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Summary: This paper proposes a nonparametric method for evaluating treatment effects in the presence of both treatment endogeneity and attrition/non‐response bias, based on two instrumental variables. Using a discrete instrument for the treatment and an instrument with rich (in general continuous) support for non‐response/attrition, we identify the average treatment effect on compliers as well as the total population under the assumption of additive separability of observed and unobserved variables affecting the outcome. We suggest non‐ and semiparametric estimators and apply the latter to assess the treatment effect of gym training, which is instrumented by a randomized cash incentive paid out conditional on visiting the gym, on self‐assessed health among students at a Swiss university. The measurement of health is prone to non‐response, which is instrumented by a cash lottery for participating in the follow‐up survey. [ABSTRACT FROM AUTHOR]

This paper discusses identification based on difference-in-differences (DiD) approaches with multiple treatments. It shows that an appropriate adaptation of the common trend assumption underlying the DiD strategy for the comparison of two treatments restricts the possibility of effect heterogeneity for at least one of the treatments. The required assumption of effect homogeneity is likely to be violated because of non-random assignment to treatment based on both observables and unobservables. However, this paper shows that, under certain conditions, the DiD estimate comparing two treatments identifies a lower bound in absolute values on the average treatment effect on the treated compared to the unobserved non-treatment state, even if effect homogeneity is violated. This is possible if the treatments have ordered treatment effects, that is, in expectation, the effects of both treatments compared to no treatment have the same sign, and one treatment has a stronger effect than the other treatment on the respective recipients. Such assumptions are plausible if treatments are ordered or vary in intensity. [ABSTRACT FROM AUTHOR]

The efficacy of bendamustine versus chlorambucil in a phase III trial of previously untreated patients with Binet stage B/C chronic lymphocytic leukaemia ( CLL) was re-evaluated after a median observation time of 54 months in May 2010. Overall survival ( OS) was analysed for the first time. At follow-up, investigator-assessed complete response ( CR) rate (21·0% vs 10·8%), median progression-free survival (21·2 vs 8·8 months; P < 0·0001; hazard ratio 2·83) and time to next treatment (31·7 vs 10·1 months; P < 0·0001) were improved for bendamustine over chlorambucil. OS was not different between groups for all patients or those ≤65 years, >65 years, responders and non-responders. However, patients with objective response or a CR experienced a significantly longer OS than non-responders or those without a CR. Significantly more patients on chlorambucil progressed to second/further lines of treatment compared with those on bendamustine (78·3% vs 63·6%; P = 0·004). The benefits of bendamustine over chlorambucil were achieved without reducing quality of life. In conclusion, bendamustine is significantly more effective than chlorambucil in previously untreated CLL patients, with the achievement of a CR or objective response appearing to prolong OS. Bendamustine should be considered as a preferred first-line option over chlorambucil for CLL patients ineligible for fludarabine, cyclophosphamide and rituximab. [ABSTRACT FROM AUTHOR]

Background: Nucleophosmin (NPM1) and Flt3 internal tandem duplications (Flt3-ITD mutations) represent the most frequent molecular aberrations in patients with acute myeloid leukemia (AML). While NPM1 mutations are associated with favourable prognosis in younger AML patients, Flt3-ITD mutations reflect an unfavourable prognostic factor in these patients. So far, especially NPM1 mutations have not yet been evaluated exclusively in older patients. Patients and methods: We retrospectively analysed the prevalence of NPM1 and Flt3-ITD mutations and its association with complete remission (CR), and survival in 99 elderly patients (median age 71 yr, range 60–85 yr) newly diagnosed for AML. Primary treatment approach was curative in 54, and palliative in 38 patients, while seven patients received best supportive care only. The mean follow-up of surviving patients was 600 d. Results: Sixty-seven patients were tested negative for NPM1 and Flt3-ITD mutations (group 1), 16 patients carried only a NPM1 mutation (group 2) and nine patients had only a Flt3-ITD mutation (group 3) while additional seven patients were positive for both aberrations (group 4). We can demonstrate a significant higher rate of CR comparing wildtype vs. NPM1 positive patients (40.5% for group 1 vs. 80.0% for group 2, P = 0.03) for patients receiving curative therapy. Interestingly, there is no significant difference in overall survival between group 1 and group 2 (Log-rank test P = 0.22, median 440 d vs. 1125 d). In contrast, patients carrying a Flt3-ITD mutation had a significant worse overall survival compared to wildtype patients ( P = 0.03, median 210 d for group 3 + 4 vs. 634 d for group 1 + 2) while no difference of CR rate could be observed (42.8% vs. 48.9%, P = 0.91). Conclusion: As elderly but medically fit patients with AML carrying a NPM1 mutation have a high CR rate, age itself should not be a barrier for induction treatment. However, new therapeutic concepts of postremission therapy (e.g. allogeneic stem cell transplantation after dose-reduced conditioning) should be considered for these patients in first CR. [ABSTRACT FROM AUTHOR]

In 1991 the population size of the coelacanth ( Latimeria chalumnae) on Grande Comore Island, Western Indian Ocean, was estimated at 230–650 individuals, based on counts of individually recognized fish in an 8-km stretch of coastline. This census area represents about 9% of the total suitable habitat at the island. Counts in the same area in 1994 indicated a reduction of sighted coelacanths of about 30%. Additional surveys in 1995 suggested a total coelacanth population of less than 300 individuals. The local artisanal fishery is probably responsible for the observed decline. The survival of the coelacanth seems to be severely threatened if fishing pressure is not reduced. Conservation measures should focus on providing local fishermen with fishing alternatives. [ABSTRACT FROM AUTHOR]

. The coexistence of juvenile and adult territorial Pomacanthus imperator was studied in the Red Sea. The role played by their divergent colouration in the settlement of juveniles among adults on the reef is interpreted as the intraspecific equivalent of character displacement. [ABSTRACT FROM AUTHOR]