bluuebunny/crossref_metadata_2025 huggingface dataset:
A Phase Ib Open-Label, Multicenter Study of Inhaled DV281, a TLR9 Agonist, in Combination with Nivolumab in Patients with Advanced or Metastatic Non–small Cell Lung Cancer
Authors: Garon Edward B. , Spira Alexander I. , Johnson Melissa , Bazhenova Lyudmila , Leach Joseph , Cummings Amy L. , Candia Albert , Coffman Robert L. , Janatpour Mary J. , Janssen Robert , Gamelin Erick , Chow Laura Q.M.
Published: June 2021

Purpose:

Although PD-(L)1 inhibitors have shown efficacy in advanced/metastatic non–small cell lung cancer (NSCLC), many patients do not respond to this treatment and more effective combinations with acceptable toxicities are needed. To assess the potential benefit of combining localized innate immune stimulation with checkpoint blockade, the TLR9 agonist DV281 was combined with nivolumab in a phase Ib study.

Patients and Methods:

Patients after one or two prior lines of systemic therapy were enrolled in a dose-escalation study with a 3+3 design. DV281 was administered via inhalation in five dose cohorts at 1 to 25 mg; nivolumab 240 mg was administered intravenously every 2 weeks. Safety, tolerability, pharmacodynamics, and response to treatment were assessed.

Results:

Twenty-six patients with advanced NSCLC enrolled. Baseline programmed death ligand 1 (PD-L1) expression was present in 16 patients (61.5%); 21 (80.7%) had received previous anti–PD-1/PD-L1. Thirteen patients (50%) had stable disease, nine (34.6%) had progressive disease, and four (15.4%) were not evaluable. Median duration of disease control was 124 days. Adverse events were seen in 16 patients (61.5%), mostly grade 1/2 chills, fatigue, flu-like symptoms, diarrhea, and rash; there was only one grade 3 adverse event (dyspnea). Pharmacodynamic assessment, measured by IFN- inducible gene expression, showed target engagement in all dose cohorts. Systemic pharmacodynamic responses plateaued in the 2 highest dose cohorts.

Conclusions:

DV281 with nivolumab was well tolerated with target engagement observed at every dose. Pharmacodynamic advantages at doses above 10 mg were unclear. The long duration of disease control in 50% of patients suggests clinically relevant activity in this population of heavily pretreated patients.
A NGS-based Blood Test For the Diagnosis of Invasive HPV-associated Carcinomas with Extensive Viral Genomic Characterization
Authors: Sastre-Garau Xavier , Diop Mamadou , Martin Fernando , Dolivet Gilles , Marchal Frédéric , Charra-Brunaud Claire , Peiffert Didier , Leufflen Léa , Dembélé Birama , Demange Jessica , Tosti Priscillia , Thomas Jacques , Leroux Agnès , Merlin Jean-Louis , Diop-Ndiaye Halimatou , Costa Jean-Marc , Salleron Julia , Harlé Alexandre
Published: June 2021

Purpose:

Use of circulating tumor DNA (ctDNA) for diagnosis is limited regarding the low number of target molecules in early-stage tumors. Human papillomavirus (HPV)–associated carcinomas represent a privileged model using circulating viral DNA (ctHPV DNA) as a tumor marker. However, the plurality of HPV genotypes represents a challenge. The next-generation sequencing (NGS)-based CaptHPV approach is able to characterize any HPV DNA sequence. To assess the ability of this method to establish the diagnosis of HPV-associated cancer via a blood sample, we analyzed ctHPV DNA in HPV-positive or HPV-negative carcinomas.

Experimental Design:

Patients (135) from France and Senegal with carcinoma developed in the uterine cervix (74), oropharynx (25), oral cavity (19), anus (12), and vulva (5) were prospectively registered. Matched tumor tissue and blood samples (10 mL) were taken before treatment and independently analyzed using the CaptHPV method.

Results:

HPV prevalence in tumors was 60.0% (81/135; 15 different genotypes). Viral analysis of plasmas compared with tumors was available for 134 patients. In the group of 80 patients with HPV-positive tumors, 77 were also positive in plasma (sensitivity 95.0%); in the group of 54 patients with HPV-negative tumors, one was positive in plasma (specificity 98.1%). In most cases, the complete HPV pattern observed in tumors could be established from the analysis of ctHPV DNA.

Conclusions:

In patients with carcinoma associated with any HPV genotype, a complete viral genome characterization can be obtained via the analysis of a standard blood sample. This should favor the development of noninvasive diagnostic tests providing the identification of personalized tumor markers.

See related commentary by Rostami et al., p. 5158
Effect of IL-15-Mediating IFN-γ on HTR-8/SVneo Cells and a Preeclampsia Mouse Model Induced by Lipopolysaccharides
Authors: Wang Xiao-Lu
Published: June 2021

Objective: Determine the effect of interleukin (IL)-15 on HTR-8/SVneo cells and a preeclampsia (PE) mouse model induced by LPS. Methods: Transwell and Annexin-V-FITC/PI assays were performed in HTR-8/SVneo cells transfected with IL-15 activation plasmid/siRNA prior to LPS treatment. Additionally, pregnant mice were injected with LPS and IL-15 siRNA followed by measurement of systolic blood pressure (SBP), urine protein, and serum NO. HE staining was used to observe the morphological changes of the placenta and kidney. Glycogen accumulation was detected using Best’s carmine. qRT-PCR, Western blotting, and ELISA were performed to detect mRNA and protein expression. Results: LPS increased IL-15 and IFN-γ expression in HTR-8/SVneo cells, and IL-15 positively regulated IFN-γ expression in LPS-induced HTR-8/SVneo cells. Moreover, LPS promoted apoptosis and reduced the invasion and migration of HTR-8/SVneo cells, which was, further, promoted by IL-15 overexpression but attenuated by IL-15 inhibition. Furthermore, LPS increased SBP and urine protein but decreased serum NO in mice, and these factors were reversed by IL-15 siRNA. Downregulation of IL-15 also mitigated kidney injury and improved pregnancy outcomes in LPS-induced PE mice. A significantly thicker junctional zone (JZ) and thinner labyrinth layer were found in placentas of PE mice treated with IL-15 siRNA, along with increased glycogen trophoblast cells in the JZ. Moreover, decreased IFN-γ and NKp46 were found in placentas of PE mice treated with IL-15 siRNA. Conclusion: IL-15 inhibition reduced cell apoptosis and increased the invasive and migratory abilities of LPS-induced HTR-8/SVneo cells, thereby alleviating the PE-like phenotype and improving pregnancy outcome.
Near-Infrared Spectroscopy Monitoring of Cerebral Oxygenation and Influencing Factors in Neonates from High-Altitude Areas
Authors: Ze Bi , Liu Lili , Yang Jin Ge Sang , Shan Minna , Geng Yuehang , Zhou Congle , Wu Tianqi , Wu Hong , Hou Xinlin
Published: June 2021

Background: Accurate detection of cerebral oxygen saturation (rSO2) may be useful for neonatal brain injury prevention, and the normal range of rSO2 of neonates at high altitude remained unclear. Objective: To compare cerebral rSO2 and cerebral fractional tissue oxygen extraction (cFTOE) at high-altitude and low-altitude areas in healthy neonates and neonates with underlying diseases. Methods: 515 neonates from low-altitude areas and 151 from Tibet were enrolled. These neonates were assigned into the normal group, hypoxic-ischemic encephalopathy (HIE) group, and other diseases group. Near-infrared spectroscopy was used to measure rSO2 in neonates within 24 h after admission. The differences of rSO2, pulse oxygen saturation (SpO2), and cFTOE levels were compared between neonates from low- and high-altitude areas. Results: (1) The mean rSO2 and cFTOE levels in normal neonates from Tibet were 55.0 ± 6.4% and 32.6 ± 8.5%, significantly lower than those from low-altitude areas (p < 0.05). (2) At high altitude, neonates with HIE, pneumonia (p < 0.05), anemia, and congenital heart disease (p < 0.05) have higher cFTOE than healthy neonates. (3) Compared with HIE neonates from plain areas, neonates with HIE at higher altitude had lower cFTOE (p < 0.05), while neonates with heart disease in plateau areas had higher cFTOE than those in plain areas (p < 0.05). Conclusions: The rSO2 and cFTOE levels in normal neonates from high-altitude areas are lower than neonates from the low-altitude areas. Lower cFTOE is possibly because of an increase in blood flow to the brain, and this may be adversely affected by disease states which may increase the risk of brain injury.
Glass Ionomer Sealants Can Prevent Dental Caries but Cannot Prevent Posteruptive Breakdown on Molars Affected by Molar Incisor Hypomineralization: One-Year Results of a Randomized Clinical Trial
Authors: Schraverus Milou S. , Olegário Isabel C. , Bonifácio Clarissa C. , González Ana Paola R. , Pedroza Murisi , Hesse Daniela
Published: June 2021

To evaluate the preventive effect of glass ionomer cement (GIC) against dental caries and posteruptive breakdown (PEB) on molars affected by molar incisor hypomineralization (MIH). In this randomized clinical trial, 77 children aged 5–9 years with at least 1 MIH-affected molar and without PEB or dentin caries lesions (n = 228) were included and randomly allocated to one of the following groups: (1) MIH-affected molars that remained unsealed and (2) MIH-affected molars that received GIC sealants. Dental caries and PEB were clinically evaluated after 6 and 12 months. Associations between dental caries and PEB with independent variables were evaluated using logistic regression analysis (p < 0.05). The MIH-affected molars allocated to the GIC sealant group were less likely to develop dental caries compared to those allocated to the unsealed group (OR = 0.23; 95% CI 0.06–0.95). Conversely, application of a GIC sealant was not associated with prevention of PEB (p = 0.313). Furthermore, MIH-affected molars presenting yellow-brown opacities were almost 5 times more likely to develop dental caries (p = 0.013) and PEB (p = 0.001) compared to those presenting white-creamy opacities. We can conclude that GIC sealants can prevent dental caries on MIH-affected molars; however, the same protective effect was not observed for PEB.
Factors and Outcomes of Intensive Care Unit Readmission in Elderly Patients
Authors: Lee Song-I , Koh Younsuck , Huh Jin Won , Hong Sang-Bum , Lim Chae-Man
Published: June 2021

Introduction: An increase in age has been observed among patients admitted to the intensive care unit (ICU). Age is a well-known risk factor for ICU readmission and mortality. However, clinical characteristics and risk factors of ICU readmission of elderly patients (≥65 years) have not been studied. Methods: This retrospective single-center cohort study was conducted in a total of 122-bed ICU of a tertiary care hospital in Seoul, Korea. A total of 85,413 patients were enrolled in this hospital between January 1, 2007, and December 31, 2017. The odds ratio of readmission and in-hospital mortality was calculated by logistic regression analysis. Results: Totally, 29,503 patients were included in the study group, of which 2,711 (9.2%) had ICU readmissions. Of the 2,711 readmitted patients, 472 patients were readmitted more than once (readmitted 2 or more times to the ICU, 17.4%). In the readmitted patient group, there were more males, higher sequential organ failure assessment (SOFA) scores, and hospitalized for medical reasons. Length of stay (LOS) in ICU and in-hospital were longer, and 28-day and in-hospital mortality was higher in readmitted patients than in nonreadmitted patients. Risk factors of ICU readmission included the ICU admission due to medical reason, SOFA score, presence of chronic heart disease, diabetes mellitus, chronic kidney disease, transplantation, use of mechanical ventilation, and initial ICU LOS. ICU readmission and age (over 85 years) were independent predictors of in-hospital mortality on multivariable analysis. The delayed ICU readmission group (>72 h) had higher in-hospital mortality than the early readmission group (≤72 h) (20.6 vs. 16.2%, p = 0.005). Conclusions: ICU readmissions occurred in 9.2% of elderly patients and were associated with poor prognosis and higher mortality.
Results of a Gene Panel Approach in a Cohort of Patients with Incomplete Distal Renal Tubular Acidosis and Nephrolithiasis
Authors: D’Ambrosio Viola , Azzarà Alessia , Sangiorgi Eugenio , Gurrieri Fiorella , Hess Bernhard , Gambaro Giovanni , Ferraro Pietro Manuel
Published: June 2021

Background: Distal renal tubular acidosis (dRTA) is characterized by an impairment of urinary acidification resulting in metabolic acidosis, hypokalemia, and inappropriately elevated urine pH. If not treated, this chronic condition eventually leads to nephrocalcinosis, nephrolithiasis, impaired renal function, and bone demineralization. dRTA is a well-defined entity that can be diagnosed by genetic testing of 5 genes known to be disease-causative. Incomplete dRTA (idRTA) is defined as impaired urinary acidification that does not lead to overt metabolic acidosis and therefore can be diagnosed if patients fail to adequately acidify urine after an ammonium chloride (NH4Cl) challenge or furosemide and fludrocortisone test. It is still uncertain whether idRTA represents a distinct entity or is part of the dRTA spectrum and whether it is caused by mutations in the same genes of overt dRTA. Methods: In this cross-sectional study, we investigated a group of 22 stone formers whose clinical features were suspicious of idRTA. They underwent an NH4Cl challenge and were found to have impaired urinary acidification ability. These patients were then analyzed by genetic testing with sequencing of 5 genes: SLC4A1, ATP6V1B1, ATP6V0A4, FOXI1, and WDR72. Results: Two unrelated individuals were found to have two different variants in SLC4A1 that had never been described before. Conclusions: Our results suggest the involvement of other genes or nongenetic tubular dysfunction in the pathogenesis of idRTA in stone formers. However, genetic testing may represent a cost-effective tool to recognize, treat, and prevent complications in these patients.
A Case of Dentatotomy for Pain and Spasticity and Systematic Review
Authors: Villegas-López Francisco Alberto , Armas-Salazar Armando , Beltrán Jesús Q. , Téllez-León Noé , Arellano-Alcántara Ana , Navarro-Olvera José Luis , Carrillo-Ruiz José Damián
Published: June 2021

Background: Surgical interventions for spasticity aim to improve motor function and pain in cases that are refractory to medical treatment. Ablation of the cerebellar dentate nucleus (dentatotomy) may be a useful alternative. Case Report: A 55-year-old male patient with spasticity, secondary to a traumatic cervical spinal cord injury with quadriparesis, had bilateral lumbar DREZotomy with an improvement that lasted for 6 years. Ten years after the DREZotomy, a progressive increased spasticity manifested as spastic diplegia (Ashworth 4) and spontaneous muscle painful spasms (Penn 4), as well as spasticity in the upper extremities, predominantly on the right side (Ashworth 3). A right radio frequency dentatotomy was performed with intraoperative electrophysiological monitoring. Spasticity scales were applied at the following times: preoperative and at 1 and 8 months after surgery. During the first month, the patient presented a clear decrease in spasticity ipsilateral to the side of lesioning (Ashworth 1) and of painful spasms in the lower extremities (Penn 1). After 8 months, spasticity ipsilateral to the injury decreased even more to Ashworth (0), but a progressive increase in muscle spasms of lower extremities was observed (Penn 2). Conclusion: Stereotactic dentatotomy may be an effective surgical alternative for management of spasticity associated with painful spasms in selected patients.
Three-Dimensional Sonographic Evaluation of the Position of the Fetal Conus Medullaris at First Trimester
Authors: Ramirez Zegarra Ruben , Volpe Nicola , Bertelli Evelina , Amorelli Greta Michela , Ferraro Luigi , Schera Giovanni Battista Luca , Cromi Antonella , di Pasquo Elvira , Dall’Asta Andrea , Ghezzi Fabio , Frusca Tiziana , Ghi Tullio
Published: June 2021

Objective: The objective of this study was to assess the position of the conus medullaris (CM) at the first trimester 3D ultrasound in a cohort of structurally normal fetuses. Methods: This was a multicenter prospective study involving a consecutive series of structurally normal fetuses between 11 and 13 weeks of gestation (CRL between 45 and 84 mm). All fetuses were submitted to 3D transvaginal ultrasound using a sagittal view of the spine as the starting plane of acquisition. At offline analysis, the position of the CM was evaluated by 2 independent operators with a quantitative and a qualitative method: (1) the distance between the most caudal part of the CM and the distal end of the coccyx (CMCd) was measured; (2) a line perpendicular to the fetal spine joining the tip of the CM to the anterior abdominal wall was traced to determine the level of this line in relation to the umbilical cord insertion (conus to abdomen line, CAL). Interobserver agreement for the CCMd was evaluated. Linear regression analysis was used to determine the association between the CMCd and CRL, and a normal range was computed based on the best-fit model. The absence of congenital anomalies was confirmed in all cases after birth. Results: In the study period between December 2019 and March 2020, 143 fetuses were recruited. In 130 fetuses (90.9%), the visualization of the CM was feasible. The mean value of the CMCd was 1.09 ± 0.16 cm. The 95% limits of agreement for the interobserver variability in measurement of the CMCd were 0.24 and 0.26 cm. The interobserver variability based on the intra-class correlation coefficient (ICC) for the CCMd was good (ICC = 0.81). We found a positive linear relationship between the CCMd and CRL. In all these fetuses, the CAL encountered the abdominal wall at or above the level of the cord insertion. Conclusion: In normal fetuses, the assessment of the CM position is feasible at the first trimester 3D ultrasound with a good interobserver agreement. The CM level was never found below the fetal umbilical cord insertion, while the CMCd was noted to increase according to the gestational age, confirming the “ascension” of the CM during fetal life.
Immunological Microenvironment Predicts the Survival of the Patients with Hepatocellular Carcinoma Treated with Anti-PD-1 Antibody
Authors: Morita Masahiro , Nishida Naoshi , Sakai Kazuko , Aoki Tomoko , Chishina Hirokazu , Takita Masahiro , Ida Hiroshi , Hagiwara Satoru , Minami Yasunori , Ueshima Kazuomi , Nishio Kazuto , Kobayashi Yukari , Kakimi Kazuhiro , Kudo Masatoshi
Published: June 2021

Introduction: Although immune checkpoint inhibitors (ICIs) have been considered as promising agents for the treatment of advanced hepatocellular carcinoma (HCC), previous clinical trials revealed that the response to anti-programmed cell death protein 1 (anti-PD-1) monotherapy was as low as 20%. Identifying subgroups that respond well to ICIs is clinically important. Here, we studied the prognostic factors for anti-PD-1 antibody treatment based on the molecular and immunological features of HCC. Methods: Patients who were administered anti-PD1 antibody for advanced HCC at Kindai University Hospital were included. Clinicopathological backgrounds and antitumor responses were examined in 34 cases where tumor tissues before treatment were available. Transcriptome analysis was performed using 40 HCC samples obtained from surgical resection, and immune status was compared between 20 HCCs with activating mutations in β-catenin and those without the mutations using transcriptome-based immunogram. Results: Univariate analysis showed that the disease control rate was significantly better in patients with α-fetoprotein < 400 ng/mL, negative for β-catenin/glutamate synthetase (GS) staining, high combined positive score (CPS) of programmed death-ligand 1 (PD-L1), and increased infiltration of CD8+ cells in tumor tissues. Among them, negative staining of β-catenin/GS, CPS of PD-L1 ≥ 1, and high degree of CD8+ tumor-infiltrating lymphocytes (TILs) were significantly associated with longer survival in both progression-free survival (PFS) and overall survival (OS). The combination of these factors well stratified the survival of the patients on anti-PD-1 antibody in both PFS and OS (p < 0.0001 and p = 0.0048 for PFS and OS, respectively). In addition, the immunogram revealed that tumor-carrying mutations in β-catenin showed downregulation of immune-related genes, especially in those related to priming and activation by dendritic cells, interferon-γ response, inhibitory molecules, and regulatory T cells. Discussion/Conclusion: The combined score including Wnt/β-catenin activation, CPS of PD-L1, and degree of CD8+ TILs in HCC is informative for predicting the response to ICI in HCC cases. Constitutive activation of β-catenin can induce an immune cold phenotype with downregulation of immune-related genes, and immunohistochemistry-based evaluation is beneficial for identifying the subgroup that shows a good response to ICI.
Family engagement as part of managing patients with mental illness in primary care
Authors: Ong HS , Fernandez PA , Lim HK
Published: June 2021

The family unit plays a crucial role in patients with mental illness. Mental health problems have been associated with an assortment of dysfunctional social and psychological processes in one’s family of origin, yet families are now expected to be responsible for the care of the patient with mental illness. There are many short- and long-term benefits of engaging the families in the care of patients with mental illness. However, the implementation of family engagement in patients with mental illness is fraught with challenges. The primary care provider possesses several distinctive characteristics that lend an advantage to successfully engaging the families of patients with mental illness, such as better accessibility, better rapport, and being associated with less stigma. Primary care providers could engage the family in various ways, ranging from basic functions such as psychoeducation and supporting the family’s needs, to more specialised interventions such as family assessment and family therapy.
The Plausible Impossible: Chinese Adults Hold Graded Notions of Impossibility
Authors: Gong Tianwei , Shtulman Andrew
Published: June 2021

Events that violate the laws of nature are, by definition, impossible, but recent research suggests that people view some violations as “more impossible” than others (Shtulman & Morgan, 2017). When evaluating the difficulty of magic spells, American adults are influenced by causal considerations that should be irrelevant given the spell’s primary causal violation, judging, for instance, that it would be more difficult to levitate a bowling ball than a basketball even though weight should no longer be a consideration if contact is no longer necessary for support. In the present study, we sought to test the generalizability of these effects in a non-Western context – China – where magical events are represented differently in popular fiction and where reasoning styles are often more holistic than analytic. Across several studies, Chinese adults (n = 466) showed the same tendency as American adults to honor implicit causal constraints when evaluating the plausibility of magical events. These findings suggest that graded notions of impossibility are shared across cultures, possibly because they are a byproduct of causal knowledge.
Promoting Industrial Success through Organizational Culture
Authors: Moskovich Yaffa
Published: June 2021

This study shows the value of promoting organizational culture by identifying and analyzing factors of economic success in a particular factory. The research was conducted by qualitative investigation using ethnographic interviews and document analysis procedures. The findings describe how the managers merged socialist traditions of the pre-privatized kibbutz and the capitalism of the global market in order to create a dynamic strategic model. The components of the model interacted with each other, creating an unusual organizational culture and a porous boundary between the factory and the kibbutz community that owned it. The findings suggest that there are advantages to preserving the unique cultural attributes that link workers, managers and their surrounding community which reflect their roots and basic mindset. This case study offers managers of kibbutz, and non-kibbutz, factories a successful example of combining opposite trends in management style. The main contribution of this study is presenting an alternative method for examining kibbutz industries in future research. This alternative method describes a managerial culture that facilitates the combination of two seemingly contradictory paradigms. The first is the kibbutz’s socialist, cooperative, and communal principles. The second paradigm is the external capitalist realities of the domestic and global market.
The Role of ‘Spirituality’ in Religion-secular Relational Discourse: The Case of Yoga in Britain
Authors: Vollmer Laura J.
Published: June 2021

This article examines the ‘relational etymology’ of the term ‘secular’ relative to ‘religion’ and the role of the concept ‘spirituality’ in discursive change. Employing a relational methodology to the sociology of knowledge approach to discourse analysis, concept formation and transformation of these terms is considered as a specific matter of how the terms are positioned relative to one another in the discourse. It is found that while ‘spirituality’ first worked on the side of ‘religion’ to differentiate it from the ‘secular,’ it was later differentiated from ‘religion’ and placed in ‘secular’ discourse. This is exemplified with the case of yoga in Britain. Implications for the religion-secular relationship and the secularization thesis are explored.
Angels as the Shape of Energy: How the Threshold Narratives Shaped the Meaning Construction of ‘Angel’ and ‘Energy’ in a Central and Eastern European New Religious Group
Authors: Csáji László Koppány
Published: June 2021

The status-dependent access to information results in multilevel meaning construction in a charismatic Christian group. The notion of ‘angel’ is discursively transforming (during evangelization rituals, healing, angel visions, etc.). To acquire language skills, one may encounter and accept threshold narratives. After the notion of energy was introduced into the group (2012), former ideas (‘rectangular form’ and ‘shape-changing kind’ of angels) were intermixed with it. Energy became a general, fundamental principle, but it was not obvious how they could manage its dual kind: ‘positive energy’ and the evil counterpart (‘spiritual/negative energy’). My argumentation is based on discourse analysis and cognitive semantics.
The Referral of the Situation in Venezuela to the International Criminal Court: The Office of the Prosecutor Should Not Step In… Yet
Authors: Garfunkel Ianiv
Published: June 2021

On 26 September 2018, six American States Parties to the Rome Statute referred the Situation in Venezuela to the Office of the Prosecutor (‘OTP’) of the International Criminal Court, regarding crimes against humanity. Those States rested on Article 14 of the Rome Statute to proceed. That referral – namely, crimes committed outside the territory of the referring State(s) – was the second of its kind received by the icc in its more than 15-year working history. The otp is currently considering the referral under the so-called ‘Preliminary Examination’ stage, wherein the admissibility test is likely to be addressed within the complementarity principle, according to Article 17 of the Rome Statute. Despite the duty to exercise their criminal jurisdiction, as the Preamble to the Rome Statue stipulates, and the fact that those six American States recognize some sort of extraterritorial jurisdiction, those States remained inactive. What should the otp do when six democracies, who are able to act, do not even try to launch an investigation for crimes they have expressed concerns about, without providing an explanation for their inactivity? This article will analyse how the otp should deal with this referral in terms of the complementarity principle, having regard to the positive approach to complementarity. Accordingly, it will be argued that the Prosecutor should refrain from intervening until those States attempt to act and/or, in case of legal or factual inability, justify the referral.
Presenting an Admirable Self: Moral Evaluation within the Interview
Authors: Dubie Emily Z.
Published: June 2021

This article considers the complicated nature of self-reporting within the in-depth interview. Despite the adoption of ethnographic methods in Christian ethics and related disciplines, the accuracy of interview data has received relatively little attention. Drawing upon my fieldwork with Christian social workers in the American southeast, as well as sociological and anthropological sources, I argue that research participants frequently endeavor to present an admirable portrait of themselves. Through selecting, omitting, and revising their stories, they undertake a kind of moral work, assessing their actions and attitudes according to available ethical criteria. Broader cultural norms, their own moral ideals, and anticipations of the interviewer’s judgments all supply resources for self-evaluation. Rather than presenting a methodological problem, understanding this possible dynamic within the interview supplies the Christian ethicist with firsthand insights into the moral labors of naming a good life.
Stratiform Cloud-Hydrometeor Assimilation for HRRR and RAP Model Short-Range Weather Prediction
Authors: Benjamin Stanley G. , James Eric P. , Hu Ming , Alexander Curtis R. , Ladwig Therese T. , Brown John M. , Weygandt Stephen S. , Turner David D. , Minnis Patrick , Smith William L. , Heidinger Andrew K.
Published: June 2021

Accurate cloud and precipitation forecasts are a fundamental component of short-range data assimilation/model prediction systems such as the NOAA 3-km High-Resolution Rapid Refresh (HRRR) or the 13-km Rapid Refresh (RAP). To reduce cloud and precipitation spin-up problems, a non-variational assimilation technique for stratiform clouds was developed within the Gridpoint Statistical Interpolation (GSI) data assimilation system. One goal of this technique is retention of observed stratiform cloudy and clear 3D volumes into the subsequent model forecast. The cloud observations used include cloud-top data from satellite brightness temperatures, surface-based ceilometer data, and surface visibility. Quality control, expansion into spatial information content, and forward operators are described for each observation type. The projection of data from these observation types into an observation-based cloud-information 3D gridded field is accomplished via identification of cloudy, clear, and cloud-unknown 3D volumes. Updating of forecast background fields is accomplished through clearing and building of cloud water and cloud ice with associated modifications to water vapor and temperature. Impact of the cloud assimilation on short-range forecasts is assessed with a set of retrospective experiments in warm and cold seasons using the RAPv5 model. Short-range (1-9h) forecast skill is improved in both seasons for cloud ceiling and visibility and for 2-m temperature in daytime and with mixed results for other measures. Two modifications were introduced and tested with success: use of prognostic subgrid-scale cloud fraction to condition cloud building (in response to a high bias) and removal of a WRF-based rebalancing.
The Construction of Shame and Pride: A Grounded Theory Model of Identity, Emotions, and Wellbeing among Sexual Minority Adolescents
Authors: Goffnett Jacob , Routon Jaz , Flores Rey
Published: June 2021

This study explored the development and impact of shame and pride among sexual minority adolescents (SMA) to better understand emotions as psychosocial mechanisms of wellbeing. Shame and pride are salient to understanding the experiences of SMAs because American society has culturally constructed their identities to be dichotomized as shameful and something to be hidden, or prideful, and something to be celebrated. However, little empirical research has been conducted to understand the influence these emotions have on this population. This study conducted a secondary qualitative analysis of life-history interviews from 36 racially diverse SMAs. The grounded theory model suggests shame and pride emerge through an interaction between social reality, life experiences of minority stress and resilience, and perceptions of self. Furthermore, these emotions influenced health behaviors through the way they were managed. Findings are discussed in light of current literature and implications for research and practice are shared.
Impact of One-Way Streets and Contraflow on Low-Stress Bicycle Network Connectivity
Authors: Putta Theja , Furth Peter G.
Published: June 2021

One-way restrictions on local streets, which tend to have low traffic stress, can create a significant barrier to low-stress cycling. Contraflow, a treatment that undoes one-way restrictions on bike travel, has the potential to improve low-stress connectivity. Although contraflow is applied routinely in the Netherlands and Belgium, it has been sparingly applied in the United States. We propose refined measures of connectivity and accessibility that account for one-way restrictions by requiring a low-stress round trip path between origins and destinations. Different methods of associating origin–destination demand from polygons with a street network were analyzed. These methods are particularly important where there are one-way restrictions and irregular street networks because of the assumptions they entail in relation to first- and last-segment travel. In a case study of Greater Boston, we found that with the current bike network, low-stress connectivity between homes and jobs would increase from 1.2% to 8.7% if one-way restrictions on local streets were eliminated. We also found that even with a dense mesh of low-stress main bike routes, connectivity would still be 16% lower without contraflow on local streets than with. These results suggest that creating a network of main bike routes is not always enough; it is also important to provide contraflow on local streets. The Boston study also found that providing contraflow on selected links representing only 3% of local one-way street mileage delivered 40% of the connectivity impact of universal contraflow. Based on this finding, a method is proposed for prioritizing streets for contraflow conversion.
Examining Disparities in Food Access Between Historically Black Colleges and Universities and Non-Historically Black Colleges and Universities
Authors: Kornbluh Mariah , Hallum Shirelle , Wende Marilyn , Ray Joseph , Herrnstadt Zachary , Kaczynski Andrew T.
Published: June 2021

Purpose:

Examine if Historically Black Colleges and Universities (HBCUs) are more likely to be located in low food access area (LFA) census tracts compared to public non-HBCUs.

Design:

ArcGIS Pro was utilized to capture food environments and census tract sociodemographic data.

Setting:

The sample included 98 HBCUs and 777 public non-HBCUs within the United States. 28.9% of study census tracts were classified as LFA tracts.

Measures:

University data were gathered from the National Center for Education Statistics. Census tract-level LFA classification was informed by the United States Department of Agriculture’s Food Access Research Atlas. Covariates included population density and neighborhood socioeconomic status of census tracts containing subject universities.

Analysis:

Multilevel logistic regression was employed to examine the relationship between university type and LFA classification.

Results:

A higher percentage of HBCUs (46.9%) than public non-HBCUs (26.6%) were located in LFAs. After adjusting for population density and neighborhood socioeconomic status, university type was significantly associated with food access classification (B=0.71;p=.0036). The odds of an HBCU being located in LFA tracts were 104% greater than for a public non-HBCU (OR=2.04;95% CI=1.26,3.29).

Conclusion:

Findings underscore the need for policy interventions tailored to HBCU students to promote food security, environmental justice, and public health.
Gender-specific cut-off levels in colorectal cancer screening with fecal immunochemical test: A population-based study of colonoscopy findings and costs
Authors: Ribbing Wilén Hanna , Saraste Deborah , Blom Johannes
Published: June 2021

Objective

In the population-based Swedish regional colorectal cancer (CRC) screening program of Stockholm–Gotland using the fecal immunochemical test (FIT), gender-specific cut-off levels of fecal hemoglobin are applied, since previous studies have indicated a lower sensitivity of FIT for CRC in women. The aim was to evaluate the diagnostic yield and the screening costs overall and per detected CRC of this strategy.

Methods

All individuals aged 60–69 invited to screening in 2015–2017 were included. Cut-off level for positive FIT was 40 µg/g in women and 80 µg/g in men. Those with a positive FIT were referred to colonoscopy. The yield of CRC and screening cost for the study period were assessed and compared to cut-off levels of 80 µg/g in both genders.

Results

Approximately 230,000 individuals were invited. Overall participation rates were 72% in women and 65% in men ( p < 0.05). FIT was positive in 4256 individuals (2.7% in both genders). In 3758 colonoscopies, 258 (6.9%) CRCs were detected. The positive predictive value for CRC was significantly higher in men (8.3% vs. 5.8%). In 120 women with CRC, 28 (23%) had FIT < 80 µg/g. Negative colonoscopies were more common in women (24% vs. 17%, p < 0.05). Total costs for the study period were 52,000,000SEK (≈5,200,000€), i.e. 16% higher compared to using cut-off levels of 80 µg/g in both genders, and corresponding to a 3% increment in cost per detected CRC.

Conclusion

The high rate of CRC detected in women in the lowest FIT category outweighs the minor reduction in screening costs if the same cut-off level was used as for men.
Cocurricular Learning in Management Education: Lessons From Legal Education’s Use of Student-Edited Journals
Authors: Theeke Matt , Hall Matthew I.
Published: June 2021

In this essay, we draw on insights from U.S. legal education’s century-long experiment using student-edited journals as a cocurricular learning tool, to develop the argument that management education should consider introducing a new category of student-edited, practitioner-oriented journals. Student-edited journals are potentially well-suited for management education because they encourage students to learn professionally relevant skills and to develop a greater understanding of research and its role in professional education. Enlisting students to help edit practitioner journals could also benefit business professionals by increasing the availability of practitioner-oriented research. In doing so, management education can use this cocurricular learning activity to help break down barriers between research, teaching and practice. This essay contributes to the management education literature by furthering the conversation about the role that cocurricular learning plays in fostering evidence-based management.
Comparison of three regional anaesthetic techniques for infraorbital or maxillary nerve block in cats: a cadaveric study
Authors: Shilo-Benjamini Yael , Letz Shachar , Peery Dana , Abu Ahmad Wiessam , Bar-Am Yoav
Published: June 2021

Objectives

The maxillary nerve courses very close to the globe, rendering cats – with their large eyes – at risk of globe penetration during infraorbital or maxillary nerve blocks. Therefore, the goals of the study were to compare the distribution and potential complications of three infraorbital or maxillary regional injection techniques.

Methods

Twenty-three bilateral maxillae of cat cadavers were used in a randomised blinded trial. Each maxilla was injected with a 0.2 ml 1:1 mixture of lidocaine 2% and a contrast medium by one of three injection techniques: infraorbital foramen (IOF; n = 14); infraorbital canal (IOC; n = 16); or maxillary foramen (MF; transpalpebral approach; n = 16) using a 25 G 1.6 cm needle. CT imaging of each cadaver head was performed before and after injections. A radiologist scored injectate distribution (none [0], mild [1], moderate [2], large [3]) in four locations: rostral, central and caudal IOC, and at the MF, for which the distribution side was also determined. Comparisons were performed with ordinal logistic mixed effects ( P <0.05).

Results

The median (range) total distribution score of the IOC and MF technique were significantly higher compared with the IOF technique (6.5 [4–12], 4 [2–8] and 0 [0–10], respectively). The total IOC score was also significantly higher compared with the MF technique. Injectate distribution at the MF was significantly more central following IOC injection compared with MF injection, which distributed centrolaterally. None of the techniques resulted in intraocular injection.

Conclusions and relevance

The IOC and MF techniques produced a satisfactory spread of the mixture that could result in effective maxillary anaesthesia in cats. Further studies are required to determine the effectiveness and safety of these techniques.
A significant change towards cemented fixation in revision total hip arthroplasty in patients younger than 55 years in the Netherlands: results of an observational cohort study in the Dutch Arthroplasty Register in 28,516 primary hip replacements and 1285 revision procedures
Authors: Kuijpers Martijn FL , Hannink Gerjon , van Steenbergen Liza N , Schreurs B Wim
Published: June 2021

Background:

Worldwide, the majority of total hip arthroplasties (THAs) placed in patients <55 years are uncemented. However, little is known about the preferred method of fixation in revision hip arthroplasty in young patients. The aim of this study was to assess potential differences in the method of fixation used between primary and revision THA in young patients using data from the Dutch Arthroplasty Register.

Methods:

All primary THA placed in patients younger than 55 years, registered in the LROI between 2007 and 2019 were included n = 28,516). Kaplan-Meier survival analyses were used to estimate the survival of primary THA by method of fixation. Additionally, survival of revision procedures that changed or did not change in method of fixation were estimated. McNemar’s test was used to assess differences in the proportion of cemented and uncemented fixation between primary and revision THA.

Results:

In all acetabular revisions, the use of cemented fixation increased statistically significant with 39% (95% CI, 34–45, p < 0.001) from 23% in primary THA to 62% in revision procedures. In all femoral revisions, the increase of cemented fixation was also statistically significant with 25% (95% CI, 19–31, p < 0.001), from 11% in primary THA to 36% in revision surgery. For both revised acetabular and femoral components, we found no statistically significant difference in the 5-year survival between revision procedures that changed or did not change in method of fixation.

Conclusions:

There was a significant change towards cemented fixation between primary and revision THA in young patients in the Netherlands, which was especially pronounced in acetabular revisions. No significant difference in short-term survival was found between revision procedures that changed or did not change in method of fixation. Long-term follow-up data are needed to evaluate the effect of this change in fixation method on the outcome of revision procedures in young patients.
Designing hierarchical networks to improve patient access to care: a case study in veteran eye care
Authors: VanDeusen Adam , Cohn Amy , Maa April
Published: June 2021

Across the United States, many patients, including veteran patients, face barriers in accessing appropriate, timely, and affordable healthcare. When developing or modifying healthcare systems to improve patient access, we can consider strategies (e.g., telehealth) in which lower-cost, more abundant resources are used for services often performed with more constrained and/or more expensive, specialized resources. We propose a framework in which hierarchical care networks allow patients to receive frontline care from lower cost, more accessible alternatives, while specialized resources are reserved for more complex care. We use operations research tools, including mixed-integer programming and facility location models, to design and analyze these networks. We present a case study applying these methods to improve veterans’ access to eye care screenings. The case study results demonstrate that using different providers in locations throughout the system can increase the number of patients screened by nearly four times the number currently screened while increasing the budget by only 2.5%. When designing healthcare networks to improve access, decision makers must consider several trade-offs, including how resources are distributed. Operations research tools are effective methods for understanding, designing, and evaluating these trade-offs to best understand the wide-ranging impacts of resource (re)distribution.
Using Bilateral tDCS to Modulate EEG Amplitude and Coherence of Men With Opioid Use Disorder Under Methadone Therapy: A Sham-controlled Clinical Trial
Authors: Mostafavi Hossein , Dadashi Mohsen , Faridi Alireza , Kazemzadeh Fatemeh , Eskandari Zakaria
Published: June 2021

Objective. This study aimed to investigate the effect of bilateral transcranial direct current stimulation (tDCS) on the electroencephalography (EEG) amplitude and coherence in male patients with opioid use disorder (OUD), who were under methadone therapy. It compares the effects of active versus sham tDCS. Methods. This is a double-blind sham-controlled clinical trial. Participants were 30 male patients with OUD; they were divided into 3 groups of left anode/right cathode tDCS, right anode/left cathode tDCS, and sham tDCS. Their brainwave activity was measured by quantitative EEG before study and then active groups underwent tDCS (2 mA, 20 min) applied over their right/left dorsolateral prefrontal cortex (DLPFC) for 10 consecutive days. After stimulation, they were re-assessed. The collected data were analyzed in SPSS, MATLAB, and NeuroGuide v.2 applications. Results. After active tDCS, a significant decrease in amplitude of slow brain waves (delta, theta, and alpha) in prefrontal, frontal, occipital, and parietal areas, and an increase in the coherence of beta, delta, and theta frequency bands in the parietal, central, and temporal regions of addicts were reported. In the sham group, there was a significant decrease in the amplitude of the alpha wave and in the coherence of delta and theta waves. Conclusion. The active tDCS over the right/left DLPFC, as a noninvasive and complementary treatment, can modulate the amplitude and coherence of brainwaves in patients with OUD.