Therapeutic potential of targeting interleukin-1 family cytokines in chronic inflammatory skin diseases*

The interleukin (IL)-1 family of cytokines is a central regulator of a myriad of immunological responses. It comprises several cytokines, including those belonging to the IL-1, IL-36 and IL-18 subfamilies, as well as IL-33. The IL-1 family primarily plays a role in orchestrating innate immune responses, but is also involved in adaptive immunity. Increased interest in the IL-1 family occurred following the discovery that dysregulation of IL-1 signalling underlies the pathogenesis of several monogenic autoinflammatory diseases, characterized by sterile inflammation involving the skin and other organs. This also provided increased understanding of the role of innate immunity and the IL-1 family in polygenic autoinflammatory skin conditions, such as neutrophilic dermatoses, as well as in some of the most common chronic inflammatory skin diseases, such as psoriasis and hidradenitis suppurativa. Several therapeutic agents have been developed to inhibit the IL-1 family members and their signalling pathways. These have shown therapeutic efficacy in several chronic inflammatory skin disorders. The aim of this review is to thoroughly describe the consequences of pathological dysregulation of the IL-1, IL-33, IL-36 and IL-18 pathways in dermatological conditions and to provide a forward-looking update on therapeutic strategies targeting signalling by IL-1 family cytokines

Estimating the nuclear level density with the Monte Carlo shell model

A method for making realistic estimates of the density of levels in even-even nuclei is presented making use of the Monte Carlo shell model (MCSM). The procedure follows three basic steps: (1) computation of the thermal energy with the MCSM, (2) evaluation of the partition function by integrating the thermal energy, and (3) evaluating the level density by performing the inverse Laplace transform of the partition function using Maximum Entropy reconstruction techniques. It is found that results obtained with schematic interactions, which do not have a sign problem in the MCSM, compare well with realistic shell-model interactions provided an important isospin dependence is accounted for.Comment: 14 pages, 3 postscript figures. Latex with RevTex. Submitted as a rapid communication to Phys. Rev.

Statistical Theory of Parity Nonconservation in Compound Nuclei

We present the first application of statistical spectroscopy to study the root-mean-square value of the parity nonconserving (PNC) interaction matrix element M determined experimentally by scattering longitudinally polarized neutrons from compound nuclei. Our effective PNC interaction consists of a standard two-body meson-exchange piece and a doorway term to account for spin-flip excitations. Strength functions are calculated using realistic single-particle energies and a residual strong interaction adjusted to fit the experimental density of states for the targets, ^{238} U for A\sim 230 and ^{104,105,106,108} Pd for A\sim 100. Using the standard Desplanques, Donoghue, and Holstein estimates of the weak PNC meson-nucleon coupling constants, we find that M is about a factor of 3 smaller than the experimental value for ^{238} U and about a factor of 1.7 smaller for Pd. The significance of this result for refining the empirical determination of the weak coupling constants is discussed.Comment: Latex file, no Fig

What are the most effective techniques in changing obese individuals' physical activity self-efficacy and behaviour: a systematic review and meta-analysis

Increasing self-efficacy is generally considered to be an important mediator of the effects of physical activity interventions. A previous review identified which behaviour change techniques (BCTs) were associated with increases in self-efficacy and physical activity for healthy non-obese adults. The aim of the current review was to identify which BCTs increase the self-efficacy and physical activity behaviour of obese adults. A systematic search identified 61 comparisons with obese adults reporting changes in self-efficacy towards engaging in physical activity following interventions. Of those comparisons, 42 also reported changes in physical activity behaviour. All intervention descriptions were coded using Michie et al’s (2011) 40 item CALO-RE taxonomy of BCTs. Meta-analysis was conducted with moderator analyses to examine the association between whether or not each BCT was included in interventions, and size of changes in both self-efficacy and physical activity behaviour. Overall, a small effect of the interventions was found on self-efficacy (d = 0.23, 95% confidence interval (CI): 0.16-0.29, p < 0.001) and a medium sized effect on physical activity behaviour (d = 0.50, 95% CI 0.38-0.63, p < 0.001). Four BCTs were significantly associated with positive changes in self-efficacy; ‘action planning’, ‘time management’, ‘prompt self-monitoring of behavioural outcome’ and ‘plan social support/social change’. These latter two BCTs were also associated with positive changes in physical activity. An additional 19 BCTs were associated with positive changes in physical activity. The largest effects for physical activity were found where interventions contained ‘teach to use prompts/cues’, ‘prompt practice’ or ‘prompt rewards contingent on effort or progress towards behaviour’. Overall, a non-significant relationship was found between change in self-efficacy and change in physical activity (Spearman’s Rho = −0.18 p = 0.72). In summary, the majority of techniques increased physical activity behaviour, without having discernible effects on self-efficacy. Only two BCTs were associated with positive changes in both physical activity self-efficacy and behaviour. This is in contrast to the earlier review which found a strong relationship between changes in physical activity self-efficacy and behaviour. Mechanisms other than self-efficacy may be more important for increasing the physical activity of obese individuals compared with non-obese individuals

The Design and Validation of the Quantum Mechanics Conceptual Survey

The Quantum Mechanics Conceptual Survey (QMCS) is a 12-question survey of students' conceptual understanding of quantum mechanics. It is intended to be used to measure the relative effectiveness of different instructional methods in modern physics courses. In this paper we describe the design and validation of the survey, a process that included observations of students, a review of previous literature and textbooks and syllabi, faculty and student interviews, and statistical analysis. We also discuss issues in the development of specific questions, which may be useful both for instructors who wish to use the QMCS in their classes and for researchers who wish to conduct further research of student understanding of quantum mechanics. The QMCS has been most thoroughly tested in, and is most appropriate for assessment of (as a posttest only), sophomore-level modern physics courses. We also describe testing with students in junior quantum courses and graduate quantum courses, from which we conclude that the QMCS may be appropriate for assessing junior quantum courses, but is not appropriate for assessing graduate courses. One surprising result of our faculty interviews is a lack of faculty consensus on what topics should be taught in modern physics, which has made designing a test that is valued by a majority of physics faculty more difficult than expected.Comment: Submitted to Physical Review Special Topics: Physics Education Researc