Are C-Reactive Protein Associated Genetic Variants Associated with Serum Levels and Retinal Markers of Microvascular Pathology in Asian Populations from Singapore?

Introduction:C-reactive protein (CRP) levels are associated with cardiovascular disease and systemic inflammation. We assessed whether CRP-associated loci were associated with serum CRP and retinal markers of microvascular disease, in Asian populations.Methods:Genome-wide association analysis (GWAS) for serum CRP was performed in East-Asian Chinese (N = 2,434) and Malays (N = 2,542) and South-Asian Indians (N = 2,538) from Singapore. Leveraging on GWAS data, we assessed, in silico, association levels among the Singaporean datasets for 22 recently identified CRP-associated loci. At loci where directional inconsistencies were observed, quantification of inter-ethnic linkage disequilibrium (LD) difference was determined. Next, we assessed association for a variant at CRP and retinal vessel traits [central retinal artery equivalent (CRAE) and central retinal vein equivalent (CRVE)] in a total of 24,132 subjects of East-Asian, South-Asian and European ancestry.Results:Serum CRP was associated with SNPs in/near APOE, CRP, HNF1A and LEPR (p-values ≤4.7×10-8) after meta-analysis of Singaporean populations. Using a candidate-SNP approach, we further replicated SNPs at 4 additional loci that had been recently identified to be associated with serum CRP (IL6R, GCKR, IL6 and IL1F10) (p-values ≤0.009), in the Singaporean datasets. SNPs from these 8 loci explained 4.05% of variance in serum CRP. Two SNPs (rs2847281 and rs6901250) were detected to be significant (p-value ≤0.036) but with opposite effect directions in the Singaporean populations as compared to original European studies. At these loci we did not detect significant inter-population LD differences. We further did not observe a significant association between CRP variant and CRVE or CRAE levels after meta-analysis of all Singaporean and European datasets (p-value >0.058).Conclusions:Common variants associated with serum CRP, first detected in primarily European studies, are also associated with CRP levels in East-Asian and South-Asian populations. We did not find a causal link between CRP and retinal measures of microvascular disease

Greenland ice sheet surface mass loss: recent developments in observation and modeling

Surface processes currently dominate Greenland ice sheet (GrIS) mass loss. We review recent developments in the observation and modelling of GrIS surface mass balance (SMB), published after the July 2012 deadline for the Fifth Assessment Report of the Intergovernmental Panel on Climate Change (IPCC AR5). Since IPCC AR5 our understanding of GrIS SMB has further improved, but new observational and model studies have also revealed that temporal and spatial variability of many processes are still poorly quantified and understood, e.g. bio-albedo, the formation of ice lenses and their impact on lateral meltwater transport, heterogeneous vertical meltwater transport (‘piping’), the impact of atmospheric circulation changes and mixed-phase clouds on the surface energy balance and the magnitude of turbulent heat exchange over rough ice surfaces. As a result, these processes are only schematically or not at all included in models that are currently used to assess and predict future GrIS surface mass loss

Equal antipyretic effectiveness of oral and rectal acetaminophen: a randomized controlled trial [ISRCTN11886401]

BACKGROUND: The antipyretic effectiveness of rectal versus oral acetaminophen is not well established. This study is designed to compare the antipyretic effectiveness of two rectal acetaminophen doses (15 mg/kg) and (35 mg/kg), to the standard oral dose of 15 mg/kg. METHODS: This is a randomized, double-dummy, double-blind study of 51 febrile children, receiving one of three regimens of a single acetaminophen dose: 15 mg/kg orally, 15 mg/kg rectally, or 35 mg/kg rectally. Rectal temperature was monitored at baseline and hourly for a total of six hours. The primary outcome of the study, time to maximum antipyresis, and the secondary outcome of time to temperature reduction by at least 1°C were analyzed by one-way ANOVA. Two-way ANOVA with repeated measures over time was used to compare the secondary outcome: change in temperature from baseline at times1, 2, 3, 4, 5, and 6 hours among the three groups. Intent-to-treat analysis was planned. RESULTS: No significant differences were found among the three groups in the time to maximum antipyresis (overall mean = 3.6 hours; 95% CI: 3.2–4.0), time to fever reduction by 1°C or the mean hourly temperature from baseline to 6 hours following dose administration. Hypothermia (temperature < 36.5°C) occurred in 11(21.6%) subjects, with the highest proportion being in the rectal high-dose group. CONCLUSION: Standard (15 mg/kg) oral, (15 mg/kg) rectal, and high-dose (35 mg/kg) rectal acetaminophen have similar antipyretic effectiveness

Hopefulness predicts resilience after hereditary colorectal cancer genetic testing: a prospective outcome trajectories study

<p>Abstract</p> <p>Background -</p> <p>Genetic testing for hereditary colorectal cancer (HCRC) had significant psychological consequences for test recipients. This prospective longitudinal study investigated the factors that predict psychological resilience in adults undergoing genetic testing for HCRC.</p> <p>Methods -</p> <p>A longitudinal study was carried out from April 2003 to August 2006 on Hong Kong Chinese HCRC family members who were recruited and offered genetic testing by the Hereditary Gastrointestinal Cancer Registry to determine psychological outcomes after genetic testing. Self-completed questionnaires were administered immediately before (pre-disclosure baseline) and 2 weeks, 4 months and 1 year after result disclosure. Using validated psychological inventories, the cognitive style of hope was measured at baseline, and the psychological distress of depression and anxiety was measured at all time points.</p> <p>Results -</p> <p>Of the 76 participating subjects, 71 individuals (43 men and 28 women; mean age 38.9 ± 9.2 years) from nine FAP and 24 HNPCC families completed the study, including 39 mutated gene carriers. Four patterns of outcome trajectories were created using established norms for the specified outcome measures of depression and anxiety. These included chronic dysfunction (13% and 8.7%), recovery (0% and 4.3%), delayed dysfunction (13% and 15.9%) and resilience (76.8% and 66.7%). Two logistic regression analyses were conducted using hope at baseline to predict resilience, with depression and anxiety employed as outcome indicators. Because of the small number of participants, the chronic dysfunction and delayed dysfunction groups were combined into a non-resilient group for comparison with the resilient group in all subsequent analysis. Because of low frequencies, participants exhibiting a recovery trajectory (n = 3 for anxiety and n = 0 for depression) were excluded from further analysis. Both regression equations were significant. Baseline hope was a significant predictor of a resilience outcome trajectory for depression (<it>B </it>= -0.24, <it>p </it>< 0.01 for depression); and anxiety (<it>B </it>= -0.11, <it>p </it>= 0.05 for anxiety).</p> <p>Conclusions -</p> <p>The current findings suggest that hopefulness may predict resilience after HCRC genetic testing in Hong Kong Chinese. Interventions to increase the level of hope may be beneficial to the psychological adjustment of CRC genetic testing recipients.</p

Model-Based Therapeutic Correction of Hypothalamic-Pituitary-Adrenal Axis Dysfunction

The hypothalamic-pituitary-adrenal (HPA) axis is a major system maintaining body homeostasis by regulating the neuroendocrine and sympathetic nervous systems as well modulating immune function. Recent work has shown that the complex dynamics of this system accommodate several stable steady states, one of which corresponds to the hypocortisol state observed in patients with chronic fatigue syndrome (CFS). At present these dynamics are not formally considered in the development of treatment strategies. Here we use model-based predictive control (MPC) methodology to estimate robust treatment courses for displacing the HPA axis from an abnormal hypocortisol steady state back to a healthy cortisol level. This approach was applied to a recent model of HPA axis dynamics incorporating glucocorticoid receptor kinetics. A candidate treatment that displays robust properties in the face of significant biological variability and measurement uncertainty requires that cortisol be further suppressed for a short period until adrenocorticotropic hormone levels exceed 30% of baseline. Treatment may then be discontinued, and the HPA axis will naturally progress to a stable attractor defined by normal hormone levels. Suppression of biologically available cortisol may be achieved through the use of binding proteins such as CBG and certain metabolizing enzymes, thus offering possible avenues for deployment in a clinical setting. Treatment strategies can therefore be designed that maximally exploit system dynamics to provide a robust response to treatment and ensure a positive outcome over a wide range of conditions. Perhaps most importantly, a treatment course involving further reduction in cortisol, even transient, is quite counterintuitive and challenges the conventional strategy of supplementing cortisol levels, an approach based on steady-state reasoning

Neurophysiologic effects of spinal manipulation in patients with chronic low back pain

<p>Abstract</p> <p>Background</p> <p>While there is growing evidence for the efficacy of SM to treat LBP, little is known on the mechanisms and physiologic effects of these treatments. Accordingly, the purpose of this study was to determine whether SM alters the amplitude of the motor evoked potential (MEP) or the short-latency stretch reflex of the erector spinae muscles, and whether these physiologic responses depend on whether SM causes an audible joint sound.</p> <p>Methods</p> <p>We used transcranial magnetic stimulation to elicit MEPs and electromechanical tapping to elicit short-latency stretch reflexes in 10 patients with chronic LBP and 10 asymptomatic controls. Neurophysiologic outcomes were measured before and after SM. Changes in MEP and stretch reflex amplitude were examined based on patient grouping (LBP vs. controls), and whether SM caused an audible joint sound.</p> <p>Results</p> <p>SM did not alter the erector spinae MEP amplitude in patients with LBP (0.80 ± 0.33 vs. 0.80 ± 0.30 μV) or in asymptomatic controls (0.56 ± 0.09 vs. 0.57 ± 0.06 μV). Similarly, SM did not alter the erector spinae stretch reflex amplitude in patients with LBP (0.66 ± 0.12 vs. 0.66 ± 0.15 μV) or in asymptomatic controls (0.60 ± 0.09 vs. 0.55 ± 0.08 μV). Interestingly, study participants exhibiting an audible response exhibited a 20% decrease in the stretch reflex (p < 0.05).</p> <p>Conclusions</p> <p>These findings suggest that a single SM treatment does not systematically alter corticospinal or stretch reflex excitability of the erector spinae muscles (when assessed ~ 10-minutes following SM); however, they do indicate that the stretch reflex is attenuated when SM causes an audible response. This finding provides insight into the mechanisms of SM, and suggests that SM that produces an audible response may mechanistically act to decrease the sensitivity of the muscle spindles and/or the various segmental sites of the Ia reflex pathway.</p

The Oslo Health Study: The impact of self-selection in a large, population-based survey

BACKGROUND: Research on health equity which mainly utilises population-based surveys, may be hampered by serious selection bias due to a considerable number of invitees declining to participate. Sufficient information from all the non-responders is rarely available to quantify this bias. Predictors of attendance, magnitude and direction of non-response bias in prevalence estimates and association measures, are investigated based on information from all 40 888 invitees to the Oslo Health Study. METHODS: The analyses were based on linkage between public registers in Statistics Norway and the Oslo Health Study, a population-based survey conducted in 2000/2001 inviting all citizens aged 30, 40, 45, 59–60 and 75–76 years. Attendance was 46%. Weighted analyses, logistic regression and sensitivity analyses are performed to evaluate possible selection bias. RESULTS: The response rate was positively associated with age, educational attendance, total income, female gender, married, born in a Western county, living in the outer city residential regions and not receiving disability benefit. However, self-rated health, smoking, BMI and mental health (HCSL) in the attendees differed only slightly from estimated prevalence values in the target population when weighted by the inverse of the probability of attendance. Observed values differed only moderately provided that the non-attending individuals differed from those attending by no more than 50%. Even though persons receiving disability benefit had lower attendance, the associations between disability and education, residential region and marital status were found to be unbiased. The association between country of birth and disability benefit was somewhat more evident among attendees. CONCLUSIONS: Self-selection according to sociodemographic variables had little impact on prevalence estimates. As indicated by disability benefit, unhealthy persons attended to a lesser degree than healthy individuals, but social inequality in health by different sociodemographic variables seemed unbiased. If anything we would expect an overestimation of the odds ratio of chronic disease among persons born in non-western countries

Cognitive and Tactile Factors Affecting Human Haptic Performance in Later Life

Background: Vision and haptics are the key modalities by which humans perceive objects and interact with their environment in a target-oriented manner. Both modalities share higher-order neural resources and the mechanisms required for object exploration. Compared to vision, the understanding of haptic information processing is still rudimentary. Although it is known that haptic performance, similar to many other skills, decreases in old age, the underlying mechanisms are not clear. It is yet to be determined to what extent this decrease is related to the age-related loss of tactile acuity or cognitive capacity. Methodology/Principal Findings: We investigated the haptic performance of 81 older adults by means of a cross-modal object recognition test. Additionally, we assessed the subjects ’ tactile acuity with an apparatus-based two-point discrimination paradigm, and their cognitive performance by means of the non-verbal Raven-Standard-Progressive matrices test. As expected, there was a significant age-related decline in performance on all 3 tests. With the exception of tactile acuity, this decline was found to be more distinct in female subjects. Correlation analyses revealed a strong relationship between haptic and cognitive performance for all subjects. Tactile performance, on the contrary, was only significantly correlated with male subjects ’ haptic performance. Conclusions: Haptic object recognition is a demanding task in old age, especially when it comes to the exploration o

KONTAKT© for Australian adolescents on the autism spectrum: protocol of a randomized control trial

BACKGROUND:Individuals diagnosed with autism spectrum disorder (ASD) experience impairing challenges in social communication and interaction across multiple contexts. While social skills group training (SSGT) has shown moderate effects on various sociability outcomes in ASD, there is a need for (1) replication of effects in additional clinical and cultural contexts, (2) designs that employ active control groups, (3) calculation of health economic benefits, (4) identification of the optimal training duration, and (5) measurement of individual goals and quality of life outcomes.METHOD/DESIGN:With the aim of investigating the efficacy and cost-effectiveness of a SSGT, KONTAKT©, a two-armed randomized control trial with adolescents aged 12-17 years (N = 90) with ASD and an intelligence quotient (IQ) of over 70 will be undertaken. Following stratification for centre and gender, participants will be randomly assigned to either KONTAKT© or to an active control group, a group-based cooking programme. Participants will attend both programmes in groups of 6-8 adolescents, over 16 one-and-a-half-hour sessions. The primary outcome examined is adolescent self-rated achievement of personally meaningful social goals as assessed via the Goal Attainment Scaling during an interview with a blinded clinician. Secondary outcomes include adolescent self-reported interpersonal efficacy, quality of life, social anxiety, loneliness, face emotion recognition performance and associated gaze behaviour, and parent proxy reports of autistic traits, quality of life, social functioning, and emotion recognition and expression. Cost-effectiveness will be investigated in relation to direct and indirect societal and healthcare costs.DISCUSSION:The primary outcomes of this study will be evidenced in the anticipated achievement of adolescents' personally meaningful social goals following participation in KONTAKT© as compared to the active control group. This design will enable rigorous evaluation of the efficacy of KONTAKT©, exercising control over the possibly confounding effect of exposure to a social context of peers with a diagnosis of ASD.TRIAL REGISTRATION:Australian New Zealand Clinical Trials Registry (ANZCTR). ACTRN12617001117303. Registered on 31 July 2017. anzctr.org.au ClinicalTrials.gov, NCT03294668. Registered on 22 September 2017. https://clinicaltrials.gov.</p