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Brain amyloid-β protein (Aβ) deposition is a key pathology of Alzheimer's disease (AD). Cholinergic degeneration, including reductions in α7 nicotinic acetylcholine receptors (α7-nAChR), is also known as a pathophysiology of AD. Recent imaging studies have shown cognitively normal subjects with Aβ depositions, indicating a missing link between Aβ deposition and cognitive decline.
To clarify relationships among the Aβ burden, α7-nAChR availability, and cognitive declines in AD.
To measure brain Aβ deposition and α7-nAChR availability in the same patients with AD using positron emission tomography (PET).
Twenty AD patients and age-matched 20 healthy adults were studied. The α7-nAChR availability and Aβ deposition were evaluated using PET with [11C]MeQAA and [11C]PIB, respectively. Levels of specific binding were estimated by a simplified reference tissue method (BPND) for [11C]MeQAA and a tissue ratio method (SUVR) for using [11C]PIB. The values were compared with clinical measures of various cognitive functions using regions of interest (ROIs)-based and statistical parametric mapping (SPM) analyses.
[11C]MeQAA BPND levels were extensively lower in the cholinergic projection regions of AD. There was a significant negative correlation between [11C]PIB SUVR and [11C]MeQAA BPND in the nucleus basalis of Mynert (NBM). The NBM [11C]PIB SUVR was negatively correlated with the [11C]MeQAA BPND level in the anterior and posterior cingulate cortices, whereas the relation within the same region showed weak correlation. Also we found significant correlation between cognitive decline and [11C]MeQAA BPND levels in the NBM.
Aβ deposition-linked α7-nAChR dysfunction may account for cognitive decline in AD.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
There is an increasing incidence of overweight/obesity and mental health disorders in young adults and the two conditions often coexist. We aimed to investigate the influence of antenatal and postnatal factors that may underlie this association with a focus on maternal prenatal smoking, socio-economic status and gender. Data from the Western Australian Pregnancy Cohort (Raine) Study (women enrolled 1989–1991) including 1056 offspring aged 20 years (cohort recalled 2010–2012) were analyzed (2015–2016) using multivariable models for associations between offspring depression scores (DASS-21 Depression-scale) and body mass index (BMI), adjusting for pregnancy and early life factors and offspring behaviours. There was a significant positive relationship between offspring depression-score and BMI independent of gender and other psychosocial covariates. There was a significant interaction between maternal prenatal smoking and depression-score (interaction coefficient=0.096; 95% CI: 0.006, 0.19, P=0.037), indicating the relationship between depression-score and BMI differed according to maternal prenatal smoking status. In offspring of maternal prenatal smokers, a positive association between BMI and depression-score (coefficient=0.133; 95% CI: 0.05, 0.21, P=0.001) equated to 1.1 kg/m2 increase in BMI for every 1standard deviation (8 units) increase in depression-score. Substituting low family income during pregnancy for maternal prenatal smoking in the interaction (interaction coefficient=0.091; 95% CI: 0.01, 0.17, P=0.027) showed a positive association between BMI and depression score only among offspring of mothers with a low family income during pregnancy (coefficient=0.118; 95% CI: 0.06, 0.18, P<0.001). There were no significant effects of gender on these associations. Whilst further studies are needed to determine whether these associations are supported in other populations, they suggest potentially important maternal behavioural and socio-economic factors that identify individuals vulnerable to the coexistence of obesity and depression in early adulthood.
Few studies have examined the impact of cigarette smoking on the risk for herpes zoster. The Shozu Herpes Zoster (SHEZ) Study is a community-based prospective cohort study over 3 years in Japan aiming to clarify the incidence and predictive and immunological factors for herpes zoster. We investigated the associations of smoking status with past history and incidence of herpes zoster. A total of 12 351 participants provided valid information on smoking status and past history of herpes zoster at baseline survey. Smoking status was classified into three categories (current, former, never smoker), and if currently smoking, the number of cigarettes consumed per day was recorded. The participants were under the active surveillance for first-ever incident herpes zoster for 3 years. We used a logistic regression model for the cross-sectional study on the association between smoking status and past history of herpes zoster, and a Cox proportional hazards regression model for the cohort study on the association with risk of incidence. The multivariable adjusted odd ratios (95% CI) of past history of herpes zoster for current vs. never smokers were 0·67 (0·54–0·80) for total subjects, 0·72 (0·56–0·93) for men and 0·65 (0·44–0·96) for women. The multivariable adjusted hazard ratios (95% CI) of incident herpes zoster for current vs. never smokers were 0·52 (0·33–0·81) for total subjects, 0·49 (0·29–0·83) for men and 0·52 (0·19–1·39) for women. Smoking status was inversely associated with the prevalence and incidence of herpes zoster in the general population of men and women aged ⩾50 years.
It has been demonstrated that negatively distorted self-referential processing, in which individuals evaluate one's own self, is a pathogenic mechanism in subthreshold depression that has a considerable impact on the quality of life and carries an elevated risk of developing major depression. Behavioural activation (BA) is an effective intervention for depression, including subthreshold depression. However, brain mechanisms underlying BA are not fully understood. We sought to examine the effect of BA on neural activation during other perspective self-referential processing in subthreshold depression.
A total of 56 subjects underwent functional magnetic resonance imaging scans during a self-referential task with two viewpoints (self/other) and two emotional valences (positive/negative) on two occasions. Between scans, while the intervention group (n = 27) received BA therapy, the control group (n = 29) did not.
The intervention group showed improvement in depressive symptoms, increased activation in the dorsal medial prefrontal cortex (dmPFC), and increased reaction times during other perspective self-referential processing for positive words after the intervention. Also, there was a positive correlation between increased activation in the dmPFC and improvement of depressive symptoms. Additionally, there was a positive correlation between improvement of depressive symptoms and increased reaction times.
BA increased dmPFC activation during other perspective self-referential processing with improvement of depressive symptoms and increased reaction times which were associated with improvement of self-monitoring function. Our results suggest that BA improved depressive symptoms and objective monitoring function for subthreshold depression.
Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the incretin hormones secreted from the intestine in response to enteral feeding to stimulate insulin secretion. We investigated the relationship serum GIP and GLP-1 levels with gestational age, and insulin secretion in preterm infants. Serum GIP and GLP-1 levels were measured at birth and at 1, 2 and 4 weeks after birth in 30 infants, including 12 born before 30th week of gestation (early group) and 18 born after 30th week of gestation (late group). Blood glucose and serum insulin levels were measured, and the quantitative insulin sensitivity check index (QUICKI) was also calculated. The levels of GLP-1 at 2 and 4 weeks were significantly higher in the early group than those in the late group. The levels of GIP were not significantly different between two groups. At 4 weeks, serum insulin level was significantly higher and QUICKI was significantly lower in the early group. Furthermore, GLP-1 levels were significantly correlated with QUICKI and the serum insulin levels in all infants at 4 weeks. In preterm infants, enteral feeding to premature intestine may be associated with GLP-1 secretion. GLP-1 is also related to stimulated insulin secretion in early postnatal period.
Enhancement of the quality of laser wake-field accelerated (LWFA) electron beams implies the improvement and controllability of the properties of the wake waves generated by ultra-short pulse lasers in underdense plasmas. In this work we present a compendium of useful formulas giving relations between the laser and plasma target parameters allowing one to obtain basic dependences, e.g. the energy scaling of the electrons accelerated by the wake field excited in inhomogeneous media including multi-stage LWFA accelerators. Consideration of the effects of using the chirped laser pulse driver allows us to find the regimes where the chirp enhances the wake field amplitude. We present an analysis of the three-dimensional effects on the electron beam loading and on the unlimited LWFA acceleration in inhomogeneous plasmas. Using the conditions of electron trapping to the wake-field acceleration phase we analyse the multi-equal stage and multiuneven stage LWFA configurations. In the first configuration the energy of fast electrons is a linear function of the number of stages, and in the second case, the accelerated electron energy grows exponentially with the number of stages. The results of the two-dimensional particle-in-cell simulations presented here show the high quality electron acceleration in the triple stage injection–acceleration configuration.
The existence of Pt7Cu ordering phase (intermetallic compound) was investigated by ab initio calculations and high voltage electron microscopy (HVEM) focusing on irradiation-induced ordering. The Pt7Cu ordering phase (cF32, prototype Ca7Ge) was predicted at 0 K through density functional theory (DFT), and using cluster expansion (CE) method and grand canonical Monte Carlo (GCMC) simulation, the ordering temperature of fcc-based Pt7Cu ordering phase was estimated to be above room temperature. The formation of Pt7Cu ordering phase was confirmed by a short-time irradiation for 3.6×103 s at 600 K. MeV electron irradiation can reduce drastically the annealing time for the ordering in the Pt-Cu alloy system, indicating that the combination of the prediction by ab initio calculations and HVEM can offer the unique opportunity to investigate the existence of ordering phase in alloys.
Preparation of a sigma-CrFe single-phase specimen was achieved by arc melting of pure Fe and Cr, cold rolling, and subsequent annealing at 973 K or 1073 K in vacuum. Cold rolling before annealing is effective for the annealing-induced formation of sigma-CrFe from the bcc solid-solution phase. The phase stability and the structural change from sigma-CrFe to a bcc solid-solution phase under fast electron irradiation were investigated by in situ transmission electron microscope (TEM) observation in the temperature range between 22 K and 473 K by using an ultra-high voltage electron microscope (UHVEM). The phase transition of sigma-CrFe by fast electron irradiation was found to occur at a particular temperature.
Evidence suggests that breastfeeding during infancy lowers the risk of metabolic syndrome (MS) and its attendant risk factors in adult life. To investigate the influence of feeding type on the risk factors of MS, we assessed insulin sensitivity and lipid and apolipoprotein metabolism in preterm infants. Blood samples were collected from preterm infants at the time of discharge. Infants were separated into two groups: a breast milk (BM) group receiving ⩾90% of their intake from BM, and a mixed-fed (MF) group receiving ⩾50% of their intake from formula. The following indices were then compared between the two groups. Blood glucose and serum insulin levels were used to calculate the quantitative insulin sensitivity check index (QUICKI). We also measured serum total cholesterol (TC), low-density lipoprotein cholesterol (LDLc), high-density lipoprotein cholesterol (HDLc), apolipoprotein-A1 (apoA1) and apolipoprotein-B (apoB) levels, and the ratios of TC/HDLc, LDLc/HDLc and apoB/apoA1. The mean gestational age was 32.9 weeks at birth, and blood samples were collected at a mean corrected age of 37.4 weeks. There were 22 infants in the BM group and 19 in the MF group. QUICKI was significantly higher in the BM group. TC, HDLc and apoA1 were not significantly different between the groups, but LDLc and apoB levels were significantly higher in the BM group. The TC/HDLc, LDLc/HDLc and apoB/apoA1 ratios were significantly higher in the BM group. In preterm infants, the type of feeding exposure in the early postnatal period may influence glucose, lipid and apolipoprotein metabolism, and affect markers of MS.
The association between consumption of full-fat dairy foods and CVD may depend partly on the nature of products and may not apply to low-fat dairy foods. Increased circulating levels of inflammatory biomarkers after consumption of dairy product-rich meals suggest an association with CVD. In the present study, we tested the effects of low-fat and full-fat dairy diets on biomarkers associated with inflammation, oxidative stress or atherogenesis and on plasma lipid classes. Within full-fat dairy diets, we also compared fermented v. non-fermented products. In a randomised cross-over study, twelve overweight/obese subjects consumed during two 3-week periods two full-fat dairy diets containing either yogurt plus cheese (fermented) or butter, cream and ice cream (non-fermented) or a low-fat milk plus yogurt diet, with the latter being consumed between and at the end of the full-fat dairy dietary periods. The concentrations of six inflammatory and two atherogenic biomarkers known to be raised in CVD were measured as well as those of plasma F2-isoprostanes and lipid classes. The concentrations of six of the eight biomarkers tended to be higher on consumption of the low-fat dairy diet than on that of the fermented dairy diet and the concentrations of two plasmalogen lipid classes reported to be associated with increased oxidisability were also higher on consumption of the low-fat dairy diet than on that of the fermented dairy diet (P< 0·001), although plasma F2-isoprostane concentrations did not differ on consumption of any of the diets. On the other hand, the concentrations of plasma sphingomyelin and IL-6 were significantly higher on consumption of the non-fermented dairy diet than on that of the low-fat dairy diet (P< 0·02). In conclusion, short-term diets containing low-fat dairy products did not lead to a more favourable biomarker profile associated with CVD risk compared with the full-fat dairy products, suggesting that full-fat fermented dairy products may be the more favourable.
The prevalence and epidemiological traits of human immunodeficiency virus (HIV)/hepatitis B virus (HBV) infections in high-risk populations (HRPs) remained unclarified in Japan. We determined the prevalence of HIV, HBV and Treponema pallidum (TP) and the viral genotypes in HRPs who attended primary sexually transmitted infection (STI) clinics in Osaka province during 2006–2011. Of 7898 specimens, 133 (1·7%) were HIV positive, which was significantly higher than the figures reported by Japanese Red Cross (0·0019%) and public health centres (0·27%) in Japan. The frequency of HIV-1 subtype B was 88·7%, followed by CRF01_AE (2·3%) and C (0·8%), which were almost identical to the national trend. HBV seroprevalence was surprisingly high in the HIV-positive group (63·2%), which was significantly higher than that in the HIV-negative group (25·6%). By contrast, there was no statistical correlation between HIV and TP infection. Interestingly, the distinct HBV genotypes Ae and G were prevalent in the HIV-positive population (60·0% and 20·0%, respectively), although both were rarely detected during nationwide surveillance. The transmission of HIV and HBV appeared to occur largely within a closed community early in life. Of note, about one-quarter of HIV-positive cases would have remained untested if health professionals had not motivated individuals to undergo HIV testing. This is the first evidence-based assessment of HIV positivity and HIV/HBV co-infection in HRPs at primary STIs in Japan and the effect of the involvement of health professionals in the diagnosis of HIV infections in asymptomatic carriers. The genotyping of HBV provided valuable information for understanding HIV epidemical traits.
We have prepared 2% Al doped ZnO (AZO) thin films on SrTiO3 and Al2O3 substrates by Pulsed Laser Deposition (PLD) technique at various deposition temperatures (Tdep = 300 °C – 600 °C). Transport and thermoelectric properties of AZO thin films were studied in low temperature range (300 K - 600 K). AZO/STO films present superior performance respect to AZO/Al2O3 films deposited at the same temperature, except for films deposited at 400 °C. Best film is the fully c-axis oriented AZO/STO deposited at 300 °C, with electrical conductivity 310 S/cm, Seebeck coefficient -65 μV/K and power factor 0.13 × 10-3 Wm-1K-2 at 300 K. Its performance increases with temperature. For instance, power factor is enhanced up to × 10-3 Wm-1K-2 at 600 K, surpassing the best AZO film previously reported in literature.
The Shozu Herpes Zoster (SHEZ) Study was designed to clarify the incidence of and predictive and immunological factors for herpes zoster in a defined community-based Japanese population. As part of this series, a total of 5683 residents aged ⩾50 years received a varicella-zoster virus (VZV) skin test with VZV antigen, and 48 h later, the erythema and oedema were assessed by measuring the longest diameter. The diameters of both the erythema and oedema decreased with the increasing age of the subject. Sixty-three subjects contracted herpes zoster within a year after receiving the VZV skin test. Analysis of the herpes zoster incidence rate vs. the skin test reaction revealed that the shorter the diameter of erythema or oedema, the greater the likelihood of herpes zoster. These results demonstrated that the VZV skin test is an excellent surrogate marker for predicting the risk of herpes zoster.
NASA's NuSTAR observatory is the first focusing hard X-ray telescope. Launched in June 2012, NuSTAR is sensitive in the 3–79 keV range with unprecedented ~17″ FWHM angular resolution above 12 keV, a result of its multilayer-coated optics and 10-m focal length. With its large effective area (900 cm2 at 10 keV), NuSTAR has point-source sensitivity ~100 times better than previous hard X-ray telescopes. Here we describe NuSTAR and its planned work on rotation-powered pulsars and magnetars during its nominal 2-yr baseline mission that has just commenced.
Combinatorial sputtering is one of the useful methods that can be used to search for optimal composition of alloy materials or for new alloy materials. To search materials more efficiently, it is required that compositions and their distribution on samples can be easily controlled for the evaluation of their properties. Moreover, it is desirable that compositions change linearly to search for novel materials systematically. In conventional combinatorial sputtering method, it is difficult to fabricate samples having linear compositions distribution without moving hard masks or rotating substrate.
In this paper, a novel combinatorial sputtering method with New Facing Targets Sputtering (Combi-NFTS) of material search is introduced. In this method, several sputtering targets are placed in opposite direction, and substrates are placed in vertical direction of these targets. From this structure, thin film with binary/ternary composition distribution could be synthesized onto one single substrate. Moreover, it can fabricate samples having relatively linear composition distribution without moving hard masks or rotating substrate. As an example, Cu, Zr and Ti pure targets were used to confirm the performance of Combi-NFTS. Binary system of Cu-Zr and ternary system of Cu-Zr-Ti thin films were fabricated by using Combi-NFTS. After deposition, compositions of the films were characterized by the energy dispersive X-ray spectroscopy. As a result of Cu-Zr binary system, the composition of the thin film was changed as the power of targets was changed. Moreover, composition distribution was expanded as the distance from substrate to targets was decreased. In the Cu-Zr-Ti ternary system, it was obtained similar trend for composition distribution. Moreover, the composition changed two dimensional by changing the substrate position.
These results indicate that combi-NFTS can easily control the composition and composition distribution of thin films by changing the power of targets or the distance from substrate to targets which make combi-NFTS very suitable for combinatorial materials search.