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Cheng, Allan, Javier Esparza, and Jens Palsberg. "Complexity results for 1-safe nets." Theoretical Computer Science 147, no. 1-2 (August 1995): 117–36. http://dx.doi.org/10.1016/0304-3975(94)00231-7.
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Chalopin, Jérémie, and Victor Chepoi. "1-Safe Petri Nets and Special Cube Complexes." ACM Transactions on Computational Logic 20, no. 3 (July 16, 2019): 1–49. http://dx.doi.org/10.1145/3322095.
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Marchese, Ugo, Martin Gaillard, Anna Pellat, Stylianos Tzedakis, Einas Abou Ali, Anthony Dohan, Maxime Barat, Philippe Soyer, David Fuks, and Romain Coriat. "Multimodal Management of Grade 1 and 2 Pancreatic Neuroendocrine Tumors." Cancers 14, no. 2 (January 15, 2022): 433. http://dx.doi.org/10.3390/cancers14020433.
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Pancreatic neuroendocrine tumors (p-NETs) are rare tumors with a recent growing incidence. In the 2017 WHO classification, p-NETs are classified into well-differentiated (i.e., p-NETs grade 1 to 3) and poorly differentiated neuroendocrine carcinomas (i.e., p-NECs). P-NETs G1 and G2 are often non-functioning tumors, of which the prognosis depends on the metastatic status. In the localized setting, p-NETs should be surgically managed, as no benefit for adjuvant chemotherapy has been demonstrated. Parenchymal sparing resection, including both duodenum and pancreas, are safe procedures in selected patients with reduced endocrine and exocrine long-term dysfunction. When the p-NET is benign or borderline malignant, this surgical option is associated with low rates of severe postoperative morbidity and in-hospital mortality. This narrative review offers comments, tips, and tricks from reviewing the available literature on these different options in order to clarify their indications. We also sum up the overall current data on p-NETs G1 and G2 management.
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Abbes, Samy. "Toward uniform random generation in 1-safe Petri nets." Electronic Notes in Discrete Mathematics 59 (June 2017): 3–17. http://dx.doi.org/10.1016/j.endm.2017.05.002.
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Mishra, P. K. "Lower and upper bounds of shortest paths in reachability graphs." International Journal of Mathematics and Mathematical Sciences 2004, no. 57 (2004): 3023–36. http://dx.doi.org/10.1155/s0161171204403378.
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We prove the following property for safe marked graphs, safe conflict-free Petri nets, and live and safe extended free-choice Petri nets. We prove the following three results. If the Petri net is a marked graph, then the length of the shortest path is at most(|T|−1)⋅|T|/2. If the Petri net is conflict free, then the length of the shortest path is at most(|T|+1)⋅|T|/2. If the petrinet is live and extended free choice, then the length of the shortest path is at most|T|⋅|T+1|⋅|T+2|/6, whereTis the set of transitions of the net.
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Męski, Artur, Wojciech Penczek, and Agata Półrola. "BDD-based Bounded Model Checking for Temporal Properties of 1-Safe Petri Nets." Fundamenta Informaticae 109, no. 3 (2011): 305–21. http://dx.doi.org/10.3233/fi-2011-513.
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Singh, Gajendra Pratap, Sujit Kumar Singh, and Madhuri Jha. "Existence of Forbidden Digraphs for Crisp Boolean Petri Nets." International Journal of Mathematical, Engineering and Management Sciences 5, no. 1 (November 1, 2019): 83–95. http://dx.doi.org/10.33889/ijmems.2020.5.1.008.
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Boolean Petri net (BPN) and Crisp Boolean Petri net (CBPN) is a well-studied graph model since 2010 which has several applications in mathematical modeling of complex or tricky networks. Modeling any network with Petri net which can generate binary numbers as marking vectors in its reachability tree is still has much uses. In CBPN with a minimum number of transition and minimum number of steps of reachability tree, minimal execution time to run the machine has not been noted till date, thus it’s necessary to sort out this problem. Possibly it may occur due to some forbidden structure which hinders any 1-safe Petri net to be a CBPN. In this paper, we present some forbidden digraphs whose presence interrupts the generation of binary n-vectors exactly once. Any 1-safe Petri net is not a CBPN if it contains any of the subnet induced to the four forbidden structures discussed in this paper.
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Hawa, Fadi, Zeyad Sako, Than Nguyen, Andrew T. Catanzaro, Eugene Zolotarevsky, Angela N. Bartley, and Naresh T. Gunaratnam. "The band and slough technique is effective for management of diminutive type 1 gastric and duodenal neuroendocrine tumors." Endoscopy International Open 08, no. 06 (May 25, 2020): E717—E721. http://dx.doi.org/10.1055/a-1119-6698.
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Abstract Background and study aims Endoscopic resection is recommended as initial treatment for early-stage gastric and duodenal neuroendocrine tumors (G-NETs and D-NETs). However, it can cause serious adverse events. We aimed to evaluate the efficacy and safety of the band and slough (BAS) technique as a novel and less aggressive endoscopic therapy for management of such tumors.Four patients, three diagnosed with < 10-mm D-NET and one with 10-mm type I G-NET, were treated with the BAS technique without endoscopic resection. Initial follow-up endoscopy at 3 months was done to assess for residual tumor. Subsequent endoscopic surveillance was performed. After one session of banding, all patients achieved complete remission at 3-month follow-up. No tumor recurrence was detected on repeat biopsy at 12-month surveillance endoscopy. None of the patients developed any adverse events including bleeding or perforation.The BAS technique may prove to be a safe and effective endoscopic therapy for diminutive, non-metastatic type 1 G-NETs and D-NETs. Studies of larger scale and longer follow-up periods are needed to corroborate these findings.
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Czaja, Ludwik. "Extensions of Elementary Cause-Effect Structures." Fundamenta Informaticae 179, no. 2 (March 10, 2021): 93–111. http://dx.doi.org/10.3233/fi-2021-2016.
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Cause-effect structures are objects of a formal system devised for modeling, testing and verifying properties of tasks, where parallel execution of actions is the most characteristic feature. This is an algebraic system called a quasi-semiring. In this paper elementary cause-effect structures, a system behaviourally equivalent to 1-safe Petri nets, are extended by the following features: weighted edges, multi-valued nodes having capacities (counterpart of place/transition Petri nets), inhibitors and a model of time. The extensions are accomplished by modifying the notion of state and semantics, but leaving unchanged structure of the quasi-semiring expressions.
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Heljanko, Keijo. "Using Logic Programs with Stable Model Semantics to Solve Deadlock and Reachability Problems for 1-Safe Petri Nets." Fundamenta Informaticae 37, no. 3 (1999): 247–68. http://dx.doi.org/10.3233/fi-1999-37304.
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Barthet, Marc, Marc Giovannini, Nathalie Lesavre, Christian Boustiere, Bertrand Napoleon, Stéphane Koch, Mohamed Gasmi, Geoffroy Vanbiervliet, and Jean-Michel Gonzalez. "Endoscopic ultrasound-guided radiofrequency ablation for pancreatic neuroendocrine tumors and pancreatic cystic neoplasms: a prospective multicenter study." Endoscopy 51, no. 09 (January 22, 2019): 836–42. http://dx.doi.org/10.1055/a-0824-7067.
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Abstract Background Pancreatic neuroendocrine tumors (NETs) and intraductal pancreatic mucinous neoplasia (IPMN) with worrisome features are surgically managed. Endoscopic ultrasound (EUS)-guided radiofrequency ablation (RFA) has recently been developed. The safety of EUS-RFA was the primary end point of this study, its efficacy the secondary end point. Methods This was a prospective multicenter study that was planned to include 30 patients with a 1-year follow-up with either a NET < 2 cm or a pancreatic cystic neoplasm (PCN), either a branch duct IPMN with worrisome features or a mucinous cystadenoma (MCA). EUS-RFA was performed with an 18G RFA cooling needle. Results 12 patients had 14 NETs (mean size 13.1 mm, range 10 – 20 mm); 17 patients had cystic tumors (16 IPMNs, 1 MCA; mean size 28 mm, range 9 – 60 mm). Overall three adverse events occurred (10 %), two of these in the first two patients (one pancreatitis, one small-bowel perforation). After these initial patients, modifications in the protocol resulted in a decrease in complications (3.5 %), with one patient having a pancreatic ductal stenosis. Among the 14 NETs, at 1-year follow-up 12 had completely disappeared (86 % tumor resolution), with three patients having a delayed response. Among the 17 PCNs, at 12 months, there were 11 complete disappearances and one diameter that decreased by > 50 % (significant response rate 71 %). All 12 mural nodules showed complete resolution. Conclusions EUS-RFA of pancreatic NETs or PCNs is safe with a 10 % complication rate, which can be decreased by improved prophylaxis for the procedure.
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Libutti, Steven K., Lowell Brian Anthony, David J. Chaplin, and Julie Ann Sosa. "A phase II study of combretastatin A4-phosphate (CA4P) in the treatment of well-differentiated, low- to intermediate-grade, unresectable, recurrent, or metastatic pancreatic, or GI neuroendocrine tumors/carcinoid (GI-NETs/PNETs) with elevated biomarkers." Journal of Clinical Oncology 35, no. 4_suppl (February 1, 2017): 432. http://dx.doi.org/10.1200/jco.2017.35.4_suppl.432.
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432 Background: GI-NETs/PNETs are highly vascular tumors. CA4P, a vascular disrupting agent (VDA), occludes tumor vasculature resulting in ischemic necrosis. Pre-clinical studies of CA4P have shown activity in GI-NETs/PNETs. Methods: OX4218s is a phase II, single-arm, open-label study (NCT02132468) of CA4P in patients (pts) with GI-NETs/PNETs with elevated biomarkers who relapsed during or after standard-of-care treatment. Pts received CA4P 60 mg/m2 IV on days 1, 8, and 15 of a 21-day cycle for 3 cycles. Primary endpoint was change in biomarkers from baseline. Secondary endpoints were safety, tolerability, symptoms, and QOL. Exploratory endpoints were ORR (RECIST 1.1). Pts achieving biomarker or symptom response were eligible for a rollover study. Results: 18 pts were enrolled; 7 subsequently entered the rollover study. Pts were on average aged 58 years, white (89%), male (50%) with ECOG status of 0-1. The majority (94%) had well-differentiated disease (GI-NETS 78%) and received prior Tx (94%). There were no meaningful changes in biomarkers. Eleven (61%) pts had stable disease (SD) and 1 (6%) had a partial response (PR). In the rollover study, 5 (71%) had SD, and 1 had SD for 14 cycles prior to progression (PD). 77% of pts had treatment-related AEs. Key grade 3-5 AEs (> 10%): anemia, abdominal pain, fatigue, hypertension, ALT and AST increases, with 1 grade 5 carcinoid syndrome. Conclusions: The primary endpoint was not met. However, the number of pts entering the rollover study and ORR suggest that CA4P conferred some activity and was generally safe and well tolerated. These findings suggest that due to their inherent variability, tumor biomarkers may not be an ideal endpoint for this population. Clinical trial information: NCT02132468. [Table: see text]
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Al-Toubah, Taymeyah, Eleonora Pelle, Tiffany Valone, Mintallah Haider, and Jonathan R. Strosberg. "Efficacy and Toxicity Analysis of Capecitabine and Temozolomide in Neuroendocrine Neoplasms." Journal of the National Comprehensive Cancer Network 20, no. 1 (January 2022): 29–36. http://dx.doi.org/10.6004/jnccn.2021.7017.
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Background: The capecitabine/temozolomide (CAPTEM) regimen has significant activity in advanced neuroendocrine tumors (NETs). Questions exist regarding activity in pancreatic versus nonpancreatic NETs, risk of opportunistic infections, long-term myelotoxicity, and safety of prolonged treatment duration. Analysis of large patient cohorts is needed for the evaluation of rare toxicities and assessment of risk factors. Methods: We conducted a retrospective study of all patients with advanced NETs seen at Moffitt Cancer Center between January 2008 and June 2019 who received treatment with CAPTEM. Results: A total of 462 patients were eligible. The objective radiographic response rate was 46%, and the disease control rate was 81%. Median progression-free survival (PFS) was 18 months (95% CI, 14.0–21.9 months) and median overall survival was 51 months (95% CI, 42.8–59.2 months): 62 months in well-differentiated NETs versus 14 months in poorly differentiated neuroendocrine carcinomas (P<.0001). Patients with primary pancreatic tumors had the highest partial response rates and longest median PFS. Incidences of grade 4 thrombocytopenia and neutropenia were 7% and 3%, respectively, and substantially higher in women than men (P=.02 and P=.004, respectively). Only 1 case (0.2%) of suspected Pneumocystis pneumonia (PCP) was observed in a patient receiving corticosteroids. Three patients developed myelodysplastic disease, all of whom had received prior peptide receptor radiotherapy (PRRT). There were no acute treatment-related deaths; 1 patient died 2 months after a thrombocytopenic bleed. Conclusions: The CAPTEM regimen is exceptionally safe. Efficacy is particularly robust in well-differentiated pancreatic NETs. Severe myelotoxicity is rare; the risk of grade 4 cytopenias is significantly increased in women, and therefore sex-based dosing should be considered. There were no cases of myelodysplastic syndromes, except among patients who had received PRRT, a known risk factor. The risk of PCP is negligible.
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Manoharan, Prakash, Angela Lamarca, Shaunak Navalkissoor, Jose Calero, Pei San Chan, Peter Julyan, Maribel Sierra, Martyn Caplin, and Juan Valle. "Safety, tolerability and clinical implementation of ‘ready-to-use’ 68gallium-DOTA0-Tyr3-octreotide (68Ga-DOTATOC) (SomaKIT TOC) for injection in patients diagnosed with gastroenteropancreatic neuroendocrine tumours (GEP-NETs)." ESMO Open 5, no. 2 (March 2020): e000650. http://dx.doi.org/10.1136/esmoopen-2019-000650.
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Background68Ga-DOTA0-Tyr3-octreotide (68Ga-DOTATOC) positron emission tomography–CT (PET-CT) has superior diagnostic performance compared to the licensed tracer OctreoScan single photon emission CT–CT in patients with gastroenteropancreatic neuroendocrine tumours (GEP-NETs). A new preparation of 68Ga-DOTATOC using a new ‘ready-to-use’ 68Ga-DOTATOC formulation for injection has been developed (68Ga-DOTATOC (SomaKIT TOC)).ObjectivesThis study aimed to assess the safety and tolerability of 68Ga-DOTATOC (SomaKIT TOC) and evaluate the feasibility and robustness of implementing it in a NET clinical imaging service.MethodsA first-in-human phase I/II multicentre, open-label study of a single dose of 68Ga-DOTATOC (SomaKIT TOC) 2 MBq/kg±10% (range 100–200 MBq) in patients with biopsy-proven grade 1–2 GEP-NETs. PET-CT was performed post injection. Patients were followed up for 28 days. We next implemented this new synthesis methodology in a clinical service assessed over 11 months.ResultsTwenty consenting patients were recruited; 14 males, 6 females; mean (SD) age 58 years (12); NET grade 1 (70%), grade 2 (30%); and 75% with stage IV disease. Twelve patients experienced at least one adverse event (AE) during the study with no grade 3–4 toxicities. Only four AEs were classified as possibly (headache (n=1; 4%), nausea (1; 4%)) or probably (dysgeusia (1; 4%), paraesthesia (1; 4%)) related to the study preparation. One hundred thirteen vials of 68Ga-DOTATOC (SomaKIT TOC) were synthesised with the ‘kit’ over a period of 11 months for clinical utility. Only 2/113 vials (1.77%) were rejected.ConclusionsThe new ready-to-use preparation of 68Ga-DOTATOC (SomaKIT TOC) for injection was safe and well tolerated. This has led to the world’s first (EMA) licensed 68Ga-DOTATOC (SomaKIT TOC) radiopharmaceutical for the utility of PET imaging in patients with NETs. This preparation can be robustly implemented into routine clinical practice.
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Ngo, Anh T. P., Irene Yarovoi, Guohua Zhao, Amrita Sarkar, Lubica Rauova, M. Anna Kowalska, Mortimer Poncz, and Kandace Gollomp. "Platelet Factor 4 (PF4) Modulates the Prothrombotic Nature of Neutrophil-Extracellular Traps (NETs): Therapeutic Implications of a NET-Stabilization Strategy." Blood 138, Supplement 1 (November 5, 2021): 2096. http://dx.doi.org/10.1182/blood-2021-153352.
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Abstract Sepsis is a dysregulated response to infection leading to life-threating organ damage. Although it remains one of the most common causes of mortality worldwide, it lacks targeted treatments. Neutrophils play a crucial role in sepsis by releasing NETs, webs of DNA complexed with histones and antimicrobial proteins that capture pathogens and prevent bacterial dissemination. However, when NETs are degraded by circulating nucleases they release NET-degradation products (NDPs) including cell-free (cf) DNA, histones and myeloperoxidase, which trigger coagulation, induce complement activation, and cause oxidative tissue damage. We proposed a novel NET-directed therapy in sepsis, in which NETs are stabilized by the platelet chemokine PF4. Binding of PF4 enhances NET DNase-resistance, promotes NDP sequestration and increases bacterial capture, improving survival in murine sepsis. As NETs are considered prothrombotic, we were concerned that NET stabilization may increase the risk of clot formation. We therefore sought to determine the effect of PF4-NET stabilization on the thrombogenicity of NETs to learn if this strategy is safe for clinical application. To that end, we examined the effect of PF4 on the thrombotic potential of DNA and NET fragments at different states of nuclease digestion. High molecular weight (hmw) genomic DNA (hmwDNA, >50kbp) was isolated from human whole blood. hmwDNA was digested with restriction enzymes (EcoRI and AluI) for 15min to generate DNA fragments of ~4kbp and ~250bp, respectively. Neutrophils were also isolated from human blood and stimulated with 100 nM PMA to produce neutrophil-adherent NETs, which were cleaved from cell bodies by treatment with 4U/mL DNase I for 20 minutes, releasing NETs >50kbp (hmwNETs). Additional incubation of hmwNETs with DNase I yielded smaller NET fragments. We assessed in vitro activation of coagulation by DNA and NETs by measuring thrombin generation and fibrin formation in platelet-poor plasma using fluorogenic substrate and turbidity assays. Neutrophil-adherent NETs induced far less thrombin generation and fibrin formation in plasma than hmwDNA and hmwNETs. PF4 significantly increased lag time and reduced peak thrombin formation induced by both hmwDNA and hmwNETs. Binding of PF4 also delayed clot initiation time and reduced the rate of fibrin generation. Digestion of hmwDNA and hmwNETs to smaller fragments markedly enhanced thrombogenicity. We posited that shorter DNA fragments are more thrombogenic because they have a greater proportion of end-fragment DNA that exposes more single-stranded DNA. To test this hypothesis, we subjected hmwDNA and digested DNA to heat denaturation at 95°C and rapid cooling to generate single stranded DNA and found that this accelerated fibrin generation. Although the anti-thrombotic effect of PF4 was most pronounced with longer DNA and NET fragments, it continued to significantly reduce fibrin generation induced by shorter DNA fragments, perhaps by stabilizing the fragments to prevent exposure of single-stranded DNA. In conclusion, although prior studies have shown that NETs increase the risk of thrombosis in sepsis, we propose the counter-intuitive concept that PF4-stabilization decreases the risk of NET-mediated prothrombotic state by (1) inhibiting DNase cleavage of intact NETs and subsequent liberation of prothrombotic cfDNA from non-thrombogenic neutrophil-adherent NETs, and (2) preventing further digestion of circulating cfDNA into shorter and more prothrombotic fragments. Although NETs are a double-edged sword: capable of capturing pathogens but inducing host-tissue damage and thrombosis when degraded, treatment with PF4 tips the balance, limiting the capacity of NETs to induce fibrin generation and thrombosis, while enhancing their ability to fight infection by microbial entrapment. These studies add support to our hypothesis that PF4 stabilization of NETs is protective in sepsis and merits further investigation in translational studies. Disclosures No relevant conflicts of interest to declare.
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Delpassand, Ebrahim, Rouzbeh Esfandiari, Izabela Tworowska, Julien Torgue, Jason Daniel Hurt, and Rodolfo Nunez. "Targeted alpha-emitter therapy with 212Pb-DOTAMTATE in neuroendocrine tumor subjects who progressed following prior 177Lu/90Y-PRRT." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): 4128. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.4128.
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4128 Background: Targeted Alpha-Emitter Therapy (TAT) with 212Pb-DOTAMTATE has been shown to be safe and effective in subjects with neuroendocrine tumors (NET) who have not received previous PRRT, however, data is lacking for the use of TAT once progression occurs. Herein, we present the safety and efficacy of 212Pb-DOTAMTATE in subjects with recurrent NETs following prior 177Lu/90Y-PRRT. Methods: Subjects with biopsy-proven unresectable or metastatic SSTR expressing NETs from different primary sites with at least one measurable lesion who had received progressed after receiving prior PRRT were enrolled and received up to four 8-week cycles of 212Pb-DOTAMTATE at 67.6 μCi/kg/cycle. Response to treatment was measured per RECIST 1.1 criteria and by 68Ga/64Cu-DOTATATE PET/CT. Safety parameters were also obtained. Results: A total of 11 PRRT subjects were enrolled regardless of primary tumor location (pancreas (4), small bowel (3), midgut (1), ileum (1), thymus (1), and lung (1)). 8/11 subjects (73%) completed all four cycles. The mean cumulative dose was 20.9 mCi. As of January 2022, an objective radiological response (ORR) was demonstrated in 30% of evaluable subjects (1CR, 2PR, and 7 SD). In addition, 70% (7/10) evaluable subjects demonstrated a response per 68Ga/64Cu-DOTATATE PET/CT SSTR imaging. One hundred forty-five AEs were reported, with Grade 1 (79%). There were 23 (16%) Grade 2 AEs and 5 (3%) Grade 3/ 4 AEs. Of the AEs reported, 84 (58%) were considered possibly related, and 61 (42%) were considered not related or unlikely related. The most frequent AEs (reported in ≥ 4 subjects) include: alopecia (100%), fatigue (100%), nausea (91%), anemia (36%), alanine aminotransferase increased (36%), aspartate aminotransferase increased (36%) and lymphopenia (46%). Three SAEs were reported (achalasia, asthma exacerbation, and septic shock) one of which resulted in the death of the subject (septic shock). No SAEs were considered related to study drug. Conclusions: This is the first clinical trial of 212Pb-targeted alpha-emitter therapy in subjects with NETs who progressed following prior PRRT. The use of 212Pb-DOTAMTATE in the recurrent setting is highly effective with manageable toxicity and warrants further investigation. Clinical trial information: NCT03466216.
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Liberini, Virginia, Martin W. Huellner, Serena Grimaldi, Monica Finessi, Philippe Thuillier, Alfredo Muni, Riccardo E. Pellerito, et al. "The Challenge of Evaluating Response to Peptide Receptor Radionuclide Therapy in Gastroenteropancreatic Neuroendocrine Tumors: The Present and the Future." Diagnostics 10, no. 12 (December 12, 2020): 1083. http://dx.doi.org/10.3390/diagnostics10121083.
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The NETTER-1 study has proven peptide receptor radionuclide therapy (PRRT) to be one of the most effective therapeutic options for metastatic neuroendocrine tumors (NETs), improving progression-free survival and overall survival. However, PRRT response assessment is challenging and no consensus on methods and timing has yet been reached among experts in the field. This issue is owed to the suboptimal sensitivity and specificity of clinical biomarkers, limitations of morphological response criteria in slowly growing tumors and necrotic changes after therapy, a lack of standardized parameters and timing of functional imaging and the heterogeneity of PRRT protocols in the literature. The aim of this article is to review the most relevant current approaches for PRRT efficacy prediction and response assessment criteria in order to provide an overview of suitable tools for safe and efficacious PRRT.
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Matin, S. F., I. E. McCutcheon, D. S. Gombos, S. G. Waguespack, S. Wen, L. A. Smith, Y. Zhang, D. W. Davis, G. Fuller, and E. Jonasch. "Treatment of VHL patients with sunitinib: Clinical observations and translational studies." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): e22047-e22047. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.e22047.
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e22047 Background: Von Hippel Lindau (VHL) disease induces vascular lesions in multiple organs. Surgical intervention is the treatment of choice. Effective, safe systemic therapy will greatly improve the quality of life of these individuals. Methods: Patients with genetically confirmed VHL were enrolled on an IRB approved trial. Eligibility criteria included retinal angiomas, hemangioblastomas (HBs) measuring at least 5mm, renal cell carcinoma (RCC) 1 to 3 cm and pancreatic neuroendocrine tumors (NETs) 1 to 3 cm. Patients received sunitinib 50mg/day for 28 days/14 days off for four cycles. Scans were performed at baseline, and after cycles two and four. A separate set of 20 formalin-fixed paraffin embedded HBs and 20 RCCs were used for laser scanning cytometry (LSC) analysis of total and phospho vascular endothelial growth factor receptor (pVEGFR) and phospho platelet derived growth factor receptor (pPDGFR) levels in tumor endothelium. Results: Twelve patients were evaluable for response and toxicity. Eight had RCCs, nine had CNS lesions, and three had pancreatic NETs. Tumor size reduction was seen in 16/19 evaluable RCC lesions (95%CI 0.60, 0.97), 3/5 NETs (95%CI 0.15, 0.95) and 6/19 HBs (95%CI 0.13, 0.57). Two patients came off study for treatment related side effects, one patient progressed on study, and two patients did not complete the scheduled course of therapy. LSC analysis demonstrated significantly lower phospho VEGFR levels in HBs when compared with RCC. The mean (SD) of pVEGFR levels in log-transformation were 11.27 (0.49) and 11.75 (0.37) for HBs and RCC respectively (p = 0.003). The mean (SD) of pVEGFR to VEGFR ratio was .21 (0.12) versus 0.37 (0.43), for HBs and RCC respsectively (p = 0.043). Conclusions: Sunitinib treatment of patients with VHL resulted in consistent decrease of RCC and NET tumor size. The discrepant response to sunitinib in RCC and HBs may be explained by differential dependence on VEGFR activation in tumor endothelium. [Table: see text]
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Zemczak, Anna, Paweł Gut, Dariusz Pawlak, Maciej Kołodziej, Leszek Królicki, Beata Kos-Kudła, Marek Ruchała, Grzegorz Kamiński, and Jolanta Kunikowska. "The Safety and Efficacy of the Repeated PRRT with [90Y]Y/[177Lu]Lu-DOTATATE in Patients with NET." International Journal of Endocrinology 2021 (January 23, 2021): 1–10. http://dx.doi.org/10.1155/2021/6615511.
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Purpose. The peptide receptor radionuclide therapy (PRRT) is a treatment option for patients with disseminated, inoperable G1 and G2 neuroendocrine tumours (NETs). The study aims to evaluate the safety, efficacy, and progression-free survival (PFS) of patients after retreatment (R-PRRT) and re-retreatment (RR-PRRT) with tandem isotopes [90Y]Y/[177Lu]Lu-DOTATATE. Material and Methods. Out of 99 treated patients with G1 and G2 NETs, 26 were included in the study and treated with the repeated PRRT (with 5 undergoing the re-repeated PRRT treatment) after an initial positive response to four PRRT cycles and later progression of the disease. [68Ga]Ga-DOTATATE PET/CT and CT/MRI procedures were performed before and after the treatment. Patients were treated with [90Y]Y/[177Lu]Lu-DOTATATE (1 : 1) with mixed amino acid infusion for kidney protection. Toxicity was evaluated using the CTCAE 3.0 criteria. Results. The median follow-up was 88 months (the range: 42–164). The median cumulative administered activity was 22.2 GBq (the range: 17.8–30.7 GBq). Myelodysplastic syndrome occurred in one patient (3.8%), and grade 4 renal toxicity was also detected in one patient (3.8%). No other cases of grade 3 or 4 bone marrow and renal toxicity were observed. The median PFS rate was 31 months after the PRRT and 23 months following the R-PRRT. The OS rate from the diagnosis (OS-d) was 109 months and from the start of the PRRT (OS-t)-92.4 months. During the restaging, 3–6 months after the PRRT, PR, SD, and PD were observed in 19.2%, 80.8%, and 0% of the patients, respectively. After the R-PRRT, PR, SD, and PD were observed in 50%, 42.3%, and 7.7% of the patients, respectively. Conclusions. The repeated therapy with [90Y]Y/[177Lu]Lu-DOTATATE is safe and effective for patients with disseminated, inoperable G1 and G2 neuroendocrine tumours.
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Hoe, Hui Jing, and David Wyld. "Salvage 177Lu-dotatate therapy in patients with progressive metastatic neuroendocrine tumors." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e16212-e16212. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e16212.
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e16212 Background: 177Lu-dotatate (LuPRRT) is effective in selected patients with metastatic neuroendocrine tumours (NETs). Most of these patients will subsequently have progressive disease with limited treatment options available. We analyzed the outcomes and toxicities of salvage LuPRRT in this study. Methods: This is a retrospective cohort study. Patients who had salvage LuPRRT at Royal Brisbane and Women’s Hospital (RBWH) from November 2016 to January 2021 were identified and included in this study. We manually reviewed the hospital electronic medical records and radiology databases to review patient characteristics, outcomes, and toxicities from salvage LuPRRT. Results: Of the 37 patients included, 37.8% (14/37) had small bowel primary, 27.0% (10/37) had pancreatic primary and 10.8% (4/37) had pulmonary primary. 83.8% (31/37) received 4 cycles of initial LuPRRT (I-PRRT) with a median dose of 32.0 GBq. The median duration of response to I-PRRT was 31 months. These patients had salvage LuPRRT (R-PRRT) on progression with 83.8% (31/37) received 2 cycles with a median cumulative 177LuTate dose of 48.0 GBq. Partial response, stable disease and progressive disease were observed in 10.8% (4/37), 40.5% (15/37) and 27.0% (10/37) of patients respectively. Median duration of response with R-PRRT was 8 months. 2.7% (1/37) developed Grade 3 anaemia and 2.7% (1/37) developed Grade 3 thrombocytopenia with R-PRRT. 8.1% (3/37) developed nephrotoxicity Grade 1 nephrotoxicity. 21.6% (8/37) of patients had re-retreatment with further LuPRRT (RR-PRRT) on progression. The median retreatment cycles were 2 and the median cumulative 177LuTate dose received was 58.8 GBq. Partial response, stable disease and progressive disease were seen in 25% (2/8), 12.5% (1/8) and 62.5% (5/8) of patients respectively. Median duration of response with RR-PRRT was 4 months. There were no reported Grade 3 haematologic toxicities with RR-PRRT. 1 patient developed Grade 1 nephrotoxicity with RR-PRRT. At time of data analysis in April 2021, 27% (10/37) had ongoing response while 73% (27/37) had progressed. Conclusions: Salvage LuPRRT is an effective and safe treatment option for selected patients with progressive metastatic NETs.
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Chauhan, Aman, Gray Magee, Millicent Horn, Riham Khouli, Heidi Weiss, Steven J. Krohmer, and Lowell Brian Anthony. "Everolimus and transarterial embolization (TAE) for hepatic metastasis in neuroendocrine tumors (NET)." Journal of Clinical Oncology 36, no. 4_suppl (February 1, 2018): 485. http://dx.doi.org/10.1200/jco.2018.36.4_suppl.485.
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485 Background: TAE of hepatic metastases is effective loco-regional therapy for neuroendocrine tumor (NET) patients. Transarterial chemotherapy (TACE) and transarterial radiotherapy (TARE) are other options in controlling hepatic metastases but deliver cytotoxic agents only at the time of the procedure. Systemic therapies such as everolimus or sunitinib are often held 2-4 weeks prior to and after the procedure. We hypothesize that concurrent oral treatment with everolimus and transarterial hepatic embolization is safe. Methods: Medical records of all NET patients (pts) treated at the Markey Cancer Center between July 2016 to July 2017 with concurrent transarterial embolization and everolimus were reviewed. Results: Total number of pts eligible for analysis was 15. Mean age of study cohort was 57.5 years (31-77). Seven pts were small bowel, 4 were pancreatic and remaining 4 were unknown NET primaries. Nine patients had grade 1 (Ki 67 < 2%) and 6 patients had grade 2 NETs (Ki-67 between 2-20%). Mean duration of treatment with everolimus prior to embolization was 3.8 months and mean dose was 10 mg orally every other day. Mean days of hospitalization were 1.46. Eleven (73%) pts were discharged the day after procedure. Ten (67%) pts reported nausea, 9 (60%) reported abdominal pain, 5 (30%) reported emesis. One patient had hematemesis immediately post procedure. Thirteen (87%) pts had no significant change in hemoglobin pre and post procedure (within one numerical point). No patient developed infectious complications. Conclusions: Combining everolimus with TAE is safe and does not result in longer hospitalizations or toxicities greater than that expected from TAE alone.
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Chauhan, Aman, Charles Kunos, Donglin Yan, Aman Khurana, Riham Khouli, Michael J. Cavnar, Prakash Pandalai, Joseph Kim, and Lowell Brian Anthony. "Randomized, parallel arm, phase II study of telotristat (Xermelo) in combination with lutetium Lu 177 dotatate (Lutathera) in well-differentiated neuroendocrine tumors (NETs)." Journal of Clinical Oncology 40, no. 4_suppl (February 1, 2022): TPS516. http://dx.doi.org/10.1200/jco.2022.40.4_suppl.tps516.
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TPS516 Background: PRRT using Lutetium Lu 177 Dotatate, has been approved by the FDA for metastatic, progressive gastroenteropancreatic neuroendocrine tumors (GEPNETs). Despite an impressive progression-free survival noted in NETTER-1 study, most patients will eventually progress after PRRT treatment. Increased serotonin secretion is found in a number of slow-growing NETs of the diffuse neuroendocrine system. Serotonin stimulates proliferation in cell lines of a typical (NCI-H727), an atypical (NCI-H720) bronchopulmonary NET, a small intestinal NET (KRJ-I), and a functioning human pancreatic carcinoid cell line (BON). This stimulation of growth by serotonin can be performed in an autocrine manner. Telotristat ethyl is a novel oral inhibitor of tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis. In 2017, results of placebo-controlled phase III study (Telestar) evaluating Telotristat ethyl confirmed that among patients with carcinoid syndrome not adequately controlled by somatostatin analogs, treatment with Telotristat ethyl was generally safe and well tolerated and resulted in significant reductions in bowel movement frequency and urinary 5- hydroxy indoleacetic acid (u5-HIAA). Based on results of the Telestar trial, FDA approved 250 mg PO TID dosage of Telotristat for control of carcinoid syndrome diarrhea. Of note, 500 mg TID arm showed increased decline in urinary 5-HIAA as compared to 250 mg TID arm. Study Hypotheses: We hypothesize that inhibition of serotonin production will lead to cytostatic effect on neuroendocrine tumors and will complement anti-tumor activity of lutetium 177 dotatate. We anticipate our proposed combination will result in improved treatment efficacy as reflected by improved 20-month PFS as compared to historical control (NETTER-1). Methods: This is a single center, open label, randomized, parallel arm, phase II study evaluating two dose levels of Telotristat (Xermelo; 250 mg vs 500 mg) in combination with Lutetium Lu 177 Dotatate (Lutathera) in 70 well-differentiated neuroendocrine tumor patients. Study is currently enrolling patients and is expected to complete accrual in 3 years. Clinical trial information: NCT04543955.
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Adriani, Farida, and Nur Hafizah. "Keanekaragaman Musuh Alami Tanaman Padi pada Lahan Lebak di Tiga Desa Kecamatan Sungai Pandan Kabupaten HSU." RAWA SAINS : JURNAL SAINS STIPER AMUNTAI 6, no. 1 (June 21, 2016): 390–99. http://dx.doi.org/10.36589/rs.v6i1.55.
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Utilization of insect diversity is useful in overcoming pest in the field, by using parasitoids and predators to control pests, can prevent the use of toxic chemicals in the field, while providing a safe haven for other species to live and play its role in maintaining the health of the ecosystem. Insect diversity in South Kalimantan, especially paddy fields in swampy areas largely unknown, and therefore need to be examined. The aim of this study is to identify and assess the diversity of natural enemies in paddy crop in swampy areas, especially in the three villages in the district of Sungai Pandan, Hulu Sungai Utara. This study was conducted from February - June 2015. The method used in this research is survey method with direct observation with an area of rice fields has been determined, and sampling arthropod natural enemies by using a swinging nets, water traps and light traps. Results from this study are: (1) The number of arthropod natural enemies found in shallow swamps is 20 species from seven orders, mid swamps and in each of the 16 species of seven orders; (2) The highest predator arthropod population in the shallow swamp area is Micraspis sp., The middle swamp is Paederus fuscipes, and the deep swamp is Micraspis sp. ; and (3) the diversity index of natural enemies of arthropods on the third mainland is low
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Moureletou, Roza Panagis, Dimitrios Kalliouris, Konstantinos Manesis, Sotirios Theodoroleas, Angeliki Bistaraki, George Boubousis, and Efstathios Nikou. "Central Pancreatectomy with Roux-en-Y Pancreaticojejunal Anastomosis—Report of Two Cases." Surgery Journal 06, no. 04 (October 2020): e175-e179. http://dx.doi.org/10.1055/s-0040-1718699.
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Abstract Background Central pancreatectomy (CP), a partial resection of the pancreas, is indicated for the excision of neuroendocrine tumors (NETs) of the pancreas, when located at the neck or the proximal body. Specifically, CP is preferable in functional NET and in nonfunctional sized 1 to 2 cm or/with proliferation marker Ki67 < 20% (Grade I/II). Postoperative leakage from the remaining pancreas constitutes the most frequent complication of CP (up to 63%). The aim of our study was to share the experience of our center in CP for NET, with pancreaticojejunal anastomosis. Methods In 1 year, we performed CP in two patients, following the aforementioned criteria. They presented with tumor of the body of the pancreas, which was found in random check with computed tomography, with negative hormonal blood tests and they underwent magnetic resonance imaging and endoscopic ultrasound/fine-needle biopsy/pathological examination. Results The patients underwent CP with Roux-en-Y pancreaticojejunal anastomosis of the distal pancreatic stump and jejunal patch of the proximal pancreatic stump. Histological exam revealed NET sized 2.8 cm and 1.45 cm, Grade I and II, respectively. Postoperatively both patients developed small pancreatic leakage, which did not affect their physical condition and stopped after 20 and 30 days. No one needed pancreatic enzymes supplements or developed new-onset diabetes mellitus. Conclusion CP provided adequate, functional remaining pancreatic tissue in both patients. Small leakages were treated conservatively and retreated without septic complications. As a result, CP might be considered as safe and effective technique for pancreatic neck/proximal body NET.
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Abou Jokh Casas, Estephany, Nieves Purificacion Martinez, Urbano Anido Herranz, Jose Manuel Cabezas Agricola, Silvia Varela Ferreiro, Alberto Carral Maseda, Ovidio Fernandez Calvo, et al. "Real-world efficacy and safety of peptide receptor radionuclide therapy (PRRT) in gastroenteropancreatic neuroendocrine tumors (GEP-NETs)." Journal of Clinical Oncology 39, no. 3_suppl (January 20, 2021): 364. http://dx.doi.org/10.1200/jco.2021.39.3_suppl.364.
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364 Background: PRRT with 177Lu-Dotatate (Lutathera) is a radiolabeled somatostatin analog indicated treatment of somatostatin receptor (STTR) positive GEP-NETs. The study aims to establish the efficacy and safety of PRRT in GEP-NETs in a real-world setting. Methods: We conducted an observational, retrospective, multicentric study of 40 patients with GEP-NET treated with PRRT belonging to GGNET (Galician Research Group on Neuroendocrine Tumors) network at Nuclear Medicine Department of Santiago de Compostela University Hospital (Spain). Patients characteristics, overall survival (OS), progression-free survival (PFS), overall response rate (ORR) and toxicity data were retrospectively collected and analyzed. Results: Data from 40 patients (pts) treated between 2016 and 2020 were recorded in this study. Median age was 63.5 years (range 41-85) and 55% were male. The baseline ECOG PS 0/1/2 was 15 (37.5%)/16 (40%)/9 (22.5%). Tumor location was intestinal 26 pts (65%), pancreas in 11 pts (27.5%) and unknown origin in 3 pts (7.5%). 25 pts (62.5%) were none functioning. Tumor grade G1/G2/G3 were 17 pts (42.5%)/ 20 pts (50%)/ 3 pts (7.5%), and Ki 67 < 2/3-20/ > 20%/unknown was 11 pts (27.5%)/ 21 pts (52.5%)/ 3 pts (7.5%)/ 5 pts (12.5%), respectively. The most frequent site of metastasis was liver in 32 pts (80%), lymph nodes in 19 pts (47.5%), peritoneum 11 pts (27.5%) and bone 10 pts (25%). Surgery: 22 pts (55%) primary tumor surgery and 8 pts (20%) metastasectomy. Previous systemic treatments included somatostatin analogs (SSA) in 40 pts (100%), everolimus in 26 pts (65%) and sunitnib in 11 pts (27.5%), others 7 pts (17.5%). 34 pts (85%) completed 4 cycles of treatment (6 pts (15%) non-complete due to premature death). 35 pts were evaluable for early response (after 2 cycles of treatment). Early ORR and DCR were 2.8% and 74.2%, respectively. 26 pts were evaluable after finishing treatment (6 pts premature death and 8 pending evaluation). ORR and DCR were 19.2% and 92.3%. With a median follow up of 21 months, 14 pts (35%) had died. Median OS was not reached (NR) and median PFS was 27.2 m (95% CI 16.0-38.4m). Tumor grade G1-2 (p < 0.001), Ki 67 <20% (p = 0.002), primary tumor surgery (p = 0.039) and metastasectomy (p = 0.030) were associated with prolonged PFS. Mild adverse events were most frequent after the 1º doses in 27.5% patients, and medium-term toxicity was present in 25.6%, mainly hematological, G1-G2 25.6%, and G3 5%. Conclusions: 177Lu-Dotatate is a safe and effective treatment for those patients diagnosed with metastatic GEP-NET and positive somatostatin receptors, with an excellent clinical and radiological response. Furthermore, we have identified some predictive factors to OS that should be taken into consideration.
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Picman, Jaroslav, Stanislav Pribil, and Andre Isabelle. "Antipredation Value of Colonial Nesting in Yellow-Headed Blackbirds." Auk 119, no. 2 (April 1, 2002): 461–72. http://dx.doi.org/10.1093/auk/119.2.461.
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Abstract Yellow-headed Blackbirds (Xanthocephalus xanthocephalus) in Manitoba breed in dense colonies in cattail marshes. Their reproductive success is affected mainly by predation. The most important predator on blackbird nests is the Marsh Wren (Cistothorus palustris), which breaks blackbird eggs and kills small nestlings. We examined whether colonial nesting in Yellow-headed Blackbirds may represent an adaptation to reduce Marsh Wren predation. Marsh Wren predation may be reduced by (1) mutual nest defense by adult blackbirds, (2) predator satiation or dilution, or (3) selfish-herd effects. We tested these hypotheses using experimental nests and found that their safety increased with decreasing distance to the nearest blackbird nest and with increasing density of simultaneously active blackbird nests located nearby. Safety also was higher for nests placed inside a blackbird colony rather than outside. These findings support the nest-defense hypothesis. We also found that Marsh Wrens are capable of destroying a whole blackbird colony in a few days, and that colony size is not correlated with nest safety. These results suggest that the satiation or dilution benefits are negligible. Finally, we found that central nests are safer than peripheral nests in a blackbird colony, but not in an artificial colony, providing weak support for the selfish-herd hypothesis. We conclude that nest predation is reduced mainly by mutual nest defense of adult birds and may represent an important selective force favoring colonial nesting in this species.
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Aljubran, Ali Husain, Mohamed Alrowaili, Hussein Raef, Shouki Bazarbashi, Ahmed M. Alzahrani, Ahmed Almuhaideb, Hadeel Almanea, Ahmed ali Badran, Abdelmuniem Al-Dalee, and Mahmoud Tuli. "Combination of everolimus and lu-177 PRRT in treatment of G1-2 neuroendocrine tumors (NET): Phase 1-2 study." Journal of Clinical Oncology 37, no. 4_suppl (February 1, 2019): 386. http://dx.doi.org/10.1200/jco.2019.37.4_suppl.386.
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386 Background: Everolimus and Lutetium-177 PRRT were approved as monotherapy. However, animal model research showed synergistic effect of the combination. The goal of this study is to assess the safety and efficacy of the combination in treatment of unresectable G1-2 NETs of all gastrointestinal, lung and pancreatic origins. Methods: This is a phase 1-2 study. Phase 1 part involves finding the maximum tolerating dose (MTD) of everolimus and accordingly to recommend dose for phase II part. Starting everolimus dose was 5 mg OD. Patients were treated concurrently with Lu-177 DOTATOC therapy at intervals of 8 weeks (+/-1 week) with average of 4 sessions. Sample size calculation was based on the expected response of the combination to be 30% with power of 80 and type 1 of .05, compared to the known response rate of everolimus alone of 5%. Primary end point is safety. Other end points include response rate, PFS and OS. Results: Eleven patients, with progressive disease, were enrolled. Characteristics are summarized in the table. Everolimus MTD was 10 mg once daily. However, dose was reduced to 5 mg OD in 3 patients and to 5 mg once every other day in 2 patients. Median number of sessions of Lu-177: 3 sessions, and median cumulative dose: 300 mci. Most common G1-2 toxicities: stomatitis (90.9%), Nausea (72.7%), Fatigue (63.6%), anorexia (36.4%), diarrhea (36.4%) and skin and nail changes (36.4%). G3 toxicities (36%) were infection, fatigue, pneumonitis and neutropenia. No grade 4 toxicities. Reasons of discontinuation were toxicity in 3 patients, progression in 3, stroke in 1 and due to interruption of therapy in 4 patients. ORR: 1 PD, 1 PR and 9 SD. At median FU of 18.9 months, 7 patients are still alive, 3 died, and 1 lost to FU. Median PFS: 23.3 months. Conclusions: Combination of Everolimus and the Lu-177 PRRT appear to be safe and effective. Four patients, due to strict compliance criteria in the study protocol, were removed from the study prematurely resulting in undertreatment. Larger and randomized studies are required to confirm such findings.[Table: see text]
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Aggarwal, Rahul Raj, Ana Aparicio, Axel Heidenreich, Shahneen Kaur Sandhu, Yiran Zhang, Mark Salvati, Aditya Shetty, and Nooshin Hashemi Sadraei. "Phase 1b study of AMG 757, a half-life extended bispecific T-cell engager (HLE BiTEimmune-oncology therapy) targeting DLL3, in de novo or treatment emergent neuroendocrine prostate cancer (NEPC)." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): TPS5100. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.tps5100.
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TPS5100 Background: NEPC is an aggressive cancer with poor prognosis. No standard treatment approach for NEPC exists and it remains an unmet need. NEPC is usually treatment-emergent, characterized by histological transformation from adenocarcinoma to a high-grade neuroendocrine tumor (NET), and may develop in 15%–20% of patients (pts) treated with standard prostate adenocarcinoma therapies, including novel hormonal therapies. The inhibitory Notch ligand, Delta-like ligand 3 (DLL3), is highly expressed on the surface of cancer cells, including NEPC cells, making it an attractive and a promising therapeutic target. AMG 757 is an HLE BiTE immuno-oncology therapy designed to redirect cytotoxic T cells to tumor cells by binding DLL3 on cancer cells and CD3 on T cells, resulting in T cell activation and expansion and T cell-dependent killing of tumor cells. AMG 757 showed in vitro activity in DLL3-expressing NETs, including NEPC. Preliminary results of an on-going first-in-human study suggest AMG 757 is safe and effective in pts with small cell lung cancer (NCT03319940), which prompted its study in NEPC. Methods: NCT04702737 is an open-label, phase 1b study evaluating AMG 757 infusion in pts with metastatic de novo or treatment-emergent NEPC, consisting of dose exploration and then dose expansion. Key eligibility criteria include adults (≥18 y) with NEPC whose disease progressed/recurred after ≥1 treatment course including a platinum-based regimen for de novo NEPC or an androgen signaling inhibitor, measurable disease per modified RECIST 1.1 per Prostate Cancer Working Group 3 modifications, ECOG performance status ≤2, life expectancy > 3 mo, adequate organ function, and no untreated/symptomatic brain metastases. Primary objectives are to evaluate safety and tolerability and determine the maximum tolerated dose or recommended phase 2 dose of AMG 757. Secondary objectives are to evaluate antitumor activity (ie, objective response, duration of response, progression-free survival, overall response) and characterize pharmacokinetics. The starting dose for dose exploration will be based on the dose deemed safe and tolerable in the ongoing trial of AMG 757 in SCLC. The study is open to enrollment. Clinical trial information: NCT04702737.
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Wang, Yi-Zarn, Aman Chauhan, Robert A. Ramirez, Melissa A. Stevens, J. Philip Boudreaux, Eugene Woltering, and Lowell Brian Anthony. "Does the addition of adjuvant intraoperative postdissection tumor bed chemotherapy during GI neuroendocrine tumor debulking benefit patients?" Journal of Clinical Oncology 33, no. 3_suppl (January 20, 2015): 442. http://dx.doi.org/10.1200/jco.2015.33.3_suppl.442.
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442 Background: Midgut neuroendocrine tumor (NET) patients are often diagnosed at an advanced stage with extensive mesenteric lymph node and liver metastasis. The only treatment for potential cure and durable results is resection with extensive debulking. However, even with the most elegant surgical dissection/resection, macro and microscopic residual disease at the tumor resection bed remains a distinctive possibility. We hypothesize that local application of 5-florouracil (5-FU) within tumor bed would eliminate the microscopic residual disease post operatively. Methods: Surgical records of 188 consecutive patients who underwent extensive cytoreductive surgeries for stage IV, small bowel NETs with boggy mesenteric lymphadenopathy between 2003-2012 were reviewed. 85 Patients who had 5-Florouracil saturated gelfoam strips secured into their mesenteric resection defects served as the study group (n=85) with one hundred three patients who did not receive such intra-operative chemotherapy as the control (n=103). Survival from the time of diagnosis, postoperative morbidity and mortality between the two groups were collected and compared. Results: Mortality rates at immediate, 30, 60 and 90 days post operative period were 3; 0; 1; 0; and 0; 2; 0; 4 respectively for study and control group. Minor complications (Clavien-Dindo Grade I and II) at 30, 60 and 90 day postoperative period were 12; 0; 1 and 12; 5; 5 respectively. Major complications (Grade III and IV) at the same time intervals were 2; 0; 2 and 2; 3; 2 for study and control groups. Most of all, the mean survival from time of histological diagnosis for the study patients was 210 months (17.5 years) as compared to 177 months (14.7 years) for the control group with a difference of 33 months (2.75 years). Conclusions: Intra-operative tumor resection bed chemotherapy is a safe adjuvant without any discernible toxicity. Furthermore, it might provide survival benefit to midgut NET patients with extensive mesenteric lymphadenopathy undergoing extensive cytoreductive surgery without additional procedure related complications.
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ACHARJA, INDRA PRASAD. "Evaluation of nest habitat, site preferences and architecture of the critically endangered White-bellied Heron Ardea insignis in Bhutan." Bird Conservation International 30, no. 4 (November 14, 2019): 599–617. http://dx.doi.org/10.1017/s095927091900042x.
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SummaryThis research evaluated the nesting habitat, nest-site preferences, and nest architecture of the critically endangered White-bellied Heron Ardea insignis in Bhutan. There are fewer than 60 wild birds left in the world, distributed in Bhutan, India, and Myanmar with fewer than five active breeding pairs in Bhutan. From 2003 to 2018, 20 successful and two unsuccessful nests were located from which at least 76 juveniles were expected to have fledged. The population in Bhutan has remained at 22–30 individuals for the last decade. Site-specific data were collected from 22 nests, and additional vegetation and environmental data were collected from 14 nests and random sites. We used 20-m diameter circular plots to evaluate the site preferences. Ground vegetation, litter and rock cover were evaluated using four 1-m2 quadrats in both nest and random sites. Nesting habitat was analysed to compare characteristics of nesting sites to random sites. Our results suggest that the White-bellied Heron builds a simple platform nest within average distance of 74 m from water bodies on the tallest isolated trees at an average height of 18.3 m on an elevated site with a clear overview of surroundings and are sensitive to even slight disturbance. Our results also suggest that the bird has a preference for an east-facing aspect at an average slope of approximately 40° between the altitudes of 400–1,450 m. Our observations also suggest that the bird has abandoned all nesting sites used prior to 2015, and the frequency of nest re-use has decreased. Protecting each nest site from hazards, avoiding disturbance, maintaining safe feeding habitats and flight routes are essential to ensure continued breeding in current sites and survival of this population. Further research to better understand the habitat requirements for the White-bellied Heron is vital.
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Wana, Ermias Wabeto, Getamesay Aynalem Tesfaye, and Moges Getie Workie. "Chronic Undernutrition and Associated Factors Among Children Aged 6 to 59 Months in South Ari, South Omo Zone, Ethiopia: A Community-Based Cross-Sectional Study." Health Services Research and Managerial Epidemiology 10 (January 2023): 233339282211501. http://dx.doi.org/10.1177/23333928221150143.
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Background Chronic undernutrition (stunting) among children is associated with an increased risk of morbidity and mortality. The global community is committed to end all forms of malnutrition by 2030. Regardless of this, children are suffering from some form of malnutrition but the reason is unclear. This study thus was intended to identify stunting and associated factors among children aged 6 to 59 months in the South Ari Woreda of South Omo Zone. Methods A community-based cross-sectional study was conducted in South Ari Woreda from 1, January 2022 to 30, February 2022, and 409 children participated. A simple random sampling technique was used to identify study participants, and mothers/caregivers were interviewed. Data on sociodemographic, economic, and environmental determinants were collected by trained professional nurses using interviewer-administered questionnaires and anthropometric data were collected via weighting and measuring the height/length of the child. Emergency Nutrition Assessment for Standardized Monitoring and Assessment of Relief and Transitions 2020 software was used to generate an anthropometric index, and a child with a height for age index below −2standard deviations of the standard population was considered stunted. Factors of stunting were assessed using multivariate binary logistic regression at a 5% significance level. Results The study revealed that 44.0% (95% confidence interval (CI) = 39.19%-48.81%) of children were stunted in the study area. Household's wealth status (the poorest; adjusted odds ratio (AOR) = 4.14 [95% CI = 2.08-8.22] and poor; AOR = 3.31 [95% CI = 1.60-6.82]), improper solid waste management practice of the household (AOR = 2.67 [95% CI = 1.56-4.55]), and the children sleeping under insecticide-treated bed nets (ITN) (AOR = 0.37 [95%CI = 0.22-0.60]) were statistically significantly associated with stunting status of the children. Conclusion Stunting among the children in the study area was very high. Improving household's (HH) economy, safe management of domestic solid waste, and ensuring that the children are sleeping under ITNs are expected to reduce stunting.
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Giua, Alessandro, and Xiaolan Xie. "Control of safe ordinary petri nets with marking specifications using unfolding." IFAC Proceedings Volumes 37, no. 18 (September 2004): 63–68. http://dx.doi.org/10.1016/s1474-6670(17)30723-1.
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Esparza, Javier. "Reachability in live and safe free-choice Petri nets is NP-complete." Theoretical Computer Science 198, no. 1-2 (May 1998): 211–24. http://dx.doi.org/10.1016/s0304-3975(97)00235-1.
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Brodskiy, Victor. "Organization of safe execution of works with the use of trapping nets." IOP Conference Series: Materials Science and Engineering 918 (October 7, 2020): 012016. http://dx.doi.org/10.1088/1757-899x/918/1/012016.
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Dubchenko, V. S. "ANALYSIS OF IMMEDIATE AND LONG-TERM RESULTS OF SUBLAY AND TAPP TECHNIQUES IN THE TREATMENT OF VENTRAL HERNIAS." Здобутки клінічної і експериментальної медицини, no. 3 (December 1, 2021): 42–46. http://dx.doi.org/10.11603/1811-2471.2021.v.i3.12506.
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The accumulated clinical experience has proven that the “sublay” technique allows to achieve greater functional activity of the anterior abdominal wall and is the method of choice in the treatment of ventral hernia. The use of self-adhesive nets during laparoscopic transabdominal preperitoneal plasty (TAPP- Transabdominal Preperitoneal Plastic) in the treatment of small and medium ventral hernia is safe and effective, with low values of postoperative pain syndrome and rapid functional recovery after surgery, without increasing the recurrence in the short term.
The aim – was to analyze the immediate and long-term results of “sublay” and TAPP techniques in the treatment of ventral hernias of lower and median localization. The author noted that the search for technical methods aimed to reduce the intra-abdominal pressure in this hernioplasty technique was relevant and practically significant.
Material and Methods. The work was performed on the basis of the surgical department of the State Institution “Specialized Multi-Purpose Hospital №1 of Ministry of Health of Ukraine”, Department of General Surgery of the State Institution “Dnipro State Medical University of Ministry of Health of Ukraine”.
Results. Comparison of immediate and long-term results of peritoneal-prosthetic-aponeurosis thickness studies showed a statistically significant difference (p < 0.001) using different techniques. When analyzing the separated results, reliable differences (p <0.001) depending on the gender of patients were recorded. Thus, in males, when using the “sublay” technique the peritoneal-prosthetic-aponeurosis thickness was greater by 1.15 mm (by 42.43 %) in comparison with the Tapptechnique, and in females, by 1.16 mm (by 42.09 %), respectively.
Conclusions. The analysis of the immediate and long-term results of the “sublay” and TAPP techniques in the treatment of ventral hernias of lower and median localization showed that the “sublay” technique was characterized by traumatic surgical intervention, shift of the prosthesis to one side, as a consequence of its deformation. When using this technique, peritoneum-prosthetic-aponeurosis thickness values were significantly higher – by 13.16 % and 42.40 % in the early and distant postoperative periods, respectively. Also, when using the Tapp technique in the distant period the thickness was significantly reduced (p <0,0001) by 49,47 % in comparison with the immediate results.
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A, Ombugadu, Ugwu AR, Ibrahim JI, Dawam NN, Pam VA, Okoi PN, Ahmed HO, et al. "A comparative study on the abundance and diversity of butterflies in disturbed and undisturbed habitats in a tertiary institution in central Nigeria." MOJ Ecology & Environmental Sciences 6, no. 6 (November 10, 2021): 194–99. http://dx.doi.org/10.15406/mojes.2021.06.00233.
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Butterflies are among the most widely spread taxa whose distribution cut across all the continents of the world except the Antarctica. Many butterfly species are comparatively easy to sample and recognize both as individuals and as species than many other insect groups. They are extremely sensitive to changes in vegetation composition and structure in the environment. As a result of this; butterflies have widely been used as a model species to evaluate the health of the environment and changes in the environment. We investigated and compared the butterfly abundance and diversity within a newly established tertiary institution in Central Nigeria in April, 2016 using transects with the aid of sweep nets. Four transects were laid in each of the disturbed and undisturbed habitats of Federal University of Lafia (FULafia). Transects were visited in the morning and evening. An overall total of three hundred and one butterflies were seen. However, only 160 were caught which spread across 5 families, 21 genera and 25 species. The most abundant family of butterflies caught was Pieridae 49 (30.63%) followed by Lycaenidae 42 (26.25%), Nymphalidae 34 (21.25%), Papilionidae 34 (21.25%), while Hesperiidae 1 (0.63%) was the least and scarce in the study area. The most abundant genera of butterflies recorded were Eurema 29 (18.13%), Papilio 27 (16.88%) and Hypolycaena 23 (14.38%). The mean abundance of butterflies seen in relation to disturbed and undisturbed habitats showed a very high significant difference (t = -4.1952, df = 94.682, P < 0.0001). Time of day showed a very high significant difference (t = 6.2208, df = 82.469, P < 0.0001) in the mean abundance of butterflies. The undisturbed habitat was more diversified (H´ = 2.6) in butterfly diversity than the disturbed habitat (H´ = 2.5). This study being the first effort in exploring the butterfly wealth of FULafia clearly shows that the ongoing building construction in the Permanent Site of the University may have some impact on the abundance and diversity of butterflies. Hence, the Management of the Institution should ensure that the area designated for Zoological Garden is well safe guarded for biodiversity conservation amidst ongoing sustainable development.
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Opoka, Robert, Christopher Ndugwa, Teresa S. Latham, Adam Lane, Heather Ann Hume, Philip Kasirye, James L. Hodges, Russell E. Ware, and Chandy C. John. "Novel Use of Hydroxyurea in an African Region with Malaria (NOHARM): A Randomized Controlled Trial." Blood 130, Suppl_1 (December 7, 2017): 759. http://dx.doi.org/10.1182/blood.v130.suppl_1.759.759.
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Abstract Background. Hydroxyurea treatment is recommended for children with sickle cell anemia (SCA) living in high-resource malaria-free regions, but its safety and efficacy in malaria-endemic settings such as sub-Saharan Africa, where the greatest sickle cell burden exists, remain unknown. In vitro studies suggest hydroxyurea could increase malaria severity, through upregulation of intracellular adhesion molecule 1 (ICAM-1) that facilitates parasite adhesion to endothelium. In addition, hydroxyurea-associated neutropenia could worsen infections that occur in low-resource settings. Methods. NOHARM (NCT01976416) was a randomized, double-blinded, placebo-controlled trial conducted in malaria-endemic Uganda. Children between the ages of 1.00-3.99 years were enrolled, and then received 12-months of blinded treatment with either hydroxyurea or placebo at 20 ± 2.5 mg/kg/day, with dose adjustments in both arms for weight gain and hematological toxicities. All participants received standard care for SCA including folic acid, penicillin prophylaxis, and pneumococcal vaccination. For malaria prophylaxis, children received insecticide-treated mosquito nets and monthly sulphadoxine-pyrimethamine. The primary outcome was incidence of clinical malaria. Secondary outcomes included SCA-related adverse events, clinical and laboratory effects, and hematological toxicities. After completing the blinded treatment phase, all participants were offered open-label hydroxyurea, as per local Ethics Committee recommendations. Results. Study participants (median age 2.2 years) received either hydroxyurea (N=104) or placebo (N=103) for 12-months. Malaria occurred at a low rate throughout the study. The malaria incidence did not differ between children on hydroxyurea [0.05 episodes/child/year, 95% CI (0.02, 0.13)] versus placebo [0.07 episodes/child/year (0.03, 0.16)]. The hydroxyurea/placebo malaria incidence rate ratio was 0.7 [(0.2, 2.7), p=0.61], and time to infection did not differ significantly between treatment arms. A composite SCA-related clinical outcome (vaso-occlusive painful crisis, dactylitis, acute chest syndrome, splenic sequestration, or blood transfusion) was less frequent with hydroxyurea (45%) than placebo (69%, p=0.001). For individual clinical events, vaso-occlusive pain and hospitalizations were significantly less frequent with hydroxyurea than placebo; the number needed to treat to prevent one hospitalization was 6.4, while the number needed to treat to prevent a SCA-related event was 2.5. Serious adverse events, sepsis episodes, and dose-limiting toxicities were similar between treatment arms. Specifically, low hemoglobin (<6.0 g/dL) occurred more frequently in children receiving placebo than hydroxyurea, while the frequencies of neutropenia, thrombocytopenia and reticulocytopenia did not differ significantly between treatment arms. Three deaths occurred (two hydroxyurea, one placebo, none from malaria). Children receiving hydroxyurea had significantly increased hemoglobin concentration and fetal hemoglobin, along with decreased leukocytes, neutrophils, and reticulocytes. Conclusions. In this prospective randomized double-blinded placebo-controlled trial of young children with SCA living in Uganda, hydroxyurea therapy was both safe and efficacious. Based on these NOHARM data, hydroxyurea treatment appears safe for children with SCA living in malaria-endemic sub-Saharan Africa, without increased risk for severe malaria, infections, or adverse events. Hydroxyurea provides predicted SCA-related laboratory and clinical efficacy, but the optimal dosing and monitoring regimens for affected children in Africa remain undefined. Disclosures Ware: Agios: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Research Funding; Addmedica: Research Funding; Nova Laboratories: Consultancy; Global Blood Therapeutics: Consultancy.
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Adamkiewicz, Tom, Adel Driss, Hyacinth I. Hyacinth, Jacqueline Hibbert, and Jonathan K. Stiles. "Determinants Of Mortality and Survival In Children With Sickle Cell Disease (SCD) In Sub Saharan Africa." Blood 122, no. 21 (November 15, 2013): 4676. http://dx.doi.org/10.1182/blood.v122.21.4676.4676.
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In Africa, the natural history of SCD is often assumed to be same to the African Diaspora in the US, Jamaica, Europe or Latin America. Yet the environment can be different, including different pathogen exposure, such as malaria. To help better understand this, over 2000 references were identified using the names of all current or past names of African continent countries and the truncated word sickl$, followed by secondary nested and cross reference searches. Six cases series describing causes of death were identified, representing 182 children (Ndugwa, 1973, Athale, 1994, Koko, 1998, Diagne, 2000, Rahimy, 2003, Van-Dunem, 2007). Gender was reported in 172, 73 were female (42%). Age was reported in 118, 52 were < 5 years (44%). Four studies described some impediment to care or arrival for care in extremis in1/4 to over ½ of patients that died. In Uganda, 9/12 (75%) patient died at home. In Gabon 6/23 (26%) patients died within 4 hours of reaching the hospital and 11/23 (48%) within 24 hours. In Benin 2/10 (20%) died of splenic sequestration diagnosed at home; 38/64 (53%) of patients in Mozambique that died, lived outside of the capital. Causes of death were identified in 146 individuals. These included: fever/sepsis: n=59 (40%), including meningitis: n=15 (10%) and pyelonephritis: n=2 (1%); acute anemia: n=43 (29%), including spleen sequestration: n=28 (19%) and aplastic anemia: n=8 (5%); pain: n=22 (15%); acute chest syndrome/pneumonia: n=18 (12%); CNS: n=8 (5%), including stroke: n=4 (3%), seizure/ coma: n=5 (3%); liver disease: n=5 (3%) including hepatitis: n=3 (2%); Other: n=19 (13%) including wasting/ malnutrition: n=7 (5%), heart failure/cardiomyopathy: n=4 (3%), diarrhea and vomiting: n=3 (2%), transfusion reaction: n=2 (1%). Infectious pathogens were identified in 26, including malaria: n=10 (38%), S. pneumoniae: n=3 (12%), Salmonella: n=2 (8%), H. influenza, Klebsiella and Citrobacter: n=1 (4%) each; viral agents were reported in n=8 (31%) including HBV: n=5 (19%), HIV: n=3 (12%). Reported general population hemoglobinopathy surveys after birth revealed the following Relative Risk (RR) of observing individuals with hemoglobin SS compared to Hardy Weinberg expected frequencies (some age cohorts overlap; Tanzania '56, Benin '09, Burkina Faso '70, Central African Republic'75, Gabon'65/'80, Gambia'56, Ghana '56/‘57/'00/'10, Kenya '04/'10, Malawi '72/'00/'04, Mozambique '86, Nigeria '56/'70/'79/'81/'84/'05, Senegal '69, Sierra Leone '56). Age 0-1 years, total n=2112 observed n=22 (1.0%), expected n=16.5 (0.8%), RR=1.3 (95% CI=0.7,2.5), p=0.441. Age 0-6 years, total n=4078; observed n=39 (1.0%); expected n=40.6 (1.0%); RR=1.0 (95% CI=0.6,1.5), p=0.925. Age 5-19 years, total n=1880; observed n= 5 (0.3%); expected n= 24.8 (1.3%); RR=0.2 (95% CI=0.1,0.5); p<0.001. Adults, total n=12814; observed n= 20 (0.2%); expected n= 118.9 (0.9%); RR=0.2 (95% CI=0.1,0.3), p<0.001. Pregnant, total n=5815; observed n= 19 (0.3%); expected n= 78.5 (1.3%), RR=0.2 (95% CI=0.1,0.4), p<0.001. Cohorts of children with SCD are indicated in the table. In summary, access to care, as well as acute anemias are a frequent cause of mortality. Along with viral pathogens and transfusion related deaths this indicates the importance of a safe blood supply. By adulthood, the observed frequency of individuals with SCD is only 1/5 of expected. However, reported clinic cohorts suggest similar if not better survival than in the general population, possibly due to lost to follow up, but also malaria/bacterial infection prevention and nutritional support. Careful prospective studies are needed.TableCohorts of children in Africa with Sickle Cell AnemiaCountryAge median years, (range)Death/TotalnFollow up yearsPatient-yearsDeaths/100 patient-yearsU5M/100 child-yrs♦Uganda, 735 -9, (0-20)12/6282--2.7Senegal, ‘008 (0-22)11/323710331.12.2Senegal, 03330/55612--2.2Benin,032.910/2361.5-6.59831.02.4Kenya,096 (0-13)2/1241.21181.72.7♦: Under five year old mortality 2009 (source: Unicef), divided by 5Prophylactic interventions: Uganda: chloroquine; Senegal: chloroquine (wet season), nets, penicillin prophylaxis <5 yrs, folic acid, parasite treatment & iron supplement as needed; Benin: chloroquine, nets, penicillin prophylaxis, antibiotics for fever, folic acid, nutritional support; Kenya; Proguanil, folic acid, nutritional support, parasite treatment & iron supplement as needed. Disclosures: No relevant conflicts of interest to declare.
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Boytsov, B. V., L. R. Vishnyakov, M. E. Kazakov, and V. V. Krivonos. "Wire Knitted Mesh for Lightning Protection of Wind Blades." Quality and life 29, no. 1 (March 15, 2021): 93–96. http://dx.doi.org/10.34214/2312-5209-2021-29-1-93-96.
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The features of the use of lightning protection nets in the wind power industry as lightning arresters and down conductors are considered. Based on the experience gained in aviation technology, ways of improving the design of the lightning protection system for the safe operation of wind farms are proposed.
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LI, L., X. Yu, J. Liu, H. Chen, and W. Zheng. "FRI0003 ELEVATED HISTONE H4 IN NEUTROPHIL EXTRACELLULAR TRAPS PROMOTES MACROPHAGE ACTIVATION IN BEHÇET’S DISEASE." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 572.1–573. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2097.
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Background:Neutrophil-released neutrophil extracellular traps (NETs) are upregulated and promote autoinflammation and thrombosis in Behçet’s disease (BD), a multi-system inflammatory disease with unknown etiology1,2. However, whether NETs promote macrophage activation in BD remains unclear.Objectives:To investigate the potential role of NETs in promoting aberrant macrophage activation in BD.Methods:We quantified NETs by measuring dsDNA using ELISA and immunofluorescence. Macrophages were stimulated with BD- and healthy controls (HC)-derived NETs, and IL-8 and TNF-α production were measured by ELISA. NETs-stimulated macrophages were incubated with naive CD4+T cells, and Th1 cell differentiation was examined on day 7 by flow cytometry. Histones H1, H2A, H2B, H3, H4, S100A8 and neutrophil elastase in NETs were analyzed by western blot. Macrophages were stimulated with anti-Histone 4 antibody-treated NETs, and IL-8 production was measured by ELISA.Results:Circulating NETs (2336±534 ng/ml vs. 1472±549 ng/ml,P=0.0008) and neutrophil-derived NETs (909.2±485.2 ng/ml vs. 582.4±199.2 ng/ml,P=0.0108) were significantly higher in BD patients compared with those in HC. BD NETs stimulated macrophages to produce a higher level of IL-8 (17±4 ng/ml vs. 13±4 ng/ml,P=0.0474) and TNF-α (166±61 pg/ml vs. 102±48 pg/ml,P=0.0132) than HC NETs. Moreover, BD NETs promoted macrophages to facilitate Th1 differentiation than HC NETs (33±10% vs. 24±7%,P=0.0398). Western blot analysis revealed more Histone H4 (289076 (144365, 544038) IOD values vs. 42121 (6958, 129625) IOD values,P=0.0286), but not Histones H1, H2A, H2B, H3, S100A8 or neutrophil elastase in BD NETs compared to HC NETs. Importantly, neutralizing Histone H4 abrogated the BD NETs-stimulated IL-8 overproduction by macrophages (9.99±2.07 ng/ml vs. 13.95±2.91 ng/ml,P=0.021).Conclusion:BD NETs promoted macrophages activation, which might be mediated by a higher level of Histone H4.References:[1]Safi R., Kallas R., Bardawil T., et al. Neutrophils contribute to vasculitis by increased release of neutrophil extracellular traps in Behçet’s disease. J. Dermatol. Sci. 2018;92:143–150.[2]Le Joncour a, Martos r, Loyau s, et al. Critical role of neutrophil extracellular traps (NETs) in patients with Behcet’s disease. Ann Rheum Dis 2019;78:1274–1282.Disclosure of Interests:None declared
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Syahrizal, Syahrizal, and M. Yusuf Arifin. "ANALISIS KANDUNGAN MERKURI (Hg) PADA AIR DAN DAGING IKAN PATIN SIAM (Pangasius hypopthalmus) Di KJA DANAU SIPIN JAMBI." Jurnal Akuakultur Sungai dan Danau 2, no. 1 (June 15, 2017): 9. http://dx.doi.org/10.33087/akuakultur.v2i1.13.
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AbstractEnvironment Agency Jambi Province in 2014 stipulates that the Batanghari River uncategorised heavy pollution with the effluent of 0.3265 ppm. The river water flow into the Lake Sipin, so worried farmers catfish (Pangasius hypopthalmus) in the floating nets cage on heavy metal pollution Hg when exceeding quality standards. The content of Hg was observed through the method of survey study purposive sampling with 4 stations for 3 weeks of observation with sample analysis Atomic Absorption Spectrophotometer. The observation that the accumulation of heavy metals mercury (Hg) meat catfish in the lake Sipin from 0.0930 to 0.3960 ppm. Hg content is in torelansi SNI standards for heavy metals Hg categories food fishery products including mollusks and shrimp is 1 ppm and 0.5 ppm for predatory fish. So fish farming Lake Sipin still safe for consumption humans..Hg value of water is observed from 0.0001 to 0.0009 ppm. Hg content was lower when compared to the water quality standard by the Ministry of Environment No. 51 In 2004 the threshold value for the biota is 0.001 mg / l (ppm). Then the category of heavy metal content of Hg in the waters of Lake Sipin still at the threshold of normal. Occurrence repaired Hg waters presumably because the number found fish brooms, Hypostomus plecostomus and plant water hyacinth, Eichhornia crassipes which absorbed Hg in the waters. The state of water quality when the observation temperatures averaging 30-32 ° C, pH 6.6 to 7.4 and DO 7.0 to 8.4 ppm. The range of this parameter is feasible for the cultivation of catfish (Pangasius Hyphopthalmus), as it supports the growth and survival.Keywords: Bioaccumulation Hg, Lake Sipin, catfish AbstrakBadan Lingkungan Hidup Provinsi Jambi pada tahun 2014 menetapkan bahwa Sungai Batanghari dikategorikan tercemari berat dengan limbah 0,3265 ppm. Air sungai ini mengalir ke Danau Sipin, sehingga para petani ikan patin (Pangasius hypopthalmus) di KJA kawatir terjadi pencemaran logam berat Hg melebihi standar. Kandungan Hg diamati melalui metode studi survei purposive sampling dengan 4 stasiun selama 3 minggu pengamatan sampel dengan analisis Spektrofotometer Serapan Atom. Hasil pengamatan terhadap akumulasi logam merkuri (Hg) pada ikan patin di Danau Sipin dari 0,0930 sampai 0,3960 ppm. Katagori kandungan Hg yang bisa di torelansi menurut standar SNI untuk produksi pangan perikanan termasuk moluska dan udang adalah 1 ppm dan 0,5 ppm untuk ikan predator. Jadi budidaya ikan Danau Sipin masih aman untuk dikonsumsi manusia. Nilai Hg airnya dari 0,0001 sampai 0,0009 ppm. Kandungan Hg ini lebih rendah bila dibandingkan dengan standar kualitas air oleh Kementerian Lingkungan Hidup No. 51 Pada tahun 2004 nilai ambang untuk biota adalah 0,001 mg / l (ppm). Kemudian kategori kandungan logam berat Hg di perairan Danau Sipin masih di ambang normal. Terjadinya perbaikan Hg air diduga karena ditemukan sejumlah ikan sapu-sapu, Hypostomus plecostomus dan tanaman eceng gondok, Eichhornia crassipes yang dapat menyerap Hg di perairan. Keadaan kualitas air pengamatan berupa suhu rata-rata 30-32 ° C, pH 6,6 sampai 7,4 dan DO 7,0 sampai 8,4 ppm. Kisaran parameter ini layak untuk budidaya ikan patin (Pangasius Hyphopthalmus), karena mendukung untuk pertumbuhan dan kelangsungan hidup.Kata kunci: Bioakumulasi Hg, Danau Sipin, ikan patin
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Norris, Andrea R., Kathy Martin, and Kristina L. Cockle. "Weather and nest cavity characteristics influence fecundity in mountain chickadees." PeerJ 10 (November 11, 2022): e14327. http://dx.doi.org/10.7717/peerj.14327.
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Background Examining direct and indirect effects on reproduction at multiple scales allows for a broad understanding of species’ resilience to environmental change. We examine how the fecundity of the mountain chickadee (Poecile gambeli), a secondary cavity-nesting, insectivorous bird, varied in relation to factors at three scales: regional weather conditions, regional- and site-level food availability, site-level community dynamics, and nest-level cavity characteristics. We hypothesized that earlier laying dates and higher fecundity (clutch size, nest survival, brood size) would be associated with milder climatic conditions, increased food from insect outbreaks, lower densities of conspecifics and nest predators (red squirrel; Tamiasciurus hudsonicus), and safer (smaller, higher) cavities. Methods We collected data on laying date, clutch size, brood size, nest fate (success/failure), and cavity characteristics from 513 mountain chickadee nests in tree cavities in temperate mixed coniferous-broadleaf forest in interior British Columbia, Canada, from 2000 to 2011. We surveyed annual abundances of mountain chickadees and squirrels using repeated point counts, and mountain pine beetle (Dendroctonus ponderosae) and lepidopteran defoliators by monitoring host trees and by using regional-scale aerial overview forest insect survey data. We used weather data (temperature, rain, snow) from a local Environment and Climate Change Canada weather station. We modeled laying date, clutch size, daily nest survival, and brood size as a function of predictors at regional-, site-, and nest-scales. Results and Conclusions Measures of fecundity varied dramatically across years and spatial scales. At the regional (study-wide) scale, chickadees laid earlier and larger first clutches in warmer springs with minimal storms, and daily nest survival (DSR) increased with a 2-year lag in growing season temperature. Despite a doubling of mountain chickadee density that roughly accompanied the outbreaks of mountain pine beetle and lepidopteran defoliators, we found little evidence at the site scale that fecundity was influenced by insect availability, conspecific density, or predator density. At the nest scale, DSR and brood size increased with clutch size but DSR declined with nest cavity size indicating a positive reproductive effect of small-bodied cavity excavators. Double-brooding, rare in chickadees, occurred frequently in 2005 and 2007, coinciding with early breeding, high food availability from insect outbreaks, and warm spring temperatures with 0-1 spring storms. Our results support the idea that fecundity in secondary cavity-nesting species is impacted directly and indirectly by weather, and indirectly through changes in community dynamics (via cavity resource supply). We stress the importance of adopting holistic, community-level study frameworks to refine our understanding of fecundity in opportunistic and climate-sensitive species in future.
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Kumar, Ramesh, Azizi Abu Bakar, Jegan Thanabalan, Sanmugarajah Paramasvaran, Charng Jeng Toh, Ainul Jaffar, Farizal Fadzil, Palaniandy Kamalanathan, Bee Hong Soon, and Narayanaswamy Venketasubramanian. "Safety and Use of MLC601/MLC901 (NeuroAiDTM) in Primary Intracerebral Hemorrhage: A Cohort Study from the NeuroAiD Safe Treatment Registry." Brain Sciences 10, no. 8 (July 30, 2020): 499. http://dx.doi.org/10.3390/brainsci10080499.
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Background: MLC601/MLC901 (NeuroAiD™) is a combination of natural products shown to be safe and to aid neurological recovery after brain injuries, especially ischemic stroke. Few studies have investigated NeuroAiD in primary intracerebral hemorrhage (ICH). The NeuroAiD Safe Treatment (NeST) Registry explores NeuroAiD use in the real-world setting. This cohort study aimed to assess its use and safety in ICH. Methods: The online NeST Registry of subjects with ICH given NeuroAiD prospectively collected clinical data at baseline and monthly visits (V) 1 to 3. Outcome measures included compliance, side effects, Glasgow Coma Scale (GCS), National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Short Orientation-Memory-Concentration Test (SOMCT). Results: Sixty-six subjects were included. NeuroAiD was well-tolerated with fair compliance over three months. Two non-serious side effects were reported. Mean scores significantly improved on all outcome scales. The proportion of subjects with favorable outcomes significantly improved from baseline to V3: NIHSS 0–4, from 12% to 59% (p < 0.0001); GCS 13–15, from 64% to 88% (p = 0.007); mRS 0–1, from 9% to 37% (p = 0.004); and SOMCT score 0–8, from 44% to 68% (p = 0.029). Conclusions: NeuroAiD in the real-world setting was safe and showed potential for a sustained positive effect on neurological recovery after ICH.
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Bosland, Julie, and Becky Sartini. "PSV-9 The effect of management practices on eggshell cleanliness, bacteria levels and cuticle deposition in free-range poultry." Journal of Animal Science 99, Supplement_3 (October 8, 2021): 304. http://dx.doi.org/10.1093/jas/skab235.559.
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Abstract Small-scale egg production is a growing industry in New England; however, foodborne illness risk exists from small-scale free-range eggs due to lack of guidelines for safe handling and management practices. We hypothesized that the manure level (ML) of the eggs along with management practices will affect both the total bacterial levels (relative light units= RLU) and the cuticle deposition (CD) of the eggshell. Hens (n = 53) were used in this study and housed at Peckham Farm (URI; Kingston, RI) in a mobile coop that allowed free ranging. The management practice experiments were divided into nest box type, location, substrate and time/frequency of collection. The CD experiments involved nesting boxes and nest substrate. Data were analyzed using SAS proc mixed/two sample t-test (P ≤ 0.05). There is a difference in ML between level 1 and 2 and level 1 and 3 eggs. Eggs collected from the conventional (CONV; n = 37) and rollaway (n = 25) nest boxes showed no difference in RLU or CD (P ≥ 0.42). Eggs collected from CONV with different nesting substrates (straw, shavings, AstroTurf nest pad; n = 179) showed no difference in RLU and CD (P ≥ 0.28). Nest box location (mounted vs floor level) showed no difference (P ≥ 0.65) in RLU values from eggs collected from CONV nest boxes. Time of collection (1pm vs 8 am) had a significant impact (P ≤ 0.02) in RLU values; however, frequency of collection showed no impact (P ≥ 0.49). The bacteria levels were most likely lower in the afternoon collection because the eggs laid that day did not spend as much time in nest boxes. In conclusion, although different nest boxes or substrates did not change eggshell bacteria levels, management practices that minimize manure levels on eggs and increase the frequency of collection can help to maintain lower bacteria levels to reduce food safety risk.
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Fidlóczky, József, János Bagyura, Károly Nagy, Tamás Szitta, László Haraszthy, and Péter Tóth. "Bird conservation on electric-power lines in Hungary: Nest boxes for saker falcon and avian protection against electrocutions. Projects' report." Slovak Raptor Journal 8, no. 2 (December 1, 2014): 87–95. http://dx.doi.org/10.2478/srj-2014-0010.
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Abstract Bird conservation on electricity transmission lines has a 40-year history in Hungary. It started with the saker conservation program. The initial small-scale activities were considerably enlarged through the LIFE projects. In the first project, 301 nest boxes for sakers of a new type made of aluminium were installed on pylons of high-voltage transmission lines. In 201 3 nearly 70% of saker pairs nested in these new boxes. An estimated 1 00 000 different birds used to be killed annually on the transmission line pylons in Hungary. During the two LIFE projects about 1 4 300 pylons were made bird-safe using improved technology and materials. Nearly 800 new bird-safe crossarms of pylons are being installed in the second project, which is expected to completely eradicate the danger
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Vasiutina, AA, VV Popov, and AI Kondratyev. "Variation of the entropy analysis method in information flows of IBS in the concept of safe navigation development." Journal of Physics: Conference Series 2061, no. 1 (October 1, 2021): 012107. http://dx.doi.org/10.1088/1742-6596/2061/1/012107.
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Abstract The creation of a configuration by a bridge integrated system in the form of the control machine variation - artificial intelligence, becomes relevant in the concept of E-navigation development with the vector of the vessel’s directional control on the course, both in a small crew and unmanned way. It is possible to consider a large number of mathematical ideas about the basis for creating an intelligent control machine: an artificial neuron and fuzzy sets, Petri nets and Markov chains, Kolmogorov’s differential equations, which are difficult to configure and cumbersome to compute. Multiagent systems seem to be feasible. Integrated bridge systems with embedded supplementary reality assist management personnel in solving navigation issues. Saturation of the navigation control information complex of the bridge system with an increasing number of hardware and instrument units leads to a decrease in information entropy but does not bring to the full automatic control. In ergatic systems, object control is still reduced to declining the uncertainty to a minimum value by means of the operator’s control actions. The methodology for analyzing the entropy capacity of the system and elements of the augmented virtual assessment of the situation in the configuration of multifunctional machine units can be applied in the efficiency criteria development for vessel’s control systems with small crew or unmanned navigation in the concept of E-navigation.
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Sharma, Rohini, Joanne Evans, Caroline Ward, Florian Wernig, and Robert Thomas. "Artisan trial protocol: A single center, open-label, phase II trial of the safety and efficacy of TheraSphere selective internal radiation therapy (SIRT) in the treatment of inoperable metastatic (liver) neuroendocrine neoplasia (NENs)." Journal of Clinical Oncology 40, no. 16_suppl (June 1, 2022): e16208-e16208. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.e16208.
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e16208 Background: Patients(pts) with NENs present with advanced, unresectable disease, with liver metastases. Liver metastases dictates prognosis. SIRT allows targeted high dose radiation directly to tumours, with relative sparing of the surrounding liver tissue. ArTisaN is a phase II study assessing efficacy and tolerability of SIRT using TheraSpheres for management of liver metastases secondary to NENs. Methods: Pts with liver dominant NENs will receive up to 2 TheraSphere treatments. Pts will be followed until disease progression for up to 2-years. Primary endpoints: objective response rate (ORR) within the treated liver volume, incidence of adverse events. Secondary endpoints: progression-free survival (PFS), overall (OS) and quality of life (EORTC QLQ-C30 and QLQ-GI.NET21). Assuming ORR 40%, sample size 24 patients-95% confidence interval will extend 20% in either direction. Results: 13 pts completed therapy: 69% female, primary site: 23% pancreatic, 31% small bowel. Grade: 54%-1, 46% - 2. 69% had previously received more than one line of systemic therapy including 7 who had previously received peptide receptor radiotherapy. 92% received bilobar treatment-average dose 2.49GBq administered. Hepatic ORR-69%. Grade 3 treatment related events occurred in 2 patients–1 ischaemic limb and 1 radiation induced hepatitis. Quality of life-maintained across all parameters. At the time of analysis, 5 pts had progressed, 3 had extrahepatic progression. Median PFS was 15.4 months (95%CI 11.5-19.4) and median OS was 18.5months (95%CI 7.4-29.6). Conclusions: Theraspheres is a safe and effective therapy for the management of patients with liver dominant disease from NENs. Clinical trial information: NCT04362436.
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Renné, Thomas. "Basic Mechanisms of Arterial and Venous Thrombosis." Blood 124, no. 21 (December 6, 2014): SCI—1—SCI—1. http://dx.doi.org/10.1182/blood.v124.21.sci-1.sci-1.
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Abstract Combinations of proinflammatory and procoagulant reactions are the unifying principle for a variety of disorders affecting the cardiovascular system. Factor XII (FXII, Hageman factor) is a plasma protease that initiates the contact system. This system starts a cascade of procoagulant and proinflammatory reactions via the intrinsic pathway of coagulation, and the bradykinin producing kallikrein-kinin system, respectively. The biochemistry of the contact system in vitro is well understood, however its in vivo functions are just beginning to emerge. This presentation will summarize roles of the FXII-driven contact system in vivo. Genetically altered mice and large animal models have shown that FXII is essential for thrombus formation while being dispensable for hemostatic processes that terminate blood loss. Challenging the dogma of a coagulation balance, targeting FXII protected from cerebral ischemia without interfering with hemostasis. In contrast, excess FXII activity is associated with a life threatening inflammatory disorder, hereditary angioedema. Platelet polyphosphate (an inorganic polymer), neutrophil extracellular traps (NETs) and mast cell heparin activate FXII with implications on the initiation of thrombosis and edema. A key aspect of the talk will be the analysis of common principles, interactions and cross-talk between coagulation and inflammation, and the use of the novel FXII blocking antibody 3F7 in cardiopulmonary bypass system. Elucidating the FXII-driven contact system offers the exciting opportunity to develop strategies for safe interference with both thrombotic and inflammatory diseases. Disclosures No relevant conflicts of interest to declare.
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Zhu, Jinwen, Wen Liang, Siyu Yang, Huifu Wang, Chunhua Shi, Shuo Wang, Weijun Zhou, et al. "Safety of Oilseed Rape Straw Mulch of Different Lengths to Rice and Its Suppressive Effects on Weeds." Agronomy 10, no. 2 (February 1, 2020): 201. http://dx.doi.org/10.3390/agronomy10020201.
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Rice is widely grown after harvesting of oilseed rape (Brassica napus L.) in many countries. Experiments were carried out under greenhouse and field conditions to assess the impact of oilseed rape straw mulch on rice and paddy weeds. Oilseed rape mulch (900 g m−2) from straw 1-to-7 cm long was found to be safe for rice, when applied four days after sowing (DAS) in direct-seeded rice or four days after transplanting (DAT). In the meantime, the biomass of Echinochloa crus-galli (L.) P. Beauv. was reduced 65.74%, 80.18%, 81.15%, 70.99%, 55.65%, and 27.22%, respectively, when mulched with powder, and 1, 3, 5, 7, and 9-cm long oilseed rape straw, respectively, and the biomass reductions in Leptochloa chinensis (L.) Nees., Ludwigia prostrata Roxb., Ammannia auriculata Willd., and Cyperus difformis L. were all above 97% when mulched with 1 cm-length straw. The results of a field trial confirmed that oilseed rape straw mulch (900 g m−2) of 1 cm length was safe for rice. Moreover, weed suppression was as effective as the standard herbicide (oxadiargyl + butachlor 525 g ai ha−1) treatment. These findings demonstrate the potential to manage paddy rice weeds in an effective and environmentally sound manner by mulching with the straw of a preceding crop, oilseed rape.
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Bartsch, Detlef K., Sebastian Windel, Veit Kanngießer, Moritz Jesinghaus, Katharina Holzer, Anja Rinke, and Elisabeth Maurer. "Vessel-Sparing Lymphadenectomy Should Be Performed in Small Intestine Neuroendocrine Neoplasms." Cancers 14, no. 15 (July 25, 2022): 3610. http://dx.doi.org/10.3390/cancers14153610.
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Introduction: The goal of primary tumor resection with lymphadenectomy (PTR) in small intestine neuroendocrine neoplasms (SI-NENs) is to avoid local recurrence while sparing as much of the small bowel as possible, even in the case of extensive mesenteric fibrosis. The results of PTR with retrograde vessel-sparing lymphadenectomy (VS-LA) were compared to those of conventional lymphadenectomy (Con-LA). Methods: Prospectively collected clinical, surgical and pathological data of consecutive patients with SI-NENs who underwent small bowel resections were retrospectively analyzed regarding the resection technique performed. Results: In a 7-year period, 50 of 102 patients with SI-NENs had only small bowel resections; of those, 25 were VS-LA and 25 were Con-LA. Patients with VS-LA had tendentially more advanced diseases with slightly higher rates of abdominal pain, mesenteric shrinkage and more level III lymph node involvement compared to patients with Con-LA. VS-LA, however, resulted in shorter resected bowel segments (median 40 cm vs. 65 cm, p = 0.007) with similar rates of local R0 resections (72% vs. 84%) and resected lymph nodes (median 13 vs. 13). Postoperative clinically relevant complications occurred in 1 of 25 (4%) in the VS-LA and in 7 of 25 (28%) patients in the Con-LA group (p = 0.02). Three months after surgery, 1 of 25 (4%) patients of the VS-LA group and 10 of 25 (40%) patients in the Con-LA group (p = 0.002) complained about abdominal pain. One of eight patients in the VS-LA group and two of thirteen patients in the Con-LA group who had completely resected stage III disease complained about diarrhea (p = 0.31). Conclusion: VS-LA seems to be oncologically safe and should be considered in small bowel resections for SI-NENs.