bluuebunny/crossref_metadata_2025 huggingface dataset:
The (missing) subjects of research on gender and global governance: Toward inquiry into the ruling relations of development
Authors: Campbell Marie L. , Kim Elena
Published: September 2018

Responding to the Special Issue's call for “new thinking” on gender and governance in developing societies, we introduce our research on the social organization of development knowledge and its ethical implications. Our feminist‐based approach, institutional ethnography, analyses the ruling relations of development and the standpoints represented in knowledge about development and its governance. Our paper offers an alternative to what we see as “the institutional standpoint” prevailing, but taken for granted, in business and society scholarship addressing development. Instead of theorizing development relationships between institutions and their “stakeholders,” we illustrate what can be learned about the social relations of development beginning from the experiences of local subjects. Our analysis of an environmental research and development project in Uzbekistan shows that being missed is knowledge about development subjects that could have revealed what is locally relevant and needed. Instead, we discover gender inequality being constituted, unknowingly, within this project's institutionally generated knowledge and the activities it authorizes.
Teacher‐led inquiry in technology‐supported school communities
Authors: Michos Konstantinos , Hernández‐Leo Davinia , Albó Laia
Published: September 2018

Learning design is a research field which studies how to best support teachers as designers of Technology Enhanced Learning (TEL) situations. Although substantial work has been done in the articulation of the learning design process, little is known about how learning designs are experienced by students and teachers, especially in the context of schools. This paper empirically examines if a teacher inquiry model, as a tool for systematic research by teachers into their own practice, facilitates the connection between the design and data‐informed reflection on TEL interventions in two school communities. High school teachers participated in a learning design professional development program supported by a web‐based community platform integrating a teacher inquiry tool (TILE). A multiple case study was conducted aimed at understanding: (a) current teacher practice and (b) teacher involvement in inquiry cycles of design and classroom implementations with technologies. Multiple data sources were used over a one year period including focus groups transcripts, teacher interview protocols, digital artifacts, and questionnaires. Sharing teacher‐led inquiries together with learning analytics was perceived as being useful for connecting pedagogical intentions with the evaluation of their enactment with learners, and this differed from their current practice. Teachers’ reflections about their designs focused on the time management of learning activities and their familiarity with the enactment and analytics tools. Results inform how technology can support teacher‐led inquiry and collective reflective practice in schools.
Innovations in Practice: Dialectical behaviour therapy for adolescents: multisite implementation and evaluation of a 16‐week programme in a public community mental health setting
Authors: Flynn Daniel , Kells Mary , Joyce Mary , Corcoran Paul , Gillespie Conall , Suarez Catalina , Swales Michaela , Arensman Ella
Published: September 2018

Background

Dialectical behaviour therapy for adolescents (DBT‐A) is an intervention with a growing evidence base for treating adolescents with emotional and behavioural dysregulation. This study describes the implementation and effectiveness of 16‐week DBT‐A across multiple sites in publicly funded child/adolescent mental health services (CAMHS) in Ireland.

Method

The Consolidated Framework for Implementation Research was used to guide this national implementation. Fifty‐four clinicians from seven CAMHS teams completed DBT training and delivered the 16‐week DBT‐A programme. Eighty‐four adolescents with emotional and behavioural dysregulation participated in the intervention and outcome measures were administered at preintervention, postintervention and 16‐week follow‐up.

Results

Significant reductions on all outcome measures were observed for DBT‐A participants including presence and frequency of self‐harm, suicidal ideation and depression. Reductions in the number of acute inpatient admissions, bed days and emergency department visits were also reported.

Conclusions

DBT‐A can be successfully implemented in CAMHS settings and yield positive outcomes for adolescents with emotional and behavioural dysregulation.
NLRP3 inflammasome activation contributes to the pathogenesis of rheumatoid arthritis
Authors: Guo C , Fu R , Wang S , Huang Y , Li X , Zhou M , Zhao J , Yang N
Published: September 2018

Nucleotide-binding, oligomerization domain (NOD)-like receptor family, pyrin domain containing 3 (NLRP3) gene polymorphism was reported to be associated with susceptibility, disease activity or anti-tumour necrosis factor (TNF) treatment response in rheumatoid arthritis (RA). However, the roles of NLRP3 inflammasome in the development of RA have not yet been elucidated fully. The present study aimed to study the role of NLRP3 inflammasome in RA. NLRP3 inflammasome activation in synovial tissues from RA and osteoarthritis (OA) patients were assessed by Western blot. Active caspase-1 in synovia was stained by a FAM-FLICA caspase-1 probe. Mice with collagen-induced arthritis (CIA) were treated with MCC950, a selective NLRP3 inhibitor, or vehicle for 2 weeks. The clinical score of arthritis, synovial inflammation and cartilage erosion were assessed. Proinflammatory cytokines were measured by enzyme-linked immunosorbent assay (ELISA). The results showed that NLRP3 inflammasome was highly activated in both synovia from RA patients and CIA mice. Activation of NLRP3 inflammasome occurred mainly in the infiltrating monocyte/macrophages in synovia, but not in fibroblast-like synoviocytes. Treatment with MCC950 resulted in significantly less severe joints inflammation and bone destruction. NLRP3 inflammasome activation in the synovia was inhibited significantly by MCC950 with reduced production of interleukin (IL)-1β. The inhibition of NLRP3 inflammasome activation by MCC950 was confirmed further in a human monocytic cell line, THP-1. In conclusion, NLRP3 inflammasome is involved in the pathogenesis of RA. Targeting NLRP3 inflammasome with a small molecule inhibitor might be a novel therapeutic strategy for RA.
Underage alcohol sales in community sporting clubs
Authors: Kremer Peter , Crooks Nicholas , Rowland Bosco , Hall Jessica , Toumbourou John W.
Published: September 2018

Introduction and Aims

Adolescent alcohol consumption and associated harms are significant public health issues in Australia. One strategy to reduce this problem is restricting alcohol supply to adolescents below age 18. To ensure compliance with laws that forbid underage alcohol sales, effective monitoring systems that operate across a range of settings, including sporting clubs, are required. This study investigated compliance with regulations requiring proof of age identification and refusal of underage alcohol sales in community sporting clubs.

Design and Methods

Compliance with alcohol sales laws was monitored using a male confederate that appeared under 18 who attempted to purchase alcohol at community sporting clubs in two regional areas of Victoria, Australia during the 2016–2017 sporting seasons.

Results

Purchase observations were completed at 43 clubs (observations could not be conducted at 14 clubs); alcohol was purchased at 41 (95%) clubs. Four (9%) clubs asked the confederate‐purchaser to provide identification of age—in two instances the purchaser was not sold alcohol and in two instances was sold alcohol after not showing identification. Rates of compliance with proof of age identification and alcohol sales did not vary according to staff‐ and club‐related variables.

Discussion and Conclusions

This study indicates the need for more rigorous enforcement of alcohol sales regulations in community sporting clubs. Community health agencies could work with sporting clubs to assist them to improve compliance with alcohol sales regulations and to provide information on the significant role clubs play in shaping the adolescent alcohol culture.
Mycophenolate mofetil in paediatric autoimmune or immune‐mediated diseases of the central nervous system: clinical experience and recommendations
Authors: Nosadini Margherita , Gadian Jonathan , Lim Ming , Sartori Stefano , Thomas Terrence , Dale Russell C
Published: September 2018

Aim

To gather data on mycophenolate mofetil (MMF) in paediatric autoimmune/immune‐mediated central nervous system (CNS) conditions, focusing on safety and factors that may affect MMF efficacy.

Method

Retrospective, multicentre study based on four paediatric neurology centres.

Results

Forty‐four children were included (30 females, 14 males): 19 had proven/suspected autoimmune encephalitis, 14 had inflammatory demyelinating CNS diseases, and 11 had other autoimmune/immune‐mediated CNS conditions. Before MMF, all received first‐line immune therapies, and 17 had second‐line rituximab and/or cyclophosphamide. MMF was started at a median of 9.5 months from disease onset (range 1–127mo) (median age 9y 4mo, range 1y 5mo–16y 5mo), and was used for median 18 months (range 0.3–73mo). On MMF, 31 patients were relapse‐free, whereas eight relapsed (excluding patients with chronic–progressive course). Relapses on MMF were associated with medication weaning/cessation, or with suboptimal MMF dosage/duration. Adverse events of MMF occurred in eight patients: six moderate (gastrointestinal, movement disorder, dermatological) and two severe (infectious).

Interpretation

MMF use in paediatric neuroimmunology is heterogeneous, although relatively safe. We have identified factors that may affect MMF efficacy and provide recommendations on MMF usage.

What this paper adds

Mycophenolate mofetil (MMF) use was heterogeneous with relatively common adverse events, although mostly not severe.

MMF treatment reduced median annualized relapse rate, although 20% of patients relapsed on MMF.

A high relapse rate pre‐MMF and late MMF start were associated with higher probability of relapsing on MMF.

Most relapses were associated with suboptimal MMF dosage, short MMF duration, or concurrent medication weaning/discontinuation.
Impact of social disadvantage on cerebral palsy severity
Authors: Woolfenden Sue , Galea Claire , Smithers‐Sheedy Hayley , Blair Eve , Mcintyre Sarah , Reid Sue , Delacy Michael , Badawi Nadia ,   On Behalf of the Australian Cerebral Palsy Register Group,   CP Quest
Published: September 2018

Aim

To investigate the impact of socio‐economic disadvantage on indicators of cerebral palsy (CP) severity – motor impairment, intellectual disability, and the presence of severe comorbidities – in children withCPin Australia.

Method

Data from the Australian Cerebral Palsy Register were analysed. Socio‐economic disadvantage was assessed using maternal age, maternal country of birth, and a measure of neighbourhood socio‐economic status (SES) at the time of the child's birth. Descriptive bivariate analysis, trend analysis, risk ratios, and mediation analysis were undertaken to examine the impact of disadvantage on the indicators ofCPseverity.

Results

A socio‐economic gradient was demonstrated with an increasing proportion of children with non‐ambulant status, at least moderate intellectual disability, and the presence of severe comorbidities (having epilepsy, functional blindness, bilateral deafness, and/or no verbal communication) with decreasing neighbourhoodSES, adolescent motherhood, and maternal minority ethnicity.

Interpretation

In Australia, socio‐economic disadvantage at birth impacts adversely onCPseverity at age 5 years. By identifying that socio‐economically disadvantaged children withCPare at greater risk of more severe functional outcomes, we can inform targeted interventions at the family and neighbourhood level to reduce these inequities for children withCP.

What this paper adds

Socio‐economic disadvantage is associated with increased severity of cerebral palsy functional outcomes.

This encompasses low neighbourhood socio‐economic status, adolescent motherhood, and maternal minority ethnicity.
Isolated seizures during the first episode of relapsing myelin oligodendrocyte glycoprotein antibody‐associated demyelination in children
Authors: Ramanathan Sudarshini , O'grady Gina L , Malone Stephen , Spooner Claire G , Brown David A , Gill Deepak , Brilot Fabienne , Dale Russell C
Published: September 2018

Myelin oligodendrocyte glycoprotein (MOG) antibodies have a strong association with acute disseminated encephalomyelitis (ADEM) in children, and bilateral and recurrent optic neuritis in children and adults. Recent reports suggest that seizures and encephalopathy may occur in children and adults with MOG antibody‐associated disease. We describe the clinical, laboratory, and radiological course of four MOG antibody‐positive children who first presented with isolated seizures without fulfilling clinical or radiological criteria for ADEM or other central nervous system demyelination syndromes, who months to years later developed more typical demyelination. This case series highlights a novel observation that isolated seizures in the absence of ADEM may be the index presentation for MOG antibody‐associated disease, which should therefore be considered a form of autoimmune epilepsy. It would be reasonable to test for MOG antibodies in children with seizures accompanied by subtle inflammatory changes on magnetic resonance imaging or cerebrospinal fluid analyses, particularly if followed by demyelination, given the clinical and therapeutic implications of an expedited diagnosis in minimizing long‐term disability.

What this paper adds

Isolated seizures in the absence of acute disseminated encephalomyelitis may be the index presentation for myelin oligodendrocyte glycoprotein antibody‐associated demyelination.
Leveraging technology to identify subclinical deficits in radiologically isolated syndrome
Authors: Okuda D. T.
Published: September 2018

Click here to view the accompanying paper in this volume.
The structure of INI1/hSNF5 RPT1 and its interactions with the c‐MYC:MAX heterodimer provide insights into the interplay between MYC and the SWI/SNF chromatin remodeling complex
Authors: Sammak Susan , Allen Mark D. , Hamdani Najoua , Bycroft Mark , Zinzalla Giovanna
Published: September 2018

c‐MYC and the SWI/SNF chromatin remodeling complex act as master regulators of transcription, and play a key role in human cancer. Although they are known to interact, the molecular details of their interaction are lacking. We have determined the structure of the RPT1 region of the INI1/hSNF5/BAF47/SMARCB1 subunit of the SWI/SNF complex that acts as a c‐MYC‐binding domain, and have localized the interaction regions on both INI1 and on the c‐MYC:MAX heterodimer. c‐MYC interacts with a highly conserved groove on INI1, while INI1 binds to the c‐MYC helix‐loop‐helix region. The binding site overlaps with the c‐MYC DNA‐binding region, and we show that binding of INI1 and E‐box DNA to c‐MYC:MAX are mutually exclusive.
Labour and the city: Some notes across theory and research
Authors: Buckley Michelle
Published: September 2018

At a time of growing interest in research and theory concerning urban space and urban workers, this article explores three divergent strands of scholarly research and theory that are producing new perspectives on the relations of labour, work, and employment with processes of urbanization, the production of urban space or city life. Drawing together research and debates both within geography and outside of it, this article briefly reviews emerging urban scholarship on labour in the so‐called “sharing economy,” historical research on the distinctly urban histories of slavery in North America, the Caribbean, Africa, and South America, and the often unpaid and highly gendered labour of urban homesteading and autonomous self‐provisioning in cities. This article does not strive to present comprehensive or masterful readings of these literatures but rather to explore some of the very different ways that “labour” is mobilized in them, noting the differences between them but also pointing to some of the insights about knowledge production on labour and city life that is offered by reading them together.
Influence of lack of posterior occlusal support on cognitive decline among 80‐year‐old Japanese people in a 3‐year prospective study
Authors: Hatta Kodai , Ikebe Kazunori , Gondo Yasuyuki , Kamide Kei , Masui Yukie , Inagaki Hiroki , Nakagawa Takeshi , Matsuda Ken‐ichi , Ogawa Taiji , Inomata Chisato , Takeshita Hajime , Mihara Yusuke , Fukutake Motoyoshi , Kitamura Masahiro , Murakami Shinya , Kabayama Mai , Ishizaki Tatsuro , Arai Yasumichi , Sugimoto Ken , Rakugi Hiromi , Maeda Yoshinobu
Published: September 2018

Aim

Previous studies have reported significant associations between tooth loss or periodontal status and cognitive function; however, animal experimental studies have shown that occlusion might be a more important factor in cognitive decline. The purpose of the present study was to investigate the influence of a lack of posterior occlusal support by residual teeth on the decline of cognitive function over a 3‐year period among 80‐year‐old Japanese people.

Methods

Participants were community‐dwelling older adults (n = 515, age 79–81 years). Cognitive function was measured using the Japanese version of the Montreal Cognitive Assessment. At baseline, participants were divided into two groups: those with and without posterior occlusal support. Participants whose Japanese version of the Montreal Cognitive Assessment score decreased by ≥3 points over the 3‐year period were defined as the declined group. Logistic regression was carried out for the decline in Japanese version of the Montreal Cognitive Assessment scores, including dental status and possible risk factors as independent variables.

Results

More participants without posterior occlusal support tended to be in the cognitive decline group (49.4%) than in the maintained group (38.5%; χ2‐test, P = 0.02). Logistic regression analysis showed that a lack of posterior occlusal support was a significant variable (odds ratio 1.55, P = 0.03) for cognitive decline, even after adjusting for other risk factors. However, the number of teeth or mean periodontal pocket depth was not significantly correlated with cognitive decline.

Conclusions

The present findings suggest that a lack of posterior occlusal support predicted the incidence of cognitive decline, even after adjusting for possible risk factors in community‐dwelling old‐old people. Geriatr Gerontol Int 2018; 18: 1439–1446.
Frequent false‐negative immunohistochemical staining with IDH1 (R132H)‐specific H09 antibody on frozen section control slides: a potential pitfall in glioma diagnosis
Authors: Yoshida Akihiko , Satomi Kaishi , Ohno Makoto , Matsushita Yuko , Takahashi Masamichi , Miyakita Yasuji , Hiraoka Nobuyoshi , Narita Yoshitaka , Ichimura Koichi
Published: September 2018

Aims

Intraoperative consultation using frozen sections (FSs) is an integral component of clinical practice. As a quality control measure, FS diagnosis is subsequently compared with the findings on a FS control slide. These control slides can be used for immunohistochemistry, and the immunohistochemical performance in FS controls is known to be antibody‐dependent. Isocitrate dehydrogenase (IDH) is mutated in >80% of lower‐grade infiltrating gliomas in adults and in ~10% of glioblastomas, with IDH1 (R132H) being the most common mutation. IDH status is used as a major classifier of glioma. An IDH1 (R132H)‐specific antibody (H09) has been accepted as a robust surrogate for genetic testing. In this study, we aimed to determine how previous freezing and thawing affects IDH1 immunohistochemistry.

Methods and results

Thirty cases of IDH1 (R132H)‐mutant diffuse glioma, which were originally assessed on FSs, were retrieved. The positive IDH1 (R132H) status of each case was previously determined with pyrosequencing and H09 immunohistochemistry on permanent sections. The FS control tissue of each case was immunostained with H09 antibody. Among 30 gliomas, 25 showed negative reactivity on FS control slides, whereas, in the remaining five, the staining was uninterpretable, owing to a high diffuse background. Of the former 25 specimens, 20 showed at least focal areas with variably increased levels of background staining, whereas the remaining five specimens showed a relatively pristine background.

Conclusions

We conclude that IDH1 (R132H)‐specific (H09) immunohistochemistry often results in false‐negative reactions on FS controls with focally increased background staining, and this application should be avoided in clinical practice.
SOX11: a potentially useful marker in surgical pathology: a systematic analysis of SOX11 expression in epithelial and non‐epithelial tumours
Authors: Xu Sanpeng , Dong Yuting , Huo Zitian , Yu Lu , Xue Jin , Wang Guoping , Duan Yaqi
Published: September 2018

Aims

SOX11 is known as an essential transcription factor for regulating neurogenesis. Recently, SOX11 has been suggested to be a diagnostic marker and oncogene because of its significant expression in mantle cell lymphoma (MCL). However, SOX11 expression in other tumour types has not yet been extensively studied.

Methods and results

Herein, we examined SOX11 expression in 2026 cases of neuroectodermal, germ cell, mesenchymal and epithelial tumours by immunohistochemistry. SOX11 was consistently expressed in all neuroectodermal tumours with neural differentiation, as well as in immature teratomas revealing neurogenesis. Less frequently, SOX11 expression was observed in only 50% of astrocytomas and 24% of malignant peripheral nerve sheath tumours, and was mainly sporadic and weak/intermediate. In epithelial tumours, significant SOX11 expression was identified in 97% of salivary ductal carcinomas (SDCs) and a high percentage of high‐grade neuroendocrine carcinomas (NECs), especially the small‐cell lung carcinomas (68%), and was absent in most other carcinomas, except for less and/or focal and weak expression in adenocarcinomas from the lung, genital tract and breast, and salivary adenoid cystic carcinomas and epithelial–myoepithelial carcinomas. In mesenchymal tumours, in addition to MCLs, prominent SOX11 expression was observed in 90% of rhabdomyosarcomas and all myxoid/round cell liposarcomas (MRCLs). Less frequent and/or focal and weak expression was observed in lymphoblastic, Burkitt and follicular lymphomas, synovial sarcoma and angiosarcoma.

Conclusion

SOX11 showed prominent expression in neuroectodermal tumours with neural differentiation, high grade‐NEC, SDC, rhabdomyosarcoma and MRCL. The high sensitivity and specificity of SOX11 in SDC and MRCL make it a useful diagnostic marker.
Improving taxonomic resolution in large‐scale freshwater biodiversity monitoring: an example using wetlands and Odonata
Authors: Bried Jason T. , Hinchliffe Robert P.
Published: September 2018

Immature aquatic insects are a major source of taxonomic difficulty in large‐scale freshwater biodiversity monitoring. Adult stages could improve taxonomic resolution for assessing distributions and trends of biodiversity. Odonata (dragonflies and damselflies) have accessible adult stages that should greatly enhance the amount of species‐level information.

We used Odonata and a wetland monitoring programme in Alberta, Canada to illustrate how much taxonomic information can be lost in larval collections, and an extensive adult records database to estimate what could be gained from adult surveys.

Despite processing 22 638 odonate specimens from 975 wetlands throughout Alberta, larval monitoring failed to collect or identify almost 60% of the lentic‐breeding Odonata species known from adult records. A total of 25 lentic‐breeding dragonfly species and 12 lentic‐breeding damselfly species were present in adult records and not the larval data, including species of conservation concern. Due to the abundance of early instars, a substantial 82% of the processed damselfly collection and 62% of the processed dragonfly collection was left at suborder.

We recommend supplementing aquatic sampling with adult rearing, collecting, and observing (at least Odonata) to improve the basic inventory and overall status assessment in large‐scale freshwater biodiversity monitoring. This is especially true when aquatic sampling is restricted to a suboptimal time of year for species identifications.
Efficacy of an agonist of α‐MSH, the palmitoyl tetrapeptide‐20, in hair pigmentation
Authors: Almeida Scalvino S. , Chapelle A. , Hajem N. , Lati E. , Gasser P. , Choulot J‐C. , Michel L. , Hocquaux M. , Loing E. , Attia J. , Wdzieczak‐Bakala J.
Published: September 2018

Objective

Hair greying (i.e., canities) is a component of chronological ageing and occurs regardless of gender or ethnicity. Canities is directly linked to the loss of melanin and increase in oxidative stress in the hair follicle and shaft. To promote hair pigmentation and reduce the hair greying process, an agonist of α‐melanocyte‐stimulating hormone (α‐MSH), a biomimetic peptide (palmitoyl tetrapeptide‐20; PTP20) was developed. The aim of this study was to describe the effects of the designed peptide on hair greying.

Methods

Effect of the PTP20 on the enzymatic activity of catalase and the production of H2O2 by Human Follicle Dermal Papilla Cells (HFDPC) was evaluated. Influence of PTP20 on the expression of melanocortin receptor‐1 (MC1‐R) and the production of melanin were investigated. Enzymatic activity of sirtuin 1 (SIRT1) after treatment with PTP20 was also determined. Ex vivo studies using human micro‐dissected hairs allowed to visualize the effect of PTP20 on the expression in hair follicle of catalase, TRP‐1, TRP‐2, Melan‐A, ASIP, and MC1‐R. These investigations were completed by a clinical study on 15 human male volunteers suffering from premature canities.

Results

The in vitro and ex vivo studies revealed the capacity of the examined PTP20 peptide to enhance the expression of catalase and to decrease (30%) the intracellular level of H2O2. Moreover, PTP20 was shown to activate in vitro and ex vivo the melanogenesis process. In fact, an increase in the production of melanin was shown to be correlated with elevated expression of MC1‐R, TRP‐1, and Melan‐A, and with the reduction in ASIP expression. A modulation on TRP‐2 was also observed. The pivotal role of MC1‐R was confirmed on protein expression analysed on volunteer's plucked hairs after 3 months of the daily application of lotion containing 10 ppm of PTP20 peptide.

Conclusion

The current findings demonstrate the ability of the biomimetic PTP20 peptide to preserve the function of follicular melanocytes. The present results suggest potential cosmetic application of this newly designed agonist of α‐MSH to promote hair pigmentation and thus, reduce the hair greying process.
LPS expands MDSCs by inhibiting apoptosis through the regulation of the GATA2/let‐7e axis
Authors: Yang Yi , Sun Di , Zhou Ji , Tan Chensheng , Zhang Hong , Chen ZhengRong , Hao ChuangLi , Zhang Jinping
Published: September 2018

Myeloid‐derived suppressor cells (MDSCs) represent a group of immature myeloid cells composed of myeloid progenitor cells and immature myeloid cells that can negatively regulate immune responses by inhibiting T‐cell function. In mice, MDSCs are broadly defined by the expression of CD11b and Gr1. We and others have shown that injection of a lethal or sublethal dose of lipopolysaccharide (LPS) into mice could result in the expansion of MDSCs in the bone marrow (BM), spleen and blood. Until now, the molecular mechanisms responsible for this expansion are poorly studied; specifically, the roles of the individual microRNAs (miRNAs) which may be involved remain largely unknown. We performed microarray analysis to compare the miRNA expression profiles of CD11b+Gr1+ cells sorted from the BM of LPS‐injected and phosphate‐buffered saline‐injected mice. We identified let‐7e, which was highly upregulated in the LPS‐treated group, as a potent regulator of LPS‐induced MDSC expansion. Furthermore, let‐7e overexpression in BM chimeric mice led to a noticeable increase in the population of CD11b+Gr1+ cells, which resulted from reduced cellular apoptosis. Further studies showed that let‐7e could directly target caspase‐3 to inhibit cell apoptosis, and upregulation of let‐7e in LPS‐stimulated MDSCs could be due to the relieved repression of let‐7e transcription exerted by downregulated GATA2. Our findings suggest that LPS expands MDSCs by inhibiting apoptosis through the regulation of the GATA2/let‐7e axis.
Prevalence of diabetes and its effects on stroke outcomes: A meta‐analysis and literature review
Authors: Lau Lik‐Hui , Lew Jeremy , Borschmann Karen , Thijs Vincent , Ekinci Elif I
Published: September 2018

Aims/Introduction

Diabetes mellitus is an established risk factor for stroke and maybe associated with poorer outcomes after stroke. The aims of the present literature review were to determine: (i) the prevalence of diabetes in acute stroke patients through a meta‐analysis; (ii) the association between diabetes and outcomes after ischemic and hemorrhagic stroke; and (iii) to review the value of glycated hemoglobin and admission glucose‐based tests in predicting stroke outcomes.

Materials and Methods

Ovid MEDLINE and EMBASE searches were carried out to find studies relating to diabetes and inpatient stroke populations published between January 2004 and April 2017. A meta‐analysis of the prevalence of diabetes from included studies was undertaken. A narrative review on the associations of diabetes and different diagnostic methods on stroke outcomes was carried out.

Results

A total of 66 eligible articles met inclusion criteria. A meta‐analysis of 39 studies (n = 359,783) estimated the prevalence of diabetes to be 28% (95% confidence interval 26–31). The rate was higher in ischemic (33%, 95% confidence interval 28–38) compared with hemorrhagic stroke (26%, 95% confidence interval 19–33) inpatients. Most, but not all, studies found that acute hyperglycemia and diabetes were associated with poorer outcomes after ischemic or hemorrhagic strokes: including higher mortality, poorer neurological and functional outcomes, longer hospital stay, higher readmission rates, and stroke recurrence. Diagnostic methods for establishing diagnosis were heterogeneous between the reviewed studies.

Conclusions

Approximately one‐third of all stroke patients have diabetes. Uniform methods to screen for diabetes after stroke are required to identify individuals with diabetes to design interventions aimed at reducing poor outcomes in this high‐risk population.
Assessing the methodological quality of the Canadian Psychiatric Association's anxiety and depression clinical practice guidelines
Authors: Middleton Jerry C. , Kalogeropoulos Christopher , Middleton Jason A. , Drapeau Martin
Published: September 2018

Rationale, aims, and objectives

Clinical practice guidelines (CPGs) endeavour to incorporate the best available research evidence together with the clinically informed opinions of leading experts in order to guide clinical practice when dealing with a given condition. There has been increased interest in CPGs that are evidence based and that promote best practice, a central component of which is incorporating the best available research predicated on strong study designs. Despite this soaring interest, there remains heterogeneity in the methodological quality of many CPGs, which may have an effect on the quality of services that clinicians offer. In light of this, this study examined the quality of the methodology used to develop two CPGs of the Canadian Psychiatric Association (CPA).

Method

The CPA's guidelines for the management of anxiety disorders (2006) and for the treatment of depressive disorders (2001) were assessed by trained raters using the Appraisal of Guidelines for Research and Evaluation II Instrument scale.

Results

The blind ratings of three trained raters demonstrated that the anxiety and depression CPGs had a number of strengths and important weaknesses.

Conclusion

Implications for the development of future CPGs on anxiety and depression, including recommendations to improve guideline quality in psychiatry in particular, are discussed.
Genomic African and Native American Ancestry and 15‐Year Cognitive Trajectory: Bambui Study, Brazil
Authors: Lima‐Costa M. Fernanda , Gouveia Mateus H. , Cesar Cibele C. , Tarazona‐Santos Eduardo , Stewart Rob , Ferri Cleusa P. , Castro‐Costa Erico
Published: September 2018

Objectives

To investigate the association between African and Native American genomic ancestry and long‐term cognitive trajectories in admixed Brazilians.

Design

Population‐based longitudinal study.

Setting

Bambui‐Epigen (Brazil) cohort study.

Participants

Adults aged 60 and older (N=1,215)

Measurements

Participants were followed from January 1997 to December 2011. Cognitive function was assessed annually using the Mini‐Mental State Examination (MMSE), totaling 12,208 measurements. We used linear mixed‐effects pattern models to assess MMSE score trajectories. Ancestry was assessed using a genome‐wide approach.

Results

After adjustments for covariates, the highest quintile of African ancestry was associated with poorer baseline cognitive performance (β=–0.73, 95% confidence interval (CI)=–1.36 to –0.11) but not with cognitive trajectory. Educational level modified the baseline association between highest African ancestry and cognitive performance in that the association was observed only in those with very low (<4 years) education (β=–1.13, 95% CI=–2.02 to –0.23). No association was found between Native American ancestry and baseline cognitive function or its trajectory.

Conclusion

Genomic African and Native American ancestry levels had no prognostic value for age‐related cognitive decline in this admixed population.
Hard Work, Big Changes: American Geriatrics Society Efforts to Improve Payment for Geriatrics Care
Authors: Hollmann Peter A. , Zorowitz Robert A. , Lundebjerg Nancy E. , Goldstein Alanna C. , Lazaroff Alan E.
Published: September 2018

This article examines the work and leadership of the American Geriatrics Society in making payment for services provided under new, innovative payment codes a reality for geriatrics healthcare professionals. We examine more than a decade of work spanning from a proposal to pay for comprehensive geriatric assessments in 2003 to the multiyear effort that led to Medicare coverage for transitional care management (2013), chronic care management (2015, 2017), and assessment and care planning for cognitive impairment (2017). We review the forces that created an environment for change and the concurrent work of the American Medical Association and the Centers for Medicare and Medicaid Services that made this possible. We highlight opportunities seized that led to seats on crucial panels and legislative victories that helped us make our case for improved payment for geriatrics care. Finally, we address lessons learned and address opportunities where we are currently active. J Am Geriatr Soc 66:2059–2064, 2018.
Enhancement of fluorescence emission difference microscopy using conjugated vortex phase modulation
Authors: ZHU D. , LIU W. , ZHANG Z. , ZHENG C. , CHEN Y. , LI C. , KUANG C. , FAN J. , XU Y. , LIU X. , HUSSAIN A.
Published: September 2018

In this paper, we propose and demonstrate an improved fluorescence emission difference microscopy (FED) method, exploiting programmable phase modulation for image enhancement. The main novelty of the proposed approach lies in the matched size and intensity of two excitation spots. The proposed method improves the FED performance on image quality via artefact elimination. We demonstrate the feasibility of this method through theoretical studies and experimental tests. The experimental results of nanobeads and cells validate the practical performance of this method, which can enable reliable observations at superresolution in biomedical studies.

Lay Description

In this paper, we propose a method to improve the imaging quality of regular fluorescence emission difference (FED) microscopy. In regular FED imaging, a solid and a doughnut excitation beam are successively used to acquire two images which are then subtracted with each other to improve the resolution of confocal microscopy. The doughnut beam can be generated by modulating the excitation beam with a vortex phase mask. Note that both of the excitation beam and the vortex phase mask must have the same handed direction in regular FED microscopy. However, some negative values may be produced and some information may be lost due to the subtraction process in regular FED imaging, which is mainly caused by the mismatched size and intensity of these two excitation spots.

To address this issue, we propose conjugated FED (cFED) microscopy which additionally uses a conjugated vortex phase mask to modulate the solid beam to extend its focal spot size to be matched with the doughnut spot, which means the handed direction of the solid beam and the vortex phase mask is different. Besides, in order not to damage the resolution, the doughnut beam needs to be saturated to some degree. The experiment results show that, at the same resolution level, the negative values and the information loss in cFED image are all less than that of regular FED image.
Current challenges in cancer gene therapy
Authors: HWU P.
Published: September 2018

The ability to transfer novel genes into mammalian cells has allowed us to conceive of novel strategies towards cancer therapy. Since the initial gene‐transfer clinical trial in 1989, over 300 cancer patients have been enrolled in gene therapy trials. Despite this, an NIH‐sponsored panel concluded that ‘clinical efficacy has not been definitively demonstrated at this time in any gene therapy protocol’ [1]. However, the first 8 years of gene therapy research have provided us with insights regarding the areas that require further scientific progress. For example, it is now clear that while in vitro assays of gene‐modified haemotopoietic progenitor cells suggest high transduction efficiencies, once these cells are infused in vivo, only a small percentage of circulating transduced cells can be detected. While the initial clinical studies have demonstrated that gene transfer in patients can be safe and feasible, they have also indicated that future research is necessary towards the development of improved gene transfer techniques for these approaches to be successful.
Treatment of von Willebrand's disease
Authors: MANNUCCI P.M.
Published: September 2018

von Willebrand's disease is the most frequent of inherited bleeding disorders (1:100 affected individuals in the general population). The aim of therapy is to correct the dual defects of haemostasis, i.e. abnormal coagulation expressed by low levels of factor VIII and abnormal platelet adhesion expressed by a prolonged bleeding time. There are two main options available for the management of von Willebrand's disease: desmopressin and transfusion therapy with blood products. Desmopressin is the treatment of choice in patients with Type 1 von Willebrand's disease, who account for approximately 80% of cases. The pharmacological compound raises endogenous factor VIII and von Willebrand factor and corrects the prolonged bleeding time in most patients. In Type 3 and in the majority of Type 2 patients, desmopressin is not effective and it is necessary to resort to plasma concentrates containing factor VIII and von Willebrand factor. Treated with virucidal methods, these concentrates are currently effective and quite safe, even though the bleeding time defect is not always corrected by them. Platelet concentrates or desmopressin can be used as adjunctive treatments when poor correction of the bleeding time is associated with continued bleeding.
Is there a rationale for the use of antimicrobial prophylaxis in neutropenic patients?
Authors: DONNELLY J.P.
Published: September 2018

Antimicrobial prophylaxis in neutropenic patients has been practised in one form or another for several decades but the goal is no longer clear. From being initially solely an attempt at decontamination, drugs such as co‐trimoxazole and later the fluoro‐quinolones were preferred to non‐absorbable regimens because they achieve reliable protection against bacteraemia due to Gram‐negative bacilli. Nevertheless, fever still invariably occurs during neutropenia leading to the initiation of traditional empirical therapy. Not only is this approach illogical but it also ignores the flexibility afforded the oral and parenteral formulations of the fluoroquinolones. Instead, it might be as effective and less costly if these agents were given orally until the end of neutropenia unless there was evidence of malabsorption or poor oral intake, in which case treatment would be continued parenterally. Should patients develop fever, an attempt would be made to complement treatment with another anti‐microbial agent for microbiologically or clinically defined infection. This would be carried out at diagnosis, before any changes in the prophylactic regimen could be made. Otherwise, treatment with the prophylactic regimen would continue without modification. There is a less compelling need for prophylaxis against candidosis, herpes simplex and cytomegalovirus disease as these would be better managed pre‐emptively when there is evidence of yeast carriage or re‐activation of viral infection. Similarly, prophylaxis of aspergillosis is a forlorn hope and again a pre‐emptive approach might serve us better once there is a screening test available and a safe and effective drug.
Challenge and hindrance demands in relation to self‐reported job performance and the role of restoration, sleep quality, and affective rumination
Authors: Van Laethem Michelle , Beckers Debby G. J. , de Bloom Jessica , Sianoja Marjaana , Kinnunen Ulla
Published: September 2018

Longitudinal research on the relationship between job demands and job performance and its underlying mechanisms is scarce. The aims of this longitudinal three‐wave study among 920 Finnish employees were to ascertain whether (1) challenge job demands (i.e., workload, cognitive demands) and self‐reported job performance are positively related over time, (2) job insecurity (i.e., a hindrance demand) and job performance are negatively related over time, (3) restorative experiences during off‐job time and sleep quality are underlying mechanisms in these relations, and (4) affective rumination mediates the proposed relations of job demands and job insecurity with restoration and sleep quality. Self‐report data were analysed with structural equation modelling. The results revealed a positive, temporal relationship between challenge job demands and job performance (task and contextual performance) across 1 year, but no temporal relationship between job insecurity and self‐reported job performance. Moreover, high challenge job demands were positively related to the restorative value of off‐job activities, and favourable restoration was positively related to subsequent task performance. Finally, affective rumination mediated the relationship of challenge job demands with both restoration and sleep quality. Job insecurity was not longitudinally related to restoration, sleep quality, or affective rumination. The implications of our findings for occupational health psychology are discussed.

Practitioner points

Provide employees with sufficient job resources (e.g., high autonomy and social support) to adequately deal with high job demands.

Allow employees sufficient time to recover from high job demands during off‐job time and provide training sessions in recovery, relaxation, meditation, and goal setting.

Employees may attempt to counteract perseverative thoughts by actively pursuing distracting restoration activities (e.g., exercise, meditation).
Extrahepatic autoimmune diseases in patients with autoimmune hepatitis and their relatives: A Danish nationwide cohort study
Authors: Grønbæk Lisbet , Vilstrup Hendrik , Pedersen Lars , Jepsen Peter
Published: September 2018

Background & Aims

It is widely accepted that patients with autoimmune hepatitis have an increased prevalence of extrahepatic autoimmune diseases. It is believed that the patients' relatives share this trait, but it has not been studied in a satisfactory setting. We conducted a nationwide registry‐based cohort study on this issue.

Methods

From Danish healthcare registries 1994‐2015, we included 2745 patients with autoimmune hepatitis, 17 812 of their first‐ and second‐degree relatives and 27 450 general population controls matched with the patients for sex and age. We compared the sex‐ and age‐specific prevalence of extrahepatic autoimmune diseases between the patients with autoimmune hepatitis, their relatives and the controls. We computed the prevalence ratio as a measure of the relative prevalence, using the controls as reference group.

Results

In the patients with autoimmune hepatitis, the prevalence ratio of extrahepatic autoimmune diseases ranged from 7 to 10 until age 30 years (prevalence ratio at age 20 = 9.92; 95% confidence interval 6.21‐15.83), after which it gradually decreased to about 2 (prevalence ratio at age 80 = 2.37; 95% confidence interval 1.89‐3.00). Neither first‐ nor second‐degree relatives had an increased prevalence of extrahepatic autoimmune diseases (prevalence ratio for relatives at age 20 = 1.11; 95% confidence interval 0.72‐1.70; prevalence ratio at age 80 = 0.96; 95% confidence interval 0.70‐1.31).

Conclusions

Danish patients with autoimmune hepatitis were highly prone to extrahepatic autoimmune diseases, but their relatives were not.
Species‐complex diversification and host‐plant associations in Bemisia tabaci: A plant‐defence, detoxification perspective revealed by RNA‐Seq analyses
Authors: Malka Osnat , Santos‐Garcia Diego , Feldmesser Ester , Sharon Elad , Krause‐Sakate Renate , Delatte Hélène , van Brunschot Sharon , Patel Mitulkumar , Visendi Paul , Mugerwa Habibu , Seal Susan , Colvin John , Morin Shai
Published: September 2018

Insect–plant associations and their role in diversification are mostly studied in specialists. Here, we aimed to identify macroevolution patterns in the relationships between generalists and their host plants that have the potential to promote diversification. We focused on the Bemisia tabaci species complex containing more than 35 cryptic species. Mechanisms for explaining this impressive diversification have focused so far on allopatric forces that assume a common, broad, host range. We conducted a literature survey which indicated that species in the complex differ in their host range, with only few showing a truly broad one. We then selected six species, representing different phylogenetic groups and documented host ranges. We tested whether differences in the species expression profiles of detoxification genes are shaped more by their phylogenetic relationships or by their ability to successfully utilize multiple hosts, including novel ones. Performance assays divided the six species into two groups of three, one showing higher performance on various hosts than the other (the lower performance group). The same grouping pattern appeared when the species were clustered according to their expression profiles. Only species placed in the lower performance group showed a tendency to lower the expression of multiple genes. Taken together, these findings bring evidence for the existence of a common detoxification “machinery,” shared between species that can perform well on multiple hosts. We raise the possibility that this “machinery” might have played a passive role in the diversification of the complex, by allowing successful migration to new/novel environments, leading, in some cases, to fragmentation and speciation.