bluuebunny/crossref_metadata_2025 huggingface dataset:
Superimposition: How Indian city bureaucracies are responding to climate change
Authors: Bhardwaj Ankit , Khosla Radhika
Published: August 2020

City governments are facing complex challenges due to climate change, but those in the global South often have limited capacities and governance arrangements to develop and execute a response. Cities must also manage other existing priorities such as housing, water and waste management, which have established bureaucratic practices and incentives. How are such cities with limited climate governance capacity and with existing non-climate priorities developing a climate response? From interviews and participant observation in two Indian cities that are pioneering climate action, we find that actors are ‘superimposing’ climate objectives onto existing bureaucratic practices. Building on analysis of ongoing projects in the two cities, we theorize superimposition as an approach taken by bureaucracies that have the intention of responding to climate change but have limited control over their planning practices and mandates, high levels of institutional inertia to change existing practices, and multiple other objectives related to development that dominate agendas. As superimposition does not involve the modification of existing bureaucratic practices or incentives, the types of climate actions which emerge from this approach reflect the features, scope and limitations of existing political arrangements. We highlight five such features of how Indian city bureaucracies respond to climate change: (1) the primacy of central and state ‘schemes’, (2) the prioritization of ‘development’ as an objective, and the imperative to implement (3) ‘quick win’, (4) ‘visible’ and (5) ‘bankable’ projects. Superimposition has led to creative and politically tenable climate projects that meet both climate objectives and those of existing schemes on housing, water and waste. But these projects are also limited by existing governance arrangements with tradeoffs for long-term planning, urban justice and public ownership of infrastructure.
Characterizing EBV-associated lymphoproliferative diseases and the role of myeloid-derived suppressor cells
Authors: Collins Paul J. , Fox Christopher P. , George Lindsay , Pearce Hayden , Ryan Gordon , De Santo Carmela , Mussai Francis , Lewis David , Long Heather , Shannon-Lowe Claire
Published: August 2020

Chronic active Epstein-Barr virus (CAEBV) typically presents as persistent infectious mononucleosis-like disease and/or hemophagocytic lymphohistocytosis (HLH), reflecting ectopic Epstein-Barr virus (EBV) infection and lymphoproliferation of T and/or NK cells. Clinical behavior ranges from indolent, stable disease through to rapidly progressive, life-threatening disease. Although it is thought the chronicity and/or progression reflect an escape from immune control, very little is known about the phenotype and function of the infected cells vs coresident noninfected population, nor about the mechanisms that could underpin their evasion of host immune surveillance. To investigate these questions, we developed a multicolor flow cytometry technique combining phenotypic and functional marker staining with in situ hybridization for the EBV-encoded RNAs (EBERs) expressed in every infected cell. This allows the identification, phenotyping, and functional comparison of infected (EBERPOS) and noninfected (EBERNEG) lymphocyte subset(s) in patients’ blood samples ex vivo. We have characterized CAEBV and HLH cases with monoclonal populations of discrete EBV-activated T-cell subsets, in some cases accompanied by EBV-activated NK-cell subsets, with longitudinal data on the infected cells’ progression despite standard steroid-based therapy. Given that cytotoxic CD8+ T cells with relevant EBV antigen specificity were detectable in the blood of the best studied patient, we searched for means whereby host surveillance might be impaired. This revealed a unique feature in almost every patient with CAEBV studied: the presence of large numbers of myeloid-derived suppressor cells that exhibited robust inhibition of T-cell growth. We suggest that their influence is likely to explain the host’s failure to contain EBV-positive T/NK-cell proliferation.
Roles of metabolic regulation in developing Quercus variabilis acorns at contrasting geologically-derived phosphorus sites in subtropical China
Authors: Yuan Jun , Sun Ningxiao , Du Hongmei , Yin Shan , Kang Hongzhang , Umair Muhammad , Liu Chunjiang
Published: August 2020

Background

Phosphorus (P) -rich soils develop in phosphorite residing areas while P-deficient soils are ubiquitous in subtropical regions. Little has been reported that how metabolites participate in the seed development and the processes involved in their coping with contrasting-nutrient environments.

Results

Here we quantified the metabolites ofQuercus variabilisacorns in the early (July), middle (August), late (September) development stages, and determined element (C, H, O, N, P, K, Ca, Mg, S, Fe, Al, Mn, Na, Zn, and Cu) concentrations of acorns in the late stage, at geologically-derived contrasting-P sites in subtropical China. The primary metabolic pathways included sugar metabolism, the TCA cycle, and amino acid metabolism. Most metabolites (especially C- and N-containing metabolites) increased and then decreased from July to September. Acorns between the two sites were significantly discriminated at the three stages, respectively, by metabolites (predominantly sugars and organic acids). Concentrations of P, orthophosphoric acid and most sugars were higher; erythrose was lower in late-stage acorns at P-rich sites than those at P-deficient sites. No significant differences existed in the size and dry mass of individual acorns between oak populations at the two sites.

Conclusions

Oak acorns at the two sites formed distinct metabolic phenotypes related to their distinct geologically-derived soil conditions, and the late-stage acorns tended to increase P-use-efficiency in the material synthesis process at P-deficient sites, relative to those at P-rich sites.
Explicating practice norms and tensions between values in resident training in family medicine
Authors: Al Achkar Morhaf
Published: August 2020

Background

Residency programs have the intricate and complex role of training health care providers. But little is known about what residents and attendings consider norms of practice or the tensions among different values residents are expected to uphold. Thus, dialogical and reflective frameworks are being explored for resident learning.

Methods

This study examined the use of facilitated conversations with groups of residents and attending physicians while reviewing video-recorded resident–patient interactions. The conversations were recorded, transcribed, and qualitatively analyzed.

Results

A total of 24 residents and 10 attendings participated in conversations while separately and in parallel groups reviewing 15 resident sessions. Residents explicated the norms of practice and evaluated their performance, which often agreed with those of attending physicians in calling out important learning opportunities. When disagreement occurred, residents’ explications of their reasoning were often relevant and, via reflection and dialogue, helped clarify intentions that were not apparent in the videos. Residents and attendings often judged actions on more than one domain of value. For instance, if a resident addressed problems, built relationships in a timely manner, and acted autonomously without jeopardizing the quality of care, she satisfactorily performed her duty.

Conclusions

Practice norms and value struggles were addressed by participants during reviews, which provided a promising framework for learning and assessment. Also, the non-hierarchical structure opened space to acknowledge a diversity of positions and for tensions among values to be explicated.
Evaluation of changes in choroidal thickness after implantable collamer lens surgery in high myopia patients with graves’ Ophthalmopathy (inactive phase)
Authors: He Fanglin , Liu Yan , Jia Renbing , Zhang Jing
Published: August 2020

Background

To evaluate the safety and effectiveness of the Visian Implantable Collamer Lens (ICL) implantation in high myopic patients with inactive Graves’ ophthalmopathy (GO) by observing the changes of choroidal thickness (CT).

Methods

Eight patients (16 eyes) with high myopia accompanied with inactive GO were selected as the experimental group (group A) and 18 high myopic patients (36 eyes) without GO were selected as a control group (group B). The outcomes of uncorrected visual acuity (UCVA), best spectacle-corrected visual acuity (BCVA), safety index, efficacy index, intraocular pressure (IOP), vault, corneal endothelial count, and choroidal thickness (CT) were observed. The values of CT were measured using swept-source optical coherence tomography (SS-OCT) scans.

Results

The UCVA and BCVA in all operated eyes were better than that before surgery. The postoperative safety index and efficacy index were 1.23 and 1.19 in the group A, respectively, and 1.26 and 1.21 in the group B, respectively. In both groups, foveal CT increased significantly in high myopic patients at 2 h and at 3 months after surgery, compared to preoperative values. The same tendencies were observed in the inner nasal and outer nasal regions. Compared with patients without GO, the increase of CT was more obvious in GO patients, 2 h postoperatively (P = 0.006) and 3 months postoperatively (P = 0.011).

Conclusions

The ICL implantation is safe and effective in high myopic patients with inactive GO. Subfoveal and nasal CT may be useful parameters for monitoring the activity of GO patients.
Surgery outcomes of lamellar macular eyes with or without lamellar hole-associated epiretinal proliferation: a meta-analysis
Authors: Xu Hanyue , Qin Ling , Zhang Yifan , Xiao Yinan , Zhang Ming
Published: August 2020

Background

Given the two different kinds of epiretinal membranes, this study aimed to compare both the structural and functional outcomes of lamellar macular holes with and without lamellar hole-associated epiretinal proliferation (LHEP) after surgery.

Method

Publications up to July 2020 that compared the surgical outcomes of lamellar macular hole with and without LHEP were included. Forest plots were created by using a weighted summary of proportion meta-analysis. Fixed or random effects models were used on the basis of I2 heterogeneity estimates. Meanwhile, to evaluate the stability of the meta-analysis, a sensitivity analysis was carried out.

Results

Eight pertinent publications that contained a total of 176 eyes without LHEP and 173 eyes with LHEP were included. They were all retrospective studies and had a follow-up of at least 6 months. In all studies, the preoperative best corrected visual acuity showed no significant differences between the two groups, and the visual acuity improved in both groups after surgery. The pooled result for the improved best corrected visual acuity was 0.18 (95% confidence interval (CI), 0.10 to 0.26; P < 0.01) between the with and without LHEP groups. The restored ellipsoid zone odds ratio was 0.80 (95% CI, 0.26 to 2.44; P = 0.69) for the group with LHEP compared to the group without LHEP.

Conclusion

Patients without LHEP had better postoperative visual acuity than patients with LHEP. No significant difference in restored ellipsoid zone was found between the two groups.
Adolescents exposed to discrimination: are they more prone to excessive internet use?
Authors: Bitto Urbanova Laura , Holubcikova Jana , Madarasova Geckova Andrea , van Dijk Jitse P. , Reijneveld Sijmen A.
Published: August 2020

Background

The Internet may serve as a suitable environment for discriminated adolescents as they may consider the online space as the place where they have possibility to build social ties they are missing in their offline life or manage their self-presentation. Therefore, our aim was to explore the association between different types of discrimination by peers (because of gender, physical appearance, culture/skin color/language, unfavorable family situation) and excessive Internet use (EIU), and whether gender moderates this association.

Methods

We used data from a representative sample of 6,462 Slovak adolescents (mean age: 13.00, 49.6% boys) from the HBSC study conducted in 2018. Data were collected through online self-reported questionnaires. We assessed the association between various types of discrimination by peers and EIU using linear regression, and the role of gender as potential moderator.

Results

Discrimination because of physical appearance was most prevalent (18.0%). Adolescents exposed to discrimination by peers reported higher levels of EIU. We found an interaction of gender on the association of discrimination because unfavorable family situation with EIU. Boys who experienced this type of discrimination were at higher risk of EIU compared to girls.

Conclusion

Discriminated adolescents are more likely to use the Internet excessively, with some associations being stronger for boys than for girls. Prevention strategies focused on raising adolescent awareness of the risks and benefits of the Internet should target discriminated adolescents, especially boys, as they seem to be the vulnerable group.
Changes in sedentary behaviour in European Union adults between 2002 and 2017
Authors: López-Valenciano A. , Mayo X. , Liguori G. , Copeland R. J. , Lamb M. , Jimenez A.
Published: August 2020

Background

Sedentary behaviour (SB) has been identified as an important mortality risk factor. Health organizations have recognised SB as a public health challenge with major health, social, and economic consequences. Researchers have alerted the need to develop specific strategies, to monitor, prevent, and reduce SB. However, there is no systematic analysis of the SB changes in European Union adults. We aimed to examine SB changes between 2002 and 2017 in the European Union (EU) adult population.

Methods

SB prevalence (>4h30mins of sitting time/day) of 96,004 adults as a whole sample and country-by-country was analysed in 2002, 2005, 2013, and 2017 of the Sport and Physical Activity EU Special Eurobarometers’ data. The SB question of a modified version of the International Physical Activity Questionnaire was considered. SB prevalence between countries and within years was analysed with a χ2 test, and SB between genders was analysed with the Z-Score test for two population proportions.

Results

An association between the SB prevalence and the years was found (p <  0.001), with increases for the whole sample (2002: 49.3%, 48.5–50.0 95% confidence interval (CI); 2017: 54.5%, 53.9–55.0 95% CI) and men (2002: 51.2%, 50.0–52.4 95% CI; 2017: 55.8%, 55.0–56.7 95% CI) and women (2002: 47.6%, 46.6–48.7 95% CI; 2017: 53.4%, 52.6–54.1 95% CI) separately. The adjusted standardised residuals showed an increase in the observed prevalence versus the expected during 2013 and 2017 for the whole sample and women and during 2017 for men. For all years, differences were observed in the SB prevalence between countries for the whole sample, and men and women separately (p <  0.001). Besides, the SB prevalence was always higher in men versus women in the overall EU sample (p <  0.001).

Conclusions

SB prevalence increased between 2002 and 2017 for the EU as a whole and for both sexes separately. Additionally, differences in SB prevalence were observed for all years between EU countries in the whole sample and both sexes separately. Lastly, SB was consistently higher in men than women. These findings reveal a limited impact of current policies and interventions to tackle SB at the EU population level.
Canadian after-school care providers’ perceived role promoting healthy lifestyles: a focused ethnography
Authors: Elias Pierrette H. , Montemurro Genevieve , Sulz Lauren , Torrance Brian , Storey Kate E.
Published: August 2020

Background

After-school care programs have garnered interest in recent years as the hours of 3:00–6:00 p.m. are an opportune time for children to engage in healthy behaviours, specifically healthy eating and physical activity. Care providers are major influencers within the after-school care setting, impacting health promoting opportunities for children. However, little is known regarding the role care providers play in health promotion interventions in the after-school care setting, specifically those using comprehensive approaches. The purpose of this research was to explore care providers’ role and experience promoting healthy eating and physical activity through the after-school care health promotion intervention School’s Out … Let’s Move (SOLMo). SOLMo was guided by the evidence-based comprehensive school health framework. SOLMo had two main goals: [1] to serve a healthy snack with vegetable or fruit, and milk or water as the drink; [2] to include 30 min of moderate to vigorous physical activity. The intervention included resources and coaching for care providers to promote healthy eating and physical activity for children and took place in four after-school sites over a six-month period. Three of four sites were located in a school. The primary researcher was engaged with the sites over 22-months.

Methods

This research was guided by the qualitative method focused ethnography. Semi-structured interviews with care providers (n = 13) taking part in SOLMo were conducted. Participant observation was included as part of data generation to further understand care provider roles. Latent content analysis was utilized iteratively and concurrently throughout data generation.

Results

Overall, care providers were supportive of promoting health behaviours in the after-school setting. Through analysis, five themes and eight subthemes emerged related to care providers’ role and experience promoting healthy eating and physical activity through SOLMo: 1) enhanced awareness; 2) improved programming; 3) strong relationships; 4) collaborative approach; and 5) role tension.

Conclusions

As major influencers, care providers play a crucial role in promoting healthy lifestyle behaviours for children. This research provides valuable insight into this role and the implementation of comprehensive health promotion approaches in the after-school setting. Findings contribute to the implementation knowledge base and help inform the promotion of healthy lifestyle behaviours for children.
TALKING TIME: A pilot randomized controlled trial investigating social support for informal caregivers via the telephone
Authors: Dichter Martin Nikolaus , Albers Bernd , Trutschel Diana , Ströbel Armin Michael , Seismann-Petersen Swantje , Wermke Katharina , Halek Margareta , Berwig Martin
Published: August 2020

Background

Caring for people with dementia at home requires considerable time, organization and commitment. Therefore, informal caregivers of people with dementia are often overburdened. This study examined the effects of the telephone-based Talking Time intervention, which is an approach used to strengthen the psychological health-related quality of life (HRQoL) and social support of informal caregivers of people with dementia living at home.

Methods

This study was a Medical Research Council framework phase two randomized controlled trial. The intervention consisted of a preliminary talk, information booklet, six structured telephone-based support group meetings and a structured written self-evaluation of each support group meeting. The control participants performed their usual individual self-organized care. After completing the data collection, the control group received the Talking Time intervention for fidelity reasons. The primary outcome was the self-rated psychological HRQoL of the informal caregivers, which was measured with the mental component summary of the General Health Survey Questionnaire Short Form 12 (SF-12).

Results

Thirty-eight informal caregivers and their relatives were included and allocated to the intervention or control groups (n = 19 each). After 3 months, the Talking Time intervention group demonstrated an increase in the self-rated psychological HRQoL scores, whereas the scores decreased in the control group. However, the standardized effect size of 1.65 (95% Confidence Interval, − 0.44 – 3.75) was not significant. Additionally, the secondary outcomes demonstrated no significant results. The differences between the groups in most outcomes were in the expected direction. No adverse effects were identified due to the intervention.

Conclusions

The Talking Time intervention is feasible and shows nonsignificant promising results with regard to the self-rated psychological HRQoL. After further adjustment, the intervention needs to be evaluated in a full trial.

Trial registration

Clinical Trials:NCT02806583, June 9, 2016 (retrospectively registered).
Visualizing healthcare system variability and resilience: a longitudinal study of patient movements following discharge from a Swedish psychiatric clinic
Authors: Svensson Jakob , Bergström Johan
Published: August 2020

Background

As healthcare becomes increasingly complex, new methods are needed to identify weaknesses in the system that could lead to increased risk. Traditionally, the focus for patient safety is to study incident reports and adverse events, but that starting point has been contested with a new era of safety investigations: the analysis of everyday clinical work, and the resilient healthcare.

This study introduces a new approach of system monitoring as a way to strengthen patient safety and has focused on discharge in psychiatry as a risk for adverse outcomes. The aim was to analyse a psychiatric clinic’s everyday ‘normal’ performance variability of discharge from inpatient psychiatric care to outpatient care.

Method

A retrospective longitudinal correlation study with a strategic selection. Data consist of 70,797 patient visits within one psychiatric clinic, and the visits were compared between 81 different wards in Stockholm County by using a model of time-lapse visualization.

Results

The time-lapse visualization shows a discrepancy in types of visits and the proportion of cancelled visits to the outward units. 42% of all patients that were scheduled as an outward patient, did not complete this transition, but instead, they revisit the clinics’ emergency ward and did not receive the planned care treatment. The patients who visit the emergency ward instead of their planned outpatient visit did this within 20 days.

Conclusions

The findings show a potential increased demand for emergency psychiatric care from 2010 to 2018 within the clinic. It also suggests that the healthcare system creates a space of temporal as well as functional variability, and that patients use this space to adapt to their changing conditions. This understanding can assist management in prioritising allocation of resources and thereby strengthen patient safety. Today’s incident reporting systems in healthcare are ineffective in monitoring patterns of more cancelled visits in outward units and sooner visit to the emergency ward. By using time-lapse visualization of patient interactions, stakeholders might analyse current-, and estimate future, stressors within the system to identify and understand potential system migration towards risk in healthcare. This could help healthcare management understand where resources should be prioritized.
Facilitators and “deal breakers”: a mixed methods study investigating implementation of the Goal setting and action planning (G-AP) framework in community rehabilitation teams
Authors: Scobbie Lesley , Duncan Edward A. S. , Brady Marian C. , Thomson Katie , Wyke Sally
Published: August 2020

Background

High quality goal setting in stroke rehabilitation is vital, but challenging to deliver. The G-AP framework (including staff training and a stroke survivor held G-AP record) guides patient centred goal setting with stroke survivors in community rehabilitation teams. We found G-AP was acceptable, feasible to deliver and clinically useful in one team. The aim of this study was to conduct a mixed methods investigation of G-AP implementation in diverse community teams prior to a large-scale evaluation.

Methods

We approached Scottish community rehabilitation teams to take part. Following training, G-AP was delivered to stroke survivors within participating teams for 6 months. We investigated staff experiences of G-AP training and its implementation using focus groups and a training questionnaire. We investigated fidelity of G-AP delivery through case note review. Focus group data were analysed using a Framework approach; identified themes were mapped into Normalisation Process Theory constructs. Questionnaire and case note data were analysed descriptively.

Results

We recruited three teams comprising 55 rehabilitation staff. Almost all staff (93%, 51/55) participated in G-AP training; of those, 80% (n = 41/51) completed the training questionnaire. Training was rated as ‘good’ or ‘very good’ by almost all staff (92%, n = 37/41). G-AP was broadly implemented as intended in two teams. Implementation facilitators included - G-AP ‘made sense’; repetitive use of G-AP in practice; flexible G-AP delivery and positive staff appraisals of G-AP impact. G-AP failed to gain traction in the third team. Implementation barriers included - delays between G-AP training and implementation; limited leadership engagement; a poor ‘fit’ between G-AP and the team organisational structure and simultaneous delivery of other goal setting methods. Staff recommended (i) development of training to include implementation planning; (ii) ongoing local implementation review and tailoring, and (iii) development of electronic and aphasia friendly G-AP records.

Conclusions

The interaction between G-AP and the practice setting is critical to implementation success or failure. Whilst facilitators support implementation success, barriers can collectively act as implementation “deal breakers”. Local G-AP implementation efforts should be planned, monitored and tailored. These insights can inform implementation of other complex interventions in community rehabilitation settings.
RETRACTED ARTICLE: Circular RNA circ_0000517 regulates hepatocellular carcinoma development via miR-326/IGF1R axis
Authors: He Shuwei , Yang Jianzeng , Jiang Shitao , Li Yuan , Han Xingmin
Published: August 2020

Background

Circular RNAs (circRNAs) play vital roles in hepatocellular carcinoma development. However, the role and mechanism of circRNA hsa_circ_0000517 (circ_0000517) in hepatocellular carcinoma development were largely unknown.

Methods

45 paired tumor and adjacent nontumor samples were collected from hepatocellular carcinoma patients. The levels of circ_0000517, miR-326 and insulin-like growth factor type 1 receptor (IGF1R) were detected via quantitative reverse transcription polymerase chain reaction or western blot. Cell viability, colony ability, migration, invasion and glycolysis were assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, western blot, transwell assay, glucose consumption, lactate production or adenosine triphosphate (ATP) production. The target correlation between miR-326 and circ_0000517 or IGF1R was analyzed via dual-luciferase reporter analysis. The function of circ_0000517 in vivo was assessed via xenograft model.

Results

circ_0000517 expression was elevated in hepatocellular carcinoma tissues and cell lines. circ_0000517 knockdown suppressed cell viability, colony formation, migration, invasion and glycolysis. miR-326 was sponged via circ_0000517 and miR-326 knockdown reversed the effect of circ_0000517 silence on hepatocellular carcinoma development. miR-326 overexpression inhibited hepatocellular carcinoma development through targeting IGF1R. circ_0000517 knockdown decreased IGF1R expression by modulating miR-326. circ_0000517 downregulation reduced xenograft tumor growth.

Conclusion

circ_0000517 knockdown repressed hepatocellular carcinoma development in vitro and in vivo by modulating miR-326 and IGF1R.
Environmental health literacy and household air pollution-associated symptoms in Kenya: a cross-sectional study
Authors: Raufman Jill , Blansky Deanna , Lounsbury David W. , Mwangi Esther Wairimu , Lan Qing , Olloquequi Jordi , Hosgood H. Dean
Published: August 2020

Background

Household air pollution (HAP) is a significant source of the global burden of disease. Our objective was to evaluate the association between environmental health literacy (EHL), a domain of health literacy (HL) that describes the ability to use environmental health information to reduce health risks, and symptoms associated with HAP.

Methods

We performed a cross-sectional population-based study of 353 households in Kasarani, Kenya. One individual from each household was surveyed using our novel EHL survey tool. Baseline characteristics were compared between individuals who were symptomatic (i.e., experiencing cough, shortness of breath, phlegm production, wheeze, chest tightness, headache, eye irritation, or burns from cooking at least 5 times per month) versus individuals who were asymptomatic (i.e., experiencing none or symptoms no more than once per month). Multivariate logistic regression was used to determine the odds ratios (OR) of self-reported symptoms associated with HL, stratified by median EHL, adjusting for education, self-perceived health and solid fuel use.

Results

A total of 100 individuals (28%) reported experiencing one or more symptoms at least 5 times per month, including 31.2% of solid fuel users and 30.3% of non-solid fuel users. Among individuals with high EHL, higher HL was associated with lower risk of experiencing symptoms (OR = 0.26; 95% CI 0.10–0.67), however, there was no association among individuals with low EHL (OR = 0.85; 95% CI 0.34–2.13). Among solid fuel users, the association between HL and risk of experiencing symptoms was driven by individuals with high EHL (OR = 0.30; 95% CI 0.05–1.84), rather than those with low EHL (OR = 1.22; 95% CI 0.36–4.16).

Conclusions

To the best of our knowledge, this was the first study to assess the association between EHL, HL, and HAP-associated symptoms. Our findings highlight the potential importance of EHL in promoting sustainable interventions to reduce symptoms associated with HAP from solid fuel use among communities in Kenya.
Prenatal diagnosis of mosaic trisomy 2 and literature review
Authors: Wang Ting , Lian Jufei , Ren Congmian , Huang Huamei , Huang Yanlin , Xu Ling , Zheng Laiping , Cai Chanhui , Guo Li
Published: August 2020

Background

We presented two cases of mosaic trisomy 2 with high risk of maternal serum screening and non-invasive prenatal testing (NIPT). The invasive amniocentesis was performed and genetic tests including karyotype, single nucleotide polymorphism array(SNP-array), interphase fluorescence in situ hybridization (FISH) were employed to detect the chromosomal abnormality.

Results

Cytogentic analysis of the case 1 and 2 showed a mosaic karyotype consisting of two cell lines (mos 47,XY,+2[8]/46,XY[19] and mos 47,XX,+2[7]/46,XX[28], respectively). SNP-array using DNA extracted from uncultured amniotic fluid cells revealed a result of arr[GRCh38](2)x2~3, which indicated that chromosome 2 may be trisomy of mosaicism in both two cases. The results of interphases FISH confirmation test showed that three red signals of the CEP 2 specific probe in 14%(14/100) and 12%(12/100) of the two cases’ cells, respectively, which indicated a mosaicism for trisomy 2 in the uncultured amniocytes. Fetal ultrasound of case 1 suggested that the long bone is smaller than the gestational age, while the case 2 showed that the biparietal diameter (BPD), head circumference (HC) and femur length (FL) were smaller than gestational age along with abnormal cardiac structure.

Conclusions

We presented two cases with mosaic trisomy 2 and performed confirmatory genetic testing using cultured and uncultured amniocytes. When maternal serum screening and NIPT suggesting high risk, genetic counselor should be alert for increasing possibility of chromosomal anomalies if combined with abnormal ultrasound findings.
Assessing physicians’ and nurses’ experience of dying and death in the ICU: development of the CAESAR-P and the CAESAR-N instruments
Authors: Boissier Florence , Seegers Valérie , Seguin Amélie , Legriel Stéphane , Cariou Alain , Jaber Samir , Lefrant Jean-Yves , Rimmelé Thomas , Renault Anne , Vinatier Isabelle , Mathonnet Armelle , Reuter Danielle , Guisset Olivier , Cracco Christophe , Durand-Gasselin Jacques , Éon Béatrice , Thirion Marina , Rigaud Jean-Philippe , Philippon-Jouve Bénédicte , Argaud Laurent , Chouquer Renaud , Papazian Laurent , Dedrie Céline , Georges Hugues , Lebas Eddy , Rolin Nathalie , Bollaert Pierre-Edouard , Lecuyer Lucien , Viquesnel Gérald , Leone Marc , Chalumeau-Lemoine Ludivine , Garrouste-Orgeas Maité , Azoulay Elie , Kentish-Barnes Nancy
Published: August 2020

Background

As an increasing number of deaths occur in the intensive care unit (ICU), studies have sought to describe, understand, and improve end-of-life care in this setting. Most of these studies are centered on the patient’s and/or the relatives’ experience. Our study aimed to develop an instrument designed to assess the experience of physicians and nurses of patients who died in the ICU, using a mixed methodology and validated in a prospective multicenter study.

Methods

Physicians and nurses of patients who died in 41 ICUs completed the job strain and the CAESAR questionnaire within 24 h after the death. The psychometric validation was conducted using two datasets: a learning and a reliability cohort.

Results

Among the 475 patients included in the main cohort, 398 nurse and 417 physician scores were analyzed. The global score was high for both nurses [62/75 (59; 66)] and physicians [64/75 (61; 68)]. Factors associated with higher CAESAR-Nurse scores were absence of conflict with physicians, pain control handled with physicians, death disclosed to the family at the bedside, and invasive care not performed. As assessed by the job strain instrument, low decision control was associated with lower CAESAR score (61 (58; 65) versus 63 (60; 67), p = 0.002).

Factors associated with higher CAESAR-Physician scores were room dedicated to family information, information delivered together by nurse and physician, families systematically informed of the EOL decision, involvement of the nurse during implementation of the EOL decision, and open visitation. They were also higher when a decision to withdraw or withhold treatment was made, no cardiopulmonary resuscitation was performed, and the death was disclosed to the family at the bedside.

Conclusion

We described and validated a new instrument for assessing the experience of physicians and nurses involved in EOL in the ICU. This study shows important areas for improving practices.
Challenges and contexts in establishing adaptive learning in higher education: findings from a Delphi study
Authors: Mirata Victoria , Hirt Franziska , Bergamin Per , van der Westhuizen Christo
Published: August 2020

Higher education institutions are increasingly interested in using adaptive learning as an innovative data-driven approach to teaching. The actual use of adaptive learning in courses remains, however, low. This is despite positive attitudes of institutional leaders towards its adoption and promising results of early studies on its effectiveness.

This study examines the challenges that prevent higher education institutions from adopting adaptive learning concepts in teaching. We used a four-stage Delphi design to empirically identify, categorise, and prioritise the challenges of adaptive learning raised and rated by experts from two universities with different organisational and socioeconomic contexts, one from Switzerland and one from South Africa. Considering different contexts allowed us to include various perspectives on the research topic and thus broaden the view on the challenges of adaptive learning. Overall, three main dimensions related to technological, teaching and learning, and organisational challenges with eight corresponding categories were identified. Our findings revealed clear differences between the two universities regarding the emerged challenges and their rankings. These differences are linked to different socioeconomic backgrounds (South Africa and Switzerland) and organisational contexts (e.g., type of the university, teaching model, and implementation phase) of the universities. We conclude by proposing practical recommendations for institutional leaders and project implementers on the factors to be considered when implementing adaptive learning in higher education settings. These recommendations relate to the necessary infrastructure, institutional commitment, support and resources.
Let there be blue-depleted light: in-patient dark therapy, circadian rhythms and length of stay
Authors: Scott Jan , Langsrud Knut , Goulding Ingunn Ro , Kallestad Havard
Published: August 2020

Light is the most important environmental influence (zeitgeber) on the synchronization of the circadian system in humans. Excess light exposure during the evening and night-time affects secretion of the hormone melatonin, which in turn modifies the temporal organization of circadian rhythms, including the sleep–wake cycle. As sleep disturbances are prominent in critically ill medical and psychiatric patients, researchers began to examine the impact of light exposure on clinical outcomes and length of hospitalization. In psychiatric inpatients, exposure to bright morning light or use of blue blocking glasses have proved useful interventions for mood disorders. Recently, knowledge about light and the circadian system has been applied to the design of inpatient facilities with dynamic lighting systems that change according to time of day. The installation of ‘circadian lighting’ alongside technologies for monitoring sleep–wake patterns could prove to be one of the most practical and beneficial innovations in inpatient psychiatric care for more than half a century.
How effective is augmentation with psychotherapy as a next-step option for treatment-resistant depression?
Authors: Silman Daniel
Published: August 2020

Determining the optimum next-step treatment for the numerous patients with depression who do not adequately respond to an initial trial of medication remains a source of uncertainty in clinical practice. Although a number of psychological treatments are known to be effective for depression, their relative merits in the treatment-resistant group have not been ascertained. The Cochrane Collaboration has recently published a meta-analysis of the evidence available for the use of various psychotherapies as an adjunct to antidepressants compared with antidepressants alone in treatment-resistant depression. This article provides a commentary and appraisal of the clinical utility of these findings.
Expression of CD133 and poor outcome in neuroblastoma associated with chemoresistance mediated by AKT pathway
Authors: Sartelet H. , Haddad E. , Imbriglio T. , Arsenault M. , Ohta S. , Barrette S. , Sinnett D. , Laverdiere C. , Oligny L. , Vassal G.
Published: August 2020

10007

Background: Neuroblastoma is a frequent childhood cancer with very heterogeneous prognosis. Recent studies showed that CD133 expression is an independent prognostic marker for low survival in several cancers like medulloblastoma. The aim of our study is to determine the prognostic value of CD133 expression in a large population of neuroblastoma and to determine the chemoresistance of neuroblasts expressing CD133. Methods: 280 tumor samples of neuroblastoma were screened for CD133 expression. Patients had a median follow-up of 7.15 years. One hundred eighteen patients were under one year of age with a median age of 27 months. There were 67 stage 1, 46 stage 2, 43 stage 3, 99 stage 4, and 25 stage 4S. The association of CD133 expression with relapse and survival were determined through univariate and multivariate analysis. Sensitivity of purified CD133+ neuroblasts isolated from 2 human neuroblastoma cell lines (SKNSH and NB10) to doxorubicin, vincristine and cisplatin was evaluated in vitro, as single agents or in combination with LY294002, a AKT inhibitor. Results: CD133 was expressed in 95 of 280 tumors (33%). There was a significant association between CD133 expression and the following poor prognosis co-variates: age (p<0.0001), INSS stage (p<0.0001), MYCN amplification (p<0.0001). Patients with a CD133+ tumor had a three year event-free and overall survival of 43±5% and 51±5%, respectively, as compared to patients with a CD133- tumor with 88±2% (P<0.001) and 95±2% (p<0.001). In a multivariate model, CD133 expression was independently associated with a decreased overall survival (p = 0.003) in the entire cohort. In vitro purified CD133+ neuroblasts were significantly resistant to chemotherapy as compared to their CD133- cells counterpart, but not in presence of the AKT inhibitor. In vitro treatment of unsorted neuroblasts with the three anticancer drugs significantly enriched the CD133+ subpopulation but not in presence of the AKT inhibitor. CD133plus; significantly expressed higher levels of activated proteins in the AKT pathway than CD133−. Conclusions: CD133 is independently associated with a worse outcome in patents with neuroblastoma. This prognosis factor is associated with in vitro resistance to chemotherapy involving activation of the AKT pathway.

No significant financial relationships to disclose.
Inhibition of ALK mutated neuroblastomas by the selective inhibitor PF-02341066
Authors: Wood A. C. , Laudenslager M. , Haglund E. A. , Attiyeh E. F. , Pawel B. , Courtright J. , Plegaria J. , Christensen J. G. , Maris J. M. , Mosse Y. P.
Published: August 2020

10008b

Background: Mutations in the ALK oncogene are the major cause of hereditary neuroblastoma (NB), and may offer a tractable therapeutic target. Methods: We resequenced the ALK tyrosine kinase domain in 496 primary NBs. We integrated data from 76 primary tumors analyzed using Illumina HumanHap550 SNP and Human-6 mRNA expression arrays. We stained a tissue microarray (TMA) of 134 NBs with anti-ALK and anti-pALK antibodies. We evaluated the in vitro and in vivo activity of PF-02341066, a small molecule inhibitor of ALK. Computational chemistry was used to homology map ALK interaction with PF-02341066. Results: Mutations were discovered in 38/496 NBs (8%), across the spectrum of phenotypes. R1275Q substitutions were most common (45%), followed by F1174L (15%). Evaluation of matched constitutional DNAs demonstrated 10% carried occult germline mutations. Integration of primary tumor microarrays from 76 samples showed that ALK mRNA expression was highly correlated with ALK DNA copy number (p=0.0005). ALK protein was nearly universally expressed (129/134; 93%), and there was evidence for ALK activation in 15% of tumors (pALK moderate or strong staining in 20/134), suggesting an additional and alternative pathway to ALK activation. A panel of 18 NB cell lines showed differential in vitro sensitivity to PF-2341066 dependent on ALK mutation and copy number status. A wild type (WT) amplified line and 2 lines harboring R1275Q mutations were sensitive (IC50 145 - 301 nM). Lines harboring F1174L mutations were more resistant (IC50 >950nM) as were lines with no ALK aberrations. Inhibition of proliferation was associated with abolishing phosphorylation of ALK, STAT3 and AKT. PF-02341066 caused complete regression of R1275Q xenografts, but caused only minimal growth delay in F1174L and WT xenografts. Based on homology mapping to a crystal structure of PF-02341066 bound to c-Met, the F1174L mutation is predicted to destabilize the specific conformation of the kinase activation loop required for binding PF-02341066. Conclusions: ALK pathway activation occurs in at least 15% of human neuroblastomas. PF-02341066 is a potent inhibitor of the most common ALK mutation, but there is a structural basis for resistance to F1174L mutations. Co-crystallization studies are ongoing and a phase 1 study is planned.

No significant financial relationships to disclose.
Irinotecan plus temozolomide in children with recurrent or refractory neuroblastoma: A phase II Children's Oncology Group study
Authors: Bagatell R. , Wagner L. M. , Cohn S. L. , Maris J. M. , Reynolds C. P. , Stewart C. F. , Voss S. D. , Gelfand M. , Kretschmar C. S. , London W. B.
Published: August 2020

10011

Background: Treatment of children with relapsed or refractory neuroblastoma (NB) remains a challenge. Responses to irinotecan (IRN) + temozolomide (TEM) were seen in NB xenograft-bearing mice, and objective responses were observed in patients with NB treated on a phase I study of this combination. Methods: A phase II study of IRN (10 mg/m2/dose IV daily × 5 days times; 2 weeks) + TEM (100 mg/m2/dose PO daily × 5 days) for children with relapsed or refractory NB was conducted. A one-stage design (endpoint: best overall response) required 5 or more responders out of the first 25 evaluable patients on each of two strata: 1) patients with disease measurable by CT or MRI; and 2) patients with disease detected only by bone marrow aspirate/biopsy and/or MIBG scan. Patients with stable disease or better after 3 cycles could receive an additional 3 cycles of study therapy. International Neuroblastoma Response Criteria were used for response assessment. Radiographic responses were centrally reviewed. Results: Fifty-five eligible and evaluable patients were enrolled, 28 on stratum 1 and 27 on stratum 2. Four responses were observed in the first 25 evaluable stratum 1 patients, and five responses were observed in the first 25 evaluable stratum 2 patients. Three patients had complete responses, but the overall objective response rate (CR+PR) was 16% (9/55). Eleven (stratum 1) and 13 (stratum 2) patients had stable disease. Less than 5% of patients experienced Grade 3 or 4 diarrhea. Although 18% of patients on stratum 1 and 35% of patients on stratum 2 experienced Grade 3 or 4 neutropenia during the first 3 cycles of therapy, <10% of all patients developed evidence of infection while neutropenic. Thrombocytopenia (Grade 3 or 4) was observed in only 7% of patients on stratum 1 and 12% on stratum 2. Conclusions: The combination of IRN+TEM was well tolerated in patients with recurrent or refractory NB. There were 9 objective responses, including 3 complete responses. The minimum desired response rate was attained within stratum 2, but not stratum 1. IRN+TEM may be an appropriate backbone for further study in the relapse setting in combination with novel, targeted agents.

No significant financial relationships to disclose.