Laparoscopic vs open surgery during the COVID-19 pandemic: what are the risks?

INTRODUCTION: The initial intercollegiate surgical guidance from the UK during the COVID-19 pandemic resulted in significant changes to practice. Avoidance of laparoscopy was recommended, to reduce aerosol generation and risk of virus transmission. Evidence on the safety profile of laparoscopy during the pandemic is lacking. This study compares patient outcomes and risk to staff from laparoscopic and open gastrointestinal operations during the COVID-19 pandemic. METHODS: Single-centre retrospective study of gastrointestinal operations performed during the peak of the COVID-19 pandemic. Demographic, comorbidity, perioperative and survival data were collected from electronic medical records and supplemented with patient symptoms reported at telephone follow up. Outcomes assessed were: patient mortality, illness among staff, patient COVID-19 rates, length of hospital stay and postdischarge symptomatology. RESULTS: A total of 73 patients with median age of 56 years were included; 55 (75%) and 18 (25%) underwent laparoscopic and open surgery, respectively. All-cause mortality was 5% (4/73), was related to COVID-19 in all cases, with no mortality after laparoscopic surgery. A total of 14 staff members developed COVID-19 symptoms within 2 weeks, with no significant difference between laparoscopic and open surgery (10 vs 4; p=0.331). Median length of stay was shorter in the laparoscopic versus the open group (4.5 vs 9.9 days; p=0.011), and postdischarge symptomatology across 15 symptoms was similar between groups (p=0.135-0.814). CONCLUSIONS: With appropriate protective measures, laparoscopic surgery is safe for patients and staff during the COVID-19 pandemic. The laparoscopic approach maintains an advantage of shorter length of hospital stay compared with open surgery.

Radiographic characterisation of spinal curvature development in farmed New Zealand Chinook salmon Oncorhynchus tshawytscha throughout seawater production.

Spinal anomalies are a recognised source of downgrading in finfish aquaculture, but identifying their cause(s) is difficult and often requires extensive knowledge of the underlying pathology. Late-onset spinal curvatures (lordosis, kyphosis, scoliosis) can affect up to 40% of farmed New Zealand Chinook (king) salmon (Oncorhynchus tshawytscha) at harvest, but little is known about their pathogenesis. Curvature development was radiographically documented in two related cohorts of commercially-farmed Chinook salmon throughout seawater production to determine (1) the timing of radiographic onset and relationships between (2) the curvature types, (3) the spinal regions in which they develop and (4) their associations with co-existing vertebral body anomalies (vertebral compression, fusion and vertical shift). Onset of curvature varied between individuals, but initially occurred eight months post-seawater transfer. There were strong associations between the three curvature types and the four recognised spinal regions: lordosis was predominantly observed in regions (R)1 and R3, kyphosis in R2 and R4, manifesting as a distinct pattern of alternating lordosis and kyphosis from head to tail. This was subsequently accompanied by scoliosis, which primarily manifested in spinal regions R2 and R3, where most of the anaerobic musculature is concentrated. Co-existing vertebral body anomalies, of which vertebral compression and vertical shift were most common, appeared to arise either independent of curvature development or as secondary effects. Our results suggest that spinal curvature in farmed New Zealand Chinook salmon constitutes a late-onset, rapidly-developing lordosis-kyphosis-scoliosis (LKS) curvature complex with a possible neuromuscular origin.

Efficient non-Markovian quantum dynamics using time-evolving matrix product operators.

In order to model realistic quantum devices it is necessary to simulate quantum systems strongly coupled to their environment. To date, most understanding of open quantum systems is restricted either to weak system-bath couplings or to special cases where specific numerical techniques become effective. Here we present a general and yet exact numerical approach that efficiently describes the time evolution of a quantum system coupled to a non-Markovian harmonic environment. Our method relies on expressing the system state and its propagator as a matrix product state and operator, respectively, and using a singular value decomposition to compress the description of the state as time evolves. We demonstrate the power and flexibility of our approach by numerically identifying the localisation transition of the Ohmic spin-boson model, and considering a model with widely separated environmental timescales arising for a pair of spins embedded in a common environment.

Antagonistic Interactions and Biofilm Forming Capabilities Among Bacterial Strains Isolated from the Egg Surfaces of Lake Sturgeon (Acipenser fulvescens).

Characterization of interactions within a host-associated microbiome can help elucidate the mechanisms of microbial community formation on hosts and can be used to identify potential probiotics that protect hosts from pathogens. Microbes employ various modes of antagonism when interacting with other members of the community. The formation of biofilm by some strains can be a defense against antimicrobial compounds produced by other taxa. We characterized the magnitude of antagonistic interactions and biofilm formation of 25 phylogenetically diverse taxa that are representative of isolates obtained from egg surfaces of the threatened fish species lake sturgeon (Acipenser fulvescens) at two ecologically relevant temperature regimes. Eight isolates exhibited aggression to at least one other isolate. Pseudomonas sp. C22 was found to be the most aggressive strain, while Flavobacterium spp. were found to be one of the least aggressive and the most susceptible genera. Temperature affected the prevalence and intensity of antagonism. The aggressive strains identified also inhibited growth of known fish pathogens. Biofilm formations were observed for nine isolates and were dependent on temperature and growth medium. The most aggressive of the isolates disrupted biofilm formation of two well-characterized isolates but enhanced biofilm formation of a fish pathogen. Our results revealed the complex nature of interactions among members of an egg associated microbial community yet underscored the potential of specific microbial populations as host probiotics.

Genetically Engineering Entomopathogenic Fungi.

Entomopathogenic fungi have been developed as environmentally friendly alternatives to chemical insecticides in biocontrol programs for agricultural pests and vectors of disease. However, mycoinsecticides currently have a small market share due to low virulence and inconsistencies in their performance. Genetic engineering has made it possible to significantly improve the virulence of fungi and their tolerance to adverse conditions. Virulence enhancement has been achieved by engineering fungi to express insect proteins and insecticidal proteins/peptides from insect predators and other insect pathogens, or by overexpressing the pathogen's own genes. Importantly, protein engineering can be used to mix and match functional domains from diverse genes sourced from entomopathogenic fungi and other organisms, producing insecticidal proteins with novel characteristics. Fungal tolerance to abiotic stresses, especially UV radiation, has been greatly improved by introducing into entomopathogens a photoreactivation system from an archaean and pigment synthesis pathways from nonentomopathogenic fungi. Conversely, gene knockout strategies have produced strains with reduced ecological fitness as recipients for genetic engineering to improve virulence; the resulting strains are hypervirulent, but will not persist in the environment. Coupled with their natural insect specificity, safety concerns can also be mitigated by using safe effector proteins with selection marker genes removed after transformation. With the increasing public concern over the continued use of synthetic chemical insecticides and growing public acceptance of genetically modified organisms, new types of biological insecticides produced by genetic engineering offer a range of environmentally friendly options for cost-effective control of insect pests.

Superabsorption of light via quantum engineering.

Almost 60 years ago Dicke introduced the term superradiance to describe a signature quantum effect: N atoms can collectively emit light at a rate proportional to N(2). Structures that superradiate must also have enhanced absorption, but the former always dominates in natural systems. Here we show that this restriction can be overcome by combining several well-established quantum control techniques. Our analytical and numerical calculations show that superabsorption can then be achieved and sustained in certain simple nanostructures, by trapping the system in a highly excited state through transition rate engineering. This opens the prospect of a new class of quantum nanotechnology with potential applications including photon detection and light-based power transmission. An array of quantum dots or a molecular ring structure could provide a suitable platform for an experimental demonstration.

DEER-Stitch: combining three- and four-pulse DEER measurements for high sensitivity, deadtime free data.

Over approximately the last 15 years the electron paramagnetic resonance (EPR) technique of double electron electron resonance (DEER) has attracted considerable attention since it allows for the precise measurement of the dipole-dipole coupling between radicals and thus can lead to distance information between pairs of radicals separated by up to ca. 8 nm. The "deadtime free" 4-pulse DEER sequence is widely used but can suffer from poor sensitivity if the electron spin-echo decays too quickly to allow collection of a sufficiently long time trace. In this paper we present a method which takes advantage of the much greater sensitivity that the 3-pulse sequence offers over the 4-pulse sequence since the measured electron spin-echo intensity (for equal sequence lengths) is greater. By combining 3- and 4-pulse DEER time traces using a method coined DEER-Stitch (DEERS) accurate dipole-dipole coupling measurements can be made which combine the sensitivity of the 3-pulse DEER sequence with the deadtime free advantage of the 4-pulse DEER sequence. To develop the DEER-Stitch method three systems were measured: a semi-rigid bis-nitroxide labeled nanowire, the bis-nitroxide labeled protein CD55 with a distance between labels of almost 8 nm and a dimeric copper amine oxidase from Arthrobacter globiformis (AGAO).

Entangling remote nuclear spins linked by a chromophore.

Molecular nanostructures may constitute the fabric of future quantum technologies, if their degrees of freedom can be fully harnessed. Ideally one might use nuclear spins as low-decoherence qubits and optical excitations for fast controllable interactions. Here, we present a method for entangling two nuclear spins through their mutual coupling to a transient optically excited electron spin, and investigate its feasibility through density-functional theory and experiments on a test molecule. From our calculations we identify the specific molecular properties that permit high entangling power gates under simple optical and microwave pulses; synthesis of such molecules is possible with established techniques.

Damping of exciton Rabi rotations by acoustic phonons in optically excited InGaAs/GaAs quantum dots.

We report experimental evidence identifying acoustic phonons as the principal source of the excitation-induced-dephasing (EID) responsible for the intensity damping of quantum dot excitonic Rabi rotations. The rate of EID is extracted from temperature dependent Rabi rotation measurements of the ground-state excitonic transition, and is found to be in close quantitative agreement with an acoustic-phonon model.

Phonon-induced Rabi-frequency renormalization of optically driven single InGaAs/GaAs quantum dots.

We study optically driven Rabi rotations of a quantum dot exciton transition between 5 and 50 K, and for pulse areas of up to 14π. In a high driving field regime, the decay of the Rabi rotations is nonmonotonic, and the period decreases with pulse area and increases with temperature. By comparing the experiments to a weak-coupling model of the exciton-phonon interaction, we demonstrate that the observed renormalization of the Rabi frequency is induced by fluctuations in the bath of longitudinal acoustic phonons, an effect that is a phonon analogy of the Lamb shift.

Spin lifetimes in quantum dots from noise measurements.

We present a method of obtaining information about spin lifetimes in quantum dots from measurements of electrical transport. The dot is under resonant microwave irradiation and at temperatures comparable to or larger than the Zeeman energy. We find that the ratio of the spin coherence times T_{1}/T_{2} can be deduced from a measurement of current through the quantum dot as a function the applied magnetic field. We calculate the noise power spectrum of the dot current and show that a dip occurs at the Rabi frequency with a linewidth given by 1/T_{1}+1/T_{2}.

Selective spin coupling through a single exciton.

We present a novel scheme for performing a conditional phase gate between two spin qubits in adjacent semiconductor quantum dots through delocalized single exciton states, formed through the interdot Förster interaction. We consider two resonant quantum dots, each containing a single excess conduction band electron whose spin embodies the qubit. We demonstrate that both the two-qubit gate and arbitrary single-qubit rotations may be realized to a high fidelity with current semiconductor and laser technology.

Nanoscale solid-state quantum computing.

Most experts agree that it is too early to say how quantum computers will eventually be built, and several nanoscale solid-state schemes are being implemented in a range of materials. Nanofabricated quantum dots can be made in designer configurations, with established technology for controlling interactions and for reading out results. Epitaxial quantum dots can be grown in vertical arrays in semiconductors, and ultrafast optical techniques are available for controlling and measuring their excitations. Single-walled carbon nanotubes can be used for molecular self-assembly of endohedral fullerenes, which can embody quantum information in the electron spin. The challenges of individual addressing in such tiny structures could rapidly become intractable with increasing numbers of qubits, but these schemes are amenable to global addressing methods for computation.

Near-precise interchromosomal recombination and functional DNA topoisomerase II cleavage sites at MLL and AF-4 genomic breakpoints in treatment-related acute lymphoblastic leukemia with t(4;11) translocation.

We analyzed the der(11) and der(4) genomic breakpoint junctions of a t(4;11) in the leukemia of a patient previously administered etoposide and dactinomycin by molecular and biochemical approaches to gain insights about the translocation mechanism and the relevant drug exposure. The genomic breakpoint junctions were amplified by PCR. Cleavage of DNA substrates containing the normal homologues of the MLL and AF-4 translocation breakpoints was examined in vitro upon incubation with human DNA topoisomerase IIalpha and etoposide, etoposide catechol, etoposide quinone, or dactinomycin. The der(11) and der(4) genomic breakpoint junctions both involved MLL intron 6 and AF-4 intron 3. Recombination was precise at the sequence level except for the overall gain of a single templated nucleotide. The translocation breakpoints in MLL and AF-4 were DNA topoisomerase II cleavage sites. Etoposide and its metabolites, but not dactinomycin, enhanced cleavage at these sites. Assuming that DNA topoisomerase II was the mediator of the breakage, processing of the staggered nicks induced by DNA topoisomerase II, including exonucleolytic deletion and template-directed polymerization, would have been required before ligation of the ends to generate the observed genomic breakpoint junctions. These data are inconsistent with a translocation mechanism involving interchromosomal recombination by simple exchange of DNA topoisomerase II subunits and DNA-strand transfer; however, consistent with reciprocal DNA topoisomerase II cleavage events in MLL and AF-4 in which both breaks became stable, the DNA ends were processed and underwent ligation. Etoposide and/or its metabolites, but not dactinomycin, likely were the relevant exposures in this patient.

Etoposide metabolites enhance DNA topoisomerase II cleavage near leukemia-associated MLL translocation breakpoints.

Chromosomal breakage resulting from stabilization of DNA topoisomerase II covalent complexes by epipodophyllotoxins may play a role in the genesis of leukemia-associated MLL gene translocations. We investigated whether etoposide catechol and quinone metabolites can damage the MLL breakpoint cluster region in a DNA topoisomerase II-dependent manner like the parent drug and the nature of the damage. Cleavage of two DNA substrates containing the normal homologues of five MLL intron 6 translocation breakpoints was examined in vitro upon incubation with human DNA topoisomerase IIalpha, ATP, and either etoposide, etoposide catechol, or etoposide quinone. Many of the same cleavage sites were induced by etoposide and by its metabolites, but several unique sites were induced by the metabolites. There was a preference for G(-1) among the unique sites, which differs from the parent drug. Cleavage at most sites was greater and more heat-stable in the presence of the metabolites compared to etoposide. The MLL translocation breakpoints contained within the substrates were near strong and/or stable cleavage sites. The metabolites induced more cleavage than etoposide at the same sites within a 40 bp double-stranded oligonucleotide containing two of the translocation breakpoints, confirming the results at a subset of the sites. Cleavage assays using the same oligonucleotide substrate in which guanines at several positions were replaced with N7-deaza guanines indicated that the N7 position of guanine is important in metabolite-induced cleavage, possibly suggesting N7-guanine alkylation by etoposide quinone. Not only etoposide, but also its metabolites, enhance DNA topoisomerase II cleavage near MLL translocation breakpoints in in vitro assays. It is possible that etoposide metabolites may be relevant to translocations.

Emergency surgery: half a day does make a difference.

The emergency operating patterns in a district general hospital were significantly altered by the introduction of an afternoon emergency theatre list co-ordinated by a consultant anaesthetist. Before the introduction of the list, 88% of emergency operations were carried out after 17.00, with 40% of cases waiting until after 22.00. Introduction of the emergency session significantly reduced the operations performed after 17.00 to 53%, with only 12% being delayed until after 22.00.