1/2 cells revealed that FGF‐2/PDGF‐BB induced epsin‐2 expression and enhanced the VEGF receptor‐2 degradation, which negatively regulated pericyte function consistent with the in vivo data. These results showed that the combination of FGF‐2 and PDGF‐BB promoted the function and maturation of plaque neovessels, thereby representing a novel potential treatment strategy for vulnerable plaques.
Furman at 45: Constitutional Challenges from California's Failure to (Again) Narrow Death Eligibility
Authors: Baldus David C. , Woodworth George , Grosso Catherine M. , Laurence Michael , Fagan Jeffrey A. , Newell Richard
Published: November 2019

The Eighth Amendment's “narrowing” requirement for capital punishment eligibility has challenged states since it was recognized in Furman v. Georgia in 1972. This article examines whether California's death penalty scheme complies with this requirement by empirically analyzing 27,453 California convictions for first‐degree murder, second‐degree murder, and voluntary manslaughter with offense dates between January 1978 and June 2002. Using a 1,900‐case sample, we examine whether California's death penalty statute fails to comply with the Eighth Amendment's narrowing test. Our findings support two conclusions. First, the death‐eligibility rate among California homicide cases is the highest in the nation during that period and in the ensuing decade. We find that 95 percent of all first‐degree murder convictions and 59 percent of all second‐degree murder and voluntary manslaughter convictions were death eligible under California's 2008 statute. Second, a death sentence is imposed in only a small fraction of the death‐eligible cases. The California death sentencing rate of 4.3 percent among all death‐eligible cases is among the lowest in the nation and over two‐thirds lower than the death‐sentencing rate in pre‐Furman Georgia.
Investigating Cohort Similarity as an Ex Ante Alternative to Patent Forward Citations
Authors: Ashtor Jonathan H.
Published: November 2019

Forward citations are arguably the most widely used empirical metric for patents, including as indicators of patent information content, cumulative innovation, value, and knowledge flows. However, forward citations have major shortcomings. Citations require long time horizons to accrue, and therefore they cannot be observed until several years after a patent issues. Citation data are often noisy, discontinuous, and highly skewed, complicating empirical analysis. Moreover, recent studies have questioned the reliability of citation data. As such, the most widely used empirical metric of patents is also the most suspect. This study constructs a measure of patents that correlates with forward citations, but is observable ex ante, immediately upon patent issuance or even earlier upon publication of a patent application. In addition, this measure is continuous and evenly distributed, such that it is suitable for large‐scale patent analytics applications. Finally, unlike citations, the measure is portable across patent systems, facilitating cross‐border comparisons of portfolios and datasets. Specifically, I construct a measure of the similarity of a patent to its technological‐temporal cohort, based on linguistic analysis of claim text. I employ advanced computational linguistic techniques to analyze the claims of all U.S. patents issued in the period 1976–2017, over 6 million patents in total, and I calculate the average degree of conceptual similarity of each patented invention to all others in the same technology field and time period cohort. I then extend the methodology to all issued EP patents, over 1.6 million in total. I validate the resulting measures against multiple established patent metrics for U.S. and EP patents. I test the robustness of this measure as a forecast for future patent citations in empirical research and big‐data applications. I find that cohort similarity correlates significantly with forward citations received by both U.S. and EP patents. Cohort similarity also substitutes for citations in leading prior studies of R&D output and innovation. Finally, I demonstrate that, unlike citations, cohort similarity is comparable across the U.S. and EP patent systems. Accordingly, cohort similarity may be useful for empirical patent research, comparative studies of patent policy, and analytics of large‐scale patent portfolios.
Population and size‐specific distribution of Atlantic salmon Salmo salar in the Baltic Sea over five decades
Authors: Jacobson Philip , Gårdmark Anna , Huss Magnus
Published: November 2019

Population‐specific assessment and management of anadromous fish at sea requires detailed information about the distribution at sea over ontogeny for each population. However, despite a long history of mixed‐stock sea fisheries on Atlantic salmon, Salmo salar, migration studies showing that some salmon populations feed in different regions of the Baltic Sea and variation in dynamics occurs among populations feeding in the Baltic Sea, such information is often lacking. Also, current assessment of Baltic salmon assumes equal distribution at sea and therefore equal responses to changes in off‐shore sea fisheries. Here, we test for differences in distribution at sea among and within ten Atlantic salmon Salmo salar populations originating from ten river‐specific hatcheries along the Swedish Baltic Sea coast, using individual data from >125,000 tagged salmon, recaptured over five decades. We show strong population and size‐specific differences in distribution at sea, varying between year classes and between individuals within year classes. This suggests that Atlantic salmon in the Baltic Sea experience great variation in environmental conditions and exploitation rates over ontogeny depending on origin and that current assessment assumptions about equal exploitation rates in the offshore fisheries and a shared environment at sea are not valid. Thus, our results provide additional arguments and necessary information for implementing population‐specific management of salmon, also when targeting life stages at sea.
Rapid transmission of Bonamia exitiosa by cohabitation causes mortality in Ostrea angasi
Authors: Buss Jessica Jamuna , Harris James Owen , Elliot Tanner Jason , Helen Wiltshire Kathryn , Deveney Marty Robert
Published: November 2019

The haplosporidian Bonamia was first detected in Australian shellfish in 1991. Australian isolates in Ostrea angasi Sowerby, 1871 were identified as Bonamia exitiosa Hine, Cochennac and Berthe, 2001, which threatens development of an O. angasi aquaculture industry. European field data suggest that Bonamia ostreae Pichot, Comps, Tigé, Grizel and Rabouin, 1980 infections in Ostrea edulis Linnaeus, 1758 build slowly, but infection dynamics of B. exitiosa in O. angasi are unknown. We investigated B. exitiosa infection in O. angasi by cohabiting uninfected juvenile O. angasi with adults infected with B. exitiosa. Oysters were sampled at 10, 21 and 40 days after cohabitation, and B. exitiosa prevalence and intensity were assessed. Bonamia exitiosa rapidly infected and caused disease in O. angasi. Mortalities began at 12 days, with ˜50% mortality by day 21 and >85% mortality by day 40. Mortalities displayed pathology consistent with clinical B. exitiosa infection. Time to first infection is likely influenced by a combination of parasite infectivity, host exposure and host immune capacity. Host death is not required for transmission, but probably facilitates release of parasites from decaying tissue. Understanding B. exitiosa transmission informs design and interpretation of field studies and aids development of management strategies for oyster aquaculture.
Longer Term Effects of Diet and Exercise on Neurocognition: 1‐Year Follow‐up of the ENLIGHTEN Trial
Authors: Blumenthal James A. , Smith Patrick J. , Mabe Stephanie , Hinderliter Alan , Welsh‐Bohmer Kathleen , Browndyke Jeffrey N. , Doraiswamy P. Murali , Lin Pao‐Hwa , Kraus William E. , Burke James R. , Sherwood Andrew
Published: November 2019

OBJECTIVES

To evaluate the longer term changes in executive functioning among participants with cardiovascular disease (CVD) risk factors and cognitive impairments with no dementia (CIND) randomized to a diet and exercise intervention.

DESIGN

A 2 (Exercise) × 2 (Dietary Approaches to Stop Hypertension [DASH] eating plan) factorial randomized clinical trial.

SETTING

Academic tertiary care medical center.

PARTICIPANTS

Volunteer sample of 160 older sedentary adults with CIND and at least one additional CVD risk factor enrolled in the ENLIGHTEN trial between December 2011 and March 2016.

INTERVENTIONS

Six months of aerobic exercise (AE), DASH diet counseling, combined AE + DASH, or health education (HE) controls.

MEASUREMENTS

Neurocognitive battery recommended by the Neuropsychological Working Group for Vascular Cognitive Disorders including measures of executive function, memory, and language/verbal fluency. Secondary outcomes included the Clinical Dementia Rating‐Sum of Boxes (CDR‐SB), Six‐Minute Walk Distance (6MWD), and CVD risk including blood pressure, body weight, and CVD medication burden.

RESULTS

Despite discontinuation of lifestyle changes, participants in the exercise groups retained better executive function 1 year post‐intervention (P = .041) compared with non‐exercise groups, with a similar, albeit weaker, pattern in the DASH groups (P = .054), without variation over time (P's > .867). Participants in the exercise groups also achieved greater sustained improvements in 6MWD compared with non‐Exercise participants (P < .001). Participants in the DASH groups exhibited lower CVD risk relative to non‐DASH participants (P = .032); no differences in CVD risk were observed for participants in the Exercise groups compared with non‐Exercise groups (P = .711). In post hoc analyses, the AE + DASH group had better performance on executive functioning (P < .001) and CDR‐SB (P = .011) compared with HE controls.

CONCLUSION

For participants with CIND and CVD risk factors, exercise for 6 months promoted better executive functioning compared with non‐exercisers through 1‐year post‐intervention, although its clinical significance is uncertain. J Am Geriatr Soc 68:559–568, 2020
Child and Adolescent Time Use: A Cross‐National Study
Authors: Gracia Pablo , Garcia‐Roman Joan , Oinas Tomi , Anttila Timo
Published: November 2019

Objective

This study examined the differences in child and adolescent time use across the following three countries with distinct policy and cultural regimes: Finland, Spain, and the United Kingdom.

Background

Studying children's time use cross‐nationally is urgent to better understand how societal contexts influence children's daily lives in ways that affect their future lifestyles, development, and identity formation. Yet previous studies have largely omitted this important question.

Method

The study used 2009 to 015 time‐diary data on children aged 10 to 17 from Finland, Spain, and the United Kingdom (N= 3,491). Multivariate linear regression models examined (a) between‐country and (b) within‐country variations.

Results

Finnish children spent 153 daily minutes less with parents, 128 more with “others” and 54 daily minutes more alone when compared with Spanish children. The United Kingdom fell between Finland and Spain in children's time allocated with parents and time with “others.” In family‐oriented Spain, children spent more time eating; in individualistic Finland and United Kingdom, child screen‐based time was highest. Parental education generally led to more time in educational activities, but with minor country variations. Maternal employment was generally not associated with child time use, except in Spain, where it led to less parent–child time.

Conclusion

The strong cross‐national differences in child and adolescent time use seem only partly driven by sociostructural factors. Cross‐cultural variations in family values and parenting ideologies seem to critically influence children's daily activities.
Spillover effects in spatial models: Generalizations and extensions
Authors: Kelejian Harry , Piras Gianfranco
Published: November 2019

In this paper, we consider two different cases of spillover effects: the first is a case where the model does not contain any additional endogenous regressors. Related to this, we give a variance formula that can be used to make inference for estimated spillover effects. In the second case, we extend the discussion of spillover effects to a model containing additional endogenous variables. We suggest approximations to the spillover effects that according to the results of our Monte Carlo experiment are quite accurate. However, our variance formula can not be determined unless the equations of the entire system are known. Suggestions for approximations in this case are left for future research.