Artificial Intelligence for Radiotherapy Auto-Contouring: Current Use, Perceptions of and Barriers to Implementation.

AIMS: Artificial intelligence has the potential to transform the radiotherapy workflow, resulting in improved quality, safety, accuracy and timeliness of radiotherapy delivery. Several commercially available artificial intelligence-based auto-contouring tools have emerged in recent years. Their clinical deployment raises important considerations for clinical oncologists, including quality assurance and validation, education, training and job planning. Despite this, there is little in the literature capturing the views of clinical oncologists with respect to these factors. MATERIALS AND METHODS: The Royal College of Radiologists realises the transformational impact artificial intelligence is set to have on our specialty and has appointed the Artificial Intelligence for Clinical Oncology working group. The aim of this work was to survey clinical oncologists with regards to perceptions, current use of and barriers to using artificial intelligence-based auto-contouring for radiotherapy. Here we share our findings with the wider clinical and radiation oncology communities. We hope to use these insights in developing support, guidance and educational resources for the deployment of auto-contouring for clinical use, to help develop the case for wider access to artificial intelligence-based auto-contouring across the UK and to share practice from early-adopters. RESULTS: In total, 78% of clinical oncologists surveyed felt that artificial intelligence would have a positive impact on radiotherapy. Attitudes to risk were more varied, but 49% felt that artificial intelligence will decrease risk for patients. There is a marked appetite for urgent guidance, education and training on the safe use of such tools in clinical practice. Furthermore, there is a concern that the adoption and implementation of such tools is not equitable, which risks exacerbating existing inequalities across the country. CONCLUSION: Careful coordination is required to ensure that all radiotherapy departments, and the patients they serve, may enjoy the benefits of artificial intelligence in radiotherapy. Professional organisations, such as the Royal College of Radiologists, have a key role to play in delivering this.

Temporal expression of inflammatory mediators in brain basilar artery vasculitis and cerebrospinal fluid of rabbits with coccidioidal meningitis.

Strokes due to transmural vasculitis associated with coccidioidal meningitis result in significant morbidity and mortality. The immunological and inflammatory processes responsible are poorly understood. To determine the inflammatory mediators, i.e. cytokines, chemokines, iNOS, matrix metalloproteinase-9 (MMP-9), that possibly contribute to vasculitis, temporal mRNA expression in brain basilar artery samples and MMP-9 protein in the CSF of male NZW rabbits infected intracisternally with 6.5 x 10(4) arthroconidia of Coccidioides immitis were assessed. Five infected and 3 sham-injected rabbits at each time point were euthanized 4, 9, 14 and 20 days post infection. All infected rabbits had neurological abnormalities and severe vasculitis in the basilar arteries on days 9-20. In basilar arteries of infected animals versus controls, mRNAs encoding for IL-6, iNOS, IFN-gamma, IL-2, MCP-1, IL-1beta, IL-10, TNF-alpha, CCR-1, MMP-9, TGF-beta, as well as MMP-9 protein in CSF, were found to be significantly up-regulated. Thus, this study identified inflammatory mediators associated with CNS vasculitis and meningitis due to C. immitis infection. Assessment of the individual contribution of each mediator to vasculitis may offer novel approaches to the treatment of coccidioidal CNS infection. This study also provides unique methodology for immunology studies in a rabbit model.

Handedness in boys with gender identity disorder.

Handedness preference was assessed in 205 boys with gender identity disorder and 205 clinical control boys referred for other reasons. Boys with gender identity disorder were significantly more likely to be left-handed than the clinical control boys (19.5% vs. 8.3%, respectively). The boys with gender identity disorder, but not the clinical control boys, also had a significantly higher rate of left-handedness compared to three independent, general population studies of nonreferred boys (11.8%; N = 14,253) by Hardyck, Goldman, and Petrinovich (1975), Calnan and Richardson (1976), and Eaton, Chipperfield, Ritchot, and Kostiuk (1996). Left-handedness appears to be a behavioral marker of an underlying neurobiological process associated with gender identity disorder in boys.

Levels of mycophenolic acid and its glucuronide derivative in the plasma of liver, small bowel and kidney transplant patients receiving tacrolimus and cellcept combination therapy.

In order to help assess the usefulness of mycophenolate mofetil (MMF) as an immunosuppressive agent in recipients of organs other than kidneys, we measured the trough levels of the active metabolite of MMF, mycophenolic acid (MPA), and its inactive glucuronide derivative (MPAG), in the plasma of liver (n = 83) and small bowel transplant patients (n = 15) receiving MMF in combination with tacrolimus. These levels were compared with a group of renal transplant patients (n = 25) receiving the same drug regimen. All patient groups were otherwise comparable except the small bowel patient group which contained more pediatric patients (average age 18.7 +/- 3.9 years), and, therefore, received a higher average drug dose (in mg/kg). Despite this, these patients displayed the lowest levels of MPA of any group (0.39 +/- 0.08 microg/ml, P < 0.001 vs. 1.10 +/- 0.17 microg/ml for liver transplant patients, P < 0.001 or 2.46 +/- 0.37 microg/ml for renal transplant patients, P < 0.001). There were no statistically significant differences in MPAG levels between any of the groups. Although preliminary, these data demonstrate significant transplanted organ-specific differences in MMF pharmacology and/or bioavailability, and suggest the need for separate evaluation of MMF dosing for each transplant type.

Fraternal birth order and sexual orientation in pedophiles.

Whether homosexual pedophiles have more older brothers (a higher fraternal birth order) than do heterosexual pedophiles was investigated. Subjects were 260 sex offenders (against children age 14 or younger) and 260 matched volunteer controls. The subject's relative attraction to male and female children was assessed by phallometric testing in one analysis, and by his offense history in another. Both methods showed that fraternal birth order correlates with homosexuality in pedophiles, just as it does in men attracted to physically mature partners. Results suggest that fraternal birth order (or the underlying variable it represents) may prove the first identified universal factor in homosexual development. Results also argue against a previous explanation of the high prevalence of homosexuality in pedophiles (25% in this study), namely, that the factors that determine sexual preference in pedophiles are different from those that determine sexual preference in men attracted to adults. An alternative explanation in terms of canalization of development is suggested.

Birth order in a contemporary sample of gay men.

The birth order of a contemporary North American sample of 97 gay men was quantified using Slater's Index. For the 84 probands with at least one sibling, the results showed a late mean birth order compared with the expected value of .50. Additional birth order indices derived from Slater's Index suggested that the mean later birth order was accounted for more strongly by the proband's number of older brothers than by his number of older sisters. The present findings constitute a replication of a series of recent studies and add to the growing body of evidence that birth order is a reliable correlate of sexual orientation in males.

Sexual orientation and handedness in men and women: a meta-analysis.

Recent findings suggest that sexual orientation has an early neurodevelopmental basis. Handedness, a behavioral marker of early neurodevelopment, has been associated with sexual orientation in some studies but not in others. The authors conducted a meta-analysis of 20 studies that compared the rates of non-right-handedness in 6,987 homosexual (6,182 men and 805 women) and 16,423 heterosexual (14,808 men and 1,615 women) participants. Homosexual participants had 39% greater odds of being non-right-handed. The corresponding values for homosexual men (20 contrasts) and women (9 contrasts) were 34% and 91%, respectively. The results support the notion that sexual orientation in some men and women has an early neurodevelopmental basis, but the factors responsible for the handedness-sexual orientation association require elucidation. The authors discuss 3 possibilities: cerebral laterality and prenatal exposure to sex hormones, maternal immunological reactions to the fetus, and developmental instability.

Laparoscopically assisted colon resection for colon carcinoma: perioperative results and long-term outcome.

BACKGROUND: The role of laparoscopic colon resection in the management of colon cancer is unclear. The aims of this study were to compare perioperative results and long-term outcomes in patients randomized to either open (O) or laparoscopically assisted (LA) colon resection for colon cancer. METHODS: A prospective randomized trial comparing O to LA colon resection was conducted from January 1993 to November 1995. Preoperative workup, intraoperative results, complications, length of stay, pathologic findings, and long-term outcomes were compared between the two groups. Statistical analysis was performed with t-test. Follow-up periods ranged from 3.5 to 6.3 years (mean, 4.9 years). RESULTS: No port-site or abdominal wall recurrences were noted in any patients. [table: see text] CONCLUSIONS: These results suggest that laparoscopically assisted colon resection for malignant disease can be performed safely, with morbidity, mortality, and en bloc resections comparable with those of open laparotomy. Long-term (5-year) follow-up assessment shows similar outcomes in both groups of patients, demonstrating definite perioperative advantages with LA surgery and no perioperative or long-term disadvantages.

Laparoscopic management of gastric diverticula.

Gastric diverticular are rare and usually are diagnosed incidentally on radiographic examination. Surgical treatment, consisting of simple excision or inversion of the diverticulum, has been reserved for patients with proven symptoms or complications. These procedures have typically required laparotomy, but with the development of advanced endoscopic techniques, a minimally invasive approach may be appropriate. The authors report two cases of gastric diverticula managed laparoscopically and review the literature related to this entity. Between 1993 and 1996, two patients were evaluated for dyspepsia-like gastrointestinal complaints. Both patients were found to have a gastric diverticulum on a contrast study, and one diverticulum was also seen on upper endoscopy. Laparoscopic resection was undertaken in both cases. Flexible gastroscopy was performed intraoperatively to help localize the diverticulum, which was resected with an endoscopic stapling device. Nissen fundoplication was performed in conjunction with the diverticulectomy in the second patient for gastroesophageal reflux. Both procedures were completed laparoscopically without complications. The postoperative course was uneventful in both patients. At long-term follow-up, the patients are asymptomatic. This experience indicates that laparoscopic resection of symptomatic gastric diverticula is a feasible alternative to laparotomy. A prospective analysis to verify the safety and efficacy of this procedure should be done.

Laparoscopic reoperation for failed antireflux procedures.

BACKGROUND: Laparoscopic fundoplication has become the criterion standard for the surgical treatment of gastroesophageal reflux disease. Recently, several patients were referred with recurrent symptoms of gastroesophageal reflux disease or severe dysphagia following previous antireflux surgery for possible laparoscopic reoperation. HYPOTHESIS: To determine the safety and efficacy of this procedure. DESIGN: Case series, consecutive sample. SETTING: University-affiliated and community tertiary care hospitals. PATIENTS: Prospective study of 27 consecutive patients undergoing attempted laparoscopic reoperation for symptoms of recurrent gastroesophageal reflux disease or intractable dysphagia following antireflux surgery. Patients were available for follow-up for 1 to 60 months postoperatively. INTERVENTIONS: All patients underwent preoperative workup and attempted laparoscopic reoperation for treatment of symptoms. MAIN OUTCOME MEASURES: Data were collected on preoperative symptoms and evaluation, operative time, blood loss, time to regular diet, length of hospitalization, morbidity, mortality, and long-term results. RESULTS: Twenty-six patients underwent successful laparoscopic operations, with no mortality and minimal morbidity. One patient underwent conversion to open laparotomy and then developed a proximal gastric leak, which was treated conservatively. Twenty-four patients began a liquid diet by postoperative day 1, and most were discharged from the hospital by postoperative day 3. One patient required dilation for postoperative dysphagia. The remaining patients are doing well and none have required treatment with acid-reducing medication. CONCLUSIONS: Although technically challenging, laparoscopic reoperation for recurrent gastroesophageal reflux disease can be performed safely and with excellent results. In the hands of experienced endoscopic surgeons, patients who have undergone unsuccessful antireflux surgery should be offered laparoscopic reoperation.

Evidence that tacrolimus augments the bioavailability of mycophenolate mofetil through the inhibition of mycophenolic acid glucuronidation.

We previously reported an unexpected augmentation of mycophenolic acid (MPA) levels (trough and AUC0-12) in patients receiving mycophenolate mofetil (MMF) in combination with tacrolimus versus patients receiving the same dose of MMF in combination with cyclosporin A (CsA). This finding was accompanied by a corresponding reduction of the inactive glucuronide metabolite of MPA (MPAG) in patients, suggesting that tacrolimus may effect the conversion of MPA to MPAG by the enzyme UDP-glucuronosyltransferase (UDPGT). To investigate this possibility directly, UDPGT was extracted from human liver and kidney tissue and its activity was characterized using MPA as a substrate in vitro, assessing the conversion of MPA to MPAG using analysis by high-performance liquid chromatography. With crude microsomal preparations, amounts of UDPGT at least 100 times higher in specific activity (i.e., units to milligrams of protein) could be extracted per gram of tissue from kidney as opposed to liver. This result did not appear to be related to the coextraction of a liver-specific UDPGT inhibitor because initial enzyme kinetic values (Vmax and km) were identical for kidney and liver extracts, and further purification of the liver enzyme did not enhance activity (as is seen when inhibitors are removed during purification). With further UDPGT purification (approximately 200-fold) from kidney extracts using a combination of ammonium sulfate precipitation, followed by anion exchange, hydroxyapatite, and size exclusion chromatography, the enzyme was more than 80% pure when assessed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Initial enzyme kinetic analysis of this purified product showed a km value for MPA of 35.4+/-5.7 microg/mL and a Vmax of 2.87+/-0.31 MPAG produced per hour (n = 7). The addition of clinically relevant concentrations of CsA (200-1,000 ng/mL) or tacrolimus (10-25 ng/mL) resulted in a dose-dependent inhibition of the UDPGT enzyme by both agents with tacrolimus, which was approximately 60-fold more efficient as an inhibitor. The calculated inhibition constants (KI) of tacrolimus and CsA for the purified UDPGT were 27.3+/-5.6 ng/ml and 2,518+/-1473 ng/ml. respectively. Both agents displayed an inhibition profile characteristic of a competitive inhibitor (substrate) that could be demonstrated in a reciprocal experiment with CsA as a substrate, but not with tacrolimus. This finding suggested that the significantly more efficient inhibition of UDPGT by tacrolimus may occur by a more complicated mechanism that is yet to be determined.

Gender constancy judgments in children with gender identity disorder: evidence for a developmental lag.

Gender constancy judgments in children referred for problems in their gender identity development (N = 206) and controls (N = 95) were compared. On Slaby and Frey's (1975) gender constancy interview, the gender-referred children performed more poorly than the controls at three stage levels: gender identity, gender stability, and gender consistency. On the Boy-Girl Identity Task, a second measure of gender constancy (Emmerich et al., 1977), the gender-referred children also performed more poorly. Gender-referred children who had not attained gender consistency engaged in significantly less same-sex-typed play on a free-play task than the gender-referred children who had, but there were no gender consistency effects for the controls. Two other measures of sex-typed behavior were unrelated to gender consistency. In the gender-referred group alone, children who "failed" the gender identity or gender stability stages were more likely to draw an opposite-sex person first on the Draw-a-Person test and to evince more affective gender confusion on the Gender Identity Interview (Zucker et al., 1993) than children who had "passed." It is concluded that children referred for problems in their gender identity development have a developmental lag in gender constancy acquisition. Possible reasons for the lag are discussed.

Adoptee overrepresentation among clinic-referred boys with gender identity disorder.

OBJECTIVES: To test the hypothesis that adoptees are overrepresented among a sample of clinic-referred boys with gender identity problems (N = 238). To compare the adoptees and nonadoptees on demographic, behaviour problem, and gender-typed measures. METHOD: The percentage of clinic-referred boys with gender identity problems adopted in the first 2 years of life ("early adoptees") was compared to the base rate of boys adopted in Ontario. Parent-report and behavioural measures were used to compare the early adoptees with "late adoptees" (adopted after the second year of life) and nonadoptees. RESULTS: The percentage of boys with gender identity problems who were early adoptees (7.6%) was significantly higher than the base rate of males adopted in Ontario in the first 2 years of life (1.5%). Both the early and late adoptees were significantly less intelligent than the nonadoptees. The early adoptees also had significantly higher externalizing T scores on the Child Behavior Checklist than did the late adoptees and the nonadoptees. The 3 groups did not differ in the percentage who met the complete Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria for gender identity disorder and on 4 other measures of gender-typed behaviour. CONCLUSION: Adoptees are overrepresented among clinic-referred boys with gender identity problems. The reasons for this finding are not clear but may be accounted for by general risk factors that increase the likelihood of clinical referral or by psychosocial and biological factors associated with adoption.

The relation of birth order to sexual orientation in men and women.

Homosexual men have a higher mean birth order than do heterosexual men, primarily because they have a greater number of older brothers. The purpose of this study was to determine whether the same difference occurs in homosexual vs heterosexual women. The probands were 964 homosexual and heterosexual, male and female volunteers, from whom birth order data were collected with self-administered questionnaires. The homosexual men had more older brothers than the heterosexual men, but they did not have more older sisters, younger brothers, or younger sisters. The homosexual women did not differ from the heterosexual women with regard to any class of sibling. These results are consistent with the hypothesis that the high birth order of homosexual men reflects the progressive immunization of certain mothers to H-Y antigen by succeeding male fetuses, and the increasing effects of H-Y antibodies on sexual differentiation of the brain in succeeding male fetuses.

Is growth influencing diameter and function of laparoscopic TESA hepaticojejunostomy? A comparison of adult minipigs and juvenile domestic swine.

Current treatment of obstructive jaundice includes endoscopic stenting and open surgical bypass. To combine the advantages of surgical bypass with the minimal invasive approach of endoscopic stenting we developed a laparoscopic technique, transient endoluminally stented anastomosis (TESA). As shown previously, small-diameter anastomoses (e.g., hepaticojejunostomy) by TESA technique can be performed reliably in growing domestic swine. This further preclinical trial was designed to exclude growth of the animals as the main reason for these excellent results. After ligation of the common bile duct, a laparoscopic Roux-en-y hepaticojejunostomy was performed 7 days later by TESA with a reabsorbable radiopaque polyglycolic acid stent. In group A (n = 7) growing domestic pigs and in group B (n = 5) adult minipigs were operated on. Laboratory parameters were controlled weekly. Stent degradation was followed by weekly abdominal x-ray. At necropsy 6 months after surgery, cholangiography was performed and the anastomoses were measured. Mean weight gain was 140.7 +/- 10.9 kg in domestic pigs versus 5.8 +/- 1.6 kg in minipigs. Cholestasis normalized within 7 days postoperatively. Duration of stenting was not significantly different between groups. Cholangiography at necropsy showed immediate runoff through the anastomoses in both groups. The diameter of the anastomosis was 4.7 +/- 0.5 mm in group A versus 3.0 +/- 0.4 mm in group B (p = 0.03). In conclusion, functionality of the small-diameter TESA hepaticojejunostomy is not related to age and growing factors in pigs, justifying its application in human as the next step of investigation.