The lack of strong association between brain beta-amyloid deposition and cognitive impairment has been a challenge for the Alzheimer's disease (AD) field. Although beta-amyloid is necessary for the ...pathologic diagnosis of AD, it is not sufficient to make the pathologic diagnosis or cause dementia. We sought to identify the genetic modifiers of the relation between cortical beta-amyloid burden (measured using
FFlorbetapir-PET) and cognitive dysfunction (measured using ADAS-cog) by conducting a genome-wide interaction study on baseline data from participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) phases GO/2 (n=678). Near genome-wide significant interaction effect was observed for rs73069071 within the IAPP (amylin) and SLCO1A2 genes (P=6.2 × 10
). Congruent results were found using data from participants followed up from ADNI-1 (P
=0.028, n=165). Meta-analysis across ADNI-GO/2 and ADNI-1 revealed a genome-wide significant interaction effect (P=1.1 × 10
). Our results were further supported by similar interaction effects on temporal lobe cortical thickness (whole-brain voxelwise analysis: familywise error corrected P=0.013) and longitudinal changes in ADAS-cog score and left middle temporal thickness and amygdalar volume (P
=0.026, 0.019 and 0.003, respectively). Using postmortem beta-amyloid immunohistochemistry data from 243 AD participants in the Religious Orders Study and Memory and Aging Project, we also observed similar rs73069071-by-beta-amyloid deposition interaction effect on global cognitive function (P
=0.005). Our findings provide insight into the complexity of the relationship between beta-amyloid burden and AD-related cognitive impairment. Although functional studies are required to elucidate the role of rs73069071 in AD pathophysiology, our results support the recently growing evidence on the role of amylin in AD.
This paper experimentally studies the efficiency of a multi-task geosynthetic comprised of a geogrid and a nonwoven geotextile layer in diminishing the required thickness of base course constructed ...over different soft subgrades in container yards pavements. In this research, a total number of 24 laboratory static plate load tests (PLT) were conducted in a large-scale steel test box. In all tests, the reinforcement was embedded at the interface of the base course and subgrade to get both reinforcing and separation functions involved simultaneously. The investigated parameter was bearing capacity coefficient K
30
obtained directly from the results of laboratory PLTs through a 305 mm-diameter circular steel plate. Results illustrated that in the case of composite-geosynthetic inclusion, the required thickness of the base course could be reduced from 17 to 23 percent depending on the strength of the underlying subgrade layer. This could be both economically and environmentally instrumental in real heavy-duty pavement design. Moreover, considering the geosynthetic end-fixation led to better functionalities of all reinforcements in fixed-end models compared to free-end ones. The results also demonstrated that the efficiency of the geocomposite is contingent on the thickness of the base course. As the thickness increases, the efficiency of the reinforcement reduces.
ABSTRACT
Aims
This study assessed the efficacy and safety of once‐daily insulin initiation using insulin detemir (detemir) or insulin glargine (glargine) added to existing metformin in type 2 ...diabetes (T2D).
Methods
This 26‐week, multinational, randomized, treat‐to‐target trial involved 457 insulin‐naïve adults with T2D (HbA1c 7–9%). Detemir or glargine was added to current metformin therapy any second oral antidiabetic drug (OAD) discontinued and titrated to a target fasting plasma glucose (FPG) ≤90 mg/dl (≤5.0 mmol/l). Primary efficacy endpoint was change in HbA1c.
Results
Mean (s.d.) HbA1c decreased with detemir and glargine by 0.48 and 0.74%‐points, respectively, to 7.48% (0.91%) and 7.13% (0.72%) estimated between‐treatment difference, 0.30 (95% CI: 0.14–0.46). Non‐inferiority for detemir at the a priori level of 0.4%‐points was not established. The proportions of patients reaching HbA1c ≤ 7% at 26 weeks were 38% and 53% (p = 0.026) with detemir and glargine, respectively. FPG decreased ∼43.2 mg/dl (∼2.4 mmol/l) in both groups non‐significant (NS). Treatment satisfaction was good for both insulins. Hypoglycaemia, which occurred infrequently, was observed less with detemir than glargine rate ratio 0.73 (95% CI 0.54–0.98). The proportions of patients reaching HbA1c ≤ 7% without hypoglycaemia in the detemir and glargine groups were 32% and 38% (NS), respectively. Weight decreased with detemir −0.49 (3.3) kg and increased with glargine +1.0 (3.1) kg (95% CI for difference: −2.17 to −0.89 kg).
Conclusion
While both detemir and glargine, when added to metformin therapy, improved glycaemic control, glargine resulted in greater reductions in HbA1c, while detemir demonstrated less weight gain and hypoglycaemia.
Summary
Low seminal plasma concentrations of coenzyme Q10 (CoQ10) have been correlated with impaired sperm parameters, but the exact mechanism remains of dominating interest. This randomised, ...placebo‐controlled study examined the effect of CoQ10 on catalase, superoxide dismutase (SOD) and F2‐isoprostanes in seminal plasma in infertile men and their relation with CoQ10 concentration. Sixty infertile men with idiopathic oligoasthenoteratozoospermia (OAT) were randomised to receive 200 mg d−1 of CoQ10 or placebo for 3 months. 47 persons of them completed the study. Semen analysis, anthropometric measurements, diet and physical activity assessment were performed for subjects before and after treatment. Independent and paired t‐test, chi‐square test and ancova were compared outcomes of supplementation between two groups. CoQ10 levels increased from 44.74 ± 36.47 to 68.17 ± 42.41 ng ml−1 following supplementation in CoQ10 (P < 0.001). CoQ10 group had higher catalase and SOD activity than the placebo group. There was a significant positive correlation between CoQ10 concentration and normal sperm morphology (P = 0.037), catalase (P = 0.041) and SOD (P < 0.001). Significant difference was shown between the mean of changes in seminal plasma 8‐isoprostane in two groups (P = 0.003) after supplementation. Three‐month supplementation with CoQ10 in OAT infertile men can attenuate oxidative stress in seminal plasma and improve semen parameters and antioxidant enzymes activity.
Automated volumetric analysis of structural MR imaging allows quantitative assessment of brain atrophy in neurodegenerative disorders. We compared the brain segmentation performance of the AI-Rad ...Companion brain MR imaging software against an in-house FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline.
T1-weighted images of 45 participants with de novo memory symptoms were selected from the OASIS-4 database and analyzed through the AI-Rad Companion brain MR imaging tool and the FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline. Correlation, agreement, and consistency between the 2 tools were compared among the absolute, normalized, and standardized volumes. Final reports generated by each tool were used to compare the rates of detection of abnormality and the compatibility of radiologic impressions made using each tool, compared with the clinical diagnoses.
We observed strong correlation, moderate consistency, and poor agreement between absolute volumes of the main cortical lobes and subcortical structures measured by the AI-Rad Companion brain MR imaging tool compared with FreeSurfer. The strength of the correlations increased after normalizing the measurements to the total intracranial volume. Standardized measurements differed significantly between the 2 tools, likely owing to differences in the normative data sets used to calibrate each tool. When considering the FreeSurfer 7.1.1/Individual Longitudinal Participant pipeline as a reference standard, the AI-Rad Companion brain MR imaging tool had a specificity of 90.6%-100% and a sensitivity of 64.3%-100% in detecting volumetric abnormalities. There was no difference between the rate of compatibility of radiologic and clinical impressions when using the 2 tools.
The AI-Rad Companion brain MR imaging tool reliably detects atrophy in cortical and subcortical regions implicated in the differential diagnosis of dementia.
Thermoluminescence dosimetry most typically concerns the sensing and quantification of ionizing radiation exposures, with evaluation of absorbed dose arising from electron-hole trapping in ...well-disposed insulating/semi-conducting media. In this passive form of dosimetry the signal derives from photons released post-irradiation heating of the dosimeter over a specific temperature range. Herein, for entrance doses from 2 Gy up to 250 kGy, investigation is made of the thermoluminescence properties of electron irradiated borosilicate glass (SiO2–B2O3), the samples deriving from commercial microscope slides (coverslips) of thickness 1.0 mm. The coverslips provide linear TL response over a wide range of radiation dose, through use of a clinical linear accelerator in a lower dose regime (2–10 Gy) and use of a product-irradiation electron linac in a higher dose regime (25 kGy–250 kGy), obtaining a regression coefficient in excess of 96%. In the high dose regime comparison has been made with the response of Ge–B doped Flat Fibre (FF) and Ge–B doped photonic crystal fibre (PCF) (collapsed). Deconvolution shows the glow curves of the borosilicate glass to be formed of five overlapping peaks, with figures of merit (FOM) of between 0.62 – 1.72 and 0.87–1.00 for the particular dose ranges 2–10 Gy and 25 kGy–250 kGy respectively. Through use of Glowfit deconvolution software, the key trapping parameters of activation energy and frequency factor were calculated for the borosilicate glass slide.
•Borosilicate glass slide of 1 mm thickness irradiated to electrons.•The glow curve deconvolution appears five overlapping peaks.•Si–Si and Si–O oxygen interactions are responsible of the overlapping peaks.
Microgrids as local area power systems are changing the power system landscape due to their potential to offer a viable solution for integrating renewable energy resources into the main grid. From ...the operational point of view, microgrids should have appropriate power electronic interfaces, control schemes, and monitoring and automation infrastructure to provide the required flexibility and meet the related IEEE 1547 standard requirements. This study describes some of the efforts made at the smart microgrid educational laboratory to provide such facilities and create real-world conditions needed to conduct research and teach the related courses. Laboratory works not only increase the practical skills of the students but also can motivate them to pursue theoretical courses with a strong passion. The introduced facilities are somehow unique for the integration of both electric and communication infrastructures which can resolve the problem of disregard for data transfer challenges in the studies. Complete hardware design of power plant components and incorporation of solar photovoltaic (PV) and two types of wind turbine generations are some of the efforts made to bring the real-world conditions into the laboratory.
Atypical cartilaginous tumor and enchondroma are similar in histopathologic aspects. Although the clinical course, radiologic and pathologic examinations enable distinction in most cases, ...difficulties are still encountered by the pathologists. There is no known biomarker to help make a distinction between benign and malignant cartilaginous tumors. Insulin-like growth factor II mRNA binding protein (IMP3) is a member of an oncofetal family of proteins that is expressed in different human malignancies and rapidly emerging as a prognostic and diagnostic marker in surgical pathology. In this study, IMP3 expression was examined by immunohistochemistry in 36 enchondromas and 42 chondrosarcomas of different histologic grades. The results showed that all 36 cases of enchondroma were negative for IMP3, while it was overexpressed in 15 of 42 chondrosarcomas (36%) (P<0.01). Significant higher levels of IMP3 were detected in grade III chondrosarcomas (6 of 7; 85.7%) when compared to low-grade tumors (6 of 19; 31.5% in grade II and 3 of 16; 18.7% in Atypical Cartilaginous Tumor). We proved statistically significant difference in IMP3 expression between enchondromas and ACTs (P=0.025). Our study clearly demonstrated differentiation-dependent expression of IMP3 in chondrosarcoma, and suggests IMP3 as a novel marker for differentiating problematic cases of enchondroma from well-differentiated chondrosarcomas. To our knowledge, this study is the first study to clarify expression of IMP-3 in chondromas and chondrosarcomas.
Aims
Evaluate the safety and efficacy of once‐daily insulin detemir initiated in routine clinical practice in patients with type 2 diabetes mellitus inadequately controlled with oral hypoglycaemic ...agents (OHAs).
Methods
This large observational study was conducted in 10 countries. Adverse event data (including hypoglycaemia) and glycaemic control were recorded before and 24 weeks following insulin initiation while patients continued routine clinical management.
Results
In this study, 17 374 patients (53% male) were included. Mean pre‐insulin values (±s.d.) were: age 62 ± 12 years; body mass index (BMI) 29.3 ± 5.4 kg/m2; diabetes duration 10 ± 7 years; haemoglobin A1c (HbA1c) 8.9 ± 1.6%. During the study, 27 patients experienced serious adverse drug reaction, severe hypoglycaemic events or both; and there were 31 episodes of severe hypoglycaemia in 21 patients. After 24 weeks, HbA1c was 7.5 ± 1.2% (change of −1.3%; p < 0.001) and mean weight change was −0.6 kg (confidence interval −0.7, −0.5 kg, p < 0.001). Daily insulin dose increased from 13 ± 6 U (0.16 ± 0.09 U/kg) to 22 ± 16 U (0.27 ± 0.17U/kg) by 24 weeks. Multivariate regression analysis identified several independent demographic and treatment predictors of end of study HbA1c.
Conclusions
Addition of once‐daily insulin detemir to patients with type 2 diabetes mellitus on OHA therapy resulted in few adverse events, significant improvements in glycaemic control, small reductions in weight and low rates of hypoglycaemia. On the basis of this study, concerns about hypoglycaemia or weight gain should not preclude initiation of basal insulin analogues in patients with poor glycaemic control on OHAs.
Atypical cartilaginous tumor and enchondroma are similar in histopathologic aspects. Although the clinical course, radiologic and pathologic examinations enable distinction in most cases, ...difficulties are still encountered by the pathologists. There is no known biomarker to help make a distinction between benign and malignant cartilaginous tumors. Insulin-like growth factor II mRNA binding protein (IMP3) is a member of an oncofetal family of proteins that is expressed in different human malignancies and rapidly emerging as a prognostic and diagnostic marker in surgical pathology. In this study, IMP3 expression was examined by immunohistochemistry in 36 enchondromas and 42 chondrosarcomas of different histologic grades. The results showed that all 36 cases of enchondroma were negative for IMP3, while it was overexpressed in 15 of 42 chondrosarcomas (36%) (P<0.01). Significant higher levels of IMP3 were detected in grade III chondrosarcomas (6 of 7; 85.7%) when compared to low-grade tumors (6 of 19; 31.5% in grade II and 3 of 16; 18.7% in Atypical Cartilaginous Tumor). We proved statistically significant difference in IMP3 expression between enchondromas and ACTs (P=0.025). Our study clearly demonstrated differentiation-dependent expression of IMP3 in chondrosarcoma, and suggests IMP3 as a novel marker for differentiating problematic cases of enchondroma from well-differentiated chondrosarcomas. To our knowledge, this study is the first study to clarify expression of IMP-3 in chondromas and chondrosarcomas.
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