Irreversible electroporation versus radiofrequency ablation for hepatocellular carcinoma: a single centre propensity-matched comparison.

BACKGROUND AND AIMS: Irreversible electroporation (IRE) is a relatively new non-thermal ablative method for unresectable hepatocellular carcinoma (HCC). We aimed to compare the longer-term efficacy of IRE to the standard thermal technique of radiofrequency ablation (RFA) in HCC. METHODS: All patients who underwent IRE or RFA for HCC in our centre were identified and demographic and clinical data were analysed up until 1st March, 2020. Local recurrence-free survival (LRFS) was compared between groups after propensity score matching for age, gender, Child-Pugh grade, BCLC stage, lesion size and alpha-fetoprotein (AFP) level. RESULTS: A total of 190 HCC ablations (31 IRE and 159 RFA) were identified. After propensity score matching, we compared 25 IRE procedures (76% males, median age 62.4 years, median tumour size 20 mm) to 96 RFA procedures (84.4% males, median age 64.3 years, median tumour size 18.5 mm). LRFS did not differ between groups, with a 1-, 2- and 5-year LRFS of 80.4% (95% CI 55.8-92.2), 69.1% (95% CI 43.3-84.9) and 44.9% (95% CI 18.9-68.1%), respectively for IRE and 84.8% (95% CI 75.2-90.9), 71.3% (95% CI 58.3-81.0) and 52.1% (95% CI 35.4-66.4%), respectively for RFA (p = .63). There were no major procedure-related complications or deaths in either group. CONCLUSIONS: Whilst IRE remains a relatively novel therapy for HCC cases where standard thermal ablation is contraindicated, the LRFS in our centre is comparable to that of RFA. IRE should therefore be considered as a treatment option in such cases when available before stage-migration to non-curative therapies such as transarterial chemoembolization (TACE).

Hearing through Your Eyes: Neural Basis of Audiovisual Cross-activation, Revealed by Transcranial Alternating Current Stimulation.

Some people experience auditory sensations when seeing visual flashes or movements. This prevalent synaesthesia-like visually evoked auditory response (vEAR) could result either from overexuberant cross-activation between brain areas and/or reduced inhibition of normally occurring cross-activation. We have used transcranial alternating current stimulation (tACS) to test these theories. We applied tACS at 10 Hz (alpha band frequency) or 40 Hz (gamma band), bilaterally either to temporal or occipital sites, while measuring same/different discrimination of paired auditory (A) versus visual (V) Morse code sequences. At debriefing, participants were classified as vEAR or non-vEAR, depending on whether they reported "hearing" the silent flashes. In non-vEAR participants, temporal 10-Hz tACS caused impairment of A performance, which correlated with improved V; conversely under occipital tACS, poorer V performance correlated with improved A. This reciprocal pattern suggests that sensory cortices are normally mutually inhibitory and that alpha-frequency tACS may bias the balance of competition between them. vEAR participants showed no tACS effects, consistent with reduced inhibition, or enhanced cooperation between modalities. In addition, temporal 40-Hz tACS impaired V performance, specifically in individuals who showed a performance advantage for V (relative to A). Gamma-frequency tACS may therefore modulate the ability of these individuals to benefit from recoding flashes into the auditory modality, possibly by disrupting cross-activation of auditory areas by visual stimulation. Our results support both theories, suggesting that vEAR may depend on disinhibition of normally occurring sensory cross-activation, which may be expressed more strongly in some individuals. Furthermore, endogenous alpha- and gamma-frequency oscillations may function respectively to inhibit or promote this cross-activation.

Long-term outcomes of primary sclerosing cholangitis: an Australian non-transplant tertiary hospital perspective.

BACKGROUND: There are limited Australian epidemiological and outcome data on primary sclerosing cholangitis (PSC), with the only published study involving a state liver transplantation service. AIM: The aim of this retrospective study was to evaluate the natural history, and morbidity and mortality of PSC in an Australian population managed in a large metropolitan non-transplant teaching hospital. METHODS: We identified all PSC patients managed at The Alfred Hospital over a 10-year period and analysed their clinical and demographic data. Primary outcomes were liver transplantation and death. Secondary outcomes included cholangiocarcinoma, development of cirrhosis, liver decompensation, cholangitis requiring hospital admission and the development of dominant strictures requiring dilatation. RESULTS: We identified 39 PSC patients (69% male) with a median follow-up time of 63 months (range 5-289). Median age at diagnosis was 45 years (range 10-81) and 29 (74%) patients had concurrent inflammatory bowel disease. Five patients had cirrhosis at diagnosis and 10 (26%) developed cirrhosis after a median follow up of 54 months. Three (8%) patients developed cholangiocarcinoma and one with overlap syndrome required liver transplantation. The 10- and 20-year survival rates for the entire cohort were 77.4% (95% confidence interval 55.6-89.4) and 68.8% (95% confidence interval 42.1-85) respectively. Survival in patients with small-duct disease was not different from those without. CONCLUSION: Although the PSC population in this Australian cohort appears typical of the disease, rates of liver decompensation are relatively low and the overall transplant-free survival may be better than that reported in overseas cohorts or from cohorts derived from liver transplantation centres.

A deafening flash! Visual interference of auditory signal detection.

In some people, visual stimulation evokes auditory sensations. How prevalent and how perceptually real is this? 22% of our neurotypical adult participants responded 'Yes' when asked whether they heard faint sounds accompanying flash stimuli, and showed significantly better ability to discriminate visual 'Morse-code' sequences. This benefit might arise from an ability to recode visual signals as sounds, thus taking advantage of superior temporal acuity of audition. In support of this, those who showed better visual relative to auditory sequence discrimination also had poorer auditory detection in the presence of uninformative visual flashes, though this was independent of awareness of visually-evoked sounds. Thus a visually-evoked auditory representation may occur subliminally and disrupt detection of real auditory signals. The frequent natural correlation between visual and auditory stimuli might explain the surprising prevalence of this phenomenon. Overall, our results suggest that learned correspondences between strongly correlated modalities may provide a precursor for some synaesthetic abilities.

Commonalities for numerical and continuous quantity skills at temporo-parietal junction.

How do our abilities to process number and other continuous quantities such as time and space relate to each other? Recent evidence suggests that these abilities share common magnitude processing and neural resources, although other findings also highlight the role of dimension-specific processes. To further characterize the relation between number, time, and space, we first examined them in a population with a developmental numerical dysfunction (developmental dyscalculia) and then assessed the extent to which these abilities correlated both behaviorally and anatomically in numerically normal participants. We found that (1) participants with dyscalculia showed preserved continuous quantity processing and (2) in numerically normal adults, numerical and continuous quantity abilities were at least partially dissociated both behaviorally and anatomically. Specifically, gray matter volume correlated with both measures of numerical and continuous quantity processing in the right TPJ; in contrast, individual differences in number proficiency were associated with gray matter volume in number-specific cortical regions in the right parietal lobe. Together, our new converging evidence of selective numerical impairment and of number-specific brain areas at least partially distinct from common magnitude areas suggests that the human brain is equipped with different ways of quantifying the outside world.

Surveillance MRI is associated with improved survival in patients with primary sclerosing cholangitis.

BACKGROUND: The benefits of regular surveillance imaging for cholangiocarcinoma in patients with primary sclerosing cholangitis (PSC) are unclear. Hence, we aimed to evaluate the impact of regular magnetic resonance cholangiopancreatography (MRCP) on outcomes of patients with PSC in Australia, where the practice of MRCP surveillance is variable. METHODS: The relationship between MRCP surveillance and survival outcomes was assessed in a multicenter, retrospective cohort of patients with PSC from 9 tertiary liver centers in Australia. An inverse probability of treatment weighting approach was used to balance groups across potentially confounding covariates. RESULTS: A total of 298 patients with PSC with 2117 person-years of follow-up were included. Two hundred and twenty patients (73.8%) had undergone MRCP surveillance. Regular surveillance was associated with a 71% reduced risk of death on multivariate weighted Cox analysis (HR: 0.29, 95% CI: 0.14-0.59, p < 0.001) and increased likelihood of having earlier endoscopic retrograde cholangiopancreatography from the date of PSC diagnosis in patients with a dominant stricture (p < 0.001). However, survival posthepatobiliary cancer diagnosis was not significantly different between both groups (p = 0.74). Patients who had surveillance of less than 1 scan a year (n = 41) had comparable survival (HR: 0.46, 95% CI 0.16-1.35, p = 0.16) compared to patients who had surveillance at least yearly (n = 172). CONCLUSIONS: In this multicenter cohort study that employed inverse probability of treatment weighting to minimize selection bias, regular MRCP was associated with improved overall survival in patients with PSC; however, there was no difference in survival after hepatobiliary cancer diagnosis. Further prospective studies are needed to confirm the benefits of regular MRCP and optimal imaging interval in patients with PSC.

fMRI correlates of subjective reversals in ambiguous structure-from-motion.

We used fMRI to examine the neural correlates of subjective reversals for bistable structure-from-motion. We compared transparent random-dot kinematograms depicting either a cylinder rotating in depth or two flat surfaces translating in opposite directions at apparently different depths. For both such stimuli, the motion of dots on the different apparent depth planes typically appears to reverse direction periodically on prolonged viewing. Yet for cylindrical but not flat stimuli, such subjective reversals also coincide with apparent reversal of 3D rotation direction. We hypothesized that the lateral occipital complex (region LOC), sensitive to 3D form, might show greater event-related activity for subjective reversals of cylindrical than flat stimuli; conversely, motion-sensitive hMT+/V5 should respond in common to subjective reversals for either type of stimuli, as both are perceived as changes in planar motion. We obtained an event-related measure of neural activity associated with subjective reversals after first factoring out block-related differences between cylindrical versus flat stimuli (and thereby the associated low-level blocked stimulus differences). In support of our hypothesis, only the cylindrical stimuli produced reversal-related activity in contralateral human LOC. In contrast, the hMT+/V5 complex was activated alike by subjective reversals for both cylindrical and flat stimuli. Intriguingly, V1 also showed (contralateral) specificity for rotational reversals, suggesting a possible feedback influence from LOC. These results reveal specific neural correlates for subjective switches of 3D rotation versus translation, as distinct from subjective reversals in general.

Does visual flicker phase at gamma frequency modulate neural signal propagation and stimulus selection?

Oscillatory synchronization of neuronal populations has been proposed to play a role in perceptual integration and attentional processing. However, some conflicting evidence has been found with respect to its causal relevance for sensory processing, particularly when using flickering visual stimuli with the aim of driving oscillations. We tested psychophysically whether the relative phase of gamma frequency flicker (60 Hz) between stimuli modulates well-known facilitatory lateral interactions between collinear Gabor patches (Experiment 1) or crowding of a peripheral target by irrelevant distractors (Experiment 2). Experiment 1 assessed the impact of suprathreshold Gabor flankers on detection of a near-threshold central Gabor target ("Lateral interactions paradigm"). The flanking stimuli could flicker either in phase or in anti-phase with each other. The typical facilitation of target detection was found with collinear flankers, but this was unaffected by flicker phase. Experiment 2 employed a "crowding" paradigm, where orientation discrimination of a peripheral target Gabor patch is disrupted when surrounded by irrelevant distractors. We found the usual crowding effect, which declined with spatial separation, but this was unaffected by relative flicker phase between target and distractors at all separations. These results imply that externally driven manipulations of gamma frequency phase cannot modulate perceptual integration in vision.

Lenvatinib for the treatment of hepatocellular carcinoma-a real-world multicenter Australian cohort study.

INTRODUCTION: Hepatocellular carcinoma (HCC) is a serious complication of chronic liver disease. Lenvatinib is an oral multikinase inhibitor registered to treat advanced HCC. This study evaluates the real-world experience with lenvatinib in Australia. METHODS: We conducted a retrospective cohort study of patients treated with lenvatinib for advanced HCC between July 2018 and November 2020 at 11 Australian tertiary care hospitals. Baseline demographic data, tumor characteristics, lenvatinib dosing, adverse events (AEs) and clinical outcomes were collected. Overall survival (OS) was the primary outcome. Progression free survival (PFS) and AEs were secondary outcomes. RESULTS: A total of 155 patients were included and were predominantly male (90.7%) with a median age of 65 years (interquartile range [IQR]: 59-75). The main causes of chronic liver disease were hepatitis C infection (40.0%) and alcohol-related liver disease (34.2). Median OS and PFS were 7.7 (95% confidence interval [CI]: 5.8-14.0) and 5.3 months (95% CI: 2.8-9.2) respectively. Multivariate predictors of mortality were the need for dose reduction due to AEs (Hazard ratio [HR] 0.41, p < 0.01), new or worsening hypertension (HR 0.42, p < 0.01), diarrhoea (HR 0.47, p = 0.04) and more advanced BCLC stage (HR 2.50, p = 0.04). Multivariable predictors of disease progression were higher Child-Pugh score (HR 1.25, p = 0.04), the need for a dose reduction (HR 0.45, p < 0.01) and age (HR 0.96, p < 0.001). AEs occurred in 83.9% of patients with most being mild (71.6%). CONCLUSIONS: Lenvatinib remains safe and effective in real-world use. Treatment emergent diarrhoea and hypertension, and the need for dose reduction appear to predict better OS.

Direction of visual apparent motion driven solely by timing of a static sound.

In temporal ventriloquism, auditory events can illusorily attract perceived timing of a visual onset [1-3]. We investigated whether timing of a static sound can also influence spatio-temporal processing of visual apparent motion, induced here by visual bars alternating between opposite hemifields. Perceived direction typically depends on the relative interval in timing between visual left-right and right-left flashes (e.g., rightwards motion dominating when left-to-right interflash intervals are shortest [4]). In our new multisensory condition, interflash intervals were equal, but auditory beeps could slightly lag the right flash, yet slightly lead the left flash, or vice versa. This auditory timing strongly influenced perceived visual motion direction, despite providing no spatial auditory motion signal whatsoever. Moreover, prolonged adaptation to such auditorily driven apparent motion produced a robust visual motion aftereffect in the opposite direction, when measured in subsequent silence. Control experiments argued against accounts in terms of possible auditory grouping, or possible attention capture. We suggest that the motion arises because the sounds change perceived visual timing, as we separately confirmed. Our results provide a new demonstration of multisensory influences on sensory-specific perception [5], with timing of a static sound influencing spatio-temporal processing of visual motion direction.

Looming sounds enhance orientation sensitivity for visual stimuli on the same side as such sounds.

Several recent multisensory studies show that sounds can influence visual processing. Some visual judgments can be enhanced for visual stimuli near a sound occurring around the same time. A recent TMS study (Romei et al. 2009) indicates looming sounds might influence visual cortex particularly strongly. But unlike most previous behavioral studies of possible audio-visual exogenous effects, TMS phosphene thresholds rather than judgments of external visual stimuli were measured. Moreover, the visual hemifield assessed relative to the hemifield of the sound was not varied. Here, we compared the impact of looming sounds to receding or "static" sounds, using auditory stimuli adapted from Romei et al. (2009), but now assessing any influence on visual orientation discrimination for Gabor patches (well-known to involve early visual cortex) when appearing in the same hemifield as the sound or on the opposite side. The looming sounds that were effective in Romei et al. (2009) enhanced visual orientation sensitivity (d') here on the side of the sound, but not for the opposite hemifield. This crossmodal, spatially specific effect was stronger for looming than receding or static sounds. Similarly to Romei et al. (2009), the differential effect for looming sounds was eliminated when using white noise rather than structured sounds. Our new results show that looming structured sounds can specifically benefit visual orientation sensitivity in the hemifield of the sound, even when the sound provides no information about visual orientation itself.

The role of right and left parietal lobes in the conceptual processing of numbers.

Neuropsychological and functional imaging studies have associated the conceptual processing of numbers with bilateral parietal regions (including intraparietal sulcus). However, the processes driving these effects remain unclear because both left and right posterior parietal regions are activated by many other conceptual, perceptual, attention, and response-selection processes. To dissociate parietal activation that is number-selective from parietal activation related to other stimulus or response-selection processes, we used fMRI to compare numbers and object names during exactly the same conceptual and perceptual tasks while factoring out activations correlating with response times. We found that right parietal activation was higher for conceptual decisions on numbers relative to the same tasks on object names, even when response time effects were fully factored out. In contrast, left parietal activation for numbers was equally involved in conceptual processing of object names. We suggest that left parietal activation for numbers reflects a range of processes, including the retrieval of learnt facts that are also involved in conceptual decisions on object names. In contrast, number selectivity in right parietal cortex reflects processes that are more involved in conceptual decisions on numbers than object names. Our results generate a new set of hypotheses that have implications for the design of future behavioral and functional imaging studies of patients with left and right parietal damage.

Hearing what you see: Distinct excitatory and disinhibitory mechanisms contribute to visually-evoked auditory sensations.

Visual motion or flashing lights can evoke auditory sensations in some people. This large-scale internet study aimed to validate a combined subjective/objective test of the genuineness of this putative form of synaesthesia (visually-evoked auditory response, vEAR). Correlations were measured between each individual's ratings of the vividness of auditory sensations evoked by a series of looping videos, and measurement of the videos' physical low-level motion energy, calculated using Adelson and Bergen's (1985) computational model of low-level visual motion processing. The strength of this association for each individual provided a test of how strongly subjective vEAR was driven by objective motion energy ('ME-sensitivity'). A second aim was to infer whether vEAR depends on cortical excitation and/or disinhibition of early visual and/or auditory brain areas. To achieve this, correlations were measured between the above vEAR measures and visual contrast surround-suppression, which is thought to index lateral inhibition in the early visual system. As predicted by a disinhibition account of vEAR, video ratings were overall higher in individuals showing weaker surround-suppression. Interestingly, surround-suppression and ME-sensitivity did not correlate. Additionally, both surround-suppression and ME-sensitivity each independently predicted different clusters of trait measures selected for their possible association with cortical excitability and/or disinhibition: Surround-suppression was associated with vEAR self-ratings and auditory-evoked visual phosphenes, while ME-sensitivity was independently associated with ratings of other traits including susceptibility to migraine and pattern glare. Altogether, these results suggest there are two independent mechanisms underlying vEAR and its associated traits, based putatively on cortical disinhibition versus excitability.

Concurrent TMS-fMRI and psychophysics reveal frontal influences on human retinotopic visual cortex.

BACKGROUND: Regions in human frontal cortex may have modulatory top-down influences on retinotopic visual cortex, but to date neuroimaging methods have only been able to provide indirect evidence for such functional interactions between remote but interconnected brain regions. Here we combined transcranial magnetic stimulation (TMS) with concurrent functional magnetic resonance imaging (fMRI), plus psychophysics, to show that stimulation of the right human frontal eye-field (FEF) produced a characteristic topographic pattern of activity changes in retinotopic visual areas V1-V4, with functional consequences for visual perception. RESULTS: FEF TMS led to activity increases for retinotopic representations of the peripheral visual field, but to activity decreases for the central field, in areas V1-V4. These frontal influences on visual cortex occurred in a top-down manner, independently of visual input. TMS of a control site (vertex) did not elicit such visual modulations, and saccades, blinks, or pupil dilation could not account for our results. Finally, the effects of FEF TMS on activity in retinotopic visual cortex led to a behavioral prediction that we confirmed psychophysically by showing that TMS of the frontal site (again compared with vertex) enhanced perceived contrast for peripheral relative to central visual stimuli. CONCLUSIONS: Our results provide causal evidence that circuits originating in the human FEF can modulate activity in retinotopic visual cortex, in a manner that differentiates the central and peripheral visual field, with functional consequences for perception. More generally, our study illustrates how the new approach of concurrent TMS-fMRI can now reveal causal interactions between remote but interconnected areas of the human brain.

Wohlfahrtiimonas chitiniclastica Bloodstream Infection Due to a Maggot-infested Wound in a 54-Year-Old Male.

We report a case of Wohlfahrtiimonas chitiniclastica bacteremia and sepsis, in the setting of lower limb wounds with maggot infestation. This is the first documented infection by this organism in the Australasia/Pacific region, identified using matrix-assisted laser desorption ionization-time of flight mass spectrometry and 16S ribosomal ribonucleic acid sequencing. Clinicians should be aware of this emerging pathogen.

Voluntary control of long-range motion integration via selective attention to context.

Ambiguous stimuli can look different in different contexts. Here we demonstrate that subjective appearance of motion depends not only on current visual input but critically on which aspects of the context are attended. Observers fixated a central oblique test grating flanked by two pairs of orthogonally oriented context gratings arranged in a cross (+) configuration. Each context pair could induce the test stimulus to appear to switch from diagonal motion to either horizontal motion (due to one context pair) or vertical motion (due to the other). Spontaneous switching between these motion states was observed under free viewing. We demonstrate that observers can voluntarily select between specific states when cued to attend selectively to one or other context pair in an alternating manner. Concurrent reports of perceived test stimulus motion depended specifically on which context was currently attended, indicating a high degree of "cued-control" over subjective state via attended context. Further experiments established that the perception was nevertheless still constrained by physical stimulus context as well as by attentional selection among that context. Moreover, the attentional control evident here did not seem reducible solely to local contrast gain modulation of the attended vs. ignored context elements. Selective attention to different parts of the context can evidently resolve the ambiguity of the test grating, with integration arising selectively for those components that are jointly attended. Such selective integration can result in substantial voluntarily controlled changes in phenomenal perception.

Correlation of individual differences in audiovisual asynchrony across stimuli and tasks: New constraints on temporal renormalization theory.

Sight and sound are out of synch in different people by different amounts for different tasks. But surprisingly, different concurrent measures of perceptual asynchrony correlate negatively (Freeman et al., 2013). Thus, if vision subjectively leads audition in one individual, the same individual might show a visual lag in other measures of audiovisual integration (e.g., McGurk illusion, Stream-Bounce illusion). This curious negative correlation was first observed between explicit temporal order judgments and implicit phoneme identification tasks, performed concurrently as a dual task, using incongruent McGurk stimuli. Here we used a new set of explicit and implicit tasks and congruent stimuli, to test whether this negative correlation persists across testing sessions, and whether it might be an artifact of using specific incongruent stimuli. None of these manipulations eliminated the negative correlation between explicit and implicit measures. This supports the generalizability and validity of the phenomenon, and offers new theoretical insights into its explanation. Our previously proposed "temporal renormalization" theory assumes that the timings of sensory events registered within the brain's different multimodal subnetworks are each perceived relative to a representation of the typical average timing of such events across the wider network. Our new data suggest that this representation is stable and generic, rather than dependent on specific stimuli or task contexts, and that it may be acquired through experience with a variety of simultaneous stimuli. Our results also add further evidence that speech comprehension may be improved in some individuals by artificially delaying voices relative to lip-movements. (PsycINFO Database Record

Sounds from seeing silent motion: Who hears them, and what looks loudest?

Some people hear what they see: car indicator lights, flashing neon shop signs, and people's movements as they walk may all trigger an auditory sensation, which we call the visual-evoked auditory response (vEAR or 'visual ear'). We have conducted the first large-scale online survey (N > 4000) of this little-known phenomenon. We analysed the prevalence of vEAR, what induces it, and what other traits are associated with it. We assessed prevalence by asking whether respondents had previously experienced vEAR. Participants then rated silent videos for vividness of evoked auditory sensations, and answered additional trait questions. Prevalence appeared higher relative to other typical synaesthesias. Prior awareness and video ratings were associated with greater frequency of other synaesthesias, including flashes evoked by sounds, and musical imagery. Higher-rated videos often depicted meaningful events that predicted sounds (e.g., collisions). However, even videos containing abstract flickering or moving patterns could also elicit higher ratings, despite having no predictable association with sounds. Such videos had higher levels of raw 'motion energy' (ME), which we quantified using a simple computational model of motion processing in early visual cortex. Critically, only respondents reporting prior awareness of vEAR tended to show a positive correlation between video ratings and ME. This specific sensitivity to ME suggests that in vEAR, signals from visual motion processing may affect audition relatively directly without requiring higher-level interpretative processes. Our other findings challenge the popular assumption that individuals with synaesthesia are rare and have ideosyncratic patterns of brain hyper-connectivity. Instead, our findings of apparently high prevalence and broad associations with other synaesthesias and traits are jointly consistent with a common dependence on normal variations in physiological mechanisms of disinhibition or excitability of sensory brain areas and their functional connectivity. The prevalence of vEAR makes it easier to test such hypotheses further, and makes the results more relevant to understanding not only synaesthetic anomalies but also normal perception.