Background
Spinocerebellar ataxias (SCAs) are a group of autosomal dominantly inherited degenerative diseases. As the pathological process probably commences years before the first appearance of ...clinical symptoms, preclinical carriers of a SCA mutation offer the opportunity to study the earliest stages of cerebellar dysfunction and degeneration. Eyeblink classical conditioning (EBCC) is a motor learning paradigm, crucially dependent on the integrity of the olivocerebellar circuit, and has been shown to be able to detect subtle alterations of cerebellar function, which might already be present in preclinical carriers.
Methods
In order to acquire conditioned responses, we performed EBCC, delay paradigm, in 18 preclinical carriers of a SCA3 mutation and 16 healthy, age-matched controls by presenting repeated pairings of an auditory tone with a supraorbital nerve stimulus with a delay interval of 400 ms.
Results
Preclinical carriers acquired significantly less conditioned eyeblink responses than controls and learning rates were significantly reduced. This motor learning defect was, however, not associated with the predicted time to onset.
Conclusions
EBCC is impaired in preclinical carriers of a SCA3 mutation, as a result of impaired motor learning capacities of the cerebellum and is thus suggestive of cerebellar dysfunction. EBCC can be used to detect but probably not monitor preclinical cerebellar dysfunction in genetic ataxias, such as SCA3.
We report on a new measurement of the beam transverse single spin asymmetry in electron-proton elastic scattering, A_{⊥}^{ep}, at five beam energies from 315.1 to 1508.4 MeV and at a scattering angle ...of 30°<θ<40°. The covered Q^{2} values are 0.032, 0.057, 0.082, 0.218, 0.613 (GeV/c)^{2}. The measurement clearly indicates significant inelastic contributions to the two-photon-exchange (TPE) amplitude in the low-Q^{2} kinematic region. No theoretical calculation is able to reproduce our result. Comparison with a calculation based on unitarity, which only takes into account elastic and πN inelastic intermediate states, suggests that there are other inelastic intermediate states such as ππN, KΛ, and ηN. Covering a wide energy range, our new high-precision data provide a benchmark to study those intermediate states.
Molecular profiling of NSCLC is essential for optimising treatment decisions, but often incomplete. We assessed the efficacy of protocolised molecular profiling in the current standard-of-care (SoC) ...in a prospective observational study in the Netherlands and measured the effect of providing standardised diagnostic procedures. We also explored the potential of plasma-based molecular profiling in the primary diagnostic setting. This multi-centre prospective study was designed to explore the performance of current clinical practice during the run-in phase using local SoC tissue profiling procedures. The subsequent phase was designed to investigate the extent to which comprehensive molecular profiling (CMP) can be maximized by protocolising tumour profiling. Successful molecular profiling was defined as completion of at least EGFR and ALK testing. Additionally, PD-L1 tumour proportions scores were explored. Lastly, the additional value of centralised plasma-based testing for EGFR and KRAS mutations using droplet digital PCR was evaluated. Total accrual was 878 patients, 22.0% had squamous cell carcinoma and 78.0% had non-squamous NSCLC. Stage I-III was seen in 54.0%, stage IV in 46.0%. Profiling of EGFR and ALK was performed in 69.9% of 136 patients included in the run-in phase, significantly more than real-world data estimates of 55% (p<0.001). Protocolised molecular profiling increased the rate to 77.0% (p = 0.049). EGFR and ALK profiling rates increased from 77.9% to 82.1% in non-squamous NSCLC and from 43.8% to 57.5% in squamous NSCLC. Plasma-based testing was feasible in 98.4% and identified oncogenic driver mutations in 7.1% of patients for whom tissue profiling was unfeasible. This study shows a high success rate of tissue-based molecular profiling that was significantly improved by a protocolised approach. Tissue-based profiling remains unfeasible for a substantial proportion of patients. Combined analysis of tumour tissue and circulating tumour DNA is a promising approach to allow adequate molecular profiling of more patients.
Using a low background data sample of 9.7×10^{5} J/ψ→γη^{'}, η^{'}→γπ^{+}π^{-} events, which are 2 orders of magnitude larger than those from the previous experiments, recorded with the BESIII ...detector at BEPCII, the decay dynamics of η^{'}→γπ^{+}π^{-} are studied with both model-dependent and model-independent approaches. The contributions of ω and the ρ(770)-ω interference are observed for the first time in the decays η^{'}→γπ^{+}π^{-} in both approaches. Additionally, a contribution from the box anomaly or the ρ(1450) resonance is required in the model-dependent approach, while the process specific part of the decay amplitude is determined in the model-independent approach.
BACKGROUND:A great need exists in traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (aSAH) for objective biomarkers to better characterize the disease process and to serve as early ...endpoints in clinical studies. Diffusion tensor imaging (DTI) has shown promise in TBI, but much less is known about aSAH.
OBJECTIVE:To explore the use of whole-brain DTI tractography in TBI and aSAH as a biomarker and early endpoint.
METHODS:Of a cohort of 43 patients with severe TBI (n = 20) or aSAH (n = 23) enrolled in a prospective, observational, multimodality monitoring study, DTI data were acquired at approximately day 12 (median, 12 days; interquartile range, 12-14 days) after injury in 22 patients (TBI, n = 12; aSAH, n = 10). Whole-brain DTI tractography was performed, and the following parameters quantifiedaverage fractional anisotropy, mean diffusivity, tract length, and the total number of reconstructed fiber tracts. These were compared between TBI and aSAH patients and correlated with mortality and functional outcome assessed at 6 months by the Glasgow Outcome Scale Extended.
RESULTS:Significant differences were found for fractional anisotropy values (P = .01), total number of tracts (P = .03), and average tract length (P = .002) between survivors and nonsurvivors. A sensitivity analysis showed consistency of results between the TBI and aSAH patients for the various DTI measures.
CONCLUSION:DTI parameters, assessed at approximately day 12 after injury, correlated with mortality at 6 months in patients with severe TBI or aSAH. Similar patterns were found for both TBI and aSAH patients. This supports a potential role of DTI as early endpoint for clinical studies and a predictor of late mortality.
ABBREVIATIONS:aSAH, aneurysmal subarachnoid hemorrhageDTI, diffusion tensor imagingFA, fractional anisotropyGOSE, Glasgow Outcome Scale ExtendedTBI, traumatic brain injuryTE, echo timeTR, repetition time
A model for computing acoustic scattering by swimbladdered fish is presented. The effect of acoustic coupling between the fish tissue and the swimbladder is included. The swimbladder is considered a ...gas-filled object whereas the fish tissue is assumed to behave as a homogeneous fluid. Mathematically, this corresponds to considering the problem of two penetrable scatterers immersed in a homogeneous medium, one of which is wholly embedded in the other. The model is formulated in the frame of boundary integral equations whose solution is achieved using the Boundary Element Method (BEM) for a planar triangle mesh. The numerical implementation is verified against benchmark solutions reported in the literature. The model is then applied to a specimen of Argentine hake (Merluccius hubbsi), whose morphometry was determined by CT scanning of a frozen sample, for evaluating its forward and backscattering responses. From the acoustic scattering viewpoint, the swimbladder is considered as a gas-filled object while the flesh constituting the fish body acts like a weak scatterer. The numerical results suggest the swimbladder and the fish body responses, when fully coupled, can lead to substantial differences with respect to the simplified models normally in use in the area of aquatic ecosystem research.
Background
Patients with a pathological complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT) for oesophageal cancer may benefit from non‐surgical management. The aim of this study was ...to determine the diagnostic performance of visual response assessment of the primary tumour after nCRT on T2‐weighted (T2W) and diffusion‐weighted (DW) MRI.
Methods
Patients with locally advanced oesophageal cancer who underwent T2W‐ and DW‐MRI (1·5 T) before and after nCRT in two hospitals, between July 2013 and September 2017, were included in this prospective study. Three radiologists evaluated T2W images retrospectively using a five‐point score for the assessment of residual tumour in a blinded manner and immediately rescored after adding DW‐MRI. Histopathology of the resection specimen was used as the reference standard; ypT0 represented a pCR. Sensitivity, specificity, area under the receiver operating characteristic (ROC) curve (AUC) and interobserver agreement were calculated.
Results
Twelve of 51 patients (24 per cent) had a pCR. The sensitivity and specificity of T2W‐MRI for detection of residual tumour ranged from 90 to 100 and 8 to 25 per cent respectively. Respective values for T2W + DW‐MRI were 90–97 and 42–50 per cent. AUCs for the three readers were 0·65, 0·66 and 0·68 on T2W‐MRI, and 0·71, 0·70 and 0·70 on T2W + DW‐MRI (P = 0·441, P = 0·611 and P = 0·828 for readers 1, 2 and 3 respectively). The κ value for interobserver agreement improved from 0·24–0·55 on T2W‐MRI to 0·55–0·71 with DW‐MRI.
Conclusion
Preoperative assessment of residual tumour on MRI after nCRT for oesophageal cancer is feasible with high sensitivity, reflecting a low chance of missing residual tumour. However, the specificity was low; this results in overstaging of complete responders as having residual tumour and, consequently, overtreatment.
Treatment of locally advanced oesophageal cancer consists of neoadjuvant chemoradiotherapy (nCRT) followed by surgery. In 25–30 per cent of these patients, the resection specimen shows a pathological complete response. This study shows that preoperative response assessment after nCRT performed visually on (diffusion‐weighted) MRI has promising overall diagnostic performance. To further increase the accuracy of response assessment, larger studies are needed, ideally using a multimodal approach combining (diffusion‐weighted) MRI with endoscopy/endoscopic ultrasonography and fluorodeoxyglucose PET/CT. T2W, T2‐weighted; DW, diffusion weighted.
Not there yet
Many publications lack sufficient background information (e.g. location) to be interpreted, replicated, or reused for synthesis. This impedes scientific progress and the application of science to ...practice. Reporting guidelines (e.g. checklists) improve reporting standards. They have been widely taken up in the medical sciences, but not in ecological and agricultural research. Here, we use a community-centred approach to develop a reporting checklist (AgroEcoList 1.0) through surveys and workshops with 23 experts and the wider agroecological community. To put AgroEcoList in context, we also assessed the agroecological community's perception of reporting standards in agroecology. A total of 345 researchers, reviewers, and editors, responded to our survey. Although only 32% of respondents had prior knowledge of reporting guidelines, 76% of those that had said guidelines improved reporting standards. Overall, respondents agreed on the need of AgroEcolist 1.0; only 24% of respondents had used reporting guidelines before, but 78% indicated they would use AgroEcoList 1.0. We updated AgroecoList 1.0 based on respondents' feedback and user-testing. AgroecoList 1.0 consists of 42 variables in seven groups: experimental/sampling set-up, study site, soil, livestock management, crop and grassland management, outputs, and finances. It is presented here, and is also available on github (https://github.com/AgroecoList/Agroecolist). AgroEcoList 1.0 can serve as a guide for authors, reviewers, and editors to improve reporting standards in agricultural ecology. Our community-centred approach is a replicable method that could be adapted to develop reporting checklists in other fields. Reporting guidelines such as AgroEcoList can improve reporting standards and therefore the application of research to practice, and we recommend that they are adopted more widely in agriculture and ecology.
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