Search

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. POUT was a phase III, randomized, open-label trial, including 261 patients with muscle-invasive or lymph node–positive, nonmetastatic upper tract urothelial cancer (UTUC) randomly assigned after radical nephroureterectomy to platinum-based chemotherapy (132) or surveillance (129). Primary outcome analysis demonstrated that chemotherapy improved disease-free survival (DFS). At that time, the planned secondary outcome analysis of overall survival (OS) was immature. By February 2022, 50 and 67 DFS events had occurred in the chemotherapy and surveillance groups, respectively, at a median follow-up of 65 months. The 5-year DFS was 62% versus 45%, univariable hazard ratio (HR) = 0.55 (95% CI, 0.38 to 0.80, P = .001). The restricted mean survival time (RMST) was 18 months longer (95% CI, 6 to 30) in the chemotherapy arm. There were 46 and 60 deaths in the chemotherapy and control arms, respectively. The 5-year OS was 66% versus 57%, with univariable HR = 0.68 (95% CI, 0.46 to 1.00, P = .049) and RMST difference 11 months (95% CI, 1 to 21). Treatment effects were consistent across chemotherapy regimens (carboplatin or cisplatin) and disease stage. Toxicities were similar to those previously reported, and there were no clinically relevant differences in quality of life between arms. In summary, although OS was not the primary outcome measure, the updated results add further support for the use of adjuvant chemotherapy in patients with UTUC, suggesting long-term benefits.

Since its national debut in 1987, Fresh Air with Terry Gross has been a highly acclaimed and much adored weekday magazine among public radio listeners. Each week, nearly 4.8 million people turn to Peabody Award-winning host Terry Gross for insightful conversations with the leading voices in contemporary arts and issues. The renowned program reaches a global audience, with over 620 public radio stations broadcasting Fresh Air, and 3 million podcast downloads each week. Fresh Air has broken the mold of 'talk show' by weaving together superior journalism and intimate storytelling from modern-day intellectuals, politicians and artists alike. Through probing questions and careful research, Gross's interviews are lauded for revealing a fresh perspective on cultural icons and trends. Her thorough conversations are often complemented by commentary from well-known contributors. Fresh Air is produced at WHYY-FM in Philadelphia and broadcast nationally by NPR., (1.) Two of the co-creators and stars of the HULU series Pen 15, MAYA ERSKINE & ANNA KONKLE. It's about two 13 year old girls in middle school, and it's based on their experiences when they were friends in school together. ERSKINE & KONKLE star in it even though they are both in their 30s, but the other kids in the show are teenagers. The show has completed season one and has been renewed for a second season. (INTERVIEW BY PRODUCER SAM BRIGER) (THIS INTERVIEW CONTINUES INTO THE SECOND HALF OF THE SHOW) (2.) Documentary film director JOHN CHESTER and his wife MOLLY CHESTER. Their new documentary The Biggest Little Farm is about their eight year effort to transform a piece of land in Southern California into an environmentally sustainable and diverse farm. (INTERVIEW BY DAVE DAVIES).

In the middle of the first millennium BCE in India, there were a number of movements of ascetics who sought th liberate the self or soul from the cycle of birth, death and rebirth through various combinations of meditation and physical regimens designed to eliminate attachment to the world. Siddhartha Gautama - referred to by Buddhists as 'Buddha', meaning 'Awakened One', began to teach others and created an order of monks and nuns, and following his death his monastic and lay followers spread his messaged beyond India to surrounding countries. At some point in the past 2,500 years, Buddhism has been a major religion in most areas of Asia, and today millions of people in North and South America, Europe, Australia and Africa identify themselves as Buddhists.

According to Tibetan Buddhist doctrine, the Dalai Lamas are physical manifestations of the bodhisattva of compassion, Chenrezi. This bodhisattva created the incarnational lineage fro the benefit of Tibetans in particular, but the present incumbent (Tenzin Gyatso, born Hlamo Tondrup in 1935) has also become an international figure and gives teachings all over the world.

Losang Drakba (1357-1419) was born in the Tsongkha Valley of Amdo, and is popularly referred to as Tsongkhapa, 'Man from Tsongkha'. Members of the Gelukpa, the order he founded, also refer to him as Je Rinpoche, 'Glorious Precious Jewel'. He was one of the great reformers of Tibetan Buddhism and is renowned for his erudition, his meditative accomplishments, and for reforming monastic practice.

The present volume contains new research by some of the leading scholars in the field, who describe the histories, practices, and distinctive doctrines of the various regions in which Buddhism has set down roots, analyze the innovations of some of its most influential figures, and why they are revered as paradigms, and discuss important topics that are intended to provide broad coverage of distinctive developments within Buddhist countries and schools, as well as issues with which adherents have wrestled during the more than 2,500 years since the time of its founder, Siddhartha Gautama, the Sakyamuni Buddha.

BACKGROUND: Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder. METHODS: This intergroup, open-label, randomised, phase 3 trial recruited patients from hospitals across Europe and Canada. Eligible patients had histologically proven urothelial carcinoma of the bladder, pT3-pT4 disease or node positive (pN1-3) M0 disease after radical cystectomy and bilateral lymphadenectomy, with no evidence of any microscopic residual disease. Within 90 days of cystectomy, patients were centrally randomly assigned (1:1) by minimisation to either immediate adjuvant chemotherapy (four cycles of gemcitabine plus cisplatin, high-dose methotrexate, vinblastine, doxorubicin, and cisplatin [high-dose MVAC], or MVAC) or six cycles of deferred chemotherapy at relapse, with stratification for institution, pT category, and lymph node status according to the number of nodes dissected. Neither patients nor investigators were masked. Overall survival was the primary endpoint; all analyses were by intention to treat. The trial was closed after recruitment of 284 of the planned 660 patients. This trial is registered with ClinicalTrials.gov, number NCT00028756. FINDINGS: From April 29, 2002, to Aug 14, 2008, 284 patients were randomly assigned (141 to immediate treatment and 143 to deferred treatment), and followed up until the data cutoff of Aug 21, 2013. After a median follow-up of 7.0 years (IQR 5.2-8.7), 66 (47%) of 141 patients in the immediate treatment group had died compared with 82 (57%) of 143 in the deferred treatment group. No significant improvement in overall survival was noted with immediate treatment when compared with deferred treatment (adjusted HR 0.78, 95% CI 0.56-1.08; p=0.13). Immediate treatment significantly prolonged progressi

Thich Nhat Hanh is one of the most prominent Buddhist leaders in the world today. A prolific author, he has had a profound impact on both theory and practice for many contemporary Buddhists, particularly with regard to his efforts to integrate mindfulness training into daily life as a mechanism for promoting peace. He is widely credited with coining the term 'Engaged Buddhism' as a description of how Buddhists should manifest their beliefs in concrete activities in the world aimed at improving the lives of disadvantaged people, transforming societies, and promoting peace.

BACKGROUND: Patients with muscle-invasive urothelial carcinoma of the bladder have poor survival after cystectomy. The EORTC 30994 trial aimed to compare immediate versus deferred cisplatin-based combination chemotherapy after radical cystectomy in patients with pT3-pT4 or N+ M0 urothelial carcinoma of the bladder.METHODS: This intergroup, open-label, randomised, phase 3 trial recruited patients from hospitals across Europe and Canada. Eligible patients had histologically proven urothelial carcinoma of the bladder, pT3-pT4 disease or node positive (pN1-3) M0 disease after radical cystectomy and bilateral lymphadenectomy, with no evidence of any microscopic residual disease. Within 90 days of cystectomy, patients were centrally randomly assigned (1:1) by minimisation to either immediate adjuvant chemotherapy (four cycles of gemcitabine plus cisplatin, high-dose methotrexate, vinblastine, doxorubicin, and cisplatin [high-dose MVAC], or MVAC) or six cycles of deferred chemotherapy at relapse, with stratification for institution, pT category, and lymph node status according to the number of nodes dissected. Neither patients nor investigators were masked. Overall survival was the primary endpoint; all analyses were by intention to treat. The trial was closed after recruitment of 284 of the planned 660 patients. This trial is registered with ClinicalTrials.gov, number NCT00028756.FINDINGS: From April 29, 2002, to Aug 14, 2008, 284 patients were randomly assigned (141 to immediate treatment and 143 to deferred treatment), and followed up until the data cutoff of Aug 21, 2013. After a median follow-up of 7.0 years (IQR 5.2-8.7), 66 (47%) of 141 patients in the immediate treatment group had died compared with 82 (57%) of 143 in the deferred treatment group. No significant improvement in overall survival was noted with immediate treatment when compared with deferred treatment (adjusted HR 0.78, 95% CI 0.56-1.08; p=0.13). Immediate treatment significantly prol

In his April 3, 2008 interview with Kristin Malone, John Chester details his service overseas in Europe during WWII. Included are stories of interactions with German soldiers and the rules and regulations of the United States Military. This interview was conducted for inclusion into the Louise Pettus Archives and Special Collections Oral History Program.

• Religious or spiritual values often influence health care decision-making by patients and their families, particularly in times of crisis. • Though religious values might seem to be irrelevant where continuing treatment is judged to be "futile", suc

This document contains the slide presentation entitled 'High- Frequency Acoustic Backscatter From the Sea Surface,' given at the 107th meeting of the Acoustic Society of America on 8 May 1984 in Norfolk, Virginia. A high resolution scattering experiment was conducted in the shallow waters of the North Atlantic. A narrow beam parametric array, which was rotatable in both azimuth and elevation, was utilized as a broadband high-frequency acoustic projector. Acoustic surface scattering data were obtained at normal incidence and low grazing angles (less than 10 deg) as a function of acoustic transmit frequency and sea state conditions. Meteorologic and oceanographic data were obtained in concert with the acoustic measurements and included wind speed and direction, ocean surface wave spectra and currents, and ocean sound speed. Surface backscattering strength, Doppler spectra (shift and spread), and envelope statistics were some of the measured parameters. It will be shown that the Doppler spectra are approximately Gaussian and the spectral shift could be predicted from Bragg diffraction theory modified by the induced Doppler due to surface currents. The measured Doppler spreads, however, were greater than those predicted by composite roughness theory., Presented at the Meeting of the Acoustical Society of America (107th), 8 May 1984, Norfolk, VA.

This document is a letter written to Mary Jane Chester on October 17, 1840, and contains two letters. The first letter is from her brother John, and discusses family events, mainly one involving a dinner where Andrew Jackson, Governor Polk, and Judge Grundy were in attendance. The second letter is from her mother, Elizabeth, and expresses feelings of love for her daughter.

This document is a letter written to Mary Jane Chester on October 17, 1840, and contains two letters. The first letter is from her brother John, and discusses family events, mainly one involving a dinner where Andrew Jackson, Governor Polk, and Judge Grundy were in attendance. The second letter is from her mother, Elizabeth, and expresses feelings of love for her daughter.

Zirconium-89 is a promising radionuclide in the development of new immuno-PET agents for in vivo imaging of cancerous tumours and radioimmunotherapy (RIT) planning. Besides the convenient half-life of 78.4 h, 89Zr has a beta plus emission rate of 23% and a low maximum energy of 0.9 MeV, delivering good spatial resolution as a result of short positron range in tissue (around 1 mm). Cyclotron production for the radiometal of 89Zr was investigated to find optimal conditions according to results of FLUKA code Monte Carlo modelling of irradiation processes, nuclear reactions and target design. This was followed by reasonably detailed experimental validation (making cyclotron productions for expected high product yield and low impurities levels followed by activity measurements, spectra acquisitions and chemical separation procedures), in which the strategies developed by computer models were carried out in the IBA Cyclone 18/9 cyclotron, permitting a comparison of the predicted and actual yields of 89Zr and isotopic by-products (impurities). Once the in silica model was validated experimentally, then optimal method of the radiometal production in the cyclotron was developed.

The rabbit erythroid-specific lipoxygenase (RBC 15-LOX) is a member of a family of enzymes which catalyse the addition of molecular oxygen to certain polyunsaturated fatty acids. It functions in the inactivation and degradation of mitochondria during the final stages of erythroid maturation, following extrusion of the nucleus. The protein has been purified to homogeneity and extensively characterised (Rapoport et al, 1979), and both cDNA and genomic clones have recently been obtained (Thiele et al, 1987). RBC 15-LOX expression shows several interesting features, including an erythroid-specific accumulation of its mRNA (Thiele et al, 1987), and translational inactivation of the messenger (Thiele et al, 1982) . Data presented in this thesis includes the sequencing of the recently-cloned RBC 15-LOX gene in the region surrounding the ATG translation initiation codon, and mapping of the transcription initiation site to a position 28nt upstream of the ATG codon by a combination of primer extension and S1 nuclease protection analyses. No transcripts arising from the available 2.7kb of sequences upstream of this point have been detected by Northern blot, primer extension or SI nuclease protection analyses. A unique mRNA sequence, matching the genomic sequence immediately downstream of the putative transcription initiation site, has been obtained by primer extension mRNA sequencing. Functional analysis of 5' flanking sequences reveals two regions which affect transient expression of a cis-linked bacterial chloramphenicol acetyItransferase (CAT) reporter gene in established murine erythroleukaemia (MEL) and murine fibroblast cell lines. A proximal region within 150nt of the transcription initiation site functions as a promoter in both erythroid and non-erythroid cell lines, elevating CAT enzyme activity 7- to 8-fold above background, and can respond to a heterologous Friend Murine Leukaemia Virus enhancer. A distal region between 1.0 and 2.7kb upstream of the transcription in