Quantitative Micro-Elastography Enables In Vivo Detection of Residual Cancer in the Surgical Cavity during Breast-Conserving Surgery.

Breast-conserving surgery (BCS) is commonly used for the treatment of early-stage breast cancer. Following BCS, approximately 20% to 30% of patients require reexcision because postoperative histopathology identifies cancer in the surgical margins of the excised specimen. Quantitative micro-elastography (QME) is an imaging technique that maps microscale tissue stiffness and has demonstrated a high diagnostic accuracy (96%) in detecting cancer in specimens excised during surgery. However, current QME methods, in common with most proposed intraoperative solutions, cannot image cancer directly in the patient, making their translation to clinical use challenging. In this proof-of-concept study, we aimed to determine whether a handheld QME probe, designed to interrogate the surgical cavity, can detect residual cancer directly in the breast cavity in vivo during BCS. In a first-in-human study, 21 BCS patients were scanned in vivo with the QME probe by five surgeons. For validation, protocols were developed to coregister in vivo QME with postoperative histopathology of the resected tissue to assess the capability of QME to identify residual cancer. In four cavity aspects presenting cancer and 21 cavity aspects presenting benign tissue, QME detected elevated stiffness in all four cancer cases, in contrast to low stiffness observed in 19 of the 21 benign cases. The results indicate that in vivo QME can identify residual cancer by directly imaging the surgical cavity, potentially providing a reliable intraoperative solution that can enable more complete cancer excision during BCS. SIGNIFICANCE: Optical imaging of microscale tissue stiffness enables the detection of residual breast cancer directly in the surgical cavity during breast-conserving surgery, which could potentially contribute to more complete cancer excision.

MAPO-18 Catalysts for the Methanol to Olefins Process: Influence of Catalyst Acidity in a High-Pressure Syngas (CO and H2) Environment.

The transition from integrated petrochemical complexes toward decentralized chemical plants utilizing distributed feedstocks calls for simpler downstream unit operations. Less separation steps are attractive for future scenarios and provide an opportunity to design the next-generation catalysts, which function efficiently with effluent reactant mixtures. The methanol to olefins (MTO) reaction constitutes the second step in the conversion of CO2, CO, and H2 to light olefins. We present a series of isomorphically substituted zeotype catalysts with the AEI topology (MAPO-18s, M = Si, Mg, Co, or Zn) and demonstrate the superior performance of the M(II)-substituted MAPO-18s in the conversion of MTO when tested at 350 °C and 20 bar with reactive feed mixtures consisting of CH3OH/CO/CO2/H2. Co-feeding high pressure H2 with methanol improved the catalyst activity over time, but simultaneously led to the hydrogenation of olefins (olefin/paraffin ratio < 0.5). Co-feeding H2/CO/CO2/N2 mixtures with methanol revealed an important, hitherto undisclosed effect of CO in hindering the hydrogenation of olefins over the Brønsted acid sites (BAS). This effect was confirmed by dedicated ethene hydrogenation studies in the absence and presence of CO co-feed. Assisted by spectroscopic investigations, we ascribe the favorable performance of M(II)APO-18 under co-feed conditions to the importance of the M(II) heteroatom in altering the polarity of the M-O bond, leading to stronger BAS. Comparing SAPO-18 and MgAPO-18 with BAS concentrations ranging between 0.2 and 0.4 mmol/gcat, the strength of the acidic site and not the density was found to be the main activity descriptor. MgAPO-18 yielded the highest activity and stability upon syngas co-feeding with methanol, demonstrating its potential to be a next-generation MTO catalyst.

Surface mining and low birth weight in central appalachia.

BACKGROUND: Surface mining has become a significant method of coal mining in the Central Appalachian region of the eastern United States alongside the traditional underground mining. Concerns have been raised about the health effects of this surface mining, particularly mountaintop removal mining where coal is mined upon steep mountaintops by removing the mountaintop through clearcutting forests and explosives. METHODS: We used a control group design with a pretest and a posttest to assess the associations of surface mining in Central Appalachia with low birth weight and other adverse birth outcomes. The pretest period is 1977-1989, a period of low surface mining activity. We consider three posttest periods: 1990-1998, 1999-2011 and 2012-2017, with 1999-2011 as the primary analysis and the other periods as secondary analyses. Surface mining in Central Appalachia increased after 1989, partly resulting from the Clean Air Act Amendments of 1990 which made surface mining in Appalachia more financially attractive. For the primary analysis, we fit a logistic regression model of the primary outcome (low birth weight, <2500 g) on dummy variables for county and year; individual level maternal/infant covariates (maternal race, maternal age, infant sex and whether birth was a multiple birth); and the amount of surface mining during the year of the birth in the maternal county of residence. RESULTS: Our analysis sample consisted of 783,328 infants -- 482,284 infants born from 1977 to 2017 to women residing in substantial surface mining activity counties and 301,044 infants born from 1977 to 2017 to women residing in matched control counties. Compared to the pre-period of low surface mining from 1977 to 1989, for the primary analysis posttest period of 1999-2011, there was an estimated relative increase in low birth weight in surface mining counties compared to matched control counties that was not statistically significant (odds ratio for a 5 percentage point increase in area disturbed by surface mining: 1.07, 95% confidence interval (0.96, 1.20), p-value: .22). For the secondary analysis posttest period of 1990-1998, there was no increase (odds ratio: 0.91, 95% confidence interval: (0.74, 1.13), p-value: .41). For the secondary analysis posttest period of 2012-2017, there was a statistically significant relative increase (odds ratio: 1.28, 95% confidence interval: (1.08, 1.50), p-value: .004). Qualitatively similar results were found for the outcomes of very low birth weight, preterm birth and small-for-gestational age. CONCLUSIONS: We examined the hypothesis that surface mining activity in Central Appalachia contributes to low birth weight using an observational study. We found evidence in secondary analyses that surface mining was associated with low birth weight in the 2012-2017 time period and potentially beginning in the early to mid 2000's. Evidence for an association was not found prior to 2000. A potential explanation for this pattern of association is that surface mining caused an increase in low birth weight but its onset was delayed. Future research is needed to clarify the findings and if replicated, identify the mechanism necessary to mitigate the impacts of mining on adverse birth outcomes.

In situ solid-state NMR and XRD studies of the ADOR process and the unusual structure of zeolite IPC-6.

The assembly-disassembly-organization-reassembly (ADOR) mechanism is a recent method for preparing inorganic framework materials and, in particular, zeolites. This flexible approach has enabled the synthesis of isoreticular families of zeolites with unprecedented continuous control over porosity, and the design and preparation of materials that would have been difficult-or even impossible-to obtain using traditional hydrothermal techniques. Applying the ADOR process to a parent zeolite with the UTL framework topology, for example, has led to six previously unknown zeolites (named IPC-n, where n = 2, 4, 6, 7, 9 and 10). To realize the full potential of the ADOR method, however, a further understanding of the complex mechanism at play is needed. Here, we probe the disassembly, organization and reassembly steps of the ADOR process through a combination of in situ solid-state NMR spectroscopy and powder X-ray diffraction experiments. We further use the insight gained to explain the formation of the unusual structure of zeolite IPC-6.

Use of Angle-Independent M-Mode Sonography for Assessment of Diaphragm Displacement.

OBJECTIVES: Sonographic assessment of diaphragm displacement has conventionally been conducted with M-mode sonography via an anterior subcostal approach. This method is subject to measurement errors when diaphragm displacement is not in line with the M-mode plane. We aimed to compare measurements obtained by offline angle-independent (anatomic) M-mode sonography with conventional M-mode sonography. METHODS: Fifty healthy adults were imaged with conventional and angle-independent M-mode sonography of the bilateral hemidiaphragms at 60% maximal inspiratory capacity using an inspiratory spirometer. RESULTS: Left hemidiaphragm displacement was successfully imaged by conventional M-mode sonography in only 70% (n = 35), as lung expansion obscured imaging, whereas 92% (n = 46) were assessable by angle-independent M-mode sonography. All right hemidiaphragm displacement could be assessed. Conventional M-mode results were higher than angle-independent M-mode results on the right (mean ± SD, 4.9 ± 1.4 versus 4.6 ± 1.2 cm, respectively; P= .003) and left (5.4 ± 1.3 versus 4.6 ± 1.0 cm; P < .001). Displacement values were different for right versus left hemidiaphragms on conventional M-mode sonography (mean difference, 0.6 ± 0.2 cm; P = .005), with only mild agreement (R2 = 0.35; P < .001). There was no laterality seen in the diaphragm displacement on angle-independent M-mode sonography (mean difference, 0.1 ± 0.1 cm; P = .47), with good agreement (R2 = 0.76; P < .001). CONCLUSIONS: Angle-independent M-mode sonography leads to better visualization and assessment of the left hemidiaphragm. It records lower displacement than conventional M-mode sonography in the bilateral diaphragms, likely because of fewer orientation and translation errors. Future study is indicated to assess the clinical utility of angle-independent M-mode sonography in a population with diaphragm dysfunction.

Post-Synthesis Stabilization of Germanosilicate Zeolites ITH, IWW, and UTL by Substitution of Ge for Al.

Germanosilicate zeolites often suffer from low hydrothermal stability due to the high content of Ge. Herein, we investigated the post-synthesis introduction of Al accompanied by stabilization of selected germanosilicates by degermanation/alumination treatments. The influence of chemical composition and topology of parent germanosilicate zeolites (ITH, IWW, and UTL) on the post-synthesis incorporation of Al was studied. Alumination of ITH (Si/Ge=2-13) and IWW (Si/Ge=3-7) zeolites resulted in the partial substitution of Ge for Al (up to 80 %), which was enhanced with a decrease of Ge content in the parent zeolite. In contrast, in extra-large pore zeolite UTL (Si/Ge=4-6) the hydrolysis of the interlayer Ge-O bonds dominated over substitution. The stabilization of zeolite UTL was achieved using a novel two-step degermanation/alumination procedure by the partial post-synthesis substitution of Ge for Si followed by alumination. This new method of stabilization and incorporation of strong acid sites may extend the utilization of germanosilicate zeolites, which has been until now been limited.

Diaphragm assessment by two dimensional speckle tracking imaging in normal subjects.

BACKGROUND: Conventionally, ultrasonographic assessment of diaphragm contractility has involved measuring respiratory changes in diaphragm thickness (thickening fraction) using B-mode or caudal displacement with M-mode. Two-dimensional speckle-tracking has been increasingly used to assess muscle deformation ('strain') in echocardiography. We sought to determine in a pilot study if this technology could be utilized to analyze diaphragmatic contraction. METHODS: Fifty healthy adult volunteers with normal exercise capacity underwent ultrasound imaging. A linear array transducer was used for the assessment of diaphragm thickness, thickening fraction (TF), and strain in the right anterior axillary line at approximately the ninth intercostal space. A phased array transducer was applied subcostally for the assessment of diaphragm displacement on the right mid-clavicular line. Diaphragmatic images were recorded from the end of expiration through the end of inspiration at 60 % maximal inspiratory capacity. Diaphragm strain was analyzed off-line by speckle tracking imaging. Blinded inter- and intra-rater variability was tested in 10 cases. RESULTS: Mean right diaphragm thickness at end-expiration (±SD: standard deviation) was 0.24 cm (±0.1), with TF of 45.1 % (±12) at 60 % peak inspiratory effort. Mean right diaphragm caudal displacement was 4.9 cm (±1). Mean right diaphragm strain was -40.3 % (±9). A moderate correlation was seen between longitudinal strain and TF (R(2) 0.44, p < 0.0001). A weak correlation was seen between strain and caudal displacement (R(2) 0.14, p < 0.01), and an even weaker correlation was seen between caudal displacement and TF (R(2) 0.1, p = 0.04). Age, gender, and body mass index were not significantly associated with right diaphragm strain or TF. Although inter- and intra-rater variability was overall good for TF, caudal displacement, and strain (inter-rater R(2); 0.8, 0.9, and 0.7, respectively [p < 0.01], intra-rater R(2); 0.9, 0.7, and 0.9, respectively [p < 0.01]), strain values did have a slightly lower inter-rater repeatability. CONCLUSIONS: Diaphragmatic strain estimated by speckle tracking imaging was associated with conventional ultrasound measures of diaphragmatic function (TF and caudal displacement). Further clinical studies are warranted to investigate its clinical utility.

Archaeological bone lipids as palaeodietary markers.

RATIONALE: Stable isotope analysis of archaeological and fossil bone samples can provide important insights into past environments, ecologies and diets. Previous studies have focused on stable carbon and nitrogen isotopes in bone collagen, or carbon isotopes in bone mineral (bioapatite). Carbon isotope analysis of lipids from archaeological bone has received much less attention, partly due to the lack of suitable methodologies allowing sufficient recovery of compounds for structural and isotopic characterisation. Here we show that lipids can be easily and reliably recovered from archaeological bone using a modified protocol, and that these provide complementary dietary information to other bone components. METHODS: Human and animal bones were obtained from a variety of archaeological contexts. Lipids were sequentially extracted using solvent extraction (dichloromethane/methanol), followed by acidified methanol extraction (methanol/H2SO4). The lipids were then analysed by gas chromatography/mass spectrometry (GC/MS) and gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS). RESULTS: Appreciable amounts of endogenous lipid were recovered from archaeological bone. Importantly, a comparison between compound-specific and bulk collagen isotopic data shows that archaeological bone lipids reflect dietary input and can be used to distinguish between marine and terrestrial consumers, as well as between C3 and C4 plant consumers. Furthermore, the presence of essential fatty acids directly incorporated from diet to bone may provide additional palaeodietary information. CONCLUSIONS: Our findings suggest that archaeological bone lipids are a hitherto untapped resource of dietary information that offer additional insights to those gained from other isotopic analyses of bone.