The effects and interactions of GABAergic and dopaminergic agents in the prevention of form deprivation myopia by brief periods of normal vision

Intravitreal injections of GABA antagonists, dopamine agonists and brief periods of normal vision have been shown separately to inhibit form-deprivation myopia (FDM). Our study had three aims: (i) establish whether GABAergic agents modify the myopia protective effect of normal vision, (ii) investigate the receptor sub-type specificity of any observed effect, and (iii) consider an interaction with the dopamine (DA) system. Prior to the period of normal vision GABAergic agents were applied either (i) individually, (ii) in combination with other GABAergic agents (an agonist with an antagonist), or (iii) in combination with DA agonists and antagonists. Water injections were given to groups not receiving drug treatments so that all experimental eyes received intravitreal injections. As shown previously, constant form-deprivation resulted in high myopia and when diffusers were removed for 2 h per day the period of normal vision greatly reduced the FDM that developed. GABA agonists inhibited the protective effect of normal vision whereas antagonists had the opposite effect. GABAA/C agonists and D2 DA antagonists when used in combination were additive in suppressing the protective effect of normal vision. A D2 DA agonist restored some of the protective effect of normal vision that was inhibited by a GABA agonist (muscimol). The protective effect of normal vision against form-deprivation is modifiable by both the GABAergic and DAergic pathways.

Towards persistent visual navigation using SMART

In this paper, we present SMART (Sequence Matching Across Route Traversals): a vision- based place recognition system that uses whole image matching techniques and odometry information to improve the precision-recall performance, latency and general applicability of the SeqSLAM algorithm. We evaluate the system’s performance on challenging day and night journeys over several kilometres at widely varying vehicle velocities from 0 to 60 km/h, compare performance to the current state-of- the-art SeqSLAM algorithm, and provide parameter studies that evaluate the effectiveness of each system component. Using 30-metre sequences, SMART achieves place recognition performance of 81% recall at 100% precision, outperforming SeqSLAM, and is robust to significant degradations in odometry.

Persistent robot tasking for environmental monitoring through crowd-sourcing

Persistent monitoring of the ocean is not optimally accomplished by repeatedly executing a fixed path in a fixed location. The ocean is dynamic, and so should the executed paths to monitor and observe it. An open question merging autonomy and optimal sampling is how and when to alter a path/decision, yet achieve desired science objectives. Additionally, many marine robotic deployments can last multiple weeks to months; making it very difficult for individuals to continuously monitor and retask them as needed. This problem becomes increasingly more complex when multiple platforms are operating simultaneously. There is a need for monitoring and adaptation of the robotic fleet via teams of scientists working in shifts; crowds are ideal for this task. In this paper, we present a novel application of crowd-sourcing to extend the autonomy of persistent-monitoring vehicles to enable nonrepetitious sampling over long periods of time. We present a framework that enables the control of a marine robot by anybody with an internet-enabled device. Voters are provided current vehicle location, gathered science data and predicted ocean features through the associated decision support system. Results are included from a simulated implementation of our system on a Wave Glider operating in Monterey Bay with the science objective to maximize the sum of observed nitrate values collected.

Escape from apoptosis after prolonged serum deprivation is associated with the regulation of the mitochondrial death pathway by Bcl-x(l)

Bcl-x(l) and Bax play important roles in the regulation of apoptosis. This study investigated the involvement of the mitochondrial death pathway and the role of Bcl-x(l) and Bax in the escape from apoptosis after prolonged serum deprivation in Madin-Darby canine kidney (MDCK) cells. Low level apoptosis and basal activity of the mitochondrial death pathway were detectable in normal cell growth. In serum deprivation, mitosis was partially suppressed, and the mitochondrial activity was stimulated. The level of apoptosis continuously rose over 48 h. This rise was concomitant with the increasing presence of cytochrome c in cytosol. However, both apoptosis and cytosolic cytochrome c fell dramatically at 72 h. Elevation of whole cell Bcl-x(l) and redistribution of Bcl-x(l) protein from cytosol to the membrane at 48 h and 72 h was observed. Redistribution of Bax protein from the membrane to cytosol occurred at 24 h, and remained steady to 72 h. Bax/Bcl-x(l) coimmunoprecipitation by anti-Bax antibody showed reduced Bax/Bcl-x(l) interaction at the membrane at 72 h, but not at 24 or 48 h. These results suggest that apoptosis upon serum withdrawal results from the leakage of cytochrome c to cytosol. Amelioration of the leakage of cytochrome c and apoptosis requires not only the increase of Bcl-x(l)/Bax ratio, but also the release of Bcl-x(l) from Bax at the membrane.

A preliminary study on assessing body burden of persistent organic pollutants (POPs) in infants through analysis of faeces

Most persistent organic pollutants (POPs) like polychlorinated biphenyls (PCBs), a range of polybrominated diphenyl ethers (PBDEs) and organochlorine pesticides (OCPs) are readily absorbed (via the ingestion and inhalation) and accumulate in fatty tissue, including adipose tissue and human milk [1]. Health effects related to exposure to these chemicals may include neurological effects, altered functioning of the nervous system and/or endocrine disruption [2-4]. The burden of environmental disease is recognized as much higher for children than adults, especially in young children under 5 years of age worldwide [5]. There is increased concern regarding the environmental impact on the health of children who have been disproportionately affected by environmental problems. For example they may be subjected to relatively higher exposure, have greater physiological susceptibility and/or suffer more extreme consequences due to growth [6-9]. It is therefore worthwhile to assess the correlation between burden of disease and exposure to xenobiotic chemical pollutants like POPs. Such assessment may provide guidance for legislative changes regarding chemical bans and give reliable advice to parents including lactating mothers.

Direct Detection of a Persistent Carbonyloxyl Radical in the Gas Phase

Long lived: Carbonyloxyl radicals (RCO2 .) are reactive intermediates that play key roles in initiating polymerization reactions. This reactivity also makes their direct observation difficult. For the first time a persistent organic RCO2 . radical is detected in the gas phase, its extraordinary longevity is attributed to the high barrier towards fragmentation owing to the endothermicity of the decarboxylation products. Grant Numbers ARC/DP0986738, ARC/DP120102922, ARC/DE120100467

Host-pathogen checkpoints and population bottlenecks in persistent and intracellular uropathogenic Escherichia coli bladder infection

Bladder infections affect millions of people yearly, and recurrent symptomatic infections (cystitis) are very common. The rapid increase in infections caused by multidrug-resistant uropathogens threatens to make recurrent cystitis an increasingly troubling public health concern. Uropathogenic Escherichia coli (UPEC) cause the vast majority of bladder infections. Upon entry into the lower urinary tract, UPEC face obstacles to colonization that constitute population bottlenecks, reducing diversity, and selecting for fit clones. A critical mucosal barrier to bladder infection is the epithelium (urothelium). UPEC bypass this barrier when they invade urothelial cells and form intracellular bacterial communities (IBCs), a process which requires type 1 pili. IBCs are transient in nature, occurring primarily during acute infection. Chronic bladder infection is common and can be either latent, in the form of the quiescent intracellular reservoir (QIR), or active, in the form of asymptomatic bacteriuria (ASB/ABU) or chronic cystitis. In mice, the fate of bladder infection, QIR, ASB, or chronic cystitis, is determined within the first 24 h of infection and constitutes a putative host–pathogen mucosal checkpoint that contributes to susceptibility to recurrent cystitis. Knowledge of these checkpoints and bottlenecks is critical for our understanding of bladder infection and efforts to devise novel therapeutic strategies.

The effect of sleep deprivation on BOLD activity elicited by a divided attention task

Sleep loss, widespread in today’s society and associated with a number of clinical conditions, has a detrimental effect on a variety of cognitive domains including attention. This study examined the sequelae of sleep deprivation upon BOLD fMRI activation during divided attention. Twelve healthy males completed two randomized sessions; one after 27 h of sleep deprivation and one after a normal night of sleep. During each session, BOLD fMRI was measured while subjects completed a cross-modal divided attention task (visual and auditory). After normal sleep, increased BOLD activation was observed bilaterally in the superior frontal gyrus and the inferior parietal lobe during divided attention performance. Subjects reported feeling significantly more sleepy in the sleep deprivation session, and there was a trend towards poorer divided attention task performance. Sleep deprivation led to a down regulation of activation in the left superior frontal gyrus, possibly reflecting an attenuation of top-down control mechanisms on the attentional system. These findings have implications for understanding the neural correlates of divided attention and the neurofunctional changes that occur in individuals who are sleep deprived.

Population variation in biomonitoring data for persistent organic pollutants (POPs) : an examination of multiple population-based datasets for application to Australian pooled biomonitoring data

Background Australian national biomonitoring for persistent organic pollutants (POPs) relies upon age-specific pooled serum samples to characterize central tendencies of concentrations but does not provide estimates of upper bound concentrations. This analysis compares population variation from biomonitoring datasets from the US, Canada, Germany, Spain, and Belgium to identify and test patterns potentially useful for estimating population upper bound reference values for the Australian population. Methods Arithmetic means and the ratio of the 95th percentile to the arithmetic mean (P95:mean) were assessed by survey for defined age subgroups for three polychlorinated biphenyls (PCBs 138, 153, and 180), hexachlorobenzene (HCB), p,p-dichlorodiphenyldichloroethylene (DDE), 2,2′,4,4′ tetrabrominated diphenylether (PBDE 47), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS). Results Arithmetic mean concentrations of each analyte varied widely across surveys and age groups. However, P95:mean ratios differed to a limited extent, with no systematic variation across ages. The average P95:mean ratios were 2.2 for the three PCBs and HCB; 3.0 for DDE; 2.0 and 2.3 for PFOA and PFOS, respectively. The P95:mean ratio for PBDE 47 was more variable among age groups, ranging from 2.7 to 4.8. The average P95:mean ratios accurately estimated age group-specific P95s in the Flemish Environmental Health Survey II and were used to estimate the P95s for the Australian population by age group from the pooled biomonitoring data. Conclusions Similar population variation patterns for POPs were observed across multiple surveys, even when absolute concentrations differed widely. These patterns can be used to estimate population upper bounds when only pooled sampling data are available.

The influence of psychosocial factors on expectations and persistent symptom report after mild traumatic brain injury

This thesis examines how psychosocial factors influence the report of persistent symptoms after mild traumatic brain injury. Using quasi-experimental methods, the research program demonstrates how factors unrelated to trauma-induced physiological brain damage can contribute to persistent symptoms after a mild traumatic brain injury. The results of this thesis highlight the possibility that outcome from mild traumatic brain injury could be improved by targeting psychosocial factors.

Inhibition of form-deprivation myopia by a GABAAOr receptor antagonist, (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA), in guinea pigs

Purpose To investigate the effects of the relatively selective GABAAOr receptor antagonist (1,2,5,6-tetrahydropyridin-4-yl) methylphosphinic acid (TPMPA) on form-deprivation myopia (FDM) in guinea pigs. Methods A diffuser was applied monocularly to 30 guinea pigs from day 10 to 21. The animals were randomized to one of five treatment groups. The deprived eye received daily sub-conjunctival injections of 100 μl TPMPA at a concentration of (i) 0.03 %, ( ii) 0.3 %, or (iii) 1 %, a fourth group (iv) received saline injections, and another (v) no injections. The fellow eye was left untreated. An additional group received no treatment to either eye. Prior to and at the end of the treatment period, refraction and ocular biometry were performed. Results Visual deprivation produced relative myopia in all groups (treated versus untreated eyes, P < 0.05). The amount of myopia was significantly affected by the drug treatment (one-way ANOVA, P < 0.0001); myopia was less in deprived eyes receiving either 0.3 % or 1 % TPMPA (saline = −4.38 ± 0.57D, 0.3 % TPMPA = −3.00 ± 0.48D, P < 0.01; 1 % TPMPA = −0.88 ± 0.51D, P < 0.001). The degree of axial elongation was correspondingly less (saline = 0.13 ± 0.02 mm, 0.3 % TPMPA = 0.09 ± 0.01 mm, P < 0.01, 1 % TPMPA = 0.02 ± 0.01 mm, P < 0.001) as was the VC elongation (saline = 0.08 ± 0.01 mm, 0.3 % TPMPA = 0.05 ± 0.01 mm, P < 0.01, 1 % TPMPA = 0.01 ± 0.01 mm; P < 0.001). ACD and LT were not affected (one-way ANOVA, P > 0.05). One percent TPMPA was more effective at inhibiting myopia than 0.3 % (P < 0.01), and 0.03 % did not appreciably inhibit the myopia (0.03 % TPMPA versus saline, P > 0.05). Conclusions Sub-conjunctival injections of TPMPA inhibit FDM in guinea pig models in a dose-dependent manner.

The effect of deprivation and disease-severity on malnutrition risk in chronic obstructive pulmonary disease (COPD)

Deprivation has previously been shown to be an independent risk factor for the high prevalence of malnutrition observed in COPD (Collins et al., 2010). It has been suggested the socioeconomic gradient observed in COPD is greater than any other chronic disease (Prescott & Vestbo, 1999). The current study aimed to examine the infl uence of disease severity and social deprivation on malnutrition risk in outpatients with COPD. 424 COPD outpatients were screened using the ‘Malnutrition Universal Screening Tool’ (‘MUST’). COPD disease severity was recorded in accordance with the GOLD criteria and deprivation was established according to the patient’s geographical location (postcode) at the time of nutritional screening using the UK Government’s Index of Multiple Deprivation (IMD). IMD ranks postcodes from 1 (most deprived) to 32,482 (least deprived). Disease severity was posi tively associated with an increased prevalence of malnutrition risk (p < 0.001) both within and between groups, whilst rank IMD was negatively associated with malnutrition (p = 0.020), i.e. those residing in less deprived areas were less likely to be malnourished. Within each category of disease severity the prevalence of malnutrition was two-fold greater in those residing in the most deprived areas compared to those residing in the least deprived areas. This study suggests that deprivation and disease severity are independent risk factors for malnutrition in COPD both contributing to the widely variable prevalence of malnutrition. Consideration of these issues could assist with the targeted nutritional management of these patients.

Visual place recognition for persistent robot navigation in changing environments

This thesis demonstrates that robots can learn about how the world changes, and can use this information to recognise where they are, even when the appearance of the environment has changed a great deal. The ability to localise in highly dynamic environments using vision only is a key tool for achieving long-term, autonomous navigation in unstructured outdoor environments. The proposed learning algorithms are designed to be unsupervised, and can be generated by the robot online in response to its observations of the world, without requiring information from a human operator or other external source.

A phase II trial of brivanib in recurrent or persistent endometrial cancer: An NRG oncology/gynecologic oncology group study

PURPOSE Brivanib, an oral, multi-targeted tyrosine kinase inhibitor with activity against vascular endothelial growth factor (VEGF) and fibroblast growth factor receptor (FGFR) was investigated as a single agent in a phase II trial to assess the activity and tolerability in recurrent or persistent endometrial cancer (EMC). PATIENTS AND METHODS Eligible patients had persistent or recurrent EMC after receiving one to two prior cytotoxic regimens, measurable disease, and performance status of ≤2. Treatment consisted of brivanib 800 mg orally every day until disease progression or prohibitive toxicity. Primary endpoints were progression-free survival (PFS) at six months and objective tumor response. Expression of multiple angiogenic proteins and FGFR2 mutation status was assessed. RESULTS Forty-five patients were enrolled. Forty-three patients were eligible and evaluable. Median age was 64 years. Twenty-four patients (55.8%) received prior radiation. Median number of cycles was two (range 1-24). No GI perforations but one rectal fistula were seen. Nine patients had grade 3 hypertension, with one experiencing grade 4 confusion. Eight patients (18.6%; 90% CI 9.6%-31.7%) had responses (one CR and seven PRs), and 13 patients (30.2%; 90% CI 18.9%-43.9%) were PFS at six months. Median PFS and overall survival (OS) were 3.3 and 10.7 months, respectively. When modeled jointly, VEGF and angiopoietin-2 expression may diametrically predict PFS. Estrogen receptor-α (ER) expression was positively correlated with OS. CONCLUSION Brivanib is reasonably well tolerated and worthy of further investigation based on PFS at six months in recurrent or persistent EMC.