A geographic cline induced by negative frequency-dependent selection

<p>Abstract</p> <p>Background</p> <p>Establishment of geographic morph frequency clines is difficult to explain in organisms with limited gene flow. Balancing selection, such as negative frequency-dependent selection (NFDS), is instead suggested to establish a morph frequency cline on a geographic scale at least theoretically. Here we tested whether a large-scale smooth cline in morph frequency is established by NFDS in the female-dimorphic damselfly, <it>Ischnura senegalensis</it>, where andromorphs and gynomorphs are maintained by NFDS.</p> <p>Results</p> <p>We found a large-scale latitudinal cline in the morph frequency: andromorph frequency ranged from 0.05 (South) to 0.79 (North). Based on the empirical data on the numbers of eggs, the number of ovariole, abdomen length and latitude, the potential fitness of andromorphs was estimated to be lower than that of gynomorphs in the south, and higher in the north, suggesting the gene-by-environment interaction. From the morph-specific latitudinal cline in potential fitness, the frequency of andromorphs was expected to shift from 0 to 1 without NFDS, because a morph with higher potential fitness wins completely and the two morphs will switch at some point. In contrast, NFDS led to the coexistence of two morphs with different potential fitness in a certain geographic range along latitude due to rare morph advantage, and resulted in a smooth geographic cline of morph frequency.</p> <p>Conclusion</p> <p>Our results provide suggestive evidence that the combination of NFDS and gene-by-environment interaction, i.e., multi-selection pressure on color morphs, can explain the geographic cline in morph frequency in the current system.</p

Statistical analysis of patient-reported outcome data in randomised controlled trials of locally advanced and metastatic breast cancer: a systematic review

Although patient-reported outcomes (PROs), such as health-related quality of life, are important endpoints in randomised controlled trials (RCTs), there is little consensus about the analysis, interpretation, and reporting of these data. We did a systematic review to assess the variability, quality, and standards of PRO data analyses in advanced breast cancer RCTs. We searched PubMed for English language articles published in peer-reviewed journals between Jan 1, 2001, and Oct 30, 2017. Eligible articles were those that reported PRO results from RCTs of adult patients with advanced breast cancer receiving anti-cancer treatments with reported sample sizes of at least 50 patients—66 RCTs met the selection criteria. Only eight (12%) RCTs reported a specific PRO research hypothesis. Heterogeneity in the statistical methods used to assess PRO data was observed, with a mixture of longitudinal and cross-sectional techniques. Not all articles addressed the problem of multiple testing. Fewer than half of RCTs (28 [42%]) reported the clinical significance of their findings. 48 (73%) did not report how missing data were handled. Our systematic review shows a need to improve standards in the analysis, interpretation, and reporting of PRO data in cancer RCTs. Lack of standardisation makes it difficult to draw robust conclusions and compare findings across trials. The Setting International Standards in the Analyzing Patient-Reported Outcomes and Quality of Life Data Consortium was set up to address this need and develop recommendations on the analysis of PRO data in RCTs

Development and validation of the self-completed ascites impact measure to understand patient motivation for requesting a paracentesis

Bruce Crawford,1 Elizabeth Piault,2 Walter Gotlieb,3 Florence Joulain41Mapi Values, Tokyo, Japan; 2Mapi Values, Boston, MA, USA; 3McGill University, Montreal, Quebec, Canada; 4Sanofi, Paris, FranceBackground: The Ascites Impact Measure (AIM) was developed to record patients&amp;#39; daily experiences of symptoms that trigger a request for a paracentesis.Methods: Development of the AIM followed a rigorous step-wise approach, including a review of the literature, expert opinions, and qualitative research involving patients who experience symptomatic malignant ascites. The AIM&amp;#39;s measurement properties were assessed using data from two international trials, including 59 ovarian cancer patients with symptomatic malignant ascites.Results: Following the literature review and expert discussions to develop the conceptual model, ten patients with symptomatic malignant ascites were interviewed in the item elicitation phase, resulting in a draft questionnaire with four questions. Validation analyses consisted of 59 patients pooled from two international trials. Inter-items correlations for the AIM were good (r &amp;gt; 0.60), except for the Pain item. Internal consistency reliability (&amp;alpha; = 0.89) improved after removing the Pain item from the Total Symptom score (TSS). Test-retest reliability was sufficient. Scores significantly improved after paracentesis except for the Pain item. Preliminary estimates indicate that a two-point improvement on the three-item TSS (without the Abdominal Pain item) could be interpreted as clinically meaningful.Conclusion: The Abdominal Pain item appears to behave differently than the other three items, and could be more related to cancer. While the validity of the AIM TSS (four-item) is acceptable, removing the Pain item from the TSS scoring algorithm demonstrated better construct validity. In addition, test-retest reliability and responsiveness were found to be similar to the results for the four-item AIM TSS. The Pain item should be used as a supplemental item to the three-item AIM TSS, as it provides additional information about the underlying cancer state.Keywords: ascites impact measure, symptoms, ovarian cancer, paracentesi

Forty years of Sr-90 in situ migration : importance of soil characterization in modeling transport phenomena

In 1960 experiments were carried out on the transfer of Sr-90 between soil, grapes and wine. The experiments were conducted in Situ on a piece of land limited by two control strips. The Sr-90 migration over the last 40 years was studied by performing radiological and physico-chemical characterizations of the soil on eight 70 cm deep cores. The vertical migration modeling of Sr-90 required the definition of a triple layer conceptual model integrating the rainwater infiltration at constant flux as the only external factor of influence. Afterwards the importance of a detailed soil characterization for modeling was discussed and satisfactory simulation of the Sr-90 vertical transport was obtained and showed a calculated migration rate of about 1.0 cm year(-1) in full agreement with the in situ measured values. The discussion was regarding some of the key parameters such as granulometry, organic matter content (in the Van Genuchten parameter determination), Kd and the efficient rainwater infiltration. Besides the experimental data, simplifying assumptions in modeling such as water-soil redistribution calculation and factual discontinuities in conceptual model were examined