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Background: Deep brain stimulation (DBS) in Parkinson’s disease (PD) requires extensive trial-and-error programming, often taking over a year to optimize. An objective, rapid biomarker of stimulation success is needed. Our team developed a functional magnetic resonance imaging (fMRI)-based algorithm to identify optimal DBS settings. This study prospectively compared fMRI-guided programming with standard-of-care (SoC) clinical programming in a double-blind, crossover, non-inferiority trial. Methods: Twenty-two PD-DBS patients were prospectively enrolled for fMRI using a 30-sec DBS-ON/OFF cycling paradigm. Optimal settings were identified using our published classification algorithm. Subjects then underwent >1 year of SoC programming. Clinical improvement was assessed under SoC and fMRI-determined stimulation conditions. Results: fMRI optimization significantly reduced the time required to determine optimal settings (1.6 vs. 5.6 months, p<0.001). Unified Parkinson’s Disease Rating Scale (UPDRSIII) improved comparably with both approaches (23.8 vs. 23.6, p=0.9). Non-inferiority was demonstrated within a predefined margin of 5 points (p=0.0018). SoC led to greater tremor improvement (p=0.019), while fMRI showed greater bradykinesia improvement (p=0.040). Conclusions: This is the first prospective evaluation of an algorithm able to suggest stimulation parameters solely from the fMRI response to stimulation. It suggests that fMRI-based programming may achieve equivalent outcomes in less time than SoC, reducing patient burden while potentially enhancing bradykinesia response.
Background: Subthalamic nucleus (STN) deep brain stimulation (DBS) improves the cardinal symptoms of Parkinson’s disease (PD). However, the therapeutic mechanisms are incompletely understood. By leveraging patient-specific brain responses to DBS using functional magnetic resonance imaging (fMRI) acquired during stimulation, we identify and validate symptom-specific networks associated with clinical improvement. Methods: Forty PD patients with STN-DBS were enrolled for fMRI using a 30-sec DBS-ON/OFF cycling paradigm. The four cardinal motor outcomes of PD were chosen a priori and measured using the Movement Disorder Society-Sponsored Revision of the Unified Parkinson’s Disease Rating Scale, part III (MDS-UPDRSIII): axial instability, tremor, rigidity, bradykinesia. Stimulation-dependent changes in blood oxygen level-dependent (BOLD) signal were correlated with each symptom. Results: The relationship between BOLD response and outcomes revealed significant networks of clinical response (p<0.001). Using BOLD responses from the network hubs, each symptom-specific model was significantly predictive of actual improvement: axial instability (R2=0.38, p=0.000026), bradykinesia (R2=0.29, p=0.00033), rigidity (R2=0.40, p=0.000013), tremor (R2=0.26, p=0.00073). Conclusions: Using patient-specific imaging, we provide evidence of an association between DBS-evoked fMRI response and individual symptom improvement. Brain networks associated with clinical improvement were different depending on the PD symptom examined, suggesting the presence of symptom-specific networks of efficacy which may allow personalization of DBS therapy.
Background: Success of deep brain stimulation (DBS) in Parkinson’s disease (PD) relies on time-consuming trial-and-error testing of stimulation settings. Here, we prospectively compared an fMRI-based stimulation optimization algorithm with >1 year of standard-of-care (SoC) programming in a double-blind, crossover, non-inferiority trial. Methods: Twenty-seven PD-DBS patients were prospectively enrolled for fMRI using a 30-sec DBS-ON/OFF cycling paradigm. Optimal settings were identified using our published classification algorithm. Subjects then underwent >1 year of SoC programming. Clinical improvement was assessed, after an overnight medication washout period, under SoC and fMRI-determined stimulation conditions. A predefined non-inferiority margin was -5 points on the Unified Parkinson’s Disease Rating Scale (UPDRSIII). Results: UPDRSIII improved from 45.3 (SD=14.6) at baseline to 24.9 (SD=10.9) and 24.1 (SD=10.9) during SoC and fMRI-determined stimulation, respectively. The mean difference in scores was 0.8 (SD=8.5; 95% CI -4.5 to 6.2). The non-inferiority margin was not contained within the 95% confidence interval, establishing non-inferiority (p=0.013). Conclusions: This is the first prospective evaluation of an algorithm able to suggest stimulation parameters solely from the fMRI response to stimulation. It suggests equivalent outcomes may be achieved in 3 hours of fMRI scanning immediately after surgery compared to SoC requiring 6 or more in-person clinic visits throughout >1 year.
The Classic Maya polities of Baking Pot and Lower Dover developed along two dramatically different trajectories. At Baking Pot, the capital and associated apical elite regime grew concomitantly with surrounding populations over a thousand-year period. The smaller polity of Lower Dover, in contrast, formed when a Late Classic political center was established by an emergent apical elite regime amidst several long-established intermediate elite-headed districts. The different trajectories through which these polities formed should have clear implications for residential size variability. We employ the Gini coefficient to measure variability in household volume to compare patterns of residential size differentiation between the two polities. The Gini coefficients, while similar, suggest greater differentiation in residential size at Baking Pot than at Lower Dover, likely related to the centralized control of labor by the ruling elite at Baking Pot. While the Gini coefficient is synonymous with measuring wealth inequalities, we suggest that in the Classic period Belize River Valley, residential size was more reflective of labor control.
Background: In Parkinson’s disease, deep brain stimulation (DBS) of the subthalamic nucleus (STN) or globus pallidus internus (GPi) produces comparable motor benefits. Although both increases the risk of cognition and verbal fluency (VF) decline, the risk is greater following STN-DBS. The consequences of stimulating these different sites on brain network activity is unknown. We use functional magnetic resonance imaging (fMRI) during in vivo stimulation to investigate differences between STN-DBS and GPi-DBS and correlate with change in VF. Methods: Left-sided, stimulation-cycling block-design fMRI was acquired at 3-Tesla in 51 STN-DBS and 15 GPi-DBS following routine clinical programming. Blood oxygen level-dependent (BOLD) response to stimulation was compared between groups. Phonemic VF was assessed pre- and postoperatively. Results: Voxel-wise t-test between STN-DBS and GPi-DBS BOLD response maps revealed areas of significant difference (p<0.001) in the left frontal operculum and the left caudate head. Stimulation BOLD response appears to show slight inverse correlation with postoperative VF decline. The trend is reversed at the left frontal operculum in STN-DBS compared to GPi-DBS. Conclusions: Decline in VF in PD-DBS seems associated with the stimulation BOLD response at the left frontal operculum and the left caudate head. The effect differs depending on stimulation site, suggesting differing effects on brain network activity.
A small spheroid settling in a quiescent fluid experiences an inertial torque that aligns it so that it settles with its broad side first. Here we show that an active particle experiences such a torque too, as it settles in a fluid at rest. For a spherical squirmer, the torque is $\boldsymbol {T}^\prime = -{\frac {9}{8}} m_f (\boldsymbol {v}_s^{(0)} \wedge \boldsymbol {v}_g^{(0)})$ where $\boldsymbol {v}_s^{(0)}$ is the swimming velocity, $\boldsymbol {v}_g^{(0)}$ is the settling velocity in the Stokes approximation and $m_f$ is the equivalent fluid mass. This torque aligns the swimming direction against gravity: swimming up is stable, swimming down is unstable.
The epidemic of tuberculosis has posed a serious burden in Qinghai province, it is necessary to clarify the epidemiological characteristics and spatial-temporal distribution of TB for future prevention and control measures. We used descriptive epidemiological methods and spatial statistical analysis including spatial correlation and spatial-temporal analysis in this study. Furthermore, we applied an exponential smoothing model for TB epidemiological trend forecasting. Of 43 859 TB cases, the sex ratio was 1.27:1 (M:F), and the average annual TB registered incidence was 70.00/100 000 of 2009–2019. More cases were reported in March and April, and the worst TB stricken regions were the prefectures of Golog and Yushu. High TB registered incidences were seen in males, farmers and herdsmen, Tibetans, or elderly people. 7132 cases were intractable, which were recurrent, drug resistant, or co-infected with other infections. Three likely cases clusters with significant high risk were found by spatial-temporal scan on data of 2009–2019. The exponential smoothing winters' additive model was selected as the best-fitting model to forecast monthly TB cases in the future. This research indicated that TB in Qinghai is still a serious threaten to the local residents' health. Multi-departmental collaboration and funds special for TB treatments and control are still needed, and the exponential smoothing model is promising which could be applied for forecasting of TB epidemic trend in this high-altitude province.
In the livestock husbandry compensatory growth may be explored as a means to improve nutrient utilization, to reduce gut health problems due to excess protein intake, to simplify feeding strategies and thus to improve production efficiencies. This study investigated the effects of early protein restriction (EPR) and early antibiotic intervention (EAI) on growth performance, intestinal morphology, colonic bacteria, metabolites and mucosal gene expressions during the restriction phase and re-alimentation phase. A total of 64 piglets (10.04 ± 0.73 kg) were randomly divided into four treatment groups according to a 2 × 2 factorial arrangement with two levels of proteins (14% v. 20%) and two levels of antibiotics (0 v. 50 mg/kg kitasamycin and 20 mg/kg colistin sulphate). After a 30-day restriction phase with four kinds of diets, all groups were fed the same diets for another 74 days. The results showed that EPR decreased BW, average daily gain (ADG), average daily feed intake in the restriction phase (P < 0.01) and increased ADG on days 66 to 104 of the late re-alimentation phase. Early protein restriction could decrease the villus height in the jejunum (P < 0.05), while shifting to the same diets restored the villus height. Meanwhile, during the re-alimentation phase, pigs in the protein restriction groups had increased concentrations of total short chain fatty acids (P < 0.05), and modified the abundances of Firmicutes and Bacteroidetes in the colon. Furthermore, the lower microbial diversity caused by EPR was improved, and gene expression analysis indicated a better barrier function in the colon. During the whole trial, EAI had no interaction with EPR and played a dispensable role in compensatory growth. Collectively, the retardation of growth caused by EPR can be compensated for in the later stages of pig raising, and accompanied by altered intestinal morphology, microbial composition.
Non-suicidal self-injury (NSSI) is highly prevalent in adolescents and may be a behavioural marker for emergent mental illnesses.
Aims
To determine whether sporadic or recurrent NSSI up to the age of 14 years predicted increased risk of new onset of psychiatric disorder in the subsequent 3 years, independent of psychiatric symptoms and social risk factors.
Method
In total, 945 individuals aged 14 years with no past/present history of mental illness completed a clinical interview and completed a questionnaire about NSSI at the ages of 14 and 17 years.
Results
Recurrent NSSI at baseline predicted total disorders, depression and eating disorders. Sporadic baseline NSSI predicted new onset of anxiety disorders only.
Conclusions
NSSI (especially recurrent NSSI) in the early-adolescent years is a behavioural marker of newly emerging mental illnesses. Professionals should treat both recurrent and sporadic NSSI as important risk factors, and prevention strategies could be targeted at this vulnerable group.
Chemically exfoliated two-dimensional (2D) materials have shown promise in a variety of applications such as thin film transistors and photovoltaic devices. Here, we present a scalable method for preparing black phosphorus membranes via direct liquid-phase exfoliation of the bulk crystal in organic solvents. The black phosphorus sheets are characterized by Raman and Photoluminescence (PL) spectroscopy, and optical microscopy. The properties of these chemically exfoliated black phosphorus was compared to mechanically exfoliated nanomembranes. The liquid-phase exfoliation nonetheless yields the potential for large-area scalability. Our results highlight the important aspects of forming solution dispersions of 2D black phosphorus which can subsequently be the stepping stone for future work on the ink-jet printing of such dispersions over a wide range of substrates.
Methicillin-resistant Staphylococcus aureus (MRSA) has emerged as a serious hospital and community-acquired infection and some strains are associated with greater severity. We investigated the clinical variability and molecular characteristics of MRSA infections in Shenzhen, China through a study at nine sentinel hospitals from January to December 2014. MRSA infections were classified as community-associated (CA-MRSA), healthcare-associated (HA-MRSA), and healthcare-associated community-onset (HACO-MRSA). In total, 812 MRSA isolates were collected and 183 of these were selected for further study. Patients with HA-MRSA infections were generally of greater age compared to other groups. Distinct body site and clinical presentations were evident in infected patients, e.g. CA-MRSA (skin and soft tissue, 53%), HA-MRSA (respiratory tract, 22%; surgical site, 20%; trauma wounds, 20%) and HACO-MRSA (mastitis, 47%). In contrast to HA-MRSA, other categories of strains were significantly more susceptible to gentamicin, sulfamethoxazole/trimethoprim, and tetracycline. No resistance to vancomycin or linezolid was recorded. The predominant clonal lineage within each strain category was CC59-t437-SCCmec IV/V-agr I (CA, 51·4%; HA, 28·9%; HACO, 52·9%) which exhibited characteristics of a traditional CA clone together with agr I which is more often associated with HA clones. In conclusion, for the three categories of MRSA infections, there were significant differences in clinical characteristics of patients, but the predominant clone in each category shared a similar genetic background which suggests that transmission of MRSA strains has occurred between the community and hospitals in Shenzhen.
Scolytus amygdali is a polyphagous insect pest that feeds on fruit trees and forest trees. Our study assessed the host preference and reproductive potential of S. amygdali on four tree species: almond (Prunus dulcis), apricot (Prunus armeniaca), peach (Prunus persica), and plum (Prunus domestica). Females of S. amygdali produced maternal galleries that were longer on peach than the other three trees, and female fecundity was highest on peach. Females with longer maternal galleries produced more eggs, indicating a positive correlation between maternal gallery length and female fertility. The under-bark development time of S. amygdali is significantly shorter on plum (45 days) and almond (56 days) than on apricot (65 days) and peach (64 days). Despite this longer development time on peach, our results still suggest that, of the four types of tree tested, peach is the most preferred host for S. amygdali.
As graphene technologies progress to commercialization and large-scale manufacturing, issues of material and processing safety will need to be more seriously considered. The single word “graphene” actually represents a family of related materials with large variations in number of layers, surface area, lateral dimensions, stiffness, and surface chemistry. Many of these materials have aerodynamic diameters below 5 μm and can potentially be inhaled into the human lung. Graphene materials show several unique modes of interaction with biological molecules, tissues, and cells. The limited literature suggests that graphene materials can be either benign or harmful and that the biological response varies according to a material’s physicochemical properties and biologically effective dose. The present article reviews the current literature on the graphene–biological interface with an emphasis on the mechanisms and fundamental biological responses relevant to material safety and also to potential biomedical applications
In Western countries, a history of major depression (MD) is associated with reports of received parenting that is low in warmth and caring and high in control and authoritarianism. Does a similar pattern exist in women in China?
Method
Received parenting was assessed by a shortened version of the Parental Bonding Instrument (PBI) in two groups of Han Chinese women: 1970 clinically ascertained cases with recurrent MD and 2597 matched controls. MD was assessed at personal interview.
Results
Factor analysis of the PBI revealed three factors for both mothers and fathers: warmth, protectiveness, and authoritarianism. Lower warmth and protectiveness and higher authoritarianism from both mother and father were significantly associated with risk for recurrent MD. Parental warmth was positively correlated with parental protectiveness and negatively correlated with parental authoritarianism. When examined together, paternal warmth was more strongly associated with lowered risk for MD than maternal warmth. Furthermore, paternal protectiveness was negatively and maternal protectiveness positively associated with risk for MD.
Conclusions
Although the structure of received parenting is very similar in China and Western countries, the association with MD is not. High parental protectiveness is generally pathogenic in Western countries but protective in China, especially when received from the father. Our results suggest that cultural factors impact on patterns of parenting and their association with MD.
VT (Visible Telescope) is an instrument onboard SVOM (Space-based multi-band astronomical Variable Objects Monitor) satellite working in the visible band, which will play an important role in follow-up of two categories of GRBs: very distant events at higher redshift and faint/soft nearby events in SVOM mission. To fulfill these primary science requirements, decent sensitivity and wavelength coverage are fundamental for VT design. VT performance and data process strategy were successfully studied on its feasibility in Phase A, which is presented in this poster. Additionally, preliminary VT image simulator is also introduced here.
A new application of multilayer structures containing single-negative material is proposed as spatial filter. The spatial filter has an ultra-compact structure (only two periods) and is based on that the transmittance of waves through the structure is not sensitive to the incident angle. Through optimised structure parameters, the filter permits waves propagating within a wide spatial-frequency bandwidth and with perfect transmittance. The spatial-frequency bandwidth is tunable by adjusting structure parameter and frequency.
The X-ray emission, especially the K-shell emission, from a neon gas-puff Z-pinch powered by the Qiang Guang-I accelerator, about 1.5 MA in amplitude and 100 ns in rise time, were calculated based on the two-level model and measured with X-ray diodes and an eight-frame X-ray pinhole camera. The simulation results showed that the K-shell yield is highly sensitive to the peak current. The experimental results confirmed that the matching of the Z-pinch load (mass and initial radius) to the current is crucial for getting a higher X-ray yield. Being determined by the imploding time, the pinch current plays a more important role than the current amplitude in K-shell emission. It seems that the preferable imploding time is about 110 ns. The K-shell radiation power with double shells, as a whole, is higher than that using single neon shell. While an implosion of a light (32 µg/cm) and small (20 mm in diameter) neon shell evolves with rather twist and asymmetries, a heavier (41 µg/cm) and bigger (25 mm in diameter) neon shell implodes more symmetrically. The double neon shells, 30 mm and 30 µg/cm for the outer shell, and 15-mm and 10 µg/cm for the inner shell, create almost “perfect” implosions evidenced by the early-time plasma shells with little perturbation and late stagnated pinch liners with a good axial uniformity. It was found that the “Zippering” effect leads to an earlier K-shell emission in the cathode region than that in the anode region, which extends the pulse width of K-shell emission.
The present study was conducted to determine the effects of a polysaccharide of Atractylodes macrophala Koidz (PAM) as a dietary additive on growth performance, immunoglobulin concentration and IL-1β expression in weaned piglets. One hundred and twenty Landrace×Yorkshire piglets weaned at 28 days old (body weight 7·5±0·07 kg) were assigned to five treatment groups (three pens/group, eight piglets/pen) fed maize/soybean-based diets supplemented with 0, 3, 6 or 9 g of PAM/kg diet or antibiotics (0·4 g flavomycin/kg+0·13 g olaquindox/kg). The experimental period was 28 days. With increasing PAM supplementation levels, average daily gain was greater (quadratic, P<0·05) and the ratio of amount fed to live weight (LW) gain (feed/gain) improved (quadratic, P<0·05) during days 14–28 and overall, and diarrhoea incidence decreased (linear, P<0·05) during days 14–28. Supplementation of PAM also increased (quadratic, P<0·05) serum concentrations of interleukin (IL)-2 and IL-6 on day 14, and increased (quadratic, P<0·05) IL-1β expression in jejunal mucosa and lymph nodes. Concentrations of PAM between 6 and 9 g/kg presented the strongest bioactivity compared to the control group or antibiotic-fed group. These findings indicate that PAM is effective in improving growth performance and cytokine response, which suggests that PAM can be used as a diet additive for weanling piglets.
The developmental, survivorship and reproductive biology of Eretmocerus sp. nr furuhashii Rose & Zolnerowich parasitizing Bemisia tabaci (Gennadius) biotype B on tomato, cucumber, eggplant and collard at 26±0.5°C was studied. The mean longevity ranged from 6.5 days on tomato to 8.1 days on collard. The mean lifetime fecundities on tomato, cucumber, eggplant and collard were 35.4, 37.3, 41.4 and 46.4 eggs, whereas the mean lifetime fertility was 20.2, 22.7, 28.3 and 33.6 offspring, respectively. Developmental time was longest on cucumber (17.1 days) and shortest on collard (15.9 days). Survival rates varied significantly across host plants. Sex ratio (♀:♂) varied from 1.71 to 1.93 across the four hosts. The intrinsic rate of increase (rm) was highest (0.157) on collard and lowest on tomato (0.133). Mean generation time (R0) ranged from 14.7 to 20.9 days. All the data demonstrated that the reproductive success and overall performance of E. sp. nr furuhashii increased as the density of leaf hairs declined. As leaf hairs play a key role in determining efficacy, it is unlikely that effective biological control of B. tabaci using E. sp. nr furuhashii will be achieved on non-glabrous crop varieties.