An ethnographic study of the effects of cognitive symptoms in patients with major depressive disorder: the IMPACT study.

BACKGROUND: The manifestation of major depressive disorder (MDD) may include cognitive symptoms that can precede the onset of MDD and persist beyond the resolution of acute depressive episodes. However, little is known about how cognitive symptoms are experienced by MDD patients and the people around them. METHODS: In this international (Brazil, Canada, China, France, and Germany) ethnographic study, we conducted semi-structured interviews and observations of remitted as well as symptomatic MDD patients (all patients self-reported being diagnosed by an HCP and self-reported being on an antidepressant) aged 18-60 years with self-reported cognitive symptoms (N = 34). In addition, participating depressed patients' close family or friends (N = 31) were interviewed. Separately recruited from depressed participants, work colleagues (N = 21) and healthcare providers (HCPs; N = 13) of depressed individuals were interviewed. RESULTS: Key insights were that: (1) patients were generally unaware that their cognitive symptoms were linked to their depression and, instead, attributed these symptoms to negative aspects of their person (e.g., age, separate disease, laziness, exhaustion); (2) cognitive symptoms in MDD appeared to negatively impact patients' social relationships and patients' ability to handle daily tasks at work and at home; (3) patients' cognitive symptoms also impacted relationships with family members and coworkers; (4) patients' cognitive symptoms increased stress and feelings of failure, which in turn seemed to worsen the cognitive symptoms, thereby creating a destructive cycle; and (5) although HCPs recommended that patients re-engage in everyday activities to help overcome their depression, cognitive symptoms seemed to impede such functional recovery. CONCLUSIONS: Taken together, these findings highlight a negative impact of patients' cognitive symptoms on their social functioning, work performance, and quality of life on the people close to them, and consequently on the degree of functional recovery after depression.

SCUMBLE: a method for systematic and accurate detection of codon usage bias by maximum likelihood estimation.

The genetic code is degenerate--most amino acids can be encoded by from two to as many as six different codons. The synonymous codons are not used with equal frequency: not only are some codons favored over others, but also their usage can vary significantly from species to species and between different genes in the same organism. Known causes of codon bias include differences in mutation rates as well as selection pressure related to the expression level of a gene, but the standard analysis methods can account for only a fraction of the observed codon usage variation. We here introduce an explicit model of codon usage bias, inspired by statistical physics. Combining this model with a maximum likelihood approach, we are able to clearly identify different sources of bias in various genomes. We have applied the algorithm to Saccharomyces cerevisiae as well as 325 prokaryote genomes, and in most cases our model explains essentially all observed variance.

Analysis of evolution through competitive selection.

Recent studies of in vitro evolution of DNA via protein binding indicate that the evolution behavior is qualitatively different in different parameter regimes. I here present a general theory that is valid for a wide range of parameters, and which reproduces and extends previous results. Specifically, the mean-field theory of a general translation-invariant model can be reduced to the basic diffusion equation with a dynamic boundary condition. The simple analytical form yields both quantitatively accurate predictions and valuable insight into the principles involved.

Pattern formation within Escherichia coli: diffusion, membrane attachment, and self-interaction of MinD molecules.

In E. coli, accurate cell division depends upon the oscillation of Min proteins from pole to pole. We provide a model for the polar localization of MinD based only on diffusion, a delay for nucleotide exchange, and different rates of attachment to the bare membrane and the occupied membrane. We derive analytically the probability density, and correspondingly the length scale, for MinD attachment zones. Our simple analytical model illustrates the processes giving rise to the observed localization of cellular MinD zones.

Simulation and analysis of in vitro DNA evolution.

We study theoretically the in vitro evolution of a DNA sequence by binding to a transcription factor. Using a simple model of protein-DNA binding and available binding constants for the Mnt protein, we perform large-scale, realistic simulations of evolution starting from a single DNA sequence. Varying the evolution parameters reveals three different regimes characterized by distinct evolutionary behaviors, and for each regime we find analytical estimates which agree well with simulation results. We also study how the details of the DNA-protein interaction affect the evolution.