A time-driven activity-based costing model to improve health-care resource use in Mirebalais, Haiti.

Background: In resource-limited settings, efficiency is crucial to maximise resources available for patient care. Time driven activity-based costing (TDABC) estimates costs directly from clinical and administrative processes used in patient care, thereby providing valuable information for process improvements. TDABC is more accurate and simpler than traditional activity-based costing because it assigns resource costs to patients based on the amount of time clinical and staff resources are used in patient encounters.

Geospatial mapping to estimate timely access to surgical care in nine low-income and middle-income countries.

Background: The Lancet Commission on Global Surgery calls for universal access to safe, affordable, and timely surgical care. Two requisite components of timely access are (1) the ability to reach a surgical provider in a given timeframe, and (2) the ability to receive appropriately prompt care from that provider. We chose a threshold of 2 h in view of its relevance in time-to-death in post-partum haemorrhage.

A qualitative study exploring contextual challenges to surgical care provision in 21 LMICs.

Background: Billions of people worldwide are without access to safe, affordable, and timely surgical care. The Lancet Commission on Global Surgery (LCoGS) conducted a qualitative study to understand the contextual challenges to surgical care provision in low-income and middle-income countries (LMICs), and how providers overcome them.

Methods: A semi-structured interview was administered to 143 care providers in 21 LMICs using stratified purposive sampling to include both urban and rural areas and reputational case selection to identify individual providers.

Endoscopic mucosal resection of early oesophageal neoplasia in patients requiring anticoagulation: is it safe?

Background And Aim: Endoscopic mucosal resection (EMR) has become the standard treatment for early oesophageal neoplasia. The mucosal defect caused by EMR usually takes several weeks to heal. Despite guidelines on high-risk endoscopic procedures in patients on anticoagulation, evidence is lacking whether EMR is safe in such patients.

Diffusion MRI with Semi-Automated Segmentation Can Serve as a Restricted Predictive Biomarker of the Therapeutic Response of Liver Metastasis.

Purpose: To assess the value of semi-automated segmentation applied to diffusion MRI for predicting the therapeutic response of liver metastasis.

Methods: Conventional diffusion weighted magnetic resonance imaging (MRI) was performed using b-values of 0, 150, 300 and 450s/mm(2) at baseline and days 4, 11 and 39 following initiation of a new chemotherapy regimen in a pilot study with 18 women with 37 liver metastases from primary breast cancer. A semi-automated segmentation approach was used to identify liver metastases.

Evaluation of CAIX and CAXII Expression in Breast Cancer at Varied O2 Levels: CAIX is the Superior Surrogate Imaging Biomarker of Tumor Hypoxia.

Purpose: Hypoxia is commonly observed in regions of primary tumors and metastases, and is associated with resistance to treatment, more aggressive tumor phenotypes and poor prognosis. Reliable and validated imaging biomarkers of hypoxia are needed for pre-clinical studies and clinical use. Expression of cell-surface carbonic anhydrases IX and XII (CAIX and CAXII) in tumor cells has been associated with tumor hypoxia.

The effect of SUV discretization in quantitative FDG-PET Radiomics: the need for standardized methodology in tumor texture analysis.

FDG-PET-derived textural features describing intra-tumor heterogeneity are increasingly investigated as imaging biomarkers. As part of the process of quantifying heterogeneity, image intensities (SUVs) are typically resampled into a reduced number of discrete bins. We focused on the implications of the manner in which this discretization is implemented.

Out-of-pocket expenses incurred by patients obtaining free breast cancer care in Haiti: A pilot study.

Background: Women in low- and middle-income countries account for 51% of breast cancer cases globally. These patients often delay seeking care and, therefore, present with advanced disease, partly because of fear of catastrophic health care expenses. Although there have been efforts to make health care affordable in low- and middle-income countries, the financial burden of out-of-pocket (OOP) expenses for nonmedical costs, such as transportation and lost wages, often is overlooked.

Therapeutic Targeting of the Warburg Effect in Pancreatic Cancer Relies on an Absence of p53 Function.

The "Warburg effect" describes a peculiar metabolic feature of many solid tumors, namely their increased glucose uptake and high glycolytic rates, which allow cancer cells to accumulate building blocks for the biosynthesis of macromolecules. During aerobic glycolysis, pyruvate is preferentially metabolized to lactate by the enzyme lactate dehydrogenase-A (LDH-A), suggesting a possible vulnerability at this target for small-molecule inhibition in cancer cells. In this study, we used FX11, a small-molecule inhibitor of LDH-A, to investigate this possible vulnerability in a panel of 15 patient-derived mouse xenograft (PDX) models of pancreatic cancer.

Semiquantitative Computed Tomography Characteristics for Lung Adenocarcinoma and Their Association With Lung Cancer Survival.

Unlabelled: In this study we developed 25 computed tomography descriptors among 117 patients with lung adenocarcinoma to semiquantitatively assess their association with overall survival. Pleural attachment was significantly associated with an increased risk of death and texture was most important for distinguishing histological subtypes. This approach has the potential to support automated analyses and develop decision-support clinical tools.

Tongue-tie Repair: Z-Plasty Vs Simple Release.

Introduction: Ankyloglossia is a congenital anomaly in which the lingual frenulum is unusually short and thick, thus decreasing tongue mobility. In the context of the newborn or young infant it is a subject of ongoing controversy within and between medical specialties. The controversy involves not only the definition but also the management of this anomaly.

Heterogeneity in intratumoral regions with rapid gadolinium washout correlates with estrogen receptor status and nodal metastasis.

Purpose: To evaluate heterogeneity within tumor subregions or "habitats" via textural kinetic analysis on breast dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) for the classification of two clinical prognostic features; 1) estrogen receptor (ER)-positive from ER-negative tumors, and 2) tumors with four or more viable lymph node metastases after neoadjuvant chemotherapy from tumors without nodal metastases.

Materials And Methods: Two separate volumetric DCE-MRI datasets were obtained at 1.5T, comprised of bilateral axial dynamic 3D T1 -weighted fat suppressed gradient recalled echo-pulse sequences obtained before and after gadolinium-based contrast administration.

Impact of metabolic heterogeneity on tumor growth, invasion, and treatment outcomes.

Histopathologic knowledge that extensive heterogeneity exists between and within tumors has been confirmed and deepened recently by molecular studies. However, the impact of tumor heterogeneity on prognosis and treatment remains as poorly understood as ever. Using a hybrid multiscale mathematical model of tumor growth in vascularized tissue, we investigated the selection pressures exerted by spatial and temporal variations in tumor microenvironment and the resulting phenotypic adaptations.

Metabolism and its sequelae in cancer evolution and therapy.

Cancers progress through a series of events that can be characterized as "somatic evolution." A central premise of Darwinian evolutionary theory is that the environment imparts pressure to select for species that are most fit within that particular microenvironmental context. Furthermore, the rate of evolution is proportional to both (1) the strength of the environmental selection and (2) the phenotypic variance of the selected population.

Intermittent hypoxia selects for genotypes and phenotypes that increase survival, invasion, and therapy resistance.

Hypoxia in tumors correlates with greater risk of metastases, increased invasiveness, and resistance to systemic and radiation therapy. The evolutionary dynamics that links specific adaptations to hypoxia with these observed tumor properties have not been well investigated. While some tumor populations may experience fixed hypoxia, cyclical and stochastic transitions from normoxia to hypoxia are commonly observed in vivo.

Quantitative computed tomographic descriptors associate tumor shape complexity and intratumor heterogeneity with prognosis in lung adenocarcinoma.

Two CT features were developed to quantitatively describe lung adenocarcinomas by scoring tumor shape complexity (feature 1: convexity) and intratumor density variation (feature 2: entropy ratio) in routinely obtained diagnostic CT scans. The developed quantitative features were analyzed in two independent cohorts (cohort 1: n = 61; cohort 2: n = 47) of patients diagnosed with primary lung adenocarcinoma, retrospectively curated to include imaging and clinical data. Preoperative chest CTs were segmented semi-automatically.

Analysis of the entire ryanodine receptor type 1 and alpha 1 subunit of the dihydropyridine receptor (CACNA1S) coding regions for variants associated with malignant hyperthermia in Australian families.

Defects in the genes coding for the skeletal muscle ryanodine receptor (RYR1) and alpha 1 subunit of the dihydropyridine receptor (CACNA1S) have been identified as causative for malignant hyperthermia (MH). Sixty-two MH susceptible individuals presenting to the same diagnostic centre had copy deoxyribonucleic acid, derived from muscle ribonucleic acid, sequenced to identify variants with the potential to be responsible for the MH phenotype in both RYR1 and CACNA1S. These genetic findings were combined with clinical episode details and in vitro contracture test results to improve our understanding of the Australian MH cohort.

Synthesis of [(18) F] 4-amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide (IDO5L): a novel potential PET probe for imaging of IDO1 expression.

To synthesize (18) F-labeled positron emission tomography (PET) ligands, reliable labeling techniques inserting (18) F into a target molecule are necessary. The (18) F-fluorobenzene moiety has been widely utilized in the synthesis of (18) F-labeled compounds. The present study utilized [(18) F]-labeled aniline as intermediate in [(18) F]-radiolabeling chemistry for the facile radiosynthesis of 4-amino-N-(3-chloro-4-fluorophenyl)-N'-hydroxy-1,2,5-oxadiazole-3-carboximidamide ([(18) F]IDO5L) as indoleamine 2,3-dioxygenase 1 (IDO1) targeted tracer.

Pyruvate sensitizes pancreatic tumors to hypoxia-activated prodrug TH-302.

Background: Hypoxic niches in solid tumors harbor therapy-resistant cells. Hypoxia-activated prodrugs (HAPs) have been designed to overcome this resistance and, to date, have begun to show clinical efficacy. However, clinical HAPs activity could be improved.

Introversion and medical student education: challenges for both students and educators.

Issue: Introversion is one of the personality factors that has been shown to be associated with performance in medical school. Prior cross-sectional studies highlight performance evaluation differences between introverted and extraverted medical students, though the mechanisms and implications of these differences remain relatively unexplained and understudied. This gap in the literature has become more salient as medical schools are employing more interactive learning strategies into their curricula which may disproportionately challenge introverted learners.