bluuebunny/crossref_metadata_2025 huggingface dataset:
ANZSREI consensus statement on elective oocyte cryopreservation
Authors: Lew Raelia , Foo Jinny , Kroon Ben , Boothroyd Clare , Chapman Michael ,   Australasian CREI Consensus Expert Panel on Trial evidence (ACCEPT) group
Published: July 2019

Background

One in six Australian women and couples suffer infertility. A rising proportion relates to advanced maternal age, associated with poorer oocyte quality and in vitro fertilisation (IVF) outcomes. Internationally, oocyte cryopreservation technology applied to oocytes vitrified before 35 years provides similar live‐birth statistics compared to IVF treatment using fresh oocytes. Oocyte cryopreservation is accessible in Australasian settings and elective uptake is increasing. For women accessing treatment, oocyte cryopreservation may expand future family building options.

Aims

To develop the first Australasian Certification in Reproductive Endocrinology and Infertility (CREI) subspecialist‐led consensus guideline on oocyte cryopreservation.

Methods

The ANZSREI ACCEPT (Australasian CREI Consensus Expert Panel on Trial evidence group) met in 2017 and 2018 and identified clinical aspects of care for inclusion and review. Review of the available evidence was conducted and consensus statements prepared. Areas of dissent of expert opinion and for further research were noted.

Results

Consensus was reached on definition and best practice in oocyte cryopreservation for freeze method, controlled ovarian stimulation, medical risk reduction and treatment and outcomes counselling. The term ‘social egg freezing’ may marginalise, stigmatise or attribute social blame to women, and there is a need to revise this to a neutral and non‐judgemental term such as elective or planned oocyte cryopreservation.

Conclusion

Oocyte cryopreservation has the potential to improve cumulative live birth outcomes for women. Implementation of this guideline should facilitate an optimal approach for providing care.
Efficacy, safety and pharmacokinetics of ilaprazole infusion in healthy subjects and patients with esomeprazole as positive control
Authors: Wang Hongyun , Shao Feng , Liu Xuemei , Xu Wen , Ou Ning , Qin Xianghong , Liu Fang , Hou Xuemei , Hu Haitang , Jiang Ji
Published: July 2019

Aims

The objectives were to investigate the pharmacokinetics, pharmacodynamics and safety of ilaprazole infusion in healthy subjects and patients with esomeprazole as positive control, and then recommend the dosage regimen for Phase 2b/3 studies.

Methods

Three clinical studies were performed. First, 16 healthy subjects received infusion of ilaprazole 30 mg or esomeprazole 80 mg. Second, 12 healthy subjects received ilaprazole 20 mg followed by 10 mg once daily for 2 days. Finally, 20 patients with duodenal ulcers received ilaprazole 20 mg followed by 10 mg for 2 days or esomeprazole 40 mg twice daily for 3 days. Serial blood samples were collected and intragastric pH was recorded.

Results

The mean percentages time of intragastric pH >6 was 63.6 and 51.7% for healthy subjects after receiving ilaprazole 30 mg and esomeprazole 80 mg. Linear pharmacokinetics was observed when the dose was increased to 30 mg but the effect was saturated. Ilaprazole 20 mg followed by 10 mg for 2 days provided higher plasma exposure in healthy subjects than patients, but the effect was comparable. After multiple administrations, ilaprazole provided similar effect to esomeprazole. Ilaprazole infusion was safe and well tolerated without serious adverse events.

Conclusions

Ilaprazole provided comparable effect of pH control to esomeprazole, with lower dose and fewer times of administration. There was no significant difference of ilaprazole between healthy subjects and patients regarding intragastric acid inhibition. A loading dose of ilaprazole 20 mg followed by 10 mg once daily for 2 days was recommended for Phase 2b/3 studies.
When friends behave badly: Loneliness and children's expectations of friends and responses to transgressions
Authors: Nowland Rebecca A. , Balmer Dawn , Qualter Pamela
Published: July 2019

Previous research has shown that friendships buffer against loneliness, but some children remain lonely despite having best friends. The current study examines relationships between loneliness and Friendship Functions, expectations, and responses to friendship transgressions in children with best friends (8–11 years; N = 177). Children completed questionnaires that measured loneliness, fulfilment of Friendship Functions, Friendship Expectations, and the Transgressions of Friendship Expectations Questionnaire (MacEvoy & Asher, Child Development, 83, 2012, 104). Findings in the current study showed that loneliness was associated with lower Friendship Expectations and higher reliable alliance in existing best friendships. Loneliness was also associated with lower sadness and lower perceptions of feeling controlled and devalued by their friend when they transgress. Thus, children with best friends experiencing high loneliness may be more permissiveness of friendship transgressions and may need support to ensure that they do not allow their friends to be unfair to them.

Statement of contribution

What is already known on the subject?

Friendships buffer children from loneliness, but some remain lonely despite having friends.

Loneliness has been associated with poor‐quality friendships.

But there is no examination of why children remain lonely when they have friends.

What the present study adds?

Lonely children overemphasize friendship qualities that help to maintain the relationship.

Loneliness was linked to expectations of being friends with less popular and well‐liked peers.

Lonely children placed less blame on their friends when they violated Friendship Expectations.
A qualitative transcriptional signature for the early diagnosis of colorectal cancer
Authors: Guan Qingzhou , Zeng Qiuhong , Yan Haidan , Xie Jiajing , Cheng Jun , Ao Lu , He Jun , Zhao Wenyuan , Chen Kui , Guo You , Guan Guoxian , Guo Zheng
Published: July 2019

Currently, using biopsy specimens for the early diagnosis of colorectal cancer (CRC) is not entirely reliable due to insufficient sampling amount and inaccurate sampling location. Thus, it is necessary to develop a signature that can accurately identify patients with CRC under these clinical scenarios. Based on the relative expression orderings of genes within individual samples, we developed a qualitative transcriptional signature to discriminate CRC tissues, including CRC adjacent normal tissues from non‐CRC individuals. The signature was validated using multiple microarray and RNA sequencing data from different sources. In the training data, a signature consisting of 7 gene pairs was identified. It was well validated in both biopsy and surgical resection specimens from multiple datasets measured by different platforms. For biopsy specimens, 97.6% of 42 CRC tissues and 94.5% of 163 non‐CRC (normal or inflammatory bowel disease) tissues were correctly classified. For surgically resected specimens, 99.5% of 854 CRC tissues and 96.3% of 81 CRC adjacent normal tissues were correctly identified as CRC. Notably, we additionally measured 33 CRC biopsy specimens by the Affymetrix platform and 13 CRC surgical resection specimens, with different proportions of tumor epithelial cells, ranging from 40% to 100%, by the RNA sequencing platform, and all these samples were correctly identified as CRC. The signature can be used for the early diagnosis of CRC, which is also suitable for minimum biopsy specimens and inaccurately sampled specimens, and thus has potential value for clinical application.
Carfilzomib monotherapy in Japanese patients with relapsed or refractory multiple myeloma: A phase 1/2 study
Authors: Iida Shinsuke , Watanabe Takashi , Matsumoto Morio , Suzuki Kenshi , Sunami Kazutaka , Ishida Tadao , Ando Kiyoshi , Chou Takaaki , Ozaki Shuji , Taniwaki Masafumi , Uike Naokuni , Shibayama Hirohiko , Hatake Kiyohiko , Izutsu Koji , Ishikawa Takayuki , Shumiya Yoshihisa , Tobinai Kensei
Published: July 2019

This multicenter, open‐label phase 1/2 study evaluated single‐agent carfilzomib in 50 heavily pretreated Japanese patients with relapsed/refractory multiple myeloma (median of five prior treatments). In phase 1, patients were dosed at three levels: 15, 20, or 20/27 mg/m2. Maximum tolerated dosage was not reached at the tolerability evaluation. Patients in phase 2 were treated with 20/27 mg/m2 carfilzomib. Median duration of exposure to carfilzomib in the 20/27 mg/m2 group at this final analysis was 4.7 months (range: 0.3‐39.4). Overall response rate in the 20/27 mg/m2 group, primary endpoint of the study, was 22.5% (n = 9) (95% confidence interval, 12.3‐37.5) with 2.5% (n = 1) stringent complete response. Median progression‐free survival and overall survival in the 20/27 mg/m2 group were 5.1 months (95% CI, 2.8‐13.6) and 22.9 months (95% CI, 14.1‐not estimable), respectively. Frequently occurring grade ≥3 adverse events in the 20/27 mg/m2 group included lymphopenia (72.5%), neutropenia (40.0%), and leukopenia (32.5%). Giving long‐term carfilzomib monotherapy led to long‐term overall survival for heavily pretreated multiple myeloma patients with a favorable safety profile. Carfilzomib monotherapy can be a good option for heavily pretreated multiple myeloma patients.
SALL4 promotes the tumorigenicity of cervical cancer cells through activation of the Wnt/β‐catenin pathway via CTNNB1
Authors: Chen Mei , Li Lu , Zheng Peng‐Sheng
Published: July 2019

SALL4 is overexpressed in many cancers and is found to be involved in tumorigenesis and tumor progression. However, the function of SALL4 in cervical cancer remains unknown. Here, we showed that the expression of SALL4 was gradually increased from normal cervical tissue to high‐grade squamous intraepithelial lesions and then to squamous cervical carcinoma. SALL4 was upregulated or downregulated in cervical cancer cells by stably transfecting a SALL4‐expressing plasmid or a shRNA plasmid targeting SALL4, respectively. In vitro, cell growth curves and MTT (3‐(4,5‐dimethylthiazole‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assays showed that SALL4 promoted the cell proliferation of cervical cancer cells. In vivo, xenograft experiments verified that SALL4 enhanced the tumor formation of cervical cancer cells in female BALB/c Nude mice. Cell cycle analysis by fluorescence‐activated cell sorting found that SALL4 accelerates cell cycle transition from the G0/G1 phase to the S phase. TOP/FOP‐Flash reporter assay revealed that SALL4 significantly upregulates the activity of Wnt/β‐catenin pathway. Western blotting showed that the expression levels of β‐catenin and important downstream genes, including c‐Myc and cyclin D1, were increased by SALL4 in cervical cancer cells. Furthermore, dual‐luciferase reporter and chromatin immunoprecipitation assays confirmed that SALL4 transcriptionally activated CTNNB1 by physically interacting with its promoters. Taken together, The results of this study demonstrated that SALL4 may promote cell proliferation and tumor formation of cervical cancer cells by upregulating the activity of the Wnt/β‐catenin signaling pathway by directly binding to the CTNNB1 promoter and trans‐activating CTNNB1.
What do children think about their social worker? A Q‐method study of children's services
Authors: Stabler Lorna , Wilkins David , Carro Hester
Published: July 2019

Understanding how children experience social work interventions is an important part of gauging whether what is provided is genuinely helpful. In this paper, we describe the findings from a research project using Q‐method, aimed at understanding what children involved with statutory services think about their social workers and how they experience the time they spend together. Using a pre‐existing practice framework, we explored skills including empathy, collaboration, and purposefulness from the point of view of children and young people. The participants in our study (n = 22) were insightful observers of social work practice, able to describe not only how they experienced time spent with their workers but also inferring differences in motivation and approach. In addition, workers who were described in similar terms by different young people were nevertheless experienced differently. This suggests not an archetypal “good social worker”—instead, there are skills that are good for specific children at specific times within the context of specific relationships.
dl‐3‐n‐butylphthalide preserves white matter integrity and alleviates cognitive impairment in mice with chronic cerebral hypoperfusion
Authors: Han Qin‐Yu , Zhang He , Zhang Xi , He Dong‐Sheng , Wang Sun‐Wei , Cao Xiang , Dai Yu‐Tian , Xu Yun , Han Li‐Juan
Published: July 2019

Aims

Effects of dl‐3‐n‐butylphthalide (NBP) on white matter damage and cognitive impairment in vascular cognitive impairment (VCI) have not been well studied. This study aimed to investigate the effects of NBP treatment on chronic cerebral hypoperfusion‐induced white matter lesions and cognitive dysfunction in mice.

Methods

Mice were subjected to bilateral common carotid artery stenosis (BCAS) for over 30 days. The cerebral blood flow was detected using a laser Doppler flowmetry. Cognitive functions were assessed by several behavioral tests. We also evaluated the effects of NBP on the blood‐brain barrier (BBB) disruption and reactive astrogliosis, using Evans Blue extravasation, Western blot, CBA, and immunofluorescence in BCAS mice and cultured astrocytes.

Results

The results indicated that NBP treatment attenuated spatial memory dysfunction while promoted cerebral perfusion and white matter integrity in BCAS mice. Moreover, NBP treatment prevented BBB leakage and damage of endothelial cells, as well as disruption of endothelial tight junctions. Furthermore, NBP administration effectively decreased the number of activated astrocytes and pro‐inflammatory cytokines, as well as the production of MMPs, in BCAS‐induced mice and LPS‐stimulated astrocytes.

Conclusion

Our results indicated that NBP represents a promising therapy for chronic cerebral hypoperfusion‐induced white matter damage and cognitive impairment.
Urinary dysfunction in patients with rectal cancer: a prospective cohort study
Authors: Karlsson L. , Bock D. , Asplund D. , Ohlsson B. , Rosenberg J. , Angenete E.
Published: July 2019

Aim

Urinary dysfunction is one of many complications after treatment for rectal cancer. The aim of this study was to evaluate the prevalence of patient‐reported urinary dysfunction at the time of diagnosis and at 1‐year follow‐up and to assess the risk factors linked to urinary incontinence.

Method

Patients with newly diagnosed rectal cancer were included in the QoLiRECT study between 2012 and 2015. Questionnaires from the time of diagnosis and 1‐year follow‐up were analysed, with 1085 and 916 patients, respectively, eligible for analysis. Regression analyses were made to investigate possible risk factors for incontinence. The patient cohort was also compared with a cohort from the Swedish general population.

Results

At baseline, the prevalence of urinary dysfunction (14% of women, 8% of men) was similar to that in the general population. At 1‐year follow‐up, 20% of patients experienced urinary incontinence (29% of women, 14% of men). Emptying difficulties were experienced by 46% (41% of women, 49% of men) and urgency by 58% across both sexes. Abdominoperineal excision and urinary dysfunction at baseline were found to be independent risk factors for incontinence at 1‐year follow‐up. Among patients who were continent at baseline, risk factors were female sex, physical inactivity at baseline, comorbidity and abdominoperineal excision.

Conclusion

Urinary dysfunction is frequent among patients with rectal cancer, with up to a two‐fold increase in symptoms 1 year after diagnosis. Unfortunately, few factors are modifiable and these results stress the importance of informing patients of possible outcomes related to urinary dysfunction after treatment for rectal cancer.
Cognitive assessment in a predominantly Hispanic and Native American population in New Mexico and its association with kidney transplant wait‐listing
Authors: Ng Yue‐Harn , Al Mawed Saleem , Pankratz Vernon Shane , Argyropoulos Christos , Singh Pooja , Shaffi Saeed Kamran , Myaskovsky Larissa , Unruh Mark , Harford Antonia
Published: July 2019

The association between cognitive function and the likelihood of kidney transplant (KT) wait‐listing, especially in minority populations, has not been clearly delineated. We performed a retrospective review of our pre‐KT patients, who consist mainly of Hispanics and Native Americans, over a 16‐month period. We collected data on baseline demographics and the Montreal Cognitive Assessment (MoCA) score, at the initial KT evaluation. We defined cognitive impairment as MoCA scores of <24. We constructed linear regression models to identify associations between baseline characteristics with MoCA scores and used Cox proportional hazards models to assess associations between MoCA score and KT wait‐listing. During the study period, 154 patients completed the MoCA during their initial evaluation. Mean (standard deviation) MoCA scores were 23.9 (4.6), with 58 (38%) participants scoring <24. Advanced age, lower education and being on dialysis were associated with lower MoCA scores. For every one‐point increase in MoCA, the likelihood of being wait‐listed increased 1.10‐fold (95% CI 1.01‐1.19, P = .022). Being Native American and having kidney disease due to diabetes or hypertension were associated with longer time to wait‐listing. Cognitive impairment was common in our pre‐KT patients and was associated with a lower likelihood of KT wait‐listing.
Optimistically biased perception of one's own skin cancer risk: Representative nationwide findings
Authors: Diehl Katharina , Görig Tatiana , Osenbrügge Nina , Schilling Laura , Greinert Rüdiger , Schneider Sven
Published: July 2019

Background

Previous research has shown that individuals tend to have unrealistic comparative optimism (UCO) for different diseases and health outcomes. Our aim was to analyze UCO in relation to skin cancer for the first time in a representative nationwide sample. The results will be important for planning future prevention.

Methods

The National Cancer Aid Monitoring on Sunbed Use (NCAM, wave 3) is a representative nationwide German survey (n = 3,000, 14–45 years). We assessed UCO in relation to skin cancer and analyzed its association with sociodemographics, tanning and health‐related risk behaviors, skin cancer risk, and skin cancer risk awareness.

Results

Four out of ten (43.3 %) respondents believed themselves to have a lower risk of developing skin cancer than other people of the same age and sex. Younger individuals were more likely to be optimistic. Individuals with an increased risk of skin cancer were more likely to perceive this higher risk.

Conclusion

While it is realistic for those who actually have a higher risk of skin cancer to perceive it that way, the findings for the general population (and specifically for younger individuals) are concerning. It seems important to explain to people that their perception of their own risk of skin cancer is unrealistic, as this may affect their individual screening and prevention behavior.
Development of dopaminergic genetic associations with visuospatial, verbal and social working memory
Authors: Dumontheil Iroise , Kilford Emma J. , Blakemore Sarah‐Jayne
Published: July 2019

Dopamine transmission in the prefrontal cortex (PFC) supports working memory (WM), the temporary holding, processing and manipulation of information in one's mind. The gene coding the catechol‐O‐methyltransferase (COMT) enzyme, which degrades dopamine, in particular in the PFC, has a common single nucleotide polymorphism leading to two versions of the COMT enzyme which vary in their enzymatic activity. The methionine (Met) allele has been associated with higher WM performance and lower activation of the PFC in executive function tasks than the valine (Val) allele. In a previous study, COMT genotype was associated with performance on verbal and visuospatial WM tasks in adults, as well as with performance on a novel social WM paradigm that requires participants to maintain and manipulate information about the traits of their friends or family over a delay. Here, data collected in children and adolescents (N = 202) were compared to data from the adult sample (N = 131) to investigate possible age differences in genetic associations. Our results replicate and extend previous work showing that the pattern of superior WM performance observed in Met/Met adults emerges during development. These findings are consistent with a decrease in prefrontal dopamine levels during adolescence. Developmentally moderated genetic effects were observed for both visuospatial and social WM, even when controlling for non‐social WM performance, suggesting that the maintenance and manipulation of social information may also recruit the dopamine neurotransmitter system. These findings show that development should be considered when trying to understand the impact of genetic polymorphisms on cognitive function.
Evaluation of lipoprotein‐associated phospholipase A2 as a marker for renal microvasculopathy in adolescents with Type 1 diabetes
Authors: Seyfarth J. , Herebian D. , Reinauer C. , Baechle C. , Roden M. , Holl R. W. , Reinehr T. , Mayatepek E. , Meissner T. , Rosenbauer J.
Published: July 2019

Aim

To assess the relevance of lipoprotein‐associated phospholipase A2 activity as a diagnostic and prognostic marker for renal microvascular diseases.

Methods

We analysed lipoprotein‐associated phospholipase A2 activity and lysophosphatidylcholine levels (as a surrogate marker of oxidative stress) in 165 adolescents (aged 17.0 ± 2.3 years) with a history of Type 1 diabetes greater than 10 years. Clinical data were obtained from the German/Austrian nationwide Diabetes‐Patients Follow‐up (DPV) registry at blood collection and on average 2.4 ± 1.3 years later at follow‐up. Relationships between lipoprotein‐associated phospholipase A2 activity and clinical, demographic and laboratory variables, lysophosphatidylcholine levels and presence of albuminuria were evaluated by multivariable linear and logistic regression.

Results

Lipoprotein‐associated phospholipase A2 activity was higher in male than female adolescents (P = 0.002). Albuminuria was present in 14% (22/158) of participants at baseline, and 5% (4/86) of participants without albuminuria at baseline developed albuminuria until follow‐up. Lipoprotein‐associated phospholipase A2 activity was associated neither with present nor with incident albuminuria. Lysophosphatidylcholine did not correlate with lipoprotein‐associated phospholipase A2 activity. Cross‐sectional bivariate correlation as well as multivariable linear regression analysis revealed a negative correlation of lipoprotein‐associated phospholipase A2 activity with HbA1c and HDL‐cholesterol.

Conclusions

Lipoprotein‐associated phospholipase activity was not associated with surrogate markers for oxidative stress and early diabetic nephropathy. The association of decreased lipoprotein‐associated phospholipase A2 activity with poor glucose control might limit its function as a predictor of micro‐ and macrovascular diseases in Type 1 diabetes.
Commentary: SGLT inhibitors in type 1 diabetes: Place in therapy and a risk mitigation strategy for preventing diabetic ketoacidosis ‐ the STOP DKA protocol
Authors: Rendell Marc S.
Published: July 2019

In the accompanying article, Goldenberg et al. review the promotion of diabetic ketoacidosis by SGLT2 inihibitors. They have carried out a metanalysis showing a 3.5‐fold increase in the risk of diabetic ketoacidosis (DKA) in patients with type 1 diabetes under treatment with SGLT2 inhibitors. They make a number of suggestions for attempting to mitigate the risk of DKA in these patients, notably including blood ketone monitoring and the use of supplemental carbohydrates with additional insulin when ketones suggest incipient DKA. Their proposal merits evaluation in a clinical trial involving type 1 diabetes, which should also assess the possible cardiorenal benefits demonstrated with treatment with SGLT2 inhibitors in type 2 diabetes.
Using Real‐Life Major League Baseball Data in an Introductory Statistics Course
Authors: Wathen Samuel , Rhew Nicholas D.
Published: July 2019

A primary goal of introductory statistics courses is to develop a student's ability to think statistically. To motivate students to this end, the literature suggests that statistics courses use exercises that are relevant and familiar to students. Work in educational psychology highlights the importance of connecting new concepts to pre‐existing knowledge, mental models, or schema. One method to meet these criteria is to develop exercises and problems that use real‐life data. While real‐life data provide a context for the application of statistical methods, the data does not necessarily provide a context or process for developing the ability to think statistically. This teaching brief describes a set of logical, sequential, and ready‐to‐use exercises that motivate statistical inquiry and thought in line with the GAISE College Report recommendations. The exercises use real‐life data freely sourced from Major League Baseball and the nonfiction story ofMoneyball: The Art of Winning an Unfair Game. Student reactions indicate that these exercises, which are anchored in real‐life data with a real‐life story, are successful in motivating student interest in statistics.
Identifying Cognitive Processing Events during Clicker Exercises and Exploring Their Relationship with Student Learning
Authors: D'Souza Derrick E. , Daspit Joshua J. , Sigdyal Pratigya
Published: July 2019

The use of clickers in the classroom has been linked to student learning. However, studies that examine the effects of clickers on learning often conceptualize a clicker exercise as a single, homogeneous cognitive processing (CP) event. We offer a conceptualization of sequenced cognitive activities that unfold during a clicker exercise. An inductive approach is adopted to identify three CP events that occur during a clicker exercise: an investigation event, a confirmation event, and a ratification event. We then use data collected from a sample of 187 students in an undergraduate business capstone course to explore the relationships between the three CP events and student learning. Contrary to expectations, not all CP events contribute positively to student learning. We discuss the implications of these findings and offer directions for future research that advance the understanding of clicker‐enhanced student learning. These insights afford instructors new options for optimizing the contributions of clicker exercises to student learning in their courses.
In vitro evidence consistent with an interaction between wild‐type and mutant SOD1 protein associated with canine degenerative myelopathy
Authors: Qi Yao , Montague Paul , Loney Colin , Campbell Clare , Shafie Intan N. F. , Anderson Thomas J. , McLaughlin Mark
Published: July 2019

Canine degenerative myelopathy (DM) is a progressive neurological disorder that may be considered to be a large animal model for specific forms of the fatal human disease, familial amyotrophic lateral sclerosis (fALS). DM is associated with a c118G>A mutation of the superoxide dismutase 1 (Sod1) gene, and a significant proportion of cases are inherited in an autosomal recessive manner in contrast to the largely, but not exclusively, dominant mode of inheritance in fALS. The consensus view is that these Sod1/SOD1 mutations result in a toxic gain of function but the mechanisms remain unclear. Here we used an in vitro neuroblastoma cell line transfection system to monitor wild‐type and mutant forms of SOD1 fusion proteins containing either a Cherry or an enhanced green fluorescent protein (EGFP) tag. These fusion proteins retained SOD1 enzymatic activity on a native gel assay system. We demonstrate that SOD1 aggregate density is significantly higher in DM transfectants compared to wild‐type. In addition, we show by co‐immunoprecipitation and confocal microscopy, evidence for a potential interaction between wild‐type and mutant forms of SOD1 in co‐transfected cells. While in vitro studies have shown SOD1 heterodimer formation in fALS models, this is the first report for DM SOD1. Therefore, despite for the majority of cases there is a difference in the mode of inheritance between fALS and DM, a similar interaction between wild‐type and mutant SOD1 forms can occur. Clarifying the role of SOD1 in DM may also be of benefit to understanding the role of SOD1 in fALS.
Influence of age at seizure onset on the acquisition of neurodevelopmental skills in an SCN8A cohort
Authors: Encinas Alejandra C. , Moore Ida (Ki) M. , Watkins Joseph C. , Hammer Michael F.
Published: July 2019

Objective

To characterize a cohort of patients with SCN8A‐related epilepsy and to perform analyses to identify correlations involving the acquisition of neurodevelopmental skills.

Methods

We analyzed patient data (n = 91) submitted to an online registry tailored to characteristics of children with SCN8A variants. Participants provided information on the history of their child's seizures, medications, comorbidities, and developmental skills based on the Denver II items. Spearman rank tests were utilized to test for correlations among a variety of aspects of seizures, medications, and neurodevelopmental progression.

Results

The 91 participants carried 71 missense variants (41 newly reported) and three truncating variants. Ages at seizure onset ranged from birth to >12 months of age (mean ± SD = 5 months 21 days ± 7 months 14 days). Multiple seizure types with multimodal onset times and developmental delay were observed as general features of this cohort. We found a positive correlation between a developmental score based upon percentage of acquired skills and the age at seizure onset, current seizure freedom, and initial febrile seizures. Analyses of cohort subgroups revealed clear distinctions between patients who had a single reported variant in SCN8A and those with an additional variant reported in a gene other than SCN8A, as well as between patients with different patterns of regression before and at seizure onset.

Significance

This is the first study of an SCN8A patient cohort of this size and for which correlations between age at seizure onset and neurodevelopment were investigated. Our correlation studies suggest that variants of uncertain significance should be considered in assessing children with SCN8A‐related disorders. This study substantially improves the characterization of this patient population and our understanding of the neurodevelopmental effects associated with seizures for SCN8A patients, and provides a clinical context at initial presentation that may be prognostic for developmental outcome.
Predatory potential of eleven native Moroccan adult ladybird species on different stages of Dactylopius opuntiae (Cockerell) (Hemiptera: Dactylopiidae)
Authors: El Aalaoui M. , Bouharroud R. , Sbaghi M. , El Bouhssini M. , Hilali L.
Published: July 2019

Dactylopius opuntiae is an insect pest of cactus which is currently causing severe damage to cactus crops in Morocco. It was first observed in 2014 in the Sidi Bennour region 120 km northwest of Marrakech, and has spread very quickly to destroy the prickly pear cactus crops (Opuntia ficus‐indica (L.) Miller) in several regions of country, causing very heavy economic losses. To control this pest, the predatory potential of eleven species of native Moroccan ladybird predators was investigated under laboratory conditions at 26 ± 2°C, 60 ± 10% RH and a 12 h light:12 h dark regime. The experiments were conducted in no‐choice feeding tests (only eggs, first instar or second instar of mealybugs were offered at one time) and free‐choice feeding tests (eggs and first and second instar larvae were offered simultaneously). In the no‐choice feeding tests, Exochomus nigripennis, Chilocorus bipustulatus and Chilocorus politus consumed the highest mean number of mealybug eggs and first instars, and the highest mean number of second instars was consumed by Hippodamia convergens. In the free‐choice feeding tests the highest mean number of mealybug eggs was eaten by Chilocorus bipustulatus and Chilocorus politus and Hippodamia convergens consumed the highest mean number of first and second instars of the mealybug.
First report of Thrips setosus in Belgium
Authors: Goedefroit T. , Bonte J. , Reybroeck E. , Bosmans L. , San Martin G. , Witters J.
Published: July 2019

The Japanese flower thrips, Thrips setosus, is a polyphagous insect which in Europe has mainly been observed on hydrangeas (Hydrangea spp.). The first report of T. setosus in the EPPO region was in the Netherlands (2014). Since then it has been observed in four other countries inside the EPPO region: Germany (2015), the United Kingdom (2016), France (2016) and Croatia (2016). Its dispersal is most likely to be related to trade. Because of its polyphagous nature, there is a risk of spread to other economically important crops. Therefore, T. setosus was included in the national survey project ‘STATREGO’, during which the status of several invasive plant pests and diseases in Belgium was determined.
Reshaping Couple Configurations that Get in the Way of Relationship Repair and Healing
Authors: Butler Mark H. , Spencer Travis J. , Seedall Ryan B.
Published: July 2019

In the context of relationship trauma, partners' reactive patterns of engagement can disrupt and derail attempts at relationship correction and healing. A circumplex typology of couple patterns of engagement in relational trauma context is defined in terms of partners' underlying views of self in relation to other (VSIRO). VSIRO is conceptualized along a continuum anchored at opposite poles by inflated (self‐aggrandizing) versus collapsed (self‐abnegating) VSIRO, with a balanced (egalitarian) VSIRO, characterized by accountability and forbearance, as the target position. The circumplex model delineates four problematic couple configurations—a dejected couple, a taker–enabler couple, an ultimate fighting couple, and a debtor–collector couple. Where problematic engagement occurs, therapists need to reshape couple engagement toward the balanced, egalitarian position prior to relational trauma work. Clinical vignettes depict these couples and springboard an analysis of unique needs and interventions associated with each couple configuration. Reshaping couple patterns of engagement using a circumplex model of couple configurations is an essential prerequisite to effective and ethical relational trauma work.
What Does it Mean to be a Common Factors Informed Family Therapist?
Authors: Davis Sean D. , Hsieh Alexander L.
Published: July 2019

The common factors paradigm in couple and family therapy has gained popularity over the past several decades, leading many therapists to refer to themselves as common factors family therapists. Despite this, no consensus exists on what it means to be a common factors family therapist, or if such a designation even makes sense given that the common factors paradigm is not a model. Synthesizing the existing common factors literature, a case is made for the designation “common factors informed family therapist,” and the following six core principles are outlined that characterize this designation: (1) sees overlap among theories; (2) passionate about theory, notatheory; (3) client centered; (4) monitors hope and the therapeutic alliance; (5) views clients as people rather than objects; and (6) prioritizes healing over therapy. Each of the concepts is discussed in depth, and clinical implications are provided.
Protective effect of metformin on a rat model of lipopolysaccharide‐induced preeclampsia
Authors: Hu Jilin , Zhang Jinman , Zhu Baosheng
Published: July 2019

Recent in vitro and clinical studies have found that metformin (MET) may play a preventive or therapeutic role in preeclampsia (PE) and may be a candidate drug for the prevention and/or treatment of PE. In this study, we used lipopolysaccharide (LPS) to induce a PE‐like rat model and investigated the intervention effect of MET from the perspectives of clinical manifestations, placental morphology, serum marker for placental injury, systemic inflammatory response and oxidative/nitrative stress, and placental nuclear factor‐κB (NF‐κB) signaling. The results showed that MET improved LPS‐induced hypertension, proteinuria, fetal growth restriction (FGR) and stillbirth, alleviated placental injury and decreased maternal serum marker alpha‐fetoprotein (MS‐AFP) level; MET suppressed LPS‐induced TNF‐α and IL‐6 productions, reduced oxidative/nitrative stress as evidenced by increased superoxide dismutase (SOD) activity, decreased inducible nitric oxide synthase (iNOS) activity, and decreased levels of malondialdehyde (MDA) and nitric oxide (NO); MET inhibited LPS‐induced NF‐κB activation in placentas. Based on these findings, it can be concluded that MET is beneficial to the PE‐like rat model by protecting placentas from injury, suppressing systemic inflammatory response and oxidative/nitrative stress, and inhibiting placental NF‐κB signaling pathway. MET is a promising drug for prevention and/or treatment of PE.
Le rôle des initiatives de responsabilité sociale dans le contrôle des audits sociaux et la responsabilisation de leurs auteurs
Authors: TERWINDT Carolijn , ARMSTRONG Amy
Published: July 2019

En 2018, l'effondrement du Rana Plaza braquait le projecteur sur les conditions de travail parfois déplorables dans la confection. Si la grande distribution est depuis pointée du doigt, la responsabilité des cabinets d'audit social est rarement mentionnée. Les auteures examinent les moyens disponibles à ce stade pour repérer et sanctionner les audits négligents ou complaisants, qui taisent les atteintes aux droits des travailleurs. Elles constatent que les contrôles et les rappels à l'ordre restent limités dans les faits. Elles s'interrogent alors sur l'apport des initiatives de responsabilité sociale pour un contrôle véritable de la qualité des audits et une responsabilisation de leurs auteurs.
Le non‐respect des dispositions relatives au salaire minimum en Europe centrale et orientale
Authors: GORAUS‐TAŃSKA Karolina , LEWANDOWSKI Piotr
Published: July 2019

L'étude porte sur l'inobservation du salaire minimum dans dix pays d'Europe centrale et orientale dotés de cette institution. Les auteurs estiment la fréquence et la gravité des infractions à partir des données de l'EU‐SILC (2003–2012), en reprenant la méthode de Bhorat, Kanbur et Mayet (2013). Ils tiennent compte dans leurs régressions des caractéristiques individuelles, des caractéristiques de l'emploi et des données macroéconomiques. Les infractions restent relativement peu fréquentes mais touchent d'abord les groupes que les politiques de salaire minimum devraient protéger. Par ailleurs, la hausse du rapport entre salaire minimum et salaire moyen dans le temps s'accompagne d'une hausse de la fréquence des infractions.
Les disparités salariales entre effectifs permanents et effectifs temporaires chez les jeunes, dans trois pays européens
Authors: REGOLI Andrea , D'AGOSTINO Antonella , GRANDNER Thomas , GSTACH Dieter
Published: July 2019

Les auteurs étudient les disparités salariales chez les jeunes (25–40 ans) dans trois pays européens (Allemagne, France et Italie) en utilisant les statistiques de l'EU‐SILC (2010). La méthode fait appel à des régressions fondées sur la fonction d'influence recentrée et à des techniques d'estimation par repondération. Elle vise à faire apparaître le rôle des caractéristiques relatives à l'individu et au poste de travail aux différents points de la répartition des salaires. La part de l'écart qui reste inexpliquée est considérable en Italie, pour tous les centiles. En France, elle s'atténue dans le haut de la répartition. En Allemagne, elle n'est jamais significative.
Travailler ou ne pas travailler: la motivation professionnelle autre que pécuniaire et ses prédicteurs, une question d'époque
Authors: SHARABI Moshe , HARPAZ Itzhak
Published: July 2019

Pour mesurer la motivation professionnelle autre que pécuniaire, on demande généralement aux gens s'ils continueraient à travailler s'ils gagnaient au loto. Les auteurs rappellent les conclusions des études menées sur la base des réponses à cette question dans différents pays dont Israël, tout en recherchant l'influence en la matière des variables démographiques et des différentes dimensions du sens du travail. Ils constatent un net recul de la motivation professionnelle autre que pécuniaire au nouveau millénaire, et une évolution des facteurs en cause. Ils analysent ces résultats et leurs effets potentiels sur le travail et l'emploi au regard de l'évolution économique et sociale en Israël.
New frontiers in applied veterinary point‐of‐capture diagnostics: Toward early detection and control of zoonotic influenza
Authors: Schar Daniel , Padungtod Pawin , Tung Nguyen , O’Leary Michael , Kalpravidh Wantanee , Claes Filip
Published: July 2019

Among the chief limitations in achieving early detection and control of animal‐origin influenza of pandemic potential in high‐risk livestock populations is the existing lag time between sample collection and diagnostic result. Advances in molecular diagnostics are permitting deployment of affordable, rapid, highly sensitive, and specific point‐of‐capture assays, providing opportunities for targeted surveillance driving containment strategies with potentially compelling returns on investment. Interrupting disease transmission at source holds promise of disrupting cycles of animal‐origin influenza incursion to endemicity and limiting impact on animal production, food security, and public health. Adoption of new point‐of‐capture diagnostics should be undertaken in the context of promoting robust veterinary services systems and parallel support for operationalizing pre‐authorized plans and communication strategies that will ensure that the full potential of these new platforms is realized.
Bioinspired multilevel interconnected networks with porous multiwalled nanotubes built by heterogeneous nanocrystallites
Authors: Chen Shikun , Yang Chengzhi , Wu Lingling , Su Huilan , Zhu Yifu , Li Guoyao , Song Fang , Zhang Wang , Gu Jiajun , Liu Qinglei
Published: July 2019

Inspired by fiber‐interwoven eggshell membrane (ESM) with associated specific permeability and transport performance, interconnected nanotube networks are constructed to empolder relevant distinctive properties and functional advantages. In this work, a typical ESM‐templated procedure combined with stepwise impregnation and gradient calcination is developed to accomplish the fabrication of multilevel frameworks from TiO2 nanocrystallites to porous multiwalled nanotubes (NTs) to final interconnected networks. During the impregnation process, in situ mineralization occurs on ESM fiber substrate to generate Ti‐impregnant coating with variant composition and layered structure. Followed by the calcination, anatase TiO2 porous NTs come into being as ESM templates decompose at 500°C, then heterogeneous nanocrystallites are achieved at higher temperature. Thus, the final ESM‐morphic nanocomposites present interconnected networks woven by porous multiwalled NTs. Benefiting from interconnected multichannels of multilevel networks and controllable heterogeneous nanocrystallites, the ESM‐inspired TiO2 would behave higher light‐excitation and transport efficiency, which can achieve more valuable applications such as photocatalytic degradation to some organic pollutants.
To change or not to change experimenters: caveats for repeated behavioural and physiological measures in Montagu's harrier
Authors: Rabdeau Juliette , Badenhausser Isabelle , Moreau Jérôme , Bretagnolle Vincent , Monceau Karine
Published: July 2019

Animals facing anthropogenic disturbances may exhibit different anti‐predator responses depending on their perception of the risk. Experimental measures of behavioural and physiological traits may be impacted by the disturbance due to experimenter handlings and activities. In this study, we assessed the behavioural and physiological responses of Montagu's harrier chicks Circus pygargus from 14 nests, visited four times from hatching to fledgling by either the same (group I) or different (group NI) experimenters. Escape, aggressiveness and stress‐induced corticosterone concentration increased for both groups over time but chicks from group I showed a higher increase in their behavioural and physiological responses than chicks from group NI. This increase occurred after the second visit when experimenters took the first blood sampling on nestlings. Handling by the same experimenters throughout the study did not result in habituation but in sensitization. Our results suggest that Montagu's harrier nestlings may discriminate between the people who visit their nest and respond to experimenters’ identity. Therefore, we urge researchers working on behaviour and/or the physiology of stress including repeated measurements (such as animal personality studies for instance) to consider whether the experiments should or should not be conducted by the same experimenters (as usually done to minimize bias) as it can influence the outcomes of the experiments.
Achieving durable mitral isthmus block: Challenges, pitfalls, and methods of assessment
Authors: Hamoud Naktal S. , Abrich Victor A. , Shen Win‐Kuang , Mulpuru Siva K. , Srivathsan Komandoor
Published: July 2019

Background and objectives

Macroreentrant atrial tachycardias often occur following atrial fibrillation ablation, most commonly due to nontransmural lesions in prior ablation lines. Perimitral atrial flutter is one such arrhythmia which requires ablation of the mitral isthmus. Our objectives were to review the literature regarding ablation of the mitral isthmus and to provide our approach for assessment of mitral isthmus block.

Methods

We review anatomical considerations, ablation strategies, and assessment of conduction block across the mitral isthmus, which is subject to several pitfalls. Activation sequence and spatial differential pacing techniques are discussed for assessment of both endocardial and epicardial bidirectional mitral isthmus block.

Results

Traditional methods for verifying mitral isthmus block include spatial differential pacing, activation mapping, and identification of double potentials. Up to 70% of cases require additional ablation in the coronary sinus (CS) to achieve transmural block. Interpretation of transmural block is subject to six pitfalls involving pacing output, differentiation of endocardial left atrial recordings from epicardial CS recordings, identification of a slowly conducting gap in the line, and catheter positioning during spatial differential pacing. Interpretation of unipolar electrograms can identify nontransmural lesions. We employ a combined epicardial and endocardial assessment of mitral isthmus block, which involves using a CS catheter for epicardial recording and a duodecapolar Halo catheter positioned around the mitral annulus for endocardial recording.

Conclusions

The assessment of transmural mitral isthmus block can be challenging. Placement of an endocardial mapping catheter around the mitral annulus can provide a precise assessment of conduction across the mitral isthmus.