Computational model of functional connectivity distance predicts neural alterations

Modelling brain signals play a crucial role in analysing the brain’s architecture, functions and associated disorders. This paper aims to model the brain topology by exploring the relationship between complex neural correlates and functional connectivity-based distances. A computational model inspired by multivariate visibility graphs (VG) algorithm and Euclidean distance is proposed to analyse quantitatively the brain network data. When applied to resting-state EEG signals from three groups (typically developing (TD), autism spectrum disorder (ASD), and epilepsy (E)), the network topological properties (e.g., global efficiency, modularity, small-worldness, and betweenness centrality) demonstrate variations in connectivity distance probabilities among brain regions (e.g., frontal, temporal, parietal, and occipital) via the model’s delay and connection distance parameters. The results showed a higher delay and skewed distribution towards short functional connections in ASD than in TD, while a lower delay in E than in ASD and TD. Additionally, ASD had more short-distance connections, while E had more long-distance connections compared to TD. ASD and E significantly overlapped over short-distance connections within the temporal lobe. In summary, the proposed model illustrates that delay parameter and connection distance obtained from brain network data have the potential to objectively identify and associate co-occurring neurological conditions (e.g., ASD and E

Association between diagnosis code expansion and changes in 30-day risk-adjusted outcomes for cardiovascular diseases

BACKGROUND In January 2011, Centers for Medicare and Medicaid Services expanded the number of inpatient diagnosis codes from 9 to 25, which may influence comorbidity counts and risk-adjusted outcome rates for studies spanning January 2011. This study examines the association between (1) limiting versus not limiting diagnosis codes after 2011, (2) using inpatient-only versus inpatient and outpatient data, and (3) using logistic regression versus the Centers for Medicare and Medicaid Services risk-standardized methodology and changes in risk-adjusted outcomes. METHODS AND RESULTS Using 100% Medicare inpatient and outpatient files between January 2009 and December 2013, we created 2 cohorts of fee-for-service beneficiaries aged ≥65 years. The acute myocardial infarction cohort and the heart failure cohort had 578 728 and 1 595 069 hospitalizations, respectively. We calculate comorbidities using (1) inpatient-only limited diagnoses, (2) inpatient-only unlimited diagnoses, (3) inpatient and outpatient limited diagnoses, and (4) inpatient and outpatient unlimited diagnoses. Across both cohorts

A novel, rapid method to compare the therapeutic windows of oral anticoagulants using the Hill coefficient

A central challenge in designing and administering effective anticoagulants is achieving the proper therapeutic window and dosage for each patient. The Hill coefficient, nH, which measures the steepness of a dose-response relationship, may be a useful gauge of this therapeutic window. We sought to measure the Hill coefficient of available anticoagulants to gain insight into their therapeutic windows. We used a simple fluorometric in vitro assay to determine clotting activity in platelet poor plasma after exposure to various concentrations of anticoagulants. The Hill coefficient for argatroban was the lowest, at 1.7±0.2 (95% confidence interval, CI), and the Hill coefficient for fondaparinux was the highest, at 4.5±1.3 (95% CI). Thus, doubling the dose of fondaparinux from its IC50 would decrease coagulation activity by nearly a half, whereas doubling the dose of argatroban from its IC50 would decrease coagulation activity by merely one quarter. These results show a significant variation among the Hill coefficients, suggesting a similar variation in therapeutic windows among anticoagulants in our assay

Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials

BACKGROUND: Randomized controlled trials (RCTs) suggest that supplementation with omega-3 polyunsaturated fatty acids (n-3PUFAs) may favourably modify cardiometabolic biomarkers in type 2 diabetes (T2DM). Previous meta-analyses are limited by insufficient sample sizes and omission of meta-regression techniques, and a large number of RCTs have subsequently been published since the last comprehensive meta-analysis. Updated information regarding the impact of dosage, duration or an interaction between these two factors is therefore warranted. The objective was to comprehensively assess the effect of n-3PUFAs supplementation on cardiometabolic biomarkers including lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control, in people with T2DM, and identify whether treatment dosage, duration or an interaction thereof modify these effects. METHODS: Databases including PubMed and MEDLINE were searched until 13th July 2017 for RCTs investigating the effect of n-3PUFAs supplementation on lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control. Data were pooled using random-effects meta-analysis and presented as standardised mean difference (Hedges g) with 95% confidence intervals (95% CI). Meta-regression analysis was performed to investigate the effects of duration of supplementation and total dosage of n-3PUFAs as moderator variables where appropriate. RESULTS: A total of 45 RCTs were identified, involving 2674 people with T2DM. n-3PUFAs supplementation was associated with significant reductions in LDL [ES: - 0.10, (95% CI - 0.17, - 0.03); p = 0.007], VLDL (ES: - 0.26 (- 0.51, - 0.01); p = 0.044], triglycerides (ES: - 0.39 (- 0.55, - 0.24; p ≤ 0.001] and HbA1c (ES: - 0.27 (- 0.48, - 0.06); p = 0.010]. Moreover, n-3PUFAs supplementation was associated with reduction in plasma levels of TNF-α [ES: - 0.59 (- 1.17, - 0.01); p = 0.045] and IL-6 (ES: - 1.67 (- 3.14, - 0.20); p = 0.026]. All other lipid markers, indices of glycaemic control, inflammatory parameters, and blood pressure remained unchanged (p > 0.05). CONCLUSIONS: n-3PUFAs supplementation produces favourable hypolipidemic effects, a reduction in pro-inflammatory cytokine levels and improvement in glycaemia. Neither duration nor dosage appear to explain the observed heterogeneity in response to n-3PUFAs. Trial registration This trial was registered at http://www.crd.york.ac.uk as CRD42016050802

Colour as a cue to eat : effects of plate colour on snack intake in pre-school children

Environmental cues, such as the colour of food and dishware, have been shown to influence food and drink consumption in adult populations. This proof of concept study investigated whether plate colour could be utilised as a strategy to reduce intake of high energy density (HED) snacks and increase intake of low energy density (LED) snacks in pre-school children. In a between and within-subjects design, children were randomly assigned to either a control group (no colour message) or intervention group (received a colour message: red = stop, green = go) and were provided a snack at nursery on three occasions on differently coloured plates (red, green and white), for each snack type (HED, LED). Snack intake, colour preference, colour association, and anthropometrics were recorded for each child. The results showed that there was no effect of group (control vs intervention) on HED (p=0.540) and LED intake (p=0.575). No effect of plate colour on HED (p=0.147) or LED snack intake (p=0.505) was evident. Combining red and green plates for a chromatic versus achromatic comparison showed that there was no significant effect of chromatic plate on HED (p=0.0503) and LED (p=0.347) intakes. Despite receiving a brief learning intervention, the use of plate colour was found in the present study to be an ineffective strategy to control snack food intake in pre-school aged children. Rather, we suggest that food intake in young children may best be predicted by portion size, energy density and eating behaviour traits

AIDing Contraception: HIV and Recent Trends in Abortion Rates

Since the onset of HIV/AIDS awareness in the early 1980s, much attention has centered around the substantial negative effects of the disease throughout the world. This paper provides evidence of a secondary effect the disease has had on sexual behavior in the United States. Using a difference-in-differences estimation framework and state level data, we show that the perceived threat of HIV resulted in a drop in unwanted pregnancies, as demonstrated by a lower incidence of abortions. Our results suggest that each additional reported case of HIV per 1,000 individuals resulted in 85.5 fewer abortions per 1,000 live births

Active multiple myeloma suppresses and typically eliminates coexisting MGUS

Background: Myeloma is consistently preceded by premalignant monoclonal gammopathy of undetermined significance (MGUS). In >5% of MGUS patients there is a second MGUS clone (biclonal gammopathy of undetermined significance; BGUS), yet, at myeloma diagnosis, presentation of biclonal gammopathy myeloma (BGMy) is considered less frequent, implying that myeloma eradicates coexisting MGUS. Methods: In the largest study of its kind, we assessed BGMy frequency amongst 6399 newly diagnosed myeloma patients enrolled in recent UK clinical trials. Results: Compared to expected prevalence (i.e., >5% of MGUS have BGUS), only 58 of 6399 (0.91%) newly diagnosed myeloma patients had BGMy, indicating myeloma typically eliminates coexistent MGUS. In these 58 BGMy cases, the MGUS plasma cell clone was greatly suppressed in size compared to typical levels observed in conventional MGUS; contrarily, the MGUS clone did not inhibit the myeloma plasma cell clone in BGMy. Conclusion: Myeloma eliminates the majority of competing MGUS, and when it does not, the MGUS clone is substantially reduced in size

The Lipid Paradox is present in ST-elevation but not in non-ST-elevation myocardial infarction patients:Insights from the Singapore Myocardial Infarction Registry

Lowering low-density lipoprotein (LDL-C) and triglyceride (TG) levels form the cornerstone approach of cardiovascular risk reduction, and a higher high-density lipoprotein (HDL-C) is thought to be protective. However, in acute myocardial infarction (AMI) patients, higher admission LDL-C and TG levels have been shown to be associated with better clinical outcomes - termed the 'lipid paradox'. We studied the relationship between lipid profile obtained within 72 hours of presentation, and all-cause mortality (during hospitalization, at 30-days and 12-months), and rehospitalization for heart failure and non-fatal AMI at 12-months in ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) patients treated by percutaneous coronary intervention (PCI). We included 11543 STEMI and 8470 NSTEMI patients who underwent PCI in the Singapore Myocardial Infarction Registry between 2008-2015. NSTEMI patients were older (60.3 years vs 57.7 years, p < 0.001) and more likely to be female (22.4% vs 15.0%, p < 0.001). In NSTEMI, a lower LDL-C was paradoxically associated with worse outcomes for death during hospitalization, within 30-days and within 12-months (all p < 0.001), but adjustment eliminated this paradox. In contrast, the paradox for LDL-C persisted for all primary outcomes after adjustment in STEMI. For NSTEMI patients, a lower HDL-C was associated with a higher risk of death during hospitalization but in STEMI patients a lower HDL-C was paradoxically associated with a lower risk of death during hospitalization. For this endpoint, the interaction term for HDL-C and type of MI was significant even after adjustment. An elevated TG level was not protective after adjustment. These observations may be due to differing characteristics and underlying pathophysiological mechanisms in NSTEMI and STEMI