A Recent Increase in Long-Lived Heatwaves in China Under the Joint Influence of South Asia and Western North Pacific Subtropical Highs

Long-lived (≥6 days) heatwaves (HWs) have strong social impacts with serious health implications. Using homogenized historical daily temperatures from China and ECMWF reanalysis data, this study investigates its frequency between 1979 and 2018 and driving mechanisms. It is found that the occurrence of HWs is strongly associated with the joint actions of the South Asian high and the western North Pacific subtropical high, which can be described by a synergy index measured by the boundary distance between the two subtropical high-pressure systems. When the synergy index is positive, there are more long-lived HWs occurrence in the east of the Tibetan Plateau, the lower reaches of the Yangtze River and the southern region in China, and vice versa. A Mann-Kendall test shows a significant interdecadal shift around 2004/2005 towards increased occurrence that is consistent with enhanced subtropical high systems. This study shows the important roles of large-scale dynamic systems in regional climate extremes and their future changes.

Association of siblings’ presence and oral health-related quality of life among children: a cross-sectional study

Background The quantity–quality trade-off theory indicates that an increase in siblings might decrease a child’s well-being, but little is known about the impacts of sibling number on children’s oral health-related quality of life (OHRQoL). This study aims to investigate the effects of presence of siblings on children’s OHRQoL, and to further test whether there is an interaction effect between siblings’ presence and locations on children’s OHRQoL. Methods Data were obtained from an oral-health survey of 12-year-old children in Beijing, China, which was a part of the 4th National Oral Health Survey in the Mainland of China (2015–2016). This study included 2158 children data for analysis. OHRQoL was assessed by the child’s Oral Impacts on Daily Performance (OIDP). OIDP prevalence served as an indicator of OHRQoL. Children with and without siblings were recorded as non-single and single children, respectively. Dental variables, including active caries, gingival bleeding, and calculus, were reported. A logistic regression model was applied to investigate the association of siblings’ presence and OIDP prevalence. A synergy index was used to assess the possible interaction effect between siblings’ presence and location on OIDP prevalence. Results Sixty percent of Chinese children reported suffering OIDP in the previous six months. OIDP prevalence for non-single and single children were 68.3% and 56.9%, respectively. The adjusted odds ratio (OR) of OIDP for non-single children was 1.31 (95% CI: 1.05, 1.63), and the adjusted OR of OIDP for non-single and rural children was 2.03 (95% CI: 1.47, 2.81). The synergy index between siblings’ presence and location on OIDP was 2.18 (85% CI: 1.30, 3.67), which indicates that an excessive risk increase for OIDP was observed among non-single and rural children. Conclusions Children with siblings are more likely to report OIDP and have lower OHRQoL, especially those from rural areas. These findings indicate that oral-health interventions should be given priority for non-single and rural children.

Diabetes, Hypertension, and Incidence of Chronic Kidney Disease: Is There any Multiplicative or Additive Interaction?

Background: The burden of chronic kidney disease (CKD) is on the rise worldwide; diabetes and hypertension are mentioned as the main contributors. Objectives: The current study aimed to investigate the multiplicative and additive interaction of diabetes and hypertension in the incidence of CKD. Methods: In this population-based cohort study, 7342 subjects aged 20 years or above (46.8% male) were divided into four groups: no diabetes and hypertension; diabetes and no hypertension; no diabetes but suffer from hypertension; and both diabetes and hypertension. The multivariable Cox regression was used to determine the effect of diabetes, hypertension, and their multiplicative interaction on CKD. The following indices were used to determine the additive interaction of diabetes and hypertension: the relative excess risk of interaction, the attributable proportion due to interaction, and the synergism index. Results: Diabetes and hypertension had no significant multiplicative interaction in men (hazard ratio of 0.93, P value: 0.764) and women (hazard ratio of 0.79, P value: 0.198); furthermore, no additive interaction was found in men (Relative Excess Risk due to Interaction of 0.79, P value: 0.199; Attributable Proportion due to Interaction of 0.22, P value: 0.130; Synergy index of 1.44, P value: 0.183) and women (Relative Excess Risk due to Interaction of -0.26, P value: 0.233, Attributable Proportion due to Interaction of -0.21, P value: 0.266; Synergy index of 0.48, P value: 0.254). Conclusions: This study demonstrated no synergic effect between diabetes and hypertension on the incidence of CKD.

Treatment of Cattle Manure by Anaerobic Co-Digestion with Food Waste and Pig Manure: Methane Yield and Synergistic Effect

The management of cattle manure (CM) has become increasingly challenging because its production continues to rise, while the regulations on manure management have become increasingly stringent. In Korea, most farms produce CM as a dry mixture with lignocellulosic bedding materials (mainly sawdust), making it impractical to treat CM by anaerobic digestion. To address this problem, this study examined whether anaerobic co-digestion with food waste (FW) and pig manure (PM) could be an effective approach for the treatment of CM. The batch anaerobic digestion tests at different CM: FW: PM mixing ratios showed that more methane was produced as the FW fraction increased, and as the CM fraction decreased. The response surface models describing how the substrate mixing ratio affects the methane yield and synergistic effect (methane yield basis) were successfully generated. The models proved that the methane yield and synergistic effect respond differently to changes in the substrate mixing ratio. The maximum 30-day methane yield was predicted at 100% FW, whereas the maximum 30-day synergy index was estimated for the mixture of 47% CM, 6% FW, and 47% PM (total solids basis). The synergy index model showed that CM, FW, and PM could be co-digested without a substantial loss of their methane potential at any mixing ratio (30-day synergy index, 0.89–1.22), and that a possible antagonistic effect could be avoided by keeping the FW proportion less than 50%. The results suggest that co-digestion with PM and FW could be flexibly applied for the treatment and valorization of CM in existing anaerobic digestion plants treating FW and PM.

Influence of Physical Activity, Protein Intake and Social Network on the Frailty development

Background Frailty, a geriatric syndrome, is associated with many adverse health outcomes. Risk factors include physical inactivity, low protein intake and an inadequate social network. In this analysis we aimed to assess the influence of these factors and their combination in an 11-year-follow-up study on a Europe-wide level. Methods The analysed dataset included 22,226 community-dwelling robust and prefrail persons aged ≥50 years (11 countries) from the Study on Health, Ageing and Retirement in Europe (SHARE). Frailty was measured with the “Frailty Instrument for Primary care of the Survey of Health, Ageing and Retirement in Europe”. Additionally, self-reported level of vigorous physical activity (PA), protein intake and satisfaction with social network were assessed. The impact of these parameters on the development of frailty was calculated using Cox regressions, adjusted for age, education, smoking, alcohol BMI, depression, long-term illness and each other. Results People who do not engage in PA, had a higher HRs for frailty development compared to people performing PA regularly [women: 1.62 (95%CI: 1.22-2.13); men: 1.83 (95%CI: 1.44-2.33)]. People with low protein intake did not have significant higher HR [women: 1.05 (95%CI: 0.80-1.37); men: 1.16 (95%CI: 0.93-1.46)]. Women with poor social network showed HRs of 1.34 (95%CI: 1.24-2.15)], men with poor social network had a HR of 0.88 (95%CI: 0.70-1.10). In general, we found that persons with a combination of two risk factors had a higher risk for frailty compared to those with no or only one. However, no significant synergy index could be found. Conclusions Regular PA, but also adequate social networks seem to be important factors in frailty prevention. Key messages Sufficient PA and satisfaction with social network were shown as modifiable factors to prevent frailty in an 11-year-follow-up study. A combination of two risk factors was associated with a higher risk for frailty compared to one, however, with no significant synergy index.

The Combined Effect of Nonalcoholic Fatty Liver Disease and Metabolic Syndrome on Osteoporosis in Postmenopausal Females in Eastern China

The present study evaluated the potential combined effects of NAFLD and MetS on the development of osteoporosis. The relationship between NAFLD and MetS and osteoporosis was assessed in 938 postmenopausal female participants. Moderate and severe NAFLDs were combined as significant NAFLD (SNAFLD). All the subjects were divided into 4 subgroups based on the status of SNAFLD and MetS. Relative excess risk of interaction (RERI), attributable proportion (AP) of interaction, and synergy index (SI) were used to investigate the additive interaction of those two factors. NAFLD, SNAFLD, and MetS were independent factors for osteoporosis with the adjustment of age and other confounders. The incidence of osteoporosis in MetS (+) SNAFLD (+) group was significantly higher than that in other three groups. RERI was 2.556 (95% CI = 0.475–4.636), AP was 0.454 (95% CI = 0.201–0.706), and SI was 2.231 (95% CI = 1.124 to 4.428), indicating the significant combined interaction of SNAFLD and MetS on the development of osteoporosis. SNAFLD and MetS are independent risk factors for osteoporosis in postmenopausal females, respectively. Moreover, SNAFLD and MetS have an additive effect on the development of osteoporosis.

Functional connectivity in the neuromuscular system underlying bimanual coordination

Neural synchrony has been suggested as a mechanism for integrating distributed sensorimotor systems involved in coordinated movement. To test the role of corticomuscular and intermuscular coherence in bimanual coordination, we experimentally manipulated the degree of coordination between hand muscles by varying the sensitivity of the visual feedback to differences in bilateral force. In 16 healthy participants, cortical activity was measured using EEG and muscle activity of the flexor pollicis brevis of both hands using high-density electromyography (HDsEMG). Using the uncontrolled manifold framework, coordination between bilateral forces was quantified by the synergy index R V in the time and frequency domain. Functional connectivity was assessed using corticomuscular coherence between muscle activity and cortical source activity and intermuscular coherence between bilateral EMG activity. The synergy index increased in the high coordination condition. R V was higher in the high coordination condition in frequencies between 0 and 0.5 Hz; for the 0.5- to 2-Hz frequency band, this pattern was inverted. Corticomuscular coherence in the beta band (16–30 Hz) was maximal in the contralateral motor cortex and was reduced in the high coordination condition. In contrast, intermuscular coherence was observed at 5–12 Hz and increased with bimanual coordination. Within-subject comparisons revealed a negative correlation between R V and corticomuscular coherence and a positive correlation between R V and intermuscular coherence. Our findings suggest two distinct neural pathways: 1) corticomuscular coherence reflects direct corticospinal projections involved in controlling individual muscles; and 2) intermuscular coherence reflects diverging pathways involved in the coordination of multiple muscles.

The Influential Knowledge Factors of Companies’ Performance in Slovenia

Background: Knowledge plays a crucial role in supporting the European Union model based on economic growth, social responsibility, and sustainable development. To improve companies’ performance, one must reflect on new forms of knowledge and develop new indicators to measure them. Objectives: The goal of the paper is to investigate the impact of the selected factors of knowledge on companies’ performance in Slovenia. Methods/Approach: A questionnaire was created and sent to small and medium-sized enterprises in Slovenia. The principle axis factoring method was used to identify the factors of knowledge and of companies’ performance, and a regression analysis was conducted to determine the influence of the selected knowledge factors on companies’ performance. Results: The establishment of scientists’ collaboration with companies has a positive impact on companies’ performance, but the obstacles to the establishment of scientists’ collaboration with companies do not have any impact. Conclusions: The results could be useful for governments and companies in the adoption of measures aimed at strengthening scientists’ collaboration with companies. Further research can be oriented toward the common synergy index (e.g., the knowledge triangle).

Modeling Combination Chelation Regimes To Optimize Cellular Iron Removal and Explore Mechanisms Of Enhanced Chelation

Introduction Monotherapy with clinically available chelators, namely deferoxaime (DFO), deferasirox (DFX) or deferiprone (DFP) is effective but often slow and suboptimal. Combinations of DFO with DFP have been used clinically to enhance cellular iron mobilization but the conditions under which this occurs have not been studied systematically. With the emergence of DFX, the possibility exists to combine this with either DFO or DFP to enhance chelation. We have developed a system to study the optimal concentrations and times of exposure to these chelators, alone or in combination for maximising cellular iron removal. Isobol modeling has been used to determine whether interaction is additive or synergistic. The demonstration of synergy would imply the primary chelator acting as a ‘sink’ for iron chelated and donated to this sink by low concentrations of a secondary ‘shuttle’ chelator as shown in plasma (Evans et al. TransL. Res, 2010). Methods Human hepatocellular carcinoma (HuH-7) cells were chosen as hepatocytes are the major cell of iron storage in iron overload. Iron concentration was determined using the ferRozine (Riemer et al. Anal Biochem. 2004). A threefold increase of intracellular iron compared to control was obtained by serially treating cells with 10% FBS RPMI media. The cells were then exposed to iron chelator then lysed and intracellular iron concentration determined via the ferrozine assay, normalized against protein content. Cell viability was assessed using 0.4% Trypan blue as well as Acridine Orange /Propidium Iodide and was consistently > 98%. Isobolograms were constructed (Tallarida et al, Pharmacol Ther, 2010) as well as a the synergy index (QUOTE 1-1/R) x 100 (%), where R = difference of areas between the line of additivity and the curve of synergy on the isobologram. This index represents how much of the obtained effect exceeds that expected by additivity of two chelators. Results Monotherapy with DFP, DFX or DFO at clinically relevant concentrations of 1 to 30µM iron binding equivalents (IBE), induced both dose and time dependent cellular iron removal. Dual therapy combinations of all 3 chelators enhanced iron removal at 4, 8 and 12 hours. At 4 hours of incubation, whereas 10µM DFO alone had no demonstrable effect on cellular iron removal, addition of DFP at as little as 1µM IBE increased cellular iron removal. Table 1 shows examples of cellular iron removal at specimen chelator concentrations alone or in combination at 8h. The combination of DFX with DFO, DFX with DFP and DFP with DFO all resulted in enhanced cellular iron removal. The combination of DFP and DFX was the most effective. Isobol plot analysis from multiple chelator concentrations demonstrated synergy for all pairs at 4 and 8 hours of exposure. The derived synergy index at 8h indicates that when DFX and DFO are combined, 49% of the chelation effect is due to synergy in this system and 51% in the case of DFP and DFO combination. Most interestingly, the synergistic effect is even greater, in the case of the two oral chelators DFP and DFX when in combination (59%). Figure 1. Conclusion Remarkably low concentrations of a second chelator are required to enhance cellular iron removal by the primary chelator. Isobol analysis shows synergy rather than additivity as the mechanism for enhanced chelation for all 3 combinations, implying a ‘shuttle’ and ‘sink’ effect. Interestingly, the combination of two oral chelators DFP and DFX showed the most marked enhancement of cellular iron removal, without cellular toxicity, suggesting a potentially powerful therapeutic approach, provided this is also well tolerated clinically. The long plasma half life of once daily oral DFX will allow a continuous ‘sink’ for iron shuttled by the shorter acting DFP. Line of Additivity Curve of Synergy below the line Disclosures: Porter: Novartis: Consultancy, Honoraria, Research Funding; Shire: Consultancy, Honoraria; Celgene: Consultancy.