Статті в журналах з теми "Albury Mill"
Щоб переглянути інші типи публікацій з цієї теми, перейдіть за посиланням: Albury Mill.
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-50 статей у журналах для дослідження на тему "Albury Mill".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте статті в журналах для різних дисциплін та оформлюйте правильно вашу бібліографію.
1
Needleman, Ruth. "John Hinshaw, Steel and Steelworkers: Race and Class Struggle in Twentieth-Century Pittsburgh. Albany: State University of New York Press, 2002. 320 pp. $75.50 cloth; $25.95 paper." International Labor and Working-Class History 65 (April 2004): 227–29. http://dx.doi.org/10.1017/s0147547904420134.
Повний текст джерелаАнотація:
Richly descriptive and well documented, Steel and Steelworkers: Race and Class Struggle in Twentieth-Century Pittsburgh by John Hinshaw makes a significant contribution to the growing body of historical research on steel unionism in the twentieth century. Over the past few years, a number of new studies have broadened our understanding of unionization and work practices in the nation's steel mills, by examining in greater detail the patterns of organization in specific mills and mill towns.
2
Kinder, Renee. "Coding for Mild Cognitive Impairment." Perspectives on Gerontology 19, no. 2 (May 2014): 72–77. http://dx.doi.org/10.1044/gero19.2.72.
Повний текст джерелаАнотація:
Appropriate coding when providing skilled therapy interventions for individuals with Mild Cognitive Impairment (MCI) begins by obtaining an adequate understanding of the diagnostic criteria for the disorder. Current diagnostic criteria for MCI include: a. reported change in cognition, which is preferably corroborated by an informant in comparison with previous level with concern of patient, family, or clinician with one or more impaired cognitive domains for age and education. b. decline which is evident over time and greater than expected for age and education in a variety of domains including memory, executive function, attention, language, visuospatial skills, and episodic memory. c. not normal, not demented. d. intact activities of daily living (Albert et al., 2011). Individual may present with mild problems with complex tasks such as paying bills, preparing a meal, and shopping and may require more time and be less efficient, with more errors during tasks.
3
Silva, Josué Cândido da. "A controvérsia entre Habermas e Albert sobre a intransitividade das ciências humanas." Especiaria: Cadernos de Ciências Humanas 18, no. 32 (September 26, 2018): 175–201. http://dx.doi.org/10.36113/especiaria.v18i32.2246.
Повний текст джерелаАнотація:
A questão da intransitividade das ciências humanas remonta à controvérsia entre compreender (Verstehen) e elucidar (Erklären), que tem origem na reação de Dilthey à pretensão de Stuart Mill de integrar as “ciências morais” dentro de um projeto de ciência unificada. Tal controvérsia adentrou o século XX, tendo, entre seus episódios, o debate sobre a lógica das ciências sociais em que se confrontaram as teses de Karl Popper e Theodor Adorno e seus discípulos, respectivamente, Hans Albert e Jürgen Habermas. No presente artigo, apresentaremos os principais elementos da controvérsia entre Habermas e Albert sobre a epistemologia das ciências humanas. Coerente com a tradição hermenêutica, Habermas postula que os critérios de objetividade das ciências naturais não se aplicam às ciências humanas, já que o pesquisador não pode assumir uma postura neutra e anular sua vivência individual no processo de investigação, pois a mesma é a condição de possibilidade do estudo da história e da sociedade, ao prover ao pesquisador uma conexão entre a experiência individual e coletiva. Para Habermas, portanto, os critérios de objetividade nas ciências humanas e nas ciências naturais não podem ser reduzidos a um mesmo padrão de cientificidade. Albert, por seu turno, postula que a realidade a que se refere nosso conhecimento é um todo conexo, sendo as fronteiras que separam as diferentes disciplinas resultado apenas de uma divisão científica do trabalho. Além disso, tanto cientistas sociais quanto naturais têm valores, mas que a ciência tem sua neutralidade axiológica garantida por seus procedimentos metodológicos. Albert vê o corte epistemológico operado por Habermas como resultado de seu dualismo metafísico entre mundo da vida, como esfera inacessível da subjetividade, e mundo objetivo. A polêmica entre Habermas e Albert permite reconstruir um importante debate que marca a história da filosofia contemporânea e que permanece aberto até hoje.
4
Gates, Michelle, Rhona M. Hanning, Allison Gates, Ian D. Martin, and Leonard JS Tsuji. "Intakes of milk and alternatives among on-reserve First Nations youth in northern and southern Ontario, Canada." Public Health Nutrition 16, no. 3 (July 4, 2012): 515–23. http://dx.doi.org/10.1017/s1368980012003035.
Повний текст джерелаАнотація:
AbstractObjectiveTo assess the adequacy of milk and alternatives, Ca and vitamin D intakes in First Nations (FN) youth in Ontario, Canada. Intakes were compared with the general population and dietary standards. Variation in intakes by community (proxy for remoteness) and BMI was examined.DesignData were collected by 24 h recall between November 2003 and June 2010. Intakes were analysed descriptively. Variation in intakes, by community and BMI category, was assessed using ANOVA.SettingFive remote FN communities of the Mushkegowuk Territory (northern Ontario, Canada) and two less-remote southern Ontario FN communities.SubjectsSchoolchildren (n457) in grades 6 to 12.ResultsCompared with Canada's Food Guide recommendations, 72·6 to 84·7 % had an inadequate intake of milk and alternatives depending on age and sex group; 86·2 % of individuals fell below the RDA for Ca; 96·4 % fell below the RDA for vitamin D. Community variation in intakes was detected, although in all cases Fort Albany had higher intakes, even when it was the more northern (remote) community. A BMI × sex interaction was found for intake of milk and alternatives (P= 0·041): an inverse relationship between intake and BMI was seen in females; in males, those who were overweight had the highest intake, followed by normal-weight and obese youth.ConclusionsThe nutritional inadequacies parallel the results of other Canadian studies of Aboriginal populations. Population health interventions to improve intakes are warranted. Moreover, community variation in intakes exists among FN youth in the present study (Fort Albany pairs only), but results were not as expected.
5
T., A. "The content of microbes in the cavity of the pregnant uterus Albert (Arch. f. G., Bd. 125, H. 3)." Kazan medical journal 22, no. 8 (September 4, 2021): 971. http://dx.doi.org/10.17816/kazmj78692.
Повний текст джерелаАнотація:
The content of microbes in the cavity of the pregnant uterus could have been detected by Albert (Arch. F. G., Bd. 125, H. 3) during an abortion by a small Caesar section. The author believes that the vagina always contains microbes that can infect the cervix and the uterine cavity at any time; in some cases, this infection, after a short and mild acute period, can go into a latent state, during which pregnancy is possible.
6
Baars, C., H. Jahangir, L. E. Popov, M. G. Pour, and M.-R. K. Zadeh. "First record of the Ordovician fauna in Mila-Kuh, eastern Alborz, northern Iran." Estonian Journal of Earth Sciences 64, no. 2 (2015): 121. http://dx.doi.org/10.3176/earth.2015.22.
Повний текст джерела
7
Kwai, Ching Kan, Ponnusamy Subramani, Rosdinom Razali, and Shazli Ezzat Ghazali. "Piloting Digital Memory Album Project for Older Adult with Mild to Moderate Dementia in Malaysia – A Feasibility Study." Jurnal Sains Kesihatan Malaysia 16, Special Issue (January 15, 2018): 243. http://dx.doi.org/10.17576/jskm-2018-16si-44.
Повний текст джерела
8
Kwai, Ching Kan, Ponnusamy Subramaniam, Rosdinom Razali, and Shazli Ezzat Ghazali. "Piloting Digital Memory Album Project for Older Adult with Mild to Moderate Dementia in Malaysia – A Feasibility Study." Jurnal Sains Kesihatan Malaysia 16, si (January 15, 2018): 243. http://dx.doi.org/10.17576/jskm-2018-44.
Повний текст джерела
9
Ritchie, Karen, and Craig W. Ritchie. "Mild cognitive impairment (MCI) twenty years on." International Psychogeriatrics 24, no. 1 (November 18, 2011): 1–5. http://dx.doi.org/10.1017/s1041610211002067.
Повний текст джерелаАнотація:
Cognitive decline has commonly been considered an inevitable result of brain aging and has been of clinical interest principally because of related difficulties with everyday functioning. Since the 1990s the “normality” of age-related cognitive decline has been called into question, being commonly attributed to a number of underlying disorders. Numerous concepts have been proposed which link subclinical cognitive change to pathological states (mild cognitive disorder, mild neurocognitive disorder, mild cognitive impairment). Of these, mild cognitive impairment (MCI) has become the most popular, driven on the one hand by industrial interests seeking to extend new dementia treatments for a more prevalent subclinical syndrome, and on the other by researchers attempting to identify at-risk populations. MCI has been both criticized for “medicalizing” behavior still within normal limits (Stephan et al., 2008; Moreira et al., 2008) and welcomed in that it suggests cognitive decline with aging may not be inevitable, but rather due to abnormalities which could ultimately be treated. Recently, in both Europe (DuBois et al., 2007) and the USA (Albert et al., 2011), panels of experts have scrutinized the concept of MCI and more broadly the pre-dementia stages of neurodegenerative diseases and offered new research diagnostic criteria. These proposed criteria have highlighted the (potential) value of biomarkers in assisting diagnosis, although some have considered the elevation of biomarkers to this level of importance in diagnosing disease before dementia develops to be premature given both the extent and quality of diagnostic biomarker data currently available (McShane et al., 2011a; 2011b).
10
Rama Raj, Palaniraj, Prateepan Varatharajullu, and Paul A. Adler. "Atypical Christmas Eye Disease: A Case Report and Literature Review." Open Ophthalmology Journal 15, no. 1 (December 23, 2021): 264–69. http://dx.doi.org/10.2174/1874364102115010264.
Повний текст джерелаАнотація:
Background: Christmas Eye Disease (CED), also known as the “Albury-Wodonga syndrome” or “Harvester's Keratitis”, is a seasonal acute corneal ulceration syndrome, which is geographically limited to Australia, specifically in the south-west region of New South Wales (NSW) and north-east region of Victoria. The mechanism of injury is unknown, but the secretions from native beetles of the genus Orthoperus have been implicated. There remains a dearth of literature on CED, particularly with atypical disease presentations. We present the first reported case of CED in the upper Blue Mountains Region, presenting atypically with mild pain and foreign body sensation. We also aim to explore the possible entomological precipitants of the disease. Case Presentation: A 77-year-old man with a 1-day history of a mildly painful red eye was found to have acute corneal ulceration. He experienced mild discomfort in his right eye while asleep and woke the following morning with persistent blur, foreign body sensation, and photophobia. He had no history of ocular trauma or chemical exposure. He reported going for daily bushwalks in the upper Blue Mountains region but did not recall any exposure to environmental or entomological precipitants. Clinical Findings and Outcomes: Slit-lamp examination revealed a substantial corneal epithelial loss in the right eye with fluorescein staining, revealing a characteristic ‘green splash’ over 90% of the cornea. Other clinical findings included marked corneal edema, moderate conjunctival injection, mild palpebral swelling, and mild papillae. No anterior uveitis was observed, and the posterior segment examination was normal. There was a considerable reduction in his right visual acuity from baseline. He was empirically treated with 1% tropicamide ocular drops, 1% chloramphenicol ointment, and lubricant ocular drops. The bacterial and viral conjunctival swabs were unremarkable. Clinical progression was self-limiting, and complete resolution of the ulcer was achieved after one month. Conclusion: CED is a clinical diagnosis, and medical practitioners should be aware of atypical features, such as the absence of debilitating pain. Additionally, our case demonstrates that the geographic distribution of CED appears to be far more extensive than previously thought, thereby raising the possibility of disease manifestation in regions not commonly associated with it. Entomological precipitants of this condition remain circumstantial and warrant further validation.
11
Babaee, Zohreh, Maryam Norouzi, Samaneh Mosaferi, and Maryam Keshavarzi. "Karyotype analysis and chromosome number for two Cirsium taxa (Asteraceae) in Iran." Turczaninowia 24, no. 1 (March 26, 2021): 83–88. http://dx.doi.org/10.14258/turczaninowia.24.1.10.
Повний текст джерелаАнотація:
Cirsium Mill. contains more than 250 species in the world mainly distributed in the Northern hemisphere. Different chromosome numbers with different ploidy levels were reported in this genus. In this study, karyotype details and chromosome numbers were established for two Cirsium taxa in Iran. C. ciliatum subsp. szovitsii and C. echinus had the mitotic chromosome numbers of 2n = 2x = 34. Karyotype analyses showed that chromosomes were generally metacentric and sub-metacentric. In C. echinus, Lowshan population had the longest chromosome (19.10 µm) and Heyran Canyon population (4.73 µm) the shortest one while in C. ciliatum, the longest chromosome was observed in Urmia to Salmas population (14.67 µm) and the shortest one (4.71 µm) in Doshanlu population. Total haploid chromosome length ranged from 275.29 to 376.42 µm in populations studied. Both taxa were grouped in 2B class. B-chromosomes were recorded for two taxa studied too. Chromosome type, mitotic chromosome numbers and occurrence of B-chromosomes were in agreement with previous results (Albers, Pröbsting, 1998; Lövkvist, Hultgård, 1999; Yüksel et al., 2013; Yildiz et al., 2016).
12
Kangi, Abas, Ali Asgar Aryaei, and Abolghasem Maasoomi. "Synsedimentary deformations in member 2 of the Mila Formation in the Central Alborz Mountains, Northern Iran." Arabian Journal of Geosciences 3, no. 1 (April 9, 2009): 33–39. http://dx.doi.org/10.1007/s12517-009-0044-2.
Повний текст джерела
13
Tyler, Melissa. "Sex, Strategy and the Stratosphere — Airlines and the Gendering of Organizational Culture – By Albert J. Mills." British Journal of Industrial Relations 45, no. 4 (December 2007): 872–74. http://dx.doi.org/10.1111/j.1467-8543.2007.00659.x.
Повний текст джерела
14
Eftekhari, Mohsen, and Nader Mosavari. "Isolation and molecular identification of Mycobacterium from commercially available pasteurized milk and raw milk samples collected from two infected cattle farms in Alborz Province, Iran." International Journal of Mycobacteriology 5 (December 2016): S222—S223. http://dx.doi.org/10.1016/j.ijmyco.2016.10.005.
Повний текст джерела
15
Goreta, Smiljana, and Daniel I. Leskovar. "Screening Spinach Cultivars for White Rust Resistance and Bolting." HortTechnology 16, no. 1 (January 2006): 162–66. http://dx.doi.org/10.21273/horttech.16.1.0162.
Повний текст джерелаАнотація:
Areas with mild climate conditions are suitable for growing winter spinach (Spinacia oleracea L.). Successful production depends on choosing slow-bolting cultivars resistant to major diseases in each area. Field experiments with a total of 18 cultivars were conducted during 8 years in the Winter Garden region of Texas, an area known for its high white rust (Albugo occidentalis G.W. Wils) inoculum. Spinach cultivars differed widely in their resistance to both white rust and bolting, and the incidence of both traits was more severe as the season progressed. White rust infection increased linearly with average monthly minimal air temperature. Cultivars Fidalgo, Springfield, and Springer were slow bolting and are suitable for areas with no white rust incidence, while cvs. ASR-318, DMC 66-09, Fall Green, Samish, and San Juan were more white rust resistant.
16
Namvar, Zahra, Abbas Akhavan Sepahy, Robab Rafiei Tabatabaei, and Sassan Rezaie. "Molecular Investigation of Diversity Normal Yeast Flora in Cow Raw Milk Industrial Farms of Tehran Province and Alborz." Iranian Journal of Medical Microbiology 15, no. 3 (June 1, 2021): 317–26. http://dx.doi.org/10.30699/ijmm.15.3.317.
Повний текст джерела
17
Noike, Kohei, Ryo Matsumoto, M. Hosein Mahmudy Gharaie, Wang Yinxi, Reza Salamati, and Shiguehiko Nilo Matsuda. "Carbon isotope anomaly of the “Yellow Beds” in the Lower Cambrian Mila Formation in Shahmirzad, Alborz, northern Iran." Journal of the Sedimentological Society of Japan 64 (2007): 121–24. http://dx.doi.org/10.4096/jssj.64.121.
Повний текст джерела
18
Fallahi, Esmaeil. "Horticulture in Iran Can Be an Alternative to Petroleum and a Major Source of International Business with Unique Potential and Challenges." HortScience 52, no. 9 (September 2017): 1145–47. http://dx.doi.org/10.21273/hortsci12080-17.
Повний текст джерелаАнотація:
The art and science of horticulture and horticultural crops are integral parts of Iranian’s rich and ancient culture and modern economy. Many deciduous fruit, flowers, and vegetables are native to Iran (Persia), and from there, they were distributed to the rest of the world through the Silk Road established by the Achaemenid, the Royal Pars Dynasty. Variations in climate and presence of numerous mountains, lakes, rivers, and natural springs have created a unique country capable of producing all types of fruits, vegetables, and flowers. Apples and other deciduous fruits are commercially produced in mountain ranges of Alborz and Zagrous and in many central provinces of Iran. The Caspian Sea area in the north of Iran is one of the most unique regions in the world where mild Mediterranean climate meshed with the adjacent Alborz mountain ranges has created a home to numerous species of edible horticultural plants, ranging from tea to cherries and pomegranates. Pistachio, olive, citrus, banana, and date are produced in Kerman, Fars, and Khuzestan regions. However, the Iranian horticultural industry faces many challenges, including global and regional political issues. Although some attempt has been made to preserve invaluable germplasm, a large number of native fruits, vegetables, and flowers are becoming extinct. Postharvest transportation and storage of horticultural crops is one of the most important issues facing Iranian horticulture. The future of horticulture in Iran can potentially be bright, and horticultural products have the potential to replace the oil income after reserves disappear, particularly if peace prevails in the region.
19
Premlata Devi, Yengkhom. "Effect of Traditional Agronomic Practices on White Rust of Rapeseed – Mustard under Organic Farming System in Manipur." Current Agriculture Research Journal 5, no. 3 (October 31, 2017): 354–58. http://dx.doi.org/10.12944/carj.5.3.14.
Повний текст джерелаАнотація:
Rapeseed – mustard is one of the most important cruciferous oilseed crops basically raise for oils and vegetables to meet domestic consumption of marginal farmers during rabi season in Manipur. Field experiments were conducted under organic condition for two consecutive years ( 2014 & 2015) during rabi seasons at Kakching. Weekly surveys detected white rust of rapeseed –mustard on the four varieties used. Amendments of agronomic practices including sowing dates, intercropping and plant density besides addition of soil with FYM (Farmyard Manure) were found effective on fungal disease of the crop. The disease parameters were monitored through disease incidence (DI) and disease severity (DS) assessment technique. The least disease severity (9.57%) was found in plant density followed by date of sowing (11.06%) and intercropping (12.29%). White rust caused by Albugo candida attacked the crop from mild to severe form and the effect of agronomic practices applied were significant in controlling the white rust disease of the crop.
20
Sawyer, Logan Everett. "Constitutional Principle, Partisan Calculation, and the Beveridge Child Labor Bill." Law and History Review 31, no. 2 (May 2013): 325–53. http://dx.doi.org/10.1017/s0738248013000059.
Повний текст джерелаАнотація:
Following the 1906 midterm elections, Indiana Senator Albert Beveridge was excited to return to Washington to introduce a bill that would prohibit child labor in the nation's factories, mines, and mills. He hoped the bill would curtail the unpopular practice and help rebrand his Republican Party as the nation's progressive party. The Party's old guard, however, proved uncooperative. Recognizing the unpopularity of child labor, they fought the bill on constitutional grounds and challenged Beveridge with a parade of horribles. If Congress could constitutionally regulate child labor, they asked, could it not also regulate the hours or wages of adults? Could it not prevent a man from joining a labor union? Or require it? One would have expected Beveridge—who opposed such regulations—to blunt that criticism with some legal distinction. Instead, he embraced it. Would Beveridge go so far as to claim that Congress could prohibit the interstate shipment of cotton picked by children, asked one Senator. “Yes,” Beveridge retorted, “or [by] a redheaded girl.”
21
Quick, R. C., W. J. Sonnenstuhl, and H. M. Trice. "Educating the Employee Assistance Professional: Cornell University's Employee Assistance Education and Research Program." Public Personnel Management 16, no. 4 (December 1987): 333–43. http://dx.doi.org/10.1177/009102608701600406.
Повний текст джерелаАнотація:
This article outlines in considerable detail Cornell University's Employee Assistance Education and Research Program which is funded by the New York State Department of Alcoholism and Alcohol Abuse, in cooperation with the Christopher D. Smithers Foundation of Mill Neck, NY. It utilizes an academic curriculum in combination with field experience to further develop the EAP profession. It has been on-going since the Fall of 1985 in various New York State cities (Syracuse, New York, Rochester, and Albany) and will soon expand to include Buffalo and Long Island. The authors were assisted with implementation of the program by Bernard Flaherty, who acts as its co-director, and who is Director of the Central District of Cornell's Extension Division of the School of Industrial and Labor Relations. In addition, the article addresses a dilemma faced by personnel executives as they try to reach decisions about how to assure quality in the EAP programs, and in the personnel who staff them. On the one hand, they seek practical, applied programs that can be readily implemented and attractive to employees. On the other, there is a need to feel confident that the EAP personnel they employ are thoroughly acquainted with the workplace, and with the treatment place, and have a sound understanding of the emotional disturbances that cause troubled employees to be poor performers.
22
Reavley, Martha A. "Organizational Behaviour in a Global Context. Albert J. Mills, Jean C. Helms Mills, Carolyn Forshaw and John Bratton (2007). Peterborough, Ontario: Broadview Press, 599 pages (softcover) ISBN: 1-551-93057-9." Canadian Journal of Administrative Sciences / Revue Canadienne des Sciences de l'Administration 24, no. 2 (2007): 146. http://dx.doi.org/10.1002/cjas.8.
Повний текст джерела
23
Spinnato, Paolo, Elena Pedrini, Miriana Rosaria Petrera, Paola Zarantonello, Giovanni Trisolino, Luca Sangiorgi, Maria Carpenzano, Amandine Crombé, and Cecilia Tetta. "Spectrum of Skeletal Imaging Features in Osteopetrosis: Inheritance Pattern and Radiological Associations." Genes 13, no. 11 (October 28, 2022): 1965. http://dx.doi.org/10.3390/genes13111965.
Повний текст джерелаАнотація:
Osteopetrosis (from the Greek “osteo”: bone; “petrosis”: stone) is a clinically and genetically heterogeneous group of rare diseases of the skeleton, sharing the same main characteristic of an abnormally increased bone density. Dense bones in radiological studies are considered the hallmark of these diseases, and the reason for the common term used: “Marble bone disease”. Interestingly, a radiologist, Dr. Albers-Schonberg, described this disease for the first time in Germany in 1904. Indeed, radiology has a key role in the clinical diagnosis of osteopetrosis and is fundamental in assessing the disease severity and complications, as well as in follow-up controls and the evaluation of the response to treatment. Osteopetrosis includes a broad spectrum of genetic mutations with very different clinical symptoms, age onset, and prognosis (from mild to severe). This diversity translates into different imaging patterns related to specific mutations, and different disease severity. The main recognized types of osteopetrosis are the infantile malignant forms with autosomal recessive transmission (ARO—including the rarer X-linked recessive form); the intermediate autosomal recessive form (IAO); and the autosomal dominant ones ADO, type I, and type II, the latter being called ‘Albers-Schonberg’ disease. Imaging features may change among those distinct types with different patterns, severities, skeletal segment involvement, and speeds of progression. There are several classical and well-recognized radiological features related to osteopetrosis: increased bone density (all types with different degrees of severity assuming a ‘Marble Bone Appearance’ especially in the ARO type), different metaphyseal alterations/enlargement including the so-called ‘Erlenmeyer flask deformity’ (particularly of femoral bones, more frequent in ADO type 2, and less frequent in ARO and IAO), ‘bone in bone’ appearance (more frequent in ADO type 2, less frequent in ARO and IAO), and ‘rugger-jersey spine’ appearance (typical of ADO type 2). After conducting an overview of the epidemiological and clinical characteristic of the disease, this review article aims at summarizing the main radiological features found in different forms of osteopetrosis together with their inheritance pattern.
24
Kriegel, Maurice. "Le marranisme Histoire intelligible et mémoire vivante." Annales. Histoire, Sciences Sociales 57, no. 2 (April 2002): 323–34. http://dx.doi.org/10.3406/ahess.2002.280048.
Повний текст джерелаАнотація:
«Les miracles qu’ils [les Juifs] racontent pourraient lasser mille bavards. Mais ce dont ils s’enorgueillissent le plus, c’est qu’ils comptent beaucoup plus de martyrs que n’importe quelle autre nation et que chaque jour s’accroît le nombre de ceux d’entre eux qui, pour leur foi, souffrent avec une extraordinaire force d’âme; et ceci n’est pas une légende; parmi bien d’autres, j’ai connu moi-même un certain Judas, dit le Fidèle, qui s’est mis à chanter au milieu des flammes, et tandis qu’on le croyait mort, l’hymne: “À toi, mon Dieu, j’offre mon âme”: il est mort en chantant.» Spinoza a été apparemment trahi par sa mémoire, puisqu’il n’a pu rencontrer «Judas le Fidèle», brûlé à Valladolid en 1644 sans avoir jamais quitté la péninsule Ibérique, mais il fait en tout cas écho, dans ce passage de sa réponse à Albert Burgh, à la célébration des martyrs telle que la pratiquait de son temps la communauté juive d’Amsterdam. Des martyrs, ou en tout cas de ceux qui, au gré de cette communauté, sont «les siens»: toutes les victimes de l’Inquisition espagnole ou portugaise ne se sont certes pas réclamées de ce judaïsme pour lequel on les envoyait au bûcher.
25
Mohammed, I. U., M. M. Abarshi, B. Muli, R. J. Hillocks, and M. N. Maruthi. "The Symptom and Genetic Diversity of Cassava Brown Streak Viruses Infecting Cassava in East Africa." Advances in Virology 2012 (2012): 1–10. http://dx.doi.org/10.1155/2012/795697.
Повний текст джерелаАнотація:
The genetic and symptom diversity of six virus isolates causing cassava brown streak disease (CBSD) in the endemic (Kenya, Mozambique, and Tanzania) and the recently affected epidemic areas (Uganda) of eastern Africa was studied. Five cassava varieties; Albert, Colombian, Ebwanateraka, TMS60444 (all susceptible) and Kiroba (tolerant) were graft inoculated with each isolate. Based on a number of parameters including the severity of leaf and root symptoms, and the extent of virus transmission by grafting, the viruses were classified as either severe or relatively mild. These results were further confirmed by the mechanical inoculation of 13 herbaceous hosts in which the virulent isolates caused plant death inNicotiana clevelandiiandN. benthamianawhereas the milder isolates did not. Phylogenetic analysis of complete coat protein gene sequences of these isolates together with sequences obtained from 14 other field-collected samples from Kenya and Zanzibar, and reference sequences grouped them into two distinct clusters, representing the two species of cassava brown streak viruses. Put together, these results did not suggest the association of a hypervirulent form of the virus with the current CBSD epidemic in Uganda. Identification of the severe and milder isolates, however, has further implications for disease management and quarantine requirements.
26
Ernst, Daniel R. "The Politics of Administrative Law: New York's Anti-Bureaucracy Clause and the O'Brian-Wagner Campaign of 1938." Law and History Review 27, no. 2 (2009): 331–72. http://dx.doi.org/10.1017/s0738248000002030.
Повний текст джерелаАнотація:
In April 1938 New York's first constitutional convention since 1915 convened in Albany. When it adjourned in late August, one of the amendments slated for a referendum that fall was an “anti-bureaucracy clause,” a provision that would greatly increase the New York courts' oversight of the state's agencies. Although voters rejected it, contemporaries saw the anti-bureaucracy clause as a harbinger of a national campaign against the New Deal. In September 1938 Charles Wyzanski, a former member of the Solicitor General's office, warned Attorney General Homer Cummings that the anti-bureaucracy clause was “the advance signal of an approaching partisan attack on a national scale.” Wyzanski was right: in early 1939 a bill endorsed by the American Bar Association's House of Delegates was introduced in Congress by Representative Francis Walter and Senator Marvel Mills Logan. Just as the New York provision “would have almost certainly destroyed the effectiveness of the state administrative agencies,” the New Dealer Abe Feller warned Cummings's successor, so would the Walter-Logan bill hamstring the federal government. When President Franklin Roosevelt vetoed the bill in December 1940, he declared it part of a national campaign that had begun with the anti-bureaucracy clause.
27
Gates, M., R. M. Hanning, A. Isoga, A. Gates, J. Metatawabin, and L. J. S. Tsuji. "A comprehensive school nutrition program improves knowledge and intentions for milk and alternatives intake among youth in Fort albany First Nation (FN)." Canadian Journal of Diabetes 35, no. 2 (January 2011): 208. http://dx.doi.org/10.1016/s1499-2671(11)52253-1.
Повний текст джерела
28
Batchman, Amy. "Book Review: Boswell-Penc, M. (2006). Tainted Milk: Breastmilk, Feminisms, and the Politics of Environmental Degradation. Albany: State University of New York Press." Violence Against Women 13, no. 4 (April 2007): 444–47. http://dx.doi.org/10.1177/1077801207299207.
Повний текст джерела
29
Mazrui, Ali A. "Islam in a More Conservative Western World." American Journal of Islam and Society 13, no. 2 (July 1, 1996): 246–49. http://dx.doi.org/10.35632/ajis.v13i2.2317.
Повний текст джерелаАнотація:
My findings are tentative and subject to further research. This presentationrests on three paradoxes of great relevance to Muslims in the West.The first paradox is that, from the point of views of Muslims in the West,western secularism might be good news and western materialism might bebad news. In other words, western secularism is perhaps a blessing in disguisefor Muslims, whereas western materialism is a curse. The secondparadox is that recent Republican, rather than Democratic, foreign policyhas been more friendly to Muslims, wherea Democratic, rather thenRepublican, domestic policies are probably more friendly to Muslims. Thethird paradox concerns the two Islams in the United States: indigenou andimmigrant. In the United States, western secularism has protected minorityreligious groups by insisting on the separation of church and state. Thisis as major reason why American Jews have been among the greatestdefenders of the separation of church and state, for any breach could leadto the imposition of some practices of the religious majority, such as forcingJewish children to participate in Christian prayers at school.The secular state permits religious minorities to practice their religionsin relative peace. Of course, like all doctrines, secularism has its fanaticwho sometimes want to degrade, rather than protect, the sacred. But at itsbest, a secular state is a refuge of safety for minority religions. It is in thissense that western secularism is a friend of Muslims living in the West.But while secularism represents a divorce from formal religion, materialismis a dilution of spirituality. One can be without a formal religion andstill be deeply spiritual in a humanistic sense. John Stuart Mill and BertrandRussell, for example, had no formal religion, yet each had deeply spiritualvalues. Albert Schweitzer, the Nobel Laureate for Peace and an eventualagnostic, remained deeply committed to the principle of reverence for life,even to the extent of protecting the lives of insects in Africa ...
30
Prášilová, Marie, Lucie Severová, Lenka Kopecká, and Roman Svoboda. "Duopoly price competition on markets with agricultural products." Acta Universitatis Agriculturae et Silviculturae Mendelianae Brunensis 59, no. 4 (2011): 241–50. http://dx.doi.org/10.11118/actaun201159040241.
Повний текст джерелаАнотація:
A situation, in which two firms compete, is in the economic theory described by duopoly models. Market equilibrium on the duopoly market is formed in a reciprocal adjustment process of market prices and materialized market opportunities. The goal of the analysis is to find out whether the agricultural products market is significantly influenced by appearance of duopolies, what form they have and if they can fundamentally influence the price level of food. That food chain stores endeavour to mutually adapt food product prices is generally known; it is set especially by the inelastic demand for the mentioned goods on the side of consumers, i.e., by the need to demand basic food. Duopoly reactions to price competition in food chain stores are particularly strong in the case of commodities of milk and tomatoes, where the reactions and approximation of prices can be clearly seen. Based on statistical research it is obvious that the reactions are most reflected on sales of the food chain stores Billa and Albert. To identify specific reactions of price duopoly at retail chains the ANOVA statistical method was used. The firm’s duopoly behaviour as such on the food market need not be a subject for applying punishment from the antimonopoly bureau, if it does not have the cartel agreement character. An example can be the identical potato prices inquiry in the supermarkets of food chain stores.
31
Amin-Rasouli, Hadi, and Yaghoob Lasemi. "Facies changes and a major negative d13C shift suggest the base of Mila Formation as the likely base of the Miaolingian Series, Alborz Mountains, northern Iran." Sedimentary Record 19, no. 1 (March 30, 2021): 11–14. http://dx.doi.org/10.2110/sedred.2021.1.04.
Повний текст джерела
32
Mandal, Partha Sarathi. "Politics of Self and Other, Act of Ambivalence and Resistance, Cricket and Colonialism, Indian Pluralism, Anti-colonial Propagan." Journal of English Language and Literature 11, no. 2 (April 30, 2019): 1120–27. http://dx.doi.org/10.17722/jell.v11i2.413.
Повний текст джерелаАнотація:
Narayan’s Swami and Friends (1935) luminously portrays its child protagonist Swaminathan’s adventures in soul making, his skirmishes with his little comrades and reconciliations in his soupy school, his contact with the experienced adult world vis-à-vis apparently apolitical, shallow and banal Swami and Friends (1935) also postulates encoded political and cultural resistance so strategically camouflaged by Narayan’s narrative devise. Narayan’s Anti-colonial propaganda, his aversion to fundamentalism and authoritarianism, his earnest desire to bring the subaltern narrative into our mainstream narrative give him a special place in literary world. Kudos to the Nietzschean Will to Power of the common inhabitants of Malgudi and the little urchins of Albert Mission School that they dared to join the protest march against the hegemony of their white colonial masters. Swami much like Ishaan of Aamir Khan’s Taare Zameen Par (2007) used to shudder at the very thought of his monotonous school where his wings of freedom used to be crushed under the fatal mill of the authoritarian and strict teachers except D.Pillai who was famous among the students. Swaminathan’s hybrid identity, Rajam’s Europeanized existence, overlapping associations of tradition and modernity, class struggle, Centre/Periphery, Self/Other, Master/Slave dichotomy in Swami and Friends (1935) actually celebrate Narayan’s deep concern for our pluralistic and multicultural Indian identity where Narayan has also given space to the subaltern existence like Rajam’s family cook who was insulted and undervalued by Rajam only because Rajam belonged to the centre of a power structure. In this paper I would like to investigate in which way Narayan has pointed out the various agathokakological entities of human life through the artistic representation of his characters, his celebration of India’s heterogeneous identity, class struggle, the marginalized and peripheralized existence of subaltern voices, politics of colonial masters’ Self and the muted Other in an unequal power structure where a very limited number of people actually get access to the resources , ambivalence, hybrid identity etc. with reference to Swami and Friends (1935).
33
Ganguli, Mary, and Eric Rodriguez. "Age, Alzheimer's disease, and the big picture." International Psychogeriatrics 23, no. 10 (September 16, 2011): 1531–34. http://dx.doi.org/10.1017/s1041610211001906.
Повний текст джерелаАнотація:
The recently published revised National Institute on Aging/Alzheimer's Association clinical diagnostic criteria for Alzheimer's disease (AD) (Albert et al., 2011; Jack et al., 2011; McKhann et al., 2011; Sperling et al., 2011) have been hailed for incorporating a number of timely and important advances. They reflect new understanding that has been gained since the previous criteria were published in 1984 (McKhann et al., 1984). They include recognition of the state of mild cognitive impairment that is present before the threshold is crossed into dementia; they recognize the potential role of biomarkers in enhancing the specificity of diagnosis; they also address emerging work in the preclinical stage of AD that could help in understanding the sequence and stages of the core pathology before symptoms emerge. Among the previously listed diagnostic features that have disappeared was the requirement that onset of dementia occur before the age of 90 years. Meanwhile, the Neurocognitive Disorders Work Group for DSM-5 (the 5th edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders; American Psychiatric Association, 2010) is also doing away with the previous distinction between early-onset and late-onset dementia in AD, where an arbitrary division had been placed at age 65 (American Psychiatric Association, 2000). These changes are driven by the lack of biological data to support the age-based dichotomy, while recognizing the unique genetic characteristics of the relatively rare, autosomal dominantly inherited forms of AD which typically occur early. However, the disappearance of the age-based diagnostic dichotomy by no means implies that age is irrelevant to AD.
34
Cui, Min-Hui, Craig A. Branch, and Rhoda Elison Hirsch. "Magnetic Resonance Imaging Reveals Significantly Increased Cerebral Blood Flow in the Hemoglobin E Mouse Model." Blood 138, Supplement 1 (November 5, 2021): 2034. http://dx.doi.org/10.1182/blood-2021-149578.
Повний текст джерелаАнотація:
Abstract Hemoglobin E (HbE) is the most common hemoglobin mutation world-wide. EE individuals exhibit a mild anemia as do those with β-thalassemia trait. A paradox arises with the combination of two relatively benign genes in HbE/β-thalassemia (HbE/β-thal) giving rise to highly morbid symptoms, anemia, growth retardation, developmental retardation, thalassemic bone type development, chronic leg ulcers (for a review, S Fucharoen and DJ Weatherall 2012) and often early mortality arising from cardiac failure (N Olivieri, Z Pakbaz et al. 2011). One approach to understanding the characteristics of HbE and this paradox was to generate a transgenic mouse model, expressing solely human HbE. This HbE mouse model exhibits a mild oxidative stress that parallels that observed in human EE individuals (QY Chen, EE Bouhassira et al. 2004, QY Chen, ME Fabry et al. 2012). These transgenic mice also exhibit mild cardiac dysfunction with depressed left ventricular contraction. We present here the first evidence of a significant increase in cerebral blood flow in the full knockout HbE (HbEKO) transgenic mouse model expressing solely human HbE compared to both the HbE+HbF (γ, gamma)-globin transgenic mouse, and the normal background C57 mouse. Cerebral blood flow is assessed non-invasively by MRI imaging. All protocols were approved by the Albert Einstein Institutional Animal Care and Use Committee. Comparing the HbEKO mouse (without human γ globin) to the C57 normal background mouse, a significant increase of over 20% in thalamus cerebral blood flow at baseline is observed (p=0.008). There is also an approximate 18% reduction in thalamus cerebral blood flow comparing HbE low γ mice to the full HbEKO (no γ) (p=0.011). Concomitant with these observations, no significant difference is observed comparing these low gamma HbE mice to the normal C57 background mouse (p=0.384). The goodness of the data is also seen in the relatively small variation in cerebral blood flow amongst the individual mice in each subset. These findings are of particular relevance to reports of neurologic symptoms, intracerebral hemorrhage, and brain infarct in HbE/β-thal patients (V Wong, YL Yu et al. 1990, S Das, S Dubey et al. 2019). In conclusion, these results suggest a direct role of HbE RBC initiating altered cerebral blood flow that when further complexed with β-thal could lead to intracerebral hemorrhage and other cerebral pathophysiology. The finding that the HbEKO mice with high HbF are not significantly different in cerebral blood flow from C57 mice may lend further support to therapeutic approaches enhancing the production of HbF in severe hemoglobinopathies, such as in sickle cell anemia, HbE/β-thal, and β-thal individuals. Disclosures No relevant conflicts of interest to declare.
35
Murtola, Anna-Maria. "Book review: The Dark Side: Critical Cases on the Downside of Business Emmanuel Raufflet and Albert J. Mills (eds). Sheffield: Greenleaf Publishing, 2009. 294 + vi pp. £24.95 (hbk). ISBN 9781906093204." Management Learning 41, no. 5 (October 27, 2010): 612–15. http://dx.doi.org/10.1177/13505076100410050606.
Повний текст джерела
36
McFadden, Margaret H. "Wendy M. Gordon. Mill Girls and Strangers: Single Women's Independent Migration in England, Scotland, and the United States, 1850–1881. Albany, N.Y.: State University of New York Press. 2002. Pp. x, 234. $22.95 paper. ISBN 0-7914-5526-2." Albion 35, no. 4 (2004): 685–86. http://dx.doi.org/10.2307/4054336.
Повний текст джерела
37
Chaudhry, Rafia, Anum Bilal, Adam Austin, Swati Mehta, Loay Salman, Llewellyn Foulke, Paul Feustel, Roman Zuckerman, and Arif Asif. "ANCA associated vasculitis: experience of a tertiary care referral center." Brazilian Journal of Nephrology 41, no. 1 (March 2019): 55–64. http://dx.doi.org/10.1590/2175-8239-jbn-2018-0040.
Повний текст джерелаАнотація:
ABSTRACT Background and objectives: Anti-neutrophil cytoplasmic autoantibodies (ANCA) associated vasculitis is a small vessel vasculitis with insufficient epidemiologic estimates in the United States. We aimed to determine demographic and clinical features of ANCA associated vasculitis patients presenting to a large tertiary care referral center in Upstate New York. Design, setting, participants, and measurements: A retrospective analysis of cases with pauci-immune GN on renal biopsy and clinical diagnosis of ANCA vasculitis presenting over 11 years was conducted. Outcomes of interest were: demographics, ANCA antibody positivity, patient and renal survival, and regional trends. Results: 986 biopsies were reviewed, 41 cases met the criteria for inclusion: 18 GPA, 19 MPA, and 4 double positive (anti-GBM disease plus ANCA vasculitis). Mean age at presentation was 52.4 years (SD 23.7), 23 (56%) were male and median creatinine was 2.6 mg/dL. The median patient follow up was 77 weeks (IQR 10 - 263 weeks), with a 3-month mortality rate of 5.7% and a 1-year estimated mortality rate of 12%. Thirteen patients required hemodialysis at the time of diagnosis; 7 patients came off dialysis, with median time to renal recovery of 4.86 weeks (IQR 1.57 - 23.85 weeks). C-ANCA positivity (p < 0.001) and C-ANCA plus PR3 antibody pairing (p = 0.005) was statistically significant in GPA versus MPA. P-ANCA positivity was observed in MPA versus GPA (p = 0.02) and double positive versus GPA (p = 0.002), with P-ANCA and MPO antibody pairing in MPA versus GPA (p = 0.044). Thirty-seven of the 41 cases were referred locally, 16 cases were from within a 15-mile radius of Albany, Schenectady, and Saratoga counties. Conclusions: ANCA vasculitis is associated with end stage renal disease and increased mortality. Our study suggests the possibility of higher regional incidence of pauci-immune GN in Upstate New York. Further studies should investigate the causes of clustering of cases to specific regions.
38
Seyhan, Azade. "Why Major in Literature—–What Do We Tell Our Students?" PMLA/Publications of the Modern Language Association of America 117, no. 3 (May 2002): 510–12. http://dx.doi.org/10.1632/003081202x61296.
Повний текст джерелаАнотація:
It is precisely because of the elusive character of real life that we need the help of fiction to organize life retrospectively, after the fact, prepared to take as provisional and open to revision any figure of emplotment borrowed from fiction or from history.–Paul RicoeurIn the aftermath of what has come to be known as Nine One One, literary texts became the last resort of consolation in a vast desert of mindless media commentary and aggressive but ultimately futile political rhetoric. The Philadelphia Inquirer promptly published email messages exchanged by four University of Pennsylvania students trying to grapple with the tragic enormity of the historical moment. For these students “[t]he old world died on Tuesday [11 Sept. 2001],” and they had to learn to live in a new reality. To make sense of this not-so-brave new world, they sought for answers in “books and literature” (“Facing”). Mass-circulated email carried messages of consolation in literary format across the cyber globe. W. H. Auden's “September 1, 1939” was reprinted in all the major newspapers and forwarded to countless e-mail accounts. The conservative columnist George F. Will quoted liberally from the closing lines of Albert Camus's The Plague. “Today's president, his rhetorical rheostat turned way up, vows that the current military campaign 'will rid the world of evil,'” observed Will with undisguised sarcasm. He countered the president's naiveté by citing Camus's allegory of the plague as the permanence of evil in the world. In the final paragraph of the novel, Camus's narrator, Dr. Rieux, muses that the plague bacillus never dies but lies dormant until its time comes to unleash its terror on an unsuspecting world once again. By invoking The Plague, Will wanted to remind his fellow Americans “who are mild in temperament and amnesiac in tendency” that for America “there are only two kinds of years, the war years and the interwar years.” The banality of this conclusion contrasts sharply with the profundity of Camus's final lines.
39
Albert, J., T. Hosey, and B. Lamoreaux. "THU0431 PEGLOTICASE RESPONSE RATE IN UNCONTROLLED GOUT PATIENTS CO-TREATED WITH METHOTREXATE: EXPERIENCE IN A COMMUNITY RHEUMATOLOGY PRACTICE." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 453.2–454. http://dx.doi.org/10.1136/annrheumdis-2020-eular.2076.
Повний текст джерелаАнотація:
Background:Pegloticase is an infused biologic approved to treat uncontrolled gout. The drug is highly effective, but patients can develop anti-drug antibodies that interfere with efficacy.1Randomized clinical trials have shown that 42% of patients treated with bi-weekly pegloticase had a serum uric acid (sUA) below 6.0 mg/dl at 3 and 6 months.2Mild-to-moderate immunomodulation has been shown to lower the prevalence of anti-drug antibody formation in patients with other autoimmune diseases (rheumatoid arthritis, Crohn’s disease, juvenile idiopathic arthritis).3Cases published in the literature suggest that low-to-moderate doses of methotrexate4,5or azathioprine6may also attenuate anti-pegloticase antibody formation in uncontrolled gout patients. Therefore, immunomodulation may allow patients to remain on pegloticase therapy longer and achieve a more complete therapeutic response.Objectives:To examine pegloticase treatment response in patients co-treated with methotrexate.Methods:This retrospective chart review included patients from a single community rheumatology practice who began pegloticase (8 mg every 2 weeks) therapy between January 2017 and September 2019 and were co-treated with methotrexate. Unless contraindicated, methotrexate co-treatment with pegloticase is now standard in this practice and all patients undergo close monitoring of laboratory parameters including serum uric acid level (sUA), blood counts, and liver function tests (LFTs). To maximize the number of cases, patients administered methotrexate in any form were included. Collected data included demographic information, laboratory values, methotrexate treatment parameters (timing with respect to pegloticase therapy, dose, route), pegloticase response parameters (number of infusions, duration of therapy), and adverse events. Main outcome measures included the number of pegloticase infusions administered (responder defined as ≥12 infusions administered) and therapy duration.Results:Ten patients (9 male) were included. All patients had visible tophi and average patient age was 52.3 ± 13.5 years. Nine patients began subcutaneous methotrexate (25 mg weekly) an average of 19.9 ± 7.0 days (range: 14 to 35 days) before the first pegloticase infusion. The remaining patient began oral methotrexate (12.5 mg weekly) 14 days after the first pegloticase infusion. Eight of 10 patients (80%) were considered responders, receiving an average of 15.5 ± 3.8 pegloticase infusions (range: 12-21 infusions) over 31.8 ± 9.5 weeks (range: 22.1 to 48.3 weeks). In these 8 responders, mean sUA was 0.2 ± 0.0 mg/dL immediately prior to the last pegloticase infusion. All 10 patients had an initial, rapid decrease in sUA, but two patients discontinued treatment before infusion 12. One patient had increased sUA with a mild infusion reaction, and one patient was lost to follow-up after infusion 5. No new safety concerns emerged. A gout flare occurred in 1 patient and was treated with prednisone. LFT and blood cell parameters were stable over the study period, except in two patients. One had a mild, transient LFT elevation that resolved without treatment, one had an LFT elevation and pancytopenia that improved with methotrexate discontinuation and transfusion, respectively. This patient remained on pegloticase and continued as a responder.Conclusion:This case series suggests that methotrexate, when used as a co-therapy with pegloticase, allows more patients to complete therapy and to achieve the full therapeutic response. No new safety concerns emerged.References:[1]Lipsky PE, et al.Arthritis Res Ther2014;16:R60.[2]Sundy JS, et al.JAMA2011;306:711-20.[3]Krieckaert CL, et al.Arthritis Res Ther2010;12:217.[4]Botson J and Peterson J.Ann Rheum Dis.2019; 78: A1289.[5]Bessen SY, et al.Semin Arthritis Rheum.2019;49:56-61.[6]Berhanu AA, et al.Semin Arthritis Rheum.2017;46:754-758.Disclosure of Interests: :John Albert Consultant of: Horizon Therapeutics, Speakers bureau: Horizon Therapeutics, Tony Hosey Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Brian LaMoreaux Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics
40
Widdicombe, John. "Book Review Fatal Asthma Edited by Albert L. Sheffer, with William W. Busse, Peyton A. Eggleston, Thomas A.E. Platt-Mills, Malcolm R. Sears, and Kevin B. Weiss. 607 pp. New York, Marcel Dekker, 1998. $195. 0-8247-0155-0." New England Journal of Medicine 339, no. 25 (December 17, 1998): 1864–65. http://dx.doi.org/10.1056/nejm199812173392521.
Повний текст джерела
41
Mangwende, E., J. B. Kalonji Kabengele, M. Truter, and T. A. S. Aveling. "First Report of White Rust of Rocket (Eruca sativa) Caused by Albugo candida in South Africa." Plant Disease 99, no. 2 (February 2015): 290. http://dx.doi.org/10.1094/pdis-09-14-0947-pdn.
Повний текст джерелаАнотація:
Garden rocket (Eruca sativa syn.: E. vesicaria subsp. sativa (Mill) Thell.) is an annual plant of the Brassicaceae grown for fresh consumption as a salad vegetable. During winter (May to July) of 2013 and 2014 in South Africa, typical symptoms of white rust were observed in two commercial crops (each ~0.5 ha) of the garden rocket cv. Rucola coltivata in Centurion, Gauteng Province, at 33 and 80% incidence, respectively. Symptomatic leaves were deposited in the National Collection of Fungi, Plant Protection Research Institute, Agricultural Research Council, Pretoria, South Africa (PREM 61073). Early infections appeared as white to cream, blister-like sori on the lower leaf surfaces, and pale yellow lesions on the corresponding upper leaf surfaces. Later stages of infection were characterized by coalescing of lesions into large, irregular, necrotic blotches and development of additional sori on the petioles and stems. Sporangiophores were hyaline, clavate or cylindrical, and measured 24 to 30 × 11 to 14 μm (n = 50). Sporangia developed in basipetal chains and were hyaline, globose or polyangular, and 15 to 20 μm (n = 100). Based on these morphological characters and the host plant, the pathogen was identified as Albugo candida (Pers.) Kunze (2). Genomic DNA was extracted using the DNeasy Plant Mini DNA extraction kit (Qiagen) from sori containing sporangia collected from naturally infected leaves, according to the manufacturer's specifications. The internal transcribed spacer (ITS) region of ribosomonal DNA (rDNA) and the cytochrome c oxidase subunit II (COX2) region were amplified and sequenced (1). The ITS (GenBank Accession No. KM588081) and COX2 (KM588082) sequences confirmed identity of the pathogen as A. candida with 100% homology to the corresponding sequences of several A. candida isolates, including DQ418503 for the ITS sequence and DQ418514 for the COX2 sequence, of a voucher specimen of A. candida on E. sativa (BPI 184870) from Pakistan. Inoculum was prepared by scraping sporangia from infected leaves of the cv. Rucola coltivata collected from the 2014 field and placing the material in sterilized, distilled water (SDW) for 12 h at 5°C to induce zoospore formation. Pathogenicity tests were performed by spraying a suspension of 1 × 105 sporangia/ml onto each of 10 5-week-old rocket seedlings of the cv. Rucola coltivata. Ten additional seedlings were inoculated similarly with SDW to serve as a control treatment. The plants were maintained at 12 to 15°C and 95% RH for 72 h (3) before being moved to a shaded greenhouse at 20 to 24°C and 90% RH. Control plants remained symptomless, whereas white rust symptoms similar to those observed in the original fields developed on leaves of inoculated seedlings 10 to 14 days later, demonstrating that A. candida was the causal agent of the disease on E. sativa. To our knowledge, this is the first report of A. candida infecting garden rocket in South Africa. References: (1) Y.-J. Choi et al. Mol. Phylogenet. Evol. 40:400, 2006. (2) K. Mukerji. Descriptions of Pathogenic Fungi and Bacteria No. 458. CMI, Kew, Surrey, UK, 1975. (3) M. J. Sullivan et al. Plant Dis. 86:753, 2002.
42
Albert, J., A. Broadwell, K. Masri, L. Padnick-Silver, and B. Lamoreaux. "AB1048 ESTIMATED GLOMERULAR FILTRATION RATE CHANGES IN UNCONTROLLED GOUT PATIENTS CO-TREATED WITH PEGLOTICASE AND METHOTREXATE: A RETROSPECTIVE CASE SERIES." Annals of the Rheumatic Diseases 81, Suppl 1 (May 23, 2022): 1646.2–1647. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1908.
Повний текст джерелаАнотація:
BackgroundGout patients are at increased risk for developing chronic kidney disease (CKD)1 and hyperuricemia is an independent risk factor for CKD worsening,2,3 particularly in women.3 As a result, renal function is of concern in uncontrolled gout patients. Pegloticase, a recombinant PEGylated uricase, can rapidly decrease serum uric acid levels (sUA) in uncontrolled gout patients, but with pegloticase monotherapy <50% have sustained urate-lowering during Month 6 of treatment.4 Pegloticase treatment response rate is markedly higher when immunomodulating therapies such as methotrexate (MTX) are co-administered,5,6 but MTX use can be limited by renal impairment. Clinical trials excluded CKD patients, but real-world published cases of immunomodulation-pegloticase co-therapy have included patients with a pre-therapy eGFR <60 ml/min/1.73 m2.ObjectivesThis study examined pooled case data from prior studies, focusing on renal function changes during MTX-pegloticase co-treatment in patients with and without pre-therapy CKD.MethodsThis retrospective study examined deidentified case data collected for prior retrospective studies.7-9 All patients who underwent MTX-pegloticase co-therapy were included and categorized as CKD (baseline eGFR <60 ml/min/1.73 m2) or non-CKD (baseline eGFR ≥60 ml/min/1.73 m2). sUA, renal function, blood cell counts, and liver function were closely monitored during therapy. Patient characteristics, pegloticase treatment parameters, proportion of treatment responders (≥12 infusions received and sUA <6 mg/dL at infusion 12 [ongoing patients with <12 infusions excluded]), renal function changes (eGFR, CKD stage), and adverse events were examined.Results15 uncontrolled gout patients with CKD (9 stage 3a, 4 stage 3b, 2 stage 4; pre-therapy mean[±SD] eGFR: 43.2±11.3 ml/min/1.73 m2, sUA: 8.5±2.2 mg/dL) and 27 without CKD (pre-therapy eGFR: 82.9±19.0 ml/min/1.73 m2; sUA: 9.5±1.7 mg/dL) were included. Patient characteristics and comorbidity profiles were similar, but CKD patients were older (72.0±9.9 vs. 52.3±14.3 yrs) and more often female (33% vs. 7%). On average, MTX was initiated ~4 wks before pegloticase in both CKD status groups. MTX dose was lower in CKD patients (14.8±5.8 vs. 19.3±4.9 mg/wk). Pegloticase treatment was similar between groups (CKD: 14.7±8.1 infusions over 28.5±17.1 wks, non-CKD: 14.1±7.1 infusions over 27.9±15.1 wks), with similar urate-lowering response rate (92% vs. 86%). eGFR increased during therapy in 60% and 44% of CKD and non-CKD patients, respectively, with mean eGFR increase of 11.5±20.9 and 4.2±15.0 ml/min/1.73m2, respectively. In the CKD group, CKD stage either improved or was stable in 13/15 patients (87%). The 2 patients with CKD progression both moved from stage 3a to 3b, and both stage 4 CKD patients had an eGFR increase, improving to stage 3a. In the non-CKD group, 3 patients developed stage 3 CKD (2 stage 3a, 1 stage 3b). 7/15 (47%) CKD and 13/27 (48%) non-CKD patients had ≥1 AE noted, with gout flare most reported (47% vs. 41%). A mild infusion reaction and pancytopenia occurred in 1 non-CKD patient each.ConclusionIn this retrospective real-world review of a limited number of cases, MTX-pegloticase co-therapy resulted in sustained sUA lowering in uncontrolled gout patients with and without CKD. Close monitoring of renal function indicated stability or improvement during therapy in 86% of uncontrolled gout patients with CKD. Further study is needed to better understand therapy tolerance and treatment response rates of uncontrolled gout patients with CKD undergoing MTX-pegloticase co-therapy.References[1]Roughley MJ et al. Arthritis Res Ther 2015;17:90[2]Edwards NL. Cleve Clin J Med 2008;75:S13-6[3]Iseki K et al. Am J Kidney Dis 2004;44:642-50[4]Sundy et al. JAMA 2011;306:711-20[5]Botson J et al. J Rheum 2021;48:767-74[6]Keenan RT et al. Semin Arthritis Rheum 2021;51:347-52[7]Albert J et al. Rheumatol Ther 2020;7:639-48[8]Broadwell A et al. Arthritis Rheumatol 2021;73 (suppl 10)[9]Masri KR et al. Ann Rheum Dis 2020;79:450Disclosure of InterestsJohn Albert Speakers bureau: Horizon Therapeutics, Consultant of: Horizon Therapeutics, Aaron Broadwell Speakers bureau: Horizon Therapeutics, Consultant of: Horizon Therapeutics, Karim Masri Shareholder of: Horizon Therapeutics, Speakers bureau: Horizon Therapeutics, Consultant of: Horizon Therapeutics, Lissa Padnick-Silver Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics, Brian LaMoreaux Shareholder of: Horizon Therapeutics, Employee of: Horizon Therapeutics
43
Latijnhouwers, D. A. J. M., C. H. Martini, R. G. H. H. Nelissen, H. M. J. Van der Linden, T. P. M. Vliet Vlieland, and M. G. J. Gademan. "FRI0412 DOES SEVERE ACUTE POSTOPERATIVE PAIN RESULT IN MORE LONG-TERM PAIN AFTER TOTAL HIP OR KNEE ARTHROPLASTY (THA OR TKA) FOR OSTEOARTHRITIS?" Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 805.2–805. http://dx.doi.org/10.1136/annrheumdis-2020-eular.493.
Повний текст джерелаАнотація:
Background:Chronic pain is a frequently reported unfavourable outcome of total hip and knee arthroplasties (THA/TKA) (7-23% and 10-34%, respectively) in osteoarthritis (OA) patients (1), which is difficult to treat as underlying mechanisms are not fully understood. Acute postoperative pain has been identified as risk factor for development of long-term pain in other surgical procedures, such as mastectomy and thoracotomy (2). However, the effect of acute postoperative pain on development of long-term pain in THA and TKA patients is unknown.Objectives:To investigate if acute pain following THA/TKA in OA patients is associated with long-term pain and if acute pain affects the course of pain up to 1-year postoperatively.Methods:From a longitudinal multicenter study, OA patients scheduled for primary THA or TKA were included. Acute pain scores, using Numeric Rating Scale (NRS), were routinely collected as part of standard care (≤72 hours after surgery). In case of ≥2 NRS scores the two highest scores were averaged (n=160), else the single score was taken. Pain was dichotomized into severe (NRS≥5) and mild (NRS<5). Pain was assessed preoperatively, at 3 (only THA), 6 and 12 months postoperatively using HOOS/KOOS subscale pain. Separate mixed-effect models for THA and TKA patients were used, with dichotomized acute pain as fixed-effect and long-term pain as outcome, while adjusting for confounders (age, sex, BMI, preoperative pain, mental component scale of the SF12 (MCS-12), and duration of the surgery and hospitalization). We included an interaction between time of measurement and acute postoperative pain to analyse whether effect modification was present. Missing values in preoperative pain and MCS-12 were imputed using multiple imputation methods.Results:81 THA and 87 TKA patients were included, of whom 32.1% and 56.3% reported severe acute pain. The results did not show an associated between severe acute pain and long term pain (THA: β=2.0, 95%-CI:-10.9-7.0; TKA: β=3.8, 95%-CI:-10.6-2.9). Furthermore, It seems that there is no effect present of difference in severity of acute pain and the course of pain over time (THA 6-months: β=6.4, 95%-CI:1.9-10.9 and 12-months: β=0.2, 95%-CI:-4.4-4.8; TKA 12-months: β=3.2, 95%-CI:-0.5-6.8).Conclusion:We did not find an association between acute pain and the development of long-term pain nor that severity of acute pain affects the course of postoperative pain in THA and TKA patients. The fact that THA and TKA patients often experience chronic preoperative pain might be a possible explanation for this finding. Nonetheless, future studies including additional measures of acute pain and pain sensitization in patients with chronic preoperative pain are necessary to draw stronger conclusions.References:[1]Beswick AD, Wylde V, Gooberman-Hill R, Blom A, Dieppe P. What proportion of patients report long-term pain after total hip or knee replacement for osteoarthritis? A systematic review of prospective studies in unselected patients. BMJ open. 2012;2(1):e000435.[2]Katz J, Seltzer Ze. Transition from acute to chronic postsurgical pain: risk factors and protective factors. Expert review of neurotherapeutics. 2009;9(5):723-44.Acknowledgments:We would like to thank the study group that consists of: B.L. Kaptein, Leiden University Medical Center, Leiden; S.B.W Vehmeijer, Reinier de Graaf Hospital, Delft; R. Onstenk, Groene Hart Hospital, Gouda; S.H.M. Verdegaal, Alrijne Hospital, Leiderdorp; H.H. Kaptijn, LangeLand Hospital, Zoetermeer; W.C.M. Marijnissen, Albert Schweitzer Hospital, Dordrecht; P.J. Damen, Waterland Hospital, Hoorn; the NetherlandsDisclosure of Interests:None declared
44
Zoellner, Anna-Katharina, Dusan Prevalsek, Thomas Köhnke, Susanne Fritsch, Christoph Schulz, Max Hubmann, Stephanie Lippl, et al. "Alternative Donor Transplantation Using Intensified Conditioning, T-Cell-Replete HLA-Haploidentical Grafts and Post-Transplantation Cyclophosphamide in the Treatment of High-Risk and Advanced ALL: Feasibility and Outcome." Blood 128, no. 22 (December 2, 2016): 2224. http://dx.doi.org/10.1182/blood.v128.22.2224.2224.
Повний текст джерелаАнотація:
Abstract Unmanipulated, T-cell-replete (TCR) HLA-haploidentical hematopoietic stem cell transplantation (haplo-HSCT) using post-transplantation cyclophosphamide (PTCY) for selective in vivo T-cell depletion of allo-reactive T-cells has become a valuable treatment alternative in patients with various hematologic disorders who lack a conventional donor or need timely transplant due to aggressive disease. However, as of yet few data are available for the treatment of ALL with this approach, particularly in relapsed and refractory disease. To evaluate the outcome of TCR haplo-HSCT utilizing PTCY in the context of intensified conditioning in patients with high-risk, relapsed and refractory ALL, we retrospectively analysed 29 patients (B-ALL n=27, T-ALL n=2; 12 male; median age 42 years: range 8-68) transplanted between 2010 and 2015 in five German transplant centers including one pediatric. Disease was active (relapsed/refractory) in 14 patients (48%) while others were in first (35%) or subsequent remission (17%). Eleven patients (38%) had relapsed after a previous allogeneic transplantation. Patients not in CR received cytoreductive chemotherapy prior to the conditioning regimen, according to the "sequential therapy" concept (Schmid C et al., JCO 2005; Tischer J et al, Ann Hematol 2013). Conditioning was TBI-based in 15 adults consisting of fludarabine and +/- cyclophosphamide plus either 12 Gy TBI or 8 Gy TBI applied in patients older than 55 years; children (n=3) received 10-12 Gy TBI plus etoposide. In adults with relapse after a first allogeneic transplantation conditioning was drug-based replacing TBI with treosulfan (3 x 10-12 g/m2) and etoposide. Post-grafting immunosuppression was high-dose cyclophosphamide, tacrolimus or cyclosporine A (n=4) and MMF in all patients. 27/29 patients engrafted, while 2 patients died early in aplasia. No primary graft rejection was observed. Acute GvHD grade II-IV occurred in 7 patients (24%); no patient developed grade IV acute GvHD. Mostly mild to moderate chronic GvHD was observed in 6 patients (21%), and CI of chronic GvHD at 2 years was 25%. No patient died due to GvHD. Severe toxicity (grade III-IV) was observed in 12 patients (41%), most commonly mucositis (n=34%), diarrhoea (31%), hyperbilirubinemia and transient elevation of transaminases (28%) and hemorrhagic cystitis (21%). CMV reactivated in 11/23 patients at risk and EBV in 3 while no patient developed CMV disease or PTLD. Proven invasive aspergillosis was diagnosed in 2, probable invasive aspergillosis in 5 patients. One-year non-relapse mortality (NRM) was 10%. Patients grafted with active disease experienced a one-year NRM of 14%. One-year relapse incidence was 35%. After a median follow up of 31 months (range 7.1-53.6), estimated one-year and three-year overall and relapse-free survival was 72/49% and 55/41%, respectively. In summary, intensification of the preparative regimen is well tolerated in the setting of TCR haplo-HSCT using PTCY as GvHD prophylaxis with low GVHD rates and NRM in patients with high-risk, relapsed and refractory ALL, while providing effective anti-leukemic activity. Results are at least comparable to HLA-matched transplantation. Thus, we suggest that the donor pool can be safely expanded in patients with high-risk and advanced ALL who lack a conventional donor, and that unrelated donor transplantation might be challenged in patients suffering from aggressive disease in the future. Disclosures Albert: GSK: Research Funding.
45
Bodman, Herbert. "Lebanon: A History of Conflict and Consensus, edited by Nadim Shehadi & Dana Haffar Mills. Foreword by Albert Hourani. 337 pages, bibliography, index. London: The Centre for Lebanese Studies in association with I.B. Tauris & Co., Ltd., 1992. Distributed in the US by St. Martin’s Press. $69.50 (Cloth) ISBN 1-85043-119-1." Middle East Studies Association Bulletin 28, no. 1 (July 1994): 86–87. http://dx.doi.org/10.1017/s0026318400028856.
Повний текст джерела
46
Tebas, Pablo, Joseph Agnes, Mary Giffear, Kimberly A. Kraynyak, Elliott Blackwood, Dinah Amante, Emma Reuschel, et al. "571. Safety and Immunogenicity of INO-4800, a COVID-19 DNA Vaccine as a Primary Series and Booster." Open Forum Infectious Diseases 8, Supplement_1 (November 1, 2021): S387—S388. http://dx.doi.org/10.1093/ofid/ofab466.769.
Повний текст джерелаАнотація:
Abstract Background DNA vaccines are safe, tolerable, elicit humoral and cellular responses, allow for repeated dosing over time, are thermostable at room temperature, and are easy to manufacture. We present a compilation of Phase 1 and Phase 2 data of Inovio’s US COVID-19 DNA Vaccine (INO-4800) targeting the full-length Spike antigen of SARS-CoV-2. A South Korean Phase 2 study is ongoing. Methods Participants in the open-label Phase 1 trial received 0.5 mg, 1.0 mg or 2.0 mg intradermally (ID) followed by electroporation (EP) at Days 0 and 28. An optional booster dose was administered >6 months post-dose 2. The Phase 2 further compared the 1.0 mg and 2.0 mg doses against placebo in a total of 401 participants randomized at a 3:3:1:1 ratio. ClinicalTrials.gov identifiers: NCT04336410 and NCT04642638 Results The majority of adverse events (AEs) related to INO-4800 across both trials were mild in severity and did not increase in frequency with age and subsequent doses. In Phase 1, 78% (14/18) and 84% (16/19) of subjects generated neutralizing antibody responses with geometric mean titers (GMTs) of 17.4 (95%CI 8.3, 36.5) and 62.3 (95% CI 36.4, 106.7) in the 1.0 and 2.0 groups, respectively (Figure 1). By week 8, 74% (14/19) and 100% (19/19) subjects generated T cell responses by Th1- associated IFNγ ELISPOT assay . Following a booster dose, neutralizing GMTs rose to 82.2 (95% CI 38.2, 176.9) and 124.7 (95% CI 62.8, 247.7) in the 1.0 mg and 2.0 mg groups, respectively, demonstrating the ability of INO-4800 to boost (Figure 2). In Phase 2, neutralizing antibody responses demonstrated GMTs of 93.6 (95%CI 77.3, 113.4) in the 1.0 mg dose group and 150.6 (95%CI 123.8, 183.1) in the 2.0 mg dose group (Figure 3). Conclusion INO-4800 appears safe and tolerable as a primary series and as a booster with the induction of both humoral and cellular immune responses. In addition to eliciting neutralizing antibodies, INO-4800 also induced T cell immune responses as demonstrated by IFNγ ELISpot. Finally, as a homologous booster, INO-4800, when administered 6-10.5 months following the primary series, resulted in an increased immune response without increase in reactogenicity. The 2.0 mg dose was selected for Phase 3 evaluation. Disclosures Joseph Agnes, PhD, Inovio (Employee, Shareholder) Mary Giffear, BS, Inovio Pharmaceuticals, Inc. (Employee) Kimberly A. Kraynyak, PhD, Inovio Pharmaceuticals (Employee, Other Financial or Material Support, Stock options) Dinah Amante, BS, Inovio (Employee) Emma Reuschel, PhD, Inovio Pharmaceuticals (Employee) Aaron Christensen-Quick, PhD, Inovio Pharmaceuticals, Inc (Employee) Viviane M. Andrade, PhD, Inovio Pharmaceuticals Inc. (Employee) Gabriella Garufi, PhD, Inovio Pharmaceuticals, Inc. (Employee) Albert Sylvester, MS, Inovio (Employee, Shareholder) Matthew P. Morrow, PhD, Inovio Pharmaceuticals (Employee) Patrick P. Pezzoli, BS, Inovio Pharmaceuticals, Inc. (Employee) Jan Pawlicki, PhD, Inovio Pharmaceuticals (Employee) Elisabeth Gillespie, PhD, Inovio Pharmaceuticals, Inc. (Employee) Katherine Schultheis, MSc, Inovio Pharmaceuticals (Employee) Hedieh Badie, PhD, INOVIO Pharmaceuticals (Employee) Timothy A. Herring, MPH, Inovio Pharmaceuticals, Inc. (Employee, Other Financial or Material Support, Own stock in the company) Keiko O. Simon, PhD, Inovio Pharmaceuticals (Employee) Trevor R. F. Smith, PhD, Inovio (Employee, Shareholder) Stephanie Ramos, PhD, Inovio Pharmaceuticals (Employee) Jessica Lee, MPH, Inovio Pharmaceuticals (Employee) Michael Dallas, PhD, Inovio Pharmaceuticals, Inc. (Employee, Shareholder) Ami Shah Brown, PhD, Abbot Laboratories (Shareholder)IBB Biotech ETF (Shareholder)Inovio Pharmaceuticals (Employee)J & J (Shareholder)Moderna (Shareholder) Jacqueline E. Shea, PhD, Inovio Pharmaceuticals (Employee, Shareholder) J Joseph Kim, PhD, Inovio (Employee) David Weiner, PhD, Inovio (Board Member, Grant/Research Support, Shareholder, I serve on the SAB in addition to the above activities) Kate Broderick, PhD, Inovio (Employee) Trevor McMullan, MSc, Inovio (Shareholder) Jean Boyer, PhD, Inovio (Employee) Laurent Humeau, PhD, Inovio Pharmaceuticals (Employee) Mammen P. Mammen Jr., MD, Inovio Pharmaceuticals (Employee)
47
Bogeska, Ruzhica, Paul Kaschutnig, Stella V. Paffenholz, Julia Knoch, Jan-Philipp Mallm, Malak Fawaz, Florian Buettner, et al. "No Evidence for Hematopoietic Stem Cell Self-Renewal in-Vivo Following Inflammatory Challenge." Blood 134, Supplement_1 (November 13, 2019): 456. http://dx.doi.org/10.1182/blood-2019-125744.
Повний текст джерелаАнотація:
Elevated levels of inflammation have been previously linked to both inherited and acquired bone marrow failure (BMF) syndromes, as well as to normal aging, suggesting a role in the etiology of these conditions. One potential explanation for this phenomenon is that repeated inflammation can promote the suppression of hematopoietic stem cell (HSC) function.We have previously demonstrated that interferon-α can accelerate HSC attrition by driving HSCs out of quiescence, leading to the development of BMF in a mouse model of Fanconi anemia (Walter et al. Nature, 2015). To more broadly address the impact of repetitive inflammatory challenge on HSC regeneration, we challenged C57BL6 wild type (WT) mice with polyinosinic:polycytidylic acid (pI:C), a TLR3 agonist that mimics viral infection. Injection with 1-3 rounds of pI:C (8 injections per round) in WT mice had no sustained impact on hematopoiesis, since peripheral blood (PB) and bone marrow (BM) counts were within normal ranges at 5 weeks (5wk) post-treatment. However, in vitro analysis of the clonal proliferation potential of 411 individual sorted long-term (LT)-HSCs revealed a 2-fold reduction (p<0.0001) in the total number of progeny produced per HSC. Additionally, cell fate tracking experiments showed accelerated entry into first division and differentiation following treatment. In line with this data, competitive repopulation assays demonstrated a progressive depletion of functional HSC numbers, with an approximate 2-fold decrease in multi-lineage competitive repopulating activity with each additional round of inflammatory challenge (p<0.01). In order to assess in vivo recovery of HSCs following inflammatory challenge, competitive and limiting dilution transplantation assays were used to quantify HSC frequencies using BM harvested from mice at 5, 10 or 20wk after 3 rounds of pI:C treatment. In both assays we observed a sustained ~18 fold decrease in functional HSCs, with no evidence of recovery within the 20wk window. To exclude microenvironment effects on HSC function, we performed reverse transplantation experiments in which pI.C challenged WT mice were injected with saturating doses of LT-HSCs from non-treated WT donors, in the absence of additional irradiation conditioning. We observed a durable suppression of endogenous HSCs that was sufficient to facilitate robust engraftment of donor LT-HSCs up to 20wk post-treatment. We next used the inducible transgenic Scl-tTA;H2B-GFP mouse model (Wilson et al., Cell, 2008) in order to prospectively segregate quiescent label retaining LT-HSCs (LRCs) from LT-HSCs that proliferate in vivo in response to pI:C (nonLRCs). Following a single round of pI:C challenge, label retention was reduced as a result of LT-HSC proliferation (Table 1). Importantly, the clonal proliferative potential of individual LRCs was preserved upon pI:C challenge while that of nonLRCs was more than halved. This suggests that LT-HSCs fail to undergo self-renewal divisions in vivo under these conditions but rather are functionally compromised in line with increasing proliferative history. We hypothesized that this apparent progressive irreversible depletion of functional HSCs may eventually lead to compromised hematopoiesis. We therefore assessed the hematologic parameters of aged mice that had been exposed to repetitive pI:C treatment in early to mid-life. While these mice had normal PB counts at 5wk post-treatment, upon reaching 2 years of age, treated mice demonstrated mild PB cytopenias, BM hypocellularity and a relative expansion of BM adipocytes (Table 2). Taken together, our data contradict the canonical view that HSCs demonstrate extensive self-regenerative capacity following injury. Rather, in the context of inflammatory challenge, HSCs are progressively and irreversibly depleted as they are driven out of their quiescent state. These findings have broad implications regarding the role of inflammation in the suppression of hematopoiesis that are likely relevant to BMF and also normal aging. Disclosures Lipka: InfectoPharm GmbH: Employment. Frenette:Pfizer: Consultancy; Cygnal Therapeutics: Equity Ownership; Ironwood Pharmaceuticals: Research Funding; Albert Einstein College of Medicine, Inc: Patents & Royalties.
48
Rivers, Bronwyn. ": Hao Li ,Memory and History in George Eliot: Transfiguring the Past(Hound-mills, Basingstoke: Macmillan, 2000), 227 pages, hardback, £45 (ISBN 0 312 22834 1); Marlene Tromp , Pamela K. Gilbert , and Aeron Haynie , eds,Beyond Sensation: Mary Elizabeth Braddon in Context(Albany: State University of New York Press, 2000), 302 pages, paperback, £15.50 (ISBN 0 7914 4419 8), hardback (0 7914 4420 1)." Journal of Victorian Culture 7, no. 1 (April 2002): 155–59. http://dx.doi.org/10.3366/jvc.2002.7.1.155.
Повний текст джерела
49
Di Paola, Jorge. "Novel Congenital Platelet Disorders." Blood 128, no. 22 (December 2, 2016): SCI—39—SCI—39. http://dx.doi.org/10.1182/blood.v128.22.sci-39.sci-39.
Повний текст джерелаАнотація:
The processes of megakaryocyte differentiation, proplatelet formation, and the daily release of 1011 platelets into the bloodstream are tightly regulated. Genetic disturbances can lead to a cascade of downstream molecular alterations that markedly affect the function of megakaryocytes and platelets. Therefore, identifying new genes and their function in megakaryocytes and platelets is critical for understanding how these unique cells contribute to health and disease. Over the last decade advances in genomics, specifically next generation sequencing, have allowed for the discovery of several mutations and genetic variants that cause disease or influence associated hematological traits. By performing platelet RNA-Seq we were among the first to identify NBEAL2 as the causative gene for gray platelet syndrome (GPS) and showed that NBEAL2 regulates megakaryocyte development and platelet function.1-3 Mice carrying targeted Nbeal2 null alleles not only replicated the thrombocytopenia and lack of alpha granules observed in humans, but also provided new information about the role of platelets in thromboinflammation, wound healing, myelofibrosis and metastasis dissemination.4-7 More recently, we and others found that germline mutations in ETV6 lead to thrombocytopenia, red cell macrocytosis, and predisposition to lymphoblastic leukemia.8,9ETV6 encodes an ETS family transcriptional repressor, which exerts its activity by binding a consensus sequence in the promoter regions of DNA. Mice with conditional Etv6 knockout in megakaryocytic-erythroid cells are thrombocytopenic indicating the involvement of Etv6 in thrombopoiesis.10 Several of the families recently described have a missense mutation in the central domain of ETV6 (p.P214L). This mutation results in aberrant cellular localization of ETV6, decreased transcriptional repression, and impaired megakaryocyte maturation. The bone marrow of individuals affected by this mutation show hyperplasia of immature megakaryocytes suggesting a differentiation arrest. Deep sequencing of the platelet transcriptome also revealed significant differences in mRNA expression levels between patients with the ETV6 p.P214L mutation and non-affected family members, indicating that ETV6 is critically involved in defining the molecular phenotype and function of platelets. Consistent with this notion, individuals with the ETV6 p.P214L mutation experience bleeding that is disproportionate to their mild thrombocytopenia. We have also used CRISPR/Cas9 technology to generate a mouse colony where the human p.P214L ETV6 mutation was inserted into the conserved site of Etv6. Mice with this mutation (Etv6H.P214L) have reduced platelet counts. In summary, advances in human genetics that led to the discovery of novel congenital platelet disorders coupled with relevant animal models will likely contribute to our understanding of megakaryopoiesis and platelet function. References 1. Kahr WH, Hinckley J, Li L, et al. Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome. Nature genetics. 2011;43(8):738-740. 2. Gunay-Aygun M, Falik-Zaccai TC, Vilboux T, et al. NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet alpha-granules. Nature genetics. 2011;43(8):732-734. 3. Albers CA, Cvejic A, Favier R, et al. Exome sequencing identifies NBEAL2 as the causative gene for gray platelet syndrome. Nature genetics. 2011;43(8):735-737. 4. Deppermann C, Cherpokova D, Nurden P, et al. Gray platelet syndrome and defective thrombo-inflammation in Nbeal2-deficient mice. The Journal of clinical investigation. 2013. 5. Kahr WH, Lo RW, Li L, et al. Abnormal megakaryocyte development and platelet function in Nbeal2(-/-) mice. Blood. 2013;122(19):3349-3358. 6. Guerrero JA, Bennett C, van der Weyden L, et al. Gray platelet syndrome: proinflammatory megakaryocytes and alpha-granule loss cause myelofibrosis and confer metastasis resistance in mice. Blood.2014;124(24):3624-3635. 7. Tomberg K, Khoriaty R, Westrick RJ, et al. Spontaneous 8bp Deletion in Nbeal2 Recapitulates the Gray Platelet Syndrome in Mice. PLoS One. 2016;11(3):e0150852. 8. Noetzli L, Lo RW, Lee-Sherick AB, et al. Germline mutations in ETV6 are associated with thrombocytopenia, red cell macrocytosis and predisposition to lymphoblastic leukemia. Nature Genetics. 2015;47(5):535-538. 9. Zhang MY, Churpek JE, Keel SB, et al. Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy. Nature genetics. 2015;47(2):180-185. 10. Wang LC, Swat W, Fujiwara Y, et al. The TEL/ETV6 gene is required specifically for hematopoiesis in the bone marrow. Genes & development. 1998;12(15):2392-2402. Disclosures Di Paola: CSL BEhring: Consultancy; Biogen: Consultancy.
50
Campbell, Andrew, Biree Andemariam, Fredericka Sey, Connie M. Piccone, Baba PD Inusa, Silverio Perrotta, Imma Tartaglione, et al. "Sickle Cell Disease Proteinuria Is Not Associated With Systolic Blood Pressure, CSSCD-Defined Hypertension, or Family History Of Hypertension In An International Cohort Of SCD Patients." Blood 122, no. 21 (November 15, 2013): 981. http://dx.doi.org/10.1182/blood.v122.21.981.981.
Повний текст джерелаАнотація:
Abstract Background The prevalence of renal disease in sickle cell disease (SCD) is strikingly high and is associated with morbidity and mortality (Becker et al 2010, Powars et al 2005). In SCD children there is initially hyperfiltration with high GFRs followed by increasing proteinuria in the adolescent and adult SCD pts. (Becker at al 2010). Historically, hypertension (HTN) has been associated with Renal Disease in the general population and a few adult sickle cell nephropathy studies. HTN has been associated with Stroke in SCD. In an ongoing multicenter, international Renal SCD Cohort Study, we investigated the association Microalbuminuria and Macroalbuminuria to Patients Blood Pressure (SBP and DBP), Hypertension based on CSSCD Group Age Defined BP for SCD patients >90%tile (Pegelow et al 1997), and Family history (FH) of Hypertension and Renal Disease in a Crossectional (Peds and Adults), International, Multicenter group of SCD patients. Methods 272 pediatric and adult SCD (3-59 y/o) patients were recruited at baseline from 6 Centers (USA: Univ of Michigan, Case Medical Center/Rainbow Babies, Albert Einstein-Montefiore Medical Center, Univ of Connecticut; Italy: Univ. of Padova, Univ of Naples; Ghana: Korle-Bu Teaching Hospital). 88%(N=236) were severe SCD (SSorSBeta Zero) and 12%(N=31) were Mild Phenotype (SC or SBetaPlus). 58% were Children (<18y/o) and 42%(>18y/o) adults. FH of HTN and Renal Disease were obtained in 1st and 2nddegree relatives. Clinical history and laboratory studies including Pain crises patterns, SBP, DBP, BMI, CBC, Serum Crt, were collected. We obtained Urine Microalbumin/Crt(UMA) (mg/gm) obtained in 169 patients and categorized patients into 1) No Microalbuminuria(No UMA)<30mg/gm, 2) Microalbuminuria(MicroUMA) 30-299mg/gm and 3) Macroalbuminuria (MacroUMA) and obtained Urine protein/crt gm/gm(UProtCrt) in 101 SCD pts and were categorized 1) No proteinuria(NoUProt) <0.2 and 2) Macroproteinuria(MacroUProt)>0.2. Patient’s HTN was defined based on CSSCD SBP or DBP> 90%tile for each specifically defined age group( Pegelow et al 1997). Results In our SCD Renal Cohort Study, NoUMA in 71%(110/169), MicroUMA in 29%(48/169), MacroUMA in 2.2%(6/169) were observed. We also found NoUProt in 75%(N=75) and MacroUProt in 25%(n=25) within our cohort. Severe SCD pts represented 96%(n=46) of the MicroUMA pts, 100% or MacroUMA pts(N=6), and 92% MacroUProt pts(N=23). Proteinuria was disproportionately represented within the Adult SCD pts : 50% of Adults with MicroUMA(n=31) while only 16%(n=17) of Peds. UMA Mean Adult levels was 102(mean) vs. Peds UMA levels of 22(mean),(p=0.009); Also, Adult UProtCrt=0.21(mean)levels were >Peds=0.16, (p<0.001). HTN defined as SBP>90%tile or DBP >90%tile was present in 30%of the subjects(n=77).Thirty-One Percent(n=32) of Adults and 30%(n=45) of Peds pts had HTN. In a Bivariate Analysis(Pearson’s Correlation), HTN was not associated with UMA levels(p=0.919) or UPrtCrt levels(p=0.330). Further, mean UMA was lower in HTN SCD pts( m=24) vs NonHTN(SBP) pts(m=51). Mean UProt levels lower in the HTN group(0.15 ) vs NonHTN(0.20). SBP alone was not associated with UMA( p=0.083), UPrt( p=0.804) levels, MicroUMA(p=0.596). While FH of HTN was common in 75% of pts, FH HTN was not associated with UMA and UProtCrt levels, MicroUMA, MacroUMA, MacroUProt( p>0.05) patients. FH of Renal Disease was not associated with Proteinuria within our Cohort. However, Age( p<0.001: UProtCrt levels, UMA levels, MicroUMA, SBP) and hemoglobin(p=0.034: UProt Crt levels) was significantly associated with proteinuria within our cohort based on Bivariate Analysis. BMI was associated with SBP(p<0.001) and DBP(p<0.001) but not UProt or UMA levels. Further analysis revealed increasing proteinuria(UMA) within aging SCD pts:( 6-10 UMA= 15, 11-19 UMA =42, >20y/o UMA=114)(p=.035 One Way Anova) Conclusions Systolic Blood Pressure, HTN defined as SBP>90%tile or DBP >90%tile from the CSSCD Group, FH of HTN was not associated with Micro or Macroproteinuria based on UProtCrt and UMA levels in an international, cross-sectional cohort of SCD patients. Hemoglobin level and older age were strongly associated with proteinuria within our cohort of patients, consistent with previously well established studies. These findings are supportive of other factors outside of HTN including those intrinsic to SCD contributing to early onset SCD nephropathy. Disclosures: Perrotta: Novartis: Research Funding.