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.
Individuals with tardive dyskinesia (TD) who completed a long-term study (KINECT 3 or KINECT 4) of valbenazine (40 or 80 mg/day, once-daily for up to 48 weeks followed by 4-week washout) were enrolled in a subsequent study (NCT02736955) that was primarily designed to further evaluate the long-term safety of valbenazine.
Participants were initiated at 40 mg/day (following prior valbenazine washout). At week 4, dosing was escalated to 80 mg/day based on tolerability and clinical assessment of TD; reduction to 40 mg/day was allowed for tolerability. The study was planned for 72 weeks or until termination due to commercial availability of valbenazine. Assessments included the Clinical Global Impression of Severity-TD (CGIS-TD), Patient Satisfaction Questionnaire (PSQ), and treatment-emergent adverse events (TEAEs).
At study termination, 85.7% (138/161) of participants were still active. Four participants had reached week 60, and none reached week 72. The percentage of participants with a CGIS-TD score ≤2 (normal/not ill or borderline ill) increased from study baseline (14.5% [23/159]) to week 48 (64.3% [36/56]). At baseline, 98.8% (158/160) of participants rated their prior valbenazine experience with a PSQ score ≤2 (very satisfied or somewhat satisfied). At week 48, 98.2% (55/56) remained satisfied. Before week 4 (dose escalation), 9.4% of participants had ≥1 TEAE. After week 4, the TEAE incidence was 49.0%. No TEAE occurred in ≥5% of participants during treatment (before or after week 4).
Valbenazine was well-tolerated and persistent improvements in TD were found in adults who received once-daily treatment for >1 year.
Glufosinate inhibits glutamine synthetase (GS), a key enzyme for amino acid metabolism and photorespiration. Protoporphyrinogen oxidase (PPO) inhibitors block chlorophyll biosynthesis and cause protoporphyrin accumulation, a highly photodynamic intermediate. Both herbicides ultimately lead to plant death by a massive accumulation of reactive oxygen species (ROS) through different mechanisms. We investigated a potential synergistic effect by the mixture of the two herbicide mechanisms of action (MoA). The tank mix between a low rate of glufosinate (280 g ai ha-1) with an ultra-low dose of saflufenacil (1 g ha-1) provided enhanced herbicidal activity compared to the products applied individually on Palmer amaranth (Amaranthus palmeri S. Watson). The synergism between the two herbicides was also confirmed by isobole analysis and field trials. The herbicide combination provided high levels of efficacy when applied at low temperature and low humidity. Mechanistically, glufosinate caused a transient accumulation of glutamate, the building block for chlorophyll biosynthesis. Consequently, inhibition of both GS and PPO resulted in greater accumulation of protoporphyrin and ROS, forming the physiological basis for the synergism between glufosinate and PPO-inhibitors. While the synergy between the two herbicide MoAs provided excellent efficacy on weeds, it caused low injury to PPO-resistant waterhemp [Amaranthus tuberculatus (Moq.) Sauer] and high injury to both glufosinate-resistant and -susceptible soybean [Glycine max (L.) Merr.]. Glufosinate enhances the activity of PPO-inhibitors through glutamate and protoporphyrin accumulation, leading to increased levels of ROS and lipid peroxidation. The synergism between the two herbicide MoAs can help to overcome environmental effects limiting the efficacy of glufosinate. Future research is needed to optimize the uses for this herbicidal composition across different cropping systems.
Recently several industrialized countries reported a stabilization or even a decrease in childhood overweight and obesity prevalence rates. In Germany, this trend started in 2004. The present study therefore aimed to evaluate whether this trend has continued or even leads in a clear direction.
BMI (>90th percentile (overweight), >97th percentile (obesity)) from the CrescNet database was analysed in 326 834 children and adolescents according to three age groups (4–7·99, 8–11·99 and 12–16 years), gender and between time points (2005–2015).
Trend analysis from 2005 to 2010 demonstrated that the prevalence of overweight and obesity decreased significantly in boys and girls in the entire group (4–16 years) and in 4–7·99-year-olds. From 2010 to 2015 there was a significant decrease in boys for overweight and obesity in the entire group and for overweight among 8–11·99-year-olds. Within the cross-sectional analysis, prevalence rates for overweight decreased significantly for both genders in the age groups of 4–7·99 and 8–11·99 years (2005 v. 2015). For obesity, prevalence rates showed a significant decrease for boys (2005 v. 2015) and girls (2005 v. 2010) in 4–7·99-year-olds.
We observed a further stabilization of overweight and obesity prevalence rates for all age groups and even a decrease in the rates for the younger ages (4–7·99 years, 8–11·99 years). As other industrialized countries have also reported similar trends, it seems that the epidemic of childhood overweight and obesity is reaching a turning point in the industrial part of the world.
Sensor technologies are expedient tools for precision agriculture, aiming for yield protection while reducing operating costs. A portable sensor based on chlorophyll fluorescence imaging was used in greenhouse experiments to investigate the response of sugar beet and soybean cultivars to the application of herbicides. The sensor measured the maximum quantum efficacy yield in photosystem II (PS-II) (Fv/Fm). In sugar beet, the average Fv/Fm of 9 different cultivars 1 d after treatment of desmedipham plus phenmedipham plus ethofumesate plus lenacil was reduced by 56% compared to the nontreated control. In soybean, the application of metribuzin plus clomazone reduced Fv/Fm by 35% 9 d after application in 7 different cultivars. Sugar beets recovered within few days from herbicide stress while maximum quantum efficacy yield in PS-II of soybean cultivars was reduced up to 28 d. At the end of the experiment, approximately 30 d after treatment, biomass was reduced up to 77% in sugar beet and 92% in soybean. Chlorophyll fluorescence imaging is a useful diagnostic tool to quantify phytotoxicity of herbicides on crop cultivars directly after herbicide application, but does not correlate with biomass reduction.
There is an ongoing controversial discussion as to whether n-alkane lipid biomarkers—and organic matter of loess in general—reflect a synsedimentary paleoenvironmental/climate signal or whether they are significantly affected by postdepositional “contamination,” for example related to root and rhizomicrobial activity. In order to address this issue at our study site (the Middle to Late Weichselian loess-paleosol sequence Gleina in Saxony, Germany), we determined and compared radiocarbon ages of bulk n-alkanes and sedimentation ages, as assessed by optically stimulated luminescence (OSL) dating. The bulk n-alkanes of the four dated samples yielded calibrated 14C ages ranging from 24.1 to 49.7 cal ka BP (95.4% probability ranges). While the three uppermost n-alkane samples are well within the range or even slightly older than the OSL-inferred sedimentation ages, the lowermost n-alkane sample is slightly younger than the OSL ages. There is hence little or no evidence at our study site for n-alkanes in loess-paleosol sequences being significantly “contaminated” by deep subsoil rooting or microbial processes. We propose a 14C isotope mass balance calculation for estimating such contaminations quantitatively. Radiocarbon dating of bulk n-alkanes might have great potential for Quaternary research, and we encourage further comparative 14C and OSL studies.
The Galactic centre is a hotbed of astrophysical activity, with the injection of wind material from ~30 massive Wolf-Rayet (WR) stars orbiting within 12″ of the super-massive black hole (SMBH) playing an important role. Hydrodynamic simulations of such colliding and accreting winds produce a complex density and temperature structure of cold wind material shocking with the ambient medium, creating a large reservoir of hot, X-ray-emitting gas. This work aims to confront the 3Ms of Chandra X-ray Visionary Program (XVP) observations of this diffuse emission by computing the X-ray emission from these hydrodynamic simulations of the colliding WR winds, amid exploring a variety of SMBH feedback mechanisms. The major success of the model is that it reproduces the spectral shape from the 2″–5″ ring around the SMBH, where most of the stellar wind material that is ultimately captured by Sgr A* is shock-heated and thermalised. This naturally explains that the hot gas comes from colliding WR winds, and that the wind speeds of these stars are in general well constrained. The flux level of these spectra, as well as 12″×12″ images of 4–9 keV, show the X-ray flux is tied to the SMBH feedback strength; stronger feedback clears out more hot gas, thereby decreasing the thermal X-ray emission. The model in which Sgr A* produced an intermediate-strength outflow during the last few centuries best matches the observations to within about 10%, showing SMBH feedback is required to interpret the X-ray emission in this region.
A clear excess in the Fermi-LAT data is present at energies around a few GeV. The spectrum of this so-called ’GeV excess’ is remarkably similar to the expected annihilation signal of WIMP dark matter. However, a large bulge population of millisecond pulsars living below the Fermi–LAT detection threshold could also explain the excess spectrum. In a recent work we optimized the search for sub-threshold sources, by applying a wavelet transform to the Fermi–LAT gamma-ray data. In the Inner-Galaxy the wavelet signal is significantly enhanced, providing supportive evidence for the point source interpretation of the excess. In these proceedings we will extent our previous work with a spectral analysis and elaborate on the potential contamination from substructures in the gas.
Between 2010 and 2012, 3 outbreaks of nosocomial infections in German neonatal intensive care units (NICUs) attracted considerable public interest. Headlines on national television channels and in newspapers had important consequences for the involved institutions and a negative impact on the relationship between families and staff in many German NICUs.
To determine whether NICU outbreaks reported in the media influenced provider behavior in the community of neonatal care and led to more third-line antibiotic prescribing.
Observational cohort study.
To investigate secular trends, we evaluated data for very-low-birth-weight infants (VLBWIs, birth weight <1,500 g) enrolled in the German Neonatal Network (GNN) between 2009 and 2014 (N=10,253). For outbreak effects, we specifically analyzed data for VLBWIs discharged 6 months before (n=2,428) and 6 months after outbreaks (n=2,508).
The exposure of all VLBWIs to third-line antibiotics increased after outbreaks (19.4% before vs 22.5% after; P=.007). This trend particularly affected male infants (4.6% increase; P=.005) and infants with a birth weight between 1,000 and 1,499 g (3.5% increase; P=.001)
In a logistic regression analysis, month of discharge as linear variable of time was associated with increased exposure to third-line antibiotics (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.009–1.014; P<.001), and discharge within the 6-month period after outbreak reports independently contributed to this long-term trend (OR, 1.14; 95% CI, 1.017–1.270; P=.024).
Media reports directly affect medical practice, eg, overuse of third-line antibiotics. Future communication and management strategies must be based on objective dialogues between the scientific community and investigative journalists.
The impressive architecture of Angkor Wat conveys a sense of harmonious design, but recent survey using ground-penetrating radar (GPR), coupled with targeted excavation, reveals a more complex picture. Fragmentary traces of a quincunx of earlier towers have been detected, which were partially demolished when the outer enclosure and western gateway were completed. Are these the remains of a shrine used during the construction period? If so, they throw new light on associated ritual activity during the building of Angkor Wat.
The temple of Angkor Wat, visited annually by tens of thousands of tourists, is without question one of the great archaeological sites of mainland Southeast Asia. Less obvious to the casual visitor is that it was but a single element in a large dispersed city. The papers in this special section demonstrate how recent research using LiDAR, ground-penetrating radar and targeted excavation have transformed our understanding of Angkor Wat and its surroundings.
We present preliminary results of models of terrestrial planet formation using on the one hand classical numerical integration of hundreds of small bodies on CPUs and on the other hand—for comparison—the results of our GPU code with thousands of small bodies which then merge to larger ones. To be able to determine the outcome of collision events we use our smooth particle hydrodynamics (SPH) code which tracks how water is lost during such events.
Little is known about the impact of corn and energy prices on the profitability of irrigating corn in Tennessee. We evaluated the probability of a positive net present value (NPV) for center-pivot irrigation in Tennessee corn production. Three corn price series were employed to evaluate the effects of the shift in corn prices on the feasibility of irrigation. The recent rise in corn prices increased the probability of NPV being positive for irrigation investment. Future corn prices will need to remain high for investment in center-pivot irrigation to remain profitable under Tennessee growing conditions.
The effect of weed interference on corn yield and the critical period for
weed control (CPWC) were determined in Germany and Benin. Treatments with
weed control starting at different crop growth stages and continuously kept
weed-free until harvest represented the “weed-infested interval.” Treatments
that were kept weed-free from sowing until different crop growth stages
represented the “weed-free interval.” Michaelis–Menten, Gompertz, logistic
and log–logistic models were employed to model the weed interference on
yield. Cross-validation revealed that the log–logistic model fitted the
weed-infested interval data equally well as the logistic and slightly better
than the Gompertz model fitted the weed-free interval. For Benin, economic
calculations considered yield revenue and cost increase due to mechanical
weeding operations. Weeding once at the ten-leaf stage of corn resulted
already profitable in three out of four cases. One additional weeding
operation may optimize and assure profit. Economic calculations for Germany
determined a CPWC starting earlier than the four-leaf stage, challenging the
decade-long propagated CPWC for corn. Differences between Germany and Benin
are probably due to the higher yields and high costs in Germany. This study
provides a straightforward method to implement economic data in the
determination of the CPWC for chemical and nonchemical weed control
We investigate the outcome of collisions of Ceres-sized planetesimals composed of a rocky core and a shell of water ice. These collisions are not only relevant for explaining the formation of planetary embryos in early planetary systems, but also provide insight into the formation of asteroid families and possible water transport via colliding small bodies. Earlier studies show characteristic collision velocities exceeding the bodies' mutual escape velocity which—along with the distribution of the impact angles—cover the collision outcome regimes ‘partial accretion’, ‘erosion’, and ‘hit-and-run’ leading to different expected fragmentation scenarios. Existing collision simulations use bodies composed of strengthless material; we study the distribution of fragments and their water contents considering the full elasto-plastic continuum mechanics equations also including brittle failure and fragmentation.
Deterministic and stochastic yield response plateau functions were estimated to determine the expected profit-maximizing nitrogen rates, yields, and net returns for corn grown after corn, cotton, and soybeans. The stochastic response functions were more appropriate than their deterministic counterparts, and the linear response stochastic plateau described the data the best. The profit-maximizing nitrogen rates were similar for corn after corn, cotton, and soybeans, but relative to corn after corn, the expected corn yield plateaus increased by 12% and 16% after cotton and soybeans, respectively. Expected net returns increased for corn after cotton and soybeans relative to corn after corn.