Weibull parametric model for survival analysis in women with endometrial cancer using clinical and T2-weighted MRI radiomic features.

BACKGROUND: Semiparametric survival analysis such as the Cox proportional hazards (CPH) regression model is commonly employed in endometrial cancer (EC) study. Although this method does not need to know the baseline hazard function, it cannot estimate event time ratio (ETR) which measures relative increase or decrease in survival time. To estimate ETR, the Weibull parametric model needs to be applied. The objective of this study is to develop and evaluate the Weibull parametric model for EC patients' survival analysis. METHODS: Training (n = 411) and testing (n = 80) datasets from EC patients were retrospectively collected to investigate this problem. To determine the optimal CPH model from the training dataset, a bi-level model selection with minimax concave penalty was applied to select clinical and radiomic features which were obtained from T2-weighted MRI images. After the CPH model was built, model diagnostic was carried out to evaluate the proportional hazard assumption with Schoenfeld test. Survival data were fitted into a Weibull model and hazard ratio (HR) and ETR were calculated from the model. Brier score and time-dependent area under the receiver operating characteristic curve (AUC) were compared between CPH and Weibull models. Goodness of the fit was measured with Kolmogorov-Smirnov (KS) statistic. RESULTS: Although the proportional hazard assumption holds for fitting EC survival data, the linearity of the model assumption is suspicious as there are trends in the age and cancer grade predictors. The result also showed that there was a significant relation between the EC survival data and the Weibull distribution. Finally, it showed that Weibull model has a larger AUC value than CPH model in general, and it also has smaller Brier score value for EC survival prediction using both training and testing datasets, suggesting that it is more accurate to use the Weibull model for EC survival analysis. CONCLUSIONS: The Weibull parametric model for EC survival analysis allows simultaneous characterization of the treatment effect in terms of the hazard ratio and the event time ratio (ETR), which is likely to be better understood. This method can be extended to study progression free survival and disease specific survival. TRIAL REGISTRATION: ClinicalTrials.gov NCT03543215, https://clinicaltrials.gov/ , date of registration: 30th June 2017.

The Hammersmith Score optimises patient selection and predicts for overall survival in early-phase cancer trial participants independent of tumour burden.

INTRODUCTION: As tumour response rates are increasingly demonstrated in early-phase cancer trials (EPCT), optimal patient selection and accurate prognostication is paramount. Hammersmith Score (HS), a simple prognostic index derived on routine biochemical measures (Albumin <35g/L, Lactate Dehydrogenase (LDH) >450 IU/L, Sodium <135mmol/L) is a validated predictor of response and survival in EPCT participants. HS has not been validated in the cancer immunotherapy era. METHODS: We retrospectively analysed characteristics and outcomes of unselected referrals to our early-phase unit (12/2019-12/2022). Independent predictors for overall survival (OS) were identified from univariable and multivariable models. HS was calculated for 66 eligible trial participants and compared with the Royal Marsden Score (RMS) to predict OS. Multivariable logistic regression and c-index was used to compare predictive ability of prognostic models. RESULTS: Of 212 referrals, 147 patients were screened and 82 patients treated in EPCT. Prognostic stratification by HS identifies significant difference in median OS and HS was confirmed as a multivariable predictor for OS (HR: HS 1 vs. 0 2.51, 95%CI: 1.01-6.24, p=0.049; HS 2/3 vs. 0: 10.32, 95%CI: 2.15-49.62, p=0.004; C-index 0.771) with superior multivariable predictive ability than RMS (HR: RMS 2 vs. 0/1 5.46, 95%CI: 1.12-26.57, p=0.036; RMS 3 vs. 0/1 6.83, 95%CI: 1.15-40.53, p<0.001; C-index 0.743). CONCLUSIONS: HS is a validated prognostic index for patients with advanced cancer treated in the context of modern EPCTs, independent of tumour burden. HS is a simple, inexpensive prognostic tool to optimise referral for EPCT.

Next-Generation Remote Hand Assessments: Cross-Platform DIGITS Web Application.

Purpose: We have previously developed DIGITS, a platform for remote evaluation of range of motion, dexterity, and swelling of fingers for reducing barriers to accessing clinical resources. The current study was aimed at evaluating DIGITS across different devices with varied operating systems and camera resolutions using a single person's hands. Methods: Our team has now developed a web application version of the DIGITS platform, which makes it accessible on any device that is equipped with a camera, including computers, tablets, and smartphones. In the present study, we aimed to validate this web application by comparing flexion and extension measurements on the same person's hands using three different devices with cameras of different resolutions. The absolute difference, SD, standard mean error, and intraclass correlation coefficient were calculated. Additionally, equivalency testing was performed using the confidence interval approach. Results: Our findings indicated that the differences in degree measured between the devices ranged from 2° to 3° when digit extension was assessed (all hand landmarks are visible in the camera's direct view) and from 3° to 8° when digit flexion was assessed (some of the hand landmarks are hidden from view). The intraclass correlation coefficient of individual trials ranged from 0.82 to 0.96 for extension and 0.77 to 0.87 for flexion across all devices. Additionally, within a 90% confidence interval, our data showed equivalency with measurements using three different devices. Conclusions: The absolute differences were within an acceptable 9° tolerance for measurements taken between devices for flexion and extension. Equivalency was observed for measurements of finger range of motion taken using DIGITS, regardless of devices, platforms, or camera resolutions. Clinical relevance: In summary, the DIGITS web application has good test-retest reliability to generate data on finger range of motion for hand telerehabilitation. DIGITS can reduce costs to patients, providers, and health care facilities for conducting postoperative follow-up assessments.

Prediction of Deep Myometrial Infiltration, Clinical Risk Category, Histological Type, and Lymphovascular Space Invasion in Women with Endometrial Cancer Based on Clinical and T2-Weighted MRI Radiomic Features.

PURPOSE: To predict deep myometrial infiltration (DMI), clinical risk category, histological type, and lymphovascular space invasion (LVSI) in women with endometrial cancer using machine learning classification methods based on clinical and image signatures from T2-weighted MR images. METHODS: A training dataset containing 413 patients and an independent testing dataset consisting of 82 cases were employed in this retrospective study. Manual segmentation of the whole tumor volume on sagittal T2-weighted MRI was performed. Clinical and radiomic features were extracted to predict: (i) DMI of endometrial cancer patients, (ii) endometrial cancer clinical high-risk level, (iii) histological subtype of tumor, and (iv) presence of LVSI. A classification model with different automatically selected hyperparameter values was created. The area under the curve (AUC) of the receiver operating characteristic (ROC) curve, F1 score, average recall, and average precision were calculated to evaluate different models. RESULTS: Based on the independent external testing dataset, the AUCs for DMI, high-risk endometrial cancer, endometrial histological type, and LVSI classification were 0.79, 0.82, 0.91, and 0.85, respectively. The corresponding 95% confidence intervals (CI) of the AUCs were [0.69, 0.89], [0.75, 0.91], [0.83, 0.97], and [0.77, 0.93], respectively. CONCLUSION: It is possible to classify endometrial cancer DMI, risk, histology type, and LVSI using different machine learning methods.

Personalized Prehabilitation Improves Tolerance to Chemotherapy in Patients with Oesophageal Cancer.

BACKGROUND: Prehabilitation programmes aim to optimise patients before and after cancer treatment including surgery. Previous studies in surgical patients demonstrate that prehabilitation improves pre-operative fitness and overcomes the negative impact of neoadjuvant chemotherapy on fitness. The aim of this study was to assess the impact of prehabilitation on the tolerance of neoadjuvant chemotherapy in patients with oesophageal cancer. METHODS: Patients with oesophageal or gastroesophageal junction (GOJ) cancer from two oncology centres were retrospectively included in the present comparative cohort study; one provided a multimodal prehabilitation programme and one did not offer any prehabilitation. Tolerance of chemotherapy, defined as completion of the full chemotherapy regime as per protocol, was compared between the two groups. RESULTS: In terms of participants, 92 patients were included in this study, 47 patients in the prehabilitation cohort and 45 in the control cohort. Compared with the control group, the prehabilitation group demonstrated an improved rate of chemotherapy completion (p = 0.029). In multivariate analysis, participation in prehabilitation was significantly associated with an improved rate of chemotherapy completion. CONCLUSION: The findings of this exploratory study suggest that prehabilitation is associated with better tolerance for chemotherapy. Further research is needed to establish the long-term impact of prehabilitation on oncological outcomes.

An Integrated Clinical-MR Radiomics Model to Estimate Survival Time in Patients With Endometrial Cancer.

BACKGROUND: Determination of survival time in women with endometrial cancer using clinical features remains imprecise. Features from MRI may improve the survival estimation allowing improved treatment planning. PURPOSE: To identify clinical features and imaging signatures on T2-weighted MRI that can be used in an integrated model to estimate survival time for endometrial cancer subjects. STUDY TYPE: Retrospective. POPULATION: Four hundred thirteen patients with endometrial cancer as training (N = 330, 66.41 ± 11.42 years) and validation (N = 83, 67.60 ± 11.89 years) data and an independent set of 82 subjects as testing data (63.26 ± 12.38 years). FIELD STRENGTH/SEQUENCE: 1.5-T and 3-T scanners with sagittal T2-weighted spin echo sequence. ASSESSMENT: Tumor regions were manually segmented on T2-weighted images. Features were extracted from segmented masks, and clinical variables including age, cancer histologic grade and risk score were included in a Cox proportional hazards (CPH) model. A group least absolute shrinkage and selection operator method was implemented to determine the model from the training and validation datasets. STATISTICAL TESTS: A likelihood-ratio test and decision curve analysis were applied to compare the models. Concordance index (CI) and area under the receiver operating characteristic curves (AUCs) were calculated to assess the model. RESULTS: Three radiomic features (two image intensity and volume features) and two clinical variables (age and cancer grade) were selected as predictors in the integrated model. The CI was 0.797 for the clinical model (includes clinical variables only) and 0.818 for the integrated model using training and validation datasets, the associated mean AUC value was 0.805 and 0.853. Using the testing dataset, the CI was 0.792 and 0.882, significantly different and the mean AUC was 0.624 and 0.727 for the clinical model and integrated model, respectively. DATA CONCLUSION: The proposed CPH model with radiomic signatures may serve as a tool to improve estimated survival time in women with endometrial cancer. EVIDENCE LEVEL: 4 TECHNICAL EFFICACY: Stage 2.

Deep Ensemble Learning for Retinal Image Classification.

Purpose: Vision impairment affects 2.2 billion people worldwide, half of which is preventable with early detection and treatment. Currently, automatic screening of ocular pathologies using convolutional neural networks (CNNs) on retinal fundus photographs is limited to a few pathologies. Simultaneous detection of multiple ophthalmic pathologies would increase clinical usability and uptake. Methods: Two thousand five hundred sixty images were used from the Retinal Fundus Multi-Disease Image Dataset (RFMiD). Models were trained (n = 1920) and validated (n = 640). Five selected CNN architectures were trained to predict the presence of any pathology and categorize the 28 pathologies. All models were trained to minimize asymmetric loss, a modified form of binary cross-entropy. Individual model predictions were averaged to obtain a final ensembled model and assessed for mean area under the receiver-operator characteristic curve (AUROC) for disease screening (healthy versus pathologic image) and classification (AUROC for each class). Results: The ensemble network achieved a disease screening (healthy versus pathologic) AUROC score of 0.9613. The highest single network score was 0.9586 using the SE-ResNeXt architecture. For individual disease classification, the average AUROC score for each class was 0.9295. Conclusions: Retinal fundus images analyzed by an ensemble of CNNs trained to minimize asymmetric loss were effective in detection and classification of ocular pathologies than individual models. External validation is needed to translate machine learning models to diverse clinical contexts. Translational Relevance: This study demonstrates the potential benefit of ensemble-based deep learning methods on improving automatic screening and diagnosis of multiple ocular pathologies from fundoscopy imaging.

Minimally Invasive Rehabilitation of Posterior Erosive Tooth Wear: Two Case Reports of the One-Stage Dahl Approach.

Rehabilitation of posterior erosive tooth wear can be especially challenging in the presence of substantial tooth structure loss and limited inter-occlusal space. This article describes two case reports illustrating a conservative approach using the one-step Dahl approach in the management of localized posterior erosive tooth wear. The occlusal surfaces of worn teeth in both cases were successfully restored using direct composite resin and gold onlay, respectively. The material was placed in supra-occlusion during the initial stage. This technique enables intrusion of affected worn teeth and the opposing counterpart. Eruption of the remaining dentition will occur after two to three months to re-establish a complete occlusal relationship. With proper treatment planning, the one-step Dahl approach offers a simpler and predictable positive outcome in restoring structurally compromised posterior worn teeth.

Capillary module haemodynamics and mechanisms of blood flow regulation in skeletal muscle capillary networks: Experimental and computational analysis.

The capillary module (CM), consisting of parallel capillaries from terminal arteriole to post-capillary venule, is classically considered to be the building block of complex capillary networks. In skeletal muscle, CMs form interconnected columns spanning thousands of microns, which we recently described as the capillary fascicle. However, detailed evaluation of CM haemodynamics has not been described, and may provide insight into mechanisms of blood flow regulation in the microcirculation. We used intravital videomicroscopy from resting extensor digitorum longus muscle in rats (n = 9 networks, 112 capillary modules), as well as dual-phase computational modelling of blood flow in simulated CM geometries. We found that the mean driving pressure across CMs was 3.236 ± 1.833 mmHg. Red blood cell (RBC) flow was independent of CM resistance, and the ratio of blood flow in adjacent modules was not correlated with their ratio of resistances. In simulated CM geometries, increases to driving pressure produced a direct linear increase to RBC and plasma flow, with no changes to RBC distribution; increases to arteriolar inflow haematocrit resulted in increased RBC flow, but with viscosity-dependent increases to CM resistance. CM RBC flow heterogeneity was higher than plasma flow heterogeneity in experimental data, in contrast to simulated geometries, suggesting that time-dependent flow variability may have important consequences for RBC distribution. In summary, these findings suggest that CMs are active participants in microvascular flow regulation, likely achieved through adjustments to CM driving pressure using pre- and post-capillary loci of flow control. Increases to CM viscosity may be important during the regulation of functional hyperaemia. KEY POINTS: The capillary module (CM), consisting of parallel capillaries from the arteriole to venule, is classically considered to be the building block of capillary networks in skeletal muscle. A detailed evaluation of module haemodynamics may provide insight into mechanisms of blood flow regulation in the microcirculation. Using experimental data from resting skeletal muscle in rats, as well as dual-phase computational models of blood flow, we analysed haemodynamic relationships and the impact of variations to boundary conditions on red blood cell and plasma distribution. We showed that driving pressure across CMs is low, and that simulated increases to inflow haematocrit have important viscosity-dependent effects on module resistance. We found that red blood cell flow was independent from module resistance, which strongly suggests the regulation of driving pressure at the level of the capillary module using pre- and post-capillary loci of flow control. These findings place CMs as central participants in microvascular flow regulation, with important consequences for disease and functional hyperaemia.

The capillary fascicle in skeletal muscle: Structural and functional physiology of RBC distribution in capillary networks.

KEY POINTS: The capillary module, consisting of parallel capillaries from arteriole to venule, is classically considered as the building block of complex capillary networks. In skeletal muscle, this structure fails to address how blood flow is regulated along the entire length of the synchronously contracting muscle fibres. Using intravital video microscopy of resting extensor digitorum longus muscle in rats, we demonstrated the capillary fascicle as a series of interconnected modules forming continuous columns that align naturally with the dimensions of the muscle fascicle. We observed structural heterogeneity for module topology, and functional heterogeneity in space and time for capillary-red blood cell (RBC) haemodynamics within a module and between modules. We found that module RBC haemodynamics were independent of module resistance, providing direct evidence for microvascular flow regulation at the level of the capillary module. The capillary fascicle is an updated paradigm for characterizing blood flow and RBC distribution in skeletal muscle capillary networks. ABSTRACT: Capillary networks are the fundamental site of oxygen exchange in the microcirculation. The capillary module (CM), consisting of parallel capillaries from terminal arteriole (TA) to post-capillary venule (PCV), is classically considered as the building block of complex capillary networks. In skeletal muscle, this structure fails to address how blood flow is regulated along the entire length of the synchronously contracting muscle fibres, requiring co-ordination from numerous modules. It has previously been recognized that TAs and PCVs interact with multiple CMs, creating interconnected networks. Using label-free intravital video microscopy of resting extensor digitorum longus muscle in rats, we found that these networks form continuous columns of linked CMs spanning thousands of microns, herein denoted as the capillary fascicle (CF); this structure aligns naturally with the dimensions of the muscle fascicle. We measured capillary-red blood cell (RBC) haemodynamics and module topology (n = 9 networks, 327 modules, 1491 capillary segments). The average module had length 481 µm, width 157 µm and 9.51 parallel capillaries. We observed structural heterogeneity for CM topology, and functional heterogeneity in space and time for capillary-RBC haemodynamics within a module and between modules. There was no correlation between capillary RBC velocity and lineal density. A passive inverse relationship between module length and haemodynamics was remarkably absent, providing direct evidence for microvascular flow regulation at the level of the CM. In summary, the CF is an updated paradigm for characterizing RBC distribution in skeletal muscle, and strengthens the theory of capillary networks as major contributors to the signal that regulates capillary perfusion.

Prescription of opioids to post-operative orthopaedic patients at time of discharge from hospital: a prospective observational study.

BACKGROUND AND AIMS: Excessive opioid prescribing can lead to adverse consequences including stockpiling, misuse, dependency, diversion and mortality. Increased prescriptions to post-operative inpatients as part of their discharge planning may be a significant contributor. Primary aims included comparing the amount of opioids prescribed, consumed, left unused and their relationship with pain and functionality. METHODS: A total of 132 consecutive patients who underwent elective orthopaedic surgery were prospectively audited. Daily oral morphine equivalent (DME) of opioids prescribed was compared with opioids consumed and amount left unused 7-10 days after discharge. For analysis, patients were split into three groups: total knee replacement (TKR), hand surgery (Hands), and miscellaneous (Misc). RESULTS: The mean dose of opioid prescribed per patient was 108.5 mg DME. TKR consumed 33-35% more opioids than Misc (p=0.0283) and Hands (p=0.0975). Age was a significant independent factor for opioid consumption in the 50th and 75th percentiles of Hands (p≤0.05). An average of 36 mg DME per patient was left unused with Hands having the highest median DME (37 mg) unused. In the total cohort, 26% of patients were discharged with more DME than their last 24 h as an inpatient and had at least 50% of their tablets left unused at follow-up. CONCLUSIONS: Over-prescription of opioids occurs at discharge which can increase the risk of harm. New intervention is needed to optimise prescribing practises. IMPLICATIONS: Changes to prescribing habits and workplace culture are required to minimise unnecessary opioid prescribing but will be challenging to implement. A multi-layered approach of electronic prescribing, opioid stewardship and targeted educational awareness programmes is recommended.

Bilateral Condylar Hyperplasia-Nonsurgical Management: A Clinical Report.

Background: Patients present with malocclusions in the form of bilateral open bite with functional and esthetic challenges. These are particularly so whereby these are acquired through growth anomalies that create a change in the occlusal status whereby a patient has to adapt to the challenge of the occlusal change. While surgical intervention is a considered option to correct such changes, not all patients are willing to endure the consequences of this intervention and as such this report presents a conservative minimally invasive approach. Aim: This clinical report demonstrates a nonsurgical approach in the management of a patient with bilateral metabolically active condylar hyperplasia. Case report: The patient presented with a bilateral open bite with occlusal contacts only present on her second molars. The severity of the open bite was reported to be recently progressing and getting worse. This condition had impaired her chewing function and quality of life over an 8-year period. Bone scintigraphy was performed and metabolically active bilateral condylar hyperplasia was diagnosed. The patient refused surgical intervention and instead a conservative overlay denture was prescribed, which successfully restored her function and esthetics. Conclusion: Removable overlay dentures can be a relatively simple and effective treatment option for patients presenting with newly acquired bilateral open bites to give a functional and esthetic outcome. Clinical significance: This clinical report shows the conservative management of bilateral condylar hyperplasia with a simple removable overlay appliance. The occlusion has stabilized and the patient functions well. Keywords: Bone scintigraphy, Condylar hyperplasia, Open bite, Overlay denture.

Prevalence of Acute Deep Vein Thrombosis in Patients with Ankle and Foot Fractures Treated with Nonoperative Management-A Pilot Study.

The prevalence of deep vein thrombosis (DVT) among patients with ankle and foot fractures in Australia treated nonsurgically is unknown. Indications for thromboprophylaxis screening and management are unclear. The primary outcome was the prevalence rate of DVT among nonsurgically managed ankle and foot fracture patients. Patients were enrolled into a prospective cross-sectional pilot study at an outpatient hospital fracture clinic. DVT risk factors and symptoms were recorded at time of recruitment followed by referral for compression duplex ultrasonography. Independent t-test and Fisher exact test were used to assess the significance of these variables with DVT. A total of 72 patients were included in the final analysis. Overall, 11% (8/72) of patients had DVT-seven distal DVTs and one proximal DVT. Four were symptomatic including the patient with a proximal thrombus. In comparison, the majority of patients were asymptomatic of DVT (63/72). A significant risk factor found to be associated with DVT was age ≥ 45 (p = 0.013) years, and a lack of symptoms (p = 0.006) was associated with no DVT. This pilot study is the first in Australia to investigate the prevalence of DVT in this specific subgroup of patients. We found a prevalence of 11% of DVT in a small group of patients with age ≥ 45 years, being the only significant associated risk factor. Future larger scale prospective studies are warranted to confirm these results.

Surgery for Recurrent Uterine Cancer: Surgical Outcomes and Implications for Survival-A Case Series.

OBJECTIVE: The purpose of this study was to describe the patterns of relapse in uterine cancer (UC) and the role of surgery in the recurrent setting. METHODS: We describe surgical and clinical outcomes of all patients who underwent surgery for recurrent UC in a gynecological oncology tertiary referral center between May 1, 2013, and April 30, 2016. Progression-free survival and overall survival were estimated using Kaplan-Meier methods with the surgery at relapse being the starting point. RESULTS: We evaluated 15 patients with a median age of 66 years. The predominant histology was the endometrioid variant (n = 11; 73.3%). The median interval between the end of previous treatment and relapse surgery was 24 months (range, 8-164). Locoregional pelvic recurrences were the most common type of recurrence (n = 13; 86.7%) with the para-aortic lymph node space being the most commonly affected extrapelvic site (13%). Patients predominantly presented with a multifocal pattern of relapse (n = 10; 66.7%) requiring multivisceral resections such as bowel (n = 7; 46.6%) and/or bladder/ureteric resections (n = 8; 53.3%) to achieve complete tumor clearance. All patients were operated tumor free with a 30-day major morbidity and mortality rate of 6.7% and 0%, respectively. Five patients (33.3%) received postoperative chemotherapy or radiotherapy. Five patients (33.3%) relapsed, and 3 died within a mean follow-up of 12.4 months (95% confidence interval [CI], 6.5-18.2). Two of those patients had a sarcoma.Mean progression-free survival and overall survival for the entire cohort postrelapse surgery was 21.7 months (95%CI, 13.9-29.5) and 26.0 months (95%CI, 18.4-33.7), respectively. Survival was significantly worse in patients with nonendometrioid histology (P < 0.0001). CONCLUSIONS: Surgery for UC relapse seems feasible with acceptable morbidity and high complete resection rates despite the multifocal patterns of relapse in a selected group of patients in a reference center for gynecological cancers. Larger scale studies are warranted to establish the value of surgery at relapse for UC.

Post-Radiation Therapy Imaging Appearances in Cervical Carcinoma.

Locally advanced and node-positive cervical cancers are usually treated with external beam radiation therapy and intracavitary brachytherapy with concomitant chemotherapy. In patients with locally advanced cervical cancer, imaging plays a vital role in pretreatment planning, assessment of primary tumor response to treatment, follow-up, and evaluation of treatment-related complications. Radiation therapy planning is crucial to successful local and regional control of disease. Patient selection criteria for radiation therapy with concomitant chemotherapy are described, as is assessment of treatment response of the primary cervical tumor at magnetic resonance (MR) imaging. Image interpretation can be challenging because of radiation therapy-related changes in the pelvic organs. Expected changes in the bladder, bowel, and bone marrow after radiation therapy are described, and multimodality imaging findings at computed tomography, MR imaging, and fluorine 18 fluorodeoxyglucose positron emission tomography are illustrated. Complications after radiation therapy have declined over recent years because of targeted radiation therapy. These complications can be divided into acute and chronic effects, where acute toxic effects occur within weeks of treatment. Chronic complications include cervical stenosis, small bowel stricture, fistula formation, and insufficiency fractures. Imaging is an essential tool in the care of patients with cervical cancer treated with chemotherapy and radiation therapy. The reporting radiologist should be familiar with the expected imaging appearances of the pelvic organs after radiation therapy, as well as potential complications, to avoid pitfalls in image interpretation.

Hox11 genes regulate postnatal longitudinal bone growth and growth plate proliferation.

Hox genes are critical regulators of skeletal development and Hox9-13 paralogs, specifically, are necessary for appendicular development along the proximal to distal axis. Loss of function of both Hoxa11 and Hoxd11 results in severe malformation of the forelimb zeugopod. In the radius and ulna of these mutants, chondrocyte development is perturbed, growth plates are not established, and skeletal growth and maturation fails. In compound mutants in which one of the four Hox11 alleles remains wild-type, establishment of a growth plate is preserved and embryos develop normally through newborn stages, however, skeletal phenotypes become evident postnatally. During postnatal development, the radial and ulnar growth rate slows compared to wild-type controls and terminal bone length is reduced. Growth plate height is decreased in mutants and premature growth plate senescence occurs along with abnormally high levels of chondrocyte proliferation in the reserve and proliferative zones. Compound mutants additionally develop an abnormal curvature of the radius, which causes significant distortion of the carpal elements. The progressive bowing of the radius appears to result from physical constraint caused by the disproportionately slower growth of the ulna than the radius. Collectively, these data are consistent with premature depletion of forelimb zeugopod progenitor cells in the growth plate of Hox11 compound mutants, and demonstrate a continued function for Hox genes in postnatal bone growth and patterning.

Disseminated cancer in pregnancy: krukenberg tumour.

Disseminated cancer presenting in pregnancy is extremely rare and its presentation can easily be obscured by pregnancy and physiological changes that occur with it. This case describes a patient who was diagnosed incidentally following investigations for preeclampsia. Despite initially being thought to be of low risk, the final diagnosis was that of metastasis from a primary cancer of an unknown origin, most likely a gastric adenocarcinoma. Although patients are under thorough observation throughout their pregnancy, this case highlights the potential need for additional investigations or adjustment of current practices. It also draws attention to the lack of sufficient reporting of cancer in pregnancy, which, considering its rarity, greatly influences how patients are managed.

Rehabilitation of molar-incisor hypomineralization (MIH) complicated with localized tooth surface loss: a case report.

Molar-incisor hypomineralization (MIH) is a developmental enamel hypomineralized condition characteristically involving the first permanent molars and sometimes also the incisors. The affected teeth are predisposed to tooth surface loss (TSL) which may not only compromise the esthetics and function but also endanger the pulp and longevity of the teeth. This report describes the management of a patient with MIH complicated with localized TSL and lack of occlusal clearance due to dentoalveolar compensation. The atypical TSL pattern involved all anterior teeth and required the placement of Dahl appliances on both arches.

Rehabilitation of amelogenesis imperfecta using a reorganized approach: a case report.

Amelogenesis imperfecta is a genetic disorder that causes defective enamel development in both the primary and permanent dentitions. Significant tooth structure damage often results in various pulpal symptoms, occlusal disharmony, impaired function, and esthetic disfigurement. These problems pose great challenges to the clinician when rehabilitating patients with amelogenesis imperfecta. This case report describes an uncomplicated and logical way to reorganize, temporize, and completely restore an extensively damaged dentition caused by amelogenesis imperfecta.

Information search in the testing of quantified hypotheses: how "all," "most," "some," "few," and "none" hypotheses are tested.

A series of experiments examined how the search for information in the testing of hypotheses is affected by quantifiers that specify the frequency of the test relation. The experiments showed that a positive search is used more in the testing of propositions in which some instances are predicted to have the test relation than in the testing of propositions in which most or few instances are predicted to have the test relation. In addition, the studies demonstrated that a negative or disconfirmatory search is more likely to characterize tests of absolute hypotheses than tests of hypotheses of the majority or minority form. Finally, the findings indicated that a negative search also is more common in tests of hypotheses predicting the absence rather than the presence of a phenomenon. Thus, as expected, participants generally engaged in a diagnostic search rather than the confirmatory search for information that has been so ubiquitous in previous research.