Objectives Patients starting highly active antiretroviral therapy (HAART) may have a suboptimal CD4 increase despite rapid virological suppression. The frequency and the significance for patient care of this discordant response are uncertain. This study was designed to determine the incidence of a discordant response at two time‐points, soon after 6 months and at 12 months, and to determine the relationship with clinical outcomes. Methods Data obtained in the UK Collaborative HIV Cohort Study were analysed. A total of 2584 treatment‐naïve patients starting HAART with HIV viral load (VL)>1000 HIV‐1 RNA copies/mL at baseline and <50 copies/mL within 6 months were included in the analysis. Patients were classified at either 6–10 (midpoint 8) months or 10–14 (midpoint 12) months as having a discordant (CD4 count increase <100 cells/μL from baseline) or concordant response (CD4 count increase ≥100 cells/μL). Results Discordant responses occurred in 32.1% of patients at 8 months and in 24.2% at 12 months; 35% of those discordant at 8 months were concordant at 12 months. A discordant response was associated with older age, lower baseline VL, and (at 12 months) higher baseline CD4 cell count. In a multivariate analysis it was associated with an increased risk of death, more strongly at 12 months [incidence rate ratio (IRR) 3.35, 95% confidence interval (CI) 1.73–6.47, P<0.001] than at 8 months (IRR 2.08, 95% CI 1.19–3.64, P=0.010), but not with new AIDS events. Conclusions Discordant responders have a worse outcome, but assessment at 12 months may be preferred, given the number of ‘slow’ responders. Management strategies to improve outcomes for discordant responders need to be investigated.

In this study of HIV positive MSM, fisting is strongly associated with HCV infection. Where individuals report high risk sexual behaviours, clinicians should offer appropriate testing for HCV infection.

The range of c. 10 12 ambient light levels to which we can be exposed massively exceeds the <10 3 response range of neurons in the visual system, but we can see well in dim starlight and bright sunlight. This remarkable ability is achieved largely by a speeding up of the visual response as light levels increase, causing characteristic changes in our sensitivity to different rates of flicker. Here, we account for over 65 years of flicker-sensitivity measurements with an elegantly-simple, physiologically-relevant model built from first-order low-pass filters and subtractive inhibition. There are only two intensity-dependent model parameters: one adjusts the speed of the visual response by shortening the time constants of some of the filters in the direct cascade as well as those in the inhibitory stages; the other parameter adjusts the overall gain at higher light levels. After reviewing the physiological literature, we associate the variable gain and three of the variable-speed filters with biochemical processes in cone photoreceptors, and a further variable-speed filter with processes in ganglion cells. The variable-speed but fixed-strength subtractive inhibition is most likely associated with lateral connections in the retina. Additional fixed-speed filters may be more central. The model can explain the important characteristics of human flicker-sensitivity including the approximate dependences of low-frequency sensitivity on contrast (Weber’s law) and of high-frequency sensitivity on amplitude (“high-frequency linearity”), the exponential loss of high-frequency sensitivity with increasing frequency, and the logarithmic increase in temporal acuity with light level (Ferry-Porter law). In the time-domain, the model can account for several characteristics of flash sensitivity including changes in contrast sensitivity with light level (de Vries-Rose and Weber’s laws) and changes in temporal summation (Bloch’s law). The new model provides fundamental insights into the workings of the visual system and gives a simple account of many visual phenomena.

HighlightsContent outweighs saliency when watching films.Variance between eye movements decreases with age.Gaze patterns show similar (qualitative) strategies across development.

No abstract

PurposeProgressive retinal ganglion cell (RGC) loss is the pathological hallmark of autosomal dominant optic atrophy (DOA) caused by pathogenic OPA1 mutations. The aim of this study was to conduct an in-depth psychophysical study of the visual losses in DOA and to infer any selective vulnerability of visual pathways subserved by different RGC subtypes.MethodsWe recruited 25 patients carrying pathogenic OPA1 mutations and age-matched healthy individuals. Spatial contrast sensitivity functions (SCSFs) and chromatic contrast sensitivity were quantified, the latter using the Cambridge Colour Test. In 11 patients, long (L) and short (S) wavelength–sensitive cone temporal acuities were measured as a function of target illuminance, and L-cone temporal contrast sensitivity (TCSF) as a function of temporal frequency.ResultsSpatial contrast sensitivity functions were abnormal, with the loss of sensitivity increasing with spatial frequency. Further, the highest L-cone temporal acuity fell on average by 10 Hz and the TCSFs by 0.66 log10 unit. Chromatic thresholds along the protan, deutan, and tritan axes were 8, 9, and 14 times higher than normal, respectively, with losses increasing with age and S-cone temporal acuity showing the most significant age-related decline.ConclusionsLosses of midget parvocellular, parasol magnocellular, and bistratified koniocellular RGCs could account for the losses of high spatial frequency sensitivity and protan and deutan sensitivities, high temporal frequency sensitivity, and S-cone temporal and tritan sensitivities, respectively. The S-cone–related losses showed a significant deterioration with increasing patient age and could therefore prove useful biomarkers of disease progression in DOA.

When M- or L-cone-isolating sawtooth waveforms flicker at frequencies between 4 and 13.3 Hz, there is a mean hue shift in the direction of the shallower sawtooth slope. Here, we investigate how this shift depends on the alignment of the first and second harmonics of sawtooth-like waveforms. Below 4 Hz, observers can follow hue variations caused by both harmonics, and reliably match reddish and greenish excursions. At higher frequencies, however, the hue variations appear as chromatic flicker superimposed on a steady light, the mean hue of which varies with second-harmonic alignment. Observers can match this mean hue against a variable-duty-cycle rectangular waveform and, separately, set the alignment at which the mean hue flips between reddish and greenish. The maximum hue shifts were approximately frequency independent and occurred when the peaks or troughs of the first and second harmonics roughly aligned at the visual input-consistent with the hue shift's being caused by an early instantaneous nonlinearity that saturates larger hue excursions. These predictions, however, ignore phase delays introduced within the chromatic pathway between its input and the nonlinearity that produces the hue shifts. If the nonlinearity follows the substantial filtering implied by the chromatic temporal contrast-sensitivity function, phase delays will alter the alignment of the first and second harmonics such that at the nonlinearity, the waveforms that produce the maximum hue shifts might well be those with the largest differences in rising and falling slopes-consistent with the hue shift's being caused by a central nonlinearity that limits the rate of hue change.

The mean hue of flickering waveforms comprising only the first two harmonics depends on their temporal alignment. We evaluate explanatory models of this hue-shift effect using previous data obtained using L- and M-cone-isolating stimuli together with chromatic sensitivity and hue discrimination data. The key questions concerned what type of nonlinearity produced the hue shifts, and where the nonlinearities lay with respect to the early band-pass and late low-pass temporal filters in the chromatic pathways. We developed two plausible models: (a) a slew-rate limited nonlinearity that follows both early and late filters, and (b) a half-wave rectifying nonlinearity-consistent with the splitting of the visual input into ON- and OFF-channels-that lies between the early and late filters followed by a compressive nonlinearity that lies after the late filter.