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The diagnosis of central nervous system tumours has been transformed in recent years from a microscopic morphology-based process to one dominated by the identification of somatic genetic alterations in tumour cells. This switch requires implementing radically different methods, for which appropriate training and financial resources must be allocated. The Canadian Association of Neuropathologists (CANP) has followed a process based on the scientific literature and consensus to develop recommendations for molecular testing of tumours of the brain and spinal cord, aiming to balance the need for treatment-determinant accurate diagnosis and the current limitations inherent in the transition to a new paradigm. The Professional Affairs Committee was charged with this task. A draft was discussed during the CANP general assembly, along with presentations from groups who had implemented molecular technologies, as well as others who relied on external laboratories. The Professional Affairs Committee summarised the consensus and submitted their recommendation to the CANP’s Executive Committee. A final report was posted on the CANP website for a month to allow all members to comment. The recommendations below apply to intrinsic tumours of the central nervous system and do not include metastatic disease or tumours impinging upon the nervous system from outside. These recommendations should be considered clinically relevant, as the results have direct consequences on the patient’s treatment, either through the use of targeted therapies or the trial-proven best application of radiation and/or chemotherapy.
Adolescence is a period marked by highest vulnerability to the onset of depression, with profound implications for adult health. Neuroimaging studies have revealed considerable atrophy in brain structure in these patients with depression. Of particular importance are regions responsible for cognitive control, reward, and self-referential processing. However, the causal structural networks underpinning brain region atrophies in adolescents with depression remain unclear.
Objectives
This study aimed to investigate the temporal course and causal relationships of gray matter atrophy within the brains of adolescents with depression.
Methods
We analyzed T1-weighted structural images using voxel-based morphometry in first-episode adolescent patients with depression (n=80, 22 males; age = 15.57±1.78) and age, gender matched healthy controls (n=82, 25 males; age = 16.11±2.76) to identify the disease stage-specific gray matter abnormalities. Then, with granger causality analysis, we arranged the patients’ illness duration chronologically to construct the causal structural covariance networks that investigated the causal relationships of those atypical structures.
Results
Compared to controls, smaller volumes in ventral medial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), middle cingulate cortex (MCC) and insula areas were identified in patients with less than 1 year illness duration, and further progressed to the subgenual ACC, regions of default, frontoparietal networks in longer duration. Causal network results revealed that dACC, vmPFC, MCC and insula were prominent nodes projecting exerted positive causal effects to regions of the default mode and frontoparietal networks. The dACC, vmPFC and insula also had positive projections to the reward network, which included mainly the thalamus, caudate and putamen, while MCC also exerted a positive causal effect on the insula and thalamus.
Conclusions
These findings revealed the progression of structural atrophy in adolescent patients with depression and demonstrated the causal relationships between regions involving cognitive control, reward and self-referential processes.
Depression and anxiety are common and highly comorbid, and their comorbidity is associated with poorer outcomes posing clinical and public health concerns. We evaluated the polygenic contribution to comorbid depression and anxiety, and to each in isolation.
Methods
Diagnostic codes were extracted from electronic health records for four biobanks [N = 177 865 including 138 632 European (77.9%), 25 612 African (14.4%), and 13 621 Hispanic (7.7%) ancestry participants]. The outcome was a four-level variable representing the depression/anxiety diagnosis group: neither, depression-only, anxiety-only, and comorbid. Multinomial regression was used to test for association of depression and anxiety polygenic risk scores (PRSs) with the outcome while adjusting for principal components of ancestry.
Results
In total, 132 960 patients had neither diagnosis (74.8%), 16 092 depression-only (9.0%), 13 098 anxiety-only (7.4%), and 16 584 comorbid (9.3%). In the European meta-analysis across biobanks, both PRSs were higher in each diagnosis group compared to controls. Notably, depression-PRS (OR 1.20 per s.d. increase in PRS; 95% CI 1.18–1.23) and anxiety-PRS (OR 1.07; 95% CI 1.05–1.09) had the largest effect when the comorbid group was compared with controls. Furthermore, the depression-PRS was significantly higher in the comorbid group than the depression-only group (OR 1.09; 95% CI 1.06–1.12) and the anxiety-only group (OR 1.15; 95% CI 1.11–1.19) and was significantly higher in the depression-only group than the anxiety-only group (OR 1.06; 95% CI 1.02–1.09), showing a genetic risk gradient across the conditions and the comorbidity.
Conclusions
This study suggests that depression and anxiety have partially independent genetic liabilities and the genetic vulnerabilities to depression and anxiety make distinct contributions to comorbid depression and anxiety.
In the present study, we investigated the influence of different mid-stage N compensation timings on agronomic and physiological traits associated with grain yield and quality in field experiments. Two japonica rice cultivars with a good tasting quality (Nangeng 9108 and Nangeng 5055) were examined under eight N compensation timings (N1–N6: one-time N compensation at 7-2 weeks before heading; N7: split N compensation at 5 and 3 weeks before heading; N8: split N compensation at 4 and 2 weeks before heading) and a control with no N compensation. The highest yield was obtained with N7, followed by N3. The yield advantage is mainly attributable to the improved population structure (higher productive tiller rate with a stable number of effective panicles), higher total number of spikelets per unit area (large panicles with more grains per panicle), larger leaf area index in the late period and higher photosynthetic production capacity (more dry matter accumulation and transportation in the middle and late periods). Delaying N compensation timing improved the processing and nutritional quality of rice, but decreased the quality of appearance and cooking/eating traits. Our results suggest that, from the perspective of achieving relative coordination between high yield and high quality of japonica rice, the optimal N compensation should be divided equally at 5 and 3 weeks before heading. However, if simplifying the number of operations and the pursuit of eating quality were considered, one-time N compensation should be conducted at 5 weeks before heading.
Patients with bipolar disorder (BPD) are prone to engage in risk-taking behaviours and self-harm, contributing to higher risk of traumatic injuries requiring medical attention at the emergency room (ER).We hypothesize that pharmacological treatment of BPD could reduce the risk of traumatic injuries by alleviating symptoms but evidence remains unclear. This study aimed to examine the association between pharmacological treatment and the risk of ER admissions due to traumatic injuries.
Methods
Individuals with BPD who received mood stabilizers and/or antipsychotics were identified using a population-based electronic healthcare records database in Hong Kong (2001–2019). A self-controlled case series design was applied to control for time-invariant confounders.
Results
A total of 5040 out of 14 021 adults with BPD who received pharmacological treatment and had incident ER admissions due to traumatic injuries from 2001 to 2019 were included. An increased risk of traumatic injuries was found 30 days before treatment [incidence rate ratio (IRR) 4.44 (3.71–5.31), p < 0.0001]. After treatment initiation, the risk remained increased with a smaller magnitude, before returning to baseline [IRR 0.97 (0.88–1.06), p = 0.50] during maintenance treatment. The direct comparison of the risk during treatment to that before and after treatment showed a significant decrease. After treatment cessation, the risk was increased [IRR 1.34 (1.09–1.66), p = 0.006].
Conclusions
This study supports the hypothesis that pharmacological treatment of BPD was associated with a lower risk of ER admissions due to traumatic injuries but an increased risk after treatment cessation. Close monitoring of symptoms relapse is recommended to clinicians and patients if treatment cessation is warranted.
The average maturity of newly issued corporate bonds has declined substantially over the past 40 years, and the traditional determinants of debt maturity fail to explain this decline fully. We show that the changing composition of investors in the corporate bond market influences bond maturities. The results of a Granger causality test, an instrumental variable approach, and a natural experiment suggest that a decline in the insurance companies’ – which prefer long-term bonds – ownership share in the corporate bond market explains a significant part of the unexplained maturity decline. These findings illustrate how investor preferences can have real effects on corporations.
The location of the vertical segment of the facial nerve varies greatly among patients undergoing otological surgery. Its position relative to the incus determines facial recess width, which has implications for ease of cochlear implantation.
Objective
To investigate the variation in facial nerve depth, relative to the incus, on pre-operative computed tomography in patients undergoing cochlear implantation.
Methods
A retrospective cohort study was conducted of paediatric patients undergoing cochlear implantation at a tertiary referral centre. Distance between the incus short process and facial nerve, in the transverse (medial-lateral) dimension, was measured at six imaging slices, ranging from 1.25 to 7.25 mm below the tip of the incus short process.
Results
Facial nerve depth relative to the incus short process demonstrated significant variability. Among all subjects and at all measurements taken inferior to the incus, the mean dimension between the facial nerve and the incus short process was 1.71 mm.
Conclusion
This paper presents a rapid, repeatable technique to assess the depth of the facial nerve vertical segment on pre-operative computed tomography, as measured relative to the tip of the incus short process. This allows the surgeon to anticipate facial recess width and round window access during cochlear implantation.
Manure is a primary source of methane (CH4) emissions into the atmosphere. A large proportion of CH4 from manure is emitted during storage, but this varies with storage methods. In this research, we tested whether covering a manure heap with plastic reduces CH4 emission during a short-term composting process. A static chamber method was used to detect the CH4 emission rate and the change of the physicochemical properties of cattle manure which was stored either uncovered (treatment UNCOVERED) or covered with plastic (treatment COVERED) for 30-day periods during the four seasons? The dry matter content of the COVERED treatment was significantly less than the UNCOVERED treatment (P < 0.01), and the C/N ratio of the COVERED treatment significantly greater than the UNCOVERED treatment (P > 0.05) under high temperature. In the UNCOVERED treatment, average daily methane (CH4) emissions were in the order summer > spring > autumn > winter. CH4 emissions were positively correlated with the temperature (R2 = 0.52, P < 0.01). Compared to the UNCOVERED treatment, the daily average CH4 emission rates from COVERED treatment manure were less in the first 19 days of spring, 13 days of summer, 10 days of autumn and 30 days of winter. In summary, covering the manure pile with plastic reduces the evaporation of water during storage; and in winter, long-term covering with plastic film reduces the CH4 emissions during the storage of manure.
Glutamine synthetase (GS) and glutamate synthase (GOGAT) play a central role in plant nitrogen (N) metabolism. In order to study the effect of powdery mildew (Blumeria graminis f. sp. tritici, Bgt) on N metabolism, field experiments were carried out to evaluate GS and GOGAT activity, GS expression and grain protein content (GPC) in susceptible (Xi'nong 979) and resistant (Zhengmai 103) wheat cultivars under three treatments. The three treatments were no inoculation (CK), inoculated once with Bgt (MP) and inoculated nine times with Bgt (HP). For Xi'nong 979, the activities of GS and GOGAT in grains as well as GS activity in flag leaves increased at 10–15 days after anthesis (DAA), and decreased significantly at 15 or 20–30 DAA in HP and MP. However, GS activity in grains decreased from 20 DAA, which was later than that of flag leaves (15 DAA). At the same time, GS expression in grains was up-regulated at early stage, with GS1 at 10 DAA and GS2 at 15 DAA, followed by a continuous down-regulation. This result indicated that GS and GOGAT activity as well as GS expression were inhibited by powdery mildew, indicating that N metabolism in grains was inhibited at 20–30 DAA. The current study also found out that the yield of the susceptible cultivar decreased significantly, while its GPC increased obviously in HP. It was shown that the increase of GPC was not due to the enhancement of N metabolism, but due to the passive increase caused by yield reduction.
Dry wind-tunnel (DWT) flutter test systems model the unsteady distributed aerodynamic force using various electromagnetic exciters. They can be used to test the aeroelastic and aeroservoelastic stability of smart aircraft or high-speed flight vehicles. A new parameterised modelling method at the full system level based on the generalised force equivalence for DWT flutter systems is proposed herein. The full system model includes the structural dynamic model, electromechanical coupling model and fast aerodynamic computation model. An optimisation search method is applied to determine the best locations for measurement and excitation by introducing Fisher’s information matrix. The feasibility and accuracy of the proposed system-level numerical DWT modelling method have been validated for a plate aeroelastic model with four exciters/transducers. The effects of key parameters including the number of exciters, the control time delay, the noise interference and the electrical parameters of the electromagnetic exciter model have also been investigated. The numerical and experimental results indicate that the proposed modelling method achieves good accuracy (with deviations of less than 1.5% from simulations and 4.5% from experimental test results for the flutter speed) and robust performance even in uncertain environments with a 10% noise level.
The Dayao Paleolithic site, located in Inner Mongolia on the eastern margin of China's vast northwestern drylands, was a lithic quarry-workshop utilized by Pleistocene human migrants through the region. Determining the age of this activity has previously yielded controversial results. Our magnetostratigraphic and OSL dating results suggest the two artifact-bearing paleosols are correlated with MIS 5 and 7, respectively. Correlating paleoclimatic data with marine δ18O records leads us to conclude that two sandy gravel layers containing many artifacts in the lower part of the Dayao sequence were formed during MIS 9 and 11, if not earlier. Our results reveal that the earliest human occupation at the Dayao site occurred before ca. 400 ka during a relatively warm and moist interglacial period, similar to several subsequent occupations, documenting the earliest and northernmost archaeological assemblage yet reported in China's arid northwest. We conclude that the northward and southward displacements of the East Asian summer monsoon rain belt during past interglacial-glacial cycles were responsible for the discontinuous human occupation detected at the Dayao site. The penetration of this precipitation regime into dryland ecologies via the Huanghe (Yellow River) Valley effectively created a corridor for hominin migration into China's arid northwest.
Active flow control for aerofoils has been proven to be an effective way to improve the aerodynamic performance of aircraft. A conceptual hybrid design with surfaces embedded with Shape-Memory Alloy (SMA) and trailing Macro Fibre Composites (MFC) is proposed to implement active flow control for aerofoils. A Computational Fluid Dynamics (CFD) model has been built to explore the feasibility and potential performance of the proposed conceptual hybrid design. Accordingly, numerical analysis is carried out to investigate the unsteady flow characteristics by dynamic morphing rather than using classical static simulations and complicated coupling. The results show that camber growth by SMA action could cause an evident rise of Cl and Cd in the take-off/landing phases when the Angle-of-Attack (AoA) is less than 10°. The transient tail vibration behaviour in the cruise period when using MFC actuators is studied over wide ranges of frequency, AoA and vibration amplitude. The buffet frequency is locked in by the vibration frequency, and a decrease of 1.66–2.32% in Cd can be achieved by using a proper vibration frequency and amplitude.
Systemic venous hypertension and low cardiac output are believed to be important mediators of liver injury after the Fontan procedure. Pulmonary vasodilators have the potential to improve such haemodynamics. The aim of this study was to assess the acute effects of exercise on liver stiffness and venous pressures and to assess the impact of inhaled Treprostinil on this response.
Methods:
In this prospective, double-blind, placebo-controlled, crossover trial, 14 patients with a Fontan circulation were randomised to inhalation of placebo and Treprostinil. Incremental and constant work rate exercise tests were performed to assess the effect of Treprostinil on exercise tolerance. Venous pressures were measured throughout and liver stiffness at rest and immediately after peak exercise.
Results:
Mean age was 27.8 ± 7.9 years and 66% were females. Exercise acutely increased liver stiffness by 30% (mean shear wave speed: 2.38 ± 0.71 versus 2.89 ± 0.51 ms, p = 0.02). Peripheral venous pressures increased acutely during both incremental (12.1 ± 2.4 versus 22.6 ± 8.0 mmHg, p < 0.001) and constant work rate exercise (12.5 ± 2.5 versus 23.4 ± 5.2 mmHg, p < 0.001). Overall, Treprostinil failed to attenuate exercise-induced increases in liver stiffness. Compared with placebo, Treprostinil did not significantly impact venous pressure responses, VO2peak, nor exercise endurance times.
Conclusions:
Peripheral venous pressure increased acutely during exercise by an average of 88% above baseline and was not altered by administration of inhaled Treprostinil. Liver stiffness measured immediately post-exercise increased acutely by an average of 30%, with no attenuation following Treprostinil inhalation.
The present study was undertaken to evaluate the influence of rumen-protected folic acid (RPFA) on slaughter performance, visceral organ and gastrointestinal tract coefficients, and meat quality in lambs. Sixty-six lambs from 120 Hu ewes were selected based on body weight and maternal diets and then assigned to six groups using a randomised block experimental design in a 3 × 2 factorial arrangement. The first factor was folic acid (FA) as RPFA in the maternal diet (0 mg/kg (M0F), 16 mg/kg (M16F) or 32 mg/kg (M32F) on DM basis). The second factor was FA in the lambs’ diet from weaning until slaughter (0 mg/kg (OC) or 4·0 mg/kg (OF)). The results indicated that the addition of 16 mg/kg FA to the maternal diet increased pre-slaughter weight (PSW), dressing and meat percentage, the reticulum and omasum coefficients, length of the jejunum and ileum, tail fat and perirenal fat coefficient and a* value of the meat colour. The addition of RPFA to the lambs’ diet increased PSW, dressing and meat percentage, eye muscle area, abomasum weight, weight and length of the small intestine, but reduced the coefficients of tail fat. An M × O interaction was observed for the weights of heart, lungs, rumen and total stomach, weight and coefficient of omental fat and the girth rib value. Collectively, RPFA in the maternal and lambs’ diet improved slaughter performance and meat quality by stimulating the morphological development of the gastrointestinal tract and the distribution of fat in the body.
Fluid motion has two well-known fundamental processes: the vector transverse process characterized by vorticity, and the scalar longitudinal process consisting of a sound mode and an entropy mode, characterized by dilatation and thermodynamic variables. The existing theories for the sound mode involve the multi-variable issue and its associated difficulty of source identification. In this paper, we define the source of sound inside the fluid by the objective causality inherent in dynamic equations relevant to a longitudinal process, which naturally favours the material time-rate operator $D/Dt$ rather than the local time-rate operator $\unicode[STIX]{x2202}/\unicode[STIX]{x2202}t$, and describes the sound mode by inhomogeneous advective wave equations. The sources of sound physical production inside the fluid are then examined at two levels. For the conventional formulation in terms of thermodynamic variables at the first level, we show that the universal kinematic source can be condensed to a scalar invariant of the surface deformation tensor. Further, in the formulation in terms of dilatation at the second level, we find that the sound mode in viscous and heat-conducting flow has sources from rich nonlinear couplings of vorticity, entropy and surface deformation, which cannot be disclosed at the first level. Preliminary numerical demonstration of the theoretical findings is made for two typical compressible flows, i.e. the interaction of two corotating Gaussian vortices and the unsteady type IV shock/shock interaction. The results obtained in this study provide a new theoretical basis for, and physical insight into, understanding various nonlinear longitudinal processes and the interactions therein.
We describe an ultra-wide-bandwidth, low-frequency receiver recently installed on the Parkes radio telescope. The receiver system provides continuous frequency coverage from 704 to 4032 MHz. For much of the band (
${\sim}60\%$
), the system temperature is approximately 22 K and the receiver system remains in a linear regime even in the presence of strong mobile phone transmissions. We discuss the scientific and technical aspects of the new receiver, including its astronomical objectives, as well as the feed, receiver, digitiser, and signal processor design. We describe the pipeline routines that form the archive-ready data products and how those data files can be accessed from the archives. The system performance is quantified, including the system noise and linearity, beam shape, antenna efficiency, polarisation calibration, and timing stability.
To evaluate the upper airway morphology changes associated with ageing in adult Chinese patients with obstructive sleep apnoea.
Methods
A total of 124 male patients diagnosed with obstructive sleep apnoea by overnight polysomnography, who underwent upper airway computed tomography, were enrolled. The linear dimensions, cross-sectional area and volume of the upper airway region and the surrounding bony frame were measured. The association between ageing and upper airway morphology was analysed.
Results
Soft palate length, minimum cross-sectional area of the retroglossal region, lateral dimensions at the minimum cross-sectional area of the retropalatal and retroglossal regions, nasopharyngeal volume, and average cross-sectional area of the nasopharyngeal region were found to significantly increase with ageing in all patients, while the upper airway shape flattened with ageing. The volume of the retropalatal region increased with ageing among the patients with a body mass index of less than 24 kg/m2. The volume of parapharyngeal fat pad increased with ageing among patients with a body mass index greater than 28 kg/m2.
Conclusion
A number of dimensional, cross-sectional and volumetric parameters of the pharynx increased with age, indicating that non-anatomical factors may play a more important role in the pathogenesis of obstructive sleep apnoea in aged patients.
Feathers play a critical role in thermoregulation and directly influence poultry production. Poor feathering adversely affects living appearance and carcass quality, thus reducing profits. However, producers tend to ignore the importance of feather development and do not know the laws of feather growth and development. The objective of this study was to fit growth curves to describe the growth and development of feathers in yellow-feathered broilers during the embryonic and posthatching periods using different nonlinear functions (Gompertz, logistic and Bertalanffy). Feather mass and length were determined during the embryonic development and posthatching stages to identify which growth model most accurately described the feather growth pattern. The results showed that chick embryos began to grow feathers at approximately embryonic (E) day 10, and the feathers grew rapidly from E13 to E17. There was little change from E17 to the day of hatching (DOH). During the embryonic period, the Gompertz function (Y = 798.48e−203 431exp(−0.87t), Akaike’s information criterion (AIC) = −0.950 × 103, Bayesian information criterion (BIC) = −0.711 × 103 and mean square error (MSE) = 559.308) provided the best fit for the feather growth curve compared with the other two functions. After hatching, feather mass and length changed little from the DOH to day (D) 14, increased rapidly from D21 to D91 and then grew slowly after D91. The first stage of feather molting occurred from 2 to 3 weeks of age when the down feathers were mostly shed and replaced with juvenile feathers, and the second stage occurred at approximately 13 to 15 weeks of age. The three nonlinear functions could overall fit the feather growth curve well, but the Bertalanffy model (Y = 116.88 × (1−0.86e−0.02t)3, AIC = 1.065 × 105, BIC = 1.077 × 105 and MSE = 11.308) showed the highest degree of fit among the models. Therefore, the Gompertz model exhibited the best goodness of fit for the feather growth curve during the embryonic development, while the Bertalanffy model was the most suitable model due to its accurate ability to predict the growth and development of feathers during the growth period, which is an important commercial characteristic of yellow-feathered chickens.
The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.