bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of reimbursement restriction policy on the use of benzodiazepines in the Netherlands: an interrupted time series analysis
Authors: Stoker Lennart Jan , Heerdink Eibert Roelof , Janssen Richard , Egberts Toine C G
Published: September 2019

Objectives

Use of benzodiazepines has health risks. Reimbursement was restricted in the Netherlands from January 2009 onwards with the goal to reduce chronic use and healthcare expenditures. The aim of this study is to assess the initial and long-term effects of this policy on benzodiazepine use.

Design

Interrupted time series analysis, segmented regression models, Kaplan-Meier survival analysis and Cox proportional hazards analysis.

Setting

A 10% random sample of benzodiazepine dispensings by outpatient pharmacies between January 2002 and August 2015 were obtained from the PHARMO database. This database covered a catchment area representing about 3.6 million residents in 2015.

Participants

2 500 800 benzodiazepine prescriptions from 128 603 patients were included.

Intervention

Reimbursement restriction policy from January 2009 onwards.

Outcome measures

Changes in: the volume of dispensed prescriptions and doses, the incidence, prevalence of incidental, regular and chronic use and discontinuation rates of benzodiazepines.

Results

The volume of dispensed prescriptions and doses decreased by 12.5% (95% CI 9.0% to 15.9%) and 15.1% (95% CI 11.4% to 17.3%) respectively in January 2009 compared with December 2008. A clear initial effect on the overall incidence (−14.7%; 95% CI −19.8% to 9.6%) and the prevalence of incidental (−17.8%; 95% CI −23.9% to 11.7%), regular (−20.0%; 95% CI −26.1% to 13.9%) and chronic (−16.0%; 95% CI −23.1% to 8.9%) use was observed. A statistically significant reduction in the monthly trend per 1000 medication users was observed for the overall incidence (−0.017; 95% CI −0.031 to 0.003) and the prevalence of incidental (−3.624; 95% CI −4.996 to 2.252) but not for regular (−0.304; 95% CI −1.204 to 0.596) and chronic (0.136; 95% CI −0.858 to 1.130) use. Patients who started treatment before policy had a slightly higher probability of discontinuation (HR=1.013; 95% CI 1.004 to 1.022).

Conclusions

The reimbursement policy had a significant initial effect on the volume, incidence and prevalence of benzodiazepine use. In addition, there is a statistically significant reduction in the monthly trend of overall incidence and of the prevalence of incidental use. No statistically significant reduction in the monthly trend of chronic use, the main purpose of the reimbursement restriction, could be demonstrated.
PP14 Soiled airway tracheal intubation and the effectiveness of decontamination (SATIATED) by paramedics: a randomised controlled manikin study
Authors: Pilbery Richard , Dawn Teare M
Published: September 2019

Background

In more than one-in-five cases of out-of-hospital cardiac arrest, the patient’s airway is soiled by vomit and blood. If a paramedic cannot clear the airway, the patient will die. A new method of clearing the airway called suction assisted laryngoscopy and airway decontamination (SALAD) has been developed, but it’s not known whether the method can assist paramedics to intubate. This study aims to determine whether paramedics can intubate a simulated soiled airway more often on their first attempt, using SALAD.

Methods

A modified airway manikin, with the oesophagus connected to a reservoir of ‘vomit’ that was propelled up the oesophagus by a pump, was used to simulate a soiled airway. The intervention consisted of a brief SALAD training session with a demonstration and opportunity to practice. Participants were randomly allocated into two groups: AAB who made two pre-training intubation attempts and one post-training attempt, and ABB, who made one pre-training and two post-training attempts, to adjust for improvement in performance due to repetition.

Results

164 paramedics took part in the study. First-pass intubation success with and without SALAD was 90.2% and 53.7% respectively, a significant difference of 36.6% (95%CI 24–49.1%, p<0.001). The mean successful intubation time for each attempt and patient group (AAB and ABB) was as follows: 61.8 (95%CI 55.8–67.8) and 59.4 (95%CI 53.6–65.1) seconds on the first attempt, 50.8 (95%CI 45.7–55.9) and 51.5 (95%CI 48.6–54.4) seconds on the second attempt and 53.5 (95%CI 50.4–56.6) and 46.6 (95%CI 44.0–49.1) seconds on the third attempt. There was no significant difference in success rates on the third attempt between AAB and ABB 89% vs 86.6% respectively, a difference of 2.4% (95%CI 7.6–12.4%, p=0.63).

Conclusions

In this study, paramedics were able to intubate a simulated soiled airway on their first attempt, significantly more often when using the SALAD technique.
02 ‘Have you had the surgery?’: A survey of transgender and non-binary patients’ experiences of interacting with the ambulance service
Authors: Barley Chloé , Tooms Alec
Published: September 2019

Background

Pre-hospital research around the experience of transgender and non-binary (TNB) patients is scarce, with existing articles lacking input from TNB patients.

This research aimed to collate TNB patients’ experiences of interacting with the ambulance service. A secondary aim was to gather TNB patients’ opinions regarding the education of ambulance clinicians on TNB health issues.

Method

An online-based, mixed-methods survey was created. A range of free text, multiple choice and Likert-scaled questions were used. Advertisement on social media was tailored to target TNB individuals who have had patient contact with the ambulance service. All respondents were anonymous and voluntary. This survey was conducted by TNB individuals in a personal capacity, without funding.

Results

72% of the 25 respondents rated their experience as satisfactory or above. 40% reported that identifying as TNB affected the way they were treated and 40% reported that they were asked about their gender by the ambulance crew.

In free text answers, the main themes identified were the misidentification of gender, the use of incorrect pronouns, hospital handovers, intrusive/irrelevant questioning and the need for training.

Conclusions

The responses suggest that TNB patients feel that being asked about their gender is important however ambulance staff sometimes struggled to address this sensitively. Positive experiences included having gender and pronouns addressed in hospital handover which can form a recommendation for best practice. Negative experiences were associated with being misgendered, using incorrect pronouns and intrusive/irrelevant questioning. Survey responses led to practical recommendations for ambulance staff interacting with TNB patients, including the authors creating a training session which has received positive feedback from clinicians. Limitations include small sample size, potential for response bias due to survey being self-selecting and missing demographic data. Recommendations for further research are to provide a more in-depth exploration of TNB experience and of ambulance staff views.
PP21 Non-technical skills in the out-of-hospital cardiac arrest – identification for future practice
Authors: Cormack Stef , Scott Steve , Stedmon Alex
Published: September 2019

Background

The use and assessment of non-technical skills (NTS) in healthcare has gained recognition in recent years. Mainly adopted from aviation key NTS have enabled specific teams such as surgical and anaesthetics, to improve leadership, communication and situational awareness. Paramedic NTS have been identified but in the out-of-hospital cardiac arrest (OHCA) there is limited evidence. This study aims to identify NTS in the OHCA to inform the design of an assessment tool to improve overall management of an OHCA.

Methods

A review of the literature including NTS in the OHCA and existing behavioural marker tools was completed using online databases (Medline, PubMed, AMED, PsycINFO, PsycARTICLES and CINAHL) and MeSH terms (out-of-hospital, prehospital, paramedic, ambulance, EMS, non-technical skills, soft skills, human factors and behavioural marker systems). Key NTS were taken from the literature and explored by three focus groups (numbers 5, 6, 6). Focus groups comments were transcribed and thematic analysis used to identify noteworthy NTS that could be used to design a tool for assessing NTS in a simulated OHCA. Participants were also asked to rank the most important NTS relevant to an OHCA.

Results

The literature review revealed limited evidence for NTS in the OHCA but identified existing behavioural marker systems in healthcare, although not for the OHCA. Focus groups explored NTS relevant to the OHCA and ranked in order the most important. Situational awareness, communication, leadership, followership and decision making including knowledge and procedures were identified as the most important NTS relevant to an OHCA.

Conclusions

There is no existing assessment or behavioural marker tool for assessing NTS in the OHCA. Focus groups identified key NTS relevant to the OHCA which could be used to design an assessment/behavioural marker tool to assess individuals in a simulated OHCA.
PP22 Box randomisation- a novel method for allocation in pre-hospital randomised controlled trials: the ACUTE study experience
Authors: McKenzie Thomas , Keating Samuel , Goodacre Steve , Fuller Gordon
Published: September 2019

Background

Allocation concealment is essential to avoid selection bias in randomised trials. The ACUTE pilot trial compared the effectiveness of pre-hospital CPAP vs standard oxygen therapy for acute respiratory failure (ARF). The randomisation schedule was implemented, and treatment allocation concealed, with a novel method using identical boxes.

Methods

Investigation of allocation concealment in the ACUTE trial proceeded in 4 stages. Firstly, the characteristics of recruited ACUTE trial patients were compared across arms. Secondly, the findings of a weekly trial box audit log were examined. Thirdly, allocation concealment was explored in paramedic focus groups and survey. Finally, a convenience sample of West Midlands and Yorkshire Ambulance Service paramedics were presented with a random pair of ACUTE boxes from each trial arm, and asked to identify any differences. If a difference was noted, they were asked to indicate which box contained CPAP and why.

Results

The ACUTE study enrolled 77 participants (42 CPAP, 35 control). Baseline characteristics were similar, although patients in the CPAP arm appeared to have slightly more severe ARF. In week 10, audit of trial boxes revealed that intervention arm boxes were ‘rattling’, secondary to deflation of CPAP masks packaged under tension. All boxes were consequently re-packaged and resupplied. No comments in the paramedic survey, but a focus group participant stated that one box had appeared different when shaken. 278 paramedics participated in the observational study. 115 participants (41.4%) felt they were able to tell which box contained CPAP, predominantly due to weight difference. Of these, 81 paramedics (70%, p<0.05) were correct.

Conclusions

Although the majority of paramedics were unable to determine box contents, a significant minority correctly determined the CPAP arm. Taken together with the development of a ‘rattle’ during the trial, and slight baseline imbalance in characteristics of trial participants, loss of allocation concealment cannot be excluded.
PP28 ‘They are not silly people – they know the difference’: clinician focus group views on a pilot randomised controlled trial of prehospital continuous positive airway pressure (CPAP)
Authors: Miller Joshua , Keating Samuel , Scott Alex , Fuller Gordon , Goodacre Steve
Published: September 2019

Background

Continuous positive airway pressure (CPAP) is not in widespread use in UK ambulance services, but could benefit patients with acute respiratory failure (ARF). As a new treatment in this context, clinician acceptability is an important factor in the feasibility of conducting definitive research in the prehospital arena.

Methods

As part of a pilot randomised controlled trial (the ACUTE study), nine trial-trained paramedics took part in three semi-structured focus groups. 204 trained staff had been given the opportunity to take part. The sample included six staff who had recruited to the trial, one who had not, and two who had withdrawn from it. Audio-recordings were transcribed and analysed thematically.

Results

Participants described facilitators to trial participation including: clear eligibility criteria and patient documentation, access to demonstration equipment, training away from the work environment, and repeated patient recruitment. Barriers to taking part included: the lack of protected time for training, inadequate workplace facilities for the electronic learning package used, adverse responses by receiving hospital staff, and infrequent patient exposure. Both paramedics who withdrew cited the inconvenience of carrying packs each shift. Some participants described anxiety and distress when opening packs to find a standard-care mask, and reported patients having similar reactions.

Conclusions

Future researchers could promote improved workplace computing facilities and increased provision of face-to-face training days, which were praised by participants in these focus groups, but limited to a single event distant from some staff. Greater stakeholder engagement by researchers could reduce the difficulties at hospital handover reported by some ambulance staff. Where blinding is not possible, the perceptions of clinicians and patients should be considered carefully, as this study shows both may have adverse emotional responses to being treated with standard care, particularly when prospective consent discussions describe the trial intervention as potentially beneficial.
PP32 Electronic records in ambulances – an observational study (ERA)
Authors: Porter Alison , Black Sarah , Dale Jeremy , Harris-Mayes Robert , Lawrenson Robin , Lyons Ronan , Mason Suzanne , Morrison Zoe , Potts Henry , Siriwardena Niro , Rees Nigel , Snooks Helen , Williams Victoria
Published: September 2019

Background

The introduction of information technology (IT) in emergency ambulance services to electronically capture, interpret and store patient data can support out of hospital care. Although electronic health records (EHR) in ambulances and other digital technology are encouraged by national policy across the UK, there is considerable variation across services in terms of implementation. We aimed to understand how electronic records can be most effectively implemented in a pre-hospital context, in order to support a safe and effective shift from acute to community-based care.

Methods

We conducted a mixed-methods study with four work packages (WPs): a rapid literature review, a telephone survey of all 13 freestanding UK ambulance services, detailed case studies in four selected sites, and a knowledge sharing workshop.

Results

We found considerable variation in hardware and software. Services were in a state of constant change, with services transitioning from one system to another, reverting to paper, or upgrading. Ambulance clinicians were dealing with partial or unclear information, which may not fit comfortably with the EHR. Clinicians continued to use indirect data input approaches such as first writing on a glove. The primary function of EHR in all services seemed to be as a store for patient data. There was, as yet, limited evidence of their full potential being realised to transfer information, support decision making or change patient care.

Conclusions

Realising the full benefits of EHR requires engagement with other parts of the local health economy, dealing with the challenges of interoperability. Clinicians and data managers are likely to want very different things from a data set, and need to be presented with only the information that they need.
Emerging glucose-lowering therapies: a guide for cardiologists
Authors: Gulsin Gaurav S , Graham-Brown Matthew P M , Davies Melanie J , McCann Gerry P
Published: September 2019

In recent large-scale cardiovascular outcome trials, two new classes of glucose-lowering medications—sodium glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RAs)—demonstrated cardiovascular benefits in adults with type 2 diabetes mellitus (T2DM). These findings have prompted growing optimism among clinicians regarding the potential for these agents to reduce the burden of cardiovascular disease in people with T2DM. GLP-1RAs and SGLT2i are now advocated as second-line agents in European and US guidelines for management of both hyperglycaemia and for primary prevention of cardiovascular disease in people with T2DM. Given the high prevalence of T2DM in patients with cardiovascular disease, cardiologists will increasingly encounter these agents in routine clinical practice. In this review, we summarise evidence from cardiovascular outcome trials of GLP-1RAs and SGLT2i, give practical advice on prescribing and detail safety considerations associated with their use. We also highlight areas where further work is needed, giving details on active clinical trials. The review aims to familiarise cardiologists with these emerging treatments, which will be increasingly encountered in clinical practice, given the expanding representation of T2DM in patients with cardiovascular disease. Whether these drugs will be initiated by cardiologists remains to be determined.
Jeans instability and turbulent gravitational collapse of Bose–Einstein condensate dark matter halos
Authors: Harko Tiberiu
Published: September 2019

We consider the Jeans instability and the gravitational collapse of the rotating Bose–Einstein condensate dark matter halos, described by the zero temperature non-relativistic Gross–Pitaevskii equation, with repulsive interparticle interactions. In the Madelung representation of the wave function, the dynamical evolution of the galactic halos is described by the continuity and the hydrodynamic Euler equations, with the condensed dark matter satisfying a polytropic equation of state with index $$n=1$$n=1. By considering small perturbations of the quantum hydrodynamical equations we obtain the dispersion relation and the Jeans wave number, which includes the effects of the vortices (turbulence), of the quantum pressure and of the quantum potential, respectively. The critical scales above which condensate dark matter collapses (the Jeans radius and mass) are discussed in detail. We also investigate the collapse/expansion of rotating condensed dark matter halos, and we find a family of exact semi-analytical solutions of the hydrodynamic evolution equations, derived by using the method of separation of variables. An approximate first order solution of the fluid flow equations is also obtained. The radial coordinate dependent mass, density and velocity profiles of the collapsing/expanding condensate dark matter halos are obtained by using numerical methods.
Teaching Energy Physics for Environmental Studies: A Course Summary
Authors: Groff Jeffrey R.
Published: September 2019

This article summarizes a college course on energy physics for an environmental studies curriculum. The course was developed as an upper-division course. However, it has no physics prerequisite and could be offered as a lower-division course or a core curriculum course with minimal modification. The rationale for the course in the wider curriculum is explained followed by an overview of the course learning goals organized by unit. The course texts are discussed, and useful laboratory and demonstration equipment is referenced. The article concludes with a discussion of the evolution of the course and the impact the course has had on our curriculum.
Development of a Science Demonstration Laboratory in National University of Singapore
Authors: Lim Kim Yong , Sow Chorng Haur
Published: September 2019

Science demonstrations are a good way of promoting, teaching and learning science. This is provided that there exists carefully crafted “software” and communication methods to go along with the hardware. During the past few years, we have developed a Science Demonstration Laboratory at NUS aiming to play an active role in science outreach, science communication and science education. Our approach has evolved from an initial “show-and-tell” model to a more engaging “minds-on” approach where participants are consistently required to make predictions of the outcomes of scientific phenomena before witnessing the demonstrations. We also learnt that the education and development of talented science educators and communicators are crucial to ensure and project the effectiveness of a “hands-on”, “minds-on” approach to science education.
Fractured basement play development on the UK and Norwegian rifted margins
Authors: Trice Robert , Hiorth Cecile , Holdsworth Robert
Published: September 2019

Fractured crystalline basement reservoirs (basement) on the UK Continental Shelf (UKCS) and the Norwegian Continental Shelf (NCS) have been underexplored. Over the last 12 years, Hurricane Energy has deliberately set out to explore basement potential by exploring and appraising the Rona Ridge, West of Shetland; and the Rona Ridge Lancaster Field is now being progressed towards being the first UK basement field development. The Norwegian basement play is also recognized as a potentially material resource through serendipitous oil discoveries, with the 16/1-15 well, drilled in 2011, being the first successful full-scale basement test on the NCS. Building on this success, the 2018 Rolvsnes appraisal well (16/1-28 S) has demonstrated the significant basement potential of the extensive Utsira High and confirmed the materiality of a Norwegian basement play. The Rona Ridge and Utsira basement discoveries are used as a comparison with two other, yet to be evaluated, prospective basement plays on the NCS, with the objective of establishing technical subject areas where future UKCS and NCS collaboration would aid in accelerating understanding of the UKCS–NCS basement play.
The Role of Tumor-Infiltrating B Cells in Tumor Immunity
Authors: Guo Fei Fei , Cui Jiu Wei
Published: September 2019

Earlier studies on elucidating the role of lymphocytes in tumor immunity predominantly focused on T cells. However, the role of B cells in tumor immunity has increasingly received better attention in recent studies. The B cells that infiltrate tumor tissues are called tumor-infiltrating B cells (TIBs). It is found that TIBs play a multifaceted dual role in regulating tumor immunity rather than just tumor inhibition or promotion. In this article, latest research advances focusing on the relationship between TIBs and tumor complexity are reviewed, and light is shed on some novel ideas for exploiting TIBs as a possible tumor biomarker and potential therapeutic target against tumors.
Radiosynthesis and Preclinical Evaluation of 11C-VA426, a Cyclooxygenase-2 Selective Ligand
Authors: Carpinelli Assunta , Rainone Paolo , Belloli Sara , Reale Annalisa , Cappelli Andrea , Germano Giuliani , Murtaj Valentina , Coliva Angela , Di Grigoli Giuseppe , Valeri Angela , Gilardi Maria Carla , Gianolli Luigi , Anzini Maurizio , Moresco Rosa Maria
Published: September 2019

Cyclooxygenase-2 (COX-2) is involved in the inflammatory response, and its recurrent overexpression in cancers as well as in neurodegenerative disorders has made it an important target for therapy. For this reason, noninvasive imaging of COX-2 expression may represent an important diagnostic tool. In this work, a COX-2 inhibitor analogue, VA426 [1-(4-fluorophenyl)-3-(2-methoxyethyl)-2-methyl-5-(4-(methylsulfonil)phenyl)-1H-pyrrole], was synthesized and radiolabelled with the 11C radioisotope. The ex vivo biodistribution profile of 11C-VA426 was evaluated in the brain and periphery of healthy rats and mice and in brain and periphery of inflammation models, based on the administration of LPS. 11C-VA426 synthesis with the tBuOK base showed optimal radiochemical yield (15 ± 2%) based on triflate activity, molar activity (range 37–148 GBq/μmol), and radiochemical purity (>95%). Ex vivo biodistribution studies showed a fast uptake of radioactivity but a rapid washout, except in regions expressing COX-2 (lungs, liver, and kidney) both in rats and in mice, with maximum values at 30 and 10 minutes p.i., respectively. LPS administration did not show significant effect on radioactivity accumulation. Celecoxib competition experiments performed in rats and mice treated with LPS produced a general target unrelated reduction of radioactivity concentration in all peripheral tissues and brain areas examined. Finally, in agreement with the negative results obtained from biodistribution experiments, radiometabolites analysis revealed that 11C-VA426 is highly unstable in vivo. This study indicates that the compound 11C-VA426 is not currently suitable to be used as radiopharmaceutical for PET imaging. This family of compounds needs further implementation in order to improve in vivo stability.
RNA-Binding Protein ZFP36L1 Suppresses Hypoxia and Cell-Cycle Signaling
Authors: Loh Xin-Yi , Sun Qiao-Yang , Ding Ling-Wen , Mayakonda Anand , Venkatachalam Nachiyappan , Yeo Mei-Shi , Silva Tiago C. , Xiao Jin-Fen , Doan Ngan B. , Said Jonathan W. , Ran Xue-Bin , Zhou Si-Qin , Dakle Pushkar , Shyamsunder Pavithra , Koh Angele Pei-Fern , Huang Ruby Yun-Ju , Berman Benjamin P. , Tan Soo-Yong , Yang Henry , Lin De-Chen , Koeffler H. Phillip
Published: September 2019

ZFP36L1 is a tandem zinc-finger RNA-binding protein that recognizes conserved adenylate-uridylate–rich elements (ARE) located in 3′untranslated regions (UTR) to mediate mRNA decay. We hypothesized that ZFP36L1 is a negative regulator of a posttranscriptional hub involved in mRNA half-life regulation of cancer-related transcripts. Analysis of in silico data revealed that ZFP36L1 was significantly mutated, epigenetically silenced, and downregulated in a variety of cancers. Forced expression of ZFP36L1 in cancer cells markedly reduced cell proliferation in vitro and in vivo, whereas silencing of ZFP36L1 enhanced tumor cell growth. To identify direct downstream targets of ZFP36L1, systematic screening using RNA pull-down of wild-type and mutant ZFP36L1 as well as whole transcriptome sequencing of bladder cancer cells {plus minus} tet-on ZFP36L1 was performed. A network of 1,410 genes was identified as potential direct targets of ZFP36L1. These targets included a number of key oncogenic transcripts such as HIF1A, CCND1, and E2F1. ZFP36L1 specifically bound to the 3′UTRs of these targets for mRNA degradation, thus suppressing their expression. Dual luciferase reporter assays and RNA electrophoretic mobility shift assays showed that wild-type, but not zinc-finger mutant ZFP36L1, bound to HIF1A 3′UTR and mediated HIF1A mRNA degradation, leading to reduced expression of HIF1A and its downstream targets. Collectively, our findings reveal an indispensable role of ZFP36L1 as a posttranscriptional safeguard against aberrant hypoxic signaling and abnormal cell-cycle progression.

Significance:

RNA-binding protein ZFP36L1 functions as a tumor suppressor by regulating the mRNA stability of a number of mRNAs involved in hypoxia and cell-cycle signaling.
Genome-Wide CRISPR-Cas9 Screen Reveals Selective Vulnerability of ATRX-Mutant Cancers to WEE1 Inhibition
Authors: Liang Junbo , Zhao Hong , Diplas Bill H. , Liu Song , Liu Jianmei , Wang Dingding , Lu Yan , Zhu Qing , Wu Jiayu , Wang Wenjia , Yan Hai , Zeng Yi-Xin , Wang Xiaoyue , Jiao Yuchen
Published: September 2019

The tumor suppressor gene ATRX is frequently mutated in a variety of tumors including gliomas and liver cancers, which are highly unresponsive to current therapies. Here, we performed a genome-wide synthetic lethal screen, using CRISPR-Cas9 genome editing, to identify potential therapeutic targets specific for ATRX-mutated cancers. In isogenic hepatocellular carcinoma (HCC) cell lines engineered for ATRX loss, we identified 58 genes, including the checkpoint kinase WEE1, uniquely required for the cell growth of ATRX null cells. Treatment with the WEE1 inhibitor AZD1775 robustly inhibited the growth of several ATRX-deficient HCC cell lines in vitro, as well as xenografts in vivo. The increased sensitivity to the WEE1 inhibitor was caused by accumulated DNA damage–induced apoptosis. AZD1775 also selectively inhibited the proliferation of patient-derived primary cell lines from gliomas with naturally occurring ATRX mutations, indicating that the synthetic lethal relationship between WEE1 and ATRX could be exploited in a broader spectrum of human tumors. As WEE1 inhibitors have been investigated in several phase II clinical trials, our discovery provides the basis for an easily clinically testable therapeutic strategy specific for cancers deficient in ATRX.

Significance:

ATRX-mutant cancer cells depend on WEE1, which provides a basis for therapeutically targeting WEE1 in ATRX-deficient cancers.

See related commentary by Cole, p. 375
Epigenomic Profiling Discovers Trans-lineage SOX2 Partnerships Driving Tumor Heterogeneity in Lung Squamous Cell Carcinoma
Authors: Sato Takashi , Yoo Seungyeul , Kong Ranran , Sinha Abhilasha , Chandramani-Shivalingappa Prashanth , Patel Ayushi , Fridrikh Maya , Nagano Osamu , Masuko Takashi , Beasley Mary Beth , Powell Charles A. , Zhu Jun , Watanabe Hideo
Published: September 2019

Molecular characterization of lung squamous cell carcinoma (LUSC), one of the major subtypes of lung cancer, has not sufficiently improved its nonstratified treatment strategies over decades. Accumulating evidence suggests that lineage-specific transcriptional regulators control differentiation states during cancer evolution and underlie their distinct biological behaviors. In this study, by investigating the super-enhancer landscape of LUSC, we identified a previously undescribed “neural” subtype defined by Sox2 and a neural lineage factor Brn2, as well as the classical LUSC subtype defined by Sox2 and its classical squamous partner p63. Robust protein–protein interaction and genomic cooccupancy of Sox2 and Brn2, in place for p63 in the classical LUSC, indicated their transcriptional cooperation imparting this unique lineage state in the “neural” LUSC. Forced expression of p63 downregulated Brn2 in the “neural” LUSC cells and invoked the classical LUSC lineage with more squamous/epithelial features, which were accompanied by increased activities of ErbB/Akt and MAPK–ERK pathways, suggesting differential dependency. Collectively, our data demonstrate heterogeneous cell lineage states of LUSC featured by Sox2 cooperation with Brn2 or p63, for which distinct therapeutic approaches may be warranted.

Significance:

Epigenomic profiling reveals a novel subtype of lung squamous cell carcinoma with neural differentiation.
Longitudinal Photoacoustic Imaging of the Pharmacodynamic Effect of Vascular Targeted Therapy on Tumors
Authors: Johnson S. Peter , Ogunlade Olumide , Lythgoe Mark F. , Beard Paul , Pedley R. Barbara
Published: September 2019

Purpose:

Photoacoustic imaging (PAI) is a novel noninvasive and nonionizing imaging technique that allows longitudinal imaging of tumor vasculature in vivo and monitoring of response to therapy, especially for vascular targeted chemotherapy agents. In this study, we used a novel high-resolution all-optical PAI scanner to observe the pharmacodynamic response to the vascular-disrupting agent OXi4503.

Experimental Design:

Two models of colorectal carcinoma (SW1222 and LS174T) that possess differing pathophysiologic vascularization were established as subcutaneous tumors in mice. Monitoring of response was performed over a 16-day “regrowth” period following treatment at 40 mg/kg, and at day 2 for a “dose response” study at 40 mg/kg, 10 mg/kg, 1 mg/kg, and sham dose.

Results:

Qualitative and quantitative changes in PA signal are observed, with an initial decrease followed by a plateau and subsequent return of signal indicating regrowth. Both tumor types exhibited a decrease in signal; however, the more vascularized SW1222 tumors show greater response to treatment. Decreasing the dose of OXi4503 led to a decrease in PA signal intensity of 60%, 52%, and 20% in SW1222 tumors and 30%, 26%, and 4% for LS174T tumors.

Conclusions:

We have shown for the first time that PAI can observe the pharmacodynamic response of tumor vasculature to drug treatment both longitudinally and at different dose levels. Assessment of differing response to treatment based on vascular pathophysiologic differences among patients has the potential to provide personalized drug therapy; we have demonstrated that PAI, which is clinically translatable, could be a powerful tool for this purpose.
Teaching Helping Babies Breathe via Telehealth: A New Application in Rural Guatemala
Authors: Jones-Bamman Caitlin , Niermeyer Susan , McConnell Kelly , Thomas John F. , Olson Christina
Published: September 2019

Background: Helping Babies Breathe (HBB) is a neonatal resuscitation curriculum that teaches life-saving interventions utilized in the first minutes after birth, reducing morbidity and mortality. Traditionally, it requires in-person facilitators for didactic and hands-on training. Objectives: The aim of this study was to offer HBB to nurses and nursing students in Guatemala, with the lead facilitator presenting concepts via telehealth and in-person facilitators providing hands-on demonstration. Methods: Learners completed pre- and post-tests that included the standard HBB knowledge check, as well as an assessment of the course teaching model. Learners also completed the standard Objective Structured Clinical Evaluations (OSCEs). Results: Eighteen learners were included in the analysis. All but one learner (94%) passed the course, and the average percent improvement from the pre- to post-test was 12%. All learners achieved passing scores on the OSCEs. Learners responded positively to questions regarding the technology, connection with the instructor, and ability to ask questions. Ninety-four percent of the learners agreed with the statement “this lecture was as good via telehealth as in person.” A cost analysis demonstrated approximately USD 3,979.00 in savings using telehealth compared to a standard in-person course. Conclusions: The telehealth model was successful in delivering course material to the learners and was well received. This model represents a cost-effective way to improve access to HBB. This study may not be generalizable to other populations, and the ability to use telehealth requires reliable internet connectivity, which may not be available in all settings. Further study and expansion of this pilot are needed to assess success in other settings.
An Idealized Description for the Diurnal Cycle of the Dry Atmospheric Boundary Layer
Authors: Antoon van Hooft J. , Baas Peter , van Tiggelen Maurice , Ansorge Cedrick , van de Wiel Bas J. H.
Published: September 2019

We present a conceptual model for the diurnal cycle of the dry atmospheric boundary layer (ABL). It may serve as a framework for future numerical studies on the transitional dynamics that characterize the ABL over land. The conceptual model enables us to define expressions for relevant physical scales as a function of the most prominent forcing parameters and the low degree of complexity facilitates a dimensionless description. This is useful to help generalize boundary layer dynamics that occur on a diurnal time scale. Further, the model’s application for numerical studies is illustrated herein with two examples: a single-column-model study that assesses the effect of wind forcing on the main characteristics of the diurnal cycle, and a large-eddy-simulation study on the daily evolution of turbulence under weak-wind-forcing conditions. The results from these studies sketch the general evolution of the present set of diurnal-cycle systems in more detail. We discuss how the setups are able to reproduce well-known dynamical features of the ABL and also highlight limitations, where the simple conceptual system is unable to describe realistic ABL behavior. We conclude that the present conceptual model has an interesting balance between model-system complexity and physical realism, such that it is useful for future idealized studies on the diurnal cycle of the ABL.
Examining Prisoner Misconduct: A Multilevel Test Using Personal Characteristics, Prison Climate, and Prison Environment
Authors: Bosma Anouk Q. , C. van Ginneken Esther F. J. , Sentse Miranda , Palmen Hanneke
Published: September 2019

The aim of the current study was to examine if prisoner characteristics (personal characteristics and prison climate) and prison environment were related to prisoner misconduct, using data from a nationwide prospective cohort study examining the experience of prison climate in the Netherlands ( N = 4,427). The results indicated that both personal characteristics and certain (social) domains of prison climate, such as the quality of staff–prisoner relationships, were related to prisoner misconduct, as well as prison regime. Furthermore, it was shown that registration data, which underestimate misconduct, may be (more than self-reported data) influenced by unit-level factors, such as regime characteristics. When using registration data, it is therefore particularly important to properly control for unit-level influences.
Porosity analysis of carbon fibre-reinforced polymer laminates manufactured using automated fibre placement
Authors: Oromiehie Ebrahim , Garbe Ulf , Gangadhara Prusty B
Published: September 2019

Automated fibre placement-based manufacturing technology is increasingly being used in several engineering applications. Manufacture of carbon fibre-reinforced plastic’s small/large structures have been made possible due to its remarkable capabilities like productivity and accuracy. Nevertheless, making high-quality composite laminate using automated fibre placement relies on the proper selection of critical processing variables to avoid internal flaws during the fibre placement process. Consequently, a reliable non-destructive inspection technique is required for quality assurance and structural integrity of fabricated laminates. Neutron radiography/tomography offers unique imaging capabilities over a wide range of applications including fibre-reinforced polymer composites. The application of this technique towards tomographic reconstruction of automated fibre placement-made thermoplastic composites is presented in this paper. It is shown that the porosity analysis using neutron imaging technique provides reliable information. Additionally, using such technique valuable data regarding the size and the location of the voids in the laminate can be acquired and informed. This will assist the composite structural analysts and designers to select the appropriate processing parameters towards a defect free automated fibre placement part manufacture.
The Biology of Social Adversity Applied to Oral Health
Authors: Gomaa N. , Tenenbaum H. , Glogauer M. , Quiñonez C.
Published: September 2019

Biological embodiment is a concept derived from Engel’s biopsychosocial model to health, theorized as the process by which adverse social exposures trigger neuroendocrine and immune responses, leading to disease and/or increased disease susceptibility. This critical review discusses the biopsychosocial model as applied to oral health and its relevance to oral health policy while deciphering some of the pathobiological processes underlying social adversity. In periodontal disease, for example, such processes can occur via the activation of the hypothalamic-pituitary-adrenal axis and the consequent release of the chronic stress hormone cortisol. The latter contributes to a proinflammatory immune state that increases the risk for periodontal inflammation. Recent research shows that cortisol relates to an elevated oral inflammatory load, demonstrated as hyperactive neutrophils that are pivotal to periodontal tissue damage. Consistent with the biopsychosocial model, this relationship is amplified in those of lower income and higher financial stress. Similarly, among children from lower socioeconomic backgrounds, cortisol is linked to a higher cariogenic bacterial load. Such findings implicate the stress pathway as key in the oral pathogenic process, particularly under social/socioeconomic adversity. Collectively, this work emphasizes the importance of addressing social factors in alleviating oral disease burden and reducing the social gaps therein.
Gemination in Northern versus Central and Southern Varieties of Italian: A Corpus-based Investigation
Authors: Mairano Paolo , De Iacovo Valentina
Published: September 2019

It is often claimed that patterns of gemination are different across varieties of Italian. In particular, northern speakers are sometimes said to degeminate, or to produce shorter geminates than central and southern speakers. However, experimental data proving such claims is largely missing. In this article, we perform an analysis of the CLIPS corpus with the aim of comparing gemination for northern versus central and southern speakers of Italian. The analysis of different data types (target words in isolated position, read sentences, dialogues, local radio and TV broadcasts) revealed that: (a) geminate consonants are produced by all speakers, incl. northern speakers; (b) differences in the magnitude of consonant lengthening are small (< 19 ms) and reach significance only for some data types; (c) the shortening of vowels preceding geminate consonants is mainly restricted to isolated target words in nuclear position, with no significant differences between northern and central/southern speakers. We argue that regional differences in Italian gemination have been overestimated and overemphasized in the literature. In fact, the evidence suggests that they are not as sizeable as previously thought, probably because of the progressive standardization of the language.
Attitude Toward Online Relationship Formation and Psychological Need Satisfaction: The Moderating Role of Loneliness
Authors: Ang Chin-Siang
Published: September 2019

Our study explores the moderating role of loneliness in the relationship between attitude toward online relationship formation and psychological need satisfaction in online friendships. Participants included 1572 adolescents who completed self-report measures of loneliness, attitude toward online relationship formation, and psychological need satisfaction in online friendships. As hypothesized, attitude toward online relationship formation was positively related to psychological need satisfaction in online friendships. Results of moderation also demonstrated that lonely adolescents would report more positive attitude toward online relationship formation and higher psychological need satisfaction in online friendships compared to adolescents with nonlonely. Overall, these results extend self-determination theory’s contentions regarding the critical role of socialization initiatives to increase the fulfilment of psychological needs for adolescents, regardless of whether the relationship was formed through the Internet or in-person.
An international instant-messaging journal club: a modern, fun and global approach to a traditional teaching tool
Authors: Peponis Christos , Khaliq Mehnoor , Ismail Ali Abdirashid , Bose Deepa , Wicks Laurence , Tessema Geletaw
Published: September 2019

The aim of this study was to introduce a modern, engaging and easily accessible approach to medical education. A virtual journal club (VJC) was established for the orthopaedic trainees of Ethiopia using instant messaging via Viber. Group discussions included research articles, case reports and radiographs. In addition, senior participants posed quiz questions, with a leaderboard for best performance. Finally, a satisfaction survey was conducted using Google Forms. We have accumulated data from the first five months of educational activity with 73 participants. Seven articles were analysed and debated, covering a broad range of orthopaedic topics, with 56 messages per article on average and 60 quiz questions overall. Our survey received 20 responses, where 95% perceived the VJC as superior to the traditional journal club. Instant messaging is recommended as an educational tool, utilised as an effective VJC. It provides continuous interactive distance learning, without the restrictions of traditional methods.
Perceptions of mindful teaching are associated with longitudinal change in adolescents’ mindfulness and compassion
Authors: Colaianne Blake A. , Galla Brian M. , Roeser Robert W.
Published: September 2019

The purpose of this study was to examine how student perceptions of mindful teaching are associated with changes in students’ mindfulness, self-compassion, and compassion for others across a single high school year. We hypothesized two pathways of effect: a direct path whereby when high school students perceive their teachers as demonstrating mindful qualities, they are more likely to emulate these qualities, and an indirect path whereby mindful teaching affects student outcomes by providing an environment that fulfills the developmental needs of students. To test these hypotheses, a short-term longitudinal study of high school students ( N = 599) was conducted in which student outcomes from the beginning to the end of the school year were regressed on perceptions of mindful teaching at the beginning of the year and school need fulfillment during the midpoint of the school year. Results revealed support for the indirect path: student perceptions of mindful teaching predicted changes in student perceptions of school need fulfillment, which then predicted changes in students’ own mindfulness, self-compassion, and compassion for others over time. Results are discussed in terms of how mindful teaching might represent a kind of social affordance for students, one in which the needs of students are seen and fulfilled, and, as a result, one in which the students may be more willing to emulate and internalize the qualities of their teachers.
Posthuman Sustainability: An Ethos for our Anthropocenic Future
Authors: Cielemęcka Olga , Daigle Christine
Published: September 2019

Confronted with an unprecedented scale of human-induced environmental crisis, there is a need for new modes of theorizing that would abandon human exceptionalism and anthropocentrism and instead focus on developing environmentally ethical projects suitable for our times. In this paper, we offer an anti-anthropocentric project of an ethos for living in the Anthropocene. We develop it through revisiting the notion of sustainability in order to problematize the linear vision of human-centric futurity and the uniform ‘we’ of humanity upon which it relies. We ground our analyses in posthumanism and material feminism, using works by posthumanist and material feminist thinkers such as Stacy Alaimo, Rosi Braidotti, Donna Haraway and Jane Bennett, among others. In dialogue with them, we offer the concept of posthuman sustainability that decenters the human, re-positions it in its ecosystem and, while remaining attentive to difference, fosters the thriving of all instances of life.
A case of metastasis of small cell lung cancer to the parotid gland: a case report and literature review
Authors: Cui Yu , Cui Xiang-Yan , Wu Yu , Yin Wan-Zhong , Zhu Zhan-Peng
Published: September 2019

Small cell lung cancer metastasizing to the parotid gland is very rare and only a few cases have been reported. A 64-year-old man presented with a painless mass and peripheral facial paralysis. Neck ultrasound identified a solid mass in the right parotid gland with enlargement of the lymph nodes in the gland and the right submandibular lymph nodes. Lung computed tomography imaging demonstrated abnormalities in the upper and middle lobes of the right lung and intermediate bronchus, with obstructive pneumonia, as well as enlargement of the right hilar and mediastinal lymph nodes. Postoperative histopathological analysis identified small cell carcinoma in the right parotid gland with involvement of the right neck lymph nodes (one of eight). Bronchoscopy was performed and immunohistochemical analysis of the specimen demonstrated possible metastasis of small cell lung cancer to the parotid gland. From postoperative day 15, the patient started to undergo six cycles of an adjuvant chemotherapy regimen. No complications of the chemotherapy regimen were observed after three cycles. Treatment and follow-up are ongoing.