Background
Desmoid tumors are rare and exhibit a highly unpredictable natural history. We sought to analyze prognostic factors associated with recurrence in a large single-institution study of ...patients with desmoid tumors.
Methods
We performed a retrospective review of 177 patients with desmoid tumor who underwent macroscopically complete surgical resection, with or without the addition of radiotherapy (RT) or systemic therapy, from 1970 to 2009. We examined patterns of presentation, all known risk factors for recurrence, and their association with recurrence-free survival (RFS).
Results
Twenty-two patients (12 %) had intra-abdominal desmoid tumors, and 155 (88 %) had extra-abdominal tumors. Patterns of presentation included primary (
n
= 133, 75 %) and locally recurrent (
n
= 44, 25 %) disease. Treatment was surgery alone in 125 patients (71 %), surgery and RT in 36 (20 %), and surgery and systemic therapy with or without RT in 20 (11 %). Median follow-up was 40 months. Overall, the local relapse rate was 29 %, and 10-year RFS was 60 %. R0 resection status was the only predictor of freedom from local recurrence on multivariate analysis (odds ratio 0.32; 95 % confidence interval 0.15–0.66;
P
= 0.002). The selective use of adjuvant RT appeared to improve local control in patients with positive margins.
Conclusions
For patients with desmoid tumors undergoing surgery, wide excision with negative margins should be the goal, but not at the expense of function, as fewer than half of patients with positive margins will experience recurrence.
Background Aortic arch reconstruction after hypoplastic left heart syndrome (HLHS) palliation can vary widely in shape and dimensions between patients. Arch morphology alone may affect cardiac ...function and outcome. We sought to uncover the relationship of arch three-dimensional shape features with functional and short-term outcome data after total cavopulmonary connection (TCPC). Methods Aortic arch shape models of 37 patients with HLHS (age, 2.89 ± 0.99 years) were reconstructed from magnetic resonance data before TCPC completion. A novel, validated statistical shape analysis method was used to compute a three-dimensional anatomic mean shape from the cohort and calculate the deformation vectors of the mean shape toward each patient’s specific anatomy. From these deformations, three-dimensional shape features most related to ventricular ejection fraction, indexed end-diastolic volume, and superior cavopulmonary pressure were extracted by partial least-square regression analysis. Shape patterns relating to intensive care unit and hospital lengths of stay after TCPC were assessed. Results Distinct deformation patterns, which result in an acutely mismatched aortic root and ascending aorta, and a gothic-like transverse arch, correlated with increased indexed end-diastolic volume and higher superior cavopulmonary pressure but not with ejection fraction. Specific arch morphology with pronounced transverse arch and descending aorta mismatch also correlated with longer intensive care unit and hospital lengths of stay after TCPC completion. Conclusions Independent of hemodynamically important arch obstruction, altered aortic morphology in HLHS patients appears to have important associations with higher superior cavopulmonary pressure and with short-term outcomes after TCPC completion as highlighted by statistical shape analysis, which could act as adjunct to risk assessment in HLHS.
The increasing consumption of nonrenewable materials urgently calls for the design and fabrication of sustainable alternatives. New generations of materials should be derived from renewable sources, ...processed using environmentally friendly methods, and designed considering their full life cycle, especially their end-of-life fate. Here, we review recent advances in developing sustainable polymers from biological matter (biomatter), including progress in the extraction and utilization of bioderived monomers and polymers, as well as the emergence of polymers produced directly from unprocessed biomatter (entire cells or tissues). We also discuss applications of sustainable polymers in bioplastics, biocomposites, and cementitious biomaterials, with emphasis on relating their performance to underlying fundamental mechanisms. Finally, we provide a future outlook for sustainable material development, highlighting the need for more accurate and accessible tools for assessing life-cycle impacts and socioeconomic challenges as this field advances.
Hepatic stellate cells (HSCs) drive hepatic fibrosis. Therapies that inactivate HSCs have clinical potential as antifibrotic agents. We previously identified acid ceramidase (aCDase) as an ...antifibrotic target. We showed that tricyclic antidepressants (TCAs) reduce hepatic fibrosis by inhibiting aCDase and increasing the bioactive sphingolipid ceramide. We now demonstrate that targeting aCDase inhibits YAP/TAZ activity by potentiating its phosphorylation-mediated proteasomal degradation via the ubiquitin ligase adaptor protein β-TrCP. In mouse models of fibrosis, pharmacologic inhibition of aCDase or genetic knockout of aCDase in HSCs reduces fibrosis, stromal stiffness, and YAP/TAZ activity. In patients with advanced fibrosis, aCDase expression in HSCs is increased. Consistently, a signature of the genes most down-regulated by ceramide identifies patients with advanced fibrosis who could benefit from aCDase targeting. The findings implicate ceramide as a critical regulator of YAP/TAZ signaling and HSC activation and highlight aCDase as a therapeutic target for the treatment of fibrosis.
The Scanning Habitable Environments with Raman and Luminescence for Organics
and Chemicals (SHERLOC) is a robotic arm-mounted instrument on NASA’s Perseverance
rover. SHERLOC has two primary ...boresights. The Spectroscopy boresight generates
spatially resolved chemical maps using fluorescence and Raman spectroscopy coupled to
microscopic images (10.1 μm/pixel). The second boresight is a Wide Angle Topographic
Sensor for Operations and eNgineering (WATSON); a copy of the Mars Science Laboratory
(MSL) Mars Hand Lens Imager (MAHLI) that obtains color images from microscopic
scales (∼13 μm/pixel) to infinity. SHERLOC Spectroscopy focuses a 40 μs pulsed deep UV
neon-copper laser (248.6 nm), to a ∼100 μm spot on a target at a working distance of ∼48
mm. Fluorescence emissions from organics, and Raman scattered photons from organics
and minerals, are spectrally resolved with a single diffractive grating spectrograph with a
spectral range of 250 to ∼370 nm. Because the fluorescence and Raman regions are naturally
separated with deep UV excitation (<250 nm), the Raman region ∼ 800 – 4000 cm−1
(250 to 273 nm) and the fluorescence region (274 to ∼370 nm) are acquired simultaneously
without time gating or additional mechanisms. SHERLOC science begins by using an Autofocus
Context Imager (ACI) to obtain target focus and acquire 10.1 μm/pixel greyscale
images. Chemical maps of organic and mineral signatures are acquired by the orchestration
of an internal scanning mirror that moves the focused laser spot across discrete points on
the target surface where spectra are captured on the spectrometer detector. ACI images and
chemical maps (< 100 μm/mapping pixel) will enable the first Mars in situ view of the spatial
distribution and interaction between organics, minerals, and chemicals important to the
assessment of potential biogenicity (containing CHNOPS). Single robotic arm placement
chemical maps can cover areas up to 7x7 mm in area and, with the < 10 min acquisition
time per map, larger mosaics are possible with arm movements. This microscopic view of
the organic geochemistry of a target at the Perseverance field site, when combined with
the other instruments, such as Mastcam-Z, PIXL, and SuperCam, will enable unprecedented
analysis of geological materials for both scientific research and determination of which samples
to collect and cache for Mars sample return.
Conducting HIV surveys in resource-limited settings is challenging because of logistics, limited availability of trained personnel, and complexity of testing. We described the procedures and systems ...deemed critical to ensure high-quality laboratory data in the population-based HIV impact assessments and large-scale household surveys.
Laboratory professionals were engaged in every stage of the surveys, including protocol development, site assessments, procurement, training, quality assurance, monitoring, analysis, and reporting writing. A tiered network of household, satellite laboratories, and central laboratories, accompanied with trainings, optimized process for blood specimen collection, storage, transport, and real-time monitoring of specimen quality, and test results at each level proved critical in maintaining specimen integrity and high-quality testing. A plausibility review of aggregate merged data was conducted to confirm associations between key variables as a final quality check for quality of laboratory results.
Overall, we conducted a hands-on training for 3355 survey staff across 13 surveys, with 160-387 personnel trained per survey on biomarker processes. Extensive training and monitoring demonstrated that overall, 99% of specimens had adequate volume and 99.8% had no hemolysis, indicating high quality. We implemented quality control and proficiency testing for testing, resolved discrepancies, verified >300 Pima CD4 instruments, and monitored user errors. Aggregate data review for plausibility further confirmed the high quality of testing.
Ongoing engagement of laboratory personnel to oversee processes at all levels of the surveys is critical for successful national surveys. High-quality population-based HIV impact assessments laboratory data ensured reliable results and demonstrated the impact of HIV programs in 13 countries.
Confocal endoscopy has been widely used to obtain fine optically sectioned images. However, confocal endomicroscopic images are formed by point‐by‐point scanning in both lateral and axial directions, ...which results in long image acquisition time. Here, an endomicroscope with telecentric configuration is presented to achieve nonmechanical and rapid axial scanning for volumetric fluorescence imaging. In our system, optical sectioning in wide‐field fashion is obtained through HiLo imaging with a digital micromirror device. Axial scanning, without mechanical moving parts, is conducted by digital focus adjustment using an electrically tunable lens, offering constant magnification and contrast. We demonstrate imaging performance of our system with optically sectioned images using fluorescently labeled beads, as well as ex vivo mice cardiac tissue samples. Our system provides multiple advantages, in terms of improved scanning range, and reduced image acquisition time, which shows great potentials for three‐dimensional biopsies of volumetric biological samples.
Digital‐scanning‐based HiLo optical sectioning endo‐microscopy with an electrically tunable for imaging ex‐vivo cardiac tissues.
We examine the sophistication of analysts' cash flow forecasts to better understand what accrual adjustments, if any, analysts make when forecasting cash flows. As a preliminary step, we first ...demonstrate that prior empirical tests used to evaluate the sophistication of analysts' cash flow forecasts are not diagnostic. We then present three sets of evidence to triangulate our conclusion that analysts' cash flow forecasts incorporate meaningful accrual adjustments. First, we review a stratified random sample of 90 analyst reports and find that the majority of these analysts include explicit adjustments for working capital and other accruals in their cash flow forecasts. Second, using a large sample of analysts' cash flow forecasts from 1993–2008, we find that these forecasts outperform time‐series cash flow forecasts in correctly predicting the sign and magnitude of accruals. Finally, we find a significant market reaction to analysts' cash flow forecast revisions, suggesting that investors find these revisions informative. Collectively, our findings demonstrate that analysts' cash flow forecasts are not simply naïve extensions of their own earnings forecasts, but that they reflect meaningful and useful accrual adjustments. These findings are relevant to researchers who examine analysts' cash flow forecasts in a variety of settings, and to investors and practitioners who employ these forecasts for valuation purposes.
Speckle contrast imaging enables rapid mapping of relative blood flow distributions using camera detection of back-scattered laser light. However, speckle derived flow measures deviate from direct ...measurements of erythrocyte speeds by 47 ± 15% (n = 13 mice) in vessels of various calibers. Alternatively, deviations with estimates of volumetric flux are on average 91 ± 43%. We highlight and attempt to alleviate this discrepancy by accounting for the effects of multiple dynamic scattering with speckle imaging of microfluidic channels of varying sizes and then with red blood cell (RBC) tracking correlated speckle imaging of vascular flows in the cerebral cortex. By revisiting the governing dynamic light scattering models, we test the ability to predict the degree of multiple dynamic scattering across vessels in order to correct for the observed discrepancies between relative RBC speeds and multi-exposure speckle imaging estimates of inverse correlation times. The analysis reveals that traditional speckle contrast imagery of vascular flows is neither a measure of volumetric flux nor particle speed, but rather the product of speed and vessel diameter. The corrected speckle estimates of the relative RBC speeds have an average 10 ± 3% deviation in vivo with those obtained from RBC tracking.
Learning Objectives
Describe the frequency of CTNNB1 mutations in sporadic desmoid tumors.
Summarize findings regarding CTNNB1 mutation status and disease outcome.
Background.
Mutations in the ...gene‐encoding β‐catenin, CTNNB1, are highly prevalent in sporadic desmoid tumors and may predict the risk for recurrence. We sought to determine the prevalence of CTNNB1 mutations in a large cohort of sporadic desmoid tumors and to determine whether CTNNB1 mutation status correlates with disease outcome.
Methods.
Single‐base extension genotyping of the CTNNB1 gene was performed on 145 sporadic, paraffin‐embedded desmoid tumor specimens. Correlation of mutation status with outcome was performed on a subset of 115 patients who underwent macroscopically complete surgical resection.
Results.
CTNNB1 mutations were detected in 106 of 145 (73%) tumor specimens and in 86 of 115 (75%) specimens from patients who underwent curative‐intent surgical resection, including discrete mutations in the following codons of CTNNB1 exon 3: T41A (46%), S45F (25%), S45P (1.7%), and S45C (0.9%). Desmoid tumors of the superficial trunk were significantly less likely to harbor CTNNB1 mutations than tumors located elsewhere, but none of the other examined clinicopathologic factors were found to be associated with CTNNB1 mutation status. At a median follow‐up of 31 months, 5‐year recurrence‐free survival was slightly, although not statistically significantly, worse for patients with β‐catenin‐mutated tumors than for those with wild‐type tumors (58% vs. 74%, respectively). The specific CTNNB1 codon mutation did not correlate with the risk for recurrence.
Conclusion.
CTNNB1 mutations are indeed common in sporadic desmoid tumors. However, our study did not detect a statistically significant difference in recurrence risk according to either the CTNNB1 mutation status or the specific CTNNB1 mutation.
Mutations in the gene‐encoding β‐catenin, CTNNB1, are highly prevalent in sporadic desmoid tumors and may predict the risk for recurrence. We sought to determine the prevalence of CTNNB1 mutations and to determine whether the CTNNB1 mutation status correlates with disease outcome.
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