We report on the development and airborne field deployment of a mid-IR laser-based spectrometer. The instrument was configured for the simultaneous in situ detection of formaldehyde (CH
2
O) and ...ethane (C
2
H
6
). Numerous mechanical, optical, electronic, and software improvements over a previous instrument design resulted in reliable highly sensitive airborne operation with long stability times yielding 90 % airborne measurement coverage during the recent air quality study over the Colorado Front Range, FRAPPÉ 2014. Airborne detection sensitivities of ~15 pptv (C
2
H
6
) and ~40 pptv (CH
2
O) were generally obtained for 1 s of averaging for simultaneous detection.
A rapid and accurate radiative transfer model (RRTM) for climate applications has been developed and the results extensively evaluated. The current version of RRTM calculates fluxes and cooling rates ...for the longwave spectral region (10–3000 cm−1) for an arbitrary clear atmosphere. The molecular species treated in the model are water vapor, carbon dioxide, ozone, methane, nitrous oxide, and the common halocarbons. The radiative transfer in RRTM is performed using the correlated‐k method: the k distributions are attained directly from the LBLRTM line‐by‐line model, which connects the absorption coefficients used by RRTM to high‐resolution radiance validations done with observations. Refined methods have been developed for treating bands containing gases with overlapping absorption, for the determination of values of the Planck function appropriate for use in the correlated‐k approach, and for the inclusion of minor absorbing species in a band. The flux and cooling rate results of RRTM are linked to measurement through the use of LBLRTM, which has been substantially validated with observations. Validations of RRTM using LBLRTM have been performed for the midlatitude summer, tropical, midlatitude winter, subarctic winter, and four atmospheres from the Spectral Radiance Experiment campaign. On the basis of these validations the longwave accuracy of RRTM for any atmosphere is as follows: 0.6 W m−2 (relative to LBLRTM) for net flux in each band at all altitudes, with a total (10–3000 cm−1) error of less than 1.0 W m−2 at any altitude; 0.07 K d−1 for total cooling rate error in the troposphere and lower stratosphere, and 0.75 K d−1 in the upper stratosphere and above. Other comparisons have been performed on RRTM using LBLRTM to gauge its sensitivity to changes in the abundance of specific species, including the halocarbons and carbon dioxide. The radiative forcing due to doubling the concentration of carbon dioxide is attained with an accuracy of 0.24 W m−2, an error of less than 5%. The speed of execution of RRTM compares favorably with that of other rapid radiation models, indicating that the model is suitable for use in general circulation models.
Amyotrophic lateral sclerosis (ALS) is a terminal neurodegenerative disease. Genetic predisposition, epigenetic changes, aging and accumulated life-long environmental exposures are known ALS risk ...factors. The complex and dynamic interplay between these pathological influences plays a role in disease onset and progression. Recently, the gut microbiome has also been implicated in ALS development. In addition, immune cell populations are differentially expanded and activated in ALS compared to healthy individuals. However, the temporal evolution of both the intestinal flora and the immune system relative to symptom onset in ALS is presently not fully understood. To better elucidate the timeline of the various potential pathological factors, we performed a longitudinal study to simultaneously assess the gut microbiome, immunophenotype and changes in ileum and brain epigenetic marks relative to motor behavior and muscle atrophy in the mutant superoxide dismutase 1 (SOD1
) familial ALS mouse model. We identified alterations in the gut microbial environment early in the life of SOD1
animals followed by motor dysfunction and muscle atrophy, and immune cell expansion and activation, particularly in the spinal cord. Global brain cytosine hydroxymethylation was also altered in SOD1
animals at disease end-stage compared to control mice. Correlation analysis confirmed interrelationships with the microbiome and immune system. This study serves as a starting point to more deeply comprehend the influence of gut microorganisms and the immune system on ALS onset and progression. Greater insight may help pinpoint novel biomarkers and therapeutic interventions to improve diagnosis and treatment for ALS patients.This article has an associated First Person interview with the joint first authors of the paper.
Two studies were conducted in order to develop a multidimensional instrument of driving style. In Study 1, we developed a self-report scale assessing four broad domains of driving style—the ...multidimensional driving style inventory (MDSI). A factor analysis revealed eight main factors, each one representing a specific driving style—dissociative, anxious, risky, angry, high-velocity, distress reduction, patient, and careful. In addition, significant associations were found between the eight factors, on the one hand, and gender, age, driving history, and personality measures of self-esteem, need for control, impulsive sensation seeking, and extraversion, on the other. In Study 2, further associations were found between the eight driving style factors and measures of trait anxiety and neuroticism. The discussion focused on the validity and utility of a multidimensional conceptualization of driving style.
A functional serotonin transporter promoter polymorphism, HTTLPR, alters the risk of disease as well as brain morphometry and function. Here, we show that HTTLPR is functionally triallelic. The LG ...allele, which is the L allele with a common G substitution, creates a functional AP2 transcription-factor binding site. Expression assays in 62 lymphoblastoid cell lines representing the six genotypes and in transfected raphe-derived cells showed codominant allele action and low, nearly equivalent expression for the S and LG alleles, accounting for more variation in HTT expression than previously recognized. The gain-of-function LALA genotype was approximately twice as common in 169 whites with obsessive-compulsive disorder (OCD) than in 253 ethnically matched controls. We performed a replication study in 175 trios consisting of probands with OCD and their parents. The LA allele was twofold overtransmitted to the patients with OCD. The HTTLPR LALA genotype exerts a moderate (1.8-fold) effect on risk of OCD, which crystallizes the evidence that the HTT gene has a role in OCD.
Ultrasonic wave propagation may be used in non-invasive sensing to identify the properties of a fluid in a container. An ultrasonic excitation can be coupled into the liquid or the gas through the ...walls of the container and detected by a receiver on the other side. However, in addition to this fluid path, another signal will also propagate through the structure and is referred as noise in this study. For most materials, this structural noise will be of higher amplitude compared to the fluid signal due to the large acoustic impedance difference between the solid container and the fluid. In this paper, an active noise cancellation (ANC) method is developed and demonstrated on an experimental setup. It was shown that this method cancels more than 90% of the noise signal in a given time window of interest. A sequential version of this cancellation method is also proposed, and it was shown that its performance improves as the number of canceling excitations is increased. The performance was found to be independent of the location of canceling transducers and position of the silence window but dependent on the width of the silence window. As an example, the ANC method was applied to noise cancellation of a signal travelling through water in a stainless-steel container. The signal-to-noise ratio (SNR) of the water signal in the window of interest was increased by 148% from 13.98 dB to 34.68 dB by using the proposed ANC method.
Conventional imaging using CT and bone scan has insufficient sensitivity when staging men with high-risk localised prostate cancer. We aimed to investigate whether novel imaging using ...prostate-specific membrane antigen (PSMA) PET-CT might improve accuracy and affect management.
In this multicentre, two-arm, randomised study, we recruited men with biopsy-proven prostate cancer and high-risk features at ten hospitals in Australia. Patients were randomly assigned to conventional imaging with CT and bone scanning or gallium-68 PSMA-11 PET-CT. First-line imaging was done within 21 days following randomisation. Patients crossed over unless three or more distant metastases were identified. The primary outcome was accuracy of first-line imaging for identifying either pelvic nodal or distant-metastatic disease defined by the receiver-operating curve using a predefined reference-standard including histopathology, imaging, and biochemistry at 6-month follow-up. This trial is registered with the Australian New Zealand Clinical Trials Registry, ANZCTR12617000005358.
From March 22, 2017 to Nov 02, 2018, 339 men were assessed for eligibility and 302 men were randomly assigned. 152 (50%) men were randomly assigned to conventional imaging and 150 (50%) to PSMA PET-CT. Of 295 (98%) men with follow-up, 87 (30%) had pelvic nodal or distant metastatic disease. PSMA PET-CT had a 27% (95% CI 23–31) greater accuracy than that of conventional imaging (92% 88–95 vs 65% 60–69; p<0·0001). We found a lower sensitivity (38% 24–52 vs 85% 74–96) and specificity (91% 85–97 vs 98% 95–100) for conventional imaging compared with PSMA PET-CT. Subgroup analyses also showed the superiority of PSMA PET-CT (area under the curve of the receiver operating characteristic curve 91% vs 59% 32% absolute difference; 28–35 for patients with pelvic nodal metastases, and 95% vs 74% 22% absolute difference; 18–26 for patients with distant metastases). First-line conventional imaging conferred management change less frequently (23 15% men 10–22 vs 41 28% men 21–36; p=0·008) and had more equivocal findings (23% 17–31 vs 7% 4–13) than PSMA PET-CT did. Radiation exposure was 10·9 mSv (95% CI 9·8–12·0) higher for conventional imaging than for PSMA PET-CT (19·2 mSv vs 8·4 mSv; p<0·001). We found high reporter agreement for PSMA PET-CT (κ=0·87 for nodal and κ=0·88 for distant metastases). In patients who underwent second-line image, management change occurred in seven (5%) of 136 patients following conventional imaging, and in 39 (27%) of 146 following PSMA PET-CT.
PSMA PET-CT is a suitable replacement for conventional imaging, providing superior accuracy, to the combined findings of CT and bone scanning.
Movember and Prostate Cancer Foundation of Australia.
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Receptor activator of nuclear factor-κB (RANKL)-mediated osteoclastogenesis plays a pivotal role in inflammatory bone resorption. The aim of this study was to identify the cellular source of RANKL in ...the bone resorptive lesions of periodontal disease. The concentrations of soluble RANKL, but not its decoy receptor osteoprotegerin, measured in diseased tissue homogenates were significantly higher in diseased gingival tissues than in healthy tissues. Double-color confocal microscopic analyses demonstrated less than 20% of both B cells and T cells expressing RANKL in healthy gingival tissues. By contrast, in the abundant mononuclear cells composed of 45% T cells, 50% B cells, and 5% monocytes in diseased gingival tissues, more than 50 and 90% of T cells and B cells, respectively, expressed RANKL. RANKL production by nonlymphoid cells was not distinctly identified. Lymphocytes isolated from gingival tissues of patients induced differentiation of mature osteoclast cells in a RANKL-dependent manner
in vitro
. However, similarly isolated peripheral blood B and T cells did not induce osteoclast differentiation, unless they were activated
in vitro
to express RANKL; emphasizing the osteoclastogenic potential of activated RANKL-expressing lymphocytes in periodontal disease tissue. These results suggest that activated T and B cells can be the cellular source of RANKL for bone resorption in periodontal diseased gingival tissue.
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