Artificial intelligence model GPT4 narrowly fails simulated radiological protection exam.

This study assesses the efficacy of Generative Pre-Trained Transformers (GPT) published by OpenAI in the specialised domains of radiological protection and health physics. Utilising a set of 1064 surrogate questions designed to mimic a health physics certification exam, we evaluated the models' ability to accurately respond to questions across five knowledge domains. Our results indicated that neither model met the 67% passing threshold, with GPT-3.5 achieving a 45.3% weighted average and GPT-4 attaining 61.7%. Despite GPT-4's significant parameter increase and multimodal capabilities, it demonstrated superior performance in all categories yet still fell short of a passing score. The study's methodology involved a simple, standardised prompting strategy without employing prompt engineering or in-context learning, which are known to potentially enhance performance. The analysis revealed that GPT-3.5 formatted answers more correctly, despite GPT-4's higher overall accuracy. The findings suggest that while GPT-3.5 and GPT-4 show promise in handling domain-specific content, their application in the field of radiological protection should be approached with caution, emphasising the need for human oversight and verification.

Plasma HPV cell-free DNA monitoring in advanced HPV-associated oropharyngeal cancer.

Background: Measuring cell-free (cf)DNA in blood and tissues holds significant potential as a minimally invasive method for disease monitoring in cancer. Cancers arising in the oropharynx and causally linked to human papillomavirus (HPV) represent an ideal model in which to interrogate these methods. Patients and methods: We designed an ultrasensitive and quantitative droplet digital (dd)PCR assay to detect the five dominant high-risk HPV subtypes linked to oropharyngeal cancer (OPC). We enrolled a pilot observational cohort of 22 patients with advanced HPV+ OPC to evaluate the clinical utility of our assay and explore its predictive and prognostic potential. Results: Total tumor burden (TTB) strongly correlated with HPV cfDNA levels (R = 0.91, P = 2.3×10-6) at this cohort size, and in most cases more distant anatomic disease locations predicted increasing HPV cfDNA levels. All participants demonstrated a corresponding change in their HPV cfDNA levels at a median of 16 days (range 12-38) before restaging scans confirming treatment response or progression. Patients with locoregional disease in the head and neck or pulmonary-only metastases had worse outcomes (P = 0.01). Both TTB and median plasma HPV cfDNA levels negatively correlated with survival (R=-0.65, P = 0.01; R=-0.48, P = 0.05, respectively). Conclusion(s): Plasma HPV cfDNA monitoring recapitulates fluctuations in disease status. While blood-based HPV DNA monitoring does not currently have a role in managing HPV+ OPC, these data speak to their broad clinical potential in an era of precision medicine.

Comparison of CE-FDG-PET/CT with CE-FDG-PET/MR in the evaluation of osseous metastases in breast cancer patients.

BACKGROUND: Despite improvements in treatments, metastatic breast cancer remains difficult to cure. Bones constitute the most common site of first-time recurrence, occurring in 40-75% of cases. Therefore, evaluation for possible osseous metastases is crucial. Technetium 99 ((99)Tc) bone scintigraphy and fluorodexossyglucose (FDG) positron emission tomography (PET)-computed tomography (PET-CT) are the most commonly used techniques to assess osseous metastasis. PET magnetic resonance (PET-MR) imaging is an innovative technique still under investigation. We compared the capability of PET-MR to that of same-day PET-CT to assess osseous metastases in patients with breast cancer. METHODS: One hundred and nine patients with breast cancer, who underwent same-day contrast enhanced (CE)-PET-CT and CE-PET-MR, were evaluated. CE-PET-CT and CE-PET-MR studies were interpreted by consensus by a radiologist and a nuclear medicine physician. Correlations with prior imaging and follow-up studies were used as the reference standard. Binomial confidence intervals and a χ(2) test were used for categorical data, and paired t-test was used for the SUVmax data; a non-informative prior Bayesian approach was used to estimate and compare the specificities. RESULTS: Osseous metastases affected 25 out 109 patients. Metastases were demonstrated by CE-PET-CT in 22 out of 25 patients (88%±7%), and by CE-PET-MR in 25 out of 25 patients (100%). CE-PET-CT revealed 90 osseous metastases and CE-PET-MR revealed 141 osseous metastases (P<0.001). The estimated sensitivity of CE-PET-CT and CE-PET-MR were 0.8519 and 0.9630, respectively. The estimated specificity for CE-FDG-PET-MR was 0.9884. The specificity of CE-PET-CT cannot be determined from patient-level data, because CE-PET-CT yielded a false-positive lesion in a patient who also had other, true metastases. CONCLUSIONS: CE-PET-MR detected a higher number of osseous metastases than did same-day CE-PET-CT, and was positive for 12% of the patients deemed osseous metastasis-negative on the basis of CE-PET-CT.

In vivo reflectance confocal microscopy of shave biopsy wounds: feasibility of intraoperative mapping of cancer margins.

BACKGROUND: Reflectance confocal microscopy (RCM) images skin at cellular resolution and has shown utility for the diagnosis of nonmelanoma skin cancer in vivo. Topical application of aluminium chloride (AlCl(3)) enhances contrast in RCM images by brightening nuclei. OBJECTIVES: To investigate feasibility of RCM imaging of shave biopsy wounds using AlCl(3) as a contrast agent. METHODS: AlCl(3) staining was optimized, in terms of concentration vs. immersion time, on excised tissue ex vivo. RCM imaging protocol was tested in patients undergoing shave biopsies. The RCM images were retrospectively analysed and compared with the corresponding histopathology. RESULTS: For 35% AlCl(3) , routinely used for haemostasis in clinic, minimum immersion time was determined to be 1 min. We identified three consistent patterns of margins on RCM mosaic images by varying depth: epidermal margins, peripheral dermal margins, and deep dermal margins. Tumour islands of basal cell carcinoma were identified at peripheral or deep dermal margins, correlating on histopathology with aggregates of neoplastic basaloid cells. Atypical cobblestone or honeycomb patterns were identified at the epidermal margins in squamous cell carcinomas, correlating with a proliferation of atypical keratinocytes extending to biopsy margins. CONCLUSIONS: RCM imaging of shave biopsy wounds is feasible and demonstrates the future possibility of intraoperative mapping in surgical wounds.

In vivo imaging of tumors with protease-activated near-infrared fluorescent probes.

We have developed a method to image tumor-associated lysosomal protease activity in a xenograft mouse model in vivo using autoquenched near-infrared fluorescence (NIRF) probes. NIRF probes were bound to a long circulating graft copolymer consisting of poly-L-lysine and methoxypolyethylene glycol succinate. Following intravenous injection, the NIRF probe carrier accumulated in solid tumors due to its long circulation time and leakage through tumor neovasculature. Intratumoral NIRF signal was generated by lysosomal proteases in tumor cells that cleave the macromolecule, thereby releasing previously quenched fluorochrome. In vivo imaging showed a 12-fold increase in NIRF signal, allowing the detection of tumors with submillimeter-sized diameters. This strategy can be used to detect such early stage tumors in vivo and to probe for specific enzyme activity.

Select men benefit from androgen deprivation therapy delivered with salvage radiation therapy after prostatectomy.

BACKGROUND: Which men benefit most from adding androgen deprivation therapy (ADT) to salvage radiation therapy (SRT) after prostatectomy has not clearly been defined; therefore, we evaluated the impact of ADT to SRT on failure-free survival (FFS) in men with a rising or persistent PSA after prostatectomy. METHODS: We identified 332 men who received SRT after prostatectomy from 1987 to 2010. Recursive partitioning analysis (RPA) identified favorable, intermediate and unfavorable groups based on the risk of failure after SRT alone. Kaplan-Meier and log-rank tests compared FFS with and without ADT. RESULTS: Forty-three percent received SRT alone and 57% received SRT with ADT (median 6.6 months (interquartile range (IQR) 5.8-18.1) ADT). Median SRT dose was 70 Gy (IQR 70-70), and median follow-up after SRT was 6.7 years (IQR 4.5-10.8). On Cox's proportional hazard regression, ADT improved FFS (adjusted hazard ratio 0.60, 95% confidence interval: 0.42-0.86; P=0.006). RPA classified unfavorable disease as negative surgical margins (SMs) and preradiation PSA of ⩾0.5 ng ml-1. Favorable disease had neither adverse factor, and intermediate disease had one adverse factor. The addition of ADT to SRT improved 5-year FFS for men with unfavorable disease (70.3% vs 23.4%; P<0.001) and intermediate disease (69.8% vs 48.0%; P=0.003), but not for men with favorable disease (81.2% vs 78.0%; P=0.971). CONCLUSIONS: The addition of ADT to SRT appears to improve FFS for men with a preradiation PSA of ⩾0.5 ng ml-1 or with negative SM at prostatectomy. Men with involved surgical margins and PSA <0.5 ng ml-1 appear to be at a lower risk of failure after SRT alone and may not derive as much benefit from the administration of ADT with SRT. These results are hypothesis-generating only, and further prospective data are required to see if ADT can safely be omitted in this select group of men.

A new alkylated benzoquinone from rhizomes of Iris kumaonensis.

A novel alkylated unsaturated p-benzoquinone designated as 3-[(z)-12'-heptadecenyl]-2-hydroxy-5-methoxy-1,4-benzoquinone was isolated from hexane extract of the rhizomes of Iris kumaonensis and it's structure was confirmed by extensive spectroscopic analysis, IR, MS, HREIMS, 1D, 2D NMR and comparison with the literature data of known compounds.

In vivo imaging of proteolytic enzyme activity using a novel molecular reporter.

The single biggest challenge facing in vivo imaging techniques is to develop biocompatible molecular beacons that are capable of specifically and accurately measuring in vivo targets at the protein, RNA, or DNA level. Our efforts have focused on developing activatable imaging probes to measure specific enzyme activities in vivo. Using cathepsin D as a model target protease, we synthesized a long-circulating, synthetic graft copolymer bearing near-infrared (NIR) fluorochromes positioned on cleavable substrate sequences. In its native state, the reporter probe was essentially nonfluorescent at 700 nm due to energy resonance transfer among the bound fluorochromes (quenching) but became brightly fluorescent when the latter were released by cathepsin D. NIR fluorescence signal activation was linear over at least 4 orders of magnitude and specific when compared with scrambled nonsense substrates. Using matched rodent tumor models implanted into nude mice expressing or lacking the targeted protease, it could be shown that the former generated sufficient NIR signal to be directly detectable and that the signal was significantly different compared with negative control tumors. The developed probes should find widespread applications for real-time in vivo imaging of a variety of clinically relevant proteases, for example, to detect endogenous protease activity in disease, to monitor the efficacy of protease inhibitors, or to image transgene expression.

In vitro and in vivo 31P nuclear magnetic resonance measurements of metabolic changes post radiation.

Radiation-induced metabolic changes previously observed in tumors using phosphorus nuclear magnetic resonance spectroscopy include changes in the relative amounts of the phospholipid precursors phosphoethanolamine and phosphocholine, increases in membrane catabolites, and increases in energy status. To elucidate the degree to which these in vivo alterations are a result of intrinsic cellular changes versus radiation-induced systemic effects, the Radiation-Induced Fibrosarcoma-1 tumor model was studied before and over the course of 7 days after a single dose of 17 Gy. In vivo studies were performed with tumors implanted in C3H/He mice; in vitro studies used cells that were perfused in agarose gel threads after being grown, radiated, and maintained in monolayer. The statistically significant increases in the downfield component of the phosphomonoester peak, which consists primarily of phosphoethanolamine, compared to the upfield component, phosphocholine, were qualitatively similar in vivo and in vitro post radiation. Statistically significant increases in the membrane catabolite glycerophosphocholine, a phosphodiester, were also observed in both tumors and cell culture after irradiation, with a greater percentage change in vitro. This suggests that changes in the phosphomonoester and phosphodiester concentrations are primarily an intrinsic effect of radiation on cellular metabolism, modulated to a lesser degree by systemic effects. In contrast, the statistically significant increases in energy status after the 17-Gy dose showed markedly different temporal responses in the two systems. Therefore, energy status changes observed in vivo are due largely to systemic changes, such as changes in blood flow. Flow cytometry data obtained from the cultured cells showed a sustained increase in the G2-M fraction starting at 24 h, the first time point measured after irradiation, which continued for the 7 days studied post radiation. These data indicate that the in vivo changes detected by nuclear magnetic resonance in phospholipid precursors and catabolites occur directly at the cellular level and may reflect cell death or growth inhibition after antineoplastic therapy.

Radiation dose-dependent changes in tumor metabolism measured by 31P nuclear magnetic resonance spectroscopy.

The effects of radiation dose upon a hypoxic murine mammary carcinoma were followed using 31P nuclear magnetic resonance spectroscopy. Animals were studied before and over the course of 9 days after tumors were irradiated with a single dose of 0, 4, 8, or 17 Gy. The current data is compared to our previous studies of the effects of 32 or 65 Gy on the same tumor model. The energy status of the tumors, as reflected in nucleotide triphosphate:Pi and phosphocreatine:Pi ratios, improved after receiving a dose of 8 to 65 Gy and decreased after receiving 0 or 4 Gy doses. The energy status of the 8- to 65-Gy dose cohorts reached a maximum between 1 and 4 days after irradiation. Additionally, the change in the hypoxic cell fraction 48 h after a 17-Gy dose was determined; it was calculated from changes in the doses required to control 50% of the tumors post radiation for clamped (hypoxic) and unclamped (normoxic) tumors in parallel animal cohorts. A significant decrease compared to preirradiation values was observed in the hypoxic cell fraction following 17 Gy irradiation. This decrease was temporally coincident with increases in tumor energy status measured using nuclear magnetic resonance and was similar to our previously reported results of the change in hypoxic fraction 48 h after a 32-Gy dose. Changes in the relative ratio of phosphomonoesters showed a strong dose dependence after irradiation. The downfield component of the phosphomonoester peak, which consists largely of phosphoethanolamine, increased relative to the upfield component, phosphocholine. This dose-dependent ratio reached a maximum approximately 7 days post radiation. Changes in the levels of membrane phospholipid precursors may be related to alterations in cell proliferation or may be a result of radiation-induced membrane damage.

Quantitative changes in tumor metabolism, partial pressure of oxygen, and radiobiological oxygenation status postradiation.

Hypoxia is considered to be a major cause of tumor radioresistance. Reoxygenation of previously hypoxic areas after a priming dose of radiation is associated with an increase in tumor radiosensitivity. In a study of a hypoxic mammary carcinoma, 31P nuclear magnetic resonance spectra showed statistically significant increases in metabolite ratios (phosphocreatine/Pi and nucleotide triphosphate/Pi) after 65 and 32 Gy. The maximum changes in metabolite ratios after 32 Gy occurred at 48 h, although significant changes were detected at 24 h. A corresponding increase in the mean tumor pO2 (polarographic microelectrode measurements) and a decrease in hypoxic cell fraction [changes in paired (clamped versus unclamped) tumor control dose for 50% of tumors] were also shown to occur 48 h after a priming dose of 32 Gy. A significant increase in the mean tumor pO2, phosphocreatine/Pi, and nucleotide triphosphate/Pi, compared to initial values, was noted at 24, 48, and 96 h post 65-Gy radiation. An increase in the downfield component of the phosphomonoester peak relative to the upfield component (phosphoethanolamine), is also noted after doses of 65 and 32 Gy. These are likely to be due to cell kill and/or decreased cell proliferation. In this tumor model, 31P nuclear magnetic resonance spectroscopic changes postradiation are temporally coincident with and may be indicative of tumor reoxygenation as measured by the tumor control dose for 50% of tumors and oxygen-sensitive microelectrodes.

MRI-guided prostate adaptive radiotherapy - A systematic review.

Dose escalated radiotherapy improves outcomes for men with prostate cancer. A plateau for benefit from dose escalation using EBRT may not have been reached for some patients with higher risk disease. The use of increasingly conformal techniques, such as step and shoot IMRT or more recently VMAT, has allowed treatment intensification to be achieved whilst minimising associated increases in toxicity to surrounding normal structures. To support further safe dose escalation, the uncertainties in the treatment target position will need be minimised using optimal planning and image-guided radiotherapy (IGRT). In particular the increasing usage of profoundly hypo-fractionated stereotactic therapy is predicated on the ability to confidently direct treatment precisely to the intended target for the duration of each treatment. This article reviews published studies on the influences of varies types of motion on daily prostate position and how these may be mitigated to improve IGRT in future. In particular the role that MRI has played in the generation of data is discussed and the potential role of the MR-Linac in next-generation IGRT is discussed.

A novel index for predicting intraocular pressure reduction following cataract surgery.

AIM: The results of a study designed to investigate the predictive value of preoperative anterior chamber depth (ACD) and intraocular pressure (IOP) are reported. The relation between these factors and their effect on the reduction in IOP following phacoemulsification cataract surgery was also studied. METHODS: The ACD and IOP were prospectively measured in 103 non-glaucomatous eyes of 103 patients who underwent uneventful phacoemulsification and posterior chamber intraocular lens (PCIOL) implantation. Other data which were recorded included best corrected visual acuity, axial length, lens thickness, and severity of lens opacity. RESULTS: The ACD increased by a mean (SD) of 1.10 (0.44) mm (p<0.00001) and this increase was significantly and inversely related to preoperative ACD (r(2) = 68%; p<0.01). IOP dropped by a mean of 2.55 (1.78) mm Hg following cataract surgery (p<0.0001), and this reduction was significantly and positively related to preoperative IOP (r(2) = 56%; p<0.01), and significantly and inversely related to preoperative ACD (r(2) = 21%; p<0.01). A novel ratio, the pressure to depth (PD) ratio (preoperative IOP/preoperative ACD), was found to be significantly and positively related to the surgically induced reduction in IOP (r(2) = 73%; p<0.01), and IOP was reduced by > or =4 mm Hg in all patients with a PD ratio >7. CONCLUSION: The reduction in IOP following cataract surgery was found to be positively related to preoperative IOP, and inversely related to preoperative ACD. Furthermore, these results indicate that a novel index, the PD ratio, is strongly predictive for IOP reduction following cataract extraction, and may prove useful in surgical decision making.

Ahmed valve drainage implant surgery in the management of paediatric aphakic glaucoma.

BACKGROUND: Paediatric aphakic glaucoma presents months or years after cataract surgery in children and is a major long term complication. The results of surgical treatment are poor and many children require multiple and repeat procedures with poor visual outcomes. METHODS: 13 children (19 eyes) had Ahmed valve implantation surgery, nine of the children had previous procedures such as cycloablation or trabeculectomy. Mitomycin was used at surgery in some patients and valve needling with Healon GV and 5-fluorouracil in some blebs after surgery. SF(6) gas was also used at the time of surgery in most children to reform the anterior chamber. RESULTS: 12 of the children (18 eyes) achieved intraocular pressure control of 15 mm Hg or less with a valve alone or with additional medical therapy. CONCLUSION: Ahmed valve implantation surgery alone or in combination with medical therapy is successful and safe in the management of paediatric aphakic glaucoma.

Burns in Nepal: A population based national assessment.

BACKGROUND: Burns are ranked in the top 15 leading causes of the burden of disease globally, with an estimated 265,000 deaths annually and a significant morbidity from non-fatal burns, the majority located in low and middle-income countries. Given that previous estimates are based on hospital data, the purpose of this study was to explore the prevalence of burns at a population level in Nepal, a low income South Asian country. METHODS: A cluster randomized, cross sectional countrywide survey was administered in Nepal using the Surgeons OverSeas Assessment of Surgical Need (SOSAS) from May 25th to June 12th, 2014. Fifteen of the 75 districts of Nepal were randomly chosen proportional to population. In each district, three clusters, two rural and one urban, were randomly selected. The SOSAS survey has two portions: the first collects demographic data about the household's access to healthcare and recent deaths in the household; the second is structured anatomically and designed around a representative spectrum of surgical conditions, including burns. RESULTS: In total, 1350 households were surveyed with 2695 individuals with a response rate of 97%. Fifty-five burns were present in 54 individuals (2.0%, 95% CI 1.5-2.6%), mean age 30.6. The largest proportion of burns was in the age group 25-54 (2.22%), with those aged 0-14 having the second largest proportion (2.08%). The upper extremity was the most common anatomic location affected with 36.4% of burns. Causes of burns included 60.4% due to hot liquid and/or hot objects, and 39.6% due to an open fire or explosion. Eleven individuals with a burn had an unmet surgical need (20%, 95% CI 10.43-32.97%). Barriers to care included facility/personnel not available (8), fear/no trust (1) and no money for healthcare (2). CONCLUSION: Burns in Nepal appear to be primarily a disease of adults due to scalds, rather than the previously held belief that burns occur mainly in children (0-14) and women and are due to open flames. This data suggest that the demographics and etiology of burns at a population level vary significantly from hospital level data. To tackle the burden of burns, interventions from all the public health domains including education, prevention, healthcare capacity and access to care, need to be addressed, particularly at a community level. Increased efforts in all spheres would likely lead to a significant reduction of burn-related death and disability.

Redesigning services for the management of vitreomacular traction and macular hole.

Vitreomacular traction (VMT) and VMT with macular hole (MH) are serious conditions, being associated with visual disturbance, for example, metamorphopsia, and diminished visual acuity (VA). Pars plana vitrectomy is the routine treatment for symptomatic VMT and VMT+MH. However, ocriplasmin has demonstrated favourable efficacy and safety in specific patient groups with VMT/MH and is now recommended as a treatment option for certain patients by the National Institute of Health and Care Excellence. This means that services for managing patients with VMT/MH may need to be revised, as patients can now potentially receive treatment earlier in the course of the disease. VMT triage clinics could provide a more efficient way of managing VMT/MH patients. Patient assessment should always include high-definition optical coherence tomography, as this is the most accurate means of assessing abnormalities in the vitreoretinal (VR) interface, and an accurate measurement of best-corrected VA. It has been proposed that patients with VMT+MH be managed as a routine 6-week referral, with the complete patient journey-from initial referral to treatment-taking no longer than 6 months. It is important that patients are entered onto VR surgical lists so that there is no delay if ocriplasmin treatment is unsuccessful. Patients will need appropriate counselling about the expected outcomes and possible side effects of ocriplasmin treatment. One-year follow-up data should be collected by treatment centres in order to evaluate the new VMT service.

Factors associated with improved biochemical response to neoadjuvant androgen deprivation therapy before definitive radiation therapy in prostate cancer patients.

BACKGROUND: In prostate cancer patients treated with androgen deprivation therapy (ADT) and radiation therapy (RT), a pre-RT PSA level 0.5 ng ml(-1), determined after neoadjuvant ADT and before RT, predicts for worse survival measures. The present study sought to identify patient, tumor and treatment characteristics associated with the pre-RT PSA in prostate cancer patients. METHODS: We reviewed the charts of all patients diagnosed with intermediate- and high-risk prostate cancer and treated with a combination of neoadjuvant (median, 2.2 and 2.5 months, respectively), concurrent, and adjuvant ADT and RT between 1990 and 2011. RESULTS: A total of 170 intermediate- and 283 high-risk patients met inclusion criteria. On multivariate analysis, both intermediate- and high-risk patients with higher pre-treatment PSA (iPSA) were significantly less likely to achieve a pre-RT PSA <0.5 ng ml(-1) (iPSA 10.1-20 ng ml(-1): P=0.005 for intermediate risk; iPSA 10.1-20 ng ml(-1): P=0.005, iPSA >20 ng ml(-1): P<0.001 for high risk). High-risk patients undergoing total androgen blockade were more likely to achieve a pre-RT PSA <0.5 ng ml(-1) (P=0.031). We observed an interaction between race and type of neoadjuvant ADT (P=0.074); whereas African-American men on total androgen blockade reached pre-RT PSA <0.5 ng ml(-1) as frequently as other men on total androgen blockade (P=0.999), African-American men on luteinizing hormone-releasing hormone (LH-RH) agonist monotherapy/orchiectomy were significantly less likely to reach pre-RT PSA <0.5 ng ml(-1) compared with other men on LH-RH monotherapy/orchiectomy (P=0.001). CONCLUSIONS: Our findings suggest that total androgen blockade in the neoadjuvant period may be beneficial compared with LH-RH monotherapy for achieving a pre-RT PSA <0.5 ng ml(-1) in African-American men with high-risk prostate cancer. In addition, men with higher iPSA are more likely to have a pre-RT PSA greater than 0.5 ng ml(-1) in response to neoadjuvant ADT and are therefore candidates for clinical trials testing newer, more aggressive hormone-ablative therapies.