Determining the relative contribution of retinal disparity and blur cues to ocular accommodation in Down syndrome

Individuals with Down syndrome (DS) often exhibit hypoaccommodation alongside accurate vergence. This study investigates the sensitivity of the two systems to retinal disparity and blur cues, establishing the relationship between the two in terms of accommodative-convergence to accommodation (AC/A) and convergence-accommodation to convergence (CA/C) ratios. An objective photorefraction system measured accommodation and vergence under binocular conditions and when retinal disparity and blur cues were removed. Participants were aged 6–16 years (DS n = 41, controls n = 76). Measures were obtained from 65.9% of participants with DS and 100% of controls. Accommodative and vergence responses were reduced with the removal of one or both cues in controls (p < 0.007). For participants with DS, removal of blur was less detrimental to accommodative responses than removal of disparity; accommodative responses being significantly better when all cues were available or when blur was removed in comparison to when proximity was the only available cue. AC/A ratios were larger and CA/C ratios smaller in participants with DS (p < 0.00001). This study demonstrates that retinal disparity is the main driver to both systems in DS and illustrates the diminished influence of retinal blur. High AC/A and low CA/C ratios in combination with disparity-driven responses suggest prioritisation of vergence over accurate accommodation

Deletion of chromosomal region 8p21 confers resistance to Bortezomib and is associated with upregulated Decoy trail receptor expression in patients with multiple myeloma

Loss of the chromosomal region 8p21 negatively effects survival in patients with multiple myeloma (MM) that undergo autologous stem cell transplantation (ASCT). In this study, we aimed to identify the immunological and molecular consequences of del(8)(p21) with regards to treatment response and bortezomib resistance. In patients receiving bortezomib as a single first line agent without any high-dose therapy, we have observed that patients with del(8)(p21) responded poorly to bortezomib with 50% showing no response while patients without the deletion had a response rate of 90%. In vitro analysis revealed a higher resistance to bortezomib possibly due to an altered gene expression profile caused by del(8)(p21) including genes such as TRAIL-R4, CCDC25, RHOBTB2, PTK2B, SCARA3, MYC, BCL2 and TP53. Furthermore, while bortezomib sensitized MM cells without del(8)(p21) to TRAIL/APO2L mediated apoptosis, in cells with del(8)(p21) bortezomib failed to upregulate the pro-apoptotic death receptors TRAIL-R1 and TRAIL-R2 which are located on the 8p21 region. Also expressing higher levels of the decoy death receptor TRAIL-R4, these cells were largely resistant to TRAIL/APO2L mediated apoptosis. Corroborating the clinical outcome of the patients, our data provides a potential explanation regarding the poor response of MM patients with del(8)(p21) to bortezomib treatment. Furthermore, our clinical analysis suggests that including immunomodulatory agents such as Lenalidomide in the treatment regimen may help to overcome this negative effect, providing an alternative consideration in treatment planning of MM patients with del(8)(p21)

Impact of resolving the diurnal cycle in an ocean-atmosphere GCM. Part 1: A diurnally forced OGCM

The diurnal cycle is a fundamental time scale in the climate system, at which the upper ocean and atmosphere are routinely observed to vary. Current climate models, however, are not configured to resolve the diurnal cycle in the upper ocean or the interaction of the ocean and atmosphere on these time scales. This study examines the diurnal cycle of the tropical upper ocean and its climate impacts. In the present paper, the first of two, a high vertical resolution ocean general circulation model (OGCM), with modified physics, is developed which is able to resolve the diurnal cycle of sea surface temperature (SST) and current variability in the upper ocean. It is then validated against a satellite derived parameterization of diurnal SST variability and in-situ current observations. The model is then used to assess rectification of the intraseasonal SST response to the Madden–Julian oscillation (MJO) by the diurnal cycle of SST. Across the equatorial Indo-Pacific it is found that the diurnal cycle increases the intraseasonal SST response to the MJO by around 20%. In the Pacific, the diurnal cycle also modifies the exchange of momentum between equatorially divergent Ekman currents and the meridionally convergent geostrophic currents beneath, resulting in a 10% increase in the strength of the Ekman cells and equatorial upwelling. How the thermodynamic and dynamical impacts of the diurnal cycle effect the mean state, and variability, of the climate system cannot be fully investigated in the constrained design of ocean-only experiments presented here. The second part of this study, published separately, addresses the climate impacts of the diurnal cycle in the coupled system by coupling the OGCM developed here to an atmosphere general circulation model