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In this study, the thermal deformation of a machine tool structure due to the heat generated during operation was analyzed, and embedded cooling channels were applied to exchange the heat generated during the operation to achieve thermal error suppression. Then, the finite volume method was used to simulate the effect of cooling oil temperature on thermal deformation, and the effect of thermal suppression was experimentally studied using a feed system combined with a cooler to improve the positioning accuracy of the machine tool. In this study, the supply oil temperature in the structural cooling channels was found to significantly affect the position accuracy of the moving table and moving carrier. If the supply oil temperature in the cooling channels is consistent with the operational ambient temperature, the position accuracy of the moving table in the Y direction and the moving carrier in the X and Z directions has the best performance under different feed rates. From the thermal suppression experiments of the embedded cooling channels, the positioning accuracy of the feed system can be improved by approximately 25.5 % during the dynamic feeding process. Furthermore, when the hydrostatic guideway is cooled and dynamic feeding is conducted, positioning accuracy can be improved by up to 47.8 %. The machining accuracy can be improved by approximately 60 % on average by using the embedded cooling channels in this study. Therefore, thermal suppression by the cooling channels in this study can not only effectively improve the positioning accuracy but also enhance machining accuracy, proving that the method is effective for enhancing machine tool accuracy.
Laser interaction with an ultra-thin pre-structured target is investigated with the help of both two-dimensional and three-dimensional particle-in-cell simulations. With the existence of a periodic structure on the target surface, the laser seems to penetrate through the target at its fundamental frequency even if the plasma density of the target is much higher than the laser’s relativistically critical density. The particle-in-cell simulations show that the transmitted laser energy behind the pre-structured target is increased by about two orders of magnitude compared to that behind the flat target. Theoretical analyses show that the transmitted energy behind the pre-structured target is actually re-emitted by electron ‘islands’ formed by the surface plasma waves on the target surfaces. In other words, the radiation with the fundamental frequency is actually ‘surface emission’ on the target rear surface. Besides the intensity of the component with the fundamental frequency, the intensity of the high-order harmonics behind the pre-structured target is also much enhanced compared to that behind the flat target. The enhancement of the high-order harmonics is also related to the surface plasma waves generated on the target surfaces.
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.
Recent work has implicated one type of horizontal strabismus (exotropia) as a risk factor for schizophrenia. This new insight raises questions about a potential common developmental origin of the two diseases. Seasonality of births is well established for schizophrenia. Seasonal factors such as light exposure affect eye growth and can cause vision abnormalities, but little is known about seasonality of births in strabismus. We examined birth seasonality in people with horizontal strabismus in a retrospective study in Washoe County, Nevada, and re-examined similar previously obtained data from Osaka, Japan. We then compared seasonal patterns of births between strabismus, refractive error, schizophrenia and congenital toxoplasmosis. Patients with esotropia had a significant seasonality of births, with a deficit in March, then increasing to an excess in September, while patients with exotropia had a distinctly different pattern, with an excess of births in July, gradually decreasing to a deficit in November. These seasonalities were statistically significant with either χ2 or Kolmogorov–Smirnov-type statistics. The birth seasonality of esotropia resembled that for hyperopia, with an increase in amplitude, while the seasonality for myopia involved a phase-shift. There was no correlation between seasonality of births between strabismus and congenital toxoplasmosis. The pattern of an excess of summer births for people with exotropia was remarkably similar to the well-established birth seasonality of one schizophrenia subtype, the deficit syndrome, but not schizophrenia as a whole. This suggests a testable hypothesis: that exotropia may be a risk factor primarily for the deficit type of schizophrenia.
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.
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.
The gastrointestinal tract (GIT) of animals is capable of sensing various kinds of nutrients via G-protein coupled receptor-mediated signaling transduction pathways, and the process is known as ‘gut nutrient chemosensing’. GPR40, GPR41, GPR43 and GPR119 are chemoreceptors for free fatty acids (FFAs) and lipid derivatives, but they are not well studied in small ruminants. The objective of this study is to determine the expression of GPR40, GPR41, GPR43 and GPR119 along the GIT of kid goats under supplemental feeding (S) v. grazing (G) during early development. In total, 44 kid goats (initial weight 1.35±0.12 kg) were slaughtered for sampling (rumen, abomasum, duodenum, jejunum, ileum, cecum, colon and rectum) between days 0 and 70. The expression of GPR41 and GPR43 were measured at both mRNA and protein levels, whereas GPR40 and GPR119 were assayed at protein level only. The effects of age and feeding system on their expression were variable depending upon GIT segments, chemoreceptors and expression level (mRNA or protein), and sometimes feeding system × age interactions (P<0.05) were observed. Supplemental feeding enhanced expression of GPR40, GPR41 and GPR43 in most segments of the GIT of goats, whereas G enhanced expression of GPR119. GPR41 and GPR43 were mainly expressed in rumen, abomasum and cecum, with different responses to age and feeding system. GPR41 and GPR43 expression in abomasum at mRNA level was greatly (P<0.01) affected by both age and feeding system; whereas their expression in rumen and abomasum at protein level were different, feeding system greatly (P<0.05) affected GPR41 expression, but had no effect (P>0.05) on GPR43 expression; and there were no feeding system×age interactions (P>0.05) on GPR41 and GPR43 protein expression. The expression of GPR41 and GPR43 in rumen and abomasum linearly (P<0.01) increased with increasing age (from days 0 to 70). Meanwhile, age was the main factor affecting GPR40 expression throughout the GIT. These outcomes indicate that age and feeding system are the two factors affecting chemoreceptors for FFAs and lipid derivatives expression in the GIT of kids goats, and S enhanced the expression of chemoreceptors for FFAs, whereas G gave rise to greater expression of chemoreceptors for lipid derivatives. Our results suggest that enhanced expression of chemoreceptors for FFAs might be one of the benefits of early supplemental feeding offered to young ruminants during early development.
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.
Compensatory gain describes an accelerated growth seen in animals following a period of nutrient restriction. Methionine (Met) is the second limiting amino acid in typical swine diets and is essential for muscle growth. This study was conducted to determine (1) if a Met-deficient diet can cause growth retardation in growing pigs, (2) if returning to a normal feeding can yield compensatory gain in the pigs previously fed the Met-deficient diet, and (3) if this Met-deficiency followed by the normal feeding program affects carcass characteristics. Twenty individually-penned crossbred young barrows were randomly allotted to two dietary treatments (n = 10). One Met-deficient (D1) and one Met-adequate (D2) diets were formulated based on corn and soybean meal and fed to respective pigs for 31 days. After that, all pigs were fed the same commercial grower-finisher diet until market weight (around 125 kg), then slaughtered, and carcass characteristics measured. The D1 and D2 pigs began with similar body weights (23.5 vs. 23.6 kg; P = 0.935), but after 31-days on the dietary treatments, D1 pigs were lighter than D2 pigs (51.6 vs. 55.0 kg; P = 0.102). After feeding the normal diet for 55 days, D1 and D2 pigs had similar body weights (122.7 vs. 122.6 kg; P = 0.989). In terms of carcass characteristics, however, D1 pigs had thicker back-fat (at 10th rib; 2.95 vs. 2.51 cm; P = 0.015), heavier belly weight (11.0 vs. 9.6 kg; P = 0.005), lighter ham weights (untrimmed: 20.8 vs. 21.6 kg; P = 0.043; trimmed: 19.6 vs. 20.6 kg; P = 0.016), lighter picnic shoulder weight (8.72 vs. 9.80 kg; P = 0.041), lighter total lean cut weight (51.8 vs. 53.8 kg; P = 0.055), and lower lean cut percentage (56.4 vs. 59.0%; P = 0.012). These results indicate that the Met-deficient diet produced growth-retarded pigs, which showed compensatory gain after the normal feeding. At slaughter, the pigs previously fed the Met-deficient diet had more fat and less lean tissue than their non-deficient counterparts.
Background: The role of extent of surgical resection (EOR) on clinical outcomes in patients with low-grade glioma requires further examination. Methods: We systematically searched MEDLINE, Embase, and the Cochrane Library for studies published between January 1, 1990 and January 5, 2018 on predefined patient outcomes regarding different EOR of low-grade glioma. Results: Our literature search yielded 60 studies including 13,289 patients. Pooled estimates of overall survival showed an increase from 3.79 years (95% CI, 2.37–5.22) in the biopsy group to 6.68 years (95% CI, 4.19–9.16) in STR to 10.65 years (95% CI, 6.78–14.52) in GTR. When compared to STR, GTR prolonged progression-free survival by 2.08 years (95% CI, 0.26–3.89; P=0.025). Pooled estimates of seizure control showed an improvement from 47.8% (95% CI, 26.7–69.6) with biopsy to 54.2% (95% CI, 48.7–59.6) with STR to 81.0% (95% CI, 74.6–86.2) with GTR. Compared to STR, GTR delayed malignant transformation (RR, 0.43; 95% CI, 0.20–0.93; P=0.032), without increasing postoperative mortality (RR, 0.38; 95% CI, 0.07–1.97; P=0.250) or morbidity (RR, 1.22; 95% CI, 0.65–2.28; P=0.540). Conclusions: Among patients with low grade gliomas, higher degrees of safe EOR, were associated with longer overall and progression-free survival, better seizure control, and delayed malignant transformation, without increased mortality or morbidity.
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.
Background: Post-craniotomy pain can be severe and undermanaged. While opioids are the mainstay treatment, they have the potential to interfere with neurological monitoring. The objectives of this review are: 1) to identify measures to provide opioid-free analgesia 2) to compare the effectiveness of non-opioid to opioid analgesia in post-craniotomy pain. Methods: A comprehensive search of EMBASE, MEDLINE, and the Cochrane Central Registry of Controlled Trials (CENTRAL) databases was conducted for RCTs evaluating the effect of opioid vs non-opioid pain control strategies in patients undergoing supratentorial craniotomy. Results: The literature search yielded 462 citations, 5 RCTs that met the inclusion criteria for a total of 250 patients. Scalp infiltration/block was found to provide equivalent analgesia to morphine1 and fentanyl.2 Morphine was associated with slightly higher postoperative nausea and vomiting. Paracetamol was less likely to induce nausea and vomiting,3,4 but provided inadequate pain relief compared to nalbuphine,3 tramadol,3 morphine4 and sufentanil.4 Dexmedetomidine5 provided similar analgesia to remifentanil but did delay the time to first dose of rescue analgesia with similar side effects. Conclusions: Based on the limited number of RCTs comparing opioid to non-opioid techniques, no definite recommendations can be made with regards to the optimal management of post-craniotomy pain. Considerations should be made for use of multimodal analgesia-including adjuvant analgesics.
Background: CNS innate immune cells, microglia and macrophages (MMs), are the largest component of the inflammatory infiltrate in glioblastoma (GBM). They initially participate in tumor surveillance, but are co-opted by GBM to further angiogenesis and invasion. There are no effective immunotherapies against GBM in part because GBM-associated MMs are not well understood. We hypothesized that the extent and inflammatory phenotype of MM infiltration into GBM is variable between patients. This variability could have important implications on immunotherapy selection and treatment outcomes. Methods: Using automated quantitation of fluorescently labeled human GBMs, flow cytometry/live cell sorting, collection of conditioned GBM-associated MM media, and corroboration with TCGA and previously published scRNA-seq data, we have uncovered there is surprisingly marked variation in the amount of MM infiltration between tumors. Results: MM infiltration can range from almost non-existent, to comprising ~70% of GBM cells. By detecting cell surface markers and secreted cytokines, we determined that a mixture of pro- and anti-inflammatory MMs are found in each tumor. The overall inflammatory phenotype did not depend on the amount of infiltration. Interestingly, IDH-mutant GBM-associated MMs are more pro-inflammatory and less heterogeneous than IDH-wildtype GBMs. Conclusions: Taken together, the highly variable immunologic status of GBMs suggests the success of immunotherapies hinges on selecting appropriately vulnerable tumors.
Introduction: Hereditary angioedema (HAE) patients (both diagnosed and undiagnosed) commonly present to the emergency department (ED). Presenting symptoms (swelling and pain) may be erroneously attributed to common allergic and gastrointestinal conditions resulting in major delays in diagnosis and appropriate treatment. No published tools currently exist for HAE screening and management in undiagnosed disease. The overall goal of the study was to develop a HAE-RT tool for ED settings. Methods: A two-phase mixed methods approach was used to develop the HAE-RT Tool including: Phase 1: A Delphi Study [HAE specialists (N=9) and National Patient Advocacy Group Members (N=3)] was conducted to reach consensus (80% agreement) on predictor variables to include. Phase 2: A retrospective chart review was conducted to assess the predictive findings of the predictor variables. A convenient sample of patients presenting with angioedema (with and without HAE) between January 2012 January 2017 were included in the study. Results: Of the 12 experts invited, 9 (75%) participated in the Delphi study. Of 8 HAE-specific predictive variables, 4 reached consensuses including: (1) recurrent angioedema; (2) absence of urticaria; (3) past recurrent abdominal pain/swelling; (4) response to allergic therapy. The retrospective study included 85 patients (N=46 with HAE; N=39 non-HAE; overall 72% female). HAE patients were significantly more likely to have a family history of HAE (72% vs 0%; P<0.0001); previous recurrent angioedema (96%; P<0.009); present with no hives (91%; P<0.036); previous recurrent abdominal pain (80%; P<0.0001); and only 2% responded positively to allergy treatments (P<0.0001). Conclusion: Our study emphasizes the importance of key stakeholder involvement and feedback to facilitate the prioritization of important information that must be included in the design of an HAE-RT tool. The next step is to observe the effect of the HAE-RT tool on patient triage in the ED.
In vivo and in vitro trials were conducted to assess the effects of tributyrin (TB) supplementation on short-chain fatty acid (SFCA) concentrations, fibrolytic enzyme activity, nutrient digestibility and methanogenesis in adult sheep. Nine 12-month-old ruminally cannulated Small Tail ewes (initial body weight 55 ± 5.0 kg) without pregnancy were used for the in vitro trial. In vitro substrate made to offer TB at 0, 2, 4, 6 and 8 g/kg on a dry matter (DM) basis was incubated by ruminal microbes for 72 h at 39°C. Forty-five adult Small Tail ewes used for the in vivo trial were randomly assigned to five treatments with nine animals each for an 18-d period according to body weight (55 ± 5.0 kg). Total mixed ration fed to ewes was also used to offer TB at 0, 2, 4, 6 and 8 g/kg on a DM basis. The in vitro trial showed that TB supplementation linearly increased apparent digestibility of DM, crude protein, neutral detergent fibre and acid detergent fibre, and enhanced gas production and methane emissions. The in vivo trial showed that TB supplementation decreased DM intake, but enhanced ruminal fermentation efficiency. Both in vitro and in vivo trials showed that TB supplementation enhanced total SFCA concentrations and carboxymethyl cellulase activity. The results indicate that TB supplementation might exert advantage effects on rumen microbial metabolism, despite having an enhancing effect on methanogenesis.
It is difficult to control Holotrichia parallela Motschulsky with chemical insecticides due to the larvae's soil-living habit, thus the pest has caused great economic losses in agriculture. In addition, uridine diphosphate-glycosyltransferases (UGTs) catalyze the glycosylation process of a variety of small lipophilic molecules with sugars to produce water-soluble glycosides, and play multiple roles in detoxification, endobiotic modulation, and sequestration in an insect. Some UGTs were found specifically expressed in antennae of Drosophila melanogaster and Spodoptera littoralis, and glucurono-conjugated odorants could not elicit any olfactory signals, suggesting that the UGTs may play roles in odorant inactivation by biotransformation. In the current study, we performed a genome-wide analysis of the candidate UGT family in the dark black chafer, H. parallela. Based on a UGT gene signature and the similarity of these genes to UGT homologs from other organisms, 20 putative H. parallela UGT genes were identified. Bioinformatics analysis was used to predict sequence and structural features of H. parallela UGT proteins, and revealed important domains and residues involved in sugar donor binding and catalysis by comparison with human UGT2B7. Phylogenetic analysis of these 20 UGT protein sequences revealed eight major groups, including both order-specific and conserved groups, which are common to more than one order. Of these 20 UGT genes, HparUGT1265-1, HparUGT3119, and HparUGT8312 were highly (>100-fold change) expressed in antennae, suggesting a possible role in olfactory tissue, and most likely in odorant inactivation and olfactory processing. The remaining UGT genes were expressed in all tissues (head, thorax, abdomen, leg, and wing), indicating that these UGTs likely have different biological functions. This study provides the fundamental basis for determining the function of UGTs in a highly specialized olfactory organ, the H. parallela antenna.
The regular solar observations are operated at Huairou Solar Observing Station (HSOS) since 1987, which make the construction of long-term magnetic field datasets available to understand solar magnetic field and cycles. There exist some inconveniences for solar physicist to use these data, because the data storage medium and format at HSOS experienced some changes. Additionally, the processes of magnetic field calibration are not easy to deal with for who are not familiar with these data. Here shows that the magnetic field of HSOS are further processed toward international standards, in order to explore HSOS observations data for scientific research.