Journal articles: '1934, May 13-May 27' – Grafiati (2024)

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Britten‘s music is usually thought of as tonal, even if the term is sometimes qualified.’ Much of the drama of his operas (at least, up to and including A Midsummer Night's Dream, op. 64 (1960)) has been discussed in terms of ‘tonal action’, as have the structures of individual songs, song cycles and purely instrumental works. Yet his earliest published works are not tonal in the same way as later, more widely known ones. Not until the works of his American years (1939–42) do we begin to see the kind of tonal structure that enabled Peter Grimes, op. 33 (1945), to be conceived – structures like the highly focused tritonal opposition of Les illuminations, op. 18 (1939), or the E/C ambiguity (eventually resolved in favour of E) of the Hymn to St Cecilia, op. 27 (1942). Nevertheless Britten's first three works with opus numbers, written while he was a student at the Royal College of Music from 1930 to 1933 (the Sinfonietta, op. 1, completed in July 1932; the Phantasy Quartet, op. 2, completed in October 1932; and A Boy was Born, op. 3, completed in May 1933), are quite clearly diatonic in basis. This essay explores the ways in which this diatonicism is structured, and sketches the subsequent history of the main procedure involved.

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Alan Cuthbert carried out ground-breaking work on epithelial ion transport. He used radiolabelled amiloride and benzamil to measure the sodium channel density in epithelia from frog skin and toad bladder, tissues that are good models for the distal section of the mammalian kidney tubule. This work shed important new light on how the properties of these channels are modified by hormones such as aldosterone and antidiuretic hormone, and increased our understanding of how diuretics affect kidney function. Later, he focused on the ion transport deficits that underlie cystic fibrosis (CF), and was a member of the team that showed that the ion transport defect could be corrected in CF transgenic mice by gene therapy. Alan was Sheild Professor of Pharmacology and Head of the Department of Pharmacology at the University of Cambridge from 1979 until his retirement in 1999. During this time he was instrumental in moving the Department from the Addenbrooke's Hospital site to a new building in the centre of town. He was also Master of Fitzwilliam College from 1991 until 1999. Alan made major contributions to pharmacology nationally and internationally, serving as chairman of the editorial board of the British Journal of Pharmacology for eight years, and as President of the Federation of European Pharmacological Societies for two years. In recognition of his contributions to the subject, the British Pharmacological Society awarded him their Wellcome Gold Medal in 2005. After his retirement, he continued his research in the Department of Medicine, pursuing novel pharmacological approaches to the treatment of CF.

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We constructed a reporter influenza A/Puerto Rico/8/1934 virus expressing truncated 124aa N-terminal NS1 protein fused to a luciferase reporter sequence (NanoLuc) without signal peptide. The reproduction activity of the vector correlated well with the luminescent activity in the lysates of infected cell cultures or mouse respiratory organ suspensions. Surprisingly, we found that luciferase enzymatic activity was present not only in the intracellular compartments but also in cell culture supernatants as well as in the sera or bronchiolar lavages of infected mice. This fact allowed us to formulate a working hypothesis about the extracellular delivery mechanism of the NS1 protein. To test this idea, we conducted co-transfection experiments in Vero cells with different combinations of plasmids encoding influenza genomic segments and chimeric NS1-NanoLuc encoding plasmid. We found that the emergence of the luciferase reporter in the extracellular compartment was promoted by the formation of the ribonucleoprotein complex (RNP) from the co-transfection of plasmids expressing PB1, PB2, PA, and NP proteins. Therefore, influenza NS1 protein may be delivered to the extracellular compartment together with the nascent RNP complexes during the maturation of virus particles.

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Abstract Background In 2015, adolescents 13–24 years were disproportionately affected and accounted for 22% of new HIV infections in the United States. In New York State (NYS), the rate of adolescents (13–19 years) living with HIV infection is more than twice the national rate (44.4 vs. 19.4 per 100,000 population). As part of the ending the epidemic (ETE) program, the NYS Department of Health spearheaded access to pre-exposure prophylaxis (PrEP) for high-risk individuals to keep them HIV negative. This study aims to test the hypothesis that adolescents at risk may not be utilizing PrEP and that there are barriers to adopting it. Methods A cross-sectional survey (Qualtrics) was conducted from Aug 2017 to May 2018 using a 13-item multiple choice and Lickert scale validated questionnaire that takes <5 minutes to complete. Descriptive and nonparametric tests (GraphPad Prism v5.04) were used to characterize knowledge and acceptance of PrEP among adolescents in Capital District NY after the initiation of the ETE program in NYS. Results There were 97 respondents and 89 (92%) completed all questions. Most of the respondents identify themselves as female (36%), straight (27%), middle aged adolescents 15–17 years (64%), African American (46%) and currently in high school (69%). Majority have seen a medical provider in the past 12 months (90%), at the doctor’s office (61%), and majority have never been offered HIV test (60%). Majority have not heard of a medicine that can prevent HIV infection (58%), most have not heard of PrEP (57%), and many do not know where to go to learn more about PrEP (56%). Most have not been offered PrEP (86%) and respondents were split in adopting PrEP (yes 49% vs. no 51%). The reasons for not agreeing to start PrEP are shown in Figure 1. Majority are interested in attending educational program on PrEP (57%). Adolescents are likely to adopt PrEP if they heard about it (P = 0.01), if they know where to go to learn about it (P = 0.02), and if someone offered it (P = 0.03). Conclusion Adolescent knowledge of PrEP may be suboptimal and presents barriers to adopting it. However, they are willing to accept PrEP if offered. This study demonstrates potential avenues for intervention and provider-initiated programs should be evaluated in scaling-up PrEP into adolescent health services. Disclosures All authors: No reported disclosures.

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IntroductionThe emergence of new antipsychotics, such as Paliperidone Extended Release, demands a constant effort on behalf of the clinics to outline an appropriate profile for those patients who may benefit more.ObjectiveTo collect clinical and social-demographic data to develop a profile of the patient who has used Paliperidone Extended Release in our hospitalisation unit.MethodThis is a naturalistic, descriptive and retrospective study; we will include 36 patients admitted to our Acute Patients Unit. The inclusion and exclusion criteria were clinical.ResultsA total of 44.4% were over the age of 40 years; positive symptoms (52.8%) and behavioural alterations (19.4%) prevailed; the most common diagnosis was schizophrenia (47.2%). A total of 61.1% of cases were associated with other APs, especially Injectable Risperidone Extended Release or antipsychotics with a sedation profile. A total of 83.3% did not require mechanical restraint, and 80.6% did not present side effects. The most common side effects were extrapyramidal symptoms. The mean duration of hospitalisation was 19.60 ± 12.07 days. The mean dose of Paliperidone Extended Release was 14.41 ± 4.83 mg/day. Initially, a dose of 13 ± 4.42 mg/day was used, while the maximum dose was 27 mg/day.ConclusionsOur experience with Paliperidone Extended Release in the hospital scope allows us to state that it is a drug with a very positive efficacy and safety-tolerability profile. Therefore, we may consider Paliperidone Extended Release a first line antipsychotic due to its contributions in different patient elements (clinical, functionality, tolerability, etc.)

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Abstract. A first assessment of the main climatic drivers that modulate the tree-ring width (RW) and maximum latewood density (MXD) along the Italian Peninsula and northeastern Sicily was performed using 27 forest sites, which include conifers (RW and MXD) and broadleaves (only RW). Tree-ring data were compared using the correlation analysis of the monthly and seasonal variables of temperature, precipitation and standardized precipitation index (SPI, used to characterize meteorological droughts) against each species-specific site chronology and against the highly sensitive to climate (HSTC) chronologies (based on selected indexed individual series). We find that climate signals in conifer MXD are stronger and more stable over time than those in conifer and broadleaf RW. In particular, conifer MXD variability is directly influenced by the late summer (August, September) temperature and is inversely influenced by the summer precipitation and droughts (SPI at a timescale of 3 months). The MXD sensitivity to August–September (AS) temperature and to summer drought is mainly driven by the latitudinal gradient of summer precipitation amounts, with sites in the northern Apennines showing stronger climate signals than sites in the south. Conifer RW is influenced by the temperature and drought of the previous summer, whereas broadleaf RW is more influenced by summer precipitation and drought of the current growing season. The reconstruction of the late summer temperatures for the Italian Peninsula for the past 300 years, based on the HSTC chronology of conifer MXD, shows a stable model performance that underlines periods of climatic cooling (and likely also wetter conditions) in 1699, 1740, 1814, 1914 and 1938, and follows well the variability of the instrumental record and of other tree-ring-based reconstructions in the region. Considering a 20-year low-pass-filtered series, the reconstructed temperature record consistently deviates < 1 °C from the instrumental record. This divergence may also be due to the precipitation patterns and drought stresses that influence the tree-ring MXD at our study sites. The reconstructed late summer temperature variability is also linked to summer drought conditions and it is valid for the west–east oriented region including Sardinia, Sicily, the Italian Peninsula and the western Balkan area along the Adriatic coast.

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The aim of the Ukrainian Bureau in Washington was propaganda of Ukrainian question among US government and American publicity in general. Functioning of the Bureau is not represented non in Ukrainian neither in foreign historiographies, so that’s why the main goal of presented paper is to investigate its activity. The research is based on personal papers of Ukrainian diaspora representatives (O. Granovskyi, E. Skotzko, E. Onatskyi) and articles from American and Ukrainian newspapers. The second mass immigration of Ukrainians to the US (1914‒1930s) has often been called the «military» immigration and what it lacked in numbers, it made up in quality. Most immigrants were educated, some with college degrees. The founder of the Ukrainian Bureau Eugene Skotzko was born near Western Ukrainian town of Zoloczhiv and immigrated to the United States in late 1920s after graduating from Lviv Polytechnic University. In New York he began to collaborate with OUN member O. Senyk-Hrabivskyi who gave E. Skotzko task to create informational bureau for propaganda of Ukrainian case. On March 23 1939 the Bureau was founded in Washington D. C. E. Skotzko was an editor of its Informational Bulletins. The Bureau biggest problem was lack of financial support. It was the main reason why it stopped functioning in May 1940. During 14 months of functioning Ukrainian Bureau in Washington posted dozens of informational bulletins and send it to hundreds of addressees; E. Skotzko, as a director, personally wrote to American governmental institutions and foreign diplomats informing about Ukrainian problem in Europe. Ukrainian Bureau activity is an inspiring example for those who care for informational policy of modern Ukraine.Keywords: Ukrainian small encyclopedia, Yevhen Onatsky, journalism, worldview, Ukrainian state. Keywords: Ukrainian Bureau in Washington, Eugene Skotzko, public opinion, history of journalism, diaspora.

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Bearing in mind the dramatic impact of radioastronomy upon our knowledge of the Universe during the years after World War II, it is remarkable that the seminal discovery of radio emission from our galaxy by Karl Jansky in the USA in 1931 attracted so little attention from the astronomical community at that time. It was, in fact, the radio amateur Grote Reber, of Wheaton, Illinois, and not the professionals, who first followed up Jansky's discovery. Designing his own radio telescopes, the first of which were unsuitable because the wavelengths were too short, Reber persevered until, in 1941, he successfully performed surveys of the distribution of radio noise intensity across the sky that indicated a strong concentration towards the galactic centre. In this country the key figure was J.S. Hey, who was engaged in wartime operational research concerned with anti-aircraft radar when, in February 1942, radar stations along the south coast of England were seriously affected by radio interference of unknown origin. From the direction of the interfering signals Hey concluded that the Sun must be responsible, so he contacted the Royal Greenwich Observatory and was informed that a large sunspot group was near the centre of the solar disc. He correctly deduced that some kind of disturbance in the solar atmosphere must have generated the radio signals, but this remained a wartime secret until the cessation of hostilities. Returning to his discovery in 1946, when the Sun was again active, Hey and his team made more detailed observations and showed that the intense bursts of radiation were often associated with solar flares. In the same year, while following up the work of Jansky and Reber, Hey noticed that radiation from the direction of the constellation Cygnus often showed fluctuations of intensity on a time-scale of a few seconds. With his experience of solar radiation, Hey deduced that a discrete source must have been responsible and more were soon located by other groups. Initially called radio stars, but later found to be supernova remnants, normal galaxies and new types of galaxy located near, or beyond, the limits of optical telescopes, Hey's discovery initiated an era of research that transformed observational astronomy. Such was the pace and excitement of this period that the significance of Hey's pioneering contributions tended to be overlooked. He was not proposed for Fellowship of The Royal Society until 1978, and he was elected in the same year.

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The article is devoted to the Abyssinian poems by Pavel Bulygin, a poet and a prose writer who left Russia after the revolution, whose poems were published in Harbin weekly “Rubezh” (Border) (1935–1936). Exotic motives are analysed in the poet's work, for whom, following Nikolay Gumilyov, Africa became a “guiding star”: Bulygin's collection of poems “Alien Stars” is dedicated to Abyssinia – the name of the cycle clearly refers to Gumilyov's “Alien Sky”. Special attention is paid to the May issue of “Rubezh” (1936), where Bulygin’s five poems from the cycle “Alien Stars” were published under the general title “The poems about Abyssinia”. These texts are considered as a microcycle, united thematically – Bulygin's poetic bestiary is described, focused on Gumilyov in many respects; the literary nature of the poet's affection to African travels is noted not only through Gumilyov’s lyrics, but also through James Fenimore Cooper and Jack London’s adventure novels; it is pointed out that the poet uses the technique of “imaginary” ekphrasis, when instead of a really existing picture, his own one is recreated – poetic and as if picturesque at the same time. In addition to the publication in the May issue of “Rubezh” in 1936, there are Bulygin’s works, published in Harbin weekly in 1935 (“Saw Gin” (“Hyena-Man”), “Russian in Abyssinia”, “From a heated red stone...”). Immersion in African topos, warmed for Bulygin by Gumilyov's poetry and travels, helps the emigrant poet escape from loneliness, anguish and nostalgia.

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Abstract Background Yersinia pestis remains endemic in Africa, Asia, and the Americas and is a known bioterrorism agent. Treatment with aminoglycosides such as streptomycin or gentamicin is effective when initiated early in illness but can have serious side effects. Alternatives such as fluoroquinolones, tetracyclines, and sulfonamides are potentially safer but lack robust human data on efficacy. Methods We searched PubMed Central, Medline, Embase, and other databases for articles in any language with terms related to plague and antimicrobials. Articles that contained case-level information on antimicrobial treatment and patient outcome were included. We abstracted information related to patient demographics, clinical features, treatment, and fatality. Results Among 5837 articles screened, we found 762 published cases of treated plague reported from 1937 to 2019. Fifty-nine percent were male; median age was 22 years (range, 8 days–80 years). The case fatality rate was 20% overall. Most patients had primary bubonic (63%), pneumonic (21%), or septicemic (5%) plague, with associated case fatality rates of 17%, 27%, and 38%, respectively. Among those treated with an aminoglycoside (n = 407 [53%]), the case fatality rate was 13%. Among those treated with a sulfonamide (n = 322 [42%]), tetracycline (n = 171 [22%]), or fluoroquinolone (n = 61 [8%]), fatality was 23%, 10%, and 12%, respectively. Case fatality rate did not substantially differ between patients treated with 1 vs 2 classes of antimicrobials considered to be effective for plague. Conclusions In addition to aminoglycosides, other classes of antimicrobials including tetracyclines, fluoroquinolones, and sulfonamides are effective for plague treatment, although publication bias and low numbers in certain treatment groups may limit interpretation.

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Abstract. On 27 May 1937, after one week of sustained heavy rainfall, a voluminous flood caused the death of at least 300 people and the destruction of the historic El Carmen church and several neighborhoods in the mining region of Tlalpujahua, Michoacán, central Mexico. This destructive flood was triggered by the breaching of the impoundment of the Los Cedros tailings and the sudden release of circa 16 Mt of water-saturated waste materials. The muddy silty flood, moving at estimated speeds of 20–25 m s−1, was channelized along the Dos Estrellas and Tlalpujahua drainages and devastated everything along its flow path. After advancing 2.5 km downstream, the flood slammed into El Carmen church and surrounding houses at estimated speeds of ~ 7 m s−1, destroying many construction walls and covering the church floor with ~ 2 m of mud and debris. Revision of eyewitness accounts and newspaper articles, together with analysis of archived photographic materials, indicated that the flood consisted of three muddy pulses. Stratigraphic relations and granulometric data for selected proximal and distal samples show that the flood behaved as a hyperconcentrated flow along most of its trajectory. A total volume of the Lamas flood deposit was estimated as 1.5 × 106 m3. The physically based bidimensional (2-D) hydraulic model FLO-2D was implemented to reproduce the breached flow (0.5 sediment concentration) with a maximum flow discharge of 8000 m3 s−1 for a total outflow volume (sediment + water) of 2.5 × 106 m3, similar to the calculations obtained using field measurements. Even though premonitory signs of possible impoundment failure were reported days before the flood, and people living downstream were alerted, authorities ordered no evacuations or other mitigative actions. The catastrophic flood at Tlalpujahua provides a well-documented, though tragic, example of impoundment breaching of a tailings dam caused by the combined effects of intense rainfall, dam weakness, and inadequate emergency-management protocols – unfortunately an all-too-common case scenario for most of the world's mining regions.

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Abstract. On 27 May 1937, after one week of sustained heavy rainfall, a voluminous flood caused the death of at least 300 people and the destruction of the historic El Carmen church and several neighborhoods in the mining region of Tlalpujahua, Michoacán, central Mexico. This destructive flood was triggered by the breaching of the impoundment of the Los Cedros tailings and the sudden release of 16 Mt of water-saturated waste materials. The muddy silty flood, moving at estimated speeds of 20–25 m s−1, was channelized along the Dos Estrellas and Tlalpujahua drainages and devastated everything along its flow path. After advancing 2.5 km downstream, the flood slammed into El Carmen church and surrounding houses at estimated speeds of ~7 m s−1, destroying many of construction walls and covering the church floor with ~2 m of mud and debris. Eyewitness accounts and newspaper articles, together with analysis of archived photographic materials, indicated that the flood consisted of three muddy pulses. This interpretation is confirmed and extended by the results of our geological investigations during 2013 and 2014. Stratigraphic relations and granulometric data for selected proximal and distal samples show that the flood behaved as a hyperconcentrated flow along most of its trajectory. Even though premonitory signs of possible impoundment failure were reported days before the flood, and people living downstream were alerted, authorities ordered no evacuations or other mitigative actions. The catastrophic flood at Tlalpujahua provides a well-documented, though tragic, example of impoundment breaching of a tailings dam caused by the combined effects of intense rainfall, dam weakness, and inadequate emergency-management protocols – unfortunately an all too common case-scenario for most of the world's mining regions.

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On 27 May 2019, we bid farewell to Józef Poklewski, a trusted Colleague and Friend, professor at the Nicolaus Copernicus University (UMK) in Toruń. Born in Kowalewo in the Vilnius Region, following WWII, orphaned by his father Władysław, he moved to Giżycko with his mother Emilia, with whom he felt a strong bond until the very last days. This was his individual feature: the long-lasting character of and reliability in relationships. Following the studies in history of art at the University of Poznań, he became assistant lecturer at UMK, with which he was bonded throughout all of his academic and scientific career. He remained strongly influenced by his teacher and mentor Gwidon Chmarzyński, professor at both universities. In his research Poklewski initially concentrated on Baroque art (doctoral dissertation on the Marian Jesuit Sanctuary at Święta Lipka), gradually more intensely focusing on the topic of the history of art and artistic life, as well as education in art, history of art, and conservation in Vilnius (post-doctoral dissertation) and in Toruń. An appreciated and dedicated lecturer, at UMK Józef Poklewski performed the function of the head of the Department of the History of Mediaeval and Modern Art, and of the Director of the Institute of Monument and Conservation Expertise; furthermore, he was the University’s Senate member. Actively participating in the scientific life, he was tutor of graduate theses, as well as of doctoral dissertations, reviewing also post-doctoral ones; moreover, he organized scientific conferences. Poklewski strongly committed himself to the activities of the Toruń Scientific Society and the Association of Art Historians (beginning from the Secretary, to the President of the Toruń Branch, member of the Main Board, finally becoming its Deputy President). Furthermore, he sat on Museum Boards: at the National Museum in Gdańsk, District Museum in Toruń, and the Leon Wyczółkowski District Museum in Bydgoszcz. Prof. Józef Poklewski died in Toruń, and was buried there, too.

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AbstractObjective:On-scene prehospital conditions and patient instability may warrant a during-transport ultrasound (US) exam. The objective of this study was to assess the effect of ambulance turbulence on the performance of the Focused Assessment with Sonography in Trauma (FAST) with a handheld US device.Methods:This was a randomized controlled trial in which participants were randomized to perform a FAST in either a stationary or an in-motion military ambulance. Participants were physicians and physician assistants (PAs) with previous FAST training. All exams were performed on an US phantom model. The primary outcome was FAST completion time, reported as a mean, in seconds. Secondary outcomes included image acquisition score (range of 0-24, reported as a mean), diagnostic accuracy (reported as sensitivity and specificity), and a post-participation survey with five-item Likert-type scales.Results:Twenty-seven participants performed 27 FASTs, 14 in the stationary ambulance and 13 in the in-motion ambulance. All participants obtained the four requisite views of the FAST. A significant difference was detected in image acquisition scores in favor of the stationary ambulance group (19.4 versus 16.7 [95% CI for difference, 0.9-4.4]; P <.01). Significant differences in survey items between groups were related to obtaining and maintaining US images and the exam conditions. There was not a difference in FAST completion time between groups (98.5 seconds versus 78.7 seconds [95% CI for difference, -13.5 seconds to 53.1 seconds]; P = .23). Sensitivity and specificity of FAST in the stationary ambulance was 85.7% (95% CI, 67.3%-96.0%) and 96.4% (95% CI, 81.7%-99.9%) versus 96.2% (95% CI, 80.4%-99.9%) and 100.0% (95% CI, 86.8%-100.0%) in the in-motion ambulance group (P = .21).Conclusion:Vehicular motion did not affect FAST completion time and diagnostic accuracy; however, it did reduce FAST image acquisition scores. The results suggest timely and diagnostically accurate FASTs may be completed by experienced sonographers during moderate levels of ambulance turbulence. Further investigation assessing the utility and limitations of newer handheld US devices in various prehospital conditions is warranted.

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<p>This short biography details the life and medical activities of Rosa Einhorn, mariée Bloch (1872–1950), who practised as an Austro-Hungarian (AH) official female physician in Travnik in occupied Bosnia and Herzegovina (BH) from 1902 to 1904, and as a semi-official private physician from 1905 to 1912/13. Born in Hrodna district in the Russian Pale of Crescent, Einhorn had qualified and practised as a “<em>feldsheritsa</em>” in Russia and went to Switzerland to study medicine in 1896. Upon receiving her medi­cal doctorate from the University of Lausanne in 1901, she became recommended as a particularly adequate candidate for the not-yet-created position of an AH official female physician in BH. After Einhorn functioned as a general practitioner for women and children in Travnik and the adjacent districts for two years, the AH public health authorities officially dismissed her due to her engagement and marriage to the AH judiciary Sigismund Bloch (1850–1927). However, she obtained a right to private practice in 1905 and was employed as a private physician in AH anti-syphilis campaigning. Struggling for her reinstatement as an official female physician in Travnik, she also strove for the accreditation of her Swiss diploma in Austria, though in vain. After two attempts to emigrate to the United States in 1904 and 1913, Rosa Einhorn finally left Europe to work as a physician in the United States and Mandatory Palestine/Eretz Israel in 1923. She died in New York on May 27, 1950.</p><p><strong>Conclusion. </strong>Rosa Einhorn was employed as a provisory official female physician in Travnik in 1903/1904, the AH authorities accepting her only as a lo­cal private female physician after her marriage in 1905. Struggling in vain for her reinstatement, she finally left Bosnia in 1913.</p>

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Abstract Abstract 4114 The metabolic syndrome, which includes obesity, hypertension, dyslipidemia, and insulin resistance, has been reported to occur in excess among long term survivors of pediatric acute lymphoblastic leukemia (ALL). Among known risk factors are exposure to corticosteroids and cranial radiotherapy. However, at what point along the trajectory of therapy that the metabolic abnormalities develop is unclear. Twenty-two consecutively enrolled patients with pre-B or T cell ALL treated on or according to Children's Oncology Group protocols at Vanderbilt Children's Hospital were evaluated for components of the metabolic syndrome at the start of maintenance chemotherapy. The overall prevalence of metabolic syndrome traits in this cohort was high, with 19 (86%) subjects exhibiting at least 1 component of the metabolic syndrome. Of those, 4 (21%) met full criteria for metabolic syndrome (demonstrating at least 3/5 components) (Table 1). Dyslipidemia was common with 11/22 (50%) having a fasting HDL ≤ 40mg/dl [median= 35mg/dl; 1st/3rd quartiles (29, 38)] and 8/22 (36%) having fasting triglycerides >110 mg/dl [median=165mg/dl; (129, 340)]. Patients with ALL NCI high risk classification had higher fasting triglycerides (p<0.01) and lower HDL (p=0.02) versus those who were classified as standard risk. Hypertriglyceridemia, but not HDL, was correlated with increased patient age (Spearman's ρ=0.45; p=0.03); neither was associated with sex or other components of the metabolic syndrome. Obesity was noted in 6/22 patients (27%) with BMI ≥ 90th percentile, controlled for age and sex. Hypertension was also frequent, observed in 11/22 (50%) subjects. Elevated systolic blood pressure correlated with decreasing age (ρ=-0.45, p=0.03) but not with other components of the metabolic syndrome. Only 1 subject had fasting hyperglycemia. Fasting leptin levels [median=2.6μg/ml (0.9, 4.4)] were significantly correlated with the BMI z-score (ρ=0.44, p=0.05) but did not significantly correlate with other components of the metabolic syndrome. Fasting adiponectin levels [median=21 μg/ml; (13, 25)] did not significantly correlate with any of the components of the metabolic syndrome. No subject had growth hormone deficiency. In summary, although the sample size was small, components of the metabolic syndrome were common at the start of maintenance chemotherapy, prior to significant further exposure to corticosteroids. Dyslipidemia was particularly common, and routine screening may be considered as there is the potential for successful intervention. The patients in this cohort are currently being followed longitudinally during maintenance chemotherapy to assess for changes in metabolic abnormalities with ongoing leukemia therapy, particularly corticosteroids. Determining the nature and onset of metabolic abnormalities can further inform future interventions to prevent or mitigate the abnormalities which, if untreated, may lead to long-term chronic health conditions that may increase cardiovascular risk. Table 1 Characteristics of subjects meeting at least 3 of 5 criteria for the metabolic syndrome (Cook Criteria*) Subjects 1 2 3 4 Age (years) 14 8 16 6 Gender Female Male Male Male ALL Risk Classification High High High Standard BMI Z-Score at Diagnosis 2.15 2.08 2.39 -0.16 BMI Z-Score at Start of Maintenance 2.24 2.23 2.68 -0.08 Fasting Triglycerides (mg/dl) 352 288 153 336 Fasting HDL (mg/dl) 27 36 35 18 Systolic BP Z-Score -0.13 2.44 0.70 0.77 Diastolic BP Z-Score 0.82 1.76 1.34 1.44 Fasting Glucose (mg/dl) 73 75 86 78 Fasting Leptin (μg/ml) 40.2 19.4 45.7 1.4 Fasting Adiponectin (μg/ml) 27 10 11 21 IGF-1 (ng/ml) 211 288 153 41 *Cook et al. Arch Pediatr Adolesc Med 2003 Disclosures: No relevant conflicts of interest to declare.

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Abstract Abstract 1924 Innovative therapeutic approaches are needed to reduce the morbidity and high relapse rates in patients with advanced AML or high-risk MDS following myeloablative hematopoietic cell transplantation (HCT). Success with stable donor chimerism and low toxicity following infusion of allogeneic peripheral blood stem cells (PBSC) with reduced-intensity regimens affords an opportunity to induce a graft-versus-leukemia (GVL) effect with minimal acute morbidity. GVL effects, however, appear to be most potent in patients with low tumor burden at the time of HCT. In an attempt to improve outcomes, we previously transplanted 58 patients older than age 50 with advanced AML (beyond first remission) or high-risk MDS (≥5% marrow blasts at the time of HCT) in a Phase I trial using 131I-labeled anti-CD45 antibody (BC8) in conjunction with fludarabine (FLU) and 2Gy total-body irradiation (TBI). Data from this study suggested that 131I-anti-CD45-targeted radiotherapy could be safely integrated into a reduced-intensity conditioning regimen for older, high-risk patients with AML or MDS yielding encouraging survival outcomes. These results prompted us to evaluate a similar strategy in younger patients (ages 16–50) with advanced AML or high-risk MDS who may not be able to receive a high dose HCT conditioning regimen. In this phase I dose–escalation trial 14 patients received a dose of 131I-BC8 that delivered 10–27 Gy of targeted radiation to the healthy organ receiving the highest dose combined with FLU (30 mg/m2 daily for 3 days), 2 Gy TBI, and HLA-matched related (n = 7) or unrelated (n = 7) PBSC grafts. Graft-versus-host disease (GVHD) prophylaxis consisted of cyclosporine and mycophenolate mofetil. The 131I radiation dose was escalated until the maximum planned dose of 28 Gy was reached without any appreciable dose limiting toxicity. The median patient age was 39.5 (range, 23.8–49.7) years. Thirteen patients had AML, with 9 patients in second complete remission, 3 with primary refractory disease, and 1 in active relapse. One patient had advanced CMML with >5% blasts. Treatment with the 131I-BC8 Ab/FLU/TBI regimen produced a complete remission in 7 patients (50%), and 11 of the 12 evaluable patients had 100% donor CD3+ and CD33+cell engraftment by day 28 after HCT; an additional patient had 79% CD3 and 82% CD33 positive donor marrow cells at day 28. The absolute neutrophil count surpassed 500/μL at a median of 15 (range, 13–22) days. Self-sustained platelet levels of 20,000/μL were reached at a median of 11 (range, 11–27) days after HCT. Five patients (36%) are surviving relapse-free 46 to 99 months (median 87 months) after HCT. Seven patients (50%) have died, with five patients relapsing 0.9 to 45 months after HCT. No non-relapse mortality occured by day 100; however, two patients died 14 and 18 months after HCT of cardiomyopathy and GVHD complications, respectively. This study demonstrates that, in addition to a standard reduced intensity conditioning regimen, an average of 27 Gy of targeted 131I radiotherapy can be delivered to bone marrow, an average of 20Gy to the liver, and an average of 84 Gy to the spleen without a marked increase in day 100 mortality for younger patients. This strategy may thus provide a reasonable alternative for patients with high-risk AML/MDS who may not be able to tolerate a high dose conditioning HCT. Disclosures: No relevant conflicts of interest to declare.

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27 members were present: Bankovskiy, Vertsinskiy, Voff, Hermonius, Gorayskiy, Danilovich, Dovnarovich, Eremeev, Zheltukhin, Zabolotskiy, Zamshin, Lichkus, Misevich, Ott, Piotrovich, Popov, Savchenko, Salmanov, Slavyanskiy, Stravinskiy, Strogonov, Tarnovskiy, Fisher A., Fisher B., Tsokhanovetskiy, Shverdlov, Shtol and 9 guests.

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Abstract Background A high proportion of Inflammatory Bowel Disease (IBD) patients will develop extraintestinal manifestations (EIMs). Choosing the most appropriate therapeutic strategy among currently available biologics for each patient may often be challenging. Data regarding the effects of gut-selective therapies such as vedolizumab (VDZ) on new-onset and pre-existing EIMs are scarce and often discordant. The main aims of this study were to assess the cumulative incidence of new-onset EIMs and the course of pre-existing EIMs in a large cohort of IBD patients treated with VDZ compared to non-gut selective biologic agents. Methods This multicenter retrospective study collected data of IBD patients on biologic therapy in clinical follow-up at 6 tertiary referral IBD units in Lombardy. Clinical and demographic data of IBD patients were collected. We calculated the cumulative incidence of new-onset EIMs since the introduction of the ongoing biologic therapy, comparing patients on VDZ with patients on non-gut selective therapies. Furthermore, we analyzed the course of pre-existing and new-onset EIMs in these two cohorts of patients. Results Data about 973 IBD patients (624 CD, 339 UC, 10 IBD-U; median age 46 years; 59% males) on biologic therapy were collected. Of them, 215 were on VDZ and 758 were on non-gut-selective agents, with a median treatment duration with the ongoing therapy of 3 years. The overall prevalence of EIMs in this IBD cohort of patients was 19.8% (193/973 patients). The overall cumulative incidence of new-onset EIMs was of 4.1 % (40/973): 13 on VDZ (13/215) versus 27 (27/758) in the non-gut selective group (6% vs 3.6%, p = 0.1). Regardless of the type of biologic agents, the female sex and the duration of the ongoing biologic treatment were statistically associated with a higher risk of developing EIMs. About 17% of IBD patients reported a pre-existing EIM. Compared to non-gut selective therapies, patients on VDZ showed a significantly higher rate of worsening or absence of response (8.1% vs 19.4%, 12/148 vs 7/36, p=0.04). However, in both groups, a modification of the therapeutic protocol has been necessary with the introduction of adjunctive therapy, the switch, or the optimisation of the ongoing biologic therapy (27.8% patients on VDZ versus 25% on non-gut selective therapies, p=0.7). Conclusion Our study suggests that the type of biologic treatment does not affect the risk of new-onset of EIMs. However, in the case of pre-existing EIMs, a subtle higher risk of worsening can be speculated after starting VDZ, even if the proportion of patients who will need adjunctive therapy, the optimisation or switch of the ongoing treatment would be similar between gut-selective and non-gut selective therapies.

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At the tum of the 19,h and 20th centuries lots of religious communities were founded in the St John Baptist parish in Sokołów Małopolski. One of the most important was the Third Order of St Francis. Its foundation was preceded by many years of endeavours. The very idea was propagated by the inhabitant of Sokołów, Katarzyna Koziarz, who became the member of the secular family of Franciscan family in Rzeszów in 1890. Since then morę and morę people from Sokołów had joined the Tertiary.At the beginning of the 20“’ century those who took steps to popularize the Third Order were Katarzyna Koziarz in Sokołów, Maria Ożóg and Małgorzata Maksym in Wólka Sokołowska and Katarzyna Bąk in Trzebuska while the parish priests, Franciszek Stankiewicz and Leon Szado did little for this matter. The members of the Third Order got involved in lots of activities such as sup- porting the building of the church, providing necessary things for the church and making mass of- ferings.Serious steps to found the Third Order in Sokołów were taken by the parish priest Ludwik Bukała. He organized monthly meetings for the Third Order members. He also established contact with the Bemardine Father, Wiktor Biegus, who 27 April 1936 came to Sokołów and became ac- ąuainted with the tertiaries in the parish. The permission for the canonical establishment of tertiary congregation was granted 4 May 1936 by the ordinary of Przemyśl, Bishop Franciszek Bard.The official foundation of the congregation in Sokołów took place 24 May 1936. The local tertiaries chose St Ludwik as their patron. The congregation govemment was constituted at the first meeting. The parish priest became the director of the community and Katarzyna Koziarz was ap- pointed the superior. On the day of the foundation there were about 100 members. In the first three years of the existence of the Third Order there were 30 people who received the habits and 28 who were admitted to the profession.After the canonical establishment of the congregation, the tertiaries became morę active. They provided the church with sacred appurtenances and fumishings, as well as organising public adora- tion of the Holy Sacrament. They would also wash liturgical linens and adom altars. In 1937 they bought a chasuble with the image of St Francis, and in 1939 they donated a banner with the images of Mother of God and St Francis. In addition, the tertiaries founded their own library with religious books and magazines.The congregation gathered for meetings in the parish church every month. Besides, they had occasional private gatherings. In the first years of the existence of the congregation there were 19 meetings of the Counsel. There were also two visitations of the Sokołów congregation held by Father Cyryl from Rzeszów 11 July 1937 and 6 August 1939. The activities of the tertiaries were hindered by the outbreak of the Second World War.

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459 Background: Biliary tract cancers do not respond well to multipmodal treatment and generally show poor prognosis, and this may be a reason to make elderly patient consider best supportive care only. Methods: We reviewed 108 elderly patients of 80 years of age or older who diagnosed as biliary tract cancers from 2008 to 2014 at Seoul St. Mary's Hospital, Korea. Results: The mean age was 83.76 years ranging from 80 to 100. The patients included 24 intrahepatic(22.2%), 17 common bile duct(15.7%), 21 perihilar(19.4%), 37 gall bladder(34.3%), and 9 Ampulla of Vater(8.3%) cancers. 47 patients (43.5%) was initially resectable and 19(40.4%) of them underwent curative surgery, 17(36.2%) had percutaneous or endoscopic biliay drainage, and 11(23.4%) had best supportive care only. Mean survival was 29.8 months, 15.1 months, and 12 months, following the above treatment, respectively(p = 0.004). The mean hospitalized time for the curatively resected patients was 9.8 days. One died of traumatic SAH after surgery, 2 underwent adjuvant chemotherapy, and 10 experienced recurrence. Unresectable patients included 13 (12%) with locally advanced disease and 48 (44.4%) with distant metastasis. Among them, 4(6.6%) received palliative radiotherapy or chemotherapy, 30(49.2%) had biliary drainage, and 27(44.3%) had just best supportive care. Mean survival was 10.2 months, 7.3 months, and 3.6 months, respectively(p = 0.109). One with radiotherapy did not completed his treatment course due to intolerance. Three received chemotherapy with dose reduction from 75% to 70% considering their old age and poor performance status. Among those patients, 1 patient with stage IV intrahepatic cholangiocarcinoma showed partial response at 1st line of chemotherapy and had received totally 3 lines of chemotherapy. He survived 16.4 months. Conclusions: Elderly patients with early stage cancers who undewent curative resection and some selected advanced stage patients with palliative chemotherapy showed good response and survival improvement. There should be careful decision making for the management for geriatric biliary tract cancer patients and further investigations are needed to find more predictive factors.

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Abstract Abstract 1717 Scientific and clinical evidence support a role for immune dysregulation in the pathogenesis of myelodysplastic syndromes (MDS) in some patients, and immunosuppressive therapy (IST) is considered a standard treatment for selected patients with MDS. Despite a number of studies showing its efficacy in MDS, IST has not been widely adopted because of uncertainty about therapeutic benefit, perceived toxicities of antibody treatment, and confusion about patient selection. To better define the place of IST in MDS, we reviewed all published clinical trials of IST for adult patients with MDS to determine its therapeutic benefit and treatment-related toxicity. We also sought to define clinical and laboratory predictors for response to IST. IST was defined as T cell directed therapies, including the following drugs administered alone or in combination: cyclosporine A (CsA), rabbit or horse anti-thymocyte globulin (ATG), alemtuzumab, sirolimus, tacrolimus, mycophenolate mofetil, or daclizumab. Electronic databases were scanned for all peer-reviewed clinical trial reports concerning IST for MDS from inception through August 1, 2011. Risk of bias for each study was assessed by two independent investigators using the Cochrane Risk of Bias Tool, and the Newcastle-Ottawa Scale. The searches of MEDLINE, Cochrane Clinical Trials Register, SCOPUS, Web of Science and EMBASE yielded a total of 1950 articles, and 1937 were subsequently discarded based on our a priori exclusion criteria. A total of 13 reports from 13 individual clinical trials enrolling 358 patients met criteria for this review. IST was well tolerated with a treatment-related mortality rate of 1.3%. Hematologic improvements (HI), partial response (PR), and complete response (CR) was defined using International Working Group for MDS criteria. The overall response rate (ORR) to IST was 41% (HI 18%, PR 15%, and CR 8%). ORR according to treatment regimen were alemtuzumab 68% (n= 31 patients), CsA 56% (n=111 patients), h-ATG 35%, (n=83 patients), r-ATG/CsA 30% (n= 20 patients), r-ATG 27%, (n=15 patients), and h-ATG/CSA 25% (n=79 patients). Response rates were higher when patients were treated on protocols incorporating specific selection criteria versus unselected patients (ORR 59% vs 41%, p=0.01). Patients with a hypocellular bone marrow had response rates that were equal to individuals with normal or increased marrow cellularity: ORR 63% vs 63%, (p=0.99); PR 25% vs 23%, (p=0.81); CR 15% vs 11%, (p=0.46). Patients younger than 60 years had significantly higher response rates to IST than older individuals (ORR 59% vs 40%, p=0.004), irrespective of the treatment regimen administered. Patients who were transfusion dependent had response rates equal to those who were transfusion independent at the time of treatment (ORR 60% vs 55%, p=0.57). Response rates in patients with low and intermediate cytogenetic risk groups as defined by the International Prognostic Scoring Scale (IPSS) were 51% and 49%, respectively. Response rates varied according to World Health Organization (WHO) Prognostic Scoring Scale (WPSS) morphology categories, with overall response rates of 57% (n=128 patients), 10% (n=10 patients), and 21% (n=39 patients) in individuals with very low, low, and intermediate morphology categories, respectively. Response rates did not vary according to gender or cell lineages involved. These results indicate that the choice of IST may be critical in optimizing responses and that IST should be considered for MDS patients younger than 60 years old, with low and intermediate risk IPSS cytogenetics and very low WHO morphology categories, regardless of bone marrow cellularity and duration of transfusion dependence. CsA Alemtuzumab hATG hATG/CsA rATG rATG/CsA Sirolimus ANOVA Response R% (range) No. R% (range) No. R% (range) No. R% (range) No. R% (range) No. R% (range) No. R% (range) No. P-value CR 3 3/111 23 7/31 5 4/83 10 8/79 20 3/15 15 3/20 0 0/19 0.002 (1–8) (10–41) (1–12) (5–19) (4–48) (3–38) — PR 24 27/111 13 4/31 16 13/83 4 3/79 7 1/15 15 3/20 16 3/19 0.013 (17–33) (4–30) (9–25) (1–11) (0.1–32) (3–38) (3–40) HI 29 32/111 32 10/31 15 12/83 11 9/79 0 0/15 0 0/20 0 0/19 <0.0001 (21–38) (17–51) (8–24) (5–21) — — — ORR 56 62/111 68 21/31 35 29/83 25 20/79 27 4/15 30 6/20 16 3/19 <0.00001 (46–65) (49–83) (25–46) (16–36) (8–55) (12–54) (3–40) Disclosures: No relevant conflicts of interest to declare.

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The article deals with a very crucial question of the legal status of physicians in Poland. The question asked is whether a physician who works as a sole practitioner may be recognized as a person performing a liberal profession, a public trust profession (a category specifi c only as far as Polish domestic law concerned), or a regulated profession (according to Directive 2005/36/EC of the European Parliament and of the Council of 7 September 2005 on the recognition of professional qualifi cations). Consequently, first the concepts of a liberal, regulated and public trust professions are analysed. Another important question to be answered is if physicians practicing as sole traders are undertakings in the meaning of the EU law and if they are what their status is. The vastest exclusion in terms of the subject and object of the legislation was provided by the Regulation on Industrial Law issued by Poland’s President on 7 June 1927 which excluded the activity conducted by physicians. Under Article 3 of the President’s Regulation the Commercial Code 27 June 1934, all liberal professions were also excluded from activities considered to be a form of entrepreneurship. This attitude changed in postwar Poland and the Act of 23 December 1988 on Economic Activity provided for no exclusion for any liberal profession from being regarded as economic activity. The Act of 19 November 1999 on Economic Activity excluded from its scope only entities that provided legal services (barristers and solicitors) and those rendering services in the area of industrial property. Today, under Polish law physicians are considered to be an undertaking in two situations: when they conduct their activities in the form of so-called ‘private practice’ (one-person undertaking), or when they conduct their practice within so-called ‘collective practice’ (partnership). They are not regarded as undertakings when they are employed by a medical institution or another medical entity on the basis of an employment contract. In such a case they fall under the provisions of the Act of 15 April 2011 on Medical Activities, but still keep the status of liberal profession.

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Abstract Abstract 3466 Donor cell leukemia (DCL) in the setting of bone marrow/hematopoietic stem cell transplant (HCT) has not been well characterized. We analyzed 9 cases of DCL and performed a literature review (table). The indications for transplant and subtypes of DCL are shown (table). The 6 myelodysplastic syndrome (MDS) cases included 1 case of refractory cytopenia with multilineage dysplasia (RCMD), 2 cases of refractory anemia and 3 cases which were unclassifiable. Conventional cytogenetic analysis was performed on all 9 cases of DCL (table). All 9 cases had engraftment studies performed either by short tandem repeat analysis (3) or FISH analysis for donor gonosomal complement (6) when DCL was diagnosed. Seven cases had either engraftment studies or cytogenetic analysis performed periodically after HCT to test the donor cell engraftment and engraftment was confirmed in all. FISH analysis for monosomy 7, del(7q) and del(5q) was retrospectively performed on preserved donor cells in 4 cases after DCL was diagnosed. A low level of abnormalities was observed in preserved donor cells for the cases with del(7q) (2.9%) and del(5q) (8.2%). The 2 cases of AML received chemotherapy. Of the MDS cases, 2 received donor cell infusion, 1 received 6 cycles of revlimid, and 3, along with the case of CLL, received either supportive therapy or were simply observed. Six cases have clinical follow up ≥ 5 months and of these, 1 died of disease (AML) while the other 5 are alive, including 4 MDS and the 1 CLL. The disproportionate detection of DCL in sex mismatched HCT suggests a probable under-detection in the sex-matched population. In our analysis, the interval between HCT and diagnosis of DCL (table) falls within the range of currently reported cases. When stratified by type of DCL, the T-LGL group demonstrates presentation significantly earlier than other groups (Fig. A), indicating pathogenesis of T-LGL may involve a distinct pathway. When stratified by types of primary disease, the interval of the neoplastic group is shorter than that of benign group (Fig. B), implying that pre-HCT treatment may play a role in the pathogenesis of DCL. When stratified by stem cell sources, UCB group shows shorter latency than the other sources (Fig. C), suggesting a higher risk of DCL in this cell source. The low level cytogenetic abnormalities of preserved donor cells in our series and the longer latency of the benign group suggest that donor cells with an intrinsic defect may be predisposed to evolve into DCL. Total cases (%) Reported cases (%) Current cases (%) Number of cases 83 74 9 Age (years) Median/range 37.0/3~70 36.0/4~62 53.0/3~70 Gender Male 43 (52.4) 38 (52.0) 5 (55.6) Female 39 (47.6) 35 (48.0) 4 (44.4) Primary disease Neoplasms 76 (91.6) 67 (90.5) 9 (100) Non-neoplasms 7 (8.4) 7 (9.5) 0 (0.0) Donor Related 59 (72.0) 54 (74.0) 5 (55.6) Unrelated 23 (28.0) 19 (26.0) 4 (44.4) Sex-matched 28 (34.6) 27 (37.5) 1 (11.1) Sex-mismatched 53 (65.4) 45 (62.5) 8 (88.9) Donor cell source BM 48 (63.2) 44 (65.7) 4 (44.4) BHSC 16 (21.0) 13 (19.4) 3 (33.3) UCB 12 (15.8) 10 (14.9) 2 (22.2) 2nd neoplasm (DCL) AML 31 (37.4) 29 (39.2) 2 (22.2) MDS/MPN* 27 (32.5) 21 (28.4) 6 (66.7) ALL 20 (24.1) 20 (27.0) 0 (0.0) T-LGL 4 (4.8) 4 (5.4) 0 (0.0) CLL 1 (1.2) 0 (0.0) 1 (11.1) Interval (months) Median/range 24.0/1~312 24.0/2~312 26.0/1~193 Cytogenetics Normal 21 (28.0) 20 (30.3) 1 (11.1) Abnormal 54 (72.0) 46 (69.7) 8 (88.9) -7 or del(7q)** 15 (27.8) 10 (21.7) 5 (62.5) +8** 2 (3.7) 2 (4.4) 0 (0.0) Del(20)** 4 (7.4) 2 (4.4) 2 (25.0) Del(5q)** 2 (3.7) 1 (2.2) 1 (12.5) 11q23** 3 (5.6) 3 (6.5) 0 (0.0) Other abnormalities** 28 (51.9) 28 (60.9) 0 (0.0) Follow up (months) Median/range 8.5/1~108 9.0/1~108 6.0/1~68 Died of disease 28 (46.7) 27 (52.9) 1 (11.1) DCL, donor cell leukemia; BM, bone marrow; BHSC, blood hematopoietic stem cells; UCB, umbilical cord blood; AML, acute myeloid leukemia; MDS, myelodysplastic syndrome; ALL, acute lymphoblastic leukemia (including B-cell and T-cell ALL); T-LGL, T-cell large granular lymphocyte leukemia; CLL, chronic lymphocytic leukemia. All the numbers represent the cases with data available. * One case of myeloproliferative neoplasm is included in this category. ** The percentage is calculated using number of total cytogenetic abnormalities in each column as denominator. Disclosures: No relevant conflicts of interest to declare.

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Abstract Objectives Food insecurity is a public health concern in the US. Collegiate student-athletes may be at increased risk due to the nutritional and physical demands of performance and, limited time for employment and food preparation/intake. The objective of this study was to determine the rate of food insecurity and its characteristics among The National Collegiate Athletic Association (NCAA) student-athletes. Methods A cross-sectional analysis of student-athletes attending a public university in rural East Texas in 2018 was conducted. A 26-item questionnaire including sociodemographic characteristics and the six-item U.S. Household Food Security Survey Module (US-HFSSM), adapted to reflect the prior six months while training, was administered electronically to NCAA student-athletes. Each affirmative response to the US-HFSSM was given a score of “1” and summed to create a raw score ranging from 0–6. Participants with a score of 0–1 were considered food secure; those with a score of 2–4 (low food secure) or 5–6 (very low food secure) were considered food insecure. Results Ninety-one student-athletes (27% response rate) representing 13 sports completed the questionnaire. Participants were 19.81 ± 1.3 years old, mostly female (85.7%), Caucasian (67%), and of normal weight (BMI of 18.5–24.9 kg/m2; 74.7%). Nearly half (39.6%) reported food insecurity despite receiving wide-ranging assistance via scholarship support (86.1%) and/or the possession of a meal plan (42.9%). Food insecure participants reported limited money (25%) and time (19.4%) as barriers to food intake. Independent-samples t tests were conducted to compare grade point average (GPA) and BMI of food secure and food insecure groups. GPA was lower in the food insecure (M = 3.26, SD = .52) than the food secure group (M = 3.58, SD = .41); (t(63) = 3.06, P = .003) while BMI was higher in the food insecure (M = 24.05, SD = 3.56) than the food secure group (M = 22.85, SD = 2.17); (t(52) = –1.807, P = .077). Conclusions Despite the provision of scholarships and meal plans, the prevalence of food insecurity reported among NCAA student-athletes was similar to previous reports among the general collegiate population. Unique solutions that address the increased nutrient demands and time constraints associated with sport participation are warranted. Funding Sources N/A.

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Treatment of lupus nephritis (LN) with cyclophosphamide (CYC) is effective but retains a certain severe adverse effect. Tacrolimus (TAC) may be a suitable treatment for LN. Forty patients with diffuse proliferative or membranous LN were recruited for this non-randomized open-label study — 67.5% (27/40) had nephrotic proteinuria (>3.5 g/day) and 50.0% (20/40) had low estimated glomerular filtration rate (eGFR) (<60 mL/min/1.73m2). We compared the efficacy and adverse effects of TAC (0.04–0.08 mg/kg/d)/prednisone for 12 months (TAC group, n = 20) with intravenous CYC (750 mg/m2 per month)/prednisone for six months followed by azathioprine (Aza) (100 mg/day)/prednisone for six months (CYC group, n = 20). The TAC target concentration was 6–8 ng/mL or 4–6 ng/mL, respectively, when induction or maintenance therapy was required and 4.0 ng/mL for patient with renal insufficiency. In the TAC group, mean urinary protein excretion decreased significantly from 5.00 ± 1.91 g/day at baseline to 2.54 ± 1.68 g/day after two weeks of therapy ( P < 0.001), compared with the CYC group (4.9 ± 19.4 g/day), P = 0.001, and 65.0% (13/20) achieved partial remission at one month, compared with the CYC group (0/20), P < 0.001. The incidence of complete remission (CR) was significantly higher in the TAC group than in the CYC group (55.0% vs.15.0% by five months, P = 0.008, and 75.0% vs.40.0% by 12 months, P = 0.025, respectively). The significant improvement in serum anti-dsDNA and systemic lupus erythematosus (SLE) disease activity index (DAI) was in the TAC group relative to the CYC group at 12 months ( P = 0.031, P = 0.003, respectively). The eGFR improved in the TAC group from 59.90 ± 23.64 mL/min/1.73m2 at baseline to 93.75 ± 28.52 mL/min/1.73m2 after 12 months, P = 0.001. In the CYC group, two patients developed end-stage renal disease (ESRD), three patients experienced serious pneumonia, and one patient died. Our preliminary study showed TAC is a safe and effective treatment for LN with severe renal disease, and with less-severe adverse events compared with CYC followed Aza therapy. Further larger sample studies are needed to confirm our conclusion.

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Abstract Background: The control of hemoglobin F (Hb F) expression has proven an elusive puzzle with several postulated but not mutually exclusive hypotheses. A silencing mechanism hypothesis, which predicts the existence of a regulatory element that suppresses HbF expression, has been supported by recent investigations into a 3.5 kb region upstream from the delta globin gene (HBD). To test this hypothesis, we have investigated our historical case files in a tertiary care high-throughput clinical laboratory and compared the patient phenotype (Hgb, MCV, MCH, RDW, Hb F %, and flow cytometry Hb F distribution) with the status of this 3.5 kb region. Methods: A query of clinical testing patient files from Mayo Clinic Metabolic Hematology Laboratory yielded 179 patients confirmed by Multiplex Ligation-dependent Probe Amplification (MLPA) to contain large deletions located within the epsilon through beta globin genes. Of these, 27 unrelated patients with breakpoints between the pseudobeta (HBBP1) and HBD genes were identified. Four additional MLPA probe pairs were placed in this region and the patient phenotypes were compared. Results: The interior two (of the four added) probes between HBBP1 and HBD stratified all 27 cases. The other two (flanking) probes were never discriminatory, thus refining the area of interest to 2.4 kb. Sixteen cases showed breakpoints within hg19 g.5260154-5259135 (5' region) and eleven cases showed breakpoints within hg19 g.5259136-5257692 (3' region) upstream of HBD. Patients who displayed a phenotype of HPFH (n = 9) contained breakpoints in the 5' region whereas those with a delta beta thalassemia (DBT) phenotype (n = 11) were associated with breakpoints in the 3' region. A subset (n = 7) with breakpoints in the 5' region had indefinite phenotypic features, but of these, all but one showed hom*ocellular Hb F distribution. Conclusion: Our molecular and phenotypic correlation of 27 patients with large deletional breakpoints between HBBP1 and HBD supports the hypothesis of a silencing element located upstream of HBD and further narrows the area that segregates many HPFH and DBT patient phenotypes from 3.5 kb to 2.4 kb. Several potential silencing effectors with binding sites in this region include HDAC1, GATA1 and H3K27me3; interestingly, the BCL11A binding site may be outside of the regulatory area. Table 1. Phenotypic data of patients with deletions between HBBP1 and HBD. Case Age/Sex Hb F Hb A2 Hb X Hgb RBC MCV MCH MCHC RDW Hb F Flow (Y) (%) (%) (%) (g/dL) ( 10^12/L) (fL) (pg/cell) (hg/cell) (%) 3' Region 1 47 M 25.5 2.1 16.7 6.3 81.4 26.7 32.8 15.7 H 2 5 M 28.3 2.4 12.5 4.9 74.6 25.4 34 15.9 H 3 24 F 30.3 1.7 11.6 4.23 92.7 27.4 29.6 15.2 H 4 9 F 36.3 2.2 S = 62 13.1 5.2 69.9 NA NA 14.8 5 24 F 37.3 2.1 C = 61 12.9 5.1 72.9 25.5 35 14.3 6 3 M 39.7 2.1 12.4 4.4 88.7 28.1 31.7 16.3 7 27 F 40.2 3.4 S = 56 12.2 4.4 79.7 27.8 34.9 15 8 16 M 43.7 2.2 S = 54 15.9 6.8 71.5 23.5 32.9 14.1 9 7m M 100.0* 0.0 12.8 4.8 76 26.5 34.9 16.8 3' Region 10 28 F 20.9 2 10.11 4.4 70.9 22.7 32.1 19 H 11 64 M 21.4 2.3 10.51 4.1 81.1 25.8 31.8 18.1 12 2.5 M 24 2.1 10.21 5.3 59.4 19.3 32.5 20.9 H 13 58 F 24 2.1 9.51 4.4 72.2 21.5 29.8 17.7 H 14 14 F 25.4 1.5 10.81 4.9 69.4 22 31.8 17.6 H 15 52 F 26.9 1.8 8.42 3.6 72 23.5 32.7 19.4 T 16 34 M 38.7 1.7 S = 60 11.4 4.7 71.6 NA NA 21.6 5' Region 17 24 F 2.7 2.9 12.3 6.1 62.2 20 32.2 18.2 18 32 F 6.1 2.7 10.2 5.1 61.3 19.9 32.5 19.3 19 27 F 7.2 2.9 11 5.1 72.9 21.7 29.8 19.9 20 29 F 7.8 2.7 10.2 4.7 72.2 21.7 30 20.5 21 15 M 7.8 2.5 12.7 6.2 64.7 20.4 31.5 21.2 22 42 M 7.8 3.1 10.6 4.9 75.1 21.5 28.6 23.7 23 60 M 10.1 2.5 11 4.5 74.8 24.7 33 23.4 24 41 M 10.7 2.8 8.6 4.1 73.3 21.2 29 26.8 25 30 F 11.5 2.7 12.1 5.5 67.4 21.9 32.5 21.8 26 25 F 13.2 2.8 12.1 5.3 68.4 22.8 33.3 21.6 27 3 F 18.3 2.6 11.9 5.79 63.6 20.6 32.3 22.7 T Normal values <1 2-3.3 0 H = hom*ocellular; T= heterocellular; I = indeterminate; *hom*ozygous deletion -- = no deletion; + = deletion present (all alpha deletions were single -3.7 kb 'rightward' deletions) 1 = Suspected Fe deficiency; 2 = recent transfusion Disclosures No relevant conflicts of interest to declare.

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The case of the Soviet military periodicals during the Red Army's campaign in Europe (March 1944 – May 1945) is analyzed in the paper based on the materials from the Central Archives of the Ministry of Defense of the Russian Federation (TsAMO RF) and the Russian State Archive of Socio-Political History (RGASPI). The author analyzes the structure of military periodicals, characterizes the norms established by the Main Political Directorate of the Red Army (GlavPURKKA) regulating the work of military periodicals, and traces the relationship between editorial boards and war correspondents. It is stated that the editorial boards of military periodicals consisted, as a rule, of 27 employees: 19 military personnel and 8 civilian employees. GlavPURKKA controlled the military periodical press. The circulation of military newspapers was determined by the orders of the chief of GlavPURKKA and was repeatedly increased or reduced. The content was controlled by the political administrations of the fronts. GlavPURKKA regulated the main directions of newspapers’ development and revealed shortcomings in the work of editorial boards. Constant supervision by GlavPURKKA and political administrations of the fronts protruded “relations” between editorial boards and war correspondents. The political administrations urged the editorial boards to establish a comprehensive contact with war correspondents and to eliminate the existing shortcomings in working with them. On the whole, the institute of military periodicals was a rather complex “organism” that underwent various changes and improvements throughout the period.

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Patrick Arnaud was born in Paris on 27 May 1939. He completed his secondary school education at the Lycée Buffon and undergraduate studies at the Faculty of Sciences of the Sorbonne, before his doctoral studies in Biological oceanography in 1960, a field developed in France, at Marseille, by Professor Jean-Marie Pérès.

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Abstract Even before, in May 1933, the new Nazi regime in Germany began to ostracize, and burn the books of, so-called »un-German« authors, Constantin Brunner went into exile in The Hague. That he decided to go to the Netherlands is not surprising. The Netherlands were the homeland of Baruch de Spinoza, whose thinking is the most important influence on Brunner’s philosophical work. In The Hague he continued his philosophical studies and exchanged opinions and countless letters with friends, companions and followers in all corners of the world. But although Constantin Brunner was out of harm’s way and was, even in exile and far from home, able to dedicate himself wholly to his work, his health declined rapidly. He died on August 27, 1937. But his work has survived in The Hague where, in 1947, Magdalena Kasch founded the »Internationaal Brunner Instituut«.

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Abstract Introduction: Lutetium-177(177Lu) DOTATATE is a form of peptide receptor radionuclide therapy (PRRT) targeting somatostatin receptor-2 (SSTR2), that is utilized in the treatment of neuroendocrine tumors. As various endocrine glands express SSTR2, 177Lu-DOTATATE can potentially disrupt endocrine function. The immediate post-treatment effects of 177Lu-DOTATATE on endocrine function are not known. Methods: We performed a retrospective analysis of data obtained from patients (≥18 years) enrolled under the 177Lu-DOTATATE trial (NCT03206060) for treatment of SSTR2 positive inoperable/metastatic pheochromocytoma/paraganglioma. 177Lu-DOTATATE (200 mCi) was administered intravenously every 8 weeks, for a total of 4 cycles. Endocrine evaluation was performed on blood samples obtained through an indwelling intravenous catheter during each cycle of PRRT on day 1 (pre-PRRT), day 2 (post-PRRT day 1), day 3 (post-PRRT day 2), day 30 (post-PRRT day 29), and day 60 (day 1 of the next cycle). Hormonal evaluation included ACTH, cortisol, TSH, free T4, GH, FSH, LH, testosterone, estradiol, and prolactin. Baseline abnormal hormonal values, and gonadotrophs in premenopausal women were excluded. Results: Data from 27 subjects (age: 54 ± 12.7 years; 13 female, 14 male) were analyzed. Three out of 27 patients (11.1%) developed clinically significant persistent endocrinopathies - secondary adrenal insufficiency (AI): (n=1 male), primary hypothyroidism: (n=1 male) and hypergonadotropic hypogonadism: (n=1 female). Compared to day 1, there were significant reductions in 1) ACTH (pg/mL) levels on day 2 (36.8 ± 34.1 vs. 23.1 ± 21; p&lt;0.0001), day 3 (36.8 ± 34.1 vs. 24.3 ± 19.4; p&lt;0.0001), and day 30 (36.8 ± 34.1 vs. 27.7 ± 19.1; p=0.01), without significant changes in average cortisol level, apart from 1 patient with undetectable cortisol, who developed secondary AI after 2nd cycle 2) LH (IU/L) levels on day 3 (16.4 ± 13.5 vs. 15.4 ± 13.5; p=0.014), 3) prolactin (ng/mL) on day 2 (9.9 ± 7.0 vs. 7.1 ± 5.7; p&lt;0.0001), day 3 (9.9 ± 7.0 vs. 7.1 ± 5.4; p&lt;0.0001), and day 30 (9.9 ± 7.0 vs. 7.6 ± 5.7; p=0.005), without significant changes in average estrogen and testosterone levels, apart from 1 woman with low estrogens developing hypergonadotropic hypogonadism after 3rd cycle 4) TSH (microIU/L) on day 2 (2.2 ± 1.4 vs. 1.4 ± 0.9; p&lt;0.0001), and day 3 (2.2 ± 1.4 vs. 1.7 ± 1.3; p=0.001), and 5) free T4 (ng/dL) on day 2 (1.1 ± 0.2 vs. 1 ± 0.2; p=0.002). Hormonal values on day 60 were not significantly different from those on day 1, suggesting that majority of these changes were transient. Conclusions:177Lu-DOTATATE can be associated with transient endocrine disruption in the immediate post-treatment period. However, some of these changes may lead to persistent endocrinopathies which are likely associated with radiation exposure to the tissues expressing SSTR2. It is therefore important to periodically assess endocrine function during PRRT.

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ABSTRACT The MICs of 13 antibiotics (doxycycline, thiamphenicol, rifampin, amoxicillin, gentamicin, co-trimoxazole, ciprofloxacin, pefloxacin, ofloxacin, erythromycin, josamycin, clarithromycin, and pristinamycin) were determined for 27 available rickettsial species or strains. We used two in vitro cell culture methods described previously: the plaque assay and the microplaque colorimetric assay. Our results confirm the susceptibilities of rickettsiae to doxycycline, thiamphenicol, and fluoroquinolones. Beta-lactams, aminoglycosides, and co-trimoxazole were not active. Typhus group rickettsiae were susceptible to all macrolides tested, whereas the spotted fever group rickettsiae,R. bellii, and R. canada were more resistant, with josamycin, a safe alternative for the treatment of Mediterranean spotted fever, being the most effective compound. Strain Bar 29,R. massiliae, R. montana, R. aeschlimannii, and R. rhipicephali, which are members of the same phylogenetic subgroup, were more resistant to rifampin than the other rickettsiae tested. Heterogeneity in susceptibility to rifampin, which we report for the first time, may explain in vivo discrepancies in the effectiveness of this antibiotic for the treatment of rickettsial diseases. We hypothesize that rifampin resistance and erythromycin susceptibility may reflect a divergence during the evolution of rickettsiae.

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Abstract BACKGROUND: MM is the second most common hematalogical malignancy in the U.S. The expansion of myeloma cells in bone, which is characteristic of MM, results in increased osteoclast activity that cause osteolytic lesions, which can lead to spinal cord compression, pathologic fracture, surgery or radiation therapy to bone, and bone pain. Denosumab is a fully human monoclonal antibody that can inhibit bone resorption by reducing the number and activity of osteoclasts by inhibiting RANK ligand, a key mediator of osteoclast activity. The objective of this analysis was to evaluate the pain and HRQoL in patients with MM being treated with denosumab. METHODS: 96 patients with either ≥2 prior treatment regimens and relapsed following a response to any conventional MM therapy (relapsed) or response to the most recent MM therapy and stable M-protein for ≥3 months (PP) were enrolled in a phase 2, multicenter, open-label, single-arm study of denosumab. Patients received 120mg denosumab SC on days 1, 8, 15, and 29 then every 28 days thereafter until disease progression or discontinuation. The Brief Pain Inventory-Short Form (BPI) and Functional Assessment of Cancer Therapy-General (FACT) were assessed at baseline (BL) and prior to treatment on day 1 of each 28-day cycle. BPI “pain at worst in the past 24 hours” scores were categorized as no pain (BPI 0), mild pain (BPI 1–4), moderate pain (BPI 5–6) or severe pain (BPI 7–10). BL and month 3 (relapsed) and month 5 (PP) pain and HRQoL data were analyzed. Longitudinal data regarding pain and HRQoL data were reported at BL and the latest assessment timepoint where &lt;30% of patients had dropped out. RESULTS: 45 patients with relapsed MM (Table 1) and 37 patients with PP MM (Table 2) had BL and ≥1 post-BL assessment. 30% or more patients dropped out after month 3 of treatment in relapsed patients and after month 5 in PP patients. In relapsed patients, 12 (27%), 21 (47%), 8 (18%), and 4 (9%) patients reported no pain, mild pain, moderate pain and severe pain at BL, respectively. In PP patients, 15 (41%), 13 (35%), 5 (14%), and 4 (11%) patients reported no pain, mild pain, moderate pain and severe pain at BL, respectively. 68% and 89% of relapsed and PP patients, respectively, demonstrated improvement or no categorical change in pain. At BL, mean (sd) FACT total scores (0–108, higher score indicating better HRQoL) for relapsed and PP patients were 77.4 (15.3) and 82.5 (11.2), respectively. FACT total scores remained relatively constant in relapsed and PP patients, 77.9 (19.4) and 83.6 (13.3), respectively. In addition, mean change from baseline in FACT domain scores varied between 1.2 to 0.2 in relapsed patients and between 0.3 to 1.1 in PP patients. CONCLUSION: The majority of patients with relapsed and PP MM demonstrated maintenance or improvement in pain and maintenance of HRQoL during treatment with denosumab. These results suggest denosumab may be associated with stabilization of pain and maintenance of HRQoL in patients with MM. Randomized trials are needed to further understand the impact of denosumab on pain and HRQoL in patients with MM. Table 1. “Pain at Worst in the past 24 hours” Category Shift between BL and month 3 in relapsed patients (n=45). Follow-up Pain Category No Pain Mild Moderate Severe TOTAL BL Pain Category No Pain 7 2 2 1 12 Mild 4 10 4 3 21 Moderate 2 3 1 2 8 Severe 0 0 2 2 4 TOTAL 13 15 9 8 45 Table 2. “Pain at Worst in the past 24 hours” Category Shift between BL and month 5 in PP patients (n=37). Follow-up Pain Category No Pain Mild Moderate Severe TOTAL BL Pain Category No Pain 13 2 0 0 15 Mild 4 7 1 1 13 Moderate 1 2 1 1 5 Severe 0 0 2 2 4 TOTAL 18 11 4 4 37

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AbstractThe word σαβαχθανι appearing in Jesus’ cry of despair in Matt 27:46 and Mark 15:34 may be read as the Hebrew סבכתני, “you have tangled me up.” On this reading, Jesus may be expressing his connection with the ram which Abraham sacrificed instead of his son Isaac, since that ram was described as being caught by the horns in a סבך (Gen 22:13).

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Barry Anderson died in Paris on 27 May 1987, a few hours after the first performance of his new chamber work, ARC. His hectic life-style with its incessant demands had burned him out. The immediate cause of death was heart failure, but the real cause was exhaustion from years of overwork as a composer, teacher, concert organizer, ‘ghost’ writer, and pioneer in the dissemination of electro-acoustic music in this country. He was 52 years old and, sadly, just beginning to be recognized as a composer of international stature.

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4012 Background: Overall survival (OS) in phase III studies with 1st line combination therapy in ACC may be influenced by imbalances in salvage treatments. This is the first study that prospectively investigates the sequential vs the combined use of all available effective cytotoxic drugs. Methods: Previously untreated patients (pts), WHO PS 0–2 were randomized between 1st line capecitabine (Cap), 2nd line irinotecan (Iri), and 3rd line Cap + oxaliplatin (CapOx) (Arm A, sequential) vs 1st line CapIri and 2nd line CapOx (Arm B, combination). The dose of Cap was 1250 mg/m2 (mono) or 1,000 mg/m2 (combination) b.i.d. day 1–14, Iri 350 mg/m2 (mono) or 250 mg/m2 (combination), and Ox 130 mg/m2. All cycles were q 3 weeks with Iri/Ox given i.v. on day 1. Response was assessed q 3 cycles. Primary endpoint was OS. The study was designed to detect a 20% reduction in the hazard of death (HR=0.80) for an increase in median OS from 14 to 17.5 months (a=0.05, 2-tailed test). Results: 820 pts were randomized between Jan ‘03 and Dec ‘04 in 74 Dutch hospitals. Of 804 eligible pts, 796 received = 1 cycle. Median age was 63 (27–84) yrs, median WHO PS 0 (0–2), median follow-up 32 months. Pts (n) in arm A: 398 (1st line), 248 (2nd line), 141 (3rd line); arm B: 398 (1st line), 210 (2nd line). Median OS in arm A was 16.3 months (95%CI 14.3–18.2) and in arm B 17.7 months (95%CI 15.2–19.4), logrank p=0.2. Overall gr 3–4 toxicity over all lines did not differ significantly except for gr 3 hand-foot syndrome (HFS) (13% in A and 6% in B, p=0.0009). Death was probably related to treatment in 11 pts (neutropenic sepsis and/or diarrhea, 8 arm A, 3 arm B) and involved protocol violations in some. In 1st line significant differences in gr 3–4 toxicity in arm A vs arm B were diarrhea (10% vs 25%, p<0.0001), febrile neutropenia (1% vs 6%, p=0.0001) and HFS (12% vs 5%, p=0.0004). All-cause 60-day mortality was 3.0% (n=12) in arm A and 4.5% (n=18) in arm B. Updated results will be presented at the meeting, including data on QoL (EORTC QLQ C30). Conclusions: Combination therapy does not significantly improve OS compared with sequential therapy. Both treatment strategies are valid options for pts with ACC. No significant financial relationships to disclose.

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Abstract Sickle cell disease (SCD) is highly prevalent in sub-Saharan Africa; however, there are relatively few studies describing the clinical profile for children with laboratory-confirmed SCD. Prior to December 2014, neither neonatal screening nor standardized methods for SCD diagnosis were routinely available in Malawi, as hemoglobin electrophoresis and alternative diagnostic methods were absent. We describe implementation of hemoglobin electrophoresis for children with clinically suspected SCD at Kamuzu Central Hospital, one of two national teaching hospitals in Malawi. Children with clinically suspected SCD were recruited January - May 2015 and underwent comprehensive clinical and laboratory characterization. 137 total patients were recruited and 117 were confirmed to have HbSS disease. Among children who were being cared for as SCD prior to enrollment, 86% had HbSS suggesting generally accurate clinical diagnosis by local providers. Baseline clinical parameters and self-reported SCD complications for the study population are displayed in Table 1. Of those with confirmed SCD, median age was 7.3 years (IQR 2.7-10.4) with 53% males. Prior malaria was reported by 39% of patients, and was higher in the 0-5 age group compared with the over 5 age group (46% vs. 31%, p=0.03). The most commonly reported SCD complications were anemia (72%), joint pain (56%), jaundice (52%), and acute pain episodes (50%). Children with confirmed SCD had median hemoglobin of 7.3 g/dL (IQR 6.9-7.9), total bilirubin of 1.7 mg/dL (IQR 1.1-2.6) and lactate dehydrogenase of 658 IU/L (IQR 527-773). Urinalysis demonstrated 26% of patients with blood and 7% with proteinuria by dipstick. As of May 2015, more than 250 samples for enrolled children as well as routine clinical care had been batch-processed weekly with an average turn-around time of 36 hours for results. Three Malawian laboratory technicians were trained to perform hemoglobin electrophoresis, all of whom have been performing the test independently since April 2015. Our findings highlight a need for wider implementation of resource-appropriate diagnostics as an essential foundation for care and research. Children had substantial clinical and laboratory evidence of SCD-related morbidity. Earlier diagnosis can improve care for this population by facilitating earlier therapeutic interventions, as well as providing a basis for research to better understand SCD-related morbidity in sub-Saharan Africa. These efforts can ultimately inform management strategies to improve outcomes and increase life expectancy among children with SCD in Malawi. Table 1. All (n=117) Male (n= 62) Female (n=55) p value Age years, median (IQR) 7.3 (2.7-10.4) 5.3 (2.3-9.4) 8.9 (4.2-11.9) 0.004 Height cm, median (IQR, n) 115 (88-131, 60) 111 (89-128, 36) 119.5 (93-140, 24) 0.21 Weight kg, median (IQR, n) 19 (13-27, 108) 16.5 (12-23.6, 58) 21 (14-30, 50) 0.01 Blood Pressure Systolic mmHg, median (IQR, n) 103 (98-110, 83) 101 (94-108, 43) 103 (99-110, 40) 0.37 Blood Pressure Diastolic mmHg, median (IQR, n) 60 (55-65, 83) 58 (53-65, 43) 61 (56-68, 40) 0.13 Heart Rate BPM, median (IQR, n) 104 (91-118, 114) 105 (94-123, 61) 104 (88-112, 53) 0.15 O2 Saturation %, median (IQR, n) 93 (88-97, 108) 91 (85-96, 59) 95 (91-98, 49) 0.004 % Hypoxemic (SPO2 < 90%), n (%) 36 (30.7) 26 (41.9) 10 (18.2) 0.005 Body Temperature Celsius, median (IQR, n) 37 (36.7-37.4, 91) 37 (36.7-37, 46) 37 (36.4-37.2, 45) 0.22 Positive History of: Malaria, n (%) 45 (38.5) 22 23 0.34 0-5 years, n (%) 25 (46.3) - - 0.03 6-18 years, n (%) 20 (31.7) - - Pneumonia, n (%) 29 (24.8) 10 (16.1) 19 (34.5) 0.02 HIV, n (%) 0 0 0 - Anemia, n (%) 84 (71.8) 49 (79.0) 35 (63.6) 0.06 Pallor, n (%) 16 (13.7) 7 (11.3) 9 (16.4) 0.43 Jaundice, n (%) 61 (52.1) 33 (53.2) 28 (50.9) 0.82 Received Blood Transfusion, n (%) 87 (74.4) 47 (75.8) 40 (72.7) 0.47 Days since last transfusion, median (IQR) 316 (133-1144) 240 (111-410) 577 (180-1784) 0.03 Pain episodes, n (%) 58 (49.6) 27 (43.5) 31 (56.4) 0.16 Joint pain, n (%) 66 (56.4) 33 (53.2) 33 (60.0) 0.34 Dactylitis, n (%) 41 (35.0) 19 (30.6) 22 (40.0) 0.29 Leg ulcers, n (%) 5 (4.3) 5 (8.1) 0 0.03 Stroke, n (%) 10 (8.5) 5 (8.1) 5 (9.1) 0.84 Nocturnal Enuresis, n (%) 24 (20.5) 12 (19.4) 12 (21.8) 0.74 Disclosures No relevant conflicts of interest to declare.

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Abstract Abstract 3487 Background: Drug metabolism and disposition genes have a substantial impact on the pharmacology of many medications. For CML, the human organic cation transporter (hOCT1) actively transports imatinib mesylate (IM) into cells, thus is a crucial factor in the response to IM therapy, without a known effect on plasma levels. A number of single nucleotide polymorphisms (SNPs) are believed to affect the activity of hOCT1 and therefore may influence IM accumulation in cells. We therefore studied hOCT1 SNPs and correlated with IM plasma levels and clinical response to IM. We studied a SNP in exon 2 of hOCT1 (480C>G, Phe160Leu, rs683369), which, in the hom*ozygous state (GG), has been associated with treatment failure on IM (DH Kim, Clin Cancer Res., 15:4750, 2009), and a SNP in exon 7 (1222A>G, Met408Val) which has been hypothesized as having increased activity (A Giannoudis, Haematologica 96(s2):87, 2011). Both of these are prevalent SNPs; the exon 2 SNP is found in 22% of Caucasians and the exon 7 SNP, in 60% of Caucasians (R Kerb, Cancer Letters 234:4, 2006). Methods: We studied 48 patients with CML in chronic phase (M:F 21:27 aged 17–89 years. Time since CML diagnosis was between 10 months and 18 years. IM therapy was between 10–128 months' duration. Most of the patients were on a dose of 400 mg/once daily, with the exception of 11 patients who were on doses >400 mg/once daily (mean 609.1 mg/day +/− 70.1 mg), and 9 patients, whose dose was <400 mg/once daily (mean 281 mg/day +/− 35.4 mg). Trough IM levels were performed by Novartis Pharmaceuticals on samples taken 24 hours after last dose, reported in ng/ml. Compliance was verified by a patient diary during the trough drug testing period, but not throughout the entire period of IM therapy. Genotyping for hOCT1 SNPs was performed on 36 patients. The exon 2 SNP was detected by PCR amplification and Dde I restriction enzyme analysis. The exon 7 was detected by PCR and restriction with BmgB1. Detailed molecular data was available on 36 patients, and partial molecular data on 8 others. Complete molecular remission (CMR) was defined as PCR negativity using RT-PCR until 2004, and thereafter, using a highly sensitive real time PCR assay. Results: The mean IM trough level for all 48 patients was 1,153.0 (+/−493.1). There was much variation between IM levels in individual patients and levels also varied by dose. Patients who were on 400 mg/day had a mean IM level of 1064.1 (+/− 399.2). Patients on higher IM doses (>400 mg) had IM levels averaging 1397.2 (+/− 493.1). Patients on doses <400 mg/day had mean IM levels of 1057.3 (+/− 667.0), which was nearly identical to that of patients on 400 mg/day. Genotyping for the hOCT1 exon 2 SNP demonstrated that 66.7% of the 36 patients analyzed were hom*ozygous for the wild type allele, 13.9% were heterozygous for the polymorphism and 19.4% were hom*ozygous polymorphic. GG hom*ozygotes had higher IM levels than CG/CC genotypes (1562.75 +/− 560 compared to 1310.6 +/− 470). This is because the patients were on doses greater than 400 mg/day (mean 483 mg/day compared to 405 mg/day). These patients took an average of 8.8 months to achieve a molecular CR and one transiently lost molecular CMR. Genotyping for the hOCT1 exon 7 SNP demonstrated that 47% of the 36 patients analyzed were heterozygous AG for the polymorphism and 53% of the patients were GG hom*ozygotes. IM levels for the GG hom*ozygotes were higher than for AG heterozygotes (1413 +/− 549.6 compared to 1254.0 +/− 393.9 ng/ml), despite the fact that they were on a slightly lower average dose (mean: 390.1 mg/day compared to 436.7 mg/day). For 13 of these GG hom*ozygous patients, detailed molecular followup was available. Two of these patients never achieved CMR and 2 transiently lost CMR. The time to achieve complete molecular remission was generally long, 17.6 months (range 3–83 months). Importantly, 12 out of 13 of these patients with unsatisfactory clinical responses to IM were CC or CG at the exon 2 SNP, which are considered favorable genotypes for IM response (DH Kim, Clin Cancer Res., 15:4750, 2009). Conclusions: These data may suggest that the GG genotype for exon 7 in hOCT1 (rs628031), independent of the exon 2 (rs683369) genotype, is an adverse prognostic parameter despite adequate IM levels. These patients may be candidates for an alternate tyrosine kinase inhibitor. Further studies are necessary on larger groups of patients to confirm these results, which are important in view of the high frequency of the polymorphic rs628031 allele. Disclosures: Cohen: Novartis Pharmaceutical Company: Research Funding. Rund:Novartis Pharmaceutical Company: Honoraria, Research Funding.

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Abstract Abstract 1937 Poster Board I-960 Background. Waldenstrom's macroglobulinemia is a rare B cell neoplasm characterized by the production of a monoclonal IgM protein and a lymphoplasmacytic infiltrate in the bone marrow. The clinical manifestations related to tumor infiltration include hepatomegaly (20%), splenomegaly (15%) and lymphadenopathy (15%). Organomegaly was associated with adverse prognosis in a large series of WM. More sensitive tools of tumor burden and prognosis are needed in these patients. The use of FDG-PET has not been previously studied in WM but has proved an effective diagnostic and prognostic tool in other in low-grade lymphomas. Therefore the objective of this study was to determine whether FDG-PET was an effective tool in evaluating pts with WM. Methods. We prospectively studied PET/CT in 39 WM patients hom*ogeneously treated with bortezomib-rituximab (given IV bortezomib 1.6mg/m2 at days 1, 8, 15 q 28 days × 6 cycles and rituxan 375 mg/m2 at days 1, 8, 15, 22 on cycles 1 and 4) on a phase II clinical trial, at diagnosis (N=12) and with relapsed/refractory disease (N=27). All pts underwent staging evaluation by FDG-PET in combination with CT scan before and after therapy. PET results were analyzed as positive or negative. Response (ORR) was assessed after cycle 3, confirmed with 2 consecutive values and included minor response or better. Overall (OS) and treatment free survivals (TFS) were calculated from start of treatment to date of last follow up and time of next treatment, respectively. Results. The median age of the population was 62 years (range, 43-78), Male/Female ratio 1.64, WM-International staging score breakdown was 46% low, 23% intermediate, 31% high. Serum M-spike was 2.5g/L (0.41-4.62) with 8% patients >= 4g/L. The overall response rate was 89.7% with minor response in 13 pts and major response in 22 pts. With a median (+/-se) follow-up of 15 months (+/-1.22), death occurred in 2 patients, and the median OS was not reached with a 3-year probability of survival of 89%. The median TFS was 21 months (+/-2.09). Twenty-five (64.1%) and 13 (37.1%) patients had a positive PET before and after treatment, respectively. 11 (45.8%) patients had a negative post treatment PET which was positive before treatment, 1 (4.8%) had a positive PET after treatment while initially negative and all other patients had no change. Patients with positive PET before treatment had no clinical-biological difference (age, gender, hemoglobin level, serum beta 2-microglobulin value, platelet count, IgM spike and ISS-WM score) with other patients. A positive PET before treatment had no influence on either OS or TFS or ORR or MR. However, a normal PET after treatment, including a negative PET after treatment which initially was positive before treatment, correlated with response (p=0.04). The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) for a normal PET after treatment and for a negative PET after treatment while initially positive before treatment in predicting ORR were 68.7%, 100%, 100%, 23% and 52.4%, 100%, 100%, 23.1%, respectively. Although the number of deaths is low in this series, a positive PET after treatment was an adverse prognostic factor for OS. The median survival and the 2-year probability of survival was not reached and 100% for patients with a normal (negative) PET after treatment (number of death/number of pts in the group, O/N=0/22) while it was 20 months and 46% for patients with a positive PET after treatment (O/N=2/13 ), respectively (p=0.019). Conclusion: Over 60% of WM pts demonstrated FDG-avid disease when using FDG-PET scans with the majority showing negative imaging after therapy. PET positive scans after therapy correlated with poor prognosis. FDG-PET scans may prove an effective tool in the diagnosis and prognosis in WM. Disclosures: No relevant conflicts of interest to declare.