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Gill, K. S., E. L. Lubbers, B. S. Gill, W. J. Raupp und T. S. Cox. „A genetic linkage map of Triticum tauschii (DD) and its relationship to the D genome of bread wheat (AABBDD)“. Genome 34, Nr. 3 (01.06.1991): 362–74. http://dx.doi.org/10.1139/g91-058.
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One hundred and seventy-eight loci have been mapped in Triticum tauschii (Coss.) Schmal. (2n = 14, DD) and Triticum aestivum L. em. Thell. (2n = 42, AABBDD). Thirty-five loci were mapped by aneuploid analysis in T. aestivum. One hundred and fifty-two loci, including 143 restriction fragment length polymorphisms (RFLPs), 8 proteins, and 1 leaf rust resistance gene, were mapped in an F2 population (60 plants) of T. tauschii. One hundred and twenty-seven loci were placed in linkage groups belonging to seven D-genome chromosomes of T. tauschii. The source of the probes was a PstI genomic library of T. tauschii, which gave 13% single-low copy clones. Four restriction endonucleases (DraI, EcoRI, EcoRV, HindIII) gave 75% polymorphism between the two parents. Nineteen clones detected multiloci ranging from two to nine in number. Deletions–insertions and point mutations were equally important for generating RFLPs. A hypervariable sequence was identified, which may have potential use in varietal fingerprinting. One marker was found to be linked to a rust-resistance gene. The map will be useful for determining genetic relationships in the Triticeae and for tagging genes of economic importance.Key words: restriction fragment length polymorphism, Triticum aestivum, leaf rust, isozymes, Aegilops squarrosa.
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Mahrt, L., und Robert Heald. „Common Marginal Cold Pools“. Journal of Applied Meteorology and Climatology 54, Nr. 2 (Februar 2015): 339–51. http://dx.doi.org/10.1175/jamc-d-14-0204.1.
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AbstractThis study examines marginal cold pools forming in a shallow valley. “Marginal” refers to cold pools that are generally weak and intermittent. Nineteen stations were instrumented with sonic anemometers and accurate slow-response temperature measurements. The vertical structure of the cold pool is determined from a 20-m tower on the valley floor that includes eight levels of sonic anemometers and eight additional levels of slow-response temperature. On the basis of the data analysis, the traditional concept of a cold pool must be generalized to include cold-pool intermittency, complex variation of temperature related to some three-dimensional effects of terrain, and a diffuse cold-pool top. Different types of cold pools are classified in terms of the stratification and gradient of potential temperature along the slope. The strength of the cold pool is related to a forcing temperature scale that is proportional to the net radiative cooling divided by the wind speed above the valley. The scatter is large partly because of nonstationarity of the marginal cold pool in this shallow valley.
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Kaymakoglu, Sabahattin, Cetin Karaca, Kadir Demir, Sule Poturoglu, Ahmet Danalioglu, Selim Badur, Murvet Bozaci, Fatih Besisik, Yilmaz Cakaloglu und Atilla Okten. „Alpha Interferon and Ribavirin Combination Therapy of Chronic Hepatitis D“. Antimicrobial Agents and Chemotherapy 49, Nr. 3 (März 2005): 1135–38. http://dx.doi.org/10.1128/aac.49.3.1135-1138.2005.
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ABSTRACT The success of alpha interferon (IFN-α) monotherapy for the treatment of chronic hepatitis D is very limited. In this study, the efficacy of IFN-α and ribavirin combination therapy for chronic hepatitis D was investigated. Nineteen patients (15 males; mean age ± standard deviation, 36.8 ± 12.8 years) with chronic hepatitis D who were treated with IFN-α2b (10 million U, three times/week, subcutaneously) and ribavirin (1,000 to 1,200 mg/day, orally) for 24 months were studied. All patients had compensated liver disease (15 were precirrhotic), elevated transaminase levels, and hepatitis D virus RNA positivity at baseline. Genotypic analyses revealed hepatitis D virus genotype I and hepatitis B virus genotype D. All patients completed the 24 months of treatment and at least 6 months (7 to 19 months) of a follow-up period. Biochemical responses were observed in eight patients (42.1%) at the end of treatment and in seven patients (36.8%) at the end of follow-up. Eight patients (42.1%) at the end of treatment and four patients (21%) at the end of follow-up had virological responses. In conclusion, combination treatment of IFN-α and ribavirin for chronic hepatitis D is not able to induce virological responses at a sufficient rate, despite its partial effectiveness in improving biochemical responses, and is not superior to IFN-α monotherapy.
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Yaya, Kane, Leye Mamadou Mokhtar Mbacké, Zeinabou Maiga Moussa Tondi, Lemrabott Ahmed Tall, Faye Maria, Cisse Mouhamadou Moustapha, Ka El Hadj Fary und Diouf Boucar. „Décentralisation De La Dialyse Au Sénégal : Expérience D’1 An Du Centre De Tambacounda A l’Est Du Pays“. European Scientific Journal, ESJ 12, Nr. 36 (31.12.2016): 164. http://dx.doi.org/10.19044/esj.2016.v12n36p164.
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Hemodialysis has made numerous and significant progress in recent decades resulting in life expectancy increase (thirty or forty years). The aim of our study was to assess the treatment of acute and chronic hemodialysis in the reference center of Tambacounda. Patients and methods: This was a prospective study over a one-year period (April 2013 to March 2014) in the hemodialysis center of the regional hospital of Tambacounda, 450km away from Dakar. The study focused on epidemiological, clinical, paraclinical and scalable data. Results: Fifty-nine patients were involved in the study. The sex ratio was 0.85 (32F/ 27M). The mean age was 41.3 years [12-72 years old]. Nineteen patients were on dialysis treatment for acute renal failure (ARF) (32.2%) and 40 were chronic hemodialysis patients (67.79%). Fifty patients were under emergency dialysis (84.7%) including 17 in intensive care (28.8%). Most chronic hemodialysis patients had 3 sessions per week (98.3%). Only 9 patients were monitored in nephrology prior to dialysis (22%). Thirty-two patients had a femoral double-lumen catheter (54.23%), 6 patients used ordinary double- lumen jugular catheters (10.17%) and 3 received tunneled jugular catheters (5.09%). Eighteen patients had functional arteriovenous (AV) fistula (18.51%). The mean hemoglobin was 7 g/dl. Only 11 patients had erythropoietin-based therapy. In acute renal impairment there were 8 deaths (42.10%), whereas in chronic renal failure the fatality rate was 18.8% (n = 9). Conclusion: Our study has demonstrated the benefits of decentralizing dialysis treatment in the provinces. However there is a need to implement the accompanying measures, such as the availability of some essential medicines for all hemodialysis patients, and equipment of intensive care units.
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Papadaki, Angeliki, und Jane A. Scott. „The Mediterranean Eating in Scotland Experience project: evaluation of an Internet-based intervention promoting the Mediterranean diet“. British Journal of Nutrition 94, Nr. 2 (August 2005): 290–98. http://dx.doi.org/10.1079/bjn20051476.
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A 6-month intervention study with a quasi-experimental design was conducted to evaluate the effectiveness of an Internet-based, stepwise, tailored-feedback intervention promoting four key components of the Mediterranean diet. Fifty-three (intervention group) and nineteen (control group) healthy females were recruited from the Universities of Glasgow and Glasgow Caledonian, Scotland, respectively. Participants in the intervention group received tailored dietary and psychosocial feedback and Internet nutrition education over a 6-month period, while participants in the control group were provided with minimal dietary feedback and general healthy-eating brochures. Internet education was provided via an innovative Mediterranean Eating Website. Dietary changes were assessed with 7 d estimated food diaries at baseline and 6 months, and data were analysed to calculate the Mediterranean Diet Score, a composite score based on the consumption of eight components of the traditional Mediterranean diet. The ‘intention-to-treat’ analyses showed that, at 6 months, participants in the intervention group had significantly increased their intake of vegetables, fruits and legumes, as well as the MUFA:saturated fatty acid ratio in their diet, and had significantly increased plasma HDL-cholesterol levels and a reduced ratio of total:HDL-cholesterol. Participants in the control group increased their intake of legumes but showed no other favourable significant changes compared with baseline. This Internet-based, tailored-feedback intervention promoting components of the Mediterranean diet holds promise in encouraging a greater consumption of plant foods, as well as increasing monounsaturated fat and decreasing saturated fat in the Scottish diet; it also shows that the Mediterranean diet can be adopted by healthy individuals in northern European countries.
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Yazji, Bashour, Nha Voduc, Sunita Mulpuru und Juthaporn Cowan. „Pulmonary sequelae of SARS-CoV-2 infection and factors associated with persistent abnormal lung function at six months after infection: Prospective cohort study“. PLOS ONE 17, Nr. 11 (17.11.2022): e0277624. http://dx.doi.org/10.1371/journal.pone.0277624.
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Background Information on the long-term pulmonary sequelae following SARS-CoV-2 infection is limited. Methods Prospective cohort study of hospitalized and non-hospitalized adult patients age >18 with documented SARS-CoV-2 infection by RT-PCR three months prior to enrolment between June and December 2020. Participants underwent full pulmonary function test (PFT), cardiopulmonary exercise testing at 3 months and 6 months. Primary outcome was mean differences of forced vital capacity (FVC), diffuse capacity of lung for carbon monoxide (DLCO), and oxygen consumption (VO2) at 6 vs. 3 months. Secondary outcomes were respiratory outcomes classified into 5 clinical groups–no lung disease, resolved lung disease, persistent lung disease, PFT abnormalities attributable to pre-existing lung disease or other factors, and mild PFT abnormalities of uncertain clinical significance. Results Fifty-one, 30 hospitalized and 21 non-hospitalized, participants were included. Median age was 51 years; 20 (39.2%) were female. Mean (±SD) percent predicted values of FVC, DLCO and VO2 at 3 vs 6-month-visits were 96.2 ± 15.6 vs. 97.6 ± 15.5, 73.74 ±18 vs. 78.5 ± 15.5, and 75.5 ± 18.9 vs. 76.1 ± 21.5, respectively. Nineteen (37%) patients had physiologic and/or radiographic evidence of lung disease at 3 months with eight (15.7%) continuing to have persistent disease at 6 months. History of diabetes, hypertension, ICU admission and elevated D-Dimer levels were associated with persistent lung disease at 6 months. Interpretation Persistent lung disease at 6 months post SARS-CoV-2 infection exists. Changes of lung function between 3- and 6-months are not significant. A longer follow-up is required to determine long-term prognosis.
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DAMBORG, P., S. S. NIELSEN und L. GUARDABASSI. „Escherichia colishedding patterns in humans and dogs: insights into within-household transmission of phylotypes associated with urinary tract infections“. Epidemiology and Infection 137, Nr. 10 (10.03.2009): 1457–64. http://dx.doi.org/10.1017/s095026880900226x.
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SUMMARYWithin-household transmission ofEscherichia colimay contribute to the pathogenesis of urinary tract infection but understanding of transmission is limited by the lack of longitudinal data on individual shedding patterns. In this study, faecalE. coliwas isolated over 6 months from 18 humans and 13 dogs in eight households. Typing 322E. coliisolates by amplified fragment length polymorphism showed high overall diversity as indicated by the average diversity index (0·66). However, individual shedding patterns varied considerably: two persons carried a single residentE. coliclone throughout the study whereas distinct clones were isolated from other individuals on each sampling time. Nineteen clones were shared within six of the eight households and seven of these clones were shared between humans and dogs. The frequent sharing of clones belonging to phylotypes B2 (n=7) or D (n=4) supports the hypothesis that urovirulentE. coliare transmitted between household members, including dogs, or may be acquired by a common source such as food.
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López-Argumedo, G., G. López-Vivanco, R. Fernández, I. Díaz de Corcuera, A. Sancho, I. Rubio, A. Martínez-Bueno, J. Mañé, A. Muñoz und R. Barceló. „Concurrent chemoradiotherapy (crt) with weekly docetaxel (d) for advanced head and neck cancer“. Journal of Clinical Oncology 24, Nr. 18_suppl (20.06.2006): 15516. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.15516.
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15516 Background: Concomitant CRT has become a standard treatment for advanced head and neck cancer. The aim of this study was to evaluate the efficacy and toxicity of concurrent CRT with D in patients (pts) with advanced squamous cell carcinoma of head and neck (SCCHN). Methods: Patients with untreated and unresectable stage III or IV (M0) squamous cell carcinoma of head and neck were included. Treatment consisted of D 20 mg/m2 weekly with concomitant radiotherapy 70 Gy (2 Gy per day, 7 weeks). Results: From September 03 to October 05, sixty-four pts with advanced SCCHN, were recruited. Gender: 61 male, 3 female. Mean age: 56.5 years old (range 42–77). ECOG PS 0/1/2: 0/57/7. Primary sites of disease: oral cavity 8, oropharynx 26, hypopharynx 15 and larynx 15. Stage III 16 pts and stage IV 48 pts. Compliance: 393 administrations of D were given, median 6, mean 6 (range 1–8). Fifty-five pts (86%) completed the radiotherapy dose planned (mean dose of RT was 66 Gy). One refused more treatment with D after first administration. Nineteen pts required supportive percutaneous gastrostomy or nasogastric tubes previously or during therapy. Grade 2/3/4 toxicity per patient: anemia 4/2/0, mucositis 21/24/0, dermatitis 21/20/0. Neither thrombopenia nor neutropenia were observed. Four pts died of aspiration pneumonia during treatment, one of gastric perforation and two of unknown causes. Fifty-six pts were evaluable for response: CR 28 (44%), PR 23 (36%), SD 2 (3%), PD 3 (5%), with an overall response rate of 80%. Median overall survival was 74.86 weeks (95% CI: 40.40–109.32) and median progression free survival was 48 weeks (95% CI: 18.80–77.20). With a median follow up of 40 weeks 34 pts (53%) were alive and 21 of them (33%) remained free of disease. Conclusions: Concurrent weekly D with conventional radiotherapy showed a high response rate. Toxicity was manageable and allowed maintaining radiotherapy administration. Taking into account poor prognostic factors of our series, survival results seem promising. No significant financial relationships to disclose.
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Langlois, Julie, und Damien Denimal. „Clinical and Imaging Outcomes after Vitamin D Supplementation in Patients with Multiple Sclerosis: A Systematic Review“. Nutrients 15, Nr. 8 (18.04.2023): 1945. http://dx.doi.org/10.3390/nu15081945.
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The link between vitamin D and multiple sclerosis (MS) has been suggested in epidemiological, genetic, immunological, and clinical studies. The aim of the present systematic review of the literature was to assess the effects of vitamin D supplementation on clinical and imaging outcomes in patients with MS. The outcomes we assessed included relapse events, disability progression, and magnetic resonance imaging (MRI) lesions. The search was conducted using PubMed, ClinicalTrials.gov, and EudraCT databases, and it included records published up until 28 February 2023. The systematic review was reported according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. Nineteen independent clinical studies (corresponding to 24 records) were included in the systematic review. The risk of bias in randomized controlled trials (RCTs) was analyzed using the Cochrane risk-of-bias tool. Fifteen trials investigated relapse events, and most of them reported no significant effect of vitamin D supplementation. Eight of 13 RCTs found that vitamin D supplementation had no effect on disability [assessed by Expanded Disability Status Scale (EDSS) scores] compared to controls. Interestingly, recent RCTs reported a significant reduction in new MRI lesions in the central nervous system of MS patients during supplementation with vitamin D3.
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Sanchez-Castillo, Claudia P., David Grubb, Maria De Lourdes Solano, Michael F. Franklin und W. Philip T. James. „Non-starch polysaccharide intakes in Mexican villagers and residents of Mexico City“. British Journal of Nutrition 77, Nr. 3 (März 1997): 345–57. http://dx.doi.org/10.1079/bjn19970037.
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A study was performed in a rural Mexican community and in Mexico City to investigate possible differences in non-starch polysaccharide (NSP) intakes. One hundred and fourteen women (fifty-five rural and fitty-nine urban) and forty-three men (twenty-four rural and nineteen urban) completed 24 h recall questionnaires for three consecutive days with NSP intakes being estimated from a specially prepared set of new food composition tables. Potential underestimation of intakes was assessed by estimating individual BMR and dividing the estimated energy intakes by BMR to give a ratio. Excluding severe underrecording (ratio < 1·01) suggested NSP intakes of 21·8 and 17·3 g/d in rural men and women and 17·7 and 15·6 g/d in urban men and women respectively. NSP sources differed, with a marked fall in intake from pulses in the urban areas but a compensatory increase of tortilla intakes and a rise in NSP-rich fruit consumption. Both soluble- and insoluble-NSP intakes were higher in rural areas. NSP intakes scaled by probable energy intakes of moderately active adults in developing countries suggest that NSP intakes in Mexico are similar to adjusted values in Africa, i.e. 26·9 g/d in Mexico v. 28·5 g/d in Africa in rural men and 22·9 v. 21·0 g/d respectively in rural women. The NSP: energy density ratio (g/MJ) of the rural diet conformed with the World Health Organization (1990) goal. Data available on urban and rural communities for three countries showed that in each case the intake of NSP was lowest in the urban community.
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Skorova, Larisa V., und Daria K. Suvorova. „Semantic Structure of a Movie Hero Favored by Teenagers“. SibScript 25, Nr. 2 (04.05.2023): 183–92. http://dx.doi.org/10.21603/sibscript-2023-25-2-183-192.
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The authors used the psychosemiotic content analysis, projective method, personal differential, and factor analysis to study the semantics of a movie character preferred by teenagers. An incomplete-sentence test and a blog analysis revealed eight categories and nineteen corresponding analysis units based on the occurrence / non-occurrence of selected units in the text and their frequency. Osgood’s matrices revealed the measure of the random coincidence of classification units (≥ 70 %) with other categories. The integrative semantic structure of the favored movie hero was determined by such categories and content units as a) gender (male); b) appearance (look); c) intellect (mental abilities); d) interaction (relations with other people); e) character traits (moral and volitional qualities, attitude to others, attitude to work); f) actions (struggle for justice, readiness to do something for others); g) attitude to the family (willingness to sacrifice with something for the family).
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Booth, Alison O., Catherine E. Huggins, Naiyana Wattanapenpaiboon und Caryl A. Nowson. „Effect of increasing dietary calcium through supplements and dairy food on body weight and body composition: a meta-analysis of randomised controlled trials“. British Journal of Nutrition 114, Nr. 7 (03.08.2015): 1013–25. http://dx.doi.org/10.1017/s0007114515001518.
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This meta-analysis of randomised controlled trials assessed the effect of Ca on body weight and body composition through supplementation or increasing dairy food intake. Forty-one studies met the inclusion criteria (including fifty-one trial arms; thirty-one with dairy foods (n 2091), twenty with Ca supplements (n 2711). Ca intake was approximately 900 mg/d higher in the supplement groups compared with control. In the dairy group, Ca intake was approximately 1300 mg/d. Ca supplementation did not significantly affect body weight (mean change ( − 0·17, 95 % CI − 0·70, 0·37) kg) or body fat (mean change ( − 0·19, 95 % CI − 0·51, 0·13) kg) compared to control. Similarly, increased dairy food intake did not affect body weight ( − 0·06, 95 % CI − 0·54, 0·43) kg or body fat change ( − 0·36, 95 % CI − 0·80, 0·09) kg compared to control. Sub-analyses revealed that dairy supplementation resulted in no change in body weight (nineteen studies, n 1010) ( − 0·32, 95 % CI − 0·93, 0·30 kg, P= 0·31), but a greater reduction in body fat (thirteen studies, n 564) ( − 0·96, 95 % CI − 1·46, − 0·46 kg, P < 0·001) in the presence of energy restriction over a mean of 4 months compared to control. Increasing dietary Ca intake by 900 mg/d as supplements or increasing dairy intake to approximately 3 servings daily (approximately 1300 mg of Ca/d) is not an effective weight reduction strategy in adults. There is, however, an indication that approximately 3 servings of dairy may facilitate fat loss on weight reduction diets in the short term.
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Chung, Arlene S., Annemarie Cardell, Smruti Desai, Evelyn Porter, Ridhima Ghei, Joanna Akinlosotu und Chinwe Ogedegbe. „Educational Outcomes of Diversity Curricula in Graduate Medical Education“. Journal of Graduate Medical Education 15, Nr. 2 (01.04.2023): 152–70. http://dx.doi.org/10.4300/jgme-d-22-00497.1.
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ABSTRACT Background Education is an important step toward achieving equity in health care. However, there is little published literature examining the educational outcomes of curricula for resident physicians focused on diversity, equity, and inclusion (DEI). Objective Our objective was to review the literature to assess the outcomes of curricula for resident physicians of all specialties focused on DEI in medical education and health care. Methods We applied a structured approach to conducting a scoping review of the medical education literature. Studies were included for final analysis if they described a specific curricular intervention and educational outcomes. Outcomes were characterized using the Kirkpatrick Model. Results Nineteen studies were included for final analysis. Publication dates ranged from 2000 to 2021. Internal medicine residents were the most studied. The number of learners ranged from 10 to 181. The majority of studies were from a single program. Educational methods ranged from online modules to single workshops to multiyear longitudinal curricula. Eight studies reported Level 1 outcomes, 7 studies reported Level 2 outcomes, 3 studies reported Level 3 outcomes, and only 1 study measured changes in patient perceptions due to the curricular intervention. Conclusions We found a small number of studies of curricular interventions for resident physicians that directly address DEI in medical education and health care. These interventions employed a wide array of educational methods, demonstrated feasibility, and were positively received by learners.
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Anwan, Henry Robert, und Martins Agenuma Anetekhai. „Ichthyofaunal composition and diversity of Stubbs Creek, Ibeno, in Akwa Ibom State, Nigeria“. Brazilian Journal of Biological Sciences 7, Nr. 17 (2020): 297–303. http://dx.doi.org/10.21472/bjbs(2020)071705.
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The fish abundance and distribution of Stubbs Creek were examined in order to provide information for the management and sustainable exploitation of the ecosystem services. Fish samples obtained from the fishermen landing sites were identified using FAO species identification guide. Data were analyzed using descriptive statistics. Species diversity and community abundance were determined using Shannon-Weiver diversity index (H) and Margalef's species richness (d). Twenty nine fish species, twenty two genera in nineteen families and eight orders were identified from the three landing stations during the study. Station 1 (Iwokpom) recorded the highest taxa (24) consisting of 993 fishes (43.14%) of the total catch. Landing site 2 (Iwuchang) and 3 (Ubenekang) both recorded 22 taxa each comprising 556 (24.15%) and 753 (32.71%) fishes, respectively. Iwokpom recorded the highest diversity in fish species d = 3.333, but the lowest general ecosystem diversity (H = 2.781). Ubenekang (Station 3) had the lowest species richness d = 3.17, but recorded the highest biodiversity (H = 2.839) in the study. Evenness was generally high among the stations but Iwopom recorded the lowest value of e = 0.6722 and Ubenekang had the highest, e = 0.7769. Iwuchang (Station 2) came next to Iwopon in species richness d = 3.322, but was next to Ubenekang in general diversity (H = 2.833) and evenness e = 0.7725, respectively. The present study indicated that stub creek is rich in fish biodiversity. Therefore users of this water body should maintain responsible fishing activities in order to conserve this biodiversity.
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Heap, Sarah, Jessica Ingram, Marron Law, Amy J. Tucker und Amanda J. Wright. „Eight-day consumption of inulin added to a yogurt breakfast lowers postprandial appetite ratings but not energy intakes in young healthy females: a randomised controlled trial“. British Journal of Nutrition 115, Nr. 2 (01.12.2015): 262–70. http://dx.doi.org/10.1017/s0007114515004432.
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AbstractIncreasing feelings of satiety may reduce appetite and energy intake. The role of inulin consumption in impacting satiety is unclear. A randomised double-blind controlled crossover trial aimed to determine the effects of inulin+yogurt on satiety after 1 and 8-d consumption. The preload breakfast included 100 g vanilla yogurt with (yogurt-inulin (YI)) and without (yogurt-control (YC)) 6 g inulin. A total of nineteen healthy females (22·8 (sd 2·7) years) with non-restrained eating behaviour and taking hormonal contraceptives participated in the study. Day 1 and 8 visual analogue scale (VAS) ratings of Hunger, Fullness, Desire to Eat and Prospective Food Consumption (PFC) were collected at fasting and every 30 min for 180 min. Energy intake was calculated from a weighed ad libitum lunch and remainder of day food records. Total AUC was calculated for each VAS. Day 1 (VAS only) and 8 (VAS and energy intakes) data were compared between YI and YC using ANCOVA, and ANOVA was used to compare energy intakes on Day 1. There were no significant differences between Day 1 YI and YC AUC appetite ratings or energy intakes. However, 8-d consumption of YI v. YC was associated with lower Desire to Eat and PFC ratings but similar lunch and total day energy intakes. Therefore, the addition of 6 g inulin to a commercially available yogurt affected feelings of appetite, but not energy intake, after repeated consumption. These results suggest that inulin may be a suitable ingredient to increase dietary fibre consumption, with potential to impact appetite.
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Baselga, J., D. Rischin, M. Ranson, H. Calvert, E. Raymond, D. G. Kieback, S. B. Kaye et al. „Phase I Safety, Pharmacokinetic, and Pharmacodynamic Trial of ZD1839, a Selective Oral Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor, in Patients With Five Selected Solid Tumor Types“. Journal of Clinical Oncology 20, Nr. 21 (01.11.2002): 4292–302. http://dx.doi.org/10.1200/jco.2002.03.100.
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PURPOSE: To establish the safety and tolerability of ZD1839 (Iressa), a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, and to explore its pharmacokinetic and pharmacodynamic effects in patients with selected solid tumor types. PATIENTS AND METHODS: This was a phase I dose-escalating trial of oral ZD1839 150 mg/d to a maximum of 1,000 mg/d given once daily for at least 28 days. Patients with either advanced non–small-cell lung, ovarian, head and neck, prostate, or colorectal cancer were recruited. RESULTS: Eighty-eight patients received ZD1839 (150 to 1,000 mg/d). At 1,000 mg/d, five of 12 patients experienced dose-limiting toxicity (grade 3 diarrhea [four patients] and grade 3 somnolence [one patient]). The most frequent drug-related adverse events (AEs) were acne-like rash (64%) and diarrhea (47%), which were generally mild (grade 1/2) and reversible on cessation of treatment. No change in ZD1839 safety profile was observed with prolonged administration. Pharmacokinetic analysis showed steady-state exposure to ZD1839 in 98% of patients by day 7. Nineteen patients had stable disease and received ZD1839 for ≥ 3 months; seven of these patients remained on study drug for ≥ 6 months. Serial skin biopsies taken before treatment and at approximately day 28 revealed changes indicative of inhibition of the EGFR signaling pathway. CONCLUSION: ZD1839 was generally well tolerated, with manageable and reversible AEs at doses up to 600 mg/d and dose-limiting toxicity observed at 1,000 mg/d. ZD1839 treatment resulted in clinically meaningful disease stabilization across a range of tumor types and doses. Pharmacodynamic changes in skin confirmed inhibition of EGFR signaling, which was predicted from the mode of action of ZD1839.
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Dann, E. J., J. Anastasi und R. A. Larson. „High-dose cladribine therapy for chronic myelogenous leukemia in the accelerated or blast phase.“ Journal of Clinical Oncology 16, Nr. 4 (April 1998): 1498–504. http://dx.doi.org/10.1200/jco.1998.16.4.1498.
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PURPOSE A phase II clinical trial was performed to evaluate the effectiveness of high-dose cladribine (2CDA) for treatment of chronic myelogenous leukemia (CML) in the accelerated or blast phase. PATIENTS AND METHODS Nineteen patients were treated. The median age was 55 years (range, 30 to 73). Six were older than 60 years. Eight had progressed after intensive combination chemotherapy and three after allogeneic or autologous transplantation. For the first course, 16 patients received 2CDA at 15 mg/m2/d intravenously (i.v.) over 1 hour for 5 days. Two received 18 mg/m2 and one received 21.5 mg/m2 daily. The second course was escalated to 20 mg/m2/d in five patients. RESULTS Rapid cytoreduction of leukemia occurred in the blood, with the nadir at 10 to 12 days. The median WBC count decreased from 36,900/microL before treatment to 500/microL at the nadir and recovered to 5,200/microL at day 30. The median platelet count changed from 113,000/microL to 24,000/microL at the nadir and 71,000/microL at day 30. The complete remission (CR) plus partial remission (PR) rate was 47% (95% confidence interval [CI], 23% to 72%). One 64-year-old man with lymphoid blast phase of CML had a morphologic and cytogenetic CR that lasted 9 months. The median survival for all patients was 34 weeks, and the median survival for the eight responders was 56 weeks (range, 11 to 167). The median number of days spent in hospital over the entire treatment period was 19 (range, 4 to 60). CONCLUSION High-dose 2CDA therapy provides effective palliation for CML in accelerated or blast phases, even for heavily pretreated patients.
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Rydberg, Michael G., Leslie K. Appleton, Aaron J. Fried, Daniel M. Cable und Debra L. Bynum. „Implementation of a “Best Self” Exercise to Decrease Imposter Phenomenon in Residents“. Journal of Graduate Medical Education 16, Nr. 3 (01.06.2024): 308–11. http://dx.doi.org/10.4300/jgme-d-23-00873.1.
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Background Imposter phenomenon (IP) is common in medicine. An intervention from the business world, the Reflected Best Self Exercise (RBSE), in which an individual elicits stories of themselves at their best, has not been studied in medical residents. Objective To determine the feasibility of implementing the RBSE and its potential for reducing IP in residents. Methods All incoming internal medicine and medicine-pediatrics interns in the 2022-2023 academic year at a single institution were invited to complete the RBSE. Participants elicited stories from contacts prior to beginning residency and received their stories during intern orientation in a 1-hour session led by one author with no prior training. Cost and time requirements were assessed. IP was measured via the Clance Impostor Phenomenon Scale (CIPS) at baseline, 1 month, and 6 months following the RBSE. Informal feedback on the RBSE was collected via surveys at 1 month and 6 months. Results Nineteen of 35 interns (54.3%) completed the RBSE. It cost $75 per participant, for a total cost of $1,425. Twenty-eight of 35 (80%) completed the baseline CIPS, with scores similar between participants and nonparticipants (64.9 vs 68.9). CIPS scores were lower in participants at 1 month (57.6 vs 69.6) and 6 months (55.6 vs 64.5) but did not meet statistical significance. Survey feedback from participants suggested the intervention was beneficial. Conclusions Implementing the RBSE in residents was feasible with reasonable cost and time commitment. It appeared highly acceptable to residents, with some promise of effects on an IP scale.
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Henry, C. Jeya K., Helen J. Lightowler und Jonathan Marchini. „Intra-individual variation in resting metabolic rate during the menstrual cycle“. British Journal of Nutrition 89, Nr. 6 (Juni 2003): 811–17. http://dx.doi.org/10.1079/bjn2003839.
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Little information exists on the extent of day-to-day intra-individual variation in resting metabolic rate (RMR) in women. The present study has investigated the intra-individual variation in RMR of women during the menstrual cycle. Nineteen women (naturally cycling non-pill users) were recruited to the study. Anthropometric and RMR measurements were taken at least three times per week for the duration of one complete menstrual cycle; measurements were taken for a second, consecutive cycle in eight of the nineteen subjects. RMR was measured by indirect calorimetry using a ventilated hood system under standardized conditions. The measurements made throughout each complete menstrual cycle were averaged and the levels of inter- and intra-individual variation in RMR were assessed by determining the CV (%). Mean RMR of the group was 5686 (SD 674) kJ/d; inter-individual variation in RMR was 11·8 %. There were wide differences in the intra-individual variation in RMR of women (CV range 1·7–10·4 %). The CV in ten subjects was small (2–4 %), while the CV in nine women was high (5–10 %), indicating a significant variation in RMR during the menstrual cycle in certain subjects. Using statistical models, it has been shown that there was a significant effect on RMR due to a subject-specific level of variability; this was the case even when accounting for a possible training effect. In conclusion, the findings from our present study show that RMR cannot be assumed to be ‘stable’ in all women. The implications of intra-individual variation in RMR and its impact on energy balance needs further research.
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Borgwardt, Lise, Liselotte Højgaard, Henrik Carstensen, Henning Laursen, Markus Nowak, Carsten Thomsen und Kjeld Schmiegelow. „Increased Fluorine-18 2-Fluoro-2-Deoxy-D-Glucose (FDG) Uptake in Childhood CNS Tumors Is Correlated With Malignancy Grade: A Study With FDG Positron Emission Tomography/Magnetic Resonance Imaging Coregistration and Image Fusion“. Journal of Clinical Oncology 23, Nr. 13 (01.05.2005): 3030–37. http://dx.doi.org/10.1200/jco.2005.02.074.
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Purpose Positron emission tomography (PET) has been used in grading of CNS tumors in adults, whereas studies of children have been limited. Patients and Methods Nineteen boys and 19 girls (median age, 8 years) with primary CNS tumors were studied prospectively by fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) PET with (n = 16) or without (n = 22) H215O-PET before therapy. Image processing included coregistration to magnetic resonance imaging (MRI) in all patients. The FDG uptake in tumors was semiquantitatively calculated by a region-of-interest–based tumor hotspot/brain index. Eight tumors without histologic confirmation were classified as WHO grade 1 based on location, MRI, and clinical course (22 to 42 months). Results Four grade 4 tumors had a mean index of 4.27 ± 0.5, four grade 3 tumors had a mean index of 2.47 ± 1.07, 10 grade 2 tumors had a mean index of 1.34 ± 0.73, and eight of 12 grade 1 tumors had a mean index of −0.31 ± 0.59. Eight patients with no histologic confirmation had a mean index of 1.04. For these 34 tumors, FDG uptake was positively correlated with malignancy grading (n = 34; r = 0.72; P < .01), as for the 26 histologically classified tumors (n = 26; r = 0.89; P < .01). The choroid plexus papilloma (n = 1) and the pilocytic astrocytomas (n = 3) had a mean index of 3.26 (n = 38; r = 0.57; P < .01). H215O-uptake showed no correlation with malignancy. Digitally performed PET/MRI coregistration increased information on tumor characterization in 90% of cases. Conclusion FDG PET of the brain with MRI coregistration can be used to obtain a more specific diagnosis with respect to malignancy grading. Improved PET/MRI imaging of the benign hypermetabolic tumors is needed to optimize clinical use.
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Cezard, Jean‐Pierre, Nizar Nouaili, Cécile Talbotec, Jean‐Pierre Hugot, Jean‐Gérard Gobert, Jacques Schmitz, Jean‐François Mougenot, Corinne Alberti und Olivier Goulet. „A Prospective Study of the Efficacy and Tolerance of a Chimeric Antibody to Tumor Necrosis Factors (Remicade) in Severe Pediatric Crohn Disease“. Journal of Pediatric Gastroenterology and Nutrition 36, Nr. 5 (Mai 2003): 632–36. http://dx.doi.org/10.1002/j.1536-4801.2003.tb08084.x.
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ABSTRACTObjectivesTo evaluate the efficacy and toxicity of infliximab in children with severe Crohn disease (CD), the authors prospectively monitored 21 children aged 15 ± 2 years with severe CD who they treated with infliximab (5 mg/kg) on days 0, 15, and 45. One patient received only one injection. Eighteen patients were corticosteroid dependent, and 6 were receiving parenteral nutrition. Three patients were corticoid resistant (1 mg/kg/d >15 days). Sixteen had perianal disease.ResultsThe Harvey‐Bradshaw index (HB) decreased from 8 ± 3 on day 0 to 1 ± 2 on day 45 (P = 0.001). The inflammation factors decreased (P = 0.001), and albumin increased (P = 0.002). Nineteen children were in complete remission (HB < 4) on day 45, and 2 had improved (HB = −6 points). Tumor necrosis factor‐α (TNFα) in the stools (n = 16) decreased (P = 0.04). All perianal fistulas (n = 12) were closed by day 90. Fourteen of 21 patients had stopped taking steroids at 3 months, and all had stopped parenteral nutrition. Growth velocity was significantly greater after infliximab administration (Z score, +0.5) than before (−0.45;P = 0.004). Nineteen of 21 patients had relapsed (90%) at 1 year despite continued immunosuppressors. Seven had surgery because of an uncontrolled relapse (5), stenosis (1), or fistula (1). Six patients developed antinuclear antibodies (1/40–1/640e), and two had anti‐DNA antibodies. Epstein‐Barr virus (EBV) polymerase chain reaction (PCR) values increased (>100‐fold) in eight patients. One child developed an anaphylactic reaction to the medication, and one had a catheter‐related sepsis.ConclusionInfliximab produces spectacular results for children with severe CD and is well tolerated. However, its effect is transitory for many (90%), with frequent relapses despite continued immunosuppressors. Long‐term management with infliximab should be tested despite its worrying side effects.
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Zwierko, Teresa, Piotr Lesiakowski, Beatriz Redondo und Jesús Vera. „Examining the ability to track multiple moving targets as a function of postural stability: a comparison between team sports players and sedentary individuals“. PeerJ 10 (02.09.2022): e13964. http://dx.doi.org/10.7717/peerj.13964.
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Background The ability to track multiple objects plays a key role in team ball sports actions. However, there is a lack of research focused on identifying multiple object tracking (MOT) performance under rapid, dynamic and ecologically valid conditions. Therefore, we aimed to assess the effects of manipulating postural stability on MOT performance. Methods Nineteen team sports players (soccer, basketball, handball) and sixteen sedentary individuals performed the MOT task under three levels of postural stability (high, medium, and low). For the MOT task, participants had to track three out of eight balls for 10 s, and the object speed was adjusted following a staircase procedure. For postural stability manipulation, participants performed three identical protocols (randomized order) of the MOT task while standing on an unstable platform, using the training module of the Biodex Balance System SD at levels 12 (high-stability), eight (medium-stability), and four (low-stability). Results We found that the ability to track moving targets is dependent on the balance stability conditions (F2,66 = 8.7, p < 0.001, η² = 0.09), with the disturbance of postural stability having a negative effect on MOT performance. Moreover, when compared to sedentary individuals, team sports players showed better MOT scores for the high-stability and the medium-stability conditions (corrected p-value = 0.008, Cohen’s d = 0.96 and corrected p-value = 0.009, Cohen’s d = 0.94; respectively) whereas no differences were observed for the more unstable conditions (low-stability) between-groups. Conclusions The ability to track moving targets is sensitive to the level of postural stability, with the disturbance of balance having a negative effect on MOT performance. Our results suggest that expertise in team sports training is transferred to non-specific sport domains, as shown by the better performance exhibited by team sports players in comparison to sedentary individuals. This study provides novel insights into the link between individual’s ability to track multiple moving objects and postural control in team sports players and sedentary individuals.
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Ciausu, Vlad, Marcin Ostrowski, Bethany Dudley, Iain McKinnon und Chris Ince. „Revisiting vitamin D status and supplementation for inpatients with intellectual and developmental disability in the north of England, UK“. BJPsych Open 7, S1 (Juni 2021): S14. http://dx.doi.org/10.1192/bjo.2021.95.
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AimsVitamin D deficiency is common among people with Intellectual and Developmental Disability (IDD) and is linked to worse health outcomes.Our aims were to re-evaluate vitamin D testing and supplementation among inpatients with IDD, examine any correlates with physical health conditions including COVID-19 and make recommendations for the current regime of supplementation and testing within inpatient IDD services.MethodThe study population comprised inpatients who were in any of the Northgate Hospital IDD inpatient services in Northumberland, UK. The wards sampled were the Medium Secure Unit, Low Secure Unit, Hospital Based Rehabilitation Wards and Specialist Autism Inpatient Service. Records of all inpatients between January 2019 and July 2020 were examined for 25-hydroxyvitamin D [25(OH)D] level, ward area, supplementation status, test seasonality, medication, and health status.We performed a correlation to see whether there was an association between vitamin D level and length of time on treatment. In addition, comparison of the replete and inadequate group for age, ethnicity, seasonality, ward location and psychotropic medication was undertaken.Data on physical health risk factors, obesity and COVID-19 infection were also collected. The physical comorbidities were described in order to evaluate whether any emerging patterns relating to COVID-19 infection were emerging.ResultThere were 67 inpatients in Northgate IDD services on 1 January 2019, with 11 further patients admitted up to the end of the sampling period on 31 July 2020. Nineteen patients were discharged during that period, so the sample comprised 78 patients.Ages were comparable across three of the ward areas, except for an older group of patients in the hospital-based rehabilitation setting. Mean 25(OH)D level for supplemented (800IU/day) patients was 75nmol/l (SD 20) compared to 40nmol/l (SD 19) in the non-supplemented group (p < 0.001).Thirty-eight percent of those who were inpatients during the first wave of the COVID-19 pandemic developed symptoms, but the small sample size could not establish vitamin D levels as a predictor of outcome.ConclusionOur findings show that clinicians continue to offer vitamin D supplementation for inpatients, at a dose of 800IU (20μg) per day.The mean vitamin D levels we observed were higher for those on supplements compared to our 2013 baseline data, whereas patients not on supplementation now had levels akin to those found previously. Vitamin D (800IU/day) supplementation is effective but adequacy of the nationally recommended dose of 400IU/day is unclear. Links to COVID-19 merit further research.
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Nol, Pauline, Morgan E. Wehtje, Richard A. Bowen, Suelee Robbe-Austerman, Tyler C. Thacker, Kristina Lantz, Jack C. Rhyan et al. „Effects of Inactivated Mycobacterium bovis Vaccination on Molokai-Origin Wild Pigs Experimentally Infected with Virulent M. bovis“. Pathogens 9, Nr. 3 (07.03.2020): 199. http://dx.doi.org/10.3390/pathogens9030199.
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The wild pig population on Molokai, Hawaii, USA is a possible reservoir for bovine tuberculosis, caused by Mycobacterium bovis, and has been implicated in decades past as the source of disease for the island’s domestic cattle. Heat-inactivated vaccines have been effective for reducing disease prevalence in wild boar in Spain and could prove useful for managing M. bovis in Molokai wild pigs. We designed an experiment to test this vaccine in wild pigs of Molokai genetics. Fifteen 3–4-month-old pigs were orally administered 106–107 colony forming units (cfu) of heat-inactivated M. bovis (Vaccinates; n = 8; 0.2 mL) or phosphate buffered saline (Controls; n = 7; 0.2 mL). Each dose was administered in a 0.5 mL tube embedded in a fruit candy/cracked corn mix. Boosters were given seven weeks post-prime in the same manner and dose. Nineteen weeks post-prime, pigs were orally challenged with 1 × 106 cfu of virulent M. bovis. Twelve weeks post-challenge, pigs were euthanized and necropsied, at which time 23 different tissues from the head, thorax, and abdomen were collected and examined. Each tissue was assigned a lesion score. Ordinal lesion score data were analyzed using non-parametric Wilcoxon Signed Rank test. Effect size was calculated using Cohen’s d. Four of eight Vaccinates and four of seven Controls had gross and microscopic lesions, as well as culture-positive tissues. Vaccinates had statistically lower lesion scores than Controls in the following areas: gross thoracic lesion scores (p = 0.013 Cohen’s d = 0.33) and microscopic thoracic lesion scores (p = 0.002, Cohen’s d = 0.39). There were no differences in head lesion scores alone, both gross and microscopic, nor were there differences when comparing combined gross and microscopic head and thoracic lesion scores. These results are indicative that this vaccination protocol affords a modest degree of infection containment with this vaccine in Molokai wild pigs.
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CRISTINO, MARIA DA GLÓRIA G., CARLA CAROLINA F. DE MENESES, MALÚCIA MARQUES SOEIRO, JOÃO ELIAS V. FERREIRA, ANTONIO FLORÊNCIO DE FIGUEIREDO, JARDEL PINTO BARBOSA, RUTH C. O. DE ALMEIDA, JOSÉ C. PINHEIRO und ANDRÉIA DE LOURDES R. PINHEIRO. „COMPUTATIONAL MODELING OF ANTIMALARIAL 10-SUBSTITUTED DEOXOARTEMISININS“. Journal of Theoretical and Computational Chemistry 11, Nr. 02 (April 2012): 241–63. http://dx.doi.org/10.1142/s0219633612500162.
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Nineteen 10-substitued deoxoartemisinin derivatives and artemisinin with activity against D-6 strains of malarial falciparum designated as Sierra Leone are studied. We use molecular electrostatic potential maps in an attempt to identify key structural features of the artemisinins that are necessary for their activities and molecular docking to investigate the interaction with the molecular receptor (heme). Chemometric modeling: Principal Component Analysis (PCA), Hierarchical Cluster Analysis (HCA), K-Nearest Neighbor (KNN), Soft Independent Modeling of Class Analogy (SIMCA) and Stepwise Discriminant Analysis (SDA) are employed to reduce dimensionality and investigate which subset of descriptors are responsible for the classification between more active (MA) and less active (LA) artemisinins. The PCA, HCA, KNN, SIMCA and SDA studies showed that the descriptors LUMO (Lowest Unoccupied Molecular Orbital) energy, DFeO1 (Distance between the O 1 atom from ligand and iron atom from heme), X1A (Average Connectivity Index Chi-1) and Mor15u (Molecular Representation of Structure Based on Electron Diffraction) code of signal 15, unweighted, are responsible for separating the artemisinins according to their degree of antimalarial activity. The prediction study was done with a new set of eight artemisinins by using the chemometric methods and five of them were predicted as active against D-6 strains of falciparum malaria. In order to verify if the key structural features that are necessary for their antimalarial activities were investigated for the interaction with the heme, we also carried out calculations of the molecular electrostatic potential (MEP) and molecular docking. MEP maps and molecular docking were analyzed for more active compounds of the prediction set.
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Primrose, W. J., G. D. L. Smyth, A. G. Kerr und D. S. Gordon. „Vestibular nerve section and saccus decompression: An evaluation of long-term results“. Journal of Laryngology & Otology 100, Nr. 7 (Juli 1986): 775–84. http://dx.doi.org/10.1017/s0022215100100076.
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AbstractThe 1972 AAOO committee (Alford, 1972) guidelines brought some uniformity into the evaluation of therapy for Meniere's Disease. We have adhered to its recommendations in this long-term follow-up report of 21 saccus decompressions and 29 vestibular nerve sections performed on 46 patients between 1968 and 1977. Comparisons between these and other groups have been possible with regard to: 1. control of vertigo; 2. hearing; 3. tinnitus; and 4. development of hydrops in the contralateral ear. All the vestibular nerve section group have enjoyed sustained relief from vertigo. Class D results (recurrent vertigo) account for 14 per cent of the saccus decompression group at one year and 29 per cent at eight to 10-year follow-up. Hearing levels in both groups deteriorated in parallel as time progressed but tinnitus became less noticeable. Nineteen per cent of the long-term review patients showed evidence of developing cochlear hydrops in the contralateral ear. Conservative surgical procedures should be employed whilst any useful hearing exists, though the emphasis remains on controlling vertigo. Saccus decompression, despite its controversial therapeutic basis, will remain the first-line surgical procedure for many otologists. However, in the fit young Meniere's cripple or saccus decompression failure with serviceable hearing, vestibular nerve section remains the treatment of choice.
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Taylor, E. G., R. P. Lemenager und K. R. Stewart. „Using corn gluten feed in post-partum diets of young beef cows to optimize reproductive performance“. Translational Animal Science 1, Nr. 3 (01.09.2017): 296–303. http://dx.doi.org/10.2527/tas2017.0034.
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Abstract Forty-eight primiparous and diparous Angus-Simmental cows were fed 1 of 3 diets; 1) total mixed ration (TMR) based of corn silage and corn stalks (CON), 2) TMR with 3.3 kg/d DM of corn gluten feed (CGF; MID), or 3) TMR with 6.7 kg/d DM of CGF (HIGH). From 11 ± 5 days post-partum (DPP) to 105 ± 5 DPP, all diets were formulated to be isocaloric for a post-partum ADG targeted at 0.22 kg, but CP exceeded requirements in both CGF diets. Blood samples were collected from cows starting at trial initiation until estrous synchronization for determination of plasma progesterone concentration (7 d intervals), as an indicator of resumption of cyclicity, as well as for plasma urea nitrogen (PUN; 21 d intervals). Milk production was assessed at 62 ± 5 DPP via a weigh-suckle-weigh procedure, and milk samples were collected at 64 ± 5 DPP for composition analysis. A 5 d Co-Synch + Control Internal Drug Release (CIDR) protocol was used and cows were bred by timed artificial insemination (TAI). Trans-rectal ultrasonography was used for the evaluation of the dominant follicle at TAI, as well as pregnancy diagnosis. Nineteen days post-TAI, cow and calf pairs were managed as a single group until weaning (205 ± 5 DPP) and exposed to natural mating for a total of a 60 d breeding season. Dam ADG was not significantly different among treatments (P = 0.849), but, DMI decreased with increasing CGF in the diet (P = 0.049). There were no differences in final BW (P = 0.779), however, final BCS was lower in the HIGH treatment when compared to the MID (P = 0.042). Milk production (P = 0.457), as well as, milk components (P ≥ 0.188) were not different, with the exception of milk fat, which tended to be greater in the HIGH treatment (P = 0.059) when compared to the MID. A treatment by week interaction (P < 0.0001) was found for PUN concentrations. Concentrations were greater in the HIGH treatment compared to the MID treatment at 63, 84, and 105 d, and greater than the CON treatment at all time points except d-42. There were no differences in resumption of cyclicity (P = 0.419), dominant follicle (P = 0.648), or TAI conception rates (P = 0.761). However, season long pregnancy rates were significantly greater in the CGF treatments when compared to the CON (P = 0.009). In summary, feeding high or intermediate amounts of CGF neither has a positive nor negative effect on TAI conception rates of beef cows, however, it positively affected season long pregnancy.
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Bailey, H., J. Kolesar, T. Fass, J. Weiss, J. Heideman, D. Alberti und S. Morgan-Meadow. „A phase I study of LR-103 (1,24α(OH)2D2) in patients with refractory malignancies“. Journal of Clinical Oncology 24, Nr. 18_suppl (20.06.2006): 14608. http://dx.doi.org/10.1200/jco.2006.24.18_suppl.14608.
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14608 Background: Preclinical studies of calcitriol and vitamin D analogs demonstrate potent growth inhibition of tumor cell lines. The clinical development of calcitriol and other analogs have been hindered by hypercalcemia. 1α (OH)D2 is a Vitamin D analog which has produced objective responses in advanced androgen-independent prostate cancer patients and can be administered daily at 10mcg. LR103 is an active metabolite of 1α (OH)D2 with equivalent anti-tumor activity and significantly less calcemic effects in preclinical studies. This phase I study explores the maximal tolerated dose and toxicity of LR-103. Methods: LR-103 was administered daily beginning at a dose of 5 μg/day with a cycle length of 14 to 28 days. Dose escalation proceeded in two stages. In step A, intra-patient dose escalation (starting dose of 5mcg daily) was allowed based on degree of toxicity regardless of attribution. Step A escalation continued until 2 patients had ≥ grade 2 toxicity at a dose level. Step B is a standard, inter-patient only, dose-escalation trial (starting dose based on Step A) with cohorts of three. Dose limiting toxicity is defined as ≥ grade 3 toxicity. Results: Nineteen patients have enrolled between May and December 2005, eight to step A and eleven to step B. During step A escalation, two patients at 15 μg/day experienced severe toxicity (grade 4 hyperuricemia and grade 3 alkaline phosphatase) and two patients at 15 μg/day experienced grade 1 hypercalcemia. Hypercalciuria has been common. No hypercalcemia ≥ grade 2 has been observed. Step B enrollment continues at 30 μg/day without hypercalcemia. Conclusions: Daily administration of LR-103 has not resulted in significant hypercalcemia to date. Dose escalation continues. No significant financial relationships to disclose.
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Mole, Christopher. „Nineteen Fifty-Eight: Information Technology and the Reconceptualisation of Creativity“. Cambridge Quarterly 40, Nr. 4 (01.12.2011): 301–27. http://dx.doi.org/10.1093/camqtly/bfr030.
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Mathias, R., I. Salusky, W. Harman, A. Paredes, J. Emans, G. Segre und W. Goodman. „Renal bone disease in pediatric and young adult patients on hemodialysis in a children's hospital.“ Journal of the American Society of Nephrology 3, Nr. 12 (Juni 1993): 1938–46. http://dx.doi.org/10.1681/asn.v3121938.
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Renal bone disease has been well defined in adult patients receiving chronic dialysis and in children on peritoneal dialysis/continuous ambulatory peritoneal dialysis. However, little is known about the histologic features in patients undergoing chronic hemodialysis in a children's hospital center. Twenty one patients, aged 17.5 +/- 1.5 yr, on hemodialysis for 35 +/- 6 months underwent iliac crest bone biopsies and deferoxamine infusion tests. Nineteen of 21 patients were receiving oral calcitriol. The 21 patients were classified by histomorphometry as follows: osteitis fibrosa, 5; mild hyperparathyroidism, 3; normal histology, 3; aplastic, 6; and mixed lesions, 4. Four of 21 patients were surface positive for aluminum, and seven other patients stained positive for iron in bone. Serum parathyroid hormone (PTH) levels correlated directly with the bone formation rate (r = 0.84) and with eroded bone perimeter (r = 0.67). Eight of the nine patients with serum PTH levels above 125 pg/mL had marrow fibrosis. All patients with serum calcium levels < 10.0 mg/dL and serum PTH levels > 125 pg/mL had either osteitis fibrosa or mixed bone lesions--a group of patients that might benefit from aggressive vitamin D therapy. In contrast, an examination of patients with serum calcium levels > 10.0 mg/dL and serum PTH levels < 65 pg/mL correctly identified three out of three patients with aluminum-related bone disease. These findings suggest that measurements of serum intact PTH levels by the immunoradiometric assay method may be valuable in distinguishing high-turnover lesions from normal or low-turnover skeletal lesions in this population.
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Johnson, D. H., A. T. Turrisi, A. Y. Chang, R. Blum, P. Bonomi, D. Ettinger und H. Wagner. „Alternating chemotherapy and twice-daily thoracic radiotherapy in limited-stage small-cell lung cancer: a pilot study of the Eastern Cooperative Oncology Group.“ Journal of Clinical Oncology 11, Nr. 5 (Mai 1993): 879–84. http://dx.doi.org/10.1200/jco.1993.11.5.879.
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PURPOSE This pilot study was undertaken to determine the efficacy and feasibility of alternating cisplatin and etoposide with multiple daily fractions of thoracic radiotherapy (TRT) in patients with limited-stage small-cell lung cancer (SCLC). PATIENTS AND METHODS Thirty-four SCLC patients received four courses of cisplatin (30 mg/m2/d x 3) plus etoposide (120 mg/m2/d x 3) (PE) every 3 weeks. TRT was administered twice daily (1.5 Gy per fraction) for 5 consecutive days in the week after cycles 1, 2, and 3 of chemotherapy (total TRT dose, 45 Gy). Patients who achieved a complete response (CR) received one course of late-intensification (LI) treatment consisting of cyclophosphamide (4 g/m2) and etoposide (900 mg/m2). Prophylactic cranial irradiation (PCI) was optional. RESULTS Nineteen of 32 assessable patients achieved a CR (59%) and 12 had a partial response (38%), for an overall response rate of 97% (95% confidence interval [CI], 84% to 99%). Median survival was 18 months, while 2-year progression-free survival was 47%. Leukopenia < or = 1,000/microL occurred in 12% of induction treatment cycles. Severe esophagitis was uncommon. Pulmonary fibrosis that was asymptomatic or minimally symptomatic was observed in eight patients (25%). There was one episode of adult respiratory distress syndrome (ARDS) during LI chemotherapy. Life-threatening neutropenia (< or = 500/microL) developed in all patients who underwent LI chemotherapy, with a median duration of 10 days (range, 8 to 19). Two patients died of sepsis during LI chemotherapy. CONCLUSION Alternating PE and TRT as performed in this trial is an effective brief induction regimen for limited-stage SCLC. However, this particular regimen did not appear to be substantially different in terms of efficacy or toxicity compared with regimens using concurrent chemotherapy and standard-fraction TRT. LI chemotherapy was associated with unacceptable toxicity and did not appear to have a favorable impact on survival.
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Zhou, Gaoshi, Rirong Chen, Yueyun Jiang, Li Li, Jieqi Zheng, Chao Li, Shenghong Zhang und Minhu Chen. „Development and validation of a non-invasive biomarker-based model to identify endoscopic recurrences of Crohn’s disease“. Therapeutic Advances in Gastroenterology 15 (Januar 2022): 175628482210890. http://dx.doi.org/10.1177/17562848221089096.
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Background: Endoscopic recurrence is common in postoperative patients with Crohn’s disease (CD). Monitoring endoscopic recurrence is important for selecting an appropriate treatment to prevent the development of postoperative disease. The aim of this study was to develop and validate a diagnostic model to identify endoscopic recurrence. Methods: This was a retrospective cohort study recruiting postoperative CD patients who underwent endoscopy at the First Affiliated Hospital, Sun Yat-sen University from January 2016 to June 2020. Endoscopic recurrence was defined as Rutgeerts score > i1. Thirty non-invasive biomarkers, including C-reactive protein, erythrocyte sedimentation rate, vitamin D, complete blood count, and biochemical blood indices, were used as candidate predictors to build a multivariate logistic regression diagnostic model. The predictive ability of the diagnostic models was assessed by receiving the area under the characteristic curve (AUC) and calibration plots, and internal validation was performed by the bootstrap method. Results: Two hundred and nineteen eligible patients were included in this study, and 135 (61.6%) patients had a postoperative endoscopic recurrence. The final diagnostic model included eight biomarkers with an AUC (95% confidence interval (CI)) of 0.796 (0.737–0.855) to identify endoscopic recurrence. The AUC, sensitivity, and specificity of this diagnostic model were 0.781 (0.780–0.782), 0.647 (0.643–0.651) and 0.811 (0.807–0.815), respectively, by internal validation. In addition, the diagnostic model exhibited good calibrability with calibration slope, calibration-in-the-large (‘mean calibration’) and Brier scores of 1.00, 0.00, and 0.175, respectively. Conclusion: This non-invasive biomarker-based diagnostic model has an excellent ability to identify endoscopic recurrence in patients with CD. Application of the model to clinical practice to monitor postoperative patients may be helpful for patient management.
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Sangeda, Raphael Z., Perpétua Gómes, Soo-Yon Rhee, Fausta Mosha, Ricardo J. Camacho, Eric Van Wijngaerden, Eligius F. Lyamuya und Anne-Mieke Vandamme. „Development of HIV Drug Resistance in a Cohort of Adults on First-Line Antiretroviral Therapy in Tanzania during the Stavudine Era“. Microbiology Research 12, Nr. 4 (12.11.2021): 847–61. http://dx.doi.org/10.3390/microbiolres12040062.
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As more HIV patients start combination antiretroviral therapy (cART), the emergence of HIV drug resistance (HIVDR) is inevitable. This will have consequences for the transmission of HIVDR, the success of ART, and the nature and trend of the epidemic. We recruited a cohort of 223 patients starting or continuing their first-line cART in Tanzania towards the end of the stavudine era in 2010. Patients were then followed for one year. Of those with a viral load test at baseline and follow-up time, 34% had a detectable viral load at the one-year endpoint. For 41 patients, protease and reverse transcriptase genotyping were successful. Eighteen samples were from cART-naïve patients, and 23 samples were taken under therapy either at baseline for cART-experienced patients or from follow-up samples for both cART–naïve and cART–experienced patients. The isolates were subtype A, followed by C and D in 41.5%, 22%, and 12.2% of the patients, respectively. No transmitted HIVDR was detected, as scored using the surveillance drug resistance mutations (DRMs) list. However, in 3 of the 18 samples from cART-naïve patients, the clinical Rega interpretation algorithm scored 44D or 138A as non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance-associated polymorphisms. The most observed nucleoside reverse transcriptase inhibitor (NRTI) mutation was 184V. The mutation was found in 16 patients, causing resistance to lamivudine and emtricitabine. Nineteen patients had NNRTI resistance mutations, the most common of which was 103N, observed in eight patients. These high levels of resistance call for regular drug resistance surveillance in Tanzania to inform the control of the emergence and transmission of HIVDR.
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Soverini, Simona, Giovanni Martinelli, Gianantonio Rosti, Simona Bassi, Marilina Amabile, Angela Poerio, Barbara Giannini5 et al. „ABL Mutations in Late-Chronic Phase Chronic Myeloid Leukemia Patients with Cytogenetic Refractoriness to Imatinib Are Associated with a Greater Likelihood of Progression to Blast Crisis and Shorter Survival. on behalf of the GIMEMA Working Party on Chronic Myeloid Leukemia.“ Blood 104, Nr. 11 (16.11.2004): 1005. http://dx.doi.org/10.1182/blood.v104.11.1005.1005.
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Abstract Using a novel denaturing-high performance liquid chromatography (D-HPLC)-based screening method, we investigated the frequency and prognostic relevance of ABL mutations in 47 CML patients who never achieved a major cytogenetic response in 12 months of Imatinib therapy. Seven patients were enrolled in the CML/011/STI571 trial (early-CP patients treated with Imatinib 400 mg/d and peghilated-interferon) while the remaining 40 were enrolled in the CML/002/STI571 trial (late-CP patients resistant/refractory to α-interferon, treated with Imatinib 400 mg/d). For each patient, a longitudinal analysis was done on all the available samples collected from Imatinib start up to the twelfth month of therapy. A nested RT-PCR was set up and, for each sample, two fragments of 393 and 482 bp spanning the ABL kinase domain were analysed. Two out of 7 (29%) early-CP patients had mutations, resulting in both cases in novel aminoacid substitutions (F311I, E355D). Mutations were already detectable at 6 and 9 months, respectively, from Imatinib start. Nineteen out of 40 (48%) late-CP patients had mutations. Eleven patients showed mutations falling in close proximity (M244V) or within (G250E, Y253F, Y253H, E255K, E255V) the P-loop. Eight patients showed mutations outside the P-loop (F311L, F317L, M351, E355G, F359V, H396R and a silent mutation at codon 298). Mutations were already detectable after a median of 3 months (range, 1–6) from onset therapy. At the time of mutation detection, all patients but four had sustained hematologic response. Presence of a missense mutation was significantly associated with a greater likelihood of subsequent progression to accelerated phase/blast crisis (AP/BC)(P=0.0002) and shorter survival (P=0.001). Patients with mutations falling in close proximity or within the P-loop had a particularly poor outcome in terms of time to progression to AP/BC with respect to the remaining mutated patients (P=0.03). Our results indicate that: i) ABL kinase domain mutations may be found also in the setting of early-CP CML patients, even though they are not the predominant mechanisms of resistance; ii) as many as 50% of late-CP patients who fail to achieve cytogenetic control of the disease in the first 6 months of therapy already have evidence of a mutation by D-HPLC analysis; iii) within cytogenetic nonresponders, presence of ABL mutations may identify a subset of patients with particularly poor prognosis. Thus, irrespective of the hematologic response, regular monitoring for emerging mutations in the first months of Imatinib administration may play a crucial role in detecting patients for whom a revision of the therapeutic strategy should be considered.
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Luo, Yi, Yamin Tan, Xiaoyu Lai, Jimin Shi, Weiyan Zheng und He Huang. „HLA-Haploidentical Stem Cell Transplantation for Malignant Hematological Diseases Using G-CSF Mobilized Bone Marrow and Peripheral Blood Stem Cells“. Blood 116, Nr. 21 (19.11.2010): 2384. http://dx.doi.org/10.1182/blood.v116.21.2384.2384.
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Abstract Abstract 2384 Introduction: Allogeneic haematopoietic stem cell transplantation (HSCT) has been used to treat malignant hematological diseases. For patients who do not have a matched sibling donor or a matched unrelated donor (MUD) for transplantation, an eligible HLA-haploidentical donor can be identified rapidly in nearly all cases. However, HLA-haploidentical BMT has been associated with significant risks of complication, such as graft rejection and severe GVHD and infection. Materials and Methods: Thirty eight consecutive patients with malignant hematological diseases received HLA-haploidentical stem cell transplant from April 2008 to June 2010. Eligible patients were 9– 48 years of age with acute myeloid leukemia (n=10),acute lymphocytic leukemia (n=17), myelodysplastic syndrome(n=5), chronic myeloid leukemia (n=4), non Hodgkin lymphoma (n=2). Transplantation conditioning consisted of Ara-C (4 g/m2/d, i.v.) on day -10 and -9, Bu (9.6mg/kg i.v. in 12 doses) on day -8, -7 and -6, Cy (1.8 g/m2/d, i.v.) on day -5 and -4, Me-CCNU (250 mg/kg, i.v.) on day -3, and ATG (2.5 mg/kg/d i.v.) on day -5 to -2. The prophylaxis of aGVHD consisted of cyclosporine A (CsA), mycophenolate mofetil (MMF), and short-term methotrexate. Donors were primed with rhG-CSF (7.5 mg/kg per day) injected subcutaneous (s.c.). Bone marrow cells and peripheral blood stem cells(PBSC) were harvested in nineteen donors, and only PBSC were harvested in the other 19 donors. Results: Primary engraftment was achieved in all patients. All the patients achieved complete donor chimerism in the peripheral blood before day +28. Seven patients (18.4%) had grade I aGVHD, ten (26.3%) had grade II aGVHD, four(10.5%) had grade III aGVHD and four (10.5%) had grade IV aGVHD. II-IV aGVHD occurred in nine patients treated with bone marrow cells and PBSCs, the same number patients suffered from II-IV aGVHD treated with only PBSCs. Transplant related mortality within 100 days after transplantation was 15.8%. At a median follow-up of 10 months (range 2–28months), the overall survival was 68.4%. Conclusion: Haploidentical stem cell transplantation is relatively safe and efficient for the patients who have no HLA matched donors.The results require to confirm and show that G-BM combined with PBSC or G-PBSC from haploidentical family donors have equal effect. Disclosures: No relevant conflicts of interest to declare.
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Androulakis, Nikos, Charalambos Kourousis, Meletios A. Dimopoulos, George Samelis, Stelios Kakolyris, Nikos Tsavaris, Kostas Genatas et al. „Treatment of Pancreatic Cancer With Docetaxel and Granulocyte Colony-Stimulating Factor: A Multicenter Phase II Study“. Journal of Clinical Oncology 17, Nr. 6 (Juni 1999): 1779. http://dx.doi.org/10.1200/jco.1999.17.6.1779.
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PURPOSE: To determine the efficacy and tolerance of single-agent docetaxel and granulocyte colony-stimulating factor in patients with advanced pancreatic cancer. PATIENTS AND METHODS: Thirty-three chemotherapy-naive patients (median age, 65 years) with histologically confirmed pancreatic cancer were treated, after appropriate premedication, with docetaxel (100 mg/m2) and granulocyte colony-stimulating factor (150 μg/m2/d subcutaneously days 2 through 10) every 3 weeks. World Health Organization performance status was 0 to 1 in 28 patients (85%) and 2 in 5 patients (15%). Twenty-nine patients had stage III and IV disease. RESULTS: One complete response (3%) and one partial response (3%) were observed for an overall response rate of 6% (95% confidence interval, 2.1% to 14.2%). Nineteen patients (58%) had stable disease and 12 (36%) had progressive disease. The duration of the two objective responses was 10 and 28 weeks, and the median time to tumor progression was 20 weeks. The median overall survival was 36 weeks. The actuarial 1-year survival was 36.4%. The performance status improved in seven of 21 assessable patients (24%) and pain improved in 14 of 21 (67%) assessable patients; five patients (29%) experienced weight gain during treatment. Disease-related asthenia, anorexia, vomiting, and diarrhea improved in 29%, 15%, 67%, and 47% of the assessable patients, respectively. Serum concentrations of CA 19-9 were decreased by more than 50% in seven patients (35%). Grade 3 and 4 neutropenia occurred in four patients (12%) and eight patients (24%), respectively, with two episodes of febrile neutropenia. There were no treatment-related deaths. Grade 3/4 asthenia occurred in three patients. CONCLUSION: Although docetaxel has a marginal objective activity in pancreatic cancer, it seems to have an important effect on tumor growth control, conferring a clinical benefit.
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Lee, Kyu Eun, und Euy-Soon Choi. „The Effect of Dance Movement Program on Psychological Health in Middle Age Women“. Korean Journal of Women Health Nursing 5, Nr. 1 (28.03.1999): 43–53. http://dx.doi.org/10.4069/kjwhn.1999.5.1.43.
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This study was designed to confirm the effects of the Dance Movement Program on psychological health in middle-age women with depression tendency. 67 women with mile to moderate depression scoring between 16-25 were selected among 235 responded to CES-D (Radloff, 1977, Cho and Kim, 1993). The 46 volunteered to participate in the study were assigned the control. 7 attritions occurred during the course of the experiment leaving thirty-nine subject : nineteen experimental and twenty control, for the final analysis. Research subjects revealed to be homogenous demographically and by health-related variables. The 50-minute Dance Movement Program was performed by the experimental group 3 times a week for eight weeks, from October 6 to November 29, 1997. Depression, life satisfaction, self efficacy were measured before and after the course of Dance Movement Program. Plasma serotonin was measured to identify its relationship with depression, Homogeneity tests revealed satisfactory level on relevant research variables. Data were analyzed by chi2-test, paired and unpaired t-tests.The results are as follows : 1) The hypothesis that depresson score of experimental group will decreased than control group was supported by t-test(t=2.20, P=.0021) 2) The hypothesis that life satisfaction score of experimental group will increased than control group was supported by t-test(t=1.42, P=.0049).3) The hypothesis that self-efficacy score of experimental group will increased than control group was not supported by t-test(t=6.20, P=.0616).4) The hypothesis that level of plasma serotonin will increased than control group was not supported by t-test(t=1.88, P=.0524) Thus, the effects of the Dance Movement Program for the improvement of psychological health gram for the improvement of psychological health for the middle-aged women with depression tendency are scientifically confirmed by this study.
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Kimmick, Gretchen, Smrithi Davakaran, Heather Moore, Cynthia Rose, Pamela Gentry, Michael Willis, Susan Dent et al. „Abstract P4-10-06: Best quality care from a distance (BQual-D): Maintaining high quality care for hormone receptor positive (HR+) metastatic breast cancer (MBC) during the COVID pandemic, description of the program and provider satisfaction“. Cancer Research 82, Nr. 4_Supplement (15.02.2022): P4–10–06—P4–10–06. http://dx.doi.org/10.1158/1538-7445.sabcs21-p4-10-06.
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Abstract Background: During the COVID pandemic, we designed and implemented a program, called BQual-D, to maintain high quality care for patients with HR+, HER2 negative MBC who were taking oral anti-cancer therapy and needed to shelter at home. This program augmented available clinical resources with (1) trained nurse coaches to manage side effects, improve adherence, monitor for cancer progression and screen for psychological distress via telehealth, and (2) a care coordinator to arrange blood testing at local labs to facilitate timely medication dose adjustments. BQual-D served patients from August, 2020 through April of 2021. Here, we describe survey results assessing provider satisfaction with BQual-D. Methods: Surveys assessing provider satisfaction were distributed in December, 2020 (Survey#1) and in April, 2021 (Survey#2). Provider demographics were collected with Survey#1. Eight questions assessed satisfaction with different aspects of the BQual-D program, including content of the nurse coach notes, communication with the program, timeliness of communication, frequency of notes, ease of reading the notes, ease of referring patients, and turnaround time for labs, which were rated on a Likert scale of 1 (strongly dissatisfied) to 10 (strongly satisfied), with an additional response choice of 0 (unable to assess). Providers were also asked if BQual-D led to changes in patient management (yes/no), the degree to which BQual-D supported the medical management of the patient (from 1=not at all to 7=significantly), the influence of BQual-D on patient wellbeing (positive effects, no change, negative effects), and the overall quality of care delivered by the program (from 1=excellent to 4=poor). Finally, we asked providers if they would continue to recommend their patients to BQual-D (yes, in the same way as the program has been deployed; yes but with improvements; or no). Results are described by frequencies and means. Results: Nineteen providers responded to Survey#1. Providers were physicians (31.6%), advanced practice providers (31.6%), nurses (31.6%) and a clinical pharmacist (5.3%). Respondents were 89.5% female, 94.7% White, and had a mean age of 44 years and mean 11 years in practice. Providers rated the quality of care provided by the BQual-D program as excellent (44%) or good (57%), all providers surveyed indicated that they would continue to recommend the program to patients, and 95% of providers indicated that the program had a positive effect on patients’ well-being. Half of the respondents indicated that BQual-D resulted in changes in or addition to patient management and 90% indicated that BQual-D significantly supported medical management. Providers were strongly satisfied (scores of 8-10 on the Likert scale) with overall communication with the BQual-D team (74%) and timeliness of communications (79%). Providers were also strongly satisfied with the content (68.4%), frequency (74%), and ease of reading (68%) program notes. Seven providers completed Survey#2, in which providers rated the overall quality of the program as excellent (57%) or good (43%); 86% indicated that they would continue to recommend the program to patients, and 86% indicated that the program had a positive effect on patients’ well-being. Conclusions: During the COVID pandemic, when sheltering at home was encouraged, provider satisfaction with BQual-D, which provided additional health resources (nurse coaches, care coordinator) to support patients on oral therapy for HR+ MBC, was high. Resources needed to implement BQual-D should be explored as a way of providing additional support for patients and providers in order to minimize the requirement for in-person visits. Funding: Supported by a grant from Pfizer. Citation Format: Gretchen Kimmick, Smrithi Davakaran, Heather Moore, Cynthia Rose, Pamela Gentry, Michael Willis, Susan Dent, Sarah Sammons, Jeremy Force, Kelly Westbrook, Carey Anders, Rebecca Shelby. Best quality care from a distance (BQual-D): Maintaining high quality care for hormone receptor positive (HR+) metastatic breast cancer (MBC) during the COVID pandemic, description of the program and provider satisfaction [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-10-06.
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Li, Hongmin, Liru Wang, Yue Wu, Li Su, Hong Zhao, Yongqing Zhang, Zhao Wang et al. „Very Low-Dose Decitabine Is Effective in Treating Intermediate or High Risk Myelodysplastic Syndrome“. Blood 128, Nr. 22 (02.12.2016): 5536. http://dx.doi.org/10.1182/blood.v128.22.5536.5536.
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Abstract Background: As an available hypomethylating agent, decitabine has significantly improved the outcome of patients with myelodysplastic syndrome (MDS). Nowadays the regular recommendation dose of decitabine is 20 mg/m2/d for five consecutive days with relatively high incidence of treatment related morbidities and costs. In this study, we aim to explore the efficacy and safety of very low-dose decitabine in the treatment of patients with MDS. Methods: The clinical data of twenty-nine newly diagnosed consecutive MDS patients with IPSS intermediate-1-risk or above from fourteen hospitals in Beijing between Nov. 2015 to May. 2016 were collected retrospectively. Twenty-four patients received decitabine monotherapy (decitabine 7mg/m2/d for 7 days, repeated every 4 weeks), five patients received decitabine combined with decreased dose of CAG (Acla 10mg, d1-7; cytarabine 10mg q12h, d1-8; G-CSF150ug q12h, d1-14, repeated every 4-6 weeks). The overall response (ORR), complete remission (CR), partial response (PR) and hematologic improvement (HI) rate was evaluated. The safety profile and the treatment cost were documented. Factors affecting the efficacy were also analyzed in the end using the chi-square test or Fisher's exact test for categorical data and the Wilcoxon rank-sum test or the Student's t test for continuous data. Results: Of the twenty-nine patients, twenty-one were males and eight were females. The median age was 63 years (36~85 years). Two patients (6.9%) were diagnosed as MDS-RCUD, three (10.3%) as MDS-RCMD, ten (34.5%) as MDS-RAEB1, and fourteen (48.3%) as MDS-RAEB2. At the end of follow-up time, the medium course was 2 (range 1-11 courses). Nine patients (31%) finished one course, seven patients (24.1%) finished two courses, five patients (17.2%) finished three courses, eight patients (27.4%) finished four or more courses. Ten patients achieved CR (34.5%), eight (27.6%) PR, one (3.4%) HI, eight (27.6%) stable disease (SD), two (6.8%) progress disease (PD) or death. The overall response rate (ORR) was 65.5%. Infection and bleeding rate were recorded in 44.9% of the courses, respectively, with 21.7% severe infections and 11.6% severe bleedings. Other side effects were rare and mild including unstable angina pectoris, vomiting, low serum albumin etc. (less than 2%). Two patients died, one died of cerebral hemorrhage within 30 days, and the other died of disease progression after 4 courses of treatment. The median cost of each course of treatment was 7.3 (1.4~28.4), 3.9(1.4~8.9), 3.1 (1.3~10.9), 2.6 (1.2~5.7) thousand dollars respectively. Nineteen patients who achieved at least HI (responders) were compared with the rest ten patients who did not benefit from the treatment (non-responders). Only difference in age (67.3±11.8 years for responders vs 56.1±11.9 years for non-responders, p=0.023) and proportion of bone marrow blast cells (10.8±4.9% for responders vs 5.8±5.3% for non-responders, p=0.016) was found between responders and non-responders, whereas no other differences were noticed between the two groups either in sex ratio (M:F 2.2:1 vs 4:1, p=0.675), high ECOG percentage (57.9% vs 20%, p=0.114), peripheral blood cell counts (hemoglobin 71 g/L vs 66 g/L, p=0.522; neutrophils 0.71 vs 0.6 × 109/L, p=0.426; or platelet 33 vs 75 × 109/L, p=0.218), percentage of adverse prognostic karyotypes (26.3% vs10% , P =0.633), or percent of intermediate -2 or high risk IPSS ( 68.4% vs 40%, p=0.236). Conclusions: Verylow-dose decitabine alone or combined with decreased dose CAG regimen showed relatively good efficacy, well-tolerance and low medical cost in the treatment of intermediate or high risk MDS. Elderly patients or patients with a higher proportion of blast cells may be the better candidates for this regimen. Disclosures No relevant conflicts of interest to declare.
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Garety, Philippa, Thomas Ward, Richard Emsley, Kathryn Greenwood, Daniel Freeman, David Fowler, Elizabeth Kuipers, Paul Bebbington, Graham Dunn und Amy Hardy. „Digitally supported CBT to reduce paranoia and improve reasoning for people with schizophrenia-spectrum psychosis: the SlowMo RCT“. Efficacy and Mechanism Evaluation 8, Nr. 11 (August 2021): 1–90. http://dx.doi.org/10.3310/eme08110.
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Background Reasoning may play a causal role in paranoid delusions in psychosis. SlowMo, a new digitally supported cognitive–behavioural therapy, targets reasoning to reduce paranoia. Objectives To examine the effectiveness of SlowMo therapy in reducing paranoia and in improving reasoning, quality of life and well-being, and to examine its mechanisms of action, moderators of effects and acceptability. Design A parallel-arm, assessor-blind, randomised controlled trial comparing SlowMo plus treatment as usual with treatment as usual alone. An online independent system randomised eligible participants (1 : 1) using randomly varying permuted blocks, stratified by site and paranoia severity. Setting Community mental health services in three NHS mental health trusts in England, plus patient identification centres. Participants A total of 362 participants with schizophrenia-spectrum psychosis. Eligibility criteria comprised distressing and persistent (≥ 3 months) paranoia. Interventions Eight face-to-face SlowMo sessions over 12 weeks plus treatment as usual, or treatment as usual alone (control group). Main outcome measures The primary outcome measure was paranoia measured by the Green Paranoid Thoughts Scale and its revised version, together with observer-rated measures of persecutory delusions (The Psychotic Symptom Rating Scales delusion scale and delusion items from the Scale for the Assessment of Positive Symptoms). The secondary outcome measures were reasoning (measures of belief flexibility, jumping to conclusions, and fast and slow thinking), well-being, quality of life, schemas, service use and worry. Results A total of 362 participants were recruited between 1 May 2017 and 14 May 2019: 181 in the SlowMo intervention group and 181 in the treatment-as-usual (control) group. One control participant subsequently withdrew. In total, 325 (90%) participants provided primary Green Paranoid Thoughts Scale outcome data at 12 weeks (SlowMo, n = 162; treatment as usual, n = 163). A total of 145 (80%) participants in the SlowMo group completed all eight therapy sessions. SlowMo was superior to treatment as usual in reducing paranoia on all three measures used: Green Paranoid Thoughts Scale total at 12 weeks (Cohen’s d = 0.30, 95% confidence interval 0.09 to 0.51; p = 0.005) and 24 weeks (Cohen’s d = 0.20, 95% confidence interval –0.02 to 0.40; p = 0.063); Psychotic Symptom Rating Scales delusions at 12 weeks (Cohen’s d = 0.47, 95% confidence interval 0.17 to 0.78; p = 0.002) and 24 weeks (Cohen’s d = 0.50, 95% confidence interval 0.20 to 0.80; p = 0.001); and Scale for the Assessment of Positive Symptoms persecutory delusions at 12 weeks (Cohen’s d = 0.43, 95% confidence interval 0.03 to 0.84; p = 0.035) and 24 weeks (Cohen’s d = 0.54, 95% confidence interval 0.14 to 0.94; p = 0.009). Reasoning (belief flexibility, possibility of being mistaken and Fast and Slow Thinking Questionnaire measure) improved, but jumping to conclusions did not improve. Worry, quality of life, well-being and self-concept also improved, improving most strongly at 24 weeks. Baseline characteristics did not moderate treatment effects. Changes in belief flexibility and worry mediated changes in paranoia. Peer researcher-led qualitative interviews confirmed positive experiences of the therapy and technology. Nineteen participants in the SlowMo group and 21 participants in the treatment-as-usual group reported 54 adverse events (51 serious events, no deaths). Limitations The trial included treatment as usual as the comparator and, thus, the trial design did not control for the effects of time with a therapist. Conclusions To the best of our knowledge, this is the largest trial of a psychological therapy for paranoia in people with psychosis and the first trial using a brief targeted digitally supported therapy. High rates of therapy uptake demonstrated acceptability. It was effective for paranoia, comparable to longer therapy, and equally effective for people with different levels of negative symptoms and working memory. Mediators were improvements in belief flexibility and worry. Our results suggest that targeting reasoning helps paranoia. Future work Further examination of SlowMo mechanisms of action and implementation. Trial registration Current Controlled Trials ISRCTN32448671. Funding This project was funded by the Efficacy and Mechanism Evaluation (EME) programme, a MRC and National Institute for Health Research (NIHR) partnership. This will be published in full in Efficacy and Mechanism Evaluation; Vol. 8, No. 11. See the NIHR Journals Library website for further project information.
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Zhao, Hehe, Jianxing Wang, Jianhua Chen, Ruifang Huang, Yong Zhang, Jinbo Xiao, Yang Song et al. „Molecular Epidemiology and Evolution of Coxsackievirus A9“. Viruses 14, Nr. 4 (15.04.2022): 822. http://dx.doi.org/10.3390/v14040822.
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Nineteen CVA9 isolates were obtained between 2010 and 2019 from six provinces of mainland China, using the HFMD surveillance network established in China. Nucleotide sequencing revealed that the full-length VP1 of 19 CVA9 isolates was 906 bases encoding 302 amino acids. The combination of the thresholds of the phylogenetic tree and nucleotide divergence of different genotypes within the same serotype led to a value of 15–25%, and enabled CVA9 worldwide to be categorized into ten genotypes: A–J. The phylogenetic tree showed that the prototype strain was included in genotype A, and that the B, C, D, E, H, and J genotypes disappeared during virus evolution, whereas the F, I, and G genotypes showed co-circulation. Lineage G was the dominant genotype of CVA9 and included most of the strains from nine countries in Asia, North America, Oceania, and Europe. Most Chinese strains belonged to the G genotype, suggesting that the molecular epidemiology of China is consistent with that observed worldwide. The 165 partial VP1 strains (723 nt) showed a mean substitution rate of 3.27 × 10−3 substitution/site/year (95% HPD range 2.93–3.6 × 10−3), dating the tMRCA of CVA9 back to approximately 1922 (1911–1932). The spatiotemporal dynamics of CVA9 showed the spread of CVA9 obviously increased in recent years. Most CVA9 isolates originated in USA, but the epidemic areas of CVA9 are now concentrated in the Asia–Pacific region, European countries, and North America. Recombination analysis within the enterovirus B specie (59 serotypes) revealed eight recombination patterns in China at present, CVB4, CVB5, E30, CVB2, E11, HEV106, HEV85, and HEV75. E14, and E6 may act as recombinant donors in multiple regions. Comparison of temperature sensitivity revealed that temperature-insensitive strains have more amino acid substitutions in the RGD motif of the VP1 region, and the sites T283S, V284M, and R288K in the VP1 region may be related to the temperature tolerance of CVA9.
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Pérez-Alvarez, Lucía, Rocío Carmona, Mercedes Muñoz, Elena Delgado, Michael M. Thomson, Gerardo Contreras, José D. Pedreira et al. „High Incidence of Non-B and Recombinant HIV-1 Strains in Newly Diagnosed Patients in Galicia, Spain: Study of Genotypic Resistance“. Antiviral Therapy 8, Nr. 4 (01.05.2002): 355–60. http://dx.doi.org/10.1177/135965350300800413.
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The objectives of this study are to describe the incidence of non-B and recombinant HIV-1 strains in newly diagnosed HIV-1 infections in Galicia, northwest of Spain, during a 2-year period (May 2000 to June 2002), and the frequency of resistance-associated mutations in reverse transcriptase (RT) and protease (PR) genes, analysing the polymorphisms more frequently detected in non-B and recombinant viruses. All newly diagnosed HIV-1-infected patients attending the nine public hospitals of the seven main cities of Galicia were included in this study. RT, PR and V3 regions from HIV-1 RNA plasma were amplified and sequenced, being the corrected sequences sent to the Stanford HIV RT and Protease Sequence Database. Nineteen of 85 patients (22.3%) were infected by non-B or recombinant viruses: three subtype C, two G, one F1, one Dpol/A1V3, five CRF02_AG, one CRF14_BG, five BGpol/BV3 and one UKpol/UV3 (U, unknown fragment). Eleven of these 19 patients (57.9%) were foreign individuals living in Galicia infected through heterosexual contact, and the other eight (42.1%) were Spanish intravenous drug users who had shared injection equipment. Five of 85 patients (5.9%), all infected with B subtype viruses, showed resistance-associated mutations in RT (M184V, M41L, L210W, T215Y/D and K219Q). In one patient (1.2%) infected with a subtype G strain, resistance-associated mutations in PR (K20I+M36I+M46I+V82I) were detected. In subtype B viruses resistance mutations in PR were not detected. Several polymorphisms in RT: D123S, Q174K, D177E, T200A, V245Q, and PR: I13V, K20I, M36I, R41K, H69K, L89M were detected more frequently in non-B and recombinants than in B strains ( P<0.01 to P<0.001). This study reports a high incidence (22.3%) of newly diagnosed patients infected by different non-B and recombinant HIV-1 strains, in a geographical area of Spain, showing also a high frequency of polymorphisms in RT and PR genes.
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Dholakia, Ravindra H. „Exports of Agri-Products from Gujarat: Problems and Prospects“. Vikalpa: The Journal for Decision Makers 28, Nr. 4 (Oktober 2003): 41–52. http://dx.doi.org/10.1177/0256090920030404.
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This paper follows a narrow definition of agri-products that include products of agriculture, horticulture, floriculture, animal husbandry, and poultry. Like most other states in India, Gujarat has also prepared several reports and policy papers assessing the potential for agro-processing, identifying constraints in the development and exports of agri-products, suggesting or announcing several important policy measures for removing physical and financial infrastructural bottlenecks, and promoting R&D activities in the sector. However, these exercises lack realistic assessment of the potential, important features of agri-exports from the state, and Gujarat's comparative advantage over the rest of the country in specific product categories. This paper addresses these aspects. A recent survey of exports originating from Gujarat conducted by the Gujarat Industrial Technical Consultancy Organization (GITCO) estimated that, during the year 2000–01, Gujarat contributed Rs 495 billion (or 20.8%) out of the total national exports of Rs 2,385 billion. However, excluding gems and jewellery and petroleum products, Gujarat's share in the national exports is only 9.2 per cent. Compared to this overall proportion, Gujarat's share in national exports in commodities like groundnut, oil-meals, castor oil, poultry, dairy products, spices, sesame and niger seeds, and processed food, fruits, and vegetables is much higher indicating Gujarat's revealed comparative advantage in these product categories. Some important features of the exports activity in Gujarat are: Only 20 per cent are pure traders in the export business. Only a quarter of the units have ‘export house’ or upward status for special benefits. More than 40 per cent of the exporting units have come up after 1991–92. Two-thirds of the exporters belong to small and medium enterprises. Export intensity of Gujarat's agricultural sector is about 12 per cent. Agri-exports represent excess supply and hence highly volatile and fluctuating activity over time. Agri-exports are price elastic. Agri-exports would be highly responsive to exchange rate depreciation. In recent years, Gujarat's agriculture shows considerable dynamic characteristics in contrast to the gloomy official income estimates in the sector. Nineteen out of 30 crops show significant positive time trend in area while five crops show significant negative trend. The cropping pattern in Gujarat has been shifting away from the low value traditional crops to high value commercial crops with business and export potential. A detailed consideration of yield rates of different crops in the state and other states over the past three decades indicates a realistic potential of 5 per cent per annum growth rate for agriculture in Gujarat over the next eight to ten years. In order to ensure exclusive and regular supply to the export market, quality standards have to be according to the foreign destination and not the domestic market. This calls for large-scale production, assured input supplies, good logistics, infrastructural facilities, R&D activities, and technological upgradation. This involves giving priority to investments in several infrastructural facilities and agricultural R&D besides perfecting agricultural land market and encouraging contract farming in the state.
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Vornicu, A., B. Obrisca, R. Jurubita, B. Sorohan, A. Andronesi, C. Achim, E. Rusu, D. Zilisteanu und G. Ismail. „SAT0188 HIGH-DOSE STEROIDS ARE IMPORTANT CONTRIBUTORS TO THE INFECTION BURDEN OF PATIENTS WITH LUPUS NEPHRITIS“. Annals of the Rheumatic Diseases 79, Suppl 1 (Juni 2020): 1036.1–1036. http://dx.doi.org/10.1136/annrheumdis-2020-eular.1344.
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Background:Infection remains a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE) and lupus nephritis (LN) treated with systemic immunosuppression (IS).Objectives:We sought to describe the infection profile in patients with LN treated with aggressive immunosuppression (induction and maintenance therapy) and to identify the associated risk factors.Methods:Patients with LN followed in the Nephrology Department of Fundeni Clinical Institute, were retrospectively reviewed for any infection that occurred from initiation of induction therapy. Infections were graded (1-5) according to the Common Terminology Criteria for Adverse Events. Infection site and type of microorganism were also recorded. Univariate and multivariate Cox proportional hazard regression analysis were performed in order to identify independent risk factors for infection.Results:The study cohort comprised 101 patients (86.1% females) with a mean age of 34 ± 14 years. Forty-eight patients (47.5%) had at least one infection with a total 92 episodes of infection occurring during a median follow-up of 17 months (IQR:8.5-52.5 months). The majority of patients (31 of 48) had infections during the first 12 months since IS treatment initiation. The most common site was lung infection (in 24.8% of patients), followed by urinary tract (20.8% of patients) and cutaneous/mucosal infections (11% of patients). Thirty-eight percent of patients had bacterial infections. Nineteen percent of patients had severe infections (grade 3 or higher) with 3.3% of infection-related deaths (3 patients). The most common induction regimen was cyclophosphamide in addition to corticosteroids (48.5%), with 44.6% of patients receiving pulse methylprednisolone and 45.5% of patients receiving more than 30 mg/d of prednisone as the maximum oral dose. In univariate Cox regression analysis, female gender (HR 3.34; 95% CI, 1.03-10.8, p=0.04), pulse methylprednisolone (HR 2.9; 95% CI, 1.6-5.24, p=0.001), high-dose (≥30 mg/day) oral corticosteroids (HR 4.22; 95% CI, 2.21-8.02,p=0.001) and SLEDAI score (HR 1.047; 95% CI, 1.012-1.084, p=0.008) were risk factors for infection. In multivariate Cox regression analysis, female gender (HR 6.35; 95%CI, 1.86-21.64,p=0.003), high-dose oral corticosteroids (HR 4.7; 95% CI, 2.25-9.87, p=0.003) and SLEDAI score (HR 1.046; 95% CI, 1.003-1.09, p=0.034) remained independent predictors of infection risk. Of the risk factors associated with severe infections (grade 3 or higher), in univariate analysis we identified younger age (HR 0.96, 95%CI, 0.92-0.99, p=0.035), neurological involvement (HR 2.59; 95%, 0.86-7.83, p=0.09), pulse methylprednisolone (HR 5.42; 95% CI, 1.79-16.35, p=0.003) and high-dose oral corticosteroids (HR 8.32; 95% CI, 2.4-28.77, p=0.001) as risk factors for infection. After multivariate adjustment, neurological involvement (HR 4.33; 95%, 1.29-14.51, p=0.01) and high-dose oral corticosteroids (HR 7.6; 95% CI, 1.6-35.39, p=0.01) were identified as independent predictors of infection risk.Conclusion:A high-dose oral corticosteroid regimen increased the risk for any infection and for severe infections by 4.7-fold and 7.6-fold, respectively. In addition, female gender and a higher SLEDAI score were identified as risk factors for any infection, while neurological involvement was associated with an increased risk for severe infections.References:[1]Jung JY, Yoon D, Choi Y, Kim HA, Suh CH. Associated clinical factors for serious infections in patients with systemic lupus erythematosus. Sci Rep. 2019;9(1):9704.Disclosure of Interests: :None declared
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SULEHRI, MUHAMMAD ANWAR, und NIAZ MUHAMMAD SHEIKH. „LEVEL OF EMPOWERMENT OF WOMEN“. Professional Medical Journal 17, Nr. 04 (10.12.2010): 721–27. http://dx.doi.org/10.29309/tpmj/2010.17.04.3033.
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Objective: To Investigate the Level of Empowerment of Women in accordance with human rights. Design: A cross-sectional study. Setting: Residence Colony of Punjab Medical College, Faisalabad. Period: August - September 2007. Material & Methods: There were 600 houses and 6 Blocks A, B, C, D, E & F in the Colony. By Simple random sampling 10 houses were taken from each Block by drawing lots. Sixty married women’s between the age of 25 – 45 years (One from each house) were interviewed using a pre-tested structured questionnaire. Results: The mean age of the respondents was 37.2 years. Among the total 60 (100%) Women, 16 (26.6%) were illiterate, while 44 (73.3%) had primary education and above. Only 10(22.2%) out of 44 educated women had graduate and above degree. Thirty-Eight (63.3%) women had the opportunity to use the reproductive health services and family planning, while 22 (36.6%) could not utilize the family planning methods. A total of 40 (66.6%) women had good nutritional status, while 20 (33.3%) had imbalances in nutrition. Nineteen (31.6%) women were doing jobs in different public and private institutions, while 41(68.3%) had not got opportunity for jobs. Thirty-Three (55%) women had monthly income lessthan Rs.10,000/- per month and 27(45%) had Rs.10,000/- and above. Forty (66.6%) women were given importance and active participation in decision making, in children marriages. house-hold and in political process (vote casting) at all levels, while 20(33.3%) were not given importance in decision making of above matters. Forty -Three (71.6%) woman were given their right of inheritance / property. Fourteen (23.3%)women were forced to wear veil while going out of house. Forty (66.6%) woman admitted to have suffered from violence either psychological, physical or sexual in their life. Safe drinking water supply was available to 30 (50%) women, however sewage disposal, toilet facilities with in house were available to majority of the respondents. A total of 40 (66.6%) women were over all empowered. Conclusions: Women do havehuman rights as well. The results obtained from this study are encouraging but not up to the standards of International Human rights Principles, which are universal, inalienable; indivisible; interdependent and interrelated.
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Heston, Lee, Ayman El-Guindy, Jill Countryman, Charles Dela Cruz, Henri-Jacques Delecluse und George Miller. „Amino Acids in the Basic Domain of Epstein-Barr Virus ZEBRA Protein Play Distinct Roles in DNA Binding, Activation of Early Lytic Gene Expression, and Promotion of Viral DNA Replication“. Journal of Virology 80, Nr. 18 (15.09.2006): 9115–33. http://dx.doi.org/10.1128/jvi.00909-06.
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ABSTRACT The ZEBRA protein of Epstein-Barr virus (EBV) drives the viral lytic cycle cascade. The capacity of ZEBRA to recognize specific DNA sequences resides in amino acids 178 to 194, a region in which 9 of 17 residues are either lysine or arginine. To define the basic domain residues essential for activity, a series of 46 single-amino-acid-substitution mutants were examined for their ability to bind ZIIIB DNA, a high-affinity ZEBRA binding site, and for their capacity to activate early and late EBV lytic cycle gene expression. DNA binding was obligatory for the protein to activate the lytic cascade. Nineteen mutants that failed to bind DNA were unable to disrupt latency. A single acidic replacement of a basic amino acid destroyed DNA binding and the biologic activity of the protein. Four mutants that bound weakly to DNA were defective at stimulating the expression of Rta, the essential first target of ZEBRA in lytic cycle activation. Four amino acids, R183, A185, C189, and R190, are likely to contact ZIIIB DNA specifically, since alanine or valine substitutions at these positions drastically weakened or eliminated DNA binding. Twenty-three mutants were proficient in binding to ZIIIB DNA. Some DNA binding-proficient mutants were refractory to supershift by BZ-1 monoclonal antibody (epitope amino acids 214 to 230), likely as the result of the increased solubility of the mutants. Mutants competent to bind DNA could be separated into four functional groups: the wild-type group (eight mutants), a group defective at activating Rta (five mutants, all with mutations at the S186 site), a group defective at activating EA-D (three mutants with the R179A, S186T, and K192A mutations), and a group specifically defective at activating late gene expression (seven mutants). Three late mutants, with a Y180A, Y180E, or K188A mutation, were defective at stimulating EBV DNA replication. This catalogue of point mutants reveals that basic domain amino acids play distinct functions in binding to DNA, in activating Rta, in stimulating early lytic gene expression, and in promoting viral DNA replication and viral late gene expression. These results are discussed in relationship to the recently solved crystal structure of ZEBRA bound to an AP-1 site.
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Yuan, Aihua, Sylvie Crasquin-Soleau, Qinglai Feng und Songzhu Gu. „Latest Permian deep-water ostracods from southwestern Guangxi, South China“. Journal of Micropalaeontology 26, Nr. 2 (01.10.2007): 169–91. http://dx.doi.org/10.1144/jm.26.2.169.
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Abstract. A very diverse ostracod fauna was discovered in the latest Permian strata of the Dongpan section, southwestern Guangxi, South China. Fifty-one species belonging to twenty-eight genera were identified and described, including two new species (Bairdia dongpanensis n. sp. and Spinomicrocheilinella anterocompressa n. sp). This type of assemblage, with nineteen palaeopsychrospheric species and four pelagic species, is the first world-wide deep-water ostracod fauna reported from the latest Permian strata and the first one recorded in the Permian of China. The palaeoenvironmental analysis allows one to propose an evaluation of the bathymetry variation along the Dongpan section.
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Yang, Wenrui, Bing Han, Hong Chang, Bingyi Wu, Fankai Meng, Dexiang Ji, Yingmei Li et al. „Real-World Effectiveness and Safety of Eltrombopag in Patients with Aplastic Anemia: A Chinese Nationwide Survey“. Blood 134, Supplement_1 (13.11.2019): 5020. http://dx.doi.org/10.1182/blood-2019-126441.
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Immunosuppressive therapy (IST) based on antithymoglobin (ATG) and cyclosporin (CsA) is the first-line treatment for severe aplastic anemia (SAA) patients who are unfit for transplantation,and the overall response rate (ORR) is about 70%.The utility of eltrombopag (EPAG),a TPO receptor agonist, achieved robust hematologic response in refractory and treatment-naïve SAA patients in clinical trials and some other studies. However, only a few data came from Asia countries where higher incidence of AA has been reported. A retrospective study on the use of EPAG in AA was conducted in mainland China. Aplastic anemia (transfusion dependent non-severe, severe, and very severe) patients who started eltrombopag before Feb 2019 and continued for at least 3 months either as first-line treatment or as rescue treatment, were enrolled. The maximum daily dosage of EPAG used continuously for at least 2 weeks is defined as the stable dosage. Response criteria were referred to that used in previous reports (Townsley DM, NEJM 2017; BCSH, BJH 2016). Fifty-six patients from eleven centers were enrolled in this study, including 26 males and 30 females at the median age of 39 (7-80) years. All patients were transfusion-dependent by the time of EPAG administration, and there were 14 VSAA, 24 SAA and 18 transfusion dependent non-severe aplastic anemia (TD-NSAA). Nineteen treatment-naïve patients received EPAG and IST (ATG+CsA, n=10; CsA/CsA+androgen, n=9) as first-line treatment. Thirty-seven patients were refractory to IST. Eltrombopag was administered at a median dose of 75 (25-150) mg per day for 7 (3-31) month. The median follow-up time was 9 (3-40) months. The overall response rate in patients receiving EPAG as first-line therapy was 78.9% (15/19), and most patients achieved complete response (CR) (10/15). Among the 10 patients receiving ATG+CsA, 6 patients achieved hematologic response (HR) at 3 months post-treatment, including 3 CR. Six patients were diagnosed as VSAA and three achieved HR. For the 9 patients treated with CsA/CsA+androgen, 8 achieved HR (88.9%) and 4 were CR (44.4%) at 3 months. By last follow-up, the cumulative HR rate was 70% in ATG+CsA group and 89% in CsA/CsA+ androgen group. Among the 14 responders, 11 patients receiving EPAG at a stable dosage ≤75mg/d and achieved HR at 3 months. The overall response rate in IST-refractory patients was 46% (17/37), with trilineage response in 27% patients at 3 months. For the 18 ATG+CsA refractory SAA patients,trilineage HR occurred in 4 patients (22.2%, 4/18), bi-lineage HR in one patient and single lineage HR in one patient. Thus, the total HR was 33.3% (6/18) at 3 months and increased to 44% (8/18) by last follow-up. Among the 19 CsA/CsA+ androgen refractory patients, 6 (31.5%, 6/19) achieved trilineage HR, one achieved bi-lineage HR and 4 achieved single lineage response. Total HR rate was 57.9% (11/19) at 3 months after EPAG initiation and 68% (13/19) by last follow-up, including 9 patients with trilineage HR. Among 17 responders, 13 received a stable EPAG dose of≤75mg/d. Most patients tolerated EPAG well. Adverse events occurred in 29 patients (52%) and most were mild to moderate, including gastrointestinal symptom (n=15, e.g. abdominal pain, nausea), impaired liver function (n=5), skin changes (n=7, e.g. skin pruritus and rash) and musculoskeletal pain (n=6), and venous thrombus (n=2). Eltrombopag dosage was reduced in 2 patients due to severe digestive symptoms at 100 mg/d and discontinued in one patient who suffered from upper limb venous thrombus. In conclusion, EPAG is effective and safe in treating Chinese AA patients at a daily dose of 75mg and less. The real-world result of EPAG in Chinese patients is similar to those reported in Western countries. Disclosures No relevant conflicts of interest to declare.
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Plate, Markus, Rosy Priya Kodiyanplakkal, Michael J. Satlin, Rosemary Soave, Alexander Christian Drelick, Nina Orfali, David Helfgott et al. „532. COVID-19 Pneumonia in Patients with Hematologic Malignancies – A Report from the US Epicenter“. Open Forum Infectious Diseases 7, Supplement_1 (01.10.2020): S333. http://dx.doi.org/10.1093/ofid/ofaa439.726.
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Abstract Background Limited data are available for risk assessment and outcome of COVID-19 in patients with hematologic malignancies (HM). We present a single center study of COVID-19 pneumonia in a cohort of 31 patients with HM. Methods Data were abstracted from electronic medical records for patients admitted to NYPH between 3/5/20 and 4/17/20 and entered into a REDCap database. Results Twenty (64.5%) were male; median age was 71 years. There were 8 patients with Multiple Myeloma (MM), 8 with Chronic Lymphocytic Leukemia (CLL), 6 (19.4%) had AML, 5 (16.1%) NHL, 2 (3.2%) ALL; CML, MDS and Polycythemia Vera occurred in 1 patient each. Twenty-four (77.4%) had active HM; 6 (19.4%) were in remission; and 1 relapsed. Nineteen patients (61.3%) received recent chemotherapy and 11 (35.5%) immunosuppressive therapies. There were 7 (22.6%) hematopoietic stem cell transplant (HSCT) recipients (4 allogeneic and 3 autologous). Comorbidities were evenly distributed among all malignancies: 18 (58.1%) had hypertension, 9 (38.7%) obesity, 7 (22.6%) diabetes mellitus, and 11 (35.5%) were former smokers. The most common symptoms included cough (90.3%), fever (83.9%) and dyspnea (61.3%); 7 (22.6%) had nausea and vomiting; 7 (22.6%) had diarrhea. On presentation, hypoxia (O2 sat ≤94% on room air) occurred in 64.5%; median ALC was 330/ml; 23 (74.2%) had ALC< 1000/ml; median CRP was 15.9 mg/dl (2.5–40.4), ferritin 1162 ng/ml (264 - > 16500), and D-dimers 456 ng/ml (< 150–2418). Thirteen patients (41.9%) required ICU admission and were intubated; among those 9 (69.2%) had either MM or CLL. Co-infections were uncommon; two patients developed HSV1 pneumonitis and one of these also had CMV pneumonitis. Twenty-eight (90.3%) were treated with hydroxychloroquine, 5 (16.1%) remdesivir, 2 (6.5%) tocilizumab, 1 (3.2%) sarilumab, and 4 (12.9%) with methylprednisolone 0.5mg/kg Q12h. Seventeen patients (54.8%) recovered and were discharged, 12 (38.7%) died; 2 (6.5%) were still hospitalized but left the ICU. Conclusion In our cohort, there were predominantly more patients with MM and CLL and 56% of these were intubated; larger cohort studies will further define the risk and outcome for COVID-19 in patients with HM. Disclosures Michael J. Satlin, MD, MS, Achaogen (Consultant)Allergan (Grant/Research Support)Merck (Grant/Research Support)Shionogi Inc. (Consultant)
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Tall, B. D., S. Fall, M. R. Pereira, M. Ramos-Valle, S. K. Curtis, M. H. Kothary, D. M. T. Chu et al. „Characterization of Vibrio fluvialis-Like Strains Implicated in Limp Lobster Disease“. Applied and Environmental Microbiology 69, Nr. 12 (Dezember 2003): 7435–46. http://dx.doi.org/10.1128/aem.69.12.7435-7446.2003.
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ABSTRACT Studies were undertaken to characterize and determine the pathogenic mechanisms involved in a newly described systemic disease in Homarus americanus (American lobster) caused by a Vibrio fluvialis-like microorganism. Nineteen isolates were obtained from eight of nine lobsters sampled. Biochemically, the isolates resembled V. fluvialis, and the isolates grew optimally at 20°C; none could grow at temperatures above 23°C. The type strain (1AMA) displayed a thermal reduction time (D value) of 5.77 min at 37°C. All of the isolates required at least 1% NaCl for growth. Collectively, the data suggest that these isolates may embody a new biotype. Pulsed-field gel electrophoresis (PFGE) analysis of the isolates revealed five closely related subgroups. Some isolates produced a sheep hemagglutinin that was neither an outer membrane protein nor a metalloprotease. Several isolates possessed capsules. The isolates were highly susceptible to a variety of antibiotics tested. However, six isolates were resistant to erythromycin. Seventeen isolates harbored plasmids. Lobster challenge studies revealed that the 50% lethal dose of a plasmid-positive strain was 100-fold lower than that of a plasmid-negative strain, suggesting that the plasmid may enhance the pathogenicity of these microorganisms in lobsters. Microorganisms that were recovered from experimentally infected lobsters exhibited biochemical and PFGE profiles that were indistinguishable from those of the challenge strain. Tissue affinity studies demonstrated that the challenge microorganisms accumulated in heart and midgut tissues as well as in the hemolymph. Culture supernatants and polymyxin B lysates of the strains caused elongation of CHO cells in tissue culture, suggesting the presence of a hitherto unknown enterotoxin. Both plasmid-positive and plasmid-negative strains caused significant dose-related intestinal fluid accumulations in suckling mice. Absence of viable organisms in the intestinal contents of mice suggests that these microorganisms cause diarrhea in mice by intoxication rather than by an infectious process. Further, these results support the thermal reduction data at 37°C and suggest that the mechanism(s) that led to fluid accumulation in mice differs from the disease process observed in lobsters by requiring neither the persistence of viable microorganisms nor the presence of plasmids. In summary, results of lobster studies satisfy Koch's postulates at the organismal and molecular levels; the findings support the hypothesis that these V. fluvialis-like organisms were responsible for the originally described systemic disease, which is now called limp lobster disease.