The number of years lived with obesity and the risk of all-cause and cause-specific mortality

Background The role of the duration of obesity as an independent risk factor for mortality has not been investigated. The aim of this study was to analyse the association between the duration of obesity and the risk of mortality.

Methods A total of 5036 participants (aged 28–62 years) of the Framingham Cohort Study were followed up every 2 years from 1948 for up to 48 years. The association between obesity duration and all-cause and cause-specific mortality was analysed using time-dependent Cox models adjusted for body mass index. The role of biological intermediates and chronic diseases was also explored.

Results The adjusted hazard ratio (HR) for mortality increased as the number of years lived with obesity increased. For those who were obese for 1–4.9, 5–14.9, 15–24.9 and ≥25 years of the study follow-up period, adjusted HRs for all-cause mortality were 1.51 [95% confidence interval (CI) 1.27–1.79], 1.94 (95% CI 1.71–2.20), 2.25 (95% CI 1.89–2.67) and 2.52 (95% CI 2.08–3.06), respectively, compared with those who were never obese. A dose–response relation between years of duration of obesity was also clear for all-cause, cardiovascular, cancer and other-cause mortality. For every additional 2 years of obesity, the HRs for all-cause, cardiovascular disease, cancer and other-cause mortality were 1.06 (95% CI 1.05–1.07), 1.07 (95% CI 1.05–1.08), 1.03 (95% CI 1.01–1.05) and 1.07 (95% CI 1.05–1.11), respectively.

Conclusions The number of years lived with obesity is directly associated with the risk of mortality. This needs to be taken into account when estimating its burden on mortality.

Copy number variation and transposable elements feature in recent, ongoing adaptation at the Cyp6g1 locus

The increased transcription of the Cyp6g1 gene of Drosophila melanogaster, and consequent resistance to insecticides such as DDT, is a widely cited example of adaptation mediated by cis-regulatory change. A fragment of an Accord transposable element inserted upstream of the Cyp6g1 gene is causally associated with resistance and has spread to high frequencies in populations around the world since the 1940s. Here we report the existence of a natural allelic series at this locus of D. melanogaster, involving copy number variation of Cyp6g1, and two additional transposable element insertions (a P and an HMS-Beagle). We provide evidence that this genetic variation underpins phenotypic variation, as the more derived the allele, the greater the level of DDT resistance. Tracking the spatial and temporal patterns of allele frequency changes indicates that the multiple steps of the allelic series are adaptive. Further, a DDT association study shows that the most resistant allele, Cyp6g1-[BP], is greatly enriched in the top 5% of the phenotypic distribution and accounts for ~16% of the underlying phenotypic variation in resistance to DDT. In contrast, copy number variation for another candidate resistance gene, Cyp12d1, is not associated with resistance. Thus the Cyp6g1 locus is a major contributor to DDT resistance in field populations, and evolution at this locus features multiple adaptive steps occurring in rapid succession.

Probability distributions of number of children and maternal age at various order births using age-specific fertility rates by birth order

In this study, a simple analytical framework to find the probability distributions of number of children and maternal age at various order births by making use of data on age-specific fertility rates by birth order was proposed. The proposed framework is applicable to both the period and cohort fertility schedules. The most appealing point of the proposed framework is that it does not require stringent assumptions. The proposed framework has been applied to the cohort birth order-specific fertility schedules of India and its different regions and period birth order-specific fertility schedules, including the United States of America, Russia, and the Netherlands, to demonstrate its usefulness.

Treatment response for acute depression is not associated with number of previous episodes: lack of evidence for a clinical staging model for major depressive disorder

Mental illness has been observed to follow a neuroprogressive course, commencing with prodrome, then onset, recurrence and finally chronic illness. In bipolar disorder and schizophrenia responsiveness to treatment mirrors these stages of illness progression, with greater response to treatment in the earlier stages of illness and greater treatment resistance in chronic late stage illness.

Using data from 5627 participants in 15 controlled trials of duloxetine, comparator arm (paroxetine, venlafaxine, escitalopram) or placebo for the treatment of an acute depressive episode, the relationship between treatment response and number of previous depressive episodes was determined. Data was dichotomised for comparisons between participants who had >3 previous episodes (n=1697) or ≤3 previous episodes (n=3930), and additionally for no previous episodes (n=1381) or at least one previous episode (n=4246). Analyses were conducted by study arm for each clinical trial, and results were then pooled.

There was no significant difference between treatment response and number of previous depressive episodes. This unexpected finding suggests that treatments to reduce symptoms of depression during acute illness do not lose efficacy for patients with a longer history of illness.

Estimating nephron number in the developing kidney using the physical disector/fractionator combination

Over the last decade the development of new molecular biology tools, advanced microscopy, live imaging and systems biology approaches have revolutionized our conception of how embryonic development proceeds. One fundamental aspect of development biology is the concept of morphogenesis: understanding how a group of multipotent cells organize and differentiate into a complex organ. In Kidney Development: Methods and Protocols, expert researchers in the field detail different approaches to tackle kidney development. These approaches include culture and live imaging aspects of kidney development, analyzing the 3-dimensional aspects of branching morphogenesis as well as nephrogenesis, manipulation of the gene/protein expression during kidney development as well as in the adult kidney, and how to assess kidney malformation and disease. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Kidney Development: Methods and Protocols seeks to aid scientists in the further study of the process of morphogenesis which is fundamental important not only for studying developmental biology but also for regenerative medicine.

Estimating the number of green and loggerhead turtles nesting annually in the Mediterranean

Most species of marine turtle breed every two or more years and it is the norm for females to lay more than one clutch of eggs within a nesting season. Knowing the interval between breeding seasons and the clutch frequency (number of clutches laid by an individual in a breeding season) of females allows us to assess the status of a nesting population. At Alagadi Beach, Northern Cyprus, over a period of 6 years (1995–2000), we attributed 96% of green Chelonia mydas and 80% of loggerhead Caretta caretta turtle clutches to known individual females. This intensive level of monitoring enabled us to estimate the clutch frequency for both species. Using four different methods we estimated clutch frequency to be 2.9–3.1 clutches per female for green turtles and 1.8–2.2 clutches per female for loggerhead turtles. The median interval between nesting seasons for green turtles was 3 years, and for loggerhead turtles it was 2 years. Utilizing these parameters and available data from other beaches that are monitored regularly, we estimate that there are 2,280–2,787 logger-head and 339–360 green turtles nesting annually at these sites in the Mediterranean. This highlights the Critically Endangered status of this population of green turtles. Furthermore, as conventional beach patrols underestimate clutch frequency, these population estimates are likely to be optimistic.

Mixing Matrix Estimation From Sparse Mixtures With Unknown Number of Sources

In blind source separation, many methods have been proposed to estimate the mixing matrix by exploiting sparsity. However, they often need to know the source number a priori, which is very inconvenient in practice. In this paper, a new method, namely nonlinear projection and column masking (NPCM), is proposed to estimate the mixing matrix. A major advantage of NPCM is that it does not need any knowledge of the source number. In NPCM, the objective function is based on a nonlinear projection and its maxima just correspond to the columns of the mixing matrix. Thus a column can be estimated first by locating a maximum and then deflated by a masking operation. This procedure is repeated until the evaluation of the objective function decreases to zero dramatically. Thus the mixing matrix and the number of sources are estimated simultaneously. Because the masking procedure may result in some small and useless local maxima, particle swarm optimization (PSO) is introduced to optimize the objective function. Feasibility and efficiency of PSO are also discussed. Comparative experimental results show the efficiency of NPCM, especially in the cases where the number of sources is unknown and the sources are relatively less sparse.