Electrocautery, diathermy, and surgical energy devices: are surgical teams at risk during the COVID-19 pandemic?

OBJECTIVE: The aim of the study was to provide a rapid synthesis of available data to identify the risk posed by utilizing surgical energy devices intraoperatively due to the generation of surgical smoke, an aerosol. Secondarily it aims to summarize methods to minimize potential risk to operating room staff. SUMMARY BACKGROUND DATA: Continuing operative practice during the coronavirus disease-19 (COVID-19) pandemic places the health of operating theatre staff at potential risk. SARS-CoV2 is transmitted through inhaled droplets and aerosol particles, thus posing an inhalation threat even at considerable distance. Surgical energy devices generate an aerosol of biological particular matter during use. The risk to healthcare staff through use of surgical energy devices is unknown. METHODS: This review was conducted utilizing a rapid review methodology to enable efficient generation and dissemination of information useful for concurrent clinical practice. RESULTS: There are conflicting stances on the use of energy devices and laparoscopy by different surgical governing bodies and societies. There is no definitive evidence that aerosol generated by energy devices may carry active SARS-CoV2 virus. However, investigations of other viruses have demonstrated aerosolization through energy devise use. Measures to reduce potential transmission include appropriate personal protective equipment, evacuation and filtration of surgical plume, limiting energy device use if appropriate, and adjusting endoscopic and laparoscopic practice (low CO2 pressures, evacuation through ultrafiltration systems). CONCLUSIONS: The risk of transmission of SARS-CoV2 through aerosolized surgical smoke associated with energy device use is not fully understood, however transmission is biologically plausible. Caution and appropriate measures to reduce risk to healthcare staff should be implemented when considering intraoperative use of energy devices

Accumulation of copy number alterations and clinical progression across advanced prostate cancer.

BACKGROUND: Genomic copy number alterations commonly occur in prostate cancer and are one measure of genomic instability. The clinical implication of copy number change in advanced prostate cancer, which defines a wide spectrum of disease from high-risk localised to metastatic, is unknown. METHODS: We performed copy number profiling on 688 tumour regions from 300 patients, who presented with advanced prostate cancer prior to the start of long-term androgen deprivation therapy (ADT), in the control arm of the prospective randomised STAMPEDE trial. Patients were categorised into metastatic states as follows; high-risk non-metastatic with or without local lymph node involvement, or metastatic low/high volume. We followed up patients for a median of 7 years. Univariable and multivariable Cox survival models were fitted to estimate the association between the burden of copy number alteration as a continuous variable and the hazard of death or disease progression. RESULTS: The burden of copy number alterations positively associated with radiologically evident distant metastases at diagnosis (P=0.00006) and showed a non-linear relationship with clinical outcome on univariable and multivariable analysis, characterised by a sharp increase in the relative risk of progression (P=0.003) and death (P=0.045) for each unit increase, stabilising into more modest increases with higher copy number burdens. This association between copy number burden and outcome was similar in each metastatic state. Copy number loss occurred significantly more frequently than gain at the lowest copy number burden quartile (q=4.1 × 10-6). Loss of segments in chromosome 5q21-22 and gains at 8q21-24, respectively including CHD1 and cMYC occurred more frequently in cases with higher copy number alteration (for either region: Kolmogorov-Smirnov distance, 0.5; adjusted P<0.0001). Copy number alterations showed variability across tumour regions in the same prostate. This variance associated with increased risk of distant metastases (Kruskal-Wallis test P=0.037). CONCLUSIONS: Copy number alteration in advanced prostate cancer associates with increased risk of metastases at diagnosis. Accumulation of a limited number of copy number alterations associates with most of the increased risk of disease progression and death. The increased likelihood of involvement of specific segments in high copy number alteration burden cancers may suggest an order underlying the accumulation of copy number changes. TRIAL REGISTRATION: ClinicalTrials.gov NCT00268476 , registered on December 22, 2005. EudraCT  2004-000193-31 , registered on October 4, 2004

Quantum superposition of a single microwave photon in two different "colour" states

The ability to coherently couple arbitrary harmonic oscillators in a fully-controlled way is an important tool to process quantum information. Coupling between quantum harmonic oscillators has previously been demonstrated in several physical systems by use of a two-level system as a mediating element. Direct interaction at the quantum level has only recently been realized by use of resonant coupling between trapped ions. Here we implement a tunable direct coupling between the microwave harmonics of a superconducting resonator by use of parametric frequency conversion. We accomplish this by coupling the mode currents of two harmonics through a superconducting quantum interference device (SQUID) and modulating its flux at the difference (~ 7 GHz) of the harmonic frequencies. We deterministically prepare a single-photon Fock state and coherently manipulate it between multiple modes, effectively controlling it in a superposition of two different "colours". This parametric interaction can be described as a beam-splitter-like operation that couples different frequency modes. As such, it could be used to implement linear optical quantum computing protocols on-chip.Comment: 21 pages, 10 figure

Accumulation of copy number alterations and clinical progression across advanced prostate cancer

Background: Genomic copy number alterations commonly occur in prostate cancer and are one measure of genomic instability. The clinical implication of copy number change in advanced prostate cancer, which defines a wide spectrum of disease from high-risk localised to metastatic, is unknown. Methods: We performed copy number profiling on 688 tumour regions from 300 patients, who presented with advanced prostate cancer prior to the start of long-term androgen deprivation therapy (ADT), in the control arm of the prospective randomised STAMPEDE trial. Patients were categorised into metastatic states as follows; high-risk non-metastatic with or without local lymph node involvement, or metastatic low/high volume. We followed up patients for a median of 7 years. Univariable and multivariable Cox survival models were fitted to estimate the association between the burden of copy number alteration as a continuous variable and the hazard of death or disease progression. Results: The burden of copy number alterations positively associated with radiologically evident distant metastases at diagnosis (P=0.00006) and showed a non-linear relationship with clinical outcome on univariable and multivariable analysis, characterised by a sharp increase in the relative risk of progression (P=0.003) and death (P=0.045) for each unit increase, stabilising into more modest increases with higher copy number burdens. This association between copy number burden and outcome was similar in each metastatic state. Copy number loss occurred significantly more frequently than gain at the lowest copy number burden quartile (q=4.1 × 10−6). Loss of segments in chromosome 5q21-22 and gains at 8q21-24, respectively including CHD1 and cMYC occurred more frequently in cases with higher copy number alteration (for either region: Kolmogorov–Smirnov distance, 0.5; adjusted P<0.0001). Copy number alterations showed variability across tumour regions in the same prostate. This variance associated with increased risk of distant metastases (Kruskal-Wallis test P=0.037). Conclusions: Copy number alteration in advanced prostate cancer associates with increased risk of metastases at diagnosis. Accumulation of a limited number of copy number alterations associates with most of the increased risk of disease progression and death. The increased likelihood of involvement of specific segments in high copy number alteration burden cancers may suggest an order underlying the accumulation of copy number changes

PIM1 kinase regulates cell death, tumor growth and chemotherapy response in triple-negative breast cancer

Triple-negative breast cancers (TNBCs) have poor prognosis and lack targeted therapies. Here we identified increased copy number and expression of the PIM1 proto-oncogene in genomic data sets of patients with TNBC. TNBC cells, but not nonmalignant mammary epithelial cells, were dependent on PIM1 for proliferation and protection from apoptosis. PIM1 knockdown reduced expression of the anti-apoptotic factor BCL2, and dynamic BH3 profiling of apoptotic priming revealed that PIM1 prevents mitochondrial-mediated apoptosis in TNBC cell lines. In TNBC tumors and their cellular models, PIM1 expression was associated with several transcriptional signatures involving the transcription factor MYC, and PIM1 depletion in TNBC cell lines decreased, in a MYC-dependent manner, cell population growth and expression of the MYC target gene MCL1. Treatment with the pan–PIM kinase inhibitor AZD1208 impaired the growth of both cell line and patient-derived xenografts and sensitized them to standard-of-care chemotherapy. This work identifies PIM1 as a malignant-cell-selective target in TNBC and the potential use of PIM1 inhibitors for sensitizing TNBC to chemotherapy-induced apoptotic cell death

Polarization of brown algal zygotes

Brown algae are a group of multicellular, heterokont algae that have convergently evolved developmental complexity that rivals that of embryophytes, animals or fungi. Early in development, brown algal zygotes establish a basal and an apical pole, which will become respectively the basal system (holdfast) and the apical system (thallus) of the adult alga. Brown algae are interesting models for understanding the establishment of cell polarity in a broad evolutionary context, because they exhibit a large diversity of life cycles, reproductive strategies and, importantly, their zygotes are produced in large quantities free of parental tissue, with symmetry breaking and asymmetric division taking place in a highly synchronous manner. This review describes the current knowledge about the establishment of the apical-basal axis in the model brown seaweeds Ectocarpus, Dictyota, Fucus and Saccharina, highlighting the advantages and specific interests of each system. Ectocarpus is a genetic model system that allows access to the molecular basis of early development and life-cycle control over apical-basal polarity. The oogamous brown alga Fucus, together with emerging comparative models Dictyota and Saccharina, emphasize the diversity of strategies of symmetry breaking in determining a cell polarity vector in brown algae. A comparison with symmetry-breaking mechanisms in land plants, animals and fungi, reveals that the one-step zygote polarisation of Fucus compares well to Saccharomyces budding and Arabidopsis stomata development, while the two-phased symmetry breaking in the Dictyota zygote compares to Schizosaccharomyces fission, the Caenorhabditis anterior-posterior zygote polarisation and Arabidopsis prolate pollen polarisation. The apical-basal patterning in Saccharina zygotes on the other hand, may be seen as analogous to that of land plants. Overall, brown algae have the potential to bring exciting new information on how a single cell gives rise to an entire complex body plan

SARS-CoV-2 and obesity: "CoVesity"-a pandemic within a pandemic

Individuals who are overweight or suffering from obesity are in a chronic state of low-grade inflammation, making them particularly susceptible to developing severe forms of respiratory failure. Studies conducted in past pandemics link obesity with worse health outcomes. This population is thus of particular concern within the context of the COVID-19 pandemic, considering the cessation of obesity management services. This systematic review highlights [1] the reciprocal link between the obesity and COVID-19 pandemics, [2] obesity as a risk factor for more severe disease in past pandemics, [3] potential mechanisms that make individual’s suffering from obesity more susceptible to severe disease and higher viral load, and [4] the need to safely resume bariatric services as recommended by expert guidelines, in order to mitigate the health outcomes of an already vulnerable population

Clinical nutrition and human rights. An international position paper

The International Working Group for Patients' Right to Nutritional Care presents its position paper regarding nutritional care as a human right intrinsically linked to the right to food and the right to health. All people should have access to food and evidence-based medical nutrition therapy including artificial nutrition and hydration. In this regard, the hospitalized malnourished ill should mandatorily have access to screening, diagnosis, nutritional assessment, with optimal and timely nutritional therapy in order to overcome malnutrition associated morbidity and mortality, while reducing the rates of disease-related malnutrition. This right does not imply there is an obligation to feed all patients at any stage of life and at any cost. On the contrary, this right implies, from an ethical point of view, that the best decision for the patient must be taken and this may include, under certain circumstances, the decision not to feed. Application of the human rights-based approach to the field of clinical nutrition will contribute to the construction of a moral, political and legal focus to the concept of nutritional care. Moreover, it will be the cornerstone to the rationale of political and legal instruments in the field of clinical nutrition