Co-occurrence and clustering of health conditions at age 11: cross-sectional findings from the Millennium Cohort Study

OBJECTIVES: To identify patterns of co-occurrence and clustering of 6 common adverse health conditions in 11-year-old children and explore differences by sociodemographic factors. DESIGN: Nationally representative prospective cohort study. SETTING: Children born in the UK between 2000 and 2002. PARTICIPANTS: 11 399 11-year-old singleton children for whom data on all 6 health conditions and sociodemographic information were available (complete cases). MAIN OUTCOME MEASURES: Prevalence, co-occurrence and clustering of 6 common health conditions: wheeze; eczema; long-standing illness (excluding wheeze and eczema); injury; socioemotional difficulties (measured using Strengths and Difficulties Questionnaire) and unfavourable weight (thin/overweight/obese vs normal). RESULTS: 42.4% of children had 2 or more adverse health conditions (co-occurrence). Co-occurrence was more common in boys and children from lower income households. Latent class analysis identified 6 classes: 'normative' (57.4%): 'atopic burdened' (14.0%); 'socioemotional burdened' (11.0%); 'unfavourable weight/injury' (7.7%); 'eczema/injury' (6.0%) and 'eczema/unfavourable weight' (3.9%). As with co-occurrence, class membership differed by sociodemographic factors: boys, children of mothers with lower educational attainment and children from lower income households were more likely to be in the 'socioemotional burdened' class. Children of mothers with higher educational attainment were more likely to be in the 'normative' and 'eczema/unfavourable weight' classes. CONCLUSIONS: Co-occurrence of adverse health conditions at age 11 is common and is associated with adverse socioeconomic circumstances. Holistic, child focused care, particularly in boys and those in lower income groups, may help to prevent and reduce co-occurrence in later childhood and adolescence

Lactones and Flavonoids isolated from the Leaves of Globimetula braunii

The dried powdered leaves of Globimetula braunii (Engler) Van Tiegh were effectively extracted by the cold extraction method. Purification of the EtOAc-soluble and MeOH-soluble extracts successfully yielded two lactones namely (R)-6-[(S)-2-hydroxy-4-(4-hydroxyphenyl)butyl]–5,6-dihydropyran-2-one (dodoneine) 1 and (1R,5S,7S)-[2-(4-hydroxyphenyl)ethyl]-2,6-dioxabicyclo[3.3.1]-nonan-3-one (2), together with five flavonoids namely quercetin 3, (+)-catechin 4, quercitrin 5, rutin 6 and avicularin 7. Their structures were established by spectroscopic means, and the absolute configuration of compound 1 was confirmed by X-ray analysis

An automated search for transiting exocomets

This paper discusses an algorithm for detecting single transits in photometric time-series data. Specifically, we aim to identify asymmetric transits with ingress that is more rapid than egress, as expected for cometary bodies with a significant tail. The algorithm is automated, so can be applied to large samples and only a relatively small number of events need to be manually vetted. We applied this algorithm to all long cadence light curves from the Kepler mission, finding 16 candidate transits with significant asymmetry, 11 of which were found to be artefacts or symmetric transits after manual inspection. Of the 5 remaining events, four are the 0.1% depth events previously identified for KIC 3542116 and 11084727. We identify HD 182952 (KIC 8027456) as a third system showing a potential comet transit. All three stars showing these events have H-R diagram locations consistent with $\sim$100Myr-old open cluster stars, as might be expected given that cometary source regions deplete with age, and giving credence to the comet hypothesis. If these events are part of the same population of events as seen for KIC 8462852, the small increase in detections at 0.1% depth compared to 10% depth suggests that future work should consider whether the distribution is naturally flat, or if comets with symmetric transits in this depth range remain undiscovered. Future searches relying on asymmetry should be more successful if they focus on larger samples and young stars, rather than digging further into the noise.GMK is supported by the Royal Society as a Royal Society University Research Fellow. STH acknowledges support from an STFC Consolidated Grant

Bat Eyes Have Ultraviolet-Sensitive Cone Photoreceptors

Mammalian retinae have rod photoreceptors for night vision and cone photoreceptors for daylight and colour vision. For colour discrimination, most mammals possess two cone populations with two visual pigments (opsins) that have absorption maxima at short wavelengths (blue or ultraviolet light) and long wavelengths (green or red light). Microchiropteran bats, which use echolocation to navigate and forage in complete darkness, have long been considered to have pure rod retinae. Here we use opsin immunohistochemistry to show that two phyllostomid microbats, Glossophaga soricina and Carollia perspicillata, possess a significant population of cones and express two cone opsins, a shortwave-sensitive (S) opsin and a longwave-sensitive (L) opsin. A substantial population of cones expresses S opsin exclusively, whereas the other cones mostly coexpress L and S opsin. S opsin gene analysis suggests ultraviolet (UV, wavelengths <400 nm) sensitivity, and corneal electroretinogram recordings reveal an elevated sensitivity to UV light which is mediated by an S cone visual pigment. Therefore bats have retained the ancestral UV tuning of the S cone pigment. We conclude that bats have the prerequisite for daylight vision, dichromatic colour vision, and UV vision. For bats, the UV-sensitive cones may be advantageous for visual orientation at twilight, predator avoidance, and detection of UV-reflecting flowers for those that feed on nectar

Ethical and Scientific Considerations Regarding Animal Testing and Research

In 1959, William Russell and Rex Burch published the seminal book, The Principles of Humane Experimental Technique, which emphasized reduction, refinement, and replacement of animal use, principles which have since been referred to as the ‘‘3 Rs’’. These principles encouraged researchers to work to reduce the number of animals used in experiments to the minimum considered necessary, refine or limit the pain and distress to which animals are exposed, and replace the use of animals with non-animal alternatives when possible. Despite the attention brought to this issue by Russell and Burch and since, the number of animals used in research and testing has continued to increase, raising serious ethical and scientific issues. Further, while the ‘‘3 Rs’’ capture crucially important concepts, they do not adequately reflect the substantial developments in our new knowledge about the cognitive and emotional capabilities of animals, the individual interests of animals, or an updated understanding of potential harms associated with animal research. This Overview provides a brief summary of the ethical and scientific considerations regarding the use of animals in research and testing, and accompanies a Collection entitled Animals, Research, and Alternatives: Measuring Progress 50 Years Later, which aims to spur ethical and scientific advancement

New technologies for examining neuronal ensembles in drug addiction and fear

Correlational data suggest that learned associations are encoded within neuronal ensembles. However, it has been difficult to prove that neuronal ensembles mediate learned behaviours because traditional pharmacological and lesion methods, and even newer cell type-specific methods, affect both activated and non-activated neurons. Additionally, previous studies on synaptic and molecular alterations induced by learning did not distinguish between behaviourally activated and non-activated neurons. Here, we describe three new approaches—Daun02 inactivation, FACS sorting of activated neurons and c-fos-GFP transgenic rats — that have been used to selectively target and study activated neuronal ensembles in models of conditioned drug effects and relapse. We also describe two new tools — c-fos-tTA mice and inactivation of CREB-overexpressing neurons — that have been used to study the role of neuronal ensembles in conditioned fear

The PINE study: rationale and design of a randomised comparison of epidural injection of local anaesthetics and steroids versus care-as-usual to prevent postherpetic neuralgia in the elderly [ISRCTN32866390]

BACKGROUND: Postherpetic neuralgia (PHN) is by far the most common complication of herpes zoster (HZ) and one of the most intractable pain disorders. Since PHN is seen most often in the elderly, the number of patients with this disorder is expected to increase in our ageing society. PHN may last for months to years and has a high impact on the quality of life. The results of PHN treatment are rather disappointing. Epidural injection of local anaesthetics and steroids in the acute phase of HZ is a promising therapy for the prevention of PHN. Since randomised trials on the effectiveness of this intervention are lacking, the PINE (Prevention by epidural Injection of postherpetic Neuralgia in the Elderly) study was set up. The PINE study compares the effectiveness and cost-effectiveness of a single epidural injection of local anaesthetics and steroids during the acute phase of HZ with that of care-as-usual (i.e. antivirals and analgesics) in preventing PHN in elderly patients. METHODS / DESIGN: The PINE study is an open, multicenter clinical trial in which 550 elderly (age ≥ 50 yr.) patients who consult their general practitioner in the acute phase of HZ (rash < 7 days) are randomised to one of the treatment groups. The primary clinical endpoint is the presence of HZ-related pain one month after the onset of the rash. Secondary endpoints include duration and severity of pain, re-interventions aiming to treat the existing pain, side effects, quality of life, and cost-effectiveness. CONCLUSION: The PINE study is aimed to quantify the (cost-) effectiveness of a single epidural injection during the acute phase of HZ on the prevention of PHN

Aortic stiffness in aortic stenosis assessed by cardiovascular MRI: a comparison between bicuspid and tricuspid valves

Objectives To compare aortic size and stiffness parameters on MRI between bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV) patients with aortic stenosis (AS). Methods MRI was performed in 174 patients with asymptomatic moderate-severe AS (mean AVAI 0.57 ± 0.14 cm2/m2) and 23 controls on 3T scanners. Valve morphology was available/analysable in 169 patients: 63 BAV (41 type-I, 22 type-II) and 106 TAV. Aortic cross-sectional areas were measured at the level of the pulmonary artery bifurcation. The ascending and descending aorta (AA, DA) distensibility, and pulse wave velocity (PWV) around the aortic arch were calculated. Results The AA and DA areas were lower in the controls, with no difference in DA distensibility or PWV, but slightly lower AA distensibility than in the patient group. With increasing age, there was a decrease in distensibility and an increase in PWV. After correcting for age, the AA maximum cross-sectional area was higher in bicuspid vs. tricuspid patients (12.97 [11.10, 15.59] vs. 10.06 [8.57, 12.04] cm2, p < 0.001), but there were no significant differences in AA distensibility (p = 0.099), DA distensibility (p = 0.498) or PWV (p = 0.235). Patients with BAV type-II valves demonstrated a significantly higher AA distensibility and lower PWV compared to type-I, despite a trend towards higher AA area. Conclusions In patients with significant AS, BAV patients do not have increased aortic stiffness compared to those with TAV despite increased ascending aortic dimensions. Those with type-II BAV have less aortic stiffness despite greater dimensions. These results demonstrate a dissociation between aortic dilatation and stiffness and suggest that altered flow patterns may play a role. Key Points • Both cellular abnormalities secondary to genetic differences and abnormal flow patterns have been implicated in the pathophysiology of aortic dilatation and increased vascular complications associated with bicuspid aortic valves (BAV). • We demonstrate an increased ascending aortic size in patients with BAV and moderate to severe AS compared to TAV and controls, but no difference in aortic stiffness parameters, therefore suggesting a dissociation between dilatation and stiffness. • Sub-group analysis showed greater aortic size but lower stiffness parameters in those with BAV type-II AS compared to BAV type-I

Vision Impairs the Abilities of Bats to Avoid Colliding with Stationary Obstacles

Background: Free-flying insectivorous bats occasionally collide with stationary objects they should easily detect by echolocation and avoid. Collisions often occur with lighted objects, suggesting ambient light may deleteriously affect obstacle avoidance capabilities. We tested the hypothesis that free-flying bats may orient by vision when they collide with some obstacles. We additionally tested whether acoustic distractions, such as ‘‘distress calls’ ’ of other bats, contributed to probabilities of collision. Methodology/Principal Findings: To investigate the role of visual cues in the collisions of free-flying little brown bats (Myotis lucifugus) with stationary objects, we set up obstacles in an area of high bat traffic during swarming. We used combinations of light intensities and visually dissimilar obstacles to verify that bats orient by vision. In early August, bats collided more often in the light than the dark, and probabilities of collision varied with the visibility of obstacles. However, the probabilities of collisions altered in mid to late August, coincident with the start of behavioural, hormonal, and physiological changes occurring during swarming and mating. Distress calls did not distract bats and increase the incidence of collisions. Conclusions/Significance: Our findings indicate that visual cues are more important for free-flying bats than previously recognized, suggesting integration of multi-sensory modalities during orientation. Furthermore, our study highlight

Ce-Duox1/BLI-3 Generated Reactive Oxygen Species Trigger Protective SKN-1 Activity via p38 MAPK Signaling during Infection in C. elegans

Infected animals will produce reactive oxygen species (ROS) and other inflammatory molecules that help fight pathogens, but can inadvertently damage host tissue. Therefore specific responses, which protect and repair against the collateral damage caused by the immune response, are critical for successfully surviving pathogen attack. We previously demonstrated that ROS are generated during infection in the model host Caenorhabditis elegans by the dual oxidase Ce-Duox1/BLI-3. Herein, an important connection between ROS generation by Ce-Duox1/BLI-3 and upregulation of a protective transcriptional response by SKN-1 is established in the context of infection. SKN-1 is an ortholog of the mammalian Nrf transcription factors and has previously been documented to promote survival, following oxidative stress, by upregulating genes involved in the detoxification of ROS and other reactive compounds. Using qRT-PCR, transcriptional reporter fusions, and a translational fusion, SKN-1 is shown to become highly active in the C. elegans intestine upon exposure to the human bacterial pathogens, Enterococcus faecalis and Pseudomonas aeruginosa. Activation is dependent on the overall pathogenicity of the bacterium, demonstrated by a weakened response observed in attenuated mutants of these pathogens. Previous work demonstrated a role for p38 MAPK signaling both in pathogen resistance and in activating SKN-1 upon exposure to chemically induced oxidative stress. We show that NSY-1, SEK-1 and PMK-1 are also required for SKN-1 activity during infection. Evidence is also presented that the ROS produced by Ce-Duox1/BLI-3 is the source of SKN-1 activation via p38 MAPK signaling during infection. Finally, for the first time, SKN-1 activity is shown to be protective during infection; loss of skn-1 decreases resistance, whereas increasing SKN-1 activity augments resistance to pathogen. Overall, a model is presented in which ROS generation by Ce-Duox1/BLI-3 activates a protective SKN-1 response via p38 MAPK signaling