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"Gregory, W M"
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Something of a Peasant Paradise?
Were Acadians better off than their rural counterparts in old regime France? Did they enjoy a Golden Age? To what degree did a distinct Acadian identity emerge before the wars and deportations of the mid-eighteenth century? In Something of a Peasant Paradise?, Gregory Kennedy compares Acadie in North America with a region of western France, the Loudunais, from which a number of the colonists originated. Kennedy considers the natural environment, the role of the state, the economy, the seigneury, and local governance in each place to show that similarities between the two societies have been greatly underestimated or ignored. The Acadian colonists and the people of the Loudunais were frontier peoples, with dispersed settlement patterns based on kin groups, who sought to make the best use of the land and to profit from trade opportunities. Both societies were hierarchical, demonstrated a high degree of political agency, and employed the same institutions of local governance to organize their affairs and negotiate state demands. Neither group was inherently more prosperous, egalitarian, or independent-minded than the other. Rather, the emergence of a distinct Acadian identity can be traced to the gradual adaptation of traditional methods, institutions, and ideas to their new environmental and political situations. A compelling comparative analysis based on archival evidence on both sides of the Atlantic, Something of a Peasant Paradise? Challenges the traditional historiography and demonstrates that Acadian society shared many of its characteristics with other French rural societies of the period.
eBook
Prediction of outcome in newly diagnosed myeloma: a meta-analysis of the molecular profiles of 1905 trial patients
Robust establishment of survival in multiple myeloma (MM) and its relationship to recurrent genetic aberrations is required as outcomes are variable despite apparent similar staging. We assayed copy number alterations (CNA) and translocations in 1036 patients from the NCRI Myeloma XI trial and linked these to overall survival (OS) and progression-free survival. Through a meta-anlysis of these data with data from MRC Myeloma IX trial, totalling 1905 newly diagnosed MM patients (NDMM), we confirm the association of t(4;14), t(14;16), t(14;20), del(17p) and gain(1q21) with poor prognosis with hazard ratios (HRs) for OS of 1.60 (P=4.77 × 10-7 ), 1.74 (P=0.0005), 1.90 (P=0.0089), 2.10 (P=8.86 × 10-14 ) and 1.68 (P=2.18 × 10-14 ), respectively. Patients with 'double-hit' defined by co-occurrence of at least two adverse lesions have an especially poor prognosis with HRs for OS of 2.67 (P=8.13 × 10-27 ) for all patients and 3.19 (P=1.23 × 10-18 ) for intensively treated patients. Using comprehensive CNA and translocation profiling in Myeloma XI we also demonstrate a strong association between t(4;14) and BIRC2/BIRC3 deletion (P=8.7 × 10-15 ), including homozygous deletion. Finally, we define distinct sub-groups of hyperdiploid MM, with either gain(1q21) and CCND2 overexpression (P<0.0001) or gain(11q25) and CCND1 overexpression (P<0.0001). Profiling multiple genetic lesions can identify MM patients likely to relapse early allowing stratification of treatment.
Journal Article
The Eagle has landed : 50 years of lunar science fiction
\"In celebration of the 50th anniversary of the Apollo 11 landing, the endlessly-mysterious moon is explored in this reprint short science fiction anthology from award-winning editor and anthologist Neil Clarke ... On July 20, 1969, mankind made what had only years earlier seemed like an impossible leap forward: when Apollo 11 became the first manned mission to land on the moon, and Neil Armstrong the first person to step foot on the lunar surface. While there have only been a handful of new missions since, the fascination with our planet's satellite continues, and generations of writers and artists have imagined the endless possibilities of lunar life. From adventures in the vast gulf of space between the earth and the moon, to journeys across the light face to the dark side, to the establishment of permanent residences on its surface, science fiction has for decades given readers bold and forward-thinking ideas about our nearest interstellar neighbor and what it might mean to humankind, both now and in our future. [This book] collects the best stories written in the fifty years since mankind first stepped foot on the lunar surface, serving as a shining reminder that the moon is and always has been our most visible and constant example of all the infinite possibility of the wider universe\"-- Provided by publisher.
BOOK
A novel prognostic model in myeloma based on co-segregating adverse FISH lesions and the ISS: analysis of patients treated in the MRC Myeloma IX trial
The association of genetic lesions detected by fluorescence
in situ
hybridization (FISH) with survival was analyzed in 1069 patients with newly presenting myeloma treated in the Medical Research Council Myeloma IX trial, with the aim of identifying patients associated with the worst prognosis. A comprehensive FISH panel was performed, and the lesions associated with short progression-free survival and overall survival (OS) in multivariate analysis were +1q21, del(17p13) and an adverse immunoglobulin heavy chain gene (
IGH
) translocation group incorporating t(4;14), t(14;16) and t(14;20). These lesions frequently co-segregated, and there was an association between the accumulation of these adverse FISH lesions and a progressive impairment of survival. This observation was used to define a series of risk groups based on number of adverse lesions. Taking this approach, we defined a favorable risk group by the absence of adverse genetic lesions, an intermediate group with one adverse lesion and a high-risk group defined by the co-segregation of >1 adverse lesion. This genetic grouping was independent of the International Staging System (ISS) and so was integrated with the ISS to identify an ultra-high-risk group defined by ISS II or III and >1 adverse lesion. This group constituted 13.8% of patients and was associated with a median OS of 19.4 months.
Journal Article
Second malignancies in the context of lenalidomide treatment: an analysis of 2732 myeloma patients enrolled to the Myeloma XI trial
We have carried out the largest randomised trial to date of newly diagnosed myeloma patients, in which lenalidomide has been used as an induction and maintenance treatment option and here report its impact on second primary malignancy (SPM) incidence and pathology. After review, 104 SPMs were confirmed in 96 of 2732 trial patients. The cumulative incidence of SPM was 0.7% (95% confidence interval (CI) 0.4–1.0%), 2.3% (95% CI 1.6–2.7%) and 3.8% (95% CI 2.9–4.6%) at 1, 2 and 3 years, respectively. Patients receiving maintenance lenalidomide had a significantly higher SPM incidence overall (
P
=0.011). Age is a risk factor with the highest SPM incidence observed in transplant non-eligible patients aged >74 years receiving lenalidomide maintenance. The 3-year cumulative incidence in this group was 17.3% (95% CI 8.2–26.4%), compared with 6.5% (95% CI 0.2–12.9%) in observation only patients (
P
=0.049). There was a low overall incidence of haematological SPM (0.5%). The higher SPM incidence in patients receiving lenalidomide maintenance therapy, especially in advanced age, warrants ongoing monitoring although the benefit on survival is likely to outweigh risk.
Journal Article
Prognostic utility of pre-operative circulating osteopontin, carbonic anhydrase IX and CRP in renal cell carcinoma
Background:
Objectively measured circulating biomarkers of prognosis complementing existing clinicopathological models are needed in renal cell carcinoma (RCC).
Methods:
Blood samples collected from 216 RCC patients in Leeds before nephrectomy (median follow-up 7 years) were analysed for C-reactive protein (CRP), osteopontin (OPN) and carbonic anhydrase IX (CA9) and prognostic significance determined.
Results:
CA9, OPN and CRP were univariately prognostic for overall survival (OS), cancer-specific survival (CSS) and disease-free survival (DFS) with CRP and CA9 being independently prognostic for OS/CSS and OS, respectively. Including CA9, OPN and CRP with other conventional prognostic factors gave a superior predictive capacity when compared with a previously published pre-operative clinical nomogram (
Karakiewicz et al, 2009
). Osteopontin outperformed this nomogram and the post-operative SSIGN score for OS but not for CSS, being significantly predictive for non-cancer deaths. Osteopontin, CRP and CA9 outperformed stage (c-index 76% compared with 70% for stage) and OPN or CA9 identified several subsets of poor prognosis patients including in T1 patients, who may benefit from adjuvant therapy and increased surveillance.
Conclusion:
Circulating CA9, OPN and CRP add value to existing clinicopathological prognostic factors/models and support further studies to investigate their potential use in improving the clinical management of RCC.
Journal Article
Mental health of hospital consultants: the effects of stress and satisfaction at work
Summary
Background Burnout and psychiatric morbidity among gastroenterologists, surgeons, radiologists, and oncologists in the UK have been estimated by means of a questionnaire-based survey. The relationship between consultants' mental health and their job stress and satisfaction, as well as their job and demographic characteristics, were also examined.
Methods Psychiatric morbidity was estimated using the 12-item General Health Questionnaire. The three components of burnout—emotional exhaustion, depersonalisation, and low personal accomplishment—were assessed using the Maslach Burnout Inventory. Job stress and satisfaction were measured using study-specific questions.
Findings Of 1133 consultants, 882 (78%) returned questionnaires. The estimated prevalence of psychiatric morbidity was 27%, with no significant differences between the four specialist groups. Radiologists reported the highest level of burnout in terms of low personal accomplishment. Job satisfaction significantly protected consultants' mental health against job stress. Three sources of stress were associated with both burnout and psychiatric morbidity: feeling overloaded, and its effect on home life; feeling poorly managed and resourced; and dealing with patients' suffering. Burnout was also associated with low satisfaction in three domains: relationships with patients, relatives, and staff; professional status/esteem; intellectual stimulation. In addition, being aged 55 years or less and being single were independent risk factors for burnout. Burnout was also more prevalent among consultants who felt insufficiently trained in communication and management skills.
Interpretation Consultants' mental health is likely to be protected against the high demands of medical practice by maintaining or enhancing job satisfaction, and by providing training in communication and management skills.
Journal Article
The SABRTooth feasibility trial protocol: a study to determine the feasibility and acceptability of conducting a phase III randomised controlled trial comparing stereotactic ablative radiotherapy (SABR) with surgery in patients with peripheral stage I non-small cell lung cancer (NSCLC) considered to be at higher risk of complications from surgical resection
Background
Stage I non-small cell lung cancer (NSCLC) is potentially curable, and surgery is considered to be the standard of care for patients with good performance status and minimal co-morbidity. However, a significant proportion of patients with stage I NSCLC have a poorer performance status and significant medical co-morbidity that make them at higher risk of morbidity and mortality from surgery.
Stereotactic ablative radiotherapy (SABR), which uses modern radiotherapeutic techniques to deliver large doses of radiation, has shown superiority over conventional radiotherapy in terms of local control and toxicity and is a standard of care for patients with stage I NSCLC who are at too high risk for surgery. However, it is not known whether surgery or SABR is the most effective in patients with stage I NSCLC who are suitable for surgery but are less fit and at higher risk surgical complications. Previous randomised studies have failed to recruit in this setting, and therefore, a feasibility study is required to see whether a full randomised control trial would be possible.
Methods/design
SABRTooth is a UK-based, multi-centre, open-label, two-group individually (1:1) randomised controlled feasibility study in patients with peripheral stage I NSCLC considered to be at higher risk from surgical resection. The study will assess the feasibility of conducting a definitive large-scale phase III trial. The primary objective is to assess recruitment rates to provide evidence that, when scaled up, recruitment to a large phase III trial would be possible; the target recruitment being 54 patients in total, over a 21-month period. There are multiple secondary and exploratory objectives designed to explore the optimum recruitment and data collection strategies to help optimise the design of a future phase III trial.
Discussion
To know whether SABR is a better, equivalent or inferior alternative to surgery for higher risk patients is a key question in lung cancer. Other studies comparing SABR to surgery have closed early due to poor recruitment, and therefore, the SABRTooth feasibility study has been designed around the UK National Health Service (NHS) cancer pathway incorporating many design features in order to maximise recruitment for a future definitive phase III trial.
Trial registration
controlled-trials.com
ISRCTN13029788
Journal Article