Reaction mechanism of the Me3AuPMe3-H2 plasma-enhanced ALD process.

The reaction mechanism of the recently reported Me3AuPMe3-H2 plasma gold ALD process was investigated using in situ characterization techniques in a pump-type ALD system. In situ RAIRS and in vacuo XPS measurements confirm that the CH3 and PMe3 ligands remain on the gold surface after chemisorption of the precursor, causing self-limiting adsorption. Remaining surface groups are removed by the H2 plasma in the form of CH4 and likely as PHxMey groups, allowing chemisorption of new precursor molecules during the next exposure. The decomposition behaviour of the Me3AuPMe3 precursor on a Au surface is also presented and linked to the stability of the precursor ligands that govern the self-limiting growth during ALD. Desorption of the CH3 ligands occurs at all substrate temperatures during evacuation to high vacuum, occurring faster at higher temperatures. The PMe3 ligand is found to be less stable on a gold surface at higher substrate temperatures and is accompanied by an increase in precusor decomposition on a gold surface, indicating that the temperature dependent stability of the precursor ligands is an important factor to ensure self-limiting precursor adsorption during ALD. Remarkably, precursor decomposition does not occur on a SiO2 surface, in situ transmission absorption infrared experiments indicate that nucleation on a SiO2 surface occurs on Si-OH groups. Finally, we comment on the use of different co-reactants during PE-ALD of Au and we report on different PE-ALD growth with the reported O2 plasma and H2O process in pump-type versus flow-type ALD systems.

Crowdsourcing for translational research: analysis of biomarker expression using cancer microarrays.

BACKGROUND: Academic pathology suffers from an acute and growing lack of workforce resource. This especially impacts on translational elements of clinical trials, which can require detailed analysis of thousands of tissue samples. We tested whether crowdsourcing - enlisting help from the public - is a sufficiently accurate method to score such samples. METHODS: We developed a novel online interface to train and test lay participants on cancer detection and immunohistochemistry scoring in tissue microarrays. Lay participants initially performed cancer detection on lung cancer images stained for CD8, and we measured how extending a basic tutorial by annotated example images and feedback-based training affected cancer detection accuracy. We then applied this tutorial to additional cancer types and immunohistochemistry markers - bladder/ki67, lung/EGFR, and oesophageal/CD8 - to establish accuracy compared with experts. Using this optimised tutorial, we then tested lay participants' accuracy on immunohistochemistry scoring of lung/EGFR and bladder/p53 samples. RESULTS: We observed that for cancer detection, annotated example images and feedback-based training both improved accuracy compared with a basic tutorial only. Using this optimised tutorial, we demonstrate highly accurate (>0.90 area under curve) detection of cancer in samples stained with nuclear, cytoplasmic and membrane cell markers. We also observed high Spearman correlations between lay participants and experts for immunohistochemistry scoring (0.91 (0.78, 0.96) and 0.97 (0.91, 0.99) for lung/EGFR and bladder/p53 samples, respectively). CONCLUSIONS: These results establish crowdsourcing as a promising method to screen large data sets for biomarkers in cancer pathology research across a range of cancers and immunohistochemical stains.

Microsurgical Reconstruction of Large Oncologic Chest Wall Defects for Locally Advanced Breast Cancer or Osteoradionecrosis: A Retrospective Review of 26 Cases over a 5-Year Period.

BACKGROUND: Locally advanced breast cancer (LABC) and chest wall osteoradionecrosis (ORN) often require extensive and composite tissue resection, including muscles, ribs, pleura, and lung parenchyma. As such, these cases necessitate complex reconstructive procedures for skeletal chest wall reconstruction and soft tissue resurfacing of extensive defects. Traditional local and regional flaps are often inadequate, and many such cases are prospectively labeled "unresectable." METHODS: We report a single-center experience with the microsurgical reconstruction of such defects over a 5-year period. Between 2007 and 2011, 1,077 microvascular reconstructive cases following breast cancer resection were performed, of which 26 cases comprised LABC or ORN requiring reconstruction. Surgical indications, defect parameters, choice of reconstruction, and outcomes were assessed. RESULTS: Thirty free flap microsurgical reconstructions were undertaken in 26 cases, with a 96.2% flap survival rate. Complications were low, and mean hospital stay was 8.7 days. An algorithmic approach to management is presented. CONCLUSION: Wide resection and microvascular free tissue transfer provide versatile solutions for the reconstruction of extensive chest wall defects. With good reported perioperative outcomes even in advanced cases, surgical resection of LABC may offer a useful approach in difficult and/or palliative cases.

Recommendations for the Improved Effectiveness and Reporting of Telemedicine Programs in Developing Countries: Results of a Systematic Literature Review.

BACKGROUND: A lack of decisive evidence on the impact of telemedicine on financial and clinical outcomes has not prohibited significant investment in developing countries. Understanding characteristics that facilitate effective telemedicine programs is required to allow telemedicine to be used to its full potential. This systematic review aimed to identify organizational, technological, and financial features of successful telemedicine programs providing direct clinical care in developing countries. MATERIALS AND METHODS: Databases were searched, and the results were reviewed systematically according to predefined inclusion/exclusion criteria. Information on location(s), measure of success, and organizational, technological, and financial characteristics were extracted. This review was impeded by inadequate program reporting, and so a concise checklist was developed to aid improved reporting, enabling future reviews to identify key characteristics of effective programs. RESULTS: This systematic review identified 46 articles reporting 36 programs that fulfilled the inclusion/exclusion criteria. Programs were distributed globally, including regional, national, and international programs. Technological modalities included synchronous technology, real-time teleconsultations, and asynchronous technology. Program integration with existing systems and twinning of international institutions were identified as factors enabling program success. Other factors included simple and easy-to-use technology, ability to reduce the burden on healthcare professionals, and technology able to maintain functionality in challenging environmental circumstances. Reports describing effectiveness and costs were limited. CONCLUSIONS: This systematic review identified key factors associated with telemedicine program success. However, inconsistencies in reporting represent an obstacle to establishment of successful programs in developing countries by limiting the application of previous experiences. Adhering to the guidelines suggested here may allow more quantitative assessments of effectiveness and impact for future programs.

Police Mental Health Partnership project: Police Ambulance Crisis Emergency Response (PACER) model development.

OBJECTIVES: To review internationally recognized models of police interactions with people experiencing mental health crises that are sometimes complex and associated with adverse experience for the person in crisis, their family and emergency service personnel. To develop, implement and review a partnership model trial between mental health and emergency services that offers alternative response pathways with improved outcomes in care. METHODS: Three unique models of police and mental health partnership in the USA were reviewed and used to develop the PACER (Police Ambulance Crisis Emergency Response) model. A three month trial of the model was implemented and evaluated. RESULTS: Significant improvements in response times, the interactions with and the outcomes for people in crisis were some of the benefits shown when compared with usual services. CONCLUSIONS: The pilot showed that a partnership involving mental health and police services in Melbourne, Australia could be replicated based on international models. Initial data supported improvements compared with usual care. Further data collection regarding usual care and this new model is required to confirm observed benefits.

Throwing light on petroleum: simulated exposure of crude oil to sunlight and characterization using atmospheric pressure photoionization fourier transform ion cyclotron resonance mass spectrometry.

The change in profile of crude oil following a release into the environment is a topic of significant interest, and there is a need to develop analytical methodologies for understanding natural processes which affect related complex mixture profiles. One such process is the exposure to sunlight. In the following investigation, three oil samples were studied: one served as a control, a second was subjected to irradiation by an ultraviolet lamp, and a third sample was irradiated by a SoLux light source which closely models the solar emission profile. The usage of the SoLux light source represents a new method which enables a controlled experiment to mimic the effects of sunlight upon the sample. Atmospheric pressure photoionization was selected as the primary ionization method due to the ability to ionize a broad range of compounds, including low polarity components which could not be observed using electrospray ionization. During a test of sample preparation methods, the addition of a protic cosolvent to the sample solutions was shown to broaden the range of heteroatom-containing components observed. Following characterization, it was found that the polyaromatic hydrocarbons did not change in profile, while compounds containing a heteroatom exhibited a tendency to oxidize following photoirradiation. Sulfur-containing compounds with a low number of double bond equivalents were among the most reactive components of the complex mixture. The photooxidation of compounds in petroleum, following exposure to sunlight, is expected to have significance with regards to solubility and potential toxicity.

Polarization-dependent properties of the cladding modes of a single mode fiber covered with gold nanoparticles.

The properties of the high order cladding modes of standard optical fibers are measured in real-time during the deposition of gold nanoparticle layers by chemical vapor deposition (CVD). Using a tilted fiber Bragg grating (TFBG), the resonance wavelength and peak-to-peak amplitude of a radially polarized cladding mode resonance located 51 nm away from the core mode reflection resonance shift by 0.17 nm and 13.54 dB respectively during the formation of a ~200 nm thick layer. For the spectrally adjacent azimuthally polarized resonance, the corresponding shifts are 0.45 nm and 16.34 dB. In both cases, the amplitudes of the resonance go through a pronounced minimum of about 5 dB for thickness between 80 and 100 nm and at the same time the wavelengths shift discontinuously. These effects are discussed in terms of the evolving metallic boundary conditions perceived by the cladding modes as the nanoparticles grow. Scanning Electron Micrographs and observations of cladding mode light scattering by nanoparticle layers of various thicknesses reveal a strong correlation between the TFBG polarized transmission spectra, the grain size and fill factor of the nanoparticles, and the scattering efficiency. This allows the preparation of gold nanoparticle layers that strongly discriminate between radially and azimuthally polarized cladding mode evanescent fields, with important consequences in the plasmonic properties of these layers.

Selective killing of ATM- or p53-deficient cancer cells through inhibition of ATR.

Here we report a comprehensive biological characterization of a potent and selective small-molecule inhibitor of the DNA damage response (DDR) kinase ATR. We show a profound synthetic lethal interaction between ATR and the ATM-p53 tumor suppressor pathway in cells treated with DNA-damaging agents and establish ATR inhibition as a way to transform the outcome for patients with cancer treated with ionizing radiation or genotoxic drugs.

A Systematic Review and Meta-analysis of Clinical Outcomes in Autologous Breast Reconstruction Using Internal Mammary Artery Perforators as Recipient Vessels.

Recipient vessel selection is vital for successful autologous free-flap breast reconstruction. Internal mammary artery perforators have gained interest as a recipient vessel option. However, previous studies on their microsurgical safety and efficacy are limited and inconsistent. Thus, we conducted a systematic review and meta-analysis to assess the safety and effectiveness of using internal mammary artery perforators as recipient vessels in breast reconstruction. Methods: The protocol has been previously published in PROSPERO (CRD42020190020). The PubMed, Scopus, Web of Science, and PROSPERO databases were searched. Two independent reviewers evaluated the articles for inclusion in the study. Study quality was assessed using the Newcastle-Ottawa Scale and the MINORS instrument (Methodological Index for Non-Randomized Studies). Results: Of the 361 articles screened, 13 studies were included (313 patients with 318 flaps; 223 unilateral, 31 bilateral, mean average age 51.2 and mean BMI 27.8 ± 1.9). The mean overall success rate was 99.8%, the pooled surgical success rate was 100% [95% confidence interval (CI): 97%-100%], and the overall rate of complications was 11% (95% CI: 7%-18%). The most common complication was vascular-related to microanastomoses, with an incidence of 5% (95% CI: 2%-10%). The fat necrosis rate was 3% (95% CI: 2%-6%). Conclusions: This study verified that internal mammary artery perforator vessels are reliable in breast reconstruction, with a high success rate and a relatively low complication rate. Moreover, in selected microsurgical breast reconstruction patients, internal mammary artery perforators may be the primary recipient vessel choice over the internal mammary artery or thoracodorsal vessels.

Thermal atomic layer deposition of gold nanoparticles: controlled growth and size selection for photocatalysis.

Gold nanoparticles have been extensively studied for their applications in catalysis. For Au nanoparticles to be catalytically active, controlling the particle size is crucial. Here we present a low temperature (105 °C) thermal atomic layer deposition approach for depositing gold nanoparticles on TiO2 with controlled size and loading using trimethylphosphino-trimethylgold(iii) and two co-reactants (ozone and water) in a fluidized bed reactor. We show that the exposure time of the precursors is a variable that can be used to decouple the Au particle size from the loading. Longer exposures of ozone narrow the particle size distribution, while longer exposures of water broaden it. By studying the photocatalytic activity of Au/TiO2 nanocomposites, we show how the ability to control particle size and loading independently can be used not only to enhance performance but also to investigate structure-property relationships. This study provides insights into the mechanism underlying the formation and evolution of Au nanoparticles prepared for the first time via vapor phase atomic layer deposition. Employing a vapor deposition technique for the synthesis of Au/TiO2 nanocomposites eliminates the shortcomings of conventional liquid-based processes opening up the possibility of highly controlled synthesis of materials at large scale.

Colorectal cancer: texture analysis of portal phase hepatic CT images as a potential marker of survival.

PURPOSE: To assess the utility of texture analysis of liver computed tomographic (CT) images by determining the effect of acquisition parameters on texture and by comparing the abilities of texture analysis and hepatic perfusion CT to help predict survival for patients with colorectal cancer. MATERIALS AND METHODS: The study comprised a phantom test and a clinical evaluation of 48 patients with colorectal cancer who had consented to retrospective analysis of hepatic perfusion CT data acquired during a research study approved by the institutional review board. Both components involved texture analysis to quantify the relative contribution of CT features between 2 and 12 pixels wide to overall image brightness and uniformity. The effect of acquisition factors on texture was assessed on CT images of a cylindric phantom filled with water obtained by using tube currents between 100 and 250 mAs and voltages between 80 and 140 kVp. Texture on apparently normal portal phase CT images of the liver and hepatic perfusion parameters were related to patient survival by using Kaplan-Meier survival analysis. RESULTS: A texture parameter that compared the uniformity of distribution of CT image features 10 and 12 pixels wide exhibited the least variability with CT acquisition parameters (maximum coefficient of variation, 2.6%) and was the best predictor of patient survival (P < .005). There was no significant association between survival and hepatic perfusion parameters. CONCLUSION: The study provides preliminary evidence that analysis of liver texture on portal phase CT images is potentially a superior predictor of survival for patients with colorectal cancer than CT perfusion imaging. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/2502071879/DC1.

Nested Basin-Sampling.

We report an embarrassingly parallel method for the evaluation of thermodynamic properties over an energy landscape exhibiting broken ergodicity, nested is the likelihood of the observed data D givenbasin-sampling (NBS). We also introduce the No Galilean U-Turn Sampler (NoGUTS), a new sampling scheme based on the No U-Turn Sampler (NUTS) introduced by Hoffman and Gelman (2014) that works with the Galilean Monte Carlo scheme introduced by Betancourt (2012) to aid the efficient generation of new live points. NoGUTS can be thought of as a form of reflective slice sampling with an automatic stopping criterion. We apply this approach to a benchmark atomic cluster of 31 Lennard-Jones atoms, which exhibits a low temperature solid-solid heat capacity peak. The calculated heat capacity is compared with results generated by parallel tempering (PT), basin-sampling parallel tempering (BSPT), and standard nested sampling (NS) simulations. NBS reproduces the full heat capacity curve predicted by PT and BSPT, while the NS calculation with similar computational cost fails to resolve the low-temperature solid-solid phase transition.

Plasma-Enhanced Atomic Layer Deposition of Nanostructured Gold Near Room Temperature.

A plasma-enhanced atomic layer deposition (PE-ALD) process to deposit metallic gold is reported, using the previously reported Me3Au(PMe3) precursor with H2 plasma as the reactant. The process has a deposition window from 50 to 120 °C with a growth rate of 0.030 ± 0.002 nm per cycle on gold seed layers, and it shows saturating behavior for both the precursor and reactant exposure. X-ray photoelectron spectroscopy measurements show that the gold films deposited at 120 °C are of higher purity than the previously reported ones (<1 at. % carbon and oxygen impurities and <0.1 at. % phosphorous). A low resistivity value was obtained (5.9 ± 0.3 µΩ cm), and X-ray diffraction measurements confirm that films deposited at 50 and 120 °C are polycrystalline. The process forms gold nanoparticles on oxide surfaces, which coalesce into wormlike nanostructures during deposition. Nanostructures grown at 120 °C are evaluated as substrates for free-space surface-enhanced Raman spectroscopy (SERS) and exhibit an excellent enhancement factor that is without optimization, only one order of magnitude weaker than state-of-the-art gold nanodome substrates. The reported gold PE-ALD process therefore offers a deposition method to create SERS substrates that are template-free and does not require lithography. Using this process, it is possible to deposit nanostructured gold layers at low temperatures on complex three-dimensional (3D) substrates, opening up opportunities for the application of gold ALD in flexible electronics, heterogeneous catalysis, or the preparation of 3D SERS substrates.

Rational Design of 5-(4-(Isopropylsulfonyl)phenyl)-3-(3-(4-((methylamino)methyl)phenyl)isoxazol-5-yl)pyrazin-2-amine (VX-970, M6620): Optimization of Intra- and Intermolecular Polar Interactions of a New Ataxia Telangiectasia Mutated and Rad3-Related (ATR) Kinase Inhibitor.

The DNA damage response (DDR) is a DNA damage surveillance and repair mechanism that can limit the effectiveness of radiotherapy and DNA-damaging chemotherapy, commonly used treatment modalities in cancer. Two related kinases, ataxia telangiectasia mutated (ATM) and ATM and Rad3-related kinase (ATR), work together as apical proteins in the DDR to maintain genome stability and cell survival in the face of potentially lethal forms of DNA damage. However, compromised ATM signaling is a common characteristic of tumor cells, which places greater reliance on ATR to mediate the DDR. In such circumstances, ATR inhibition has been shown to enhance the toxicity of DNA damaging chemotherapy to many cancer cells in multiple preclinical studies, while healthy tissue with functional ATM can tolerate ATR inhibition. ATR therefore represents a very attractive anticancer target. Herein we describe the discovery of VX-970/M6620, the first ATR inhibitor to enter clinical studies, which is based on a 2-aminopyrazine core first reported by Charrier ( J. Med. Chem. 2011 , 54 , 2320 - 2330 , DOI: 10.1021/jm101488z ).

Plastic Surgeon-Led Ultrasound.

BACKGROUND: Portable high-frequency ultrasound is a useful adjunct to a plastic surgeon's practice. With a short learning curve, this patient-friendly imaging modality has a variety of uses that aid patient management/treatment plans. The authors describe clinical cases and review the literature regarding ultrasound performed by the surgeon. METHODS: The Sonosite S-Nerve machine with the L25X transducer was used (depth, 4.3 cm). Clinical cases that ordinarily would have been referred to the radiology department were taken from the day-to-day practice of the senior author (M.G.). The clinical scenarios ranged from acute presentations to planned elective settings. RESULTS: Ultrasound was a useful adjunct in a variety of applications, ranging from acute hand trauma visualizing neurovascular bundles and tendons, to elements of reconstructive breast surgery such as fat grafting over an implant and scar release. The ultrasound machine was also used for determination of the depth and size of collections such as seromas to facilitate drainage, for identification of lymph nodes before transfer, and for acute presentations of conditions ranging from undiagnosed swelling to foreign body localization. CONCLUSIONS: The portable ultrasound machine has become an invaluable tool in the senior author's practice. In a short time and with a short learning curve, the authors' unit identified numerous applications for its use. From a patient perspective, it is noninvasive/nonpainful and has no deleterious radiation effects, and treatment plans can be enacted without delay. It is highly recommended that surgeons become familiar with this imaging modality and assimilate it into their daily practice. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Use of key performance indicators in histological dissection.

AIMS: Reports into standards in the National Health Service and quality in pathology have focused on the way we work in pathology and how to provide assurance that this is of a high standard. There are a number of external quality assurance schemes covering pathology and histopathology specifically; however, there is no scheme covering the process of histological surgical dissection. This is an area undergoing development, emerging from the sole preserve of medically qualified pathologists to a field populated by a number of highly trained biomedical scientists, but remains without any formal quality assurance. METHODS: This work builds on Barnes, taking the guidance of the Royal College of Pathologists (RCPath)and Institute of Biomedical Science (IBMS)to form a series of key performance indicators relating to dissection. These were developed for use as an indicator of individual practice, highlighting areas of variation, weakness or strength. Once identified, a feedback event provided opportunities to address these errors and omissions, or to enable areas of strength to be shared. RESULTS: The data obtained from the checklists demonstrate a large variation in practice at the outset of this study. The use of the checklists alone served to reduce this variation in practice, the addition of the training event showed further reduction in variation. The combination of these two tools was an effective method for enhancing standardisation of practice. CONCLUSIONS: The results of this work show that training events serve to reduce variation in practice by, and between, dissectors, driving up standards in dissection-directly addressing the needs of the modern pathology service.

Optimal Alignment of Structures for Finite and Periodic Systems.

Finding the optimal alignment between two structures is important for identifying the minimum root-mean-square distance (RMSD) between them and as a starting point for calculating pathways. Most current algorithms for aligning structures are stochastic, scale exponentially with the size of structure, and the performance can be unreliable. We present two complementary methods for aligning structures corresponding to isolated clusters of atoms and to condensed matter described by a periodic cubic supercell. The first method (Go-PERMDIST), a branch and bound algorithm, locates the global minimum RMSD deterministically in polynomial time. The run time increases for larger RMSDs. The second method (FASTOVERLAP) is a heuristic algorithm that aligns structures by finding the global maximum kernel correlation between them using fast Fourier transforms (FFTs) and fast SO(3) transforms (SOFTs). For periodic systems, FASTOVERLAP scales with the square of the number of identical atoms in the system, reliably finds the best alignment between structures that are not too distant, and shows significantly better performance than existing algorithms. The expected run time for Go-PERMDIST is longer than FASTOVERLAP for periodic systems. For finite clusters, the FASTOVERLAP algorithm is competitive with existing algorithms. The expected run time for Go-PERMDIST to find the global RMSD between two structures deterministically is generally longer than for existing stochastic algorithms. However, with an earlier exit condition, Go-PERMDIST exhibits similar or better performance.

Indocyanine green-based fluorescent angiography in breast reconstruction.

BACKGROUND: Fluorescent angiography (FA) has been useful for assessing blood flow and assessing tissue perfusion in ophthalmology and other surgical disciplines for decades. In plastic surgery, indocyanine green (ICG) dye-based FA is a relatively novel imaging technology with high potential in various applications. We review the various FA detector systems currently available and critically appraise its utility in breast reconstruction. METHODS: A review of the published English literature dating from 1950 to 2015 using databases, such as PubMed, Medline, Web of Science, and EMBASE was undertaken. RESULTS: In comparison to the old fluorescein dye, ICG has a superior side effect profile and can be accurately detected by various commercial devices, such as SPY Elite (Novadaq, Canada), FLARE (Curadel LLC, USA), PDE-Neo (Hamamatsu Photonics, Japan), Fluobeam 800 (Fluoptics, France), and IC-View (Pulsion Medical Systems AG, Germany). In breast reconstruction, ICG has established as a safer, more accurate tracer agent, in lieu of the traditional blue dyes, for detection of sentinel lymph nodes with radioactive isotopes ((99m)-Technetium). In prosthesis-based breast reconstruction, intraoperative assessment of the mastectomy skin flap to guide excision of hypoperfused areas translates to improved clinical outcomes. Similarly, in autologous breast reconstructions, FA can be utilized to detect poorly perfused areas of the free flap, evaluate microvascular anastomosis for patency, and assess SIEA vascular territory for use as an alternative free flap with minimal donor site morbidity. CONCLUSIONS: ICG-based FA is a novel, useful tool for various applications in breast reconstruction. More studies with higher level of evidence are currently lacking to validate this technology.