Nanoscale Material Heterogeneity of Glowworm Capture Threads Revealed by AFM.

Adhesive materials used by many arthropods for biological functions incorporate sticky substances and a supporting material that operate synergistically by exploiting substrate attachment and energy dissipation. While there has been much focus on the composition and properties of the sticky glues of these bio-composites, less attention has been given to the materials that support them. In particular, as these materials are primarily responsible for dissipation during adhesive pull-off, little is known of the structures that give rise to functionality, especially at the nano-scale. In this study we used tapping mode atomic force microscopy (TM-AFM) to analyze unstretched and stretched glowworm (Arachnocampa tasmaniensis) capture threads and revealed nano-scale features corresponding to variation in surface structure and elastic modulus near the surface of the silk. Phase images demonstrated a high resolution of viscoelastic variation and revealed mostly globular and elongated features in the material. Increased vertical orientation of 11-15 nm wide fibrillar features was observed in stretched threads. Fast Fourier transform analysis of phase images confirmed these results. Relative viscoelastic properties were also highly variable at inter- and intra-individual levels. Results of this study demonstrate the practical usefulness of TM-AFM, especially phase angle imaging, in investigating the nano-scale structures that give rise to macro-scale function of soft and highly heterogeneous materials of both natural and synthetic origins.

Numerical study of optical feedback coherence in semiconductor laser dynamics.

The nonlinear dynamics of a semiconductor laser with coherent, as compared to incoherent, delayed optical feedback systems have been discussed and contrasted in prior research literature. Here, we report simulations of how the dynamics change as the coherence of the optical feedback is systematically varied from being coherent, through several levels of partial coherence, to incoherent. An increasing rate of phase disturbance is used to vary the coherence. An edge-emitting, 830 nm, Fabry-Perot semiconductor laser with a long external cavity is simulated. Following this study, consideration of prior and future experimental studies should include evaluation of where on the continuum of partial coherence the delayed optical feedback sits. The level of partial coherence is an important factor affecting the dynamics.

Mapping the dynamical regimes of a SESAM mode-locked VECSEL with a long cavity using time series analysis.

The different dynamical regions of an optically-pumped SESAM mode-locked, long-cavity VECSEL system with a fundamental pulse repetition frequency of ~200 MHz are investigated. The output power, captured as 250 µs long time series using a sampling rate of 200 GSa/s, for each operating condition of the system, is analyzed to determine the dynamical state. A wavelength range of 985-995 nm and optical pump powers of 10 W-16.3 W is studied. The system produces high quality fundamental passive mode-locking (FML) over an extensive part of the parameter space, but the different dynamical regions outside of FML are the primary focus of this study. We report five types of output: CW emission, FML, mode-locking of a few modes, double pulsing, and, semi-stable 4th harmonic mode-locking. The high sampling rate of the oscilloscope, combined with the long duration of the time series analyzed, enables insight into how the structure and substructure of pulses vary systematically over thousands of round trips of the laser cavity. Higher average output power is obtained in regions characterized by semi-stable 4th harmonic mode-locking than observed for FML, raising whether such average powers might be achieved for FML. The observed dynamic transitions from fundamental mode-locking provide insights into instability challenges in developing a stable, widely tunable, low repetition rate, turn-key system; and to inform future modelling of the system.

Exploring the Role of In-Person Components for Online Health Behavior Change Interventions: Can a Digital Person-to-Person Component Suffice?

The growth of the digital environment provides tremendous opportunities to revolutionize health behavior change efforts. This paper explores the use of Web-based, mobile, and social media health behavior change interventions and determines whether there is a need for a face-to-face or an in-person component. It is further argued that that although in-person components can be beneficial for online interventions, a digital person-to-person component can foster similar results while dealing with challenges faced by traditional intervention approaches. Using a digital person-to-person component is rooted in social and behavioral theories such as the theory of reasoned action, and the social cognitive theory, and further justified by the human support constructs of the model of supportive accountability. Overall, face-to-face and online behavior change interventions have their respective advantages and disadvantages and functions, yet both serve important roles. It appears that it is in fact human support that is the most important component in the effectiveness and adherence of both face-to-face and online behavior change interventions, and thoughtfully introducing a digital person-to-person component, to replace face-to-face interactions, can provide the needed human support while diminishing the barriers of in-person meetings. The digital person-to-person component must create accountability, generate opportunities for tailored feedback, and create social support to successfully create health behavior change. As the popularity of the online world grows, and the interest in using the digital environment for health behavior change interventions continues to be embraced, further research into not only the use of online interventions, but the use of a digital person-to-person component, must be explored.

High-order external cavity modes and restabilization of a laser diode subject to a phase-conjugate feedback.

We experimentally report the sequence of bifurcations destabilizing and restabilizing a laser diode with phase-conjugate feedback when the feedback rate is increased. Specifically, we successively observe the initial steady state, undamped relaxation oscillations, quasi-periodicity, chaos, and oscillating solutions at harmonics up to 13 times the external cavity frequency but also the restabilization to a steady state. The experimental results are qualitatively well reproduced by a model that accounts for the time the light takes to penetrate the phase-conjugate mirror. The theory points out that the system restabilizes through a Hopf bifurcation whose frequency is a harmonic of the external cavity frequency.

Integrated semiconductor laser with optical feedback: transition from short to long cavity regime.

A 4-section semiconductor laser with integrated optical feedback has been shown experimentally to be capable of operating in either the short- or long-cavity regime, by controlling the device relaxation oscillation frequency relative to the external cavity frequency. Systematic increase of the laser injection current, and the resulting increase in relaxation oscillation frequency, allowed the transition between the two regimes of operation to be observed. The system displayed a gradual transition from a dynamic dominated by regular pulse packages in the short-cavity regime to one dominated by broadband chaotic output when operating in the long-cavity regime. This suggests that the "short cavity" regular pulse packages continue to co-exist with the "long cavity" broadband chaotic dynamic in the system studied. It is the relative power associated with each of these dynamics that changes. This may occur more generally in similar systems.

Complexity in pulsed nonlinear laser systems interrogated by permutation entropy.

Permutation entropy (PE) has a growing significance as a relative measure of complexity in nonlinear systems. It has been applied successfully to measuring complexity in nonlinear laser systems. Here, PE and weighted permutation entropy (WPE) are discovered to show an unexpected inversion to higher values, when characterizing the complexity at the characteristic frequencies of nonlinear drivers in laser systems, for output power sequences which are pulsed. The cause of this inversion is explained and its presence can be used to identify when irregular dynamics transform into a fairly regular pulsed signal (with amplitude and timing jitter). When WPE is calculated from experimental output power time series from various nonlinear laser systems as a function of delay time, both the minimum value of WPE, and the width of the peak in the WPE plot are shown to be indicative of the level of amplitude variation and timing jitter present in the pulsed output. Links are made with analysis using simulated time series data with systematic variation in timing jitter and/or amplitude variations.

Subdiffraction-limited radius measurements of microcylinders using conventional bright-field optical microscopy.

A technique for measuring the radius of dielectric microcylinders with subdiffraction-limited precision is presented. Diffraction fringes arising from the dielectric cylinder are measured using conventional bright-field optical microscopy and compared with theory to deduce the radii. The technique has been demonstrated measuring the radii of the major-ampullate silks from Plebs eburnus spiders. Precision better than 50 nm is demonstrated, using a standard optical microscope with a numerical aperture of 0.6 for the objective. Accuracy was verified using scanning electron microscopy. This technique will facilitate rapid, precise measurement of dielectric microcylinder radii, enabling a new optical-microscopy-based measurement approach for these challenging micro-optics.

DNA Vaccines for Epidemic Preparedness: SARS-CoV-2 and Beyond.

We highlight the significant progress in developing DNA vaccines during the SARS-CoV-2 pandemic. Specifically, we provide a comprehensive review of the DNA vaccines that have progressed to Phase 2 testing or beyond, including those that have received authorization for use. DNA vaccines have significant advantages with regard to the rapidity of production, thermostability, safety profile, and cellular immune responses. Based on user needs and cost, we compare the three devices used in the SARS-CoV-2 clinical trials. Of the three devices, the GeneDerm suction device offers numerous benefits, particularly for international vaccination campaigns. As such, DNA vaccines represent a promising option for future pandemics.

Immune response enhancement with GLS-5310 DNA primary vaccine against SARS-CoV-2 followed by administration of an mRNA vaccine heterologous boost.

Heterologous boost regimens are being increasingly considered against SARS-CoV-2. We report results for the 32 of 45 participants in the Phase 1 CoV2-001 clinical trial (Kim et al., Int J Iinfect Dis 2023, 128:112-120) who elected to receive an EUA-approved SARS-CoV-2 mRNA vaccine 6 to 8 months following a two-dose primary vaccination with the GLS-5310 bi-cistronic DNA vaccine given intradermally and followed by application of suction using the GeneDerm device. Receipt of EUA-approved mRNA vaccines after GLS-5310 vaccination was well-tolerated, with no reported adverse events. Immune responses were enhanced such that binding antibody titers, neutralizing antibody titers, and T-cell responses increased 1,187-fold, 110-fold, and 2.9-fold, respectively. This paper is the first description of the immune responses following heterologous vaccination with a DNA primary series and mRNA boost.

Safety and immunogenicity of the bi-cistronic GLS-5310 COVID-19 DNA vaccine delivered with the GeneDerm suction device.

OBJECTIVES: The CoV2-001 phase I randomized trial evaluated the safety and immunogenicity of the GLS-5310 bi-cistronic DNA vaccine through 48 weeks of follow-up. DESIGN: A total of 45 vaccine-naïve participants were recruited between December 31, 2020, and March 30, 2021. GLS-5310, encoding for the SARS-CoV-2 spike and open reading frame 3a (ORF3a) proteins, was administered intradermally at 0.6 mg or 1.2 mg per dose, followed by application of the GeneDerm suction device as part of a two-dose regimen spaced either 8 or 12 weeks between vaccinations. RESULTS: GLS-5310 was well tolerated with no serious adverse events reported. Antibody and T cell responses were dose-independent. Anti-spike antibodies were induced in 95.5% of participants with an average geometric mean titer of ∼480 four weeks after vaccination and declined minimally through 48 weeks. Neutralizing antibodies were induced in 55.5% of participants with post-vaccination geometric mean titer of 28.4. T cell responses were induced in 97.8% of participants, averaging 716 site forming units/106 cells four weeks after vaccination, increasing to 1248 at week 24, and remaining greater than 1000 through 48 weeks. CONCLUSION: GLS-5310 administered with the GeneDerm suction device was well tolerated and induced high levels of binding antibodies and T-cell responses. Antibody responses were similar to other DNA vaccines, whereas T cell responses were many-fold greater than DNA and non-DNA vaccines.

Bullying in undergraduate clinical nursing education.

Although a limited number of studies have focused on bullying in nursing education to date, all of those studies demonstrate the existence of bullying in clinical settings, where nursing students undertake a significant amount of their nursing education. The purpose of this study was to examine the state of bullying in clinical nursing education among Canadian undergraduate nursing students (N = 674) in all 4 years of their nursing program. Results suggest that nursing students experience and witness bullying behaviors at various frequencies, most notably by clinical instructors and staff nurses. Third-year and fourth-year students experience more bullying behaviors than first-year and second-year students. Implications for practice include ensuring that clinical instructors are well prepared for their role as educators. Policies must be developed that address the issue of bullying within nursing programs and within health care facilities where nursing students undertake their clinical nursing education.

Adverse events related to ultrasound-guided regional anesthesia performed by Emergency Physicians: Systematic review protocol.

The use of ultrasound-guided regional anesthesia for pain management has become increasingly prevalent in Emergency Medicine, with studies noting excellent pain control while sparing opioid use. However, the use of ultrasound-guided regional anesthesia may be hampered by concern about risks for patient harm. This systematic review protocol describes our approach to evaluate the incidence of adverse events from the use of ultrasound-guided regional anesthesia by Emergency Physicians as described in the literature. This project will also seek to document the scope of ultrasound-guided regional anesthesia applications being performed in Emergency Medicine literature, and potentially serve as a framework for future systematic reviews evaluating adverse events in Emergency Medicine.

Hybrid immersion-polarization method for measuring birefringence applied to spider silks.

A technique for accurate measurement of the principle refractive indices and birefringence for silklike samples is presented. It is based on rotating the linear polarization of the illuminating light on a silk immersed in reference liquid to achieve index matching at the silk/liquid interface. The technique was used to measure the principal refractive indices of a P. eburnus radial silk at different strains. This in turn allows the calculation of strain-optic coefficients. The first measurement of the strain-optic coefficients of spider silk is presented. The technique is more generally applicable to strain-optic study of birefringent micro-optic samples.

Point-of-care Ultrasound-guided Central Venous Catheter Confirmation in Ultrasound Nonexperts.

OBJECTIVE: Emerging evidence suggests that chest radiography (CXR) following central venous catheter (CVC) placement is unnecessary when point-of-care ultrasound (POCUS) is used to confirm catheter position and exclude pneumothorax. However, few providers have adopted this practice, and it is unknown what contributing factors may play a role in this lack of adoption, such as ultrasound experience. The objective of this study was to evaluate the diagnostic accuracy of POCUS to confirm CVC position and exclude a pneumothorax after brief education and training of nonexperts. METHODS: We performed a prospective cohort study in a single academic medical center to determine the diagnostic characteristics of a POCUS-guided CVC confirmation protocol after brief training performed by POCUS nonexperts. POCUS nonexperts (emergency medicine senior residents and critical care fellows) independently performed a POCUS-guided CVC confirmation protocol after a 30-minute didactic training. The primary outcome was the diagnostic accuracy of the POCUS-guided CVC confirmation protocol for malposition and pneumothorax detection. Secondary outcomes were efficiency and feasibility of adequate image acquisition, adjudicated by POCUS experts. RESULTS: Twenty-six POCUS nonexperts collected data on 190 patients in the final analysis. There were five (2.5%) CVC malpositions and six (3%) pneumothoraxes on CXR. The positive likelihood ratios of POCUS for malposition detection and pneumothorax were 12.33 (95% confidence interval [CI] = 3.26 to 46.69) and 3.41 (95% CI = 0.51 to 22.76), respectively. The accuracy of POCUS for pneumothorax detection compared to CXR was 0.93 (95% CI = 0.88 to 0.96) and the sensitivity was 0.17 (95% CI = 0.00 to 0.64). The median (interquartile range) time for CVC confirmation was lower for POCUS (9 minutes [8.5-9.5 minutes]) compared to CXR (29 minutes [1-269 minutes]; Mann-Whitney U, p < 0.01). Adequate protocol image acquisition was achieved in 76% of the patients. CONCLUSION: Thirty-minute training of POCUS in nonexperts demonstrates adequate diagnostic accuracy, efficiency, and feasibility of POCUS-guided CVC position confirmation, but not exclusion of pneumothorax.

Safety and immunogenicity of an anti-Middle East respiratory syndrome coronavirus DNA vaccine: a phase 1, open-label, single-arm, dose-escalation trial.

BACKGROUND: Middle East respiratory syndrome (MERS) coronavirus causes a highly fatal lower-respiratory tract infection. There are as yet no licensed MERS vaccines or therapeutics. This study (WRAIR-2274) assessed the safety, tolerability, and immunogenicity of the GLS-5300 MERS coronavirus DNA vaccine in healthy adults. METHODS: This study was a phase 1, open-label, single-arm, dose-escalation study of GLS-5300 done at the Walter Reed Army Institute for Research Clinical Trials Center (Silver Spring, MD, USA). We enrolled healthy adults aged 18-50 years; exclusion criteria included previous infection or treatment of MERS. Eligible participants were enrolled sequentially using a dose-escalation protocol to receive 0·67 mg, 2 mg, or 6 mg GLS-5300 administered by trained clinical site staff via a single intramuscular 1 mL injection at each vaccination at baseline, week 4, and week 12 followed immediately by co-localised intramuscular electroporation. Enrolment into the higher dose groups occurred after a safety monitoring committee reviewed the data following vaccination of the first five participants at the previous lower dose in each group. The primary outcome of the study was safety, assessed in all participants who received at least one study treatment and for whom post-dose study data were available, during the vaccination period with follow-up through to 48 weeks after dose 3. Safety was measured by the incidence of adverse events; administration site reactions and pain; and changes in safety laboratory parameters. The secondary outcome was immunogenicity. This trial is registered at ClinicalTrials.gov (number NCT02670187) and is completed. FINDINGS: Between Feb 17 and July 22, 2016, we enrolled 75 individuals and allocated 25 each to 0·67 mg, 2 mg, or 6 mg GLS-5300. No vaccine-associated serious adverse events were reported. The most common adverse events were injection-site reactions, reported in 70 participants (93%) of 75. Overall, 73 participants (97%) of 75 reported at least one solicited adverse event; the most common systemic symptoms were headache (five [20%] with 0·67 mg, 11 [44%] with 2 mg, and seven [28%] with 6 mg), and malaise or fatigue (five [20%] with 0·67 mg, seven [28%] with 2 mg, and two [8%] with 6 mg). The most common local solicited symptoms were administration site pain (23 [92%] with all three doses) and tenderness (21 [84%] with all three doses). Most solicited symptoms were reported as mild (19 [76%] with 0·67 mg, 20 [80%] with 2 mg, and 17 [68%] with 6 mg) and were self-limiting. Unsolicited symptoms were reported for 56 participants (75%) of 75 and were deemed treatment-related for 26 (35%). The most common unsolicited adverse events were infections, occurring in 27 participants (36%); six (8%) were deemed possibly related to study treatment. There were no laboratory abnormalities of grade 3 or higher that were related to study treatment; laboratory abnormalities were uncommon, except for 15 increases in creatine phosphokinase in 14 participants (three participants in the 0·67 mg group, three in the 2 mg group, and seven in the 6 mg group). Of these 15 increases, five (33%) were deemed possibly related to study treatment (one in the 2 mg group and four in the 6 mg group). Seroconversion measured by S1-ELISA occurred in 59 (86%) of 69 participants and 61 (94%) of 65 participants after two and three vaccinations, respectively. Neutralising antibodies were detected in 34 (50%) of 68 participants. T-cell responses were detected in 47 (71%) of 66 participants after two vaccinations and in 44 (76%) of 58 participants after three vaccinations. There were no differences in immune responses between dose groups after 6 weeks. At week 60, vaccine-induced humoral and cellular responses were detected in 51 (77%) of 66 participants and 42 (64%) of 66, respectively. INTERPRETATION: The GLS-5300 MERS coronavirus vaccine was well tolerated with no vaccine-associated serious adverse events. Immune responses were dose-independent, detected in more than 85% of participants after two vaccinations, and durable through 1 year of follow-up. The data support further development of the GLS-5300 vaccine, including additional studies to test the efficacy of GLS-5300 in a region endemic for MERS coronavirus. FUNDING: US Department of the Army and GeneOne Life Science.

Automatic Estimation of the Optic Nerve Sheath Diameter from Ultrasound Images.

We present an algorithm to automatically estimate the diameter of the optic nerve sheath from ocular ultrasound images. The optic nerve sheath diameter provides a proxy for measuring intracranial pressure, a life threating condition frequently associated with head trauma. Early treatment of elevated intracranial pressures greatly improves outcomes and drastically reduces the mortality rate. We demonstrate that the proposed algorithm combined with a portable ultrasound device presents a viable path for early detection of elevated intracranial pressure in remote locations and without access to trained medical imaging experts.

Sanitizing in Dry-Processing Environments Using Isopropyl Alcohol Quaternary Ammonium Formula.

Dry-processing environments are particularly challenging to clean and sanitize because introduced water can favor growth and establishment of pathogenic microorganisms such as Salmonella. Our objective was to determine the efficacy of an isopropyl alcohol quaternary ammonium (IPAQuat) formula for eliminating potential Salmonella contamination on food contact surfaces. Clean stainless steel coupons and conveyor belt materials used in dry-processing environments were spot inoculated in the center of coupons (5 by 5 cm) with a six-serotype composite of Salmonella (approximately 10 log CFU/ml), subjected to IPAQuat sanitizer treatments with exposure times of 30 s, 1 min, or 5 min, and then swabbed for enumeration of posttreatment survivors. A subset of inoculated surfaces was soiled with a breadcrumb-flour blend and allowed to sit on the laboratory bench for a minimum of 16 h before sanitation. Pretreatment Salmonella populations (inoculated controls, 0 s treatment) were approximately 7.0 log CFU/25 cm(2), and posttreatment survivors were 1.31, 0.72, and < 0.7 (detection limit) log CFU/25 cm(2) after sanitizer exposure for 30 s, 1 min, or 5 min, respectively, for both clean (no added soil) and soiled surfaces. Treatment with the IPAQuat formula using 30-s sanitizer exposures resulted in 5.68-log reductions, whereas >6.0-log reductions were observed for sanitizer exposures of 1 and 5 min. Because water is not introduced into the processing environment with this approach, the IPAQuat formula could have sanitation applications in dry-processing environments to eliminate potential contamination from Salmonella on food contact surfaces.

If they do call you a nurse, it is always a "male nurse": experiences of men in the nursing profession.

BACKGROUND AND PURPOSE: Men are underrepresented in nursing, accounting for less than 6% of Canadian nurses. This research explores issues surrounding recruitment, retention, and work life satisfaction for men who are nurses working in acute care settings. METHOD AND FINDINGS: Purposive and snowball sampling was used in this descriptive, qualitative study. Sixteen men participated in four focus groups conducted in three communities in southwestern Ontario. The participants revealed that work stress, lack of full-time opportunities, and gender-based stereotypes contributed to job dissatisfaction. Providing care to patients and making a difference were personal rewards that influenced their desire to stay in the profession. To promote nursing as a viable profession, unrestricted by gender, the participants recommended that recruitment strategies begin at an earlier age. DISCUSSION AND CONCLUSION: Findings are discussed in relation to recruitment and retention issues with implications for education, practice, and management.