Is colchicine prophylaxis required with start-low go-slow allopurinol dose escalation in gout? A non-inferiority randomised double-blind placebo-controlled trial.

OBJECTIVES: To determine whether placebo is non-inferior to low-dose colchicine for reducing gout flares during the first 6 months of allopurinol using the 'start-low go-slow' dose approach. METHODS: A 12-month double-blind, placebo-controlled non-inferiority trial was undertaken. Adults with at least one gout flare in the preceding 6 months, fulfilling the American College of Rheumatology (ACR) recommendations for starting urate-lowering therapy and serum urate ≥0.36 mmol/L were recruited. Participants were randomised 1:1 to colchicine 0.5 mg daily or placebo for the first 6 months. All participants commenced allopurinol, increasing monthly to achieve target urate <0.36 mmol/L. The primary efficacy outcome was the mean number of gout flares/month between 0 and 6 months, with a prespecified non-inferiority margin of 0.12 gout flares/month. The primary safety outcome was adverse events over the first 6 months. RESULTS: Two hundred participants were randomised. The mean (95% CI) number of gout flares/month between baseline and month 6 was 0.61 (0.47 to 0.74) in the placebo group compared with 0.35 (0.22 to 0.49) in the colchicine group, mean difference 0.25 (0.07 to 0.44), non-inferiority p=0.92. There was no difference in the mean number of gout flares/month between randomised groups over the 12-month period (p=0.68). There were 11 serious adverse events in 7 participants receiving colchicine and 3 in 2 receiving placebo. CONCLUSIONS: Placebo is not non-inferior to colchicine in prevention of gout flares in the first 6 months of starting allopurinol using the 'start-low go-slow' strategy. After stopping colchicine, gout flares rise with no difference in the mean number of gout flares/month between groups over a 12-month period. TRIAL REGISTRATION NUMBER: ACTRN 12618001179224.

Individual conscious and unconscious perception of emotion: Theory, methodology and applications.

In this manuscript we review a seminal debate related to subliminality and concerning the relationship of consciousness, unconsciousness, and perception. We present the methodological implementations that contemporary psychology introduced to explore this relationship, such as the application of unbiased self-report metrics and Bayesian analyses for assessing detection and discrimination. We present evidence concerning an unaddressed issue, namely, that different participants and stimulus types require different thresholds for subliminal presentation. We proceed to a step-by-step experimental illustration of a method involving individual thresholds for the presentation of masked emotional faces. We show that individual thresholds provide Bayesian evidence for null responses to the presented faces. Conversely, we show in the same database that when applying established but biased non-individual criteria for subliminality physiological changes occur and relate - correctly, and most importantly incorrectly - to perception concerning the emotional type, and the valence and intensity of a presented masked emotional face.

"There Is No (Where a) Face Like Home": Recognition and Appraisal Responses to Masked Facial Dialects of Emotion in Four Different National Cultures.

The theory of universal emotions suggests that certain emotions such as fear, anger, disgust, sadness, surprise and happiness can be encountered cross-culturally. These emotions are expressed using specific facial movements that enable human communication. More recently, theoretical and empirical models have been used to propose that universal emotions could be expressed via discretely different facial movements in different cultures due to the non-convergent social evolution that takes place in different geographical areas. This has prompted the consideration that own-culture emotional faces have distinct evolutionary important sociobiological value and can be processed automatically, and without conscious awareness. In this paper, we tested this hypothesis using backward masking. We showed, in two different experiments per country of origin, to participants in Britain, Chile, New Zealand and Singapore, backward masked own and other-culture emotional faces. We assessed detection and recognition performance, and self-reports for emotionality and familiarity. We presented thorough cross-cultural experimental evidence that when using Bayesian assessment of non-parametric receiver operating characteristics and hit-versus-miss detection and recognition response analyses, masked faces showing own cultural dialects of emotion were rated higher for emotionality and familiarity compared to other-culture emotional faces and that this effect involved conscious awareness.

The effect of a secondary task on drivers' gap acceptance and situational awareness at junctions.

The current studies explored the roles of the visuospatial and phonological working memory subsystems on drivers' gap acceptance and memory for approaching vehicles at junctions. Drivers' behaviour was measured in a high-fidelity driving simulator when at a junction, with, and without a visuospatial or phonological load. When asked to judge when to advance across the junction, gap acceptance thresholds, memory for vehicles and eye movements were not different when there was a secondary task compared to control. However, drivers' secondary task performance was more impaired in the visuospatial than phonological domain. These findings suggest that drivers were able to accept impairment in the secondary task while maintaining appropriate safety margins and situational awareness. These findings can inform the development of in-car technologies, improving the safety of road users at junctions. Practitioner summary: Despite research indicating that concurrent performance on working memory tasks impairs driving, a matched visuospatial or phonological memory load did not change drivers' gap acceptance or situational awareness at junctions. Drivers displayed appropriate compensatory behaviour by prioritising the driving task over the visuospatial secondary task. Abbreviations: ROW: right of way; RIG: random time interval generation.

Lack of effect of tart cherry concentrate dose on serum urate in people with gout.

OBJECTIVES: Cherry concentrate has been suggested to reduce serum urate (SU) and gout flares. The aims of this study were to determine the magnitude of the effect of tart cherry concentrate on SU in people with gout, the most effective dose of tart cherry concentrate for lowering SU, and adverse effects. METHODS: Fifty people with gout and SU > 0.36 mmol/l were recruited. Half were on allopurinol and half were on no urate-lowering therapy. Participants were randomized to receive tart cherry juice concentrate: placebo, 7.5 ml, 15 ml, 22.5 ml or 30 ml twice daily for 28 days. Blood samples were taken at baseline, then at 1, 3 and 5 h post cherry and then on days 1, 3, 7, 14, 21 and 28. The area under the curve for SU was calculated over the 28-day study period. RESULTS: Cherry concentrate dose had no significant effect on reduction in SU area under the curve, urine urate excretion, change in urinary anthocyanin between day 0 and day 28, or frequency of gout flares over the 28-day study period (P = 0.76). There were 24 reported adverse events, with only one (hyperglycaemia) considered possibly to be related to cherry concentrate. Allopurinol use did not modify the effect of cherry on SU or urine urate excretion. CONCLUSION: Tart cherry concentrate had no effect on SU or urine urate excretion. If there is an effect of cherry concentrate on gout flares over a longer time period, it is not likely to be mediated by reduction in SU. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=368887, ANZCTR 12615000741583).

"I can see you; I can feel it; and vice-versa": consciousness and its relation to emotional physiology.

In this paper, we explore whether masked emotional faces can elicit changes in physiology without awareness. We also explore whether emotional miss-discrimination involves the physiological correlates associated with the perception of an emotion. We adjust the discrimination threshold of presentation per participant and stimulus type to chance-level performance using hit rates and receiver-operating characteristics (ROC). We assess subliminality using an adjusted Bayesian criterion for awareness (A = .167). We measure skin-conductance, heart-rate, facial-emotional and engagement-task force-pressure responses to masked fearful, angry, happy, sad and neutral faces. We report that when faces were subjectively adjusted using unbiased ROC criteria for awareness, we found non-significant differences between emotions and Bayesian evidence for null responses. Hit-rate adjustments were associated with physiological changes for hits and misses for fearful, angry and happy faces. For misses for discrimination performance, participants could correctly appraise the valence and arousal of the presented face. Miss-discrimination for seeing a fearful face when presented with innocuous cues was also associated with high arousal responses. These findings suggest that if physiological arousal is elicited during the presentation of masked emotion, conscious assessment is, upon explicit post-trial inquiry, involved in the evaluation of the elicited emotion and the emotional elicitor.

Anger and hostility: are they different? An analytical exploration of facial-expressive differences, and physiological and facial-emotional responses.

Previous research has proposed the exploratory hypotheses that hostility could differ from anger in the sense that it involves higher possibility for inflicting physical harm while anger could involve higher frustration and stress compared to hostility. Based on these hypotheses we tested whether there are expressive differences and discrete emotional responses between angry and hostile faces. We used participant assessment to preselect faces. We found that using action unit analysis, faces labelled as angry and hostile revealed differences in expressive characteristics and that hostile faces were - as predicted - rated by the participants higher for the intent to inflict physical harm. Subsequently, we presented these faces, as well as fearful, sad and neutral faces, overtly and using masking and measured skin-conductance, heart-rate and facial-emotional responses. We found that in both conditions faces expressing hostility led to higher physiological arousal. Detection of a face was a necessary condition for physiological responses to angry and hostile expressions when faces were presented using masking. We found that during overt presentations, hostility elicited fearful facial-emotional responses while anger elicited mirroring responses. Our findings suggest that hostility is a fear-eliciting emotion related to anger with distinguishable expressive characteristics.

The unconscious mind: From classical theoretical controversy to controversial contemporary research and a practical illustration of the "error of our ways".

In this manuscript, the authors present an overview of the history, an account of the theoretical and methodological controversy, and an illustration of contemporary and revised methods for the exploration of unconscious processing. Initially we discuss historical approaches relating to unconsciousness that are, arguably, defamed and considered extraneous to contemporary psychological research. We support that awareness of the history of the current subject is pedagogically essential to understand the transition to empirical research and the reasons for which the current area is still so contentious among contemporary psychologists. We proceed to explore the current experimental canon. Contemporary theoretical and methodological issues relating to unconscious processing are discussed in detail and key issues and key advancements in contemporary research are presented. Developments that have, in recent years, being suggested to contribute to a possibly reliable method for the assessment of unconscious processing are practically - methodologically and statistically - illustrated using easy-to-follow steps applied in real experimental data. Mindful of our own place in the long history of this topic, we conclude the manuscript with suggestions concerning the future of the current area.

Serum urate levels and therapy in adults treated with long-term dialysis: a retrospective cross-sectional study.

BACKGROUND: The management of gout in chronic kidney disease and end-stage renal disease is challenging and remains controversial. There are limited data on the use of urate-lowering therapy in people receiving dialysis. AIM: To estimate the point prevalence of gout, gout treatment and achievement of target serum urate (SU) among adults treated with long-term dialysis. METHODS: Three secular cohorts of adults receiving dialysis for at least 90 days on 1 February 2017, 1 January 2016 and 1 January 2015 were identified. Medical records were reviewed for SU concentrations. Results were compared between haemodialysis (HD) and peritoneal dialysis (PD), and participants prescribed and not prescribed urate-lowering therapy. The percentage reduction in SU 24- and 48-h post-HD was estimated based on data from a previous study. SU concentrations were then used to estimate the percentage time the SU was <0.36 mmol/L using linear interpolation. RESULTS: Of 216 dialysis patients, 61 (point prevalence 28.2%, 95% confidence interval 22.35-34.8%) had a diagnosis of gout. The mean (SD) age among those with gout was 61 years (14.4), 46 (75.4%) were men and 18 (31.1%) identified as Maori or Pacific Island. Forty-two (68.9%) were prescribed allopurinol (mean (SD) dose 116.0 ± 66.9 mg/day). 46% had a predialysis SU ≤0.36 mmol/L on less than 25% of occasions and 23% were below target on 76-100% of occasions. SU was below target 41% of time, with no statistically significant difference in those on HD or PD (P = 0.39), and those prescribed or not prescribed allopurinol (P = 0.55). CONCLUSIONS: Gout is experienced by approximately one in four adults treated with dialysis and two-thirds are prescribed allopurinol. A minority have SU at a target sufficient to prevent gout despite allopurinol and HD. A treat to target SU should be considered in those with SU above target.

Beauty Is in the Eye of the Beholder: The Appraisal of Facial Attractiveness and Its Relation to Conscious Awareness.

Previous research suggests that facial attractiveness relies on features such as symmetry, averageness and above-average sexual dimorphic characteristics. Due to the evolutionary and sociobiological value of these characteristics, it has been suggested that attractiveness can be processed in the absence of conscious awareness. This raises the possibility that attractiveness can also be appraised without conscious awareness. In this study, we addressed this hypothesis. We presented neutral and emotional faces that were rated high, medium and low for attractiveness during a pilot experimental stage. We presented these faces for 33.33 ms with backwards masking to a black and white pattern for 116.67 ms and measured face-detection and emotion-discrimination performance, and attractiveness ratings. We found that high-attractiveness faces were detected and discriminated more accurately and rated higher for attractiveness compared with other appearance types. A Bayesian analysis of signal detection performance indicated that faces were not processed significantly at-chance. Further assessment revealed that correct detection (hits) of a presented face was a necessary condition for reporting higher ratings for high-attractiveness faces. These findings suggest that the appraisal of attractiveness requires conscious awareness.

A Pilot Randomized Controlled Double-Blind Trial of High- Versus Low-Dose Weekly Folic Acid in People With Rheumatoid Arthritis Receiving Methotrexate.

BACKGROUND/OBJECTIVE: The aim of this study was to determine whether reducing the dose of supplemental folic acid used in conjunction with methotrexate (MTX) therapy in people with active rheumatoid arthritis (RA) improved disease control and/or increased MTX-related adverse effects. METHODS: A randomized double-blind randomized controlled trial comparing 5 mg/wk and 0.8 mg/wk folic acid was undertaken. Rheumatoid arthritis patients on MTX for 3 months or more at a stable dose for 1 month or more were recruited. All participants had DAS28 of 3.2 or greater or required a change in therapy determined by the treating clinician. Disease activity, full blood count, liver function tests, red blood cell (RBC) folate, and RBC MTX polyglutamates were assessed at weeks 0, 4, 8, 16, and 24 along with reports of adverse events. RESULTS: Forty participants were recruited. The mean (SD) change in RBC folate between week 0 and 24 was +87.9 (57.4) nmol/L in the high-dose group and -113.3 (65.7) nmol/L in the low-dose group (p < 0.05). There was no significant difference in the change in DAS28 between the high- and low-dose groups at 24 weeks (-0.13 [95% confidence interval, -0.69 to 0.43] vs -0.25 [-0.87 to 0.37], respectively [p = 0.78]). There was no significant difference in MTX-related adverse effects between the 2 groups. CONCLUSIONS: A reduction in RBC folate secondary to reduction in folic acid dose was not associated with a change in RA disease activity or MTX-related adverse effects. The prevention of MTX-related adverse effects remains the primary reason for coprescribing folic acid with MTX. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR12610000739011).

Can we predict inadequate response to allopurinol dose escalation? Analysis of a randomised controlled trial.

Objectives: To determine factors that predict inadequate serum urate (SU) lowering response in a randomized controlled trial of allopurinol dose escalation (DE) in gout. Methods: Participants undergoing allopurinol DE were classified as: complete response (CR)-reached target SU at month 9 and 12 of the DE phase or if still dose escalating at month 9 reached target SU by month 12; partial response (PR)-reached target at some stage but not fulfilling criteria for CR; or inadequate response (IR)-did not reach target SU at any time. Results: IR was uncommon, occurring in 13/150 (8.7%), compared with 82 (54.7%) CR, and 55 (36.6%) PR. Mean (s.e.m.) SU was higher at the end of the 12-month DE in IR compared with both CR and PR groups; 7.6 (0.31) vs 5.01 (0.06) and 5.97 (0.17) mg/dl respectively (P < 0.001). In univariate analysis, compete responders tended to be older, be receiving less allopurinol, have longer gout duration and were more likely to be New Zealand (NZ) European ethnicity, compared with IR+PR. Using multi-variate logistic regression analysis, only longer duration of gout and NZ European ethnicity remained significant independent predictors of CR. Baseline SU ⩾ 8 mg/dl had a sensitivity of 69.2% and specificity of 85.1% in predicting IR. The odds ratio for an IR if baseline SU was ⩾8 mg/dl was 11.7 (95% CI 3.3, 41.2). Conclusion: A minority of people with gout never reach target SU when allopurinol dose is increased in a treat-to-target manner. Approximately one-third of those with SU ⩾ 8mg/dl despite allopurinol ⩾300mg/d have an IR to DE. Trial registration: Australian New Zealand Clinical Trails Registry, https://www.anzctr.org.au, ACTRN12611000845932.

Target meta-awareness is a necessary condition for physiological responses to masked emotional faces: Evidence from combined skin conductance and heart rate assessment.

Much heated debate surrounds the extent to which we can process emotional stimuli without awareness. In particular the extent to which masked emotional faces can elicit changes in physiology measurements, such as heart rate and skin conductance responses, has produced controversial findings. In the present study, we aimed to determine whether briefly presented faces can elicit physiological changes and, specifically, whether this is due to unconscious processing. We measured and adjusted for individual differences in the detection threshold using both receiver operating characteristics and hit rates. For this we also used a strict Bayesian assessment of participant thresholds. We then measured physiological responses to threshold adjusted emotional faces and for hits, misses and post-binary subdivisions of target meta-awareness. Our findings based on receiver operating characteristics revealed that, when faces were successfully masked there were no significant physiological differences in response to stimuli with different emotional connotations. In contrast, when targets were masked based on hit rates we did find physiological responses to masked emotional faces. With further analysis we found that this effect was specific to correct detection of angry and fearful faces and that increases in experienced arousal were associated with higher confidence ratings for correct detection of these stimuli. Collectively, our results do not support the notion of unconscious processing when using markers of physiological processes. Rather they suggest that target meta-awareness is a necessary condition for - and possibly determined by - physiological changes in response to masked emotional faces.

Skin Conductance Responses to Masked Emotional Faces Are Modulated by Hit Rate but Not Signal Detection Theory Adjustments for Subjective Differences in the Detection Threshold.

The biological preparedness model suggests that survival-related visual cues elicit physiological changes without awareness to enable us to respond to our environment. Previous studies have reported some evidence for this effect. In the current article, we argue that this evidence is subject to methodological confounds. These include the use of a universal masked presentation threshold, the employment of hit rates (HRs) to measure meta-awareness, and the assertion of overall guess-level target detection using nonsignificance. In the current report, we address these issues and test whether masked emotional faces can elicit changes in physiology. We present participants with subjectively adjusted masked angry, fearful, happy, and neutral faces using HRs and signal detection theory. We assess detection performance using a strict Bayesian criterion for meta-awareness. Our findings reveal that HR adjustments in the detection threshold allow higher skin conductance responses to happy, fearful, and angry faces, but that this effect could not be reported by the same participants when the adjustments were made using signal detection measures. Combined these findings suggest that very brief biologically relevant stimuli can elicit physiological changes but cast doubt to the extent that this effect can occur in response to truly unconscious emotional faces.

Drivers' Visual Search Behavior Toward Vulnerable Road Users at Junctions as a Function of Cycling Experience.

OBJECTIVES: The current study investigated the behavior and visual attention of two groups of drivers with differing pedal cycling experience (pedal cyclists and nonpedal cyclists) towards vulnerable road users at junctions in a driving simulator. BACKGROUND: Pedal cyclists and motorcyclists are involved in a disproportionate number of crashes given the distance they travel, with a high proportion of these crashes occurring at junctions. Many studies have found that car drivers who also hold a motorcycle license have increased awareness towards motorcycles. METHODS: The task involved approaching a T-junction and turning right when it was deemed to be safe. In Study 1, the junction was controlled by a give way sign, and in Study 2, the junction was controlled by a stop sign. Each T-junction contained a target vehicle (car, motorcycle, or pedal cycle), approaching from a near, medium, or far distance from the junction. RESULTS: Participants did not look at pedal cycles approaching from a far distance for as long as they looked at approaching motorcycles and cars, despite all vehicles travelling at identical speeds. No differences were found between pedal cyclists and nonpedal cyclists on any visual attention measures, indicating that pedal cycling experience was not associated with differences in drivers' attention toward pedal cycles. CONCLUSIONS: Findings have implications for road safety, demonstrating subtle differences in drivers' everyday visual attention toward differing vehicle types. APPLICATIONS: This research has the potential to inform the development of in-car technical assistive systems, improving the safety of vulnerable road users at junctions.

Negatives and Positives: Contaminants and Other Stressors in Aquatic Ecosystems.

Published research is reviewed to provide examples of both positive and negative interactions of contaminants and: climate change; habitat change; invasive and introduced species; and, eutrophication including harmful algal blooms. None of these stressor interactions results solely in negative effects. Research must shift from examining contaminants or other stressors in isolation to considering potential positive and negative effects of interactions, with the ultimate goal of providing the necessary information for the effective management of ecosystem services.

Allopurinol dose escalation to achieve serum urate below 6 mg/dL: an open-label extension study.

OBJECTIVES: To determine the long-term safety and efficacy of allopurinol dose escalation (DE) to achieve target serum urate (SU) in gout. METHODS: People, including those with chronic kidney disease, who completed the first 12 months of a randomised controlled trial continued into a 12-month extension study. Participants randomised to continue current dose for the first 12 months began allopurinol DE at month 12 if SU was ≥6 mg/dL (control/DE). Immediate DE participants who achieved target SU maintained allopurinol dose (DE/DE). The primary endpoints were reduction in SU and adverse events (AEs) at month 24. RESULTS: The mean (SE) change in SU from month 12 to 24 was -1.1 (0.2) mg/dL in control/DE and 0.1 (0.2) mg/dL in DE/DE group (p<0.001). There was a significant reduction in the percentage of individuals having a gout flare in the month prior to months 12 and 24 compared with baseline in both groups and in mean tophus size over 24 months, but no difference between randomised groups. There were similar numbers of AEs and serious adverse events between groups. CONCLUSIONS: The majority of people with gout tolerate higher than creatinine clearance-based allopurinol dose and achieve and maintain target SU. Slow allopurinol DE may be appropriate in clinical practice even in those with kidney impairment. TRIAL REGISTRATION NUMBER: ACTRN12611000845932.

A randomised controlled trial of the efficacy and safety of allopurinol dose escalation to achieve target serum urate in people with gout.

OBJECTIVES: To determine the efficacy and safety of allopurinol dose escalation using a treat-to-target serum urate (SU) approach. METHODS: A randomised, controlled, parallel-group, comparative clinical trial was undertaken. People with gout receiving at least creatinine clearance (CrCL)-based allopurinol dose for ≥1 month and SU ≥6 mg/dL were recruited. Participants were randomised to continue current dose (control) or allopurinol dose escalation for 12 months. In the dose escalation group, allopurinol was increased monthly until SU was <6 mg/dL. The primary endpoints were reduction in SU and adverse events (AEs). RESULTS: 183 participants (93 control, 90 dose escalation) were recruited. At baseline, mean (SD) urate was 7.15 (1.6) mg/dL and allopurinol dose 269 mg/day. 52% had CrCL<60 mL/min. Mean changes in SU at the final visit were -0.34 mg/dL in the control group and -1.5 mg/dL in the dose escalation group (p<0.001) with a mean difference of 1.2 mg/dL (95% CI 0.67 to 1.5, p<0.001). At month 12, 32% of controls and 69% in the dose escalation had SU <6 mg/dL. There were 43 serious AEs in 25 controls and 35 events in 22 dose escalation participants. Only one was considered probably related to allopurinol. Five control and five dose escalation participants died; none was considered allopurinol related. Mild elevations in LFTs were common in both groups, a few moderate increases in gamma glutamyl transferase (GGT) were noted. There was no difference in renal function changes between randomised groups. CONCLUSIONS: Higher than CrCL-based doses of allopurinol can effectively lower SU to treatment target in most people with gout. Allopurinol dose escalation is well tolerated. TRIAL REGISTRATION NUMBER: ANZCTR12611000845932; Results.

A population pharmacokinetic model to predict oxypurinol exposure in patients on haemodialysis.

PURPOSE: The aims of this study were to characterise the population pharmacokinetics of oxypurinol in patients receiving haemodialysis and to compare oxypurinol exposure in dialysis and non-dialysis patients. METHODS: Oxypurinol plasma concentrations from 6 gout people receiving haemodialysis and 19 people with gout not receiving dialysis were used to develop a population pharmacokinetic model in NONMEM. Deterministic simulations were used to predict the steady-state area under the oxypurinol plasma concentration time curve over 1 week (AUC7days). RESULTS: The pharmacokinetics of oxypurinol were best described by a one-compartment model with a separate parameter for dialytic clearance. Allopurinol 100 mg daily produced an AUC7days of 279 µmol/L h in dialysis patients, a value 50-75 % lower than the AUC7days predicted for patients with normal renal function taking 200 to 400 mg daily (427-855 µmol/L h). Dosing pre-dialysis resulted in about a 25-35 % reduction in exposure compared to post-dialysis. CONCLUSIONS: Oxypurinol is efficiently removed by dialysis. The population dialytic and total (non-dialytic) clearance of oxypurinol were found to be 8.23 and 1.23 L/h, standardised to a fat-free mass of 70 kg and creatinine clearance of 6 L/h, respectively. Our results suggest that if the combination of low-dose allopurinol and haemodialysis does not result in sustained urate lowering below treatment targets (serum urate ≤0.36 mmol/L), then allopurinol doses may be increased to optimise oxypurinol exposure.

Total Suspended Solids Effects on Freshwater Lake Biota Other than Fish.

Protective benchmarks for the effects of total suspended solids (TSS) on freshwater aquatic biota primarily focus on fish; whether these benchmarks will also protect their prey or co-existing lower trophic level aquatic biota was uncertain. We conducted an extensive literature review of TSS effects on those organisms comprising the food webs upon which fish living in lakes depend: phytoplankton, zooplankton, periphyton, and benthic invertebrates. The available literature indicates that TSS benchmarks that protect sensitive life stages of lake fish will also protect their supporting food webs; in other words, the function of lake aquatic communities will be protected and maintained.