The effect of repeated early injury on reward-related processing in the adult rat

Pain during early life can affect the developing central nervous system, leading to altered neural function in the adult organism. In this thesis, I investigate the long-term effects of repeated early pain on reward-related processing in the adult rat. I hypothesised that the reward system was likely to be sensitive to early activation of pain pathways, as the brain systems involved in both pain and reward overlap extensively, and virtually all centrally acting analgesic drugs are also drugs of reward. To begin, I investigate the extent to which the developing reward system is activated by a classic analgesic and drug of abuse, morphine. Comparing neonatal and adult activation of the dopaminergic system, results show that a single morphine challenge activates neonatal reward pathways, but that there are qualitative differences in the neonatal response to repeated morphine. Next, I show how reward-related behaviours of adult animals repeatedly injured as neonates differ from those of uninjured littermates, and finally propose the lateral hypothalamic orexin system as a biomarker reflecting this behaviour. The results provide evidence that neonatal injury interferes with the normal development of reward systems during a critical period of development, resulting in characteristic changes in reward behaviour and cell signalling in the adult animal

Organs-on-chips: into the next decade

Organs-on-chips (OoCs) could be useful at various stages of drug discovery and development, providing insight regarding human organ physiology in both normal and disease contexts, as well as accurately predicting developmental drug safety and efficacy. This Review discusses the advances that have enabled OoCs to demonstrate physiological relevance, and the challenges and opportunities that need to be tackled to tap the full potential of OoC utility for translational research.Organs-on-chips (OoCs), also known as microphysiological systems or 'tissue chips' (the terms are synonymous), have attracted substantial interest in recent years owing to their potential to be informative at multiple stages of the drug discovery and development process. These innovative devices could provide insights into normal human organ function and disease pathophysiology, as well as more accurately predict the safety and efficacy of investigational drugs in humans. Therefore, they are likely to become useful additions to traditional preclinical cell culture methods and in vivo animal studies in the near term, and in some cases replacements for them in the longer term. In the past decade, the OoC field has seen dramatic advances in the sophistication of biology and engineering, in the demonstration of physiological relevance and in the range of applications. These advances have also revealed new challenges and opportunities, and expertise from multiple biomedical and engineering fields will be needed to fully realize the promise of OoCs for fundamental and translational applications. This Review provides a snapshot of this fast-evolving technology, discusses current applications and caveats for their implementation, and offers suggestions for directions in the next decade

Strong, weak and flavor scalar triplets for the CDF Wjj anomaly

A model describing the 4.1\sigma\ Wjj anomaly observed by the CDF experiment at the Tevatron collider is introduced. It features new scalar particles which are charged both under the SU(3)_C and the SU(2)_L gauge groups and which couple to pairs of quarks. We introduce several identical replicas of the scalar multiplets in order to leave an unbroken U(3)_Q x U(3)_U x U(3)_D flavor symmetry to satisfy the constraints coming from flavor physics. We discuss the LHC reach on the new scalar resonances both in the resonant production channel (with the Wjj final state) and in the QCD pair production channel (with the 4j final state).Comment: 17 pages, 6 figures and 4 table

On the structure and evolution of a polar crown prominence/filament system

Polar crown prominences are made of chromospheric plasma partially circling the Suns poles between 60 and 70 degree latitude. We aim to diagnose the 3D dynamics of a polar crown prominence using high cadence EUV images from the Solar Dynamics Observatory (SDO)/AIA at 304 and 171A and the Ahead spacecraft of the Solar Terrestrial Relations Observatory (STEREO-A)/EUVI at 195A. Using time series across specific structures we compare flows across the disk in 195A with the prominence dynamics seen on the limb. The densest prominence material forms vertical columns which are separated by many tens of Mm and connected by dynamic bridges of plasma that are clearly visible in 304/171A two-color images. We also observe intermittent but repetitious flows with velocity 15 km/s in the prominence that appear to be associated with EUV bright points on the solar disk. The boundary between the prominence and the overlying cavity appears as a sharp edge. We discuss the structure of the coronal cavity seen both above and around the prominence. SDO/HMI and GONG magnetograms are used to infer the underlying magnetic topology. The evolution and structure of the prominence with respect to the magnetic field seems to agree with the filament linkage model.Comment: 24 pages, 14 figures, Accepted for publication in Solar Physics Journal, Movies can be found at http://www2.mps.mpg.de/data/outgoing/panesar

4pi Models of CMEs and ICMEs

Coronal mass ejections (CMEs), which dynamically connect the solar surface to the far reaches of interplanetary space, represent a major anifestation of solar activity. They are not only of principal interest but also play a pivotal role in the context of space weather predictions. The steady improvement of both numerical methods and computational resources during recent years has allowed for the creation of increasingly realistic models of interplanetary CMEs (ICMEs), which can now be compared to high-quality observational data from various space-bound missions. This review discusses existing models of CMEs, characterizing them by scientific aim and scope, CME initiation method, and physical effects included, thereby stressing the importance of fully 3-D ('4pi') spatial coverage.Comment: 14 pages plus references. Comments welcome. Accepted for publication in Solar Physics (SUN-360 topical issue

Impact of Chlamydia trachomatis in the reproductive setting: British Fertility Society Guidelines for practice

Chlamydia trachomatis infection of the genital tract is the most common sexually transmitted infection and has a world-wide distribution. The consequences of infection have an adverse effect on the reproductive health of women and are a common cause of infertility. Recent evidence also suggests an adverse effect on male reproduction. There is a need to standardise the approach in managing the impact of C. trachomatis infection on reproductive health. We have surveyed current UK practice towards screening and management of Chlamydia infections in the fertility setting. We found that at least 90% of clinicians surveyed offered screening. The literature on this topic was examined and revealed a paucity of solid evidence for estimating the risks of long-term reproductive sequelae following lower genital tract infection with C. trachomatis. The mechanism for the damage that occurs after Chlamydial infections is uncertain. However, instrumentation of the uterus in women with C. trachomatis infection is associated with a high risk of pelvic inflammatory disease, which can be prevented by appropriate antibiotic treatment and may prevent infected women from being at increased risk of the adverse sequelae, such as ectopic pregnancy and tubal factor infertility. Recommendations for practice have been proposed and the need for further studies is identified

Cluster Density and the IMF

Observed variations in the IMF are reviewed with an emphasis on environmental density. The remote field IMF studied in the LMC by several authors is clearly steeper than most cluster IMFs, which have slopes close to the Salpeter value. Local field regions of star formation, like Taurus, may have relatively steep IMFs too. Very dense and massive clusters, like super star clusters, could have flatter IMFs, or inner-truncated IMFs. We propose that these variations are the result of three distinct processes during star formation that affect the mass function in different ways depending on mass range. At solar to intermediate stellar masses, gas processes involving thermal pressure and supersonic turbulence determine the basic scale for stellar mass, starting with the observed pre-stellar condensations, and they define the mass function from several tenths to several solar masses. Brown dwarfs require extraordinarily high pressures for fragmentation from the gas, and presumably form inside the pre-stellar condensations during mutual collisions, secondary fragmentations, or in disks. High mass stars form in excess of the numbers expected from pure turbulent fragmentation as pre-stellar condensations coalesce and accrete with an enhanced gravitational cross section. Variations in the interaction rate, interaction strength, and accretion rate among the primary fragments formed by turbulence lead to variations in the relative proportions of brown dwarfs, solar to intermediate mass stars, and high mass stars.Comment: 14 pages, 3 figures, to be published in ``IMF@50: A Fest-Colloquium in honor of Edwin E. Salpeter,'' held at Abbazia di Spineto, Siena, Italy, May 16-20, 2004. Kluwer Academic Publishers; edited by E. Corbelli, F. Palla, and H. Zinnecke

Flavor Production in Pb(160AGeV) on Pb Collisions: Effect of Color Ropes and Hadronic Rescattering

Collective interactions in the preequilibrium quark matter and hadronic resonance gas stage of ultrarelativistic nucleus-nucleus collisions are studied in the framework of the the transport theoretical approach RQMD. The paper reviews string fusion into color ropes and hadronic rescattering which serve as models for these interactions. Hadron production in central Pb(160AGeV) on Pb collisions has been calculated. The changes of the final flavor composition are more pronounced than in previous RQMD studies of light ion induced reactions at 200AGeV. The ratio of created quark pairs $s\bar{s}$/($u\bar{u}$+$d\bar{d}$) is enhanced by a factor of 2.4 in comparison to $pp$ results. Color rope formation increases the initially produced antibaryons to 3 times the value in the `NN mode', but only one quarter of the produced antibaryons survives because of subsequent strong absorption. The differences in the final particle composition for Pb on Pb collisions compared to S induced reactions are attributed to the hadronic resonance gas stage which is baryon-richer and lasts longer.Comment: 60 pages + 11 postscript figures (uuencoded and included

The Origin, Early Evolution and Predictability of Solar Eruptions

Coronal mass ejections (CMEs) were discovered in the early 1970s when space-borne coronagraphs revealed that eruptions of plasma are ejected from the Sun. Today, it is known that the Sun produces eruptive flares, filament eruptions, coronal mass ejections and failed eruptions; all thought to be due to a release of energy stored in the coronal magnetic field during its drastic reconfiguration. This review discusses the observations and physical mechanisms behind this eruptive activity, with a view to making an assessment of the current capability of forecasting these events for space weather risk and impact mitigation. Whilst a wealth of observations exist, and detailed models have been developed, there still exists a need to draw these approaches together. In particular more realistic models are encouraged in order to asses the full range of complexity of the solar atmosphere and the criteria for which an eruption is formed. From the observational side, a more detailed understanding of the role of photospheric flows and reconnection is needed in order to identify the evolutionary path that ultimately means a magnetic structure will erupt

Dense Stellar Populations: Initial Conditions

This chapter is based on four lectures given at the Cambridge N-body school "Cambody". The material covered includes the IMF, the 6D structure of dense clusters, residual gas expulsion and the initial binary population. It is aimed at those needing to initialise stellar populations for a variety of purposes (N-body experiments, stellar population synthesis).Comment: 85 pages. To appear in The Cambridge N-body Lectures, Sverre Aarseth, Christopher Tout, Rosemary Mardling (eds), Lecture Notes in Physics Series, Springer Verla