The impurity density in high-purity germanium detectors is crucial to understand and simulate such detectors. However, the information about the impurities provided by the manufacturer, based on Hall ...effect measurements, is typically limited to a few locations and comes with a large uncertainty. As the voltage dependence of the capacitance matrix of a detector strongly depends on the impurity density distribution, capacitance measurements can provide a path to improve the knowledge on the impurities. The novel method presented here uses a machine-learned surrogate model, trained on precise GPU-accelerated capacitance calculations, to perform full Bayesian inference of impurity distribution parameters from capacitance measurements. All steps use open-source Julia software packages. Capacitances are calculated with
SolidStateDetectors.jl
, machine learning is done with
Flux.jl
and Bayesian inference performed using
BAT.jl
. The capacitance matrix of a detector and its dependence on the impurity density is explained and a capacitance bias-voltage scan of an
n
-type true-coaxial test detector is presented. The study indicates that the impurity density of the test detector also has a radial dependence.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To evaluate the efficacy of dichloroacetate (DCA) in the treatment of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS).
High levels of ventricular lactate, the ...brain spectroscopic signature of MELAS, correlate with more severe neurologic impairment. The authors hypothesized that chronic cerebral lactic acidosis exacerbates neuronal injury in MELAS and therefore, investigated DCA, a potent lactate-lowering agent, as potential treatment for MELAS.
The authors conducted a double-blind, placebo-controlled, randomized, 3-year cross-over trial of DCA (25 mg/kg/day) in 30 patients (aged 10 to 60 years) with MELAS and the A3243G mutation. Primary outcome measure was a Global Assessment of Treatment Efficacy (GATE) score based on a health-related event inventory, and on neurologic, neuropsychological, and daily living functioning. Biologic outcome measures included venous, CSF, and 1H MRSI-estimated brain lactate. Blood tests and nerve conduction studies were performed to monitor safety.
During the initial 24-month treatment period, 15 of 15 patients randomized to DCA were taken off study medication, compared to 4 of 15 patients randomized to placebo. Study medication was discontinued in 17 of 19 patients because of onset or worsening of peripheral neuropathy. The clinical trial was terminated early because of peripheral nerve toxicity. The mean GATE score was not significantly different between treatment arms.
DCA at 25 mg/kg/day is associated with peripheral nerve toxicity resulting in a high rate of medication discontinuation and early study termination. Under these experimental conditions, the authors were unable to detect any beneficial effect. The findings show that DCA-associated neuropathy overshadows the assessment of any potential benefit in MELAS.
Events from alpha interactions on the surfaces of germanium detectors are a major contribution to the background in germanium-based searches for neutrinoless double-beta decay. Surface events are ...subject to charge trapping, affecting their pulse shape and reconstructed energy. A study of alpha events on the passivated end-plate of a segmented true-coaxial n-type high-purity germanium detector is presented. Charge trapping is analysed in detail and an existing pulse-shape analysis technique to identify alpha events is verified with mirror pulses observed in the non-collecting channels of the segmented test detector. The observed radial dependence of charge trapping confirms previous results. A dependence of the probability of charge trapping on the crystal axes is observed for the first time. A first model to describe charge trapping effects within the framework of the simulation software
SolidStateDetectors.jl
is introduced. The influence of metalisation on events from low-energy gamma interactions close to the passivated surface is also presented.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To investigate the value of objective biomarkers for upper (UMN) and lower (LMN) motor neuron involvement in ALS.
We prospectively studied 64 patients with ALS and its subsets using clinical ...measures, proton MR spectroscopic imaging ((1)H MRSI), diffusion tensor imaging, transcranial magnetic stimulation, and the motor unit number estimation (MUNE) at baseline and every 3 months for 15 months and compared them with control subjects.
(1)H MRSI measures of the primary motor cortex N-acetyl-aspartate (NAA) concentration were markedly reduced in ALS (p = 0.009) and all UMN syndromes combined (ALS, familial ALS fALS, and primary lateral sclerosis; p = 0.03) vs control values. Central motor conduction time to the tibialis anterior was prolonged in ALS (p < 0.0005) and combined UMN syndromes (p = 0.001). MUNE was lower in ALS (p < 0.0005) and all LMN syndromes combined (ALS, fALS, and progressive muscular atrophy; p = 0.001) vs controls. All objective markers correlated well with the ALS Functional Rating Scale-Revised, finger and foot tapping, and strength testing, suggesting these markers related to disease activity. Regarding changes over time, MUNE changed rapidly, whereas neuroimaging markers changed more slowly and did not significantly differ from baseline.
(1)H MR spectroscopic imaging measures of the primary motor cortex N-acetyl-aspartate (NAA) concentration and ratio of NAA to creatine, central motor conduction time to the tibialis anterior, and motor unit number estimation significantly differed between ALS, its subsets, and control subjects, suggesting they have potential to provide insight into the pathobiology of these disorders.
Background American College of Surgeons Oncology Group (ACOSOG) Z0011 results support the omission of axillary lymph node dissection (ALND) in women with less than 3 positive sentinel lymph nodes ...(SLNs) undergoing breast-conserving surgery (BCS) and radiation therapy. We sought to determine if abnormal axillary imaging is predictive of the need for ALND in this population. Study design Patients with cT1-2N0 breast cancer by physical examination undergoing BCS were managed according to Z0011 criteria independent of axillary imaging. Patient characteristics and rates of ALND were compared among those with and without abnormal lymph nodes (LNs) detected by mammogram, ultrasound (US), or MRI. All available axillary imaging was reviewed by 1 breast radiologist. Results Between August 2010 and December 2013, 3,253 breast cancer patients were treated with BCS and SLN biopsy; 425 patients met Z0011 criteria (cT1-2N0) and had nodal metastasis on SLN biopsy. Clinicopathologic features were median patient age, 58 years; median tumor size, 1.8 cm; 85% ductal histology; and 89% estrogen receptor positive. All women had a mammogram, 242 had axillary US, 172 had MRI. Abnormal LNs were seen on 7%, 25%, and 30% of mammograms, US, and MRIs, respectively. Although abnormal LNs on mammogram or US were associated with a significant increase in ALND and a non-significant trend was seen with MRI, 68% to 73% of women with abnormal axillary imaging did not require ALND. Conclusions Among clinically node-negative patients with abnormal axillary imaging, 71% did not meet criteria for ALND and were spared further surgical morbidity. Abnormal nodes on US, MRI, or mammogram in clinically node-negative patients are not reliable indicators of the need for ALND.
Background
Oropharyngeal dysphagia is prevalent in individuals with amyotrophic lateral sclerosis (ALS) leading to malnutrition, aspiration pneumonia, and death. These factors necessitate early ...detection of at‐risk patients to prolong maintenance of safe oral intake and pulmonary function. This study aimed to evaluate the discriminant ability of the Eating Assessment Tool (EAT‐10) to identify ALS patients with unsafe airway protection during swallowing.
Methods
Seventy ALS patients completed the EAT‐10 survey and underwent a standardized videofluoroscopic evaluation of swallowing. Two blinded raters determined airway safety using the Penetration Aspiration Scale (PAS). A between groups anova (safe vs penetrators vs aspirators) was conducted and sensitivity, specificity, area under the curve (AUC), and likelihood ratios calculated.
Key Results
Mean EAT‐10 scores for safe swallowers, penetrators, and aspirators (SEM) were: 4.28 (0.79) vs 7.10 (1.79) vs 20.50 (3.19), respectively, with significant differences noted for aspirators vs safe swallowers and aspirators vs penetrators (p < 0.001). The EAT‐10 demonstrated good discriminant ability to accurately identify ALS penetrator/aspirators (PAS ≥3) with a cut off score of 3 (AUC: 0.77, sensitivity: 88%, specificity: 57%). The EAT‐10 demonstrated excellent accuracy at identifying aspirators (PAS ≥6) utilizing a cut off score of 8 (AUC: 0.88, sensitivity: 86%, specificity: 72%, likelihood ratio: 3.1, negative predictive value: 95.5%).
Conclusions & Inferences
The EAT‐10 differentiated safe vs unsafe swallowing in ALS patients. This patient self‐report scale could represent a quick and meaningful aide to dysphagia screening in busy ALS clinics for the identification and referral of dysphagic patients for further instrumental evaluation.
Mean (SEM) Eating Assessment Tool‐10 scores for ALS patients with safe swallowing (PAS<2), penetrators (PAS:2‐5) and aspirators (PAS>6). ALS aspirators EAT‐10 score was significantly higher (worse) then both safe swallowers and penetrators (p<0.001).
•Accurate error estimates are found for unsteady flow by the error transport equation.•Higher order accuracy in error estimates is preserved if used to correct solutions.•Higher order in space and ...time is possible without discretizing both to higher order.•Co-advancing requires only local solutions in time, unlike unsteady adjoints.•Only one auxiliary equation needs to be solved, agnostic to choice of functionals.
A numerical estimation of discretization error for solutions to unsteady laminar compressible flow equations is performed using the error transport equation (ETE) on unstructured meshes. This method is an extension to our previous work on steady problems, where it was found that solving the ETE can be more efficient and robust than solving the higher order primal problem. Computing the time-dependent ETE source term accurately is critical to the accuracy of the discretization error estimate, and several methods of doing so are considered. It was found that computing the ETE source term directly by a finite-difference approximation in time gives accurate error estimates, which we show is equivalent to an accurate corrected solution. A truncation error analysis was performed for the ETE to determine the expected accuracy of the error estimate, where a term that mixes the space and time discretization was observed. Although more stringent requirements for error estimation are needed when using unstructured meshes, constant time steps can be used and the best schemes we found were still able to attain an estimate of the discretization error that is higher order accurate in space and time, without discretizing both to higher order. Furthermore, unlike unsteady adjoints, the ETE requires only one other auxiliary equation to be solved, agnostic to the choice and number of output functionals, and co-advancing with the primal problem requires the storage of only local solutions in time, reducing memory requirements.
Benign breast disease (BBD) is a heterogenous group of lesions often classified as nonproliferative or proliferative, with the latter group further categorized based on the presence of atypia. ...Although nonproliferative lesions are more common, the risk of breast cancer is elevated in women with proliferative lesions. Historically, the majority of proliferative lesions were excised due to concern for future and/or concomitant breast cancer at the site of the index lesion. However, contemporary data suggest that the risk of cancer associated with various proliferative lesions may be lower than previously thought, and management of BBD has become more nuanced. In this review, we will focus on recent updates in the management of a select group of benign and high-risk lesions.
The objective of this study was to evaluate the efficacy and safety of tramadol in treating the pain of diabetic neuropathy.
The pain of diabetic neuropathy is a major cause of morbidity among these ...patients and treatment, as with other small-fiber neuropathies, is often unsatisfactory. Tramadol is a centrally acting analgesic for use in treating moderate to moderately severe pain.
This multicenter, outpatient, randomized, double-blind, placebo-controlled, parallel-group study consisted of a washout/screening phase, during which all analgesics were discontinued, and a 42-day double-blind treatment phase. A total of 131 patients with painful diabetic neuropathy were treated with tramadol (n=65) or placebo (n=66) tramadol, which were administered as identical capsules in divided doses four times daily. The primary efficacy analysis compared the mean pain intensity scores in the tramadol and placebo groups obtained at day 42 of the study or at the time of discontinuation. Secondary efficacy assessments were the pain relief rating scores and a quality of life evaluation based on daily activities and sleep characteristics.
Tramadol, at an average dosage of 210 mg/day, was significantly (p < 0.001) more effective than placebo for treating the pain of diabetic neuropathy. Patients in the tramadol group scored significantly better in physical (p=0.02) and social functioning (p=0.04) ratings than patients in the placebo group. No statistically significant treatment effects on sleep were identified. The most frequently occurring adverse events with tramadol were nausea, constipation, headache, and somnolence.
The results of this placebo-controlled trial showed that tramadol was effective and safe in treating the pain of diabetic neuropathy.
PDF
