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Keane, M. G., and G. J. More O'Ferrall. "Comparison of Friesian, Canadian Hereford × Friesian and Simmental × Friesian steers for growth and carcass composition." Animal Science 55, no. 3 (December 1992): 377–87. http://dx.doi.org/10.1017/s0003356100021061.
Анотація:
AbstractOne hundred and twenty spring-born steers comprised of 40 Friesians (FR), 40 Canadian Hereford × Friesians (HF) and 40 Simmental × Friesians (SM) were reared together from shortly after birth to slaughter after a mean period of 740 days. During the finishing winter there was a 3 (breed types) × 2 (3 and 6 kg supplementary concentrates per head daily with grass silage ad libitum) × 2 (222- and 225-day finishing periods) factorial arrangement of treatments. One side from each of 96 carcasses (eight per treatment) was completely separated into bone, muscle, intermuscular fat and subcutaneous fat and a 10th rib sample of m. longissimus was chemically analysed.Carcass weights per day of age and carcass weights were 404, 433 and 449 (s.e. 4·6) g and 301, 320 and 330 (s.e. 3·4) kg for FR, HF and SM, respectively. Corresponding proportions of carcass muscle were 602, 577 and 628 (s.e. 4·8) g/kg. FR and HF had similar proportions of their total muscle in the hindquarter, whereas SM had more of their muscle in the hindquarter. M. longissimus lipid concentrations for FR, HF and SM were 36, 39 and 26 (s.e. 1·96) g/kg. Increasing supplementary concentrate level from 3 to 6 kg/day increased side weight by 7 kg, of which proportionately 0·48 was fat. Extending the finishing period from 121 to 225 days increased side weight by 22 kg of which proportionately 0·45 was fat. Both the higher concentrate level and the longer finishing period reduced carcass muscle and bone proportions, and increased carcass fat proportion. Allometric regression coefficients for side muscle, bone and fat weights on side weight were 0·75, 0·51 and 2·13, respectively. It was calculated that FR, HF and SM would have similar carcass fat proportions at approximate carcass weights of 320, 290 and 380 kg, respectively.
2
Didi, Abdessamad, Ahmed Dadouch, Otman Jai, and Fatima Zahra Bouhali. "Toward for production of Molybdenum-99 by irradiation of MoO3 target in a neutron flux." Bangladesh Journal of Medical Science 17, no. 4 (September 19, 2018): 567–72. http://dx.doi.org/10.3329/bjms.v17i4.38317.
Анотація:
Background: Molybdenum- 99 is a parent isotope of Technetium-99m (99mTc) as intermediate to diagnosis and radiation treatment. This production is made according to irradiation of Molybdenum-98 with thermal neutrons. The cycle comprises a complex of MoO3 or the percentage of Mo-98 is 24.13%, this compressed mixture in an irradiation capsule of aluminum; the latter is disposed in the central thimble of a nuclear reactor so that the thermal neutron flux is at a maximum in order to generate 98Mo to 99Mo by nuclear reaction of (n, γ) where the crosssection of molybdenum is (0.13 ± 0.0013) barn.Method: The purpose of this study is to validate of MoO3 target that will be used for the production of Molybdenum-99 in the central thimble irradiation position of the TRIGA Mark II research reactor at CNESTEN (Morocco National Center for Nuclear Energy, Sciences and Techniques), The thermal neutron flux used for activity calculation of Mo-99 used reactor of research TRIGA Mark-II is 3.1 1011 n/cm²s at 250 KW, 2.4E+13 n/cm2s at 1.1 MW and 3.01 1013n/cm²s at 2MW, we are using Fortran-90 code for calculate the activity.Result: The result’s finding was validated by other studies.Bangladesh Journal of Medical Science Vol.17(4) 2018 p.567-572
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Joyce, Brian T., Huikun Liu, Leishen Wang, Jun Wang, Yinan Zheng, Drew Nannini, Alex Drong, et al. "Novel epigenetic link between gestational diabetes mellitus and macrosomia." Epigenomics 13, no. 15 (August 2021): 1221–30. http://dx.doi.org/10.2217/epi-2021-0096.
Анотація:
Background & objectives: Examine maternal gestational diabetes mellitus (GDM), macrosomia and DNA methylation in candidate genes IGF1, IGF2, H19, ARHGRF11, MEST, NR3C1, ADIPOQ and RETN. Materials & methods: A total of 1145 children (572 GDM cases and 573 controls) from the Tianjin GDM study, including 177 with macrosomia, had blood DNA collection at median age 5.9 (range: 3.1–10.0). We used logistic regression to screen for associations with GDM and model macrosomia on 37 CpGs, and performed mediation analysis. Results: One CpG was associated with macrosomia at false discovery rate (FDR) <0.05 (cg14428359 in MEST); two (cg19466922 in MEST and cg26263166 in IGF2) were associated at p < 0.05 but mediated 26 and 13%, respectively. Conclusion: MEST and IGF2 were previously identified for potential involvement in fetal growth and development ( Trial Registration number: NCT01554358 [ClinicalTrials.gov] ).
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Biagini, Eugenio F. "Religious thought in the Victorian age. Challenges and reconceptions. By James C. Livingston. Pp. viii+304. New York–London: T&T Clark, 2007. £50. 13 978 0 567 02513 5; 10 0 567 02513 6; 13 978 0 567 02646 0; 10 0 567 02646 9." Journal of Ecclesiastical History 59, no. 4 (October 2008): 797–98. http://dx.doi.org/10.1017/s0022046908005514.
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Tamai, S., J. Kamada, K. Goto, and A. Yamaguchi. "Preparation and Properties of Novel Aromatic Polyimides from 5,7-Diamino-1,1,4,6-Tetramethylindan and Aromatic Tetracarboxylic Dianhydrides." High Performance Polymers 13, no. 3 (September 2001): 173–82. http://dx.doi.org/10.1088/0954-0083/13/3/309.
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Peronnet, F., E. Adopo, D. Massicotte, G. R. Brisson, and C. Hillaire-Marcel. "Method for computing the oxidation of two 13C-substrates ingested simultaneously during exercise." Journal of Applied Physiology 75, no. 3 (September 1, 1993): 1419–22. http://dx.doi.org/10.1152/jappl.1993.75.3.1419.
Анотація:
This study presents a method for computing the respective amounts of two simultaneously ingested exogenous substrates (A and B) that are oxidized during a period of prolonged exercise by use of 13C labeling. This method is based on the observation that the total volume of 13CO2 produced (V13CO2tot) is the sum of 1) V13CO2 arising from the oxidation of endogenous substrates (V13CO2endo), 2) V13CO2 arising from the oxidation of substrate A (V13CO2A), and 3) V13CO2 arising from the oxidation of substrate B (V13CO2B). The equation, V13CO2tot = V13CO2endo+V13CO2A+V13CO2B, with three unknowns, can be solved from the results of three experiments conducted under the same conditions but with at least two values for the isotopic composition of A and B. This method has been used on five healthy male subjects to compute the amounts of glucose and fructose oxidized when a mixture of 15 g of glucose and 15 g of fructose is ingested (in 300 ml of water) over 60 min of cycle ergometer exercise at 65% of maximal O2 uptake. Results from three experiments indicated that 9.8 +/- 3.1 and 5.7 +/- 2.1 g of glucose and fructose, respectively, were oxidized. The total amount of exogenous carbohydrates oxidized (15.5 +/- 4.3 g) is in agreement with the oxidation rates of exogenous glucose computed in similar conditions when 30 g of glucose were ingested (13 g; Peronnet et al. Med. Sci. Sports Exercise 25: 297–302, 1993). The difference between the oxidation rates of exogenous glucose and fructose is also in line with data from the literature.
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Wamafma, Sonya, and Pratita Puradjatmika. "Inventarisasi Mezofauna di Daerah Reklamasi PT. Freeport Indonesia, Timika–Papua." JURNAL BIOLOGI PAPUA 1, no. 2 (October 20, 2018): 43–50. http://dx.doi.org/10.31957/jbp.571.
Анотація:
This study was conducted to identify the mesofauna inhabiting the reclamation area (Grasberg) and the natural succession (Ertsberg), to observe the development of mesofauna and to know the species compotition in the given area. Research method was pitfall trap that set up in reclamation area, natural succession and in control area. The result revealed that mesofauna in reclamation area were dominated by the family Isotomidae and Neelidae (Ordo Collembola) with the relative dominancy value 23,90% and 24,37% respectively, the presence or relative frequency 9,23% and 9,23%, and relative density value 23,90% dan 24,37% individuals/m³. Mesofauna in succession area Ertsberg were dominated by the family Neelidae (Ordo Collembola) with the relative dominancy value 31,85%, the presence or relative frequency 5,41% and relative dencity value 31,85% individual/m³. The dominant mesofauna in control area was famili Neelidae (Ordo Collembola) with the relative dominancy value 22,5%, the presence or relative frequency 4,17%, and the relative density value was 22,5% individual/m³. Phylum Arthropoda dominated the whole study area with the total individual 2089, whereas Phylum Annelida consisted of 33 individuals. The highest species composition was found in Menado Leach Pad (509 individuals) followed by Jayapura Crusher (322 individuals) and Ertsberg Lower (301 individuals). Species composition of mesofauna in the study area was generally grouped into two phyilum; Arthropoda and Annelida which consisted of 4 classes, 13 ordo, 38 families and 2122 individuals. Environmental recovery undertaken by the Freeport Company through reclamation and natural succession was successfully done as indicated by the occurrence of various vegetation and mesofauna that interact each other.Key words: Mesofauna, reclamation area Grasberg, natural succession Erstberg, Freeport Company, Timika.
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Hartmann, Katrin, and Jutta Hein. "Labordiagnostische Referenzbereiche bei Kaninchen." Tierärztliche Praxis Ausgabe K: Kleintiere / Heimtiere 31, no. 05 (2003): 321–28. http://dx.doi.org/10.1055/s-0037-1622371.
Анотація:
ZusammenfassungZiel der Arbeit war, Referenzwerte für Blutparameter bei Kaninchen verschiedener Rassen mit einer für die Praxis geeigneten Blutentnahmemethode zu erstellen. Zur Sammlung der Daten wurde Blut von 155 klinisch gesunden Kaninchen im Alter von sechs Wochen bis neuneinhalb Jahren aus der V. saphena lateralis entnommen. Für die folgenden Parameter wurden Referenzbereiche bestimmt: Hämatokrit (Hkt; 0,36-0,55 l/l), Hämoglobinkonzentration (Hb; 7,03-10,63 mmol/l), Erythrozytenzahl (5,36-8,13 ×1012/l), Erythrozytenindices (MCHC: 18,4-20,1 mmol/l, MCH: 1,14-1,37 fmol/l, MCV 59,3-69,6 fl), Leukozytenzahl (3,02-11,91 × 109/l), Differenzialblutbild (Monozyten: 0-756 × 106/l [0-12%], Lymphozyten: 1576-7870 × 106/l [32-81%], stabkernige neutrophile Granulozyten: 0 × 106/l (0%), segmentkernige neutrophile Granulozyten: 820-5031 × 106/l [15-61%], eosinophile Granulozyten: 0-82 × 106/l [0-1%], basophile Granulozyten: 0-518 × 106/l [0-7%], Thrombozytenzahl (193-725 × 109/l), die Enzymaktivitäten von Alaninaminotransferase (ALT; 0-61 IU/l), alkalische Phosphatase (AP; 0-397 IU/l), Aspartataminotransferase (AST; 0-28 IU/l), Glutamatdehydrogenase (0-19 IU/l), γ-Glutamyltransferase (γ-GT; 0-13 IU/l), Laktatdehydrogenase (LDH; 0-571 IU/l), Kreatinkinase (CK; 0-958 IU/l), α-Amylase (0-459 IU/l), Lipase (0-1587 IU/l) und Cholinesterase (0-3.564 IU/l), die Konzentrationen der Substrate Glukose (5,83-14,83 mmol/l), Fruktosamin (314-527 µmol/l), Gesamteiweiß (48,9-73,9 g/l) mit Auftrennung durch Elektrophorese (Albumin: 35,6-56,8 g/l [66,7-86,1%], α1-Globulin: 0,1-3,6 g/l [0,1-5,7%], α2-Globulin: 1,7-4,5 g/l [2,9-7,0%], α1-Globulin: 4,1-10,7 g/l [6,9-16,8%], γ-Globulin: 0,5-8,7 g/l [0,9-12,1%]), Cholesterin (0,31 bis 2,66 mmol/l), Triglyzeride (0,45-3,35 mmol/l), Serumgallensäuren (0,0-77,6 µmol/l), Bilirubin (0,29-2,53 µmol/l), Harnstoff (2,05-8,42 mmol/l) und Kreatinin (34-166 µmol/l) sowie der Elektrolyte Kalzium (3,1-3,9 mmol/l), Phosphat (0,81 bis 3,15 mmol/l), Magnesium (0,90-1,66 mmol/l), Natrium (139 bis 149 mmol/l), Kalium (3,7-6,3 mmol/l), Chlorid (93-109 mmol/l) und Eisen (20-59 µmol/l). Alters-(≤ 4 Monate und > 4 Monate) und Geschlechtsabhängigkeiten (männlich/weiblich) wurden ermittelt.
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Stubbs, Robert H. "Penis Lengthening – A Retrospective Review of 300 Consecutive Cases." Canadian Journal of Plastic Surgery 5, no. 2 (May 1997): 93–100. http://dx.doi.org/10.1177/229255039700500205.
Анотація:
Between November 1993 and July 1995, 300 patients underwent penis lengthening surgery. Twelve of these patients had previous genital surgery and/or congenital anomalies, and their procedures could be considered reconstructive. The remaining surgical procedureswere cosmetic. Average patient age was 37 years (range 18 to 74 years). The average preoperative erect length was 12.5 cm (range 7.5 to 16 cm, SD 1.5). ‘Locker room phobia’, adverse female comments and body disproportion were common reasons for patients desiring surgery. All racial groups were represented, with European ancestry the most common. Surgery involved releasing all the superficial (fundiform) ligament and most of the deep suspensory ligament. The defect was filled with plicated gracilis muscle along with shifted skin and subcutaneous tissues. Postoperative traction was used to reduce the chance of scar and penis retraction. The most common major complication was wound infection (5.7%). The most frequent minor problem was dermatitis (13%). Long term (mean10months, range sixto18months) objective measurements using the stretch technique were obtained for 42 patients. One patient lost 1 cm in length, while 41 gained length (mean 3.2 cm, range 0.5 to 6 cm). Poor patient compliance with the postoperative protocol appears to be the most significant factor limiting the success of the procedure.
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Curti, Brendan D., Jon M. Richards, Sigrun Hallmeyer, Mark B. Faries, Robert Hans Ingemar Andtbacka, Gregory A. Daniels, Mark Grose, and Darren Shafren. "Activity of a novel immunotherapy combination of intralesional Coxsackievirus A21 and systemic ipilimumab in advanced melanoma patients previously treated with anti-PD1 blockade therapy." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 3014. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.3014.
Анотація:
3014 Background: CAVATAK is a novel bio-selected oncolytic and immunotherapeutic strain of Coxsackievirus A21 (CVA21) that when injected into melanoma lesions can increase immune-cell infiltration, up-regulation of γ-INF response and immune-checkpoint genes, including CD122, which may be a potential marker for enhanced anti-tumor activity by anti-CTLA-4 blockade. Intratumoral replication of CVA21 may act as a strong “immune-sequestration signal” to circulating activated T-cells following CTLA-4 blockade. A large unmet need exists for active therapies in melanoma patients (pts) following treatment (tx) with anti-PD1 therapies. We present in a Phase 1 study, the clinical activity of a CVA21/ ipilimumab (ipi) combination following anti–PD1 therapy in advanced melanoma pts. Methods: The Phase Ib MITCI study (NCT02307149) investigated the efficacy and safety of i.t. CVA21 and i.v. ipi in 26 pts with unresectable Stage IIIB/C-IVM1c melanoma with 13 pts previously treated with anti-PD1 therapies. Pts received up to 3 x 108 TCID50CVA21 i.t. on study days 1, 3, 5, 8 and 22, and then q3w for a further 6 series of injections. Ipi (3 mg/kg) q3w was given as 4 i.v. infusions starting at Day 22. Results: Analysis of the prior anti–PD1 treated pts (n=13) revealed that the combination tx was generally well-tolerated with one case of Gr 3 ipi-related liver toxicity observed. Of the tx population, 54% (7/13) had received prior ipi tx in addition to anti-PD1, 85% (11/13) of pts were stage IV M1b/c, with the median time between the last anti-PD1 and first CVA21 and ipi doses being 5.7 and 8.7 weeks, respectively. The mean number of prior systemic therapies including anti-PD1 tx was 2.6. For all pts completing at least the first investigator response assessment (irWHO criteria at Day 106) we observed a confirmed BORR of 38.0% (3/8) and a DCR (CR+PR+SD) of 88% (7/8). Conclusions: Intratumoral CVA21 + ipilimumab treatment in anti–PD1 treated pts has displayed promising clinical activity together with low adverse toxicity and as such this regimen may represent a valuable tx option for pts that have been administered previous lines of immune checkpoint therapy. Clinical trial information: NCT02307149.
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Wu, Jianhua, Alistair S. Hall, and Chris P. Gale. "Long-term survival benefit of ramipril in patients with acute myocardial infarction complicated by heart failure." Heart 107, no. 5 (January 15, 2021): 389–95. http://dx.doi.org/10.1136/heartjnl-2020-316823.
Анотація:
AimsACE inhibition reduces mortality and morbidity in patients with heart failure after acute myocardial infarction (AMI). However, there are limited randomised data about the long-term survival benefits of ACE inhibition in this population.MethodsIn 1993, the Acute Infarction Ramipril Efficacy (AIRE) study randomly allocated patients with AMI and clinical heart failure to ramipril or placebo. The duration of masked trial therapy in the UK cohort (603 patients, mean age=64.7 years, 455 male patients) was 12.4 and 13.4 months for ramipril (n=302) and placebo (n=301), respectively. We estimated life expectancy and extensions of life (difference in median survival times) according to duration of follow-up (range 0–29.6 years).ResultsBy 9 April 2019, death from all causes occurred in 266 (88.4%) patients in placebo arm and 275 (91.1%) patients in ramipril arm. The extension of life between ramipril and placebo groups was 14.5 months (95% CI 13.2 to 15.8). Ramipril increased life expectancy more for patients with than without diabetes (life expectancy difference 32.1 vs 5.0 months), previous AMI (20.1 vs 4.9 months), previous heart failure (19.5 vs 4.9 months), hypertension (16.6 vs 8.3 months), angina (16.2 vs 5.0 months) and age >65 years (11.3 vs 5.7 months). Given potential treatment switching, the true absolute treatment effect could be underestimated by 28%.ConclusionFor patients with clinically defined heart failure following AMI, ramipril results in a sustained survival benefit, and is associated with an extension of life of up to 14.5 months for, on average, 13 months treatment duration.
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O'Grady, Michael J., Conor Hensey, Miriam Fallon, Hilary Hoey, Nuala Murphy, Colm Costigan, and Declan Cody. "Requirement for age-specific peak cortisol responses to insulin-induced hypoglycaemia in children." European Journal of Endocrinology 169, no. 2 (August 2013): 139–45. http://dx.doi.org/10.1530/eje-13-0084.
Анотація:
ObjectiveBased on adult data, a peak cortisol response ≥500 nmol/l to insulin-induced hypoglycaemia constitutes a normal. Age-specific reference ranges for basal morning cortisol have been developed for clinical use in the paediatric population. Such reference ranges are not clearly established for peak cortisol responses to insulin-induced hypoglycaemia despite limited data suggesting an effect of age on peak cortisol. The aims of this study were to assess factors affecting the cortisol response to insulin-induced hypoglycaemia in children and to determine whether the peak cortisol response was related to age.DesignThe present study was a retrospective cohort study.MethodsRetrospective analysis of children and adolescents aged ≤18 years undergoing the insulin tolerance test with adequate hypoglycaemia was undertaken. Patients with hypopituitarism or severe hypothalamic–pituitary–adrenal axis impairment (peak cortisol value <400 nmol/l) or using systemic glucocorticoids were excluded.ResultsTwo hundred and twenty-three tests were analysed. Peak cortisol responses ≥500 nmol/l occurred in 183 (82%) tests. Age was negatively associated with peak cortisol responses (r=−0.15, P=0.03). A peak cortisol response <500 nmol/l was significantly less common in patients aged <12 years (9/97 (9%) vs 31/126 (25%); P=0.004). In children aged <12 years, the median (5th–95th centiles) peak cortisol values were 610 (480–806) nmol/l compared with 574 (442–789) nmol/l in children aged ≥12 years (P<0.004). Similarly, median cortisol increment was significantly higher in younger patients (301 nmol/l compared with 226 nmol/l (P=0.0004)).ConclusionsUse of a single peak cortisol threshold in children of all ages is not appropriate and will result in overdiagnosis of adrenal insufficiency in adolescents.
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Cuestas, Eduardo, María Isabel Gaido, and Raúl Horacio Capra. "Transient neonatal hyperthyrotropinemia is a risk factor for developing persistent hyperthyrotropinemia in childhood with repercussion on developmental status." European Journal of Endocrinology 172, no. 4 (April 2015): 483–90. http://dx.doi.org/10.1530/eje-13-0907.
Анотація:
ObjectiveTransient neonatal hyperthyrotropinemia (TNH) is defined as a neonatal abnormality of thyroid function, which reverts to normal at re-examination after 2 weeks of life. The thyroid function of these infants has not been sufficiently studied in terms of the risk of developing persistent hyperthyrotropinemia (PH) in later childhood and its impact on growth and development.DesignA prospective cohort study included all babies born in our hospital between 2001 and 2006 and screened for hypothyroidism, whose thyroid function was re-examined 6 years later. Exclusion criteria included the following conditions: preterm birth, birth weight <2500 g, Down's syndrome, descendants of mothers with immune thyroid disease, congenital malformations, cardiac, renal, hepatic, and metabolic diseases, and steroid or dopamine medication. The variables included are TSH and thyroxine at neonatal screening and 6 years later. Main outcomes are the risk of developing PH in childhood, linear growth, and development using Parents' Evaluation of Developmental Status (PEDS).ResultsOut of 5040 normal-term newborns, 301 (6.0%, 95% CI 5.3–6.6%) have TSH ≥10 mU/l (TNH). Six years later, we re-examined 65 randomly selected children with TNH and 185 controls. In the TNH cohort, we found six out of 65 children (9.2%, 95% CI 1.4–17.0%) with PH (TSH ≥6.4 mU/l), and three out of 185 (1.6%, 95% CI 0.3–4.7%) among controls, relative risk 5.7 (95% CI 1.5–22.1), P=0.0114. TSH and developmental delay were found to be significantly higher in the TNH cohort (4.7±1.3 mU/l vs 2.1±0.5 mU/l, P<0.0001 and 15/65 (23%, 95% CI 12–34.1) vs 21/185 (11.3%, 95% CI 6.5–16.2) P=0.0348).ConclusionsNewborns with TNH have a higher risk of developing PH in childhood, with repercussion on developmental status.
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Masoodi, Tariq, Sarah Siraj, Abdul K. Siraj, Saud Azam, Zeeshan Qadri, Sandeep K. Parvathareddy, and Khawla S. Al-Kuraya. "Abstract 5776: Predictors of radioactive iodine refractoriness in papillary thyroid carcinomas." Cancer Research 82, no. 12_Supplement (June 15, 2022): 5776. http://dx.doi.org/10.1158/1538-7445.am2022-5776.
Анотація:
Abstract Optimized surgery and radioactive iodine (131I, RAI) are the cornerstone of treatment for papillary thyroid carcinoma (PTC). Although standard treatment is curative for most, 5-20% of PTC patients develop RAI refractory disease – the main cause of thyroid cancer-related deaths. Early predictors indicating therapeutic response to RAI therapy in PTC are yet to be elucidated. We performed whole-exome sequencing (at a median depth of 198x) on 158 patient-matched primary PTCs and germline DNA. Clinical data was used to categorize RAI avidity in the PTC cohort. Whereby, 66 RAI refractory and 92 RAI avid tumors were identified. Clinical data and somatic variants were analyzed to compare the clinicopathological presentation, genomic landscape and mutational signatures between RAI refractory and avid PTCs. RAI refractory tumors were significantly associated with distinct aggressive clinicopathological features, including positive surgical margins (65.5% versus 26.7%; p=0.016) and the presence of lymph node metastases at primary diagnosis (62.5% versus 30.1%; p=0.012); higher nonsilent tumor mutation burden (p=0.011); and the enrichment of APOBEC-related single base substitution (SBS) COSMIC mutational signatures 2 (p=0.03) and 13 (p<0.001). APOBEC mutational signatures were not associated with BRAFV600E mutation. Notably, using multivariate logistic regression analysis only the SBS13 (odds ratio 13.01, 95% confidence intervals 1.20-140.94) APOBEC mutational signature was revealed to be an independent predictor of RAI refractoriness in PTC (p=0.035). Furthermore, using Cox proportional hazards SBS13-positive tumors (hazard ratio 3.52, 95% confidence intervals 1.79-6.91) were also significantly associated with poorer progression-free survival (p<0.001), albeit only in univariate analysis. This study highlights distinct clinical and genomic features in RAI refractory PTC, but above all proposes the APOBEC SBS13 mutational signature as an independent predictor of RAI refractoriness in a more aggressive subgroup of PTC. Where detection of RAI refractory disease following standard surgical PTC removal, and more suitable therapeutic interventions may potentially improve patient outcomes. Citation Format: Tariq Masoodi, Sarah Siraj, Abdul K. Siraj, Saud Azam, Zeeshan Qadri, Sandeep K. Parvathareddy, Khawla S. Al-Kuraya. Predictors of radioactive iodine refractoriness in papillary thyroid carcinomas [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5776.
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Emmerick, Isabel Cristina Martins, Mônica Rodrigues Campos, Debora Castanheira, Jessica Muzy, Aline Marques, Luisa Arueira Chaves, and Mario Jorge Sobreira da Silva. "Lung Cancer Screening in Brazil Comparing the 2013 and 2021 USPSTF Guidelines." JAMA Network Open 6, no. 12 (December 11, 2023): e2346994. http://dx.doi.org/10.1001/jamanetworkopen.2023.46994.
Анотація:
ImportanceIt is estimated that, from 2023 to 2025, lung cancer (LC) will be the second most frequent cancer in Brazil, but the country does not have an LC screening (LCS) policy.ObjectiveTo compare the number of individuals eligible for screening, 5-year preventable LC deaths, and years of life gained (YLG) if LC death is averted by LCS, considering 3 eligibility strategies by sociodemographic characteristics.Design, Setting, and ParticipantsThis comparative effectiveness research study assessed 3 LCS criteria by applying a modified version of the LC-Death Risk Assessment Tool (LCDRAT) and the LC-Risk Assessment Tool (LCRAT). Data are from the 2019 Brazilian National Household Survey. Participants included ever-smokers aged 50 to 80 years. Data analysis was performed from February to May 2023.ExposuresExposures included ever-smokers aged 50 to 80 years, US Preventive Services Task Force (USPSTF) 2013 guidelines (ever-smokers aged 55 to 80 years with ≥30 pack-years and &lt;15 years since cessation), and USPSTF 2021 guidelines (ever-smokers aged 50 to 80 years with 20 pack-years and &lt;15 years since cessation).Main Outcomes and MeasuresThe primary outcomes were the numbers of individuals eligible for LCS, the 5-year preventable deaths attributable to LC, and the number of YLGs if death due to LC was averted by LCS.ResultsIn Brazil, the eligible population for LCS was 27 280 920 ever-smokers aged 50 to 80 years (13 387 552 female [49.1%]; 13 249 531 [48.6%] aged 50-60 years; 394 994 Asian or Indigenous [1.4%]; 3 111 676 Black [11.4%]; 10 942 640 Pardo [40.1%]; 12 830 904 White [47.0%]; 12 428 536 [45.6%] with an incomplete middle school education; and 12 860 132 [47.1%] living in the Southeast region); 5 144 322 individuals met the USPSTF 2013 criteria for LCS (2 090 636 female [40.6%]; 2 290 219 [44.5%] aged 61-70 years; 66 430 Asian or Indigenous [1.3%]; 491 527 Black [9.6%]; 2 073 836 Pardo [40.3%]; 2 512 529 [48.8%] White; 2 436 221 [47.4%] with an incomplete middle school education; and 2 577 300 [50.1%] living in the Southeast region), and 8 380 279 individuals met the USPSTF 2021 LCS criteria (3 507 760 female [41.9%]; 4 352 740 [51.9%] aged 50-60 years; 119 925 Asian or Indigenous [1.4%]; 839 171 Black [10.0%]; 3 330 497 Pardo [39.7%]; 4 090 687 [48.8%] White; 4 022 784 [48.0%] with an incomplete middle school education; and 4 162 070 [49.7%] living in the Southeast region). The number needed to screen to prevent 1 death was 177 individuals according to the USPSTF 2013 criteria and 242 individuals according to the USPSTF 2021 criteria. The YLG was 23 for all ever-smokers, 19 for the USPSTF 2013 criteria, and 21 for the USPSTF 2021 criteria. Being Black, having less than a high school education, and living in the North and Northeast regions were associated with increased 5-year risk of LC death.Conclusions and RelevanceIn this comparative effectiveness study, USPSTF 2021 criteria were better than USPSTF 2013 in reducing disparities in LC death rates. Nonetheless, the risk of LC death remained unequal, and these results underscore the importance of identifying an appropriate approach for high-risk populations for LCS, considering the local epidemiological context.
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أ.م.د. صبيحة حسن طعيس. "(كَم) الاستفهامية و(كَم) الخبرية عند (مُهذَّب الدين المهلَّبي) المتوفى سنة (572هـ)". Journal of the College of Basic Education 21, № 90 (11 грудня 2022): 217–35. http://dx.doi.org/10.35950/cbej.v21i90.6812.
Анотація:
هو " مهذَّب الدين أبو المحاسن مهلَّب بن الحسين بن بركات بن علي بن مهلَّب المصري ، الشهير بالمهلبي "([i]) البهنسي([ii]) اللغوي النحوي الأديب . والبهنسي نسبة إلى مدينة " البَهْنَسا بالفتح ثمَّ السكون وسين مهملة مقصورة ، مدينة بمصر من الصعيد الأدنى غربي النيل ... ينسب إليها جماعة من أهل العلم "([iii])، ويُكنَّى المهلبي بأبي المحاسن([iv])، ولُقِّبَ بمهذَّب الدين والمهلب البهنسي([v]). ([i]) هدية العارفين : 2/485 . ([ii]) يُنظر : معجم المؤلفين : 13/32 . ([iii]) مُعجم البلدان : 1/516 – 517 ، ويُنظر : اللباب في تهذيب الأنساب : 1/192 . ([iv]) يُنظر : هدية العارفين : 2/485 ، وأنباه الرواة : 4/290 ، وبغية الوعاة : 2/204 . ([v]) يُنظر : هدية العارفين : 2/485 ، وبغية الوعاة : 2/304 .
17
Phelan, John. "Positive Linking: How Networks Can Revolutionise the World by Paul Ormerod. London: Faber and Faber (2012), 308 pp. ISBN-13: 978 0 571 27920 3 (pb); £12.99." Economic Affairs 33, no. 3 (October 2013): 400–401. http://dx.doi.org/10.1111/ecaf.12030.
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Nath, Samir K., Ravi Kambadur, C. H. Chris Yun, Mark Donowitz, and Chung-Ming Tse. "NHE2 contains subdomains in the COOH terminus for growth factor and protein kinase regulation." American Journal of Physiology-Cell Physiology 276, no. 4 (April 1, 1999): C873—C882. http://dx.doi.org/10.1152/ajpcell.1999.276.4.c873.
Анотація:
The cloned epithelial cell-specific Na+/H+exchanger (NHE) isoform NHE2 is stimulated by fibroblast growth factor (FGF), phorbol 12-myristate 13-acetate (PMA), okadaic acid (OA), and fetal bovine serum (FBS) through a change in maximal velocity of the transporter. In the present study, we used COOH-terminal truncation mutants to delineate specific domains in the COOH terminus of NHE2 that are responsible for growth factor and/or protein kinase regulation. Five truncation mutants (designated by the amino acid number at the truncation site) were stably expressed in NHE-deficient PS120 fibroblasts. The effects of PMA, FGF, OA, FBS, and W-13 [a Ca2+/calmodulin (CaM) inhibitor] were studied. Truncation mutant E2/660, but not E2/573, was stimulated by PMA. OA stimulated E2/573 but not E2/540. FGF stimulated E2/540 but not E2/499. The most truncated mutant, E2/499, was stimulated by FBS. W-13 stimulated the basal activity of the wild-type NHE2. However, W-13 had no effect on E2/755. By monitoring the emission spectra of dansylated CaM fluorescence, we showed that dansylated CaM bound directly to a purified fusion protein of glutathione S-transferase and the last 87 amino acids of NHE2 in a Ca2+-dependent manner, with a stoichiometry of 1:1 and a dissociation constant of 300 nM. Our results showed that the COOH terminus of NHE2 is organized into separate stimulatory and inhibitory growth factor/protein kinase regulatory subdomains. This organization of growth factor/protein kinase regulatory subdomains is very similar to that of NHE3, suggesting that the tertiary structures of the putative COOH termini of NHE2 and NHE3 are very similar despite the minimal amino acid identity in this part of the two proteins.
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Fabris, Sonia, Giovanna Cutrona, Massimo Gentile, Serena Matis, Emanuela Anna Pesce, Francesco Di Raimondo, Caterina Musolino, et al. "Incidence of Cytogenetic Abnormalities in Newly Diagnosed Binet Stage A B-CLL and Relationship with Prognostic Biomarkers: Preliminary Results On 305 Patients Included in the Prospective O-CLL1 GISL Study." Blood 114, no. 22 (November 20, 2009): 2341. http://dx.doi.org/10.1182/blood.v114.22.2341.2341.
Анотація:
Abstract Abstract 2341 Poster Board II-318 Background. The clinical heterogeneity of chronic lymphocytic leukemia (CLL) requires parameters to stratify patients into prognostic subgroups to adapt treatment ranging from ‘watch and wait’ to allogeneic stem cell transplantation. To this end, several parameters such as lymphocyte doubling time, β-2 microglobulin, CD38 and ZAP-70 expression, immunoglobulin variable heavy chain (IgVH) mutation status and genetic abnormalities, as assessed by fluorescence in situ hybridization (FISH), have been integrated in clinical practice. Aims. In the present study, we investigated by FISH the incidence of the known major cytogenetic alterations (+12 and 13q14, 17p13, 11q23 deletions) in a series of Binet A B-CLL patients included in the prospective O-CLL1 GISL study started in April 2007. Methods. Molecular markers characterization and FISH analyses were performed as previously reported (Cutrona et al. Haematologica, 2008; Fabris et al. GCC, 2008). A cut-off value of 2% was used to distinguish mutated and unmutated patients. CD38 and ZAP-70 were determined by flow-cytometry and a 30% cut-off was used to distinguish between positive or negative cases. Results. Up to date, 326 patients have been enrolled in the trial and FISH data concerning trisomy 12 and 13q14, 17p13, 11q23 deletions were available in 305 patients. At least one abnormality was found in 197 (64%) cases. The most frequent was del(13)(q14) (150/305, 49%), followed by +12 (40/303, 13%) (in one and three cases accompanied by 17p13 and 13q14 deletions, respectively), del(17)(p13) (7/305, 2%) and del(11)(q23) (17/305, 5%). 13q14 deletion was found as a sole abnormality in 134 patients; in the remaining cases, it was combined with +12 (3 pts) and 17p13 (3 pts) or 11q23 (10 pts) deletions. Among patients with 13q14 deletions, 99 were monoallelic, 12 biallelic and 39 showed a combination of the two patterns. Biomarkers data were available in all of the patients: 95/305 (31%) cases had unmutated IgVH genes; ZAP-70 and CD38 were positive in 117/305 (38%) and 72/305 (23%) cases, respectively. Concerning the distribution of cytogenetic aberrations, the unmutated IgVH group included 29/150 (19%) 13q14 deleted cases, 23/40 (57%) cases with trisomy 12 and 4/7 (57%) and 16/17 (94%) with 17p13 and 11q23 deletions, respectively. ZAP-70-positive groups included 43/150 (28%) 13q14 deleted cases, 26/40 (65%) cases showing trisomy 12 and 5/7 (71%) and 12/17 (70%) with 17p13 and 11q23 deletions, respectively. Finally, CD38-positive cases included 18/150 (12%) 13q14 deleted cases, 26/40 (65%) cases carrying trisomy 12 and 5/7 (71%) and 7/17 (41%) with 17p13 and 11q23 deletions, respectively. The percentages of IgVH mutations significantly correlated with cytogenetic alterations; namely, 5.8±0.3 for cases with del(13)(q14), 4.6±0.4 for normal karyotype, 2.6±0.5 in +12, 0.3±0.2 in del(11)(q23), and 1.7±0.9 in del(17)(p13) cases (p for trend <0.0001). A significant correlation was also found for ZAP-70 expression: namely 32±1.8 for cases with del(13)(q14), 38.6±2.2 for normal karyotype, 47.6±3.7 for +12, 55.8±7.0 for del(11)(q22) and 42.4±11.7 for del(17)(p13) (p<0.0001). Similarly, CD38 percentages were (mean value ± sem) 9.3±1.7, 16.9±2.1, 52.9±5.7, 26.8±6.2, 37.0±12.7 for del(13)(q14), normal karyotype, +12, del(11)(q23) and del(17)(p13) alterations, respectively (p for trend <0.0001). Finally, cytogenetic abnormalities were clustered in 3 risk groups [i.e. low del(13)(q14) and normal; intermediate (+12); and high risk del(11)(q23) and del(17)(p13)] and significantly correlated (p<0.0001) with a scoring system in which cases were stratified in 4 different groups according to the absence (group 0) or presence of 1 (group 1), 2 (group 2) or 3 (group 3) biomarkers (Morabito et al., BJH, 2009, voce). Interestingly, 147/154 cases scoring 0, gathered in the low FISH group, whereas 17/22 high FISH risk cases clustered in scoring 2-3. Conclusions. Our preliminary results indicate that in Binet stage A B-CLL patients at diagnosis cytogenetic abnormalities with an expected negative clinical impact are relatively few (7.2%) but significantly associated with prognostic biomarkers which negatively predict the clinical outcome in B-CLL. Disclosures: No relevant conflicts of interest to declare.
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Liu, Wen Jiun, and Lai Seong Hooi. "Complications after Tenckhoff Catheter Insertion: A Single-Centre Experience using Multiple Operators over Four Years." Peritoneal Dialysis International: Journal of the International Society for Peritoneal Dialysis 30, no. 5 (September 2010): 509–12. http://dx.doi.org/10.3747/pdi.2009.00083.
Анотація:
Objective To analyze the complications after Tenckhoff catheter insertion among patients with renal failure needing dialysis. Patients and Methods The open, paramedian approach is the commonest technique to insert the 62-cm coiled double-cuffed Tenckhoff peritoneal catheter. All patients with catheters inserted between January 2004 and November 2007 were retrospectively analyzed for demographics and followed for up to 1 month for complications. We excluded patients whose catheters had been anchored to the bladder wall and who underwent concurrent omentectomy or readjustment without removal of a malfunctioning catheter ( n = 7). Intravenous cloxacillin was the standard preoperative antibiotic prophylaxis. Results Over the 4-year study period, 384 catheters were inserted under local anesthetic into 319 patients [201 women (62.8%); mean age: 49.4 ± 16.7 years (range: 13 – 89 years); 167 (52.2%) with diabetes; 303 (95%) with end-stage renal disease] by 22 different operators. All Tenckhoff catheters were inserted by the general surgical ( n = 223) or urology ( n = 161) team. There were 29 cases (7.6%) of catheter migration, 22 (5.7%) of catheter obstruction without migration, 24 (6.3%) of exit-site infection, 12 (3.1%) of leak from the main incision, 14 (3.6%) of culture-proven wound infection, 11 (2.9%) post-insertion peritonitis, and 1 (0.3%) hemoperitoneum. No deaths were attributed to surgical mishap. Conclusions The most common complication was catheter migration. The paramedian insertion technique was safe, with low complication rates.
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Weydt, Leandra M., Ángel Andrés Ramírez-Guzmán, Antonio Pola, Baptiste Lepillier, Juliane Kummerow, Giuseppe Mandrone, Cesare Comina, et al. "Petrophysical and mechanical rock property database of the Los Humeros and Acoculco geothermal fields (Mexico)." Earth System Science Data 13, no. 2 (February 23, 2021): 571–98. http://dx.doi.org/10.5194/essd-13-571-2021.
Анотація:
Abstract. Petrophysical and mechanical rock properties are key parameters for the characterization of the deep subsurface in different disciplines such as geothermal heat extraction, petroleum reservoir engineering or mining. They are commonly used for the interpretation of geophysical data and the parameterization of numerical models and thus are the basis for economic reservoir assessment. However, detailed information regarding petrophysical and mechanical rock properties for each relevant target horizon is often scarce, inconsistent or distributed over multiple publications. Therefore, subsurface models are often populated with generalized or assumed values resulting in high uncertainties. Furthermore, diagenetic, metamorphic and hydrothermal processes significantly affect the physiochemical and mechanical properties often leading to high geological variability. A sound understanding of the controlling factors is needed to identify statistical and causal relationships between the properties as a basis for a profound reservoir assessment and modeling. Within the scope of the GEMex project (EU H2020, grant agreement no. 727550), which aims to develop new transferable exploration and exploitation approaches for enhanced and super-hot unconventional geothermal systems, a new workflow was applied to overcome the gap of knowledge of the reservoir properties. Two caldera complexes located in the northeastern Trans-Mexican Volcanic Belt – the Acoculco and Los Humeros caldera – were selected as demonstration sites. The workflow starts with outcrop analog and reservoir core sample studies in order to define and characterize the properties of all key units from the basement to the cap rock as well as their mineralogy and geochemistry. This allows the identification of geological heterogeneities on different scales (outcrop analysis, representative rock samples, thin sections and chemical analysis) enabling a profound reservoir property prediction. More than 300 rock samples were taken from representative outcrops inside the Los Humeros and Acoculco calderas and the surrounding areas and from exhumed “fossil systems” in Las Minas and Zacatlán. Additionally, 66 core samples from 16 wells of the Los Humeros geothermal field and 8 core samples from well EAC1 of the Acoculco geothermal field were collected. Samples were analyzed for particle and bulk density, porosity, permeability, thermal conductivity, thermal diffusivity, and heat capacity, as well as ultrasonic wave velocities, magnetic susceptibility and electric resistivity. Afterwards, destructive rock mechanical tests (point load tests, uniaxial and triaxial tests) were conducted to determine tensile strength, uniaxial compressive strength, Young's modulus, Poisson's ratio, the bulk modulus, the shear modulus, fracture toughness, cohesion and the friction angle. In addition, X-ray diffraction (XRD) and X-ray fluorescence (XRF) analyses were performed on 137 samples to provide information about the mineral assemblage, bulk geochemistry and the intensity of hydrothermal alteration. An extensive rock property database was created (Weydt et al., 2020; https://doi.org/10.25534/tudatalib-201.10), comprising 34 parameters determined on more than 2160 plugs. More than 31 000 data entries were compiled covering volcanic, sedimentary, metamorphic and igneous rocks from different ages (Jurassic to Holocene), thus facilitating a wide field of applications regarding resource assessment, modeling and statistical analyses.
22
Naik, V., A. Voulgarakis, A. M. Fiore, L. W. Horowitz, J. F. Lamarque, M. Lin, M. J. Prather, et al. "Preindustrial to present-day changes in tropospheric hydroxyl radical and methane lifetime from the Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP)." Atmospheric Chemistry and Physics 13, no. 10 (May 27, 2013): 5277–98. http://dx.doi.org/10.5194/acp-13-5277-2013.
Анотація:
Abstract. We have analysed time-slice simulations from 17 global models, participating in the Atmospheric Chemistry and Climate Model Intercomparison Project (ACCMIP), to explore changes in present-day (2000) hydroxyl radical (OH) concentration and methane (CH4) lifetime relative to preindustrial times (1850) and to 1980. A comparison of modeled and observation-derived methane and methyl chloroform lifetimes suggests that the present-day global multi-model mean OH concentration is overestimated by 5 to 10% but is within the range of uncertainties. The models consistently simulate higher OH concentrations in the Northern Hemisphere (NH) compared with the Southern Hemisphere (SH) for the present-day (2000; inter-hemispheric ratios of 1.13 to 1.42), in contrast to observation-based approaches which generally indicate higher OH in the SH although uncertainties are large. Evaluation of simulated carbon monoxide (CO) concentrations, the primary sink for OH, against ground-based and satellite observations suggests low biases in the NH that may contribute to the high north–south OH asymmetry in the models. The models vary widely in their regional distribution of present-day OH concentrations (up to 34%). Despite large regional changes, the multi-model global mean (mass-weighted) OH concentration changes little over the past 150 yr, due to concurrent increases in factors that enhance OH (humidity, tropospheric ozone, nitrogen oxide (NOx) emissions, and UV radiation due to decreases in stratospheric ozone), compensated by increases in OH sinks (methane abundance, carbon monoxide and non-methane volatile organic carbon (NMVOC) emissions). The large inter-model diversity in the sign and magnitude of preindustrial to present-day OH changes (ranging from a decrease of 12.7% to an increase of 14.6%) indicate that uncertainty remains in our understanding of the long-term trends in OH and methane lifetime. We show that this diversity is largely explained by the different ratio of the change in global mean tropospheric CO and NOx burdens (ΔCO/ΔNOx, approximately represents changes in OH sinks versus changes in OH sources) in the models, pointing to a need for better constraints on natural precursor emissions and on the chemical mechanisms in the current generation of chemistry-climate models. For the 1980 to 2000 period, we find that climate warming and a slight increase in mean OH (3.5 ± 2.2%) leads to a 4.3 ± 1.9% decrease in the methane lifetime. Analysing sensitivity simulations performed by 10 models, we find that preindustrial to present-day climate change decreased the methane lifetime by about four months, representing a negative feedback on the climate system. Further, we analysed attribution experiments performed by a subset of models relative to 2000 conditions with only one precursor at a time set to 1860 levels. We find that global mean OH increased by 46.4 ± 12.2% in response to preindustrial to present-day anthropogenic NOx emission increases, and decreased by 17.3 ± 2.3%, 7.6 ± 1.5%, and 3.1 ± 3.0% due to methane burden, and anthropogenic CO, and NMVOC emissions increases, respectively.
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Alsahlawi, Aysha K., Hassan Alkhateeb, Mrinal M. Patnaik, Kebede Begna, Michelle Elliott, William Hogan, Rhett P. Ketterling, Mark R. Litzow, and Aref Al-Kali. "Monosomal Karyotype Predicts Adverse Prognosis In Patients With Chronic Myelomonocytic Leukemia." Blood 122, no. 21 (November 15, 2013): 1334. http://dx.doi.org/10.1182/blood.v122.21.1334.1334.
Анотація:
Abstract Background Chronic myelomonocytic leukemia (CMML) is a clonal hematologic disorder that was classified by the World Health Organization (WHO) as a myelodysplastic/ myeloproliferative overlap disease. Cytogenetic abnormalities have a significant prognostic role in many hematologic neoplasms, but their prognostic value in CMML has been debatable. Recently, monosomal karyotype (MK) has been reported to be a marker of poor prognosis in patients with myelodysplastic syndromes (MDS) and primary myelofibrosis, but its value in CMML is unknown. Aim To study MK effect on clinical outcome for patients diagnosed with CMML Method A retrospective study of all cases diagnosed with CMML at Mayo Clinic Rochester between 1994 to 2011 was performed. Only pts with complete cytogenetic analysis at presentation to our institution were included. MK was defined as the presence of ≥ 2 autosomal monosomies or one autosomal monosomy with at least one structural abnormality (Breems et al, JCO 2008). CK was defined as the presence of at least 3 chromosomal abnormalities. Appropriate IRB approval was obtained in accordance with Helsinki declaration. Comparison between groups’ medians was done using Wilcoxon test, while survival estimates were calculated using Kaplan-Meier curves using JMP V9. Results A total of 262 pts diagnosed with CMML had available cytogenetic data at diagnosis. Median age was 72 years, 176 (67%) were male. Median hemoglobin 10.5 g/dL, white blood cells (wbc) 12 x109/L, platelet 89 x109/L, peripheral blood (PB) blast 0, and bone marrow (BM) blast 4%. CMML2 was seen in 9% while 47% were proliferative (wbc >13). Leukemic transformation was documented in 34 pts (13%). Median overall survival was 513 days. Cytogenetic (CG) analysis was diploid in 167 pts (64%). Trisomy 8 was the most frequent cytogenetic abnormality at 8% (22), followed by complex karyotype (CK) 5% (14), then -7 at 4% (10) and MK 3% (7, six of which were also CK). Comparing pts with diploid CG to other categories indicates: to abnormal CG pts had lower wbc (0.001), PB blasts (p<0.0001), and BM blasts (p=0.0001); to CK pts had lower PB blasts (p=0.003) and higher platelets (p=0.03); to -7 pts had lower wbc (p=0.005), PB blast (p=0.0004), BM blasts (p=0.03) and higher platelets (p=0.03); to +8 pts had lower PB blast (p=0.02) and BM blasts (p= 0.01); no difference was noted when compared to MK. Median OS was statistically significantly worse in MK+ vs MK- (24 vs 527 days, p= 0.002), but not in other comparisons: -7 vs others (250 vs 527 days, p=0.2), CK+ vs CK- (256 vs 527 days, p=0.05), diploid vs others (570 vs 365 days, p=0.1), +8 vs others (312 vs 527 days, p=0.1). Pts with MK+ only or MK+CK+ did worse than CK+ only or other groups (4, 63, 304, 527 days, respectively, p<0.0001). On a multivariate analysis, MK+ (in addition to platelet, BM blast, hemoglobin, and wbc) did have an impact on OS (p=0.0004), while CK+, -7, +8, diploid CG, age, PB blast did not. Conclusion Cytogenetic abnormalities were not frequent findings in pts diagnosed with CMML (36%), but did affect wbc, PB and BM blasts. The most common cytogenetic abnormality was +8 while MK was present at 3% (less than published data in MDS). Only MK predicted statistically significant shorter mOS between all other cytogenetic categories on both univariate and multivariate analysis. This finding needs to be validated by larger cohorts of pts due to its rare occurrence in CMML. Disclosures: No relevant conflicts of interest to declare.
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Moxon, T., and S. J. B. Reed. "Agate and chalcedony from igneous and sedimentary hosts aged from 13 to 3480 Ma: a cathodoluminescence study." Mineralogical Magazine 70, no. 5 (October 2006): 485–98. http://dx.doi.org/10.1180/0026461067050347.
Анотація:
AbstractChalcedony and agates from a variety of world-wide hosts have been examined using cathodoluminescence (CL). Gaussian fitting of the experimental data shows that there are two dominant spectral emissions at ∼400 and ∼660 nm. A third subordinate peak is also found at ∼470, ∼560 or ∼620 nm. An age-related link is shown between the respective decreasing and increasing relative intensities of the 660 and 620 nm emissions. It is proposed that this change is due to a condensation reaction between neighbouring Si–OH groups eliminating water and forming a strained Si-O-Si bond.Agates from a variety of hosts and regions produced no clear demonstrable CL distinctions. However, a set of Western Australian agates was examined from host rocks that had been subjected to burial metamorphism. Cathodoluminescence produced different spectral emissions in the petrographic fibrous and granular regions of these agates. One agate shows a partial transformation of the petrographic fibrosity into granularity. This conversion is characterized by emission bands at 570 nm and 460 nm. Similar emission-band changes were produced by heating Brazilian agates for 35 days at 300°C. The identification of these changes in agate could serve as an indicator of palaeoheating within the parent rock.
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Rodríguez Grullón, Julio Manuel, Mildre Disla Meléndez, Kao Chia-Cheng, Delfis A. Taveras Crespo, Yenny Gil Caraballo, Lázaro Montero García, Akemi Tabata Tabata, and Romy Amparo Grullón. "Determinación de presencia de virus en infecciones respiratorias agudas en niños en la República Dominicana, período noviembre 2018 – noviembre 2021." Asociación Dominicana de Pediatría 1, no. 1 (January 1, 2023): 101–10. http://dx.doi.org/10.58994/adopa.v1i1.7.
Анотація:
Introducción: los virus respiratorios son una causa frecuente de morbilidad y mortalidad en el mundo, de ahí la importancia de conocer los virus que circulan en la República Dominicana.
Materiales y métodos: realizamos un estudio prospectivo de corte trasversal en el Centro de Educación Médica de Amistad Dominico Japonés (CEMADOJA), en el que se analizaron muestras de hisopados orofaríngeos, transportados en medio apropiado, de niños ingresados con infección Respiratoria Aguda en hospitales de la República Dominicana en el período noviembre 2018 - noviembre 2021.
Resultados: estudiamos un total de 301 niños, entre 3 semanas de nacidos y 15 años; mascu- linos, 169 (56.4 %), y femeninos, 132 (43.6 %). Del total de la muestra, encontramos positivos 201 (67 %). Los virus hallados con mayor frecuencia fueron: Rhinovirus, 52 (25.7 %), Influenza A, 41 (20.6 %), Respiratorio Sincitial, 36 (18.2 %). Para Influenza, 32 (16.3 %), HMVP, 9 (4.5 %), Influenza B, 9 (4.5 %), Cov-Hku1, 9 (4.5 %), y otros 13 (5.7 %).
Conclusiones: si en 67 % de los casos de infecciones respiratorias agudas en niños, hay virus presente, el uso indiscriminado de antibióticos en estos casos debe ser revisado.
26
Thomson, David J., David E. Beever, Michael J. Haines, Stephen B. Cammell, Roger T. Evans, Mewa S. Dhanoa, and Anthony R. Austin. "Yield and composition of milk from Friesian cows grazing either perennial ryegrass or white clover in early lactation." Journal of Dairy Research 52, no. 1 (February 1985): 17–31. http://dx.doi.org/10.1017/s0022029900023852.
Анотація:
SUMMARYThe yield and composition of milk from Friesian cows grazing either perennial ryegrass (Lolium perenne) (G, ten cows) or white clover (Trifolium repens) (C, nine cows) were evaluated between d 21 and 129 post partum. The two forages, of similar digestible energy content, were the sole source of nutrients and were offeredad lib. (exp. 1). Digestion and flow at the duodenum were measured on 13 occasions in early lactation with comparable cows fitted with rumen and duodenal cannulae and grazing similar forages (exp. 2). The gross milk yield (22·2, G; 25·0, C, kg/dP< 0·05) and the yield of protein (0·66, G; 0·77, C, kg/d,P< 0·01) were higher, but the protein content was similar and the fat content lower for cows fed C compared with G. Cows fed G were heavier at the beginning of the experiment and lost weight more rapidly than cows fed C. Milk energy output, adjusted for tissue energy gain or loss, was 83·9 for cows fed C compared with 71·8 MJ/d for cows fed G (P< 0·001), during the period of tissue energy repletion (weeks 11–18). From week 18 to the end of lactation all cows from exp. 1 were fed silagead lib. and 502 kg dry matter of concentrates. The total (305 d) difference in lactation response to grazing C compared with G was 931 1 (5657 1, C; 4726 1, G); this was a direct response during the experiment of 301 1 and a residual response of 630 1. In exp. 2, more organic matter (6·47, G; 8·01, C, kg/ d,P< 0·001), and more non-ammonia N (433, G; 575, C, g/d,P< 0·001) entered the duodenum of cows grazing C compared with G.
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van de Ven, Annenienke C., Romana T. Netea-Maier, Femmie de Vegt, H. Alec Ross, Fred C. G. J. Sweep, Lambertus A. Kiemeney, Johannes W. Smit, Ad R. Hermus, and Martin den Heijer. "Associations between thyroid function and mortality: the influence of age." European Journal of Endocrinology 171, no. 2 (August 2014): 183–91. http://dx.doi.org/10.1530/eje-13-1070.
Анотація:
ObjectiveThe aim of this study was to investigate the influence of age on the association between thyroid function and mortality.DesignThe Nijmegen Biomedical Study is a population-based study, comprising 5816 randomly selected adults of all age groups without previously known thyroid disease.MethodsTSH, free thyroxine (FT4) and peroxidase antibodies were measured in 2002–2003. The number of deaths were established in 2012 (median follow-up time 9.4 years).ResultsSubclinical thyrotoxicosis was associated with mortality in subjects aged <65 years (hazard ratio (HR) 2.5, 95% CI 1.1–5.7), but not in subjects aged >65 years. As for thyroid function within the normal range: in the 493 participants aged 80 years or older, an FT4 level in the high-normal range (18.5–22 pmol/l) was associated with a higher mortality in comparison with FT4 levels in the middle range (11.5–15.0 pmol/l): HR 1.7 (95% CI 1.0–2.9). In these elderly, TSH levels within the high-normal range (3.0–4.0 mIU/l) were also associated with a higher mortality in comparison with TSH levels within the middle range (1.0–2.0 mIU/l): HR 1.8 (95% CI 1.0–3.1).ConclusionsThe relationship between thyroid function and mortality differs according to age. This finding might (partially) explain the discrepant results of previous studies examining the relationship between thyroid function and mortality in different age groups.
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Hafeez, Shaista, Karole Warren-Oseni, Helen McNair, Vibeke Hansen, Fiona McDonald, Susan Lalondrelle, Alan Thompson, et al. "Prospective phase 1 study assessing feasibility of IMRT and IGART to deliver simultaneous integrated high-dose tumor boost (up to 70 Gy) for the radical treatment of localized muscle-invasive bladder cancer." Journal of Clinical Oncology 33, no. 7_suppl (March 1, 2015): 307. http://dx.doi.org/10.1200/jco.2015.33.7_suppl.307.
Анотація:
307 Background: Advances in IGART offer individualized solutions to improve target coverage and reduce normal tissue irradiation allowing opportunity to increase radiation tumour dose and spare normal bladder. Methods: A library of 3 IMRT plans were created (small, medium and large) from planning CT scans performed at 30 and 60 minutes; treating whole bladder to 52 Gy and tumour to 70 Gy in 32 fractions. Where normal tissue dose constraints were not met consideration was made to boosting tumour to lower dose (68 Gy-64 Gy). Cone beam CT (CBCT) imaging was performed prior to each fraction. Appropriate PTV was selected from the library for treatment delivery. Post treatment CBCT was acquired weekly in order to assess intra-fraction filling and coverage. Results: 22 patients have been planned using this technique. All have met tissue constraints for treatment to 70 Gy. 21 patients have completed radiotherapy, 18 completed treatment to 70 Gy; 1 patient was planned and treated to 68 Gy prior to dose escalation using this technique; 1 patient was treated to a total dose of 65.6 Gy because dose limiting toxicity occurred before dose escalation. 572 CBCTs have been evaluated. Treatment was delivered using small, medium, and large plans in 35%, 52%, and 13% cases respectively. Mean intra-fraction filling was 14 cm3 (SD 16.3, range 0.23-107.9). Mean time between pre- and post-CBCTs was 13 min (SD 2.1, range 9-18). Mean D 98% as assessed on post-radiotherapy CBCT was 98.7% (SD 1.78, range 89.9-100%). At median follow-up of 8 months (range 1-24 months), 18 patients remain alive and disease free. 2 superficial recurrences and 3 deaths from metastatic bladder cancer have occurred. No muscle invasive recurrences have occurred within this cohort. Using this technique one patient has experienced late toxicity (grade 3 cystitis) 5.3 months after radiotherapy (now resolved). Conclusions: IGART using IMRT to delivery a simultaneous integrated tumour boost is feasible with acceptable toxicity. Trial recruitment continues at 70 Gy and will be evaluated in a randomised trial (RAIDER). Clinical trial information: NCT01124682.
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Fondevila, M., C. Castrillo, J. Gasa, and J. A. Guada. "Effect of ammonia treatment and supplementation on barley straw intake by sheep." Proceedings of the British Society of Animal Production (1972) 1989 (March 1989): 105. http://dx.doi.org/10.1017/s0308229600010965.
Анотація:
Twenty-eight lamb ewes (44 + 0.45 kg live weight) were used to study the effect of type and level of supplementation on voluntary intake of barley straw, treated with 30 g/kg of anhydrous ammonia (TS) or untreated (US) but given with urea to ensure the same nitrogen content as TS (18 g/kg DM). Each type of straw was offered ad libitum, supplemented with grass hay, rolled barley and sugar beet pulp at rates of 150, 300, 4 50 and 600 g/d, in 6 Latin Squares (4 x 4). In addition, another 2 sheep received each straw alone during the same periods. Supplements were totally consumed, except hay, which was refused in 10 - 13 and 28 - 34 per cent for US and TS, respectively.Daily dry matter intake (DMI) of US (OMD = 0.423) and TS (OMD = 0.515) offer as sole feed were 511 ± 29.1 and 858 ± 45.2 g. As show TABLE 1, US was consumed at rates of 527, 576 and 568 g DM when supplemented with 150 g of hay, barley and sugar beet pulp, and no significant differences were found with further levels of supplementation. DMI of TS decreased linearly from 850 to 618 g/d (r = 0.75) and from 717 to 518 g/d (r = 0.63) when the level of barley and sugar beet pulp increased from 150 to 600 g/d. Substitution rates were estimated to be 0.31 and 0.27 for barley and sugar beet pulp, respectively. Decrease in TS intake when supplemented since 150 to 600 g/d of hay (720 to 605 g, respectively) were found not significative.
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Jung, Diane, Nimesh Nagururu, Ferdinand Hui, Monica S. Pearl, John P. Carey, and Bryan K. Ward. "2D Measurements of the Angle of the Vestibular Aqueduct Using CT Imaging." Brain Sciences 13, no. 1 (December 26, 2022): 47. http://dx.doi.org/10.3390/brainsci13010047.
Анотація:
Recently, Bächinger et al. developed a software that measures the angle between the vestibular aqueduct proximal to the vestibule and the distal vestibular aqueduct on computed tomography (CT) scans and found differences in the vestibular aqueduct angle between the hypoplastic and degenerative categories of Meniere’s disease (MD). Hypoplastic radiological findings were associated with the development of bilateral MD and hypoplastic changes were not found outside of fetal temporal bones and individuals with MD. The purpose of this study is to examine how the software developed by Bächinger et al. performs when applied to a large dataset of adult patients with varied otologic diagnoses. Adult patients who underwent high resolution flat panel CT scans without intravenous contrast (n = 301) were retrospectively reviewed. Measurements of the angle of the vestibular aqueduct were made using the previously developed software tool. The tool could be applied to measure the vestibular aqueduct angle in most CT scans of the temporal bones (n = 572 ears, 95%). While the majority of ears fell within the normal range of <120 degrees (n = 462, 80%), fourteen ears (2.3%) in 13 patients were found to have vestibular aqueduct angles that meet criteria for hypoplastic MD (>140 degrees). Only one of the 13 patients had a diagnosis of MD and not in the ear in the hypoplastic category. An inconsistent pattern of other otologic diagnoses were found among the 13 individuals meeting criteria for hypoplastic MD. Although prior reports indicate the software has prognostic value in individuals with MD, these results suggest that the software may have lower positive predictive value when applied to a large population of individuals with varied otologic diagnoses.
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Noor, Aqil, Shaista Kanwal, Suleman Elahi Malik, Zafran Ullah, Tahir Ghaffar, and Khalid Usman. "FREQUENCY OF HYPERURICEMIA IN TYPE 2 DIABETES MELLITUS PATIENTS WITH BMI >23 KG/M2- STUDY AT A TERTIARY CARE HOSPITAL." Journal of Medical Sciences 31, no. 02 (May 23, 2023): 111–15. http://dx.doi.org/10.52764/jms.23.31.2.4.
Анотація:
OBJECTIVE: To determine the frequency of hyperuricemia in type 2 diabetes mellitus (T2DM) patients with BMI >23 kg/m2 MATERIALS AND METHODS: This descriptive study was conducted from February 2020 to September 2021. All patients with Type 2 Diabetes Mellitus (T2DM )with body mass index (BMI) >23 kg/m2 were assessed for hyperuricemia through Roche Cobas 6000 series C501 in MTI Hayatabad Medical Complex’s laboratory. RESULTS: Total number of patients was 300, out of which 60 % were males. The studied population has a mean age of 59 (SD =±7) years, mean systolic blood pressure was 151 (SD = ±17) mmHg, mean duration of T2DM was 13 (SD = ±4) years, mean HbA1c was 10.9 (SD = ±2.5) %, mean BMI was 28.8 (SD = ±3.1) kg/m2 and mean serum uric acid was 5.7 (SD=±1.3) mg/dl. The overall prevalence of Hyperuricemia was 47% (36.7 % males and 62.5% females). Of those with hyperuricemia, 73 % were also found to have hypertension. Results showed that patients with hyperuricemia belonged to older age, and have higher Systolic blood pressure, raised BMI, and HbA1c. The mean differences were considered statistically significant with a p-value < 0.05 by using an independent sample t-test. CONCLUSION: The current study demonstrated a higher prevalence of hyperuricemia in T2DM patients with BMI> 23 kg/m2. Patients with hyperuricemia had a higher mean HbA1c, higher mean BMI, and raised systolic component of blood pressure. KEY WORDS: BMI, Hyperuricemia, Hypertension, Type 2 diabetes mellitus, HbA1c
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Calderón-Garcidueñas, Ana Laura, Mónica Sanabria-Mondragón, Lourdes Hernández-Beltrán, Noé López-Amador, and Ricardo M. Cerda-Flores. "Mammographic Breast Density Patterns in Asymptomatic Mexican Women." Radiology Research and Practice 2012 (2012): 1–7. http://dx.doi.org/10.1155/2012/127485.
Анотація:
Breast density (BD) is a risk factor for breast cancer.Aims. To describe BD patterns in asymptomatic Mexican women and the pathological mammographic findings.Methods and Material. Prospective, descriptive, and comparative study. Women answered a questionnaire and their mammograms were analyzed according to BI-RADS. Univariate () and conditional logistic regression analyses were performed.Results. In 300 women studied the BD patterns were fat 56.7% (170), fibroglandular 29% (87), heterogeneously dense 5.7% (17), and dense pattern 8.6% (26). Prevalence of fat pattern was significantly different in women under 50 years (37.6%, 44/117) and older than 50 (68.8%, 126/183). Patterns of high breast density (BD) (dense + heterogeneously dense) were observed in 25.6% (30/117) of women ≤50 years and 7.1% (13/183) of women >50. Asymmetry in BD was observed in 22% (66/300). Compression cone ruled out underlying disease in 56 cases. In the remaining 10, biopsy revealed one fibroadenoma, one complex cyst, and 6 invasive and 2 intraductal carcinomas. 2.6% (8/300) of patients had non-palpable carcinomas. Benign lesions were observed in 63.3% (190/300) of cases, vascular calcification in 150 cases (78.9%), and fat necrosis in 38 cases (20%).Conclusions. Mexican women have a low percentage of high-density patterns.
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Aharinejad, Seyedhossein, Mohamed Salama, Patrick Paulus, Karin Zins, Andreas Berger, and Christian F. Singer. "Elevated CSF1 serum concentration predicts poor overall survival in women with early breast cancer." Endocrine-Related Cancer 20, no. 6 (December 2013): 777–83. http://dx.doi.org/10.1530/erc-13-0198.
Анотація:
Colony-stimulating factor 1 (CSF1) is a key regulator of mammary gland development, and a modulator of tissue macrophages. Expression of the CSF1 receptor geneC-FMS(CSF1R) is strongly associated with poor outcome in breast cancer and results in tumor cell invasiveness and pro-metastatic behaviorin vitro. However, CSF1's role as a predictive factor in breast cancer remains unclear. We have prospectively measured circulating CSF1 using ELISA in 572 women with early breast cancer and in 688 women with benign breast lesions, and correlated these concentrations with overall survival (OS), nodal status, and other clinical and histological parameters. Serum CSF1 concentrations were significantly elevated in patients with early breast cancer when compared with those with benign tumors (P<0.0001). Within breast cancer patients, CSF1 was higher in women with axillary lymph nodes (P=0.03). Serum CSF1 correlated with tumor size (P=0.002), age (P<0.001), and Ki67 expression (P=0.006). Log CSF1 serum concentrations were predictive of poor survival in both univariate (hazard ratio (HR): 3.77, 95% CI: 1.65–8.65,P=0.002) and multivariate analyses (HR: 3.1, 95% CI: 1.03–9.33,P=0.04). Post- but not premenopausal women with CSF1 serum concentrations >873 pg/ml experienced a significantly poorer outcome (P=0.004 log-rank test). Serum CSF1 concentrations are elevated in women with malignant breast tumors. In early breast cancer, elevated serum CSF1 is associated with nodal involvement, and in postmenopausal women also with poor OS.
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Tomberg, Joshua, Magnus Unemo, Makoto Ohnishi, Christopher Davies, and Robert A. Nicholas. "Identification of Amino Acids Conferring High-Level Resistance to Expanded-Spectrum Cephalosporins in thepenAGene from Neisseria gonorrhoeae Strain H041." Antimicrobial Agents and Chemotherapy 57, no. 7 (April 15, 2013): 3029–36. http://dx.doi.org/10.1128/aac.00093-13.
Анотація:
ABSTRACTThe recent identification of a high-level-ceftriaxone-resistant (MIC = 2 to 4 μg/ml) isolate ofNeisseria gonorrhoeaefrom Japan (H041) portends the loss of ceftriaxone as an effective treatment for gonococcal infections. This is of grave concern because ceftriaxone is the last remaining option for first-line empirical antimicrobial monotherapy. ThepenAgene from H041 (penA41) is a mosaicpenAallele similar to mosaic alleles conferring intermediate-level cephalosporin resistance (Cephi) worldwide but has 13 additional mutations compared to the mosaicpenAgene from the previously studied Cephistrain 35/02 (penA35). When transformed into the wild-type strain FA19, thepenA41allele confers 300- and 570-fold increases in the MICs for ceftriaxone and cefixime, respectively. In order to understand the mechanisms involved in high-level ceftriaxone resistance and to improve surveillance and epidemiology during the potential emergence of ceftriaxone resistance, we sought to identify the minimum number of amino acid alterations above those inpenA35that confer high-level resistance to ceftriaxone. Using restriction fragment exchange and site-directed mutagenesis, we identified three mutations, A311V, T316P, and T483S, that, when incorporated into the mosaicpenA35allele, confer essentially all of the increased resistance ofpenA41. A311V and T316P are close to the active-site nucleophile Ser310 that forms the acyl-enzyme complex, while Thr483 is predicted to interact with the carboxylate of the β-lactam antibiotic. These three mutations have thus far been described only forpenA41, but dissemination of these mutations in other mosaic alleles would spell the end of ceftriaxone as an effective treatment for gonococcal infections.
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Kheiralla, Lamia Sayed, and Jihan Farouk Younis. "Peri-Implant Biomechanical Responses to Standard, Short-Wide, and Mini Implants Supporting Single Crowns Under Axial and Off-Axial Loading (an In Vitro Study)." Journal of Oral Implantology 40, no. 1 (February 1, 2014): 42–52. http://dx.doi.org/10.1563/aaid-joi-d-11-00102.
Анотація:
This study compared the biomechanical responses of 3 single crowns supported by 3 different implants under axial and off-axial loading. A standard implant (3.75 mm diameter, 13 mm length), a mini implant (3 mm diameter, 13 mm length), and a short-wide implant (5.7 mm diameter, 8 mm length) were embedded in epoxy resin by the aid of a surveyor to ensure their parallelism. Each implant supported a full metal crown made of Ni-Cr alloy with standardized dimensions. Strain gauges and finite element analysis (FEA) were used to measure the strain induced under axial and off-axial functional loads of 300 N. Results showed that mini implants recorded the highest microstrains, under both axial and off-axial loading. All implants showed a considerable increase in strain values under off-axial loading. Standard and short-wide implants proved to be preferable in supporting crowns, as the standard implant showed the lowest strains under axial and off-axial loading using FEA simulation, while the short-wide implant showed the lowest strains under nonaxial loading using strain gauge analysis.
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HÂNGAN, Ilie Daniel, Ionuţ Bogdan HULUJAN, Teodora FLORIAN, and Ion OLTEAN. "Monitoring of Epigean Beetles from the Grassland Located in Bilbor, Harghita County." Bulletin of University of Agricultural Sciences and Veterinary Medicine Cluj-Napoca. Agriculture 79, no. 2 (November 20, 2022): 18–24. http://dx.doi.org/10.15835/buasvmcn-agr:2022.0030.
Анотація:
Barber traps were used to monitor the coleopteran fauna of grasslands in the Bilbor area. In 2017, 268 specimens were collected using Barber traps. They belong to 55 species, systematically classified in 13 families. Of the total catches, 58.2% are represented by phytophagous beetles and 41.8% of them are predatory beetles. Most catches belong to the Carabidae family, with 75 specimens represented by 14 species. Most of the specimens caught belong to the species Carabus ulrichii Germar. In 2018, 305 copies were collected. They belong to 56 species, systematically classified in 13 families. This year too, most catches belong to the Carabidae family, which means 25.9% of the total catches. Most of the captured specimens belong to the species Harpalus tardus Panz. In the two years, 573 beetles, belonging to 65 species, were captured. Of the species reported, 31 are phytophagous species and 34 are zoophagous. According to the Ecological Significance Index (W) 5 species are accessory with the value of the index between 1.1-5.0% (Carabus ulrichii Germar, Harpalus distinguendus Duft., Ips amitinus Eichh., Ips typographus L. and Olibrus affinis Sturm.).
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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.
Анотація:
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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Lowe, Dana Ruminski, Benedicta Forson, Matthew G. Butler, Yves Konigshofer, Catherine Huang, Omoshile Clement, Russell K. Garlick, and Bharathi Anekella. "Abstract 537: Development of blood TMB (bTMB) reference materials for validation of cfDNA-based targeted NGS assays that measure tumor mutational burden (TMB) in patient blood samples." Cancer Research 82, no. 12_Supplement (June 15, 2022): 537. http://dx.doi.org/10.1158/1538-7445.am2022-537.
Анотація:
Abstract TMB is a biomarker with potential for predicting positive patient response to immune checkpoint inhibitors. TMB measurements can be determined using genomic DNA extracted from FFPE-preserved tissue biopsy samples. However, assessment of TMB from a liquid biopsy, or blood TMB (bTMB), is an attractive alternative clinical diagnostic tool that would allow clinicians and patients to avoid the invasive challenge of tissue biopsies. Accurately measuring bTMB with targeted gene panels has been problematic, thus we have developed the new Seraseq® bTMB reference materials at various mutational burden levels from genomic DNA extracted from tumor-derived and SNP-matched normal cell lines. Somatic variants were identified in each cell line by whole exome sequencing (WES). TMB assessments were made by an in-house developed TMB bioinformatics pipeline based on recommendations by the Friends of Cancer Research (FoCR) TMB Harmonization Consortium. DNA from tumor and normal cell lines were blended at 0%, 0.5%, and 2% tumor fractions and fragmented to approximate the size of cell free DNA (cfDNA). The resulting bTMB mixes were enriched with the TruSight™ Oncology 500 ctDNA Assay (2x151 bp), in triplicate, and sequenced on a NovaSeq™ 6000. Blood TMB scores were determined using the DRAGEN™ TruSight Oncology 500 ctDNA Analysis Software v1.1. The observed bTMB scores for the tumor-containing materials were slightly lower in the TF 0.5% mix versus the TF 2% mix due to variants moving below the limit of detection of the TSO500 ctDNA assay (Table 1). As is the case with patient samples and clonal hematopoiesis, there are background variants in 0% tumor content material that may elevate apparent bTMB scores, thus adjusted bTMB scores are shown. The Seraseq Blood TMB Score reference materials provide a tumor-normal matched blood TMB control to aid development, validation and QC of cfDNA NGS assays for accurate determination of bTMB Scores. Table 1. Average bTMB scores and adjusted bTMB scores for each mix. Mix Average bTMB Score (mutations/megabase ± 1 SD) Adjusted bTMB Score (mutations/megabase ± 1 SD) Score 7 0% 7.5 ± 1.7 0 Score 7 0.5% 13.1 ± 2.6 5.6 ± 3.1 Score 7 2% 17.9 ± 1.3 10.4 ± 2.1 Score 13 0% 4.6 ± 0.5 0 Score 13 0.5% 18.7 ± 2.1 14.1 ± 2.2 Score 13 2% 24.6 ± 0.8 20.0 ± 0.9 Score 20 0% 7.5 ± 1.4 0 Score 20 0.5% 26.0 ± 2.3 18.5 ± 2.7 Score 20 2% 35.6 ± 1.0 28.1 ± 1.7 Score 26 0% 6.0 ± 0.5 0 Score 26 0.5% 20.7 ± 5.5 14.7 ± 5.5 Score 26 2% 30.4 ± 1.5 24.4 ± 1.9 Citation Format: Dana Ruminski Lowe, Benedicta Forson, Matthew G. Butler, Yves Konigshofer, Catherine Huang, Omoshile Clement, Russell K. Garlick, Bharathi Anekella. Development of blood TMB (bTMB) reference materials for validation of cfDNA-based targeted NGS assays that measure tumor mutational burden (TMB) in patient blood samples [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 537.
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Lefkou, Eleftheria, Kiran Parmar, Apostolos Mamopoulos, Sevasti Masouridou, Vassilios Karagiannis, and Beverley J. Hunt. "Peripartum Haemostatic Changes in Women in Labour." Blood 112, no. 11 (November 16, 2008): 5475. http://dx.doi.org/10.1182/blood.v112.11.5475.5475.
Анотація:
Abstract Introduction: Obstetric haemorrhage (OH) is a major cause of maternal mortality and morbidity worldwide. Appropriate management requires understanding of normal peripartum haemostatic changes during labour, and yet there are few studies. Aim: In this pilot study we aimed to evaluate peripartum haemostatic changes in healthy women. Methods: We collected blood samples from 20 women peripartum, into 0.102 M trisodium citrate tubes (ratio9:1) (Becton Dickinson) from the antecubital fossa using flawless venepuncture at the following time-points: antepartum; after delivery of the placenta; 24hrs post-partum and 48hrs post-partum. Plasma was aliquoted and stored in −70°C until the following ELIZA assays were performed: D-Dimer levels (Dade Behring, Sysmex UK), prothrombin fragments 1+ 2 (PF 1+2) (Dade Behring, Sysmex, UK) and tissue plasminogen activator antigen (t-PA:Ag) (Biopool, Trinity Biotech, UK). Prothrombin time (PT) (PT-Fib HS), activated partial thromboplastin time (APTT) (APTT micronized silica) and clauss fibrinogen (Fib-C), reagents were from Instrumentation Laboratories Ltd UK. Statistical analysis was performed using XLSTAT 2008. Results: The median (range) age was 28 (19–36) years and the body mass index (BMI) 28.9 (21.7– 35.3). Table 1: To show the median (range) for the haemostatic assays Assay (normal ranges) D-dimers (4–52ug/l) PF1+2 (0.2–1.2 pmol/l) t-PA:Ag: 3–11 ng/ml) PT (12–16s) APTT (26–38s) Fibrinogen (1.52–4.12 g/l) * p<0.05 using the Mann Whitney U test between the 1st and each of the other three samples Antepartum 231 (122–900) 570 (352–1533 12 (7.2–23) 12 (10–14) 31 (24–36) 5.2 (3.1–8.7) Post Labour 482 (117–1044) 968 (480–1858)* 18 (8.6–40.6)* 13 (10–15) 30 (24–36) 5.3 (2.2–9.8) 24h 309 (65–931) 568 (264–1080)* 7 (4–23)* 13 (10–16)* 33 (27–41)* 5.3 (4–11) 48hrs 235 (85–614) 648 (371–2287) 7 (3–18)* 12 (10–16) 31 (23–43) 5.7 (3.5–11) Conclusion: These findings demonstrate that peripartum haemostasis is prothrombotic with shortened PT, APTT and prolonged fibrinogen. There is increased thrombin generation and fibrinolytic activity. t-PA antigen is most notably elevated immediately post delivery.
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Assmann, Taís Silveira, Letícia de Almeida Brondani, Andrea Carla Bauer, Luis Henrique Canani, and Daisy Crispim. "Polymorphisms in the TLR3 gene are associated with risk for type 1 diabetes mellitus." European Journal of Endocrinology 170, no. 4 (April 2014): 519–27. http://dx.doi.org/10.1530/eje-13-0963.
Анотація:
IntroductionViral pathogens seem to play a role in triggering the autoimmune destruction that leads to the development of type 1 diabetes mellitus (T1DM). Toll-like receptor 3 (TLR3) has been shown to recognize double-stranded RNA, a molecular signature of most viruses. It is expressed at high levels in pancreatic β-cells and immune cells, suggesting a role for it in the pathogenesis of T1DM. Therefore, the aim of this study was to investigate whetherTLR3polymorphisms are associated with T1DM.MethodsFrequencies of theTLR3rs11721827, rs13126816, rs5743313, rs7668666, and rs3775291 polymorphisms were analyzed in 449 T1DM patients and in 507 nondiabetic subjects. Haplotypes constructed from the combination of these polymorphisms were inferred using a Bayesian statistical method.ResultsThe rs3775291 and rs13126816 polymorphisms were associated with T1DM, and the strongest association was observed for the additive model (odds ratio (OR)=2.3, 95% CI 1.3–4.2 and OR=2.1, 95% CI 1.3–3.1 respectively). In the same way, the frequency of T1DM was higher as more risk alleles of the five polymorphisms were present (P-trend=0.001). Moreover, in T1DM patients, the minor alleles of the rs5743313 and rs117221827 polymorphisms were associated with an early age at diagnosis and worse glycemic control.ConclusionTheTLR3rs3775291 and rs13126816 polymorphisms are associated with risk for T1DM, while the rs5743313 and rs11721827 polymorphisms are associated with age at T1DM diagnosis and poor glycemic control. The number of risk alleles of the fiveTLR3polymorphisms in the haplotypes seems to influence the risk for T1DM, suggesting that these polymorphisms might interact in the susceptibility for the disease.
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Geurkink, Youri, Jan Boone, Steven Verstockt, and Jan G. Bourgois. "Machine Learning-Based Identification of the Strongest Predictive Variables of Winning and Losing in Belgian Professional Soccer." Applied Sciences 11, no. 5 (March 8, 2021): 2378. http://dx.doi.org/10.3390/app11052378.
Анотація:
This study aimed to identify the strongest predictive variables of winning and losing in the highest Belgian soccer division. A predictive machine learning model based on a broad range of variables (n = 100) was constructed, using a dataset consisting of 576 games. To avoid multicollinearity and reduce dimensionality, Variance Inflation Factor (threshold of 5) and BorutaShap were respectively applied. A total of 13 variables remained and were used to predict winning or losing using Extreme Gradient Boosting. TreeExplainer was applied to determine feature importance on a global and local level. The model showed an accuracy of 89.6% ± 3.1% (precision: 88.9%; recall: 90.1%, f1-score: 89.5%), correctly classifying 516 out of 576 games. Shots on target from the attacking penalty box showed to be the best predictor. Several physical indicators are amongst the best predictors, as well as contextual variables such as ELO -ratings, added transfers value of the benched players and match location. The results show the added value of the inclusion of a broad spectrum of variables when predicting and evaluating game outcomes. Similar modelling approaches can be used by clubs to identify the strongest predictive variables for their leagues, and evaluate and improve their current quantitative analyses.
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Colombo Breda, Jéssica, Adriana Dalpicolli Rodrigues, Patrícia Wilmsen Dalla Santa Spada, and Tânia Torriani. "Hemoparasitoses em cães: análise de dados laboratoriais." Revista Acadêmica Ciência Animal 16 (November 26, 2018): 1. http://dx.doi.org/10.7213/1981-4178.2018.16016.
Анотація:
AO objetivo desse trabalho foi avaliar a ocorrência de hemoparasitos em cães, consultando os laudos de análises sanguíneas de um laboratório de análises clínicas veterinárias do município de Bento Gonçalves, RS. Para tanto, foram avaliados 413 laudos emitidos de janeiro a junho do ano de 2013, cuja técnica utilizada foi a hematoscopia. Dos laudos avaliados com hemoparasitos, 45/53 (84,9%) apontaram eritrócitos parasitados por Babesia sp./Rangelia vitalli, 5/53 (9,4%) para leucócitos parasitados e níveis plaquetários diminuídos devido à Ehrlichia sp., e 3/53 (5,7%) parasitados simultaneamente por Babesia sp./R. vitalli e Ehrlichia sp. As amostras também foram caracterizadas pela evidência de anemia, sendo que 120/413 cães (29,1%) apresentavam quadro anêmico, 40 desses hemoparasitados; 293/413 (70,9%) não apresentaram anemia e 13/293 desses eram hemoparasitados. Na série vermelha, estavam laudados quadros de anisocitose, policromatofilia e/ou presença de eritroblastos para 129/413 (31,2%) cães, sendo 43/129 hemoparasitados; já 284/413 (68,8%) cães não apresentaram alterações da série vermelha, sendo 10/284 hemoparasitados. Para a série branca, 301/413 cães (72,9%) foram indicados com quadros de leucocitose, leucopenia, linfocitose e/ou neutrofilia, sendo que 50/301 desses (24,9%) eram hemoparasitados; 112/413 (27,1%) não apresentaram alterações da série branca, onde 3/112 eram hemoparasitados. Quanto às alterações plaquetárias, a trombocitopenia foi detectada em 131/413 (31,7%) cães, sendo 37/131 desses hemoparasitados; 282/413 (68,3%) não apresentaram alterações, dos quais 16/282 eram hemoparasitados. Mediante esses achados, pode-se constatar que as alterações hematológicas geralmente estão associadas à presença de hemoparasitos e os resultados servem para alertar sobre a importância do manejo adequado do local de vivência dos cães, certificando-se da ausência de carrapatos.
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Giordano, Federica, Stefania Lenna, Riccardo Rampado, Gherardo Baudo, Matteo Massaro, Ashley Rivera, Enrica De Rosa, Jason T. Yustein, and Francesca Taraballi. "Abstract 307: Ponatinib loaded leukocyte-based nanoparticles: A new platform for treating osteosarcoma." Cancer Research 82, no. 12_Supplement (June 15, 2022): 307. http://dx.doi.org/10.1158/1538-7445.am2022-307.
Анотація:
Abstract The introduction of targeted anticancer drugs has revolutionized treatment. Multi-tyrosine kinase inhibitors (TKIs) are potential therapeutics targeting specific signaling pathways that contribute to cancer progression, including sarcomas. Osteosarcoma is the most common pediatric tumor with a worldwide incidence of 3.4 cases/million annually but without effective treatment. Of the TKIs, Ponatinib demonstrated potent anti-tumor activity; however, it received an FDA black box warning for potential side effects. New treatment and delivery systems must be identified to use Ponatinib clinically. Our laboratory developed novel biomimetic nanoparticles (NPs) synthesized from activated leukocytes called Leukosomes. Leukosomes maintain leukocyte tropism towards inflamed endothelium and can encapsulate and effectively release Ponatinib. We aimed to validate Leukosome technology’s therapeutic potential to specifically target and inhibit primary murine osteosarcoma growth and reduce detrimental side effects. In a 3D sarcosphere model, we observed effective penetration and internalization of NPs in both murine (RF379, 577) and human patient derived xenograft (PDX94, PDX202) osteosarcoma cell lines. Leukosome exhibited 20% increased targeting versus control liposomes. Cell viability decreased 20% after treatment with Ponatinib IC50. Leukosome-Ponatinib IC50 also induced complete inhibition of murine sarcosphere formation and ~60-80% reduction of cell viability. We developed an osteosarcoma orthotopic mouse model by intratibial injection of murine F420 osteosarcoma cells. After 3 weeks, tumor was detected and the mice were injected with Ponatinib NPs. Leukosome showed increased tumor targeting and penetration 1 and 3 hours post-NP injection. Intravenous tail injection of Ponatinib was lethal due to drug-related toxic effects, while intraperitoneal injection of Ponatinib was well tolerated. Conversely, intravenous injection of Ponatinib-loaded NPs did not show toxic effects. In vivo efficacy studies demonstrated that 3 weeks of Ponatinib treatment (2 treatments/week) inhibited tumor growth and increased survival. Similar results were also observed after Leukosome Ponatinib treatment, despite 10 times less Ponatinib in NPs than in free drug. Overall, these results show that leukocyte-derived membrane proteins enhance the accumulation of Ponatinib at the tumor site and surrounding inflamed tissue. While limited Ponatinib encapsulation in NPs remains an open challenge, this formulation underlies the possibility of reducing drug dosage and side effects. Thus, suggest Leukosome’s translational potential as a new targeted drug delivery approach with better outcomes and fewer complications for osteosarcoma patients. Citation Format: Federica Giordano, Stefania Lenna, Riccardo Rampado, Gherardo Baudo, Matteo Massaro, Ashley Rivera, Enrica De Rosa, Jason T. Yustein, Francesca Taraballi. Ponatinib loaded leukocyte-based nanoparticles: A new platform for treating osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 307.
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Cinakli, H., D. Solmaz, E. Durak Ediboglu, E. Otman Akad, G. Alp, E. Erpek, İ. Kurut Aysin, et al. "AB1169 THE PRESENCE OF PSORİASİS MIGHT INCREASES STRUCTURAL DAMAGE IN PATIENTS WITH AXIAL SPONDYLOARTHRITIS." Annals of the Rheumatic Diseases 82, Suppl 1 (May 30, 2023): 1815.2–1815. http://dx.doi.org/10.1136/annrheumdis-2023-eular.6266.
Анотація:
BackgroundPsoriasis is one of the most common extra-articular involvement in axial spondyloarthritis (axSpA) patients.ObjectivesTo examine the effect of the presence of psoriasis on the clinical and radiological features of patients with axSpA.MethodsIn this single-center study, 657 axSpA patients (mean age; 39.9±11.7, male gender n:411 [62,7%,]) were included in this analysis, according to the criteria of the Assessment of Spondyloarthritis International Society (ASAS). In addition to the initial demographic, clinical and radiological characteristics of the patients, radiological damage and progression were also evaluated. Demographic and disease-related characteristics were reviewed according to the presence of psoriasis.ResultsIn total 43 (6.5%) patients with axSpA had psoriasis. While patients with psoriasis had a higher mean age (44.8±12.4 vs 39.6±11.5; p:0.008), their gender distribution was similar (Table 1). According to the ASAS definition, positive family history (55.6% vs 24.5%; p<0.0001) and basal biological use (41.9% vs 25.9%; p:0.023) rates were also higher in psoriasis patients. While activity scores were found to be similar in patients with and without psoriasis; in the psoriasis group, patient-reported outcome measures (night and general low back pain) and function (BASFI) scores were found to be significantly higher. In addition to the presence of basal cervical (50% vs 31.6%; p:0.032), basal lumbar syndesmophytes (40% vs 18.8%; p<0.006), new syndesmophyte development in the lumbar spine (53.3% vs 10.1%); p<0.0001) rate was higher in axSpA patients with psoriasis. Although the baseline mSASS scores were higher in these patients, the difference did not reach statistical significance. There was no difference between the groups in terms of hip involvement frequency and progression.ConclusionPresence of psoriasis might contribute significantly to structural damage and function in axSpA patients, independent of activity.Table 1.Demographic, some clinical and laboratory characteristics as well as structural characteristics of patients with axial spondyloarthritis with and without psoriasisPsöriasis (+) axSpA patients n:43Psöriasis (-) axSpA patients n:614Pr-axSpA, n(%)34 (79,1)397 (64,7)0,54Age, year, (mean ±SD)44,8 (12,4)39,6 (11,5)0,008Male sex, n(%)30 (69,8)381 (62,1)0,323Disease duration, (mean ±SD)16,3 (14,4)12,1 (10,0)0,098Smoking, ever, n(%)15/20 (75)232/332 (70)0,627ASAS family history, n(%)20/36 (55,6)134/547 (24,5)<0,0001HLA-B27, n(%)17/31 (54,8)282/491 (57,4)0,777Biological agent usage, n(%)18 (41,9)156/602 (25,9)0,023Peripheral arthritis, n(%)17/38 (44,7)192/558 (34,4)0,197Heel pain, n(%)17/38 (44,7)250/519 (48,2)0,683Hip involvement, n(%)8/38 (21,1)75/507 (14,8)0,300Uveitis, n(%)5/38 (13,2)70/567 (12,3)0,883Dactylitis, n(%)3/39 (7,7)13/567 (2,3)0,077IBD history, n(%)CrohnUlcerative colitis1/37 (2,7)11/510 (2,2)12/510 (2,4)0,628CRP, (mean ±SD)20,1 (29,2)13,8 (21,5)0,422ASDAS-CRP, (mean ±SD)3,1 (1,2)2,8 (1,2)0,143HAQ, (mean ±SD)1,1 (0,8)0,9 (0,7)0,082BAS-night, (mean ±SD)5,5 (2,7)4,4 (3,0)0,032BAS-G, (mean ±SD)5,6 (2,7)4,5 (3,0)0,029PGA, (mean ±SD)5,4 (2,8)4,8 (2,8)0,220BASFI, (mean ±SD)4,6 (3,0)3,6 (2,9)0,035BASDAI, (mean ±SD)4,3 (2,3)4,3 (2,3)0,898ASQol, (mean ±SD)9,8 (5,3)9,5 (8,9)0,559mSASS basal, (mean ±SD)13,1 (21,4)7,8 (16,4)0,056Basal cervical syndesmophyte, n(%)16/32 (50)143/453 (31,6)0,032Basal lumbar syndesmophyte, n(%)12/30 (40)94/500 (18,8)0,006Cervical new syndesmophyte, n(%)5/20 (25)39/235 (16,6)0,340Lumbar new syndesmophyte, n(%)8/15 (53,3)26/257 (10,1)<0,0001New syndesmophyte, n(%)9/21 (48,8)54/285 (18,9)0,009Hip involvement, n(%)5/41 (12,2)69/583 (11,8)0,945Hip progression, n(%)1/24 (4,2)19/322 (5,9)0,725AcknowledgementsDisclosure of Interests: None Declared.
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Ahmad, Saif, Wendi Qian, Sarah Gabrielle Ellis, Muhammad Adnan Khattak, Avinash Gupta, Kiruthikah Thillai, Ruth E. Board, et al. "Ipilimumab in the real world: The U.K. expanded access programme (EAP) experience in advanced melanoma." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 3018. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.3018.
Анотація:
3018 Background: Since publication of the registration trial in 2010 (Hodi et al, NEJM 2010;363:711-23), real world use of ipilimumab (Ipi) in previously treated advanced melanoma patients has extended beyond the specific trial entry criteria of ECOG PS 0-1. We undertook a review of UK patients (pts) treated in the international EAP prior to European licensing of Ipi in August 2011, to compare real world survival outcomes. Methods: UK clinicians registered in the EAP provided anonymised data using pre-specified variable fields for all pts. The EAP stipulated pts should have previously treated, unresectable stage III or IV metastatic melanoma and receive Ipi 3 mg/kg, 3 weekly IV, for up to 4 cycles. Response using RECIST criteria was assessed 12 weekly. Grade ≥3 adverse events (AEs) using CTCAE v3.0 were collected. Results: To date, information on 162 pts has been received from 16 UK sites. Primary sites were: 78% cutaneous, 4% ocular, 1% mucosal, 17% unknown. 78% pts had M1c disease, 14% had brain metastases. No prior therapies ranged from 0-4, 72% pts received 1 prior therapy. Median age was 60 years, men>women (1.6:1). ECOG PS was: 38% 0, 47% 1, 14% 2, 1% 3. BRAF status was known in 38% cases and WT in 75% of these. 19% pts were on steroids at baseline. No cycles delivered was 4 in 52%, 3 in 13%, 2 in 16%, 1 in 17% pts. Most frequent reason for stopping early was clinical evidence of disease progression (71%), death (16%) or unacceptable AE (12%). 32% pts experienced a grade ≥3 AE, the most common being diarrhoea (13%) and fatigue (8%). Complete and partial responses were reported in 1% and 21% of treated pts. At median follow-up of 17 months, median progression free survival and overall survival (OS) were 2.8 and 5.7 months, 1 year OS was 30%. Comparing outcomes of various pt subgroups, the strongest prognostic factor for OS was ECOG PS at the start of treatment (p<0.0001). For pts with PS 0 or 1, median OS was 8.8 months (compared with 10 months in the registration trial). More detailed safety and efficacy data on pt subgroups will be presented. Conclusions: This review, representing the largest Ipi EAP UK dataset, reports overall poorer survival outcomes than in the registration trial, but pts with similar characteristics to the trial population lived longer.
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Barbosa, Marcus Levi Lopes, Marcos Alencar Abaide Balbinotti, Ricardo Pedroso Saldanha, Aline Bonini Reis Pedroso Diehl, and Carlos Adelar Abaide Balbinotti. "Validade do Modelo Hierárquico da Motivação Intrínseca e Extrínseca no Esporte Escolar." Psico-USF 24, no. 3 (September 2019): 529–40. http://dx.doi.org/10.1590/1413-82712019240310.
Анотація:
Resumo O tema do presente estudo é a autodeterminação. O objetivo foi testar o Modelo hierárquico da motivação intrínseca e extrínseca - MHMIE. Trata-se de um modelo teórico-explicativo linear, sequencial e unidirecional baseado na Teoria da Autodeterminação, que pressupõe a relação causal entre ‘fatores sociais’, ‘mediadores psicológicos’, ‘autodeterminação’ e ‘consequências’. A amostra foi composta de 517 alunos (n m = 303; n f = 214) praticantes de esporte escolar, da faixa etária de 13 a 19 anos (IMG = 15,32; σ = 1,46), regularmente matriculados em turmas que vão do último ano do ensino fundamental ao terceiro ano do ensino médio de escolas públicas e privadas do estado do Rio Grande do Sul. A pesquisa foi aprovada pelo CEP-UFRGS, 2008055. O MHMIE foi testado com path analysis e equações estruturais. Os resultados obtidos indicaram que o modelo apresenta índices adequados de validade na amostra estudada.
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Terry, P. B., H. A. Menkes, and R. J. Traystman. "Effects of maturation and aging on collateral ventilation in sheep." Journal of Applied Physiology 62, no. 3 (March 1, 1987): 1028–32. http://dx.doi.org/10.1152/jappl.1987.62.3.1028.
Анотація:
We studied collateral ventilation as a function of age by measuring the resistance (Rcoll) and time constant (Tcoll) of collateral airflow in young (2–10 mo), mature (16–24 mo), and old sheep (6–13 yr). Rcoll was 0.50 +/- 0.11 cmH2O X ml-1 X min (SE) in young sheep and decreased significantly to 0.05 +/- 0.02 and 0.02 +/- 0.01 cmH2O X ml-1 X min in mature and old sheep, respectively. Tcoll was 34.4 +/- 7.9 (SE) s in young sheep and decreased to 5.7 +/- 0.9 and 10.2 +/- 3.1 s in mature and old sheep, respectively. We conclude that a marked decrease in Rcoll and Tcoll occurs between birth and maturity but changes little with further aging. In the young an increased resistance and time constant of collateral airflow may accentuate ventilation perfusion imbalance and impair the removal of secretions in disease states.
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Senguttuvan, Rajan, David Huante, and Giselle Ricoy. "PMON322 Gigantism in 13-Year-Old Male With Pituitary Tumor." Journal of the Endocrine Society 6, Supplement_1 (November 1, 2022): A627. http://dx.doi.org/10.1210/jendso/bvac150.1300.
Анотація:
Abstract Background Pituitary gigantism is caused by excess growth hormone [GH] secretion from the pituitary gland when the growth plates are open leading to excessive linear growth and tall stature in the pediatric population. It is extremely rare with a reported incidence of 8 cases per million person-years. Clinical Case The patient is a 13-year-old male who presented with concerns of accelerated growth rate and tall stature. His father noticed the patient's tall stature when he passed his own height the last year. The patient was seen by his PCP who referred the family to pediatric endocrinology. His symptoms included snoring and bi-weekly headaches, but no vision changes. Review of his growth charts showed linear growth tracking at greater than the 95th percentile since the age of 9 years. His clinical features included large hands, large feet, prominent jaw, testicular volume >25 ml, tall stature [Ht > 99%, Z= +4.59 SD]. The patient's mid-parental height is 69.1 inches [175.5 cm] and the patient measured 76.6 inches [194.5 cm]. His predicted height was 7 feet 1.5 inches [217.2 cm] based on his bone age. His clinical features were strongly concerning for Gigantism. Initial labs showed IGF-1 of 924 ng/mL [168–576], prolactin of 20.1 ng/mL [2.8–11.0], and IGF-BP3 8.7 mg/L [3.1–9.5]. Cortisol, ACTH, TSH, FT4, LH, FSH, Testosterone were within normal limits. Bone age was concordant with chronological age. MRI showed enlarged pituitary gland measuring 1.3 cm in height, suspicious for macroadenoma. Cardiac evaluation including echocardiogram came back normal. GH suppression test resulted in a 2-hour GH level of 27.3 ng/mL [<1] and he was diagnosed with Gigantism due to GH-secreting pituitary tumor. The parents decided to consult neurosurgery team at a different facility, where transsphenoidal resection of the pituitary tumor was performed. He did not develop any postoperative complications, including Diabetes insipidus or any pituitary hormone deficiencies, and was discharged home shortly after. Follow-up MRI of the pituitary showed no evidence of residual tumor. Pathology of the macroadenoma expressed GH and prolactin on immunohistochemical stains and was negative for TSH, LH/FSH, and ACTH. Genetic studies obtained were negative, lowering the likelihood of inherited predisposition to endocrine neoplasms. The patient has remained well post-operatively and has been able to continue school and play basketball without issues. Conclusion Pituitary gigantism occurs in the pediatric population prior to skeletal epiphyseal closure and is caused by GH excess. Initial screening tests should evaluate for pituitary function including IGF-1 and prolactin levels. The gold standard for diagnosing GH excess is the GH suppression test. Even though rare, it is important for clinicians to keep a high level of suspicion for quick recognition and management of overgrowth syndromes. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.
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Hareni, Niyaz, Kari Gudlaugsson, Fredrik Strömqvist, Björn E. Rosengren, and Magnus K. Karlsson. "A comparison study on patient-reported outcome between obese and non-obese patients with central lumbar spinal stenosis undergoing surgical decompression: 14,984 patients in the National Swedish Quality Registry for Spine Surgery." Acta Orthopaedica 93 (November 28, 2022): 880–86. http://dx.doi.org/10.2340/17453674.2022.5254.
Анотація:
Background and purpose: Obesity has been associated with inferior outcomes after laminectomy due to central lumbar spinal stenosis (CLSS); we evaluated whether this occurs in surgery on national bases.Patients and methods: We retrieved pre- and 1-year postoperative data from the National Swedish Quality Registry for Spine Surgery regarding patients aged ≥ 50 with laminectomy due to CLSS in 2005–2018. 4,069 patients had normal weight, 7,044 were overweight, 3,377 had class I obesity, 577 class II obesity, and 94 class III obesity (“morbid obesity”). Patient-reported outcome included satisfaction after 1 year, leg pain (Numerical Rating Scale [NRS], rating 0–10), disability (Oswestry Disability Index [ODI], rating 0–100). Complications were also retrieved.Results: 1-year postoperatively, 69% of patient of normal weight, 67% who were overweight, and 62% with obesity (classes I–III aggregated) were satisfied (p < 0.001) and 62%, 60%, and 57% in obese groups I–III, respectively (p = 0.7). NRS leg pain improved in normal-weight patients by 3.5 (95% CI 3.4–3.6), overweight by 3.2 (CI 3.1–3.2), and obese by 2.6 (CI 2.5–2.7), and 2.8 (CI 2.7–2.9), 2.5 (CI 2.2–2.7), and 2.6 (CI 2.0–3.2) in obese classes I–III, respectively. ODI improved in normal weight by 19 (CI 19–20), overweight by 17 (CI 17–18), and obese by 14 (CI 13–15), and 16 (CI 15–17), 14 (CI 13–16), 14 (CI 11–18) in obese classes I–III, respectively. 8.1% of normal weight, 7.0% of overweight, and 8.1% of obese patients suffered complications (p = 0.04) and 8.1%, 7.0%, and 17% among obese classes I–III, respectively (p < 0.01).Conclusion: Most obese patients are satisfied after laminectomy due to CLSS, even if satisfaction rate is inferior compared with normal-weight patients. The morbidly obese have more complications than patients with lower BMI.
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Garawin, Tamer, Kimberly Lowe, George Kafatos, and Samuel Murray. "The prevalence RAS and BRAF mutations among patients in the Middle East and Northern Africa with metastatic colorectal cancer." Journal of Clinical Oncology 34, no. 4_suppl (February 1, 2016): 598. http://dx.doi.org/10.1200/jco.2016.34.4_suppl.598.
Анотація:
598 Background: Anti-EGFR therapies are recommended for metastatic colorectal cancer (mCRC) patients with confirmed wild-type RAS (exons 2, 3, 4 of KRAS and NRAS) status. There is limited published information on the prevalence of RAS mutations using real world data. The objective of this study was estimate the prevalence of RAS and BRAF mutations among patients with mCRC in the Middle East and Northern Africa (MENA) in an effort to inform the rationale for biomarker testing and treatment choice. Methods: The study included 1,669 patients from August 2013 to July 2015 with mCRC from Algeria, Bahrain, Egypt, Jordan, Kuwait, Lebanon, Libya, Morocco, Oman, Qatar, Saudi Arabia, and the United Arab Emeritus. Information on RAS mutation status was obtained from one pathology lab using High Resolution Melting Analysis. Extended RAS analysis was conducted in a subset of patients, including: overall RAS (exon 2, 3, 4 of KRAS and NRAS; n = 750), KRAS exon 2 (n = 750), KRAS exon 3 and 4 (n = 507), NRAS exon 2, 3, and 4 (n = 507), and BRAF exon 15 (n = 78). The proportion of patients with each mutation was summarized. Results: The overall RAS mutation in the full sample was 35.3% (n = 589/1669). The observed mutation for KRAS exon 2 in a subset of patients with extended RAS analysis (n = 750) was 32.4% (243/750). Out of the subjects with wild-type exon 2 (n = 507), the observed mutations rates were as follows: KRAS exon 4 (20/507 = 3.9%), KRAS exon 3 (13/507 = 2.6%), NRAS exon 2 (7/507 = 1.4%), NRAS exon 3 (6/507 = 1.2%), and NRAS exon 4 (0%). The prevalence of BRAF exon 15 was 3.8% (3/78). The most robust data on specific RAS mutations was obtained from Algeria, Egypt, and Saudi Arabia. The prevalence of KRAS exon 2 mutations in these countries was as follows: Algeria (n = 33/86 = 38.4%), Egypt (n = 83/303 = 27.4%), Saudi Arabia (n = 85/245 = 34.7%). Conclusions: To our knowledge, this is the first study to evaluate the prevalence of RAS and BRAF mutations in the Middle East using real world data. The results of this descriptive study illustrate that there is variation in the prevalence of RAS and BRAF mutations in MENA.