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Published: 25 July 2024
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1

Benito, Juliana M., Volgin Y. Andrei, Ye Chen, Lu Hongbo, Yuexi Shi, Teresa McQueen, Patrick A. Zweidler-McKay, et al. "Leukemia Microenvironment and Pathologic Hypoxia: Sensitivity to Hypoxia-Activated Cytotoxin TH-302." Blood 120, no. 21 (November 16, 2012): 1523. http://dx.doi.org/10.1182/blood.v120.21.1523.1523.

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Abstract Abstract 1523 We have recently demonstrated that the leukemic bone marrow (BM) niche is highly hypoxic and that hypoxia promotes resistance of leukemic cells to chemotherapy (Benito et al., PLoS One 2011, e23108). Our preliminary data indicate that AML cells surviving chemotherapy in the human xenograft mouse models of leukemia reside within hypoxic areas of BM microenvironment as documented by staining with the hypoxia marker CAIX. These findings support utility of hypoxia-activated pro-drugs with the goal to eliminate leukemic blasts and leukemic stem cells residing in hypoxic BM microenvironment. TH-302 is a 2-nitroimidazole linked bromo-isophosphoramide mustard cytotoxin that upon hypoxia-dependent activation induces DNA cross-linking. TH-302 exhibited potent hypoxia-selective anti-leukemia activity in pre-B ALL (REH, NALM6), AML (OCI-AML3, MOLM-13, KG-1) and CML cell lines (KBM5), with IC50s at 1% O2 ranging from 0.04μM to 2.3μM and hypoxia cytotoxicity ratio (HCR) ranging from 116 for KBM5 to 11 for REH cells. TH-302 at 5–7.5μM also exhibited hypoxia-dependent anti-leukemia activity in primary ALL and AML samples (N=3; normoxia, 2–8%; hypoxia, 28–65% apoptotic cells).To better recapitulate the multidimensional BM niche we utilized co-cultures of GFP-labeled leukemic cells with bone marrow-derived RFP-labeled mesenchymal stromal cells (MSC) immobilized within Matrigel. MSC and leukemic cells generated three-dimensional (3D) structures- “spheroids”- and co-proliferated over time with colonies of leukemic cells firmly attached to MSC, as monitored by confocal microscopy (Fig. 1). Pimonidazole staining shows that vast hypoxia is present in the MSC/AML spheroids grown at normal oxygen tension, in contrast to what is observed in plastic-based (2-D) stromal co-cultures. Anti-leukemia activity of TH-302 was next determined in 2D vs 3D co-cultures of MSCs plus MOLM-13 or OCI-AML3 cells. In 2D co-cultures, MSC protected MOLM-13 and OCI-AML3 cells from TH-302-induced cytotoxicity, while extensive apoptosis was documented in hypoxic spheroid co-cultures (at 50nM TH-302, reduction in viability 10–15% vs >60%, Fig. 1). These findings suggest that culture conditions faithfully mimicking BM microenvironment promote pathologic hypoxia generated by rapidly proliferating AML cells, which in turn leads to their increased sensitivity to hypoxia-activated cytotoxins. To validate these findings in vivo, we next tested anti-leukemia efficacy of TH-302 in the in vivo model of primary AML established in NSG mice. TH-302 (50 mg/kg IP 3 times a week for three weeks) reduced the number of circulating AML cells (control, 13.2+/−5.7 ×106/ml; TH-302, 2.5+/−2.1 ×106/ml) and prolonged survival of NSG mice engrafted with primary AML cells compared to the vehicle treated mice (median survival time: TH-302=75 days; Control=56 days; P=0.003, n= 8 mice/group). To test the ability of hypoxia-activated prodrug to target leukemia-initiating cells, secondary transplant experiments were performed in which BM cells from control or TH-302 treated mice (collected after two weeks of therapy) were serially diluted and injected into secondary NSG recipient mice at 0.01, 0.005 or 0.0001×106̂ cells/mouse (N=5 mice/dilution). Although all mice transplanted with higher cell doses died from leukemia, we observed significantly prolonged survival of animals injected with 0.01×106 cells from TH-302-treated primary recipients compared with vehicle-treated controls (median survival control=68 days; TH-302=79 days; P=0.0031) or with 0.005×106 cells (control=79 days; TH-302=83 days; P=0.0462). In summary, our findings suggest that pathologic hypoxia is a prevalent condition of leukemic BM microenvironment that promotes survival of leukemic blasts and leukemia-initiating cells. The results support targeting hypoxia with hypoxia-activated cytotoxins such as TH-302 to enhance the efficacy of therapeutic regimens in AML. A Phase 1 single agent clinical trial of TH-302 in patients with relapsed/refractory hematologic malignancies is ongoing. Figure 1. Spheroids of MSCs and MOLM-13 cells were incubated with or without TH-302 for 72hr. Effect on cell viability was determined by WST-1 assay. Figure 1. Spheroids of MSCs and MOLM-13 cells were incubated with or without TH-302 for 72hr. Effect on cell viability was determined by WST-1 assay. Disclosures: Handisides: Threshold Pharmaceuticals: Employment. Hart:Threshold Pharmaceuticals: Employment. Konopleva:Threshold Pharmaceuticals: Research Funding.
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Wunder, Gerd, and Hans-Werner Goetz. "Rezension von: Goetz, Hans-Werner, Leben im Mittelalter." Württembergisch Franken 72 (November 2, 2023): 381. http://dx.doi.org/10.53458/wfr.v72i.8223.

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Trierveiler-Pereira, Larissa, Matthew E. Smith, James M. Trappe, and Eduardo R. Nouhra. "Sequestrate fungi from PatagonianNothofagusforests:Cystangium(Russulaceae, Basidiomycota)." Mycologia 107, no. 1 (January 2015): 90–103. http://dx.doi.org/10.3852/13-302.

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4

Thomae, Heike. "Anmerkung zu Niedersächsisches OVG, Urt. v. 16.7.2020 – 13 LC 302/19 (VG Braunschweig)." Medizinrecht 39, no. 2 (February 2021): 174. http://dx.doi.org/10.1007/s00350-021-5800-7.

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5

Ahmed, Ahmed, Tariq Arshad, and Stephen Neidle. "Abstract A079: The quadruplex-binding compound QN-302 in the MIA-PaCa2 pancreatic adenocarcinoma model shows no evidence of cardiac or neurological liabilities at therapeutic doses." Cancer Research 82, no. 22_Supplement (November 15, 2022): A079. http://dx.doi.org/10.1158/1538-7445.panca22-a079.

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Abstract The human genome contains multiple sites of quadruplex (G4) arrangements, with over-representation in promoter regions of many oncogenes. Small molecule G4 stabilization down-regulates the transcription of these genes, leading to selective inhibition of cancer cell growth and anti-tumor activity. We have developed a number of novel G4-binding small molecules. QN-302, the most potent, has significant in vivo activity in animal models for pancreatic cancer and is currently in pre-clinical development with Qualigen Therapeutics. The effects of QN-302 have been examined on (1) a panel of cardiac function receptors, (2) heart rate in vivo, and (3) on the histopathology of organs from treated animals. QN-302 was initially screened in a series of in vitro industry-standard CEREP receptor binding assays. The few apparent indications of significant receptor binding were examined in vivo by means of ELISA assays. Cardiac function was examined using a cardiac heart-beat monitor attached to animals treated with QN-302 and compared to animals dosed with a vehicle control. QN-302 gave negative results in CEREP assays, apart from micromolar inhibition of acetylcholinesterase (ACE) and muscarinic (MUSC) receptors. There was no significant hERG receptor inhibition. There was no significant inhibition of ACE and MUSC receptors in vivo. Heart rate experiments, run at both the proposed therapeutic dose of 1mg/kg and at elevated levels, did not show significant deviations from values for the vehicle control arm. Histopathology of heart, liver and brain tissues from QN-302 treated animals, did not show any deleterious effects from the drug. The lack of effects on ACE and MUSC receptors in vivo, together with the absence of effects on heart, liver and brain tissue from treated animals and the normality of heart rate during treatment, demonstrate that treatment of MIA-Paca2 tumor-bearing mice with QN-302 does not have a cardio-, nephro- or neurotoxic burden at therapeutic doses. QN-302 is bio-available at therapeutic doses and is currently in pre-clinical development with Qualigen Therapeutics Inc Citation Format: Ahmed Ahmed, Tariq Arshad, Stephen Neidle. The quadruplex-binding compound QN-302 in the MIA-PaCa2 pancreatic adenocarcinoma model shows no evidence of cardiac or neurological liabilities at therapeutic doses [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr A079.
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Kim, Byung-Wook, Younghee Choe, Tae Ho Kim, Jun-Won Chung, and Joon Sung Kim. "Optimal interval of surveillance gastroscopy after endoscopic resection for gastric neoplasia: A multicenter cohort study." Journal of Clinical Oncology 41, no. 4_suppl (February 1, 2023): 316. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.316.

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316 Background: Due to the possibility of metachronous recurrence of gastric neoplasia, surveillance gastroscopy is mandatory after endoscopic resection (ER) for gastric neoplasia. However, there is no consensus on the surveillance gastroscopy interval. This study aimed to find an optimal interval of surveillance gastroscopy and to investigate the risk factors for metachronous gastric neoplasia (MGN). Methods: Medical records were reviewed retrospectively in patients who underwent ER for gastric neoplasia in 3 teaching hospitals from June 2012 to July 2022. Patients were divided into 2 groups; annual surveillance vs. biannual surveillance. The incidence of MGN was identified, and the risk factors for MGN were investigated. Results: Among the 1,533 patients, 677 patients were included (annual surveillance 302, biannual surveillance 375). The median follow-up for all patients was 22 (range, 12‒91) months. MGN was observed in 61 patients and metachronous gastric cancer (MGC) in 26 patients, both of which were not significantly different between the annual and biannual surveillance groups (annual vs. biannual: 26/302 vs. 32/273, P=0.989 in MGN; 13/302 vs. 13/373, P=0.582 in MGC). All the lesions were removed by ER successfully. In a multivariate analysis, severe atrophic gastritis on endoscopy was an independent risk factor for MGC (odds ratio 3.8, 95% confidence interval 1.4‒10.1; P=0.008). H. pylori infection was not a significant risk factor in this study. Conclusions: Meticulous observation is necessary for patients with severe atrophic gastritis during follow-up gastroscopy after ER for gastric neoplasia. Annual surveillance gastroscopy might be enough after ER for gastric neoplasia.
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Ahmed, Ahmed, William Greenhalf, Tariq Arshad, and Stephen S. Neidle. "Abstract B030: The quadruplex-binding compound QN-302 targets the S100P gene in PDAC." Cancer Research 82, no. 22_Supplement (November 15, 2022): B030. http://dx.doi.org/10.1158/1538-7445.panca22-b030.

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Abstract The compound QN-302, a tetra-substituted naphthalene diimide derivative has been previously disclosed to have single-digit nM anti-proliferative activity in a panel of human pancreatic ductal adenocarcinoma (PDAC) cell lines (Ahmed et al., ACS Med Chem Lett, 2020, 11, 1634-1644). It also has significant anti-tumor activity in the MIA-PACA2 xenograft model for PDAC as well as in the more demanding KPC model. Its novel mode of action involves the targeting of quadruplex (G4)-forming motifs in promoter regions of cancer-associated genes, where their prevalence is over-represented compared to other genes. The presence of a promoter G4 motif, stabilized by a ligand, presents an effective block to transcription. Transcriptome analyses of QN-302 in MIA-PACA2 cells has validated this concept, with the disclosure of a pattern of down-regulated genes involved in cancer-associated pathways and carrying G4 motifs in their promoters. We have also previously shown using RT-PCR and Western blots that a sub-set of these genes and their gene products are down-regulated in the MIA-PACA2 xenograft model following QN-302 treatment. We have now examined cellular changes in the expression of the 229 gene set associated with PDAC and compared these with data from cells and xenografts treated with QN-302. We find that expression of the key gene S100P, a prominent and well-authenticated marker of PDAC disease and progression, is highly down-regulated in QN-302 treated cells. The S100P gene contains 31 putative G4 motifs, including a classic G4 site in the S100P promoter, just upstream of the transcription start site. Transcriptome analyses have also been performed on tumor material from human patients, comprising a panel of poorly differentiated as well as more highly differentiated tumors, and has been compared with normal pancreas expression data. The S100P gene is statistically significantly highly over-expressed (especially in the poorly differentiated tumors), giving added confidence to the concept that the S100P gene is a therapeutic target and may also be useful as a marker of QN-302 response in future clinical use. We also find that the anti-tumor effect of QN-302 treatment in PDAC xenografts results in a high level of apoptosis, which is consistent with earlier reports that S100P in tumors binds to and suppresses p53 activity. The suppression of S100P transcription by QN-302 would thus be expected to remove this roadblock to apoptosis and cell death, in accordance with our observations. QN-302 is bio-available at therapeutic doses and is well tolerated at these levels in these animal models. It is being developed for clinical evaluation by Qualigen Therapeutics Inc and is currently at the pre-IND stage. Citation Format: Ahmed Ahmed, William Greenhalf, Tariq Arshad, Stephen S. Neidle. The quadruplex-binding compound QN-302 targets the S100P gene in PDAC [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer; 2022 Sep 13-16; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2022;82(22 Suppl):Abstract nr B030.
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8

Makimoto, Hisaki, Roland Richard Tilz, Tina Lin, Andreas Rillig, Shibu Mathew, Sebastian Deiss, Erik Wissner, et al. "Incidence and Anatomical Locations of Catheter Instability During Circumferential Pulmonary Vein Isolation Using Contact Force." International Heart Journal 55, no. 3 (2014): 249–55. http://dx.doi.org/10.1536/ihj.13-302.

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9

Matsuoka, Hideaki, Koichiro Nakano, Norimasa Takatani, Tomonori Yoshida, Shizunobu Igimi, and Mikako Saito. "Flow Cytometric Method for in situ Preparation of Standard Materials of a Small Defined Number of Microbial Cells with Colony-Forming Potentiality." Journal of AOAC INTERNATIONAL 97, no. 2 (March 1, 2014): 479–83. http://dx.doi.org/10.5740/jaoacint.13-302.

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Abstract Standard materials of a small defined number of cells with colony-forming potentiality are essential for the rational validation of food microbiological methods. An in situ flow cytometric method using viable staining with 6-carboxyfluorescein diacetate (CFDA) and tryptic soy agar (TSA) was previously proposed and its feasibility was demonstrated with five strains. In this study, this method was applied to 16 strains to support its broad applicability. The cellsorting gate was previously determined based on the CFDA stainability alone. Now the structural properties of cells designated by forward and side-scattering intensities have been introduced as the second gating criteria. Under the optimum gate condition, 100 cells have been selected and sorted on TSA. Consequently, a 95% or higher colony-forming rate has been attained for every strain. A successful application to microaerophilic Campylobacter spp. is especially of great importance because it suggests further broader applicability.
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10

Bendell, J. C., G. J. Weiss, J. R. Infante, E. G. Chiorean, M. Borad, R. Tibes, S. F. Jones, V. K. Langmuir, S. Kroll, and H. A. Burris. "Final results of a phase I study of TH-302, a hypoxia-activated cytotoxic prodrug (HAP)." Journal of Clinical Oncology 27, no. 15_suppl (May 20, 2009): 2573. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.2573.

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2573 Background: TH-302 is a 2-nitroimidazole prodrug of the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM). TH-302 is essentially inactive under normoxia but in severe hypoxia and in the presence of certain reductases, it is reduced and Br-IPM is released. Methods: Eligible patients (pts) had ECOG ≤1, advanced or metastatic solid tumors, evaluable by RECIST, and acceptable hematologic, liver and renal function. A modified accelerated titration design was used. TH-302 was administered intravenously over 30–60 minutes on Day 1, 8 and 15 of a 28-day cycle. CT scans were obtained after every 2 cycles. Detailed pharmacokinetic sampling was performed on Days 1 and 15. The primary objectives of this study were to determine the dose limiting toxicity (DLT) and the maximum tolerated dose (MTD). Results: Twenty-nine pts enrolled at 3 sites at 9 dose levels from 7.5–670 mg/m2. Median age: 64y. 20 male/9 female. ECOG 0/1: 16/13. Primary tumor: prostate (8), colorectal (8), lung (5) other (8). Two of 5 pts at 670 mg/m2 had DLT: Herpes simplex perianal/rectal ulcers and dehydration due to mucositis. Reversible skin and mucosal adverse events (AE) occurred in 12 of 15 (80%) pts at ≥480 mg/m2 including grade 3 events in 3 pts. The most common TH-302-related AEs were nausea, skin lesions, vomiting and fatigue. Hematologic toxicity was mild and limited: two pts with grade 1 and one pt with grade 2 neutropenia and five pts with grade 1 thrombocytopenia. Five pts had grade 3 and one grade 4 lymphopenia. Four pts have enrolled at an intermediate dose of 575 mg/m2 with no DLT so this is likely the MTD and is well above the predicted biologic effective dose of 100 mg/m2. One pt with SCLC treated at 480 mg/m2 and one with melanoma treated at 670 mg/m2 had unconfirmed partial responses; 12 pts had stable disease (6 continuing after 4 or more cycles), 7 had PD, 4 were unevaluable and 4 are too early to assess. Cmax and AUC for TH-302 and Br-IPM increased linearly with no accumulation at Day 15. Conclusions: Weekly TH-302 has remarkably little hematologic toxicity. Skin and mucosal AEs have developed at the higher dose levels. Skin/mucosa are known to have hypoxic regions. TH-302 is the first HAP to demonstrate tumor responses in Phase I. The MTD is likely 575 mg/m2. Studies in combination with chemotherapy are ongoing. [Table: see text]
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Ghobrial, Irene M., Jacob P. Laubach, Noopur Raje, Philippe Armand, Robert L. Schlossman, Erica N. Boswell, Courtney Hanlon, et al. "Phase 1 Study Of TH-302, An Investigational Hypoxia-Targeted Drug, and Dexamethasone In Patients With Relapsed/Refractory Multiple Myeloma." Blood 122, no. 21 (November 15, 2013): 1948. http://dx.doi.org/10.1182/blood.v122.21.1948.1948.

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Abstract Background In multiple myeloma (MM) mouse models, diseased animals demonstrate a marked expansion of areas of hypoxia in the bone marrow, suggesting that hypoxia may be a therapeutically meaningful target in this disease. TH-302 is an investigational 2-nitroimidazole prodrug of the DNA alkylator bromo-isophosphoramide (Br-IPM) designed to be selectively activated in hypoxia. TH-302 exhibited anti-tumor activity in preclinical MM models in vitro and in vivo (Hu et al, Blood 2010; Chesi et al, Blood 2012), and synergism was seen when combined with the proteasome inhibitor bortezomib (Hu et al, Mol Cancer Ther 2013). Based on these findings, a Phase 1/2 study of TH-302 plus dexamethasone was initiated for patients with relapsed/refractory MM. Methods Eligible patients in the study (NCT01522872) had ECOG PS ≤ 2, receipt of at least 2 prior therapies, and acceptable hepatorenal function and hematologic status. A standard 3+3 dose escalation design was used with a fixed oral 40 mg dose of dexamethasone (dex) and 40% dose increments of TH-302. TH-302 was administered IV with dex on days 1, 4, 8, and 11 of a 21-day cycle. The objectives were to determine dose limiting toxicities (DLTs) and the maximum tolerated dose (MTD); assess the safety, tolerability and preliminary clinical activity of TH-302 plus dex; and study the relationship between hypoxia within the bone marrow and response to TH-302. Results As of August 2013, 13 patients have been treated: 8 males/5 females with a median age of 59 years (range: 53 – 86) and 6 prior therapies (range: 3 – 10). All had previously received both bortezomib and lenalidomide/thalidomide containing regimens as well as an alkylating agent. TH-302 was dosed at 240 (n=5), 340 (n=6), and 480 (n=2) mg/m² for a median of 5 cycles (range: 1 – 18). No DLTs were reported at 240 or 340 mg/m². Two patients treated at 480 mg/m² had DLTs of grade 3 mucositis, exceeding the definition of MTD. Four patients had serious adverse events (SAEs) related to TH-302 (pneumonia (n=2), proctalgia (n=1), anemia (n=1)). Three patients continue on study after a median of 17 cycles (range: 7 – 18). Twelve patients have had efficacy evaluations: 2 patients with partial responses (PRs), 3 patients with minimal responses (MRs), and 7 patients with stable disease (SD), for a clinical benefit rate (MR or better) of 42%. Conclusions TH-302 can be administered at 340 mg/m2 biweekly together with dex, with dose limiting mucositis seen at higher doses. Initial clinical activity has been noted with a clinical benefit rate of 42% in heavily pretreated MM patients who are relapsed/refractory to both bortezomib and lenalidomide. Disclosures: Ghobrial: BMS: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Onyx: Membership on an entity’s Board of Directors or advisory committees; Noxxon: Research Funding; Genzyme: Research Funding. Raje:Celgene: Consultancy; Millenium: Consultancy; Onyx: Consultancy; Amgen: Consultancy; Acetylon: Research Funding; Eli Lilly: Research Funding. Handisides:Threshold Pharmaceuticals: Employment, Equity Ownership. Kroll:Threshold Pharmaceuticals: Employment, Equity Ownership. Anderson:Celgene: Consultancy; Onyx: Consultancy; Sanofi Aventis: Consultancy; Gilead: Consultancy; Acetylon: Equity Ownership; Oncopep: Equity Ownership. Richardson:Celgene: Membership on an entity’s Board of Directors or advisory committees; Millennium: Membership on an entity’s Board of Directors or advisory committees; Johnson&Johnson: Membership on an entity’s Board of Directors or advisory committees.
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Sugiharto, S. Yamamoto, T. Sumita, and A. Miyashita. "Preparation of TiO2-anatase film on Si(001) substrate with TiN and SrTiO3as buffer layers." Journal of Physics: Condensed Matter 13, no. 13 (March 15, 2001): 2875–81. http://dx.doi.org/10.1088/0953-8984/13/13/302.

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13

Young, K., S. A. Yeoh, M. Putman, E. Graef, F. Berenbaum, R. Conway, R. Grainger, et al. "POS0051 THE IMPACT OF COVID-19 ON RHEUMATOLOGY TRAINING: RESULTS FROM THE COVID-19 GLOBAL RHEUMATOLOGY ALLIANCE TRAINEE SURVEY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 230.2–231. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2236.

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Background:The COVID-19 pandemic has disrupted healthcare delivery and education of physicians, including rheumatology trainees.Objectives:To assess the impact of the COVID-19 pandemic on the clinical experiences, research opportunities, and well-being of rheumatology trainees.Methods:A voluntary, anonymous, web-based survey was administered in English, Spanish, or French from 19/08/2020 to 05/10/2020. Adult and paediatric rheumatology trainees worldwide in training in 2020 were invited to participate via social media and email. Using multiple choice questions, Likert scales, and free text answers, we assessed trainee patient care activities, redeployment, research, and well-being.Results:The 302 respondents were from 33 countries, with most (83%, 252/302) in adult rheumatology training. Many trainees (45%, 135/300) reported an increase in non-rheumatology clinical work (e.g. care of COVID-19 patients), with 52% of these (70/135) also continuing rheumatology clinical work. COVID-19 redeployment was not optional for 68% (91/134).Trainees reported a negative impact of the pandemic in their growth in rheumatology (Figure 1). They also reported a substantial impact on several training areas: outpatient clinics (79%, 238/302), inpatient consultations (59%, 177/302), formal teaching (55%, 167/302), procedures (53%, 147/302), teaching opportunities (52%, 157/302), and ultrasonography (36%, 110/302), with 87-96% perceiving a negative impact on these areas. Only 54% (159/294) reported feeling comfortable with their level of clinical supervision during the pandemic (Figure 1).Many trainees (46%, 128/280) reported changes in research experiences during the pandemic; 39% (110/285) reported that COVID-19 negatively affected their ability to continue their pre-pandemic research and 50% (142/285) reported difficulty maintaining research goals (Figure 1).Some rheumatology trainees reported having health condition(s) putting them at high risk for COVID-19 (10%, 30/302) and 14% of trainees (41/302) reported having had COVID-19 (Table 1). Only 53% (160/302) reported feeling physically safe in the workplace while 25% (76/302) reported not feeling physically safe; reasons included lack of training about COVID-19, lack of comfort in the clinical setting, insufficient personal protective equipment, immunocompromised state, and pregnancy. Half (151/302) reported burnout and 68% (204/302) an increase in stress from work during the pandemic (Figure 1), whilst 25% (75/302) reported that changes to their training programme negatively impacted their physical health.Conclusion:The COVID-19 pandemic has negatively impacted the experience of rheumatology training as well as the well-being of trainees globally. Our data highlight concerns for rheumatology trainees including research opportunities and clinical care which should be a focus for curriculum planning.Figure 1.Rheumatology trainee perceptions of pandemic impact and changes in training programme.Table 1.Estimated hazard ratios, adjusted for age and gender, for individuals with rheumatoid arthritisEuropen = 89ROWn = 213Combinedn = 302Disability1 (1)9 (4)10 (3)High risk7 (8)23 (11)30 (10)Pregnant4 (5)15 (7)19 (6)Shielding/Quarantining12 (13)70 (33)82 (27)Acquired COVID-1920 (22)21 (10)41 (14)Disclosure of Interests:Kristen Young: None declared, Su-Ann Yeoh: None declared, Michael Putman: None declared, Elizabeth Graef: None declared, Francis Berenbaum: None declared, Richard Conway: None declared, Rebecca Grainger Speakers bureau: Speaker fees from Abbvie, Janssen, Novartis, Pfizer, Cornerstones, all not related to this work, Consultant of: Consultancy fees from Abbvie, Janssen, Novartis, Pfizer, Cornerstones, all not related to this work, Grant/research support from: Travel assistance from Pfizer, not related to this work, Adam Kilian: None declared, Maximilian Konig: None declared, Jean Liew Grant/research support from: Research grant from Pfizer unrelated to this manuscript, Pedro M Machado Speakers bureau: Speaker fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript, Consultant of: Consulting fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript, Sebastian E. Sattui: None declared, Jeffrey Sparks Consultant of: Consultancy for Bristol-Myers Squibb, Gilead, Inova Diagnostics, Optum, and Pfizer unrelated to this manuscript, Grant/research support from: Research support from Bristol-Myers Squibb unrelated to this manuscript, Paul Sufka: None declared, Manuel Ugarte-Gil Grant/research support from: Research grants from Janssen and Pfizer unrelated to this manuscript, Laura Upton: None declared, Zachary Wallace: None declared, Jinoos Yazdany Consultant of: Consultancy for Astra Zeneca, Eli Lilly, and Pfizer, not related to this work, Grant/research support from: Research grants from Gilead and Pfizer, not related to this work, Arundathi Jayatilleke: None declared.
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Baker, Philip, and Magnus Huber. "Atlantic, Pacific, and world-wide features in English-lexicon contact languages." English World-Wide 22, no. 2 (December 31, 2001): 157–208. http://dx.doi.org/10.1075/eww.22.2.02bak.

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This article analyzes the earliest known attestations of 302 lexical, functional, and grammatical features in 13 English-lexicon contact languages in the Atlantic and the Pacific. The main aims are (i) to shed light on the historical relationships between the individual varieties, (ii) to learn about the mechanisms at work in their genesis and development, and (iii) to examine the significance of features common to both geographical regions. Overall, our intention is to demonstrate that a statistical feature-based approach as proposed here can yield valuable insights into the development and interrelationships between Pidgins and Creoles.
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Yeoh, S. A., K. Young, M. Putman, E. Graef, F. Berenbaum, R. Conway, R. Grainger, et al. "AB0674 RAPID ADOPTION OF TELEMEDICINE IN RHEUMATOLOGY TRAINING: RESULTS FROM THE COVID-19 GLOBAL RHEUMATOLOGY ALLIANCE TRAINEE SURVEY." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 1368.3–1369. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2205.

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Background:The COVID-19 pandemic led to a rapid increase in remote consultations in rheumatology care. Due to the potential impact of this change on rheumatology clinical training, we investigated trainees’ experiences with telemedicine.Objectives:To assess the impact of telemedicine use during the COVID-19 pandemic on rheumatology training, including supervision.Methods:A voluntary, anonymous web-based survey was administered in English, Spanish, or French from 19/08/2020 to 05/10/2020. Adult and paediatric rheumatology trainees worldwide in training in 2020 were invited to participate via social media and email. Using multiple choice questions, Likert scales, and free text answers, we collected data regarding prior and current telemedicine use, training, and supervision.Results:302 respondents from 33 countries completed the survey, with most (83%, 252/302) in adult rheumatology training. Reported use of telemedicine increased from 13% (39/302) pre-pandemic to 82% (247/302) (Table 1). European trainees predominantly utilised audio-only compared to trainees from the rest of the world (ROW) who predominantly utilised audio-video telemedicine.Most trainees continued to evaluate new patients using telemedicine (65%, 161/247). A larger proportion of trainees were comfortable using telemedicine to evaluate follow-up (69% 170/247) versus new patients (25%, 41/161) (Figure 1).Only 32% (97/302) were trained in telemedicine, with the highest proportion among United States (US) trainees (59%, 69/116); subjects included software, clinical skills, and billing. The majority of trainees found this helpful (92%, 89/97).Supervision was most frequently in the form of verbal discussion after the consultation (Table 1); 24% (59/247) had no telemedicine supervision during the pandemic. In general, trainees found telemedicine negatively impacted their supervision (51%, 123/242) and clinical teaching quality (70%, 171/244); only 9% reported a positive impact on these areas.Conclusion:Adoption of telemedicine during the COVID-19 pandemic has led to areas of concern for rheumatology trainees including inadequate supervision and clinical teaching. Our results suggest a need for education on evaluation of new patients using telemedicine, increasing telemedicine training, and ensuring adequate supervisory arrangements.Table 1.Telemedicine use, supervision, and training by region. Data is presented as n (%). Rest of the world (ROW) data includes Asia (50), Central and South America (23), Canada (12), Australia (8), and Africa (4).Europen = 89USn = 116ROWn = 97Combinedn = 302Telemedicine usePre-pandemic15 (17)9 (8)15 (15)39 (13)During pandemic64 (72)112 (97)71 (73)247 (82)Telemedicine modalitypre-pandemicAudio-only14 (93)3 (33)8 (53)25 (64)Audio-video1 (7)7 (78)7 (47)15 (38)Telemedicine modality during pandemicAudio-only56 (88)47 (42)51 (72)154 (62)Audio-video7 (11)100 (89)29 (41)136 (55)Supervisionpre-pandemicReal-time observation (part of visit)0 (0)4 (44)3 (20)7 (18)Real-time observation (full visit)0 (0)2 (22)2 (13)4 (10)Verbal discussion after8 (53)3 (33)7 (47)18 (46)Written communication after0 (0)0 (0)1 (7)1 (3)None7 (47)2 (22)5 (33)14 (36)Supervision during pandemicReal-time observation (part of visit)2 (3)54 (48)15 (21)71 (29)Real-time observation (full visit)3 (5)32 (29)8 (11)43 (17)Verbal discussion after32 (50)65 (58)28 (39)125 (51)Written communication after7 (11)15 (13)9 (13)31 (13)None28 (44)9 (8)22 (31)59 (24)Figure 1.Rheumatology trainee comfort levels in using telemedicine during the pandemic.Disclosure of Interests:Su-Ann Yeoh: None declared, Kristen Young: None declared, Michael Putman: None declared, Elizabeth Graef: None declared, Francis Berenbaum: None declared, Richard Conway: None declared, Rebecca Grainger Speakers bureau: Speaker fees from Abbvie, Janssen, Novartis, Pfizer, Cornerstones, all not related to this work, Consultant of: Consultancy fees from Abbvie, Janssen, Novartis, Pfizer, Cornerstones, all not related to this work, Grant/research support from: Travel assistance from Pfizer, not related to this work, Adam Kilian: None declared, Maximilian Konig: None declared, Jean Liew Grant/research support from: Research grant from Pfizer unrelated to this manuscript, Pedro M Machado Speakers bureau: Speaker fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript, Consultant of: Consulting fees from Abbvie, BMS, Celgene, Eli Lilly, Janssen, MSD, Novartis, Orphazyme, Pfizer, Roche and UCB, all unrelated to this manuscript, Sebastian E. Sattui: None declared, Jeffrey Sparks Consultant of: Consultancy for Bristol-Myers Squibb, Gilead, Inova Diagnostics, Optum, and Pfizer unrelated to this manuscript, Grant/research support from: Research support from Bristol-Myers Squibb unrelated to this manuscript, Paul Sufka: None declared, Manuel Ugarte-Gil Grant/research support from: Research grants from Janssen and Pfizer unrelated to this manuscript, Laura Upton: None declared, Zachary Wallace: None declared, Jinoos Yazdany Consultant of: Consultancy for Astra Zeneca, Eli Lilly, and Pfizer, not related to this work, Grant/research support from: Research grants from Gilead and Pfizer, not related to this work, Arundathi Jayatilleke: None declared
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RUTJES, S. A., M. BOUWKNEGT, J. W. van der GIESSEN, A. M. de RODA HUSMAN, and C. B. E. M. REUSKEN. "Seroprevalence of Hepatitis E Virus in Pigs from Different Farming Systems in The Netherlands." Journal of Food Protection 77, no. 4 (April 1, 2014): 640–42. http://dx.doi.org/10.4315/0362-028x.jfp-13-302.

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Sporadic nontravel-related hepatitis E virus (HEV) infections have been reported in industrialized countries. These infections are caused by zoonotic HEV genotypes 3 and 4 that circulate in swine, wild boar, and deer. In The Netherlands, HEV RNA has been detected in > 50% of the pig farms, and HEV-specific antibodies were detected in ~70% of the slaughter pigs. In the current study, HEV seroprevalences were investigated in pigs raised on conventional, free-range, and organic farms in The Netherlands. Differences in seroprevalence may indicate different exposure routes or transmission dynamics within pig herds for HEV. In 2004, serum samples of 846 fattening pigs were obtained from farms that applied conventional (265 pigs at 24 farms), organic (417 pigs at 42 farms), and free-range (164 pigs at 12 farms) farming. HEV-specific antibodies were detected in samples from all conventional and free-range pig farms and in 41 of 42 organic pig farms, indicating that the probability of introducing HEV on a farm appeared to be equal for the different farming types. The estimated average within-herd seroprevalence was significantly higher for pigs raised on organic farms (89%) than for pigs raised on conventional farms (72%, P = 0.04) and nearly significant for pigs raised on free-range farms (76%, P = 0.06). Six of ten organic farms were estimated to have a within-herd seroprevalence of > 95%, compared with 1 of 10 and 4 of 10 of the free-range and conventional pig farms, respectively. This suggests a higher force of infection with HEV for pigs reared on organic farms compared with pigs reared on conventional or free-range farms. This may be due to repetitive exposure to HEV caused by farming system–specific housing conditions, such as a greater contact frequency between pigs and more exposure to pig manure, increasing the transmission rate.
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Wallace, M. E., and R. Squires. "Fatal Massive Amphetamine Ingestion Associated with Hyperpyrexia." Journal of the American Board of Family Medicine 13, no. 4 (July 1, 2000): 302–4. http://dx.doi.org/10.3122/15572625-13-4-302.

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Boubekri, Abdelbaki. "Reducing Central Line-Associated Bloodstream Infections in the Blood and Marrow Transplantation Population: A Review of the Literature." Clinical Journal of Oncology Nursing 17, no. 3 (May 28, 2013): 297–302. http://dx.doi.org/10.1188/13.cjon.297-302.

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Flagel, Lex E., Jonathan F. Wendel, and Joshua A. Udall. "Duplicate gene evolution, homoeologous recombination, and transcriptome characterization in allopolyploid cotton." BMC Genomics 13, no. 1 (2012): 302. http://dx.doi.org/10.1186/1471-2164-13-302.

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Underwood, Anthony P., Garan Jones, Massimo Mentasti, Norman K. Fry, and Timothy G. Harrison. "Comparison of the Legionella pneumophila population structure as determined by sequence-based typing and whole genome sequencing." BMC Microbiology 13, no. 1 (2013): 302. http://dx.doi.org/10.1186/1471-2180-13-302.

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21

Karrakchou, Basma, Amani Fliti, Mariame Meziane, Nadia Ismaili, Syrine Hamada, Laila Benzekri, and Karima Senouci. "Pemphigus and cancer: A single-center experience over 30 years in Morocco." Our Dermatology Online 14, no. 4 (October 1, 2023): 361–66. http://dx.doi.org/10.7241/ourd.20234.4.

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Background: The aim of this study was to investigate the association between pemphigus and cancer and to analyze the characteristics of pemphigus in which a neoplasm occurs. Materials and Methods: This was a retrospective, descriptive study conducted at the Dermatology Department of Ibn Sina Hospital in Rabat from January 1993 to December 2022, including all pemphigus cases in which cancer was diagnosed before, during, or after the onset of pemphigus. Results: Among 302 pemphigus cases, 13 patients presented an associated cancer (4,3%). Only one patient had a paraneoplastic pemphigus. There was an increased incidence of various solid cancers (11/13) in deep pemphigus types yet without temporal relationship. When hematological malignancy occurred (3/13), it was mainly non-lymphoproliferative and preceded deep pemphigus types with good prognosis. Patient comorbidities and immunosuppressive treatments did not influence the onset of cancer. Conclusion: Our manuscript suggests an increased incidence of solid cancers in deep pemphigus subtypes, independently of the timeline of the latter onset. These pemphigus cases carry a good prognosis. Key words: Pemphigus, Cancer, Paraneoplastic pemphigus, Paraneoplastic autoimmune multiorgan syndrome
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ŞEVİK, Ümit. "Pozitif Psikolojik Sermayenin Mevcut ve Muhtemel Alt Boyutlarının Literatürdeki Seyri: Bibliyometrik Bir Analiz." MANAS Sosyal Araştırmalar Dergisi 12, no. 3 (July 17, 2023): 1044–61. http://dx.doi.org/10.33206/mjss.1292692.

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Bu çalışma pozitif psikolojik sermayenin literatürdeki gelişim düzeyini alt boyutlar perspektifinden değerlendirmek maksadıyla yapılmıştır. Luthans, Youssef ve Avolio (2007b) çalışmalarında pozitif psikolojik sermayenin alt boyutlarına bilişsel (yaratıcılık ve bilgelik), duyuşsal (öznel iyi oluş, akış deneyimi, mizah anlayışı), sosyal (minnettarlık, bağışlayıcılık ve duygusal zekâ) ve üst düzey (maneviyat, otantiklik ve cesaret) özellikler kapsamında potansiyel boyutların gelecekte eklenebileceğini belirtmişlerdir. Pozitif psikolojik sermayenin hali hazırda en çok kullanılan öz yeterlilik, umut, iyimserlik ve dayanıklılık alt boyutlarına eklenecek potansiyel pozitif yapılar, kavramı geliştirecek ve güçlendirecektir. Luthans vd. ’nin (2007b) pozitif psikolojik sermayenin alt boyutlarının genişletilmesi beklentilerinin karşılanma durumunu tespit etmek maksadıyla Web of Science veri tabanı kullanılarak pozitif yapıları içeren bibliyometrik analiz yapılmıştır. 18 Mart 2023 tarihi itibariyle literatürde pozitif psikolojik sermayenin çalışıldığı 1904 çalışma tespit edilmiş olup bunlardan 302 çalışmada pozitif psikolojik sermaye potansiyel pozitif yapılarla birlikte çalışılmıştır. 302 çalışmaya yönelik yapılan içerik analizi sonucunda sadece 13 çalışmada pozitif psikolojik sermayenin alt boyutlarının pozitif yapılarla genişletildiği sonucuna ulaşılmıştır. Pozitif psikolojik sermaye ile ilgili yapılan 1904 çalışmanın % 0,7’sinde alt boyutlara potansiyel pozitif yapılar eklenmiştir. Bu kapsamda literatürde pozitif psikolojik sermayenin çoğunlukla mevcut dört boyutlu yapısının kullanıldığı ancak Luthans vd. ’nin (2007b) gelecekteki eklenecek potansiyel alt boyutlara yönelik beklentilerinin karşılanmadığı sonucuna ulaşılmıştır. Çalışmada pozitif psikolojik sermayenin yapısının geliştirilmesi ve genişletilmesine yönelik gelecekte yapılacak çalışmalara tavsiyelerde bulunulmuştur.
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Niessink, Tom, Matthijs Janssen, Tim L. Jansen, and Cees Otto. "The Prevalence of Titanium Dioxide Particles in Synovial Fluid Samples Drops after European Union Ban." Gout, Urate, and Crystal Deposition Disease 2, no. 1 (February 1, 2024): 45–51. http://dx.doi.org/10.3390/gucdd2010004.

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Due to health concerns, the European Union has banned the use of titanium dioxide nanoparticles in consumables in February 2022, with a 6-month transitional period ending in August 2022. We studied the prevalence of titanium dioxide nanoparticles in synovial fluid samples during and after the transitional period. A total of 302 samples were collected as a consecutive series between 1 April 2022 and 15 June 2023 from patients visiting the department of rheumatology at VieCuri Medical Centre in Venlo, The Netherlands. The samples were primarily collected for diagnostic purposes and only clinical waste material was used for this study. From each sample, up to 40 μl of fluid was analysed with Raman spectroscopy for the presence of titanium dioxide particles. The trend in prevalence was calculated with a 3-month wide moving average. A total of 13 out of 302 samples (4.3%) contained titanium dioxide (TiO2). The prevalence of TiO2 decreased between the transitional period and the period after the ban (p = 0.0154, with a relative risk ratio of 4.9 (95% CI 1.35–17.74). There was no significant difference in patient characteristics between the TiO2 positive and the TiO2 negative group. These results are hinting towards a possible relationship between the EU-ban and the identified decrease in prevalence.
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Ward, Alton C. S. "Isolation of Pasteurellaceae from Bovine Abortions." Journal of Veterinary Diagnostic Investigation 2, no. 1 (January 1990): 59–62. http://dx.doi.org/10.1177/104063879000200111.

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A 2-year study was conducted to determine the incidence of Pasteurellaceae in abortion samples submitted for diagnostic evaluation. A total of 687 cases, including 623 with fetal tissues and/or stomach contents and 302 with placenta and/or uterine discharge, were evaluated. Pasteurellaceae were isolated on a nonselective medium from 9 (1.5%), 14 (2.8%), 13 (12.1%), and 42 (17.4%) of the fetal tissues, stomach contents, uterine discharges, and placentas, respectively. A total of 35 (19.9%) of 176 placental samples cultured on both a selective medium for Pasteurellaceae and a nonselective medium were positive for Pasteurellaceae. Fifteen (42.9%) of these isolates were detected only on the selective medium, whereas 5 (14.2%) were detected only on the nonselective medium and 15 (42.9%) grew on both media. Placentitis of different severity was evident in 13 (68.4%) of the 19 placentas from which Pasteurellaceae were isolated in the absence of other known abortifacient agents.
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Schmiel, Robert. "The ὄλβος, ϰόϱος, ὓβϱις, ἂτη Sequence." Traditio 45 (1990): 343–46. http://dx.doi.org/10.1017/s0362152900012769.

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Gildersleeve gave ὄλβος, ϰόϱος, ὓβϱις, and ἂτη as the genealogy of evil characteristic of archaic Greek thought. Greene observed a fifth item at the end of the sequences in Solon 13. Commenting on Aeschylus, Agam. 757–62 Denniston and Page note that ‘ϰόϱος—ὓβϱις—ἂτη are often linked together as successive elements in the downfall of man.’ More recently Doyle has challenged the very existence of a ‘canonical tetralogy.’ He concludes that there were three triads (ὄλβος—ὓβϱις—ἂτη; ὄλβος—ϰόϱος—ἂτη; ϰόϱος—ὓβϱις—ἂτη); and that they occur too infrequently to be seen as ‘a central doctrine of Greek thought’ (Doyle 302/45).
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García-Moreno, Antonio. "Jacques GOETTMANN, Saint Jean Evangile de la Nouvelle Genèse, Éditions Cerf-Pneumathique, Paris 1982, 302 pp., 13 x 19." Scripta Theologica 17, no. 1 (March 6, 2018): 321–23. http://dx.doi.org/10.15581/006.17.20925.

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27

Kasuga, Noriko Chikaraishi, Yusuke Saito, Hiroyasu Sato, and Kazuo Yamaguchi. "Packing polymorphism in the crystal structure of 4,5-dimethoxy-2-nitrobenzyl acetate." Acta Crystallographica Section E Crystallographic Communications 71, no. 5 (April 11, 2015): 483–86. http://dx.doi.org/10.1107/s2056989015006714.

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The title compound, C11H13NO6, shows two polymorphs, orange and yellow forms, both of which crystallize in the space groupP21/c. The molecular structures in the two polymorphs are essentially similar and adopt a planar structure, the maximum deviations for the non-H atoms being 0.1836 (13) and 0.1276 (13) Å, respectively, for the orange and yellow forms. In the orange crystal, molecules are linked by an intermolecular C—H...O interaction into a helical chain along theb-axis direction. The chains are stacked along thecaxis through a π–π interaction [centroid–centroid distance = 3.6087 (11) Å], forming a layer parallel to thebcplane. In the yellow crystal, molecules are connected through C—H...O interactions into a sheet structure parallel to (-302). No significant π–π interaction is observed. The unit-cell volume of the orange crystal is larger than that of the yellow one, and this accounts for the predominant growth of the yellow crystal.
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Anaba, Ehiaghe L., and Babawale Arabambi. "Primary drug non-adherence in dermatology patients: prevalence, pattern and reasons." International Journal of Research in Dermatology 8, no. 5 (August 25, 2022): 444. http://dx.doi.org/10.18203/issn.2455-4529.intjresdermatol20222177.

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<p class="abstract"><strong>Background:</strong> Primary drug non-adherence, a pervasive problem in dermatology is not readily documented despite the adverse effect of this phenomenon on the management of patients. The aim of the study was to document the prevalence, pattern and reasons for primary drug non-adherence in dermatology patients.</p><p class="abstract"><strong>Methods:</strong> This prospective cross-sectional questionnaire based study was conducted from June to December 2021 amongst 302 consecutive consenting adult patients returning to the dermatology clinic following an initial diagnosis and a prescription for medications. Data collected included socio-demographic parameters, primary drug adherence, and number of drugs prescribed, number not purchased, and reason for non-adherence. Data analysis was done in R Studio [R Core Team (2021)].<strong></strong></p><p class="abstract"><strong>Results:</strong> Three hundred and two (302) patients aged 13 to 87 years with a mean age of 41.72±18.8 years were recruited into the study. Prevalence of primary non-drug adherence was 26.2% (79/302). Amongst the non-adherent patients; 73.4% were females and 26.6% were males. The reasons for non-drug adherence ranged from non-availability of drug (63.3%) to patient forgetting about the prescription. (1.3%). Route of drug not adhered to was Topical in 72%, Oral in 22.7%, oral and topical in 5.3.</p><p class="abstract"><strong>Conclusions:</strong> Primary drug non-adherence is common with dermatology patients. The propensity for primary non-drug adherence is increased when the number of drugs prescribed are more than three. Dermatologists need to consider the use of drugs capable of addressing multiple symptoms and thereby reduce the number of drugs prescribed. </p><p class="abstract"> </p>
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van Dijck, José. "Review: Daniel Miller The Comfort of Things Cambridge: Polity Press, 2008. 302 pp. ISBN-13: 978-07456-4403-5 (cloth)." International Journal of Cultural Studies 12, no. 6 (October 30, 2009): 661–63. http://dx.doi.org/10.1177/1367877909342499.

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30

Gruen, Peter P. "Traumatic Brain Injury. Donald W. Marion. New York, Georg Thieme, 1999. Pages: 302. Price: $99.00. ISBN: 3-13-783402-3." Neurosurgery 47, no. 4 (October 1, 2000): 990–91. http://dx.doi.org/10.1097/00006123-200010000-00047.

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31

Stacey, Helen J., Steven De Soir, and Joshua D. Jones. "The Safety and Efficacy of Phage Therapy: A Systematic Review of Clinical and Safety Trials." Antibiotics 11, no. 10 (September 30, 2022): 1340. http://dx.doi.org/10.3390/antibiotics11101340.

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Trials of phage therapy have not consistently reported efficacy. This contrasts with promising efficacy rates from a sizeable and compelling body of observational literature. This systematic review explores the reasons why many phage trials have not demonstrated efficacy. Four electronic databases were systematically searched for safety and/or efficacy trials of phage therapy. Sixteen trials of phage therapy were included, in which 378 patients received phage. These were divided into historical (pre-2000; N = 3; n = 76) and modern (post-2000; N = 13; n = 302) trials. All 13 modern trials concluded that phage therapy was safe. Six of the 13 modern trials were exclusively safety trials. Seven modern trials investigated both safety and efficacy; efficacy was observed in two. Two of three historical trials did not comment on safety, while adverse effects in the third likely reflected the use of phage preparations contaminated with bacterial debris. None of the historical trials contained evidence of efficacy. The evidence from trials is that phage therapy is safe. For efficacy to be observed a therapeutic amount of the right phage(s) must be delivered to the right place to treat infections containing enough susceptible bacterial cells. Trials that have not demonstrated efficacy have not fulfilled one or more elements of this principle.
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Yeshitila, Yordanos Gizachew, Hagos Zewde, Tesfahun Mekene, Aseer Manilal, Serawit Lakew, and Abinet Teshome. "Prevalence and Associated Risk Factors of Intestinal Parasites among Schoolchildren from Two Primary Schools in Rama Town, Northern Ethiopia." Canadian Journal of Infectious Diseases and Medical Microbiology 2020 (August 25, 2020): 1–8. http://dx.doi.org/10.1155/2020/5750891.

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Introduction. Worldwide, about 3.5 billion people are affected by intestinal parasitic infections, and the majority of them are children. A perusal of the literature indicates that in Ethiopia, nearly one-third of schoolchildren are found to be infected by some sort of intestinal parasites. This study aimed to determine the prevalence of intestinal parasites among schoolchildren in Rama town in Northern Ethiopia. Methods. A school-based cross-sectional study was conducted among primary school children from two schools in Rama town during June 2017. A structured questionnaire was used to identify environmental, sociodemographic, and behavioral factors while stool specimens were collected and examined for parasites using direct wet smear with saline preparation. Data analysis was completed using the Statistical Program for Social Sciences version 24 statistical software. Results. A total of 312 school children with a mean age of 11.3 years were included. Among them, 24.4% (76) were found to be positive for at least one of the parasites. The overall infection rate was the highest among the 10–14 age groups (26.7%). Females were predominantly infected (26.7%). Altogether, eight species of intestinal parasites were identified. The most predominant protozoan and helminths were E. histolytica/dispar (10.9%) and Schistosoma mansoni (7.4%), respectively, and infections were mostly mono-parasitic. Coinfections with two and three intestinal parasites were identified among 13 (4.2%, [13/302]) and 2 (0.6%, [2/302]) cases, respectively. Prevalence of intestinal parasites was higher among children who did not wash their hands regularly before meals (AOR: 2.30, CI: 1.32, 4.0, p < 0.001) and those who frequently swam in streams (AOR: 3.12, CI: 1.07, 9.08, p < 0.021). Conclusions. The study revealed a high prevalence of parasitic infection and inadequate personal hygiene practices like poor handwashing and also the habit of swimming by schoolchildren in contaminated water bodies, especially the study area. To minimize the burden caused by parasitic infection, periodic deworming programs and health education should be provided to enhance the awareness of concerned participants are also warranted.
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Guevara Ríos, Enrique. "Mortalidad Materna en el Instituto Nacional Materno Perinatal." Revista Peruana de Investigación Materno Perinatal 13, no. 1 (March 30, 2024): 6–7. http://dx.doi.org/10.33421/inmp.2024404.

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A nivel nacional, el número de muertes maternas disminuyó en el 2023. En el 2019 se produjeron 302 muerte maternas, cifra que nunca se había llegado en el Perú; lamentablemente la llegada de la pandemia por COVID-19 al Perú en el 2020, puso al descubierto graves deficiencias en el sistema de salud. Ese año el número de casos de muerte materna se incrementó a 439 (incremento del 45%) y el 2021 se incrementó a 493 (incremento del 63% respecto al 2019). En el 2022 luego de la vacunación de las gestantes contra el COVID-19 y mejoras en la calidad de atención materna, se logró disminuir los casos de muerte materna a 291 y en el 2023 a 264 casos (disminución del 13% aproximadamente respecto al año 2019)(1).
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Dorofeikova, M. V., S. F. Zadvorev, N. N. Petrova, and A. A. Yakovlev. "Assessment of the Validity of the Psycho-Cardiological Comorbidity Index in the Practice of a Cardiologist." Acta Biomedica Scientifica 4, no. 2 (May 25, 2019): 51–54. http://dx.doi.org/10.29413/abs.2019-4.2.7.

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Background. The feasibility of creating a screening Index for the comorbidity of mental disorders and cardiovascular diseases in the practice of the cardiologist dictates the need to validate existing algorithms.Aim. To validate the previously proposed Index of psychocardiac comorbidity in prediction of outpatient recommendation of psycho-pharmacotherapy for cardiology patients.Materials and methods. Medical records of 302 consecutive patients of cardiac in-patient department were retrospectively analyzed with ROC-curve to estimate the predictive value of previously proposed Index of psychocardiac comorbidity for out-patient recommendation of psycho-pharmacotherapy.Results. The prevalence of outpatient psycho-pharmacotherapy in the examined patients was 15.2 %; this group of patients was more polymorbid and was characterized by a higher proportion of women and a higher prevalence of a labile course of arterial hypertension. The sedative antipsychotics, non-benzodiazepine tranquilizers and mood stabilizers were predominant pharmacological groups. An analysis of reproducibility of Index of psychocardiac comorbidity was provided on a cohort of cardiology in-patient department (n = 302). Index calculated by using the formula I = C + 3(6)×Q + 3×W + 8×A (C – number of Comorbid diagnoses, Q – Quake in the chest, palpitations or arrhythmia, onset before 55 (3 points) or 50 (6 points) years; W – Women; A – labile Arterial hypertension). Area under ROC-curve in validation cohort was 0.828 ± 0.035 (p < 0.001). Positive predictive value of Index was maximal for the score of ≥ 13.Conclusion. The proposed Index of psychocardiac comorbidity is a valid tool to predict the prescription of psychopharmacotherapy in cardiology patients.
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Kumar, Sarvesh, Rinku Bhaskar, Subhash Chandra, Ankit Kumar, Ramesh Chand, Parmanand Kumar Maurya, and Vishwajeet. "Screening of Mungbean [Vigna radiata (L.) Wilczek] Genotypes against Cercospora Leaf Spot Caused by (Cercospora canescens) for Disease Resistance." International Journal of Environment and Climate Change 13, no. 12 (December 18, 2023): 250–55. http://dx.doi.org/10.9734/ijecc/2023/v13i123681.

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In India, where vegetarianism is the norm, mungbean [Vigna radiata (L.) Wilczek] is a significant source of proteins, minerals, and vitamins. One of the most significant fungal diseases, Cercospora leaf spot caused by Cercospora canescens, appears every year with varying intensity and significantly reduces yield. The objective of the current studies was to test 100 genotypes for resistance to Cercospora canescens in vivo at the Student's Instructional Farm (S.I.F.) A.N.D.U.A. &T., Kumarganj, Ayodhya. According to the rating system, which is based on the severity of the disease, different genotypes were assigned to different grades. Out of total test entries 13 genotypes LGG 607, PM 14- 3, AKM 12-28, VGG 16- 036, Pusa 171, Pusa 172, RMG 1092, RMG 1097, JLM 302-46, IPM 312-19, IPM 312-20, MGG 387 were found free from infection, 18 genotypes SKNM 1502, COGG 13-39 , PM 1511, Type 44, , DDG3, VGG 05-006, TRAM 1, Asha ,BPMR 145, IPM 02-14, TMB -36, CO -6, BMU, MH 805, MH 2-15, MH 421, MVSKAN, Pusa 0672, were found highly resistant 14 genotypes were noticed susceptible and only 3 genotypes were recorded highly susceptible.
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36

Wan Mahzan, Mohd Syazwan, Nor Aziah Alias, and Izaham Shah Ismail. "INVESTIGATING THE NEEDS OF DEVELOPING A DIGITAL VOCABULARY LEARNING MATERIAL FOR MALAYSIAN INDIGENOUS LEARNERS IN ESL CLASSROOM." Journal of Nusantara Studies (JONUS) 5, no. 2 (June 25, 2020): 282–302. http://dx.doi.org/10.24200/jonus.vol5iss2pp282-302.

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Background and Purpose: An intervention program becomes a necessity when a learning problem arises. To ensure the program effectiveness, pedagogical and assessment decisions rely heavily on the actual needs of learners. Hence, this study aimed to conduct a needs analysis survey to investigate the indigenous learners’ needs in terms of their attitudes towards ESL learning, favorable language skills, topics of interest and preferable modes of learning. Unlike other groups of Malaysian learners, the indigenous experience extreme ESL learning disadvantage due to their struggle to assimilate themselves in a multi-ethnic school environment. Methodology: This study employed design-based research (DBR) methodology with the utilization of mixed-method tools in the forms of document analysis and close-ended questionnaire. These data variations aim for the breadth and depth of understanding and corroboration. Past public examination results were used to highlight the indigenous learning problems in ESL learning followed by a survey questionnaire on forty-eight (48) 13-year-old indigenous learners. Findings: The findings reveal that the indigenous possessed extremely poor vocabulary mastery and experienced high language anxiety. Nevertheless, they surprisingly exhibited high awareness towards the potential usage of English language, and this level of awareness posits their needs and readiness to explore other means of learning which are not currently offered to them such as digital game-based learning. Contributions: The study informs ESL practitioners on the importance of considering the needs of the targeted learners and teachers involved so that contextualized, practical, and effective instruction could be designed, developed, and successfully delivered. Keywords: Design-based research, indigenous learners, instructional design, mixed-method tools, needs analysis. Cite as: Wan Mahzan, M. S., Alias, N. A., & Ismail, I. S. (2020). Investigating the needs of developing a digital vocabulary learning material for Malaysian indigenous learners in ESL classroom. Journal of Nusantara Studies 2020, 5(2), 282-302. http://dx.doi.org/10.24200/jonus.vol5iss2pp282-302
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37

Davis, Alexandra N., Meredith McGinley, Gustavo Carlo, Seth J. Schwartz, Jennifer B. Unger, Sabrina E. Des Rosiers, Lourdes Baezconde-Garbanati, Elma I. Lorenzo-Blanco, and Daniel Soto. "Examining discrimination and familism values as longitudinal predictors of prosocial behaviors among recent immigrant adolescents." International Journal of Behavioral Development 45, no. 4 (April 26, 2021): 317–26. http://dx.doi.org/10.1177/01650254211005561.

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The current study was designed to address gaps in the existing literature by examining the role of discrimination and familism values as predictors of multiple forms of prosocial behaviors across time in a sample of recent immigrant Latino/a adolescents. Participants were 302 recent immigrant Latino/a adolescents (53.3% male; average age 14.51 years, range = 13–17). Data were collected from adolescents in two U.S. cities: Los Angeles ( n = 150) and Miami ( n = 152). Adolescents completed measures of their own discrimination experiences, familism values, and tendency to engage in six forms of prosocial behaviors. Results indicated generally positive links between familism values and prosocial behaviors. Discrimination also positively predicted public prosocial behaviors and negatively predicted altruistic prosocial behaviors. We discuss the development of cultural processes and perceptions of discrimination experiences, and how these factors predict helping behaviors among immigrant adolescents.
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38

Harasawa, Ryô, and Yasuo Kanamoto. "Differentiation of Two Biovars of Ureaplasma urealyticum Based on the 16S-23S rRNA Intergenic Spacer Region." Journal of Clinical Microbiology 37, no. 12 (1999): 4135–38. http://dx.doi.org/10.1128/jcm.37.12.4135-4138.1999.

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The 16S-23S rRNA intergenic spacer regions of 14 strains representing the 14 serovars of Ureaplasma urealyticum were amplified by PCR and sequenced for genetic differentiation between the two biovars Parvo and T960. Although the spacer region of the Parvo and T960 biovars comprised 302 nucleotides and lacked spacer tRNA genes, 15 nucleotides were different between the two biovars. The four nucleotide sequences of the 16S-23S rRNA intergenic spacer region of serovars 1, 3, 6, and 14 in the Parvo biovar were found to be identical. Similarly, the 10 nucleotide sequences of the 16S-23S rRNA intergenic spacer region of serovars 2, 4, 5, and 7 to 13 in the T960 biovar were found to be identical. The nucleotide sequence of the T960 biovar contains multiple restriction sites for restriction endonucleaseSspI, which allows differentiation of the T960 biovar from the Parvo biovar.
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39

RIBEIRO, SÍRIA, WILIAN VAZ-SILVA, and ALFREDO P. SANTOS-JR. "New pored Leposternon (Squamata, Amphisbaenia) from Brazilian Cerrado." Zootaxa 1930, no. 1 (November 12, 2008): 18–38. http://dx.doi.org/10.11646/zootaxa.1930.1.2.

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A new species of Leposternon is described from the Brazilian Cerrado, southwestern Goiás state. The new species is diagnosed mainly by the following characters: two–four precloacal pores, 299–341 dorsal postpectoral half-annuli, 302– 349 ventral postpectoral half-annuli, 13–15 tail annuli, 118–121 precloacal vertebrae, two supralabials, two infralabials, five series of large plates in dorsal head shields, diamond-shaped pectoral scales, head length 2.6–3.2% snout-vent length, rostronasal length 20.4–23.1% head length, azygous width 30.8–41.9% head width, azygous length 40.1–51.4% head length, frontal length 23.7–38.2% head length, and prefrontal length 37.2–44.4% head length. The new species here described is the only known Leposternon restricted to the Cerrado region. Additionally, we present an updated check list of non-fossil amphisbaenians according to ecoregions in the Brazilian territory.
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40

KSHANOVSKA, Yuliia. "THE POPULATION OF DNIPROPETROVSK 1959–1989: PROCESSES OF LINGUISTIC AND CULTURAL ASSIMILATION." Ukraine-Poland: Historical Heritage and Public Consciousness 13 (2020): 302–13. http://dx.doi.org/10.33402/up.2020-13-302-313.

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41

Eleonsky, V. M., V. G. Korolev, and N. E. Kulagin. "Small-amplitude 2D patterns with nontrivial symmetry in a simple nonlinear field model." Journal of Physics A: Mathematical and General 33, no. 13 (March 23, 2000): 2469–87. http://dx.doi.org/10.1088/0305-4470/33/13/302.

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42

Kopper, Ch, and W. Pedra. "Irrelevant interactions without composite operators: a remark on the universality of second-order phase transitions." Journal of Physics A: Mathematical and General 34, no. 13 (March 26, 2001): 2681–93. http://dx.doi.org/10.1088/0305-4470/34/13/302.

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43

Bertin, E., and J.-P. Bouchaud. "Dynamical ultrametricity in the critical trap model." Journal of Physics A: Mathematical and General 35, no. 13 (March 22, 2002): 3039–51. http://dx.doi.org/10.1088/0305-4470/35/13/302.

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44

Axelsson, Per. "Nonlinear wave interactions for ideal MHD plasmas." Nonlinearity 13, no. 1 (November 8, 1999): 19–28. http://dx.doi.org/10.1088/0951-7715/13/1/302.

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45

Rivas, A. M. F., M. Saraceno, and A. M. Ozorio de Almeida. "Quantization of multidimensional cat maps." Nonlinearity 13, no. 2 (January 18, 2000): 341–76. http://dx.doi.org/10.1088/0951-7715/13/2/302.

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46

Fabry, C., and J. Mawhin. "Oscillations of a forced asymmetric oscillator at resonance." Nonlinearity 13, no. 3 (February 16, 2000): 493–505. http://dx.doi.org/10.1088/0951-7715/13/3/302.

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47

Sumi, Hiroki. "Skew product maps related to finitely generated rational semigroups." Nonlinearity 13, no. 4 (May 8, 2000): 995–1019. http://dx.doi.org/10.1088/0951-7715/13/4/302.

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48

Witte, N. S., P. J. Forrester, and Christopher M. Cosgrove. "Gap probabilities for edge intervals in finite Gaussian and Jacobi unitary matrix ensembles." Nonlinearity 13, no. 5 (June 20, 2000): 1439–64. http://dx.doi.org/10.1088/0951-7715/13/5/302.

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49

Killeen, Peter R., and Thomas J. Taylor. "A stochastic adding machine and complex dynamics." Nonlinearity 13, no. 6 (August 22, 2000): 1889–903. http://dx.doi.org/10.1088/0951-7715/13/6/302.

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50

Cui, X. D., X. Zarate, J. Tomfohr, O. F. Sankey, A. Primak, A. L. Moore, T. A. Moore, D. Gust, G. Harris, and S. M. Lindsay. "Making electrical contacts to molecular monolayers." Nanotechnology 13, no. 1 (October 9, 2001): 5–14. http://dx.doi.org/10.1088/0957-4484/13/1/302.

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