Why non-technical skills matter in surgery. New paradigms for surgical leaders

The surgical literature is paying more and more attention to the topic of soft or non-technical skills (NTS), defined as those cognitive and social skills that characterize high-performing individuals and teams. NTS are essential in supporting surgeons in dealing with unexpected situations. During the COVID-19 pandemic, NTS have been considered crucial in defining situation awareness, enhancing decision making, communicating among groups and teams, and fostering leadership. With a “looking back and planning forward” approach, the current perspective aims at deepening the contribution of NTS for surgeons to deal with the unexpected challenges posed by the COVID crisis, surgical emergencies, the introduction of new technologies in clinical practice, to understand how such skills may help shape the surgical leaders of the future

Carbon/graphite fiber risk analysis and assessment study: An assessment of the risk to Douglas commercial transport aircraft

The potential hazard to electrical and electronic devices should there be a release of free carbon fibers due to an aircraft crash and fire was assessed. Exposure and equipment sensitivity data were compiled for a risk analysis. Results are presented in the following areas: DC-9/DC-10 electrical/electronic component characterization; DC-9 and DC-10 fiber transfer functions; potential for transport aircraft equipment exposure to carbon fibers; and equipment vulnerability assessment. Results reflect only a negligible increase in risk for the DC-9 and DC-10 fleets either now or projected to 1993

Upstaging nodal status in colorectal cancer using ex vivo fluorescence sentinel lymph node mapping: preliminary results

Background: Sentinel lymph node (SLN) mapping using near-infrared fluorescence (NIRF) imaging is a recent technique to improve nodal staging in several tumors. The presence of colorectal cancer (CRC) micro-metastases has recently been defined as N1 disease and no longer as N1mi, determining the need for adjuvant chemotherapy. In CRC, the reported rate of SLN micro-metastases detected by ultrastaging techniques is as high as 30%. The aim of this prospective study is to report the preliminary results of the sensitivity analysis of NIRF imaging for ex vivo SLN mapping and the research of micro-metastases in CRC, in patients with node-negative disease (NND). Material and methods: On the specimen of 22 CRC patients, 1 mL of ICG (5 mg/mL) was injected submucosally around the tumor to identify SLNs. NND SLNs were further investigated with ultrastaging techniques. Results: Three-hundred and sixty-three lymph nodes were retrieved (59 SLNs; mean per case: 2.7). The detection, sensitivity and false-negative rate were 100%, 100% and 0% respectively. Ultrastaging investigations showed no micro-metastases in the NND SLNs. Conclusions: The ex vivo SLN fluorescence-based detection in CRC was confirmed to be easy to perform and reliable. In this preliminary results report of an ongoing study, the SLN assay was congruent with the nodal status, as confirmed by histological investigations

Identification and recovery of minor HIV-1 variants using the heteroduplex tracking assay and biotinylated probes

We describe a method to identify and recover minor human immunodeficiency virus type 1 (HIV-1) sequence variants from a complex population. The original heteroduplex tracking assay (HTA) was modified by incorporating a biotin tag into the probe to allow for direct sequence determination of the query strand. We used this approach to recover sequences from minor HIV-1 variants in the V3 region of the env gene, and to identify minor drug-resistant variants in pro. The biotin-HTA targeting of the V3 region of env allowed us to detect minor V3 variants, of which 45% were classified as CXCR4-using viruses. In addition, the biotin-protease HTA was able to detect mixtures of wild-type sequence and drug-resistance mutations in four subjects that were not detected by bulk sequence analysis. The biotin-HTA is a robust assay that first separates genetic variants then allows direct sequence analysis of major and minor variants

Permissivity of Dipeptidyl Peptidase 4 Orthologs to Middle East Respiratory Syndrome Coronavirus Is Governed by Glycosylation and Other Complex Determinants

ABSTRACT Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes dipeptidyl peptidase 4 (DPP4) as an entry receptor. While bat, camel, and human DPP4 support MERS-CoV infection, several DPP4 orthologs, including mouse, ferret, hamster, and guinea pig DPP4, do not. Previous work revealed that glycosylation of mouse DPP4 plays a role in blocking MERS-CoV infection. Here, we tested whether glycosylation also acts as a determinant of permissivity for ferret, hamster, and guinea pig DPP4. We found that, while glycosylation plays an important role in these orthologs, additional sequence and structural determinants impact their ability to act as functional receptors for MERS-CoV. These results provide insight into DPP4 species-specific differences impacting MERS-CoV host range and better inform our understanding of virus-receptor interactions associated with disease emergence and host susceptibility. IMPORTANCE MERS-CoV is a recently emerged zoonotic virus that is still circulating in the human population with an ∼35% mortality rate. With no available vaccines or therapeutics, the study of MERS-CoV pathogenesis is crucial for its control and prevention. However, in vivo studies are limited because MERS-CoV cannot infect wild-type mice due to incompatibilities between the virus spike and the mouse host cell receptor, mouse DPP4 (mDPP4). Specifically, mDPP4 has a nonconserved glycosylation site that acts as a barrier to MERS-CoV infection. Thus, one mouse model strategy has been to modify the mouse genome to remove this glycosylation site. Here, we investigated whether glycosylation acts as a barrier to infection for other nonpermissive small-animal species, namely, ferret, guinea pig, and hamster. Understanding the virus-receptor interactions for these DPP4 orthologs will help in the development of additional animal models while also revealing species-specific differences impacting MERS-CoV host range

Evolution of the HIV-1 env Gene in the Rag2-/- C-/- Humanized Mouse Model

Rag2−/− γC−/− mice transplanted with human hematopoietic stem cells (DKO-hu-HSC mice) mimic aspects of human infection with human immunodeficiency virus type 1 (HIV-1), including sustained viral replication and CD4+ T-cell decline. However, the extent of HIV-1 evolution during long-term infection in these humanized mice, a key feature of the natural infection, has not been assessed fully. In this study, we examined the types of genotypic and phenotypic changes in the viral env gene that occur in the viral populations of DKO-hu-HSC mice infected with the CCR5-tropic isolate HIV-1JRCSF for up to 44 weeks. The mean rate of divergence of viral populations in mice was similar to that observed in a cohort of humans during a similar period of infection. Many amino acid substitutions were common across mice, including losses of N-linked glycosylation sites and substitutions in the CD4 binding site and in CD4-induced epitopes, indicating common selective pressures between mice. In addition, env variants evolved sensitivity to antibodies directed at V3, suggesting a more open conformation for Env. This phenotypic change was associated with increased CD4 binding efficiency and was attributed to specific amino acid substitutions. In one mouse, env variants emerged that exhibited a CXCR4-tropic phenotype. These sequences were compartmentalized in the mesenteric lymph node. In summary, viral populations in these mice exhibited dynamic behavior that included sequence evolution, compartmentalization, and the appearance of distinct phenotypic changes. Thus, humanized mice offer a useful model for studying evolutionary processes of HIV-1 in a complex host environment

Electromechanical Ski Release Binding With Mechanical Backup

FREQUENCY (Hz) Fig. 9 / axis responses for locations 2 and 3 for 1g input in X axis door assembly, so an estimated damping ratio of 0.02 was used. Conclusions The door assembly was designed and modelled within the given low mass budget. It survived the vibration tests which simulate the launch environment. These tests qualified the design for the flight structure. The door opening test which followed the vibration was satisfactory in that all the components of the door mechanism operated successfully

Quantification of the Latent HIV-1 Reservoir Using Ultra Deep Sequencing and Primer ID in a Viral Outgrowth Assay

In this study, we measured the latent HIV-1 reservoir harboring replication-competent HIV-1 in resting CD4+ T cells in participants on highly active antiretroviral therapy (HAART), quantitating the frequency of latent infection through the use of a Primer ID-based Ultra Deep Sequencing Assay (UDSA), in comparison to the readout of the quantitative viral outgrowth assay (QVOA)

Compensatory Evolution in RNA Secondary Structures Increases Substitution Rate Variation among Sites

There is growing evidence that interactions between biological molecules (e.g., RNA–RNA, protein–protein, RNA–protein) place limits on the rate and trajectory of molecular evolution. Here, by extending Kimura's model of compensatory evolution at interacting sites, we show that the ratio of transition to transversion substitutions (κ) at interacting sites should be equal to the square of the ratio at independent sites. Because transition mutations generally occur at a higher rate than transversions, the model predicts that κ should be higher at interacting sites than at independent sites. We tested this prediction in 10 RNA secondary structures by comparing phylogenetically derived estimates of κ in paired sites within stems (κp) and unpaired sites within loops (κu). Eight of the 10 structures showed an excellent match to the quantitative predictions of the model, and 9 of the 10 structures matched the qualitative prediction κp > κu. Only the Rev response element from the human immunovirus (HIV) genome showed the reverse pattern, with κp < κu. Although a variety of evolutionary forces could produce quantitative deviations from the model predictions, the reversal in magnitude of κp and κu could be achieved only by violating the model assumption that the underlying transition (or transversion) mutation rates were identical in paired and unpaired regions of the molecule. We explore the ability of the APOBEC3 enzymes, host defense mechanisms against retroviruses, which induce transition mutations preferentially in single-stranded regions of the HIV genome, to explain this exception to the rule. Taken as a whole, our findings suggest that κ may have utility as a simple diagnostic to evaluate proposed secondary structures

Chimeric GII.4 Norovirus Virus-Like-Particle-Based Vaccines Induce Broadly Blocking Immune Responses

There is currently no licensed vaccine for noroviruses, and development is hindered, in part, by an incomplete understanding of the host adaptive immune response to these highly heterogeneous viruses and rapid GII.4 norovirus molecular evolution. Emergence of a new predominant GII.4 norovirus strain occurs every 2 to 4 years. To address the problem of GII.4 antigenic variation, we tested the hypothesis that chimeric virus-like particle (VLP)-based vaccine platforms, which incorporate antigenic determinants from multiple strains into a single genetic background, will elicit a broader immune response against contemporary and emergent strains. Here, we compare the immune response generated by chimeric VLPs to that of parental strains and a multivalent VLP cocktail. Results demonstrate that chimeric VLPs induce a more broadly cross-blocking immune response than single parental VLPs and a similar response to a multivalent GII.4 VLP cocktail. Furthermore, we show that incorporating epitope site A alone from one strain into the background of another is sufficient to induce a blockade response against the strain donating epitope site A. This suggests a mechanism by which population-wide surveillance of mutations in a single epitope could be used to evaluate antigenic changes in order to identify potential emergent strains and quickly reformulate vaccines against future epidemic strains as they emerge in human populations