bluuebunny/crossref_metadata_2025 huggingface dataset:
Predictors of transitions across stages of alcohol use and disorders in an adult population with heterogeneous ethnic restrictions regarding drinking
Authors: Cole Faith , Benjet Corina , Ghimire Dirgha J. , Axinn William G.
Published: August 2020

Aims

To disaggregate associations with alcohol use disorder relative to those with early alcohol use stages in an adult population. We estimated prevalence rates and socio‐demographic correlates for the opportunity to drink and transitions into life‐time alcohol use, regular use and alcohol use disorder.

Design

A retrospective, cross‐sectional population survey within a family panel study.

Setting

Chitwan in Nepal, an ethnically diverse setting with heterogeneous ethnic restrictions regarding alcohol.

Participants

A total of 10 714 individuals aged 15–59 years (response rate = 93%).

Measurements

The Nepal‐specific Composite International Diagnostic Interview assessed life‐time alcohol use opportunity, any use, regular use, disorder and socio‐demographic characteristics.

Findings

Seventy per cent [95% confidence interval (CI) = 69.08–70.82%] of the population had the opportunity to drink, 38.06% (95% CI = 37.14–38.99%) had life‐time alcohol use, 32.37% (95% CI = 31.48–33.27%) had regular alcohol use and 6.04% (95% CI = 5.60–6.50%) developed an alcohol use disorder. Compared with high‐caste Hindus, all other ethnicities had greater odds of early stage transitions [odds ratios (OR) ranged from 1.31, 95% CI = 1.16–1.47 to 1.98, 95% CI = 1.81–2.18)], but not of development of disorder. Male sex was associated with greater odds of all transitions, from opportunity (OR = 5.71, 95% CI = 5.41–6.03) to development of disorder (OR = 1.95, 95% CI = 1.35–2.81). The youngest cohort had higher odds of all transitions, from opportunity (OR = 4.86, 95% CI = 4.47–5.29) to development of disorder (OR = 9.34, 95% CI = 6.88–12.70). Higher education was associated with lower odds of all transitions except opportunity [from use (OR = 0.77, 95% CI = 0.71–0.83) to the development of disorder (OR = 0.73, 95% CI = 0.59–0.89)].

Conclusions

The prevalence of life‐time alcohol use among adults in Nepal appears to be low, but the overall prevalence of disorder is similar to other countries. Socio‐demographic correlates of early alcohol use transitions differ from those associated with later transitions; while sex and age cohort were associated with all transitions, ethnicity was associated with early transitions (opportunity, life‐time use, regular use), but not later transitions (use and regular use to disorder).
Comprehensive analysis of lncRNA and mRNA expression changes in Tibetan chicken lung tissue between three developmental stages
Authors: Tang Ruixiang , Wang Jiao , Zhou Min , Lan Yue , Jiang Lan , Price Megan , Yue Bisong , Li Diyan , Fan Zhenxin
Published: August 2020

The Tibetan chicken is a native Chinese breed that lives at high elevations and has adapted to the extreme environmental conditions of the Tibetan Plateau. However, its hypoxic adaptation at the gene expression level is unclear. Here, we sequenced nine lung transcriptomes of the Tibetan chicken at three developmental stages (5 and 42 weeks and 4.5 years). A total of 1.02 billion clean reads were obtained. We identified 16 012 mRNAs and 6898 lncRNAs. The expression of mRNA showed that nine samples were significantly divided into three clusters, with higher correlation and closer relationship between the 5 and 42 week groups. We identified 399 differentially expressed genes (DEGs) between the 5 and 42 week groups, 3532 DEGs between the 5 week and 4.5 year groups, and 3909 DEGs between the 42 week and 4.5 year groups. The up‐regulated DEGs in the 5 week group, compared with 42 week and 4.5 year groups, were enriched in GO terms associated with growth and development, whereas the up‐regulated DEGs in the 4.5 year group were mainly enriched in many metabolic‐related categories. Moreover, the enrichment results with up‐regulated DEGs in the 5 and/or 42 week groups, compared with the 4.5 year group, were associated with hypoxic adaptation, such as oxygen transport, oxygen binding and oxygen carrier activity, and calcium signaling pathway. In addition, we identified 978 high‐correlation lncRNA and protein‐coding gene pairs, and 524 significant neighboring protein‐coding genes were also DEGs. Our results provide new insights into gene expression of lung tissue in Tibetan chickens during the aging process.
Few figs for frugivores: Riparian fig trees in Zimbabwe may not be a dry season keystone resource
Authors: Compton Stephen G. , Greeff Jaco M.
Published: August 2020

Most plants flower and fruit at times of year when probabilities of pollination and seedling establishment are high. Fig trees (Ficus spp.) are often considered as keystone resources for vertebrate frugivores, in part because of year‐round fig production. This unusual fruiting phenology results in the maintenance of fig wasp populations, but in seasonal environments this means fruiting occurs during periods when the chances of seedling establishment are low. Under these circumstances, selection is expected to favour any individuals that reduce or eliminate fruiting at these times. Here, we describe a large‐scale survey of the extent of dry season fruiting by three riparian Ficus species in Gonarezhou National Park, Zimbabwe. Few trees of two monoecious species, F. sycomorus and F. abutilifolia, had figs, and most crops of F. sycomorus were far smaller than the trees were capable of producing. Large stands of the dioecious F. capreifolia were present, but fig densities were low and no mature female (seed containing) figs were recorded. Even though fig trees may have been the only species bearing fruit, the consequences of the low investment in reproduction by the three Ficus species were clear—there were too few figs for a landscape‐scale keystone role.
Infertility duration and pre‐operative sperm progressive motility are significant factors of spontaneous pregnancy after varicocele repair
Authors: Ren Wenbiao , Qu Jiandong , Xue Bichen , Hu Jiao , Zu Xiongbing
Published: August 2020

Problem

Varicocele may lead to testicular dysfunction and male infertility. Varicocelectomy can improve both semen quality and post‐operative spontaneous pregnancy. However, different patients benefit distinctly from the surgery. Therefore, the study aims at examining the possible factors of spontaneous pregnancy after laparoscopic varicocelectomy in infertile men.

Method of study

Clinical data of 196 infertile men who underwent laparoscopic varicocelectomy at our institute were collected from December 2013 to February 2019. Follow‐up data were available for 148 patients. All the patients were treated with laparoscopic varicocelectomy performed by experienced urological doctors. Possible pre‐operative factors of spontaneous pregnancy after laparoscopic varicocelectomy were retrospectively analyzed.

Results

After a mean follow‐up of 29.1 ± 12.6 months (range 12‐74 months), 74 (50%) of couples achieved spontaneous pregnancy. Univariate analysis revealed that short infertility duration, secondary infertility, and high sperm progressive motility were significant predictors of spontaneous pregnancy after laparoscopic varicocelectomy. Multivariate analysis revealed that short infertility duration (≤2 years) and high sperm progressive motility (>30%) were independent predictors.

Conclusion

Both infertility duration and pre‐operative sperm progressive motility could serve as independent factors of spontaneous pregnancy after laparoscopic varicocelectomy.
Metabolomic signature of the seminal plasma in men with severe oligoasthenospermia
Authors: Boguenet Magalie , Bocca Cinzia , Bouet Pierre‐Emmanuel , Serri Orianne , Chupin Stéphanie , Tessier Lydie , Blanchet Odile , El Hachem Hady , Chao de la Barca Juan Manuel , Reynier Pascal , May‐Panloup Pascale
Published: August 2020

Background

Male factor is incriminated in approximately 50% of cases of infertility. The metabolomic approach has recently been used in the assessment of sperm quality and male fertility.

Materials and methods

We analyzed the metabolomic signatures of the seminal plasma in 20 men with severe oligoasthenospermia (prewash total motile sperm count < 5.106) (SOA) and compared it to 20 men with normal semen parameters, with a standardized approach of targeted and quantitative metabolomics using high‐performance liquid chromatography, coupled with tandem mass spectrometry, and the Biocrates Absolute IDQ p180 kit.

Results

Among the 188 metabolites analyzed, 110 were accurately measured in the seminal plasma. A robust model discriminating the two populations (Q2(cum) = 55.2%) was obtained by OPLS‐DA (orthogonal partial least‐squares discriminant analysis), based on the drop in concentrations of 37 metabolites with a VIP (variable important for projection) greater than 1. Overall, in men with SOA, there was a significant decrease in: 17 phosphatidylcholines and four sphingomyelins; acylcarnitines, with free L‐carnitine being the most discriminating metabolite; polyunsaturated fatty acids; six amino acids (glutamate, aspartate, methionine, tryptophan, proline, and alanine); and four biogenic amines (spermine, spermidine, serotonin, and alpha‐aminoadipate).

Discussion

Our signature includes several metabolic changes with different impacts on the sperm quality: a change in phospholipid composition and the saturation of their fatty acids that is potentially linked to the deterioration of sperm membranes; a carnitine deficiency that can negatively impact the energy production via fatty acid oxidation and oxidative phosphorylation; and a decreased level of amino acids and biogenic amines that can lead to dysregulated metabolic and signaling pathways.

Conclusion

We provide a global overview of the metabolic defects contributing to the structural and functional alteration of spermatozoa in severe oligoasthenospermia. These findings offer new insights into the pathophysiology of male factor infertility that could help to develop future specific treatments.
Real‐world long‐term effectiveness of ustekinumab in Crohn's disease: results from the ENEIDA registry
Authors: Iborra Marisa , Beltrán Belén , Fernández‐Clotet Agnes , Iglesias‐Flores Eva , Navarro Pablo , Rivero Montserrat , Gutiérrez Ana , Sierra‐Ausin Mónica , Mesonero Francisco , Ferreiro‐Iglesias Rocío , Hinojosa Joaquín , Calvet Xavier , Sicilia Beatriz , González‐Muñoza Carlos , Antolín Beatriz , González‐Vivo María , Carbajo Ana Y. , García‐López Santiago , Martín‐Cardona Albert , Surís Gerard , Martin‐Arranz María Dolores , de Francisco Ruth , Cañete Fiorella , Domènech Eugeni , Nos Pilar ,   GETECCU group (Grupo Español de trabajo de Enfermedades de Crohn y Colitis Ulcerosa)
Published: August 2020

Background

Data on the long‐term administration of ustekinumab in recommended doses are limited.

Aim

To assess the real‐world, long‐term effectiveness of ustekinumab in refractory Crohn's disease (CD).

Methods

Multi‐centre study of CD patients starting ustekinumab at the recommended dose, followed for 1 year. Values for the Harvey‐Bradshaw Index (HBI), endoscopic activity, C‐reactive protein (CRP), and faecal calprotectin (FC) were recorded at baseline and at weeks 26 and 52. Demographic and clinical data, previous treatments, adverse events (AEs) and hospitalisations were documented. Potential predictors of remission were examined.

Results

A total of 407 patients were analysed. The initial maintenance dose of 90 mg SC was administered every 12, 8 and 4 weeks in 56 (14%), 347 (85%) and 4 (1%) patients, respectively. After 52 weeks, treatment was discontinued in 112 patients (27.5%). At baseline, 295 (72%) had an HBI >4 points. Of these, 169 (57%) and 190 (64%) achieved clinical remission at weeks 26 and 52, respectively. FC levels returned to normal in 44% and 54% of patients at weeks 26 and 52, and CRP returned to normal in 36% and 37% of patients at weeks 26 and 52, respectively. AEs were recorded in 60 patients. The use of fewer previous anti‐TNFα agents and ileal localisation were associated with clinical remission, and endoscopic severity was associated with poor response. No factors correlated with endoscopic remission.

Conclusion

After 52 weeks, ustekinumab demonstrated effectiveness in inducing clinical and endoscopic remission in patients with refractory CD.
Randomised clinical study: oral aspirin 325 mg daily vs placebo alters gut microbial composition and bacterial taxa associated with colorectal cancer risk
Authors: Prizment Anna E. , Staley Christopher , Onyeaghala Guillaume C. , Vivek Sithara , Thyagarajan Bharat , Straka Robert J. , Demmer Ryan T. , Knights Dan , Meyer Katie A. , Shaukat Aasma , Sadowsky Michael J. , Church Timothy R.
Published: August 2020

Background

Aspirin is associated with decreased risk of colorectal cancer (CRC), potentially by modulating the gut microbiome.

Aims

To evaluate the effect of aspirin on the gut microbiome in a double‐blinded, randomised placebo‐controlled pilot trial.

Methods

Healthy volunteers aged 50‐75 received a standard dose of aspirin (325 mg, N = 30) or placebo (N = 20) once daily for 6 weeks and provided stool samples every 3 weeks for 12 weeks. Serial measurements of gut microbial community composition and bacterial abundance were derived from 16S rRNA sequences. Linear discriminant analysis of effect size (LEfSe) was tested for between‐arm differences in bacterial abundance. Mixed‐effect regression with binomial distribution estimated the effect of aspirin use on changes in the relative abundance of individual bacterial taxa via an interaction term (treatment × time).

Results

Over the study period, there were differences in microbial composition in the aspirin vs placebo arm. After treatment, four taxa were differentially abundant across arms: Prevotella, Veillonella, Clostridium XlVa and Clostridium XVIII clusters. Of pre‐specified bacteria associated with CRC (n = 8) or aspirin intake (n = 4) in published studies, interactions were significant for four taxa, suggesting relative increases in Akkermansia, Prevotella and Ruminococcaceae and relative decreases in Parabacteroides, Bacteroides and Dorea in the aspirin vs placebo arm.

Conclusion

Compared to placebo, aspirin intake influenced several microbial taxa (Ruminococcaceae, Clostridium XlVa, Parabacteroides and Dorea) in a direction consistent with a priori hypothesis based on their association with CRC. This suggests that aspirin may influence CRC development through an effect on the gut microbiome. The findings need replication in a larger trial.
Event(ful) spaces of organised legal encounter: Reflections from a client consultation competition on domestic violence law in Cambodia
Authors: Brickell Katherine
Published: August 2020

Over the past five years, geographers’ engagement in legal observation and/or intervention has begun to gain momentum, with a particular emphasis on the courtroom. Courtrooms are positioned as epicentres of law(yering) in‐action, yet their pre‐eminence should not deflect from efforts to build a more inclusionary geography of law attendant to other, less high‐profile and official, spaces of law. In this paper, I elaborate on this argument by interrogating a client consultation competition (CCC) that I co‐organised on domestic violence law with staff and students from a higher education institution in Phnom Penh, Cambodia. The paper hones in specifically on the political interface that the CCC event fashioned between myself, the student competitors, and the state. Drawing on participant observation and audio‐recordings of the event, in addition to post‐competition focus groups I held with students, the paper demonstrates the value of cross‐pollinating social geographic work on events and encounter with legal‐oriented scholarship in the discipline on spaces and actors of law. Chased within the political, their fusing together permits researchers to widen their horizons beyond the court event and to think creatively about other legal infrastructures in which law and legal practice comes to be known and operationalised. The paper therefore asks that geographers committed to fostering justice not only step inside the courtroom, but also venture into spaces where its future prospects are born.
Dynamic incentives in microfinance with commitment‐type borrower
Authors: Zhou Shiqu
Published: August 2020

Shapiro (2015) points out an inherent fragility of dynamic incentives in microfinance without collateral or long‐term loans. He shows that the dynamic incentive mechanism unravels for all except a single value of initial beliefs. That is, under any parameter setup, only a single efficient equilibrium exists, in which loan terms improve over time, while an infinite number of inefficient equilibria exist, in which loan terms eventually deteriorate and even the most patient borrowers would default. I show that his concern vanishes if one introduces to the environment any positive proportion of “commitment‐type” borrowers, who never default by nature. Adding an infinitesimal proportion of commitment‐type borrowers eliminates all inefficient equilibria, while preserving the unique efficient equilibrium. Moreover, given any setup of parameters, a unique efficient equilibrium exists, in which the loan terms become more favourable over time, and the proportion of non‐defaulters converges to one.

Incitations dynamiques en micro‐crédit avec emprunteurengagé. En matière de micro‐crédit, Shapiro (2015) montre qu’en l’absence de prêts à long terme ou sur nantissement, une fragilité inhérente aux incitations dynamiques demeure. Shapiro montre également qu’en matière de convictions premières, le mécanisme d’incitation dynamique échoue pour toutes les valeurs sauf une. Autrement dit, pour tous les paramètres de base, il n’existe qu’un seul équilibre efficace au sein duquel les conditions de prêt s’améliorent dans la durée, alors que parallèlement, il existe un nombre infini d’équilibres inefficaces au sein desquels les conditions de prêt finissent par se détériorer rendant le crédit impossible à rembourser même pour l’emprunteur le plus patient. Je montre que le problème soulevé par Shapiro disparaît dès lors que l’on introduit à cet environnement une proportion positive d’emprunteurs engagés qui, par nature, remboursent toujours leur dette. En introduisant une proportion infime d’emprunteurs engagés, tous les équilibres inefficaces disparaissent tout en préservant le seul qui s’avère efficace. En outre, quels que soient les paramètres de base, il n’existe qu’un seul équilibre efficace au sein duquel les conditions de prêt s’amélioreront avec le temps et où le taux de remboursement approchera un (1).
R‐CHOP‐14 versus R‐CHOP‐14/CHASER for upfront autologous transplantation in diffuse large B‐cell lymphoma: JCOG0908 study
Authors: Kagami Yoshitoyo , Yamamoto Kazuhito , Shibata Taro , Tobinai Kensei , Imaizumi Yoshitaka , Uchida Toshiki , Shimada Kazuyuki , Minauchi Koichiro , Fukuhara Noriko , Kobayashi Hirofumi , Yamauchi Nobuhiko , Tsujimura Hideki , Hangaishi Akira , Tominaga Ryo , Suehiro Youko , Yoshida Shinichiro , Inoue Yoshiko , Suzuki Sachiko , Tokuhira Michihide , Kusumoto Shigeru , Kuroda Junya , Yakushijin Yoshihiro , Takamatsu Yasushi , Kubota Yasushi , Nosaka Kisato , Morishima Satoko , Nakamura Shigeo , Ogura Michinori , Maruyama Dai , Hotta Tomomitsu , Morishima Yasuo , Tsukasaki Kunihiro , Nagai Hirokazu
Published: August 2020

The efficiency of upfront consolidation with high‐dose chemotherapy/autologous stem‐cell transplantation (HDCT/ASCT) for newly diagnosed high‐risk diffuse large B‐cell lymphoma (DLBCL) may be influenced by induction chemotherapy. To select better induction chemotherapy regimens for HDCT/ASCT, a randomized phase II study was conducted in high‐risk DLBCL patients having an age‐adjusted International Prognostic Index (aaIPI) score of 2 or 3. As induction chemotherapy, 6 cycles of R‐CHOP‐14 (arm A) or 3 cycles of R‐CHOP‐14 followed by 3 cycles of CHASER (arm B) were planned, and patients who responded proceeded to HDCT with LEED and ASCT. The primary endpoint was 2‐y progression‐free survival (PFS), and the main secondary endpoints included overall survival, overall response rate, and adverse events (AEs). In total, 71 patients were enrolled. With a median follow‐up of 40.3 mo, 2‐y PFS in arms A and B were 68.6% (95% confidence interval [CI], 50.5%‐81.2%) and 66.7% (95% CI: 48.8%‐79.5%), respectively. Overall survival at 2 y in arms A and B was 74.3% (95% CI: 56.4%‐85.7%) and 83.3% (95% CI: 66.6%‐92.1%). Overall response rates were 82.9% in arm A and 69.4% in arm B. During induction chemotherapy, 45.7% and 75.0% of patients in arms A and B, respectively, had grade ≥ 3 non‐hematologic toxicities. One patient in arm A and 6 in arm B discontinued induction chemotherapy due to AEs. In conclusion, R‐CHOP‐14 showed higher 2‐y PFS and less toxicity compared with R‐CHOP‐14/CHASER in patients with high‐risk DLBCL, suggesting the former to be a more promising induction regimen for further investigations (UMIN‐CTR, UMIN000003823).
Identification of 1‐phenyl‐4‐cyano‐5‐aminopyrazoles as novel ecdysone receptor ligands by virtual screening, structural optimization, and biological evaluations
Authors: Hu Xueping , Ma Xiaojuan , Cui Jialin , Liu Haishan , Zhu Bin , Xie Jin , Liang Pei , Zhang Li
Published: August 2020

Ecdysteroids initiate the molting process in insects by binding to the ecdysone receptor (EcR), which is a promising target for identifying insect growth regulators. This paper presents an in silico/in vitro screening procedure for identifying new EcR ligands. The three‐step virtual screening procedure uses a three‐dimensional pharmacophore model, docking and Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) rescoring routine. A novel hit (VS14) with good binding activity against Plutella xylostella EcR was identified from a library of over 200,000 chemicals. Subsequently, the 1‐phenyl‐4‐cyano‐5‐aminopyrazole scaffold and twelve EcR ligands were synthesized. Their IC50 values against Plutella xylostella EcR ranged from 0.64 to 23.21 μm. Furthermore, a preliminary analysis of the structure–activity relationship for novel scaffolds provided a basis for designing new ligands with improved activity.
Inhibitory Control Across the Preschool Years: Developmental Changes and Associations with Parenting
Authors: Geeraerts Sanne B. , Endendijk Joyce J. , Deković Maja , Huijding Jorg , Deater‐Deckard Kirby , Mesman Judi
Published: August 2020

The normative developmental course of inhibitory control between 2.5 and 6.5 years, and associations with maternal and paternal sensitivity and intrusiveness were tested. The sample consisted of 383 children (52.5% boys). During four annual waves, mothers and fathers reported on their children’s inhibitory control using the Children's Behavior Questionnaire. During the first wave, mothers’ and fathers’ sensitivity and intrusiveness were observed and coded with the Emotional Availability Scales. Inhibitory control exhibited partial scalar invariance over time, and increased in a decelerating rate. For both mothers and fathers, higher levels of sensitivity were associated with a higher initial level of children's inhibitory control, whereas higher levels of intrusiveness predicted a slower increase in children's inhibitory control.
Children’s Social Information Seeking is Sensitive to Referential Ambiguity
Authors: Hembacher Emily , deMayo Benjamin , Frank Michael C.
Published: August 2020

We examined children’s spontaneous information seeking in response to referential ambiguity. Children ages 2–5 (n = 160) identified the referents of familiar and novel labels. We manipulated ambiguity by changing the number of objects present and their familiarity (Experiments 1 and 2), and the availability of referential gaze (Experiment 2). In both experiments, children looked to the face of the experimenter more often while responding, specifically when the referent was ambiguous. In Experiment 2, 3‐ to 4‐year olds also demonstrated sensitivity to graded referential evidence. These results suggest that social information seeking is an active learning behavior that could contribute to language acquisition in early childhood.
Purpose Among Youth From Low‐Income Backgrounds: A Mixed Methods Investigation
Authors: Bronk Kendall Cotton , Mitchell Caleb , Hite Brittany , Mehoke Sam , Cheung Ryan
Published: August 2020

Theoretical and empirical research lead to conflicting perspectives on whether youth from low‐income backgrounds are likely to have access to lives of purpose. To explore this issue, this study used data collected during the 2016–2017 academic year from a sample of Southern California youth. Findings suggest (a) youth from low‐income communities are as likely as youth from middle‐income communities to report leading lives of purpose; (b) purpose among low‐income youth is associated with many of the same indicators of positive development as it is among middle‐income youth; and (c) youth from low‐income backgrounds encounter personal hardships that, in the presence of familial support and other developmental assets, can inspire purpose. Implications for purpose‐fostering interventions among low‐income youth are discussed.
Cognitive and Educational Interventions for Orphans and Vulnerable Children Affected by HIV/AIDS: A Meta‐Analysis
Authors: Thomas Tina , Ahmed Yusra , Tan Mei , Grigorenko Elena L.
Published: August 2020

Orphans and vulnerable children affected by HIV/AIDS (HIV OVC) are at risk for cognitive difficulties and lack of access to education. Interventions addressing cognitive or educational outcomes for HIV OVC worldwide were examined through systematic searches conducted from October 2016 to 2019. We examined the summative effectiveness of interventions and the specific effects of participant age and intervention length. Interventions targeting cognitive outcomes had a small, significant effect, with no effect of moderating variables. Interventions targeting educational outcomes had significant effects. Educational interventions over 1 year were effective, but effects of intervention length were not significant. Overall, this review provides support for the effectiveness of interventions targeting cognitive and educational outcomes for OVC and highlights the need for more research on such interventions.
Exploring the Associations Between Delayed School Entry and Achievement in Primary and Secondary School
Authors: Larsen Sally A. , Little Callie W. , Coventry William L.
Published: August 2020

This research investigated whether delayed school entry was associated with higher achievement in national tests of reading and numeracy in Grades 3, 5, 7, and 9 (n = 2,823). Delayed entry was related to advantages in reading (0.14 SD) and numeracy (0.08 SD) at Grade 3, although little variance was explained (1%–2%). This slight advantage persisted for both domains in Grades 5 and 7, albeit with smaller effects. In Grade 9 there was no association between delayed entry and either reading or numeracy. Exploratory analyses with subsamples in each grade (n = 424–667) revealed no associations between delayed entry and achievement after controlling for inattention and hyperactivity, and negative associations between inattention and achievement in all grades in both domains (−0.33, −0.49 SD).
The validity of the Acoustic Breathiness Index in the evaluation of breathy voice quality: A Meta‐Analysis
Authors: Barsties v. Latoszek Ben , Kim Geun‐Hyo , Delgado Hernández Jonathan , Hosokawa Kiyohito , Englert Marina , Neumann Katrin , Hetjens Svetlana
Published: August 2020

Background

The evaluation of voice quality with acoustic measurements is useful to objectify the diagnostic process. Particularly, breathiness was highly evaluated and the Acoustic Breathiness Index (ABI) might have promising features.

Objective of review

The goal of the present meta‐analysis is to quantify, from existing cross‐validation studies, the evidence for the diagnostic accuracy of ABI, including its sensitivity and specificity.

Type of review

Meta‐analysis.

Search strategy

We searched in MEDLINE, Google Scholar and Science Citation Index, and as manual search for the term Acoustic Breathiness Index from inception to February 2020.

Studies were included that used equal proportion of continuous speech and sustained vowel segments, a recording hardware with a sufficient standard for voice signal analyses, the software Praat for signal processing and the customised Praat script, and two groups of subjects (vocally healthy and voice‐disordered). Furthermore, the diagnostic accuracy of ABI was measured.

Evaluation method

The primary outcome variable was ABI. The score ranged from 0 to 10 with varying thresholds according to different languages to determine the absence or presence of breathiness.

A meta‐analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta‐analyses of diagnostic test accuracy study guidelines. Data were extracted, and the risk of bias was assessed using the QUADAS‐2 tool. The pooled sensitivity and specificity of ABI were determined using a summary receiver operating characteristic (SROC) approach to calculate also a weighted threshold value of ABI with its sensitivity and specificity.

Results

A total of 34 unique citations were screened, and 10 full‐text articles were reviewed, including six studies. In total, 3603 voice samples were considered for further analysis separating into 467 vocally healthy and 3136 voice‐disordered voice samples. The pooled sensitivity was 0.84 (95% CI, 0.83‐0.85), and the pooled specificity was 0.92 (95% CI, 0.89‐0.94). The area under the curve of the SROC curve of this analysis showed an excellent value of 0.94. The weighted ABI threshold was determined at 3.40 (sensitivity: 0.86, 95% CI, 0.84‐0.87.; specificity: 0.90, 95% CI 0.88‐0.92).

Conclusions

The results confirm the ABI as robust and valid objective measure for evaluating breathiness.
Placement of a fine‐bore rectal balloon catheter in the anal canal does not affect anal sphincter pressures: improving our understanding of physiological function with anal acoustic reflectometry
Authors: Heywood N. A. , Sharma A. , Kiff E. S. , Klarskov N. , Telford K. J.
Published: August 2020

Aim

The recto‐anal inhibitory reflex (RAIR) is currently measured using anorectal manometry catheters, which may distort the anal canal. Anal acoustic reflectometry (AAR) is considered a catheter‐free technique for evaluating the physiological function of the anal canal; however, it has yet to be used to elicit the RAIR. For the RAIR to be measured with AAR, the effect of placing an additional rectal balloon catheter on the measured AAR parameters needs to be investigated: that is the aim of this work.

Method

Patients aged over 18 years attending hospital for the investigation of pelvic floor disorders were included. AAR parameters were obtained before and after a rectal balloon catheter was placed alongside the AAR catheter. The following parameters were measured: opening pressure (Op, cmH2O), opening elastance (Oe, cmH2O/mm2), closing pressure (Cp, cmH2O), closing elastance (Ce, cmH2O/mm2), hysteresis (Hys, %), squeeze opening pressure (SqOp, cmH2O) and squeeze opening elastance (SqOe, cmH2O/mm2).

Results

Thirty‐five patients were included in the analysis, of whom 28 were women. The median age was 58 years. Comparison of median AAR parameters before and after catheter placement showed no significant difference: Op (36.36 vs 33.42, P = 0.09), Oe (1.27 vs 1.39, P = 0.19), Cp (18.62 vs 19.73, P = 0.13), Ce (1.2 vs 1.28, P = 0.33), Hys (41.08 vs 40.11, P = 0.17), SqOp (81.85 vs 81.65, P = 0.93) and SqOe (1.44 vs 1.49, P = 0.55).

Discussion

Placement of a rectal balloon catheter alongside the AAR catheter has no significant effect on the measured AAR parameters. The results of this study add to the fundamental basic science and understanding of the physiological function of the anal canal.
The evolution of the rangeland trusts network as a catalyst for community‐based conservation in the American West
Authors: Bennett Drew E. , Knapp Corrine N. , Knight Richard L. , Glenn Erik
Published: August 2020

Ranching communities in 10 Western states self‐organized to create conservation organizations affiliated with state livestock associations and supporting conservation efforts compatible with agricultural production. These “rangeland trusts” collectively conserve over 2.7 million acres through conservation easements. We identify these efforts as a type of community‐based conservation based on the collective nature of the efforts and the balance between community needs and conservation. They differ from traditional CBC efforts with ties to industry groups and a focus on private lands that provide public goods. A coalition of rangeland trusts formed in 2006, leading to a form of multilevel governance that establishes operating principles and actively advocates for ranch land conservation. We suggest that existing industry structures can assist to scale out conservation, bridging organizations can facilitate novel interactions and policy change, and tensions on the meaning and implementation of conservation must be navigated at each scale of interaction.
Early Clinical Experience With AZD4831, A Novel Myeloperoxidase Inhibitor, Developed for Patients With Heart Failure With Preserved Ejection Fraction
Authors: Nelander Karin , Lagerstrom‐Fermer Maria , Amilon Carl , Michaëlsson Erik , Heijer Maria , Kjaer Magnus , Russell Muir , Han David , Lindstedt Eva‐Lotte , Whatling Carl , Gan Li‐Ming , Ericsson Hans
Published: August 2020

We evaluated safety, tolerability, pharmacokinetics (PKs), and pharmacodynamics of AZD4831, a novel oral myeloperoxidase (MPO) inhibitor, in a randomized, single‐blind, placebo‐controlled study, following once‐daily multiple ascending dosing to steady‐state in healthy subjects. Target engagement was measured as specific MPO activity in plasma following ex vivo zymosan stimulation of whole blood. Except for generalized maculopapular rash in 4 of 13 subjects receiving the 2 highest doses, 15 and 45 mg AZD4831, no clinically relevant safety and tolerability findings were observed. AZD4831 was rapidly absorbed and plasma concentrations declined slowly with an elimination half‐life of ~ 60 hours. A dose/concentration‐effect relationship between MPO inhibition vs. AZD4831 exposure was established with > 50% MPO inhibition in plasma at concentrations in the low nanomolar range. Steady‐state levels were achieved within 10 days. Taken together, the PK profile, the sustained dose/concentration‐dependent MPO inhibition, and available clinical data support further clinical development of AZD4831 in patients with heart failure with preserved ejection fraction.
Signet‐ring cell/histiocytoid carcinoma in the axilla: A case report with genetic analysis using next‐generation sequencing
Authors: Ito Yui , Ishida Mitsuaki , Ohe Chisato , Miyasaka Chika , Tsuta Koji
Published: August 2020

Signet‐ring cell/histiocytoid carcinoma (SRCHC) is a very rare skin appendage cancer, with an extremely rare occurrence in the axilla. This study describes the 11th case of SRCHC occurring in the axilla and reports the first gene alteration analysis performed for SRCHC. An 85‐year‐old Japanese male presented with a tumor in the left axilla. Biopsy of the axilla nodule demonstrated diffuse proliferation of histiocytoid neoplastic cells and signet‐ring cells in the dermis and subcutis. Immunohistochemistry revealed loss of E‐cadherin expression in these neoplastic cells. Accordingly, SRCHC of the axilla was diagnosed. Genetic analysis using next‐generation sequencing demonstrated missense mutation of PIK3CA (c1633G>A, pGlu545Lys) and no CDH1 gene mutation.SRCHC of the axilla is considered equivalent to a histiocytoid variant of invasive lobular breast carcinoma. The present SRCHC case demonstrated a pathogenic PIK3CA mutation, which is observed in invasive lobular carcinoma. Additional large case studies are required to clarify the clinicopathological features and gene alterations in SRCHC of the axilla.
Aortic dissection and multimodality imaging
Authors: Paulraj Shweta , Ashok Kumar Prashanth , Uprety Ajay , Chaudhuri Debanik
Published: August 2020

Aortic dissection is a life‐threatening emergency warranting expeditious diagnosis. Computed tomographic angiography (CTA) is the established gold standard test but is not always fool proof. We report the case of an 18‐year‐old male patient with traumatic type A aortic dissection which was not evident on the CTA, suggestive on the transthoracic echocardiogram (TTE) and eventually confirmed with a transesophageal echocardiogram (TEE). When the clinical suspicion for dissection is high and in the presence of complications of type A dissection, such as aortic regurgitation, it would be prudent to obtain further imaging with a TTE/TEE to rule in or rule out the diagnosis.
Big data in epilepsy: Clinical and research considerations. Report from the Epilepsy Big Data Task Force of the International League Against Epilepsy
Authors: Lhatoo Samden D. , Bernasconi Neda , Blumcke Ingmar , Braun Kees , Buchhalter Jeffrey , Denaxas Spiros , Galanopoulou Aristea , Josephson Colin , Kobow Katja , Lowenstein Daniel , Ryvlin Philippe , Schulze‐Bonhage Andreas , Sahoo Satya S. , Thom Maria , Thurman David , Worrell Greg , Zhang Guo‐Qiang , Wiebe Samuel
Published: August 2020

Epilepsy is a heterogeneous condition with disparate etiologies and phenotypic and genotypic characteristics. Clinical and research aspects are accordingly varied, ranging from epidemiological to molecular, spanning clinical trials and outcomes, gene and drug discovery, imaging, electroencephalography, pathology, epilepsy surgery, digital technologies, and numerous others. Epilepsy data are collected in the terabytes and petabytes, pushing the limits of current capabilities. Modern computing firepower and advances in machine and deep learning, pioneered in other diseases, open up exciting possibilities for epilepsy too. However, without carefully designed approaches to acquiring, standardizing, curating, and making available such data, there is a risk of failure. Thus, careful construction of relevant ontologies, with intimate stakeholder inputs, provides the requisite scaffolding for more ambitious big data undertakings, such as an epilepsy data commons. In this review, we assess the clinical and research epilepsy landscapes in the big data arena, current challenges, and future directions, and make the case for a systematic approach to epilepsy big data.
Population genomic data in spider mites point to a role for local adaptation in shaping range shifts
Authors: Chen Lei , Sun Jing‐Tao , Jin Peng‐Yu , Hoffmann Ary A. , Bing Xiao‐Li , Zhao Dian‐Shu , Xue Xiao‐Feng , Hong Xiao‐Yue
Published: August 2020

Local adaptation is particularly likely in invertebrate pests that typically have short generation times and large population sizes, but there are few studies on pest species investigating local adaptation and separating this process from contemporaneous and historical gene flow. Here, we use a population genomic approach to investigate evolutionary processes in the two most dominant spider mites in China, Tetranychus truncatus Ehara and Tetranychus pueraricola Ehara et Gotoh, which have wide distributions, short generation times, and large population sizes. We generated genome resequencing of 246 spider mites mostly from China, as well as Japan and Canada at a combined total depth of 3,133×. Based on demographic reconstruction, we found that both mite species likely originated from refugia in southwestern China and then spread to other regions, with the dominant T. truncatus spreading ~3,000 years later than T. pueraricola. Estimated changes in population sizes of the pests matched known periods of glaciation and reinforce the recent expansion of the dominant spider mites. T. truncatus showed a greater extent of local adaptation with more genes (76 vs. 17) associated with precipitation, including candidates involved in regulation of homeostasis of water and ions, signal transduction, and motor skills. In both species, many genes (135 in T. truncatus and 95 in T. pueraricola) also showed signatures of selection related to elevation, including G‐protein‐coupled receptors, cytochrome P450s, and ABC‐transporters. Our results point to historical expansion processes and climatic adaptation in these pests which could have contributed to their growing importance, particularly in the case of T. truncatus.
Urbanization is associated with shifts in bumblebee body size, with cascading effects on pollination
Authors: Theodorou Panagiotis , Baltz Lucie M. , Paxton Robert J. , Soro Antonella
Published: August 2020

Urbanization is a global phenomenon with major effects on species, the structure of community functional traits and ecological interactions. Body size is a key species trait linked to metabolism, life‐history and dispersal as well as a major determinant of ecological networks. Here, using a well‐replicated urban–rural sampling design in Central Europe, we investigate the direction of change of body size in response to urbanization in three common bumblebee species, Bombus lapidarius, Bombus pascuorum and Bombus terrestris, and potential knock‐on effects on pollination service provision. We found foragers of B. terrestris to be larger in cities and the body size of all species to be positively correlated with road density (albeit at different, species‐specific scales); these are expected consequences of habitat fragmentation resulting from urbanization. High ambient temperature at sampling was associated with both a small body size and an increase in variation of body size in all three species. At the community level, the community‐weighted mean body size and its variation increased with urbanization. Urbanization had an indirect positive effect on pollination services through its effects not only on flower visitation rate but also on community‐weighted mean body size and its variation. We discuss the eco‐evolutionary implications of the effect of urbanization on body size, and the relevance of these findings for the key ecosystem service of pollination.
Insect–plant relationships predict the speed of insecticide adaptation
Authors: Crossley Michael S. , Snyder William E. , Hardy Nate B.
Published: August 2020

Herbivorous insects must circumvent the chemical defenses of their host plants and, in cropping systems, must also circumvent synthetic insecticides. The pre‐adaptation hypothesis posits that when herbivorous insects evolve resistance to insecticides, they co‐opt adaptations against host plant defenses. Despite its intuitive appeal, few predictions of this hypothesis have been tested systematically. Here, with survival analysis of more than 17,000 herbivore–insecticide interactions, we show that resistance evolution tends to be faster when herbivorous insect diets are broad (but not too broad) and when insecticides and plant defensive chemicals are similar (but not too similar). These general relations suggest a complex interplay between macro‐evolutionary contingencies and contemporary population genetic processes, and provide a predictive framework to forecast which pest species are most likely to develop resistance to particular insecticide chemistries.
Venous blood gas parameters, electrolytes, glucose and lactate concentration in sick neonatal foals: Direct venipuncture versus push‐pull technique
Authors: Del Prete Chiara , Lanci Aliai , Cocchia Natascia , Freccero Francesca , Di Maio Chiara , Castagnetti Carolina , Mariella Jole , Micieli Fabiana
Published: August 2020

Background

Blood collection by indwelling intravenous catheter (IVC) avoids repeated venipuncture, which could cause thrombophlebitis risk, anxiety and pain in patients.

Objectives

To compare blood gas parameters, electrolytes, glucose, lactate and haematocrit concentration obtained from venous blood samples collected via a jugular IVC by push‐pull (PP) technique to those obtained by venipuncture in hospitalised foals, at the time of catheter placement (T0) and 24 hours after the beginning of intravenous therapy (T24).

Study design

Prospective observational study.

Methods

Paired blood samples were drawn from hospitalised foals at T0 and T24. In each foal, one venous blood sample was collected via IVC by the following PP technique: 2.4 mL of blood was aspirated and immediately reinfused through the catheter three times consecutively, then 1 mL of blood was collected using a 1 mL heparinised syringe. Thereafter, another sample was collected by direct venipuncture of the contralateral jugular vein, with an identical 1 mL heparinised syringe, with a 1‐inch, 20‐G needle. All samples were analysed with an automated blood gas analyser within 10 minutes of collection. The agreement between the two techniques was assessed by Bland‐Altman analysis and intraclass correlation coefficient (ICC).

Results

The level of agreement of blood gas values obtained by the two different techniques was high with very small bias and clinically acceptable ICC (>0.907 at T0; >0.794 at T24) for all variables, except for haematocrit (bias −3.52 at T0; −2.44 at T24) and PvO2at T0 and T24 (ICC 0.669 and 0.733, respectively).

Main limitations

Potential sub‐clinical catheter‐related complications were not investigated by ultrasound or bacterial culture of the catheter; short duration of the study.

Conclusions

PP technique appears to be acceptable for collection of blood samples for venous blood gas parameters, as well as electrolytes, glucose and lactate in sick neonatal foals.
Remembering your enemies: mechanisms of within‐generation and multigenerational immune priming in Caenorhabditis elegans
Authors: Willis Alexandra R. , Sukhdeo Ronesh , Reinke Aaron W.
Published: August 2020

Pathogens are abundant and drive evolution of host immunity. Whilst immune memory is classically associated with adaptive immunity, studies in diverse species now show that priming of innate immune defences can also protect against secondary infection. Remarkably, priming may also be passed on to progeny to enhance pathogen resistance and promote survival in future generations. Phenotypic changes that occur independent of DNA sequence underlie both ‘within‐generation’ priming and ‘multigenerational’ priming. However, the molecular mechanisms responsible for these phenomena are still poorly understood. Caenorhabditis elegans is a simple and genetically tractable model organism that has enabled key advances in immunity and environmental epigenetics. Using both natural and human pathogens, researchers have uncovered numerous examples of innate immune priming in this animal. Viral infection models have provided key evidence for a conserved antiviral RNA silencing mechanism that is inherited in progeny. Bacterial infection models have explored mechanisms of within‐generation and multigenerational priming that span chromatin modification and transcriptional changes, small RNA pathways, maternal provisioning and pathogen avoidance strategies. Together, these studies are providing novel insight into the immune reactivity of the genome and have important consequences for our understanding of health and evolution. In this review, we present the current evidence for learned protection against pathogens in C. elegans, discuss the significance and limitations of these findings and highlight important avenues of future investigation.