Publications by authors named "Ken Brown"

It has been shown that infants can increase or modify a motorically available behavior such as sucking, kicking, arm waving, etc., in response to a positive visual reinforcement (e.g.

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Article Synopsis
  • High-grade osteosarcoma primarily affects children and young adults, and the EURAMOS-1 study aims to improve treatment outcomes through randomized controlled trials involving 2,260 eligible patients.
  • The study found that after a median follow-up of 54 months, 3-year event-free survival was 59%, while 5-year overall survival was 71%, highlighting significant factors that negatively impact prognosis, such as metastases and tumor site.
  • Histological subtypes like telangiectatic showed better survival rates compared to others, and poor histological response post-surgery was linked to worse outcomes in patients with localized disease.*
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Background: We designed the EURAMOS-1 trial to investigate whether intensified postoperative chemotherapy for patients whose tumour showed a poor response to preoperative chemotherapy (≥10% viable tumour) improved event-free survival in patients with high-grade osteosarcoma.

Methods: EURAMOS-1 was an open-label, international, phase 3 randomised, controlled trial. Consenting patients with newly diagnosed, resectable, high-grade osteosarcoma aged 40 years or younger were eligible for randomisation.

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We examined the distribution of silver in pregnant mice and embryos/fetuses following intravenous injections of 10 nm silver nanoparticles (AgNPs) or soluble silver nitrate (AgNO3) at dose levels of 0 (citrate buffer control) or 66 µg Ag/mouse to pregnant mice on gestation days (GDs) 7, 8 and 9. Selected maternal tissues and all embryos/fetuses from control, AgNP- and AgNO3-treated groups on GD10 and control and AgNP-treated groups on GD16 were processed for the measurement of silver concentrations, intracellular AgNP localization, histopathology and gross examination of tissue morphology. Inductively-coupled plasma mass spectrometry revealed silver in all examined tissues following either AgNP or AgNO3 treatment, with highest concentrations of silver in maternal liver, spleen and visceral yolk sac (VYS), and lowest concentrations in embryos/fetuses.

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A field study was initiated in 2009 with 0.5% novaluron the BASF Advance Termite Bait System, which was 100% effective in controlling Reticulitermes sp. Holmgren and Coptotermes formosanus Shiraki infestations on 11 structures in the Texas City, TX area.

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Article Synopsis
  • This study aimed to explore the feasibility and effectiveness of combining low-dose anti-angiogenic chemotherapy (vinblastine and celecoxib) with standard treatment for patients with metastatic Ewing sarcoma (ES).
  • Out of 35 enrolled patients, 90% completed most of the planned treatment, with manageable side effects, though some experienced serious toxicities, particularly those who had prior pulmonary irradiation.
  • The results showed a 24-month event-free survival rate of 35% overall, but it was notably higher (71%) for patients with isolated pulmonary metastases, indicating potential benefits despite concerns over increased toxicity in irradiated areas.
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The objective of this study was to identify an adjuvant for anesthetics coated on microneedles to provide rapid onset and prolonged analgesic action with minimal skin tissue reaction. Aqueous lidocaine or prilocaine formulations with or without clonidine or the related analogs, guanfacine and apraclonidine, were dip-coated onto polymeric microneedles. The amount of lidocaine or prilocaine coated onto the microneedles was assessed by high performance liquid chromatography (HPLC).

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The objective of this study was to evaluate the distribution of silver nanoparticles (NPs) in pregnant mice and their developing embryos. Silver NPs (average diameter 50 nm) were intravenously injected into pregnant CD-1 mice on gestation days (GDs) 7, 8, and 9 at dose levels of 0, 35, or 66 μg Ag/mouse. Mice were euthanised on GD10, and tissue samples were collected and analysed for silver content.

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Purpose: To demonstrate rapid (~1 min) lidocaine delivery using 3M's solid microstructured transdermal system (sMTS) for prolonged, local analgesic action.

Methods: Polymeric microneedles were fabricated via injection molding and then dip-coated using an aqueous lidocaine formulation. The amount of lidocaine coated onto the microneedles was determined by high performance liquid chromatography (HPLC).

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Transgenic technologies can provide important animal models for studying drug-metabolizing enzymes. Our overall aim was to generate versatile cell and animal systems that exhibited varying levels of cytochrome P450 oxidoreductase (POR) activity, more accurately modelling the human population for pharmacological and toxicology studies. Towards this goal we evaluated RNA-interference constructs designed for use in vitro and in vivo for reducing POR activity in hepatocytes.

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Purposes: The aims of the study were to compare results of clinical/radiographic studies before second-look procedures (SLP) with SLP specimens from patients with gross residual sarcoma at diagnosis and to relate tumor viability to outcome.

Patients: Seventy-three patients underwent SLP before completing chemotherapy, with (n = 59) or without (n = 14) radiotherapy. Tumor sites were bladder/prostate (n = 27), head/orbit/parameningeal (n = 22), extremity/trunk (n = 14), and retroperitoneum/pelvis (n = 10).

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Purpose: The purpose of this work is to demonstrate rapid intradermal delivery of up to 1.5 mL of formulation using a hollow microneedle delivery device designed for self-application.

Methods: 3M's hollow Microstructured Transdermal System (hMTS) was applied to domestic swine to demonstrate delivery of a variety of formulations including small molecule salts and proteins.

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The oxidative stress response is an important pathway involved in maintaining redox homeostasis in cells, preventing damage induced by free radicals and reactive oxygen species. The central regulator of this response is the transcription factor Nrf2. Nrf2 modulates expression of the oxidative stress genes via the antioxidant response element (ARE).

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Throughout development cells make the decision to proliferate, arrest or die. Control of this process is essential for normal development, with unrestrained cell proliferation and cell death underlying the origin and progression of disease. The cell-cycle is tightly regulated by a number of factors including the cyclin-dependent kinase inhibitor 1A (Cdkn1a), termed p21 (or Cip1 or WAF1).

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Transgenic reporter mice can contribute in the development of less toxic and more selective drugs to treat disease. In this brief communication we describe the generation and initial validation of transgenic mice that provide a visual spatial readout of oxidative stress. These mice carry a LacZ reporter transgene driven by the human haem oxygenase 1 promoter.

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We describe asymptomatic bone cysts in the right humerus of a 17-year-old boy with Darier disease. The cysts were found when a radiographic skeletal survey was performed to monitor for adverse effects of oral retinoid therapy. Magnetic resonance imaging was used to confirm that the lesions were cystic and to delineate their extent.

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Background: The Department of Health in the UK has suggested that older people with complex health problems may benefit from a case-management approach to meet their needs. The NHS has since invested heavily in community matrons as one method of tackling managed care. Matrons are highly trained nurses, able to diagnose, prescribe and manage patients with long-term conditions within primary care.

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Background: The prognosis for patients with recurrent Ewing sarcoma (EWS) is very poor with 5-year survival of 13%.

Methods: To evaluate prognostic factors for these patients we studied patients initially treated on the multi-institutional study INT0091.

Results: Two hundred sixty-two patients experienced disease recurrence.

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There is an urgent need to discover less toxic and more selective drugs to treat disease. The use of transgenic mice that report on toxic insult-induced transcription can provide a valuable tool in this regard. To exemplify this strategy, we have generated transgenic mice carrying a p21-LacZ transgene.

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Background: There is evidence that African-Caribbean people with diabetes have poorer outcomes than other individuals with diabetes. It is not fully understood why this happens.

Aim: To gain an understanding of how health beliefs influence the way African-Caribbean people with diabetes manage their illness.

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Background: Good blood pressure (BP) control reduces the risk of complications in people with type 2 diabetes, yet many do not achieve this. Guidelines for managing hypertension recommend increasing antihypertensive medications until control is achieved, but the effect of such recommendations in routine primary care is unknown.

Aim: To evaluate the effectiveness of a BP treatment algorithm in primary care patients with type 2 diabetes.

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Mice of the C57BL/6 strain are resistant to the development of skin squamous carcinomas (SCCs) induced by an activated Ras oncogene, whereas FVB/N mice are highly susceptible. The genetic basis of this difference in phenotype is unknown. Here we show that susceptibility to SCC is under the control of a carboxy-terminal polymorphism in the mouse Ptch gene.

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Background: Usually experts decide on which research is worthwhile, yet it is government policy to involve service users in research. There has been a lack of published research about involving patients from minority ethnic groups and people from deprived areas in setting research agendas. In this study we wanted to hear the voices of patients that are not often heard.

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