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Background: Trigeminal neuralgia (TN) is more common in multiple sclerosis (MS) patients than in the general population, likely due to demyelination impacting the trigeminal pathways. While brainstem lesions are associated with MS-TN, their precise role remains unclear. Methods: This study investigates the relationship between brainstem MS plaque location, TN symptoms, and treatment response. We retrospectively analyzed brain MRIs of MS-TN patients, segmenting and coregistering brainstem plaques in MNI space. A tractographic atlas of the trigeminal system was generated using high-resolution diffusion imaging from 30 patients. Lesion involvement was determined by intersection with the trigeminal tract, and its association with pain intensity and treatment outcomes was analyzed using linear regression. Results: Our research revealed 83% of MS-TN patients had brainstem lesions near the fourth ventricle. No single lesion hot spot was identified. Lesion volume did not predict symptom recurrence or treatment response. However, 97% of lesions intersected the trigeminal tract, supporting its association with TN symptoms. Conclusions: The strong overlap between lesions and the trigeminal tract suggests a potential pain generator in MS-TN. Further research is needed to determine whether similar lesions exist in asymptomatic MS patients and to confirm this hypothesis. Future studies will explore whether tract involvement better predicts clinical response to treatment.
Traditional wavefront control in high-energy, high-intensity laser systems usually lacks real-time capability, failing to address dynamic aberrations. This limits experimental accuracy due to shot-to-shot fluctuations and necessitates long cool-down phases to mitigate thermal effects, particularly as higher repetition rates become essential, for example, in inertial fusion research. This paper details the development and implementation of a real-time capable adaptive optics system at the Apollon laser facility. Inspired by astronomical adaptive optics, the system uses a fiber-coupled 905 nm laser diode as a pilot beam that allows for spectral separation, bypassing the constraints of pulsed lasers. A graphics processing unit-based controller, built on the open-source Compute And Control for Adaptive Optics framework, manages a loop comprising a bimorph deformable mirror and a high-speed Shack–Hartmann sensor. Initial tests showed excellent stability and effective aberration correction. However, integration into the Apollon laser revealed critical challenges unique to the laser environment that must be resolved to ensure safe operation with amplified shots.
We study the instantaneous inference of an unbounded planar flow from sparse noisy pressure measurements. The true flow field comprises one or more regularized point vortices of various strength and size. We interpret the true flow's measurements with a vortex estimator, also consisting of regularized vortices, and attempt to infer the positions and strengths of this estimator assuming little prior knowledge. The problem often has several possible solutions, many due to a variety of symmetries. To deal with this ill posedness and to quantify the uncertainty, we develop the vortex estimator in a Bayesian setting. We use Markov-chain Monte Carlo and a Gaussian mixture model to sample and categorize the probable vortex states in the posterior distribution, tailoring the prior to avoid spurious solutions. Through experiments with one or more true vortices, we reveal many aspects of the vortex inference problem. With fewer sensors than states, the estimator infers a manifold of equally possible states. Using one more sensor than states ensures that no cases of rank deficiency arise. Uncertainty grows rapidly with distance when a vortex lies outside of the vicinity of the sensors. Vortex size cannot be reliably inferred, but the position and strength of a larger vortex can be estimated with a much smaller one. In estimates of multiple vortices their individual signs are discernible because of the nonlinear coupling in the pressure. When the true vortex state is inferred from an estimator of fewer vortices, the estimate approximately aggregates the true vortices where possible.
Dicamba and 2,4-D are postemergence herbicides widely used to control broadleaf weed species in crop and non-crop areas in the United States. Currently, multiple formulations of 2,4-D and dicamba are available on the market. Even though the active ingredient is the same, the chemical formulation may vary, which can influence the volatility potential of these herbicides. Therefore, the objective of this study was to evaluate the response of soybean, cotton, and tobacco plants exposed to vapors of 2,4-D and dicamba formulations alone or mixed in humidomes for 24 h. Humidome studies were conducted in an open pavilion at the Lake Wheeler Turfgrass Field Lab of the North Carolina State University in Raleigh, NC. Dicamba and mixture treatments injured and caused a reduction in the height of soybean. Injury varied from 55% to 70%, and average plant height was 8.8 cm shorter compared with untreated control plants. Treatments with 2,4-D caused the least injury to soybean (≤21%), and differences among formulations were identified (dimethylamine > choline > dimethylamine-monomethylamine). However, soybean height was not affected by 2,4-D treatments. No differences between treatments were observed when herbicides were applied to cotton. The greatest injury to tobacco (23.3%) was caused by dicamba dimethylamine. Overall, the effect of 2,4-D and dicamba vapor was species-specific and formulation-dependent. Additionally, environmental conditions in the humidomes may have played a major role on the outcome of this study.
Background: The late-onset cerebellar ataxias (LOCAs) have until recently resisted molecular diagnosis. Contributing to this diagnostic gap is that non-coding structural variations, such as repeat expansions, are not fully accessible to standard short-read sequencing analysis. Methods: We combined bioinformatics analysis of whole-genome sequencing and long-read sequencing to search for repeat expansions in patients with LOCA. We enrolled 66 French-Canadian, 228 German, 20 Australian and 31 Indian patients. Pathogenic mechanisms were studied in post-mortem cerebellum and induced pluripotent stem cell (iPSC)-derived motor neurons from 2 patients. Results: We identified 128 patients who carried an autosomal dominant GAA repeat expansion in the first intron of the FGF14 gene. The expansion was present in 61%, 18%, 15% and 10% of patients in the French-Canadian, German, Australian and Indian cohorts, respectively. The pathogenic threshold was determined to be (GAA)≥250, although incomplete penetrance was observed in the (GAA)250-300 range. Patients developed a slowly progressive cerebellar syndrome at an average age of 59 years. Patient-derived post-mortem cerebellum and induced motor neurons both showed reduction in FGF14 RNA and protein expression compared to controls. Conclusions: This intronic, dominantly inherited GAA repeat expansion in FGF14 represents one of the most common genetic causes of LOCA uncovered to date.
Frontal ablation, the combination of submarine melting and iceberg calving, changes the geometry of a glacier's terminus, influencing glacier dynamics, the fate of upwelling plumes and the distribution of submarine meltwater input into the ocean. Directly observing frontal ablation and terminus morphology below the waterline is difficult, however, limiting our understanding of these coupled ice–ocean processes. To investigate the evolution of a tidewater glacier's submarine terminus, we combine 3-D multibeam point clouds of the subsurface ice face at LeConte Glacier, Alaska, with concurrent observations of environmental conditions during three field campaigns between 2016 and 2018. We observe terminus morphology that was predominately overcut (52% in August 2016, 63% in May 2017 and 74% in September 2018), accompanied by high multibeam sonar-derived melt rates (4.84 m d−1 in 2016, 1.13 m d−1 in 2017 and 1.85 m d−1 in 2018). We find that periods of high subglacial discharge lead to localized undercut discharge outlets, but adjacent to these outlets the terminus maintains significantly overcut geometry, with an ice ramp that protrudes 75 m into the fjord in 2017 and 125 m in 2018. Our data challenge the assumption that tidewater glacier termini are largely undercut during periods of high submarine melting.
Background: Brain metastases are frequently seen in neurosurgical practice. Standardised criteria are created to better classify these common pathologies in research studies. This study’s goal was to evaluate RANO-BM criteria’s current thresholds in a cohort of patients with brain metastases managed by SRS. Methods: We performed a retrospective metastasis-level analysis of patients treated with SRS for brain metastases. The data collected included cohort demographics, metastases characteristics, outcomes, and the rate of true positives, false negatives, true negatives and false positives as defined by RANO-BM criteria at last follow-up before second SRS. Results: 251 metastases in 50 patients were included in the analysis. RANO-BM criteria using current thresholds yielded a sensitivity of 38%, a specificity of 95%, a positive predictive value of 71% and a negative predictive value of 84%. Modified RANO-BM criteria using absolute diameter differences of 2.5 mm yielded a sensitivity of 83%, a specificity of 87%, a positive predictive value of 67% and a negative predictive value of 94%. Pseudoprogression occurred significantly earlier than tumor progression, with a median time of onset of 6.9 months and 12.1 months respectively. Conclusions: Current RANO-BM criteria unreliably identifies clinically relevant tumor progression, but are useful in assessing diameter increases caused by tumor progression and pseudoprogression.
Background: Mutations in the slow skeletal muscle troponin T (TNNT1) gene cause a congenital nemaline myopathy resulting in death from respiratory insufficiency in early infancy. We report on four French Canadians with a novel congenital TNNT1 myopathy. Methods: Patients underwent lower extremity and paraspinal MRI, quadriceps biopsy and genetic testing. TNNT1 expression in muscle was assessed by quantitative PCR and immunoblotting. Wild type or mutated TNNT1 mRNAs were co-injected with morpholinos in a zebrafish knockdown model to assess for rescue of the morphant phenotype. Results: Four patients shared a novel missense homozygous mutation in TNNT1. They developed from childhood slowly progressive limb-girdle weakness with spinal rigidity and contractures. They suffered from restrictive lung disease and recurrent episodes of rhabdomyolysis. Older patients remained ambulatory into their sixties. Lower extremity MRI showed symmetrical myopathic changes. Paraspinal MRI showed diffuse fibro-fatty involution. Biopsies showed multi-minicores. Nemaline rods were seen in half the patients. TNNT1 mRNA expression was similar in controls and patients, while levels of TNNT1 protein were reduced in patients. Wild type TNNT1 mRNA rescued the zebrafish morphants but mutant transcripts failed to do so. Conclusions: This study expands the spectrum of TNNT1-related myopathy to include a milder clinical phenotype caused by a functionally-confirmed novel mutation.
Spectral-broadening of the APOLLON PW-class laser pulses using a thin-film compression technique within the long-focal-area interaction chamber of the APOLLON laser facility is reported, demonstrating the delivery of the full energy pulse to the target interaction area. The laser pulse at 7 J passing through large aperture, thin glass wafers is spectrally broadened to a bandwidth that is compatible with a 15-fs pulse, indicating also the possibility to achieve sub-10-fs pulses using 14 J. Placing the post-compressor near the interaction makes for an economical method to produce the shortest pulses by limiting the need for high damage, broadband optics close to the final target rather than throughout the entire laser transport system.
Background: Mutations in the slow skeletal muscle troponin T (TNNT1) gene cause a congenital nemaline myopathy resulting in death from respiratory insufficiency in early infancy. We report on four French Canadians with a novel congenital TNNT1 myopathy. Methods: Patients underwent lower extremity and paraspinal MRI, quadriceps biopsy and genetic testing. TNNT1 expression in muscle was assessed by quantitative PCR and immunoblotting. Wild type or mutated TNNT1 mRNAs were co-injected with morpholinos in a zebrafish knockdown model to assess for rescue of the morphant phenotype. Results: Four patients shared a novel missense homozygous mutation in TNNT1. They developed from childhood slowly progressive limb-girdle weakness with spinal rigidity and contractures. They suffered from restrictive lung disease and recurrent episodes of rhabdomyolysis. Older patients remained ambulatory into their sixties. Lower extremity MRI showed symmetrical myopathic changes. Paraspinal MRI showed diffuse fibro-fatty involution. Biopsies showed multi-minicores. Nemaline rods were seen in half the patients. TNNT1 mRNA expression was similar in controls and patients, while levels of TNNT1 protein were reduced in patients. Wild type TNNT1 mRNA rescued the zebrafish morphants but mutant transcripts failed to do so. Conclusions: This study expands the spectrum of TNNT1-related myopathy to include a milder clinical phenotype caused by a functionally-confirmed novel mutation.
Hailstone structures have been studied for over a century, but so far mainly by manual optical means. This paper presents new texture and microstructure data (i.e. crystal lattice orientations, grain sizes and shapes) measured with an Automatic Ice Texture Analyzer, which gives access to high spatial and angular resolutions. The hailstones show two main characteristics: (1) they are structured with several concentric layers composed of alternating fine equiaxed grains and coarse elongated and radially oriented grains, and (2) they show two texture types with c-axes oriented either parallel or perpendicular to the radial direction. Such textures are compared with the ones observed in lake S1 and S2 ices, respectively. The S1 texture type (with c-axes parallel to the columnar crystals that grew in the radial direction) may result from epitaxial growth from a polycrystalline embryo, while the S2 texture (c-axes in the plane perpendicular to the column direction) may result from the growth from an embryo made of a few crystals with mainly one crystallographic orientation. Our novel high-resolution maps and measurements of both microstructure and texture may help to shed new light on the long-term discussion on the growth mechanisms of large hailstones.
The satiating efficiency of food has been increasingly quantified using the Satiety Quotient (SQ). The SQ integrates both the energy content of food ingested during a meal and the associated change in appetite sensations. This systematic review examines the available evidence regarding its methodological use and clinical utility. A literature search was conducted in six databases considering studies from 1900 to April 2020 that used SQ in adults, adolescents and children. All study designs were included. From the initial 495 references found, fifty-two were included. Of the studies included, thirty-three were acute studies (twenty-nine in adults and four in adolescents) and nineteen were longitudinal studies in adults. A high methodological heterogeneity in the application of the SQ was observed between studies. Five main utilisations of the SQ were identified: its association with (i) energy intake; (ii) anthropometric variables; (iii) energy expenditure/physical activity; (iv) sleep quality and quantity and (v) to classify individuals by their satiety responsiveness (i.e. low and high satiety phenotypes). Altogether, the studies suggest the SQ as an interesting clinical tool regarding the satiety responsiveness to a meal and its changes in responses to weight loss in adults. The SQ might be a reliable clinical indicator in adults when it comes to both obesity prevention and treatment. There is a need for more standardised use of the SQ in addition to further studies to investigate its validity in different contexts and populations, especially among children and adolescents.
Introduction: CAEP recently developed the acute atrial fibrillation (AF) and flutter (AFL) [AAFF] Best Practices Checklist to promote optimal care and guidance on cardioversion and rapid discharge of patients with AAFF. We sought to assess the impact of implementing the Checklist into large Canadian EDs. Methods: We conducted a pragmatic stepped-wedge cluster randomized trial in 11 large Canadian ED sites in five provinces, over 14 months. All hospitals started in the control period (usual care), and then crossed over to the intervention period in random sequence, one hospital per month. We enrolled consecutive, stable patients presenting with AAFF, where symptoms required ED management. Our intervention was informed by qualitative stakeholder interviews to identify perceived barriers and enablers for rapid discharge of AAFF patients. The many interventions included local champions, presentation of the Checklist to physicians in group sessions, an online training module, a smartphone app, and targeted audit and feedback. The primary outcome was length of stay in ED in minutes from time of arrival to time of disposition, and this was analyzed at the individual patient-level using linear mixed effects regression accounting for the stepped-wedge design. We estimated a sample size of 800 patients. Results: We enrolled 844 patients with none lost to follow-up. Those in the control (N = 316) and intervention periods (N = 528) were similar for all characteristics including mean age (61.2 vs 64.2 yrs), duration of AAFF (8.1 vs 7.7 hrs), AF (88.6% vs 82.9%), AFL (11.4% vs 17.1%), and mean initial heart rate (119.6 vs 119.9 bpm). Median lengths of stay for the control and intervention periods respectively were 413.0 vs. 354.0 minutes (P < 0.001). Comparing control to intervention, there was an increase in: use of antiarrhythmic drugs (37.4% vs 47.4%; P < 0.01), electrical cardioversion (45.1% vs 56.8%; P < 0.01), and discharge in sinus rhythm (75.3% vs. 86.7%; P < 0.001). There was a decrease in ED consultations to cardiology and medicine (49.7% vs 41.1%; P < 0.01), but a small but insignificant increase in anticoagulant prescriptions (39.6% vs 46.5%; P = 0.21). Conclusion: This multicenter implementation of the CAEP Best Practices Checklist led to a significant decrease in ED length of stay along with more ED cardioversions, fewer ED consultations, and more discharges in sinus rhythm. Widespread and rigorous adoption of the CAEP Checklist should lead to improved care of AAFF patients in all Canadian EDs.
Background: Mutations of the slow skeletal muscle troponin-T1 (TNNT1) gene are a rare cause of nemaline myopathy. The phenotype is characterized by severe amyotrophy and contractures. Death from respiratory insufficiency occurs in infancy. We report on four French Canadians with a novel congenital TNNT1-related myopathy. Methods: Patients underwent MRI of leg muscles, quadriceps biopsy and genetic testing. Wild type or mutated human TNNT1 mRNAs were co-injected with morpholinos in a zebrafish knockdown model to assess their relative abilities to rescue the morphant phenotype. Results: Three adults and one child shared a novel missense homozygous pathogenic variant in the TNNT1 gene. They developed from childhood slowly progressive limb-girdle weakness with spinal rigidity and contractures. They suffered from restrictive lung disease and recurrent episodes of infection-triggered rhabdomyolysis, which were relieved by dantrolene in one patient. Older patients remained ambulatory into their sixties. MRI of leg muscles showed symmetrical atrophy and fatty infiltration in a proximal-to-distal gradient. Biopsies showed multi-minicores, while nemaline rods were seen in half the patients. Wild type TNNT1 mRNA rescued the zebrafish morphants but mutant transcripts failed to rescue the morphants. Conclusions: This study expands the spectrum of TNNT1-related myopathy to include a milder clinical phenotype caused by a functionally-confirmed novel missense mutation.
Domestic spying is a cultural construct that refers to the activities of, and debate on, intelligence agencies oriented at the home population of citizens within nations. In the United States, the debate on domestic spying has been especially intense as the country has a long-standing culture and accompanying legal and political framework devoted to protecting individual rights of nonintervention. Unlike several other democratic nations, the United States has no specialized self-standing domestic intelligence agents, with such functions being handled by other agencies of law enforcement and foreign intelligence. This chapter reviews the patterns and dynamics of domestic spying in terms of the historical development of domestic intelligence work and offers a comparative overview of such activities in a number of nations. This comparative-historical outlook should be advantageous both for the analysis of domestic spying as a social problem and in terms of the normative framing of the debate within cultures committed to civil liberties as well as national security.
The practical application of yield loss prediction models using relative leaf area of weeds is limited due to the lack of a quick and accurate method of leaf area estimation. Leaf cover (the vertical projection of plant canopy on the ground) can be used to approximate leaf area at early stages of plant development. An automated digital image analysis system for measuring leaf cover has been developed. The system has an operator-assisted module aimed at validating the automated functions. The objective of this research was to demonstrate the accuracy of the operator-assisted module under different weed–crop conditions. A laboratory experiment was conducted using simulated weed–crop populations. Two additional field experiments were conducted using corn in competition with: (1) common lambsquarters, barnyardgrass, or a mixture of both species, and (2) a natural weed community. In the laboratory experiment, a narrow linear relation was observed between leaf cover estimated with the operator-assisted module and leaf area measured with an optical area meter (r2 > 0.98). In field experiments, the regression between corn leaf cover estimated by the operator-assisted module and corn leaf area measured with the optical area meter was not as good (r2 < 0.55). The poor performance of the module was probably due to the overlapping and the architecture of corn leaves (especially unexpanded leaves). Nevertheless, the system showed high precision in estimating leaf area of both grassy weeds and broadleaf weeds (r2 > 0.89). Generally, the accuracy of the estimates decreased as the growth stage became more advanced. Apart from its initial purpose as a calibration tool for the automated system, the operator-assisted module can have several potential research applications. It can be used: (1) as an alternative to destructive leaf area measurement at early stages of plant development, (2) as a tool in the study of plant competitive ability, and (3) as an objective and quantitative support to visual observations.
The relative leaf area of weeds is a good predictor of the outcome of weed-crop competition. However, this variable has not been used in decision-making tools for integrated weed management because leaf area cannot be measured quickly. A powerful image analysis system for measuring leaf cover (the vertical projection of plant canopy on the ground) has been developed and validated. This research was conducted to compare the efficiency of weed relative leaf area and relative leaf cover in predicting corn yield loss. Field studies were conducted in 1996 and 1997 using varying densities of common lambsquarters, barnyardgrass, common lambsquarters plus barnyardgrass, and a natural weed community. Corn grain yield and biomass loss varied with weed infestation type and year. Values of the relative damage coefficient of weeds (q) were smaller in 1997 compared with 1996. For both years, the relative leaf area of weeds was an adequate predictor of corn yield loss (r2 varied from 0.61 to 0.92). The precision of the predictions was not influenced by the leaf area sampling period (four- or eight-leaf stage of corn). In general, smaller values of q and m (predicted maximum yield loss) were obtained as a consequence of using the relative leaf cover of weeds in model fitting. However, percentages of variation explained by the model (from 0.67 to 0.90) were similar to values obtained with the relative leaf area. On the basis of the residual mean squares, neither of the variables could be declared superior to the other in yield loss prediction. The development of weed control decision-making tools using the relative leaf cover of weeds may require improvements prior to being used in weed management systems. Such improvements would include use of appropriate sampling and image-processing techniques, development and validation of empirical models specific to individual situations, and proper identification of the crop growth stage at which leaf cover must be assessed.