Book chapters will be unavailable on Saturday 24th August between 8am-12pm BST. This is for essential maintenance which will provide improved performance going forwards. Please accept our apologies for any inconvenience caused.
To send content items to your account,
please confirm that you agree to abide by our usage policies.
If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account.
Find out more about sending content to .
To send content items to your Kindle, first ensure email@example.com
is added to your Approved Personal Document E-mail List under your Personal Document Settings
on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part
of your Kindle email address below.
Find out more about sending to your Kindle.
Note you can select to send to either the @free.kindle.com or @kindle.com variations.
‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi.
‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.
Background: Hereditary transthyretin-mediated (hATTR) amyloidosis a hereditary, multi-systemic and life-threatening disease resulting in neuropathy and cardiomyopathy. In the APOLLO study, patisiran, an investigational RNAi therapeutic targeting hepatic TTR production resulted in significant improvement in neuropathy and QoL compared to placebo and was generally well tolerated. Methods: APOLLO, a Phase 3 study of patisiran vs. placebo (NCT01960348) prespecified a cardiac subpopulation (n=126 of 225 total) that included patients with baseline left ventricular (LV) wall thickness ≥ 13mm and no medical history of aortic valve disease or hypertension. Cardiac measures included structure and function by electrocardiography, changes in NT-proBNP and 10-MWT gait speed. Results: At 18 months, patisiran treatment resulted in a mean reduction in LV wall thickness of 1 mm (p=0.017) compared to baseline, which was associated with significant improvements relative to placebo in LV end diastolic volume (+8.31 mL, p=0.036), global longitudinal strain (-1.37%, p=0.015) and NT-proBNP (55% reduction, p=7.7 x 10-8) (Figure 1). Gait speed was also improved relative to placebo (+0.35 m/sec, p=7.4 x 10-9). Rate of death or hospitalization was lower with patisiran. mNIS+7 results in the cardiac subpopulation will also be presented. Conclusions: These data suggest patisiran has the potential to halt or reverse cardiac manifestations of hATTR amyloidosis.
Background: Microglia and macrophages (MMs) are the largest component of the inflammatory infiltrate in glioblastoma (GBM). However, whether there are immunophenotypic differences in isocitrate dehydrogenase (IDH)-mutated and -wildtype GBMs is unknown. Studies on specimens of untreated IDH-mutant GBMs are rare given they comprise 10% of all GBMs and often receive treatment at lower grades that can drastically alter MM phenotypes. Methods: We obtained large samples of untreated IDH-mutant and -wildtype GBMs. Using immunofluorescence techniques with single-cell automated segmentation, and comparison between single-cell RNA-sequencing (scRNA-seq) databases of human GBM, we discerned dissimilarities between GBM-associated MMs (GAMMs). Results: There are significantly fewer but more pro-inflammatory GAMMs in IDH-mutant GBMs, suggesting this contributes to the better prognosis of these tumors. Our pro-inflammatory score which combines the expression of inflammatory markers (CD68/HLA-A, -B, -C/TNF/CD163/IL10/TGFB2), Iba1 intensity, and GAMM surface area also indicates more pro-inflammatory GAMMs are associated with longer overall survival independent of IDH status. scRNA-seq analysis demonstrates microglia in IDH-mutants are mainly pro-inflammatory, while anti-inflammatory macrophages that upregulate genes such as FCER1G and TYROBP predominate in IDH-wildtype GBM. Conclusions: Taken together, these observations are the first head-to-head comparison of GAMMs in treatment-naïve IDH-mutant versus -wildtype GBMs that highlight biological disparities that can be exploited for therapeutic purposes.
Childhood maltreatment (CM) plays an important role in the development of major depressive disorder (MDD). The aim of this study was to examine whether CM severity and type are associated with MDD-related brain alterations, and how they interact with sex and age.
Within the ENIGMA-MDD network, severity and subtypes of CM using the Childhood Trauma Questionnaire were assessed and structural magnetic resonance imaging data from patients with MDD and healthy controls were analyzed in a mega-analysis comprising a total of 3872 participants aged between 13 and 89 years. Cortical thickness and surface area were extracted at each site using FreeSurfer.
CM severity was associated with reduced cortical thickness in the banks of the superior temporal sulcus and supramarginal gyrus as well as with reduced surface area of the middle temporal lobe. Participants reporting both childhood neglect and abuse had a lower cortical thickness in the inferior parietal lobe, middle temporal lobe, and precuneus compared to participants not exposed to CM. In males only, regardless of diagnosis, CM severity was associated with higher cortical thickness of the rostral anterior cingulate cortex. Finally, a significant interaction between CM and age in predicting thickness was seen across several prefrontal, temporal, and temporo-parietal regions.
Severity and type of CM may impact cortical thickness and surface area. Importantly, CM may influence age-dependent brain maturation, particularly in regions related to the default mode network, perception, and theory of mind.
All-printed electronics is the key technology to ultra-low-cost, large-area electronics. As a critical step in this direction, we demonstrate that femtosecond laser processing (sintering and ablation) of solution deposited metal nanoparticles enables direct metal patterning at low-temperature with ultra high resolution (∼300nm) to overcome the resolution limitation of the current inkjet direct writing processes.
This could be explained by the combined effects of novel properties of metal nanoparticles such as melting temperature drop, strong absorption of the incident laser beam at surface plasmon mode, lower conductive heat transfer loss, and the relatively weak bonding between nanoparticles. Local thermal control of the laser sintering process could minimize the heat-affected zone and the thermal damage to the substrate and further enhance the resolution of the process. This local nanoparticle deposition and energy coupling enable an environmentally friendly and cost-effective process as well as a low-temperature manufacturing sequence to realize large-area, flexible electronics on polymer substrates.
The seasonality of individual influenza subtypes/lineages and the association of influenza epidemics with meteorological factors in the tropics/subtropics have not been well understood. The impact of the 2009 H1N1 pandemic on the prevalence of seasonal influenza virus remains to be explored. Using wavelet analysis, the periodicities of A/H3N2, seasonal A/H1N1, A/H1N1pdm09, Victoria and Yamagata were identified, respectively, in Panzhihua during 2006–2015. As a subtropical city in southwestern China, Panzhihua is the first industrial city in the upper reaches of the Yangtze River. The relationship between influenza epidemics and local climatic variables was examined based on regression models. The temporal distribution of influenza subtypes/lineages during the pre-pandemic (2006–2009), pandemic (2009) and post-pandemic (2010–2015) years was described and compared. A total of 6892 respiratory specimens were collected and 737 influenza viruses were isolated. A/H3N2 showed an annual cycle with a peak in summer–autumn, while A/H1N1pdm09, Victoria and Yamagata exhibited an annual cycle with a peak in winter–spring. Regression analyses demonstrated that relative humidity was positively associated with A/H3N2 activity while negatively associated with Victoria activity. Higher prevalence of A/H1N1pdm09 and Yamagata was driven by lower absolute humidity. The role of weather conditions in regulating influenza epidemics could be complicated since the diverse viral transmission modes and mechanism. Differences in seasonality and different associations with meteorological factors by influenza subtypes/lineages should be considered in epidemiological studies in the tropics/subtropics. The development of subtype- and lineage-specific prevention and control measures is of significant importance.
A new set of exact coherent states in the form of a travelling wave is reported in plane channel flow. They are continued over a range in
, an order of magnitude higher than those discovered in the transitional regime. This particular type of exact coherent states is found to be gradually more localised in the near-wall region on increasing the Reynolds number. As larger spanwise sizes
are considered, these exact coherent states appear via a saddle-node bifurcation with a spanwise size of
and their phase speed is found to be
at all the Reynolds numbers considered. Computation of the eigenspectra shows that the time scale of the exact coherent states is given by
in channel flow at all Reynolds numbers, and it becomes equivalent to the viscous inner time scale for the exact coherent states in the limit of
. The exact coherent states at several different spanwise sizes are further continued to a higher Reynolds number,
, using the eddy-viscosity approach (Hwang & Cossu, Phys. Rev. Lett., vol. 105, 2010, 044505). It is found that the continued exact coherent states at different sizes are self-similar at the given Reynolds number. These observations suggest that, on increasing Reynolds number, new sets of self-sustaining coherent structures are born in the near-wall region. Near this onset, these structures scale in inner units, forming the near-wall self-sustaining structures. With further increase of Reynolds number, the structures that emerged at lower Reynolds numbers subsequently evolve into the self-sustaining structures in the logarithmic region at different length scales, forming a hierarchy of self-similar coherent structures as hypothesised by Townsend (i.e. attached eddy hypothesis). Finally, the energetics of turbulent flow is discussed for a consistent extension of these dynamical systems notions to high Reynolds numbers.
Heading date (HD) and flowering date (FD) are critical for yield potential and stability, so understanding their genetic foundation is of great significance in wheat breeding. Three related recombinant inbred line populations with a common female parent were developed to identify quantitative trait loci (QTL) for HD and FD in four environments. In total, 25 putative additive QTL and 20 pairwise epistatic effect QTL were detected in four environments. The additive QTL were distributed across 17 wheat chromosomes. Of these, QHd-1A, QHd-1D, QHd-2B, QHd-3B, QHd-4A, QHd-4B and QHd-6D were major and stable QTL for HD. QFd-1A, QFd-2B, QFd-4A and QFd-4B were major and stable QTL for FD. In addition, an epistatic interaction test showed that epistasis played important roles in controlling wheat HD and FD. Genetic relationships between HD/FD and five yield-related traits (YRTs) were characterized and ten QTL clusters (C1–C10) simultaneously controlling YRTs and HD/FD were identified. The present work laid a genetic foundation for improving yield potential in wheat molecular breeding programmes.
To characterise subjective symptoms in patients undergoing surgical repair of superior semicircular canal dehiscence.
Questionnaires assessing symptom severity and impact on function and quality of life were administered to patients before superior semicircular canal dehiscence surgery, between June 2011 and March 2016. Questionnaire sections included general quality of life, internal amplified sounds, dizziness and tinnitus, with scores of 0–100 points.
Twenty-three patients completed the questionnaire before surgery. Section scores (mean±standard deviation) were: 38.2 ± 25.2 for general quality of life, 52.5 ± 23.9 for internal amplified sounds, 35.1 ± 28.8 for dizziness, 33.3 ± 30.7 for tinnitus, and 39.8 ± 22.2 for the composite score. Cronbach's α statistic averaged 0.93 (range, 0.84–0.97) across section scores, and 0.83 for the composite score.
The Gopen–Yang Superior Semicircular Canal Dehiscence Questionnaire provides a holistic, patient-centred characterisation of superior semicircular canal dehiscence symptoms. Internal consistency analysis validated the questionnaire and provided a quantitative framework for further optimisation in the clinical setting.
Didymocarpus middletonii Souvann., Soulad. & Tagane, a new species of Gesneriaceae from Nam Kading National Protected Area, is described and illustrated. The new species is morphologically similar to Didymocarpus brevicalyx, D. formosus and D. puhoatensis but distinguished from the three by its fewer-flowered inflorescence, longer pedicel, and urceolate and multicellular eglandular hairy calyx. Based on the latest IUCN criteria, Didymocarpus middletonii is proposed to be Critically Endangered (CR). Our record of Didymocarpus represents a new genus record for the flora of Laos.
The aim of our study was twofold: to examine (a) whether the link between racial discrimination and adjustment showed age-related changes across early to late adolescence for Chinese-heritage youth and (b) whether the age-related associations of the discrimination–adjustment link differed by gender, nativity, and geographical region. We pooled two independently collected longitudinal data sets in the United States and Canada (N = 498, ages 12–19 at Wave 1) and used time-varying effect modeling to show that discrimination is consistently associated with poorer adjustment across all ages. These associations were stronger at certain ages, but for males and females, first- and second-generation adolescents, and US and Canadian adolescents they differed. There were stronger relations between discrimination and adjustment in early adolescence for males compared to females, in middle adolescence for first-generation compared to second-generation adolescents, and in early adolescence for US adolescents compared to Canadian adolescents. In general, negative implications for adjustment associated with discrimination diminished across the span of adolescence for females, second-generation, and US and Canadian adolescents, but not for males or first-generation adolescents. The results show that the discrimination–adjustment link must be considered with regard to age, gender, nativity, and region, and that attention to discrimination in early adolescence may be especially important.
Good canopy structure is essential for optimal maize (Zea mays L.) production. However, creating appropriate maize canopy structure can be difficult, because the characteristics of individual plants are altered by changes in plant age, density and interactions with neighbouring plants. The objective of the current study was to find a reliable method for building good maize canopy structure by analysing changes in canopy structure, light distribution and grain yield (GY). A modern maize cultivar (ZhengDan958) was planted at 12 densities ranging from 1.5 to 18 plants/m2 at two field locations in Xinjiang, China. At the silking stage (R1), plant and ear height increased with plant density as well as leaf area index (LAI), whereas leaf area per plant decreased logarithmically. The fraction of light intercepted by the plant (F) increased with increasing plant density, but the light extinction coefficient (K) decreased linearly from 0.61 to 0.39. Taking the optimum value of F (95%) as an example, and using measured values of K for each plant density at R1 and the equation from Beer's law, the corresponding (theoretical) LAI for each plant density was calculated and optimum plant density (9.72 plants/m2) obtained by calculating the difference between theoretical LAIs and actual observations. Further analysis showed that plant density ranging from 10.64 to 11.55 plants/m2 yielded a stable GY range. Therefore, taking into account the persistence time for maximum LAI, the plant density required to obtain an ideal GY maize canopy structure should be increased by 10–18% from 9.72 plants/m2.
Three-dimensional (3D) printing technology is a promising method for bone tissue engineering applications. For enhanced bone regeneration, it is important to have printable ink materials with appealing properties such as construct interconnectivity, mechanical strength, controlled degradation rates, and the presence of bioactive materials. In this respect, we develop a composite ink composed of polycaprolactone (PCL), poly(D,L-lactide-co-glycolide) (PLGA), and hydroxyapatite particles (HAps) and 3D print it into porous constructs. In vitro study revealed that composite constructs had higher mechanical properties, surface roughness, quicker degradation profile, and cellular behaviors compared to PCL counterparts. Furthermore, in vivo results showed that 3D-printed composite constructs had a positive influence on bone regeneration due to the presence of newly formed mineralized bone tissue and blood vessel formation. Therefore, 3D printable ink made of PCL/PLGA/HAp can be a highly useful material for 3D printing of bone tissue constructs.
Phenoloxidase (PO) plays a key role in melanin biosynthesis during insect development. Here, we isolated the 2310-bp full-length cDNA of PPO1 from Zeugodacus tau, a destructive horticultural pest. qRT-polymerase chain reaction showed that the ZtPPO1 transcripts were highly expressed during larval–prepupal transition and in the haemolymph. When the larvae were fed a 1.66% kojic acid (KA)-containing diet, the levels of the ZtPPO1 transcripts significantly increased by 2.79- and 3.39-fold in the whole larvae and cuticles, respectively, while the corresponding PO activity was significantly reduced; in addition, the larval and pupal durations were significantly prolonged; pupal weights were lowered; and abnormal phenotypes were observed. An in vitro inhibition experiment indicated that KA was an effective competitive inhibitor of PO in Z. tau. Additionally, the functional analysis showed that 20E could significantly up-regulate the expression of ZtPPO1, induce lower pupal weight, and advance pupation. Knockdown of the ZtPPO1 gene by RNAi significantly decreased mRNA levels after 24 h and led to low pupation rates and incomplete pupae with abnormal phenotypes during the larval-pupal interim period. These results proved that PO is important for the normal growth of Z. tau and that KA can disrupt the development of this pest insect.
This study was designed to explore the association between undernutrition in the growth period and cardiovascular risk factors in a middle-aged Chinese population. A total of 1756 subjects, aged 45–60 years, were invited to participate in the Hefei Nutrition and Health Study and divided into three groups according to their self-reported animal food intake in the growth period. Group 1, Group 2 and Group 3 were defined as undernutrition, nutritional improvement and the good nutrition group, respectively. In the three groups, the subjects in Groups 1 and 2 had more oil and salt intake (P<0.001), and less eggs and milk intake (P<0.001), when compared with the subjects in Group 3. After adjusting for age, education, smoking status and other confounding factors, it was found that male participants who experienced nutritional improvement before age 18 had higher risk of hypertension [odds ratio (OR)=1.68; 95% confidence intervals (CI): 1.05, 2.69] than those with good nutrition, and female participants with undernutrition (OR=1.52; 95% CI: 1.01, 2.29) and nutritional improvement (OR=1.68; 95% CI: 1.04, 2.69) before age 18 had a higher risk of hypertension than those with good nutrition. For diabetes, obesity, hypercholesterolemia and hypertriglyceridemia, our results did not found difference among the three groups both in male and female. Our findings indicated that nutritional deficiency in childhood was associated with bad dietary behaviors and a significantly increased risk of hypertension in middle age. Therefore, early adequate nutrition is very important for the prevention of non-communicable diseases later.
Vanadium Pentoxide (V2O5) has been identified as a potential cathode material owning to its high specific capacity, theoretically, 441 mAh g-1 for 3Li+ ions insertion/extraction. However, the intrinsic drawbacks of V2O5, i.e. structural instability and poor electronic and ionic conductivity, greatly inhibit its application as a cathode. Here, we report a cetyltrimethylammonium bromide (CTAB)-assisted hydrothermal reaction to synthesize V2O5 nanoclusters. Unique aggregated fiber structure was obtained after annealing. To achieve a porous structure and increase the conductivity, nitrogen-doped Graphene (NG) suspended in ethylene glycol was added to the reaction mixture. The obtained spherical V2O5 nanoparticles and NG sheets were randomly dispersed in the matrix of the V2O5 spheres. As a cathode material for lithium-ion batteries, the V2O5/NG hybrids demonstrate better rate performance compared to the bundle-like V2O5 fibers, delivering higher specific capacity of ∼ 300 and 150 mAh g-1 at a rate of C/10 and 5C, respectively. The enhanced performance in lithium storage are attributed to the synergistic effect of the nanostructured V2O5/NG composites.
Introduction: ex-specific diagnostic cutoffs may improve the test characteristics of high-sensitivity troponin assays for the diagnosis of myocardial infarction. Sex-specific cutoffs for ruling in MI improve the sensitivity of the assay for MI among women, and improve the specificity of diagnosis among men. We hypothesized that the use of sex-specific high-sensitivity Troponin T (hsTnT) cutoffs for ruling out MI at the time of ED arrival would improve the classification efficiency of the assay by enabling more patients to have MI ruled out at the time of ED arrival while maintaining diagnostic sensitivity. The objective of this study was to quantify the test characteristics of sex-specific cutoffs of an hsTnT assay for acute myocardial infarction (AMI) when performed at ED arrival in patients with chest pain. Methods: This retrospective study included consecutive ED patients with suspected cardiac chest pain evaluated in four urban EDs were, excluding those with ST-elevation AMI, cardiac arrest or abnormal kidney function. The primary outcomes was AMI at 7 days. Secondary outcomes included major adverse cardiac events (MACE: all-cause mortality, AMI and revascularization) and the individual MACE components. We quantified test characteristics (sensitivity, negative predictive value, likelihood ratios and proportion of patients ruled out) for multiple combinations of sex-specific rule-out cutoffs. We calculated net reclassification improvement compared to universal rule-out cutoffs of 5ng/L (the assays limit of detection) and 6ng/L (the FDA-approved limit of quantitation for US laboratories). Results: 7130 patients, including 3931 men and 3199 women, were included. The 7-day incidence of AMI was 7.38% among men and 3.78% among women. Universal cutoffs of 5 and 6 ng/L ruled out AMI with 99.7% sensitivity in 33.6 and 42.2% of patients. The best-performing combination of sex-specific cutoffs (8g/L for men and 6ng/L for men) ruled out AMI with 98.7% sensitivity in 51.9% of patients. Conclusion: Sex-specific hsTnT cutoffs for ruling out AMI at ED arrival may achieve substantial improvement in classification performance, enabling more patients to be ruled out at ED arrival, while maintaining acceptable diagnostic sensitivity for AMI. Universal and sex-specific rule-out cutoffs differ by only small changes in hsTnT concentration. Therefore, these findings should be confirmed in other datasets.