Mixed representations of sound and action in the auditory midbrain.

Linking sensory input and its consequences is a fundamental brain operation. Accordingly, neural activity of neo-cortical and limbic systems often reflects dynamic combinations of sensory and behaviorally relevant variables, and these "mixed representations" are suggested to be important for perception, learning, and plasticity. However, the extent to which such integrative computations might occur in brain regions upstream of the forebrain is less clear. Here, we conduct cellular-resolution 2-photon Ca2+ imaging in the superficial "shell" layers of the inferior colliculus (IC), as head-fixed mice of either sex perform a reward-based psychometric auditory task. We find that the activity of individual shell IC neurons jointly reflects auditory cues and mice's actions, such that trajectories of neural population activity diverge depending on mice's behavioral choice. Consequently, simple classifier models trained on shell IC neuron activity can predict trial-by-trial outcomes, even when training data are restricted to neural activity occurring prior to mice's instrumental actions. Thus in behaving animals, auditory midbrain neurons transmit a population code that reflects a joint representation of sound and action.

Hearing Impairment and Incident Frailty in Later Life: The Health in Men Study (HIMS).

OBJECTIVES: This study is designed to determine if hearing loss is associated with increased risk of frailty in later life. DESIGN: A prospective cohort study. SETTING AND PARTICIPANTS: We retrieved data of a community sample of men aged 70 years and above living in the metropolitan region of Perth, Western Australia. 3,285 participants who were free of frailty at the beginning of the study were followed for up to 17 years. Data were retrieved from the Health in Men Study (HIMS) and the Western Australian Data Linkage System (WADLS). MEASUREMENTS: Hearing loss was defined by self-report or by diagnosis recorded in the WADLS. Incident frailty was assessed using the Hospital Frailty Risk Score (HFRS). RESULTS: A total of 2,348 (71.5%) men developed frailty during follow up. The adjusted hazard ratio was 1.03 (95% CI: 0.95-1.12). The majority of the participants became frail by age 90 regardless of hearing condition. The time point where half of the group become frail was delayed by 14.4 months for men without hearing loss compared with hearing impaired men. CONCLUSIONS: Hearing loss is not associated with incident frailty in men aged 70 years or older when frailty was measured by HFRS. However, this statistically non-significant result could be due to the low sensitivity of study measures. Also, we found a trend that men with hearing loss were more likely to develop frailty compared with their normal-hearing peers, suggesting a potential association between hearing loss and frailty.

Life-history data of a key amphipod species from three NE Atlantic estuaries under different levels of anthropogenic pressure.

Knowledge on population dynamics of ecosystem's key-species is invaluable to understand how populations will respond to natural and human-induced perturbations. The amphipod Echinogammarus marinus is a key-species from European estuarine habitats with a distribution ranging from Norway to Portugal [1]. The present article contains supportive data related to a research article entitled 'Comparing production and life-history traits of a key amphipod species within and between estuaries under different levels of anthropogenic pressure' [2]. The present dataset presents the density, biomass, fecundity, and production of E. marinus in three estuaries under different anthropogenic pressure and, within each estuary, at three sampling sites, which differed in terms of the distance to the estuary mouth, vegetation cover, and organic matter content. Monthly environmental abiotic data and seasonal concentration of PAH and other contaminants are also provided. Sampling took place monthly for 13 months at low tide on intertidal mudflats. At each site, Fucus fronds containing E. marinus individuals were randomly collected. All E. marinus individuals were counted, sexed, and measured under a binocular stereo microscope to estimate the density and the biomass of E. marinus in Fucus fronds. Finally, the annual production of E. marinus at each sampling site was estimated through the size-frequency method. This dataset may be used to compare population traits of E. marinus populations across different estuaries and it may overall assist designing studies regarding population dynamics and designing management strategies in coastal systems, namely targeting at habitat conservation and restoration.

Comparing production and life-history traits of a key amphipod species within and between estuaries under different levels of anthropogenic pressure.

Inter-population variability may arise as a response to adverse natural and anthropogenic stressors. The dynamics of a key amphipod species (Echinogammarus marinus) was followed during ≈ 1-year at its southerly range (NW Portugal), in three estuaries with different levels of anthropogenic pressure (High - Ave estuary; Moderate - Mondego estuary; Low - Minho estuary). We hypothesised that E. marinus populations would present lower production and fitness, and higher intersexuality incidence with increasing anthropogenic pressure. According to a GAM model explaining ≈70% of the observed variability, E. marinus biomass depends on temperature, organic matter, Fucus area and time of the year. Significant differences were found between the gammarid biomass in Minho and Mondego estuaries and within sites from the same estuary. As expected, Ave estuary exhibited the lowest average annual production, abundance and fecundity rates. However, the highest average production was found in Mondego and not in Minho estuary, although the turnover ratio (P/B) of both estuaries was very similar. Besides the system's global ecological status, E. marinus also seems to respond to microhabitat conditions, which may explain the spatial heterogeneity observed in the amphipod production within the same estuary. Intersexuality prevalence was negligible in the three populations, which does not support the idea of a link between anthropogenic pressure and intersexuality in E. marinus. We argue that the dependence of E. marinus on Fucus sp. should be further investigated to fully understand the role of both fucoids and the gammarid in coastal foodwebs.

Faecal immunochemical testing and blood tests for prioritization of urgent colorectal cancer referrals in symptomatic patients: a 2-year evaluation.

BACKGROUND: A novel pathway incorporating faecal immunochemical testing (FIT) for rapid colorectal cancer diagnosis (RCCD) was introduced in 2017. This paper reports on the service evaluation after 2 years of pathway implementation. METHODS: The RCCD protocol was based on FIT, blood results and symptoms to stratify adult patients in primary care. Two-week-wait (2WW) investigation was indicated for patients with rectal bleeding, rectal mass and faecal haemoglobin (fHb) level of 10 µg Hb/g faeces or above or 4 µg Hb/g faeces or more in the presence of anaemia, low ferritin or thrombocytosis, in all other symptom groups. Patients with 100 µg Hb/g faeces or above had expedited investigation . A retrospective audit of colorectal cancer detected between 2017 and 2019 was conducted, fHb thresholds were reviewed and critically assessed for cancer diagnoses. RESULTS: In 2 years, 14788 FIT tests were dispatched with 13361 (90.4 per cent) completed returns. Overall, fHb was less than 4 µg Hb/g faeces in 9208 results (68.9 per cent), 4-9.9 µg Hb/g in 1583 (11.8 per cent), 10-99.9 µg Hb/g in 1850 (13.8 per cent) and 100 µg Hb/g faeces or above in 720 (5.4 per cent). During follow-up (median 10.4 months), 227 colorectal cancers were diagnosed. The cancer detection rate was 0.1 per cent in patients with fHb below 4 µg Hb/g faeces, 0.6 per cent in those with fHb 4-9.9 µg Hb/g faeces, 3.3 per cent for fHb 10-99.9 µg Hb/g faeces and 20.7 per cent for fHb 100 µg Hb/g faeces or above. The detection rate in the cohort with 10-19.9 µg Hb/g faeces was 1.4 per cent, below the National Institute for Health and Care Excellence threshold for urgent referral. The colorectal cancer rate in patients with fHb below 20 µg Hb/g faeces was less than 0.3 per cent. CONCLUSION: Use of FIT to "rule out" urgent referral from primary care misses a small number of cases. The threshold for referral may be adjusted with blood results to improve stratification .

Cyclic vomiting syndrome is a prevalent and under-recognized condition in the gastroenterology outpatient clinic.

BACKGROUND: Cyclic vomiting syndrome (CVS) is a functional gastrointestinal disorder (FGID) characterized by intermittent episodes of nausea and vomiting. Our aim was to report its prevalence and associated features. METHODS: Data concerning demographics, symptoms, and psychiatric comorbidity were collected. Symptoms compatible with CVS were classified as per Rome III criteria. We recorded whether a diagnosis of CVS was considered in patients after negative investigation. We compared demographics and association with other FGIDs in patients with and without CVS. KEY RESULTS: 920 of 1002 patients provided data. Of the 920 patients, 112 (12.2%) had symptoms compatible with CVS. Thirteen (11.6%) of these had an organic cause for their symptoms, but 99 patients (88.4%) were deemed to have CVS (prevalence=10.8%). Organic causes for symptoms compatible with CVS included gastroparesis, large hiatus hernia, achalasia, and small bowel obstruction. Only 39.4% of patients with CVS were asked about vomiting symptoms at their initial consultation, and a diagnosis of CVS was considered in only four (4.0%) of the 99 patients. CVS was associated with younger age, tobacco smoking, never having married, psychiatric comorbidity, and presence of symptoms compatible with other FGIDs (P≤.01). CONCLUSIONS AND INFERENCES: Prevalence of CVS in this outpatient gastroenterology adult population was 10.8%. Identified associations included younger age, tobacco smoking, psychiatric comorbidity, and symptoms compatible with other FGIDs. The condition was considered as a possible diagnosis in <5% of patients who met the diagnostic criteria.

Evidence of low dose effects of the antidepressant fluoxetine and the fungicide prochloraz on the behavior of the keystone freshwater invertebrate Gammarus pulex.

In recent years, behavior-related endpoints have been proposed as rapid and reliable ecotoxicological tools for risk assessment. In particular, the use of detritivores to test the toxicity of pollutants through feeding is currently becoming a well-known method. Experiments combining feeding with other behavioral endpoints can provide relevant information about direct and indirect toxicological effects of chemicals. We carried out a feeding experiment with the shredder Gammarus pulex in order to detect indirect (through leaf conditioning) and direct effects (through water exposure) of two pollutants at environmentally relevant concentrations: the fungicide prochloraz (6 µg/L) and the antidepressant fluoxetine (100 ng/L). Prochloraz inhibited fungal growth on leaves, but it did not affect either the microbial breakdown rates or the C:N ratio of the leaves. Individuals of G. pulex that were fed with treated leaves presented lower consumption rates, not only those fed with prochloraz-treated leaves, but also those fed with fluoxetine-treated leaves, and those fed with the mixture-treated leaves. Mixed-effects models revealed that the swimming velocity of the amphipods after the experiment was modulated by the exposure to fluoxetine, and also by the exposure to prochloraz. We demonstrate that both the antidepressant and the fungicide may cause significant sublethal effects at low concentrations. The combination of behavioral endpoints together with the application of mixed models provided a useful tool for early detection of the effects of toxicity mixtures in freshwater ecosystems.

Systematic review with meta-analysis: the efficacy of probiotics in inflammatory bowel disease.

BACKGROUND: Ulcerative colitis (UC) and Crohn's disease (CD) are inflammatory bowel diseases (IBD). Evidence implicates disturbances of the gastrointestinal microbiota in their pathogenesis. AIM: To perform a systematic review and meta-analysis to examine the efficacy of probiotics in IBD. METHODS: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register were searched (until November 2016). Eligible randomised controlled trials (RCTs) recruited adults with UC or CD, and compared probiotics with 5-aminosalicylates (5-ASAs) or placebo. Dichotomous symptom data were pooled to obtain a relative risk (RR) of failure to achieve remission in active IBD, or RR of relapse of disease activity in quiescent IBD, with 95% confidence intervals (CIs). RESULTS: The search identified 12 253 citations. Twenty-two RCTs were eligible. There was no benefit of probiotics over placebo in inducing remission in active UC (RR of failure to achieve remission=0.86; 95% CI=0.68-1.08). However, when only trials of VSL#3 were considered there appeared to be a benefit (RR=0.74; 95% CI=0.63-0.87). Probiotics appeared equivalent to 5-ASAs in preventing UC relapse (RR=1.02; 95% CI=0.85-1.23). There was no benefit of probiotics in inducing remission of active CD, in preventing relapse of quiescent CD, or in preventing relapse of CD after surgically induced remission. CONCLUSIONS: VSL#3 may be effective in inducing remission in active UC. Probiotics may be as effective as 5-ASAs in preventing relapse of quiescent UC. The efficacy of probiotics in CD remains uncertain, and more evidence from RCTs is required before their utility is known.

Derivation and validation of a diagnostic test for irritable bowel syndrome using latent class analysis.

BACKGROUND: The accuracy of symptom-based diagnostic criteria for irritable bowel syndrome (IBS) is modest. AIMS: To derive and validate a new test that utilises latent class analysis. METHODS: Symptom, colonoscopy, and histology data were collected from 1981 patients and 360 patients in two cohorts referred to secondary care for investigation of their gastrointestinal symptoms in Canada and the UK, respectively. Latent class analysis was used to identify naturally occurring clusters in patient-reported symptoms in the Canadian dataset, and the latent class model derived from this was then applied to the UK dataset in order to validate it. Sensitivity, specificity, and positive and negative likelihood ratios (LRs) were calculated for the latent class models. RESULTS: In the Canadian cohort, the model had a sensitivity of 44.7% (95% CI 40.0-50.0) and a specificity of 85.3% (95% CI 83.4-87.0). Positive and negative LRs were 3.03 (95% CI 2.57-3.56) and 0.65 (95% CI 0.59-0.71) respectively. A maximum positive LR of 3.93 was achieved following construction of a receiver operating characteristic curve. The performance in the UK cohort was similar, with a sensitivity and specificity of 52.5% (95% CI 42.2-62.7) and 84.3% (95% CI 79.3-88.6), respectively. Positive and negative LRs were 3.35 (95% CI 2.38-4.70) and 0.56 (95% CI 0.45-0.68), respectively, with a maximum positive LR of 4.15. CONCLUSIONS: A diagnostic test for IBS, utilising patient-reported symptoms incorporated into a latent class model, performs as accurately as symptom-based criteria. It has potential for improvement via addition of clinical markers, such as coeliac serology and faecal calprotectin.

Expression of the fetal hematopoiesis regulator FEV indicates leukemias of prenatal origin.

The origin of cancers is associated with etiology as well as therapeutics. Several studies reveal that malignancies in children can originate in utero. However, a diagnostic approach to distinguish between cancers initiated pre- or postnatally is absent. Here we identified a transcriptional factor FEV (fifth Ewing variant) that was expressed in fetal hematopoietic cells and became silent after birth. We characterized that FEV was essential for the self-renewal of hematopoietic stem cells (HSCs). We next found that FEV was expressed in most infant leukemia samples, but seldom in adult samples, in accord with the known prenatal origins of the former. We further determined the majority of pediatric acute lymphoid leukemia (ALL) and acute myeloid leukemia (AML) were FEV positive. Moreover, FEV knockdown markedly impaired the leukemia-propagating ability of leukemic stem cells. We therefore identified FEV is unique to fetal HSCs and stably expressed in leukemic cells of prenatal origin. It may also provide a tractable therapeutic target.