bluuebunny/crossref_metadata_2025 huggingface dataset:
A phase II study of short course FOLFOX chemotherapy with either nivolumab (Nivo) or Nivo plus radiation in the first line treatment of metastatic or unresectable gastroesophageal (GEA) cancers.
Authors: Mehta Rutika , Mukherjee Sarbajit , Klute Kelsey , Park Haeseong , Khan Uqba , Khan Sahrish , Puello Carina , Machado Sabrina , Christos Paul J. , Sanfilippo Nicholas J. , Shah Manish A.
Published: June 2021

TPS4157

Background: GEA remains incurable and novel therapies are needed. Studies have shown that cytotoxic chemotherapy can enhance antigenicity of tumors, leading to the recent practice changing studies that demonstrate checkpoint inhibition therapy combined with chemotherapy in PD-L1 overexpressing patients significantly improves patient survival (Keynote-590 and Checkmate-649). But long-term use can also subsequently dampen the immune response. Moreover, the stop-and-go strategy with chemotherapy can maintain patient survival while minimizing chemotherapy related side effects when compared to the traditional strategy of continuous chemotherapy. These observations prompted the inception of this trial with the hypothesis that a short course of FOFLOX therapy combined with immunotherapy will likely have similar activity to that of continuing FOFLOX until disease progression when combined with immunotherapy. We also will examine the hypothesis that low dose radiotherapy can further augment immunotherapy efficacy. Methods: This is a multicenter, randomized phase II study examining Nivo alone vs radiation therapy (RT) with Nivo in subjects who did not have disease progression with 3 months of FOLFOX + Nivo. Subjects with advanced unresectable or metastatic GEA cancer are eligible. All subjects will receive FOLFOX + Nivo therapy. Subjects who demonstrate at least stable disease, on their first imaging assessment at 2 months will receive 1 additional month of FOLFOX + Nivo, and then will be randomly assigned at a 1:1 ratio to receive either Nivo alone or Nivo + RT. After 4 mos of therapy, patients who remain on study will receive Nivo Q4WKly. The primary endpoint is to demonstrate that the addition of fractionated radiation to immunotherapy is associated with an improvement in the 12-month progression-free survival (PFS) proportion from 25% (i.e., historical control estimate; Nivo alone; Arm A) to approximately 50% (i.e., with the fractional radiation and Nivo; Arm B). A key secondary aim is to demonstrate that short course FOLFOX of 3 months + Nivo is similar in efficacy to continuing FOLFOX until disease progression. Another secondary aim of this study is to demonstrate safety of the combination of fractionated RT + Nivo. Target sample size is 74 patients. The study is now open at six sites across the United States. Clinical trial information: NCT04021108.
CaboRISE: A phase II study evaluating reduced starting dose and dose escalation of cabozantinib as second-line therapy for advanced HCC in patients with compensated liver cirrhosis.
Authors: Trojan Jorg , Pluntke Stefan , van Boemmel Florian , Ehmer Ursula , Goetze Thorsten Oliver , Jacobasch Lutz , Pink Daniel , Kopp Christina , Lehnerts Sarah , Riedel Johanna , Waidmann Oliver , Finkelmeier Fabian , Geißler Michael
Published: June 2021

TPS4163

Background: The multi-targeted tyrosine kinase inhibitor cabozantinib is approved for the treatment of advanced hepatocellular carcinoma (HCC) in adults, who have previously been treated with sorafenib. In the pivotal phase 3 CELESTIAL trial a significant improvement for OS and PFS was shown for cabozantinib in comparison to placebo treated patients (Abou-Alfa GK et al. N Engl J Med 2018; 379:54-63). However, in 62% of patients a dose reduction of cabozantinib was necessary and the median average daily dose was 35.8 mg. The discontinuation rate due to treatment-related adverse events (TRAEs) was 16% and grade 3-4 TRAEs occurred in 68% of patients. For HCC patients treated with sorafenib in first-line, a reduced starting dose of 200 mg BID was not inferior in terms of OS but showed a trend toward a decreased rate of sorafenib discontinuation(Reiss KA et al. J Clin Oncol 2017; 35:3575-3581). The aim of the CaboRISE trial is to study the effect of a reduced starting dose of cabozantinib on tolerability, safety, and efficacy. Methods: The CaboRISE trial is an open-label, single arm, multicenter phase II trial, including patients with advanced stage hepatocellular carcinoma (HCC) with compensated liver cirrhosis (Child-Pugh A) in second line treatment, after first line treatment with sorafenib or lenvatinib. Forty evaluable patients will be enrolled in the study to receive a reduced starting dose of 40 mg cabozantinib once-daily for 4 weeks and subsequent dose escalation to 60 mg cabozantinib once-daily to be maintained until disease progression or intolerable toxicities. The objective of the trial is to assess the tolerability of a reduced starting dose of cabozantinib, in order to reduce the treatment discontinuation rates due to treatment-related adverse events below 10%. Primary endpoint is the treatment discontinuation rate due to TRAEs. Secondary endpoints are overall survival, progression free survival at 10 weeks, objective response rate, time on treatment, treatment exposure, toxicity, and quality of life. Study start of the CaboRISE trial was in October 2020. By February 2021, 7 centers across Germany have been initiated and a total of 4 out of 40 planned patients have been enrolled. The study is currently ongoing. This study is financially supported by Ipsen. ClinicalTrials.gov: NCT04522908 EudraCT: 2020-000775-20. Clinical trial information: NCT04522908.
Trial in progress: Open-label, randomized, comparative phase 2/3 study of combination immunotherapy plus standard-of-care chemotherapy and SBRT versus standard-of-care chemotherapy for the treatment of locally advanced or metastatic pancreatic cancer.
Authors: Seery Tara Elisabeth , Nangia Chaitali Singh , Sender Leonard S. , Reddy Sandeep K. , Soon-Shiong Patrick
Published: June 2021

TPS4174

Background: Pancreatic cancer will claim an estimated 47,050 lives in the USA in 2020, with an expected 5 year survival of 10%. Thus there is an urgent need for novel treatment options in this disease. We hypothesize that effective response against pancreatic cancer requires a coordinated approach that orchestrates both the innate and adaptive immune system. We further hypothesize that by orchestrating the activation of the entire immune system, we could accomplish immunogenic cell death with durable responses in this disease. We describe a novel combination immunotherapy protocol of low-dose chemoradiation, cytokine-induced NK and T cell activation via N-803 (an IL-15 cytokine fusion protein), and off-the-shelf PDL1-targeted high-affinity NK cell (PDL1 t-haNK) infusion. Methods: The ongoing QUILT 88 phase II/III, multi-center, three-cohort, open-label, US study (NCT04390399) to evaluate the comparative efficacy and overall safety of standard-of-care chemotherapy versus standard-of-care chemotherapy in combination with aldoxorubicin HCl, N-803, and PD-L1 t-haNK in subjects with locally advanced or metastatic pancreatic cancer. Each treatment setting (ie, first line maintenance, second line, or third line or greater) will be evaluated independently as a separate cohort. Subjects with locally advanced or metastatic pancreatic cancer who have received at least 16 weeks of treatment with gemcitabine plus nab-paclitaxel, and have had either a partial response (PR), CR, or stable disease (SD), will be enrolled into Cohort A to receive first-line maintenance therapy. Subjects who have disease progression on or after receiving first-line treatment with gemcitabine plus nab-paclitaxel or another first-line chemotherapy regimen (eg, FOLFIRINOX), or who have discontinued first-line treatment (eg, due to toxicity or intolerance) will be enrolled into Cohort B to receive second-line therapy randomized to irinotecan-liposome/5FU/LV versus experimental arm. Subjects who have disease progression after receiving at least 2 lines of therapy for pancreatic cancer, will be enrolled into Cohort C to receive third-line or greater treatment. Primary endpoints by cohort are: A) PFS per RECIST V1., B & C) OS. The secondary endpoints include overall response rate, DoR, DCR, OS(cohort A) and QoL by patient-reported outcomes. Clinical trial information: NCT04390399.
ENGOT-ov54/Swiss-GO-2/MATAO including LOGOS (Low-Grade Ovarian cancer Sub-study): MAintenance Therapy with Aromatase inhibitor in epithelial Ovarian cancer—A randomized, double-blinded, placebo-controlled, multicenter phase III Trial.
Authors: Heinzelmann-Schwarz Viola A. , Kurzeder Christian , Schmid Seraina , Gabriel Natalie , Mueller Andreas , Fehr Mathias Konrad , Marth Christian , Du Bois Andreas , Klar Maximillian
Published: June 2021

TPS5598

Background: The prognosis of advanced epithelial ovarian cancer (OC) is poor with a relapse rate of 75% at 5 years. Some 80% of OC express estrogen receptor (ER). This is the first trial that wants to capitalize on this and prospectively evaluates letrozole, a potent aromatase inhibitor, as initial maintenance treatment for high and low grade OC. Methods: Eligible pts have primary OC, FIGO Stage II-IV with low or high grade serous or endometrioid histology, with (interval) debulking surgery, ECOG-status 0-2, Positivity (≥ 1%) for ER expression, and at least 4 cycles of platinum-based chemotherapy (neoadjuvant allowed). Pts are allowed to undergo concurrent maintenance treatment with bevacizumab and PARP inhibitors. Extensive quality of life (QoL) questionnaires via an App and physical activity measurements by a tracking device as well as G8 geriatric score, ESGO surgery questionnaire, and Charleson Comorbidity Index are routinely assessed. Primary objective is to evaluate the efficacy of letrozole maintenance therapy after standard surgical and chemotherapy treatment as measured by Progression Free Survival (PFS) compared to no maintenance therapy (placebo). Primary outcome is PFS, defined as time from date of first letrozole/placebo administration until date of progression or death by any cause. Stratification for high and low grade histologies and ER measurement is performed via a digital centralized pathology review process. Final analysis will be performed for the whole cohort and for the subgroup of low grade ovarian cancers (LOGOS subprotocol). Secondary objectives and outcomes are overall survival (OS), quality adjusted progression free survival (QAPFS), time to first subsequent treatment (TFST), quality adjusted time without symptoms (TWiST), and health related QoL. Study is designed as international, randomized (1:1 ratio), two-arm, multi-centric, double-blinded, placebo-controlled superiority phase III trial. In total, 528 pts will be randomly assigned to letrozole or placebo for 5 yrs or until unacceptable toxicity, progression of underlying disease, or study discontinuation. Final analysis is planned after 5 years without interval analysis and follow-up is collected for up to 10yr and for the low-grade cohort for up to 12yr. Clinical trial information: NCT04111978.
Clinical trial in progress: Pivotal study of VB-111 combined with paclitaxel versus paclitaxel for treatment of platinum-resistant ovarian cancer (OVAL, VB-111-701/GOG-3018).
Authors: Arend Rebecca Christian , Monk Bradley J. , Herzog Thomas J. , Ledermann Jonathan A. , Moore Kathleen N. , Secord Angeles Alvarez , Shapira-Frommer Ronnie , Tewari Krishnansu Sujata , Rachmilewitz Minei Tamar , Harats Dror , Penson Richard T.
Published: June 2021

TPS5599

Background: Ofranergene obadenovec (VB-111) is a targeted anti-cancer gene therapy with a dual mechanism of action that includes a broad antiangiogenic effect and induction of a tumor directed immune response. A phase II trial in patients with platinum resistant ovarian cancer showed that VB-111 in combination with weekly paclitaxel was well tolerated and associated with a CA-125 Objective Response Rate (ORR) of 58% with a trend for improved survival. The favorable outcomes were associated with induction of an immunotherapeutic effect of tumor infiltration with CD-8 T cells. Based on these observations, a phase III study was initiated in collaboration with the GOG Foundation, Inc. Methods: Study NCT03398655 is an international, randomized, double-blind, placebo-controlled, phase III study. Eligible patients have recurrent platinum-resistant epithelial ovarian cancer with measurable disease (RECIST 1.1), and may have been previously treated with up to 5 prior lines of therapy. Patient are randomized 1:1 to receive VB-111 (1x1013 VPs) with weekly paclitaxel (80mg/m2), or weekly paclitaxel with placebo. Randomization is stratified by number of prior treatment lines, prior antiangiogenic therapy and platinum refractory disease status. The efficacy endpoints are OS, PFS and ORR by RECIST 1.1 and by CA-125 (GCIG criteria). A pre-planned interim analysis was performed by the DSMC in the first 60 patients evaluable for CA-125 response. The analysis met the pre-defined criteria of a CA-125 ORR (GCIG) in the treatment arm at least 10% higher than in the control arm. Study enrolment is ongoing and over 220 patients were enrolled in the US, EU, and Israel. Enrolment of the full sample size of 400 patients is expected to complete by the end of 2021. Clinical trial information: NCT03398655.
CMP-001-007: Open-label, phase 2 study of intratumoral CMP-001 + pembrolizumab in patients with recurrent or metastatic head and neck squamous cell carcinoma.
Authors: Wong Deborah J.L. , Panwar Aru , Rosenberg Ari , Karivedu Vidhya , Laux Douglas Earl , Zandberg Dan Paul , Bobilev Dmitri , Zhao Luping , Wooldridge James , Krieg Art M. , Cohen Ezra E.W.
Published: June 2021

TPS6089

Background: PD-1 blockade ± chemotherapy has recently become a primary systemic therapy recommended by NCCN guidelines for patients (pts) with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC). However, most pts still do not respond to treatment, indicating a large unmet need for pts with unresectable disease. CMP-001 is a toll-like receptor 9 (TLR9) agonist comprising a CpG-A oligodeoxynucleotide packaged in a virus-like particle that can induce type I interferon secretion from tumor-associated plasmacytoid dendritic cells, promoting a Th1-like chemokine milieu in the tumor microenvironment and inducing an antitumor CD8+ T-cell response. In a phase (ph) 1b study in pts with metastatic melanoma, intratumoral (IT) injection of CMP-001 + intravenous (IV) pembrolizumab (pembro) reversed PD-1 blockade resistance, induced responses in injected and noninjected lesions, and had an acceptable safety profile (Milhem et al, SITC 2020). This combination is therefore being tested in pts with HNSCC. Methods: CMP-001-007 (NCT04633278) is an open-label, multicenter, ph 2 study designed to investigate the efficacy and safety of CMP-001 + IV pembro in adult pts with histologically or cytologically confirmed R/M HNSCC considered incurable by local therapies. Eligible pts have undergone a pretreatment tumor biopsy, received no prior systemic therapy in the R/M setting, and have primary tumor locations of oropharynx, oral cavity, hypopharynx, or larynx. In addition, pts must have PD-L1-positive tumors (combined positive score ≥1), known tumor human papillomavirus (HPV) status (for oropharyngeal cancer), and measurable disease per RECIST v1.1 with ≥1 lesion amenable to IT injection. Pts with primary tumors in the nasopharynx are excluded. Enrolled pts will receive CMP-001 10 mg once weekly for 7 doses and every 3 weeks (Q3W) thereafter. The first dose may be administered subcutaneously or via IT injection, with all subsequent doses administered IT. All pts will also receive pembro 200 mg IV Q3W after the CMP-001 injection. Treatment continues until unacceptable toxicity or disease progression. The primary endpoint is investigator-assessed objective response rate (ORR) per RECIST v1.1. Secondary endpoints include safety, duration of response (DOR), progression-free survival (PFS), overall survival, and effects of HPV infection and PD-L1 expression on ORR, DOR, and PFS. Exploratory endpoints include analyses of baseline and changes from baseline in tumor or serum biomarkers related to TLR9, immune checkpoints, and potential predictors of response, as well as serum concentrations of CXCL10 and CMP-001. Refer to clinicaltrials.gov/ct2/show/NCT04633278 for the most current information on enrolling sites. Clinical trial information: NCT04633278.
A phase 1 dose escalation and cohort expansion study of the safety and efficacy of allogeneic CRISPR-Cas9–engineered T cells (CTX110) in patients (Pts) with relapsed or refractory (R/R) B-cell malignancies (CARBON).
Authors: McGuirk Joseph , Bachier Carlos R. , Bishop Michael Russell , Ho P. Joy , Murthy Hemant S. , Dickinson Michael J. , Maakaron Joseph E. , Andreadis Charalambos , Ghobadi Armin , Waller Edmund K. , Benton Mark Daniel , Suh Susanna , Xu Huansheng , Morawa Ewelina , Awan Farrukh Tauseef , Shaughnessy Paul , Tam Constantine Si Lun , Kroeger Nicolaus , Maziarz Richard T.
Published: June 2021

TPS7570

Background: Diffuse large B-cell lymphoma (DLBCL) is the most common form of non-Hodgkin lymphoma (NHL), and although > 50% of pts achieve long-term remission with first-line therapy, pts with R/R disease as well as those with R/R grade 3b follicular lymphoma (FL), double-, or triple-hit high-grade lymphomas have poor long-term outcomes (Crump 2017; Kahl 2016; Jain 2012). Autologous (auto) chimeric antigen receptor (CAR) T cell therapy has provided additional options for pts with R/R disease, but only when leukapheresis and manufacturing prove feasible (Jacobson 2020). Allogeneic (allo) CAR-T cells were designed specifically to address these unmet needs by using healthy donor T cells to produce a readily available product and remove the need for bridging chemotherapy. We are currently investigating the safety and efficacy of CTX110, an allo anti-CD19 CAR-T cell product modified by using CRISPR/Cas9-editing to disrupt the endogenous T-cell receptor (TCR) alpha constant (TRAC) locus in order to remove TCR expression and disrupt β2-microglobulin, which eliminates major histocompatibility complex (MHC) class I expression. Disruption of the TCR should significantly reduce or eliminate risks of graft-versus-host disease and elimination of MHC class I expression may increase CAR-T cell persistence by mitigating CTX110 rejection. In addition, the anti-CD19 CAR transgene construct is precisely inserted into the TRAC locus. Methods: The Phase 1 CARBON trial (NCT04035434) is an open-label, multicenter, global study evaluating the safety and efficacy of CTX110 in pts ≥18 y with R/R DLBCL NOS, double- or triple-hit DLBCL, or transformed or grade 3b FL with ≥2 prior lines of therapy or who are ineligible for/refused prior auto hematopoietic stem cell transplant (HSCT). Pts who received prior auto CAR-T or allo HSCT are excluded. Pts will receive lymphodepleting chemotherapy with fludarabine 30mg/m2 and cyclophosphamide 500mg/m2 for 3 days, followed by CTX110 infusion. In part A, dose escalation will be performed using a 3+3 design. Upon completion of dose finding, the cohort will be expanded to further assess safety signals and efficacy including the primary efficacy endpoint of overall response rate. Key secondary efficacy endpoints include duration of response, progression-free survival, and overall survival. The trial is currently open and enrolling. Clinical trial information: NCT04035434.
Clinical trial in progress: Phase II trial of defactinib (VS-6063) combined with VS-6766 (CH5126766) in patients with metastatic uveal melanoma.
Authors: Seedor Rino S. , Orloff Marlana , Gutkind J. Silvio , Aplin Andrew E. , Terai Mizue , Sharpe-Mills Erin , Klose Haley , Mastrangelo Michael J. , Sato Takami
Published: June 2021

TPS9588

Background: Despite successful treatment of primary uveal melanomas (UM), up to 50% of patients subsequently develop systemic metastasis, with the liver involved in up to 90% of patients. Currently there is no US FDA-approved treatment for metastatic uveal melanoma (MUM). Activating mutations in genes encoding alpha subunits of the heterotrimeric G proteins, GNAQ and GNA11, are found in 80-90% of UM. Recent information suggests that GNAQ/GNA11-oncogenic signaling involves a non-canonical pathway conferring the activation of YAP1, distinct from the activation of PLCβ and PKC-MEK-ERK, which may explain the failure of MEK inhibitors in MUM patients. Focal Adhesion Kinase (FAK) is a tyrosine kinase that provides a direct link between Gαq and tyrosine phosphorylation networks controlling YAP and UM growth. Interestingly, UM represents the human cancer harboring the highest level of FAK overexpression. Recent kinome-wide CRISPR-Cas9 screens revealed that FAK and RAF/MEK co-targeting may provide a new network-based precision therapeutic strategy for MUM treatment. Methods: This is an investigator-initiated, prospective, single arm, single-institution, phase II trial evaluating the combination of a FAK inhibitor (defactinib, VS-6063) with a RAF/MEK inhibitor (VS-6766, CH5126766) for the treatment of patients with metastatic uveal melanoma [NCT04720417]. The primary endpoint of the study is disease control rate (DCR) of 50% including complete response (CR), partial response (PR), and stable disease (SD) as determined by RECIST criteria version 1.1. Secondary endpoints include progression free survival, overall survival, and causality of adverse events. Exploratory endpoints include analysis of the pharmacodynamic profile, mechanism of resistance to the combination, and investigation of circulating free DNA as a biomarker. The efficacy of this combination treatment will be assessed using the Simon’s two stage design. In stage I, a total number of 8 patients are accrued and if there are 2 or fewer overall responses among these 8 patients, further enrollment of patients may be stopped with the conclusion that DCR cannot be 50% or greater. Otherwise, an additional 10 patients will be accrued in stage II, resulting in a total sample size of 18 patients. Patients at 18 years or older with metastases from uveal melanoma will be eligible (any line of therapy). Defactinib (200 mg) will be administered orally twice a day in combination with VS-6766 (3.2 mg) administered orally twice a week for 3 weeks, in 28-day cycles. Dose modification will be considered based on toxicity. Treatment will be continued until maximum clinical benefit is obtained; disease progression or the development of intolerable side effects. Enrollment to stage 1 began in February 2021. Clinical trial information: NCT04720417.
Out-of-Pocket Costs of Complementary Medicine Following Cancer and the Financial Impact in a Setting With Universal Health Coverage: Findings From a Prospective Cohort Study
Authors: Bhoo-Pathy Nirmala , Subramaniam Shridevi , Khalil Sadia , Kimman Merel , Kong Yek-Ching , Ng Chiu-Wan , Bustamam Ros Suzanna , Yip Cheng-Har
Published: June 2021

PURPOSE:

To determine household spending patterns on complementary medicine following cancer and the financial impact in a setting with universal health coverage.

METHODS:

Country-specific data from a multinational prospective cohort study, Association of Southeast Asian Nations Costs in Oncology Study, comprising 1,249 cancer survivors were included. Household costs of complementary medicine (healthcare practices or products that are not considered as part of conventional medicine) throughout the first year after cancer diagnosis were measured using cost diaries. Study outcomes comprised (1) shares of household expenditures on complementary medicine from total out-of-pocket costs and health costs that were respectively incurred in relation to cancer, (2) incidence of financial catastrophe (out-of-pocket costs related to cancer ≥ 30% of annual household income), and (3) economic hardship (inability to pay for essential household items or services).

RESULTS:

One third of patients reported out-of-pocket household expenditures on complementary medicine in the immediate year after cancer diagnosis, accounting to 20% of the total out-of-pocket costs and 35% of the health costs. Risk of financial catastrophe was higher in households reporting out-of-pocket expenditures on complementary medicine (adjusted odds ratio: 1.39 [95% CI, 1.05 to 1.86]). Corresponding odds ratio within patients from low-income households showed that they were substantially more vulnerable: 2.28 (95% CI, 1.41 to 3.68). Expenditures on complementary medicine were, however, not associated with economic hardship in the immediate year after cancer diagnosis.

CONCLUSION:

In settings with universal health coverage, integration of subsidized evidence-based complementary medicine into mainstream cancer care may alleviate catastrophic expenditures. However, this must go hand in hand with interventions to reduce the use of nonevidence-based complementary therapies following cancer.
Associations Between Fruit Intake and Risk of Diabetes in the AusDiab Cohort
Authors: Bondonno Nicola P , Davey Raymond J , Murray Kevin , Radavelli-Bagatini Simone , Bondonno Catherine P , Blekkenhorst Lauren C , Sim Marc , Magliano Dianna J , Daly Robin M , Shaw Jonathan E , Lewis Joshua R , Hodgson Jonathan M
Published: June 2021

Context

Fruit, but not fruit juice, intake is inversely associated with type 2 diabetes mellitus (T2DM). However, questions remain about the mechanisms by which fruits may confer protection.

Objective

The aims of this work were to examine associations between intake of fruit types and 1) measures of glucose tolerance and insulin sensitivity and 2) diabetes at follow-up.

Methods

Among participants of the Australian Diabetes, Obesity and Lifestyle Study, fruit and fruit juice intake was assessed by food frequency questionnaire at baseline. Associations between fruit and fruit juice intake and 1) fasting plasma glucose, 2-hour postload plasma glucose, updated homeostasis model assessment of insulin resistance of β-cell function (HOMA2-%β), HOMA2 of insulin sensitivity (HOMA2-%S), and fasting insulin levels at baseline and 2) the presence of diabetes at follow-up (5 and 12 years) were assessed using restricted cubic splines in logistic and linear regression models.

Results

This population of 7675 Australians (45% males) had a mean ± SD age of 54 ± 12 years at baseline. Total fruit intake was inversely associated with serum insulin and HOMA2-%β, and positively associated with HOMA2-%S at baseline. Compared to participants with the lowest intakes (quartile 1), participants with moderate total fruit intakes (quartile 3) had 36% lower odds of having diabetes at 5 years (odds ratio, 0.64; 95% CI, 0.44-0.92), after adjusting for dietary and lifestyle confounders. Associations with 12-year outcomes were not statistically significant.

Conclusion

A healthy diet including whole fruits, but not fruit juice, may play a role in mitigating T2DM risk.
Απόψεις εκπαιδευτικών και μελλοντικών εκπαιδευτικών σε σχέση με τη διαχείριση της θρησκευτικής ετερότητας στο σχολικό χώρο και την προσέγγιση της προσευχής ως στοιχείο εθνικής διαπαιδαγώγησης
Authors: Λυτσιούση Στυλιανή
Published: June 2021

Η παρούσα διδακτορική διατριβή επιχειρεί να διερευνήσει τις απόψεις των εκπαιδευτικών και μελλοντικών εκπαιδευτικών της πρωτοβάθμιας εκπαίδευσης σχετικά τη διαχείριση της θρησκευτικής ετερότητας και την πρακτική της προσευχής στο σχολείο ως στοιχείο εθνικής διαπαιδαγώγησης. Η αποτύπωση αυτή θεωρήθηκε απαραίτητη, καθώς δεν υφίστανται αρκετές παρόμοιες έρευνες και μάλιστα μεγάλου δείγματος εκπαιδευτικών στην Ελλάδα. Ακόμη, η παρουσία ετερόθρησκων μαθητών στη σχολική τάξη καθιστά επιτακτικό το ζήτημα της αποτελεσματικής και δημοκρατικής διαχείρισης της θρησκευτικής ετερότητας, ειδικά με το υπάρχον πλαίσιο της θρησκευτικής εκπαίδευσης, το οποίο καθορίζεται σε σημαντικό βαθμό υπό το πρίσμα της "επικρατούσας θρησκείας" και τη συσχέτισή της με τη δόμηση της εθνικής ταυτότητας. Επίσης, η έρευνα αυτή εξετάζει κατά πόσο οι απόψεις των εκπαιδευτικών συντάσσονται με κάποια από τα μοντέλα σχετικά με την θρησκευτική ετερότητα στο σχολείο και ειδικά αυτό της ερμηνευτικής προσέγγισης (interpretive approach) του Robert Jackson. Η έρευνα είναι ποσοτική και πραγματοποιήθηκε με τη χρήση κλειστού ερωτηματολογίου σε δείγμα 1271 εκπαιδευτικών και φοιτητών παιδαγωγικών τμημάτων από όλη τη χώρα. Η ανάλυση των δεδομένων έγινε με τη χρήση του στατιστικού πακέτου spss 25. Χρησιμοποιήθηκε το t-test και η anova, έγιναν οι συσχετίσεις των κατηγορικών μεταβλητών και η ανάλυση τους (crosstabs), καθώς και παρουσίαση των περιγραφικών στατιστικών (κατανομές, και πίνακες συχνοτήτων, μέσοι όροι και τυπικές αποκλίσεις), προκειμένου να διαπιστωθεί ο βαθμός διακύμανσης των μεταβλητών. Η ανάλυση των δεδομένων έδειξε ότι οι απόψεις των εκπαιδευτικών φάνηκε να επηρεάζονται από τις νομοθετικές και κανονιστικές ρυθμίσεις της εκπαιδευτικής πολιτικής. Η σύγκριση των απόψεων δασκάλων-νηπιαγωγών έδειξε ότι διαφοροποιούνται σημαντικά, με τους/τις νηπιαγωγούς να παρουσιάζουν μία πιο φιλελεύθερη προσέγγιση στα ζητήματα της θρησκευτικής ετερότητας. Διαφοροποιήσεις αποτυπώθηκαν και στις απόψεις των εν ενεργεία εκπαιδευτικών, συγκριτικά με αυτές των φοιτητών, που δείχνουν πιο ανοιχτοί και δεκτικοί στη θρησκευτική ετερότητα. Τέλος, τα αποτελέσματα της έρευνας έδειξαν ότι η προσέγγιση των εκπαιδευτικών σχετικά με τη διαχείριση της θρησκευτικής ετερότητας έχει σημαντικές διαφορές από την ερμηνευτική προσέγγιση του Robert Jackson. Οι ομοιότητες αφορούν κυρίως σε μεμονωμένες πρακτικές. Η αποτύπωση των απόψεων των εκπαιδευτικών μπορεί να συμβάλλει στην επιμόρφωση των εκπαιδευτικών για τα ζητήματα που αναδεικνύονται και να χρησιμοποιηθούν για την υλοποίηση μελλοντικών σχετικών ερευνών. Τα αποτελέσματα μπορούν να προσφέρουν ένα θεωρητικό πλαίσιο για την το σχεδιασμό και την εφαρμογή ενός μοντέλου θρησκευτικής εκπαίδευσης, προσαρμοσμένου στην ελληνική πραγματικότητα.
Έλεγχος της ακρίβειας της υπολογιστικής τομογραφίας κωνικής δέσμης (CBCT) στην εκτίμηση του πάχους των περιεμφυτευματικών οστικών πετάλων και των πιθανών συνεπειών των σχετικών artifacts
Authors: Σαπουντζής Αλέξανδρος
Published: June 2021

Η υπολογιστική τομογραφία κωνικής δέσμης (ΥΤΚΔ) έδωσε λύση σε πολλά διαγνωστικά προβλήματα που παρουσιάζονται στην σύγχρονη οδοντιατρική. Κατά τον προ-εγχειρητικό έλεγχο στην εμφυτευματολογία παρέχει πληροφορίες που βοηθούν στην επιλογή του κατάλληλου εμφυτεύματος ως προς το μήκος και διάμετρο καθώς και αξιολογεί τις παρακείμενες ανατομικές δομές ενδιαφέροντος. Μεταεγχειρητικά συντελεί στην εκτίμηση της υγείας των περιεμφυτευματικών ιστών, δίνοντας περισσότερες πληροφορίες από αντίστοιχες δισδιάστατες απεικονιστικές μεθόδους και βοηθάει στον σχεδιασμό πιθανών διορθωτικών επεμβάσεων μετά το στάδιο της προσθετικής αποκατάστασης.Σκοπός αυτής της in vitro εργασίας είναι η αξιολόγηση της διαγνωστικής ακρίβειας της υπολογιστικής τομογραφίας κωνικής δέσμης στην μέτρηση του πάχους του περιεμφυτευματικού φλοιώδους πέταλου με την χρήση διάφορων συνδυασμών εκθεσιακών στοιχείων και τις πιθανές συνέπειες των σχετικών artifacts που προκαλούνται από την μεταλλική επιφάνεια των εμφυτευμάτων. Στην έρευνα χρησιμοποιήθηκαν 5 οστικά τεμάχια από γνάθους ενήλικων χοίρων. Σε κάθε οστικό τεμάχιο πραγματοποιήθηκαν δυο οστεοτομίες και τοποθετήθηκαν δυο εμφυτεύματα Biomet 3i Nano-tite Certain διαστάσεων 4χ10 χιλιοστών. Για κάθε οστικό τεμάχιο κατασκευάστηκε ένας ακτινοσκιερός νάρθηκας, πάνω στον οποίο σε βάθος 4 και 8 χιλιοστών από το άνω χείλος της οστεοτομίας τοποθετήθηκαν κομμάτια γουταπέρκας 1 χιλιοστού. Πάνω στα δείγματα λήφθηκαν μια σειρά τομογραφίες σε διάφορους συνδυασμούς εκθεσιακών στοιχείων με και χωρίς τα εμφυτεύματα τοποθετημένα. Σαν τομογράφος χρησιμοποιήθηκε ο Planmeca Promax mid 3D . Οι μετρήσεις του πάχους έγιναν από 2 αξιολογητές με κλινική εμπειρία στην ερμηνεία υπολογιστικών τομογραφιών κωνικής δέσμης. Προηγήθηκε εκπαίδευση των αξιολογητών στην χρήση του λογισμικού του τομογράφου και τους δόθηκαν προφορικές και γραπτές οδηγίες πριν από τις συνεδρίες αξιολόγησης. Οι μετρήσεις που προέκυψαν συγκρίθηκαν με τη ανατομική αλήθεια. Τα αποτελέσματα της εργασίας έδειξαν ότι δεν ύπαρχουν στατιστικά σημαντικές διαφορές μεταξύ των μετρήσεων στις τομογραφικές εικόνες και της ανατομικής αλήθειας για κανένα από τους συνδυασμούς εκθεσιακών στοιχείων που χρησιμοποιήθηκε (μέγεθος ογκοστοιχείου, kVp, mA).
QUALITY OF LIFE ASSESSMENT IN PATIENTS WITH ARTERIAL HYPERTENSION (LITERATURE REVIEW)
Authors: MOSKALENKO OLGA , YASKEVICH ROMAN
Published: June 2021

A review of the literature on the current problem of medicine is presented. Arterial hypertension is one of the common chronic diseases for which the current goal of therapy is not recovery, but improvement of circulatory function with a satisfactory quality of life. The study of QOL and the factors influencing it can contribute to an increase in the individual effectiveness of treatment and complex rehabilitation of patients suffering from this pathology.
Compliance to mineral supplementation among pregnant women at a public health clinic in Malaysia
Authors: Fadzil Nurul Nabilah Ahmad , Halain Azura Abdul , Nee Santhi A/P Yew Roan , Lam Soh Kim , Japar Salimah
Published: June 2021

Background

Prenatal supplementation has been introduced to pregnant women during early pregnancy to prevent complication to both mother and fetus. The complications include anaemia, postpartum haemorrhage, low birth weight and fetal defects.

Aim

To assess compliance with vitamin and mineral supplementation in pregnant women.

Methods

A cross-sectional design with simple random sampling was used in this study with 100 respondents who attended the maternal and child clinic in Selangor, Malaysia.

Findings

The findings showed that 86 respondents (86%) were compliance towards vitamin and mineral supplementation, whereas 35 respondents (35%) were non-compliance mainly due to forgetfulness. The result indicated a significant association between compliance with race (p=0.02), occupation (p<0.01), household income (p=0.02), education (p<0.01), parity (p<0.01) and trimester (p=0.02).

Conclusion

Majority of the respondents acknowledge that side effects and forgetfulness were the main influencing factors towards non-compliance.
Investigating the effect of training on health behaviours of breastfeeding mothers in Iran
Authors: Ghasemi Afsaneh , Harsini Pooyan Afzali , Jeihooni Ali Khani
Published: June 2021

Aim

This article aims to investigate the effect of training based on Pender's model on health promotion behaviours in breastfeeding mothers.

Methodology

In this quasi-experimental interventional study, 97 breastfeeding mothers referred to Fasa clinics were randomly studied in two case (n=48) and control (n=49) groups. To collect data, Walker et al's health promotion lifestyle questionnaire, including 52 questions, was used. After distributing the questionnaires in the first stage, the case group received five sessions of training. Data analysis was performed using SPSS20 software and independent t-test and paired t-test.

Results

According to the results, the highest and lowest scores were related to the areas of spiritual growth (23.29±6.16 before training and 24.65±6.56 after training) and interpersonal relationships (4.70±1.57 before training and 1.57±1.76 after training), respectively. In all six areas, a significant increase was found in scores after the training in the case group or between the case and control groups.

Conclusion

With this small sample and just one month training, the researchers demonstrated that it is possible to make changes in all areas of health. This can not only have an immediate effect but also a ‘snowball effect’ down the generations, through mother-children transfer, as well as mother-to-other family members transfer.
The role of the practice nurse in cancer care reviews
Authors: Dyer Sandra
Published: June 2021

Recent changes to the Quality and Outcomes Framework provide an ideal opportunity to improve the quality of cancer care reviews and cancer patients' experiences. Sandra Dyer explains the important role practice nurses can play in improving care

Improved outcomes for people diagnosed with cancer have led to increasing numbers of people living with and beyond the disease, and for many, cancer has transitioned to a long-term condition. There is a greater need for models of care that best meet these patients' needs, with the role of primary care becoming increasingly important. Recent changes to the Quality and Outcomes Framework (QOF) provide an ideal opportunity to improve the quality of cancer care reviews and improve cancer patients' experiences. More education and training for general practice nurses on cancer is urgently required to allow them to lead on quality improvement in this important area of care.
Cervical Screening Awareness Week: getting the facts out
Authors: Sanger Kate
Published: June 2021

Kate Sanger highlights the need to provide support and information this Cervical Screening Awareness Week
Force-based Active Compliance Control of Hydraulic Quadruped Robot
Authors: Rui Zhu , Qingjun Yang , Chen Chen , Chunli Jiang , Congfei Li , Yuxuan Wang
Published: June 2021

The hydraulically driven quadruped robot has received extensive attention from many scholars due to its high power density and adaptability to unstructured terrain. However, the research on hydraulic quadruped robots based on torque control is not mature enough, especially in the aspect of multi-rigid body dynamics. In this paper, the most commonly used gait trot is selected as the research object. First, the multi-rigid motion equation of the quadruped robot is established by the spin recursion method based on Lie groups. Next, the Lagrange multiplier is used to represent the constraint force to establish the 12-degree-of-freedom inverse dynamics model of the quadruped robot’s stance phase. And the hybrid dynamics method is used to reduce the dimension of the inversion matrix, which simplifies the solution process of the dynamics model. Then, the trajectory of the foot is planned. Through the analysis of the simplified model, it is concluded that the gait cycle and the initial position of the stance phase are important factors affecting the stability of the trot gait. Finally, the controller framework of the quadruped robot is introduced, and the effectiveness of the algorithm designed in this paper is verified through the co-simulation of the trot gait. The co-simulation results show that the inverse dynamics algorithm can be used as the feedforward of the control system, which can greatly reduce the gains of the PD controller; the robot has good compliance and can achieve stable trotting.
Identifying the Phishing Websites Using the Patterns of TLS Certificates
Authors: Sakurai Yuji , Watanabe Takuya , Okuda Tetsuya , Akiyama Mitsuaki , Mori Tatsuya
Published: June 2021

With the recent rise of HTTPS adoption on the Web, attackers have begun “HTTPSifying” phishing websites. HTTPSifying a phishing website has the advantage of making the website appear legitimate and evading conventional detection methods that leverage URLs or web contents in the network. Further, adopting HTTPS could also contribute to generating intrinsic footprints and provide defenders with a great opportunity to monitor and detect websites, including phishing sites, as they would need to obtain a public-key certificate issued for the preparation of the websites. The potential benefits of certificate-based detection include (1) the comprehensive monitoring of all HTTPSified websites by using certificates immediately after their issuance, even if the attacker utilizes dynamic DNS (DDNS) or hosting services; this could be overlooked with the conventional domain-registration-based approaches; and (2) to detect phishing websites before they are published on the Internet. Accordingly, we address the following research question: How can we make use of the footprints of TLS certificates to defend against phishing attacks? For this, we collected a large set of TLS certificates corresponding to phishing websites from Certificate Transparency (CT) logs and extensively analyzed these TLS certificates. We demonstrated that a template of common names, which are equivalent to the fully qualified domain names, obtained through the clustering analysis of the certificates can be used for the following promising applications: (1) The discovery of previously unknown phishing websites and (2) understanding the infrastructure used to generate the phishing websites. Furthermore, we developed a real-time monitoring system using the analysis techniques. We demonstrate its usefulness for the practical security operation. We use our findings on the abuse of free certificate authorities (CAs) for operating HTTPSified phishing websites to discuss possible solutions against such abuse and provide a recommendation to the CAs.
Modelling of integrated scheduling problem of capacitated equipment systems with a multi-lane road network
Authors: Luan Di , Zhao Mingjing , Zhao Qianru , Wang Nan
Published: June 2021

The coordination of different container-handling equipment is an important method for improving the overall efficiency of automated container terminals. In the real terminal, we should consider many real-life issues, such as the equipment capacity, the equipment collision, changing lanes in the multi-lane road, and choosing one of container-handling lanes for each container. This paper proposes the integrated scheduling problem of three container-handling equipment with the capacity constraint and the dual-cycle strategy, for simultaneously solving the equipment scheduling problem, the assignment problem of the container-handling lane and the conflict-free route planning problem of automated guided vehicles (AGVs). With the objective of minimizing the ship’s berth time, we propose a mixed-integer programming model based on the space-time network representation method and two bilevel optimization algorithms based on conflict resolution rules. Finally, numerical experiments are conducted to verify the effectiveness of the proposed model and two bilevel optimization algorithms.
Factors affecting prehospital time delay of the injured patients arriving at the Emergency Department of Beni-Suef University Hospital in Egypt: A cross-sectional study
Authors: Khalil Doaa Mahmoud , Elmorsy Elmorsy , Arafa Ahmed , Nafady Hesham Ahmed , Saleh Lamiaa
Published: June 2021

Purpose

This study aimed to assess the factors affecting the prehospital time delay of the injured patients arriving at the Emergency Department of Beni-Suef University Hospital in Upper Egypt.

Materials and methods

In this cross-sectional study, the following data were retrieved from the hospital records of 632 injured patients between 1/1/2018 and 31/3/2018: age, sex, residence, means of transportation to the hospital, prehospital time delay, consciousness level on admission, source of injury, and type of worst injury.

Results

The prehospital time delay (>one hour) of the injured patients was positively associated with age >60 years and rural residence but inversely associated with consciousness level with odds ratios (95% confidence intervals) of 5.14 (2.26–11.68), 3.49 (2.22–5.48), and 0.56 (0.32–0.96), respectively.

Conclusion

The prehospital time delay of the injured patients arriving at the Emergency Department of Beni-Suef University Hospital in Egypt was associated with old age, rural residence, and consciousness level.
Organization model, vertical integration, and farmers’ income growth: Empirical evidence from large-scale farmers in Lin’an, China
Authors: Ao Guiyan , Liu Qiang , Qin Li , Chen Minghao , Liu Shuai , Wu Weiguang
Published: June 2021

Since China’s reform and opening-up in 1978, the income of rural residents has increased when compared with that of urban residents. However, the income growth rate of farmers is relatively low, and the income gap between urban and rural areas is widening. Using a sample of 1,325 large-scale farming households in Lin’an, this study constructs a theoretical path for how the level of vertical integration and an organization model affect farmers’ income levels and empirically tests the path using a mediation effect analysis model. The results indicate that organization models and vertical integration are important factors that affect farmers’ income levels. The total income and agricultural operation income of farmers who participate in agricultural operation organizations are greater than that of farmers who do not participate in an operation organization. In addition, the total income and agricultural operation income of farmers who produce and process and those who produce, process, and sell are higher than those of farmers who only produce. A farmers’ organization model has both a direct and an indirect positive influence on their income level, with the indirect positive influence coming through the mediating variable of vertical integration. The application of the organizational model can promote the growth of rural households’ total family income and agricultural income by 13.48% and 14.48% respectively, consisting of direct increases of 9.67% and 10.19%, and indirect increases of 3.81% and 4.29% through vertical integration. The results also show that access to credit, agricultural technology training, and the farmer’s education level have significant positive impacts on farming income levels. The findings suggest ways to increase farmers’ income by perfecting agricultural management organization systems, promoting agricultural industrialization, strengthening rural financial support, improving agricultural technical training for farmers, and increasing their level of education.
Preface
Authors: Alexandre dit Sandretto Julien , Mullier Olivier , Chapoutot Alexandre
Published: June 2021

The Summer Workshop on Interval Methods (SWIM) is an annual meeting initiated in 2008 by the French MEA working group on Set Computation and Interval Techniques of the French research group on Automatic Control. A special focus of the MEA group is on promoting interval analysis techniques and applications to a broader community of researchers, facilitated by such multidisciplinary workshops. Since 2008, SWIM has become a keystone event for researchers dealing with various aspects of interval and set-based methods.

In 2019, the 12th edition in this workshop series was held at ENSTA Paris, France, with a total of 25 talks.

Traditionally, workshops in the series of SWIM provide a platform for both theoretical and applied researchers who work on the development, implementation, and application of interval methods, verified numerics, and other related (set-membership) techniques.For this edition, given talks were in the fields of

the verified solution of initial value problems for ordinary differential equations, differential-algebraic system models, and partial differential equations,

scientific computing with guaranteed error bounds,

the design of robust and fault-tolerant control systems,

the implementation of corresponding software libraries, and

the usage of the mentioned approaches for a large variety of system models in areas such as control engineering, data analysis, signal and image processing.

Seven papers were selected for submission to this Acta Cybernetica special issue. After a two turn peer-review process, six high-quality articles were selected for publication in this special issue. Three papers propose a contribution regarding differential equations, two papers focus on robust control, and one paper considers fault detection.