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Apolipoprotein E (APOE) E4 is the main genetic risk factor for Alzheimer’s disease (AD). Due to the consistent association, there is interest as to whether E4 influences the risk of other neurodegenerative diseases. Further, there is a constant search for other genetic biomarkers contributing to these phenotypes, such as microtubule-associated protein tau (MAPT) haplotypes. Here, participants from the Ontario Neurodegenerative Disease Research Initiative were genotyped to investigate whether the APOE E4 allele or MAPT H1 haplotype are associated with five neurodegenerative diseases: (1) AD and mild cognitive impairment (MCI), (2) amyotrophic lateral sclerosis, (3) frontotemporal dementia (FTD), (4) Parkinson’s disease, and (5) vascular cognitive impairment.
Genotypes were defined for their respective APOE allele and MAPT haplotype calls for each participant, and logistic regression analyses were performed to identify the associations with the presentations of neurodegenerative diseases.
Our work confirmed the association of the E4 allele with a dose-dependent increased presentation of AD, and an association between the E4 allele alone and MCI; however, the other four diseases were not associated with E4. Further, the APOE E2 allele was associated with decreased presentation of both AD and MCI. No associations were identified between MAPT haplotype and the neurodegenerative disease cohorts; but following subtyping of the FTD cohort, the H1 haplotype was significantly associated with progressive supranuclear palsy.
This is the first study to concurrently analyze the association of APOE isoforms and MAPT haplotypes with five neurodegenerative diseases using consistent enrollment criteria and broad phenotypic analysis.
Objective: Concussion in children and adolescents is a prevalent problem with implications for subsequent physical, cognitive, behavioral, and psychological functioning, as well as quality of life. While these consequences warrant attention, most concussed children recover well. This study aimed to determine what pre-injury, demographic, and injury-related factors are associated with optimal outcome (“wellness”) after pediatric concussion. Method: A total of 311 children 6–18 years of age with concussion participated in a longitudinal, prospective cohort study. Pre-morbid conditions and acute injury variables, including post-concussive symptoms (PCS) and cognitive screening (Standardized Assessment of Concussion, SAC), were collected in the emergency department, and a neuropsychological assessment was performed at 4 and 12 weeks post-injury. Wellness, defined by the absence of PCS and cognitive inefficiency and the presence of good quality of life, was the main outcome. Stepwise logistic regression was performed using 19 predictor variables. Results: 41.5% and 52.2% of participants were classified as being well at 4 and 12 weeks post-injury, respectively. The final model indicated that children who were younger, who sustained sports/recreational injuries (vs. other types), who did not have a history of developmental problems, and who had better acute working memory (SAC concentration score) were significantly more likely to be well. Conclusions: Determining the variables associated with wellness after pediatric concussion has the potential to clarify which children are likely to show optimal recovery. Future work focusing on wellness and concussion should include appropriate control groups and document more extensively pre-injury and injury-related factors that could additionally contribute to wellness. (JINS, 2019, 25, 375–389)
Given the vast superiority of synchrotron radiation sources for EXAFS and near-edge measurements, one might assume that conducting such experiments in the laboratory is a waste of time and resources. Upon more careful consideration of the realities of everyday research, however, one can easily see that this is not true. In fact, many people have come to this realization, so much so that a whole conference has been devoted to laboratory EXAFS facilities, their role in research and their relation to synchrotron facilities. The concensus after the conference was that laboratory instruments can and have been developed, with adequate performance for a variety of nontrivial experiments. They usually employ dedicated focusing spectrometers, rotating anode generators and fairly expensive monochromator crystals (see articles in ref. 1 and 2).
A multi-scale strategy is employed in the paper to investigate the thermo-mechanical properties of 2.5D angle-interlock woven shape memory polymer composites (SMPCs). In the study, the mesoscopic model of 2.5D woven SMPCs and microscopic model of yarns are firstly developed. After that, the themo-viscoelastic constitutive relationship of the yarn is described in the form of hereditary integral and the parameters of relaxation moduli are obtained from nonlinear fitting of Prony series based on the results of finite element method (FEM). Based on the multi-scale models and the constitutive relationship, the effects of warp and weft arranged densities on viscoelastic properties of 2.5D woven SMPCs are studied in detail. Finally, the shape memory behavior along the warp direction in small strain region is also analyzed. The research in the paper lays a foundation for design and application of woven SMPCs in engineering.
where Ω is a bounded smooth domain in ℝN (N ≥ 1), α ≥ 2 and θ is a parameter. Under the assumption that g(x, u) is sublinear near the origin with respect to u, we study the effect of the perturbation term h(x, u), which may break the symmetry of the associated energy functional. With the aid of critical point theory and the truncation method, we show that this system possesses multiple small negative energy solutions.
The response of soil microbial communities to soil quality changes is a sensitive indicator of soil ecosystem health. The current work investigated soil microbial communities under different fertilization treatments in a 31-year experiment using the phospholipid fatty acid (PLFA) profile method. The experiment consisted of five fertilization treatments: without fertilizer input (CK), chemical fertilizer alone (MF), rice (Oryza sativa L.) straw residue and chemical fertilizer (RF), low manure rate and chemical fertilizer (LOM), and high manure rate and chemical fertilizer (HOM). Soil samples were collected from the plough layer and results indicated that the content of PLFAs were increased in all fertilization treatments compared with the control. The iC15:0 fatty acids increased significantly in MF treatment but decreased in RF, LOM and HOM, while aC15:0 fatty acids increased in these three treatments. Principal component (PC) analysis was conducted to determine factors defining soil microbial community structure using the 21 PLFAs detected in all treatments: the first and second PCs explained 89.8% of the total variance. All unsaturated and cyclopropyl PLFAs except C12:0 and C15:0 were highly weighted on the first PC. The first and second PC also explained 87.1% of the total variance among all fertilization treatments. There was no difference in the first and second PC between RF and HOM treatments. The results indicated that long-term combined application of straw residue or organic manure with chemical fertilizer practices improved soil microbial community structure more than the mineral fertilizer treatment in double-cropped paddy fields in Southern China.
In this paper, the melting of stainless steel 316L using Computational Fluid Dynamics to observe the melt pool characteristics is studied. The simulation model allows the observation of the molten pool flow during the selective laser melting process due to Marangoni's effect and recoil pressure. Furthermore, different parameters are tested to show their effects on the melt pool and track formation. Different laser powers, as well as scanning speeds, were used to study the effects they have on the melt pool characteristics. The results were used to determine the relationships between these factors and the melt pool characteristics.
Knowledge about the infection transmission routes is significant for developing effective intervention strategies. We searched the PubMed databases and identified 10 studies with 14 possible inflight influenza A(H1N1)pdm09 outbreaks. Considering the different mechanisms of the large-droplet and airborne routes, a meta-analysis of the outbreak data was carried out to study the difference in attack rates for passengers within and beyond two rows of the index case(s). We also explored the relationship between the attack rates and the flight duration and/or total infectivity of the index case(s). The risk ratios for passengers seated within and beyond the two rows of the index cases were 1.7 (95% confidence interval (CI) 0.98–2.84) for syndromic secondary cases and 4.3 (95% CI 1.25–14.54) for laboratory-confirmed secondary cases. Furthermore, with an increase of the product of the flight duration and the total infectivity of the index cases, the overall attack rate increased linearly. The study indicates that influenza A(H1N1)pdm09 may mainly be transmitted via the airborne route during air travel. A standardised approach for the reporting of such inflight outbreak investigations would help to provide more convincing evidence for such inflight transmission events.
Ondansetron is increasingly administered to children suffering from concussion-associated nausea/vomiting. We examined the association between ondansetron administration and post-concussion symptoms in children at 1 week and 1 month following the concussion.
This was a secondary analysis of data collected prospectively in a cohort study conducted in nine pediatric emergency departments (EDs) (5P study). Participants were children ages between 5 and 17.99 years who sustained a concussion in the previous 48 hours. For the current study, only 5P participants who reported nausea and/or vomiting in the ED were eligible. The exposure of interest was ondansetron administration; the comparison group included all other participants. The primary outcome was an increase in at least three symptoms of the Post-Concussion Symptom Inventory score at 1 week and 1 month following trauma.
Among the 3,063 children included in the 5P study, 1805 (59%) reported nausea and provided data at 1 week and/or 1 month. Among them, 132 (7%) received ondansetron. Multivariable logistic regression adjusted for confounders did not show an association between ondansetron use and the risk of persistent post-concussion symptoms at 1 week (OR: 1.13 [95% CI: 0.86-1.49]), but it was associated with a higher risk at 1 month (OR: 1.33 [95% CI: 1.05-1.97]).
In children presenting to the ED with an acute concussion, ondansetron use was associated with a higher risk of persistent post-concussion symptoms at 1 month. Although this may be related to the limitations of the design, it highlights the importance of evaluating this association using a randomized clinical trial.
Influenza is a long-standing public health concern, but its transmission remains poorly understood. To have a better knowledge of influenza transmission, we carried out a detailed modelling investigation in a nosocomial influenza outbreak in Hong Kong. We identified three hypothesised transmission modes between index patient and other inpatients based on the long-range airborne and fomite routes. We considered three kinds of healthcare workers’ routine round pathways in 1140 scenarios with various values of important parameters. In each scenario, we used a multi-agent modelling framework to estimate the infection risk for each hypothesis and conducted least-squares fitting to evaluate the hypotheses by comparing the distribution of the infection risk with that of the attack rates. Amongst the hypotheses tested in the 1140 scenarios, the prediction of modes involving the long-range airborne route fit better with the attack rates, and that of the two-route transmission mode had the best fit, with the long-range airborne route contributing about 94% and the fomite route contributing 6% to the infections. Under the assumed conditions, the influenza virus was likely to have spread via a combined long-range airborne and fomite routes, with the former predominant and the latter negligible.
Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.
Diet has been shown to have an effect on both inflammation and oesophageal cancer. This study investigated the association between the dietary inflammatory index (DII®) and the risk of oesophageal cancer in Xinjiang Uyghur Autonomous Region, China. A case–control study was conducted during 2008–2009 in Urumqi and Shihezi. DII scores were calculated based on dietary intake assessed by a validated FFQ administered to 359 incident oesophageal cancer patients and 380 hospital-based controls. Higher DII scores indicate more pro-inflammatory diets. Logistic regression analyses were performed to assess the association between DII scores and oesophageal cancer risk. Oesophageal cancer patients had a significantly higher median DII score (−0·35; interquartile range (IQR)=−2·25, 1·86) than that of controls (−1·41; IQR −3·07, 0·40). Multivariable logistic analysis revealed a positive association between higher DII scores and oesophageal cancer risk (ORQuartile 4 v. 1 2·55; 95 % CI 1·61, 4·06; Ptrend<0·001). A pro-inflammatory diet appears to be associated with an increased risk of oesophageal cancer in Xinjiang Uyghur Autonomous Region. Specific carcinogenic mechanisms are discussed. Accumulating evidence, to which the study contributes, indicates that encouraging the intake of more anti-inflammatory foods may be a strategy to protect against oesophageal cancer in this high-risk area of China.
The mammalian target of rapamycin (mTOR) has been shown to be involved in lipopolysaccharide (LPS)-induced immune responses in many mammal cells. Here, we suggest that the mTOR pathway is involved in the intestinal inflammatory responses evoked by LPS treatment in chicken embryos. The intestinal tissue from Specific pathogen free chick embryos was cultured in the presence of LPS for 2 h. Secretory immunoglobulin A (sIgA) concentrations, messenger RNA (mRNA) expression of cytokines, and protein levels of nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), mTOR and p70 ribosomal S6 kinase (p70S6K) were determined. The results showed that LPS treatment increased sIgA concentrations in a dose-dependent manner. The mRNA levels of interleukine (IL)-6, IL-8, IL-10, tumor necrosis factor-α and Toll-like receptor (TLR) 4 were upregulated by LPS treatment (P<0.05). Lipopolysaccharide increased the phosphorylation of Jun N-terminal kinase (JNK), p38 MAPK and NF-κB (P<0.05) while decreasing the phosphorylation level of mTOR (P<0.05). Supplementation of leucine at doses of 10, 20 and 40 mM dose-dependently decreased sIgA production. Leucine supplementation at 40 mM restored the phosphorylation level of mTOR and p70S6K while suppressing the phosphorylation levels of NF-κB (P<0.05) and partially down-regulating the phosphorylation of p38 MAPK and JNK. The transcription of IL-6 was significantly decreased by leucine supplementation. These results suggested that leucine could alleviate LPS-induced inflammatory responses by down-regulating NF-κB signaling pathway and evoking mTOR/p70S6K signaling pathway, which may involve in the regulation of the intestinal immune system in chicken embryos.
About 30,000 astronomical photographic plates were digitised between 2012–2017 with a special digitising machine that has high precision in both astrometry and photometry. All the images from the plates, together with plate information and measured coordinates of all the objects on the plates, have been stored in the Chinese Virtual Observatory.
Strategies for the involvement of primary care in the management of patients with presumed or diagnosed dementia are heterogeneous across Europe. We wanted to explore attitudes of primary care physicians (PCPs) when managing dementia: (i) the most popular cognitive tests, (ii) who had the right to initiate or continue cholinesterase inhibitor or memantine treatment, and (iii) the relationship between the permissiveness of these rules/guidelines and PCP's approach in the dementia investigations and assessment.
Key informant survey. Setting: Primary care practices across 25 European countries. Subjects: Four hundred forty-five PCPs responded to a self-administered questionnaire. Two-step cluster analysis was performed using characteristics of the informants and the responses to the survey. Main outcome measures: Two by two contingency tables with odds ratios and 95% confidence intervals were used to assess the association between categorical variables. A multinomial logistic regression model was used to assess the association of multiple variables (age class, gender, and perceived prescription rules) with the PCPs’ attitude of “trying to establish a diagnosis of dementia on their own.”
Discrepancies between rules/guidelines and attitudes to dementia management was found in many countries. There was a strong association between the authorization to prescribe dementia drugs and pursuing dementia diagnostic work-up (odds ratio, 3.45; 95% CI 2.28–5.23).
Differing regulations about who does what in dementia management seemed to affect PCP's engagement in dementia investigations and assessment. PCPs who were allowed to prescribe dementia drugs also claimed higher engagement in dementia work-up than PCPs who were not allowed to prescribe.
To assess the burden of bloodstream infections (BSIs) among pediatric hematology-oncology (PHO) inpatients, to propose a comprehensive, all-BSI tracking approach, and to discuss how such an approach helps better inform within-center and across-center differences in CLABSI rate
Prospective cohort study
US multicenter, quality-improvement, BSI prevention network
PHO centers across the United States who agreed to follow a standardized central-line–maintenance care bundle and track all BSI events and central-line days every month.
Infections were categorized as CLABSI (stratified by mucosal barrier injury–related, laboratory-confirmed BSI [MBI-LCBI] versus non–MBI-LCBI) and secondary BSI, using National Healthcare Safety Network (NHSN) definitions. Single positive blood cultures (SPBCs) with NHSN defined common commensals were also tracked.
Between 2013 and 2015, 34 PHO centers reported 1,110 BSIs. Among them, 708 (63.8%) were CLABSIs, 170 (15.3%) were secondary BSIs, and 232 (20.9%) were SPBCs. Most SPBCs (75%) occurred in patients with profound neutropenia; 22% of SPBCs were viridans group streptococci. Among the CLABSIs, 51% were MBI-LCBI. Excluding SPBCs, CLABSI rates were higher (88% vs 77%) and secondary BSI rates were lower (12% vs 23%) after the NHSN updated the definition of secondary BSI (P<.001). Preliminary analyses showed across-center differences in CLABSI versus secondary BSI and between SPBC and CLABSI versus non-CLABSI rates.
Tracking all BSIs, not just CLABSIs in PHO patients, is a patient-centered, clinically relevant approach that could help better assess across-center and within-center differences in infection rates, including CLABSI. This approach enables informed decision making by healthcare providers, payors, and the public.
Driving in persons with dementia poses risks that must be counterbalanced with the importance of the care for autonomy and mobility. Physicians often find substantial challenges in the assessment and reporting of driving safety for persons with dementia. This paper describes a driving in dementia decision tool (DD-DT) developed to aid physicians in deciding when to report older drivers with either mild dementia or mild cognitive impairment to local transportation administrators.
A multi-faceted, computerized decision support tool was developed, using a systematic literature and guideline review, expert opinion from an earlier Delphi study, as well as qualitative interviews and focus groups with physicians, caregivers of former drivers with dementia, and transportation administrators. The tool integrates inputs from the physician-user about the patient's clinical and driving history as well as cognitive findings, and it produces a recommendation for reporting to transportation administrators. This recommendation is translated into a customized reporting form for the transportation authority, if applicable, and additional resources are provided for the patient and caregiver.
An innovative approach was needed to develop the DD-DT. The literature and guideline review confirmed the algorithm derived from the earlier Delphi study, and barriers identified in the qualitative research were incorporated into the design of the tool.
The effects of various parameters, such as thermal properties of substrates, thermal interface materials (TIMs) and heat sinks on the thermal performance of the light emitting diode (LED) light bars and backlight module are investigated experimentally and numerically in terms of junction temperature (Tj) and thermal resistances from junction to air (Rj-a). The results show that the measured Rj-a of the light bars by powering-on five LEDs in the test is different from one by powering-on only one LED, resulting from the extra heat coming from the adjacent LED packages affecting the Tj for the case of powering-on five LEDs. For the modules, Rj-a is significantly reduced by using the heat sinks for all backlight modules, and aluminum and iron heat sinks do not show any obvious difference in heat dissipation along with any substrates and TIMs. Furthermore, both experimental and simulation results show that the thermal conductivity of the substrates are more important and dominant than TIM and heat sink for the Rj-a of the backlight modules concerned, and also demonstrate that the thermal field for the local model can represent the one in full-scale backlight module.
Ectropis grisescens Warren and Ectropis obliqua (Prout) are two morphologically similar sibling species with overlapping ranges. In this study, manipulative laboratory experiments were conducted to examine the possibility of reproductive interference in sympatric populations of E. grisescens and E. obliqua and the potential consequences of the mating interaction. Our results showed that the presence of males or females of different species could incur mating interference and significant reduction of F1 offspring. The reduction was not significant relevant to the initial relative abundance of E. grisescens and E. obliqua. Detailed observations of mating opportunity showed that female mating frequencies of both species were not significantly affected by the absolute species density, but the mating success of E. obliqua females with conspecific males depended on species ratio. In addition, adding males to the other species resulted in lower number of offspring suggesting that the males’ behaviour might be linked with mating interference. Males of both E. grisescens and E. obliqua could interfere the intraspecific mating of the other species, but the impact of the mating interference differed. These combined data indicated that asymmetric reproductive interference existed in E. grisescens and E. obliqua under laboratory conditions, and the offspring of the mixed species were significantly reduced. The long term outcome of this effect is yet to be determined since additional reproductive factors such as oviposition rate and progeny survival to adulthood may reduce the probability of demographic displacement of one species by the other in overlapping niches.