Current practice in the modelling of Age, Period and Cohort effects with panel data: a commentary

This comment assesses how age, period and cohort (APC) effects are modelled with panel data in the social sciences. It considers variations on a 2-level multilevel model which has been used to show apparent evidence for simultaneous APC effects. We show that such an interpretation is often misleading, and that the formulation and interpretation of these models requires a better understanding of APC effects and the exact collinearity present between them. This interpretation must draw on theory to justify the claims that are made. By comparing two papers which over-interpret such a model, and another that in our view interprets it appropriately, we outline best practice for researchers aiming to use panel datasets to find APC effects, with an understanding that it is impossible for any statistical model to find and separate all three effects

Spinal neurons that contain gastrin-releasing peptide seldom express Fos or phosphorylate extracellular signal-regulated kinases in response to intradermal chloroquine

Background: Gastrin-releasing peptide (GRP) is thought to play a role in the itch evoked by intradermal injection of chloroquine. Although some early studies suggested that GRP was expressed in pruriceptive primary afferents, it is now thought that GRP in the spinal cord is derived mainly from a population of excitatory interneurons in lamina II, and it has been suggested that these are involved in the itch pathway. To test this hypothesis, we used the transcription factor Fos and phosphorylation of extracellular signal-regulated kinases (ERK) to look for evidence that interneurons expressing GRP were activated following intradermal injection of chloroquine into the calf, in mice that express enhanced green fluorescent protein (EGFP) in these cells. Results: Injection of chloroquine resulted in numerous Fos- or phospho-ERK (pERK) positive cells in the somatotopically appropriate part of the superficial dorsal horn. The proportion of all neurons in this region that showed Fos or pERK was 18% and 21%, respectively. However, among the GRP–EGFP, only 7% were Fos-positive and 3% were pERK-positive. As such, GRP–EGFP cells were significantly less likely than other neurons to express Fos or to phosphorylate ERK. Conclusions: Both expression of Fos and phosphorylation of ERK can be used to identify dorsal horn neurons activated by chloroquine injection. However, these results do not support the hypothesis that interneurons expressing GRP are critical components in the itch pathway

Weak values and the Leggett-Garg inequality in solid-state qubits

An implementation of weak values is investigated in solid-state qubits. We demonstrate that a weak value can be non-classical if and only if a Leggett-Garg inequality can also be violated. Generalized weak values are described, where post-selection on a range of weak measurement results. Imposing classical weak values permits the derivation of Leggett-Garg inequalities for bounded operators. Our analysis is presented in terms of kicked quantum nondemolition measurements on a quantum double-dot charge qubit.Comment: 4 pages, 2 figure

Substance P-expressing excitatory interneurons in the mouse superficial dorsal horn provide a propriospinal input to the lateral spinal nucleus

The superficial dorsal horn (laminae I and II) of the spinal cord contains numerous excitatory and inhibitory interneurons, and recent studies have shown that each of these groups can be divided into several neurochemically distinct populations. Although it has long been known that some neurons in this region have intersegmental (propriospinal) axonal projections, there have been conflicting reports concerning the number of propriospinal cells and the extent of their axons. In addition, little is known about the neurochemical phenotype of propriospinal neurons or about the termination pattern of their axons. In the present study we show, using retrograde tracing, that around a third of lamina I–II neurons in the lumbar enlargement project at least five segments cranially. Substance P-expressing excitatory neurons are over-represented among these cells, accounting for one-third of the propriospinal neurons. In contrast, inhibitory interneurons and excitatory PKCγ neurons are both under-represented among the retrogradely labelled cells. By combining viral vector-mediated Cre-dependent anterograde tracing with immunocytochemistry, we provide evidence that the lateral spinal nucleus (LSN), rather than the superficial dorsal horn, is the main target for axons belonging to propriospinal substance P-expressing neurons. These findings help to resolve the discrepancies between earlier studies and have implications for the role of the LSN in pain mechanisms

Forecasting eruptions from long-quiescent volcanoes

Forecasts of eruption are uncertain. The uncertainty is amplified when volcanoes reawaken after several generations in repose, because direct evidence of previous behaviour is rarely available. It fosters scepticism about warnings of volcanic activity and may compromise the success of emergency procedures. The quality of forecasts has improved over the past 50 years, owing mainly to a growing sophistication in statistical analyses of unrest. Physics-based analyses have yet to achieve the same level of maturity. Their application has been delayed by a view that volcanoes are too complex to share patterns of behaviour that can be described in a deterministic manner. This view is being increasingly challenged and an emerging line of inquiry is to understand how forecasts can be further improved by integrating statistical approaches with new constraints on possible outcomes from physics-based criteria. The introduction of deterministic reasoning yields rational explanations of why forecasts are not perfect and, as a result, offers new opportunities for increasing public confidence in warnings of eruption

p38 MAPK regulates cavitation and tight junction function in the mouse blastocyst.

UNLABELLED: Blastocyst formation is essential for implantation and maintenance of pregnancy and is dependent on the expression and coordinated function of a series of proteins involved in establishing and maintaining the trans-trophectoderm ion gradient that enables blastocyst expansion. These consist of Na/K-ATPase, adherens junctions, tight junctions (TJ) and aquaporins (AQP). While their role in supporting blastocyst formation is established, the intracellular signaling pathways that coordinate their function is unclear. The p38 MAPK pathway plays a role in regulating these proteins in other cell types and is required for embryo development at the 8-16 cell stage, but its role has not been investigated in the blastocyst. HYPOTHESIS: p38 MAPK regulates blastocyst formation by regulating blastocyst formation gene expression and function. METHODS: Embryos were cultured from the early blastocyst stage for 12 h or 24 h in the presence of a potent and specific p38 MAPK inhibitor, SB 220025. Blastocyst expansion, hatching, gene family expression and localization, TJ function and apoptosis levels were analyzed. RESULTS: Inhibition of the p38 MAPK pathway reduced blastocyst expansion and hatching, increased tight junction permeability, affected TJP1 localization, reduced Aqp3 expression, and induced a significant increase in apoptosis. CONCLUSION: The p38 MAPK pathway coordinates the overall events that regulate blastocyst formation