bluuebunny/crossref_metadata_2025 huggingface dataset:
P032 E-CIGARETTE AND CIGARETTE USE AMONG U.S. ADULT IBD PATIENTS: POPULATION-LEVEL SURVEY
Authors: Suk Ryan , Suk Heetae , Sonawane Kalyani , Deshmukh Ashish
Published: January 2020

Background

Cigarette smoking can negatively affect treatment response in inflammatory bowel disease (IBD) patients, especially among those with Crohn’s disease (CD). E-cigarette has been considered a safer alternative to delivering nicotine for IBD patients who smoke. However, given the recent large number of reported e-cigarette-related lung injury cases, CDC released an interim guidance update on those lung injuries. They also coined a term EVALI (e-cigarette, or vaping, product use associated lung injury) emphasizing the possible harms in e-cigarette smoking. To the best our knowledge, we currently do not know the recent smoking habits in American IBD patients, especially when it reveals that e-cigarette use might cause serious lung injuries.

Methods

We used National Health Interview Survey (NHIS) for 2015–2016, which is a nationally representative survey for noninstitutionalized adults in the US. Weighted counts and percentages were estimated using survey design for the population-level results. We identified those who reportedly were told by a doctor or healthcare professional that they have IBD. We first estimated the prevalence of current e-cigarette or cigarette use among IBD patients. We then estimated the frequency of use (every day or some days) among the current users. We also categorized IBD patients into 4 groups by smoking type: those using e-cigarette only, cigarette only, using both, and neither. To see the characteristics of e-cigarette users, we stratified e-cigarette users by current/former/never cigarette use status.

Results

We identified 951 participants (population estimate: 3.1 million) with IBD. Among those people, 5.0% (95% CI: 3.1–6.9) was current e-cigarette users while 17.9% (95% CI: 14.8–21.0) was current cigarette smokers. Prevalence of every-day use and some-day use of e-cigarette was similar (2.4% vs 2.6%), while there was much higher prevalence of every-day use than some-day use in cigarette (15.3% vs 2.6%). Those who were using both e-cigarette and cigarette was 3.2% (Table). Majority of e-cigarette users were also currently using cigarette (63.6%, 95% CI: 48.9–78.3), while 32.7% (95% CI: 18.4–47.0) of them were former cigarette smokers. Only 3.7% (0.0–8.9) of them never used cigarettes.

Conclusion

While numerous studies show e-cigarette use is generally increasing rapidly in the US, we found that 5% of IBD patients are currently using e-cigarette. Almost two-thirds of them were also currently smoking cigarette and one-third of them were former smokers. It is possible that most of the e-cigarette users are still in the process of transitioning from cigarette smoking and thus using both types. We lack information on effects of using e-cigarette or both e-cigarette and cigarette in IBD treatment outcomes, as well as how e-cigarette use will complicate other health risks in IBD patients (e.g. lung injuries). We need further research on these effects to properly guide IBD patients who are in need of smoking cessation.
P031 PERCEPTIONS AMONG PATIENTS WITH ULCERATIVE COLITIS: TREATMENT AND SELF MANAGEMENT METHODS
Authors: DuBois Kelli , Blake Christine , Rudisill Caroline , Harrison Sayward , Hébert James
Published: January 2020

Background

Patients with Ulcerative Colitis (UC) experience a range of gastrointestinal and extraintestinal symptoms that generate a significant burden on daily life. For the majority of individuals with UC, pharmacotherapy is insufficient to maintain a ‘normal’ lifestyle. Many of those diagnosed with UC seek out complementary or alternative treatments and undertake socio-behavioral and lifestyle adaptations to self-manage disease symptoms, reduce dependence upon pharmaceuticals, and respond to the challenges of living with chronic illness. The purpose of this qualitative study is to describe patient perspectives and experiences with UC treatment and self-management methods.

Methods

Qualitative data were collected using individual semi-structured interviews to obtain in-depth data reflecting the perspectives and experiences of individuals with UC on treatment and self-management of symptoms. Patients were recruited in collaboration with the Prisma Health Gastroenterology department in Greenville, SC and the Carolina’s Crohn’s and Colitis support group. Eligibility criteria included: 1) diagnosis of UC; 2) duration of illness ≥5 years; and 3) a minimum of one disease flare during the illness trajectory. Interviews were audio recorded and transcribed. Thematic analysis was conducted using NVivo 11 software.

Results

All participants reported active involvement with a gastroenterologist for disease management and progressive use of medications over the course of their illness in response to disease flares. Most participants identified stress reduction as beneficial to managing their UC. All participants discussed diet as a method to manage their UC. The majority of participants spoke about foods as culprits for symptom incidents. Other participants described dietary intake as essential in managing the severity of their UC and overall well-being. Patients who expressed need for formal mental health treatment perceived little support or assistance among gastroenterologists. Patients who underwent colorectal surgery described a continuing need to self-manage gastrointestinal symptoms.

Discussion

Patients expressed reliance on physicians for pharmaceutical treatment, yet identified diet restrictions and stress management as a main approach for self-management of UC. Framing patient education on how diet, stress management, and other health behaviors improve immune system functioning may lead to greater long term adoption of health behaviors and improved health outcomes among individuals with UC.
P082 ANTI-TNF EFFICACY AFTER PRIMARY VEDOLIZUMAB FAILURE IN PEDIATRIC INFLAMMATORY BOWEL DISEASE
Authors: Dolinger Michael , Rolfes Priya , Phan Becky , Pan Stephanie , Dubinsky Marla
Published: January 2020

Background

Vedolizumab (VDZ) is less effective in Inflammatory Bowel Disease (IBD) when used in anti-Tumor Necrosis Factor (TNF) failures as compared to anti-TNF naïve patients. However, the outcomes of sequencing anti-TNF after VDZ failure remain unknown. We report on the effectiveness and safety of anti-TNF as a second-line biologic after VDZ failure in pediatric IBD patients.

Methods

Data was collected as part of an ongoing pediatric IBD observational treatment registry and included demographics, disease behavior, location, disease activity (Harvey Bradshaw index (HBI) for Crohn’s disease (CD) or partial Mayo score (pMS) for ulcerative colitis (UC) and IBD-unspecified (IBD-U)), adverse events, treatment and surgical history. Primary outcome was steroid-free clinical remission at last follow up. Secondary outcomes were CRP normalization and adverse events including infusion reactions, infections, hospitalizations, and IBD related surgeries. Descriptive statistics summarized the data (median [interquartile range (IQR)]) and univariate analyses tested associations.

Results

A total of 21 children and young adults (6 CD:14 UC:1 IBD-U; 19/21 colonic only disease) were treated with VDZ for a median [IQR] duration of 25 [11–59] weeks. VDZ was discontinued due to primary non-response (57%), secondary loss of response (38%), or an adverse event (5%). Nineteen (90%) patients were induced with infliximab (IFX), 1 with adalimumab, and 1 with golimumab and were followed for a median of 100 [35–148] weeks after anti-TNF induction (Table 1). Fifteen (71%) patients remained on anti-TNF therapy at last follow up for a median duration of 53 [34–112] weeks. All 15 patients achieved steroid-free clinical remission, and 9 (60%) patients also had a normal CRP (Figure 1). Remission rates were numerically higher in UC/IBD-U vs. CD (80% vs. 50% P = 0.27). All 6 (28%) patients (3 CD and 3 UC) who discontinued anti-TNF therapy after a median duration of 15 [7–24] weeks initially had a primary non-response to VDZ. Three patents had a primary non-response to anti-TNF, 2 had a secondary loss of response, and 1 had an anaphylactic infusion reaction. No serious adverse events, hospitalizations or serious infections attributable to anti-TNF therapy occurred.

Conclusions

Our results suggest that anti-TNF therapy is efficacious and safe after primary failure with VDZ in pediatric IBD patients and this was particularly so in patients with colonic disease location, regardless of IBD classification.
P089 REAL-WORLD EXPERIENCE: CLINICAL AND ENDOSCOPIC EFFECTIVENESS OF STANDARD VEDOLIZUMAB DOSING AND MODIFIED MAINTENANCE DOSING IN PATIENTS WITH MODERATE-SEVERE CROHN’S DISEASE
Authors: Lee Scott D , Singla Anand , Kerwin Caitlin , Clark-Snustad Kindra
Published: January 2020

Background

Vedolizumab (VDZ) is an effective treatment for Crohn’s disease (CD); however, inadequate and loss of response is common. Pivotal VDZ trials evaluated alternative dosing intervals, demonstrating numeric but not statistical superiority in efficacy as compared to FDA-approved dosing. The safety and effectiveness of FDA-approved and modified-dosing schedules in a real-world population are unknown. We aimed to evaluate clinical and endoscopic effectiveness & safety of standard and modified maintenance VDZ dosing in a real world cohort.

Methods

We retrospectively reviewed CD patients (pts) treated with >3 months VDZ, assessing Harvey Bradshaw Index (HBI), Simple Endoscopic Score for Crohn’s disease (SESCD), Short Inflammatory Bowel Disease Questionnaire (SIBDQ), C-reactive protein (CRP), albumin and hematocrit prior to and following standard VDZ dosing, and prior to and following modified VDZ maintenance dosing. We measured duration on therapy and adverse events.

Results

We identified 226 eligible pts, mean age 41.5 years, 55.3% female, median disease duration 10 years, 88.9% with prior biologic exposure. Mean duration on VDZ was 28.3 months.

Standard VDZ dosing: 61.5% of pts with active clinical disease and adequate follow up data achieved clinical response after 3–12 months; 41.0% had clinical remission. 51.9% of pts with active endoscopic disease and adequate follow up data achieved mucosal improvement; 42.3% had endoscopic remission; 26.0% had mucosal healing after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized CRP after 3–12 months.

Modified maintenance dosing: 72 non-remitters to standard VDZ dosing received modified VDZ maintenance dosing. 51.5% of pts with active clinical disease prior to starting dose modification and adequate follow up data achieved clinical response after 3–12 months of modified maintenance dosing; 42.4% had clinical remission. 22.2% of pts with SESCD ≥3 prior to starting dose modification achieved mucosal improvement after 3–24 months; 22.2% had mucosal healing. 26.7% of pts with SESCD ≥4 prior to starting modified dosing had endoscopic remission after 3–24 months. 50.0% of pts with elevated CRP and adequate follow up data normalized their CRP after 3–12 months.

Safety: 82.7% of pts reported ≥1 adverse events, most commonly infection and worsening CD symptoms.

Discussion

Standard VDZ dosing resulted in clinical and endoscopic improvement in pts with moderate-severe CD, with prior exposure to multiple advanced therapies. For non-remitters to standard dosing, modified VDZ maintenance dosing improved clinical disease activity in ∼50% of pts and improved endoscopic disease activity in ∼20% of pts, suggesting that for pts who did not achieve remission with standard VDZ dosing, modified VDZ dosing may result in clinical and endoscopic improvement.
Empirical comparisons of multiple Mendelian randomization approaches in the presence of assortative mating
Authors: Minică Camelia C , Boomsma Dorret I , Dolan Conor V , de Geus Eco , Neale Michael C
Published: January 2020

Background

Mendelian randomization (MR) is widely used to unravel causal relationships in epidemiological studies. Whereas multiple MR methods have been developed to control for bias due to horizontal pleiotropy, their performance in the presence of other sources of bias, like non-random mating, has been mostly evaluated using simulated data. Empirical comparisons of MR estimators in such scenarios have yet to be conducted. Pleiotropy and non-random mating have been shown to account equally for the genetic correlation between height and educational attainment. Previous studies probing the causal nature of this association have produced conflicting results.

Methods

We estimated the causal effect of height on educational attainment in various MR models, including the MR-Egger and the MR-Direction of Causation (MR-DoC) models that correct for, or explicitly model, horizontal pleiotropy.

Results

We reproduced the weak but positive association between height and education in the Netherlands Twin Register sample (P= 3.9 × 10–6). All MR analyses suggested that height has a robust, albeit small, causal effect on education. We showed via simulations that potential assortment for height and education had no effect on the causal parameter in the MR-DoC model. With the pleiotropic effect freely estimated, MR-DoC yielded a null finding.

Conclusions

Non-random mating may have a bearing on the results of MR studies based on unrelated individuals. Family data enable tests of causal relationships to be conducted more rigorously, and are recommended to triangulate results of MR studies assessing pairs of traits leading to non-random mate selection.
Hydrodynamic shear-based purification of cancer cells with enhanced tumorigenic potential
Authors: Cermeño Efraín A , O’Melia Meghan J , Han Woojin M , Veith Austin , Barber Graham , Huang Emina H , Thomas Susan N , García Andrés J
Published: January 2020

Tumor-initiating cells (TICs), a subpopulation of cancerous cells with high tumorigenic potential and stem-cell-like properties, drive tumor progression and are resistant to conventional therapies. Identification and isolation of TICs are limited by their low frequency and lack of robust markers. Here, we characterize the heterogeneous adhesive properties of a panel of human and murine cancer cells and demonstrate differences in adhesion strength among cells, which exhibit TIC properties and those that do not. These differences in adhesion strength were exploited to rapidly (~10 min) and efficiently isolate cancerous cells with increased tumorigenic potential in a label-free manner by use of a microfluidic technology. Isolated murine and human cancer cells gave rise to larger tumors with increased growth rate and higher frequency in both immunocompetent and immunocompromised mice, respectively. This rapid and label-free TIC isolation technology has the potential to be a valuable tool for facilitating research into TIC biology and the development of more efficient diagnostics and cancer therapies.
Direct detection of intact Klebsiella pneumoniae carbapenemases produced by Enterobacterales using MALDI-TOF MS
Authors: Yoon Eun-Jeong , Lee Eun Hee , Hwang Dong Hwi , Lee Hyukmin , Baek Je-Hyun , Jeong Seok Hoon
Published: January 2020

Objectives

A MALDI-TOF MS-based identification method for KPC-producing Enterobacterales was developed.

Methods

The molecular mass of the intact KPC-2 polypeptide was estimated for blaKPC-2 transformants using MALDI Microflex and the exact mass was confirmed by LC and a high-resolution MS/MS system. A total of 1181 clinical Enterobacterales strains, including 369 KPC producers and 812 KPC non-producers, were used to set up the methodology and the results were compared with those from PCR analyses. For external validation, a total of 458 Enterobacterales clinical isolates from a general hospital between December 2018 and April 2019 were used.

Results

The exact molecular mass of the intact KPC-2 protein was 28 718.13 Da and KPC peaks were observed at m/z 28 708.87–28 728.34 using MALDI Microflex. Most of the KPC-2 (99.1%, 335/338) and KPC-3 (100%, 6/6) producers presented a clear peak via this method, while 12.0% (3/25) of the KPC-4 producers had a peak of weak intensity associated with low levels of gene expression. It took less than 20 min for the entire assay to be performed with colonies on an agar plate. External validation showed that the analytical sensitivity and specificity of the method compared with PCR were 100% (59/59) and 99.50% (397/399), respectively.

Conclusions

The MALDI-TOF MS-based method for directly detecting the intact KPC protein is applicable to routine tests in clinical microbiology laboratories, supported by its speed, low cost and excellent sensitivity and specificity.
Efficacy of piperacillin in combination with novel β-lactamase inhibitor IID572 against β-lactamase-producing strains of Enterobacteriaceae and Staphylococcus aureus in murine neutropenic thigh infection models
Authors: Growcott E J , Gamboa L , Roth T , Lopez S , Osborne C S
Published: January 2020

Objectives

The neutropenic murine thigh infection model was used to assess the effectiveness of IID572, a novel β-lactamase inhibitor, in rescuing piperacillin activity against bacterial strains expressing various β-lactamase enzymes.

Methods

Mice (n = 4/group) were inoculated with Enterobacteriaceae or Staphylococcus aureus bacterial strains expressing a range of β-lactamases via intramuscular injection. Two hours after bacterial inoculation, subcutaneous treatment with piperacillin/IID572 or piperacillin/tazobactam every 3 h was initiated. Animals were euthanized via CO2 24 h after the start of therapy and bacterial cfu (log10 cfu) per thigh was determined, and the static dose was calculated.

Results

In a dose-dependent manner, piperacillin/IID572 reduced the thigh bacterial burden in models established with Enterobacteriaceae producing class A, C and D β-lactamases (e.g. ESBLs, KPC, CMY-2 and OXA-48). Piperacillin/IID572 was also efficacious against MSSA strains, including one producing β-lactamase. Static doses of piperacillin/IID572 were calculable from animals infected with all strains tested and the calculated static doses ranged from 195 to 4612 mg/kg/day piperacillin, the active component in the combination. Of the 13 strains investigated, a 1 log10 bacterial reduction was achieved for 9 isolates and a 2 log10 reduction was achieved for 3 isolates; piperacillin/tazobactam was not efficacious against 6 of the 13 isolates tested.

Conclusions

In contrast to tazobactam, IID572 was able to rescue piperacillin efficacy in murine thigh infection models established with β-lactamase-producing strains of Enterobacteriaceae and S. aureus, including those expressing ESBLs or serine carbapenemases.
Gp120 substitutions at positions associated with resistance to fostemsavir in treatment-naive HIV-1-positive individuals
Authors: Lepore Luciana , Fabrizio Claudia , Bavaro Davide Fiore , Milano Eugenio , Volpe Anna , Lagioia Antonella , Angarano Gioacchino , Saracino Annalisa , Monno Laura
Published: January 2020

Objectives

Fostemsavir, a novel attachment inhibitor targeting the HIV-1 gp120, has demonstrated wide in vitro activity. However, the high rate of HIV gp120 substitutions could jeopardize its efficacy. We investigated envelope (env) substitutions at positions associated with resistance to fostemsavir in patients with a new HIV-1 diagnosis according to HIV subtype and tropism.

Methods

Gp120 sequences from 409 subjects were retrospectively analysed and the presence of the L116P, A204D, S375H/M/T, M426L, M434I and M475I mutations was evaluated. Other amino acid changes at the same positions were also recorded. The variability at each amino acid position was evaluated using Shannon entropy.

Results

The frequency of mutations was: S375T (13.2%); M426L (6.8%); M434I (2.9%); M475I (2.7%); S375H (1.0%)/M (0.8%) and L116P (0.31%). Statistically significant differences were found at positions 375 (R5/non-R5 strains and B/non-B subtypes) and 426 (B/non-B subtypes); post hoc analysis revealed that significance for position 375 was steered by S375T while for position 426 significance was governed by unusual substitutions, in particular M426R (B/non-B, P < 0.00001). The variability of env constant domains appeared to be more relevant in the non-B virus population.

Conclusions

In conclusion, gp120 substitutions were detected in different subtypes and in both R5 and non-R5 variants. Despite the great variability of gp120, the frequency of mutations was low overall and the predominant substitution was S375T, the role of which in reducing fostemsavir efficacy is less substantial.
Challenges of improving treatment outcomes for colorectal and anal cancers in Japan: the Colorectal Cancer Study Group (CCSG) of the Japan Clinical Oncology Group (JCOG)
Authors: Ouchi Akira , Shida Dai , Hamaguchi Tetsuya , Takashima Atsuo , Ito Yoshinori , Ueno Hideki , Ishiguro Megumi , Takii Yasumasa , Ikeda Satoshi , Ohue Masayuki , Fujita Shin , Shiozawa Manabu , Kataoka Kozo , Ito Masaaki , Tsukada Yuichiro , Akagi Tomonori , Inomata Masafumi , Shimada Yasuhiro , Kanemitsu Yukihide
Published: January 2020

Colorectal cancer is a major public health concern in Japan. While early-stage colorectal adenocarcinoma treatment entails radical resection of the primary tumor, the importance of perioperative treatment is growing as physicians seek to further improve treatment outcomes. For anal squamous cell carcinoma, definitive chemoradiotherapy is superior to radical surgery in terms of improved patient quality of life. The Colorectal Cancer Study Group of the Japanese Clinical Oncology Group was established in 2001 and has worked to provide answers to common clinical questions and improve treatment outcomes for colorectal and anal cancers through 15 large-scale prospective clinical trials. Here, we discuss the current state of perioperative treatment for early-stage colon, rectal and anal cancers in Japan and approaches taken by the Colorectal Cancer Study Group/the Japanese Clinical Oncology Group to improve treatment outcomes for these cancers.
What Difference do Mayors Make? The Role of Municipal Authorities in Turkey and Lebanon’s Response to Syrian Refugees
Authors: Betts Alexander , MemiŞoĞlu Fulya , Ali Ali
Published: January 2020

With the majority of refugees now in urban areas, mayors and municipal authorities have been recognized as increasingly important policy actors in the global refugee regime. This trend is acknowledged in the policy literature. However, there has been little systematic academic research exploring the conditions under which mayors make a difference to refugee-policy outcomes. Theoretically, we outline a heuristic framework aimed at disaggregating key variables, including the independent influence of mayors, in shaping municipal-level outcomes. Empirically, the article assesses the role of municipal authorities and mayors in the two most numerically significant host countries for Syrian refugees: Turkey and Lebanon. It comparatively examines variation across six metropolitan municipalities, three from each country: Izmir, Adana and Gaziantep (Turkey), and Qalamoun, Anjar and Zahle (Lebanon). We show that mayors matter because they may mediate the implementation of national policies and because they sometimes adopt supplementary refugee policies and practices at the municipal level, which may be more or less proactive or more or less restrictive than central-government policy.
Perspective: The History and Afterlife of Darwin’s Childhood Garden
Authors: Piesse Jude
Published: January 2020

This article examines the history and significance of Charles Darwin’s childhood garden at The Mount in Shrewsbury. Unlike the mature Darwin’s garden at Down House, Kent, his childhood garden at The Mount has only recently begun to be restored and it is not well known outside of local or specialist circles. The first part of the article aims to recover the story of the garden for a wider interdisciplinary readership. It builds upon research in the fields of garden history and biography to make a case for the garden’s importance to Darwin’s life and scientific work while also revealing the site’s afterlife as a lost garden and challenging restoration project. The second part of the article argues that the garden can be viewed as an enchanted space that enables us to connect more closely with a positive vision of a romantic, ecologically conscious Darwin who is of particular relevance to our times. I conclude by briefly outlining how these ideas were tested at the Darwin’s Childhood Garden Study Day, organized with Shropshire Wildlife Trust in 2016 following its purchase of part of the site in 2013.
Glycosyltransferase OsUGT90A1 helps protect the plasma membrane during chilling stress in rice
Authors: Shi Yao , Phan Huy , Liu Yaju , Cao Shouyun , Zhang Zhihua , Chu Chengcai , Schläppi Michael R
Published: January 2020

Due to its subtropical origins, rice (Oryza sativa) is sensitive to low-temperature stress. In this study, we identify LOC_Os04g24110, annotated to encode the UDP-glycosyltransferase enzyme UGT90A1, as a gene associated with the low-temperature seedling survivability (LTSS) quantitative trait locus qLTSS4-1. Differences between haplotypes in the control region of OsUGT90A1 correlate with chilling tolerance phenotypes, and reflect differential expression between tolerant and sensitive accessions rather than differences in protein sequences. Expression of OsUGT90A1 is initially enhanced by low temperature, and its overexpression helps to maintain membrane integrity during cold stress and promotes leaf growth during stress recovery, which are correlated with reduced levels of reactive oxygen species due to increased activities of antioxidant enzymes. In addition, overexpression of OsUGT90A1 in Arabidopsis improves freezing survival and tolerance to salt stress, again correlated with enhanced activities of antioxidant enzymes. Overexpression of OsUGT90A1 in rice decreases root lengths in 3-week-old seedlings while gene-knockout increases the length, indicating that its differential expression may affect phytohormone activities. We conclude that higher OsUGT90A1 expression in chilling-tolerant accessions helps to maintain cell membrane integrity as an abiotic stress-tolerance mechanism that prepares plants for the resumption of growth and development during subsequent stress recovery.
Planet Hunters TESS I: TOI 813, a subgiant hosting a transiting Saturn-sized planet on an 84-day orbit
Authors: Eisner N L , Barragán O , Aigrain S , Lintott C , Miller G , Zicher N , Boyajian T S , Briceño C , Bryant E M , Christiansen J L , Feinstein A D , Flor-Torres L M , Fridlund M , Gandolfi D , Gilbert J , Guerrero N , Jenkins J M , Jones K , Kristiansen M H , Vanderburg A , Law N , López-Sánchez A R , Mann A W , Safron E J , Schwamb M E , Stassun K G , Osborn H P , Wang J , Zic A , Ziegler C , Barnet F , Bean S J , Bundy D M , Chetnik Z , Dawson J L , Garstone J , Stenner A G , Huten M , Larish S , Melanson L D , Mitchell T , Moore C , Peltsch K , Rogers D J , Schuster C , Smith D S , Simister D J , Tanner C , Terentev I , Tsymbal A
Published: January 2020

We report on the discovery and validation of TOI 813 b (TIC 55525572 b), a transiting exoplanet identified by citizen scientists in data from NASA’s Transiting Exoplanet Survey Satellite (TESS) and the first planet discovered by the Planet Hunters TESS project. The host star is a bright (V = 10.3 mag) subgiant ($R_\star =1.94\, R_\odot$, $M_\star =1.32\, M_\odot$). It was observed almost continuously by TESS during its first year of operations, during which time four individual transit events were detected. The candidate passed all the standard light curve-based vetting checks, and ground-based follow-up spectroscopy and speckle imaging enabled us to place an upper limit of $2\, M_{\rm Jup}$ (99 per cent confidence) on the mass of the companion, and to statistically validate its planetary nature. Detailed modelling of the transits yields a period of $83.8911 _{ - 0.0031 } ^ { + 0.0027 }$ d, a planet radius of 6.71 ± 0.38 R⊕ and a semimajor axis of $0.423 _{ - 0.037 } ^ { + 0.031 }$ AU. The planet’s orbital period combined with the evolved nature of the host star places this object in a relatively underexplored region of parameter space. We estimate that TOI 813 b induces a reflex motion in its host star with a semi-amplitude of ∼6 m s−1, making this a promising system to measure the mass of a relatively long-period transiting planet.
Decision Making in Retroperitoneal Nerve Sheath and Nerve-Associated Tumors: A Modular Approach
Authors: Heinen Christian , Schmidt Thomas , Kretschmer Thomas
Published: January 2020

BACKGROUND

Surgical treatment of retroperitoneal nerve and nerve-associated tumors is challenging, especially in cases with large extent. A single surgical access may have limitations and jeopardize patients.

OBJECTIVE

To present a series of patients to illustrate our individually tailored treatment concept and decision pathway.

METHODS

Retrospectively, clinical findings and imaging were related to surgical features and outcome. An algorithm for choice of approach was established.

RESULTS

From 2012 to 2017, we operated on n = 13 patients with retroperitoneal tumors, of these n = 9 were included (n = 6 female, n = 3 male). Histological findings included n = 2 schwannomas, n = 2 malignant peripheral nerve sheath tumors, n = 1 non-origin sarcoma, n = 1 perineurioma, n = 1 intraneural ganglion cyst, n = 1 lymphoma, and n = 1 paraganglioma.

 In n = 6 patients, we used a monoportal (retroperitoneal/transperitoneal) approach; in n = 2 patients, a biportal retroperitoneal to inguinal/transperitoneal to dorsal approach; and in n = 1 patient, a triportal transperitoneal to dorsal to gluteal approach.

 In n = 2 patients, we performed an open biopsy only; in n = 2 patients, a tumor enucleation; in n = 3 patients, a subtotal function-sparing resection; in n = 1 patient, a complete resection; and in n = 1 patient, intraneural decompression.

 In n = 1 patient, a new motor deficit appeared. n = 4 patients required further radio-oncological treatment. n = 8/9 patients are alive without tumor progress or recurrence.

CONCLUSION

Retroperitoneal nerve or nerve-associated tumors encompass multiple entities. Depending on suspected histology and tumor extension, extensile or combined surgical approaches may be necessary. We present our algorithm for assessment and decision-making regarding surgical access ports and pathways.
Molecular profiling-based decision for targeted therapies in IDH wild-type glioblastoma
Authors: Kessler Tobias , Berberich Anne , Casalini Belen , Drüschler Katharina , Ostermann Hannah , Dormann Andrea , Walter Sandy , Hai Ling , Schlesner Matthias , Herold-Mende Christel , Jungk Christine , Unterberg Andreas , Bendszus Martin , Sahm Katharina , von Deimling Andreas , Winkler Frank , Platten Michael , Wick Wolfgang , Sahm Felix , Wick Antje
Published: January 2020

Background

Molecular profiling allows tumor classification as well as assessment of diagnostic, prognostic, and treatment-related molecular changes. Translation into clinical practice and relevance for patients has not been demonstrated yet.

Methods

We analyzed clinical and molecular data of isocitrate dehydrogenase wild-type glioblastoma patients with sufficient clinical follow-up from the Heidelberg Neuro-Oncology Center and with molecular analysis of tumor tissue that consisted of DNA methylation array data, genome-scale copy number variations, gene panel sequencing, and partly mTOR immunohistochemistry between October 2014 and April 2018.

Results

Of 536 patients screened, molecular assessment was performed in 253 patients (47%) in a prospective routine clinical setting with further clinical appointments. Therapy decision was directly based on the molecular assessment in 97 (38%) patients. Of these, genetic information from MGMT (n = 68), EGFR (n = 7), CDKN2A/B (n = 8), alterations of the PI3K–AKT–mTOR pathway (n = 5), and BRAF (n = 3) have been the most frequently used for decision making with a positive overall survival signal for patients with glioblastoma harboring an unmethylated MGMT promoter treated according to the molecular assignment. Based on detected molecular alterations and possible targeted therapies, we generated an automated web-based prioritization algorithm.

Conclusion

Molecular decision making in clinical practice was mainly driven by MGMT promoter status in elderly patients and study inclusion criteria. A reasonable number of patients have been treated based on other molecular aberrations. This study prepares for complex molecular decisions in a routine clinical decision making.
Decrease in Resting Heart Rate Measured Using Smartphone Apps to Verify Abstinence From Smoking: An Exploratory Study
Authors: Herbec Aleksandra , Parker Ella , Ubhi Harveen Kaur , Raupach Tobias , West Robert
Published: January 2020

Introduction

Verifying self-reports of smoking abstinence is challenging in studies that involve remote data collection. Resting heart rate (HR) decreases during smoking abstinence. This study assessed whether a decrease in resting HR measured using freely available smartphone apps could potentially be used to verify smoking abstinence.

Methods

This study involved a repeated measures experimental design, with data collection in natural setting. Participants were 18 adult, daily smokers. They recorded resting HR in beats per minute (bpm) using freely available smartphone apps during five timepoints (two in the morning and three postnoon) on each of 3 days. The outcome measure was the mean of the postnoon HR recordings. The experimental condition for each of the 3 days (counterbalanced order) was as follows: (1) smoking as usual, (2) not smoking without nicotine replacement therapy (NRT), or (3) not smoking but using NRT. Abstinence was verified using expired-air carbon monoxide (CO) concentration.

Results

Compared with the smoking as usual condition, mean HR was 13.4 bpm lower (95% confidence interval [CI] = 5.4 to 21.4, p = .001) in the not smoking without NRT condition and 10.4 bpm lower (95% CI = 3.1 to 17.8, p = 0.004) in the not smoking with NRT condition. There was no statistically significant difference in HR between the two not smoking conditions (p = .39). Abstinence during not smoking days without and with NRT was CO-verified in 18/18 and in 16/18 cases, respectively.

Conclusions

Self-recording of resting HR in natural setting using smartphone apps shows a reliable decrease in response to smoking abstinence and may provide a basis for remote verification in smoking cessation studies.

Implications

Remote verification of self-reported abstinence in smoking cessation studies remains challenging. Smoking abstinence has been shown to decrease resting HR under laboratory conditions. This study demonstrated that self-recording using freely available smartphone apps shows reliable decreases in resting HR during smoking abstinence and may provide a basis for inexpensive remote verification of smoking abstinence.
The Relation between the Treatise and the Enquiry
Authors: Qu Hsueh M.
Published: January 2020

This chapter outlines two critical interpretive issues: the relationship between Hume’s scepticism and his naturalism; and the relationship between the Treatise of Human Nature and the Enquiry concerning Human Understanding. In particular, it makes a preliminary case that these two interpretive issues are intimately connected: Hume changes his epistemology between the Treatise and the Enquiry due to a dissatisfaction with his treatment of scepticism in the former work. The chapter offers a preliminary investigation of Hume’s characterisation of the relationship between the Treatise and the Enquiry. It outlines a case for Hume’s motivation in writing the Advertisement and the Enquiry being a concern for his intellectual legacy. In particular, it is suggested that the Enquiry and the Advertisement are meant to rectify Hume’s treatment of scepticism in the Treatise.
Hume’s Aims
Authors: Qu Hsueh M.
Published: January 2020

This chapter compares Hume’s characterisation of his aims and methodologies in the Introduction to the Treatise of Human Nature and Section 1 of the Enquiry concerning Human Understanding. It finds that key among the differences between the two is that EHU 1 stresses the taxonomic project of ‘mental geography’ (EHU 1.13), and also a negative project of rejecting false metaphysics, both of which are absent from the Introduction to the Treatise. This ‘mental geography’ will prove crucial to the negative project of rejecting false metaphysics, and foreshadows Hume’s more comprehensive presentation of his epistemology in EHU 12. The chapter argues that these differences suggest that the Enquiry is a more normatively focused work than the Treatise.
Battling for the Story
Authors: Callison Candis , Young Mary Lynn
Published: January 2020

Social media has shifted the terrain for journalism, and offers platforms for counter-narratives, alternative views, and broader expertise. In Chapter 2, we focus on the social media response in three specific cases: (1) two separate trials for the murders of two Indigenous youth, Colten Boushie and Tina Fontaine, in central Canada, in which the two white men accused in their homicides were acquitted within a month of each other in early 2018; (2) the 2015 civil trial and discrimination case brought by Ellen Pao, a Silicon Valley venture capitalist, who was forced out of her job; (3) a 2016 #MeToo related moment in which writer Kelly Oxford asked women to share their stories through #notokay. In all three cases, we find a “battle for the story” that plays out in a range of ways from a refusal to participate, to talking back and resisting journalism’s habit of “hoarding the mic.”
Dominant Crisis Narratives and Changing Infrastructures
Authors: Callison Candis , Young Mary Lynn
Published: January 2020

In Chapter 4, we examine efforts to address reckoning at one of Canada’s most respected legacy journalism organizations: the Toronto Star. Methodologically, we draw on a number of sets of data: public and policy discourse about the journalism crisis in Canada, recent events related to race and gender at the Star, and ethnographic fieldwork and interviews with Star journalists regarding the development of data journalism. Our analysis generates questions about how news organizations are wrestling concurrently with structural critique, economic challenges, and technological transformation. The gender, race, and colonial reckoning that we find in other chapters, we see internally at the Star where long-standing issues with “the view from nowhere,” the challenge of closed systems of journalism, and legacy organizations’ openness to change are conjoined with issues such as methodological interpretation, journalism’s colonial history and its systematic whiteness, and exclusion of Indigenous and minority journalists.
Indigenous Journalisms
Authors: Callison Candis , Young Mary Lynn
Published: January 2020

Chapter 6 draws on ethnographic fieldwork and interviews with Indigenous journalists in Canada and the United States who have been addressing colonialism, race, and gender in their journalism all along. Indigenous journalists articulate the challenges of working in and among mainstream media that has largely erased and misrepresented Indigenous voices, communities, and concerns on a range of issues. They undertake a differentiated set of approaches that draw on journalism ideals and get at deeper problems structurally such that transformation within journalism as profession, identity, and method might be possible. As a result, Indigenous journalists are using digital media to transform journalism methods, decolonizing journalism ideals like “fairness and balance” by drawing from Indigenous knowledge, histories, and relational frameworks. This chapter provides a bookend to Chapter 1 by offering a pathway into discussing not only new bases for ethical consideration but also provides examples of some of the multiple journalisms available through digital media.
Hatred of Inferiority and Confrontation with the West
Authors: Daneshgar Majid
Published: January 2020

This chapter focuses particularly on the influence on Muslim approaches to the West and Westerners and the study of the Qurʾān in the Muslim academy of Edward W. Said’s important work on cultural representation, Orientalism. It looks at how Said did not, in the nature of things, accurately depict the West and Westerners and how, in respect to the study of Islam, Muslims have tended to substitute Western scientists and literary figures for Western scholars of Islam. Finally, chapter 4 seeks to explain how a Muslim “inferiority complex,” as (tacitly) played out in Orientalism, has over the years been absorbed into the religious teaching of Islam and given rise to much of the substance to the defensive quality of the “Islamic Apologetics” that the Muslim academy has opposed to historical critical Islamic studies.
BCG and Technopolitics from Europe to Empire
Authors: Velmet Aro
Published: January 2020

This chapter describes how the BCG vaccine became a technopolitical weapon in an empire divided between social hygienist and Pastorian interventionist approaches to public health. Albert Calmette and Camille Guérin’s vaccine came under attack in Europe, particularly after a batch of contaminated vaccines killed dozens of infants in Lübeck, Germany. Deploying the vaccine in the empire helped Pastorians to strengthen their claims of the vaccine’s safety and respond to critics at the League of Nations. For imperial administrators, BCG was a cheaper alternative to social hygienist solutions such as shorter working hours, vacations, and sanatoriums, which Vietnamese doctors increasingly suggested. The chapter also highlights the importance of the Rockefeller wartime mission to France.
Pushing Citizens Aside
Authors: Gastil John , Knobloch Katherine R.
Published: January 2020

Democracy has always been an experiment in institutional design. From ancient Athens to the modern jury, democratic governance abounds with attempts to introduce citizens into governing processes. As chapter 2 shows, many of these institutional innovations, however, have been replaced with replicas that do little to empower the public. Even elite institutions designed for deliberative discussions, such as legislatures, have become beholden to partisan politics that result in a line-up of speakers with no listeners. Elections have suffered a similar fate with moneyed rhetoric and media behemoths focused on profit displacing informed discussion among citizens. The problem is exacerbated by the rising power of campaign consultants motivated to win at all costs and, most recently, the exceptional disregard for facts in recent populist campaigns, such as that of Donald Trump in 2016.
Progressive Politics in the Pacific Northwest
Authors: Gastil John , Knobloch Katherine R.
Published: January 2020

Through interviews with the civic innovators responsible for bringing these civic innovations into existence, chapter 4 recounts the development of Citizens’ Juries and the Citizens’ Initiative Review (CIR). Since the 1970s, Citizens’ Juries have convened a sample of approximately twenty-four citizens, reflective of the demographics of the communities from which they are drawn, to collectively study, discuss, and assess policies and electoral candidates. The CIR was born of this idea. It asks citizens to study a ballot measure and then provide an assessment of that measure for the wider public to utilize when casting their ballots. In the chapter’s telling of these stories, readers are introduced to four civic reformers—Ned Crosby, Pat Benn, Tyrone Reitman, and Elliot Shuford. Each of these individuals played a key role in the design, lobbying, and eventual implementation of the CIR.
Describing Calvinism
Authors: Rester Todd
Published: January 2020

The term “Calvinism” and the propriety, accuracy, and utility of its usage have become the focus of debates in historical theology and in social and cultural history. The word is a terminological construction referring to an array of controversies within and between religious communities and cultures, representing contested cultural values, practices, and visions for the church and for society. These polemical constructions of Calvinism and Reformed frequently depend on confessional sources. These controversies, which took place over several centuries, must be evaluated in their varying historical, geographical, social, cultural, and intellectual contexts. This chapter evaluates the sources that have been polemically deployed for the construction of the terms “Calvinism” and “Reformed.”
Calvinism and Theater in Early Modern England and the Dutch Republic
Authors: Sierhuis Freya , Streete Adrian
Published: January 2020

The effect of Calvinism on European literary culture was powerful and long-lasting, creating a highly mobile, dynamic, transnational community of writers, publishers, translators, and readers. Many of these readers of Calvin had an interest in the stage. After all, the Institutes of the Christian Religion was translated into English in 1561 by Thomas Norton, coauthor of the blank verse, political tragedy Gorboduc. Calvin’s ideas and imagery were appropriated by English and Dutch playwrights from across the confessional spectrum. This chapter argues that there is a distinctiveness to this literature, often itself the product of the experience of religious war, persecution, and exile: a militant, combative providentialism, combined with a pronounced dualism, often shading over into apocalypticism; a preoccupation with, and fear of, the dangers of idolatry; and an inclination to a rigorous, frequently punishing, form of religious introspection and self-examination.
Critical Realism and Contrastive Ethnography
Authors: Decoteau Claire Laurier
Published: January 2020

Though critical realism has been featured in sociological debates about the philosophy of science, its relevance to methodological considerations, and especially to ethnographic scholarship, is quite limited. This chapter combines an extended case method approach to ethnography with a critical realist approach to comparison. Critical realism augments ethnographic comparison in two ways: 1) by showing that one can compare across both events and causal mechanisms due to ontological stratification; and 2) by considering the conjunctural and contingent nature of causality. However, critical realism’s emphasis on causality is also complicated by ethnographic research, which sheds light on the mutual causal relationship between structures and actors. This chapter, therefore, considers what critical realism has to offer ethnography and what ethnography, in turn, offers critical realism. It does so by comparing the experiences and beliefs of Somali refugee communities in Minneapolis and Toronto, who are contending with high rates of autism spectrum disorder and have forged epistemic communities united around an etiology, ontology, and treatment protocol that challenges mainstream science.
Using Computational Tools to Enhance Comparative Ethnography
Authors: Bernstein Alissa , Dohan and Daniel
Published: January 2020

The medical profession has invested untold treasure in quantifying bodily processes, and excellence in the quantified biological sciences has long been the surest route to professional fame. Yet the profession also recognizes that success in the healing arts requires a grasp and appreciation of narrative and culture. Culture shapes biomedicine in at least three ways, all of which may be interrogated through ethnography. First, biomedicine has imbued the provider–patient relationship with special cultural status, and ethnography can provide insights into the nature of this relationship (which has been variously interpreted as a necessary component of a functional society, a hallmark of occupational power, or an aspect of boundary work by a knowledge profession). Second, biomedicine recognizes that health is shaped by culturally mediated behaviors that typically occur outside the clinical setting and are thus beyond providers’ immediate apprehension and control. Ethnography can provide insights into these behaviors. Finally, the scale of contemporary biomedicine (healthcare spending accounts for one-sixth of gross domestic product) has produced complex cultural institutions. Ethnographic insights are needed to characterize the organizational culture of medicine and improve the practice of healing.