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1
Everhart, Joshua Scott, David C. Flanigan, Robert A. Magnussen, and Christopher C. Kaeding. "Platelet-Rich Plasma: Does It Decrease Meniscus Repair Failure Risk?" Orthopaedic Journal of Sports Medicine 7, no. 7_suppl5 (July 2019): 2325967119S0024. http://dx.doi.org/10.1177/2325967119s00247.
Abstract:
Objectives: (1) To determine whether intraoperative PRP affects meniscus repair failure risk. (2) To determine whether the effect of PRP on meniscus failure risk is influenced by ACL reconstruction status or by PRP preparation. Methods: 550 patients (mean age 28.8 years SD 11.3) who underwent meniscus repair surgery with PRP (n=203 total, n=148 prepared with GPS III system, n=55 Angel system) or without PRP (n=347) and with (n=399) or without (n=151) concurrent ACL reconstruction were assessed for meniscus repair failure within 3 years. The independent effect of PRP on meniscus repair failure risk was determined by multivariate Cox proportional hazards modeling with adjustment for age, sex, body mass index (BMI), ACL status, tear pattern, tear vascularity, repair technique, side (medial or lateral) and number of sutures or implants utilized. Results: Failures within 3 years occurred in 17.0% of patients without PRP and 14.7% of patients with PRP (p=0.52) (Angel PRP: 14.6%; GPS III PRP: 12.0%; p=0.59). Increased patient age was protective against meniscus failure regardless of ACL or PRP status (per 5-year increase in age: adjusted Hazard Ratio [aHR] 0.90, 95% confidence interval [CI] 0.81, 1.0; p=0.047). The effect of PRP on meniscus failure risk was dependent upon concomitant ACL injury status (Figure). Among isolated meniscus repairs (20.3% failures at 3 years), PRP was independently associated with lower risk of failure (aHR 0.18, 95% confidence interval (CI) 0.03, 0.59; p=0.002) with no difference between PRP vendors (p=0.84). Among meniscus repairs with concomitant ACLR (14.1% failures at 3 years), PRP was not independently associated with risk of failure (aHR 1.39 CI 0.81, 2.36; p=0.23) with no difference between PRP venders (p=0.78). Conclusion: Both PRP preparations utilized in the current study had a substantial protective effect on isolated meniscus repair failure risk over 3 years. In the setting of concomitant ACL reconstruction, intraoperative PRP does not reduce meniscus repair failure risk. [Figure: see text]
2
Everhart, Joshua S., Parker A. Cavendish, Alex Eikenberry, Robert A. Magnussen, Christopher C. Kaeding, and David C. Flanigan. "Platelet-Rich Plasma Reduces Failure Risk for Isolated Meniscal Repairs but Provides No Benefit for Meniscal Repairs With Anterior Cruciate Ligament Reconstruction." American Journal of Sports Medicine 47, no. 8 (June 5, 2019): 1789–96. http://dx.doi.org/10.1177/0363546519852616.
Abstract:
Background: The effect of platelet-rich plasma (PRP) on the risk of meniscal repair failure is unclear. Current evidence is limited to small studies without comparison between isolated repairs and meniscal repairs with concomitant anterior cruciate ligament (ACL) reconstruction. It is also unclear whether the efficacy of PRP differs between preparation systems in the setting of meniscal repair. Purpose: (1) To determine whether intraoperative PRP affects the risk of meniscal repair failure. (2) To determine whether the effect of PRP on meniscal failure risk is influenced by ACL reconstruction status or by PRP preparation system. Study Design: Cohort study; Level of evidence, 3. Methods: The study entailed 550 patients (mean ± SD age, 28.8 ± 11.2 years) who underwent meniscal repair surgery with PRP (n = 203 total; n = 148 prepared with GPS III system, n = 55 prepared with Angel system) or without PRP (n = 347) and with (n = 399) or without (n = 151) concurrent ACL reconstruction. The patients were assessed for meniscal repair failure within 3 years. The independent effect of PRP on the risk of meniscal repair failure was determined by multivariate Cox proportional hazards modeling with adjustment for age, sex, body mass index, ACL status, tear pattern, tear vascularity, repair technique, side (medial or lateral), and number of sutures or implants used. Results: Failures within 3 years occurred in 17.0% of patients without PRP and 14.6% of patients with PRP ( P = .60) (Angel PRP, 15.9%; GPS III PRP, 14.2%; P = .58). Increased patient age was protective against meniscal failure regardless of ACL or PRP status (per 5-year increase in age: adjusted hazard ratio [aHR], 0.90; 95% CI, 0.81-1.0; P = .047). The effect of PRP on meniscal failure risk was dependent on concomitant ACL injury status. Among isolated meniscal repairs (20.3% failures at 3 years), PRP was independently associated with lower risk of failure (aHR, 0.18; 95% CI, 0.03-0.59; P = .002) with no difference between PRP preparation systems ( P = .84). Among meniscal repairs with concomitant ACL reconstruction (14.1% failures at 3 years), PRP was not independently associated with risk of failure (aHR, 1.39; 95% CI, 0.81-2.36; P = .23) with no difference between PRP preparation systems ( P = .78). Conclusion: Both PRP preparations used in the current study had a substantial protective effect in terms of the risk of isolated meniscal repair failure over 3 years. In the setting of concomitant ACL reconstruction, PRP does not reduce the risk of meniscal repair failure.
3
Mowlavi, N., I. Lecoeur-Taïbi, T. Lebzelter, L. Rimoldini, D. Lorenz, M. Audard, J. De Ridder, et al. "Gaia Data Release 2." Astronomy & Astrophysics 618 (October 2018): A58. http://dx.doi.org/10.1051/0004-6361/201833366.
Abstract:
Context. Gaia Data Release 2 (DR2) provides a unique all-sky catalogue of 550 737 variable stars, of which 151 761 are long-period variable (LPV) candidates with G variability amplitudes larger than 0.2 mag (5–95% quantile range). About one-fifth of the LPV candidates are Mira candidates, the majority of the rest are semi-regular variable candidates. For each source, G, GBP, and GRP photometric time-series are published, together with some LPV-specific attributes for the subset of 89 617 candidates with periods in G longer than 60 days. Aims. We describe this first Gaia catalogue of LPV candidates, give an overview of its content, and present various validation checks. Methods. Various samples of LPVs were used to validate the catalogue: a sample of well-studied very bright LPVs with light curves from the American Association of Variable Star Observers that are partly contemporaneous with Gaia light curves, a sample of Gaia LPV candidates with good parallaxes, the All-Sky Automated Survey for Supernovae catalogue of LPVs, and the Optical Gravitational Lensing Experiment (OGLE) catalogues of LPVs towards the Magellanic Clouds and the Galactic bulge. Results. The analyses of these samples show a good agreement between Gaia DR2 and literature periods. The same is globally true for bolometric corrections of M-type stars. The main contaminant of our DR2 catalogue comes from young stellar objects (YSOs) in the solar vicinity (within ~1 kpc), although their number in the whole catalogue is only at the percent level. A cautionary note is provided about parallax-dependent LPV attributes published in the catalogue. Conclusions. This first Gaia catalogue of LPVs approximately doubles the number of known LPVs with amplitudes larger than 0.2 mag, despite the conservative candidate selection criteria that prioritise low contamination over high completeness, and despite the limited DR2 time coverage compared to the long periods characteristic of LPVs. It also contains a small set of YSO candidates, which offers the serendipitous opportunity to study these objects at an early stage of the Gaia data releases.
4
Gupta, N., C. L. Reichardt, P. A. R. Ade, A. J. Anderson, M. Archipley, J. E. Austermann, J. S. Avva, et al. "Fractional polarization of extragalactic sources in the 500 deg2 SPTpol survey." Monthly Notices of the Royal Astronomical Society 490, no. 4 (October 21, 2019): 5712–21. http://dx.doi.org/10.1093/mnras/stz2905.
Abstract:
ABSTRACT We study the polarization properties of extragalactic sources at 95 and 150 GHz in the SPTpol 500 deg2 survey. We estimate the polarized power by stacking maps at known source positions, and correct for noise bias by subtracting the mean polarized power at random positions in the maps. We show that the method is unbiased using a set of simulated maps with similar noise properties to the real SPTpol maps. We find a flux-weighted mean-squared polarization fraction 〈p2〉 = [8.9 ± 1.1] × 10−4 at 95 GHz and [6.9 ± 1.1] × 10−4 at 150 GHz for the full sample. This is consistent with the values obtained for a subsample of active galactic nuclei. For dusty sources, we find 95 per cent upper limits of 〈p2〉95 < 16.9 × 10−3 and 〈p2〉150 < 2.6 × 10−3. We find no evidence that the polarization fraction depends on the source flux or observing frequency. The 1σ upper limit on measured mean-squared polarization fraction at 150 GHz implies that extragalactic foregrounds will be subdominant to the CMB E and B mode polarization power spectra out to at least ℓ ≲ 5700 (ℓ ≲ 4700) and ℓ ≲ 5300 (ℓ ≲ 3600), respectively, at 95 (150) GHz.
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Wu, Wen, Wenxing Guo, Naifan Zhang, Min Gao, Kexin Zhang, Elizabeth N. Pearce, Shaohan Li, et al. "Adverse Effects on the Thyroid of Chinese Pregnant Women Exposed to Long-Term Iodine Excess: Optimal and Safe Tolerable Upper Intake Levels of Iodine." Nutrients 15, no. 7 (March 28, 2023): 1635. http://dx.doi.org/10.3390/nu15071635.
Abstract:
Ensuring optimal iodine nutrition in pregnant women is a global public health concern. However, there is no direct data on safe tolerable upper intake levels (ULs) for pregnant women. A cross-sectional study was performed to determine the ULs of pregnant women. A total of 744 pregnant women were enrolled in this study. The median (IQR) urinary iodine concentration (UIC) in pregnant women was 150.2 (87.6, 268.0) μg/L, and the urinary iodine excretion (UIE) over 24 h was 204.2 (116.0, 387.0) μg/day. Compared with those with a UIE figure of between 150–250 μg/day, the reference group, the prevalence of thyroid dysfunction was 5.7 times higher (95%CI: 1.7, 19.2) in pregnant women with a UIE figure of between 450–550 μg/day, and 3.9 times higher (95%CI: 1.5, 10.3) in pregnant women with a UIE figure of ≥550 μg/day. Compared with an estimated iodine intake (EII) of between 100–200 μg/day, the reference group, the prevalence of thyroid dysfunction was 4.3 times higher (95%CI: 1.3, 14.4) in pregnant women with a UIE figure of between 500–600 μg/day, and 3.6 times higher (95%CI: 1.5, 8.9) in pregnant women with UIE of ≥600 μg/day. In general, our cross-sectional study found that excessive iodine intake during pregnancy appears to directly increase the risk of thyroid dysfunction. Avoiding chronic iodine intakes of 500 μg/day or higher or having a UIE figure of ≥450 μg/day is recommended for pregnant women in China.
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Яцкевич, Н. В., Э. Гурбанова, Г. Л. Гуревич, А. Ованнесян, and Е. М. Скрягина. "Preliminary Data on the Efficacy, Predictors of Unfavorable Outcomes of 9-Month Treatment Regimes in Patients with Rifampicin-Resistant Tuberculosis in the Republic of Belarus." Рецепт, no. 1 (February 28, 2023): 23–35. http://dx.doi.org/10.34883/pi.2023.26.1.005.
Abstract:
Введение. Общая продолжительность лечения рифампицин-устойчивого туберкулеза (РУ-ТБ) составляет 18 месяцев. Эффективность применяемых режимов низкая (73% в когорте 2018 года). Разработка эффективных коротких режимов лечения РУ-ТБ является актуальной задачей. В Республике Беларусь применяются модифицированные короткие режимы лечения (мКРЛ) пациентов с РУ-ТБ в рамках операционного исследования. Цель. Провести предварительную оценку эффективности, прогностических факторов неблагоприятных исходов мКРЛ у пациентов с РУ-ТБ. Материалы и методы. Проведена предварительная оценка эффективности мКРЛ, содержащих бедаквилин, левофлоксацин, линезолид, клофазимин и циклосерин или деламанид, длительностью 39 недель в когорте пациентов с РУ-ТБ. Проведен однофакторный анализ с целью выявления прогностических факторов неблагоприятных исходов лечения пациентов с РУ-ТБ. Результаты. Из 550 пациентов, включенных в исследование с декабря 2019 по октябрь 2021 года, 13 пациентов были исключены из исследования, продолжили лечение по индивидуальной схеме, у 90,7% (493/537) был зарегистрирован успешный исход лечения, у 2,6% – неудача в лечении, 2,8% – потеря для последующего наблюдения, 3,9% – умерли. Прогностическими факторами неблагоприятного исхода лечения были возраст старше 45 лет (ОШ – 2,9, 95% ДИ 1,5–5,8, р=0,002), наличие ишемической болезни сердца (ИБС) (ОШ – 2,2, 95% ДИ 1,1–4,5, р=0,02), развитие серьезных нежелательных явлений (СНЯ) (ОШ – 2,0, 95% ДИ 1,1–3,7, р=0,004), наличие полостейраспада в легких (ОШ – 2,0, 95% ДИ 1,1–3,7, р=0,02), срок конверсии посева мокроты >90 дней (ОШ – 3,35, 95% ДИ 1,2–9,5, р=0,03). Частота развития неблагоприятных исходов не зависела от пола, индекса массы тела, наличия инфекции ВИЧ, вирусного гепатита С. Выводы. Эффективность мКРЛ у пациентов с РУ-ТБ высокая (90,7%). Пациенты с наличием полостей распада в легких до начала лечения, с более поздней конверсией посева мокроты, с наличием ИБС и развитием СНЯ имеют более низкие шансы на излечение. Introduction. The total duration of treatment for rifampicin-resistant tuberculosis (RR-TB) is 18 months. The efficacy of these regimens is low (73% in the 2018 cohort). The development of effective short regimens for RR-TB treatment is an urgent task. In the Republic of Belarus modified short treatment regimens (mSTR) are used in patients with RR-TB under operational research condition. Purpose. To conduct a preliminary assessment of the efficacy, predictors of unfavourable outcomes of mSTR for patients with RR-TB. Materials and methods. A preliminary assessment of the efficacy of 39-week mSTR containing bedaquiline, levofloxacin, linezolid, clofazimine, and cycloserine or delamanid was performed in a cohort of patients with RR-TB. Univariate analysis was used to detect factors associated with unfavourable outcomes. Results. Of 550 patients who were enrolled from December 2019 to October 2021, 13 patients were excluded from the study, continued treatment according to the individualized regimen, 90.7% (493/537) had favourable outcome of treatment, 2.6% failed, 2.8% were lost to follow-up, 3.9% died. Predictors of unfavourable outcomes were age over 45 years (OR – 2.9, 95% CI 1.5–5.8, p=0.002), presence of Ischemic heart disease (IHD) (OR – 2.2, 95% CI 1.1–4.5, p=0.02), presence of serious adverse events (SAE) (OR – 2.0, 95% CI 1.1–3.7, p=0.004), presence of cavities (OR – 2.0, 95% CI 1.1–3.7, p=0.02), time to culture conversion >90 days (OR 3.35, 95% CI 1.2–9.5, p=0.03). Frequency of unfavourable outcomes did not depend on gender, body mass index, presence of HIV infection, viral hepatitis C. Conclusion. The efficacy of mSTR for patients with RR-TB is high (90.7%). Patients with pulmonary cavitary lesions at treatment start and those, with later culture conversion, with IHD, with SAE have a lower chance of cure.
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Rentroia-Pacheco, Barbara, Lara Pozza, Yan Ting Chen, Daphne Huigh, Celeste J. Eggermont, Olivia FM Steijlen, Sheril Alex, et al. "Abstract 4869: Efficient study design for the discovery of a gene expression signature predicting metastasis in cutaneous squamous cell carcinoma." Cancer Research 84, no. 6_Supplement (March 22, 2024): 4869. http://dx.doi.org/10.1158/1538-7445.am2024-4869.
Abstract:
Abstract Background: The StepIdent study aims to develop a gene signature predicting metastasis in patients with cutaneous squamous cell carcinoma (cSCC) to improve risk stratification, thus enabling personalized decisions about follow-up schedules and treatment options. Here we describe the unique characteristics, challenges, and best practices for an efficient design of a discovery cohort for a rare outcome (metastasis prevalence: 2-5%); for retrieving, curating, and linking the clinical and pathological data through nationwide databases; and for measuring gene expression through sequencing of archived Formalin-Fixed Paraffin-Embedded (FFPE) primary tumor samples. Methods: Following a predefined protocol, we identified a nested-case control cohort (NCC) of 305 cases and 305 controls from a nationwide cohort of 19,120 patients with a first cSCC in the Netherlands from 2007 to 2009, followed up until 2020. We chose an NCC design since it is an efficient study design in a rare outcome setting (weighting is needed to accommodate the under-sampling of the controls). Patients were identified from the Dutch National Cancer Registry (NCR) and the clinical information was retrieved from the NCR which is linked to the nationwide registry of histo- and cytopathology (PALGA). Tumor blocks were requested from PALGA, and pathological characteristics were assessed by dermatopathologists. We matched controls to cases, based on a risk score estimated by a clinicopathological model. Gene expression was measured using the Illumina RNA Prep with Enrichment kit combined with the whole exome panel and paired-end sequenced on the NextSeq 550. Results: Tissue slides for 541 samples were retrieved for sequencing. 151 samples were excluded after pathology review or due to low pre-library concentration. The final cohort includes 195 case-control pairs (n=390). The median sequencing depth was 43M (Q1-Q3: 35-52M); the median Q30 was 85% (Q1-Q3: 83-87%); the median GC content was 51% (Q1-Q3: 50-52%); a median of 1.8% of base pairs (Q1-Q3: 1.4-2.1%) was trimmed prior to the mapping/alignment; a median of 69% (Q1-Q3: 65-74%) of reads were aligned as protein-coding and a median of 7% (Q1-Q3: 6-10%) as rRNA; a median of 95% (Q1-Q3: 93-96%) of reads were aligned by STAR. Two samples were excluded based on quality control. Conclusion: We described an efficient design and implementation of a nationwide discovery study in cSCC, involving the retrieval of clinicopathological data, the collection of FFPE materials, and the execution of omics measurements. This study presents the largest cohort to date, incorporating omics measurements of primary cSCC samples, combined with simultaneous access to well-curated clinical and pathological information and follow-up data. Our findings can provide guidance for similar studies involving a rare clinical endpoint, where an efficient study design is a necessity. Citation Format: Barbara Rentroia-Pacheco, Lara Pozza, Yan Ting Chen, Daphne Huigh, Celeste J. Eggermont, Olivia FM Steijlen, Sheril Alex, Jvalini Dwarkasing, Domenico Bellomo, Harmen JG van de Werken, Antien L. Mooyaart, Marlies Wakkee, Loes M. Hollestein. Efficient study design for the discovery of a gene expression signature predicting metastasis in cutaneous squamous cell carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4869.
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Bihan, Line, Emmanuel Nowak, François Anouilh, Christophe Tremouilhac, Philippe Merviel, Cécile Tromeur, Sara Robin, et al. "Development and Validation of a Predictive Tool for Postpartum Hemorrhage after Vaginal Delivery: A Prospective Cohort Study." Biology 12, no. 1 (December 29, 2022): 54. http://dx.doi.org/10.3390/biology12010054.
Abstract:
Postpartum hemorrhage (PPH) is one of the leading causes of maternal morbidity worldwide. This study aimed to develop and validate a predictive model for PPH after vaginal deliveries, based on routinely available clinical and biological data. The derivation monocentric cohort included pregnant women with vaginal delivery at Brest University Hospital (France) between April 2013 and May 2015. Immediate PPH was defined as a blood loss of ≥500 mL in the first 24 h after delivery and measured with a graduated collector bag. A logistic model, using a combination of multiple imputation and variable selection with bootstrap, was used to construct a predictive model and a score for PPH. An external validation was performed on a prospective cohort of women who delivered between 2015 and 2019 at Brest University Hospital. Among 2742 deliveries, PPH occurred in 141 (5.1%) women. Eight factors were independently associated with PPH: pre-eclampsia (aOR 6.25, 95% CI 2.35–16.65), antepartum bleeding (aOR 2.36, 95% CI 1.43–3.91), multiple pregnancy (aOR 3.24, 95% CI 1.52–6.92), labor duration ≥ 8 h (aOR 1.81, 95% CI 1.20–2.73), macrosomia (aOR 2.33, 95% CI 1.36–4.00), episiotomy (aOR 2.02, 95% CI 1.40–2.93), platelet count < 150 Giga/L (aOR 2.59, 95% CI 1.47–4.55) and aPTT ratio ≥ 1.1 (aOR 2.01, 95% CI 1.25–3.23). The derived predictive score, ranging from 0 to 10 (woman at risk if score ≥ 1), demonstrated a good discriminant power (AUROC 0.69; 95% CI 0.65–0.74) and calibration. The external validation cohort was composed of 3061 vaginal deliveries. The predictive score on this independent cohort showed an acceptable ability to discriminate (AUROC 0.66; 95% CI 0.62–0.70). We derived and validated a robust predictive model identifying women at risk for PPH using in-depth statistical methodology. This score has the potential to improve the care of pregnant women and to take preventive actions on them.
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Kisiel, Z., and L. Pszczółkowski. "The High-Frequency Rotational Spectrum of 1,1 -Dichloroethylene." Zeitschrift für Naturforschung A 50, no. 4-5 (May 1, 1995): 347–51. http://dx.doi.org/10.1515/zna-1995-4-505.
Abstract:
Abstract The b-type rotational spectrum of 1,1-dichloroethylene was investigated up to 450 GHz and was found to be dominated by type-II R-type bands. All constants in the sextic Hamiltonian for the ground states of the common isotopic species and of the 37C1 isotopomer were determined from measurements on transitions with J up to 95. Quartic and sextic planarity defects were evaluated and are compared and discussed with those for several recently investigated planar molecules
10
Lanza, Ezio, Maria Elisa Mancuso, Gaia Messana, Paola Ferrazzi, Costanza Lisi, Pierpaolo Di Micco, Stefano Barco, Luca Balzarini, and Corrado Lodigiani. "Compromised Lung Volume and Hemostatic Abnormalities in COVID-19 Pneumonia: Results from an Observational Study on 510 Consecutive Patients." Journal of Clinical Medicine 10, no. 13 (June 29, 2021): 2894. http://dx.doi.org/10.3390/jcm10132894.
Abstract:
Background: Hemostatic abnormalities have been described in COVID-19, and pulmonary microthrombosis was consistently found at autopsy with concomitant severe lung damage. Methods: This is a retrospective observational cross-sectional study including consecutive patients with COVID-19 pneumonia who underwent unenhanced chest CT upon admittance at the emergency room (ER) in one large academic hospital. QCT was used for the calculation of compromised lung volume (%CL). Clinical data were retrieved from patients’ files. Laboratory data were obtained upon presentation at the ER. Aim: The aim of this study was to evaluate the correlation between hemostatic abnormalities and lung involvement in patients affected by COVID-19 pneumonia as described using computer-aided quantitative evaluation of chest CT (quantitative CT (QCT)). Results: A total of 510 consecutive patients (68% males), aged 67 years in median, diagnosed with COVID-19 pneumonia, who underwent unenhanced CT scan upon admission to the ER, were included. In all, 115 patients had %CL > 23%; compared to those with %CL < 23%, they showed higher levels of D-dimer, fibrinogen, and CRP, greater platelet count, and longer PT ratio. Via multivariate regression analysis, BMI ≥ 30 kg/m2, D-dimer levels > 500 ng/mL, CRP > 5.0 ng/mL and PT ratio > 1.2 were found to be independent predictors of a %CL > 23% (adjusted odds ratios (95% confidence intervals): 2.1 (1.1–4.0), 3.1 (1.6–5.8), 2.4 (1.3–4.5), and 3.4 (1.4–8.5), respectively). Conclusions: Hemostatic abnormalities in patients affected by COVID-19 correlate with the severity of lung injury as measured by %CL. Our results underline the pathogenetic role of hemostasis in COVID-19 pneumonia beyond the presence of clinically evident thromboembolic complications.
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Matta, André Palma da Cunha, Soraya Vilani Bonacorsi Chiacchio, and Marcio Leyser. "Possíveis etiologias da Síndrome de West: avaliação de 95 pacientes." Arquivos de Neuro-Psiquiatria 65, no. 3a (September 2007): 659–62. http://dx.doi.org/10.1590/s0004-282x2007000400022.
Abstract:
OBJETIVO: Descrever as etiologias da síndrome de West (SW) em um grupo de crianças atendidas no ambiente de um centro de reabilitação. MÉTODO: Análise retrospectiva, avaliando-se os seguintes itens: gênero, idade por ocasião da definição do diagnóstico da SW e sua etiologia. Esta foi dividida em três categorias: sintomática, criptogênica e idiopática. Os casos sintomáticos foram divididos em pré, peri e pós-natais. RESULTADOS: Noventa e cinco pacientes foram incluídos, sendo 59 do gênero masculino (62%). A idade do diagnóstico variou entre 1 e 24 meses, com média de 4,9 (±5,0) meses. Vinte e cinco casos foram considerados criptogênicos (26,3%) e apenas um idiopático (1,1%). Os demais foram classificados com sintomáticos (72,6%), sendo predominantemente casos perinatais. CONCLUSÃO: Nossos achados se assemelham aos da literatura. Conforme se ampliam o conhecimento acerca da SW e os métodos complementares de diagnóstico, haverá tendência à diminuição dos casos hoje considerados criptogênicos ou idiopáticos.
12
Scharpenseel, H. W. "Yu, Tian-ren (ed.): Physical Chemistry of Paddy Soils; 217 Seiten, 153 Abb., 95 Tab.; Springer-Verlag Berlin-Heidelberg-New York-Tokyo; ISBN 3–540–13001–2; DM 150,–." Zeitschrift für Pflanzenernährung und Bodenkunde 149, no. 6 (1986): 738. http://dx.doi.org/10.1002/jpln.19861490613.
13
Demura, Masahiko, Ya Xu, Kyosuke Kishida, and Toshiyuki Hirano. "Nucleation Mechanism of 40˚<111> Rotated Grains during Recrystallization in Heavily Cold-Rolled Ni3Al Single Crystals." Materials Science Forum 558-559 (October 2007): 183–88. http://dx.doi.org/10.4028/www.scientific.net/msf.558-559.183.
Abstract:
Primary recrystallization textures were examined in the 84% and 95% cold-rolled boron-free Ni3Al single crystals with a Goss texture using the electron backscatter diffraction method. It was found that the main components of the textures in the specimens heat-treated at 873K/0.5h had a 40° rotation relationship about <111> to the original, Goss texture. All the eight variants of 40°<111> rotated grains existed. However, the number density is not even but dependent on whether the rotation axis is identical to the normal of slip planes activated during the prior cold rolling. The ratio of the number density among the variants was same in both the 84% and 95% cold-rolled foils. Based on these results, the formation of these 40°<111> rotated grains was explained assuming the modified multiple twinning mechanism where the annealing twinning occurred at the activated slip planes, followed by the subsequent twinning.
14
de Jonge, Robert, Wim J. E. Tissing, Jan Hendrik Hooijberg, Gerrit Jansen, Gertjan J. L. Kaspers, Jan Lindemans, Godefridus J. Peters, and Rob Pieters. "Polymorphisms in folate-related genes and risk of pediatric acute lymphoblastic leukemia." Blood 113, no. 10 (March 5, 2009): 2284–89. http://dx.doi.org/10.1182/blood-2008-07-165928.
Abstract:
Abstract Polymorphisms in folate pathway genes may influence the susceptibility to acute lymphoblastic leukemia (ALL). DNA was isolated from 245 pediatric ALL patients (cases) and from 500 blood bank donors (controls). Polymorphisms in methylene-tetrahydrofolate reductase (MTHFR 677C>T, 1298A>C), methionine synthase (MTR 2756A>G), methionine synthase reductase (MTRR 66A>G), methylenetetrahydrofolate dehydrogenase (MTHFD1 1958G>A), nicotinamide N-methyltransferase (NNMT IVS −151C>T), serine hydroxymethyl transferase (SHMT1 1420C>T), thymidylate synthase (TS 2R3R), and the reduced folate carrier (RFC1 80G>A) were detected. In ALL patients, an increased occurrence was observed of the RFC1 80AA variant (odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.3-3.2; P = .002) and the RFC1 80A allele (OR = 1.5; 95% CI, 1.1-2.1; P = .02). Likewise, the NNMT IVS −151TT genotype showed a 2.2-fold increased ALL risk (OR = 2.2; 95% CI, 1.1-4.6; P = .04). A 1.4-fold reduction in ALL risk was observed for (heterozygous or homozygous) carriers of the TS 2R allele and the MTHFR 677T allele (OR = 0.7; 95% CI, 0.5-1.0; P < .05). Furthermore, interactions between NNMT and MTHFR 677C>T and RFC1 were observed. NNMT IVS −151CC/MTHFR 677CT + TT patients exhibited a 2-fold reduction in ALL risk whereas RFC1 80AA/NNMT IVS −151CT + TT subjects had a 4.2-fold increase in ALL risk (P = .001). For the first time, we associate the RFC1 80G>A and NNMT IVS −151C>T variants to an increased ALL susceptibility.
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Kuttippurath, J., S. Godin-Beekmann, F. Lefèvre, M. L. Santee, L. Froidevaux, and A. Hauchecorne. "Variability of Antarctic ozone loss in the last decade (2004–2013): high resolution simulations compared to Aura MLS observations." Atmospheric Chemistry and Physics Discussions 14, no. 20 (November 13, 2014): 28203–30. http://dx.doi.org/10.5194/acpd-14-28203-2014.
Abstract:
Abstract. A detailed analysis of the polar ozone loss processes during ten recent Antarctic winters is presented with high resolution Mimosa-Chim model simulations and high frequency polar vortex observations from the Aura Microwave Limb Sounder (MLS) instrument. Our model results for the Antarctic winters 2004–2013 show that chemical ozone loss starts in the edge region of the vortex at equivalent latitudes (EqLs) of 65–69° S in mid-June/July. The loss progresses with time at higher EqLs and intensifies during August–September over the range 400–600 K. The loss peaks in late September/early October, where all EqLs (65–83°) show similar loss and the maximum loss (>2 ppmv [parts per million by volume]) is found over a broad vertical range of 475–550 K. In the lower stratosphere, most winters show similar ozone loss and production rates. In general, at 500 K, the loss rates are about 2–3 ppbv sh−1 (parts per billion by volume/sunlit hour) in July and 4–5 ppbv sh−1 in August/mid-September, while they drop rapidly to zero by late September. In the middle stratosphere, the loss rates are about 3–5 ppbv sh−1 in July–August and October at 675 K. It is found that the Antarctic ozone hole (June–September) is controlled by the halogen cycles at about 90–95% (ClO–ClO, BrO–ClO, and ClO–O) and the loss above 700 K is dominated by the NOx cycle at about 70–75%. On average, the Mimosa-Chim simulations show that the very cold winters of 2005 and 2006 exhibit a maximum loss of ~3.5 ppmv around 550 K or about 149–173 DU over 350–850 K and the warmer winters of 2004, 2010, and 2012 show a loss of ~2.6 ppmv around 475–500 K or 131–154 DU over 350–850 K. The winters of 2007, 2008, and 2011 were moderately cold and thus both ozone loss and peak loss altitudes are between these two ranges (3 ppmv around 500 K or 150 ± 10 DU). The modeled ozone loss values are in reasonably good agreement with those estimated from Aura MLS measurements, but the model underestimates the observed ClO, largely due to the slower vertical descent in the model during spring.
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Mcwilliam, E. L., T. N. Barry, N. Lopez-Villalobos, P. N. Cameron, P. D. Kemp, and D. J. Cameron. "Reproductive performance from feeding tree fodder to ewes grazing drought pasture during mating." NZGA: Research and Practice Series 10 (January 1, 2003): 23–34. http://dx.doi.org/10.33584/rps.10.2003.2986.
Abstract:
Grazing experiments were conducted in late summer/autumn of 2001 and 2002, at Massey University's Riverside Farm, Masterton, to determine the effects of poplar and willow supplementation during drought on ewe reproductive rate, when grazing low quality drought pasture. Ewes (55-57 kg live weight) grazed drought pasture in a rotational grazing system, with pre- and post-grazing pasture masses of 1040- 940 and 530-550 kg dry matter (DM)/ha. In 2001, poplar trimmings were offered at the rate of 1.50 and 0.75 kg/ewe/day (fresh), to the high and low treatment groups, respectively (n=100 ewes/group). In 2002, 1.40 kg/head/day (fresh) willow and poplar trimmings were offered to the willow or poplar treatment groups (n=95 ewes/group). The poplar trimmings offered to ewes in the 2002 experiment were severely contaminated by poplar leaf rust. Poplar and willow consumed was higher in mean nitrogen content and organic matter digestibility, and lower in average neutral detergent fibre content, than the low quality drought pasture consumed by the control ewes. Control ewes lost live weight (82 and 104 g/day) during the mating periods in both experiments. Supplementation with poplar and willow slightly reduced live weight loss and loss of body condition, however these differences disappeared in the post-treatment period. Reproductive rate was low in the control groups of ewes (121 & 131 lambs born/ 100 ewes mated). In the 2001 experiment, poplar supplementation increased ewe reproductive rate by 20% units (p
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Santagostino, Elena, Angiola Rocino, Maria E. Mancuso, Maria G. Mazzucconi, Giacomo Mancuso, Maria Messina, Annarita Tagliaferri, Matteo Luciani, Elio Boeri, and Pier M. Mannucci. "Impact of Early Factor VIII Exposure, Prophylaxis and Prenatal/Perinatal Events on Inhibitor Risk in Children with Hemophilia A: A Case-Control Study." Blood 104, no. 11 (November 16, 2004): 37. http://dx.doi.org/10.1182/blood.v104.11.37.37.
Abstract:
Abstract In a multicenter case-control study we investigated the impact of prenatal/perinatal events and early FVIII exposure on the inhibitor risk in hemophiliacs. Patients: 102 children (age:13–196 months) with hemophilia A (FVIII≤2%) exclusively treated with recombinant FVIII and evaluated for inhibitors every 3 months were included. Forty-seven patients who developed inhibitors at the median age of 26 months (4–80) after a median of 16 exposure days (ED, 5–150), 37 high-responders (6–500 BU/mL) and 10 low-responders (<5 BU/mL), were compared with 55 children who did not develop inhibitors after at least 20 ED (5<50, 4<100, 10<200 and 36>200 ED). Results: by univariate analysis, family history of inhibitors, intron 22 inversion and prophylaxis started after the first 20 ED were significantly associated with an increased risk of inhibitor development (OR 9.5, 95%CI 1.1–79.9; OR 2.7, 95%CI 1.1–6.6; OR 3.7, 95%CI 1.1–12.1, respectively). No statistically significant differences were found for variables such as villocentesis/amniocentesis, premature/caesarian birth, breast-feeding, surgery, central venous devices and FVIII infusions associated with infections/vaccinations. By multivariate analysis, the inhibitor risk was 2.8-folds (95%CI 1.1–7.3) in children with intron 22 inversion and 4.5-folds (95%CI 1.1–17.5) in patients who started prophylaxis after the first 20 ED. By univariate and multivariate analysis, there was not a linear trend in the inhibitor development according to the age at first FVIII exposure (≤6, 7–12, 13–18, 19–24, >24 months). Conclusions: this study showed that starting prophylaxis within the first 20 ED had a favourable impact on the inhibitor risk independently from the age at first FVIII exposure.
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Xu, Yongkang, Shumin Fu, Ye Mao, Fengming Yi, Weiming Jiang, Long Feng, and Jianbing Wu. "Efficacy and safety of hepatic arterial infusion chemotherapy combined with lenvatinib and tislelizumab for unresectable hepatocellular carcinoma: A single-arm, phase II study." Journal of Clinical Oncology 42, no. 3_suppl (January 20, 2024): 500. http://dx.doi.org/10.1200/jco.2024.42.3_suppl.500.
Abstract:
500 Background: Unresectable hepatocellular carcinoma (uHCC) patients (pts) had high unmet medical needs in practice. Retrospective studies suggested a potent antitumor effect and long-term survival benefit of hepatic arterial infusion chemotherapy (HAIC) plus programmed death-1 inhibitor and lenvatinib. This prospective phase II study aimed to evaluate the efficacy and safety of HAIC combined with lenvatinib and tislelizumab in uHCC pts. Methods: Eligible pts were aged ≥18 years and had histologically confirmed uHCC, ECOG PS ≤1, Child-Pugh (C-P) A/B, and ≥1 measurable lesion per RECIST 1.1. Pts received HAIC of modified FOLFOX (oxaliplatin, 85 mg/m2; leucovorin, 400 mg/m2; 5-fluorouracil bolus, 400 mg/m2 on day 1; 5-fluorouracil infusion, 2400 mg/m2 for 46 h), lenvatinib (8 or 12 mg once daily for body weight <60 or ≥60 kg), and tislelizumab (200 mg every 3 weeks). HAIC was allowed to repeat on demands. Primary endpoint was objective response rate (ORR) per RECIST 1.1. Secondary endpoints included ORR per mRECIST, disease control rate (DCR), surgical conversion rate, progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: Between June 2021 and January 2023, 46 pts were enrolled. The median age of pts was 51-year-old, most were male 42 (91.3%), ECOG PS 0 33 (71.7%), C-P A 44 (95.7%), tumor diameter ≥10 cm 31 (67.4%), multiple tumors 33 (71.7%), vascular invasion 38 (82.6%), extrahepatic metastasis 7 (15.2%). As of August 15, 2023, . All pts entered efficacy and safety analysis, ORR was 52.2% (0 complete response [CR], 24 partial response [PR]) per RECIST 1.1; ORR was 84.8% per mRECIST, with 5 CR and 34 PR. DCR was 95.6% per either RECIST 1.1 or mRECIST. Surgical conversion rate was 21.7% (10/46). Median PFS was 10.9 (95% CI, 8.0-13.8) months; 12-month OS rate was 41.3%. COX analysis revealed that ECOG PS 1 (HR, 3.17; 95% CI, 1.43-7.03; p=0.005), multiple tumors (HR, 3.68; 95% CI, 1.22-11.14; p=0.021), and extrahepatic metastasis (HR, 4.04; 95% CI, 1.57-10.40; p=0.004) were independently associated with poor PFS. Any-grade AEs occurred in 43 (93.5%) pts, the most common were proteinuria (43.4%), aspartate aminotransferase (AST) increased (35.8%), and alanine aminotransferase (ALT) increased (32.1%). Grades ≥3 AEs occurred in 10 (21.7%) pts and mainly included AST increased (7.5%), hypertension (3.8%), and hyperbilirubinemia (3.8%). Conclusions: HAIC combined with lenvatinib and tislelizumab showed meaningful clinical benefits and acceptable safety in uHCC pts. The study is ongoing, OS will be reported later. Clinical trial information: ChiCTR2200064384 .
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Kalita, V. I., D. I. Komlev, A. A. Radyuk, V. S. Komlev, V. F. Shamray, A. B. Mikhailova, V. N. Sokolov, M. S. Chernov, T. R. Chueva, and N. V. Gamurar. "Structure and phase composition of hydroxyapatite plasma coating." Perspektivnye Materialy 4 (2021): 26–36. http://dx.doi.org/10.30791/1028-978x-2021-4-26-36.
Abstract:
Changes in the structure, phase composition of the hydroxyapatite (HA) plasma coating were established during deposition at an initial 20 °C and 550 °C temperature of the titanium substrate and a spraying distance of 95 and 150 mm. The structure of HA coatings was analyzed by SEM and optical microscopy. DSC analysis established the transition temperatures of HA coatings to the equilibrium state. When deposited on a substrate with an initial temperature of 20 °C at a deposition distance of 95 mm, a nanostructure with a crystallite size of 21 nm is fixed in the HA coating. With an increase in the deposition distance to 150 mm, the non-equilibrium phase composition increases, the crystallite size decreases to 12 nm, the HA content decreases from 72 to 61 %, TTCP from 10 to 5 %, and the α-TCP content increases from 17 to 30 %. A non-equilibrium nano-structural state passes into a more equilibrium state with the release of heat at temperatures of 615 – 727 °C in DSC studies. The high-temperature α-TCP phase is not fixed when the coating is deposited onto a substrate with an initial temperature of 550 °C at a spraying distance of 95 mm, the content of TTCP increases by 2 times, the size of the HA phase crystallites reaches 36 nm and their size in the sprayed powder is 75 nm. The HA coating has a dendritic microstructure and does not have a thermal effect during DSC heating at an initial substrate temperature of 550 °C.
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Adim, Chidiebere Victor, and Gabby Okwudiri David. "RECOGNITION-BASED REWARD AND WORKPLACE HARMONY IN MANUFACTURING COMPANIES IN PORT HARCOURT, RIVERS STATE, NIGERIA." European Journal of Human Resource 4, no. 2 (August 25, 2020): 1–11. http://dx.doi.org/10.47672/ejh.559.
Abstract:
Purpose: This study investigated the relationship between recognition-based reward and workplace harmony in manufacturing companies in Port Harcourt, Rivers State, Nigeria.Methodology: The study adopted the cross-sectional survey in its investigation of the variables. Primary source of data was generated through self- administered questionnaire. The target population of this study consists of 253 employees of 7 manufacturing companies in Port Harcourt, Rivers State, Nigeria. The sample size of 151 was determined using Taro Yamane sample size formula. The reliability of the instrument was achieved by the use of the Cronbach Alpha coefficient with all the items scoring above 0.70. Data generated were analyzed and presented using both descriptive and inferential statistical techniques. The hypothesis was tested using the Spearman’s Rank Order Correlation Statistics. The tests were carried out at a 95% confidence interval and a 0.05 level of significance.Findings: The study findings revealed that there is significant relationship between recognition-based reward and workplace harmony in manufacturing companies in Port Harcourt, Rivers State, Nigeria.Recommendation: The study recommends that management of manufacturing firms should be keen on the use of Recognition-based because it has proven to be a way of motivating employees. Implementing recognition-based programs would create a positive work environment, followed by reinforcing positive behaviours and motivating high performance.
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Oonk, J. B. R., E. L. Alexander, J. W. Broderick, M. Sokolowski, and R. Wayth. "Spectroscopy with the Engineering Development Array: cold H+ at 63 MHz towards the Galactic Centre." Monthly Notices of the Royal Astronomical Society 487, no. 4 (July 9, 2019): 4737–50. http://dx.doi.org/10.1093/mnras/stz950.
Abstract:
Abstract The Engineering Development Array (EDA) is a single test station for Square Kilometre Array (SKA) precursor technology. We have used the EDA to detect low-frequency radio recombination lines (RRLs) from the Galactic Centre region. Low-frequency RRLs are an area of interest for future low-frequency SKA work as these lines provide important information on the physical properties of the cold neutral medium. In this project, we investigate the EDA, its bandpass, and the radio frequency interference environment for low-frequency spectroscopy. We present line spectra from 30 to 325 MHz for the Galactic Centre region. The decrease in sensitivity for the EDA at the low end of the receiver prevents carbon and hydrogen RRLs to be detected below 40 and 60 MHz, respectively. RFI strongly affects frequencies in the range 276–292, 234–270, 131–138, 95–102, and below 33 MHz. Cnα RRLs were detected in absorption for quantum levels n = 378–550 (39–121 MHz) and in emission for n = 272–306 (228–325 MHz). Cnβ lines were detected in absorption for n = 387–696 (39–225 MHz). Hnα RRLs were detected in emission for n = 272–480 (59–325 MHz). Hnβ lines were detected for n = 387–453 (141–225 MHz). The stacked Hnα detection at 63 MHz is the lowest frequency detection made for hydrogen RRLs and shows that a cold (partially) ionized medium exists along the line of sight to the Galactic Centre region. The size and velocity of this cold H+ gas indicates that it is likely associated with the nearby Riegel–Crutcher cloud.
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Barros, Paulo César. "500 ANOS DA REFORMA LUTERANA: OCASIÃO DE AVANÇAR NA COLABORAÇÃO ECUMÊNICA." Perspectiva Teológica 49, no. 1 (April 29, 2017): 11. http://dx.doi.org/10.20911/21768757v49n1p11/2017.
Abstract:
Estamos às portas da rememoração dos 500 anos da Reforma Luterana. Foi no dia 31 de outubro de 1517 que Martinho Lutero afixou (assim se diz), na porta da igreja do castelo de Wittenberg, um cartaz contendo as famosas 95 teses para suscitar o Debate para o esclarecimento do valor das indulgências.
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Arigliani, Michele, Luigi Castriotta, Ramatu Zubair, Livingstone Gayus Dogara, Chiara Zuiani, Emma Raywood, Katy Vecchiato, et al. "Differences in lung function between children with sickle cell anaemia from West Africa and Europe." Thorax 74, no. 12 (October 17, 2019): 1154–60. http://dx.doi.org/10.1136/thoraxjnl-2019-213717.
Abstract:
IntroductionLung function abnormalities are common in sickle cell anaemia (SCA) but data from sub-Saharan Africa are limited. We hypothesised that children with SCA from West Africa had worse lung function than their counterparts from Europe.MethodsThis prospective cross-sectional study evaluated spirometry and anthropometry in black African individuals with SCA (haemoglobin phenotype SS) aged 6–18 years from Nigeria and the UK, when clinically stable. Age-matched controls were also included in Nigeria to validate the Global Lung Initiative spirometry reference values.ResultsNigerian SCA patients (n=154) had significant reductions in both FEV1 and FVC of ~1 z-score compared with local controls (n=364) and ~0.5 z-scores compared with the UK patients (n=101). Wasting (body mass index z-score<−2) had a prevalence of 27% in Nigerian patients and 7% in the UK ones (p<0.001). Among children with SCA, being resident in Nigeria (OR 2.4, 95% CI 1.1 to 4.9), wasting (OR 2.3, 95% CI 1.1 to 5.0) and each additional year of age (OR 1.2, 95% CI 1.1 to 1.4) were independently associated with increased risk of restrictive spirometry (FVC z-score<−1.64+FEV1/FVC≥−1.64).ConclusionsThis study showed that chronic respiratory impairment is more severe in children with SCA from West Africa than Europe. Our findings suggest the utility of implementing respiratory assessment in African children with SCA to early identify those with chronic lung injury, eligible for closer follow-up and more aggressive therapies.
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Cheon, Jaekyung, Beodeul Kang, Sang-Hoon Jung, Chan Kim, and Hongjae Chon. "Efficacy of nivolumab and ipilimumab in patients with hepatocellular carcinoma with prior immune-checkpoint inhibitor treatment." Journal of Clinical Oncology 41, no. 4_suppl (February 1, 2023): 554. http://dx.doi.org/10.1200/jco.2023.41.4_suppl.554.
Abstract:
554 Background: Nivolumab plus ipilimumab (NIVOIPI) demonstrated promising efficacy in patients with unresectable hepatocellular carcinoma(uHCC) in the phase 1/2 CheckMate 040 trial. However, as atezolizumab plus bevacizumab (Ate/Bev) is a new first-line standard systemic therapy, it is necessary to evaluate the role of NIVOIPI after treatment with Ate/Bev. Methods: Patients with uHCC who received NIVOIPI after previous systemic treatment were included. Patients received nivolumab (1 mg/kg) plus ipilimumab (3 mg/kg) every 3 weeks (four doses), followed by nivolumab (240 mg) every 2 weeks. Patients with Child B/C class and BCLC D stage uHCC were excluded. Patients who had at least one follow-up visit after the start of NIVOIPI were included. Results: A total of 47 patients were included with characteristics as follows: median age of 60 years (range, 37–79); hepatitis B (n = 40, 85.1%), hepatitis C (n = 2, 4.3%), non-viral (n = 5, 10.5%); BCLC B/C (n = 2, 4.3%; n = 45, 95.7%); macrovascular invasion (n = 12, 25.5%); extrahepatic metastasis (n = 41, 87.2%); and AFP ≥ 400 ng/ml (n = 26, 55.3%). Thirty-five (74.5%) patients had a history of prior immune-checkpoint inhibitor (ICI) treatment (n = 35, 74.5%), including Ate/Bev (n = 23, 48.9%). According to the RECIST 1.1, 12 patients achieved a partial response, resulting in an overall response rate (ORR) of 25.5% and disease control rate (DCR) of 42.6%. The ORR and DCR were 41.7% and 58.4% in ICI-naïve patients and 20.0% and 37.1% in patients with prior ICI treatment. The median follow-up duration was 5.7 months (95% confidence interval [CI], 5.4–6.1), the median progression-free survival was 1.4 months (95% CI, 1.1–1.7) in all patients, 1.3 months (95% CI, 0.1–1.1) in prior ICI-treated patients and was not reached in ICI-naïve patients. The median overall survival was not reached. The most common grade 3–4 toxicities were aspartate aminotransferase elevation (n = 4, 8.5%), neutropenia (n = 4, 8.5%), skin toxicity (n = 3, 6.4%), alanine transaminase elevation (n = 2, 4.3%) and pneumonitis (n = 2, 4.3%). There was one treatment-related death due to toxic epidermal necrolysis. Conclusions: NIVOIPI demonstrated clinical meaningful efficacy in patients with uHCC, with and without prior ICI treatment.
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Beltai, A., B. Combe, A. Coffy, C. Gaujoux-Viala, C. Lukas, A. Saraux, M. Dougados, J. P. Daures, and C. Hua. "POS0306 IMPACT OF MULTIMORBIDITY ON DISEASE MODIFYING ANTI-RHEUMATIC DRUG THERAPY IN EARLY RHEUMATOID ARTHRITIS: DATA FROM THE ESPOIR COHORT." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 379.2–379. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2868.
Abstract:
Background:Multimorbidity is frequent in rheumatoid arthritis (RA) and could interfere with the therapeutic response.Objectives:The aim of this study was to evaluate multimorbidity in the French cohort of early arthritis (ESPOIR cohort) and its possible impact on the therapeutic response.Methods:We included patients fulfilling 2010 ACR/EULAR criteria for RA. An adapted MultiMorbidity Index (aMMI) was developed [1]. Each patient was assigned scores of binary aMMI (0= no comorbidity, 1= at least 1 comorbidity) and counted and weighted aMMI. The primary endpoint was achievement of Clinical Disease Activity Index (CDAI) low disease activity after initiation of a first disease-modifying anti-rheumatic drug (DMARD) according to the aMMI. Secondary endpoints were other disease activity scores and response criteria. We collected data from the visit preceding the first DMARD initiation (baseline visit) and the visit after at least 3 months of treatment (follow-up visit). The impact of aMMI on therapeutic maintenance at 1, 3, 5 and 10 years was evaluated.Results:Analyses involved 472 patients: 302 (64%) had at least 1 comorbidity. Overall, 45.3% and 44.7% with binary aMMI= 0 or 1, respectively (p= 0.9), achieved CDAI low disease activity (Table 1). Similar results were found with counted and weighted aMMI. Use of other disease activity scores or response criteria did not show a significant impact of multimorbidity on the therapeutic response. Therapeutic maintenance was significantly better with binary aMMI = 1 than binary aMMI = 0. Increased counted aMMI was associated with increased probability of still being on the first initiated DMARD at each time point (Table 2).Table 1.Impact of aMMIs on CDAI, DAS28 and SDAI low disease activity (LDA) achievement at follow-up visit (univariate analyses)LDA achievementCDAIpDAS28pSDAIpYesNoYesNoYesNoBinary aMMI, n (%)077 (45.3)93 (54.7)0.9*85 (50.0)85 (50.0)0.2*80 (47.1)90 (52.9)0.9*1135 (44.7)167 (55.3)131 (43.4)171 (56.6)141 (46.7)161 (53.3)Counted aMMI, mean (SD)1.0 (1.1)1.1 (1.1)0.71.0 (1.1)1.1 (1.1)0.21.1 (1.1)1.1 (1.1)1.0Weighted aMMI, mean (SD)4.1 (5.2)4.0 (4.7)0.94.0 (5.2)4.1 (4.7)0.34.0 (5.0)4.0 (4.9)1.0aMMI= adapted MultiMorbidity Index; CDAI= Clinical Disease Activity Index; SDAI= Simplified Disease Activity Index* Proportion of patients achieving LDA between patients with binary aMMI= 0 and binary aMMI= 1. Because of no statistically significant results, no multivariate analysis was performed.Table 2.Probability of first DMARD maintenance at 1, 3, 5 and 10 years (multivariate analysis)Time pointFirst DMARD maintained or stoppedBinary aMMI#Counted aMMI§011 year(n= 530)Maintenance (n= 300)22981.71 (0.93)OR [95% CI]*> 999 [286.2->999]221.3 [84.0-583.0]Withdrawal (n= 230)205250.12 (0.37)3 years(n= 493)Maintenance (n= 285)102751.66 (0.94)OR [95% CI]*153.9 [73.0-324.5]26.1 [15.1-45.3]Withdrawal (n= 208)175330.22 (0.64)5 years(n= 459)Maintenance (n= 116)91071.72 (1.05)OR [95% CI]*10.9 [5.1-23.3]2.2 [1.8-2.7]Withdrawal (n= 343)1631800.82 (1.0)10 years(n= 415)Maintenance (n= 40)2381.58 (0.84)OR [95% CI]*14.0 [3.3-59.1]1.6 [1.2-2.0]Withdrawal (n= 375)1582170.99 (1.12)#data are number of patients§ data are mean (standard error)* data are odds ratios (ORs) and 95% confidence intervals (95% CI) of still being on the first initiated DMARD at 1, 3, 5 and 10 years between patients with binary aMMI = 1 and binary aMMI = 0 and according to counted aMMI, per additional point.Conclusion:In the ESPOIR cohort, therapeutic response to a first DMARD was not affected by multimorbidity but therapeutic maintenance was better in multimorbid patients.References:[1]Radner H, Yoshida K, Mjaavatten MD, et al. Development of a multimorbidity index: Impact on quality of life using a rheumatoid arthritis cohort. Semin Arthritis Rheum 2015;45:167–73.The variables included in multivariate analyses were sex, rheumatoid factor and/or anti-citrunillated peptide antibody positivity, age, CDAI at baseline visit, number of treatments at baseline visit.Acknowledgements:We are grateful to Nathalie Rincheval (Montpellier) for expert monitoring and data management and all the investigators who recruited and followed the patients (F. Berenbaum, Paris-Saint Antoine; MC. Boissier, Paris-Bobigny; A. Cantagrel, Toulouse; B. Combe, Montpellier; M. Dougados, Paris-Cochin; P. Fardellone and P. Boumier, Amiens; B. Fautrel, Paris-La Pitié; RM. Flipo, Lille; Ph. Goupille, Tours; F. Liote, Paris- Lariboisière; O. Vittecoq, Rouen; X. Mariette, Paris-Bicêtre; P. Dieude, Paris Bichat; A. Saraux, Brest; T. Schaeverbeke, Bordeaux; and J. Sibilia, Strasbourg).Disclosure of Interests:Aurélie BELTAI: None declared, Bernard Combe Speakers bureau: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Consultant of: AbbVie; Bristol-Myers Squibb; Gilead; Janssen; Lilly; Merck; Novartis; Pfizer; Roche-Chugai; and Sanofi, Grant/research support from: Novartis, Pfizer, and Roche, Amandine Coffy: None declared, Cécile Gaujoux-Viala: None declared, Cédric Lukas Speakers bureau: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai and UCB, Consultant of: Abbvie, Amgen, Janssen, Lilly, MSD, Novartis, Pfizer, Roche-Chugai and UCB, Grant/research support from: Pfizer, Novartis and Roche-Chugai, Alain Saraux Speakers bureau: AbbVie; Bristol-Myers Squibb; Lilly; Nordic; Novartis; Pfizer; Roche-Chugai; Sanofi and UCB, Consultant of: AbbVie; Bristol-Myers Squibb; Lilly; Nordic; Novartis; Pfizer; Roche-Chugai; Sanofi and UCB, Grant/research support from: AbbVie; Bristol-Myers Squibb; Lilly; Nordic; Novartis; Pfizer; Roche-Chugai; Sanofi and UCB, Maxime Dougados Speakers bureau: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, Sandoz, Consultant of: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, Sandoz, Grant/research support from: Pfizer, Abbvie, Lilly, UCB, Merck, BMS, Roche, Biogen, Sanofi, Novartis, Sandoz, Jean-Pierre DAURES: None declared, Charlotte Hua: None declared
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Luma, Henry Namme, Servais Albert Fiacre Bagnaka Eloumou, Ellis Atemlefeh Fualefeh-Morfaw, Agnes Malongue, Elvis Temfack, Fernando Kemta Lekpa, Olivier Donfack-Sontsa, Lucy Ndip, and Ivo Che Ditah. "Anorectal pathology amongst HIV infected patients attending the Douala General Hospital: a cross-sectional study." International Journal of STD & AIDS 28, no. 4 (July 10, 2016): 389–96. http://dx.doi.org/10.1177/0956462416650817.
Abstract:
While gastrointestinal disease is common among HIV infected individuals, the prevalence and distribution of ano-rectal pathology has not been well studied in our setting. The objective of this study therefore was to determine the prevalence and determinants of ano-rectal pathology in HIV infected patients attending the Douala General Hospital HIV treatment centre. A hospital-based cross-sectional study was undertaken. We collected socio-demographic, clinical and laboratory data using a structured questionnaire and patients’ files. Each study participant had a full physical and ano-rectal examination. We further studied factors associated with having at least one ano-rectal lesion by logistic regression reporting odds ratios (ORs) and their 95% confidence intervals (CI). We included 390 HIV infected patients. The mean age was 41 (SD: 8) years and 48% were men. Median duration since HIV diagnosis was 3 (interquartile range: 2–5) years and median CD4 cell count was 411 (interquartile range: 234–601) cells/mm3. Prevalence of ano-rectal pathology was 22.8% (95% CI: 18.7–27.3). Hemorrhoids and proctitis were most common lesions found; each in 10% of patients. From multivariate logistic regression, factors associated with ano-rectal pathology were CD4 < 350 cells/ml (OR: 2.1, 95% CI: 1.1–4.2), not on highly active antiretroviral therapy (OR: 2.2, 95% CI: 1.1–4.6), inpatient (OR: 2.3, 95% CI: 1.2–4.3), ano-rectal intercourse (OR: 5.0, 95% CI: 1.7–15.1), and more than one sexual partner (OR: 2.4, 95% CI: 1.3–4.2). Ano-rectal pathology is common amongst HIV infected patients. Care givers should actively investigate and treat them as this will improve the quality of life of people living with HIV/AIDS.
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Massilamany, Chandirasegaran, Melissa Jamerson, Nandakumar Madayiputhiya, Renu Nandakumar, Francine Marciano-Cabral, Tobias Sejbaek, Zslot Illes, and Jay Reddy. "An evidence for a potential linkage between Acanthamoeba infections and multiple sclerosis (P4551)." Journal of Immunology 190, no. 1_Supplement (May 1, 2013): 197.13. http://dx.doi.org/10.4049/jimmunol.190.supp.197.13.
Abstract:
Abstract We recently observed that Acanthamoeba castellanii (ACA), a free-living amoeba, has the potential to trigger central nervous system autoimmunity by generating cross-reactive T cells for multiple myelin antigens, namely, proteolipid protein (PLP) 139-151 and myelin basic protein (MBP) 89-101. Additionally, the homology model derived for human leukocyte antigen-DR2, complexed with MBP 85-99 and its mimicry epitope, predicts the possibility of generating cross-reactive T cells for human MBP 85-99 in Acanthamoeba-exposed individuals. These observations raise a question whether prior exposure to ACA infection can trigger multiple sclerosis (MS). To address this hypothesis, we extracted DNA from cerebrospinal fluid obtained from MS patients and individuals with other neurological disorders, and subjected them to PCR that amplified a 500 bp fragment of the small subunit 18S rDNA using ACA-specific primer set. We confirmed the identity of PCR products by sequencing. To provide additional evidence for a linkage of ACA to MS pathogenesis, we asked whether anti-human PLP antibody can detect amoebic rhodanese-related sulfurtransferase (RST), since this protein contains the mimicry epitope ACA 83-95 for PLP 139-151. Through western blotting and LC/MS analyses, we noted that PLP antibody binds RST, suggesting that anti-Acanthamoeba immune responses have the potential to target myelin antigens. Collectively, the data suggest a linkage of ACA infection to MS pathogenesis.
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Thongprayoon, Charat, Wisit Cheungpasitporn, Panupong Hansrivijit, Sorkko Thirunavukkarasu, Api Chewcharat, Juan Medaura, Michael A. Mao, and Kianoush B. Kashani. "Association of serum magnesium level change with in-hospital mortality." BMJ Evidence-Based Medicine 25, no. 6 (January 24, 2020): 206–12. http://dx.doi.org/10.1136/bmjebm-2019-111322.
Abstract:
The objective of this study was to assess the association of in-hospital mortality risk based on change in serum magnesium levels in hospitalised patients. All adult patients admitted to our hospital from years 2009 to 2013 with at least two serum magnesium measurements during hospitalisation were included. Serum magnesium change, defined as the absolute difference between the highest and lowest serum magnesium, was categorised into six groups: 0–0.2, 0.3–0.4, 0.5–0.6, 0.7–0.8, 0.9–1.0, ≥1.1 mg/dL. In-hospital mortality was the outcome of interest. Logistic regression was used to assess the association between serum magnesium change and in-hospital mortality, using serum magnesium change of 0.0–0.2 mg/dL as the reference group. A total of 42 141 patients, with the median serum magnesium change during hospital stay of 0.3 (IQR 0.2–0.6) mg/dL, were studied. In-hospital mortality based on serum magnesium change of 0–0.2, 0.3–0.4, 0.5–0.6, 0.7–0.8, 0.9–1.0, ≥1.1 mg/dL was 1.3%, 2.3%, 3.1%, 5.0%, 6.5%, and 8.8%, respectively (p<0.001). After adjustment for potential confounders, increased serum magnesium change was significantly associated with higher in-hospital mortality with adjusted OR of 1.39 (95% 1.14–1.69) in serum magnesium change of 0.3–0.4, 1.48 (95% CI 1.21 to 1.81) in 0.5–0.6, 1.89 (95% CI 1.53 to 2.34) in 0.7–0.8, 1.85 (95% CI 1.45 to 2.37) in 0.9–1.0 and 1.89 (95% CI 1.48 to 2.41) in ≥1.1 mg/dL when compared with serum magnesium change group of 0–0.2 mg/dL. Increased in-hospital mortality was associated with both downward and upward trends of serum magnesium change during hospitalisation. The greater extent of change in serum magnesium levels was progressively associated with increased in-hospital mortality
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RAMZAN, HS, A. RAWAT, G. MUSTAFA, S. SATTAR, A. SHAHEEN, AAA ABDELGANI, N. LODHI, and Z. RAMZAN. "EFFECT OF SEVERITY AND ETIOLOGY OF CHRONIC KIDNEY DISEASE IN PATIENTS WITH HEART FAILURE WITH MILDLY REDUCED EJECTION FRACTION." Biological and Clinical Sciences Research Journal 2024, no. 1 (June 5, 2024): 888. http://dx.doi.org/10.54112/bcsrj.v2024i1.888.
Abstract:
This study explores the impact of chronic kidney disease (CKD) severity and etiology on patients with heart failure with mildly reduced ejection fraction (HFmrEF). Understanding these relationships is crucial for optimizing management strategies and improving patient outcomes. Methods: A cross-sectional study was conducted involving 550 patients diagnosed with HFmrEF. Patients were categorized based on CKD severity (stages 1 to 5) and etiology (diabetic nephropathy, hypertensive nephrosclerosis, glomerulonephritis, and others). Data on demographics, clinical characteristics, laboratory findings, and echocardiographic parameters were collected and analyzed. Results: Data were collected from 550 patients according to the study's criteria. The mean age of the patients was 62.5 ± 10.8 years. Of 550, 320 (58.2%) were male, and 230 (41.8%) were female. According to the NYHA classification, 40 (7.3%) belong to Class I, 290 (52.7%) to Class II, 200 (36.4%) to Class III, and 20 (3.6%) to Class IV. Advanced CKD stage (OR 2.5, 95% CI 1.6-3.8), diabetic nephropathy (OR 1.8, 95% CI 1.1-3.0), and lower eGFR (OR 2.2, 95% CI 1.5-3.2) were all associated with increased risk of mortality and hospitalizations. Conclusions: It is concluded that the severity and etiology of chronic kidney disease significantly impact the outcomes of patients with heart failure with mildly reduced ejection fraction. Advanced CKD stages and diabetic nephropathy are associated with higher mortality rates and more frequent hospitalizations.
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O'Sullivan, Brian, Shao Hui Huang, Lillian L. Siu, John Waldron, Helen Zhao, Bayardo Perez-Ordonez, Ilan Weinreb, et al. "Deintensification Candidate Subgroups in Human Papillomavirus–Related Oropharyngeal Cancer According to Minimal Risk of Distant Metastasis." Journal of Clinical Oncology 31, no. 5 (February 10, 2013): 543–50. http://dx.doi.org/10.1200/jco.2012.44.0164.
Abstract:
Purpose To define human papillomavirus (HPV) –positive oropharyngeal cancers (OPC) suitable for treatment deintensification according to low risk of distant metastasis (DM). Patients and Methods OPC treated with radiotherapy (RT) or chemoradiotherapy (CRT) from 2001 to 2009 were included. Outcomes were compared for HPV-positive versus HPV-negative patients. Univariate and multivariate analyses identified outcome predictors. Recursive partitioning analysis (RPA) stratified the DM risk. Results HPV status was ascertained in 505 (56%) of 899 consecutive OPCs. Median follow-up was 3.9 years. HPV-positive patients (n = 382), compared with HPV-negative patients (n = 123), had higher local (94% v 80%, respectively, at 3 years; P < .01) and regional control (95% v 82%, respectively; P < .01) but similar distant control (DC; 90% v 86%, respectively; P = .53). Multivariate analysis identified that HPV negativity (hazard ratio [HR], 2.9; 95% CI, 2.0 to 5.0), N2b-N3 (HR, 2.9; 95% CI, 1.8 to 4.9), T4 (HR, 1.8; 95% CI, 1.2 to 2.9), and RT alone (HR, 1.8; 95% CI, 1.1 to 2.5) predicted a lower recurrence-free survival (RFS; all P < .01). Smoking pack-years > 10 reduced overall survival (HR, 1.72; 95% CI, 1.1 to 2.7; P = .03) but did not impact RFS (HR, 1.1; 95% CI, 0.7 to 1.9; P = .65). RPA segregated HPV-positive patients into low (T1-3N0-2c; DC, 93%) and high DM risk (N3 or T4; DC, 76%) groups and HPV-negative patients into different low (T1-2N0-2c; DC, 93%) and high DM risk (T3-4N3; DC, 72%) groups. The DC rates for HPV-positive, low-risk N0-2a or less than 10 pack-year N2b patients were similar for RT alone and CRT, but the rate was lower in the N2c subset managed by RT alone (73% v 92% for CRT; P = .02). Conclusion HPV-positive T1-3N0-2c patients have a low DM risk, but N2c patients from this group have a reduced DC when treated with RT alone and seem less suited for deintensification strategies that omit chemotherapy.
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Druzhinin, A. O., I. I. Maryamova, and O. P. Kutrakov. "High temperature strain sensors based on gallium phosphide whiskers." Технология и конструирование в электронной аппаратуре, no. 3-4 (2019): 26–30. http://dx.doi.org/10.15222/tkea2019.3-4.26.
Abstract:
The paper presents a study of tensoresistive characteristics of p-type GaP whiskers with [111] crystallographic orientation coinciding with the direction of the maximal piezoresistive effect for this material. The authors present a newly-developed technology of creating the ohmic contacts to GaP crystals that allows using these crystals at high temperatures (400—600°C). Tensoresistive characteristics of p-type GaP whiskers were studied in the strain range of ±1,2•10–3 rel. un. These studies show that the gauge factor for these crystals at 20°C is rather large. Thus, for p-type GaP crystals with a resistivity of 0.025—0.03 Ω•cm, the gage factor is in the range of 90—95. The study of tensoresistive properties shows that in the temperature range of 20—300°C for p-type GaP crystals with the resistivity of 0,01—0,03 Ω•cm, the gage factor decreases as the temperature rises, but in the temperature range of 300—550°C for this crystals, very slight temperature dependence of the gage factor was observed. In this temperature range, the temperature coefficient of gage factor is no more than –0,03%/°Ñ. In the temperature range of 300—500°C, the value of gage factor is high (40—50). It could be noticed that in the entire investigated temperature range, the strain sensors based on p-type GaP whiskers have the linear resistance vs. strain dependence in the strain range of ±5,0•10–4 rel. un. The developed strain sensors based on p-type GaP whiskers have high mechanical strength at the static and dynamic strain (more than 108 cycles), which makes them operable in dynamic mode.
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Marlinda, Marlinda, Mahmud Basuki, and Rita Hartati. "Optimization of Reduction TSS (Total Suspended Solid) Levels on Skin Cracker Industrial Waste Using Chitosan Coagulant." International Journal of Progressive Sciences and Technologies 38, no. 1 (April 12, 2023): 101. http://dx.doi.org/10.52155/ijpsat.v38.1.5215.
Abstract:
Abstract—This study aimed to determine the optimum concentration of natural coagulant from chitosan to reduce the concentration of TSS in the skin cracker industrial liquid waste. The test was carried out by mixing chitosan powder which had been dissolved in 1% acetic acid. The treatment was carried out with variations in coagulant concentrations of: 100, 150, 200 and 250 mg/L added to several samples, namely the initial TSS concentration of liquid waste obtained from the initial measurement of liquid waste taken at 3 positions of waste disposal sites, namely 500, 570 and 650 mg/L. The results showed that the TSS concentration of 500 mg/L and the addition of 100 mg/L coagulant produced a concentration of 110, 150 mg/L coagulant produced 65 mg/L, 200 mg/L coagulant produced 90 mg/L, 250 mg/L coagulant reached 110 mg /l. At a TSS concentration of 570 mg/L, add 100 mg/L to 122 mg/L, coagulant 150 to 68 mg/L, coagulant 200 mg/L to 89 mg/L, coagulant 250 mg/L to 95 mg/L. TSS concentration of 650 mg/L was added 100 mg/L to 130 mg/L, coagulant 150 mg/L to 76 mg/L, coagulant 200 mg/L to 90 mg/L and coagulant 250 mg/L to 111. Conclusions from the study This shows that the most optimum reduction of TSS concentration is the addition of 150 mg/L of chitosan coagulant which can reduce the concentration of TSS in the skin cracker industrial waste water by 88.3%
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Tanyi, Janos Laszlo, Hye Sook Chon, Mark Aloysuis Morgan, Setsuko K. Chambers, Ernest Soyoung Han, Kristina A. Butler, Carrie L. Langstraat, et al. "Phase 3, randomized, single-dose, open-label study to investigate the safety and efficacy of pafolacianine sodium injection (OTL38) for intraoperative imaging of folate receptor positive ovarian cancer." Journal of Clinical Oncology 39, no. 15_suppl (May 20, 2021): 5503. http://dx.doi.org/10.1200/jco.2021.39.15_suppl.5503.
Abstract:
5503 Background: Pafolacianine sodium is under investigation as an adjunct to visual inspection and palpation by providing intra-operative imaging of folate receptor positive (FR+) ovarian cancer. Since complete resection (R0) is the strongest predictor of overall survival, methods to enhance detection of lesions are expected to benefit patient outcomes. Methods: For this phase 3, randomized, multicenter, single dose, open-label pivotal trial (NCT03180307), patients with ovarian cancer who were scheduled to undergo cytoreductive surgery were recruited from 11 sites in the US and Netherlands from March 2018 through April 2020. The study objectives were to confirm efficacy and safety of pafolacianine sodium (0.025 mg/kg i.v., ≥1 h prior to imaging) in combination with intraoperative near-infrared fluorescence (NIRF) imaging to detect additional lesions not detected by palpation and normal white light alone. Results: Pafolacianine sodium was administered to 150 total patients (safety analysis set); 109 patients comprised the full analysis set for efficacy analyses. Patients had primarily serous adenocarcinoma (n = 72; 68.6%) and advanced stage disease (n = 83; 76.1%). In 33% of patients (36 of 109), NIRF imaging with pafolacianine sodium identified additional lesions that were not planned for resection and were not detected by normal white light and palpation ( P < 0.001, 95% CI [0.243, 0.427]). Among patients who underwent interval debulking surgery, the rate was higher, at 39.7% of patients (23 of 58; 95% CI [0.270, 0.534]). At the individual lesion level, the accuracy of pafolacianine sodium with NIRF to detect ovarian cancer is reflected by sensitivity of 83% (95% CI [73.9, 89.4]) and a false positive rate of 32.7% (95% CI [25.6, 40.7]). Investigators reported achieving complete resection (R0) in 62.4% (68 of 109) of patients. Drug-related adverse events (AEs) were reported by 30% of patients (45 out of 150). The most frequently reported drug-related AEs were nausea (18.0%), vomiting (5.3%), and abdominal pain (4.7%). Infusion reactions at the time of the procedure were mostly (96%) mild or moderate in severity; 89% resolved within 24 hours of onset. No drug-related serious AEs or deaths were reported. Conclusions: This phase 3 trial of pafolacianine sodium with NIRF imaging met its primary endpoint, intraoperatively identifying additional cancer not planned for resection in a statistically significant number of patients. Therefore, pafolacianine sodium may offer a novel real-time adjunct to current surgical imaging practice in ovarian cancer surgery. Clinical trial information: NCT03180307.
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Natarajan, Abirami, Niclas Rudolfson, Daniel O'Neil, Lauren Schleimer, Jean Marie Vianney Dusengimana, Nancy Lynn Keating, Lawrence N. Shulman, et al. "Sociodemographic factors associated with cancer treatment completion among women with breast cancer at Butaro Cancer Center of Excellence (BCCOE) in Rwanda." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): e19220-e19220. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.e19220.
Abstract:
e19220 Background: Many barriers exist to delivering comprehensive breast cancer care in low-income countries. We examined sociodemographic factors associated with treatment completion among women receiving care for breast cancer at Butaro Cancer Center of Excellence (BCCOE), Rwanda’s first public cancer facility. Methods: We retrospectively measured treatment completion rates in women with early and locally advanced breast cancer diagnosed at BCCOE between July 1, 2012 and December 31, 2016. We defined treatment completion as receipt of surgery, 4 cycles of chemotherapy, and initiation of hormonal therapy for estrogen receptor positive (ER+) breast cancer. We used logistic regression to examine associations between socio-demographic and clinical factors and treatment completion. Travel time was estimated using a geographic information systems model using the WHO tool AccessMod 5.0. Results: Of 212 eligible women, 138 (65%) had surgery and 141 (66%) received 4 cycles of chemotherapy. Among 139 women with ER+ cancer, 59% initiated hormonal therapy. Overall 56% received all indicated treatment including surgery, chemotherapy, and hormonal therapy (if ER positive); 44% did not complete indicated treatment. Women who lived closer to the hospital ( <50 minutes travel time) were more likely than other women to complete treatment (OR 4.2; 95% CI 1.1-15.1). Women with early-stage disease were also more likely than women with locally advanced disease to complete treatment (OR 2.2, 95% CI 1.1-4.4). Among 100 women with available information about ubudehe (Rwandan social categorization used as a proxy for socioeconomic status), rates of treatment completion were higher for women who were eligible for social support (ie: transportation support or insurance subsidy) than women who were not (74% v. 63%), although this difference was not statistically significant (p= 0.51). Conclusions: Significant barriers exist for breast cancer patients receiving treatment in this low resource setting; nevertheless, over half of the patients completed therapy. Interventions are needed to facilitate care for women with long travel times and locally advanced disease to reduce disparities in outcomes for this population of patients. Further research is needed to determine the role of social support in treatment completion.
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Scaradavou, Andromachi, Cladd Stevens, Ludy Dobrila, Tracy Zhu, Shanlong Jiang, Diana Daniels, Patricia E. Taylor, Dorothy Sung, Maria S. Albano, and Pablo Rubinstein. "Cord Blood (CB) Unit Mononuclear Cell (MNC) Dose: Effect on Transplantation Outcome and Relevance to Processing Method and CBU Selection." Blood 112, no. 11 (November 16, 2008): 1969. http://dx.doi.org/10.1182/blood.v112.11.1969.1969.
Abstract:
Abstract Among the CB graft characteristics that affect post-transplant engraftment and survival TNC dose has become a critical variable in the selection of CB units. However, the cryopreserved TNC depends on the method of CB processing. The AXPTM system, used by the NYBC-NCBP since August 2006, automatically reduces the volume and separates the components of a CB unit in a closed system, resulting in >95% recovery of MNCs, CFU and CD34+ cells and excellent viability, consistently, while the average recovery of TNC is 80%. MNCs represent 47% (±0.07) of the pre-processing TNC. Thus, when processing has no effect on type of cells recovered, a CB unit with a TNC of 900x10^6 (cell number criterion used for inclusion in the National Cord Blood Inventory) would have an average of 425x10^6 MNCs. As a result of the differential recoveries, however, of all CBUs with a pre-processing TNC >1100x10^6, 58% will have a post-processing TNC count ≥ 900x10^6; in contrast, 81.5% will have MNC ≥ 425x10^6 (N=11012 units processed with the AXP system during the period: 2006–2008). To evaluate whether the MNC dose has an impact on transplant outcome, and compare it to that of the TNC dose, we evaluated the effect on time to engraftment (time to ANC ≥ 500) and transplant related mortality (TRM) in all patients with leukemia or myelodysplasia that received single unit CB grafts from our Bank following myeloablative cytoreduction, during the period 1993–2006. A total of 1044 patients (mean age: 13.9 years, median: 9.2 years, range: 0.2–64 years, 22% >20 years) were included, 87% had follow-up data. CBUs had 0 (5%), 1 (33%) or ≥ 2 (61%) HLA mismatches with the recipient; the median cryopreservation TNC/kg was 4.1x10^7. Pre-freezing complete counts were obtained by automated hematology analyzers (H*1, Technicon, Bayer Corporation or Sysmex XE-2100, Roche Diagnostics). Until July 2006, CBUs were processed manually [PNAS 94(22);1995]. For this study, MNC included nucleated RBC. In a multivariate Cox regression analysis TNC/kg, HLA mismatch level, GvHD prophylaxis, transplant center and year were independently predictive of time to ANC ≥ 500. When MNC/kg was added to the analysis with TNC/kg, only the MNC dose was a significant predictor (RR:1.5, p:0.03), and the TNC dose was no longer predictive (p:0.7). Low MNC/kg (<1x10^7) was associated with delayed engraftment; time to ANC ≥ 500 shortened (showed by increasing RR of engraftment) with higher doses of MNC. Similar variables: HLA mismatch level, TNC/kg, race, transplant center and year affected TRM independently, and again, the significant effect of MNC/kg on TRM, when included in the multivariate analysis, removed the significance of TNC dose. As shown, low MNC/kg (<1x10^7) was associated with increased TRM (RR:1.8, p<0.001). Time to ANC ≥ 500 Transplant-related mortality MNC/kg x(10 7 ) N=944 RR (95%CI) p value N=831 RR (95% CI) p value <1.0 154 0.6 (0.5–0.7) <0.001 159 1.8 (1.5–2.2) <0.001 1.0 – 1.9 291 Reference group 309 Reference group 2.0 – 2.9 144 1.0 (0.8–1.1) 0.559 151 0.9 (0.7–1.1) 0.264 3.0 – 3.9 92 1.2 (0.98–1.4) 0.085 99 0.8 (0.6–1.1) 0.192 ≥ 4.0 150 1.7 (1.4–2.0) <0.001 158 0.7 (0.6–0.95) 0.02 MNC dose, therefore, emerges as a better predictor of time to engraftment and TRM than the TNC dose, and thus, as a better measure of graft quality to be used in selecting CBUs for transplantation. In this context, because AXP processing retains more of the MNCs originally present in the CBU than other systems, this processing maybe used as a criterion of CBU quality when both the TNC and MNC are used as indices of CBU cellular contents.
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O'Malley, David M., Ursula A. Matulonis, Michael J. Birrer, Cesar Martin Castro, Ignace Vergote, Lainie P. Martin, Gina Mantia-Smaldone, et al. "Mirvetuximab soravtansine, a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC), in combination with bevacizumab in patients (pts) with platinum-resistant ovarian cancer: Final findings from the FORWARD II study." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 5520. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.5520.
Abstract:
5520 Background: Mirvetuximab soravtansine is an ADC comprising a FRα-binding antibody, cleavable linker, and the maytansinoid DM4, a potent tubulin-targeting agent. As part of the Phase 1b FORWARD II trial (NCT02606305), the combination of mirvetuximab soravtansine with bevacizumab (BEV) was evaluated in pts with FRα-positive, platinum-resistant ovarian cancer (recurrence within 6 months after last platinum). Methods: Pts received mirvetuximab soravtansine (6 mg/kg; adjusted ideal body weight) and BEV (15 mg/kg) on Day 1 of a 21-day cycle. Responses were assessed according to RECIST 1.1 and adverse events (AEs) evaluated by CTCAE v4.03. Results: In total, 66 pts received combination dosing at this level: 11 during escalation and 55 in expansion. The median age was 63 years, pts received a median of 3 prior lines of systemic therapy (range 1-8), and 62% had received prior therapy with BEV. The most common AEs were diarrhea (58%), nausea (50%), and blurred vision (48%), and were primarily low grade (≤ grade 2). Serious AEs were largely gastrointestinal in nature, with small intestinal obstruction the most frequent individual event (4 pts, 6%). Objective responses were seen in 27 pts for a confirmed overall response rate (ORR) of 41% (95% CI, 29, 54), median progression-free survival (mPFS) interval of 7.1 months (95% CI, 4.9, 9.5), and median duration of response (mDOR) of 8.6 months (95% CI, 4.9, 14.9). In a subset analysis of pts (n = 16) who were bevacizumab-naïve, had 1-2 prior therapies, and medium/high FRα levels (i.e., ≥ 50% of cells with at least moderate staining intensity) the ORR was 56% (95% CI, 30, 80), mPFS 9.9 months (95% CI, 4.1, 15.9), and mDOR 12 months (95% CI, 6.0, 14.9). Conclusions: The combination of mirvetuximab soravtansine with BEV exhibits favorable tolerability in pts with platinum-resistant ovarian cancer, characterized by a manageable side-effect profile. The encouraging efficacy compares favorably to reported outcomes for BEV and chemotherapy seen in similar patient populations. These data support continued exploration of the combination in ovarian cancer. Clinical trial information: NCT02606305.
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Treilleux, Isabelle, Monica Arnedos, Claire Cropet, Jean-Marc Ferrero, Sophie Abadie Lacourtoisie, Dominique Spaeth, Christelle Levy, et al. "Predictive markers of everolimus efficacy in hormone receptor positive (HR+) metastatic breast cancer (MBC): Final results of the TAMRAD trial translational study." Journal of Clinical Oncology 31, no. 15_suppl (May 20, 2013): 510. http://dx.doi.org/10.1200/jco.2013.31.15_suppl.510.
Abstract:
510 Background: Hormone resistance is linked in part to cross-talk between ER signalling and PI3K/Akt/mTOR pathway. Following results of the BOLERO-2 trial, everolimus (E), a potent mTOR inhibitor, has recently been approved in combination with exemestane in women with HR+ MBC refractory to aromatase inhibitor (AI). However, E is frequently associated with specific toxicities, and predictive markers of efficacy are needed. We report here the final results of translational studies within the TAMRAD randomized Phase II trial, comparing tamoxifen (TAM) to TAM+E in AI pre-treated MBC. Methods: Tumor samples from 51 patients among the 111 treated in the TAMRAD trial were retrieved. Hot spot mutations of PI3K (exon 9-20), and KRAS (exon 2) were described. TMA analysis evaluated IHC expression of PTEN, pAkt, PI3K, LKB1, S6K, pS6K, 4EBP1, p4EBP1, and eIF4E. Exploratory analysis of E efficacy in each biomarker subgroup (high vs low expression defined by median percentage of marked cells) was done. Results: Patients characteristics and treatment efficacy among this sub-population were similar to the results from the whole population: Time to progression was 10 months for the TAM+E treated patients vs. 5.5 months for the TAM treated patients, HR: 0.59 (95% CI 0.33-1.07). PI3K-Akt pathway: All patients derived benefit from E regardless of PI3K mutational status, PTEN or pAkt expression. Surprisingly, E efficacy was greater in patients with low PI3K expression (n=12, HR=0.11, 95%CI 0.01-0.96) than in patients with high PI3K expression (n= 28, HR=0.9; 95%CI 0.49-2.41) PI3K independent pathway: Patients with low expression of the anti-oncogene LKB1 derived greater benefit from E (n=22, HR=0.33; 95%CI 0.13-0.89) than patients with high LKB1 expression (n=25, HR=0.75; 95%CI 0.32-1.74) mTOR downstream effectors: Patients with high p4EBP1 (n=27, HR=0.37; 95%CI 0.15-0.90) or low 4EBP1 (n=21, HR=0.39; 95%CI 0.14-1.08) were the subgroups most likely to benefit from E. Conclusions: Those results are in favor of a better efficacy of E for patients with PI3K independent activation of mTOR. If confirmed, they could have important implications for future patient selection. Clinical trial information: NCT01298713.
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Uppal, Shitanshu, Paola Gehrig, Monica Hagan Vetter, Brittany Anne Davidson, Brittany F. Lees, Laurie Leigh Brunette, Katherine Tucker, et al. "Recurrence rates in cervical cancer patients treated with abdominal versus minimally invasive radical hysterectomy: A multi-institutional analysis of 700 cases." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): 5504. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.5504.
Abstract:
5504 Background: Compare outcomes between open and minimally invasive radical hysterectomy. Methods: Retrospective multi-institutional review of patients undergoing radical hysterectomy for stage IA1, IA2 and IB1 squamous, adeno- or adeno-squamous carcinoma between 01/01/2010 - 12/31/2017. Results: From 704 cases that met the inclusion criteria, 185 (26.3%) underwent open and 519 (73.7%) underwent minimally invasive surgery (MIS). Women treated with open surgery were older, had larger tumors on preoperative assessment as well as on final pathology assessment, had higher proportion of patients with IB1 stage and adjuvant therapy. Patients undergoing open surgery had longer median follow-up compared to MIS (44 vs. 30.3 months, p < 0.001). The two groups were similar in regard to race distribution, body mass index, comorbidities and preoperative histology. There were 13/185 (7%) recurrences and 10/185 (5.4%) deaths in the open compared to 42/519 (8.1%) recurrences and 26/519 (5%) deaths in MIS (p = n.s for both). However, on multivariate analysis, after controlling for race, comorbidities, preoperative tumor size, histology, grade and smoking status, MIS had higher odds of recurrence (OR 2.24, 95% CI 1.04 - 4.87, p = 0.04). On a second model, in addition to prior mentioned factors, we included lymphovascular space invasion, receipt of adjuvant therapy and vaginal margin status. Undergoing MIS remained associated with higher odds of recurrence (OR 2.37, 95% CI 1.1 - 5.1, p = 0.031). On sub-group analysis of cases with preoperative tumor size less than equal to 2 cm, there were 5/121 (4.1%) recurrence in open and 25/415 (6%) recurrences in MIS group (p = 0.34). Multivariate analysis did not show a higher rate of recurrence in MIS arm in this subgroup. In 26 cases of MIS where no vaginal manipulator was used, no recurrences were noted. In comparison 19/270 (7%) recurrences were noted in intra-uterine manipulator (V-care/Zumi/Rumi) and 22/210 (11%) in vaginal manipulators (EEA sizer/Colpo Probe) groups (p = 0.119). Conclusions: In this large retrospective analysis, patients undergoing MIS for early stage cervical cancer had higher odds of recurrence. In patients with 2 cm or less tumor on preoperative assessment, recurrence rates were similar between the two groups. Role of manipulator in increasing recurrence should be further studied in this patient population.
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Pasieczna, Aleksandra Helena, and Magdalena Joanna Szydłowska. "Estimating Model Risk of VaR under Different Approaches: Study on European Banks." Współczesne Problemy Zarządzania 9, no. 2(19) (December 31, 2021): 65–76. http://dx.doi.org/10.52934/wpz.151.
Abstract:
The objective of this research is to estimate the model risk, represented as precision, and the accuracy of the Value at Risk (VaR) measure, under three different approaches: historical simulation (HS), Monte Carlo (MC), and generalized ARCH (GARCH). In this work, to analyze the VaR model, the accuracy and precision were used. Estimation of the accuracy and precision was done under the three approaches for four European banks at 95 and 99% confidence levels. The percentage crossings and Kupiec POF were used to judge the model accuracy, whereas the ratio of the maximum and minimum VaR estimates, and the spread between the maximum and minimum VaR estimates were used to estimate the model risk. This was achieved by changing input parameters, specifically, the estimation time window (125, 250, 500 days). Implications/Recommendations: The accuracy alone is not sufficient to evaluate a model and precision is also required. The temporal evolution of the precision metrics showed that the VaR approaches were inconsistent under different market conditions. This article focuses on the accuracy and precision concepts applied to estimate model risk of the Value at Risk (VaR). VaR is the foundation for sophisticated risk metrics, including systemic risk measures like Marginal Expected Shortfall and Delta Conditional Value at Risk. Thus, understanding the risk associated with the use of VaR is crucial for finance practitioners.
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De Santis, Maria, Enrique Grande, Marina Mencinger, Jian-Ri Li, Javier Puente, Kouji Izumi, Jae-Lyun Lee, et al. "IMvigor130 clinical trial in patients (pts) with metastatic urothelial carcinoma (mUC): Analysis of upper tract (UT) and lower tract (LT) subgroups." Journal of Clinical Oncology 38, no. 6_suppl (February 20, 2020): 551. http://dx.doi.org/10.1200/jco.2020.38.6_suppl.551.
Abstract:
551 Background: IMvigor130 demonstrated a statistically significant improvement in PFS in pts receiving atezolizumab (atezo; anti–PD-L1) + platinum-based chemotherapy (plt/gemcitabine [gem]; Arm A) vs placebo + plt/gem (Arm C) as first-line treatment for mUC (Grande et al. 2019). Exploratory analyses examined efficacy outcomes in UT and LT mUC subgroups. Methods: Pts with UT and LT mUC from Arm A and Arm C were included. Chemotherapy was gem + investigator choice of plt (cisplatin or carboplatin). Tumors were assessed at baseline and every 9 wk until investigator-assessed PD per RECIST 1.1 or other events. PFS, OS and ORR in UT and LT subgroups are shown. Results: Baseline characteristics were comparable between Arm A and Arm C in the UT and LT subgroups; however, slight imbalances were noted, such as higher PD-L1–positive status (IC2/3) and lower Bajorin risk score in UT Arm A pts. With a median follow-up of 11.8 mo, median PFS was8.2 vs 6.2 mo in Arm A vs Arm C in UT pts (HR, 0.69 [95% CI: 0.51, 0.94]) and 8.1 vs 6.5 mo, respectively, in LT pts (HR, 0.85 [95% CI: 0.70, 1.02]). Interim median OS was 16.9 vs 13.5 mo in Arm A vs Arm C in UT pts (HR, 0.78 [95% CI: 0.54, 1.12]) and 15.8 vs 13.4 mo, respectively, in LT pts (HR, 0.87 [95% CI: 0.70, 1.08]). See table for additional efficacy results. Conclusions: Exploratorysubgroup analyses suggest activity of atezo + plt/gem in both UT and LT mUC, with outcomes in UT pts comparable to those seen in the LT and ITT populations. Clinical trial information: NCT02807636. [Table: see text]
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Hofman, Michael S., Louise Emmett, Shahneen Kaur Sandhu, Amir Iravani, Anthony M. Joshua, Jeffrey C. Goh, David A. Pattison, et al. "TheraP: A randomised phase II trial of 177Lu-PSMA-617 (LuPSMA) theranostic versus cabazitaxel in metastatic castration resistant prostate cancer (mCRPC) progressing after docetaxel: Initial results (ANZUP protocol 1603)." Journal of Clinical Oncology 38, no. 15_suppl (May 20, 2020): 5500. http://dx.doi.org/10.1200/jco.2020.38.15_suppl.5500.
Abstract:
5500 Background: LuPSMA is a radiolabeled small molecule that delivers therapeutic β-radiation to PSMA-expressing tumors. Encouraging efficacy and safety has been shown in non-randomized studies of mCRPC. TheraP is a randomized phase II trial comparing LuPSMA vs cabazitaxel in men with mCRPC progressing after docetaxel. Methods: Men with mCRPC, and imaging with 68Ga-PSMA-11 and 18F-FDG PET/CT that confirmed high PSMA-expression and no sites of FDG-positive/PSMA-negative disease, were randomly assigned (1:1) to LuPSMA (6-8GBq q6weeks up to 6 cycles) vs cabazitaxel (20mg/m2 q3weeks up to 10 cycles); stratified by disease burden (>20 vs ≤20 sites), prior novel antiandrogens (NAA; abiraterone or enzalutamide), and study site. The primary endpoint was PSA response rate (PSA50-RR) defined by ≥50% reduction. Secondary efficacy endpoints included PSA-progression-free survival (PSA-PFS) and overall survival (OS). Data cut-off was 31DEC19 at this first pre-specified analysis. Results: 200 (median age 72 y, prior NAA 91%, >20 lesions 78%) of 291 PET screened men were randomised to LuPSMA (N=99) or cabazitaxel (N=101). 17 patients withdrew or died before receiving study treatment (1 LuPSMA vs 16 cabazitaxel). The PSA50-RR was higher in those assigned LuPSMA than cabazitaxel (65/99 [66%; 95%CI 56-75] vs 37/101 [37%; 95%CI 27-46]; P<0.001). At a median follow-up of 11.3 months, LuPSMA significantly improved PSA-PFS (HR 0.63, 95%CI 0.45-0.88, P=0.007; 143 events with next pre-specified analysis planned after 170 events). Efficacy results were similar when analyses were restricted to per-protocol treated men. OS data remains immature (57 deaths). Grade III-IV adverse events (AEs) occurred in 31/98 (32%) LuPSMA-treated men vs 42/85 (49%) in cabazitaxel-treated men. Discontinuations for toxicity occurred in 1/98 (1%) LuPSMA vs 3/85 (4%) cabazitaxel-treated. There were no treatment-related deaths. Conclusions: In men with docetaxel-treated mCRPC, LuPSMA was more active (PSA50-RR) than cabazitaxel with relatively fewer G3-4 AEs and PSA-PFS favoring LuPSMA. Clinical trial information: NCT03392428 .
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Genge, A., M. Pasnoor, V. Bril, C. Karam, S. Peric, JL De Bleecker, H. Murai, et al. "P.043 Long-term safety, tolerability, and efficacy of efgartigimod in patients with Generalized Myasthenia Gravis: concluding analyses from ADAPT+." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 50, s2 (June 2023): S69. http://dx.doi.org/10.1017/cjn.2023.147.
Abstract:
Background: Efgartigimod is a human IgG1 antibody Fc-fragment that reduces total and pathogenic IgG autoantibody levels through FcRn blockade. ADAPT was a phase 3 trial evaluating efgartigimod in patients with generalized myasthenia gravis (gMG). Patients who completed ADAPT could enroll in ADAPT+ (open-label extension). Methods: Efgartigimod (10 mg/kg intravenous) was administered in cycles of 4 weekly infusions, with subsequent cycles initiated based on clinical evaluation. ADAPT+ evaluated long-term safety and tolerability of efgartigimod in patients with gMG. Efficacy was assessed utilizing MG-ADL and QMG scores. Results: Of 167 patients from ADAPT, 151 (90%) entered ADAPT+, and 145 received ≥1 cycle as of January 2022. Over 217.55 patient-years of follow-up (mean duration per patient, 548 days), incidence of adverse events did not increase with subsequent cycles. AChR-Ab+ patients with ≥1 year of follow-up across ADAPT/ADAPT+ (n=95) received a median (range) 5.0 (0.4–7.6) cycles per year. All AChR-Ab+ patients (n=111) demonstrated consistent improvements (mean change [SE], week 3 of cycle 1) in MG-ADL (-5.0 [0.33]; up to 14 cycles) and QMG (-4.7 [0.41]; up to 7 cycles) scores during each cycle. Conclusions: These ADAPT+ analyses suggest long-term efgartigimod treatment is well tolerated and efficacious. Additional final data cut analyses will be presented at CNSF 2023.
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Суховія, М. І., М. І. Шафраньош, М. М. Чаварга, and І. І. Шафраньош. "Іонізація та збудження молекул урацилу електронним ударом." Ukrainian Journal of Physics 57, no. 7 (July 30, 2012): 752. http://dx.doi.org/10.15407/ujpe57.7.752.
Abstract:
Експериментальним шляхом отримано дані про абсолютні величини перерізів утворення позитивних і негативних іонів азотистої основинуклеїнових кислот – урацилу. Показано, що максимальних значень переріз утворення негативних іонів досягає при енергії бомбардуючихелектронів 1,1 еВ, і його абсолютна величина становить 5,0 · 10–18 cм2. Визначено абсолютну величину та енергетичну залежність перерізу утворення позитивних іонів для урацилу в інтервалі енергій електронів від порога до 200 еВ. Максимум перерізу іонізації знаходиться при енергії 95 еВ і дорівнює (1,0 ± 0,1) · 10–15 cм2. Отримано спектри люмінесценції ізольованих молекул урацилу в області довжин хвиль 200–500 нм під дією повільних електронів. У спектрі спостерігаються близько 20 спектральних смуг і ліній. Показано, що спектр випромінювання урацилу формують процеси дисоціативного збудження молекул, дисоціативного збудження з іонізацією, збудження електронних рівнів вихідної молекули та молекулярного іона. Обговорено біофізичні наслідки отриманих результатів.
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Orlando, L., A. Cardillo, R. Ghisini, N. Rotmensz, G. Peruzzotti, P. Maisonneuve, G. Viale, A. Goldhirsch, and M. Colleoni. "Role of endocrine responsiveness and adjuvant therapy in very young women (< 35 years) with operable breast cancer and node negative disease." Journal of Clinical Oncology 24, no. 18_suppl (June 20, 2006): 558. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.558.
Abstract:
558 Background: Breast cancer rarely occurs in young women. There is limited knowledge about prognosis, and treatment effects in the population with node negative disease, largely dependent upon older series and extrapolation of data from older age cohorts. Methods: We evaluated biological features and adjuvant treatment recommendations for 841 premenopausal consecutive patients with pT1–3, pN0 and M0, operated and counseled for medical therapy from April 1997 to December 2001. We evaluated also, the prognostic role of age and adjuvant treatment. Median follow-up was 49.9. Results: Very young women (101, 12%) were more likely to have tumors with absent ER (42% v 17.6%, p < .0001) and PgR (48% v 23.2%, p < .0001), > 2 cm (36.7% v 24.8%; p = .002), grade 3 (53.9% v 33.5%; p = .0009) and elevated Ki-67 (68.5% v 51.6%; p = .002), when compared with older patients (740, 88%). Younger patients (compared with older patients) with endocrine responsive disease were prescribed more chemotherapy (67.2% v 44.3%; p = .0009) but endocrine adjuvant therapy was prescribed in a similar percentage in both groups (93.1% v 96% p = .30). A statistically significant difference in disease-free survival (DFS), risk of distant metastases and overall survival (OS) was observed at the multivariate analysis for younger patients (HR = 4.44; 95% CI, 2.53 to 7.78, p < .0001 for DFS; HR = 3.23; 95% CI, 1.32 to 7.94, p = .011 for distant metastases; HR = 2.89; 95% CI, 1.06 to 7.87, p = .038 for OS). An increased risk for younger age was observed for patients with endocrine responsive disease (ER ≥ 1%) (HR = 5.17; 95% CI, 2.72 to 9.83, p < .0001 for DFS) in particular if endocrine therapy was not performed (HR = 7.77; 95% CI, 1.98 to 30.6, p = .003 for DFS). Conclusions: We conclude that compared with less young premenopausal patients, the very young women presenting with breast cancer and ipsilateral axilla negative for disease, are at larger chance of relapse. Endocrine therapies are crucial in patients with endocrine responsive disease. No significant financial relationships to disclose.
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Kara, Stephen, Alexandra Smart, Tara Officer, Chan Dassanayake, Phil Clark, Amy Smit, and Alana Cavadino. "Guidelines, training and quality assurance: influence on general practitioner MRI referral quality." Journal of Primary Health Care 11, no. 3 (2019): 235. http://dx.doi.org/10.1071/hc19034.
Abstract:
ABSTRACT INTRODUCTIONMagnetic resonance imaging (MRI) is an accurate diagnostic test used mainly in secondary care. Uncertainty exists regarding the ability of general practitioners (GPs) to use direct access high-tech imaging pathways appropriately when managing musculoskeletal injury. AIMTo evaluate the use of primary care-centric guidelines, training and quality assurance on the appropriateness of GP MRI referrals for patients with selected musculoskeletal injuries. METHODSThis is an 18-month primary care retrospective study. GPs participated in clinical musculoskeletal training, enabling patient referral for MRI on four body sites. Two reviewers categorised referral appropriateness independently, and reviewer inter-rater agreement between categorisations was measured. MRI results and patient management pathways were described. Associations of scan status and patient management were examined using logistic regression. RESULTSIn total, 273 GPs from 72 practices attended training sessions to receive MRI referral accreditation. Of these, 150 (55%) GPs requested 550 MRI scans, with 527 (96%) eligible for analysis, resulting in 86% considered appropriate; 79% consistent with guidelines and 7% clinically useful but for conditions outside of guidelines. Inter-rater agreement was 75%. Cohen’s weighted kappa statistic was 0.38 (95% CI: 0.28–0.48). MRI referrals consistent with guidelines were more likely to show pathology requiring specialist intervention (reviewer 1: odds ratio=2.64, 95% CI 1.51–4.62; reviewer 2: odds ratio=4.44, 95% CI 2.47–7.99), compared to scan requests graded not consistent. DISCUSSIONStudy findings indicate GPs use decision support guidance well, and this has resulted in appropriate MRI referrals and higher specialist intervention rates for selected conditions.
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Kara, Stephen, Alexandra Smart, Tara Officer, Chan Dassanayake, Phil Clark, Amy Smit, and Alana Cavadino. "Corrigendum to: Guidelines, training and quality assurance: influence on general practitioner MRI referral quality." Journal of Primary Health Care 11, no. 4 (2019): 387. http://dx.doi.org/10.1071/hc19034_co.
Abstract:
ABSTRACT INTRODUCTIONMagnetic resonance imaging (MRI) is an accurate diagnostic test used mainly in secondary care. Uncertainty exists regarding the ability of general practitioners (GPs) to use direct access high-tech imaging pathways appropriately when managing musculoskeletal injury. AIMTo evaluate the use of primary care-centric guidelines, training and quality assurance on the appropriateness of GP MRI referrals for patients with selected musculoskeletal injuries. METHODSThis is an 18-month primary care retrospective study. GPs participated in clinical musculoskeletal training, enabling patient referral for MRI on four body sites. Two reviewers categorised referral appropriateness independently, and reviewer inter-rater agreement between categorisations was measured. MRI results and patient management pathways were described. Associations of scan status and patient management were examined using logistic regression. RESULTSIn total, 273 GPs from 72 practices attended training sessions to receive MRI referral accreditation. Of these, 150 (55%) GPs requested 550 MRI scans, with 527 (96%) eligible for analysis, resulting in 86% considered appropriate; 79% consistent with guidelines and 7% clinically useful but for conditions outside of guidelines. Inter-rater agreement was 75%. Cohen's weighted kappa statistic was 0.38 (95% CI: 0.28–0.48). MRI referrals consistent with guidelines were more likely to show pathology requiring specialist intervention (reviewer 1: odds ratio=2.64, 95% CI 1.51–4.62; reviewer 2: odds ratio=4.44, 95% CI 2.47–7.99), compared to scan requests graded not consistent. DISCUSSIONStudy findings indicate GPs use decision support guidance well, and this has resulted in appropriate MRI referrals and higher specialist intervention rates for selected conditions.
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Yatskevich, N. V., G. L. Gurevich, E. M. Skryagina, and E. Gurbanova. "Evaluation of Effectiveness of 9- and 6-Month Treatment Regimens in Patients with Multiple Drug Resistant or Rifampicin-Resistant Tuberculosis in the Republic of Belarus." Tuberculosis and Lung Diseases 101, no. 6 (December 25, 2023): 34–41. http://dx.doi.org/10.58838/2075-1230-2023-101-6-34-41.
Abstract:
The objective: to evaluate the effectiveness of 39- and 24-week treatment regimens in patients with multiple drug resistant or rifampicin-resistant tuberculosis (MDR/RR-TB).Subjects and Methods. We evaluated the effectiveness of 39- and 24-week treatment regimens containing bedaquiline, levofloxacin, linezolid, clofazimine, and cycloserine or delamanid (modified short-course regimens - mSCR) and bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM), in cohorts of patients with MDR/RR-TB. Results. Of the 550 and 139 patients were included in the mSCR and SMARRTT Studies (BPaLM regimen) from December 2019 to October 2021 and from March 2022 to August 2022, 90.7% (487/537) and 94.2% (131/139) achieved a successful treatment outcome, respectively, 13 patients were excluded from the mSCR Study and continued treatment according to an individual regimen. Median (ME) and quartiles [Q1-Q3] of sputum culture conversion time in patients treated with mSCR and BPaLM made 30.0 (25.0-56.0) and 27.0 (25.0-29.8) days (p<0.01) respectively. The prognostic factor for an unfavorable outcome for the BPaLM and mSCR regimens was a positive sputum microscopy result before treatment (OR – 7.92, 95% CI 1.5 – 41.0, p = 0.014; OR – 1.97, 95% CI 1.1–3.5, p=0.02, respectively), and for the mSCR regime, the time of sputum culture conversion >90 days was an additional prognostic factor (OR – 3.35, 95% CI 1.2–9.5, p=0.03) .Conclusions. The effectiveness of the mSCR and BPaLM regimens in patients with MDR/RR-TB is high (90.7% and 94.2%, respectively). Patients with positive sputum microscopy and late sputum culture conversion have a lower chance of cure.
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Bartlett, John, Irina Kalatskaya, Fouad Yousif, Jane Bayani, Quang M. Trinh, Lawrence Heisler, Lee Timms, et al. "Targeted sequencing in a phase III trial of luminal breast cancer: Identification of novel targets." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): 505. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.505.
Abstract:
505 Background: The International Cancer Genome Consortium and The Cancer Genome Atlas have had a global transformative impact on our understanding of cancer. These programs have mapped the genomic landscape of common and rare tumors setting the scene for a comprehensive change in the approach to cancer diagnosis and treatment. However, the task remains incomplete until these mutational events are linked to clinical outcomes in the context of current therapeutic intervention to drive future stratified medicine approaches. Methods: We performed targeted sequencing in patients from the Tamoxifen Exemestane Adjuvant Multicentre trial. DNA was extracted and a 101 gene panel analysed using a novel mutation calling pipeline. Both a priori and machine learning analyses were performed using distant recurrence free survival as the primary endpoint. Results: In 1,491 successfully analyzed samples 1,070 (71.76%) samples exhibited at least one single nucleotide mutation (range 0-94, 1.828+/-0.133, mean+/-s.e.). 98/101 genes were mutated in at least one patient. Only variants in PIK3CA, TP53, MLL3, CDH1 were detected in 5% or more of samples. Twenty genes were associated with increased risk of recurrence in multivariate analyses corrected for clinic-pathological variables, 50% of these genes were involved in transcriptional regulation or RNA/protein processing. In a multivariate analysis, two combined signalling modules were independently prognostic for residual risk following hormone therapy (HRvalidation 3.10 95%CI 1.78-5.40 and HRvalidation 2.70 95%CI 1.57-4.64). Conclusions: We successfully performed a signalling pathway-based targeted sequencing analysis within predefined signalling modules. In supervised and unsupervised analyses we identified multiple signalling cassettes linked to poor outcome in patients with ER+ve breast cancers treated with modern endocrine therapy in the context of a phase III clinical trial. These results identify novel candidates as targets to treat endocrine refractory breast cancers.
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Viuff, Mette Hansen, Kirstine Stochholm, Henning Grønbæk, Agnethe Berglund, Svend Juul, and Claus Højbjerg Gravholt. "Increased occurrence of liver and gastrointestinal diseases and anaemia in women with Turner syndrome – a nationwide cohort study." Alimentary Pharmacology & Therapeutics 53, no. 7 (February 7, 2021): 821–29. http://dx.doi.org/10.1111/apt.16277.
Abstract:
SummaryBackgroundLiver and gastrointestinal diseases are frequent in women with Turner syndrome. However, their association with bleeding disorders, anaemia and the impact of hormone replacement therapy is unknown.AimsTo investigate the risk of liver and gastrointestinal diseases, haemorrhage and anaemia in women with Turner syndrome compared with the female background population, and the long‐term impact of hormone replacement therapy on these conditions.MethodsOne thousand one hundred and fifty‐six women with Turner syndrome diagnosed during 1960‐2014 were identified using the Danish Cytogenetic Central Registry and linked with personal‐level data from the National Patient Registry and the Medication Statistics Registry. Statistics Denmark randomly identified 115 577 age‐matched female controls. Negative binomial regression was used to analyse hospital discharge diagnoses. Medical prescriptions, mortality and the effect of hormone replacement therapy were estimated using stratified Cox regression.ResultsLiver disease increased 13‐fold (IRR 12.9 (95% CI 5.8‐28.8)), due to toxic liver disease (IRR 8.0 (95% CI 1.8‐35.4)), liver insufficiency (IRR 6.7 (95% CI 1.7‐26.9)), fibrosis/cirrhosis (IRR 16.5 (95% CI 2.2‐122.1)) and unspecified liver disease (IRR 10.6 (95% CI 4.4‐25.3)). Furthermore, presence of abnormal liver enzymes increased 12‐fold (IRR 12.4 (95% CI 4.2‐36.6)). The risk of gastrointestinal haemorrhage (IRR 3.4 (95% CI 1.8‐6.2)), anaemia (IRR 3.2 (95% CI 2.0‐5.0)) and coagulation disorders (IRR 2.9 (95% CI 1.1‐7.1)) was increased. However these diagnoses were not associated with inflammatory bowel disease. Gastrointestinal mortality was increased three‐fold (HR 3.1 (95% CI 1.5‐6.2)), partly due to death by liver disease (HR 3.0 (95% CI 1.1‐8.2)), gastrointestinal haemorrhage (HR 29.6 (95% CI 3.1‐285.1)) and capillary malformations (HR 18.6 (95% CI 4.1‐85.0)). There was no effect of hormone replacement therapy on gastrointestinal risk but a trend towards a beneficial impact on liver diseases.ConclusionsThe risk of being diagnosed with liver disease was higher than previously reported. The occurrence of gastrointestinal haemorrhage and anaemia was increased in Turner syndrome. There was no effect of hormone replacement therapy on gastrointestinal risk but a trend towards a beneficial impact on liver diseases was detected.
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Gonçalves, Carlos Barros, Karina Kosicki Bellotti, and Leandro Seawright. "Protestantismos e História: a propósito dos 500 anos da Reforma Protestante." Fronteiras 19, no. 34 (December 30, 2017): 07–12. http://dx.doi.org/10.30612/frh.v19i34.7589.
Abstract:
No mês de outubro de 2017 foram realizadas, em diversas partes do mundo, celebrações alusivas aos 500 anos da Reforma Luterana, comumente chamada de Reforma Protestante. O centro das comemorações foi a pequena cidade alemã de Wittenberg, atualmente com pouco mais de 50 mil habitantes e que abriga a Igreja do Castelo de Wittenberg, local onde em 31 de outubro de 1517 o monge Martinho Lutero afixou suas 95 teses com críticas à Igreja Católica. Esse ato foi considerado como o desencadeador dos movimentos que provocaram a maior divisão institucional no interior do cristianismo romano.