Combination of vitamin D and photodynamic therapy enhances immune responses in murine models of squamous cell skin cancer.

Improved treatment outcomes for non-melanoma skin cancers can be achieved if Vitamin D (Vit D) is used as a neoadjuvant prior to photodynamic therapy (PDT). However, the mechanisms for this effect are unclear. Vit D elevates protoporphyrin (PpIX) levels within tumor cells, but also exerts immune-modulatory effects. Here, two murine models, UVB-induced actinic keratoses (AK) and human squamous cell carcinoma (A431) xenografts, were used to analyze the time course of local and systemic immune responses after PDT ± Vit D. Fluorescence immunohistochemistry of tissues and flow analysis (FACS) of blood were employed. In tissue, damage-associated molecular patterns (DAMPs) were increased, and infiltration of neutrophils (Ly6G+), macrophages (F4/80+), and dendritic cells (CD11c+) were observed. In most cases, Vit D alone or PDT alone increased cell recruitment, but Vit D + PDT showed even greater recruitment effects. Similarly for T cells, increased infiltration of total (CD3+), cytotoxic (CD8+) and regulatory (FoxP3+) T-cells was observed after Vit D or PDT, but the increase was even greater with the combination. FACS analysis revealed a variety of interesting changes in circulating immune cell levels. In particular, neutrophils decreased in the blood after Vit D, consistent with migration of neutrophils into AK lesions. Levels of cells expressing the PD-1+ checkpoint receptor were reduced in AKs following Vit D, potentially counteracting PD-1+ elevations seen after PDT alone. In summary, Vit D and ALA-PDT, two treatments with individual immunogenic effects, may be advantageous in combination to improve treatment efficacy and management of AK in the dermatology clinic.

Investigating the impact of cognitive biases in radiologists' image interpretation: A scoping review.

RATIONALE AND OBJECTIVE: Image interpretation is a fundamental aspect of radiology. The treatment and management of patients relies on accurate and timely imaging diagnosis. However, errors in radiological reports can negatively impact on patient health outcomes. These misdiagnoses can be caused by several different errors, but cognitive biases account for 74 % of all image interpretation errors. There are many biases that can impact on a radiologist's perception and cognitive processes. Several recent narrative reviews have discussed these cognitive biases and have offered possible strategies to mitigate their effects. However, these strategies remain untested. Therefore, the purpose of this scoping review is to evaluate the current knowledge on the extent that cognitive biases impact on medical image interpretation. MATERIAL AND METHODS: Scopus and Medline Databases were searched using relevant keywords to identify papers published between 2012 and 2022. A subsequent hand search of the narrative reviews was also performed. All studies collected were screened and assessed against the inclusion and exclusion criteria. RESULTS: Twenty-four publications were included and categorised into five main themes: satisfaction of search, availability bias, hindsight bias, framing bias and other biases. From these studies, there were mixed results regarding the impact of cognitive biases, highlighting the need for further investigation in this area. Moreover, the limited and untested debiasing methods offered by a minority of the publications and narrative reviews also suggests the need for further research. The potential of role of artificial intelligence is also highlighted to further assist radiologists in identifying and mitigating these cognitive biases. CONCLUSION: Cognitive biases can impact radiologists' image interpretation, however the effectiveness of debiasing strategies remain largely untested.

Experiences of frostbite injury from recreational use of nitrous oxide canisters in a UK burns center: Not a laughing matter.

Nitrous oxide is used as a recreational drug. Contact frostbite injury from compressed gas canisters has previously been described in the literature, but an increased number of such cases has been noted in our busy regional burns center in the UK. A single-center prospective case series of all patients referred and treated for frostbite injury secondary to misuse of nitrous oxide compressed gas canisters between January and December 2022 is presented. Data collection was performed through a referral database and patient case notes. Sixteen patients, of which 7 were male and 9 were female, satisfied the inclusion criteria. Mean patient age was 22.5 years. The median TBSA was 1%. In total, 50% of patients in the cohort had a delayed initial presentation to A&E of greater than 5 days. Eleven patients were reviewed at our burns center for further assessment and management. In total, 11 patients had bilateral inner thigh frostbite injuries, of which 8 had necrotic full-thickness injury, including subcutaneous fat. Seven patients were reviewed at our burns center and offered excision and split-thickness skin graft. Four patients presented with contact frostbite injury to the hand and one patient to the lower lip. This subgroup was managed successfully with conservative management alone. The reproducible pattern of frostbite injury secondary to the abuse of nitrous oxide compressed gas canisters is demonstrated in our case series. The distinct pattern of injury, patient cohort, and anatomical area affected presents an opportunity for targeted public health intervention in this group.

Gamma and vega hedging using deep distributional reinforcement learning.

We show how reinforcement learning can be used in conjunction with quantile regression to develop a hedging strategy for a trader responsible for derivatives that arrive stochastically and depend on a single underlying asset. We assume that the trader makes the portfolio delta-neutral at the end of each day by taking a position in the underlying asset. We focus on how trades in options can be used to manage gamma and vega. The option trades are subject to transaction costs. We consider three different objective functions. We reach conclusions on how the optimal hedging strategy depends on the trader's objective function, the level of transaction costs, and the maturity of the options used for hedging. We also investigate the robustness of the hedging strategy to the process assumed for the underlying asset.

The incidence and management of peripheral nerve injury in England (2005-2020).

Peripheral nerve injury (PNI) is a significant health problem that confers lifelong impact on those injured. Current interventions are purely surgical; however, outcomes remain poor. There is a lack of high-quality epidemiological data that is needed to identify populations involved, current healthcare demands, and ensure resources are distributed to the greatest effect, to reduce the injury burden. METHODS: Anonymized hospital episode statistical (HES) data on admitted patient care was obtained from NHS Digital for all National Health Service (NHS) patients sustaining PNI of all body regions between 2005 and 2020. Total numbers of finished consultant episodes (FCEs) or FCEs/100,000 population were used to demonstrate changes in demographic variables, anatomical locations of injury, mechanisms of injury, speciality, and main operation. RESULTS: There was a mean national incidence of 11.2 (95% CI 10.9, 11.6) events per 100,000 population per year. Males were at least twice as likely (p < 0.0001) to sustain a PNI. Upper limb nerves at or distal to the wrist were most commonly injured. Knife injuries increased (p < 0.0001), whereas glass injuries decreased (p < 0.0001). Plastic surgeons increasingly managed PNI (p = 0.002) as opposed to orthopaedic surgeons (p = 0.006) or neurosurgeons (p = 0.001). There was an increase in neurosynthesis (p = 0.022) and graft procedures (p < 0.0001) during the study period. DISCUSSION: PNI is a significant national healthcare problem predominantly affecting distal, upper limb nerves of men of working age. Injury prevention strategies, improved targeted funding and rehabilitation pathways are needed to reduce the injury burden and improve patient care.

Artificial intelligence-based human-centric decision support framework: an application to predictive maintenance in asset management under pandemic environments.

Pandemic events, particularly the current Covid-19 disease, compel organisations to re-formulate their day-to-day operations for achieving various business goals such as cost reduction. Unfortunately, small and medium enterprises (SMEs) making up more than 95% of all businesses is the hardest hit sector. This has urged SMEs to rethink their operations to survive through pandemic events. One key area is the use of new technologies pertaining to digital transformation for optimizing pandemic preparedness and minimizing business disruptions. This is especially true from the perspective of digitizing asset management methodologies in the era of Industry 4.0 under pandemic environments. Incidentally, human-centric approaches have become increasingly important in predictive maintenance through the exploitation of digital tools, especially when the workforce is increasingly interacting with new technologies such as Artificial Intelligence (AI) and Internet-of-Things devices for condition monitoring in equipment maintenance services. In this research, we propose an AI-based human-centric decision support framework for predictive maintenance in asset management, which can facilitate prompt and informed decision-making under pandemic environments. For predictive maintenance of complex systems, an enhanced trust-based ensemble model is introduced to undertake imbalanced data issues. A human-in-the-loop mechanism is incorporated to exploit the tacit knowledge elucidated from subject matter experts for providing decision support. Evaluations with both benchmark and real-world databases demonstrate the effectiveness of the proposed framework for addressing imbalanced data issues in predictive maintenance tasks. In the real-world case study, an accuracy rate of 82% is achieved, which indicates the potential of the proposed framework in assisting business sustainability pertaining to asset predictive maintenance under pandemic environments.

The Effect of Visual Hindsight Bias on Radiologist Perception.

RATIONALE AND OBJECTIVES: To measure the effect of visual hindsight bias on radiologists' perception during chest radiograph pulmonary nodule detection. MATERIALS AND METHODS: This was a prospective multi-observer study to assess the effect of hindsight bias on radiologists' perception. Sixteen radiologists were asked to interpret 15 postero-anterior chest images containing a solitary lung nodule each consisting of 25 incremental levels of blur. Participants were requested initially to detect the nodule by reducing the blur of the images (foresight). They were then asked to increase the blur until the identified nodule was undetectable (hindsight). Participants then repeated the experiment, after being informed of the potential effects of hindsight bias and asked to counteract these effects. Participants were divided into two groups (experienced and less experienced) and the nodules were given different conspicuity ratings to determine the effect of expertise and task difficulty. Eye tracking technology was also utilised to capture visual search. RESULTS: Wilcoxon analysis demonstrated significant differences between foresight and hindsight values of the radiologists (p = 0.02). However, after being informed of hindsight bias, these differences were no longer significant (p = 0.97). Friedman analysis also determined overall significance in the hindsight ratios between nodule conspicuities for both phases (phase 1: p = 0.02; phase 2: p = 0.02). There was no significance difference between the experienced and less experienced groups. CONCLUSION: This study demonstrated that radiologists exhibit hindsight bias but appeared to be able to compensate for this phenomenon once its effects were considered. Also, visual hindsight bias appears to be affected by task difficulty with a greater effect occurring with less conspicuous nodules.

Mechanical and thermal damage in cortical bone drilling in vivo.

Recently, the failure rate of fracture fixation to fractured bone has increased. Mechanical and thermal damage to the bone, which influences the contact area and cell growth between the bone and the screw, is the primary reason for fixation failure. However, research has mainly focused on force and temperature in bone drilling. In this study, the characteristics of hole edges, microcracks, empty lacunae, and osteon necrosis were investigated as viewed in the transverse and longitudinal sections after drilling. Drilling force and temperature were also recorded for comparing the relationship with mechanical and thermal damage. Experiments were conducted in vivo using five different drill geometries under the same drilling parameters. Characteristics of the hole wall were detected using computed tomography. Microcracks and necrosis were analyzed using the pathological sectioning method. The maximum microcrack was approximately 3000 and 1400 µm in the transverse section and longitudinal section, respectively, which were much larger than those observed in previous studies. Empty lacuna and osteon necrosis, starting from the Haversian canal, were also found. The drill bit geometry, chisel edge, flute number, edges, and steps had a strong effect on bone damage, particularly the chisel edge. The standard and classic surgical drill caused the greatest surface damage and necrosis of the five drill bit geometries studied. The microstructural features including osteons and matrix played an important role in numbers and length of microcracks and necrosis. More microcracks were generated in the transverse direction, while a greater length of the empty lacuna was generated in the longitudinal direction under the same drilling parameters. Microcracks mainly propagated in a straight manner in and parallel to the interstitial bone matrix and cement line. Drilling forces were not directly correlated with bone damage; thus, hole performance should be considered to evaluate the superiority and inferiority of drill bits rather than the drill force alone.

Hypertonic Saline Suppresses NADPH Oxidase-Dependent Neutrophil Extracellular Trap Formation and Promotes Apoptosis.

Tonicity of saline (NaCl) is important in regulating cellular functions and homeostasis. Hypertonic saline is administered to treat many inflammatory diseases, including cystic fibrosis. Excess neutrophil extracellular trap (NET) formation, or NETosis, is associated with many pathological conditions including chronic inflammation. Despite the known therapeutic benefits of hypertonic saline, its underlying mechanisms are not clearly understood. Therefore, we aimed to elucidate the effects of hypertonic saline in modulating NETosis. For this purpose, we purified human neutrophils and induced NETosis using agonists such as diacylglycerol mimetic phorbol myristate acetate (PMA), Gram-negative bacterial cell wall component lipopolysaccharide (LPS), calcium ionophores (A23187 and ionomycin from Streptomyces conglobatus), and bacteria (Pseudomonas aeruginosa and Staphylococcus aureus). We then analyzed neutrophils and NETs using Sytox green assay, immunostaining of NET components and apoptosis markers, confocal microscopy, and pH sensing reagents. This study found that hypertonic NaCl suppresses nicotinamide adenine dinucleotide phosphate oxidase (NADPH2 or NOX2)-dependent NETosis induced by agonists PMA, Escherichia coli LPS (0111:B4 and O128:B12), and P. aeruginosa. Hypertonic saline also suppresses LPS- and PMA- induced reactive oxygen species production. It was determined that supplementing H2O2 reverses the suppressive effect of hypertonic saline on NOX2-dependent NETosis. Many of the aforementioned suppressive effects were observed in the presence of equimolar concentrations of choline chloride and osmolytes (d-mannitol and d-sorbitol). This suggests that the mechanism by which hypertonic saline suppresses NOX2-dependent NETosis is via neutrophil dehydration. Hypertonic NaCl does not significantly alter the intracellular pH of neutrophils. We found that hypertonic NaCl induces apoptosis while suppressing NOX2-dependent NETosis. In contrast, hypertonic solutions do not suppress NOX2-independent NETosis. Although hypertonic saline partially suppresses ionomycin-induced NETosis, it enhances A23187-induced NETosis, and it does not alter S. aureus-induced NETosis. Overall, this study determined that hypertonic saline suppresses NOX2-dependent NETosis induced by several agonists; in contrast, it has variable effects on neutrophil death induced by NOX2-independent NETosis agonists. These findings are important in understanding the regulation of NETosis and apoptosis in neutrophils.

Absence of endemic measles transmission in a highly vaccinated population from 1999 to 2008: implications of sustained measles elimination in Taiwan.

BACKGROUND: Measles remains a leading vaccine-preventable cause of child mortality worldwide. The impact of vaccination programs can be seen in the increasingly low incidence of measles. However, cases of measles continue to occur in low numbers every year in Taiwan. We assessed the epidemiology of measles in Taiwan from 1999 to 2008 with a focus on domestic versus imported cases. METHODS: We analyzed the data reported to surveillance systems at the Taiwan Center for Disease Control, where viral isolation was performed. RESULTS: A total of 84 measles cases were reported from 1999 to 2008 in Taiwan with the incidence of measles varying from 0 to 1.5 per 1,000,000 people per year, peaking in 2002 and again in 2008. The incidence decreased with increasing age in both males and females. Among the 84 reported measles cases, 39 (46%) originated internationally, 8 (10%) were epidemiologically linked to imported cases and the source was unknown in 37 (44%) of the cases. The unknown-source cases were analyzed for potential evidence of endemic measles transmission. Most of the measles cases that occurred in Taiwan from 1999 to 2008 were associated with imported cases. No endemic transmission of measles in Taiwan was identified. CONCLUSIONS: This study suggests that maintaining the high rate of vaccination coverage is needed to prevent future outbreak and sustain the elimination of measles in Taiwan.

Synthesis, structure, redox properties and azide binding for a series of biphenyl-based Cu(II) complexes.

A series of biphenyl-based N(3)O ligands, 2, 4, 6, and 8 were synthesized and their Cu(II) complexes prepared. These complexes were characterized by a combination of elemental analysis, FAB-MS, UV-vis spectroscopy and electrochemistry. The structure of [Cu(N(3)O-mpy-NO2)Cl2], 12 [N(3)O-mpy = 2-(3-pyridylmethylimino)-2'-(2-methylaminophenol)biphenyl], was solved and showed that the ligand coordinates through the three nitrogens with the phenol oxygen uncoordinated. Titration of azide anion into solutions of the complexes in methanol resulted in the appearance of a new band between 485-495 nm at the expense of the starting peak at 380 nm. Cyclic voltammetry studies indicated that the complexes undergo quasi-reversible one-electron reductions in acetonitrile at potentials between 0.13-0.58 V vs. Ag/AgCl. The complexes were found to be weakly active for the oxidation of di-tert-butyl catechol (DTBC).