Pricing and Welfare in Health Plan Choice

Prices in government and employer-sponsored health insurance markets only partially reflect insurers' expected costs of coverage for different enrollees. This can create inefficient distortions when consumers self-select into plans. We develop a simple model to study this problem and estimate it using new data on small employers. In the markets we observe, the welfare loss compared to the feasible efficient benchmark is around 2-11% of coverage costs. Three-quarters of this is due to restrictions on risk-rating employee contributions; the rest is due to inefficient contribution choices. Despite the inefficiency, we find substantial benefits from plan choice relative to single-insurer options.healthcare costs, health insurance, government-sponsered health insurance, employer-sponsored health insurance

Being Different Yet Feeling Similar: The Influence Of Demographic Composition And Organizational Culture On Work Processes And Outcomes

Drawing from self-categorization theory, we tested hypotheses on the effects of an organization's demographic composition and cultural emphasis on work processes and outcomes. Using an organizational simulation, we found that the extent to which an organization emphasized individualistic or collectivistic values interacted with demographic composition to influence social interaction, conflict, productivity, and perceptions of creativity among 258 MBA students. Our findings suggest that the purported benefits of demographic diversity are more likely to emerge in organizations that, through their culture, make organizational membership salient and encourage people to categorize one another as having the organization's interests in common, rather than those that emphasize individualism and distinctiveness among members.(.)Managemen

Evidence that MEK1 positively promotes interhomologue double-strand break repair

During meiosis there is an imperative to create sufficient crossovers for homologue segregation. This can be achieved during repair of programmed DNA double-strand breaks (DSBs), which are biased towards using a homologue rather than sister chromatid as a repair template. Various proteins contribute to this bias, one of which is a meiosis specific kinase Mek1. It has been proposed that Mek1 establishes the bias by creating a barrier to sister chromatid repair, as distinct from enforcing strand invasion with the homologue. We looked for evidence that Mek1 positively stimulates strand invasion of the homologue. This was done by analysing repair of DSBs induced by the VMA1- derived endonuclease (VDE) and flanked by directly repeated sequences that can be used for intrachromatid single-strand annealing (SSA). SSA competes with interhomologue strand inva- sion significantly more successfully when Mek1 function is lost. We suggest the increase in intrachromosomal SSA reflects an opportunistic default repair pathway due to loss of a MEK1 stimulated bias for strand invasion of the homologous chromosome. Making use of an inhibitor sensitive mek1-as1 allele, we found that Mek1 function influences the repair pathway throughout the first 4-5 h of meiosis. Perhaps reflecting a particular need to create bias for successful interhomologue events before chromosome pairing is complete. © The Author(s) 2010. Published by Oxford University Pres

Positive regulation of meiotic DNA double-strand break formation by activation of the DNA damage checkpoint kinase Mec1(ATR)

During meiosis, formation and repair of programmed DNA double-strand breaks (DSBs) create genetic exchange between homologous chromosomes-a process that is critical for reductional meiotic chromosome segregation and the production of genetically diverse sexually reproducing populations. Meiotic DSB formation is a complex process, requiring numerous proteins, of which Spo11 is the evolutionarily conserved catalytic subunit. Precisely how Spo11 and its accessory proteins function or are regulated is unclear. Here, we use Saccharomyces cerevisiae to reveal that meiotic DSB formation is modulated by the Mec1(ATR) branch of the DNA damage signalling cascade, promoting DSB formation when Spo11-mediated catalysis is compromised. Activation of the positive feedback pathway correlates with the formation of single-stranded DNA (ssDNA) recombination intermediates and activation of the downstream kinase, Mek1. We show that the requirement for checkpoint activation can be rescued by prolonging meiotic prophase by deleting the NDT80 transcription factor, and that even transient prophase arrest caused by Ndt80 depletion is sufficient to restore meiotic spore viability in checkpoint mutants. Our observations are unexpected given recent reports that the complementary kinase pathway Tel1(ATM) acts to inhibit DSB formation. We propose that such antagonistic regulation of DSB formation by Mec1 and Tel1 creates a regulatory mechanism, where the absolute frequency of DSBs is maintained at a level optimal for genetic exchange and efficient chromosome segregation

Use of optoelectronic tweezers in manufacturing – accurate solder bead positioning

In this work, we analyze the use of optoelectronic tweezers (OETs) to manipulate 45 μm diameter Sn62Pb36Ag2 solder beads with light-induced dielectrophoresis force and we demonstrate high positioning accuracy. It was found that the positional deviation of the solder beads increases with the increase of the trap size. To clarify the underlying mechanism, simulations based on the integration of the Maxwell stress tensor were used to study the force profiles of OET traps with different sizes. It was found that the solder beads felt a 0.1 nN static friction or stiction force due to electrical forces pulling them towards the surface and that this force is not dependent on the size of the trap. The stiction limits the positioning accuracy; however, we show that by choosing a trap that is just larger than the solder bead sub-micron positional accuracy can be achieved

A uniform analysis of HD209458b Spitzer/IRAC lightcurves with Gaussian process models

We present an analysis of Spitzer/IRAC primary transit and secondary eclipse lightcurves measured for HD209458b, using Gaussian process models to marginalise over the intrapixel sensitivity variations in the 3.6 micron and 4.5 micron channels and the ramp effect in the 5.8 micron and 8.0 micron channels. The main advantage of this approach is that we can account for a broad range of degeneracies between the planet signal and systematics without actually having to specify a deterministic functional form for the latter. Our results do not confirm a previous claim of water absorption in transmission. Instead, our results are more consistent with a featureless transmission spectrum, possibly due to a cloud deck obscuring molecular absorption bands. For the emission data, our values are not consistent with the thermal inversion in the dayside atmosphere that was originally inferred from these data. Instead, we agree with another re-analysis of these same data, which concluded a non-inverted atmosphere provides a better fit. We find that a solar-abundance clear-atmosphere model without a thermal inversion underpredicts the measured emission in the 4.5 micron channel, which may suggest the atmosphere is depleted in carbon monoxide. An acceptable fit to the emission data can be achieved by assuming that the planet radiates as an isothermal blackbody with a temperature of $1484\pm 18$ K.Comment: 18 pages, 5 figures, 6 tables. Accepted by MNRA

A nucleotide resolution map of Top2-linked DNA breaks in the yeast and human genome

DNA topoisomerases are required to resolve DNA topological stress. Despite this essential role, abortive topoisomerase activity generates aberrant protein-linked DNA breaks, jeopardising genome stability. Here, to understand the genomic distribution and mechanisms underpinning topoisomerase-induced DNA breaks, we map Top2 DNA cleavage with strand-specific nucleotide resolution across the S. cerevisiae and human genomes—and use the meiotic Spo11 protein to validate the broad applicability of this method to explore the role of diverse topoisomerase family members. Our data characterises Mre11-dependent repair in yeast and defines two strikingly different fractions of Top2 activity in humans: tightly localised CTCF-proximal, and broadly distributed transcription-proximal, the latter correlated with gene length and expression. Moreover, single nucleotide accuracy reveals the influence primary DNA sequence has upon Top2 cleavage—distinguishing sites likely to form canonical DNA double-strand breaks (DSBs) from those predisposed to form strand-biased DNA single-strand breaks (SSBs) induced by etoposide (VP16) in vivo

Events, processes, and the time of a killing

The paper proposes a novel solution to the problem of the time of a killing (ToK), which persistently besets theories of act-individuation. The solution proposed claims to expose a crucial wrong-headed assumption in the debate, according to which ToK is essentially a problem of locating some event that corresponds to the killing. The alternative proposal put forward here turns on recognizing a separate category of dynamic occurents, viz. processes. The paper does not aim to mount a comprehensive defense of process ontology, relying instead on extant defenses. The primary aim is rather to put process ontology to work in diagnosing the current state of play over ToK, and indeed in solving it

Genome-wide association studies in ADHD

Attention-deficit/hyperactivity disorder, ADHD, is a common and highly heritable neuropsychiatric disorder that is seen in children and adults. Although heritability is estimated at around 76%, it has been hard to find genes underlying the disorder. ADHD is a multifactorial disorder, in which many genes, all with a small effect, are thought to cause the disorder in the presence of unfavorable environmental conditions. Whole genome linkage analyses have not yet lead to the identification of genes for ADHD, and results of candidate gene-based association studies have been able to explain only a tiny part of the genetic contribution to disease, either. A novel way of performing hypothesis-free analysis of the genome suitable for the identification of disease risk genes of considerably smaller effect is the genome-wide association study (GWAS). So far, five GWAS have been performed on the diagnosis of ADHD and related phenotypes. Four of these are based on a sample set of 958 parent–child trio’s collected as part of the International Multicentre ADHD Genetics (IMAGE) study and genotyped with funds from the Genetic Association Information Network (GAIN). The other is a pooled GWAS including adult patients with ADHD and controls. None of the papers reports any associations that are formally genome-wide significant after correction for multiple testing. There is also very limited overlap between studies, apart from an association with CDH13, which is reported in three of the studies. Little evidence supports an important role for the ‘classic’ ADHD genes, with possible exceptions for SLC9A9, NOS1 and CNR1. There is extensive overlap with findings from other psychiatric disorders. Though not genome-wide significant, findings from the individual studies converge to paint an interesting picture: whereas little evidence—as yet—points to a direct involvement of neurotransmitters (at least the classic dopaminergic, noradrenergic and serotonergic pathways) or regulators of neurotransmission, some suggestions are found for involvement of ‘new’ neurotransmission and cell–cell communication systems. A potential involvement of potassium channel subunits and regulators warrants further investigation. More basic processes also seem involved in ADHD, like cell division, adhesion (especially via cadherin and integrin systems), neuronal migration, and neuronal plasticity, as well as related transcription, cell polarity and extracellular matrix regulation, and cytoskeletal remodeling processes. In conclusion, the GWAS performed so far in ADHD, though far from conclusive, provide a first glimpse at genes for the disorder. Many more (much larger studies) will be needed. For this, collaboration between researchers as well as standardized protocols for phenotyping and DNA-collection will become increasingly important

Utilising family-based designs for detecting rare variant disease associations.

Rare genetic variants are thought to be important components in the causality of many diseases but discovering these associations is challenging. We demonstrate how best to use family-based designs to improve the power to detect rare variant disease associations. We show that using genetic data from enriched families (those pedigrees with greater than one affected member) increases the power and sensitivity of existing case-control rare variant tests. However, we show that transmission- (or within-family-) based tests do not benefit from this enrichment. This means that, in studies where a limited amount of genotyping is available, choosing a single case from each of many pedigrees has greater power than selecting multiple cases from fewer pedigrees. Finally, we show how a pseudo-case-control design allows a greater range of statistical tests to be applied to family data