Is treatment-resistant schizophrenia categorically distinct from treatment-responsive schizophrenia? A systematic review

Abstract Background Schizophrenia is a highly heterogeneous disorder, and around a third of patients are treatment-resistant. The only evidence-based treatment for these patients is clozapine, an atypical antipsychotic with relatively weak dopamine antagonism. It is plausible that varying degrees of response to antipsychotics reflect categorically distinct illness subtypes, which would have significant implications for research and clinical practice. If these subtypes could be distinguished at illness onset, this could represent a first step towards personalised medicine in psychiatry. This systematic review investigates whether current evidence supports conceptualising treatment-resistant and treatment-responsive schizophrenoa as categorically distinct subtypes. Method A systematic literature search was conducted, using PubMed, EMBASE, PsycInfo, CINAHL and OpenGrey databases, to identify all studies which compared treatment-resistant schizophrenia (defined as either a lack of response to two antipsychotic trials or clozapine prescription) to treatment-responsive schizophrenia (defined as known response to non-clozapine antipsychotics). Results Nineteen studies of moderate quality met inclusion criteria. The most robust findings indicate that treatment-resistant patients show glutamatergic abnormalities, a lack of dopaminergic abnormalities, and significant decreases in grey matter compared to treatment-responsive patients. Treatment-resistant patients were also reported to have higher familial loading; however, no individual gene-association study reported their findings surviving correction for multiple comparisons. Conclusions Tentative evidence supports conceptualising treatment-resistant schizophrenia as a categorically different illness subtype to treatment-responsive schizophrenia. However, research is limited and confirmation will require replication and rigorously controlled studies with large sample sizes and prospective study designs

Development of an antimicrobial blended white LED system containing pulsed 405-nm LEDs for decontamination applications

This study details the design, build and testing of a prototype antimicrobial blended white light unit containing pulsed red, yellow, green and 405nm LEDs. With a push for alternative methods of disinfection, optical methods have become a topic of interest. Ultra-violet (UV) light is widely known for its antimicrobial properties however; 405nm light has demonstrated significant antimicrobial properties against many common hospital acquired pathogens. In this study, a pulsed, blended, white-light prototype with a high content of 405 nm antimicrobial light, was designed, built and tested. Antimicrobial efficacy testing of the prototype was conducted using Staphylococcus aureus and Pseudomonas. aeruginosa, two bacteria which are common causes of hospital acquired infections. These were exposure to 3 different light outputs from the prototype and the surviving bacteria enumerated. Results showed that the mixed light output provided a much better CRI and light output under which to work. Also, the light output containing 405 nm light provided an antimicrobial effect, with decontamination of 103 CFUml-1 populations of both bacterial species. The other light content (red, yellow, green) had no beneficial or adverse effects on the antimicrobial properties of the 405nm light. The results suggest that with further development, it could be possible to produce an antimicrobial blended white light containing pulsed 405nm light that could supplement or even replace standard white lighting in certain environments

Coupling Control Variates for Markov Chain Monte Carlo

We show that Markov couplings can be used to improve the accuracy of Markov chain Monte Carlo calculations in some situations where the steady-state probability distribution is not explicitly known. The technique generalizes the notion of control variates from classical Monte Carlo integration. We illustrate it using two models of nonequilibrium transport

Streamlining analysis methods for large acoustic surveys using automatic detectors with operator validation

1.  Passive acoustic surveys are becoming increasingly popular as a means of surveying for cetaceans and other marine species. These surveys yield large amounts of data, the analysis of which is time consuming and can account for a substantial proportion of the survey budget. Semi-automatic processes enable the bulk of processing to be conducted automatically while allowing analyst time to be reserved for validating and correcting detections and classifications. 2.  Existing modules within the Passive Acoustic Monitoring software PAMGuard were used to process a large (25.4 Terabyte) dataset collected during towed acoustic ship transits. The recently developed ‘Multi-Hypothesis Tracking Click Train Detector’ and the ‘Whistle and Moan Detector’ modules were used to identify occasions within the dataset at which vocalising toothed whales (odontocetes) were likely to be acoustically present. These putative detections were then reviewed by an analyst, with false positives being corrected. Target motion analysis provided a perpendicular distance to odontocete click events enabling the estimation of detection functions for both sperm whales and delphinids. Detected whistles were assigned to the lowest taxonomical level possible using the PAMGuard ‘Whistle Classifier’ module. 3.  After an initial tuning process, this semi-automatic method required 91 hr of an analyst's time to manually review both automatic click train and whistle detections from 1,696 hr of survey data. Use of the ‘Multi-Hypothesis Tracking Click Train Detector’ reduced the amount of data for the analyst to search by 74.5%, while the ‘Whistle and Moan Detector’ reduced data to search by 85.9%. In total, 443 odontocete groups were detected, of which 55 were from sperm whale groups, six were from beaked whales, two were from porpoise and the remaining 380 were identified to the level of delphinid group. An effective survey strip half width of 3,277 and 699 m was estimated for sperm whales and delphinids respectively. 4.  The semi-automatic workflow proved successful, reducing the amount of analyst time required to process the data, significantly reducing overall project costs. The workflow presented here makes use of existing modules within PAMGuard, a freely available and open-source software, readily accessible to acoustic analysts.Publisher PDFPeer reviewe

Pulsed ultraviolet light decontamination of artificially-generated microbiological aerosols

Airborne transmission of infectious organisms is a major public health concern, particularly within healthcare and communal public environments. Methods of environmental decontamination utilising pulsed ultraviolet (UV) light are currently available, however it is important that germicidal efficacy against airborne contamination is established. This study demonstrates evidence of the dose-response kinetics of airborne bacterial contamination when exposed to pulsed UV-rich (PUV) light. Bacterial aerosols (Staphylococcus epidermidis) were generated using a 6-Jet Collison nebuliser, and introduced into a custom-designed aerosol chamber which enabled prolonged airborne suspension and circulation. Bacterial aerosols were exposed to short duration pulses (~20 µs) of UV-rich light emitted from a xenon-filled flashlamp. The lamp was operated using a 1 kV solid–state pulsed power source, with a pulse frequency of 1 Hz, and output energy of 20 J/pulse. Post-treatment, air samples were extracted from the chamber using a BioSampler liquid impinger, and the surviving fraction was enumerated using standard microbiological culture methods. Results demonstrate successful aerosol inactivation, with a 66.4% reduction achieved with only 10 pulses of UV-rich light (P=<0.0002). Inactivation using continuous UV light was also investigated in order to quantify the comparative efficacy of these antimicrobial light regions. In addition to determining the inactivation kinetics, the spectral outputs of the pulsed and continuous UV sources were captured and compared in order to assess their comparative UV-C content, and subsequently assess how this UV content relates to their germicidal efficiency. Overall, results provide evidence of the dose-response kinetics of bacterial aerosols to PUV-rich light. As with continuous UV light, safety restrictions limit its application to unoccupied environments, or within sealed enclosures such as air handling units, however the reduced treatment times with PUV provides operational advantages over continuous light treatment

Genetic consequences of improved river connectivity in brown trout (Salmo trutta L.)

Fragmentation of watercourses poses a significant threat to biodiversity, particularly for migratory fish species. Mitigation measures such as fishways, have been increasingly implemented to restore river connectivity and support fish migration. The effects of such restoration efforts are typically tested using telemetry and fisheries methods, which do not fully capture the broader population movements that may have important consequences for population viability. We performed a before-and-after control-impact (BACI) study using genetic tools (SNPs) to investigate the effect of a newly implemented fishway, aiming to enhance upstream spawning migration of brown trout (Salmo trutta Linnaeus) in a reservoir with two headwater tributaries fragmented by man-made weirs. Another reservoir with two barrier-free tributaries was also analysed as a control. Our results showed that the isolated brown trout population was spawning in the reservoir before the installation of the fishway, and we found genetic structuring and differentiation between fragmented headwater tributaries before the fishway construction, but not in the control reservoir. Unexpectedly, after the fishway construction we observed signals consistent with increased genetic differentiation between populations of newly recruited juvenile fish in the reservoir tributary and fish in the reservoir. We propose this was caused by newly enabled philopatric behaviour of brown trout to their natal spawning tributary. In contrast, we did not find any genetic changes in the tributary without a fishway or in the barrier-free reservoir system. Given the scarcity of similar studies, we advocate for an increased use of genetic analyses in BACI studies to monitor and evaluate the effect of efforts to restore habitat connectivity and inform future management strategies

Passive acoustic methods for fine-scale tracking of harbour porpoises in tidal rapids

The growing interest in generating electrical power from tidal currents using tidal turbine generators raises a number of environmental concerns, including the risk that marine mammals might be injured or killed through collision with rotating turbine blades. To understand this risk, information on how marine mammals use tidal rapid habitats and in particular, their underwater movements and dive behaviour is required. Porpoises, which are the most abundant small cetacean at most European tidal sites, are difficult animals to tag, and the limited size of tidal habitats means that any telemetered animal would be likely to spend only a small proportion of time within them. Here, an alternative approach is explored, whereby passive acoustic monitoring (PAM) is used to obtain fine scale geo-referenced tracks of harbour porpoises in tidal rapid areas. Large aperture hydrophone arrays are required to obtain accurate locations of animals from PAM data and automated algorithms are necessary to process the large quantities of acoustic data collected on such systems during a typical survey. Methods to automate localisation, including a method to match porpoise detections on different hydrophones and separate different vocalising animals, and an assessment of the localisation accuracy of the large aperture hydrophone array are presented.Publisher PDFPeer reviewe