Biot-Savart-like law in electrostatics

The Biot-Savart law is a well-known and powerful theoretical tool used to calculate magnetic fields due to currents in magnetostatics. We extend the range of applicability and the formal structure of the Biot-Savart law to electrostatics by deriving a Biot-Savart-like law suitable for calculating electric fields. We show that, under certain circumstances, the traditional Dirichlet problem can be mapped onto a much simpler Biot-Savart-like problem. We find an integral expression for the electric field due to an arbitrarily shaped, planar region kept at a fixed electric potential, in an otherwise grounded plane. As a by-product we present a very simple formula to compute the field produced in the plane defined by such a region. We illustrate the usefulness of our approach by calculating the electric field produced by planar regions of a few nontrivial shapes.Comment: 14 pages, 6 figures, RevTex, accepted for publication in the European Journal of Physic

IMMUNOHISTOCHEMISTRY EXPRESSION OF KLOTHO IN BONE MARROW BIOPSIES FROM NORMAL, MGUS, AND PLASMA CELL MYELOMA

poster abstractKlotho is an anti-aging gene, which has been shown to inhibit the insulin and insulin-like growth factor 1 (IGF-1) pathways in mice hepatocytes and myocytes. Immunochemistry analysis of Klotho expression in breast tissue arrays revealed high expression in normal breast, but very low expression in breast cancer. In this study we examined eight normal bone marrow, eight MGUS (monoclonal gammopathy of undetermined significance), and forty-two cases of plasma cell myeloma by immunohistochemistry with the Klotho antibody. The immunostaining of the Klotho antibody was localized in the cyto-plasm and as punctate granular staining of myeloma cells in the marrow. In the accompanying bone marrow clots, Klotho was seen as strong punctate granules on myeloma cells and not on other peripheral white blood cells. There was no staining of plasma cells in the eight normal bone marrow cas-es. Slight cytoplasmic staining was seen in myeloid series of cells in the normal bone marrow and in megakaryocytes. In the eight MGUS cases, there was very minimal cytoplasmic staining in a few of the myeloma cells. Minimal staining was seen in the myeloid series of cells in the marrow in these cases. Klotho was highly expressed in the myeloma cases and no staining in the normal and MGUS cases. In conclusion, Klotho was highly expressed in patients with myeloma in myelomas cells in the bone marrow. This project was sponsored by the Life Health Science Internship Progra

A prospective cohort study of the effects of adjuvant breast cancer chemotherapy on taste function, food liking, appetite and associated nutritional outcomes

\u27Taste\u27 changes are commonly reported during chemotherapy. It is unclear to what extent this relates to actual changes in taste function or to changes in appetite and food liking and how these changes affect dietary intake and nutritional status

Halofuginone inhibits the establishment and progression of melanoma bone metastases

Transforming growth factor (TGF-β) derived from bone fuels melanoma bone metastases by inducing tumor secretion of pro-metastatic factors that act on bone cells to change the skeletal microenvironment. Halofuginone is a plant alkaloid derivative that blocks TGF-β signaling with antiangiogenic and antiproliferative properties. Here, we demonstrate for the first time that halofuginone therapy decreases development and progression of bone metastasis caused by melanoma cells through inhibition of TGF-β signaling. Halofuginone treatment of human melanoma cells inhibited cell proliferation, phosphorylation of SMAD proteins in response to TGF-β, and TGF-β-induced SMAD-driven transcription. In addition, halofuginone reduced expression of TGF-β target genes that enhance bone metastases, including PTHrP, CTGF, CXCR4, and IL11. Also, cell apoptosis was increased in response to halofuginone. In nude mice inoculated with 1205Lu melanoma cells, a preventive protocol with halofuginone inhibited bone metastasis. The beneficial effects of halofuginone treatment were comparable to those observed with other anti-TGF-β strategies, including systemic administration of SD208, a small molecule inhibitor of TGF-β receptor I kinase, or forced overexpression of Smad7, a negative regulator of TGF-β signaling. Furthermore, mice with established bone metastases treated with halofuginone had significantly less osteolysis than mice receiving placebo assessed by radiographys. Thus, halofuginone is also effective in reducing the progression of melanoma bone metastases. Moreover, halofuginone treatment reduced melanoma metastasis to the brain, showing the potential of this novel treatment against cancer metastasis

Cardiac safety of adjuvant pegylated liposomal doxorubicin with concurrent trastuzumab: a randomized phase II trial

Background The cardiac safety of trastuzumab concurrent with pegylated liposomal doxorubicin (PLD) in an adjuvant breast cancer treatment regimen is unknown. Patients and methods Women with resected node-positive or intermediate-risk node-negative HER2 overexpressing breast cancer and baseline left ventricular ejection fraction (LVEF) ≥55% were randomized (1:2) to doxorubicin 60 mg/m2 (A)+cyclophosphamide 600 mg/m2 (C) every 21 days (q21d) for four cycles or PLD 35 mg/m2+C q21d+trastuzumab 2 mg/kg weekly (H) for 12 weeks. Both groups then received paclitaxel (Taxol, T) 80 mg/m2 with H for 12 weeks followed by H to complete 1 year. The primary end point was cardiac event rate or inability to administer 1 year of trastuzumab. Results Of 181 randomized patients, 179 underwent cardiac analysis. The incidence of cardiac toxicity or inability to administer trastuzumab due to cardiotoxicity was 18.6% [n=11; 95% confidence interval (CI) 9.7% to 30.9%] with A+C → T+H and 4.2% (n=5; 95% CI 1.4% to 9.5%) with PLD+C+H → T+H (P=0.0036). All events, except one, were asymptomatic systolic dysfunction or mildly symptomatic heart failure. Mean absolute LVEF reduction at cycle 8 was greater with doxorubicin (5.6% versus 2.1%; P=0.0014). Conclusion PLD+C+H → T+H is feasible and results in lower early cardiotoxicity rates compared with A+C → T+

Pfmrk, a MO15-related protein kinase from Plasmodium falciparum. Gene cloning, sequence, stage-specific expression and chromosome localization.

Cyclin-dependent kinases (Cdks) play a central role in the regulation of the eukaryotic cell cycle. A novel gene encoding a Cdk-like protein, Pfmrk, has been isolated from the human malaria parasite Plasmodium falciparum. The gene has no introns and comprises an open reading frame encoding a protein of 324 amino acids with a predicted molecular mass of 38 kDa. Database searches revealed a striking similarity to the Cdk subfamily with the highest similarity to human MO15 (Cdk7). The overall sequence of Pfmrk shares 62% similarity and 46% identity with human MO15, in comparison to the 49-58% similarity and 34-43% identity with other human Cdks. Pfmrk contains two unique inserts: one consisting of 5 amino acids just before the cyclin-binding motif and the other composed of 13 amino acids within the T-loop equivalent region. Southern blots of genomic DNA digests and chromosomal separations showed that Pfmrk is a single-copy gene conserved between several parasite strains and is located on chromosome 10. A 2500-nucleotide transcript of this gene is expressed predominantly in the sexual blood stages (gametocytes), suggesting that Pfmrk may be involved in sexual stage development

Attempts to Image the Early Inflammatory Response during Infection with the Lymphatic Filarial Nematode Brugia pahangi in a Mouse Model

Helminth parasites remain a major constraint upon human health and well-being in many parts of the world. Treatment of these infections relies upon a very small number of therapeutics, most of which were originally developed for use in animal health. A lack of high throughput screening systems, together with limitations of available animal models, has restricted the development of novel chemotherapeutics. This is particularly so for filarial nematodes, which are long-lived parasites with a complex cycle of development. In this paper, we describe attempts to visualise the immune response elicited by filarial parasites in infected mice using a non-invasive bioluminescence imaging reagent, luminol, our aim being to determine whether such a model could be developed to discriminate between live and dead worms for in vivo compound screening. We show that while imaging can detect the immune response elicited by early stages of infection with L3, it was unable to detect the presence of adult worms or, indeed, later stages of infection with L3, despite the presence of worms within the lymphatic system of infected animals. In the future, more specific reagents that detect secreted products of adult worms may be required for developing screens based upon live imaging of infected animals

Efficacy and cost-effectiveness of an outcall program to reduce carer burden and depression among carers of cancer patients (PROTECT) : rationale and design of a randomized controlled trial

Published: 6 January 2014BACKGROUND: Carers provide extended and often unrecognized support to people with cancer. The aim of this study is to test the hypothesis that excessive carer burden is modifiable through a telephone outcall intervention that includes supportive care, information and referral to appropriate psycho-social services. Secondary aims include estimation of changes in psychological health and quality of life. The study will determine whether the intervention reduces unmet needs among patient dyads. A formal economic program will also be conducted. METHODS/DESIGN: This study is a single-blind, multi-centre, randomized controlled trial to determine the efficacy and cost-efficacy of a telephone outcall program among carers of newly diagnosed cancer patients. A total of 230 carer/patient dyads will be recruited into the study; following written consent, carers will be randomly allocated to either the outcall intervention program (n = 115) or to a minimal outcall / attention control service (n = 115). Carer assessments will occur at baseline, at one and six months post-intervention. The primary outcome is change in carer burden; the secondary outcomes are change in carer depression, quality of life, health literacy and unmet needs. The trial patients will be assessed at baseline and one month post-intervention to determine depression levels and unmet needs. The economic analysis will include perspectives of both the health care sector and broader society and comprise a cost-consequences analysis where all outcomes will be compared to costs. DISCUSSION: This study will contribute to our understanding on the potential impact of a telephone outcall program on carer burden and provide new evidence on an approach for improving the wellbeing of carers.Patricia M Livingston, Richard H Osborne, Mari Botti, Cathy Mihalopoulos, Sean McGuigan, Leila Heckel, Kate Gunn, Jacquie Chirgwin, David M Ashley and Melinda William

The farnesoid X receptor regulates transcription of 3 beta-hydroxysteroid dehydrogenase type 2 in human adrenal cells

Recent studies have shown that the adrenal cortex expresses high levels of farnesoid X receptor (FXR), but its function remains not known. Herein, using microarray technology, we tried to identify candidate FXR targeting genes in the adrenal glands, and showed that FXR regulates 3β-hydroxysteroid dehydrogenase type 2 (HSD3B2) expression in human adrenocortical cells. We further demonstrated that FXR stimulated HSD3B2 promoter activity and have defined the cis-element responsible for FXR regulation of HSD3B2 transcription. Transfection of H295R adrenocortical cells with FXR expression vector effectively increased FXR expression levels and additional treatment with chenodeoxycholic acid (CDCA) caused a 25-fold increase in the mRNA for organic solute transporter alpha (OSTα), a known FXR target gene. HSD3B2 mRNA levels also increased following CDCA treatment in a concentration-dependent manner. Cells transfected with a HSD3B2 promoter construct and FXR expression vector responded to CDCA with a 20-fold increase in reporter activity compared to control. Analysis of constructs containing sequential deletions of the HSD3B2 promoter suggested a putative regulatory element between -166 and -101. Mutation of an inverted repeat between -137 and -124 completely blocked CDCA/FXR induced reporter activity. Chromatin immunoprecipitation assays further confirmed the presence of a FXR response element in the HSD3B2 promoter. In view of the emerging role of FXR agonists as therapeutic treatment of diabetes and certain liver diseases, the effects of such agonists on other FXR expressing tissues should be considered. Our findings suggest that in human adrenal cells, FXR increases transcription and expression of HSD3B2. Alterations in this enzyme would influence the capacity of the adrenal gland to produce corticosteroids

Outcomes of a randomized controlled trial assessing a smartphone Application to reduce unmet needs among people diagnosed with CancEr (ACE)

© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd. Background: Smartphone technology represents an opportunity to deliver practical solutions for people affected by cancer at a scale that was previously unimaginable, such as information, appointment monitoring, and improved access to cancer support services. This study aimed to determine whether a smartphone application (app) reduced the unmet needs among people newly diagnosed with cancer. Methods: A single blind, multisite randomized controlled trial to determine the impact of an app-based, 4-month intervention. Newly diagnosed cancer patients were approached at three health service treatment clinics. Results: Eighty-two people were randomized (intervention; n = 43 and control; n = 39), average age was 59.5 years (SD: 12.9); 71% female; 67% married or in a de facto relationship. At baseline, there were no differences in participants’ characteristics between the groups. No significant effects, in reducing unmet needs, were demonstrated at the end of intervention (4-month) or 12-month follow-up. Overall, 94% used the app in weeks 1-4, which decreased to 41% in weeks 13-16. Mean app use time per participant: Cancer Information, 6.9 (SD: 18.9) minutes; Appointment Schedule, 5.1 (SD: 9.6) minutes; Cancer Services 1.5 minutes (SD: 6.8); Hospital Navigation, 1.4 (SD: 2.8) minutes. Conclusions: Despite consumer involvement in the design of this smartphone technology, the app did not reduce unmet needs. This may have been due to the study being underpowered. To contribute to a meaningful understanding and improved implementation of smartphone technology to support people affected by cancer, practical considerations, such as recruitment issues and access to, and confidence with, apps, need to be considered. Australian New Zealand Clinical Trials Registration (ACTRN) Trial Registration: 12616001251415; WEF 7/9/2016