Blockade of Discoidin Domain Receptor Signaling with Sitravatinib Reveals DDR2 as a Mediator of Neuroblastoma Pathogenesis and Metastasis.

Oncogene-driven expression and activation of receptor tyrosine kinases (RTK) promotes tumorigenesis and contributes to drug resistance. Increased expression of the kinases DDR2 (Discoid Domain Receptor 2), RET, PDGFRA, KIT, MET, and ALK (Anaplastic Lymphoma Kinase) independently correlate with decreased overall survival (OS) and event free survival (EFS) of pediatric neuroblastoma. The multikinase inhibitor sitravatinib targets DDR2, RET, PDGFRA, KIT and MET with low nanomolar activity and we therefore tested its efficacy against orthotopic and syngeneic tumor models. Sitravatinib markedly reduced cell proliferation and migration in vitro independently of MYCN (N-Myc proto-oncogene), ALK, or MYC (c-Myc proto-oncogene) status, and inhibited proliferation and metastasis of human orthotopic xenografts. Oral administration of sitravatinib to homozygous Th-MYCN transgenic mice (Th-MYCN+/+) after tumor initiation completely arrested further tumor development with no mice dying of disease while maintained on sitravatinib treatment (control cohort 57 days median time to sacrifice). Among these top kinases, DDR2 expression has the strongest correlation with poor survival and high stage at diagnosis, and the highest sensitivity to the drug. We confirmed on-target inhibition of collagen-mediated activation of DDR2. Genetic knockdown of DDR2 partially phenocopies Sitravatinib treatment, limiting tumor development and metastasis across tumor models. Analysis of single cell sequencing data demonstrated that DDR2 is restricted to mesenchymal-type tumor subpopulations and is enriched in Schwann Cell Precursor (SCP) subpopulations found in high-risk disease. These data define an unsuspected role for sitravatinib as a therapeutic agent in neuroblastoma and reveal a novel function for DDR2 as a driver of tumor growth and metastasis.

Examining hypertension risk among Black and White breast cancer survivors.

PURPOSE: Breast cancer survivors are at increased risk of cardiovascular dysfunction following their diagnosis; however, hypertension remains underexplored within this context. This retrospective cohort study examined the incidence of hypertension in breast cancer survivors and the association of race with hypertension risk among them. METHODS: Data for this study were abstracted from the electronic health records of women diagnosed with Stages I-III breast cancer. Incident hypertension diagnosis was identified through International Classification of Diseases codes. Bivariate associations were tested using Student's t-test and chi-squared test of independence. Bivariable Cox regression analysis was used to determine demographic and clinical factors that may have been associated with the development of hypertension. RESULTS: A total of 664 women were included. Most women were 50 years of age or younger (52.0%), White (33.0% Black), and received a mastectomy (80.6%). Overall, 45.5% of the cohort developed hypertension. The 1-year hypertension-free survival estimates were 47% (95% confidence interval [CI], 41-54) in Black women and 73% (95% CI, 69-77) in White women (p < 0.0001). Besides race, statistically significant predictors of hypertension included: age greater than 50 (vs. ≤50) (adjusted Hazard Ratio [HR]: 1.40; 95% CI, 1.09-1.80) and residing in a non-metropolitan area (vs. metropolitan) (adjusted HR: 1.60; 95% CI, 1.19-2.16). CONCLUSIONS: This study suggests that breast cancer survivors who are older, Black, or residing in non-metropolitan areas may benefit from added surveillance and hypertension prevention strategies during treatment. Future studies are needed to identify contributors to the observed racial and geographic disparities.

Development of the muscular and nervous systems during the larval ontogeny of the stalked barnacle, Octolasmis angulata Aurivillius 1894 (Cirripedia: Thoracicalcerea: Poecilasmatidae).

The advancements in microscopic techniques have stimulated great interest in the muscular and neural architectures of invertebrates, specifically using muscle and neural structures to infer phylogenetic relationships. Here, we provide the data on the development of the muscular and nervous systems during the larval development of stalked barnacle, Octolasmis angulata using the phalloidin F-actin and immunohistochemical labelling (e.g. acetylated α-tubulin and serotonin) and confocal laser scanning microscopy analysis. All naupliar stages shared the same muscle and neural architectures with only the discrepancy in size. The nauplii have a complex muscle arrangement in their feeding apparatus and naupliar appendages. Most naupliar muscles undergo histolyse during the cyprid metamorphosis. The cyprid muscles form beneath the head shield at the end of nauplius VI. The naupliar and cyprid central nervous systems exhibit the typical tripartite brain comprising the protocerebrum, deutocerebrum and tritocerebrum. The serotonin-like immunoreactivity is mainly found in the naupliar brain, mandibular ganglia, cyprid brain and posterior ganglia. Our study revealed that numerous muscle and neural architectures in the naupliar and cyprids have phylogenetic significance, but future studies on the myoanatomy and neuroanatomy of other barnacle species are necessary to determine the homology of these structures.

In-situ synthesized V2CTx MXene-based immune tag for the electrochemical detection of Interleukin 6 (IL-6) from breast cancer cells.

Interleukin-6 (IL-6) is a proinflammatory cytokine with a critical role in immune regulation and treatment of many diseases, including breast cancer. Herein, we developed a novel V2CTx MXene-based immunosensor for rapid and accurate IL-6 detection. The chosen substrate was V2CTx, a 2-dimensional (2D) MXene nanomaterial with excellent electronic properties. Prussian blue (Fe4[Fe(CN)6]3), used for its electrochemical properties, and spindle-shaped gold nanoparticles (Au SSNPs), used to combine with antibodies, were in-situ synthesized on the surface of the MXene. The in-situ synthesis ensures a firm chemical connection compared to other tags formed by a less stable physical absorption. Inspired by a sandwich ELISA test, the modified V2CTx tag was captured by the electrode surface with cysteamine to detect the analyte, IL-6, after being attached with a capture antibody (cAb). Benefiting from an increased surface area, an enhanced charge transfer rate, and a firm connection of the tag, this biosensor exhibited excellent analytical performance. The high sensitivity, high selectivity, and wide detection range covering the IL-6 level of both healthy individuals and breast cancer patients were obtained to meet clinical demands. Herein, this V2CTx MXene-based immunosensor is a potential therapeutic and diagnostic point-of-care alternative to routine ELISA IL-6 detection methods.

Use of photo methods in research studies with cancer survivors and their caregivers: a scoping review.

PURPOSE: Photo methods such as photo-elicitation and photovoice have traditionally been implemented as knowledge-generation techniques; however, they have also been conceptualized as tools for community impact and as interventions in and of themselves. We performed a scoping review to document how photo methods have been used in studies of cancer, to describe participant populations, and to identify opportunities for future directions for the use of photo methods in cancer. METHODS: An a priori search strategy was implemented across health-related databases with the following inclusion criteria: (1) study participants were diagnosed with cancer and/or were caregivers of those with cancer; (2) study participants were asked to take and/or respond to photographs as part of the study protocol; (3) articles were published in peer-reviewed journals; (4) articles were written in English. RESULTS: Eighty non-duplicative articles were identified; of these, 30 articles describing 24 individual studies were included for review. All but one (95.8%) of the studies utilized photovoice solely as a knowledge-generation technique without participant outcome measurement or analysis. Across all included studies, participants were largely women with breast cancer; other demographic and cancer-related variables (e.g., race and cancer stage) were not consistently reported. Caregivers were included in 37.5% of studies. CONCLUSION: Photo methods are most frequently used in order to capture qualitative data in cancer populations; however, there are missed opportunities in their lack of use for intervention and systemic change. In addition, inconsistent reporting of demographics and cancer characteristics limits our ability to synthesize these data across studies.

Society of Behavioral Medicine (SBM) position statement: support increased knowledge and efforts to address the financial burden associated with cancer treatment.

Millions of individuals and their families struggle with both treatment-related and out-of-pocket (OOP) economic repercussions of a cancer diagnosis, an effect increasingly referred to as "financial toxicity." In 2014, the Agency for Healthcare Research and Quality (AHRQ) estimated the total U.S. expenditures for cancer at $87.8 billion dollars with patient OOP costs accounting for $3.9 billion dollars (2014). These figures do not take into account indirect costs, such as those from lost earnings. As a result, financial toxicity can extend well beyond the active treatment phase and have a substantial impact on a household's economic reserve and financial resilience well into the future. Of the 9.5 million U.S. adults aged 50 years and older diagnosed with cancer (2000-2012), 42.2% have depleted their assets at 2 years and 38.2% were financially insolvent in 4 years. Bankruptcy rates are 2.65 times higher among cancer survivors than matched controls. A full 70% of Americans want to have conversations about the costs of care with their health care providers, but only 28% report doing so. Delaying or deferring these conversations can have major financial consequences for patients. According to a polling conducted for the Robert Wood Johnson Foundation (RWJF) by Avalere Health, almost 20% of patients report forgoing care when they have questions about costs. A critical element to achieve this is to have accurate cost information, including health care insurance coverage policies. Specifically, while patients and their families look to their health care providers to help them better navigate the cost implication of their treatment choices, most who are willing to undertake this challenging task need to have accessible and comprehensive (including direct and indirect) cost information to facilitate the discussion.

Skeletal Muscle Mass Loss During Cancer Treatment: Differences by Race and Cancer Site.

OBJECTIVES: To examine skeletal muscle mass change in a racially diverse sample of patients undergoing cancer treatment, determine significant predictors of muscle mass loss, and explore the interaction of race and cancer site. SAMPLE & SETTING: A retrospective analysis was conducted for 212 patients seeking treatment at a university hospital clinic. METHODS & VARIABLES: Skeletal muscle mass index (SMI) was determined by computed tomography at the time of cancer diagnosis and with cancer treatment. RESULTS: One hundred thirty-four patients (63%) had SMI loss with cancer treatment. Race and cancer site were found to be significant predictors of SMI loss. Compared to other racial groups, non-Hispanic Black (NHB) patients had the greatest SMI loss (p < 0.001) with cancer treatment. NHB patients with rectal cancer experienced the greatest SMI loss compared to patients of other races and cancer types. IMPLICATIONS FOR NURSING: To improve survivorship care for patients with cancer, it is essential to develop strategies for assessing and managing skeletal muscle mass loss throughout treatment, particularly for NHB patients with rectal cancer.

Skeletal Muscle Mass Change During Chemotherapy: A Systematic Review and Meta-analysis.

BACKGROUND/AIM: Skeletal muscle mass loss is an emerging concern in oncology. Our systematic review and meta-analysis identified the mean difference in skeletal muscle index pre- to post-chemotherapy and synthesized potential key factors. MATERIALS AND METHODS: We searched primary original research published through October 2019 in four databases: MEDLINE via PubMed, Scopus, CINAHL, and Embase. RESULTS: Fifteen studies were included, 60% published in the past 2 years (2018-2019). Advanced non-small cell lung cancer was the most frequently reported cancer, and overall survival the most often identified key related factor. Mean difference in skeletal muscle index during chemotherapy was 2.72 (95%CI=1.77-3.67, p=0.00), with muscle loss in males (4.52, 95%CI=3.34-5.71, p=0.00) about 1.6 times higher than that in females (2.86, 95%CI=0.81-4.92, p=0.01). CONCLUSION: Oncologists should recognize sex-specific differences in skeletal muscle mass loss during chemotherapy and consider adjusting treatment accordingly.

Care Coordination for Breast Cancer Survivors in Urban Underserved Communities: Will Treatment Summaries and Survivorship Care Plans Be Enough?

BACKGROUND: Few studies have examined cancer care coordination at federally qualified health centers (FHQCs). The Commission on Cancer's (CoC) standard 3.3, i.e., treatment summaries and survivorship care plans (TS-SCPs), is aimed at improving communication between cancer specialists and primary care providers (PCPs) across all healthcare systems. Whether this will improve care at FQHCs is unclear. We sought to understand breast cancer care coordination at FQHCs before the stepwise implementation of standard 3.3. METHODS: In 2014, we conducted a retrospective chart review at five Chicago FQHCs. We used ICD-9 codes to identify 109 breast cancer cases diagnosed within 5 years of the chart review. We examined charts for (1) external cancer records, (2) PCP documentation of breast cancer histories, and (3) documentation of PCP engagement in cancer-relevant follow-up care. RESULTS: Less than 50% of the charts had PCP documentation of more than one area of cancer-relevant follow-up care. Availability of external records did not increase PCP engagement in cancer-relevant follow-up care. Instead, PCPs who documented information about their patient's breast cancer treatments also documented more cancer-relevant follow-up care. CONCLUSION: Before the stepwise implementation of TS-SCPs, less than 50% of the charts had PCP documentation of more than one area of cancer-related follow-up care. The TS-SCP is designed to facilitate care coordination between specialists and PCPs through increased communication. Our results suggest the availability of external cancer information did not necessarily translate into care delivery. This suggests communication of information alone is insufficient.

Association of Insurance Status and Racial Disparities With the Detection of Early-Stage Breast Cancer.

Importance: Compared with non-Hispanic white women, racial/ethnic minority women receive a diagnosis of breast cancer at a more advanced stage and have higher morbidity and mortality with breast cancer diagnosis. Access to care with adequate insurance may be associated with earlier diagnosis, expedited treatment, and improved prognosis. Objective: To examine the extent to which insurance is associated with access to timely breast cancer diagnosis and breast cancer stage differences among a large, diverse population of US patients with breast cancer. Design, Setting, and Participants: This retrospective, cross-sectional population-based study used data from the Surveillance, Epidemiology, and End Results Program on 177 075 women aged 40 to 64 years who received a diagnosis of stage I to III breast cancer between January 1, 2010, and December 31, 2016. Statistical analysis was performed from August 1, 2017, to October 1, 2019. Main Outcomes and Measures: The primary outcome was the risk of having a more advanced stage of breast cancer at diagnosis (ie, stage III vs stages I and II). Mediation analyses were conducted to determine associations of race/ethnicity and proportion of observed differences mediated by health insurance status with earlier stage of diagnosis. Results: A total of 177 075 women (mean [SD] age, 53.5 [6.8] years; 148 124 insured and 28 951 uninsured or receiving Medicaid) were included in the study. A higher proportion of women either receiving Medicaid or who were uninsured received a diagnosis of locally advanced breast cancer (stage III) compared with women with health insurance (20% vs 11%). In multivariable models, non-Hispanic black (odds ratio [OR], 1.46 [95% CI, 1.40-1.53]), American Indian or Alaskan Native (OR, 1.31 [95% CI, 1.07-1.61]) and Hispanic (OR, 1.35 [95% CI, 1.30-1.42]) women had higher odds of receiving a diagnosis of locally advanced disease (stage III) compared with non-Hispanic white women. When adjusting for health insurance and other socioeconomic factors, associations between race/ethnicity and risk of locally advanced breast cancer were attenuated (non-Hispanic black: OR, 1.29 [95% CI, 1.23-1.35]; American Indian or Alaskan Native: OR, 1.11 [95% CI, 0.91-1.35]; Hispanic: OR, 1.17 [95% CI, 1.12-1.22]). Nearly half (45%-47%) of racial differences in the risk of locally advanced disease were mediated by health insurance. Conclusions and Relevance: This study's findings suggest that nearly half of the observed racial/ethnic disparities in higher stage at breast cancer diagnosis are mediated by health insurance coverage.

CuO/Cu composite nanospheres on a TiO2 nanotube array for amperometric sensing of glucose.

A non-enzymatic glucose sensor based on the use of CuO-Cu nanospheres placed on a TiO2 nanotube (TNT) array with excellent performance is described. The electrode was fabricated by coating the CuO-Cu nanospheres onto the TNT array through electrochemical deposition. The CuO-Cu nanospheres with a diameter of ~200 nm are well dispersed on the TNT surface, which warrants smooth interaction and a 3D nanostructure with high uniformity. The modified electrode was then used for amperometric determination of glucose in 0.1 M NaOH solution. Figures of merit include (a) a typical working voltage of 0.65 V (vs. Ag/AgCl). (b) a linear range as wide as from 0.2-90 mM, (c) good sensitivity (234 µA mM-1 cm-2), and a 19 nM lower detection limit. The sensor is selective over ascorbic acid (AA), dopamine (DA), uric acid (UA), lactose, sucrose, and fructose. Graphical abstract.

Intensive Surveillance with Biannual Dynamic Contrast-Enhanced Magnetic Resonance Imaging Downstages Breast Cancer in BRCA1 Mutation Carriers.

PURPOSE: To establish a cohort of high-risk women undergoing intensive surveillance for breast cancer.Experimental Design: We performed dynamic contrast-enhanced MRI every 6 months in conjunction with annual mammography (MG). Eligible participants had a cumulative lifetime breast cancer risk ≥20% and/or tested positive for a pathogenic mutation in a known breast cancer susceptibility gene. RESULTS: Between 2004 and 2016, we prospectively enrolled 295 women, including 157 mutation carriers (75 BRCA1, 61 BRCA2); participants' mean age at entry was 43.3 years. Seventeen cancers were later diagnosed: 4 ductal carcinoma in situ (DCIS) and 13 early-stage invasive breast cancers. Fifteen cancers occurred in mutation carriers (11 BRCA1, 3 BRCA2, 1 CDH1). Median size of the invasive cancers was 0.61 cm. No patients had lymph node metastasis at time of diagnosis, and no interval invasive cancers occurred. The sensitivity of biannual MRI alone was 88.2% and annual MG plus biannual MRI was 94.1%. The cancer detection rate of biannual MRI alone was 0.7% per 100 screening episodes, which is similar to the cancer detection rate of 0.7% per 100 screening episodes for annual MG plus biannual MRI. The number of recalls and biopsies needed to detect one cancer by biannual MRI were 2.8 and 1.7 in BRCA1 carriers, 12.0 and 8.0 in BRCA2 carriers, and 11.7 and 5.0 in non-BRCA1/2 carriers, respectively. CONCLUSIONS: Biannual MRI performed well for early detection of invasive breast cancer in genomically stratified high-risk women. No benefit was associated with annual MG screening plus biannual MRI screening.See related commentary by Kuhl and Schrading, p. 1693.

Efficacy of a Weight Loss Intervention for African American Breast Cancer Survivors.

Purpose African American women with breast cancer have higher cancer-specific and overall mortality rates. Obesity is common among African American women and contributes to breast cancer progression and numerous chronic conditions. Weight loss interventions among breast cancer survivors positively affect weight, behavior, biomarkers, and psychosocial outcomes, yet few target African Americans. This article examines the effects of Moving Forward, a weight loss intervention for African American breast cancer survivors (AABCS) on weight, body composition, and behavior. Patients and Methods Early-stage (I-III) AABCS were randomly assigned to a 6-month interventionist-guided (n = 125) or self-guided (n = 121) weight loss program supporting behavioral changes to promote a 5% weight loss. Anthropometric, body composition, and behavioral data were collected at baseline, postintervention (6 months), and follow-up (12 months). Descriptive statistics and mixed models analyses assessed differences between groups over time. Results Mean (± standard deviation) age, and body mass index were 57.5 (± 10.1) years and 36.1 (± 6.2) kg/m2, respectively, and 82% had stage I or II breast cancer. Both groups lost weight. Mean and percentage of weight loss were greater in the guided versus self-guided group (at 6 months: 3.5 kg v 1.3kg; P < .001; 3.6% v 1.4%; P < .001, respectively; at 12 months: 2.7 kg v 1.6 kg; P < .05; 2.6% v 1.6%; P < .05, respectively); 44% in the guided group and 19% in the self-guided group met the 5% goal. Body composition and behavioral changes were also greater in the interventionist-guided group at both time points. Conclusion The study supports the efficacy of a community-based interventionist-guided weight loss program targeting AABCS. Although mean weight loss did not reach the targeted 5%, the mean loss of > 3% at 6 months is associated with improved health outcomes. Affordable, accessible health promotion programs represent a critical resource for AABCS.

First evidence for temporary and permanent adhesive systems in the stalked barnacle cyprid, Octolasmis angulata.

Although there have been extensive studies on the larval adhesion of acorn barnacles over the past few decades, little is known about stalked barnacles. For the first time, we describe the larval adhesive systems in the stalked barnacle, Octolasmis angulata and the findings differ from previous reports of the temporary (antennulary) and cement glands in thoracican barnacles. We have found that the temporary adhesives of cyprid are produced by the clustered temporary adhesive glands located within the mantle, instead of the specialised hypodermal glands in the second antennular segment as reported in the acorn barnacles. The temporary adhesive secretory vesicles (TASV) are released from the gland cells into the antennule via the neck extensions of the glands, and surrounded with microtubules in the attachment disc. Cement glands undergo a morphological transition as the cyprid grows. Synthesis of the permanent adhesives only occurs during the early cyprid stage, and is terminated once the cement glands reach maximum size. Evidence of the epithelial invaginations on the cement glands supports the involvement of exocytosis in the secretion of the permanent adhesives. This study provides new insight into the larval adhesives system of thoracican barnacles.

Monogenean anchor morphometry: systematic value, phylogenetic signal, and evolution.

Background. Anchors are one of the important attachment appendages for monogenean parasites. Common descent and evolutionary processes have left their mark on anchor morphometry, in the form of patterns of shape and size variation useful for systematic and evolutionary studies. When combined with morphological and molecular data, analysis of anchor morphometry can potentially answer a wide range of biological questions. Materials and Methods. We used data from anchor morphometry, body size and morphology of 13 Ligophorus (Monogenea: Ancyrocephalidae) species infecting two marine mugilid (Teleostei: Mugilidae) fish hosts: Moolgarda buchanani (Bleeker) and Liza subviridis (Valenciennes) from Malaysia. Anchor shape and size data (n = 530) were generated using methods of geometric morphometrics. We used 28S rRNA, 18S rRNA, and ITS1 sequence data to infer a maximum likelihood phylogeny. We discriminated species using principal component and cluster analysis of shape data. Adams's K mult was used to detect phylogenetic signal in anchor shape. Phylogeny-correlated size and shape changes were investigated using continuous character mapping and directional statistics, respectively. We assessed morphological constraints in anchor morphometry using phylogenetic regression of anchor shape against body size and anchor size. Anchor morphological integration was studied using partial least squares method. The association between copulatory organ morphology and anchor shape and size in phylomorphospace was used to test the Rohde-Hobbs hypothesis. We created monogeneaGM, a new R package that integrates analyses of monogenean anchor geometric morphometric data with morphological and phylogenetic data. Results. We discriminated 12 of the 13 Ligophorus species using anchor shape data. Significant phylogenetic signal was detected in anchor shape. Thus, we discovered new morphological characters based on anchor shaft shape, the length between the inner root point and the outer root point, and the length between the inner root point and the dent point. The species on M. buchanani evolved larger, more robust anchors; those on L. subviridis evolved smaller, more delicate anchors. Anchor shape and size were significantly correlated, suggesting constraints in anchor evolution. Tight integration between the root and the point compartments within anchors confirms the anchor as a single, fully integrated module. The correlation between male copulatory organ morphology and size with anchor shape was consistent with predictions from the Rohde-Hobbs hypothesis. Conclusions. Monogenean anchors are tightly integrated structures, and their shape variation correlates strongly with phylogeny, thus underscoring their value for systematic and evolutionary biology studies. Our MonogeneaGM R package provides tools for researchers to mine biological insights from geometric morphometric data of speciose monogenean genera.

The Breast-Thyroid Cancer Link: A Systematic Review and Meta-analysis.

Rates of thyroid cancer in women with a history of breast cancer are higher than expected. Similarly, rates of breast cancer in those with a history of thyroid cancer are increased. Explanations for these associations include detection bias, shared hormonal risk factors, treatment effect, and genetic susceptibility. With increasing numbers of breast and thyroid cancer survivors, clinicians should be particularly cognizant of this association. Here, we perform a systematic review and meta-analysis of the literature utilizing PubMed and Scopus search engines to identify all publications studying the incidence of breast cancer as a secondary malignancy following a diagnosis of thyroid cancer or thyroid cancer following a diagnosis of breast cancer. This demonstrated an increased risk of thyroid cancer as a secondary malignancy following breast cancer [OR = 1.55; 95% confidence interval (CI), 1.44-1.67] and an increased risk of breast cancer as a secondary malignancy following thyroid cancer (OR = 1.18; 95% CI, 1.09-1.26). There is a clear increase in the odds of developing either thyroid or breast cancer as a secondary malignancy after diagnosis with the other. Here, we review this association and current hypothesis as to the cause of this correlation.

Medical Student Knowledge of Oncology and Related Disciplines: a Targeted Needs Assessment.

Despite increasing numbers of cancer survivors, non-oncology physicians report discomfort and little training regarding oncologic and survivorship care. This pilot study assesses medical student comfort with medical oncology, surgical oncology, radiation oncology, hospice/palliative medicine, and survivorship care. A survey was developed with input from specialists in various fields of oncologic care at a National Cancer Institute-designated comprehensive cancer center. The survey included respondent demographics, reports of experience with oncology, comfort ratings with oncologic care, and five clinical vignettes. Responses were yes/no, multiple choice, Likert scale, or free response. The survey was distributed via email to medical students (MS1-4) at two US medical schools. The 105 respondents were 34 MS1s (32 %), 15 MS2s and MD/PhDs (14 %), 26 MS3s (25 %), and 30 MS4s (29 %). Medical oncology, surgical oncology, and hospice/palliative medicine demonstrated a significant trend for increased comfort from MS1 to MS4, but radiation oncology and survivorship care did not. MS3s and MS4s reported the least experience with survivorship care and radiation oncology. In the clinical vignettes, students performed the worst on the long-term chemotherapy toxicity and hospice/palliative medicine questions. Medical students report learning about components of oncologic care, but lack overall comfort with oncologic care. Medical students also fail to develop an increased self-assessed level of comfort with radiation oncology and survivorship care. These pilot results support development of a formalized multidisciplinary medical school oncology curriculum at these two institutions. An expanded national survey is being developed to confirm these preliminary findings.

Long-term results of radiation therapy oncology group 9903: a randomized phase 3 trial to assess the effect of erythropoietin on local-regional control in anemic patients treated with radiation therapy for squamous cell carcinoma of the head and neck.

PURPOSE: This paper reports long-term results of RTOG 9903, to determine whether the addition of erythropoietin (EPO) would improve the outcomes of radiation therapy (RT) in mildly to moderately anemic patients with head and neck squamous cell carcinoma (HNSCCa). METHODS AND MATERIALS: The trial included HNSCCa patients treated with definitive RT. Patients with stage III or IV disease received concomitant chemoradiation therapy or accelerated fractionation. Pretreatment hemoglobin levels were required to be between 9.0 and 13.5 g/dL (12.5 g/dL for females). EPO, 40,000 U, was administered weekly starting 7 to 10 days before RT was initiated in the RT + EPO arm. RESULTS: A total of 141 of 148 enrolled patients were evaluable. The baseline median hemoglobin level was 12.1 g/dL. In the RT + EPO arm, the mean hemoglobin level at 4 weeks increased by 1.66 g/dL, whereas it decreased by 0.24 g/dL in the RT arm. With a median follow-up of 7.95 years (range: 1.66-10.08 years) for surviving patients and 3.33 years for all patients (range: 0.03-10.08 years), the 5-year estimate of local-regional failure was 46.2% versus 39.4% (P=.42), local-regional progression-free survival was 31.5% versus 37.6% (P=.20), and overall survival was 36.9% versus 38.2% (P=.54) for the RT + EPO and RT arms, respectively. Late toxicity was not different between the 2 arms. CONCLUSIONS: This long-term analysis confirmed that despite the ability of EPO to raise hemoglobin levels in anemic patients with HNSCCa, it did not improve outcomes when added to RT. The possibility of a detrimental effect of EPO could not be ruled out.

Ultrastructure of head organs (anterior adhesive apparatus) and posterior secretory systems of Caballeria liewi Lim, 1995 (Monogenea, Ancyrocephalidae).

Caballeria liewi Lim, 1995, uses adhesive secretions from the head organs and posterior secretory systems to assist in locomotion and attachment. Ultrastructural investigations show that the head organs of C. liewi consist of three pairs of antero-lateral pit-like openings bearing microvilli and ducts leading from two types of uninucleated gland cells (located lateral to the pharynx), one type producing rod-like (S1) bodies with an electron-dense matrix containing less electron-dense vesicles and the second type producing oval (S2) bodies with a homogeneous electron-dense matrix. Interlinking band-like structures are observed between S1 bodies and between S2 bodies. S1 body is synthesised in the granular endoplasmic reticulum, transported to a Golgi complex to be packaged into vesicles and routed into ducts for exudation. The synthesis of the S2 body is unresolved. Haptoral secretions manifested externally as net-like structures are derived from dual electron-dense (DED) secretory body produced in the peduncular gland cells. The DED body consists of a less electron-dense oval core in a homogeneous electron-dense matrix. On exocytosis into the pyriform haptoral reservoir, DED bodies are transformed into a secretion with two types of inclusions (less electron-dense oval and electron-dense spherical inclusions) in an electron-dense matrix. The secretions are further transformed (as small, oval, electron-dense bodies) when transported to the superficial anchor grooves, and on exudation into the gill tissues, the secretions become an electron-dense matrix. Secretory bodies associated with uniciliated structures, anchor sleeves and marginal hooks are also observed.

Experimental investigation of magnetically actuated separation using tangential microfluidic channels and magnetic nanoparticles.

A novel continuous switching/separation scheme of magnetic nanoparticles (MNPs) in a sub-microlitre fluid volume surrounded by neodymium permanent magnet is studied in this work using tangential microfluidic channels. Polydimethylsiloxane tangential microchannels are fabricated using a novel micromoulding technique that can be done without a clean room and at much lower cost and time. Negligible switching of MNPs is seen in the absence of magnetic field, whereas 90% of switching is observed in the presence of magnetic field. The flow rate of MNPs solution had dramatic impact on separation performance. An optimum value of the flow rate is found that resulted in providing effective MNP separation at much faster rate. Separation performance is also investigated for a mixture containing non-magnetic polystyrene particles and MNPs. It is found that MNPs preferentially moved from lower microchannel to upper microchannel resulting in efficient separation. The proof-of-concept experiments performed in this work demonstrates that microfluidic bioseparation can be efficiently achieved using functionalised MNPs, together with tangential microchannels, appropriate magnetic field strength and optimum flow rates. This work verifies that a simple low-cost magnetic switching scheme can be potentially of great utility for the separation and detection of biomolecules in microfluidic lab-on-a-chip systems.