To see the other types of publications on this topic, follow the link: TVT and SPARC.
Journal articles on the topic 'TVT and SPARC'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 44 journal articles for your research on the topic 'TVT and SPARC.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Wein, Alan J. "TVT and Sparc Suburethral Slings: A Case-Control Series." Journal of Urology 173, no. 4 (April 2005): 1265–66. http://dx.doi.org/10.1016/s0022-5347(05)61070-1.
Full text
2
Dietz, H. P., A. J. Foote, H. L. J. Mak, and P. D. Wilson. "TVT and Sparc suburethral slings: a case?control series." International Urogynecology Journal and Pelvic Floor Dysfunction 15, no. 2 (April 1, 2004): 129–31. http://dx.doi.org/10.1007/s00192-003-1118-4.
Full text
3
Wang, Xijun, Wei Chen, and Zhigang Cao. "SPARC: Superposition-Aided Rateless Coding in Wireless Relay Systems." IEEE Transactions on Vehicular Technology 60, no. 9 (November 2011): 4427–38. http://dx.doi.org/10.1109/tvt.2011.2171773.
Full text
4
Gandhi, Sanjay, Yoram Abramov, Christina Kwon, Jennifer L. Beaumont, Sylvia Botros, Peter K. Sand, and Roger P. Goldberg. "TVT versus SPARC: comparison of outcomes for two midurethral tape procedures." International Urogynecology Journal 17, no. 2 (August 4, 2005): 125–30. http://dx.doi.org/10.1007/s00192-005-1369-3.
Full text
5
Kim, J. Y., H. C. Jung, K. H. Moon, T. C. Park, D. Y. Kim, and C. H. Park. "312 Comparisons of iris, TVT and SPARC procedure for stress urinary incontinence." European Urology Supplements 3, no. 2 (February 2004): 80. http://dx.doi.org/10.1016/s1569-9056(04)90311-9.
Full text
6
Kim, Ji Yoon, and Hee Chang Jung. "The Efficacy of IRIS Procedure in Stress Urinary Incontinence: Comparison with TVT and SPARC." Journal of the Korean Continence Society 10, no. 2 (2006): 126. http://dx.doi.org/10.5213/jkcs.2006.10.2.126.
Full text
7
&NA;. "Randomized Clinical Trial Comparing Suprapubic Arch Sling (SPARC) and Tension-Free Vaginal Tape (TVT)." Journal of Urology 175, no. 1 (January 2006): 224. http://dx.doi.org/10.1097/00005392-200601000-00063.
Full text
8
Botros, S. M., J. R. Miller, M. Akl, R. P. Goldberg, and P. K. Sand. "NON-ORAL POSTER 28: Detrusor Overactivity and Urge Incontinence in Monarc Versus TVT And SPARC." Journal of Pelvic Medicine and Surgery 12, no. 2 (March 2006): 89–90. http://dx.doi.org/10.1097/00146866-200603000-00056.
Full text
9
Andonian, Sero, Tony Chen, Benoit St-Denis, and Jacques Corcos. "Randomized Clinical Trial Comparing Suprapubic Arch Sling (SPARC) and Tension-Free Vaginal Tape (TVT): One-Year Results." European Urology 47, no. 4 (April 2005): 537–41. http://dx.doi.org/10.1016/j.eururo.2004.12.023.
Full text
10
Andonian, S., T. Chen, B. St-Denis, and J. Corcos. "Randomized Clinical Trial Comparing Suprapubic Arch Sling (SPARC) and Tension-Free Vaginal Tape (TVT): One-Year Results." Journal of Urology 175, no. 1 (January 2006): 224. http://dx.doi.org/10.1016/s0022-5347(05)00132-1.
Full text
11
Choi, S., J. Ku, H. Son, S. J. Oh, S. Kim, and J. S. Paick. "POS-01.03: Tension-free vaginal tape (TVT), suprapubic ARC (SPARC) sling and transobturator tape (TOT) in the treatment of mixed urinary incontinence in women." Urology 70, no. 3 (September 2007): 189. http://dx.doi.org/10.1016/j.urology.2007.06.891.
Full text
12
Andonian, Sero, Tony Chen, Benoit St-Denis, and Jacques Corcos. "1238: Randomized Clinical Trial Comparing Suprapubic Arch Sling (Sparc) and Tension-free Vaginal Tape (TVT): Safety and One-year Efficacy." Journal of Urology 171, no. 4S (April 2004): 326. http://dx.doi.org/10.1016/s0022-5347(18)38463-5.
Full text
13
Černiauskienė, Aušra. "Du chirurginiai moterų šlapimo nelaikymo gydymo būdai: kurį pasirinkti?" Lietuvos chirurgija 3, no. 4 (January 1, 2005): 0. http://dx.doi.org/10.15388/lietchirur.2005.4.2297.
Full textAbstract:
Aušra ČerniauskienėVilniaus universiteto ligoninės Santariškių klinikosGastroenterologijos, nefrologijos, urologijosir abdominalinės chirurgijos klinika,Nefrologijos ir urologijos centras,Santariškių g. 2, LT-08661 VilniusEl paštas: ausra.cerniauskiene@santa.lt Įvadas / tikslas Pateikti klasikinės kolposuspensijos Burch būdu vėlyvuosius rezultatus, komplikacijas ir palyginti juos su pakėlimo pouretriniais raiščiais metodika, taip pat išanalizuoti, koks gydymo būdas kokiai pacientei geriau tinka. Metodai Nuo 1996 iki 2005 metų buvo atliktos 325 kolposuspensijos Burch būdu. 2002 metais pradėtos daryti pouretrinių raiščių ("Sparc") implantacijos, tačiau jų atlikta nedaug (3 operacijos), nes rinkinys operacijai brangus. Šiame darbe retrospektyviai išnagrinėti 103 ligonių, operuotų 1996–2000 metais nuo šlapimo nelaikymo fizinio krūvio metu atvirąja Burch operacija, vėlyvieji rezultatai. Visoms ligonėms buvo nustatytas šlapimo nelaikymas fizinio krūvio metu (atlikus klinikinius, urodinaminius tyrimus ir kolpocistogramas). Ligonės buvo patikrintos ambulatoriškai, užpildė operacijos rezultatų ir savo gyvenimo kokybės vertinimų anketą. Vėlyvieji rezultatai po kolposuspensijos Burch būdu buvo vertinami praėjus 5 metams. Po raiščių implantacijos rezultatų įvertinti negalime, nes operacijų atlikome mažai. Todėl pateikiame savo atliktų atvirųjų Burch kolposuspensijų rezultatus, komplikacijas ir palyginame juos su literatūroje nurodomais pouretrinių raiščių implantacijos rezultatais. Taip pat lyginame atvirosios Burch operacijos ir pouretrinių raiščių operacijų indikacijas ir kontraindikacijas. Rezultatai Patikrinus ligones po atvirosios Burch operacijos, praėjus 5 metams, 82 (79,6%) ligonių gydymo rezultatai buvo labai geri ir geri, 16 (15,5%) – vidutiniai ir 5 (4,9%) – blogi. Literatūros duomenimis, praėjus 5 metams po Burch operacijos pasveiko 71–88% ligonių. Tai rodo, kad ši operacija iki šiol veiksminga gydant moterų šlapimo nelaikymą. Rezultatai po pouretrinių raiščių implantacijos literatūroje pateikiami tokie: po TVT operacijos praėjus 5 metams, pasveiko nuo 74% iki 90%, po "Sparc" raiščio implantacijos – 83% ligonių. Operacijos metu ir po jos (atvirosios kolposuspensijos Burch būdu ir pouretrinių raiščių implantacijos) pasitaiko chirurginių komplikacijų ir šlapinimosi sutrikimų. Literatūros duomenimis, komplikacijų po raiščių implantacijos yra daugiau negu po kolposuspensijos Burch būdu. Pouretrinių raiščių implantacija praplėtė operacinio moterų šlapimo nelaikymo gydymo indikacijas. Tai paprastos, greitai atliekamos, tačiau Lietuvos pacientėms vis dar brangios operacijos. Išvados Atvirosios kolposuspensijos Burch būdu ir pouretrinių raiščių implantacijos rezultatai panašūs. Kiekviena operacija turi savo indikacijų, nesėkmių ir komplikacijų. Nustatant chirurginio gydymo indikacijas reikia prisiminti, kad pirmoji operacija gali nulemti ligonės ateitį. Todėl kiekvienai pacientei individualiai parenkamas toks operacijos būdas, kuris užtikrintų ilgalaikį efektą, gerą prognozę ir estetinį vaizdą, suteiktų garantiją. Reikšminiai žodžiai: šlapimo nelaikymas, chirurginis gydymas, pouretriniai raiščiai Two methods of surgical treatment of urinary incontinence in women: which to choose? Aušra ČerniauskienėCentre of Nephrology and Urology,Vilnius University Hospital "Santariškių klinikos",Santariškių str. 2, LT-08661 Vilnius, LithuaniaE-mail: ausra.cerniauskiene@santa.lt Background /objective The purpose of this work was to present the distant results and complications of a classical Burch‘s colposuspension, to compare it with the method of raising by means of sub-urethral slings, and to determine which method of treatment suits the patient’s needs best. Patients and methods In the period from 1996 to 2005, 325 Burch‘s colposuspensions were performed. The implanting of sub-urethral slings ("Sparc") was started in 2002, however, only three surgeries were performed due to the high cost of the surgical set. This work retrospectively analyses distant results for 103 patients on which open Burch’s surgery was performed. All patients suffered from urinary incontinence during physical load (confirmed by clinical investigation, urodynamic tests and colpocystography). The patients were examined on an outpatient basis and filled in questionnaires on the evaluation of surgery results and quality of life. Distant results after Burch‘s colposuspension were evaluated after five years; results of sub-urethral sling implantation could not be evaluated as too few surgeries had been performed. Therefore, results of Burch‘s open colposuspensions performed by us are compared with the results of sling implantations described in the literature. Indications and contraindications to Burch‘s open surgery and sub-urethral sling implantation are also compared. Results Very good and goods results five years after Burch‘s open surgery were established for 82 patients (79.6%), medium for 16 patients (15.5%) and bad results for five patients (4.9%). According to the literature, 71 to 88% of patients recovered within five years after Burch‘s surgery. This shows the effectiveness of this operation in treating urinary incontinence in women. The following results of sub-urethral sling implantation are presented in the literature: 74 to 90% patients recovered within five years after TVT surgery and 83% patients after "Sparc" surgery. Surgical complications and urination disorders are potential complications during Burch‘s open colposuspension surgery and sub-urethral sling implantation as well as in the postoperative period. According to the literature, more complications are reported after sling implantations than after Burch‘s colposuspension. Sub-urethral sling surgery has expanded the range of indications for the surgical treatment of urinary incontinence in women. These operations are simple and do not take much time, however, they are still expensive in Lithuania. Conclusions A comparison of the results Burch‘s open colposuspension and sub-urethral sling implantation has shown that these surgeries are similar, each having its indications, failures and complications. While identifying indications for surgical treatment, one should bear in mind that the first surgery may be decisive for the patient’s future. Therefore, the choice of the method should be individual in each case and ensure long-term effects, favourable forecast and aesthetic appearance as well as guarantees to the patient. Keywords: urinary incontinence, surgical treatment, sub-urethral slings
14
Kim, Won Tae, Kyung Tae Kim, Jong Woo Kim, Jin Ho Choe, Joong Shik Lee, and Ju Tae Seo. "Comparative Study of the Tension-Free Vaginal Tape (TVT) Procedure and the Suprapubic Arc Sling (SPARC) Procedure for Treating Female Stress Urinary Incontinence: a 1-Year Follow-Up." Korean Journal of Urology 47, no. 4 (2006): 397. http://dx.doi.org/10.4111/kju.2006.47.4.397.
Full text
15
Scillieri, J. J., J. H. Buckland, and J. S. Freudenberg. "Reference Feedforward in the Idle Speed Control of a Direct-Injection Spark-Ignition Engine." IEEE Transactions on Vehicular Technology 54, no. 1 (January 2005): 51–61. http://dx.doi.org/10.1109/tvt.2004.838842.
Full text
16
Soldera, F. A., F. T. Mucklich, K. Hrastnik, and T. Kaiser. "Description of the Discharge Process in Spark Plugs and its Correlation With the Electrode Erosion Patterns." IEEE Transactions on Vehicular Technology 53, no. 4 (July 2004): 1257–65. http://dx.doi.org/10.1109/tvt.2004.830977.
Full text
17
Fengler, Alexander, Peter Jung, and Giuseppe Caire. "SPARCs for Unsourced Random Access." IEEE Transactions on Information Theory 67, no. 10 (October 2021): 6894–915. http://dx.doi.org/10.1109/tit.2021.3081189.
Full text
18
Gich, Jordi, Jordi Freixanet, Rafael García, Joan Carles Vilanova, David Genís, Yolanda Silva, Xavier Montalban, and Lluís Ramió-Torrentà. "A randomized, controlled, single-blind, 6-month pilot study to evaluate the efficacy of MS-Line!: a cognitive rehabilitation programme for patients with multiple sclerosis." Multiple Sclerosis Journal 21, no. 10 (February 25, 2015): 1332–43. http://dx.doi.org/10.1177/1352458515572405.
Full textAbstract:
Background: MS-Line! was created to provide an effective treatment for cognitive impairment in multiple sclerosis (MS) patients. Objective: To assess the efficacy of MS-Line!. Methods: A randomized, controlled, single-blind, 6-month pilot study. Patients were randomly assigned to an experimental group (cognitive rehabilitation with the programme) or to a control group (no cognitive rehabilitation). Randomization was stratified by cognitive impairment level. Cognitive assessment included: selective reminding test, 10/36 spatial recall test (10/36 SPART), symbol digit modalities test, paced auditory serial addition test, word list generation (WLG), FAS test, subtests of WAIS-III, Boston naming test (BNT), and trail making test (TMT). Results: Forty-three patients (22 in the experimental group, 21 in the control group) were analyzed. Covariance analysis showed significant differences in 10/36 SPART ( P=0.0002), 10/36 SPART delayed recall ( P=0.0021), WLG ( P=0.0123), LNS ( P=0.0413), BNT ( P=0.0007) and TMT-A ( P=0.010) scores between groups. Conclusions: The study showed a significant improvement related to learning and visual memory, executive functions, attention and information processing speed, and naming ability in those patients who received cognitive rehabilitation. The results suggest that MS-Line! is effective in improving cognitive impairment in MS patients.
19
Li Sun, Shan Sun, Tianlei Wang, Jiyun Li, and Jingsheng Lin. "Parallel ADR detection based on spark and BCPNN." Tsinghua Science and Technology 24, no. 2 (April 2019): 195–206. http://dx.doi.org/10.26599/tst.2018.9010074.
Full text
20
Cruz, Antonio Miguel, Adriana Maria Rios Rincon, and Gregory L. Haugan. "Measuring the Performance of Maintenance Service Outsourcing." Biomedical Instrumentation & Technology 47, no. 6 (November 1, 2013): 524–35. http://dx.doi.org/10.2345/0899-8205-47.6.524.
Full textAbstract:
The aims of this paper are (1) to identify the characteristics of maintenance service providers that directly impact maintenance service quality, using 18 independent covariables; (2) to quantify the change in risk these covariables present to service quality, measured in terms of equipment turnaround time (TAT). A survey was applied to every maintenance service provider (n = 19) for characterization purposes. The equipment inventory was characterized, and the TAT variable recorded and monitored for every work order of each service provider (N = 1,025). Finally, the research team conducted a statistical analysis to accomplish the research objectives. The results of this study offer strong empirical evidence that the most influential variables affecting the quality of maintenance service performance are the following: type of maintenance, availability of spare parts in the country, user training, technological complexity of the equipment, distance between the company and the hospital, and the number of maintenance visits performed by the company. The strength of the results obtained by the Cox model built are supported by the measure of the Rp,e2 = 0.57 with a value of Rp,e= 0.75. Thus, the model explained 57% of the variation in equipment TAT, with moderate high positive correlation between the dependent variable (TAT) and independent variables.
21
Hu, Zhiyao, Dongsheng Li, and Deke Guo. "Balance resource allocation for spark jobs based on prediction of the optimal resource." Tsinghua Science and Technology 25, no. 4 (August 2020): 487–97. http://dx.doi.org/10.26599/tst.2019.9010054.
Full text
22
Krigsfeld, Gabriel, Aleeza Roth, Maureen Cooper, Liisa Smith, Radhika Iyer, Adam Brown, James Pratt, John Truesdell, and Joshua Schwartz. "Observational Study of Tissue Acquisition Turnaround Time for Commercial Comprehensive Genomic Profiling in Solid Tumors." American Journal of Clinical Pathology 152, Supplement_1 (September 11, 2019): S145—S146. http://dx.doi.org/10.1093/ajcp/aqz130.009.
Full textAbstract:
Abstract Introduction Increased development and use of next-generation sequencing in clinical diagnostics has revolutionized precision medicine. Steps prior to a specimen arriving at a diagnostic facility, including pathological evaluation, are crucial parameters determining specimen quality and success of comprehensive genomic profiling (CGP). This observational study identified factors that may influence tissue acquisition for commercial CGP in clinical oncology. Methods Data were collected from deidentified patients (n = 63) from select US pathology labs enrolled in a Foundation Medicine (FMI) early access program for the CGP test FoundationOne CDx (Foundation Medicine). A representative substudy cohort (n = 20) with qualitative information available was selected. Lab visit frequency by FMI was monitored for 42 cases. Tissue acquisition turnaround time (TA-TAT) was separated into stages: (1) tissue request to pathology lab acknowledgment, (2) pathology lab acknowledgment to tissue pathology review, (3) tissue pathology review to packaging, and (4) packaging to tissue arriving at FMI. Results Median TA-TAT for the total population was 5.0 days (range, 0-27.0) and 3.5 days for the substudy cohort (range, 1.0-11.0). The duration of each TA-TAT stage was evaluated separately and varied between labs (0%-71.4% of total TA-TAT). TA-TAT was longer for unstained slides compared with formalin-fixed, paraffin-embedded (FFPE) tissue blocks. There was a trend for decreased TA-TAT when stages 1 and 2 occurred on the same day versus different days. For the cases with lab-visit frequency reported, those with biweekly visits had shorter TA-TAT (biweekly: n = 12, median = 2.0, 2.5th-97.5th percentile range, 0.3-5.7 days; single visit: n = 30, median = 5.5, 2.5th-97.5th percentile range, 0.7-13.1 days). Conclusions Understanding and optimizing the tissue acquisition workflow may reduce TA-TAT, thereby facilitating report delivery and subsequent treatment guidance to patients. Funding Bristol-Myers Squibb. Professional medical writing and editorial assistance was provided by Katerina Pipili, PhD, and Jay Rathi, MA, of Spark Medica Inc, funded by Bristol-Myers Squibb.
23
Ye, Xiaoming, Xingshu Chen, Dunhu Liu, Wenxian Wang, Li Yang, Gang Liang, and Guolin Shao. "Notice of Retraction: Efficient feature extraction using apache spark for network behavior anomaly detection." Tsinghua Science and Technology 23, no. 5 (October 2018): 561–73. http://dx.doi.org/10.26599/tst.2018.9010021.
Full text
24
Tang, Jianchao, Ming Xu, Shaojing Fu, and Kai Huang. "A scheduling optimization technique based on reuse in spark to defend against apt attack." Tsinghua Science and Technology 23, no. 5 (October 2018): 550–60. http://dx.doi.org/10.26599/tst.2018.9010022.
Full text
25
Tika, Putu Dian. "Tat Twam Asi Dan Solusi Masalah Study Chandogya Upanisad." JURNAL YOGA DAN KESEHATAN 2, no. 1 (July 3, 2020): 85. http://dx.doi.org/10.25078/jyk.v2i1.1556.
Full textAbstract:
<p><em>Mahavakya tat twam asi is contained in the chandogya upanisad 6.8.7 “which means: you are it; You are all that; All beings are You. You are the beginning of jiwatman (spirit) and substance (prakrti) of all beings. Therefore my soul and your soul are single with the soul of all beings, and you are my source and the source of all beings. Therefore I am you, and vice versa. There are still a few Hindus who understand the meaning of Tat Twam Asi. Even though Tat Twam Asi is the Teachings of the similarity of Human Dignity or the Teachings of the Brotherhood. True, indeed all humans are brothers and sisters as a big family of the world, because the Atman of every human being is the same, namely the spark of the divine light of the Almighty God. Therefore there is also interpreting Tat Twam Asi as my Atman is your Atman, on the contrary your Atman is my Atman but there are also those who interpret Tat Twam Asi as the Doctrine of Compassion, where a large number of human beings must love one another, help each other and sharpen each other, love each other and fostering each other, so that life and human life become harmonious, safe, peaceful and peaceful.</em><em></em></p><p><strong><em><br /></em></strong><em></em><em></em></p>
26
Li, Zhong, and Khiam Aik Khor. "Transparent Hydroxyapatite Obtained through Spark Plasma Sintering: Optical and Mechanical Properties." Key Engineering Materials 631 (November 2014): 51–56. http://dx.doi.org/10.4028/www.scientific.net/kem.631.51.
Full textAbstract:
Transparent bioceramics have great potential for applications in the biomedical field as they facilitate direct observation of the interactions at biomaterial – cell / tissue interfaces. Thus far, sintering of transparent hydroxyapatite (HA) usually involves application of extraordinarily high pressure and / or long duration. This study attempts to fabricate transparent HA by a direct and fast Spark Plasma Sintering (SPS) process using three different types of raw powder: micro-spheres (MS), nanorods (NR) and nanospheres (NS). The optical and mechanical properties of the sintered pellets were examined and compared. The highest total forward transmittance (TFT) showed by sintered MS pellet (~2 mm thick) was 85% in the visible spectrum, whereas sintered NR and NS pellets were either translucent or opaque. Although lowest degree of transparency was observed for NS pellets, they demonstrated highest Young’s modulus (E), hardness (H) and fracture toughness (KIC). The eminent KIC of NS pellets benefited mainly from its self-toughened microstructure.
27
Mikhaiel, Yasmin Zacaria, Heather Barfield, and Abigail Schroering. "Highlights from ATHE 2020: Theory and Criticism Focus Group: Spare Parts." Theatre Topics 31, no. 1 (2021): E—1—E—2. http://dx.doi.org/10.1353/tt.2021.0000.
Full text
28
Aydinok, Yesim, Antonio Piga, Raffaella Origa, Nina Mufti, Anna Erikson, Anne North, Katie Waldhaus, et al. "Hemoglobin Utilization in Asplenic and Non-Splenectomized Transfusion Dependent Thalassemia Patients Supported with Pathogen Reduced Red Blood Cell Concentrates in a Phase 3 Study (SPARC)." Blood 132, Supplement 1 (November 29, 2018): 3812. http://dx.doi.org/10.1182/blood-2018-99-112685.
Full textAbstract:
Abstract Introduction: Transfusion dependent thalassemia (TDT) requires regular transfusion of red cell concentrates (RBCC) to prevent the complications of anemia and excessive erythroid expansion. Despite donor testing, long-term transfusion has a substantial cumulative risk of transfusion-transmitted infection (TTI) due to undetected viruses, bacteria, and protozoa. Splenectomized (-S) TDT patients may have greater TTI morbidity than patients with spleens (+S); but may benefit from reduced use of red blood cell concentrates (RBCC) and reduced transfusion iron (Fe) loading. Pathogen reduction (PR) of RBCC with amustaline-glutathione (A-GSH) offers potential to reduce the risk of TTI. Objectives: To determine, the impact of PR-RBCC on hemoglobin (Hb) use, transfused Fe burden, incidence of RBC antibodies, and safety in -S and +S TDT patients. Methods: TDT patients at 3 sites, not stratified by spleen status, were prospectively enrolled in a two- period cross-over study randomized by sequence for RBCC preparation. Leukocyte reduced PR-RBCC (Test) were treated with 0.2mM amustaline and 20 mM GSH, re-suspended in saline-adenine-glucose mannitol (SAGM), and stored up to 35 days at 4°C. Leukocyte reduced conventional RBCC (Control) were suspended in SAGM and stored for up to 35 days at 4°C. Patients received 6 transfusions in each treatment sequence of Test or Control RBCC over ~ 5 months. Clinicians, blinded to RBCC Hb content and treatment sequence, ordered RBCC to maintain targeted pre-transfusion Hb thresholds of ~ 9-10 g/dL. Transfusion intervals or number of RBCC transfused were adjusted for clinical management. The primary efficacy outcome was assessed by non-inferiority (NI) analysis for Hb use (expressed as g/kg body weight/ day) using a pre-specified NI margin (≤ 15% of the observed Control mean). Results : Overall, mean (SD) Hb content (g) of 1024 Test RBCC = 54.6±5.9 (range: 39-73) and of 1008 Control RBCC = 55.6 ± 5.9 (range: 35-74) and varied widely. By intent-to-treat (ITT), 80 patients (40 +S and 40 -S) were transfused. For ITT patients (Table), the baseline Hb level (BL-Hb, g/dL) at first transfusion of Control periods was significantly lower than at Test periods; but the mean number of RBCC transfused, RBCC storage days, total Hb dose (g), and transfusion intervals were not significantly different for Test and Control. ITT analysis for all transfusion episodes showed Hb use for Test RBCC (0.110 g/kg/d) was not different from Control RBCC (0.112 g/kg/day). Non-inferiority was demonstrated (T-C = - 0.002 g/kg/d: 95% CI: -0.005, 0.001). ITT Test patients received a slightly lower mean total Hb dose (- 14g), and mean pre-transfusion Hb levels declined after 6 transfusions (9.4 to 8.8 g/dL). -S patients had lower BL-Hb levels (g/dL) than S+ patients in Test (9.2 vs 9.7) and Control (8.8 vs 9.2) periods (Table). -S patients received a lower mean total Hb dose of Test than Control RBCC (p=0.019); and had a decline in mean pre-transfusion Hb levels during Test periods (from 9.2 to 8.7 g/dL). Transfusion intervals were significantly longer for -S patients than +S patients with both Test and Control RBCC (p< 0.001 by 2-sample t test, respectively); and -S patients had lower Hb use than +S patients. However, Hb use of Test and Control RBCC was comparable within -S and + S cohorts (Table). Transfused Fe was less for -S patients for Test and Control RBCC. During 6 Test and 3 Control treatment periods, 8 patients (6 -S, 2 +S) had worsening anemia with pre-transfusion Hb levels (6.0-7.8 g/dL) substantially below the targeted transfusion threshold, but without evidence of hemolysis. Each of these patients received one or more Hb doses below the average RBCC transfusion episode dose (Test: 114.5 g) or (Control: 116.7 g); and 3 patients had concurrent infections. None of 80 patients had evidence of increased RBC clearance, developed antibodies to PR-RBCC, or had treatment emergent RBC alloantibodies in either treatment period. There were no differences in the overall safety profiles for Test and Control RBCC. Conclusions: Amustaline-GSH PR treatment of RBCCs offers the potential to reduce TTI risk without impacting Hb use or Fe burden in TDT. However, Hb content of Test and Control RBCC varies widely and may contribute to unexpected changes in pre-transfusion Hb levels. Spleen status affected Hb use comparably for PR-RBCC and Control RBCC, and remains an important factor in assessing transfusion requirements and Fe loading. Table. Table. Disclosures Aydinok: TERUMO: Research Funding; Cerus: Honoraria, Research Funding; CRISPR Tech: Other: DMC; Protagonist: Other: SSC; La Jolla Pharmaceuticals: Research Funding; Celgene: Research Funding; Novartis: Research Funding, Speakers Bureau. Piga:Apopharma: Honoraria, Research Funding; Celgene Corp: Membership on an entity's Board of Directors or advisory committees, Research Funding; La Jolla: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bluebird Bio: Honoraria; Acceleron: Research Funding; Novartis: Research Funding. Origa:Novartis: Honoraria; Bluebird Bio: Consultancy; Cerus Corporation: Research Funding; Apopharma: Honoraria. Mufti:Cerus Corporation: Employment, Equity Ownership. Erikson:Cerus Corporation: Employment, Equity Ownership. North:Cerus Corporation: Employment, Equity Ownership. Waldhaus:Cerus Corporation: Employment, Equity Ownership. Ernst:Cerus Corporation: Employment, Equity Ownership. Lin:Cerus Corporation: Employment, Equity Ownership. Huang:Cerus Corporation: Employment, Equity Ownership. Benjamin:Cerus Corporation: Employment, Equity Ownership. Corash:Cerus Corporation: Employment, Equity Ownership.
29
Fachrie, Yordian, and Arviansyah. "Supplier evaluation in industrial power services: a case study in gas-turbine maintenance, repair, and overhaul." E3S Web of Conferences 202 (2020): 13002. http://dx.doi.org/10.1051/e3sconf/202020213002.
Full textAbstract:
The maintenance is one of the highest costs in a gas-turbine engine, after operating cost with approximately about 14-19 % of the total cost. Some of the operators do not have spare engines, and it will lead to operation shutdown. With the current market, most MRO challenged to provide their costumer to achieve quick turnaround time (TAT) at a low cost without affecting the quality of the product. Since MRO is selling the skill services, it took applied technology, skill training, and experience to deliver quality, which needs high cost. Therefore, MRO needs to collaborate with other parties (original manufacturer or others) to increase its capacity and capability. MRO should concern more for evaluating the vendors to align with the strategies to get quick turnaround time with the right quality product. Supplier selection is the objective of this research by analyzing the selection criteria at Industrial Gas-Turbine maintenance. The highest priority is the vendor effectiveness followed by the quality, cost, risk management. The highest weight is based on the priority of the supplier.
30
Zaeynuri Setiawan, Mochamad, Fachrudin Hunaini, and Mohamad Mukhsim. "Prototype Sistem Deteksi Partial Discharge Pada Isolasi Kabel Menggunakan Sensor Microphone (Prototype Of Partial Discharge Detection System In Cable Isolation Using Microphone Sensor)." JEEE-U (Journal of Electrical and Electronic Engineering-UMSIDA) 3, no. 2 (November 13, 2019): 206. http://dx.doi.org/10.21070/jeee-u.v3i2.2450.
Full textAbstract:
The phenomenon that often arises in a substation is the problem of partial discharge in outgoing cable insulation. Partial discharge is a jump of positive and negative ions that are not supposed to meet so that it can cause a spark jump. If a partial discharge is left too long it can cause insulation failure, the sound of snakes like hissing and the most can cause a flashover on the outgoing cable. Then a partial discharge detection prototype was made in the cable insulation in order to anticipate the isolation interference in the outgoing cable. Can simplify the work of substation operators to check the reliability of insulation on the outgoing side of each cubicle. So it was compiled as a method for measuring sound waves caused by partial discharge in the process of measuring using a microphone sensor, the Arduino Mega 2560 module as a microcontroller, the LCD TFT as a monitoring and the MicroSD card module as its storage. The microphone sensor is a sensor that has a high sensitivity to sound, has 2 analog and digital readings, and is easily designed with a microcontroller. Basically the unit of measure measured at partial discharge is Decibels. The results of the prototype can be applied to the cubicle and the way it works is to match the prototype to the outgoing cubicle cable then measure from the cable boots connector to the bottom of the outgoing cable with a distance of 1 meter. Then the measurement results will be monitored on the TFT LCD screen in the form of measurement results, graphs and categories on partial discharge. In this design the measurement data made by the microphone can be stored with microSD so that it can make an evaluation of partial discharge handling in outgoing cable insulation.
31
Kaskela, Antti, Kimmo Mustonen, Patrik Laiho, Yutaka Ohno, and Esko I. Kauppinen. "Toward the Limits of Uniformity of Mixed Metallicity SWCNT TFT Arrays with Spark-Synthesized and Surface-Density-Controlled Nanotube Networks." ACS Applied Materials & Interfaces 7, no. 51 (December 16, 2015): 28134–41. http://dx.doi.org/10.1021/acsami.5b10439.
Full text
32
Bangalore, Sripal, Rana Fayyad, G. Kees Hovingh, Rachel Laskey, Liffert Vogt, David A. DeMicco, and David D. Waters. "Statin and the Risk of Renal-Related Serious Adverse Events: Analysis from the IDEAL, TNT, CARDS, ASPEN, SPARCL, and Other Placebo-Controlled Trials." American Journal of Cardiology 113, no. 12 (June 2014): 2018–20. http://dx.doi.org/10.1016/j.amjcard.2014.03.046.
Full text
33
Arsenault, Benoit J., S. Matthijs Boekholdt, Samia Mora, David A. DeMicco, Weihang Bao, Jean-Claude Tardif, Pierre Amarenco, Terje Pedersen, Philip Barter, and David D. Waters. "Impact of High-Dose Atorvastatin Therapy and Clinical Risk Factors on Incident Aortic Valve Stenosis in Patients With Cardiovascular Disease (from TNT, IDEAL, and SPARCL)." American Journal of Cardiology 113, no. 8 (April 2014): 1378–82. http://dx.doi.org/10.1016/j.amjcard.2014.01.414.
Full text
34
Vandeweyer, Luc. ""Een ruim veld voor de Studentenbeweging ligt open." Inzake oorsprong en aard van de Vlaamse 'Frontbeweging'." WT. Tijdschrift over de geschiedenis van de Vlaamse beweging 77, no. 3 (December 11, 2019): 212–30. http://dx.doi.org/10.21825/wt.v77i3.15686.
Full textAbstract:
De geschiedschrijving die de ‘Vlaamse Frontbeweging’ tot onderwerp nam, heeft tot dusver te weinig het oog gericht naar de voorgeschiedenis die in nauw verband staat met de afschaffing van de loting en de veralgemening en uitbreiding van de dienstplicht vanaf 1909. Daarbij kwam ook nog eens de eerste taalwet van 1913 die door de strijdkrachten zou moeten toegepast worden. Dit leidde tot een veel sterkere betrokkenheid binnen de Vlaamse beweging. Daarbij werd uit de aard der zaak vooral gerekend op de jonge mannen die nog naar het leger zouden moeten. Zij zouden in staat moeten zijn om de volksjongens zonder veel scholing mee in het ‘Vlaamse’ bad te trekken en zo stapsgewijs het Nederlands een plaats te geven in de strijdkrachten.Al even belangrijk voor een goed begrip is het feit dat de vooroorlogse elite er bijzonder goed in was geslaagd om het leger dienstbaar te maken bij de start van de carrière van wie hoger onderwijs kon volgen via de ‘compagnies universitaires’. In 1909 werd bovendien de categorie van de brancardiers gecreëerd die bestond uit seminaristen, novicen en student-onderwijzers. Zij moesten enkel een cursus volgen in hun vrije tijd.Er werd dus een elite geschapen die amper in contact kwam met de werkelijkheid in het leger en die mijlenver afstond van het beroepskader. Dat leverde de nodige springstof waarop de Frontbeweging kon groeien als een voortzetting van de vooroorlogse katholieke studentenbeweging. Deze jongemannen vonden dat zij hun vooroorlogse agitatie op taalvlak moesten verder zetten in oorlogstijd. Omdat de Duitse Flamenpolitik en de toenemende uitzichtloosheid leidde tot verbittering betekende dit een bedreiging voor de machtspositie van het militaire kaderpersoneel en de koning-opperbevelhebber.De hoop en de verwachting dat de Vlaamse oud-strijders zich na afloop van de oorlog en masse achter de Frontbeweging haar eisenprogramma zou scharen, bleek echter ijdel.__________
“A Wide Field for the Student Movement Lies Open.” On the Origin and Character of the Flemish Front Movement
The historiography which takes the ‘Flemish Front Movement’ as its subject has so far paid too little attention to the historical background which is closely tied to the abolition of the conscription lottery and the generalization of the service requirement from 1909. In addition to this was the first language law of 1913 that the armed forces were supposed to follow. This led to a greater participation in the Flemish Movement. This obviously included in large part the young men who still had to go into the army. They had to be up to the task of bringing boys from the common folk who did not have much schooling into the ‘Flemish’ sphere and thus work step-by-step to give Dutch a place among the armed forces.Just as important for a good understanding is the fact that the prewar elite was unusually successful in making the army a stepping stone in the career of those who could follow higher education, through the “compagnies universitaires” (university companies). Most importantly in this regard, in 1909 the category of stretcher-bearer was created, which was made up of seminary students, novice priests and student teachers. They only had to take a course in their free time.Thus, an elite was formed that was nearly never in contact with the day-to-day life of the army and which was miles away from the traditional professional circles. This provided the necessary spark from which the Front Movement could grow as an extension of the prewar Catholic student movement. These young men found that they had to continue their prewar agitation regarding language matters in wartime. Because the German Flamenpolitik (policy of coopting the Flemish Movement) and growing hopelessness led to embitterment, this constituted a threat to their position of power of the military senior staff and the king as commander-in-chief.The hope and the expectation that Flemish veterans would range themselves en masse behind the Front Movement’s list of demands after the end of the war turned out to be in vain.
35
Kadarisman, A. Effendi. "Local Wisdom with Universal Appeal: Dynamics of Indonesian Culture in Asian Context." KnE Social Sciences 1, no. 3 (April 13, 2017): 8. http://dx.doi.org/10.18502/kss.v1i3.720.
Full textAbstract:
<p>This paper argues that the dynamics of Indonesian culture in Asian context, as seen from a linguistic perspective, may occur in the form of cultural reinterpretation and semantic change. At the cultural level, this paper takes a close look at two things: apology and “Indonglish” (Indonesian English). Apology is a universal speech act. However, where, when, how, and why people apologize to one another can be culture-specific. I pick out an Islam-specific greeting which gets modified by taking a Malay-specific apology as an illustrative example. As for Indonglish, it can be viewed either as a mock term or as a serious term. As a mock term, Indonglish is characterized by Indonesian-specific errors; and as a serious sociolinguistic term, it is characterized by apology, Indonesian address terms, and religion-related expressions.</p><p>The semantic change pertains to three expressions: <em>pancasila, bhinneka tunggal ika, </em>and<em> tut wuri handayani</em>. The compound word <em>pancasila</em> means ‘five principles’, and the phrase <em>bhinneka tunggal ika</em> means ‘unity in diversity’. Both expressions originate from an old Javanese literary work <em>Sutasoma</em>, written during the second half of the 14<sup>th</sup> century. In <em>Sutasoma</em>, both expressions refer respectively to ‘five moral principles in Buddhism’ and ‘a single religious truth proposed to unite Buddhism and Hinduism’. However, in modern Indonesia, they have undergone drastic semantic change. <em>Pancasila</em> is a cover politico-philosophical term for the five state foundations; and <em>bhinneka tunggal ika</em> is a national motto intended to unite people with different backgrounds into a single Indonesian nation. The last expression <em>tut wuri handayani</em>, or ‘giving support from behind’, was part of the educational motto for Taman Siswa, an educational institution established in the early 1920s. Now, it is taken as a motto for national education, for its great relevance to principles of modern educational psychology. Briefly, cultural dynamics are observable in apology and Indonglish; and the three local expressions originating from Javanese have now become prominent terms of national treasure, whose meanings spark some global appeal.</p><p> </p><p><strong>Keywords: cultural reinterpretation, semantic change, apology, Indonglish.<em></em></strong></p>
36
Rasko, John E. J., Alexis A. Thompson, Janet L. Kwiatkowski, Suradej Hongeng, Gary J. Schiller, Usanarat Anurathapan, Marina Cavazzana, et al. "Clinical Outcomes of Lentiglobin Gene Therapy for Transfusion-Dependent β-Thalassemia Following Completion of the Northstar HGB-204 Study." Blood 132, Supplement 1 (November 29, 2018): 167. http://dx.doi.org/10.1182/blood-2018-167.
Full textAbstract:
Abstract Background Advances in red blood cell (RBC) transfusion and chelation have improved the prognosis of patients with transfusion-dependent β-thalassemia (TDT); however, many patients experience organ damage due to iron overload and other complications. While potentially curative, allogeneic hematopoietic stem cell transplantation confers significant risks of morbidity and mortality and is limited by donor availability. Gene therapy (GT) has the potential to be an effective treatment option for patients with TDT without some of these limitations. LentiGlobin GT contains autologous CD34+ cells transduced ex vivo with the BB305 lentiviral vector (LVV) encoding a β-globin gene with a T87Q substitution. Initial data from the international, multi-center, phase 1/2 Northstar (HGB-204; NCT01745120) study evaluating the safety and efficacy of LentiGlobin in patients with TDT using the original manufacturing process has been published. Herein we present updated results with longer follow-up. Methods Northstar enrolled patients with TDT (history of ≥ 100 mL/kg/yr of RBCs or ≥ 8 RBC transfusions/yr) regardless of genotype. Autologous CD34+ cells were collected by apheresis after G-CSF and plerixafor mobilization and transduced with the BB305 LVV in a centralized facility. Patients received myeloablative conditioning with single-agent busulfan before the transduced cells were infused. Patients were monitored for engraftment, vector copy number (VCN), GT-derived hemoglobin (HbAT87Q), RBC transfusions, transfusion independence (TI; defined as weighted average hemoglobin [Hb] ≥ 9g/dL without RBC transfusions for ≥ 12 months), adverse events (AEs), vector integration, and replication competent lentivirus (RCL). Patients were followed in Northstar for 2 years and then were offered participation in the long-term follow-up study, LTF-303 (NCT02633943). Results Eighteen patients with TDT, 12 - 35 years old, treated with LentiGlobin GT have completed 2-year follow-up in the Northstar study and subsequently enrolled in LTF-303. As of March 7, 2018, the median follow-up duration was 32.1 (min - max: 23.1 - 41.9) months. The median DP VCN was 0.7 (min - max: 0.3 - 1.5) copies/diploid genome (c/dg), the median cell dose was 8.1 x 106 (min - max: 5.2 - 18.1 x 106) CD34+ cells/kg, and the median proportion of transduced CD34+ cells was 32% (min - max: 17 - 58%). All patients engrafted and the median duration of hospitalization from conditioning to discharge was 40 days (min - max: 27 - 69 days). The toxicity profile was typical of myeloablative conditioning. No grade ≥ 3 events were related to LentiGlobin and there was no graft failure, death, or vector-mediated RCL, and no evidence of clonal dominance. Serious AEs reported in ≥ 2 patients were thrombosis and veno-occlusive liver disease; each occurred in 2 patients. Eight of 10 patients with non-β0/β0 genotypes were able to discontinue transfusions at 0.3 - 5.8 months post-DP infusion and have sustained TI for a median duration of 33 months (min - max: 16 - 38 months). At last study visit, peripheral blood VCN for these patients was 0.1 - 1.0 c/dg, HbAT87Q was 3.8 - 10.1 g/dL and total Hb was 9.1 - 13.5 g/dL. Sustained HbAT87Q production was observed in all patients through last follow-up (Figure 1A). The 2 remaining patients with non-β0/β0 genotypes had a reduction in transfusion volume of 82% and 27%. Their peripheral VCN and HbAT87Q levels at last study visit were 0.1 and 0.1 c/dg and 2.9 and 1.1 g/dL, respectively. Of the 8 patients with a β0/β0 genotype, 3 no longer require chronic RBC transfusions for an ongoing duration of 16.4 - 22.1 months. Peripheral VCN, HbAT87Q and total Hb at last visit were 0.7, 0.4, 0.6 c/dg; 8.9, 9.7, 8.1 g/dL (Figure 1B); and 9.3, 10.3, 9.8 g/dL, respectively. The other 5 patients with a β0/β0 genotype experienced median transfusion volume reduction of 53% (min - max: 8 - 74%). Longer follow-up and other analyses including iron measures will be presented. Summary LentiGlobin GT in patients with TDT enrolled in the Northstar study continues to demonstrate a sustained clinical benefit with up to 3.5 years of follow-up. The safety profile is consistent with myeloablative conditioning and 8/10 patients with non-β0/β0 genotypes and 3/8 patients with a β0/β0 genotype remain transfusion free. LentiGlobin GT using refined manufacturing to improve DP characteristics and patient outcomes is being evaluated in 2 ongoing phase 3 studies, Northstar-2 and Northstar-3. Disclosures Rasko: Rarecyte: Consultancy, Equity Ownership; IMAGO Biosciences: Consultancy; Takeda: Speakers Bureau; Abbvie: Speakers Bureau; Gilead: Honoraria; Novartis: Consultancy, Speakers Bureau; Cynata: Consultancy, Honoraria; bluebird bio: Honoraria, Other: Clinical trials ; Spark: Consultancy; Genea: Equity Ownership; Current Cure The Future Foundation: Membership on an entity's Board of Directors or advisory committees; FSHD Global Research Foundation: Membership on an entity's Board of Directors or advisory committees; Gene Technology Technical Advisory, OGTR, Australian Government: Other: Chair; Advisory Committee on Biologics, Therapeutics Goods Administration, Australian Government: Other: Past Chair; International Society for Cellular Therapy: Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Pfizer: Honoraria; Celgene: Honoraria. Thompson:Baxalta/Shire: Research Funding; La Jolla Pharmaceutical: Research Funding; Amgen: Research Funding; Biomarin: Research Funding; Celgene: Research Funding; bluebird bio: Consultancy, Research Funding; Novartis: Research Funding. Kwiatkowski:Apopharma: Research Funding; Agios Pharmaceuticals: Consultancy, Research Funding; Novartis: Research Funding; Terumo: Research Funding; bluebird bio: Consultancy, Honoraria, Research Funding. Schiller:bluebird bio: Research Funding; Astellas Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding. Ho:Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Other: Travel to meeting; Celgene: Other: Travel to meeting . Schmidt:GeneWerk GmbH: Employment; German Cancer Research Center: Employment; bluebird bio: Consultancy. Leboulch:bluebird bio: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties. Vichinsky:bluebird bio: Membership on an entity's Board of Directors or advisory committees; Global Blood Therapeutics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Protagonist: Research Funding. Deary:bluebird bio: Employment, Equity Ownership. Chen:bluebird bio: Consultancy. Asmal:bluebird bio: Employment, Equity Ownership. Walters:Sangamo Therapeutics: Consultancy; ViaCord Processing Lab: Other: Medical Director; AllCells Inc.: Other: Medical Director; bluebird bio: Research Funding.
37
Abdelhamed, Sherif, Noah I. Hornick, and Peter Kurre. "Residual HSPC in the Leukemia Microenvironment Are Reprogrammed Via Extracellular Vesicle Trafficking." Blood 128, no. 22 (December 2, 2016): 888. http://dx.doi.org/10.1182/blood.v128.22.888.888.
Full textAbstract:
Several groups have shown that leukemic cells create a self-reinforcing bone marrow (BM) niche that functionally impairs normal hematopoietic stem and progenitor cells (HSPC) indirectly through stroma-secreted factors. We recently demonstrated an alternative mechanism whereby extracellular vesicles (EVs) from acute myeloid leukemia (AML) patients and cell lines, but not BM CD34 controls, suppress their clonogenicity through EV trafficking of microRNA that directly downregulate critical transcription factors (c-Myb and HoxA9). Here, we aimed to clarify the fate of residual HSPC in in vivo AML xenografts, as well as ex vivo intrafemural (IF) injection and in vitro exposure of EVs experiments. Among KSL cells we observed a significant increase in the frequency of the long-term hematopoietic stem cell (SLAM, CD150+CD48−) subpopulation, but not the multipotent progenitors even at low levels of AML infiltration or direct IF injection of EVs. The HSPC pool redistribution was accompanied by cell cycle alterations in residual HSPC that showed AML EVs consistently induced quiescence (G0) in KSL (cKit+Sca1+Lin−) HSPC populations. When we assessed their DNA damage, residual HSPC showed a distinct increase in the gH2AX foci relative to control non-engrafted mice as well as the transcriptional upregulation of Rad51 and P21 genes along with gains in phosphorylation of the tumor suppressor p53. Yet, the reprogrammed KSL showed no evidence of apoptosis indicated by the lack of upregulation of the p53 target, Puma, and Annexin V staining, nor evidence of senescence (P16 and Sparc transcripts). To gain additional insight, we performed a tandem mass tag (TMT) proteomic profiling of AML-EV exposed HSPC with or without exposure to EVs derived from AML cells. The results showed significant enrichment of DNA methylation regulatory pathway such as DNMT1, HELLS and UHRF1 as well as inflammatory pathways including IL1b, NOS, CEBPB and NFkB pathway-targets, confirmed by transcriptional profiling of KSL from xeno-transplanted mice. Based on our recent report that miR-1246 is one of the most highly enriched miRNA in AML derived EVs and proceeded to determine its target transcripts using an attenuated RISC complex (RISC-Trap), followed by high-throughput sequencing. Bioinformatics analysis identified a set of 27 miR-1246-specific targets relative to control microRNAs. Strikingly, the target set was selectively enriched for a panel of negative cell-cycle regulator genes (CDK1, CDK7, CDK11, CCNF, HDAC2 and GATA3) as well as the DNA methylation regulators (DNMT1 and HELLS).Collectively, our results demonstrated that residual HSPC in the AML BM are phenotypically reprogrammed and suppressed in their proliferation along with DNA damage accumulation via paracrine EV microRNA trafficking. Our study provides insight into HSPC fates in the AML niche and echoes observations of cell competition, as a mode of non-cell autonomous regulation where p53 activation in the reprogrammed cells leads to a progressive decline in proliferation and fitness. We propose that AML EV trafficking of miR-1246 specifically may contribute to the altered fate of residual HSPC via transcriptional regulation of proliferation-related genes. Disclosures No relevant conflicts of interest to declare.
38
Kwiatkowski, Janet L., Mark C. Walters, Suradej Hongeng, Franco Locatelli, John E. J. Rasko, Marina Cavazzana, Ying Chen, Richard A. Colvin, and Alexis A. Thompson. "Long-Term Efficacy and Safety of Betibeglogene Autotemcel Gene Therapy for the Treatment of Transfusion-Dependent β-Thalassemia: Results in Patients with up to 6 Years of Follow-up." Blood 136, Supplement 1 (November 5, 2020): 51–52. http://dx.doi.org/10.1182/blood-2020-135850.
Full textAbstract:
Introduction The goal of betibeglogene autotemcel (beti-cel; LentiGlobin for β-thalassemia) gene therapy in patients with transfusion-dependent β-thalassemia (TDT) is lifelong, stable production of functional adult hemoglobin (Hb) sufficient for transfusion independence (TI) and reduction in ineffective erythropoiesis. 60 patients with TDT have been treated with beti-cel across 2 completed phase 1/2 studies (HGB-204, HGB-205) and in 2 ongoing phase 3 studies (HGB-207, HGB-212). After 2-yrs of follow-up in these 4 parent studies, patients were invited to enroll in a 13-yr long-term follow-up study, LTF-303 (NCT02633943). Interim results of patients enrolled in LTF-303 with follow-up as long as 6 years are reported. Methods Autologous CD34+ cells were transduced with BB305 lentiviral vector and infused into patients following single-agent, pharmacokinetic-adjusted busulfan myeloablation. Transduction in the phase 3 studies used a refined manufacturing process compared to the phase 1/2 studies. LTF-303 assessments include Hb, peripheral blood vector copy number (PB VCN), assessment of erythropoiesis and iron overload, quality of life, adverse events (AEs), replication-competent lentivirus (RCL), and insertion site analysis. Data are analyzed as median (min - max). Results As of 3 March 2020, all 32 patients who completed the parent studies (age at enrollment in parent study: 20 [12 - 35] yrs) enrolled in LTF-303 (22 treated in phase 1/2 studies, 10 treated in phase 3 studies). Follow-up post-infusion was 49.1 (23.3 - 71.8) months. PB VCN was detected in all patients at last follow-up (Phase 1/2: 0.4 [0.07 - 4.0] c/dg; Phase 3: 2.0 [0.13 - 3.0] c/dg). Gene therapy-derived Hb, HbAT87Q,in patients treated in the phase 1/2 studies was stable over time: 6.4 (0.5 - 10.1), 6.7 (0.4 - 10.1), 6.6 (0.5 - 10.7), and 7.1 (2.8 - 11.2) g/dL at months 24 (n=22), 36 (n=22), 48 (n=22), and 60 (n=10). Median HbAT87Q at month 24 in patients treated in the phase 3 studies was 9.5 (0.9 - 12.4) g/dL (n=10). Of the 32 patients enrolled in LTF-303, TI (defined as a weighted average Hb ≥9 g/dL without packed red blood cell transfusions for ≥12 months) was achieved in 14/22 (64%) patients treated in phase 1/2 (12 achieved TI during parent study, 2 during LTF-303) and in 9/10 (90%) patients treated in phase 3 (all achieved TI in parent study). All patients remain TI at last follow-up for 39.4 (19.4 - 69.4) months. Weighted average Hb during TI was 10.4 (9.4 - 13.3) and 12.5 (11.9 - 13.5) g/dL in patients treated in the phase 1/2 and phase 3 studies, respectively. In patients who achieved TI in the phase 3 studies, soluble transferrin receptor decreased from 144.1 (65.9 - 235.3) nmol/L at baseline to 54.1 (24.7 - 67.1) nmol/L at Month 24. Patients who achieved TI in HGB-207 had an improved health state today score from 65 - 96 at baseline to 90 - 100 at month 24 (n=8) on the EQ-5D-3L or EQ-5D-Y instrument. All patients were on iron chelation before beti-cel infusion, but post-infusion, only 26/32 (81%) patients restarted iron chelation; of these, 11 have since discontinued chelation. Phlebotomy was used for iron removal in 7/32 patients (22%; 3 patients treated in phase 1/2, 4 patients treated in phase 3) including 3 patients who also used iron chelation. Following an initial increase in liver iron concentration (LIC) after infusion, LIC in patients who achieved TI decreased, particularly in patients with an elevated baseline LIC (Figure). The median decrease in LIC from baseline to month 48 in patients who achieved TI was a 38% reduction (85% reduction to 269% increase; n=13). No drug-product-related AEs were reported >2 years post-infusion. Serious AEs during LTF-303 included gonadotropic insufficiency, ectopic pregnancy, gall bladder wall thickening/polyp, bacteremia with neutropenia. and major depression (all n=1). No deaths, RCL, or insertional oncogenesis were reported. Insertion site analysis as assessed every 6 months until month 60 showed unique insertions accounted for <30% of all insertions indicating polyclonal hematopoiesis. Summary These results demonstrate the durability and stability of response after beti-cel gene therapy in patients with TDT. Sustained levels of HbAT87Q and effective iron reduction with phlebotomy and/or iron chelation have resulted in improved hematologic parameters and iron burden. The paucity of gene therapy-related AEs observed beyond 2 years post-infusion study suggests a favorable long-term safety profile. Disclosures Kwiatkowski: bluebird bio,Inc.: Consultancy, Research Funding; Terumo Co: Research Funding; Novartis: Research Funding; Sangamo: Research Funding; Celgene: Consultancy; Apopharma: Research Funding; Imara: Consultancy; Agios: Consultancy; BMS: Consultancy. Walters:Editas: Consultancy; AllCells, Inc: Consultancy; Veevo Biomedicine: Consultancy. Locatelli:Bellicum Pharmaceutical: Membership on an entity's Board of Directors or advisory committees; Miltenyi: Speakers Bureau; Medac: Speakers Bureau; Jazz Pharmaceeutical: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Rasko:Novartis: Honoraria; Genea: Other; Imago: Consultancy; Rarecyte: Consultancy, Other; Gene Technology Technical Advisory, OGTR, Australian Government: Other; Advisory Committee on Biologics, Therapeutics Goods Administration, Australian Government: Other; NHMRC Mitochondrial Donation Expert Working Committee: Membership on an entity's Board of Directors or advisory committees; Cure The Future Foundation: Other; FSHD Global Research Foundation; Australian Cancer Research Foundation SAB: Membership on an entity's Board of Directors or advisory committees; bluebird bio, Inc.: Honoraria; Celgene: Honoraria; Pfizer: Honoraria; Cynata: Honoraria; Gilead: Honoraria; Takeda: Honoraria; GSK: Honoraria; CRISPR Therapeutics: Consultancy; Spark: Honoraria. Chen:bluebird bio, Inc.: Current Employment. Colvin:bluebird bio, Inc.: Current Employment, Current equity holder in publicly-traded company. Thompson:Novartis: Consultancy, Honoraria, Research Funding; bluebird bio, Inc.: Consultancy, Research Funding; Biomarin: Research Funding; BMS: Consultancy, Research Funding; Baxalta: Research Funding; CRISPR/Vertex: Research Funding.
39
Kwiatkowski, Janet L., Alexis A. Thompson, John E. J. Rasko, Suradej Hongeng, Gary J. Schiller, Usanarat Anurathapan, Marina Cavazzana, et al. "Long-Term Clinical Outcomes of Lentiglobin Gene Therapy for Transfusion-Dependent β-Thalassemia in the Northstar (HGB-204) Study." Blood 134, Supplement_1 (November 13, 2019): 4628. http://dx.doi.org/10.1182/blood-2019-125807.
Full textAbstract:
Background Patients with transfusion-dependent β-thalassemia (TDT) may experience transfusional iron overload and end-organ damage. While potentially curative, allogeneic hematopoietic stem cell (HSC) transplantation is limited by transplant-related risks and donor availability. Transplantation of autologous CD34+ cells encoding a βA-T87Q-globin gene (LentiGlobin gene therapy for β-thalassemia) may overcome some of these limitations. βA-T87Q-globin is incorporated into adult hemoglobin (Hb), forming gene therapy-derived HbAT87Q, which can be distinguished from other Hb species. The phase 1/2 Northstar study (HGB-204; NCT01745120) using the original manufacturing process evaluated the safety and efficacy of LentiGlobin in adolescents and adults with TDT (≥100 mL/kg/yr of red blood cells [RBCs] or ≥8 RBC transfusions/yr) and non-β0/β0 or β0/β0 genotypes. Methods HSCs were mobilized with G-CSF and plerixafor and collected via apheresis. CD34+ cells were transduced with BB305 lentiviral vector. After busulfan myeloablation, patients were infused with transduced cells. Primary efficacy endpoints were sustained production of ≥2 g/dL HbAT87Q between months 18 and 24 and transfusion independence (TI; weighted average Hb ≥9 g/dL without RBC transfusions for ≥12 months). Patients were monitored for 2 years and subsequently enrolled in the 13-year long-term follow-up study, LTF-303 (NCT02633943). Results are shown as median (min ‒ max) unless otherwise indicated. Results Eighteen patients were treated (age: 20 [12 - 35] yrs) and followed for 40.7 (29.3 - 53.8) months as of 13 December 2018. In the 2 years prior to enrollment, patients had an annualized transfusion volume of 169.0 (124.0 - 273.0) mL/kg/yr and pre-transfusion weighted mean nadir Hb of 9.3 (7.0 - 10.1) g/dL. Neutrophil and platelet engraftment occurred at 18.5 (14 - 30) and 39.5 (19 - 191) days, respectively. No patient had graft failure. Grade ≥3 non-hematologic adverse events (AEs) reported in ≥25% of patients after infusion were stomatitis, febrile neutropenia, and pharyngeal inflammation. No replication-competent lentivirus or death has been reported. The vector integration site profile in all 18 patients has remained polyclonal. The number of unique integration sites (UIS) identified was 1646 (190 - 2888), 1677 (151 - 6935), 2484 (984 - 5511), 1773 (1260 - 2693) at Months 12 (n=18), 24 (n=18), 36 (n=11), 48 (n=4), respectively. The highest mean (SD) frequency of any UIS in patients across all visits was 11.5% (5.8%). No oncogenesis has been reported. In Northstar, 16/18 (89%) patients achieved the primary endpoint of ≥2 g/dL HbAT87Q between months 18 and 24. Eight of 10 (80%) patients with non-β0/β0 genotypes achieved and maintained TI; current duration of TI was 38 (21.2 - 45.3) months (Figure 1). The weighted average total Hb during TI was 10.3 (9.1 - 13.2) g/dL. Total Hb and HbAT87Q remained stable over time. Total Hb in patients with non-β0/β0 genotypes who achieved TI was 10.3, 10.4, 10.6, and 11.1 g/dL at Months 12 (n=8), 24 (n=8), 36 (n=7), 48 (n=3), respectively. Transfusion volumes were reduced by 73% and 43% in the 2 patients still receiving transfusions. Three of 8 (38%) patients with β0/β0 genotypes achieved TI with a current duration of 16.4 (16.1 - 20.8) months. Weighted average total Hb during TI was 9.9 (9.5 - 10.1) g/dL and HbAT87Q was 8.0 - 8.9 g/dL at last visit. One additional patient was transfusion-free for 13.7 months; however, total Hb was <9 g/dL. The 4 other patients had a transfusion volume reduction of 53% (10% - 72%). Patients who achieved TI resumed iron chelation 13 (2 - 15) months after infusion and all remain on iron chelation as of last follow-up. Serum ferritin and liver iron content (LIC) (Figure 2A, 2B) were reduced in patients who achieved TI by 55% (16 - 78%) and 56% (38 - 83%) from screening to Month 48 (n=4), respectively. Of these 4 patients who had a Month 48 visit, LIC values were 0.8 - 7.1 mg/g at Month 48 compared to 4.8 - 11.5 mg/g at screening. In patients who achieved TI, cardiac T2* ranged from 27.0 - 39.0 msec at screening and 31.4 - 57.6 msec at last visit. Summary With up to 4.5 years of follow-up after LentiGlobin gene therapy, generally stable HbAT87Q levels and durable TI were observed in 8/10 and 3/8 patients with TDT and non-β0/β0 and β0/β0 genotypes, respectively. Iron burden has improved over time in patients who achieved TI. The safety profile of LentiGlobin remains consistent with myeloablative conditioning. Disclosures Kwiatkowski: Imara: Consultancy; Agios: Consultancy; bluebird bio, Inc.: Consultancy, Research Funding; Terumo: Research Funding; Apopharma: Research Funding; Novartis: Research Funding; Celgene: Consultancy. Thompson:bluebird bio, Inc.: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Baxalta: Research Funding. Rasko:GSK: Honoraria; bluebird bio: Honoraria; Imago: Consultancy; Novartis: Honoraria; Cynata: Honoraria; Spark: Honoraria; Takeda: Honoraria; NHMRC Mitochondrial Donation Expert Working Committee: Other: Advisory Committee; Gilead: Honoraria; Cure The Future Foundation: Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria; Genea: Equity Ownership; Rarecyte: Consultancy, Equity Ownership; Gene Technology Technical Advisory, Australian Government: Other: Advisory committee; Celgene: Honoraria; Advisory Committee on Biologics, Australian Government: Other: Advisory Committee; Australian Cancer Research Scientific Advisory Board: Membership on an entity's Board of Directors or advisory committees; FSHD Global Research Foundation: Membership on an entity's Board of Directors or advisory committees. Schiller:Amgen: Other, Research Funding; Agios: Research Funding, Speakers Bureau; Astellas: Research Funding; Biomed Valley Discoveries: Research Funding; Bristol Myer Squibb: Research Funding; Celgene: Research Funding, Speakers Bureau; Constellation Pharmaceutical: Research Funding; Daiichi Sankyo: Research Funding; Eli Lilly and Company: Research Funding; FujiFilm: Research Funding; Genzyme: Research Funding; Gilead: Research Funding; Incyte: Research Funding; J&J: Research Funding; Jazz Pharmaceuticals: Honoraria, Research Funding; Karyopharm: Research Funding; Novartis: Research Funding; Onconova: Research Funding; Pfizer Pharmaceuticals: Equity Ownership, Research Funding; Sangamo Therapeutics: Research Funding. Cavazzana:Smartimmune: Other: Founder of Smartimmune. Ho:Celgene: Other: investigator meeting travel costs; Janssen: Other: investigator meeting travel costs; Novartis: Other: investigator meeting travel costs; La Jolla: Other: investigator meeting travel costs. Schmidt:German Cancer Research Center, Heidelberg, Germany: Employment; GeneWerk GmbH, Heidelberg, Gemrany: Equity Ownership. Vichinsky:Agios: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; GBT: Consultancy, Research Funding; bluebird bio: Consultancy, Research Funding; Novartis: Consultancy, Research Funding. Deary:bluebird bio, Inc.: Employment, Equity Ownership. Chen:bluebird bio, Inc.: Consultancy. Petrusich:bluebird bio, Inc.: Employment, Equity Ownership. Walters:Editas Medicine: Consultancy; TruCode: Consultancy; AllCells, Inc: Consultancy.
40
Hird, K. B., and Olivier Dubrule. "Quantification of Reservoir Connectivity for Reservoir Description Applications." SPE Reservoir Evaluation & Engineering 1, no. 01 (February 1, 1998): 12–17. http://dx.doi.org/10.2118/30571-pa.
Full textAbstract:
Summary This study investigates means for efficiently estimating reservoir performance characteristics of heterogeneous reservoir descriptions with reservoir connectivity parameters. We use simulated primary and waterflood performance for two-dimensional (2D) vertical, two- and three-phase, black oil reservoir systems to identify and quantify spatial characteristics that control well performance. The reservoir connectivity parameters were found to correlate strongly with secondary recovery efficiency and drainable hydrocarbon pore volume. We developed methods for estimating primary recovery and water breakthrough time for a waterflood. We can achieve this estimation with three to five orders of magnitude less computational time than required for comparable flow simulations. Introduction Several geostatistical methods have been developed over the past decade for generating fine-scale, heterogeneous reservoir descriptions. These methods have become popular because of their ability to model heterogeneities, quantify uncertainties, and integrate various data types. However, the quality of results obtained with these stochastic methods is strongly dependent on the underlying assumed model. Reservoir heterogeneities will not be modeled correctly if the appropriate scales of heterogeneities are not considered. Uncertainties in future reservoir performance will not be quantified if the entire range of critical spatial characteristics are not explored. Simulated reservoir performance will not match historical performance if the appropriate data constraints are not imposed. The likelihood of using an inappropriate model can be greatly reduced if production data is integrated into the reservoir description process. This is because production data is influenced by those heterogeneities that impact future rates and recoveries. This paper investigates the applicability of using reservoir connectivity characteristics based on static reservoir properties as predictors of reservoir performance. We investigate two types of reservoir connectivity-based parameters. These connectivity parameters were developed to estimate secondary recovery efficiency and drainable hydrocarbon pore volume (HCPV). We use 2D vertical cross sections in the study. Previous work1–3 investigated the correlation of spatial reservoir parameters on reservoir performance for 2D areal reservoir descriptions. We first describe the general procedure. We then follow with definitions, more specific procedure details, and a discussion of the results for the two reservoir characteristics investigated. General Method We generated sets of permeability realizations, each set honoring at least the "conventional" geostatistical constraints (i.e., the univariate permeability distribution, the permeability variogram, and the wellblock permeabilities). We used simulated annealing4–6 to generate the permeability realizations and a linear porosity vs. log (permeability) relationship to obtain porosity values at each gridblock location. Porosity and permeability were the only heterogeneous reservoir properties considered during the study; reservoir thickness was assumed to be a constant. We performed all the flow simulations at the same scale as the permeability conditional simulations. The two- and three-phase black oil flow simulations were run with Amoco's in-house flow simulator, GCOMP,7 on a Sun SPARC 10 workstation.8 We used flow simulation results and analytical calculations to determine water breakthrough time (tBt) and ultimate primary oil recovery. The results for each flow simulation were plotted vs. values of various spatial permeability and porosity-based parameters. We identified the spatial parameter having the strongest correlation with each simulated performance data type. Recovery Efficiency Definitions. Secondary recovery efficiency is considered to be impacted by interwell reservoir connectivity characteristics. However, reservoir connectivity can be defined many different ways. A method has been reported that uses horizontal and vertical permeability thresholds to transform permeabilities to binary values.9 The least resistive paths are determined by finding the minimum distance required to move from one surface (i.e., a set of adjacent gridblocks) to another, for example, from an injector to a producer. We used a binary indicator approach to simplify the computations, thus resulting in an extremely fast connectivity algorithm. However, the success of the method is dependent on the applicability of the designated cutoff values. Such an approach would be most successful for systems comprised of two rock types (e.g., clean sand and shale), each having a small variance but significantly different means. The permeability distributions used in the present study do not fit in this category. Thus, attempts to correlate secondary recovery efficiency variables with the indicator-based connectivity parameters were unsuccessful. We concluded that a more sophisticated connectivity definition, accounting for actual permeability values, was needed to better quantify interwell reservoir connectivity. As a result of further investigation, the following connectivity parameter was developed for 2D cross sections: where IRe(i, k) is the secondary recovery efficiency "resistivity index" at gridblock (i, k), ?L is the distance between the centers of adjacent gridblocks, ka is the average absolute directional permeability between two adjacent gridblocks, krw(i) is the estimated relative permeability to water for the ith column, and A is the cross-sectional area perpendicular to the direction of movement. For a horizontal step, ?L/A=?Lx/?Lz, whereas for a vertical step, ?L/A=?Lz/?Lx . The resistivity index parameter is derived from the analogy between Darcy's law for linear, single-phase fluid flow, and Ohm's law for linear electric current where I is the electrical current, ?E is the voltage drop, and R is the electrical resistance. Inspection of Eqs. 2 and 3 shows that the permeance of the fluid system, kA/µL, is analogous to the reciprocal of the electrical resistance. Eq. 1 is the multiphase flow equivalent of the reciprocal of the permeance, dropping the viscosity constant µ.
41
Ala-Hakula, Riikka. "Aseemista okkultismia: Austin Osman Sparen maagiset monogrammit." Tahiti 8, no. 2 (November 17, 2018). http://dx.doi.org/10.23995/tht.76557.
Full textAbstract:
Austin Osman Spare (1886–1956) oli englantilainen okkultisti ja kuvataiteilija, joka kehitti uudenlaisen maagisen monogrammin luomisen tekniikan. Spare otti vaikutteita antiikista ja keskiajalta juontuvasta maagisten merkkien perinteestä, jonka keskeisiä tekstejä ovat olleet H. Cornelius Agrippan (1486–1535/1536) ja Giordiano Brunon (1548–1600) systemaattiset esitykset maagisista merkeistä. 1800-luvun lopun ja 1900-luvun alun Lontoossa Spareen puolestaan vaikuttivat uudet okkultistiset liikkeet, kuten Hermetic Order of the Golden Dawn, Ordo Templi Orientis ja Aleister Crowleyn (1875–1947) perustama Argentium Astrum. Myöhemmin Sparen tekniikkaa on hyödynnetty erityisesti 1970-luvulla luodun kaaosmagian piirissä. Käsittelen artikkelissa maagisten merkkien perinnettä aseemisen kirjoituksen näkökulmasta. Aseeminen kirjoitus ei välitä luonnollisille kielille tyypillisiä konventionaalisia merkityksiä, mutta se välittää visuaalisia merkityksiä. Se näyttää kirjoitukselta, mutta sitä ei voi lukea luonnollisten kielten tavoin. Käsitteen ovat ottaneet käyttöön visuaaliset runoilijat Tim Gaze ja Jim Leftwich 1990-luvun puolivälissä kirjallisuuden kentällä. Spare painottaa teoksessaan The Book of Pleasure (Self-Love): The Psychology of Ecstasy (1913), että maagista monogrammia luodessa pyritään siihen, ettei se sisällä visuaalista yhteyttä tekijän lauseeksi muotoilemaan tahtoon. Tämä tarkoittaa sitä, että Sparen järjestelmässä maagisen merkin luomisen prosessissa tavoitteena on muokata luettava teksti aseemiseksi. Sijoitan artikkelissa Sparen monogrammit osaksi maagisten merkkien historiaa ja kartoitan tästä näkökulmasta, millaisin tavoin ja millaisista syistä maagisten merkkien lukemista on vaikeutettu ja niistä on tehty aseemisia.
42
CHEN, Peiming, Tai-Wa Liu, Claudia K. Y. Lai, Raymond C. K. Chung, and Shamay S. M. Ng. "Abstract P218: Effects of Bilateral Transcutaneous Electrical Nerve Stimulation Combined With Task-Oriented Training on the Recovery of Upper Limb Motor Impairment in People With Chronic Stroke." Stroke 52, Suppl_1 (March 2021). http://dx.doi.org/10.1161/str.52.suppl_1.p218.
Full textAbstract:
Background: Transcutaneous electrical nerve stimulation(TENS) is an effective physiological intervention for people with stroke which aims at reducing muscle spasticity, enhancing muscle strength, and improving motor control and function. In view of the potentials to enhance greater cortical activation of the lesion side by eliciting spare neural pathways through bilateral intervention, this study examined whether the combined use of bilateral TENS (Bi-TENS) and task-oriented training (TOT) was superior to unilateral TENS(Uni-TENS)+TOT, placebo-TENS+TOT and no active treatment to improve the motor impairment of upper limb function in people with stroke. Method: There were 120 subjects with stroke(44 females, mean age=61.52±6.73 years, post-stroke duration=6.04±3.12years) being randomly allocated into 4 groups, including the Bi-group (n=30), Uni-group (n=30), placebo group (n=30) and control group (n=30). Subjects in the Bi-group, Uni-group and placebo group got 60 minutes TENS and TOT simultaneously per time for 20 times(3 times per week for 7 weeks). In the Bi-group, TENS stimulated the radial and median nerves of the bilateral upper limbs. In the Uni-group, TENS and placebo-TENS stimulated the affected and unaffected side, respectively. In the placebo group, placebo-TENS were placed on bilateral sides. In the control group, subjects did not receive any active treatment. Level of motor impairment was assessed by the Fugl-Meyer Assessment of Upper Extremity (FMA-UE). Result: The Bi-group had a significant greater improvement in FMA-UE than the Uni-group(mean change=2.02, p=0.005), placebo group (mean change=2.49, p=0.001) and control group(mean change=3.08, p<0.001) at post-intervention. The Bi-group(mean change=3.25, p<0.001) and Uni-group(mean change=1.23, p=0.015) showed a significant within-group improvement in FMA-UE since 10 sessions of treatment. No significant change was found in the placebo and control groups. Conclusion: Bi-TENS is superior to Uni-TENS, placebo-TENS and no active treatment in augmenting the recovery of upper limb motor impairment in people with chronic stroke. Author Disclosures: The authors received research support from the Health and Medical Research Fund12131821 from the Food and Health Bureau, HKSAR.
43
Tao, Bingdong, Santosh Kumar, Jose Gomez-Arroyo, Chunling Fan, Ailan Zhang, John Skinner, Elizabeth Hunter, et al. "Resistin-Like Molecule α Dysregulates Cardiac Bioenergetics in Neonatal Rat Cardiomyocytes." Frontiers in Cardiovascular Medicine 8 (April 26, 2021). http://dx.doi.org/10.3389/fcvm.2021.574708.
Full textAbstract:
Heart (right) failure is the most frequent cause of death in patients with pulmonary arterial hypertension. Although historically, increased right ventricular afterload has been considered the main contributor to right heart failure in such patients, recent evidence has suggested a potential role of load-independent factors. Here, we tested the hypothesis that resistin–like molecule α (RELMα), which has been implicated in the pathogenesis of vascular remodeling in pulmonary artery hypertension, also contributes to cardiac metabolic remodeling, leading to heart failure. Recombinant RELMα (rRELMα) was generated via a Tet-On expression system in the T-REx 293 cell line. Cultured neonatal rat cardiomyocytes were treated with purified rRELMα for 24 h at a dose of 50 nM. Treated cardiomyocytes exhibited decreased mRNA and protein expression of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) and transcription factors PPARα and ERRα, which regulate mitochondrial fatty acid metabolism, whereas genes that encode for glycolysis-related proteins were significantly upregulated. Cardiomyocytes treated with rRELMα also exhibited a decreased basal respiration, maximal respiration, spare respiratory capacity, ATP-linked OCR, and increased glycolysis, as assessed with a microplate-based cellular respirometry apparatus. Transmission electron microscopy revealed abnormal mitochondrial ultrastructure in cardiomyocytes treated with rRELMα. Our data indicate that RELMα affects cardiac energy metabolism and mitochondrial structure, biogenesis, and function by downregulating the expression of the PGC-1α/PPARα/ERRα axis.
44
Gellen, Barnabas, Ana-Maria Gomez, Khai Le Quang, Francois Briec, Laurent Vinet, Patricia Rouet, Jean-Pierre Benitah, et al. "Abstract 1076: Conditional Fkbp12.6 Overexpression In Mouse Cardiac Myocytes Protects From Triggered Ventricular Arrhythmia Through Specific Alteration In Ec Coupling." Circulation 116, suppl_16 (October 16, 2007). http://dx.doi.org/10.1161/circ.116.suppl_16.ii_215-c.
Full textAbstract:
In cardiac myocytes, Ca2+ release from the sarcoplasmic reticulum (SR) into the cytoplasm via the ryanodine receptor (RyR2) activates cell contraction. During diastole, RyR2 are closed and prevent Ca2+ efflux from the SR. One of the major regulators of RyR2 function is FKBP12.6. Binding of FKBP12.6 stabilizes RyR2 in the closed formation in diastole and contributes to synchronized RyR2 opening in systole. Beta-adrenergic stimulation dissociates FKBP12.6 from RyR2, leading to diastolic Ca2+ leak that can trigger ventricular tachycardias (VT). We tested the hypothesis whether FKBP12.6 overexpression in the myocardium can reduce the susceptibility to VT in stress conditions. We developed a mouse model with conditional cardiac specific overexpression of FKBP12.6 using the Tet-Off system. Transgenic (TG) mice and controls (CT) were examined by echocardiography, PV-catheterization, ECG, and underwent intracardiac stimulation to trigger VT before and after pre-treatment with isoproterenol. In isolated cardiac myocytes, SR Ca2+ load, Ca2+ sparks and Ca2+ transient were measured using confocal microscopy, and L-type Ca2+ current was determined by the patch-clamp technique. Echocardiography, PV-catheterization and ECG recording did not reveal differences between Tg (n=11) and CT (n=13) mice. Burst pacing (figure 1) could induce TV in 4 of 24 controls and in 0 of 14 TG mice (n.s.). Following pre-treatment with isoproterenol, TV could be induced in 10 of 23 controls, but only in 1 of 14 TG animals (figure 2, p<0.05). In isolated myocytes, decreased Ca2+ spark frequency, increased Ca2+ spark size, unchanged SR Ca2+ load and decreased Ca2+ transient were observed in TG cells (n=19) as compared to controls (n=48, p<0.05). L-type Ca2+ channel current was found to be decreased in Tg myocytes (n=29 vs n=32, p<0.01). We conclude that myocardial FKBP12.6 overexpression has a protective effect against VT induced by rapid pacing after pretreatment with catecholamines. This antiarrhythmic effect is probably, at least in part, linked to decreased diastolic SR Ca2+ leak. Our results support the hypothesis that increased FKBP12.6 binding to RyR2 might represent a potential therapeutical target in the prevention and treatment of ventricular arrhythmias.