Behavioural and neurochemical consequences of chronic gut microbiota depletion during adulthood in the rat

Gut microbiota colonization is a key event for host physiology that occurs early in life. Disruption of this process leads to altered brain development which ultimately manifests as changes in brain function and behaviour in adulthood. Studies using germ-free mice highlight the extreme impact on brain health that results from life without commensal microbes, however the impact of microbiota disturbances occurring in adulthood is less studied. To this end, we depleted the gut microbiota of 10-week-old male Sprague Dawley rats via chronic antibiotic treatment. Following this marked, sustained depletion of the gut bacteria, we investigated behavioural and molecular hallmarks of gut-brain communication. Our results reveal that depletion of the gut microbiota during adulthood results in deficits in spatial memory as tested by Morris water maze, increased visceral sensitivity and a greater display of depressive-like behaviours in the forced swim test. In tandem with these clear behavioural alterations we found change in altered CNS serotonin concentration along with changes in the mRNA levels of corticotrophin releasing hormone receptor 1 and glucocorticoid receptor. Additionally, we found changes in the expression of BDNF, a hallmark of altered microbiota-gut-brain axis signaling. In summary, this model of antibiotic-induced depletion of the gut microbiota can be used for future studies interested in the impact of the gut microbiota on host health without the confounding developmental influence of early-life microbial alterations.

Protocols for hyperlactatemia induction in the lactate minimum test adapted to swimming rats

The lactate minimum test (LACmin) has been considered an important indicator of endurance exercise capacity and a single session protocol can predict the maximal steady state lactate (MLSS). The objective of this study was to determine the best swimming protocol to induce hyperlactatemia in order to assure the LACmin in rats (Rattus norvegicus), standardized to four different protocols (P) of lactate elevation. The protocols were PI: 6 min of intermittent jumping exercise in water (load of 50% of the body weight - bw); P2: two 13% bw load swimming bouts until exhaustion (thin); P3: one thin 13% bw load swimming bout; and P4: two 13% bw load swimming bouts (1st 30 s, 2nd to thin), separated by a 30 s interval. The incremental phase of LACmin beginning with initial loads of 4% bw, increased in 0.5% at each 5 min. Peak lactate concentration was collected after 5, 7 and 9 min (mmol L-1) and differed among the protocols P 1 (15.2 +/- 0.4, 14.9 +/- 0.7, 14.8 +/- 0.6) and P2 (14.0 +/- 0.4, 14.9 +/- 0.4, 15.5 +/- 0.5) compared to P3 (5.1 +/- 0.1, 5.6 +/- 0.3, 5.6 +/- 0.3) and P4 (4.7 +/- 0.2, 6.8 +/- 0.2, 7.1 +/- 0.2). The LACmin determination success rates were 58%, 55%, 80% and 91% in P1, P2, P3 and P4 protocols, respectively. The MLSS did not differ from LACmin in any protocol. The LACmin obtained from P4 protocol showed better assurance for the MLSS identification in most of the tested rats. (c) 2007 Elsevier B.V. All rights reserved.

Non-exhaustive test for aerobic capacity determination in swimming rats

The aim of this study was to describe a double-bout exercise test for non-exhaustive aerobic capacity determination in swimming rats. Adult rats were Submitted to 4 swimming tests at different intensities (4%, 6%, 7%, and 8% of body mass), with intervals of 48 h between them. Two exercise bouts of equal intensity lasting 5 min were performed, separated by 2 min with blood collection for lactate analysis. For each intensity, delta lactate was determined by subtracting lactate concentration at the end of the first effort from the lactate at the end of the second effort. Individual linear interpolation of delta lactate concentration enabled determination of a null delta, equivalent to the critical load (CL). Maxima) lactate steady state (MLSS) was also determined. The estimated CL was of 4.8% body mass and the MLSS was observed at 100% of CL, with blood lactate of 5.20 mmol/L. At 90%, blood lactate stabilized, with a progressive increase to 110% CL. These results offer a potential determination of aerobic capacity in swimming rats.

The response of the lactate minimum test to a 12-week swimming training

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Automating human thought processes for a UAV forced landing

This paper describes the current status of a program to develop an automated forced landing system for a fixed-wing Unmanned Aerial Vehicle (UAV). This automated system seeks to emulate human pilot thought processes when planning for and conducting an engine-off emergency landing. Firstly, a path planning algorithm that extends Dubins curves to 3D space is presented. This planning element is then combined with a nonlinear guidance and control logic, and simulated test results demonstrate the robustness of this approach to strong winds during a glided descent. The average path deviation errors incurred are comparable to or even better than that of manned, powered aircraft. Secondly, a study into suitable multi-criteria decision making approaches and the problems that confront the decision-maker is presented. From this study, it is believed that decision processes that utilize human expert knowledge and fuzzy logic reasoning are most suited to the problem at hand, and further investigations will be conducted to identify the particular technique/s to be implemented in simulations and field tests. The automated UAV forced landing approach presented in this paper is promising, and will allow the progression of this technology from the development and simulation stages through to a prototype system

Experimental validation of an unpowered unmanned aerial system : application to forced landing scenarios

The ability to perform autonomous emergency (forced) landings is one of the key technology enablers identified for UAS. This paper presents the flight test results of forced landings involving a UAS, in a controlled environment, and which was conducted to ascertain the performances of previously developed (and published) path planning and guidance algorithms. These novel 3-D nonlinear algorithms have been designed to control the vehicle in both the lateral and longitudinal planes of motion. These algorithms have hitherto been verified in simulation. A modified Boomerang 60 RC aircraft is used as the flight test platform, with associated onboard and ground support equipment sourced Off-the-Shelf or developed in-house at the Australian Research Centre for Aerospace Automation(ARCAA). HITL simulations were conducted prior to the flight tests and displayed good landing performance, however, due to certain identified interfacing errors, the flight results differed from that obtained in simulation. This paper details the lessons learnt and presents a plausible solution for the way forward.

Spirometric studies on the adult general population of Helsinki : bronchodilation responses, determinants, and intrasession repeatability of FEV1, FEV6, FVC, and forced expiratory time

Spirometry is the most widely used lung function test in the world. It is fundamental in diagnostic and functional evaluation of various pulmonary diseases. In the studies described in this thesis, the spirometric assessment of reversibility of bronchial obstruction, its determinants, and variation features are described in a general population sample from Helsinki, Finland. This study is a part of the FinEsS study, which is a collaborative study of clinical epidemiology of respiratory health between Finland (Fin), Estonia (Es), and Sweden (S). Asthma and chronic obstructive pulmonary disease (COPD) constitute the two major obstructive airways diseases. The prevalence of asthma has increased, with around 6% of the population in Helsinki reporting physician-diagnosed asthma. The main cause of COPD is smoking with changes in smoking habits in the population affecting its prevalence with a delay. Whereas airway obstruction in asthma is by definition reversible, COPD is characterized by fixed obstruction. Cough and sputum production, the first symptoms of COPD, are often misinterpreted for smokers cough and not recognized as first signs of a chronic illness. Therefore COPD is widely underdiagnosed. More extensive use of spirometry in primary care is advocated to focus smoking cessation interventions on populations at risk. The use of forced expiratory volume in six seconds (FEV6) instead of forced vital capacity (FVC) has been suggested to enable office spirometry to be used in earlier detection of airflow limitation. Despite being a widely accepted standard method of assessment of lung function, the methodology and interpretation of spirometry are constantly developing. In 2005, the ATS/ERS Task Force issued a joint statement which endorsed the 12% and 200 ml thresholds for significant change in forced expiratory volume in one second (FEV1) or FVC during bronchodilation testing, but included the notion that in cases where only FVC improves it should be verified that this is not caused by a longer exhalation time in post-bronchodilator spirometry. This elicited new interest in the assessment of forced expiratory time (FET), a spirometric variable not usually reported or used in assessment. In this population sample, we examined FET and found it to be on average 10.7 (SD 4.3) s and to increase with ageing and airflow limitation in spirometry. The intrasession repeatability of FET was the poorest of the spirometric variables assessed. Based on the intrasession repeatability, a limit for significant change of 3 s was suggested for FET during bronchodilation testing. FEV6 was found to perform equally well as FVC in the population and in a subgroup of subjects with airways obstruction. In the bronchodilation test, decreases were frequently observed in FEV1 and particularly in FVC. The limit of significant increase based on the 95th percentile of the population sample was 9% for FEV1 and 6% for FEV6 and FVC; these are slightly lower than the current limits for single bronchodilation tests (ATS/ERS guidelines). FEV6 was proven as a valid alternative to FVC also in the bronchodilation test and would remove the need to control duration of exhalation during the spirometric bronchodilation test.

Committing to Effective Climate Governance in Northern Ireland: A Defining Test of Devolution

This is the second of a two-part analysis exploring the interaction between UK devolution and governance of the national low carbon transition. It argues that devolution shaped the national climate governance regime created by the Climate Change Act 2008, but will itself be tested and even altered as the traction of the low carbon imperative intensifies. This dynamic is explored in the specific context of the UK’s most devolved region. The first article argued that devolution facilitated and arguably forced Northern Ireland’s devolved administration to give a highly qualified and potentially illusory consent to the regional application of the UK Act. The second article argues that making a more effective commitment to climate governance will be a defining test of its devolution arrangements but will require constitutional arrangements designed for conflict resolution to mature. Failure to do so will have important implications for the UK’s putative ‘national’ low carbon transition and the longer-term viability of devolution in the region.

Swimming against the tide:Outward staffing flows from multinational subsidiaries

Studying the flows of parent country nationals in multinational enterprises (MNEs) to subsidiary operations has a relatively long tradition. Studying flows of subsidiary employees to other subsidiaries, as third country nationals, and to the corporate headquarters, as inpatriates, however, has empirically much less pedigree. Drawing on a large-scale empirical study of MNEs in Ireland, this paper provides a benchmark of outward flows of international assignees from the Irish subsidiaries of foreign-owned MNEs to both corporate headquarters and other worldwide operations. Building on insights from the resource-based view and neo-institutional theory, we develop and test a theoretical model to explain outward staffing flows. The results show that almost half of all MNEs use some form of outward staffing flows from their Irish operations. Although the impact of specific variables in explaining inter-organization variation differs between the utilization of inpatriate and third country national assignments, overall we find that a number of headquarters, subsidiary, structural, and human resource systems factors emerge as strong predictors of outward staffing flows. © 2010 Wiley Periodicals, Inc.

Shortened Lung Clearance Index is a repeatable and sensitive test in children and adults with cystic fibrosis

Background: Lung clearance index (LCI) derived from sulfur hexafluoride (SF6) multiple breath washout (MBW) is a sensitive measure of lung disease in people with cystic fibrosis (CF). However, it can be time-consuming, limiting its use clinically. Aim: To compare the repeatability, sensitivity and test duration of LCI derived from washout to 1/30th (LCI1/30), 1/20th (LCI1/20) and 1/10th (LCI1/10) to ‘standard’ LCI derived from washout to 1/40th initial concentration (LCI1/40). Methods: Triplicate MBW test results from 30 clinically stable people with CF and 30 healthy controls were analysed retrospectively. MBW tests were performed using 0.2% SF6 and a modified Innocor device. All LCI end points were calculated using SimpleWashout software. Repeatability was assessed using coefficient of variation (CV%). The proportion of people with CF with and without abnormal LCI and forced expiratory volume in 1 s (FEV1) % predicted was compared. Receiver operating characteristic (ROC) curve statistics were calculated. Test duration of all LCI end points was compared using paired t tests. Results: In people with CF, LCI1/40 CV% (p=0.16), LCI1/30 CV%, (p=0.53), LCI1/20 CV% (p=0.14) and LCI1/10 CV% (p=0.25) was not significantly different to controls. The sensitivity of LCI1/40, LCI1/30 and LCI1/20 to the presence of CF was equal (67%). The sensitivity of LCI1/10 and FEV1% predicted was lower (53% and 47% respectively). Area under the ROC curve (95% CI) for LCI1/40, LCI1/30, LCI1/20, LCI1/10 and FEV1% predicted was 0.89 (0.80 to 0.97), 0.87 (0.77 to 0.96), 0.87 (0.78 to 0.96), 0.83 (0.72 to 0.94) and 0.73 (0.60 to 0.86), respectively. Test duration of LCI1/30, LCI1/20 and LCI1/10 was significantly shorter compared with the test duration of LCI1/40 in people with CF (p<0.0001) equating to a 5%, 9% and 15% time saving, respectively. Conclusions: In this study, LCI1/20 was a repeatable and sensitive measure with equal diagnostic performance to LCI1/40. LCI1/20 was shorter, potentially offering a more feasible research and clinical measure.

Laterality as an indicator of emotional stress in ewes and lambs during a separation test

We assessed motor laterality in sheep to explore species-specific brain hemi-field dominance and how this could be affected by genetic or developmental factors. Further, we investigated whether directionality and strength of laterality could be linked to emotional stress in ewes and their lambs during partial separation. Forty-three ewes and their singleton lambs were scored on the (left/right) direction of turn in a y-maze to rejoin a conspecific (laterality test). Further, their behavioural response (i.e. time spent near the fence, vocalisations, and activity level) during forced separation by an open-mesh fence was assessed (separation test). Individual laterality was recorded for 44.2 % ewes (significant right bias) and 81.4 % lambs (equally biased to the left and the right). There was no significant association in side bias between dams and offspring. The Chi-squared test revealed a significant population bias for both groups (p < 0.05). Evolutionary adaptive strategies or stimuli-related visual laterality may provide explanation for this decision-making process. Absolute strength of laterality (irrespective of side) was high (Kolmogorov–Smirnov test, dams: D = 0.2; p < 0.001; lambs: D = 0.36, p < 0.0001). The Wilcoxon test showed that lateralised lambs and dams spent significantly more time near each other during separation than non-lateralised animals (p < 0.05), and that lateralised dams were also more active than non-lateralised ones. Arguably, the lateralised animals showed a greater attraction to their pair because they were more disturbed and thus required greater reassurance. The data show that measures of laterality offer a potential novel non-invasive indicator of separation stress.

Scoring Methods for Ordinal Multidimensional Forced-Choice Items

In most psychological tests and questionnaires, a test score is obtained by taking the sum of the item scores. In virtually all cases where the test or questionnaire contains multidimensional forced-choice items, this traditional scoring method is also applied. We argue that the summation of scores obtained with multidimensional forced-choice items produces uninterpretable test scores. Therefore, we propose three alternative scoring methods: a weak and a strict rank preserving scoring method, which both allow an ordinal interpretation of test scores; and a ratio preserving scoring method, which allows a proportional interpretation of test scores. Each proposed scoring method yields an index for each respondent indicating the degree to which the response pattern is inconsistent. Analysis of real data showed that with respect to rank preservation, the weak and strict rank preserving method resulted in lower inconsistency indices than the traditional scoring method; with respect to ratio preservation, the ratio preserving scoring method resulted in lower inconsistency indices than the traditional scoring method

Traditional scores versus IRT estimates on forced-choice tests based on a dominance model

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Analysis of cardiovascular system responses to forced vital capacity in COPD

CONTEXTUALIZAÇÃO: O teste de capacidade vital forçada (CVF) é rotineiramente realizado na avaliação da função pulmonar de pacientes com doença pulmonar obstrutiva crônica (DPOC). Entretanto, permanece pouco compreendida a influência do teste de CVF sobre o sistema cardiovascular de pacientes com DPOC. OBJETIVOS: Analisar o comportamento da frequência cardíaca (FC), pressão arterial (PA) e variabilidade da frequência cardíaca (VFC) no teste de CVF na DPOC. MÉTODOS: Dezenove homens com DPOC (72 ± 7 anos, no estágio de gravidade GOLD I=3, II=5, III=7 e IV=4 pacientes) realizaram a manobra de CVF e tiveram sua FC monitorada durante todo o exame, e a VFC analisada nos domínios do tempo (rMSSD) e da frequência (BF, AF e BF/AF) durante o repouso, antes e após a melhor manobra de CVF. A PA foi analisada no repouso, imediatamente ao final da manobra de CVF e 10 minutos após o término de todos os testes. RESULTADOS: Ao início da manobra de CVF, a FC reduziu (p<0,001) e, em seguida, aumentou progressivamente até o final do teste (p<0,001). Após término da manobra, a FC continuou a aumentar até atingir um pico (p<0,001) e depois caiu rapidamente a valores inferiores aos de repouso (p<0,001) e retornou ao seu valor basal. A PA e os índices da VFC não sofreram alterações nos períodos analisados. CONCLUSÃO: O teste de CVF influencia o comportamento da FC, sem alterar o seu controle autonômico, bem como a PA em pacientes com DPOC nos períodos analisados.