A qualitative study of the development of a multidisciplinary case conference review methodology to reduce involved margins in pelvic exenteration surgery for recurrent rectal cancer

Aim Pelvic exenteration surgery remains the only curative option for recurrent rectal cancer. Microscopically involved surgical margins (R1) are associated with a higher risk of local recurrence and decreased survival. Our study aimed to develop a post hoc multidisciplinary case conference review and investigate its potential for identifying areas for improvement. Method Results Patients who underwent pelvic exenteration surgery for recurrent rectal cancer with R1 resections at a tertiary referral centre between April 2014 and January 2016 were retrospectively reviewed from a prospectively maintained database. Patients with non-rectal cancers or who underwent palliative surgery were excluded. Cases, imaging and histopathology were evaluated by a dedicated panel including colorectal surgeons, an abdominal radiologist and a gastrointestinal pathologist. R1 resections were reported in 32 of 110 pelvic exenterations. Patients with other tumours were excluded and one patient had a palliative resection. Nine male patients with 11 exenterations were included with a median age of 56 years. All patients had positive soft tissue margins, and one patient also had an involved bony margin. Failures were due to (interdisciplinary) communication problems, specific management of tumour biology (multifocality, spiculated tumours), which can lead to radiological undercalling, and inadequate surgical technical planning. In hindsight, surgery would have been withheld from one patient. Conclusion A retrospective multidisciplinary case evaluation of pelvic exenteration patients with involved surgical margins led to a list of recommendations which included the need to plan for wider surgical soft tissue resections and improvement in interdisciplinary communication. Lessons learned may increase clear margin rates in future resections

Electrochemical titrations and reaction time courses monitored in situ by magnetic circular dichroism spectroscopy

Magnetic circular dichroism (MCD) spectra, at ultraviolet–visible or near-infrared wavelengths (185–2000 nm), contain the same transitions observed in conventional absorbance spectroscopy, but their bisignate nature and more stringent selection rules provide greatly enhanced resolution. Thus, they have proved to be invaluable in the study of many transition metal-containing proteins. For mainly technical reasons, MCD has been limited almost exclusively to the measurement of static samples. But the ability to employ the resolving power of MCD to follow changes at transition metal sites would be a potentially significant advance. We describe here the development of a cuvette holder that allows reagent injection and sample mixing within the 50-mm-diameter ambient temperature bore of an energized superconducting solenoid. This has allowed us, for the first time, to monitor time-resolved MCD resulting from in situ chemical manipulation of a metalloprotein sample. Furthermore, we report the parallel development of an electrochemical cell using a three-electrode configuration with physically separated working and counter electrodes, allowing true potentiometric titration to be performed within the bore of the MCD solenoid

Shortness coefficient of cyclically 4-edge-connected cubic graphs

Grünbaum and Malkevitch proved that the shortness coefficient of cyclically 4-edge-connected cubic planar graphs is at most 76/77. Recently, this was improved to 359/366 (< 52/53) and the question was raised whether this can be strengthened to 41/42, a natural bound inferred from one of the Faulkner-Younger graphs. We prove that the shortness coefficient of cyclically 4-edge-connected cubic planar graphs is at most 37/38 and that we also get the same value for cyclically 4-edge-connected cubic graphs of genus g for any prescribed genus g ≥ 0. We also show that 45/46 is an upper bound for the shortness coefficient of cyclically 4-edge-connected cubic graphs of genus g with face lengths bounded above by some constant larger than 22 for any prescribed g ≥ 0

Adenomatoid tumors of the male and female genital tract are defined by TRAF7 mutations that drive aberrant NF-kB pathway activation.

Adenomatoid tumors are the most common neoplasm of the epididymis, and histologically similar adenomatoid tumors also commonly arise in the uterus and fallopian tube. To investigate the molecular pathogenesis of these tumors, we performed genomic profiling on a cohort of 31 adenomatoid tumors of the male and female genital tracts. We identified that all tumors harbored somatic missense mutations in the TRAF7 gene, which encodes an E3 ubiquitin ligase belonging to the family of tumor necrosis factor receptor-associated factors (TRAFs). These mutations all clustered into one of five recurrent hotspots within the WD40 repeat domains at the C-terminus of the protein. Functional studies in vitro revealed that expression of mutant but not wild-type TRAF7 led to increased phosphorylation of nuclear factor-kappa B (NF-kB) and increased expression of L1 cell adhesion molecule (L1CAM), a marker of NF-kB pathway activation. Immunohistochemistry demonstrated robust L1CAM expression in adenomatoid tumors that was absent in normal mesothelial cells, malignant peritoneal mesotheliomas and multilocular peritoneal inclusion cysts. Together, these studies demonstrate that adenomatoid tumors of the male and female genital tract are genetically defined by TRAF7 mutation that drives aberrant NF-kB pathway activation

Outer-Sphere Contributions to the Electronic Structure of Type Zero Copper Proteins

Bioinorganic canon states that active-site thiolate coordination promotes rapid electron transfer (ET) to and from type 1 copper proteins. In recent work, we have found that copper ET sites in proteins also can be constructed without thiolate ligation (called “type zero” sites). Here we report multifrequency electron paramagnetic resonance (EPR), magnetic circular dichroism (MCD), and nuclear magnetic resonance (NMR) spectroscopic data together with density functional theory (DFT) and spectroscopy-oriented configuration interaction (SORCI) calculations for type zero Pseudomonas aeruginosa azurin variants. Wild-type (type 1) and type zero copper centers experience virtually identical ligand fields. Moreover, O-donor covalency is enhanced in type zero centers relative that in the C112D (type 2) protein. At the same time, N-donor covalency is reduced in a similar fashion to type 1 centers. QM/MM and SORCI calculations show that the electronic structures of type zero and type 2 are intimately linked to the orientation and coordination mode of the carboxylate ligand, which in turn is influenced by outer-sphere hydrogen bonding

Non-Gaussian Distributions in Extended Dynamical Systems

We propose a novel mechanism for the origin of non-Gaussian tails in the probability distribution functions (PDFs) of local variables in nonlinear, diffusive, dynamical systems including passive scalars advected by chaotic velocity fields. Intermittent fluctuations on appropriate time scales in the amplitude of the (chaotic) noise can lead to exponential tails. We provide numerical evidence for such behavior in deterministic, discrete-time passive scalar models. Different possibilities for PDFs are also outlined.Comment: 12 pages and 6 figs obtainable from the authors, LaTex file, OSU-preprint-

Evidence for Quantum Interference in SAMs of Arylethynylene Thiolates in Tunneling Junctions with Eutectic Ga-In (EGaIn) Top-Contacts

This paper compares the current density (J) versus applied bias (V) of self-assembled monolayers (SAMs) of three different ethynylthiophenol-functionalized anthracene derivatives of approximately the same thickness with linear-conjugation (AC), cross-conjugation (AQ), and broken-conjugation (AH) using liquid eutectic Ga-In (EGaIn) supporting a native skin (~1 nm thick) of Ga2O3 as a nondamaging, conformal top-contact. This skin imparts non-Newtonian rheological properties that distinguish EGaIn from other top-contacts; however, it may also have limited the maximum values of J observed for AC. The measured values of J for AH and AQ are not significantly different (J ≈ 10-1 A/cm2 at V = 0.4 V). For AC, however, J is 1 (using log averages) or 2 (using Gaussian fits) orders of magnitude higher than for AH and AQ. These values are in good qualitative agreement with gDFTB calculations on single AC, AQ, and AH molecules chemisorbed between Au contacts that predict currents, I, that are 2 orders of magnitude higher for AC than for AH at 0 < |V| < 0.4 V. The calculations predict a higher value of I for AQ than for AH; however, the magnitude is highly dependent on the position of the Fermi energy, which cannot be calculated precisely. In this sense, the theoretical predictions and experimental conclusions agree that linearly conjugated AC is significantly more conductive than either cross-conjugated AQ or broken conjugate AH and that AQ and AH cannot necessarily be easily differentiated from each other. These observations are ascribed to quantum interference effects. The agreement between the theoretical predictions on single molecules and the measurements on SAMs suggest that molecule-molecule interactions do not play a significant role in the transport properties of AC, AQ, and AH.

BR1202-0725: An Extreme Multiple Merger at z = 4.7

The radio-quiet quasar BR1202-0725 (z=4.695) is a remarkable source with a bright Northwest (NW) companion detected at submm and radio wavelengths but invisible in the optical. In the absence of amplification by gravitational lensing, BR1202-0725 would be the most luminous binary CO and FIR source in the Universe. In this paper, we report observations with the IRAM Plateau de Bure interferometer of BR1202-0725 in the redshifted emission of the CO(5-4) and (7-6) lines, the [C I](3P2-3P1) line, a high angular resolution (0.3 x 0.8 arcsec) 1.3 mm map of the rest-frame, far-IR dust continuum, and a search for the CO(11-10) line. We compare these results with recent ALMA data in the [C II] line. Both the quasar host galaxy and its NW companion are spatially resolved in the molecular line emission and the dust continuum. The CO profile of the NW companion is very broad with a full width at half maximum of 1000 +/- 130 km/s, compared to 360 +/- 40 km/s for the quasar host galaxy to the Southeast (SE). The difference in linewidths and center velocities, and the absence of any lens candidate or arc-like structure in the field, at any wavelength, show that the obscured NW galaxy and the SE quasar host galaxy cannot be lensed images of the same object. Instead, we find morphological and kinematic evidence for sub-structures in both the NW and SE sources. We interpret these results as strong indications that the BR1202-0725 complex is a group of young, interacting, and highly active starburst galaxies.Comment: Minor changes to agree with published versio

Dialectic tensions in the financial markets: a longitudinal study of pre- and post-crisis regulatory technology

This article presents the findings from a longitudinal research study on regulatory technology in the UK financial services industry. The financial crisis with serious corporate and mutual fund scandals raised the profile of compliance as governmental bodies, institutional and private investors introduced a ‘tsunami’ of financial regulations. Adopting a multi-level analysis, this study examines how regulatory technology was used by financial firms to meet their compliance obligations, pre- and post-crisis. Empirical data collected over 12 years examine the deployment of an investment management system in eight financial firms. Interviews with public regulatory bodies, financial institutions and technology providers reveal a culture of compliance with increased transparency, surveillance and accountability. Findings show that dialectic tensions arise as the pursuit of transparency, surveillance and accountability in compliance mandates is simultaneously rationalized, facilitated and obscured by regulatory technology. Responding to these challenges, regulatory bodies continue to impose revised compliance mandates on financial firms to force them to adapt their financial technologies in an ever-changing multi-jurisdictional regulatory landscape