Objective
Auditory verbal hallucinations (AVHs) are core features of psychotic illness and remain significant in predicting poor outcome and risk. There has been a wide range of approaches to ...understanding these experiences.
Method
A systematic literature review summarizing different methods of investigation and their results; phenomenology, descriptive psychopathology, psychological, cognitive neurobiology, and neuroimaging.
Results
A number of 764 papers and texts were screened and 113 reviewed. Phenomenological studies are comparably few in number, and psychopathology remains based on concepts defined in the early 20th century. Psychological models focus on voice content and emotional reaction, and suggest a continuum of AVHs from normal experience. Neuropsychological models include AVHs as misattribution of inner speech, whilst functional neuroimaging studies focus on the spontaneous activity and connectivity of auditory networks.
Conclusion
There has been a large growth in research on AVHs in recent decades dominated by neurobiological and neuroimaging studies. Future research should include focus on phenomenological aspects and AVHs change over the course of developing illness. Integration between branches of enquiry is needed, and the risk is that without this, models are proposed and investigated that bear scant relevance to the symptom itself.
This study sought to determine whether afferent feedback associated with peripheral muscle fatigue inhibits central motor drive (CMD) and thereby limits endurance exercise performance. On two ...separate days, eight men performed constant-load, single-leg knee extensor exercise to exhaustion (85% of peak power) with each leg (Leg1 and Leg2). On another day, the performance test was repeated with one leg (Leg1) and consecutively (within 10 s) with the other/contralateral leg (Leg2-post). Exercise-induced quadriceps fatigue was assessed by reductions in potentiated quadriceps twitch-force from pre- to postexercise (ΔQtw,pot) in response to supramaximal magnetic femoral nerve stimulation. The output from spinal motoneurons, estimated from quadriceps electromyography (iEMG), was used to reflect changes in CMD. Rating of perceived exertion (RPE) was recorded during exercise. Time to exhaustion (∼9.3 min) and exercise-induced ΔQtw,pot (∼51%) were similar in Leg1 and Leg2 (P > 0.5). In the consecutive leg trial, endurance performance of the first leg was similar to that observed during the initial trial (∼9.3 min; P = 0.8); however, time to exhaustion of the consecutively exercising contralateral leg (Leg2-post) was shorter than the initial Leg2 trial (4.7 ± 0.6 vs. 9.2 ± 0.4 min; P < 0.01). Additionally, ΔQtw,pot following Leg2-post was less than Leg2 (33 ± 3 vs 52 ± 3%; P < 0.01). Although the slope of iEMG was similar during Leg2 and Leg2-post, end-exercise iEMG following Leg2-post was 26% lower compared with Leg2 (P < 0.05). Despite a similar rate of rise, RPE was consistently ∼28% higher throughout Leg2-post vs. Leg2 (P < 0.05). In conclusion, this study provides evidence that peripheral fatigue and associated afferent feedback limits the development of peripheral fatigue and compromises endurance exercise performance by inhibiting CMD.
Late‐onset cytomegalovirus (CMV) disease is a significant problem with a standard 3‐month prophylaxis regimen. This multicentre, double‐blind, randomized controlled trial compared the efficacy and ...safety of 200 days’ versus 100 days’ valganciclovir prophylaxis (900 mg once daily) in 326 high‐risk (D+/R–) kidney allograft recipients. Significantly fewer patients in the 200‐day group versus the 100‐day group developed confirmed CMV disease up to month 12 posttransplant (16.1% vs. 36.8%; p < 0.0001). Confirmed CMV viremia was also significantly lower in the 200‐day group (37.4% vs. 50.9%; p = 0.015 at month 12). There was no significant difference in the rate of biopsy‐proven acute rejection between the groups (11% vs. 17%, respectively, p = 0.114). Adverse events occurred at similar rates between the groups and the majority were rated mild‐to‐moderate in intensity and not related to study medication. In conclusion, this study demonstrates that extending valganciclovir prophylaxis (900 mg once daily) to 200 days significantly reduces the incidence of CMV disease and viremia through to 12 months compared with 100 days’ prophylaxis, without significant additional safety concerns associated with longer treatment. The number needed to treat to avoid one additional patient with CMV disease up to 12 months posttransplant is approximately 5.
This multicenter randomized trial shows that, in CMV D+/R− kidney transplant recipients, extending valganciclovir prophylaxis from 100 days to 200 days decreases the incidence of CMV disease.
To assess the effect of adding interferon-alpha (IFN) +/- interleukin-2 (IL-2) to chemotherapy in patients with metastatic melanoma. METHODS A published data meta-analysis of trials of ...biochemotherapy versus chemotherapy in patients with metastatic melanoma was undertaken. End points evaluated were rates of partial response (PR), complete response (CR) and overall (partial + complete) response (OR); response duration; progression-free survival; overall survival (OS); and toxicity. The only subgroup analysis performed was by type of immunotherapy, with trials divided according to whether IFN only or IFN and IL-2 were administered in the biochemotherapy arm.
Eighteen randomized trials were identified: 11 trials of chemotherapy +/- IFN and seven trials of chemotherapy +/- IFN and IL-2. More than 2,600 patients were entered onto the trials, with 555 responses and 2,039 deaths. There was a clear benefit for biochemotherapy for PR (odds ratio = 0.66; 95% CI, 0.53 to 0.82; P = .0001), CR (odds ratio = 0.50; 95% CI, 0.35 to 0.73; P = .0003) and OR (odds ratio = 0.59; 95% CI, 0.49 to 0.72; P < .00001). For OR, these benefits were significant for both the IFN (odds ratio = 0.60; 95% CI, 0.46 to 0.79; P = .0002) and IFN + IL-2 (odds ratio = 0.58; 95% CI, 0.44 to 0.77; P = .0001) subgroups. In contrast, there was no benefit overall in OS (odds ratio = 0.99; 95% CI, 0.91 to 1.08; P = .9), but there was evidence of heterogeneity of treatment effect between the individual trials (P = .006).
This meta-analysis provides a comprehensive summary of all the data currently available, and shows that although biochemotherapy clearly improves response rates, this does not appear to translate into a survival benefit.
ULTRACAM is a portable, high-speed imaging photometer designed to study faint astronomical objects at high temporal resolutions. ULTRACAM employs two dichroic beamsplitters and three frame-transfer ...CCD cameras to provide three-colour optical imaging at frame rates of up to 500 Hz. The instrument has been mounted on both the 4.2-m William Herschel Telescope on La Palma and the 8.2-m Very Large Telescope in Chile, and has been used to study white dwarfs, brown dwarfs, pulsars, black hole/neutron star X-ray binaries, gamma-ray bursts, cataclysmic variables, eclipsing binary stars, extrasolar planets, flare stars, ultracompact binaries, active galactic nuclei, asteroseismology and occultations by Solar System objects (Titan, Pluto and Kuiper Belt objects). In this paper we describe the scientific motivation behind ULTRACAM, present an outline of its design and report on its measured performance.
We present a framework for enhancing Gaussian process regression machine learning models with a priori knowledge derived from models of the transmission physics in optical networks. This is done by ...framing the regression problem as multi-task learning, in which both the measured data and targets derived from a physical model of the system are used to optimise the kernel hyperparameters. We discuss the theoretical assumptions made and the validity of the approach. It is demonstrated that physics-informed Gaussian processes facilitate Bayesian inference with fewer data points than standard Gaussian processes, opening up application areas in which measurements are expensive. The transparency, interpretability and explainability of the proposed technique and the subsequent increased likelihood of adoption by industry are discussed.
The potential role of proteinase activated receptor 2 (PAR2) in the development of age-related obesity and insulin resistance is not well-understood. To address the hypothesis that deletion of PAR2 ...might ameliorate age-related obesity and impaired glucose homeostasis, we assessed body composition and insulin action in 18-month-old male PAR2 knockout (PAR2KO-AG), age-matched (AG) and young C57BL6 (YG, 6-month-old) mice. Body composition was measured by magnetic resonance spectroscopy (MRS) and insulin action was assessed by glucose tolerance (GT), insulin tolerance (IT) and AICAR tolerance (AT) testing. AG mice weighed significantly more than YG mice (p = 0.0001) demonstrating age-related obesity. However, PAR2KO-AG mice weighed significantly more than AG mice (p = 0.042), indicating that PAR2 may prevent a portion of age-related obesity. PAR2KO-AG and AG mice had greater fat mass and body fat percentage than YG mice. Similar to body weight, fat mass was greater in PAR2KO-AG mice compared to AG mice (p = 0.045); however, only a trend for greater body fat percentage in PAR2KO-AG compared to AG mice was observed (p = 0.09). No differences existed in lean body mass among the PAR2KO-AG, AG, and YG mice (p = 0.58). With regard to insulin action, the area under the curve (AUC) for GT was lower in PAR2KO-AG compared to AG mice (p = 0.0003) and YG mice (p = 0.001); however, no differences existed for the AUC for IT or AT. Our findings indicate that age-related obesity is not dependent on PAR2 expression.
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