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"Saunders, Mark"
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Organizational trust : a cultural perspective
\"The globalized nature of modern organizations presents new and intimidating challenges for effective relationship building. Organizations and their employees are increasingly being asked to manage unfamiliar relationships with unfamiliar parties. These relationships not only involve working across different national cultures, but also dealing with different organizational cultures, different professional cultures and even different internal constituencies. Managing such differences demands trust. This book brings together research findings on organizational trust-building across cultures. Established trust scholars from around the world consider the development and maintenance of trust between, for example, management consultants and their clients, senior international managers from different nationalities, different internal organizational groupings during times of change, international joint ventures, and service suppliers and the local communities they serve. These studies, set in a wide variety of national settings, are an important resource for academics, students and practitioners who wish to know more about the nature of cross-cultural trust-building in organizations\"--Provided by publisher.
Watch-and-wait approach versus surgical resection after chemoradiotherapy for patients with rectal cancer (the OnCoRe project): a propensity-score matched cohort analysis
by
O'Dwyer, Sarah T
,
Gollins, Simon
,
Wilson, Malcolm S
in
Adenocarcinoma
,
Adenocarcinoma - mortality
,
Adenocarcinoma - surgery
2016
Induction of a clinical complete response with chemoradiotherapy, followed by observation via a watch-and-wait approach, has emerged as a management option for patients with rectal cancer. We aimed to address the shortage of evidence regarding the safety of the watch-and-wait approach by comparing oncological outcomes between patients managed by watch and wait who achieved a clinical complete response and those who had surgical resection (standard care).
Oncological Outcomes after Clinical Complete Response in Patients with Rectal Cancer (OnCoRe) was a propensity-score matched cohort analysis study, that included patients of all ages diagnosed with rectal adenocarcinoma without distant metastases who had received preoperative chemoradiotherapy (45 Gy in 25 daily fractions with concurrent fluoropyrimidine-based chemotherapy) at a tertiary cancer centre in Manchester, UK, between Jan 14, 2011, and April 15, 2013. Patients who had a clinical complete response were offered management with the watch-and-wait approach, and patients who did not have a complete clinical response were offered surgical resection if eligible. We also included patients with a clinical complete response managed by watch and wait between March 10, 2005, and Jan 21, 2015, across three neighbouring UK regional cancer centres, whose details were obtained through a registry. For comparative analyses, we derived one-to-one paired cohorts of watch and wait versus surgical resection using propensity-score matching (including T stage, age, and performance status). The primary endpoint was non-regrowth disease-free survival from the date that chemoradiotherapy was started, and secondary endpoints were overall survival, and colostomy-free survival. We used a conservative p value of less than 0·01 to indicate statistical significance in the comparative analyses.
259 patients were included in our Manchester tertiary cancer centre cohort, 228 of whom underwent surgical resection at referring hospitals and 31 of whom had a clinical complete response, managed by watch and wait. A further 98 patients were added to the watch-and-wait group via the registry. Of the 129 patients managed by watch and wait (median follow-up 33 months [IQR 19–43]), 44 (34%) had local regrowths (3-year actuarial rate 38% [95% CI 30–48]); 36 (88%) of 41 patients with non-metastatic local regrowths were salvaged. In the matched analyses (109 patients in each treatment group), no differences in 3-year non-regrowth disease-free survival were noted between watch and wait and surgical resection (88% [95% CI 75–94] with watch and wait vs 78% [63–87] with surgical resection; time-varying p=0·043). Similarly, no difference in 3-year overall survival was noted (96% [88–98] vs 87% [77–93]; time-varying p=0·024). By contrast, patients managed by watch and wait had significantly better 3-year colostomy-free survival than did those who had surgical resection (74% [95% CI 64–82] vs 47% [37–57]; hazard ratio 0·445 [95% CI 0·31–0·63; p<0·0001), with a 26% (95% CI 13–39) absolute difference in patients who avoided permanent colostomy at 3 years between treatment groups.
A substantial proportion of patients with rectal cancer managed by watch and wait avoided major surgery and averted permanent colostomy without loss of oncological safety at 3 years. These findings should inform decision making at the outset of chemoradiotherapy.
Bowel Disease Research Foundation.
Journal Article
التعامل مع الإحصاء : كل ما تحتاج إلى معرفته
by
Brown, Reva Berman, 1939- مؤلف
,
Brown, Reva Berman, 1939-. Dealing with statistics : what you need to know
,
Saunders, Mark, 1959- مؤلف
in
الإحصاء
,
الرياضيات
2010
إن هذا الكتاب : يوضح لك السبب فى إستحالة تجنب إستخدام علم الإحصاء فى تحليل البيانات. يصف ويفسر لك اللغة الإحصائية بحيث يسهل عليك فهم المصطلحات العديدة المستخدمة. يوضح لك كيفية إستخدام الجداول والخرائط فى عرض البيانات بحيث يسهل عليك فهمها. يفسر الإحصاءات المستخدمة فى وصف البيانات وفى إستقراء الإختلافات والعلاقات بين الأشياء. ويتضمن هذا الكتاب كذلك على الأحرف الهجائية الإحصائية وعلى قاموس لأهم المصطلحات الإحصائية. يمثل هذا الكتاب الدعامة الرئيسية لهؤلاء الطلاب ممن يجرون عمل بحثى أو مشروع أو أطروحة خاصة بعلم إجتماعى أو مجال إدارى و تجارى كجزء من دراستهم الجامعية أو دراستهم العليا.
Bevacizumab plus capecitabine versus capecitabine alone in elderly patients with previously untreated metastatic colorectal cancer (AVEX): an open-label, randomised phase 3 trial
by
Marcuello, Eugenio
,
Waterkamp, Daniel
,
Lorusso, Vito
in
Aged
,
Aged, 80 and over
,
Antibodies, Monoclonal, Humanized - administration & dosage
2013
Elderly patients are often under-represented in clinical trials of metastatic colorectal cancer. We aimed to assess the efficacy and safety of bevacizumab plus capecitabine compared with capecitabine alone in elderly patients with metastatic colorectal cancer.
For this open-label, randomised phase 3 trial, patients aged 70 years and older with previously untreated, unresectable, metastatic colorectal cancer, who were not deemed to be candidates for oxaliplatin-based or irinotecan-based chemotherapy regimens, were randomly assigned in a 1:1 ratio via an interactive voice-response system, stratified by performance status and geographical region. Treatment consisted of capecitabine (1000 mg/m2 orally twice a day on days 1–14) alone or with bevacizumab (7·5 mg/kg intravenously on day 1), given every 3 weeks until disease progression, unacceptable toxic effects, or withdrawal of consent. Efficacy analyses were based on the intention-to-treat population. The primary endpoint was progression-free survival. The trial is registered with ClinicalTrials.gov, number NCT00484939.
From July 9, 2007, to Dec 14, 2010, 280 patients with a median age of 76 years (range 70–87) were recruited from 40 sites across ten countries. Patients were randomly assigned to receive either bevacizumab plus capecitabine (n=140) or capecitabine only (n=140). Progression-free survival was significantly longer with bevacizumab and capecitabine than with capecitabine alone (median 9·1 months [95% CI 7·3–11·4] vs 5·1 months [4·2–6·3]; hazard ratio 0·53 [0·41–0·69]; p<0·0001). Treatment-related adverse events of grade 3 or worse occurred in 53 (40%) patients in the combination group and 30 (22%) in the capecitabine group, and treatment-related serious adverse events in 19 (14%) and 11 (8%) patients. The most common grade 3 or worse adverse events of special interest for bevacizumab or chemotherapy were hand-foot syndrome (21 [16%] vs nine [7%]), diarrhoea (nine [7%] vs nine [7%]), and venous thromboembolic events (11 [8%] vs six [4%]). Treatment-related deaths occurred in five patients in the combination group and four in the capecitabine group. The most common any-grade adverse event of special interest for bevacizumab was haemorrhage (34 [25%] vs nine [7%]).
The combination of bevacizumab and capecitabine is an effective and well-tolerated regimen for elderly patients with metastatic colorectal cancer.
F Hoffmann-La Roche.
Journal Article
Evoking through design : contemporary moods in architecture
\"A visually stunning title, 'Evoking Through Design' features built work and speculative projects that highlight how contemporary practices are using devices such as spatial compositing, surface articulation, novel manipulations of matter and computational code in order to constitute spatial conditions radiating in delicate and sophisticated atmospheres. The theoretical foundations of the subject are explored through core essays on key themes: the historical lineage of the evocation of atmosphere and moods in architecture; the more recent preoccupation with speculative realism in architecture; the human body and atmosphere; and picturesque techniques.\"--Back cover.
Durable responses to ATR inhibition with ceralasertib in tumors with genomic defects and high inflammation
by
Patin, Emmanuel C.
,
Harrington, Kevin J.
,
Silva, Carlos
in
Antitumor activity
,
Ataxia
,
Ataxia telangiectasia
2024
BACKGROUNDPhase 1 study of ATRinhibition alone or with radiation therapy (PATRIOT) was a first-in-human phase I study of the oral ATR (ataxia telangiectasia and Rad3-related) inhibitor ceralasertib (AZD6738) in advanced solid tumors.METHODSThe primary objective was safety. Secondary objectives included assessment of antitumor responses and pharmacokinetic (PK) and pharmacodynamic (PD) studies. Sixty-seven patients received 20-240 mg ceralasertib BD continuously or intermittently (14 of a 28-day cycle).RESULTSIntermittent dosing was better tolerated than continuous, which was associated with dose-limiting hematological toxicity. The recommended phase 2 dose of ceralasertib was 160 mg twice daily for 2 weeks in a 4-weekly cycle. Modulation of target and increased DNA damage were identified in tumor and surrogate PD. There were 5 (8%) confirmed partial responses (PRs) (40-240 mg BD), 34 (52%) stable disease (SD), including 1 unconfirmed PR, and 27 (41%) progressive disease. Durable responses were seen in tumors with loss of AT-rich interactive domain-containing protein 1A (ARID1A) and DNA damage-response defects. Treatment-modulated tumor and systemic immune markers and responding tumors were more immune inflamed than nonresponding.CONCLUSIONCeralasertib monotherapy was tolerated at 160 mg BD intermittently and associated with antitumor activity.TRIAL REGISTRATIONClinicaltrials.gov: NCT02223923, EudraCT: 2013-003994-84.FUNDINGCancer Research UK, AstraZeneca, UK Department of Health (National Institute for Health Research), Rosetrees Trust, Experimental Cancer Medicine Centre.
Journal Article
The best bear in all the world : in which we join Winnie-the-Pooh for a year of adventures in the Hundred Acre Wood
by
Bright, Paul, 1949- Autumn, in which Pooh and Piglet prepare to meet a dragon
,
Sibley, Brian. Winter, in which a new friend arrives in the forest
,
Willis, Jeanne. Spring, in which Eeyore suspects another donkey is after his thistles
in
Winnie-the-Pooh (Fictitious character) Juvenile fiction.
,
Winnie-the-Pooh (Fictitious character) Fiction.
,
Bears Juvenile fiction.
2016
A collection of four original stories set in the Hundred Acre Wood, written in honor of the ninetieth anniversary of Winnie-the-Pooh.
Mitomycin or cisplatin chemoradiation with or without maintenance chemotherapy for treatment of squamous-cell carcinoma of the anus (ACT II): a randomised, phase 3, open-label, 2×2 factorial trial
by
Meadows, Helen M
,
Kadalayil, Latha
,
Gollins, Simon
in
Aged
,
Antineoplastic Combined Chemotherapy Protocols - adverse effects
,
Antineoplastic Combined Chemotherapy Protocols - therapeutic use
2013
Chemoradiation became the standard of care for anal cancer after the ACT I trial. However, only two-thirds of patients achieved local control, with 5-year survival of 50%; therefore, better treatments are needed. We investigated whether replacing mitomycin with cisplatin in chemoradiation improves response, and whether maintenance chemotherapy after chemoradiation improves survival.
In this 2×2 factorial trial, we enrolled patients with histologically confirmed squamous-cell carcinoma of the anus without metastatic disease from 59 centres in the UK. Patients were randomly assigned to one of four groups, to receive either mitomycin (12 mg/m2 on day 1) or cisplatin (60 mg/m2 on days 1 and 29), with fluorouracil (1000 mg/m2 per day on days 1–4 and 29–32) and radiotherapy (50·4 Gy in 28 daily fractions); with or without two courses of maintenance chemotherapy (fluorouracil and cisplatin at weeks 11 and 14). The random allocation was generated by computer and patients assigned by telephone. Randomisation was done by minimisation and stratified by tumour site, T and N stage, sex, age, and renal function. Neither patients nor investigators were masked to assignment. Primary endpoints were complete response at 26 weeks and acute toxic effects (for chemoradiation), and progression-free survival (for maintenance). The primary analyses were done by intention to treat. This study is registered at controlled-trials.com, number 26715889.
We enrolled 940 patients: 472 were assigned to mitomycin, of whom 246 were assigned to no maintenance, 226 to maintenance; 468 were assigned to cisplatin, of whom 246 were assigned to no maintenance, 222 to maintenance. Median follow-up was 5·1 years (IQR 3·9–6·9). 391 of 432 (90·5%) patients in the mitomycin group versus 386 of 431 (89·6%) in the cisplatin group had a complete response at 26 weeks (difference −0·9%, 95% CI −4·9 to 3·1; p=0·64). Overall, toxic effects were similar in each group (334/472 [71%] for mitomycin vs 337/468 [72%] for cisplatin). The most common grade 3–4 toxic effects were skin (228/472 [48%] vs 222/468 [47%]), pain (122/472 [26%] vs 135/468 [29%]), haematological (124/472 [26%] vs 73/468 [16%]), and gastrointestinal (75/472 [16%] vs 85/468 [18%]). 3-year progression-free survival was 74% (95% CI 69–77; maintenance) versus 73% (95% CI 68–77; no maintenance; hazard ratio 0·95, 95% CI 0·75–1·21; p=0·70).
The results of our trial—the largest in anal cancer to date—show that fluorouracil and mitomycin with 50·4 Gy radiotherapy in 28 daily fractions should remain standard practice in the UK.
Cancer Research UK.
Journal Article
Duration of Adjuvant Chemotherapy for Stage III Colon Cancer
2018
This analysis involving patients with stage III colon cancer pooled the findings of six clinical trials regarding the effect of adjuvant-therapy duration on disease-free survival. The results varied according to drug regimen and disease subgroup.
Journal Article
Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): final results from a prospective, pooled analysis of six randomised, phase 3 trials
2020
A prospective, pooled analysis of six randomised phase 3 trials was done to investigate disease-free survival regarding non-inferiority of 3 months versus 6 months of adjuvant chemotherapy for patients with stage III colon cancer; non-inferiority was not shown. Here, we report the final overall survival results.
In this prospective, pooled analysis of six randomised phase 3 trials, we included patients with stage III colon cancer aged at least 18 years with an Eastern Cooperative Oncology Group performance status of 0–1 recruited between June 20, 2007, and Dec 31, 2015, across 12 countries in the CALGB/SWOG 80702, IDEA France, SCOT, ACHIEVE, TOSCA, and HORG trials, who started any treatment (modified intention-to-treat). Patients in all trials were randomly assigned to 3 months or 6 months of adjuvant fluorouracil, leucovorin, and oxaliplatin (FOLFOX) every 2 weeks or capecitabine and oxaliplatin (CAPOX) in different doses and methods every 3 weeks, at the treating physician's discretion. The primary endpoint was disease-free survival (time to relapse, secondary colorectal primary tumour, or death due to all causes), and overall survival (time to death due to all causes) was the prespecified secondary endpoint. The non-inferiority margin for overall survival was set as a hazard ratio (HR) of 1·11. Pre-planned subgroup analyses included regimen and risk group. Non-inferiority was declared if the one-sided false discovery rate adjusted (FDRadj) p value was less than 0·025.
With median follow-up of 72·3 months (IQR 72·2–72·5), 2584 deaths among 12 835 patients were observed. 5064 (39·5%) patients received CAPOX and 7771 (60·5%) received FOLFOX. 5-year overall survival was 82·4% (95% CI 81·4–83·3) with 3 months of therapy and 82·8% (81·8–83·8) with 6 months of therapy (HR 1·02 [95% CI 0·95–1·11]; non-inferiority FDRadj p=0·058). For patients treated with CAPOX, 5-year overall survival was 82·1% (80·5–83·6) versus 81·2% (79·2–82·9; HR 0·96 [0·85–1·08]); non-inferiority FDRadj p=0·033), and for patients treated with FOLFOX 5-year overall survival was 82·6% (81·3–83·8) and 83·8% (82·6–85·0; HR 1·07 [0·97–1·18]; non-inferiority FDRadj p=0·34). Updated disease-free survival results confirmed previous findings (HR 1·08 [95% CI 1·02–1·15]; non-inferiority FDRadj p=0·25). Data on adverse events were not further recorded.
Non-inferiority of 3 months versus 6 months of adjuvant chemotherapy for patients with stage III colon cancer was not confirmed in terms of overall survival, but the absolute 0·4% difference in 5-year overall survival should be placed in clinical context. Overall survival results support the use of 3 months of adjuvant CAPOX for most patients with stage III colon cancer. This conclusion is strengthened by the substantial reduction of toxicities, inconveniencies, and cost associated with a shorter treatment duration.
US National Cancer Institute.
Journal Article