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"McDonald, J. R."
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Chronic gut inflammation impairs contextual control of fear
Chronic inflammatory diseases are highly comorbid with anxiety in humans. The extent to which chronic inflammation is responsible for this relationship remains to be determined. We therefore tested the hypothesis that prolonged, but not brief, gut inflammation is sufficient to evoke anxiety-related behaviours in mice. We used the discriminative fear to context conditioning paradigm to assess fear generalization, which is a prominent feature of anxiety disorders. Gut inflammation was induced by exposure to dextran sodium sulfate (DSS) in the drinking water, a well-established rodent model of ulcerative colitis evoking prolonged inflammation. Neither acute (1 × 5 day cycle) nor chronic (3 × 5 day cycles) exposure to DSS affected fear responses when tested shortly after conditioning. Mice in all groups generated more fear responses (freezing) in a chamber previously paired with mild shock, as compared to a chamber with no pairing. This suggests DSS exposure had no effect on acquisition or expression of conditioned fear. Acute and control animals showed this same contextual control of freezing when tested 9 days later. In contrast, at this remote time point, the chronically treated animals exhibited increased freezing in the unpaired chamber such that freezing was equivalent in both contexts. These animals, however, showed intact preference for the unpaired chamber when allowed to freely move between chambers. These data suggest that some mnemonic process engaged after training, such as memory consolidation, is affected by past chronic inflammation so as to generalize negative associations and engage fearful responding in inappropriate contexts, despite intact knowledge that the chambers have different affective associations sufficient for place preference.
Journal Article
Daptomycin versus vancomycin for osteoarticular infections due to methicillin-resistant Staphylococcus aureus (MRSA): a nested case–control study
Vancomycin is the standard antibiotic for the treatment of methicillin-resistant
Staphylococcus aureus
(MRSA) infections. While daptomycin is approved for MRSA bacteremia, its effectiveness in osteoarticular infections (OAIs) has not been established. A 1:2 nested case–control study of adult patients with MRSA OAIs admitted to an academic center from 2005 to 2010 was carried out. Clinical outcomes and drug toxicity in patients treated with daptomycin versus vancomycin were compared. Twenty patients with MRSA OAIs treated with daptomycin were matched to 40 patients treated with vancomycin. The median age of the patients was 52 years (range, 25–90), and 40 (67 %) were male. Most patients had osteomyelitis (82 %), predominantly from a contiguous source (87 %). Forty percent were diabetics. Diabetic patients were more likely to receive vancomycin than daptomycin [20 (50 %) vs. 4 (20 %);
p
= 0.03]. Vancomycin was more often combined with antibiotics other than daptomycin [22 (55 %) vs. 5 (25 %);
p
= 0.03]. The median total antibiotic treatment duration was 48 (daptomycin) vs. 46 days (vancomycin) (
p
= 0.5). Ninety percent of daptomycin-treated patients had previously received vancomycin for a median of 14.5 days (range, 2–36). Clinical success rates were similar between daptomycin and vancomycin at 3 months [15 (75 %) vs. 27 (68 %);
p
= 0.8] and 6 months [14 (70 %) vs. 23 (58 %);
p
= 0.5], even after propensity score-based adjustment for antibiotic assignment. The frequency of adverse events was similar between treatment groups [1 (5 %) vs. 7 (18 %);
p
= 0.2]. Daptomycin and vancomycin achieved similar rates of clinical success and drug tolerability. Daptomycin is a reasonable alternative for treating MRSA OAIs, particularly in patients where therapy with vancomycin has not been well tolerated.
Journal Article
Frequency and fundamental signal measurement algorithms for distributed control and protection applications
An increasing penetration of distributed generation within electricity networks leads to the requirement for cheap, integrated, protection and control systems. To minimise cost, algorithms for the measurement of AC voltage and current waveforms can be implemented on a single microcontroller, which also carries out other protection and control tasks, including communication and data logging. This limits the frame rate of the major algorithms, although analogue to digital converters (ADCs) can be oversampled using peripheral control processors on suitable microcontrollers. Measurement algorithms also have to be tolerant of poor power quality, which may arise within grid-connected or islanded power system scenarios. This study presents a \"Clarke-FLL hybrid\" architecture, which combines a three-phase Clarke transformation measurement with a frequency-locked loop (FLL). Platform-independent algorithms for three-phase nodal power flow analysis are benchmarked on three processors, including the Infineon TC1796 microcontroller, on which only 10% of the 2000 ms frame time is required, leaving the remainder free for other algorithms.
Journal Article
Developing injury indicators for First Nations and Inuit children and youth in Canada: a modified Delphi approach
The purpose of this research was to take the initial step in developing valid indicators that reflect the injury issues facing First Nations and Inuit children and youth in Canada.
Using a modified-Delphi process, relevant expert and community stakeholders rated each indicator on its perceived usefulness and ability to prompt action to reduce injury among children and youth in indigenous communities. The Delphi process included 5 phases and resulted in a refined set of 27 indicators.
Indicators related to motorized vehicle collisions, mortality and hospitalization rates were rated the most useful and most likely to prompt action. These were followed by indicators for community injury prevention training and response systems, violent and inflicted injury, burns and falls, and suicide.
The results suggest that a broad-based modified-Delphi process is a practical and appropriate method, within the OCAP™ (Ownership, Control, Access and Possession) principles, for developing a proposed set of indicators for injury prevention activity focused on First Nations and Inuit children and youth. Following additional work to validate and populate the indicators, it is anticipated that communities will utilize them to monitor injury and prompt decisions and action to reduce injuries among children and youth.
Journal Article
Active power-flow management utilising operating margins for the increased connection of distributed generation
Active power-flow management (APFM) provides a method to extend capacity for generation connections to distribution networks through the coordinated control of multiple network components in real-time. Identifying principles and strategies for active network management that hold for all situations will provide support to network operators and planners, and form the basis for a new paradigm in utility strategy concerning the connection of distributed generation. The authors build an APFM scheme concerned in facilitating increased generator connections. Operating margins have been identified as an essential element of the APFM scheme for the provision of network security and play a significant role in determining the economic viability of generation connected under the APFM scheme. An approach to the definition of the operating margins required to trigger generator output regulation (trimming) and tripping is introduced. These concepts are demonstrated through a case study using one of the UK generic distribution system models.
Journal Article
Enterococcal prosthetic valve infective endocarditis: report of 45 episodes from the International Collaboration on Endocarditis-merged database
Enterococcal prosthetic valve infective endocarditis (PVE) is an incompletely understood disease. In the present study, patients with enterococcal PVE were compared to patients with enterococcal native valve endocarditis (NVE) and other types of PVE to determine differences in basic clinical characteristics and outcomes using a large multicenter, international database of patients with definite endocarditis. Forty-five of 159 (29%) cases of definite enterococcal endocarditis were PVE. Patients with enterococcal PVE were demographically similar to patients with enterococcal NVE but had more intracardiac abscesses (20% vs. 6%; p=0.009), fewer valve vegetations (51% vs. 79%; p<0.001), and fewer cases of new valvular regurgitation (12% vs. 45%; p=0.01). Patients with either enterococcal PVE or NVE were elderly (median age, 73 vs. 69; p=0.06). Rates of in-hospital mortality, surgical intervention, heart failure, peripheral embolization, and stroke were similar in both groups. Patients with enterococcal PVE were also demographically similar to patients with other types of PVE, but mortality may be lower (14% vs. 26%; p=0.08). Notably, 93% of patients with enterococcal PVE came from European centers, as compared with only 79% of patients with enterococcal NVE (p=0.03). Thus, patients with enterococcal PVE have higher rates of myocardial abscess formation and lower rates of new regurgitation compared to patients with enterococcal NVE, but there are no differences between the groups with regard to surgical or mortality rates. In contrast, though patients with enterococcal PVE and patients with other types of PVE share similar characteristics, mortality is higher in the latter group. Importantly, the prevalence of enterococcal PVE was higher in the European centers in this study.
Journal Article
Design of trip current monitoring system for circuit breaker condition assessment
A distributed system, which supports circuit breaker maintenance and asset management, is described. It uses a client/server architecture for propagating expert knowledge from switchgear maintenance experts directly to maintenance operatives for on-site circuit breaker condition assessment and diagnosis. Prior research in the field of distribution level, circuit breaker condition monitoring has shown the trip coil of a circuit breaker yields a current profile that, when tripped, can subsequently be interpreted as an indicator of plant health. In exploiting existing circuit breaker test equipment, a centralised archive of asset condition is built from routine tests permitting experts to examine trends in the data and pass their definition of the operating conditions to personnel in the field. This provides diagnostic support to engineers in the field. The system is currently used as the subject of a pilot study conducted by SP PowerSystems which intended to improve its ongoing maintenance and asset management activities.
Journal Article
The role of medial prefrontal cortex in context-specific inhibition during reversal learning of a visual discrimination
Rats with medial prefrontal cortex or sham lesions were trained on a visual discrimination task designed for the eight-arm radial maze. After reaching asymptotic performance on this task, both groups were divided into sub-groups that would experience reversal learning in the same or different context from original training. The results showed that both groups reversed in the different context had accelerated learning compared to the groups reversed in the same context. Reversal learning in rats with medial prefrontal cortex damage was faster than sham animals in the same context. These and other results from a transfer test suggest that the medial prefrontal cortex participates in the behavioral effects of a context-specific inhibitory association acquired during visual discrimination learning.
Journal Article
UK distribution system protection issues
The paper presents a UK industry view formulated using the outcomes of questionnaires, seminars, and other academic-industry exchanges carried out under the auspices of the Department of Trade and Industry funded centre for distributed generation (DG) and sustainable electrical energy of the present and anticipated future protection system challenges in active distribution networks. A systematic methodology for opinion recording and priority assessment based on a carefully designed questionnaire has been proposed and applied to the distribution system protection domain. The industrial consultation involved all UK Distribution Network Operators and a selection of protection system manufacturers and developers. The results of this exercise provide a unique insight into the key challenges facing the ongoing development of effective power system protection for distribution systems including DG. In particular, this paper supports the assertion that a decreasing significance islanding and certain protection discrimination issues would facilitate the integration of increased levels of DG.
Journal Article