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Objective: Ultrasound-guided intervention is an essential skill for many radiologists and critical for accurate diagnosis and treatment in many radiology subspecialties. Simulation using phantoms have demonstrated statistically significant benefits for trainees within the literature. We propose a novel phantom model which the authors feel is ideal for training clinical radiology trainees in the performance of ultrasound-guided procedures. Methods: The recipe to prepare a homemade phantom is described. Results of a local survey from trainees preparing and using the phantom are also presented. Results: This realistic training simulation model can be adapted to suit a variety of biopsy devices and procedures including soft tissue biopsy and cyst aspiration. The phantom mimics the sonographic appearances of soft tissue and biopsy targets can be concealed within. The phantom was easily prepared by 22 trainees (Likert score 4.5) and it functioned well (Likert score of 4.7). Conclusion: In summary, our phantom model is ideal for training clinical radiology trainees in the performance of ultrasound-guided core biopsy. The availability and low cost of the model, combined with the ease of preparation and reproducibility, make this an efficient and effective addition to the training process. Advances in knowledge: A low cost easily handmade phantom recipe is described that could be easily implemented in training schemes.

The global outbreak of Covid-19 pneumonia in 2020 has instantly changed the appearance of the world and caused a sudden change in the interaction pattern of international actors. Actors at all levels have survived the current situation for more than a year under the premise of being forced to change. However, actors at all levels who are unwilling to succumb to the impact of the current epidemic are aiming to restore their pre-epidemic lifestyles, and are drawing up plans to rebuild the international order and respond to new challenges, including the current vaccine policies of various countries-how to respond appropriately demands on a global scale. Therefore, all past political and democratic issues have been repositioned in the post-epidemic era of environmental changes to be verified again. Most members of the international community have strengthened multilateralism in their cooperation in the fight against the epidemic. However, the Trump administration's “America First” and unilateralism pose the greatest challenge to the international multi-polarization pattern and a fair and reasonable world order. Therefore, analyzing and studying changes in the international pattern and world order under the epidemic will help improve practice and theoretical consciousness, and promote the construction of contemporary new international relations and a community with a shared future for mankind. This article attempts to analyze the international configuration in the post-Covid 19 era from the perspective of Windt's constructivism.

Traditionally B3 breast lesions are treated surgically, but overtreatment is a concern, as the majority have a final benign diagnosis. A national screening program introduced vacuum-assisted excision (VAE) for managing B3 lesions in late 2016. This retrospective study aimed to assess the outcomes associated with this approach.All B3 lesions diagnosed between 01/2017 and 12/2019 were identified at two centres. Information was obtained on the initial biopsy and final histology, and method of VAE image guidance, needle size and number of cores. Lesions were excluded if there was cancer elsewhere in the breast at the time of diagnosis; the lesion was not suitable for VAE due to position in the breast or had B3 pathology for which open biopsy was still required. The final decision to offer VAE was always made at a multidisciplinary meeting (MDM). Risk difference was used to test the significance at p ≤ .05.In total, 258 B3 lesions were diagnosed, 105 (40.7%) met the inclusion criteria and underwent VAE. VAE was performed under X-ray (89/105) or ultrasound guidance (16/105), taking an average of 18.5 cores with the 10-G needle or 10.8 cores with the 7-G needle. Nine cases (8.6%) were upgraded to a malignant diagnosis following VAE. Malignancy was found in 15.5% (9/58) of B3 lesions with epithelial atypia, but in none without atypia (0/47) (p = .004). No new lesions or malignancy has occurred at the site of the VAE with an average mammographic follow-up of 2.2 years.Upgrade to malignancy following VAE was uncommon (8.6%) and associated with atypia in the initial biopsy. VAE is an alternative approach to the management of B3 lesions, reducing open surgical procedures.• Upgrade to malignancy after a vacuum-assisted excision of a B3 breast lesion is uncommon with an 8.6% upgrade rate. • The risk of a malignant diagnosis after a vacuum-assisted excision was significantly higher for B3 lesions with atypia compared to those without (+15.5% difference, p = .004).

Purpose Burnout has been well-examined among physicians and other high-wage, high-autonomy healthcare positions. However, lower-wage healthcare workers with less workplace autonomy (e.g., medical assistants, nurses’ aides) represent a substantial proportion of the workforce but remain understudied. We aimed to examine the effects of burnout on psychotropic medication use and misuse and whether these effects differed by occupational level. Methods In March 2022, we collected data from a diverse sample of US healthcare workers (N = 200) and examined the cross-sectional relationship between burnout and changes in prescribed psychotropic medication (i.e., starting, stopping, and/or having a change in the dose/frequency) during the COVID-19 pandemic. We also separately examined the relationship between burnout and psychotropic medication misuse (i.e., without a prescription, in greater amounts, more often, longer than prescribed, and/or for a reason other than prescribed). We stratified models by occupational level (prescribers/healthcare administrators vs. other healthcare workers). Results Greater burnout was associated with higher odds of changes in prescribed psychotropic medication among physicians/administrators (aOR = 1.23, 95% CI: 1.01, 1.48), but not among other healthcare workers (aOR = 1.04, 95% CI: 0.98, 1.10). Greater burnout was not associated with psychotropic medication misuse among physicians/administrators (aOR = 0.96, 95% CI: 0.82, 1.12) but was associated with increased odds of psychotropic medication misuse among other healthcare workers (aOR = 1.07, 95% CI: 1.01, 1.14). Conclusions Potential disparities in help-seeking and healthcare access might manifest in non-medical use of prescription drugs among some healthcare workers, which has implications for worker safety and well-being.

Biomaterials display microstructures that are geometrically irregular and functionally efficient. Understanding the role of irregularity in determining material properties offers a new path to engineer materials with superior functionalities, such as imperfection insensitivity, enhanced impact absorption, and stress redirection. We uncover fundamental, probabilistic structure–property relationships using a growth-inspired program that evokes the formation of stochastic architectures in natural systems. This virtual growth program imposes a set of local rules on a limited number of basic elements. It generates materials that exhibit a large variation in functional properties starting from very limited initial resources, which echoes the diversity of biological systems. We identify basic rules to control mechanical properties by independently varying the microstructure’s topology and geometry in a general, graph-based representation of irregular materials.

Current influenza virus vaccines are focused on humoral immunity and are limited by the short duration of protection, narrow cross-strain efficacy, and suboptimal immunogenicity. Here, we combined two chemically and biologically distinct adjuvants, an oil-in-water nanoemulsion (NE) and RNA-based agonists of RIG-I, to determine whether the diverse mechanisms of these adjuvants could lead to improved immunogenicity and breadth of protection against the influenza virus. NE activates TLRs, stimulates immunogenic apoptosis, and enhances cellular antigen uptake, leading to a balanced TH1/TH2/TH17 response when administered intranasally. RIG-I agonists included RNAs derived from Sendai and influenza viral defective interfering RNAs (IVT DI, 3php, respectively) and RIG-I/TLR3 agonist, poly(I:C) (pIC), which induce IFN-Is and TH1-polarized responses. NE/RNA combined adjuvants potentially allow for costimulation of multiple innate immune receptor pathways, more closely mimicking patterns of activation occurring during natural viral infection. Mice intranasally immunized with inactivated A/Puerto Rico/8/1934 (H1N1) (PR/8) adjuvanted with NE/IVT DI or NE/3php (but not NE/pIC) showed synergistic enhancement of systemic PR/8-specific IgG with significantly greater avidity and virus neutralization activity than the individual adjuvants. Notably, NE/IVT DI induced protective neutralizing titers after a single immunization. Hemagglutinin stem-specific antibodies were also improved, allowing recognition of heterologous and heterosubtypic hemagglutinins. All NE/RNAs elicited substantial PR/8-specific sIgA. Finally, a unique cellular response with enhanced TH1/TH17 immunity was induced with the NE/RNAs. These results demonstrate that the enhanced immunogenicity of the adjuvant combinations was synergistic and not simply additive, highlighting the potential value of a combined adjuvant approach for improving the efficacy of vaccination against the influenza virus.

The 13th Global CRO Council (GCC) closed forum for bioanalysis was held in New Orleans, LA, USA on 5 April 2019. This GCC meeting was organized to discuss the contents of the 2019 ICH M10 Bioanalytical Method Validation Draft Guideline published in February 2019 and consolidate the feedback of the GCC members. While ICH M10 will cover requirements for reference standards, one of the biggest challenges facing the CRO community is the lack of consistency and completeness of Certificates of Analysis for reference standards used in regulated bioanalysis. Similar challenges exist with critical reagents (e.g., capture and detection antibodies) used for assays supporting biologics. The recommendations provided in this publication are the minimum requirements for the content that GCC members believe should be included in Certificates of Analysis for reference standards obtained from commercial vendors, sponsors and compendial suppliers, for use in regulated bioanalytical studies. In addition, recommendations for internal standards, metabolites and critical reagents are discussed.

Academic stress, depression, and anxiety among university students has been a great concern globally. Literature review shows that university students may harbor irrational beliefs that could play a significant role in causing emotional disturbances. Objective: The aims of this study were to examine the relationship of irrational beliefs with emotional disturbances in university students, and the differences in irrational beliefs and depression, anxiety, and stress between students with different socio-demographic and academic backgrounds. Participants and method: Data was collected from 655 local Hong Kong university students. Results and conclusions: University students having higher levels of irrational beliefs were more likely to have depression, anxiety, and stress. Two-way MANOVA results showed that second-year students had more awfulizing beliefs than third-year students in the faculties of Engineering and Education. Results of ANOVA and the Independent Sample t-test revealed that male students, students from low income families, Law students, those pursuing 5-year programs, or those in the second year of study were likely to have more irrational beliefs. In addition, male students, medical students, those studying 5-year programs were found having significantly higher levels of depression, anxiety, and stress. Limitations and implications were discussed.

University study has been considered to be one of the most stressful periods in a person's life. University students may have irrational beliefs that could play a significant role in causing emotional disturbance. Nevertheless, a suitable instrument for measuring irrational beliefs in college students in Chinese society has been lacking. The aim of this study was to construct a culturally relevant scale for measuring irrational beliefs among university students in the Hong Kong Chinese context. The construction of the Chinese Irrational Beliefs and Rational Attitude Scale (CIBRAS) for university students was based on (1) literature review and expert panel review for evaluation on content validity, (2) a pilot test of 200 local Hong Kong university students to determine the scale's psychometric properties and probe the exploratory factor analysis, and (3) confirmatory factor analysis to test for construct validity of the CIBRAS (conducted with a further 655 local Hong Kong university students). The results showed that the five-factor 19-item CIBRAS has good psychometric properties, including good internal consistency (Cronbach's alphas ranging from .64 to .80), content validity (content validity index = .96 for relevance, .94 for clarity, and .94 for representativeness), construct validity (explaining 60.1% of the total variance), and adequate fit indices (normed chi-square = 2.8, comparative fit index = .94, normal fit index = .93, non-normed fit index = .93, incremental fit index = .94, root-mean-square error of approximation = .077, and standardized root-mean residual = .074). The limitations and implications of the study were discussed.

Background The US is experiencing an epidemic of HPV+ oropharyngeal cancers (OPC), the rates and burden of which now exceed that for cervical cancer. Immunotherapy targeting programmed death 1 (PD-1) on tumor-infiltrating lymphocytes and/or its ligand PD-L1 on tumor cells, which was effective in several cancers has however, showed efficacy in only less than 15% of patients. Methods We used a preclinical HPV+ oral tumor model, mEER, consisting of mouse tonsil derived epithelial cells expressing HPV-16 E6 and E7 genes, along with the H-ras oncogene to test strategies for enhancing the efficacy of anti-PD-1 therapy. Results Monotherapy with PD-1 blocking antibody was ineffective against flank-implanted tumors, but induced regression in 54% of mice bearing orthotopic tongue tumors that correlated with higher CD8 T cell responses. Since the CD8+ T cells derived from tongue tumors also showed high levels of the immune checkpoint inhibitory receptor CTLA-4, we tested combination immunotherapy targeting both CTLA-4 and PD-1 together and observed 93.3% survival of mice bearing tumors in the tongue for the duration of our 100-day study. Protective immunity correlated with a significant decrease in immunosuppressive lymphoid and myeloid populations within the tumor microenvironment. Consistent with the reported capacity of interferon-driven PD-L1/PD-1 pathway induction to serve as a biomarker of response to PD-1 blockade, we observed elevated interferon signaling and significantly higher levels of PD-1/PD-L1 in tongue-implanted mEER tumors compared to those growing on the flank correlating with their preferential responsiveness to PD-1 blockade. More importantly, in a pseudometastasic mouse model bearing both flank and tongue tumors to represent metastatic disease, delivery of Stimulator of Interferon Induced Genes (STING) agonist into the flank tumors combined with systemic treatment with α-PD-1 and α-CTLA-4 antibodies resulted in sustained tumor regression in 71% of mice. In this case, productive abscopal anti-tumor immunity was associated with robust increases in the ratios of cytotoxic CD8+ T cells (CTL) versus regulatory T cells (Treg) and versus functional myeloid-derived suppressor cells (MDSC). Conclusions These results support combining α-PD-1 therapy with induction of IFN-α/β signaling via provision of STING agonist and/or through CTLA-4 blockade as potential treatment option for HNSCC patients, especially, those not responding to α-PD-1 monotherapy.

Traditionally B3 breast lesions are treated surgically, but overtreatment is a concern, as the majority have a final benign diagnosis. A national screening program introduced vacuum-assisted excision (VAE) for managing B3 lesions in late 2016. This retrospective study aimed to assess the outcomes associated with this approach. All B3 lesions diagnosed between 01/2017 and 12/2019 were identified at two centres. Information was obtained on the initial biopsy and final histology, and method of VAE image guidance, needle size and number of cores. Lesions were excluded if there was cancer elsewhere in the breast at the time of diagnosis; the lesion was not suitable for VAE due to position in the breast or had B3 pathology for which open biopsy was still required. The final decision to offer VAE was always made at a multidisciplinary meeting (MDM). Risk difference was used to test the significance at p ≤ .05. In total, 258 B3 lesions were diagnosed, 105 (40.7%) met the inclusion criteria and underwent VAE. VAE was performed under X-ray (89/105) or ultrasound guidance (16/105), taking an average of 18.5 cores with the 10-G needle or 10.8 cores with the 7-G needle. Nine cases (8.6%) were upgraded to a malignant diagnosis following VAE. Malignancy was found in 15.5% (9/58) of B3 lesions with epithelial atypia, but in none without atypia (0/47) (p = .004). No new lesions or malignancy has occurred at the site of the VAE with an average mammographic follow-up of 2.2 years. Upgrade to malignancy following VAE was uncommon (8.6%) and associated with atypia in the initial biopsy. VAE is an alternative approach to the management of B3 lesions, reducing open surgical procedures. • Upgrade to malignancy after a vacuum-assisted excision of a B3 breast lesion is uncommon with an 8.6% upgrade rate. • The risk of a malignant diagnosis after a vacuum-assisted excision was significantly higher for B3 lesions with atypia compared to those without (+15.5% difference, p = .004).

We report a light-controlled release mechanism for photocaged ciprofloxacin nanoconjugate. Validation of this bacteria-targeted strategy adds a novel modality to light-based therapies for wound treatments.

Despite their proven ability for precise and targeted release, nanoplatform systems for photocontrolled delivery often face formidable synthetic challenges, in part due to the paucity of advanced linker strategies. Here, we report on a novel linker strategy using a thioacetal ortho-nitrobenzaldehyde (TNB) cage, demonstrating its application for delivery of doxorubicin (Dox) in two nanoscale systems. This photocleavable linker, TNB(OH), which presents two identical arms, each terminated with a hydroxyl functionality, was prepared in a single step from 6-nitroveratraldehyde. TNB(OH) was used to cross-link Dox to a folate receptor (FAR)-targeting poly(amidoamine) dendrimer conjugate G5(FA)n=5.4(Dox)m=5.1, and also used to prepare an upconversion nanocrystal (UCN) conjugate, UCN-PPIX@Dox)(G5FA), a larger core/shell nanostructure. In this core/shell nanostructure, the UCN core emits UV and visible light luminescence upon near-infrared (NIR) excitation, allowing for the photocleavage of the TNB linker as well as the photostimulation of protoporphyrin IX (PPIX) coupled as a cytotoxic photosensitizer. Drug-release experiments performed in aqueous solutions with long-wavelength ultraviolet A (UVA) light showed that Dox release occurred rapidly from its TNB linked form or from its dendrimer conjugated form with comparable decay kinetics. Cellular toxicity studies in FAR-overexpressing KB carcinoma cells demonstrated that each nanoconjugate lacked intrinsic cytotoxicity until exposed to UVA or NIR (980 nm) (for the UCN nanoconjugate), which resulted in induction of potent cytotoxicity. In summary, this new TNB strategy offers synthetic convenience in drug conjugation chemistry with the ability for the temporal control of drug activation at the delivery site.

The 2016 10th Workshop on Recent Issues in Bioanalysis (10th WRIB) took place in Orlando, Florida with participation of close to 700 professionals from pharmaceutical/biopharmaceutical companies, biotechnology companies, contract research organizations, and regulatory agencies worldwide. WRIB was once again a 5-day, weeklong event – A Full Immersion Week of Bioanalysis including Biomarkers and Immunogenicity. As usual, it was specifically designed to facilitate sharing, reviewing, discussing and agreeing on approaches to address the most current issues of interest including both small and large molecule analysis involving LCMS, hybrid LBA/LCMS, and LBA approaches, with the focus on biomarkers and immunogenicity. This 2016 White Paper encompasses recommendations emerging from the extensive discussions held during the workshop, and is aimed to provide the bioanalytical community with key information and practical solutions on topics and issues addressed, in an effort to enable advances in scientific excellence, improved quality and better regulatory compliance. This white paper is published in 3 parts due to length. This part (Part 1) discusses the recommendations for small molecules, peptides and small molecule biomarkers by LCMS. Part 2 (Hybrid LBA/LCMS and regulatory inputs from major global health authorities) and Part 3 (large molecule bioanalysis using LBA, biomarkers and immunogenicity) will be published in the Bioanalysis journal, issue 23.