Overview of medical physics education and research programs in a non-academic environment.

Northwest Medical Physics Center (NMPC) is a nonprofit organization that provides clinical physics support to over 35 radiation therapy facilities concentrated in the Pacific Northwest. Although clinical service is the primary function of NMPC, the diverse array of clinical sites and physics expertise has allowed for the establishment of structured education and research programs, which are complementary to the organization's clinical mission. Three clinical training programs have been developed at NMPC: a therapy medical physics residency program accredited by the Commission on Accreditation of Medical Physics Education Programs (CAMPEP), an Applied Physics Technologist (APT) program, and a summer undergraduate internship program. A partnership has also been established with a major radiation oncology clinical vendor for the purposes of validating and testing new clinical devices across multiple facilities. These programs are managed by a dedicated education and research team at NMPC, made up of four qualified medical physicists (QMPs). The education and research work has made a significant contribution to the organization's clinical mission, and it has provided new training opportunities for early-career physicists across many different clinical environments. Education and research can be incorporated into nonacademic clinical environments, improving the quality of patient care, and increasing the number and type of training opportunities available for medical physicists.

A KLF6-driven transcriptional network links lipid homeostasis and tumour growth in renal carcinoma.

Transcriptional networks are critical for the establishment of tissue-specific cellular states in health and disease, including cancer. Yet, the transcriptional circuits that control carcinogenesis remain poorly understood. Here we report that Kruppel like factor 6 (KLF6), a transcription factor of the zinc finger family, regulates lipid homeostasis in clear cell renal cell carcinoma (ccRCC). We show that KLF6 supports the expression of lipid metabolism genes and promotes the expression of PDGFB, which activates mTOR signalling and the downstream lipid metabolism regulators SREBF1 and SREBF2. KLF6 expression is driven by a robust super enhancer that integrates signals from multiple pathways, including the ccRCC-initiating VHL-HIF2A pathway. These results suggest an underlying mechanism for high mTOR activity in ccRCC cells. More generally, the link between super enhancer-driven transcriptional networks and essential metabolic pathways may provide clues to the mechanisms that maintain the stability of cell identity-defining transcriptional programmes in cancer.

Endogenous HIF2A reporter systems for high-throughput functional screening.

Tissue-specific transcriptional programs control most biological phenotypes, including disease states such as cancer. However, the molecular details underlying transcriptional specificity is largely unknown, hindering the development of therapeutic approaches. Here, we describe novel experimental reporter systems that allow interrogation of the endogenous expression of HIF2A, a critical driver of renal oncogenesis. Using a focused CRISPR-Cas9 library targeting chromatin regulators, we provide evidence that these reporter systems are compatible with high-throughput screening. Our data also suggests redundancy in the control of cancer type-specific transcriptional traits. Reporter systems such as those described here could facilitate large-scale mechanistic dissection of transcriptional programmes underlying cancer phenotypes, thus paving the way for novel therapeutic approaches.

NF-κB-Dependent Lymphoid Enhancer Co-option Promotes Renal Carcinoma Metastasis.

Metastases, the spread of cancer cells to distant organs, cause the majority of cancer-related deaths. Few metastasis-specific driver mutations have been identified, suggesting aberrant gene regulation as a source of metastatic traits. However, how metastatic gene expression programs arise is poorly understood. Here, using human-derived metastasis models of renal cancer, we identify transcriptional enhancers that promote metastatic carcinoma progression. Specific enhancers and enhancer clusters are activated in metastatic cancer cell populations, and the associated gene expression patterns are predictive of poor patient outcome in clinical samples. We find that the renal cancer metastasis-associated enhancer complement consists of multiple coactivated tissue-specific enhancer modules. Specifically, we identify and functionally characterize a coregulatory enhancer cluster, activated by the renal cancer driver HIF2A and an NF-κB-driven lymphoid element, as a mediator of metastasis in vivo We conclude that oncogenic pathways can acquire metastatic phenotypes through cross-lineage co-option of physiologic epigenetic enhancer states.Significance: Renal cancer is associated with significant mortality due to metastasis. We show that in metastatic renal cancer, functionally important metastasis genes are activated via co-option of gene regulatory enhancer modules from distant developmental lineages, thus providing clues to the origins of metastatic cancer. Cancer Discov; 8(7); 850-65. ©2018 AACR.This article is highlighted in the In This Issue feature, p. 781.

Attitudes of medical students towards euthanasia in a multicultural setting.

A cross-sectional survey of 400 medical students of multicultural backgrounds at the University of Malaya was conducted to understand their attitudes towards euthanasia and factors related to medical decisions and ethical reasoning concerning the prolongation of life, the right to die and euthanasia. The student respondents completed self-administered questionnaires that comprised of twelve questions with multiple stems addressing personal perceptions, knowledge, attitudes, and decisions about euthanasia and the relief of suffering. The majority of respondents (52%) were for the withdrawal of active therapy in a patient suffering from a terminal painful disease while 48% of them were against it. Seventy-one percent of the students involved in the study were against the idea of active euthanasia i.e. the administration of a lethal injection. However, 27% of the respondents felt that there was a moral justification to assist patients to die. Thirty-two percent of the respondents favoured the legalization of euthanasia in Malaysia while 67% of them were strongly against it. The majority (61%) of respondents would not practice euthanasia as a doctor nor would they have performed on themselves if or when it became legal. The main issue surrounding euthanasia that concerned the respondents was the misuse of it by unethical practitioners and they felt that further debate on the matter was essential, both within the local and international communities.

Factors affecting nutritional status of Malaysian primary school children.

This paper investigates the nutritional status of a randomly selected cohort of school children and the factors affecting it. This random survey was conducted in the state of Selangor, involving 1,405 primary students (aged 9-10 years from 54 national primary schools). Physical examination was carried out on all the students. Information on the students was also obtained from the parents. Blood samples were taken by using the finger pricking technique. Body mass index (BMI) was used as a measure of physical growth. The students were mainly from urban areas (82.9%). The mean age was 9.71 years and a higher proportion was females (51%). Malays constituted 83.6%, Indians 11.6% and Chinese 4.2% of the study population. The mean weight and height were 32.30 kg and 135.18 cm respectively. The mean BMI was 17.42 kg/m2, with 1.2% of the students underweight, 76.3% normal BMI, 16.3% overweight and 6.3% were obese. Nutritional status was significantly related to blood pressure, history of breast feeding, eating fast food, taking canned/bottled drinks, income and educational level of parents. Significant differences in nutritional status between sexes and locations (rural/urban) were also found. The prevalence of overweight and obese children was of concern. There is thus an urgent need for the School Health Program to periodically monitor the school children's eating habits and physical growth. Appropriate counselling on nutritional intake and physical activities should be given not only to schoolchildren but also to their teachers and parents or caregivers.

Effects of nutritional status on academic performance of Malaysian primary school children.

Numerous factors are known to affect the academic performance of students. These include prenatal conditions, birth conditions, postnatal events, nutritional, socio-economic factors and environmental factors. This paper examines the nutritional status and its relationship with academic performance of 9-10 years old primary school children recruited randomly in Selangor, Malaysia. A standard self-administered questionnaire was utilized to obtain pertinent information and a face-to-face interview was also conducted with the parents. Results of the academic performances were extracted from the students' report cards. The intellectual performance was assessed using Raven's Coloured Progressive Matrices. Physical examination was also conducted on these students by doctors. Overall 1,405 students and 1,317 parents responded to the survey. Of these 83.6% were Malays, 11.6% Indians, and 4.2% Chinese. The majority of them (82.9%) were from urban areas. The female: male ratio was 51:49; mean age was 9.71 years. The mean height and weight were 32.3 kg and 135.2 cm respectively. Their mean BMI was 17.42 kg/cm2, with 0.9% underweight, 76.3% normal BMI, 16.3% overweight, and 6.3% obese. Academic performance was significantly correlated with breast feeding, income and educational level of their parents, BMI, and whether they have been taking breakfast. There was a weak correlation between presence of anaemia and intellectual performance. Improving the socio-economic status of the parents will lend a helping hand in the academic performance of the students. Since breast feeding is associated with better academic and intellectual performance it must be emphasized, particularly to expectant mothers in the antenatal clinics.

Isolation of Neospora caninum from a calf in Malaysia.

In order to attempt isolate the protozoan parasite Neospora caninum, an N. caninum seropositive pregnant Sahiwal Friesian cross heifer from a large-scale dairy farm in Malaysia was kept for observation until parturition at the Veterinary Research Institute, Ipoh. The heifer gave birth to a female calf that was weak, underweight and unable to rise. Precolostral serum from the calf had an N. caninum indirect fluorescent antibody test titre of 1:3200. It died 12 h after birth and necropsy was performed. Brain homogenate from the calf was inoculated into 10 BALB/c mice that were kept for 3 months after which brain tissue from the mice was inoculated onto 24 h fresh monolayer Vero cell lines. The cell cultures were examined daily until growth of intracellular protozoa was observed. DNA of the organisms from the cell cultures was analyzed by PCR and DNA sequencing. DNA fragments of the expected size were amplified from the isolate using N. caninum-specific primers, and sequence analysis of ITS1 clearly identified the isolate as N. caninum. This is the first successful isolation of N. caninum from a bovine in Malaysia, and the isolate is designated Nc-MalB1.

Comparison of matched BOLD and FAIR 4.0T-fMRI with [15O]water PET brain volumes.

Valid comparisons of functional activation volumes from fMRI and PET require accurate registration, matched spatial resolution, and if possible matched noise. We coregistered 4.0T-fMRI and PET volumes, using a series of linear and nonlinear transformations applied to the PET volumes. Because of the limited number of fMRI slices that were available, PET volumes were transformed to the fMRI space. Since 4.0T-fMRI and 4.0T-MRI volumes have significant spatial distortion due to magnet inhomogeneities, high resolution 1.5T-MRI volumes were nonlinearly transformed to 4.0T-MRI volumes as part of the transformation chain. The smoothing effects of these registration transformations were measured, in order to match the spatial resolution of the coregistered fMRI and PET volumes. Spatial resolution of the transformed PET volumes in the fMRI space was degraded by up to 60% due to the transformation process. Due to both the image acquisition characteristics and the coregistration process, the transformed PET volumes had a spatial resolution that was lower than that of tMRI. Therefore, significant smoothing of fMRI volumes was necessary to match their spatial resolution with that of the transformed PET volumes. Matching the spatial resolution of the fMRI volumes to those of the transformed PET volumes was achieved by matching the shape of their point spread functions. In order to do this, Gaussian kernels were employed to smooth the fMRI volumes. We were unable to simultaneously match the resolution and noise of fMRI and PET signals in the motor cortex. Activation maps derived from transformed PET and smoothed fMRI volumes were compared. Contralateral motor cortex was active in all modalities but there were large variations in the size of the activated region and its signal to noise ratio across BOLD, FAIR, and PET images within each subject. Nevertheless, the relative CBF changes measured by FAIR were consistent with those determined by PET.

A consistency monitor for radiation therapy treatments.

A thin, large area transparent transmission chamber mounted below the accessory tray is described and its suitability for daily treatment delivery consistency is investigated. The sensitivity of the detector to changes in monitor unit setting, field size, wedge size, missing blocks, and wedges is presented. Some of the other potential applications are also discussed.

Splenectomy in massive tropical splenomegaly: two-to six-year follow-up in 14 patients.

Between 1978 and 1982, 14 patients underwent splenectomy for disabling massive splenomegaly at the Regency Hospital in Wamena in the highlands of Irian Jaya, Indonesia. All patients were clinically diagnosed as having tropical splenomegaly syndrome (hyperreactive malarial splenomegaly), but in no case was the diagnosis confirmed. In May 1984 nurses and physicians caring for these 14 patients were asked to fill in a questionnaire regarding the patients' conditions. Two to 6 years after splenectomy, 8 of the 14 patients were alive and able to work; at least 6 of the 8 at normal or near normal capacity. One patient died 4 days after surgery and 5 died from 2 to 20 months after surgery. We conclude that splenectomy is beneficial for some highly selected patients with the clinical diagnosis of tropical splenomegaly syndrome.

Pulmonary embolism and venous thrombosis. A pattern of incidence and predisposing factors over 70 years.

Due to the frequency with which fatal pulmonary embolism gives rise to medicolegal issues when allegedly a sequel to some injury or surgical intervention, some baseline information as to the general incidence and major predisposing factors is offered, extracted from the records of a university pathology institute over a 70-year period. It is clear that the condition was vitually unrecognized during the early part of the century. Using modern autopsy techniques, the incidence of venous thrombosis can be shown to considerably higher than that revealed by more cursory routine examination. Though trauma and medical and surgical procedures are associated with the majority of fatal pulmonary emboli, there is medicolegal significance in the fact that an appreciable residue have no evidence of such predisposing factors.