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Hulin, Cyrille, Thierry Facon, Chaim Shustik, Andrew Belch, Maria Teresa Petrucci, Ulrich Dührsen, Jin Lu et al. "Effect of Age on Efficacy and Safety Outcomes in Patients (Pts) with Newly Diagnosed Multiple Myeloma (NDMM) Receiving Lenalidomide and Low-Dose Dexamethasone (Rd): The First Trial". Blood 124, n. 21 (6 dicembre 2014): 81. http://dx.doi.org/10.1182/blood.v124.21.81.81.
Abstract (sommario):
Abstract Background: In the pivotal FIRST trial, a randomized, international, multicenter phase 3 study, continuous Rd compared with melphalan-prednisone-thalidomide (MPT) improved progression-free survival (PFS) which was the primary endpoint (HR = 0.72; P < 0.01). The interim overall survival (OS) analysis showed a 22% reduction in risk of death with continuous Rd vs. MPT (HR = 0.78; P = 0.02) (Facon, Blood 2013). This analysis evaluates outcomes based on age, which was a stratification parameter, and compared pts aged ≤ 75 yrs and > 75 yrs. Methods: Pts with NDMM were randomized to continuous Rd until progressive disease (PD) (N = 535); 18 cycles (72 weeks [wks]) of Rd (Rd18; N = 541); or 12 cycles (72 wks) of MPT (N = 547). Starting doses were reduced in pts aged > 75 yrs: dexamethasone (20 vs. 40 mg), melphalan (0.20 vs. 0.25 mg/kg), and thalidomide (100 vs 200 mg). The primary endpoint was PFS (continuous Rd vs. MPT) and the secondary endpoint were OS, overall response rate, time to response, duration of response, time to Tx failure, time to 2nd AMT, health-related quality of life, safety. Results: The proportion of pts aged > 75 yrs was > 34% across treatment (Tx) arms. In pts ≤ 75 yrs, 37% had ISS stage III vs. 51% in > 75 yrs. ECOG score ≥ 1 was observed in 74% and 69% of pts aged > 75 and ≤ 75 yrs, respectively. Severe renal impairment (CrCl < 30 mL/min) was observed in 14% of pts > 75 vs. 7% in ≤ 75 yrs. PFS and OS outcomes favored continuous Rd over MPT in both age groups. With a median follow-up of 37 months (mos), PFS was 27.4 mos in continuous Rd pts vs. 21.8 mos in MPT pts aged ≤ 75 yrs (HR = 0.68; P < 0.001); a trend for improved PFS was also seen for pts aged > 75 yrs (HR = 0.81; P = 0.11) (Table 1). PFS for continuous Rd vs. Rd18 pts was also increased in both age groups (HR = 0.68; P < 0.001 and HR = 0.75; P = 0.03, respectively). Response rates were consistently higher with continuous Rd vs. MPT in pts aged ≤ 75 yrs (77% vs. 66%; P < 0.001) and > 75 yrs (71% vs. 55%; P < 0.001). Duration of response with continuous Rd was longer vs. MPT in pts aged ≤ 75 yrs (40 vs. 22 mos) and pts > 75 yrs (31 vs. 24 mos). The interim analysis of OS showed an improved trend for continuous Rd vs. MPT in pts aged ≤ 75 yrs (HR = 0.77; P = 0.06) and > 75 yrs (HR = 0.80; P= 0.16). Grade 3–4 adverse events (AEs) in ≥ 10% of pts were similar across age subgroups (Table 2). Tx discontinuation due to AEs was comparable across the Tx groups and independent of age. Conclusions:Regardless of age (≤ 75 vs. > 75 yrs), continuous Rd was effective, increased PFS and interim OS, and was generally well tolerated vs. MPT in NDMM pts. Duration of response was improved with continuous Rd vs. MPT and Rd18, irrespective of age, and with a more profound benefit observed in younger pts. Continuous Rd represents a new clinical option and standard of care for these pts in the first-line setting. Abstract 81. Table 1 PFS, OS and Response Aged ≤ 75 yrs Aged > 75 yrs All pts ITT population Continuous Rd (n = 349) Rd18 (n = 348) MPT (n = 359) Continuous Rd (n = 186) Rd18 (n = 193) MPT (n = 188) Continuous Rd (n = 535) Rd18 (n = 541) MPT (n = 547) Median PFS, mos 27.4 21.3 21.8 21.2 19.4 19.2 25.5 20.7 21.2 PFS HR (95% CI); P-value Continuous Rd vs. Rd18 0.68 (0.55–0.83); P < 0.01 0.75 (0.58–0.98); P = 0.03 0.70 (0.60–0.82); P < 0.01 Continuous Rd vs. MPT 0.68 (0.56–0.83); P < 0.01 0.81 (0.62–1.05); P = 0.11 0.72 (0.61–0.85); P < 0.01 4-yr OS, % 66 61 58 47 47 39 59 56 51 OS HR (95% CI); P-value Continuous Rd vs. Rd18 0.88 (0.67–1.16); P = 0.36 0.94 (0.69–1.29); P = 0.70 0.90 (0.73–1.10); P = 0.31 Continuous Rd vs. MPT 0.77 (0.59–1.01); P = 0.06 0.80 (0.59–1.09); P = 0.16 0.78 (0.64–0.96); P = 0.02 Response rate (≥ PR), % 77 77 66 71 66 55 75 73 62 Duration of response (≥ PR), mos 40 23 22 31 20 24 35 22 22 CI, confidence interval; ITT, intent to treat; PR, partial response. Table 2 Grade 3–4 AEs Observed in ≥ 10% of Pts Aged ≤ 75 yrs Aged > 75 yrs Safety population, % Continuous Rd (n = 347) Rd18 (n = 348) MPT (n = 357) Continuous Rd (n = 185) Rd18 (n = 192) MPT (n = 184) Neutropenia 28 25 47 28 29 40 Thrombocytopenia 8 9 13 9 7 7 Anemia 18 12 20 19 23 17 Leukopenia 5 6 11 4 5 8 Infections 29 21 16 29 23 20 DVT and/or PE 10 6 8 7 8 4 Peripheral sensory neuropathy 1 1 10 1 0 8 Tx discontinuation due to AEs 28 18 28 32 25 30 DVT, deep-vein thrombosis; PE, pulmonary embolism. Disclosures Hulin: Celgene: Honoraria. Off Label Use: Lenalidomide used in newly diagnosed multiple myeloma patients. Facon:Celgene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Belch:Janssen, Celgene, Onyx: Honoraria. Petrucci:Celgene, Janssen-Cilag, Sanofi, Bristol-Myers Squibb: Honoraria. Dührsen:Celgene: Honoraria, Research Funding. Song:Celgene: Consultancy, Honoraria, Research Funding. Houck:Celgene: Employment. Chen:Celgene: Employment. Ervin-Haynes:Celgene: Employment.
2
Sergeev, V. A., K. Liou, P. T. Newell, S. I. Ohtani, M. R. Hairston e F. Rich. "Auroral streamers: characteristics of associated precipitation,convection and field-aligned currents". Annales Geophysicae 22, n. 2 (1 gennaio 2004): 537–48. http://dx.doi.org/10.5194/angeo-22-537-2004.
Abstract (sommario):
Abstract. During the long-duration steady convection activity on 11 December 1998, the development of a few dozen auroral streamers was monitored by Polar UVI instrument in the dark northern nightside ionosphere. On many occasions the DMSP spacecraft crossed the streamer-conjugate regions over the sunlit southern auroral oval, permitting the investigation of the characteristics of ion and electron precipitation, ionospheric convection and field-aligned currents associated with the streamers. We confirm the conjugacy of streamer-associated precipitation, as well as their association with ionospheric plasma streams having a substantial equatorward convection component. The observations display two basic types of streamer-associated precipitation. In its polewardmost half, the streamer-associated (field-aligned) accelerated electron precipitation coincides with the strong (≥2–7μA/m2) upward field-aligned currents on the westward flank of the convection stream, sometimes accompanied by enhanced proton precipitation in the adjacent region. In the equatorward portion of the streamer, the enhanced precipitation includes both electrons and protons, often without indication of field-aligned acceleration. Most of these characteristics are consistent with the model describing the generation of the streamer by the narrow plasma bubbles (bursty bulk flows) which are contained on dipolarized field lines in the plasma sheet, although the mapping is strongly distorted which makes it difficult to quantitatively interprete the ionospheric image. The convective streams in the ionosphere, when well-resolved, had the maximal convection speeds ∼0.5–1km/s, total field-aligned currents of a few tenths of MA, thicknesses of a few hundreds km and a potential drop of a few kV across the stream. However, this might represent only a small part of the associated flux transport in the equatorial plasma sheet.Key words. Ionosphere (electric fiels and currents). Magnetospheric physics (aurroal phenomena; energetic particles, precipitating)
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Pereira, Stephen P., Theresa B. Cassell, Jeffrey L. Engelman, Gordon E. Sladen, Gerard M. Murphy e R. Hermon Dowling. "Plasma Arachidonic Acid-Rich Phospholipids in Crohn's Disease: Response to Treatment". Clinical Science 91, n. 4 (1 ottobre 1996): 509–12. http://dx.doi.org/10.1042/cs0910509.
Abstract (sommario):
1. Increased concentrations of plasma polyunsaturated fatty acids have been implicated in the pathogenesis of Crohn's disease. However, it is not known whether there are corresponding changes in circulating phospholipids - the major source of fatty acids in the plasma. 2. Fasting plasma samples were obtained from 17 control subjects and 13 patients with active Crohn's disease [Simple Index of Crohn's Disease Activity (SICDA) >6] before, and 2 and 8 weeks after, treatment with either a peptide diet or oral prednisolone. 3. Before treatment, the Crohn's disease patients had mildly active disease (SICDA 9.9 ± 0.8, erythrocyte sedimentation rate 26.4 ± 6.5 mm/h, serum C-reactive protein 2.8 ± 0.4 mg/l). The proportions of the polyunsaturated phosphatidylcholine species, 16:0–20:4 (10.0 ± 0.7%) and 16:0–22:6 (7.1 ± 0.8%), were both significantly higher than those in healthy controls (7.6 ± 0.5%, P < 0.01 and 5.3 ± 0.5%, P < 0.05 respectively). 4. After 2 weeks treatment, the SICDA in the Crohn's disease patients decreased to 3.2 ± 0.6 (P < 0.0001 compared with the pretreatment value), and there were corresponding falls in the erythrocyte sedimentation rate (to 12.6 ± 2.7 mm/h, P < 0.05) and C-reactive protein concentration (to 1.7 ± 0.3 mg/l, P < 0.05)—these improvements being maintained at 8 weeks. There was also a fall to normal values in 16:0–20:4 (to 7.7 ± 0.6%, P < 0.01 compared with the pretreatment value) and in 16:0–22:6 (to 5.7 ± 0.5%, P not significant), by week 8. 5. The proportions of polyunsaturated phosphatidylcholine molecular species were increased in the plasma of patients with active Crohn's disease, but fell to normal levels during disease remission. These observations are consistent with the theory that, in active Crohn's disease, the mucosal phospholipids containing polyunsaturated fatty acids are increased, contribute to eicosanoid synthesis and ‘spill’ into the plasma.
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Gouw, Samantha C., H. Marijke van den Berg, Johannes Oldenburg, Jan Astermark, Philip G. de Groot, Maurizio Margaglione, Arthur R. Thompson et al. "F8 gene mutation type and inhibitor development in patients with severe hemophilia A: systematic review and meta-analysis". Blood 119, n. 12 (22 marzo 2012): 2922–34. http://dx.doi.org/10.1182/blood-2011-09-379453.
Abstract (sommario):
Abstract This systematic review was designed to provide more precise effect estimates of inhibitor development for the various types of F8 gene mutations in patients with severe hemophilia A. The primary outcome was inhibitor development and the secondary outcome was high-titer-inhibitor development. A systematic literature search was performed to include cohort studies published in peer-reviewed journals with data on inhibitor incidences in the various F8 gene mutation types and a mutation detection rate of at least 80%. Pooled odds ratios (ORs) of inhibitor development for different types of F8 gene mutations were calculated with intron 22 inversion as the reference. Data were included from 30 studies on 5383 patients, including 1029 inhibitor patients. The inhibitor risk in large deletions and nonsense mutations was higher than in intron 22 inversions (pooled OR = 3.6, 95% confidence interval [95% CI], 2.3-5.7 and OR = 1.4, 95% CI, 1.1-1.8, respectively), the risk in intron 1 inversions and splice-site mutations was equal (pooled OR = 0.9; 95% CI, 0.6-1.5 and OR = 1.0; 95% CI, 0.6-1.5), and the risk in small deletions/insertions and missense mutations was lower (pooled OR = 0.5; 95% CI, 0.4-0.6 and OR = 0.3; 95% CI, 0.2-0.4, respectively). The relative risks for developing high titer inhibitors were similar.
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Brown, Hannah, Nicholas Spies, Mark Zaydman e Christopher Farnsworth. "Hemoglobin A1c control is an independent predictor of circulating troponin concentrations using machine learning". American Journal of Clinical Pathology 160, Supplement_1 (1 novembre 2023): S141—S142. http://dx.doi.org/10.1093/ajcp/aqad150.305.
Abstract (sommario):
Abstract Diabetes mellitus (DM) is associated with multiple comorbidities that may precipitate cardiac damage and elevated cardiac troponin (cTn) concentrations including renal failure, hyperlipidemia (HLD), hypertension (HTN), coronary artery disease (CAD), and congestive heart failure (CHF). Diabetics >70 years old have a higher likelihood of adverse outcomes including major cardiovascular events and cardiac mortality. However, the risk to younger diabetic patients and the precipitating factor(s) that facilitate cardiac injury in those with DM are unknown. The objective of this study was to investigate factors predictive of cTn concentrations in young, relatively healthy diabetic patients. We collected 1,533 remnant plasma samples from outpatients between 06/22-09/22 with physician ordered hemoglobin A1c testing. cTn was measured using the Abbott ARCHITECT High Sensitivity Troponin-I assay (limit of detection = 1.7 ng/L, imprecision = 4.76% at 50 ng/L). Demographic information (sex, race, BMI) and pertinent medical history (diabetes, HTN, HLD, CAD, CHF) were collected from the electronic medical record, along with estimated glomerular filtration rate (eGFR) and hemoglobin A1c. Exclusion criteria included: patients with missing laboratory data, those undergoing cancer treatment, or a history of myocardial infarction/cardiomyopathy/ cardiac surgery. Troponin results were classified as normal- or high-risk using a cut-off of 10 ng/L for females and 12 ng/L for males, thresholds previously shown to correlate with incidence of cardiovascular disease risk within 15 years. Univariate statistics were calculated using bootstrap resampling. An XGBoost model was trained to predict high-risk troponinemia, and summary statistics were calculated on a held-out test set. Of the 1,135 patients that met inclusion criteria, 621 (54.7%) were female. The median age was 60 years (IQR: 49-69 years) and the median A1c was 6.2% (IQR: 5.8-7.0%). A total of 746 patients (65.7%) had a prior diabetes diagnosis, with 156 patients (13.7%) having prediabetes, 42 patients (3.7%) having Type 1, and 548 patients (48.3%) having Type 2. Median troponin concentration for patients with an A1c <5.7% was 1.6 ng/L (IQR: 0.8-3.4), 5.7-6.4% was 2.2 ng/L (IQR:1.3-4.8), and ≥6.5% was 2.9 ng/L (IQR: 1.6-6.7). Univariate analysis demonstrated significant differences in troponinemia by age (CI of difference: 4.4-8.9 years), A1c (0.2-0.7%), and eGFR (28-38mL/min/1.73m2). The machine learning model demonstrated strong predictive capacity (sensitivity: 0.74, specificity: 0.86, PPV: 0.5, NPV: 0.92, area under ROC curve: 0.91). The features with the greatest impact on area under the ROC curve when removed were eGFR, Age, A1c, and CHF, suggesting a combination of clinical and laboratory variables can be used to predict circulating troponin concentrations in outpatients. Results of both univariate and multivariate analyses suggest that A1c control is an independent contributor to cTn concentrations. Ultimately, this study provides evidence that glucose control may be associated with cardiac damage and future cardiovascular events, warranting longitudinal outcome studies.
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Liu, Xiang Chun, Feng Gao, Ming Zhao e Chang Sheng Tian. "Low-Temperature Sintering and Dielectric Properties of (Zn1-xMgx)TiO3". Materials Science Forum 546-549 (maggio 2007): 2215–18. http://dx.doi.org/10.4028/www.scientific.net/msf.546-549.2215.
Abstract (sommario):
The dielectric ceramics comprised of (Zn1-xMgx)TiO3 (x=0.1~0.5, abbreviated to ZMT) were developed by conventional mixed-oxide method combined with a semi-chemical processing. V2O5 was used as sintering aids to lower the sintering temperature of ceramics. The results showed that the hexagonal phase stability region extended from 900 to 1150°C as the amount of magnesium increased. The densification temperature of ZMT ceramics could be reduced from 1200 to 875°C by V2O5 additions and using semi-chemical processing, the relative density of ZMT ceramics with 1.00wt% V2O5 addition reach 95% at 875°C. The dielectric properties of ZMT were measured at different frequencies and the results showed that there existed a decreasing tendency of the loss tangents (tg δ) with increasing measuring frequency. It is concluded that εr=22 and tg δ= 5.7×10-4 can be obtained for ZMT ceramics at sintering temperature 875°C.
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Soyal, M., M. Kaya e N. M. Çelik. "Examining the impact of musculus palmaris longus on serve speed and on certain motoric properties in tennis players". Pedagogics, psychology, medical-biological problems of physical training and sports 23, n. 4 (28 agosto 2019): 202–8. http://dx.doi.org/10.15561/18189172.2019.0407.
Abstract (sommario):
Purpose: The aim of this study is to examine the impacts of existence or absence of musculus palmaris longus (MPL) on serve speed and certain motoric properties in the tennis players. Material: In the study, 25 male volunteers participated, who are playing tennis at university level and in whom the existence of musculus palmaris longus was checked. The ages of volunteers, who participate in tennis activities under licenses, vary between 18 and 25 and they have no disability or illness in the upper extremity. The experimental group (n=7) is comprised of individuals, who do not have musculus palmaris longus, while the control group (n=18) is comprised of individuals having musculus palmaris longus. Results: The age averages of the groups participating in the study was 21, 89±2, 246 years old for the group with musculus palmaris longus, while it was 22, 00±2, 517 years old for the participants without the musculus palmaris longus; as per their average height, it was 174, 94±5, 713 cm for the group with the musculus palmaris longus, while it was 174, 71±3, 546 cm for the participants without the musculus palmaris longus; the body weight average was 70, 83±5, 79 kg for the participants with musculus palmaris longus, while it was 72, 14±4, 059 kg for the participants without the musculus palmaris longus; sports-age average was 13, 00±1, 645 years for the ones with musculus palmaris longus, while it was 12, 29±1, 380 years for the participants without musculus palmaris longus. It was determined that there was statistically significant difference for the serve speed (p<0, 001) and the hand flexion strength (p<0, 05) parameters of the participants; however, there was statistically no significant difference (p>0, 05) in other parameters. Conclusions: As the conclusion, existence of musculus palmaris longus in tennis players positively influences the hand wrist flexion strength, however, it negatively influences the serve speed.
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DESAI, MONIL A., KAMLESH A. SONI, RAMAKRISHNA NANNAPANENI, M. WES SCHILLING e JUAN L. SILVA. "Reduction of Listeria monocytogenes Biofilms on Stainless Steel and Polystyrene Surfaces by Essential Oils†". Journal of Food Protection 75, n. 7 (1 luglio 2012): 1332–37. http://dx.doi.org/10.4315/0362-028x.jfp-11-517.
Abstract (sommario):
Plant-derived essential oils were tested for their ability to eliminate biofilms of Listeria monocytogenes on polystyrene and stainless steel surfaces. Various concentrations of essential oils were tested with different contact times on biofilms of various ages. Preliminarily screening of nine essential oils and related phenolic compounds in a disk diffusion assay revealed that thyme oil, oregano oil, and carvacrol had the highest antimicrobial activity. Further screening of these three compounds against 21 L. monocytogenes strains representing all 13 serotypes indicated some strain-specific variations in antimicrobial activity. For 1-day-old biofilms of mixed L. monocytogenes strains produced at 22°C on polystyrene microtiter plates, only 0.1% concentrations of thyme oil, oregano oil, and carvacrol were needed to eliminate 7 log CFU per well. On the stainless steel coupons, a 0.5% concentration of these compounds was adequate to completely eliminate 4-day-old biofilms at 7 log CFU per coupon. Our findings indicate that these compounds are potential candidates for elimination of L. monocytogenes biofilms on stainless steel and polystyrene surfaces.
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Harrison, S. M., e D. M. Bers. "Influence of temperature on the calcium sensitivity of the myofilaments of skinned ventricular muscle from the rabbit." Journal of General Physiology 93, n. 3 (1 marzo 1989): 411–28. http://dx.doi.org/10.1085/jgp.93.3.411.
Abstract (sommario):
The steady-state myofilament Ca sensitivity was determined in skinned cardiac trabeculae from the rabbit right ventricle (diameter, 0.13-0.34 mm) at 36, 29, 22, 15, 8, and 1 degree C. Muscles were stimulated to 0.5 Hz and stretched to a length at which maximum twitch tension was generated. The preparation was then skinned with 1% vol/vol Triton X-100 in a relaxing medium (10 mM EGTA, pCa 9.0). Each preparation was exposed to a series of Ca-containing solutions (pCa 6.3-4.0) at two of the six temperatures studied (temperature was regulated to +/- 0.1 degree C). The pCa values (mean +/- SD, n = 6) corresponding to half maximal tension at 36, 29, 22, 15, 8, and 1 degree C were 5.47 +/- 0.07, 5.49 +/- 0.07, 5.34 +/- 0.05, 5.26 +/- 0.09, 4.93 +/- 0.06, and 4.73 +/- 0.04, respectively. Mean (+/- SD) maximum tension (Cmax) developed by the preparation as a percentage of that at 22 degrees C was 118 +/- 10, 108 +/- 5, 74 +/- 6, 57 +/- 7, and 29 +/- 5% at 36, 29, 15, 8, and 1 degree C, respectively. As cooling led to a shift of Ca sensitivity towards higher [Ca2+] and a reduction of Cmax, the Ca sensitivity curves over this range of temperatures do not cross over as has been described for canine Purkinje fibers (Fabiato 1985). Since tension is decreased by cooling at all levels of [Ca2+] it is unlikely that changes in myofilament Ca sensitivity play a role in the large hypothermic inotropy seen in rabbit ventricular muscle. The increase in sensitivity of the myofilaments to Ca on warming from 1 to 29 degrees C might be related to the increase in force seen on rewarming from a rapid cooling contracture in intact rabbit ventricular muscle.
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Dorn, G. W., J. Robbins, N. Ball e R. A. Walsh. "Myosin heavy chain regulation and myocyte contractile depression after LV hypertrophy in aortic-banded mice". American Journal of Physiology-Heart and Circulatory Physiology 267, n. 1 (1 luglio 1994): H400—H405. http://dx.doi.org/10.1152/ajpheart.1994.267.1.h400.
Abstract (sommario):
Using an adult mouse aortic-banded model of pressure-overload hypertrophy and isolated cardiomyocyte mechanics studies, we examined the hypothesis that contractile depression is due to altered cardiac contractile proteins rather than changes in left ventricular (LV) geometry, loading, or the extracellular matrix. FVB mice were banded at the transverse aortic arch or sham operated and studied after 7 days. In nine animals the gradient across the aortic band averaged 47 +/- 4 mmHg. Compared with sham-operated controls, banded animals had increased LV weight-to-body weight ratio (2.8 +/- 0.1 and 3.5 +/- 0.1, respectively; P = 0.035). Left ventricles from additional age-matched groups of mice that underwent identical surgical procedures were examined for altered transcriptional control of myosin heavy chains (MHCs). beta-MHC protein content increased (15 +/- 2%) vs. shams (3.8 +/- 2%; P = 0.004). Dot blots of LV RNA showed a corresponding increase in beta-MHC transcripts in banded animals (15.8 +/- 2%) vs. controls (5.7 +/- 2%; P = 0.012). Contractile performance was assessed using enzymatically disaggregated isolated LV myocytes paced at 0.5 Hz. There was no difference in percentage myocyte shortening between banded (8.6 +/- 0.5%) and control (9.1 +/- 0.5%) animals. However, maximal velocity of contraction was depressed after aortic banding (129 +/- 11 vs. 233 +/- 28 microns/s; P = 0.007), as was velocity of relaxation (105 +/- 11 vs. 188 +/- 22 microns/s; P = 0.007). These results suggest that depressed myocyte contractility after induction of pressure-overload hypertrophy in aortic-banded mice may be, in part, a consequence of transcriptional upregulation of the beta-MHC.
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Eskens, F., C. N. Oldenhuis, P. Bhargava, W. Loos, B. Esteves, L. van Doorn, M. M. Cotreau, R. Dhillon, J. A. Gietema e E. De Vries. "A phase Ib, open-label, dose-escalation study of tivozanib and FOLFOX6 in patients (pts) with advanced gastrointestinal (GI) tumors." Journal of Clinical Oncology 29, n. 4_suppl (1 febbraio 2011): 549. http://dx.doi.org/10.1200/jco.2011.29.4_suppl.549.
Abstract (sommario):
549 Background: Tivozanib (AV-951), a highly potent and selective tyrosine kinase inhibitor of vascular endothelial growth factor receptors (VEGFR)-1, -2, and -3, has shown additive antitumor activity with fluorouracil (5-FU) in preclinical studies. An open-label phase Ib study was conducted to determine the maximum tolerated dose (MTD), dose-limiting toxicities (DLTs), pharmacokinetics (PK), and antitumor activity of escalating doses of tivozanib combined with standard-dose FOLFOX6 (i.e., oxaliplatin, leucovorin, and 5-FU) in pts with advanced GI tumors. Methods: Tivozanib was administered orally once daily in 4-week cycles (3 weeks on, 1 week off), with FOLFOX6 administered on days 1 and 15 of each cycle. Pts were allowed to continue tivozanib following discontinuation of FOLFOX6. Results: 22 pts (14 male/8 female; median age of 58 years [range, 40-75]) received 0.5 mg (n = 9), 1.0 mg (n = 3), or 1.5 mg (n = 10) tivozanib plus FOLFOX6. Pts received a median of 8.1 weeks (range, 0.1 - 43.1) of treatment. DLTs were observed in 2 pts receiving 0.5 mg tivozanib (reversible grade 3 diarrhea and grade 3 and 4 transaminase elevations, respectively) and in 2 pts receiving 1.5 mg tivozanib (reversible grade 3 seizures and grade 3 vertigo, respectively). Other grade 3/4 drug-related adverse events (AEs) included neutropenia, fatigue, and hypertension (n = 2 each); and pyrexia, pulmonary embolism, and thrombosis (n = 1 each). There was no indication that drug-related AEs in this study were more frequent or severe than those observed with tivozanib or FOLFOX6 alone. The MTD was 1.5 mg tivozanib with full dose FOLFOX6. The PK profiles of tivozanib, oxaliplatin, and 5-FU will be presented. Several durable partial responses were observed. Additional safety and efficacy data are being obtained in 8 pts currently being treated at the 1.5-mg dose level. Conclusions: The combination of tivozanib and FOLFOX6 is tolerable and safe, with tivozanib given at its recommended dose of 1.5 mg. Observed clinical activity merits further exploration in several GI tumors, and these studies are being planned. [Table: see text]
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Bechman, Katie, Benjamin D. Clarke, Andrew I. Rutherford, Mark Yates, Elena Nikiphorou, Mariam Molokhia, Sam Norton, Andrew P. Cope, Kimme L. Hyrich e James B. Galloway. "Polypharmacy is associated with treatment response and serious adverse events: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis". Rheumatology 58, n. 10 (14 aprile 2019): 1767–76. http://dx.doi.org/10.1093/rheumatology/kez037.
Abstract (sommario):
Abstract Objective To evaluate whether polypharmacy is associated with treatment response and serious adverse events (SAEs) in patients with RA using data from the British Society for Rheumatology Biologics Register (BSRBR-RA). Methods The BSRBR-RA is a prospective observational cohort study of biologic therapy starters and a DMARD comparator arm. A logistic regression model was used to calculate the odds of a EULAR ‘good response’ after 12 months of biologic therapy by medication count. Cox proportional hazards models were used to identify risk of SAEs. The utility of the models were compared with the Rheumatic Disease Comorbidity Index using Receiver Operator Characteristic and Harrell’s C statistic. Results The analysis included 22 005 patients, of which 83% were initiated on biologics. Each additional medication reduced the odds of a EULAR good response by 8% [odds ratios 0.92 (95% CI 0.91, 0.93) P < 0.001] and 3% in the adjusted model [adjusted odds ratios 0.97 (95% CI 0.95, 0.98) P < 0.001]. The Receiver Operator Characteristic demonstrated significantly greater areas under the curve with the polypharmacy model than the Rheumatic Disease Comorbidity Index. There were 12 547 SAEs reported in 7286 patients. Each additional medication equated to a 13% increased risk of an SAE [hazard ratio 1.13 (95% CI 1.12, 1.13) P < 0.001] and 6% in the adjusted model [adjusted hazard ratio 1.06 (95% CI 1.05, 1.07) P < 0.001]. Predictive values for SAEs were comparable between the polypharmacy and Rheumatic Disease Comorbidity Index model. Conclusion Polypharmacy is a simple but valuable predictor of clinical outcomes in patients with RA. This study supports medication count as a valid measure for use in epidemiologic analyses.
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Fernandes, Ilha G., Maria C. G. S. Macedo, Matheus A. Souza, Gabriela Silveira-Nunes, Michelle C. S. A. Barbosa, Andreia C. C. Queiroz, Edgar R. Vieira e Alexandre C. Barbosa. "Does 8-Week Resistance Training with Slow Movement Cadenced by Pilates Breathing Affect Muscle Strength and Balance of Older Adults? An Age-Matched Controlled Trial". International Journal of Environmental Research and Public Health 19, n. 17 (31 agosto 2022): 10849. http://dx.doi.org/10.3390/ijerph191710849.
Abstract (sommario):
This study investigated the balance and dorsiflexion strength of older adults after eight weeks of resistance training, with the exercise velocity cadenced by the Pilates breathing technique and the volume modulated by the session duration. Forty-four older adults were divided into two groups: resistance training (TR; n = 22) and resistance training with the Pilates breathing technique cadencing all exercises (TR + P; n = 22), both during eight weeks. The total exercising volume was controlled by time of execution (50 min/session). The dorsiflexion strength and balance were assessed. The RT group showed higher dorsiflexion strength after the protocol: Right (RT = 29.1 ± 7.7 vs. RT + P = 22.9 ± 5.2, p = 0.001) and Left (RT = 29.5 ± 6.9 vs. RT + P = 24.0 ± 5.2, p = 0.001). All balance parameters were improved in RT + P group compared to its own baseline: Path Length (cm) (pre = 71.0 ± 14.3 vs. post = 59.7 ± 14.3, p = 0.003); Sway Velocity (cm/s) (pre = 3.6 ± 0.7; post = 2.9 ± 0.7; p = 0.001); Sway Area (cm2) (pre = 8.9 ± 5.3 vs. post = 5.7 ± 2.1, p = 0.003); Excursion Medio Lateral (cm) (pre = 3.0 ± 0.7 vs. post = 2.6 ± 0.5 cm, p = 0.002); and Excursion AP (cm) (pre = 3.6 ± 1.4 vs. post = 2.8 ± 0.7 cm, p = 0.010). Resistance training using slower velocity movement cadenced by Pilates breathing technique produced balance improvements compared to baseline (moderate to large effect sizes), but no between-group effect was observed at the end of the protocol. The dorsiflexion strength was higher in the RT group compared to RT + P group.
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Wennström, Ulfstand, Urban Bergsten e Jan-Erik Nilsson. "Early seedling growth of Pinus sylvestris after sowing with a mixture of stand and orchard seed in dense spacings". Canadian Journal of Forest Research 31, n. 7 (1 luglio 2001): 1184–94. http://dx.doi.org/10.1139/x01-050.
Abstract (sommario):
Effects on early seedling growth of seeding stand and orchard seed of Pinus sylvestris L. in different mixtures (100, 75, 50, 25, and 0% of orchard seed) at 4-cm target spacing were quantified in one nursery and one field experiment during a 2- and 5-year period, respectively. In the field experiment, 50% mixtures at 8- and 12-cm target spacing were also studied. Seedlings from orchard seeds (OS) had in general higher growth rate than seedlings from stand seed (SS). In the nursery experiment, OS were 25% taller, had 41% larger above-soil biomass, and 18% larger root biomass than SS after 2 years when sown separately. However, root/shoot ratio was 26% less and the slenderness value (height/diameter ratio) was 11% greater for OS in comparison with SS. Stand seed in high competition, compared with low competition (mixture 75% vs. mixture 0%), were 11% taller, had 15% greater slenderness value, and 25% less root biomass after 2 years. OS had 9% greater slender value in mixture 100% compared with the 25% mixture. In the field experiment, the tallest OS in each plot were 22% taller and the largest OS had 103% larger stem volume than the tallest or largest SS when sown separately after 5 years. After a height-selection thinning to one seedling per plot at year five, 79% of the seedlings in 50% mixtures would be OS. Seedlings sown in 12-cm spacing were 69% taller and had 527% larger stem volume than seedlings in 4-cm spacing after 5 years. The investigation supports that orchard and stand seed could be direct seeded in a mixture. Low dosages of the more expensive orchard seeds could be used to obtain growth advantages. Stand seeds should be added to increase the number of seedlings to the desired spacing.
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Marchessaux, Guillaume, Bruno Belloni, Justine Gadreaud e Delphine Thibault. "Predation assessment of the invasive ctenophore Mnemiopsis leidyi in a French Mediterranean lagoon". Journal of Plankton Research 43, n. 2 (4 febbraio 2021): 161–79. http://dx.doi.org/10.1093/plankt/fbab002.
Abstract (sommario):
Abstract Since 2000, the invasive ctenophore Mnemiopsis leidyi has been recorded in Mediterranean brackish lagoons. Quantitative data on its feeding behavior (i.e. potential ecological impact) in these particular environments are non-existent. In this study, we describe in situ predation dynamics of M. leidyi in the Berre Lagoon (south-eastern France) over a 22-month survey. Ctenophores were fixed in a solution of formalin in brackish water, allowing the study of the prey items in the gastric cavities at different time scales. The number of prey items ingested is influenced by the ctenophore biovolume, from 8 (0.5 mL) to 1 207 prey ind−1 (35 mL), and by temperature of 3.4°C (2 ± 2 prey ind−1) to 23.2°C (517 ± 295 prey ind−1). Gut evacuation time is strongly related to temperature and ranged from 80 (25°C) to 160 min (9°C). Mnemiopsis leidyi diet changed seasonally following in situ concentrations of prey. The less mobile preys such as mollusks and barnacles were the most impacted. The ctenophore predation pressure on the zooplankton assemblage could lead at time to a release of grazing pressure on phytoplankton and favor the eutrophication of the lagoon.
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Rovo, Alicia, Thomas Daikeler, Joerg Halter, Dominik Heim, Jan Dirk Studt, Michael Medinger, Caroline Arber et al. "Late Altered Organ Function in Long Term Survivors after Allogeneic HSCT: A Paired Comparison with Their Identical Sibling Donor". Blood 112, n. 11 (16 novembre 2008): 4298. http://dx.doi.org/10.1182/blood.v112.11.4298.4298.
Abstract (sommario):
Abstract Long term prognosis following allogeneic hematopoetic cell transplantation (HSCT) has greatly improved over the last decades. Therefore, interest of the general health status has become a major topic in the surveillance of long term survivors. To assess health status in very long term survivors (>10 years follow-up) we conducted a prospective, single center cross-sectional study, evaluating simultaneously 44 recipients and their respective sibling donors. A comprehensive clinical and biological examination was performed. We compared here in a paired analysis the results of routine clinical chemistry tests between recipients and their respective donor (table 1). At the time of this study, recipients and donors had a median age of 44.3 (24–63) and 43.4 (22–61) years respectively, and a median time of 17.5 (11–26) years since HSCT; 22/44 (50%) recipients had chronic graft-versus-host disease (cGVHD). Performance status demonstrated that 81/88 (92%) participants had a Karnofsky Score of 100%, reflecting the overall good clinical condition of both, recipients and donors (p>0.10). However, clinical chemistry tests of the recipients were systematically abnormal, with increased C-reactive protein (CRP), liver tests, lipids, von Willebrand factor antigen (vWF), creatinine, and decreased albumin, and glomerular filtration rate (GFR), compared with the donors (p<0.05; table 1). In the recipients, increased CRP, creatinine, vWF and decreased GFR were associated with chronic GvHD (p<0.05). For the other parameters no correlation with transplant related factors were found. Furthermore, we defined a scoring system to detect organ dysfunctions. All values out of range were allocated with one point. Included parameters were: high CRP, decreased GFR, low albumin, increased vWF, abnormal liver tests and dyslipidemia We compared recipients/donors with a score of ≥2 to those with a score below this value. An abnormal score was observed in 28/44 (64%), recipients, and in 7/44 (16%) donors (p<0.0001). More recipients with cGVHD had an abnormal score (13/22; 59%) compared to recipients without (5/22; 23%; p= 0.014). In conclusion, using a unique design comparing recipients with their respective donor, we demonstrate that an altered organ function may exist in clinically healthy very long term survivors. In part, this altered organ function is attributed to cGVHD reflected by an ongoing inflammatory process even in patients off immunosuppression. The clinical significance of the altered organ function not explained by cGVHD needs to be further investigated. Table 1: Clinical chemistry parameters: comparison between long-term survivors and their respective donor (with and without GvHD). Parameter Donors N 44 Recipients P-values donors versus recipients All N 44 with GVHD N 22 without GVHD N 22 All recipients with/without GVHD C-Reactive Protein (CRP) 1.0 (0.5–38.1) 3.7 (0.5–79.2) 4.5 (0.9–79.2) 1.2 (0.5–11.0) 0.034 0.001/0.125 Creatinine 66 (45–93) 79 (44–206) 88 (55–206) 77 (44–103) 0.0001 <0.0001/0.007 Glomerular Filtration Rate (GFR) 107 (72–144) 82 (30–141) 77 (30–124) 95 (66–141) <0.0001 <0.0001/0.034 Albumin 41 (29–46) 40 (31–45) 38 (31–43) 40 (32–45) 0.009 0.021/0.361 Bilirubine 9.5 (5–29) 8.0 (5–20) 8.0 (5–17) 7.0 (5–20) 0.020 0.213/0.053 ASAT 22 (16–64) 27.5 (15–65) 26 (20–65) 28 (15–44) 0.0004 0.002/0.013 ALAT 22 (10–101) 25.5 (12–72) 27 (12–70) 23 (12–72) 0.037 0.030/0.161 Gamma-GT 18 (9–140) 31 (10–319) 30 (11–319) 32 (10–91) 0.0003 0.002/0.005 Alkaline Phosphatase 56 (32–155) 69 (39–222) 70 (39–222) 68 (41–120) 0.003 0.016/0.034 Triglicerides 1.0 (0.45–3.9) 1.5 (0.53–8.9) 1.5 (0.53–8.9) 1.6 (0.69–3.7) 0.011 0.208/0.007 Cholesterol 4.7 (3.1–9.3) 5.1 (2.7–7.8) 5.0 (2.7–7.8) 5.3 (3.7–6.4) 0.118 0.407/0.058 HDL-cholesterol 1.6 (1.0–3.2) 1.5 (0.6–2.5) 1.5 (0.6–2.5) 1.5 (1.0–2.2) 0.037 0.213/0.124 Chol/HDL-chol. Ratio 2.9 (1.7–8.6) 3.2 (1.8–8.7) 3.1 (1.8–8.7) 3.4 (1.8–5.7) 0.022 0.094/0.047 LDL-cholesterol 2.4 (1.4–7.7) 2.8 (1.07–4.8) 2.7 (1.1–4.8) 2.9 (1.1–3.9) 0.126 0.284/0.145 Von Willebrand factor Antigen (vWF) 97.5 (55–188) 126 (51–296) 139 (51–296) 108 (51–235) 0.006 0.002/0.173
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Minsky, B. D., L. Coia, D. G. Haller, J. Hoffman, M. John, J. Landry, T. M. Pisansky et al. "Radiation therapy for rectosigmoid and rectal cancer: results of the 1992-1994 Patterns of Care process survey." Journal of Clinical Oncology 16, n. 7 (luglio 1998): 2542–47. http://dx.doi.org/10.1200/jco.1998.16.7.2542.
Abstract (sommario):
PURPOSE To determine the US national practice standards for patients with adenocarcinoma of the rectum treated in radiation oncology facilities. MATERIALS AND METHODS A national survey of 57 institutions identified 507 eligible patients who received radiation therapy as a component of their treatment for rectal cancer. A stratified two-stage cluster sampling with simple random sampling at each stage for each stratum was used and on-site surveys were performed. RESULTS Of the 507 patients, 378 (75%) received postoperative therapy, 110 (22%) received preoperative therapy, 17 (2%) received both preoperative and postoperative therapy, and less than 0.5% received intraoperative radiation alone. To more accurately assess the utilization of modern radiation techniques as well as recommendations of the National Cancer Institute (NCI)-sponsored, randomized, postoperative, adjuvant combined modality therapy rectal cancer trials into current practice, the analysis was limited to the 243 (48%) patients with tumor, node, and metastasis staging system classification T3 and/or N1-2M0 disease who underwent conventional surgery with negative margins. Although only 7% were treated on a clinical trial, 90% received chemotherapy for a median of 21 weeks. Most were treated with modern radiation treatment techniques. In contrast, techniques to identify and help exclude the small bowel from the radiation field were not routinely used. CONCLUSION Despite the fact that only 7% of patients with T3 and/or N1-2M0 disease were treated on a clinical trial, such trials appear to have resulted in a positive influence on the standard of practice within the oncology community. Although there are still some deficiencies, the majority of these patients received combined modality therapy and were treated with modern radiation therapy techniques.
18
Niu, Xiaoying, Wei Pu, Pingqing Fu, Yang Chen, Yuxuan Xing, Dongyou Wu, Ziqi Chen et al. "Fluorescence characteristics, absorption properties, and radiative effects of water-soluble organic carbon in seasonal snow across northeastern China". Atmospheric Chemistry and Physics 22, n. 21 (3 novembre 2022): 14075–94. http://dx.doi.org/10.5194/acp-22-14075-2022.
Abstract (sommario):
Abstract. Water-soluble organic carbon (WSOC) in the cryosphere can significantly influence the global carbon cycle and radiation budget. However, WSOC in the snowpack has received little scientific attention to date. This study reports the fluorescence characteristics, absorption properties, and radiative effects of WSOC based on 34 snow samples collected from sites in northeastern China. A significant degree of regional WSOC variability is found, with concentrations ranging from 0.5±0.2 to 5.7±3.7 µg g−1 (average concentration: 3.6±3.2 µg g−1). The three principal fluorescent components of WSOC are identified as (1) the high-oxygenated humic-like substances (HULIS-1) of terrestrial origin, (2) the low-oxygenated humic-like substances (HULIS-2) of mixed origin, and (3) the protein-like substances (PRLIS) derived from autochthonous microbial activity. In southeastern Inner Mongolia (SEIM), a region dominated by desert and exposed soils, the WSOC exhibits the highest humification index (HIX) but the lowest fluorescence (FI) and biological (BIX) indices; the fluorescence signal is mainly attributed to HULIS-1 and thus implicates soil as the primary source. By contrast, the HIX (FI and BIX) value is the lowest (highest), and the percentage of PRLIS is the highest in the remote area of northeastern Inner Mongolia (NEIM), suggesting a primarily biological source. For south and north of northeastern China (SNC and NNC), both of which are characterized by intensive agriculture and industrial activity, the fluorescence signal is dominated by HULIS-2, and the HIX, FI, and BIX values are all moderate, indicating the mixed origins for WSOC (anthropogenic activity, microbial activity, and soil). We also observe that, throughout northeastern China, the light absorption of WSOC is dominated by HULIS-1, followed by HULIS-2 and PRLIS. The contribution of WSOC to albedo reduction (average concentration: 3.6 µg g−1) in the ultraviolet–visible (UV–Vis) band is approximately half that of black carbon (BC average concentration: 0.6 µg g−1). Radiative forcing is 3.8 (0.8) W m−2 in old (fresh) snow, equating to 19 % (17 %) of the radiative forcing of BC. These results indicate that WSOC has a profound impact on snow albedo and the solar radiation balance.
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Angelucci, Emanuele, Pietro Muretto, Antonio Nicolucci, Donatella Baronciani, Buket Erer, Javid Gaziev, Marta Ripalti et al. "Effects of iron overload and hepatitis C virus positivity in determining progression of liver fibrosis in thalassemia following bone marrow transplantation". Blood 100, n. 1 (1 luglio 2002): 17–21. http://dx.doi.org/10.1182/blood.v100.1.17.
Abstract (sommario):
Abstract To identify the role of iron overload in the natural history of liver fibrosis, we reviewed serial hepatic biopsy specimens taken annually from patients cured of thalassemia major by bone marrow transplantation. The patients underwent transplantation between 1983 and 1989 and did not receive any chelation or antiviral therapy. Two hundred eleven patients (mean age, 8.7 ± 4 years) were evaluated for a median follow-up of 64 months (interquartile range, 43-98 months) by a median number of 5 (interquartile range, 3-6) biopsy samples per patient. Hepatic iron concentration was stratified by tertiles (lower, 0.5-5.6 mg/g; medium, 5.7-12.7 mg/g; upper, 12.8-40.6 mg/g dry weight). Forty-six (22%) patients showed signs of liver fibrosis progression; the median time to progression was 51 months (interquartile range, 36-83 months). In a multivariate Cox proportional hazard model, the risk for fibrosis progression correlated to medium hepatic iron content (hazard rate, 1.9; 95% confidence interval [CI], 0.74-5.0), high hepatic iron content (hazard rate, 8.7; 95% CI, 3.6-21.0) and hepatitis C virus (HCV) infection (hazard rate, 3.1; 95% CI, 1.5-6.5). A striking increase in the risk for progression was found in the presence of both risk factors. None of the HCV-negative patients with hepatic iron content lower than 16 mg/g dry weight showed fibrosis progression, whereas all the HCV-positive patients with hepatic iron concentration greater than 22 mg/g dry weight had fibrosis progression in a minimum follow-up of 4 years. Thus, iron overload and HCV infection are independent risk factors for liver fibrosis progression, and their concomitant presence results in a striking increase in risk.
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Sasaki, Koji, Nina Shah, Qaiser Bashir, Chitra M. Hosing, Uday R. Popat, Yago Nieto, Simrit Parmar et al. "Outcome of Patients with Light Chain Multiple Myeloma Compared to IgG/IgA Myeloma after Autologous Stem Cell Transplant". Blood 126, n. 23 (3 dicembre 2015): 3194. http://dx.doi.org/10.1182/blood.v126.23.3194.3194.
Abstract (sommario):
Abstract Introduction: High-dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto-HCT) is the standard of care for younger patients with newly diagnosed multiple myeloma (MM). In approximately 15% of MM patients the monoclonal (M) spike consists of k or l light chains only as opposed to heavy + light chains. It remains unclear whether light chain (LC) MM has a different prognosis compared to other monoclonal protein subtypes after an auto-HCT. Methods: We retrospectively analyzed 1067 patients with MM who underwent auto-HCT between January 1, 2004 and January 1, 2011 at our institution. We evaluated the outcome of newly diagnosed patients with LCMM and compared it to patients with IgG or IgA MM, who underwent an auto-HCT after induction therapy. Primary endpoints were complete remission (CR), progression-free survival (PFS) and overall survival (OS) from the date of auto-HCT. Kaplan-Meier analysis with the log-rank test was performed for univariate comparison of survival. Cox proportional hazards regression method was used for univariate and multivariate analyses. Results: Of 1067 patients who underwent auto-SCT during the period, 223 underwent auto-SCT after relapse, and were excluded. From the remaining 844 who underwent auto-SCT in first remission, we excluded 102 patients (AL amyloidosis 60, POEMS and other plasma cell disorders 10, non-secretory MM 15, IgD 10, IgM 6 and IgE 1) from the analysis. The remaining 742 patients were divided as follows: IgA, 162 patients (22%); IgG, 444 (60%) and LC, 136 (18%). Baseline patient characteristics are described in Table 1. Patients with LCMM were younger and had a higher CR rate to induction. Median follow-up for the entire cohort after auto-HCT was 38 months (range, 0.2-87.0). Post auto-HCT, 28% with IgG/IgA MM and 38% with LCMM achieved a CR (p=0.015). Median PFS was 26.0 months and 27.7 months in IgG/IgA MM and LCMM groups, respectively (p= 0.742). Median OS was not reached and 71.1 months in IgG/IgA MM and LCMM groups, respectively (p= 0.18, Figure 1). Multivariate Cox regression analysis for PFS identified <PR after auto-SCT, non-diploid karyotype, and induction chemotherapy without thalidomide or bortezomib as adverse prognostic factors. Multivariate Cox regression analysis for OS identified presence of hypodiploidy or monosomy 13/del13, higher lactate dehydrogenase pre-transplant, lower hemoglobin pre-transplant, and <PR after auto-HCT as adverse prognostic factors. M protein subtype did not affect PFS (hazard ratio [HR], 1.040; 95% confidence interval [CI], 0.825-1.311; p=0.742) or OS (HR, 1.313; 95% CI, 0.874-1.971; p=0.190). Conclusions: Patients with LCMM have a higher CR rate after auto-HCT, but their PFS and OS were similar to patients with IgG/IgA MM. Table 1. Patient Characteristics Variables, No. (%)/median (range) IgG/IgA myelomaN= 606 Light chain myelomaN= 136 P Median age at transplant, (y) 59 (31-80) 56 (32-78) .004 Age >65 years 138 (23) 23 (17) .134 Male 357 (59) 74 (54) .337 Ethnicity .731 Caucasian 399 (66) 94 (69) African American 99 (16) 22 (16) Mixed 87 (14) 18 (13) Asian 16 (3) 2 (2) Cytogenetic abnormalities at diagnosis by conventional cytogenetics Diploid 180 (30) 36 (27) .159 Hyperdiploid 93 (15) 9 (7) .008 Hypodiploid 27 (5) 11 (8) .082 t(11;14) 4 (1) 3 (2) .092 Monosomy 13 / del 13 44 (7) 9 (7) .789 Other high-risk abnormalities 2 (0) 1 (1) .456 Induction chemotherapy Bortezomib or IMiD-based 507 (84) 123 (90) .046 Pre-transplant evaluation Bone marrow plasma cell, (%) 2 (0-71) 2 (0-50) .136 Bone marrow plasma cell >10% 90 (15) 18 (13) .735 Hemoglobin, (g/dL) 11.3 (4.4-16.0) 10.8 (6.8-15.3) .025 Lactate dehydrogenase, (IL/L) 526 (221-5062) 526 (239-2748) .522 Calcium, (mg/dL) 9.0 (7.6-10.4) 9.0 (7.5-11.0) .055 Creatinine, (mg/dL) 0.9 (0.4-12.5) 0.9 (0.5-9.8) .017 Beta-2 microglobulin (mg/dL) 2.4 (1.1-40.0) 2.8 (1.2-33.8) .001 Time from diagnosis to auto-HCT (month) 8.0 (1.9-174.4) 6.8 (2.4-44.6) .001 Pre-transplant disease status .004 ≥ CR 24 (4) 15 (11) VGPR/PR 545 (90) 109 (80) SD/PD 37 (6) 12 (9) Conditioning regimen .008 Melphalan alone 508 (84) 126 (93) Melphalan-based regimen 98 (16) 10 (7) Final response after transplant .080 ≥ CR 168 (28) 52 (38) VGPR/PR 353 (58) 70 (52) SD/PD 81 (13) 14 (10) Figure 1. a) Progression-free survival, b) Overall survival in patients with light chain myeloma compared to those with IgG/IgA myeloma Figure 1. a) Progression-free survival, b) Overall survival in patients with light chain myeloma compared to those with IgG/IgA myeloma Disclosures Shah: Celgene: Consultancy, Research Funding. Thomas:Novartis, Celgene, Acerta Pharmaceuticals, Idera Pharmaceuticals: Research Funding.
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Williams, T. D., J. R. Seckl e S. L. Lightman. "Dependent effect of drinking volume on vasopressin but not atrial peptide in humans". American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 257, n. 4 (1 ottobre 1989): R762—R764. http://dx.doi.org/10.1152/ajpregu.1989.257.4.r762.
Abstract (sommario):
The act of drinking causes a fall in plasma arginine vasopressin (AVP) concentration that precedes changes in plasma osmolality. To investigate the specificity of this drinking stimulus on hormone secretion, six volunteers (5 male, 1 female, aged 22-39 yr) were water deprived for 36 h and then drank 15 ml/kg water at 10-12 degrees C using 15-20 swallowing actions/min over 3.5 +/- 0.5 min (mean +/- SE). This caused a fall in plasma AVP from 4.5 +/- 0.7 to 3.2 +/- 0.5 pmol/l (P less than 0.05) and in thirst (by 5.7 +/- 0.6 on a 10-cm linear analog scale) (P less than 0.05) 5 min after drinking. No significant changes occurred in mean arterial pressure, heart rate, or plasma atrial natriuretic peptide (ANP) concentration. A second study was undertaken to determine whether the reflex inhibition of AVP secretion is activated simply by the act of swallowing regardless of the volume of liquid consumed. The six volunteers were water deprived for 36 h and then sipped and swallowed 1 ml/kg water at 10-12 degrees C using 15-20 swallowing actions/min over 3.0 +/- 0.1 min. There was no change in plasma AVP concentration, although thirst was reduced by 2.3 +/- 0.6 (P less than 0.05) at 5 min. Plasma AVP 10 min after sipping and swallowing (4.2 +/- 0.8 pmol/l) was significantly greater than at 10 min after drinking 15 ml/kg (2.8 +/- 0.5 pmol/l) (P less than 0.05) despite the fact that plasma osmolality at this stage was similar in both studies. We conclude that the drinking-mediated reflex inhibition of AVP secretion in humans is dependent on swallowing an adequate volume and is not accompanied by changes in hemodynamics or in plasma ANP concentration.
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Robertson, SA, e RF Seamark. "Granulocyte macrophage colony stimulating factor (GM-CSF) in the murine reproductive tract: stimulation by seminal factors". Reproduction, Fertility and Development 2, n. 4 (1990): 359. http://dx.doi.org/10.1071/rd9900359.
Abstract (sommario):
The activity of GM-CSF during early pregnancy in the murine uterine lumen in vivo and in media conditioned by uterine cells in vitro has been assessed. GM-CSF was detected in uterine luminal fluid recovered by lavage on the morning after syngeneic mating (median level 5.7 CFUc U/uterus) and following mating with vasectomized (5.1 U/uterus) or allogeneic males (4.4 U/uterus), with significantly lesser (P less than 0.05) amounts recovered from the uteri of superovulated, mated mice. By contrast, GM-CSF was only detectable (greater than 0.5 U/uterus) in the luminal fluid of three of 22 unmated oestrous mice examined. No activity was detected in secretions from male accessory glands including seminal vesicle, epididymis, prostate and coagulating gland (less than 0.5 U/gland). GM-CSF was found at higher levels in supernatants from cell monolayers prepared by tryptic digest of the uteri of Day 1 mated mice than those from unmated oestrous mice (P less than 0.05). Little GM-CSF was detected in supernatants from ovariectomized mice. An alpha-GM-CSF polyvalent antibody neutralized the FD5/12 bioassay response confirming the identity of the lymphokine. The interleukins IL-2 and IL-3 were not detected in uterine luminal fluid nor in media conditioned by cell monolayers. We postulate that elevated uterine GM-CSF activity after mating is elicited by a non-sperm associated, non-MHC component of the ejaculate and synthesized by a hormone-responsive endometrial cell population. This cytokine may have an embryotrophic role or contribute to priming of the uterus for implantation.
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My, Tran Thi Ai, Nguyen Duy Dat e Nguyen Quoc Hung. "Occurrence and Characteristics of Microplastics in Wild and Farmed Shrimps Collected from Cau Hai Lagoon, Central Vietnam". Molecules 28, n. 12 (8 giugno 2023): 4634. http://dx.doi.org/10.3390/molecules28124634.
Abstract (sommario):
This study investigated the occurrence of microplastics (MPs) in the gastrointestinal tracts (GT) and tissues of four common shrimps (including two wild-caught shrimps and two farmed shrimps) collected from a high-diversity lagoon in central Vietnam. The numbers of MP items in greasy-back shrimp (Metapenaeus ensis), green tiger shrimp (Penaeus semisulcatus), white-leg shrimp (Litopenaeus vannamei), and giant tiger shrimp (Penaeus monodon), determined per weight and individual, were 0.7 ± 0.3, 0.6 ± 0.2, 1.1 ± 0.4, and 0.5 ± 0.3 (items/g-ww), and 2.5 ± 0.5, 2.3 ± 0.7, 8.6 ± 3.5, 7.7 ± 3.5 (items/individual), respectively. The concentration of microplastics in the GT samples was significantly higher than that in the tissue samples (p < 0.05). The number of microplastics in the farmed shrimp (white-leg shrimp and black tiger shrimp) was statistically significantly higher than the number of microplastics in the wild-caught shrimp (greasy-back and green tiger shrimps) (p <0.05). Fibers and fragments were the dominant shapes of the MPs, followed by pellets, and these accounted for 42–69%, 22–57%, and 0–27% of the total microplastics, respectively. The chemical compositions determined using FTIR confirmed six polymers, in which rayon was the most abundant polymer, accounting for 61.9% of the MPs found, followed by polyamide (10.5%), PET (6.7%), polyethylene (5.7%), polyacrylic (5.8%), and polystyrene (3.8%). As the first investigation on the MPs in shrimps from Cau Hai Lagoon, central Vietnam, this study provides useful information on the occurrences and characteristics of the microplastics in the gastrointestinal tracts and tissues of four shrimp species that live in different living conditions.
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Кемельбеков, Канатжан, Гулмира Бектенова, Кулбала Карсыбаева, Акбаян Сатымбекова e Гулжанат Онласбекова. "СТРУКТУРА ЗАБОЛЕВАЕМОСТИ ВРОЖДЕННЫХ ПОРОКОВ СЕРДЕЧНО-СОСУДИСТОЙ СИСТЕМЫ У ДЕТЕЙ ПО ТУРКЕСТАНСКОЙ ОБЛАСТИ". Международный журнал научной педиатрии, n. 8 (30 dicembre 2022): 21–22. http://dx.doi.org/10.56121/2181-2926-2022-8-21-22.
Abstract (sommario):
Врождённый порок сердца (ВПС) – дефект в структуре сердца и крупных сосудов. Большинство пороков нарушают ток крови внутри сердца или по большому (БКК) и малому (МКК) кругам кровообращения. Актуальность. В раннем неонатальном периоде диагностика ВПС может быть затруднена ввиду не специфичности симптомов. Многие, даже критические ВПС в период адаптации новорожденного могут протекать с минимальными проявлениями, либо маскироваться под симптомы других заболеваний. Цель исследования: изучение структура заболеваемости ВПС и статистика их оперативного лечения в кардиохирургическом отделении «Областная клиническая детская больница» ТО (ОКДБ). Материалы и методы исследования: проанализированы истории болезни пациентов с ВПС, находившихся на лечении в кардиохирургическом отделении «Областная клиническая детская больница» ТО (ОКДБ) за период с 2019 по 2020гг. эндоваскулярные хирургические вмешательства были выполнены у 201 больных с ВПС в возрасте от 0 до 18 лет (средний возраст 8,0±2 года). Среди них преобладали мальчики (63%). Результаты и обсуждения: за период с 2018 по 2020 эндоваскулярные хирургические вмешательства были выполнены у 201 больных с ВПС в возрасте от 0 до 18 лет (средний возраст 8,0±2 года). Операции: ДМПП с ИК было 5 (2,48%) пациентов; ДМПП-2 60 (29,8%); операции по перемещению аномально дренирующих легочных вен в левое предсердие с ИК – 1 (0,5%); ДМЖП – 23 (11,4%); открытого артериального протока – 34 (16,9%); эндовоскулярные операции с использованием окклюдеров “Амплатцера” – 110 (54,7%); измерение ДМПП баллоном – 53 (26,3%). Всем пациентам, помимо общего обследования, проводилось УЗДГ, трансторакальная ЭхоКГ, катетеризация полостей сердца и легочной артерии с регистрацией давления и ангиокардиографией. Выводы: ВПС по распространенности, в сравнении с другими врожденными пороками развития, сохраняют лидирующие позиции не только на территории РК, но и в мире в целом. Большинство факторов риска, влияющих на формирование ВПС, являются частично управляемыми, о чем говорят многочисленные исследования.
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Chen, W. C., J. Zhu, P. Fisher, D. Amarnath e K. H. S. Campbell. "235 A COMPARISON OF PARTHENOGENETIC DEVELOPMENT OF PORCINE OOCYTES SYNCHRONISED DURING MATURATION BY CYCLOHEXIMIDE OR cAMP". Reproduction, Fertility and Development 21, n. 1 (2009): 215. http://dx.doi.org/10.1071/rdv21n1ab235.
Abstract (sommario):
In vitro maturation of porcine oocytes is characterized by a high level of asynchrony between oocytes. Previous studies reported that cycloheximide (CHX) and 3′, 5′-cyclic AMP (cAMP) synchronize porcine oocytes and improve development to blastocyst stage following IVF or have been used for somatic cell nuclear transfer (SCNT) (Ye et al. 2005 Biol. Reprod. 72(2), 399–406; Betthauser et al. 2000 Nat. Biotechnol. 18(10), 1055–1059). We previously reported that cAMP was more effective than CHX in synchronizing porcine oocyte maturation, producing MII oocytes in a shorter time window and providing a more homogenous population for future SCNT studies (Chen et al. 2008 SRF conference, 2008 abst, p34). Here we compared parthenogenetic development of porcine oocytes synchronized by these two treatments. Selected cumulus–oocyte complexes (COC) obtained from slaughtered gilts were randomly divided into three groups and cultured at 39°C, 5% CO2 in air in modified NCSU-23 medium (with 1 μm glutathione, 1 mm cysteine, 5 mg L–1 insulin, 10 ng mL–1 epidermal growth factor, 10% (v/v) porcine follicular fluid, 1% essential and 0.5% nonessential amino acids) ± hormones (10 IU mL–1 PMSG and 10 IU mL–1 hCG): (1) with hormones for the first 22 h and then without hormones until 44 h; (2) with hormones and 5 μg mL–1 CHX for 12 h, and then with hormones but no CHX until 44 h; (3) with hormones and 1 mm cAMP for 22 h, and then without hormones and cAMP until 44 h. Parthenogenetic development of cycloheximide and cAMP treated oocytes was compared by cleavage rate at 48 h postactivation (hpa) and blastocyst formation at 168 hpa. No significant differences were observed in the frequency of cleavage (96.7 ± 2.1% v. 81.4 ± 11.6% v. 84.5 ± 5.7%), development to blastocyst (28.3 ± 11.4% v. 27.1 ± 5.7% v. 32.8 ± 5.3%) between control, CHX or cAMP treated oocytes, respectively (chi-square test, P > 0.05). However, total cell number was significantly higher in the CHX group than cAMP group (42.7 ± 4.1 v. 31.8 ± 2.0, respectively; t-test, P < 0.05). The results demonstrate that synchronization of porcine oocytes by treatment with CHX or cAMP does not affect subsequent parthenogenetic development if judged by the blastocyst formation, although the meaning of the difference of total cell numbers between CHX and cAMP treatments is still unclear.
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Barinov, Sergey Vladimirovich, Oksana Vyacheslavovna Lazareva, Boris Vasil’yevich Korneev, Lyudmila Leonidovna Shkabarnya, Mikhail Vladimirovich Grebenuk, Ekaterina Aleksandrovna Roshchupkina, Anna Vadimovna Belokopytova e Pavel Igorevich Sorokin. "To the matter about operational treatment of benign neoplasms of ovaries during pregnancy". Journal of obstetrics and women's diseases 64, n. 4 (15 settembre 2015): 13–20. http://dx.doi.org/10.17816/jowd64413-20.
Abstract (sommario):
Purposes and tasks. To improve the result of treatment of benign ovarian tumor during pregnancy using information of a complex comparative analysis of surgical interventions performed by laparoscopy and laparotomy. Materials and methods. We examined 69 pregnant women who undergoing treatment of benign ovarian tumors by laparoscopic and laparotomic surgery. The analysis of clinical data, postoperative pain, postoperative complications and statistic assess were performed. Results. The average age of pregnant women in laparoscopy group was 26 ± 0,5 years and 29 ± 0,7 years in laparotomy group. The main indications for intervention were threatened miscarriage and ovarian torsion. All women received therapy for saving pregnancy in postoperative period. The laparoscopy was associated with a significant reduction in time compared to laparotomy (54,7 ± 2,6 and 64,5 ± 2,5 - appropriate, р = 0,003). The blood loss was 46,67 ± 29,9 ml in laparoscopy and 108,7 ± 58,6 ml in laparotomy group (р < 0,001). Postoperative pain was less in women who undergoing laparoscopic surgery. 29 (76.3 %) women had vaginal delivery in laparoscopy group, 22(70.9 %) - in laparotomy group. Conclusion. In pregnant women undergoing surgery for benign ovarian tumours, laparoscopy was associated with less operation time, postoperative pain, blood loss compared with laparotomic surgery. The optimal time for intervention is before 24 week of pregnancy.
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Zyara, Alyaa M., Eila Torvinen, Anna-Maria Veijalainen e Helvi Heinonen-Tanski. "The effect of chlorine and combined chlorine/UV treatment on coliphages in drinking water disinfection". Journal of Water and Health 14, n. 4 (6 aprile 2016): 640–49. http://dx.doi.org/10.2166/wh.2016.144.
Abstract (sommario):
Chlorine disinfection is a globally used method to ensure the safety of drinking water. However, it has not always been successful against viruses and, therefore, it is important to find new methods to disinfect water. Seventeen different coliphages were isolated from the treated municipal wastewater. These coliphages and MS2 were treated with different dosages of chlorine in drinking water, and a combined chlorine/ultraviolet irradiation treatment for the chlorine-resistant coliphages. Chlorine disinfection with 0.3–0.5 mg/L total chlorine (free Cl-dosage 0.12–0.21 mg/L) for 10 min achieved 2.5–5.7 Log10-reductions for 11 sensitive coliphages. The six most resistant coliphages showed no reduction with these chlorine concentrations. MS2 was intermediate in chlorine resistance, and thus it is not a good indicator for viruses in chlorine disinfection. In the combined treatment total chlorine of 0.05–0.25 mg/L (free Cl-dosage 0.02–0.08 mg/L) and ultraviolet irradiation (14–22 mWs/cm2) were more effective than chlorine alone, and 3–5 Log10-reductions were achieved for the chlorine-resistant strains. The chlorination efficiency could be increased by higher dosages and longer contact times, but this could increase the formation of disinfection by-products. Therefore, the combination treatment is a recommended disinfection method.
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Leanza, Vito, Eva Intagliata, Gianluca Leanza e Rosario Vecchio. "Pelvic posterior compartment defects: comparative study of two vaginal surgical procedures". Urogynaecologia 27, n. 1 (8 novembre 2013): 5. http://dx.doi.org/10.4081/uij.2013.e5.
Abstract (sommario):
This study was undertaken to compare two surgical techniques for rectocele repair. Between January 2005 and December 2010, 180 patients with III grade symptomatic rectocele were enrolled in this alternative prospective randomized study. 90 patients (group A) were treated with perineal body anchorage of posterior septum, and 90 (group B) with the traditional Denonvilliers’ transversal suture. Pre- and post-operative data, including Ap and Bp values, recurrence rates and quality of life was assessed. The mean follow-up was 22 months (range 9-72 months). For statistical purpose, Student’s <em>t</em> test, chi-square test and logistic regression analysis were evaluated. Post-operatively, in group A Ap and Bp value were respectively –2.0±1.0 and –2.5±0.5 (P<0.001 for both values). In group B, Ap and Bp value were respectively –1.9±2.1 and –2.1±0.9 (P<0.001 for both values). A total of 81 (93.1%) patients in group A and 76 (86.3%) in group B reported improvement in symptoms (P=0.222) after surgery. Recurrence rates were 5 (5.7%) and 6 (6.8%) respectively (P=0.984). Quality of life improved significantly in both groups. In conclusion, both techniques are effective for the posterior compartment repair.
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Bao, Xinjian, Mingyue He, Zhigang Zhang e Xi Liu. "Crystal Structure and Some Thermodynamic Properties of Ca7MgSi4O16-Bredigite". Crystals 11, n. 1 (26 dicembre 2020): 14. http://dx.doi.org/10.3390/cryst11010014.
Abstract (sommario):
Bredigite with the composition Ca7MgSi4O16 (Ca7MgSi4O16-Bre) has been synthesized by a solid-state reaction method at 1.2 GPa and 1373 K for 7 days, and its structure has been determined by single-crystal X-ray diffraction data. Following a relevant genealogy analysis in the literature, we have refined the structure into two space groups, Pnnm and Pnn2, and found that Ca7MgSi4O16-Bre belongs to the space group Pnnm, which can be essentially derived from the space group Pnn2 via an atomic coordinate transformation (with an average deviation of 0.039 Å only). Furthermore, some thermodynamic properties of the Ca7MgSi4O16-Bre have been obtained in this study. Using first-principles simulations based on density functional theory, the isothermal bulk modulus has been determined as 90.6(4) GPa with a pressure derivative of 5.7(1). Using density functional perturbation technique, the phonon dispersions and vibrational density of the states (VDoS) have been calculated. The VDoS has been combined with a quasi-harmonic approximation to compute the isobaric heat capacity (Cp) and standard vibrational entropy (S2980), yielding Cp = 8.22(2) × 102 − 3.76(6) × 103T−0.5 − 1.384(4) × 107T−2 + 1.61(8) × 109T−3 J mol−1 K−1 for the T range of 298-1000 K and S2980 = 534.1 (22) J mol−1 K−1.
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Lutsey, Pamela L., Richard F. MacLehose, J’Neka S. Claxton, Rob F. Walker, Terrence J. Adam, Alvaro Alonso e Neil A. Zakai. "Impact of oral anticoagulation choice on healthcare utilization for the primary treatment of venous thromboembolism". Vascular Medicine 25, n. 6 (27 luglio 2020): 549–56. http://dx.doi.org/10.1177/1358863x20940388.
Abstract (sommario):
Little is known about the impact of oral anticoagulation (OAC) choice on healthcare encounters during venous thromboembolism (VTE) primary treatment. Among anticoagulant-naïve patients with VTE, we tested the hypotheses that healthcare utilization would be lower among users of direct OACs (DOACs; rivaroxaban or apixaban) than among users of warfarin. MarketScan databases for years 2016 and 2017 were used; healthcare utilization was identified in the first 6 months after initial VTE diagnoses. The 23,864 patients with VTE had on average 0.2 ± 0.5 hospitalizations, spent 1.3 ± 5.2 days in the hospital, had 5.7 ± 5.1 outpatient encounters, and visited an emergency department 0.4 ± 1.1 times. As compared to warfarin, rivaroxaban and apixaban were associated with fewer hospitalizations, days hospitalized, outpatient office visits, and emergency department visits after accounting for age, sex, comorbidities, and medications. Hospitalization rates were 24% lower (incidence rate ratio (IRR): 0.76; 95% CI: 0.69, 0.83) with rivaroxaban and 22% lower (IRR: 0.78; 95% CI: 0.71, 0.87) with apixaban, as compared to warfarin (IRR: 1.00 (reference)). Healthcare utilization was similar between apixaban and rivaroxaban users. Patients with VTE prescribed rivaroxaban and apixaban had lower healthcare utilization than those prescribed warfarin, while there was no difference when comparing apixaban to rivaroxaban. These findings complement existing literature supporting the use of DOACs over warfarin.
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Landi, Kristen, Carmen Gutierrez, Barbara Sampson, Richard Harruff, Ivonne Rubio, Beatriz Balbela e M. Alba Greco. "Investigation of the Sudden Death of Infants: A Multicenter Analysis". Pediatric and Developmental Pathology 8, n. 6 (novembre 2005): 630–38. http://dx.doi.org/10.1007/s10024-005-8095-1.
Abstract (sommario):
The investigation of sudden death of infants varies, and death rates may depend on local practices of death certification. We studied the extent of the investigation and the final cause of death (COD) in 3 regions: New York, New York, USA (NY); King County, Washington, USA (KC); and Montevideo, Uruguay (MU). We conducted a retrospective review of 543 cases (NY 258, KC 56, MU 229) of previously healthy babies who died suddenly without obvious trauma, at ages 0 to 12 months, over a 3-year period (1998 to 2001). All cases included a complete autopsy and histologic examination. Cases were assessed for completion of special studies (including radiographs, photos, toxicology and metabolic sampling, cultures, and vitreous humor chemistry), measurements, and scene investigation. Specialized pediatric measurements and testing were done less often than routine procedures, and were done less often in cases overall compared with cases certified as sudden infant death syndrome (SIDS). Fifty-five percent of SIDS cases in NYC and 12% of SIDS cases in KC had no scene investigation. Manhattan had a complete workup in 42% of SIDS cases, whereas the remaining sites had fewer that 15% of cases completely worked up. The most common non-natural COD was suffocation at all 3 sites. The overall most common COD were respiratory infection in MU (22%) and SIDS in NY (45%) and KC (86%). We conclude that the sudden death of infants requires special consideration and still lacks consistency. SIDS investigations are not done completely in all cases and rates may depend on regional differences in certifying infant deaths.
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Wysocka, B. A., Z. Kassam, G. Lockwood, J. Brierley, L. Dawson e J. Ringash. "Assessment of intra and interfractional organ motion during adjuvant radiochemotherapy in gastric cancer". Journal of Clinical Oncology 25, n. 18_suppl (20 giugno 2007): 15132. http://dx.doi.org/10.1200/jco.2007.25.18_suppl.15132.
Abstract (sommario):
15132 Background: Adjuvant combined chemotherapy and radiotherapy (RT) in gastric cancer improves survival, however acute toxicity is substantial. Toxicity may be improved with three-dimensional (3D) RT, but organ motion must be considered in planning target volume (PTV) delineation. Methods: Participants (n=22) had baseline free breathing planning CT (CT0) with BodyFix immobilization. Abdominal CTs in free breathing (FB), inhale (I) and exhale (E) states were obtained in weeks 1, 3 and 5 of RT. Datasets were fused to CT0 in Pinnacle3 6.2 planning system using bone registration. Volumes of interest (VOIs) [right (R) and left (L) kidney, liver, stomach, pancreas, celiac axis and porta hepatis] were contoured and points of interest (POIs) were placed at each centre of mass. POIs were manually placed at the left dome of diaphragm and splenic hilum. Organ motion was determined by the difference between POI positions in cranial-caudal (CC), anterior-posterior (AP) and right-left (RL) directions. Maximal respiratory motion was determined from the difference between I and E positions. Interfractional displacement in organs relative to bones at weeks 1, 3 and 5 was determined on FB scans as compared to baseline. Results: Interfractional organ motion was maximal in CC direction with median absolute displacements (range) in mm of: splenic hilum 10 (0–52), stomach 8 (0.4–27.2), liver 7.4 (0.5–23.6), diaphragm 6 (0–28), L kidney 5.7 (0–37.3), R kidney 5.3 (0.2–35.3), pancreas 5.7 (0.3–29.1), porta hepatis 4 (0–14) and celiac axis 1.7 (0–9.1). Median interfraction displacement (range) in CC, AP and RL in mm for all organs was: 5.7 (0- 52), 2.1 (0–23.1), 2.3 (0–15.9). Positional difference between I and E state (median for all organs) was: 16 mm CC, 5.9 mm AP, and 1.7 mm RL with maximal individual breathing excursions of 59.9, 30.2 and 21.1 mm, respectively. Conclusions: Interfraction organ displacement relative to bones can be quantified and used in the safe design of 3D conformal radiotherapy. Respiratory motion can be substantial in some individuals. Accounting for organ motion in 3D RT planning is necessary and may reduce the toxicity of treatment. No significant financial relationships to disclose.
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Marklund, Matti, Fikru Tullu, Sudhir Raj Thout, Jie Yu, Tammy M. Brady, Lawrence J. Appel, Bruce Neal, Jason H. Y. Wu e Rachita Gupta. "Estimated Benefits and Risks of Using a Reduced-Sodium, Potassium-Enriched Salt Substitute in India: A Modeling Study". Hypertension 79, n. 10 (ottobre 2022): 2188–98. http://dx.doi.org/10.1161/hypertensionaha.122.19072.
Abstract (sommario):
Background: Salt substitution (ie, replacement of table and cooking salt with potassium-enriched salt substitutes) is a promising strategy to reduce blood pressure and prevent cardiovascular disease, particularly in countries like India where there is high sodium intake, mainly from discretionary salt, and low potassium intake. Life-threatening hyperkalemia from increased potassium intake is a postulated concern for individuals with chronic kidney disease. methods: We used comparative risk assessment models to estimate the number of (1) cardiovascular deaths averted due to blood pressure reductions; (2) potential hyperkalemia-related deaths from increased potassium intake in individuals with advanced chronic kidney disease; and (3) net averted deaths from nationwide salt substitution in India. We evaluated a conservative scenario, based on a large, long-term pragmatic trial in rural China; and an optimistic scenario informed by our recent trial in India. Sensitivity analyses were conducted to assess the robustness of the findings. Results: In the conservative scenario, a nationwide salt substitution intervention was estimated to result in ≈214 000 (95% uncertainty interval, 92 764–353 054) averted deaths from blood pressure reduction in the total population and ≈52 000 (22 961–80 211) in 28 million individuals with advanced chronic kidney disease, while ≈22 000 (15 221–31 840) hyperkalemia-deaths might be caused by the intervention. The corresponding estimates for the optimistic scenario were ≈351 000 (130 470–546 255), ≈66 000 (24 925–105 851), and ≈9000 (4251–14 599). Net benefits were consistent across sensitivity analyses. Conclusions: Modeling nationwide salt substitution in India consistently estimated substantial net benefits, preventing around 8% to 14% of annual cardiovascular deaths. Even allowing for potential hyperkalemia risks there were net benefits estimated for individuals with chronic kidney disease.
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Sanei Taheri, Morteza, Farnaz Kimia, Mersad Mehrnahad, Hamidreza Saligheh Rad, Hamidreza Haghighatkhah, Afshin Moradi, Anahita Fathi Kazerooni, Mohammadreza Alviri e Abdorrahim Absalan. "Accuracy of diffusion-weighted imaging-magnetic resonance in differentiating functional from non-functional pituitary macro-adenoma and classification of tumor consistency". Neuroradiology Journal 32, n. 2 (3 dicembre 2018): 74–85. http://dx.doi.org/10.1177/1971400918809825.
Abstract (sommario):
Purpose The purpose of this study was to determine the accuracy of selected first or second-order histogram features in differentiation of functional types of pituitary macro-adenomas. Materials and methods Diffusion-weighted imaging magnetic resonance imaging was performed on 32 patients (age mean±standard deviation = 43.09 ± 11.02 years; min = 22 and max = 65 years) with pituitary macro-adenoma (10 with functional and 22 with non-functional tumors). Histograms of apparent diffusion coefficient were generated from regions of interest and selected first or second-order histogram features were extracted. Collagen contents of the surgically resected tumors were examined histochemically using Masson trichromatic staining and graded as containing <1%, 1–3%, and >3% of collagen. Results Among selected first or second-order histogram features, uniformity ( p = 0.02), 75th percentile ( p = 0.03), and tumor smoothness ( p = 0.02) were significantly different between functional and non-functional tumors. Tumor smoothness > 5.7 × 10−9 (area under the curve = 0.75; 0.56–0.89) had 70% (95% confidence interval = 34.8–93.3%) sensitivity and 33.33% (95% confidence interval = 14.6–57.0%) specificity for diagnosis of functional tumors. Uniformity ≤179.271 had a sensitivity of 60% (95% confidence interval = 26.2–87.8%) and specificity of 90.48% (95% confidence interval = 69.6–98.8%) with area under the curve = 0.76; 0.57–0.89. The 75th percentile >0.7 had a sensitivity of 80% (95% confidence interval = 44.4–97.5%) and specificity of 66.67% (95% confidence interval = 43.0–85.4%) for categorizing tumors to functional and non-functional types (area under the curve = 0.74; 0.55–0.88). Using these cut-offs, smoothness and uniformity are suggested as negative predictive indices (non-functional tumors) whereas 75th percentile is more applicable for diagnosis of functional tumors. Conclusion First or second-order histogram features could be helpful in differentiating functional vs non-functional pituitary macro-adenoma tumors.
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Noschajew, Emil, Felix Rittenschober, Harald Kindermann e Reinhold Ortmaier. "Clinical and Radiologic Outcomes after Anatomical Total Shoulder Replacement Using a Modular Metal-Backed Glenoid after a Mean Follow-Up of 5.7 Years". Journal of Clinical Medicine 11, n. 20 (17 ottobre 2022): 6107. http://dx.doi.org/10.3390/jcm11206107.
Abstract (sommario):
Background: Glenoid wear is a common complication of anatomical total shoulder arthroplasty (aTSA) with a metal-backed glenoid (MBG), and the clinical and radiological results of historical implants are poor. The aim of this work was to evaluate the clinical and radiological results of 25 participants as well as the longevity after implantation of an anatomic shoulder prosthesis with a recent, modular cementless flat metal-backed glenoid component after a mean follow-up of 5.7 years. Methods: Clinically, the Simple Shoulder Test (SST), UCLA Activity Score (UCLA), and Constant Murley Score (CMS) were evaluated. Radiographically, the radiolucent lines (RLs), humeral head migration (HHM), and lateral glenohumeral offset (LGHO) were assessed. Survival was calculated with Kaplan–Meier curves and life-table analysis. Results: The mean CMS at follow-up was 46.2 points (range: 14–77; SD: 19.5). In terms of the SST score, the average value was 6.5 points (range: 1–10; SD: 3.5). The UCLA activity score showed a mean value of 5.9 points (range: 1–9; SD: 2.1). There were 17 revisions after a mean follow-up of 68.2 months (range: 1.8–119.6; SD: 27.9). HHM occurred in every patient, with a mean measurement of 6.4 mm (range: 0.5–13.4; SD: 3.9; p < 0.0001). The mean LGHO between the initial postoperative and follow-up images was 2.6 mm (range: 0–4.0; SD: 1.5; p < 0.0001). RLs were found in 22 patients (88%) around the glenoid and in 21 patients (84%) around the humeral head prosthesis. Conclusion: The clinical and radiographic outcomes after metal-backed glenoids were poor at 2.2 to 8.4 years of follow-up. We determined devastating survival in the majority of cases (68%), with mostly inlay wear (71%) as the main reason that led to revision surgery. The use of metalback genoids cannot be recommended based on the data of this study.
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Levin, L. A., A. L. McGregor, G. F. Mendoza, C. Woulds, P. Cross, U. Witte, A. J. Gooday, G. Cowie e H. Kitazato. "Macrofaunal colonization across the Indian Margin oxygen minimum zone". Biogeosciences Discussions 10, n. 6 (13 giugno 2013): 9451–92. http://dx.doi.org/10.5194/bgd-10-9451-2013.
Abstract (sommario):
Abstract. There is a growing need to understand the ability of bathyal assemblages to recover from disturbance and oxygen stress, as human activities and expanding oxygen minimum zones increasingly affect deep continental margins. The effects of a pronounced oxygen minimum zone (OMZ) on slope benthic community structure have been studied in both the Western and Eastern Arabian Sea; however, little is known about the dynamics or resilience of these benthic populations. To examine the influence of oxygen and phytodetritus on short-term settlement patterns we conducted colonization experiments along two cross-OMZ transects on the West Indian continental margin. Four colonization trays were deployed at each depth for 4 days at 542 and 802 m (16°58′ N) and for 9 days at 817 m and 1147 m (17°31′ N). Oxygen concentrations ranged from 0.9 μM (0.02 mL L−1) at 542 m to 22 μM (0.5 mL L−1) at 1147 m. All trays contained local defaunated sediments; half of the trays at each depth also contained 13C/15N-labeled phytodetritus mixed into the sediments. Sediment cores were collected between 535 m and 1140 m for analysis of background (source) macrofaunal (> 300 μm) densities and composition. Background densities ranged from 0 ind. m−2 (at 535–542 m) to 7400 ind. m−2, with maximum values on both transects at 700–800 m. Macrofaunal colonizer densities ranged from 0 ind. m−2 at 542 m, where oxygen was lowest, to average values of 142 ind. m−2 at 800 m, and 3074 ind. m−2 at 1147 m, where oxygen concentration was highest. These were equal to 4.3% and 151% of the ambient background community at 800 m and 1147 m, respectively. Community structure of settlers showed no response to the presence of phytodetritus. Increasing depth and oxygen concentration, however, significantly influenced the community composition and abundance of colonizing macrofauna. Polychaetes constituted 92.4% of the total colonizers, followed by crustaceans (4.2%), mollusks (2.5%), and echinoderms (0.8%). The majority of colonizers were found at 1147m; 88.5% of these were Capitella sp., although they were rare in the background community. Colonists at 800 and 1147 m also included ampharetid, spionid, syllid, lumbrinerid, cirratulid, cossurid and sabellid polychaetes. Consumption of δ13C/ δ15N-labeled phytodetritus was observed for macrofaunal foraminifera (too large to be colonizers) at the 542 and 802/817 m sites, and by metazoan macrofauna mainly at the deepest, better oxygenated site. Calcareous foraminifera (Uvigerina, Hoeglundina sp.), capitellid polychaetes and cumaceans were among the major consumers. These preliminary experiments suggest that bottom-water oxygen concentrations may strongly influence ecosystem services on continental margins, as reflected in rates of colonization by benthos and colonizer processing of carbon following disturbance.
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Govender, Byron Bradley, Samuel Ayodele Iwarere e Deresh Ramjugernath. "The Effect of Cobalt Catalyst Loading at Very High Pressure Plasma-Catalysis in Fischer-Tropsch Synthesis". Catalysts 11, n. 11 (31 ottobre 2021): 1324. http://dx.doi.org/10.3390/catal11111324.
Abstract (sommario):
The influence of different catalyst cobalt loadings on the C1–C3 hydrocarbon product yields and energy consumption in plasma-catalytic Fischer-Tropsch synthesis (FTS) was investigated from the standpoint of various reactor operating conditions: pressure (0.5 to 10 MPa), current (250 to 450 mA) and inter-electrode gap (0.5 to 2 mm). This was accomplished by introducing a mullite substrate, coated with 2 wt%-Co/5 wt%-Al2O3, 6 wt%-Co/5 wt%-Al2O3 or 0 wt%-Co/5 wt%-Al2O3 (blank catalyst), into a recently developed high pressure arc discharge reactor. The blank catalyst was ineffective in synthesizing hydrocarbons. Between the blank catalyst, 2 wt%, and the 6 wt% Co catalyst, the 6 wt% improved C1–C3 hydrocarbon production at all conditions, with higher yields and relatively lower energy consumption at (i) 10 MPa at 10 s, and 2 MPa at 60 s, for the pressure variation study; (ii) 250 mA for the current variation study; and (iii) 2 mm for the inter-electrode gap variation study. The inter-electrode gap of 2 mm, using the 6 wt% Co catalyst, led to the overall highest methane, ethane, ethylene, propane and propylene yields of 22 424, 517, 101, 79 and 19 ppm, respectively, compared to 40 ppm of methane and <1 ppm of C1–C3 hydrocarbons for the blank catalyst, while consuming 660 times less energy for the production of a mole of methane. Furthermore, the 6 wt% Co catalyst produced carbon nanotubes (CNTs), detected via transmission electron microscopy (TEM). In addition, scanning electron microscopy (SEM), energy dispersive x-ray spectroscopy (EDX) and x-ray diffraction (XRD) showed that the cobalt catalyst was modified by plasma treatment.
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Stanisic, Veselin, Milorad Bakic, Milorad Magdelinic, Hamdija Kolasinac, Darko Vlaovic e Blazo Stijovic. "A prospective evaluation of laparoscopic cholecystectomy in the treatment of chronic cholelithiasis: A five-year experience". Medical review 64, n. 1-2 (2011): 77–83. http://dx.doi.org/10.2298/mpns1102077s.
Abstract (sommario):
Introduction. Laparoscopic cholecystectomy is a method of choice in the treatment of symptomatic cholecystolithiasis because of less postoperative pain, shorter hospitalization and lower cost of treatment. The study was aimed at analysing the outcome of laparoscopic cholecystectomy in patients surgically treated for chronic calculous cholecystitis (symptomatic cholelithiasis). Material and methods. The research was done in the period from December 2003 to December 2008. In the prospective study of 386 patients, we analyzed operative and postoperative complications, the reasons for conversion to open cholecystectomy, duration of hospitalization and mortality. Results. The average duration of laparoscopic cholecystectomy was 31.9?14.5 min: dissection of adhesions 3.2?0.7 min., elements of Calot?s triangle 9.8?3.2 min., gallbladder releasing from its bed 12.8?2.8 min., the abdominal cavity lavage and removal of gall?bladder from the abdomen 6.8?0.9 min. Some operative difficulties emerged in 22 (5.7%) patients - 4 (1%) during releasing of gallbladder adhesions from the surrounding structures, 9 (2.3%) during dissection of elements of the Calot?s triangle, 6 (1.5%) during gallbladder releasing from its bed, 3 (0.7%) during gallbladder removal from the abdomen. Some post-operative complications, single or associated, occurred in 36 (9.3%) patients: perforation of gallbladder 21 (5.4%), bleeding from gallbladder bed 18(4.6%)/, injury of extra hepatic bile ducts 1 (0.2%), 9 (2.3%) spillage of stones; 3 (0.7%) conversions were made. The average duration of preoperative and postoperative hospitalization was 1.1?0.3 and 1.4?0.5 days, respectively. The pathohistological examination revealed 2 (0.5%) adenocarcinoma of gallbladder. There were no lethal outcomes. Conclusion. Laparoscopic cholecystectomy is a safe procedure and rational choice in the treatment of biliary dyskinesia and symptomatic biliary calculosis with an acceptable rate of conversion.
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Marcucci, Guido, K. Mrózek, A. S. Ruppert, K. Maharry, J. E. Kolitz, R. J. Mayer, M. J. Pettenati et al. "t(8;21) Acute Myeloid Leukemia (AML) Differs from inv(16) AML in Pretreatment Characteristics, Outcome and Prognostic Factors Predicting Outcome: A Cancer and Leukemia Group B (CALGB) Study." Blood 104, n. 11 (16 novembre 2004): 2017. http://dx.doi.org/10.1182/blood.v104.11.2017.2017.
Abstract (sommario):
Abstract Since t(8;21) and inv(16) disrupt core binding factor in AML and confer a favorable prognosis, these cytogenetic groups are often treated similarly, but hitherto have not been compared in a large study. We compared 144 adult AML patients (pts) with t(8;21) with 168 with inv(16) enrolled on the cytogenetic study CALGB 8461. t(8;21) pts were less frequently white (P=.01), had lower hemoglobin levels (P=.03), WBC (P<.001) and % blood (P<.001) and BM blasts (P=.005), and had more frequently secondary chromosome aberrations (P<.001) than inv(16) pts, who more often had extramedullary disease (P<.001). Pts were induced with cytarabine/daunorubicin (AD) or cytarabine/daunorubicin/etoposide ±PSC833(ADE±P). Complete remission (CR) was achieved by 89% of t(8;21) and 87% of inv(16) pts. Upon multivariable analysis (MVA), non-white race (P=.006), lower platelets (P=.01) and higher BM blasts (P=.004) predicted negatively for CR in t(8;21), and lower platelets (P=.009) and hepatomegaly (P=.04) in inv(16) pts. Non-whites with t(8;21) had 5.7 times the odds of not achieving CR as whites. For the entire group (median follow-up 6.4 yrs), the estimated 5-yr overall survival (OS) and cumulative incidence of relapse (CIR) were 51% and 53%, respectively. Pts with t(8;21) showed a trend for shorter OS (46% vs 54%; P=.17) but no difference in CIR compared with inv(16) pts. Upon MVA, t(8;21) pts had worse OS than inv(16) pts (HR 1.5; P=.04), once adjusting for age, platelets, and WBC. Following first relapse, the 5-yr survival of t(8;21) pts (n=58) was shorter than that of inv(16) pts (n=74) (14% vs 36%; P=.01); in an age-adjusted model, the risk of death was 1.8 times higher for t(8;21) pts (P=.005). In a subanalysis of pts <60 yrs, consolidation therapy with multi-course high-dose cytarabine (HDAC x3 or 4) significantly decreased CIR compared to single-course HDAC (x1) in t(8;21) (5-yr CIR, 35% vs 64%; P=.005) and inv(16) (5-yr CIR, 44% vs 70%; P =.03) pts. Upon MVA, consolidation with multi-course HDAC reduced CIR for both t(8;21) and inv(16), but other prognostic factors differed (see Table). For t(8;21), induction with ADE±P and higher platelets increased risk of relapse. However, relatively few pts received ADE±P so its prognostic impact requires confirmation. For inv(16), +22 and other secondary cytogenetic aberrations, and male sex were favorable prognostic factors. Multivariable analysis (MVA) for CIR in pts <60 yrs achieving CR on CALGB 8221, 8525, 9022, 9222, 9621 Variable t(8;21) HR (95% CI); P inv(16) HR (95% CI); P HR=Hazard Ratio, CI=confidence intervals —, not included in final model Consolidation:Single vs multi-course HDAC 4.5 (2.1-9.4); <.001 3.4 (1.7-6.6); <.001 Induction:ADE±P vs AD 2.6 (1.1-5.9); .02 1.4 (0.6-3.2); .41 log(platelets) 1.8 (1.2-2.9); .007 — Secondary cytogenetics — 0.2 (<0.1-0.5); .002 Male vs Female — 0.5 (0.3-0.9); .03 In summary, once pretreatment factors and therapy are considered, the outcome of t(8;21) AML appears inferior to that of inv(16). Although these data should be confirmed prospectively, our analysis suggests that future studies should report the outcomes of pts with t(8;21) and inv(16) separately, and seek to identify and target therapeutically leukemogenic mechanisms accountable for these clinical differences.
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Salem, Mohamed E., Scott Kopetz, Josep Tabernero, Frank A. Sinicrope, Myriam Chalabi, Jeanne Tie, Kunal C. Kadakia et al. "Comprehensive characterization of KRAS mutations and inter-relation with primary tumor location in colorectal cancers." Journal of Clinical Oncology 41, n. 4_suppl (1 febbraio 2023): 231. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.231.
Abstract (sommario):
231 Background: The recent development of KRAS G12C inhibitors underscores the potential to target KRAS mutations. Right-sided and left-sided colon tumors (RT and LT) exhibit different molecular features. We characterize the prevalence of KRAS-variants, interrelation with primary tumor location, and association with immune biomarkers in CRC. Methods: We retrospectively reviewed CRC tumors of all stages (with known sidedness) that underwent NGS with the Tempus xT assay (DNA-seq of 648 genes at 500x coverage, full transcriptome RNA-seq). Bivariate analyses were performed to compare KRAS alterations, immune biomarkers, and co-mutations by tumor location. P-values comparing individual co-mutations between groups were adjusted for false discovery (FDR). Results: A total of 3,391 CRC were analyzed (RT: n = 442 [13%], transverse: n = 116 [3%], LT; n = 2,833 [84%]) of which 1486 (44%) tumors harbored KRAS mutations. Overall, KRAS mutations were more frequent in RT compared to transverse tumors and LT (52% vs 41% vs 43%, p<0.001, respectively). The most frequent KRAS mutation variants observed were G12D (29 %), G12V (22%), G13D (16%), and G12C (5.7%). There was no significant difference in the prevalence of KRAS variant types between LT and RT (p=0.5). Significant differences in genomic co-mutations with various KRAS variants were observed in the following genes: TP53, FBXW7, and NF1 (FDR- P<0.05). RT and transverse tumors were more likely have MSI-H and TMB-H (>10 mut/mb) status than LT (MSI-H: 18% vs 22% vs 2.2% and TMB-H (20% vs 22% vs 3%, P<0.001), respectively. CRC tumors harboring G13D variants were more likely to be associated with and MSI-H and TMB-H status (and 7.7% and 8.5%) compared to G12D (2.8 % and 3.9 %), G12V (1.8 % and 2.1%), and G12C (0% and 2.4%); P = 0.003 and 0.001. Conclusions: The most frequent KRAS mutation variants observed in CRC tumors were G12D, G12V, G13D, and G12C. There was no significant difference in the prevalence of KRAS variant types between tumors of the left vs right colon. CRC tumors that harbored G13D variants were significantly more likely to be associated with MSI-H and TMB-H status. [Table: see text]
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Gordiz, Kiarash, Daniele Vivona, Asegun Henry e Yang Shao-Horn. "Identifying the Phonon Contributions to Li+ Hop in La0.5Li0.5TiO3 Solid Electrolyte". ECS Meeting Abstracts MA2023-01, n. 6 (28 agosto 2023): 1002. http://dx.doi.org/10.1149/ma2023-0161002mtgabs.
Abstract (sommario):
Ion diffusion is important in a variety of applications, yet fundamental understanding of the interaction of lattice vibrations (phonons and vibrational motifs) and the mobile species in solids is still missing. Particularly, for Li super ionic conductors (LISICONs), several studies have reported on the important role of the poly-anion octahedral rotations (rocking modes) in facilitating solid-state Li+ ion migration.[1], [2] However, direct calculation of the contribution of these rocking modes to the Li+ hop is missing, and the provided arguments in these reports are mostly based on establishing correlations between different properties of the rocking modes and the migration properties of the hopping Li+ ion without directly quantifying the contribution of the rocking modes to the Li+ hop. For instance, rocking modes have been argued to be able to (i) provide a softer lattice environment for Li+ ion vibration,[3] (ii) increase the bottleneck area of diffusion (4-O square area),[2] (iii) induce additional force on the carrier sublattice,[1] and (iv) maintain a relatively constant coordination number for Li+ ion during its hop[1] – all conducive to Li+ hop in the lattice. Although insightful, we still lack understanding of the exact vibrational frequencies (density of states) of the rocking modes, and, more importantly, the degree of their contribution to Li+ hop with respect to other phonon modes in the structure. In this work, using a combination of ab initio nudged elastic band (NEB) and lattice dynamics calculations based on the recently proposed formalism,[4] we identify the direct contributions of all phonons, including the rocking ones, to Li+ hop in the perovskite solid-state Li+ conductor Li0.5La0.5TiO3 (LLTO). We set up our NEB Li+ hop calculations considering (i) different orderings of the LLTO lattice,[5] and (ii) different Li+ hopping mechanisms (single and concerted (cooperative)) that can occur in the LLTO lattice.2 To sample such a high degree of complexity, we performed 22 independent NEB calculations of Li+ hop in three different LLTO structures with distinct Li|La orderings and based on two different ion hop mechanisms (single and concerted). Our calculations determined that the following two groups of vibrational modes dominate the contributions to the Li+ hop in the LLTO lattice: (i) rocking modes, and (ii) modes that induce large vibrational energies on the hopping Li+ along its hopping direction. Specifically, our results confirmed that the top 5% (10%) contributing modes to the Li+ hop in the LLTO lattice were responsible for 48% (61%) of the total contributions to the Li+ hop, and the two rocking and highly energetic modes comprised >95% (>85%) of these top 5% (10%) contributing modes. Notable from our calculations was that the rocking modes were only present in the < 5.5 THz frequency region, and in this < 5.5 THz frequency region, they comprised 33% of the vibrational modes and contributed 50% to all the possible contributions to the Li+ hop in this low frequency THz region. Moreover, through static modal excitement calculations, we determined that highly contributing rocking modes of vibration were important in solid-state Li+ ion migration because of their ability to (i) increase the O-4 square bottleneck area of conduction[6] and (ii) amplify the force on the hopping Li+ ion. In summary, our observations demonstrated the strong importance of the THz vibrational region to Li+ hop in the lattice, which can be accessible for further explorations using THz spectroscopy techniques to deepen our understanding of the relation between solid-state transport of Li+ and different vibrational motifs in the lattice. References [1] J. G. Smith and D. J. Siegel, ‘Low-temperature paddlewheel effect in glassy solid electrolytes’, Nat Commun, vol. 11, no. 1, pp. 1–11, 2020. [2] S. Stramare, V. Thangadurai, and W. Weppner, ‘Lithium lanthanum titanates: a review’, Chemistry of materials, vol. 15, no. 21, pp. 3974–3990, 2003. [3] X. Li and N. A. Benedek, ‘Enhancement of ionic transport in complex oxides through soft lattice modes and epitaxial strain’, Chemistry of Materials, vol. 27, no. 7, pp. 2647–2652, 2015, doi: 10.1021/acs.chemmater.5b00445. [4] K. Gordiz, S. Muy, W. G. Zeier, Y. Shao-Horn, and A. Henry, ‘Enhancement of ion diffusion by targeted phonon excitation’, Cell Rep Phys Sci, vol. 2, no. 5, p. 100431, 2021. [5] M. Catti, ‘Ion mobility pathways of the Li+ conductor Li0. 125La0. 625TiO3 by ab initio simulations’, The Journal of Physical Chemistry C, vol. 112, no. 29, pp. 11068–11074, 2008. [6] C. Chen and J. Du, ‘Lithium ion diffusion mechanism in lithium lanthanum titanate solid‐state electrolytes from atomistic simulations’, Journal of the American Ceramic Society, vol. 98, no. 2, pp. 534–542, 2015.
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Lu, Xiao, Daniel J. Jacob, Haolin Wang, Joannes D. Maasakkers, Yuzhong Zhang, Tia R. Scarpelli, Lu Shen et al. "Methane emissions in the United States, Canada, and Mexico: evaluation of national methane emission inventories and 2010–2017 sectoral trends by inverse analysis of in situ (GLOBALVIEWplus CH<sub>4</sub> ObsPack) and satellite (GOSAT) atmospheric observations". Atmospheric Chemistry and Physics 22, n. 1 (12 gennaio 2022): 395–418. http://dx.doi.org/10.5194/acp-22-395-2022.
Abstract (sommario):
Abstract. We quantify methane emissions and their 2010–2017 trends by sector in the contiguous United States (CONUS), Canada, and Mexico by inverse analysis of in situ (GLOBALVIEWplus CH4 ObsPack) and satellite (GOSAT) atmospheric methane observations. The inversion uses as a prior estimate the national anthropogenic emission inventories for the three countries reported by the US Environmental Protection Agency (EPA), Environment and Climate Change Canada (ECCC), and the Instituto Nacional de Ecología y Cambio Climático (INECC) in Mexico to the United Nations Framework Convention on Climate Change (UNFCCC) and thus serves as an evaluation of these inventories in terms of their magnitudes and trends. Emissions are optimized with a Gaussian mixture model (GMM) at 0.5∘×0.625∘ resolution and for individual years. Optimization is done analytically using lognormal error forms. This yields closed-form statistics of error covariances and information content on the posterior (optimized) estimates, allows better representation of the high tail of the emission distribution, and enables construction of a large ensemble of inverse solutions using different observations and assumptions. We find that GOSAT and in situ observations are largely consistent and complementary in the optimization of methane emissions for North America. Mean 2010–2017 anthropogenic emissions from our base GOSAT + in situ inversion, with ranges from the inversion ensemble, are 36.9 (32.5–37.8) Tg a−1 for CONUS, 5.3 (3.6–5.7) Tg a−1 for Canada, and 6.0 (4.7–6.1) Tg a−1 for Mexico. These are higher than the most recent reported national inventories of 26.0 Tg a−1 for the US (EPA), 4.0 Tg a−1 for Canada (ECCC), and 5.0 Tg a−1 for Mexico (INECC). The correction in all three countries is largely driven by a factor of 2 underestimate in emissions from the oil sector with major contributions from the south-central US, western Canada, and southeastern Mexico. Total CONUS anthropogenic emissions in our inversion peak in 2014, in contrast to the EPA report of a steady decreasing trend over 2010–2017. This reflects offsetting effects of increasing emissions from the oil and landfill sectors, decreasing emissions from the gas sector, and flat emissions from the livestock and coal sectors. We find decreasing trends in Canadian and Mexican anthropogenic methane emissions over the 2010–2017 period, mainly driven by oil and gas emissions. Our best estimates of mean 2010–2017 wetland emissions are 8.4 (6.4–10.6) Tg a−1 for CONUS, 9.9 (7.8–12.0) Tg a−1 for Canada, and 0.6 (0.4–0.6) Tg a−1 for Mexico. Wetland emissions in CONUS show an increasing trend of +2.6 (+1.7 to +3.8)% a−1 over 2010–2017 correlated with precipitation.
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Zhu, Yuzhe, Xuzhi Liu, Xiaoran Li, Zicheng Liu e Quanwen Qi. "A Compact, Ultra-Wideband, Transformer-Based Quadrature Signal Generation Network in 45 nm CMOS SOI for 5G Applications". Electronics 11, n. 16 (11 agosto 2022): 2508. http://dx.doi.org/10.3390/electronics11162508.
Abstract (sommario):
In this article, we present an ultra-wideband, fully-differential quadrature signal generation network for 5G applications. The ultra-wideband network is composed of a passive balun and cascaded transformer-based quadrature hybrid. Passive balun converts a single-ended signal to differential with minimum insertion loss, and transformer-based quadrature hybrids are cascaded to suppress I/Q imbalance over an ultra-wide bandwidth. The coupling coefficient of the transformer-based quadrature hybrid is enhanced by adopting vertically stacked multiturn transformer topology to extend operation bandwidth and reduce passive loss and chip area. A novel layout and signal routings are proposed to reduce passive loss, undesired magnetic coupling and I/Q imbalance, making meander lines for phase matching unnecessary. The proposed ultra-wideband quadrature signal generation network is designed in GlobalFoundries 45 nm CMOS SOI process with a core area of 845 μm × 495 μm. The output I/Q magnitude mismatch is less than 0.5 dB from 16 to 60 GHz, and phase mismatch is less than 2° from 16.5 to 54.7 GHz. The input return loss is lower than −10 dB from 22 to 45 GHz, and signal loss varies from 5.74 to 7.4 dB (including 1:2 power splitting and loss from passive balun). The effective image rejection ratio (IRR) is calculated based on I/Q mismatch and is higher than 40 dB from 21.5 to 53.5 GHz.
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Rosenblüt, Andrés, María Elena Santolaya, Patricia Gonzalez, Cecilia Borel e José Cofré. "Penicillin Resistance is Not Extrapolable to Amoxicillin Resistance in Streptococcus Pneumoniae Isolated from Middle Ear Fluid in Children with Acute Otitis Media". Annals of Otology, Rhinology & Laryngology 115, n. 3 (marzo 2006): 186–90. http://dx.doi.org/10.1177/000348940611500305.
Abstract (sommario):
Objectives: We evaluated the in vitro antibacterial activity of amoxicillin against penicillin-susceptible and -nonsusceptible Streptococcus pneumoniae strains isolated from children with acute otitis media (AOM). Methods: Children more than 3 months of age with AOM who were seen in the Dr Sótero del Rio and Luis Calvo Mackenna Hospitals in Santiago, Chile, between July 1998 and December 2002 were subjected to tympanic puncture for middle ear fluid culture. The penicillin and amoxicillin susceptibilities of the S pneumoniae isolates were determined by epsilometer test (E test). Results: A bacterial pathogen was isolated in 432 of 543 children (80%) as follows: S pneumoniae, 40%; Haemophilus influenzae, 29%; Moraxella catarrhalis, 7%; and Streptococcus pyogenes, 4%. Penicillin-susceptible S pneumoniae strains were less common than amoxicillin-susceptible strains (60% versus 95%; odds ratio [OR], 0.08; 95% confidence interval [CI], 0.04 to 0.18). Both intermediate- and high-resistance strains were more common for penicillin (22% versus 4.5%; OR, 5.6; 95% CI, 2.5 to 12.7) than for amoxicillin (18% versus 0.5%; OR, 41.3; 95% CI, 6.0 to 821). Conclusions: Penicillin resistance is not extrapolable to amoxicillin among S pneumoniae strains isolated from middle ear fluid of children with AOM. Our results support the recommendation to evaluate the minimal inhibitory concentrations of penicillin-nonsusceptible S pneumoniae for amoxicillin and to continue use of this antimicrobial as a first-line antimicrobial choice for children with AOM.
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Rosenbaum, Jennifer L., R. Scott Frayo, Susan J. Melhorn, David E. Cummings e Ellen A. Schur. "Effects of multiple cycles of weight loss and regain on the body weight regulatory system in rats". American Journal of Physiology-Endocrinology and Metabolism 317, n. 5 (1 novembre 2019): E863—E870. http://dx.doi.org/10.1152/ajpendo.00110.2019.
Abstract (sommario):
We studied the effects of multiple cycles of weight loss and regain on the defended body weight in rats. Thirty-six male Wistar rats were divided into three weight-matched groups: weight cyclers ( n = 18), ad libitum-fed controls ( n = 9), and maturity controls ( n = 9). Cyclers underwent four rounds of 20% weight loss from 50% caloric restriction, each cycle followed by recovery to stable plateau weight on ad libitum feeding. Controls ate ad libitum. Maturity controls ate ad libitum and then weight cycled the final two rounds to evaluate the effect of age in later cycles. Cyclers’ postdiet plateau weight became progressively lower than that of controls. With each weight loss, ghrelin increased, while insulin and leptin decreased; the magnitude of these changes did not differ across cycles. After four rounds, cyclers’ weight (504 ± 7 vs. 540 ± 22 g; P < 0.05) and percent body fat (11.7 vs. 15.2%; P < 0.05) were lower than in controls. After a 4-mo follow-up period of ad libitum feeding, cyclers maintained a lower total fat-pad mass versus controls (8.6 ± 0.5 vs. 15.9 ± 3.6 g; P < 0.01) and a lower glucose area-under-the-curve on oral glucose tolerance tests ( P < 0.05). Repeated weight-loss cycles exerted positive effects, durably lowering defended levels of body adiposity and improving glucose tolerance.
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Lwowski, Christoph, Vladimir Rusev e Thomas Kohnen. "Assessment of Visual Habituation Measured With the Halo & Glare Simulator and Its Impact on Patient Satisfaction Following Quadrifocal IOL Implantation". Journal of Refractive Surgery 39, n. 8 (agosto 2023): 510–17. http://dx.doi.org/10.3928/1081597x-20230612-01.
Abstract (sommario):
Purpose: To evaluate the levels of habituation and its influence on outcome satisfaction in patients who underwent bilateral multifocal intraocular lens (IOL) implantation. Methods: A total of 24 patients underwent bilateral multifocal IOL implantation surgery with the AcrySof IQ PanOptix trifocal diffractive IOL (Alcon Laboratories, Inc) following cataract extraction or for refractive purposes. Data were collected 3 and 6 months after surgery, which included subjective refraction, corrected and uncorrected visual acuity (distance, intermediate, near), a contrast sensitivity test, simulation with the Halo & Glare Simulator (Carl Zeiss Meditec AG), two visual quality surveys, and a slit-lamp examination by an ophthalmologist. Results: All patients were spectacle independent for distance vision and 92% (n = 22) needed no visual aid for near vision. Minor visual acuity improvement was detected between both examinations at monocular uncorrected distance visual acuity ( P = .025). Improvements of presence, size, and intensity of visual disturbances were not statistically significant, but overall patient satisfaction ( P = .009) and Weber-Contrast sensitivity under mesopic conditions ( P = .029) increased significantly. Conclusions: Diffractive multifocal IOLs are a stable treatment for presbyopia and/or cataract with a high spectacle independence rate. Visual disturbances caused by their optics do not decrease significantly between 3 and 6 months after surgery. Habituation and neuroadaptation play a significant role in patient satisfaction and contrast sensitivity during and possibly beyond that period. [ J Refract Surg . 2023;39(8):510–517.]
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Castagna, L., S. Bramanti, A. Levis, M. Michieli, A. Anastasia, R. Mazza, B. Sarina, E. Todisco, L. Giordano e A. Santoro. "A phase II randomized study comparing pegfilgrastim (PEG) versus filgrastim (FIL) after high-dose chemotherapy (HDC) and autologous peripheral blood stem cell support (PBSC)". Journal of Clinical Oncology 27, n. 15_suppl (20 maggio 2009): 7038. http://dx.doi.org/10.1200/jco.2009.27.15_suppl.7038.
Abstract (sommario):
7038 Background: The aim of this study was to demonstrate the non-inferiority of one fixed dose of PEG compared to daily FIL, in patients (pts) receiving HDC and PBSC. Methods: Criteria for elegibility were: HDC for haematological or solid tumors; at least 3 x10^6/kg CD34+ reinfused; age >18 years; normal cardiac, renal, liver and pulmonary function; signed written informed consent. Pts were randomized to receive on day+1 subcutaneously(sc) PEG (6mg) or 5 mcg/kg/d sc of FIL until ANC >1.0 x 10^9/L. Primary end points were: absolute neutrophil count (ANC) < 0.5 x 10^9/L and the number (no.) of days to achieve an ANC > 0.5 x 10^9/L from day +1. Secondary end points were: no. of days to achieve an ANC > 1.0 x 10^9/L; no. of days with fever > 38 °C; duration of antibiotic therapy; and no. of documented infections. Results: 80 pts were enrolled (40 pts for group). The duration of ANC < 0.5 x 10^9/L, the time to reach an ANC > 0.5 x 10^9/L and the time to reach an ANC > 1.0 x 10^9/L were superimposable in the two groups (mean days 6, 11, 12 respectively ). No. significant differences between FIL versus PEG group were observed in incidence of fever (24 vs 22), no. of documented infections (12 vs 10), no. of days with fever (1.7 vs 0.97 days), duration of antibiotic therapy (5.7 vs 3.5 days). No. differences in terms of extra-hematological toxicities and time to discharge between the two groups (16 vs 14). Time to reach a platelets count > 20 x 10^9/L was significantly shorter in PEG group compared to FIL group (15 vs 11 days, p value 0.05). Conclusions: This study shows that PEG was not inferior to FIL in terms of hematological reconstitution. Additionally PEG significantly shortened duration of thrombocytopenia <20 x 10^9/L. Consequently, PEG could be safely used after PBSC infusion. No significant financial relationships to disclose.
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Levin, L. A., A. L. McGregor, G. F. Mendoza, C. Woulds, P. Cross, U. Witte, A. J. Gooday, G. Cowie e H. Kitazato. "Macrofaunal colonization across the Indian margin oxygen minimum zone". Biogeosciences 10, n. 11 (12 novembre 2013): 7161–77. http://dx.doi.org/10.5194/bg-10-7161-2013.
Abstract (sommario):
Abstract. There is a growing need to understand the ability of bathyal assemblages to recover from disturbance and oxygen stress, as human activities and expanding oxygen minimum zones increasingly affect deep continental margins. The effects of a pronounced oxygen minimum zone (OMZ) on slope benthic community structure have been studied on every major upwelling margin; however, little is known about the dynamics or resilience of these benthic populations. To examine the influence of oxygen and phytodetritus on short-term settlement patterns, we conducted colonization experiments at 3 depths on the West Indian continental margin. Four colonization trays were deployed at each depth for 4 days at 542 and 802 m (transect 1–16°58' N) and for 9 days at 817 and 1147 m (transect 2–17°31' N). Oxygen concentrations ranged from 0.9 μM (0.02 mL L−1) at 542 m to 22 μM (0.5 mL L−1) at 1147 m. All trays contained local defaunated sediments; half of the trays at each depth also contained 13C/15N-labeled phytodetritus mixed into the sediments. Sediment cores were collected between 535 m and 1140 m from 2 cross-margin transects for analysis of ambient (source) macrofaunal (>300 μm) densities and composition. Ambient macrofaunal densities ranged from 0 ind m−2 (at 535–542 m) to 7400 ind m−2, with maximum values on both transects at 700–800 m. Macrofaunal colonizer densities ranged from 0 ind m−2 at 542 m, where oxygen was lowest, to average values of 142 ind m−2 at 800 m, and 3074 ind m−2 at 1147 m, where oxygen concentration was highest. These were equal to 4.3 and 151% of the ambient community at 800 m and 1147 m, respectively. Community structure of settlers showed no response to the presence of phytodetritus. Increasing depth and oxygen concentration, however, significantly influenced the community composition and abundance of colonizing macrofauna. Polychaetes constituted 92.4% of the total colonizers, followed by crustaceans (4.2%), mollusks (2.5%), and echinoderms (0.8%). The majority of colonizers were found at 1147 m; 88.5% of these were Capitella sp., although they were rare in the ambient community. Colonists at 800 and 1147 m also included ampharetid, spionid, syllid, lumbrinerid, cirratulid, cossurid and sabellid polychaetes. Consumption of 13C/15N-labeled phytodetritus was observed for macrofaunal foraminifera (too large to be colonizers) at the 542 and 802/817 m sites, and by metazoan macrofauna mainly at the deepest, better oxygenated sites. Calcareous foraminifera (Uvigerina, Hoeglundina sp.), capitellid polychaetes and cumaceans were among the major phytodetritus consumers. These preliminary experiments suggest that bottom-water oxygen concentrations may strongly influence ecosystem services on continental margins, as reflected in rates of colonization by benthos and colonizer processing of carbon following disturbance. They may also provide a window into future patterns of settlement on the continental slope as the world's oxygen minimum zones expand.
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Krasilnikov, D. M., R. Sh Safin, D. Z. Vasil’ev, A. V. Zakharova, D. M. Mirgasimova e A. F. Yusupova. "Prevention of complications after endoscopic retrograde cholangiopancreatography and papillosphincterotomy". Kazan medical journal 93, n. 4 (15 agosto 2012): 597–601. http://dx.doi.org/10.17816/kmj1551.
Abstract (sommario):
Aim. To improving the results of treatment of patients with obstructive jaundice on the basis of analysis of the causes of complications after endoscopic cholangiopancreatography and papillosphincterotomy. Methods. Conducted was an analysis of medical records of 703 patients with obstructive jaundice for the period 2006-2010. Results. Endoscopic retrograde cholangiopancreatography was performed in 542 patients. In 22 (4.06%) patients the study could not be performed due to anatomical features in the terminal portion of the common bile duct and in the descending section of the duodenum. If cases when it was necessary, cholangiopancreatography was accompanied by papillosphincterotomy. In total this procedure was conducted in 488 patients, including repeated procedures (2 to 4 times) - in 186 patients, and with concomitant lithoextraction - in 265 patients. The overall incidence of complications after endoscopic interventions for obstructive jaundice was 8.5% (46 cases) and the mortality rate was 1.1% (6 cases). Pancreatic necrosis developed in 7 (1.3%) cases, of which 3 (0.5%) with a lethal outcome, bleeding occured in 28 (5.7%) patients from the incision zone during papillosphincterotomy, perforation of the duodenum with a lethal outcome occurred in 1 (0.2%) case, jamming of the Dormia baskets occured in 10 (3.77%) patients, 2 (0.4%) of the cases had a lethal outcome. Adequate preparation for the procedure, adequate and effective premedication, sparing technique of endoscopic retrograde cholangiopancreatography and interventions on the major duodenal papilla, adequate and rational therapy after the diagnostic procedure and the operation are believed to be effective prevention measures of acute pancreatitis after endoscopic retrograde cholangiopancreatography and endoscopic papillosphincterotomy. Prevention of bleeding is mainly attributed to patient preparation: before the intervention it is necessary to examine the coagulation and clotting of blood, haemostatic agents should be administered before the operation and in complex cases papillosphincterotomy should be conducted in several stages with an interval of 3-6 days. For prevention of duodenal perforation the usage of a catheter cannula with an atraumatic distal end, and elimination of rough manipulations are recommended. In order to prevent jamming of the Dormia basket a thorough diagnosis is required, detection of large dense concretions on the background of stenosis of the terminal common bile duct should lead to refusal of conduction of lithoextraction. Conclusion. The use of endoscopic retrograde cholangiopancreatography and endoscopic papillosphincterotomy with adequate procedure performance in specialized endosurgical departments makes it possible to enhance the quality of diagnosis, reduce the incidence of complications and improve the results of treatment of patients with obstructive jaundice.
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Coleman, Niamh, Jason Roszik, Neha K. Reddy e Vivek Subbiah. "Characterizing the genomic landscape of PIK3CA alterations from 121,221 adult patients with cancer: The next tissue-agnostic target?" Journal of Clinical Oncology 40, n. 16_suppl (1 giugno 2022): 3088. http://dx.doi.org/10.1200/jco.2022.40.16_suppl.3088.
Abstract (sommario):
3088 Background: The PI3K–AKT–mTOR signaling pathway is frequently dysregulated in cancer and small molecule inhibitors targeting various nodes in the pathway have been pursued for decades. Activating mutations in PIK3CA are recognized potent drivers of oncogenesis, though the landscape of PIK3CA fusions and amplifications has yet to be well-defined. The field has been hampered by issues such as resistance and poor tolerance, however several isoform-specific PI3K inhibitors have now received regulatory approval and allosteric pan-mutant and specific mutant selective Inhibitors of PI3Kα are being investigated in early phase clinical trials. Here, we present a comprehensive analysis of PIK3CA alterations in pan-cancer adult malignancies. Methods: We analyzed 136096 samples from 121221 patients available from AACR Project GENIE v.11 database for the prevalence of PIK3CA mutations, fusions and copy number alterations in a range of cancer types. Results: 15712 alterations in PIK3CA were detected in profiled tumor samples (12%), in 14774 of patients profiled (12%), most frequently in endometrial (44% of 4135 cases), anal (35% of 286 cases), breast (35% of 14218 cases), cervical (27% of 761 cases) and colorectal cancer (20% of 3743 cases). PIK3CA alterations identified included 17740 mutations (11%) (including duplicate mutations in patients with multiple samples). 16685 missense mutations were identified (12%);14953 were identified as missense in driver mutation (likely oncogenic)(90% of missense); 1,732 were missense of variants of uncertain significance (VUS) using OncoKB database (11%). Missense mutations most frequently involved codons 545(3347, 20% of missense), codon 1047 (3644, 22%) and codon 542 (1881, 11%). 237 truncating mutations were identified (0.2%), 442 in-frame deletions, 29 in-frame insertion mutations. PIK3CA fusions were observed in 0.06% of tumor samples and were most identified in breast, colorectal, lung, GBM and ovarian cancer (24%, 17%, 13%, 7% and 6% of identified PIK3CA fusions respectively). PIK3CA fusions were most commonly intragenic fusions(36%);common fusion partners included TBL1XR1, FNDC3B and NAALADL2(17%, 7%, 5% of identified PIK3CA fusions, respectively). PIK3CA fusions were identified as VUS, aside from KMT2C-PIK3CA (2%) . PIK3CA amplification high level gain occurred in 0.5% of samples tested(662), deletion occurred in 0.16%(21). Conclusions: Activating PIK3CA mutations occur frequently across cancer types and could be considered for tissue-agnostic drug development. PIK3CA fusion and amplification events are extremely rare. Most PIK3CA missense mutation variants are described as oncogenic, while fusions are described as VUS, which may limit the impact of precision oncology for patients with this alteration. Further functional characterization of PIK3CA variants and basket trial enrollment are warranted.