bluuebunny/crossref_metadata_2025 huggingface dataset:
Variability in the use of cut-off points with different commercial and lab-developed assays for PD-L1 expression testing in the NSCLC clinical setting in the United States.
Authors: De Richter Pieter
Published: November 2019

46

Background: Following the recent approval of several companion diagnostic and complementary diagnostic assays for PD-L1 expression testing, as well as the availability of multiple antibodies for use in laboratory testing, pathologists have a range of tools at their disposal for measuring expression levels of this predictive biomarker. While specific cut-off points for positivity are specified by the assay manufacturer and/or recommended based on trial data, clinicians can choose different cut-off points to define positivity. In this study, we explore the variety of test brands and cut-off points that are being used in clinical practice in the US by examining real-world usage data. Methods: Between June and August 2016, a panel of pathologists (n = 27) in the US were asked to report on their practices relating to PD-L1 expression testing for NSCLC patients, through the submission of online de-identified record forms (n = 167 PD-L1-tested samples). Results: Of the 167 samples, 112 (67%) were tested with the Dako 22C3 pharmDx assay, 37 (22%) with the Dako 28-8 pharmDx assay and 16 (10%) with a lab-developed test (LDT). When using 22C3 pharmDx, 72% of samples were tested with the recommended 50% cut-off point, with the remaining 28% using lower cut-off points, ranging from 1% to 25%. For 28-8 pharmDx, both the 1% cut-off point (in 54% of cases) and the 5% cut-off point (in 35% of cases) were frequently used (1% recommended; 5% being investigated in clinical trials e.g. CHEKMATE-026). LDTs were mostly (88%) employed with a cut-off of 1% across antibodies. Conclusions: The use of PD-L1 expression testing to determine eligibility for PD-(L)1 inhibitors in the clinical setting shows significant fragmentation in the US, with multiple different assays being employed. Furthermore, there is a lack of standardization in terms of the cut-off points that are used when testing with each of those assays. This lack of consistency adds a level of complexity to oncologists treatment decisions when choosing whether or not to treat with a PD-(L)1 inhibitor, and which brand to choose.
Differences in immune profiles of metastatic melanoma patients treated with anti-CTLA-4 and anti-PD-1 combined immunotherapy.
Authors: Gide Tuba Nur , Quek Camelia , Madore Jason , Menzies Alexander M. , Dent Rebecca , Carlino Matteo S. , Guminski Alex , Saw Robyn , Thompson John F. , Wilmott James S. , Scolyer Richard A. , Long Georgina V.
Published: November 2019

51

Background: Immune checkpoint inhibitors targeting the cytotoxic T-lymphocyte antigen 4 (CTLA-4) and programmed cell death 1 (PD-1) receptor have significantly improved the outcomes of metastatic melanoma patients resulting in durable response and longer overall survival. However, while some patients exhibit a complete response to immunotherapy, others have demonstrated little to no response. The aim of this study is to examine the immune cell subsets between the good and poor responders to anti-CTLA-4 and anti-PD-1 combined immunotherapy in order to determine potential mechanisms of response and resistance. Methods: Multiplex immunofluorescent staining was performed on pre-treatment formalin-fixed, paraffin-embedded (FFPE) tissue samples from good and poor responders ( n= 17; n= 11 good responders, n= 6 poor responders) for markers including CD8, PD-1, PD-L1, FOXP3 and SOX10. Spectral image analysis was conducted via the Vectra 3.0 imaging system. Quantitative analysis was carried out using the inForm software. Gene signatures associated with the T-cell signalling pathways were identified following RNA sequencing of FFPE samples. Results: Good responders displayed significantly higher levels of baseline intratumoural PD-1 and PD-L1 expression in comparison to the poor responders ( P= 0.01 and P= 0.01 respectively), highlighting their roles as predictive biomarkers of response. Additionally, the CD8+ T-cell to PD-L1 ratio was significantly higher ( P= 0.001) in the tumours of the poor responders, indicating a distinction in the CD8+ T-cell phenotypes between the good and poor responders. Furthermore, analysis of the RNA sequencing data revealed a panel of immune signatures that have been implicated in prognosis and responsiveness to immunotherapy in melanoma. Conclusions: In summary, these findings provide insight into the possible biomarkers of response and resistance to immunotherapy, thus improving our understanding of the mechanisms driving variations in response.
The prognostic impact of CD3, CD8, FoxP3, and IL17 tumor-infiltrating immune cells in periampullary cancer differs by morphological type and adjuvant chemotherapy.
Authors: Warfvinge Carl Fredrik , Lundgren Sebastian , Elebro Jacob , Heby Margareta , Krzyzanowska Agnieszka , Bjartell Anders , Nodin Bjorn , Eberhard Jakob , Leandersson Karin , Jirstrom Karin
Published: November 2019

53

Background: The prognostic impact of tumor-infiltrating T lymphocytes has been evaluated in periampullary carcinoma, but previous studies have not taken into consideration the different morphological subtypes of cancers derived from the periampullary region. Herein, we investigated the prognostic impact and distribution of tumor-infiltrating CD3+, CD8+, FoxP3+ T lymphocytes as well as IL-17+cells in periampullary adenocarcinoma, with particular reference to morpohological subtyoe. Methods: Counts of CD3+, CD8+, FoxP3+ T lymphocytes, and IL-17+cells were assessed using immunohistochemistry on tissue microarrays with tumors from a consecutive retrospective cohort of 175 patients with resected periampullary adenocarcinoma; 110 of pancreatobiliary type (PB-type) and 65 of I intestinal type (I-type). Results: Distribution of all evaluated immune cells differed significantly between PB- and I-type tumors. In I-type tumors, the ratios of IL-17+/FoxP3+ and IL-17+/CD3+ were independent factors of poor prognosis. Notably, the unfavorable prognostic impact of IL-17+ was only evident in cases that had not received adjuvant chemotherapy. In PB-type tumors, CD3+was an independent marker of good prognosis. Conclusions: The results from this study highlight that the composition and prognostic importance of various subsets of infiltrating immune cells in periampullary adenocarcinoma differ by morphological subtype, and potentially by adjuvant chemotherapy.
Estimating long-term survival of PD-L1-expressing, previously treated, non-small cell lung cancer patients who received pembrolizumab in KEYNOTE-001 and -010.
Authors: Hellmann Matthew David , Ma Junshui , Garon Edward B. , Hui Rina , Gandhi Leena , Soria Jean-Charles , Anderson Keaven M. , Lubiniecki Gregory M. , Piperdi Bilal , Herbst Roy S.
Published: November 2019

77

Background: Pembrolizumab showed promising activity in patients with advanced non–small cell lung cancer (NSCLC) in the KEYNOTE-001 study (NCT01295827) and significantly prolonged overall survival (OS) compared with docetaxel in the randomized KEYNOTE-010 study (NCT01905657). Responses to pembrolizumab appear to be remarkably durable, making long-term survival possible in some patients. Typical parametric survival models do not account for the possibility of long-term survival. An alternative, well-established class of statistical models called long-term survival models can be used to directly estimate the percentage of patients achieving long-term survival (>5 years), called “long-term survival rate.” (Berkson J, Gage RP. J Am Stat Assoc. 1952;47:501-515.)(Tsodikov AD et al. J Am Stat Assoc. 2003;98:1063-1078.) Methods: Data from patients with PD-L1–expressing (tumor proportion score ≥1%), previously treated, advanced NSCLC in KEYNOTE-001 and KEYNOTE-010 were used. KEYNOTE-001 data were used to initially estimate the long-term survival rate of pembrolizumab, while KEYNOTE-010 data were used for subsequent independent validation. Point estimates of long-term survival rates with their 95% CIs based on the model described above are reported. Results: Based on the long-term survival model, the estimated long-term survival rate in pembrolizumab-treated population in KEYNOTE-001 (n = 306) is 25.4% (95% CI, 15.2%-33.3%) and the intention-to-treat population who received pembrolizumab in KEYNOTE-010 (n = 690) is 25.3% (95% CI, 8.9%-36.9%). In contrast, the long-term survival rate of docetaxel arm (n = 343) in KEYNOTE-010 is estimated to be 3.2% (95% CI, 0%-17.4%). Conclusions: In 2 independent data sets, it is estimated that 25% of patients with previously treated PD-L1–expressing NSCLC may achieve long-term benefit from pembrolizumab monotherapy. Long-term survival models can provide an early estimate of long-term benefit from pembrolizumab using data with limited follow-up time. Long-term follow-up from these trials will further validate this finding. MDH and JM are co-first authors.
Verification of the analytical performance of a molecular diagnostic for response to anti-PD1 therapy on the nCounter Dx Analysis System.
Authors: Wallden Brett , Pekker Irena , Popa Simina , Dowidar Naeem , Ngouenet Celine , Sullivan Amy , Danaher Patrick , Mashadi-Hossein Afshin , Liu Mingdong , Marton Matthew John , Ferree Sean , Storhoff James Justin
Published: November 2019

8

Background: Pembrolizumab is a humanized anti-PD1 antibody that is approved for use in advanced melanoma, recurrent or metastatic head and neck squamous cell carcinoma, and metastatic non-small-cell lung cancer. It has also shown clinical activity in a number of other tumor types in clinical trials, but there is need for a precise and accurate test that can identify patients most likely to benefit from therapy. We have previously described the development and analytical performance of a NanoString RNA expression clinical trial assay, referred to here as the Tumor Inflammation Signature (TIS) assay, which is being evaluated as a patient enrichment biomarker in multiple solid tumor types for treatment with pembrolizumab. Here we describe additional performance data and analytical verification of reproducibility from tissue and RNA input range in multiple tumor types. Methods: Linearity and specificity were assessed with single targets or pools of in vitro transcribed RNAs with sequences matching the 18 biomarker and 10 normalization gene probe targets. The verification of the previously reported analytical precision from RNA and reproducibility from tissue was performed using independent samples from 11 tumor types. The biological variability of the signature within a patient sample was evaluated by testing multiple core punches from formalin fixed paraffin embedded (FFPE) tissue blocks. Results: The TIS assay’s measurement of the 28 genes was linear across a wide dynamic range ( ≥ 4 logs) and was highly specific with < 1% cross reactivity between probes. The assay was verified across the specified RNA input range with > 90% concordance at the low end (50ng) of the RNA input range. The total standard deviation of the anti-PD1 Predictor Score from tissue was verified as < 5% of the signature score range and > 90% concordance in biomarker high/low categorization within the biological replicates. Conclusions: The analytical performance of the NanoString TIS assay was verified to be robust. The assay is well suited for decentralized clinical testing and is currently under investigation to identify responders to anti-PD1 therapy in multiple tumor types in several clinical studies.
A 3D image-based quantification of immune cell-tumor spheroid interactions in the presence of checkpoint inhibition.
Authors: Daszkiewicz Lidia , Klop Maarten , Yan Kuan , Price Leo
Published: November 2019

82

Background: Delivering on the promises of cancer immunotherapy is hampered by a lack of in vitro testing platforms that enable the early selection of promising drugs candidates. While quantification of the number of cytotoxic T cells and IFNγ secretion can give an indication of the drug effect, it is often critical to assess the functional cytotoxicity and infiltration capacity. In addition, immunomodulatory effects of drug combinations need to be carefully assessed before these treatment modalities reach patients. However there are unlimited possibilities of new combinations, especially in the view of synergy effects observed with double checkpoint inhibition blockade and combination with standard of care drugs. To specifically address the needs of immunotherapy cancer drug developers, we developed robust assays that incorporate the human immune system into tumor spheroid cultures, with functional read-outs in a high throughput (384well plate) format. Methods: Breast cancer cells were grown in a hydrogel to form 3D tumoroids. HLA-matched PBMCs with and without pre-activation/exhaustion were added and the infiltration of T cells and subsequent tumoroid killing was quantified. The effect of immune checkpoint blockade was also assessed with the addition of pembrolizumab. Quantification of effects of stimulators and checkpoint inhibition was achieved with 3D imaging and morphometric analysis with OMiner software. Results: Automated 3D image and data analysis enabled discrimination of immune-tumour cell interactions depending on activation status of T cells. Activated T cells more efficiently infiltrated and killed tumoroids than non-activated ones. Cytotoxic activity of overactivated/exhausted T cells was supressed but this could be reversed by the presence of checkpoint inhibitor in the coculture. Conclusions: A 3D environment allows the different cell types to engage in a more realistic setting than when cells are grow in a monolayer. Using image-based analysis, immune-tumor interactions can be dissected. This represents a new, highly powerful tool for cancer immunotherapy drug developers to select the most promising compounds, allowing faster progression towards the clinic.
Immune priming by stereotactic body radiation: Dosimetric characteristics.
Authors: Castaneda Serguei A. , Shah Sunjay A , Huang David , Sims-Mourtada Jennifer , Mourtada Firas
Published: November 2019

85

Background: A systemic immune response to tumors after stereotactic body radiation therapy (SBRT) has been observed. The role of radiation dosimetry variables in priming an immune response is not well characterized. Methods: We analyzed radiation dosimetry variables in a patient with metastatic melanoma receiving pembrolizumab for about 1 year prior to concurrent use with Cyberknife SBRT for a symptomatic lesion in the right lower lobe of the lung. The patient received 50 Gy in 5 fractions prescribed to the 74% isodose line (using a Monte Carlo dose calculation) and developed a systemic immune response three months after this intervention. Results: We observed priming of the immune system as man ifested by radiological and clinical responses in non-irradiated cervical lymph nodes and a new persistent FDG-avid lesion on PET scan located in the base of the tongue. Given the concern for a new malignancy, the patient underwent hemi tongue base glossectomy; interestingly, this surgical specimen showed tonsillar mucosa with reactive lymphoid hyperplasia without evidence of tumor. Upon review of the CyberKnife SBRT plan, we identified that the planning target volume (PTV) was atypically under covered to 89.9% and also had a relatively high value of gross tumor volume (GTV) conformity index (CI) of 2.1. In our experience with CyberKnife plans for lung lesions, usually the PTV coverage is more than 95% and the GTV CI is less than 1.5. Other dosimetry variables had more typical values, including GTV coverage of 99.9%, PTV CI of 1.1, and both GTV and PTV homogeneity index of 1.4. Conclusions: Relatively low PTV coverage and high GTV CI were associated with immune system priming in a well-documented case of systemic responses in non-irradiated pathological and normal tissues, in the setting of concurrent immunotherapy and SBRT. Further studies are warranted to confirm this association.
Phase II study of nivolumab in patients with advanced non-small cell lung cancer (NSCLC) in Korea.
Authors: Park Keunchil , Cho Eun Kyung , Kang Jin Hyoung , Han Ji-Youn , Lee Jong Seok , Kim Dong-Wan , Kim Sang-We , Cho Byoung Chul , Min Young Joo , Lee Ki Hyeong , Kim Joo-Hang
Published: November 2019

92

Background: Nivolumab (BMS-936558/ONO-4538), a fully human IgG4, PD-1 immune-checkpoint inhibitor antibody, has shown durable clinical activity in several tumor types. Recently, two phase III studies (CheckMate-017 and -057) demonstrated that nivolumab improved overall survival (OS) than docetaxel in second-line of squamous (SQ) and non-squamous (NSQ) Non-Small Cell Lung Cancer (NSCLC), respectively. Here, we report the results of a phase II study to evaluate the efficacy and safety of nivolumab in Korean patients (pts) with previously treated advanced SQ and NSQ NSCLC. Methods: This study requires pts aged ≥ 20 years with ECOG Performance Status (PS) of 0 or 1, stage IIIB/IV or recurrent NSCLC and at least one prior chemotherapy including platinum containing regimen. Pts received nivolumab 3 mg/kg IV Q2W until progression or unacceptable toxicity. The primary endpoint in this study was the objective response rate (ORR) (RECIST v1.1). Results: Nivolumab was administered to 100 NSCLC pts (SQ: 44, NSQ: 56), male/female: 78 (SQ: 44, NSQ: 34)/22 (SQ: 0, NSQ: 22); PS 0/1: 14 (SQ: 6, NSQ: 8)/86 (SQ: 38, NSQ: 48); aged 29 to 80 [median: 66.5] years (SQ: 40 to 80 [median: 69.5], NSQ: 29 to 77 [median: 63.5]); Stage IIIB/IV/recurrence: 6 (SQ: 5, NSQ: 1)/91 (SQ: 37, NSQ: 54)/3 (SQ: 2, NSQ: 1)). In SQ and NSQ NSCLC, ORR was 15.9% (7/44) and 23.2% (13/56), respectively. Median progression-free survival was 2.6 mo and 5.3 mo, respectively. Complete Response was observed in 2.3% (1/44) and 1.8% (1/56), respectively. Median OS was 12.3 mo and 16.3 mo, respectively. Median follow-up was 8.9 mo and 12.3 mo, respectively. Most common adverse drug reaction (ADR) was decreased appetite 15.9% (7/44), followed by pyrexia 9.1% (4/44) in SQ NSCLC, and decreased appetite 12.5% (7/56), followed by pruritus 10.7% (6/56), fatigue 8.9% (5/56), pyrexia 5.4% (3/56) and nausea 5.4% (3/56) in NSQ NSCLC. Grade 3-4 ADR was observed in 6.8% (3/44) and 10.7% (6/56) of SQ and NSQ NSCLC, respectively. No interstitial lung disease and no grade 5 ADRs were observed in this study. Conclusions: Nivolumab was considered to be effective and used safely in Korean pts with SQ and NSQ NSCLC as well as in non-Korean pts with SQ and NSQ NSCLC. Clinical trial information: NCT02175017.
Correlation of PD-L1 with VEGF and KI-67 index in patients with primary glioma.
Authors: Xue Song , Hu Man , Yu Jinming , Fan Bingjie , Ma Ji
Published: November 2019

94

Background: The treatment strategies for glioma, especially glioblastoma multiforme, are not effective. The programmed death ligand 1 (PD-L1) immune escape and increased angiogenesis may be two of the underlying sources of treatment resistance. However, the relationship between these pathways in human glioma is still unknown. Methods: Data for 64 patients with primary glioma recorded from June 2007 to December 2013 in Shan Dong Cancer Hospital were immunohistochemically evaluated for the expressions of PD-L1, VEGF, MMP-9 and KI-67 index. Image ProPlus software was used to quantify the mean optical density (MOD) of the immunohistochemical image. Results: PD-L1 expression was observed in 65.22% of low-grade glioma and 90.24% of high-grade glioma, respectively. The whole expression rate of PD-L1 in glioma was 81.25%. The expression of PD-L1 is significantly related to pathological grade ( p <0.001), VEGF ( p= 0.017) and KI-67 index ( p= 0.009). The mean of PD-L1 MOD in High-grade group was 0.1144±0.02754, higher than that in low-grade group, 0.005129±0.001441 ( p= 0.004). In addition, Expression of VEGF, MMP-9 and KI-67 was significantly different between low-grade and high-grade gliomas ( p= 0.008, 0.04, 0.004 for VEGF, MMP-9 and KI-67, respectively). When analyzed as a continuous variable, the expressions of PD-L1 was positively correlated with VEGF (r = 0.392, p= 0.001) and KI-67 (r = 0.388, p= 0.001). Conclusions: These data suggest, for the first time, that PD-L1 play an important role in glioma angiogenesis and proliferation potential, providing the possibility for considering additional combinations of targeted VEGF therapies and anti-PD-L1 immunotherapy for the treatment of human brain glioma.
Immune checkpoint inhibitor responses in humanized mouse melanoma models using patient-derived xenografts.
Authors: Somasundaram Rajasekharan
Published: November 2019

99

Background: Melanoma patients develop resistance to both chemo- and targeted-therapy drugs. Promising pre-clinical and clinical results with immune checkpoint inhibitors using antibodies directed against CTLA-4 and PD-1 have re-energized the field of immune-based therapies in melanoma. However, only a third of melanoma patients respond to immune checkpoint blockade. Currently available mouse xenograft and transgenic mouse melanoma models have a number of short comings and are unable to address the basis of drug resistance and immune non-responsiveness that are frequently observed in melanoma patients. Thus there is an urgent need to establish an in vivo model with a human immune microenvironment that can address issues of therapy resistance. Methods: Our laboratory has developed a humanized mouse melanoma model using patient-derived xenografts (PDX). Results: Immunodeficient NSG mice were reconstituted with human CD34+ cells and after 7-9 weeks, mature human CD45+ cells were observed in circulating blood. Humanized mice were then challenged with HLA-matched melanoma PDX and the functional ability of human immune cells to restrict tumor growth was monitored. Delayed tumor growth was observed in humanized mice indicating in vivo sensitization of human immune cells to melanoma. This was confirmed by in vitro demonstration of human lymphocytes from tumor-bearing mice showing enhanced cytokine expression after stimulation with melanoma antigen peptides. Further, cytotoxic T-cells derived from melanoma peptide stimulation were able to functionally lyse tumor cells in vitro. In preliminary therapy studies, a majority of tumor-bearing humanized mice treated with anti-PD-1 antibody showed restricted tumor growth and a combination of BRAF inhibitor and anti-PD1 antibody treatment showed prolonged survival. Conclusions: Our results suggest that humanized mouse melanoma model can be explored further to understand the causes of therapy resistance and immune non-responsiveness.
To Tell or Not to Tell: Exploring the Preferences and Attitudes of Patients and Family Caregivers on Disclosure of a Cancer-Related Diagnosis and Prognosis
Authors: Ghoshal Arunangshu , Salins Naveen , Damani Anuja , Chowdhury Jayeeta , Chitre Arundhati , Muckaden Mary Ann , Deodhar Jayita , Badwe Rajendra
Published: November 2019

PURPOSE

To understand the preferences and attitudes of patients and family caregivers on disclosure of cancer diagnosis and prognosis in an Indian setting.

METHODS

Overall, 250 adult patients with cancer and 250 family caregivers attending the outpatients of a tertiary cancer hospital for the first time were recruited purposively. The mean ages of patients and caregivers were 49.9 years (range, 23-80 years) and 37.9 years (range, 19-67 years), respectively. Separately, they completed prevalidated, close-ended preference questions and were interviewed for open-ended attitude questions.

RESULTS

A total of 250 adult patients (response rate, 47.17% overall, 73.2% in men, and 26.8% in women) and 250 family caregivers (response rate, 40.65% overall, 84.0% in men, and 16.0% in women) participated. Significant differences were observed in the preference to full disclosure of the name of illness between patients (81.2%) and caregivers (34.0%) and with the expected length of survival between patients (72.8%) and caregivers (8.8%; P < .001). The patients felt that knowing a diagnosis and prognosis may help them be prepared, plan additional treatment, anticipate complications, and plan for future and family. The caregivers felt that patients knowing a diagnosis and prognosis may negatively affect the future course of illness and cause patients to experience stress, depression, loss of hope, and confidence.

CONCLUSION

Patients with cancer preferred full disclosure of their diagnoses and prognoses, whereas the family caregivers preferred nondisclosure of the same to their patients. This novel information obtained through a large study with varied participants from different parts of the country will help formulate communication strategies for cancer care.
Encounters in Borderlands
Authors: Bauer Susanne , Güttler Nils , Schlünder Martina
Published: November 2019

Focusing on a global hub of aviation, Frankfurt Airport, this essay examines encounters between animals and technology in airport operation. In order to understand how airport practices constantly negotiate the borders with local environments or even produce new ones, we draw on Gloria Anzaldúa’s concept of “borderlands.” Extending this notion from human to nonhuman inhabitants and passengers of airports opens up for novel possibilities to apprehend the affective dimension in the life-technology intersections at airports. In this sense, the airport is a site of multiple borderlands, producing intersections that include material and imaginative, sometimes violent, boundary drawing. We examine a broad set of multispecies borders and “borderlining” practices, their material cultures, and affective economies. What kind of local, historical legacies do airports struggle with and how do they cope with the underlying tensions of partially connected sites, sectors, and spaces? Throughout the essay, we historicize three encounters of the aviation infrastructure and its living environments and their affective economies: borderlining the airfield, borderlining the animal passenger, and borderlining the animal intruder. These examples highlight different modes of encounters, like clashes, coexistence, and care.
Toward an Ethological Poetics
Authors: Cooke Stuart
Published: November 2019

In an attempt to respond to the West’s general obliviousness to nonhuman semiosis, this article proposes a method for appreciating nonhuman poetics. By combining the critical tools of poetics and literary theory with insights from ethology and biosemiotics, Stuart Cooke outlines a method of criticism for nonhuman creative compositions. Drawing on the work of Gerald Bruns, Elizabeth Grosz, and Gilles Deleuze and Félix Guattari, Cooke begins by theorizing a poetics that attends to the ecology of forces that produce, and are produced by, a work rather than the intentions of a single artist. Cooke proposes that an ethological poetics emphasizes the expressive capacity of materials across a range of written, musical, visual, and performative structures. By studying these expressive forces, Cooke argues, we can extend our appreciation of art and poetics into multispecies domains. The challenge is not to focus on the “meaning” or intention of nonhuman artworks but to study their disruptive, and exciting, forces. The third part of the essay is a case study of an Australian songbird, the Albert’s lyrebird, whose remarkable performance Cooke reads in terms of an ethological poetics. Producing an operatic complex of song, instrumentation, dance, and stage design, the male lyrebird’s composition is thoroughly entangled with the flora and fauna of his umwelt. Resistant to categorization by any generic label, Cooke argues that the lyrebird’s composition is best approached in the terms of transgressive, avant-garde performative and sound poetics—although it escapes such terms, thinking about the bird’s composition in this way compels us into a relation with its territory.
Death of a Guinea Pig
Authors: García María Elena
Published: November 2019

During ethnographic research on the biopolitics of culinary nationalism in Peru, I visited a guinea pig breeding farm north of Lima. Guinea pigs are considered “food animals” in the Andes. That encounter with pregnant guinea pigs—and with one guinea pig in particular who was tossed out of her enclosure and left to die—led me to a visceral questioning of my methodological and political approaches to and commitments in multispecies ethnography. I found myself uncomfortably close to the deaths of these female bodies yet unable to voice my dismay or grief. This essay is a modest effort to theorize what grief has to offer the practice of multispecies ethnography. I explore how writing about the ethnographic encounter as one of tragedy and loss might open up the productive possibilities of mourning and grief in connecting human and nonhuman worlds.
Remixing Transfeminist Futures
Authors: Samer Rox
Published: November 2019

There are likely many ways to remix transfeminist futures. As a scholar-vidder, I focus on vidding as one form this work might take. Vidding is an especially affective form of remix art that renders literal the Foucauldian imperative “knowledge is not made for understanding; it is made for cutting.” In disturbing what was previously considered immobile, fragmenting what was thought unified, and not hiding the cuts with which it does so, vidding produces affective surplus. It is not only that a vid disassembles source media, but that its reassembly produces more than a new text; it also, often unpredictably and inexplicably, generates entirely new affects. Taken up as a transfeminist creative critical praxis, vidding could challenge the transphobic and cissexist common sense on which our reality relies, including its teleological histories that cast trans as “new,” ignoring the contributions of trans people to feminist and queer movements and the historical and geographical range of gender variance; liberal discourses that approach trans as yet another matter of civil rights, neglecting how visibility renders trans people more susceptible to violence and surveillance; and media narratives which tell the same fetishizing, isolating, and tragic stories of trans lives time and again. Through my analysis of three of my own transfeminist vids, I introduce the digital humanities methodology “remixing transfeminist futures” and propose we remix our transphobic, transmisogynistic, cissexist reality so as to make perceptible a future when trans people, queer people, people of color, and all women and femmes are free.
The Transfeminine Futurity in Knowing Where to Look
Authors: Morse Nicole Erin
Published: November 2019

In this interview, trans artist Vivek Shraya discusses the gendered politics of self-representation, the misogynistic stigma that attaches to her selfies, and the power of controlling the gaze and knowing “where to look.”
Treatment and Prognosis of Radiation-Associated Breast Angiosarcoma in a Nationwide Population
Authors: Salminen Samuli H. , Wiklund Tom , Sampo Mika M. , Tarkkanen Maija , Pulliainen Lea , Böhling Tom O. , Tukiainen Erkki , Hukkinen Katja , Blomqvist Carl P.
Published: November 2019

Background

Radiation-associated angiosarcoma of the breast (RAASB) is an aggressive malignancy that is increasing in incidence. Only a few previous population-based studies have reported the results of RAASB treatment.

Methods

A search for RAASB patients was carried out in the Finnish Cancer Registry, and treatment data were collected to identify prognostic factors for survival.

Results

Overall, 50 RAASB patients were identified. The median follow-up time was 5.4 years (range 0.4–15.6), and the 5-year overall survival rate was 69%. Forty-seven (94%) patients were operated on with curative intent. Among these patients, the 5-year local recurrence-free survival, distant recurrence-free survival, and overall survival rates were 62%, 75%, and 74%, respectively. A larger planned surgical margin was associated with improved survival.

Conclusions

We found that the majority of RAASB patients were eligible for radical surgical management in this population-based analysis. With radical surgery, the prognosis is relatively good.
Sovereign Debt and Structural Reforms
Authors: Müller Andreas , Storesletten Kjetil , Zilibotti Fabrizio
Published: November 2019

We construct a dynamic theory of sovereign debt and structural reforms with limited enforcement and moral hazard. A sovereign country in recession wishes to smooth consumption. It can also undertake costly reforms to speed up recovery. The sovereign can renege on contracts by suffering a stochastic cost. The constrained optimal allocation (COA) prescribes imperfect insurance with non-monotonic dynamics for consumption and effort. The COA is decentralized by a competitive equilibrium with markets for renegotiable GDP-linked one-period debt. The equilibrium features debt overhang: reform effort decreases in a high debt range. We also consider environments with less complete markets. (JEL D82, E21, E23, E32, F34, H63)
Self-Fulfilling Debt Crises: A Quantitative Analysis
Authors: Bocola Luigi , Dovis Alessandro
Published: November 2019

This paper investigates the role of self-fulfilling expectations in sovereign bond markets. We consider a model of sovereign borrowing featuring endogenous debt maturity, risk-averse lenders, and self-fulfilling crises à la Cole and Kehoe (2000). In this environment, interest rate spreads are driven by both fundamental and nonfundamental risk. These two sources of risk have contrasting implications for the maturity structure of debt chosen by the government. Therefore, they can be indirectly inferred by tracking the evolution of debt maturity. We fit the model to Italian data and find that nonfundamental risk played a limited role during the 2008–2012 crisis. (JEL E43, E44, F34, G01, G15, H63)
Occupations and Import Competition: Evidence from Denmark
Authors: Traiberman Sharon
Published: November 2019

I argue that the winners and losers from trade are decided primarily by occupation. In addition to fixed adjustment costs, workers build up specific human capital over time that is destroyed when they must change occupations. I show that ignoring human capital biases estimates of adjustment costs upward by a factor of 3. Estimating an occupational choice model of the Danish labor market, I show that 57 percent of the dispersion in worker outcomes is accounted for by occupations, and only 16 percent by sectors. Finally, the model suggests that rising import competition from 1995–2005 reduced lifetime earnings for 5 percent of workers. (JEL F14, F16, J24, J31)
Does Strategic Ability Affect Efficiency? Evidence from Electricity Markets
Authors: Hortaçsu Ali , Luco Fernando , Puller Steven L. , Zhu Dongni
Published: November 2019

Oligopoly models of price competition predict that strategic firms exercise market power and generate inefficiencies. However, heterogeneity in firms’ strategic ability also generates inefficiencies. We study the Texas electricity market where firms exhibit significant heterogeneity in how they deviate from Nash equilibrium bidding. These deviations, in turn, increase the cost of production. To explain this heterogeneity, we embed a cognitive hierarchy model into a structural model of bidding and estimate firms’ strategic sophistication. We find that firm size and manager education affect sophistication. Using the model, we show that mergers which increase sophistication can increase efficiency despite increasing market concentration. (JEL D24, D43, G34, L13, L25, L94)
Seroprevalence, risk factors and impact of Toxoplasma gondii infection on haematological parameters in the Ashanti region of Ghana: a cross-sectional study
Authors: Agordzo Samuel Kekeli , Badu Kingsley , Addo Mathew Glover , Owusu Christian Kwasi , Mutala Abdul-Hakim , Tweneboah Austine , Ackom Abbas Dawood , Ayisi-Boateng Nana Kwame
Published: November 2019

Background: Toxoplasma gondii is an obligate, intracellular, apicomplexan parasite that causes toxoplasmosis. Although the global prevalence of toxoplasmosis has been estimated to be approximately 30%, there is limited seroprevalence data in Ghana, with a dearth of information on the impact of T. gondii on haematological parameters in exposed persons.

Methods: Questionnaires were administered to 300 consenting individuals to obtain demographic information and assessment of their risk of exposure to T. gondii. Using anti-T. gondii IgG/IgM combo test kits, seropositivity to parasite-specific IgG and/or IgM was determined. A haematological analyser was used to measure haematological parameters.

Results: The participants included 58 males and 242 females, and ranged in age from 6 months to 84 years, with a median age of 27 years. There was an overall seroprevalence of 50.3% (n=151), with 49.7% (n=149) of the study participants seropositive for IgG and 1% (n=3) testing positive for IgM. Furthermore, the observed seroprevalence among pregnant women was 56.4% (n=62). With regards to the different communities in which the hospitals were located, a seroprevalence of 55.6% was observed in the rural community, 50.6% in the peri-urban community and 47.1% in the urban community. The study identified cat ownership, contact with cat litter [RR (95% CI: 1.76 (1.23-2.53), 1.66 (1.03-2.67), 1.25(1.00-1.57)] and age (p<0.001) as risk factors for infection. Analyses of haematological data also revealed significant differences between the red blood cell counts (p=0.038) and mean corpuscular volumes (p=0.0007) of seropositive and seronegative study participants.

Conclusions: About half of the study population, including a significant number of women of reproductive age carried antibodies against T. gondii, raising questions about the risk of congenital toxoplasmosis, as well as possible links to anaemia. We, therefore, recommend that screening for Toxoplasma gondii be included in the routine screening of pregnant women seeking antenatal care.
On the evaluation of research software: the CDUR procedure
Authors: Gomez-Diaz Teresa , Recio Tomas
Published: November 2019

Background: Evaluation of the quality of research software is a challenging and relevant issue, still not sufficiently addressed by the scientific community.

Methods: Our contribution begins by defining, precisely but widely enough, the notions of research software and of its authors followed by a study of the evaluation issues, as the basis for the proposition of a sound assessment protocol: the CDUR procedure.

Results: CDUR comprises four steps introduced as follows: Citation, to deal with correct RS identification, Dissemination, to measure good dissemination practices, Use, devoted to the evaluation of usability aspects, and Research, to assess the impact of the scientific work.

Conclusions: Some conclusions and recommendations are finally included. The evaluation of research is the keystone to boost the evolution of the Open Science policies and practices.  It is as well our belief that research software evaluation is a fundamental step to induce better research software practices and, thus, a step towards more efficient science.
Case report: Treating a combination of hidradenitis suppurativa and psoriasis with different therapeutic approaches
Authors: Tampouratzi Eleftheria , Kanni Theodora , Katsantonis John , Douvali Theodora
Published: November 2019

Hidradenitis suppurativa and psoriasis are considered chronic inflammatory diseases suggesting the existence of common pathogenetic pathways. We present two cases of comorbid psoriasis and hidradenitis suppurativa, treated with certolizumab pegol and brodalumab due to failure of response to other conventional therapies. Monoclonal antibody therapies have revolutionized the treatment of chronic inflammatory disorders such as psoriasis and hidradenitis suppurativa. Given the good clinical response to anti-IL-17 and anti-tumor necrosis factor agents in patients undergoing psoriasis and hidradenitis treatment, investigations on this direction could represent the starting point in new therapeutic approach for revolutionary treatment in these difficult-to-treat diseases.
Identification of Mycoplasma genitalium from clinical swabs by direct PCR
Authors: Irekwa Robinson M. , Ndung'u Perpetual , Kipkemboi Peter , Teya Tonny , Wanjiru Mwangi Anne , Mutinda Matthew , Njoroge Caroline , Yego Joanne , Vanessa Irumva , Muuo Nzou Samson
Published: November 2019

Mycoplasma genitalium is one of the smallest self-replicating organisms. It is an obligate parasite found in the human genital tract. In men, the bacteria cause both acute and chronic non-gonococcal urethritis (NGU). In women, it has been associated with pelvic inflammatory disease and cervicitis among other related infections. Treatment of M. genitalium related infections has been effective using antibiotics such as the macrolides (e.g. azithromycin) and fluoroquinolones. However, there have been recorded cases of resistance to these antibiotics in various parts of the world as a result of a mutation in the 23SrRNA gene, although the antibiotic resistance has not been well established. The aim of this study was to detect M. genitalium in 352 swab samples collected from a clinic for sex workers in Nairobi, Kenya. DNA was extracted from the swabs and stored as a crude extract at -31°C. The swab lysates were subjected to direct polymerase chain reaction using primers that specifically target the 16S rRNA gene for M. genitalium. A total of 29 samples tested positive for M. genitalium. The data results showed a M. genitalium prevalence of 8.24% among sex workers in Nairobi, Kenya.
Guidelines for performing Mendelian randomization investigations
Authors: Burgess Stephen , Davey Smith George , Davies Neil M. , Dudbridge Frank , Gill Dipender , Glymour M. Maria , Hartwig Fernando P. , Holmes Michael V. , Minelli Cosetta , Relton Caroline L. , Theodoratou Evropi
Published: November 2019

This paper provides guidelines for performing Mendelian randomization investigations. It is aimed at practitioners seeking to undertake analyses and write up their findings, and at journal editors and reviewers seeking to assess Mendelian randomization manuscripts. The guidelines are divided into nine sections: motivation and scope, data sources, choice of genetic variants, variant harmonization, primary analysis, supplementary and sensitivity analyses (one section on robust methods and one on other approaches), data presentation, and interpretation. These guidelines will be updated based on feedback from the community and advances in the field. Updates will be made periodically as needed, and at least every 18 months.
Incidence of postoperative delirium according to cognitive status, improved responsiveness and inflammatory response at elderly patients in urgent abdominal surgery
Authors: Demyter Inna , Gudz Dmytro , Vorotyntsev Sergey
Published: November 2019

Background. Postoperative delirium (POD) is a clinical syndrome that is manifested in impaired consciousness and attention, perception, memory, thinking and psychomotor behavior after surgery. Methods. After passing the Bioethics Commission at Zaporizhzhya State Medical University and obtaining informed consent from patients, 30 elderly patients who underwent surgical interventions on the abdominal organs under urgent procedure were sequentially included in a single-center prospective study. Patients with a history of traumatic brain injury or stroke with neurological impairments in the form of sensory-motor aphasia and plegia were excluded from the study.Results .The study involved 30 patients (16 (53%) women and 14 (47%) men), aged 62 years to 92 years, grade III-IV ASA, who underwent urgent surgery for bowel tumors (n = 8), gallstone disease (n = 7), entrained inguinal and postoperative ventral hernias (n = 10), gastric or intestinal perforation (n = 5). Postoperative delirium occurred in 33% of patients. On the first day after surgery, the cognitive status of patients in the first group decreased by 1 point relative to the primary assessment (p = 0.88), when on the second postoperative day the indicator returned to baseline. Patients in the second group showed a sharp impairment of cognitive abilities in the postoperative period, associated with POD and a significant decrease in cognitive status at day 5 (p <0.05) compared with preoperative assessment. The level of inflammatory response of the body in the preoperative period is 1.5 times higher in patients with POD (p = 0.01). The correlation between leukocytosis level and POD revealed a moderately significant relationship between these indicators (rs = 0.45 at p <0.05).Conclusions. In 33% of urgent patients, abdominal surgery revealed postoperative delirium, which is reliably dependent on cognitive deficits for surgery and the level of systemic inflammation (p = 0.01). The level of patient wear does not significantly affect the incidence of POD.
Incidence, clinical presentation and treatment of dysmenorrhea in female adolescents depending on the nature of extragenital background
Authors: Tuchkina I. A. , Dobrovolskaya L. A. , Tuchkina M. Yu.
Published: November 2019

Incidence of dysmenorrhea in female adolescents was shown to be 28.4 % of all gynecological disorders (41 %). The study involved treatment of 88girls aged 14-18 by complex of non-hormonal and physiotherapy.The effectiveness of complex non-hormonal therapy for gynecological patients was 76.6-83.3 %. No side effects and complications were observed. For most of patients the positive effect of treatment was preserved for 2-3 months.
The impact of a changing policy environment on board members in small and medium-sized voluntary organisations
Authors: Metcalf Lindsey
Published: November 2019

This article examines the experiences of volunteers serving as board members in small and medium-sized voluntary organisations (VOs) in England. It considers the ways in which policy developments, including the outsourcing of public service delivery and austerity programmes, are impacting
on this group of volunteers. Relatively little research has considered policy change from a board member perspective, despite their key role in organisational governance. The article draws on qualitative interviews with individual board members. It shows that policy changes are contributing
to an increasingly complex role for board members in small and medium-sized VOs. The policy environment impacts on board members both by driving more challenging organisational issues for the board and, in turn, by contributing to stress and a lack of confidence at an individual level. Recruitment,
training and support mechanisms are not always adequate in meeting the needs of this specific group of volunteers within this context.
The role of context in the nature and development of DIY impact measurement tools: a case study
Authors: Seymour Valentine
Published: November 2019

This article aims to explore the nature of do-it-yourself (DIY) impact measurement tools used in the voluntary sector, using a contextual inquiry approach. This is an understudied area of research, knowledge that would be considerably valuable for practitioners in the sector who wish
to create their own DIY impact measurement tool. Semi-structured interviews and observation sessions are used to explore an example of a DIY impact measurement tool, the processes of its creation and operation, and how it has been shaped, from the perspective of a UK environmental charity.
The study identifies how and why the tool was created as well as which resources are being used to build it. Findings show that the functionality and requirements of the DIY impact measurement tool are mostly shaped by the charity’s social, cultural and organisational characteristics.