Direct observation of magnetic ordering induced systematic lattice disorder in artificial rhombus spin ices.

It is critical to understand the effect of lattice geometry on the order parameter of a condensed matter system, as it controls phase transitions in such systems. Artificial spin ices (ASIs) are two-dimensional lattices of Ising-like nanomagnets that provide an opportunity to explore such phenomena by lithographically controlling the lattice geometry to observe its influence on magnetic ordering and frustration effects. Here we report a systematic approach to studying the effects of disorder in rhombus ASIs generated from combinations of five vertex motifs.

The need for worldwide policy and action plans for rare diseases.

Unlabelled: There are more than 6000 rare diseases (defined as affecting <5/10 000 individuals in Europe, <200 000 people in the United States). The rarity can create problems including: difficulties in obtaining timely, accurate diagnoses; lack of experienced healthcare providers; useful, reliable and timely information may be hard to find; research activities are less common; developing new medicines may not be economically feasible; treatments are sometimes very expensive; and in developing countries, the problems are compounded by other resource limitations. Emphasis is required to support appropriate research and development leading to better prevention, diagnosis and treatments of rare diseases.

Clinical pharmacology as a cornerstone of orphan drug development.

A recent US Food and Drug Administration (FDA) advisory committee meeting highlighted the potential of clinical pharmacology to overcome challenges in orphan drug development.

Regulatory considerations for developing drugs for rare diseases: orphan designations and early phase clinical trials.

The development of drug and biological products intended to treat rare diseases (Orphan diseases) is one of the fastest growing areas of clinical research, and also one of the most challenging. This article provides an introduction to two important regulatory considerations for Orphan drugs: Orphan status designations and general considerations for the administration of investigational agents in early phase clinical trials. Incentives available to orphan drug developers under the Orphan Drug Act (ODA) and requirements for obtaining an orphan status designation are discussed.

Database identifies FDA-approved drugs with potential to be repurposed for treatment of orphan diseases.

Facing substantial obstacles to developing new therapies for rare diseases, some sponsors are looking to 'repurpose' drugs already approved for other conditions and use those therapies to treat rare diseases. In an effort to facilitate such repurposing and speed the delivery of new therapies to people who need them, we have established a new resource, the Rare Disease Repurposing Database (RDRD). The advantages of repurposed compounds include their demonstrated efficacy (in some clinical contexts), their observed toxicity profiles and their clearly described manufacturing controls.

Accelerating orphan drug development.

Interest in developing drugs for rare diseases has increased substantially in recent years. This article from the US Food and Drug Administration highlights the role of regulators in catalysing further progress in this field.

The Orphan Drug Act and the development of stem cell-based products for rare diseases.

The Orphan Drug Act encourages the development of products for rare diseases and conditions. Many conditions that stand to benefit from stem cell-based products are rare diseases. We address the Orphan Drug Act in relation to the development of stem cell-based products.

Therapies for inborn errors of metabolism: what has the orphan drug act delivered?

Objective: The 1983 US Orphan Drug Act established a process through which promising therapies are designated as orphan products and, later, with satisfactory safety and efficacy data, receive marketing approval and fiscal incentives. We examined accomplishments in drug development for inborn errors of metabolism (IEMs).

Methods: Food and Drug Administration data were used to identify orphan product designations and approvals for IEMs, and the trends for the past 26 years were summarized.

Emergence of orphan drugs in the United States: a quantitative assessment of the first 25 years.

The 1983 US Orphan Drug Act has stimulated the development of new therapies for rare diseases. To provide the first comprehensive overview of orphan-designated products and their indications, this article quantitatively analyses the characteristics and distribution of orphan designations and approvals by the US Food and Drug Administration from 1983 to August 2008. Of the 1,892 orphan-designated products, 326 received marketing approval, representing 247 different drugs and more than 200 different diseases.

Duchenne muscular dystrophy: Drug development and regulatory considerations.

Duchenne muscular dystrophy (DMD) is one of the most commonly recognized dystrophinopathies. There are no approved therapeutic options available for this disease but recent discoveries have led to hope that effective therapies might be forthcoming. With funding from patient advocacy groups, private investors, and governmental bodies such as the Food and Drug Administration Office of Orphan Product Development (FDA/OOPD), gene modification and other molecular therapies are being actively investigated.

Primary melanomas of the esophagus and anorectum: epidemiologic comparison with melanoma of the skin.

The objective of this study was to use recently available data to describe the epidemiology of melanomas of the esophagus and the anorectum in contrast to melanoma of the skin. The methods used include descriptive epidemiology using cases reported to the Surveillance Epidemiology and End Results registry, 1973-2003. All rates were age adjusted.

Autologous cultured chondrocytes: adverse events reported to the United States Food and Drug Administration.

Background: Carticel is an autologous cultured chondrocyte product that has been approved by the United States Food and Drug Administration for the repair of symptomatic cartilaginous defects of the femoral condyle that are caused by acute or repetitive trauma in patients who have been previously managed with arthroscopy or other surgical procedures. The present report describes the adverse events following Carticel implantation as reported to the Food and Drug Administration from 1996 to 2003.

Methods: We reviewed adverse event reports that had been submitted to the Food and Drug Administration's MedWatch system for information on demographic characteristics, adverse events, and surgical revisions.

Botulinum toxin type A injections: adverse events reported to the US Food and Drug Administration in therapeutic and cosmetic cases.

Background: Botulinum toxin type A (BTA) (Botox) received Food and Drug Administration (FDA) approval for therapeutic treatment of strabismus and blepharospasm in 1989, cervical dystonia in 2000, and cosmetic treatment of glabellar wrinkles (Botox Cosmetic) in 2002. In 2002 alone there were approximately 1.1 to 1.

Tissues from population-based cancer registries: a novel approach to increasing research potential.

Population-based cancer registries, such as those included in the Surveillance, Epidemiology, and End-Results (SEER) Program, offer tremendous research potential beyond traditional surveillance activities. We describe the expansion of SEER registries to gather formalin-fixed, paraffin-embedded tissue from cancer patients on a population basis. Population-based tissue banks have the advantage of providing an unbiased sampling frame for evaluating the public health impact of genes or protein targets that may be used for therapeutic or diagnostic purposes in defined communities.

CK20 and CK7 protein expression in colorectal cancer: demonstration of the utility of a population-based tissue microarray.

The ability to use archival tissue to test externally valid hypotheses of carcinogenesis is dependent on the availability of population-based samples of cancer tissue. Tissue microarrays (TMAs) provide an efficient format for developing population-based samples of tissue. A TMA was constructed consisting of archival tissue from patients diagnosed with invasive colorectal cancer in the state of Hawaii in 1995.

Tuberculosis following the use of etanercept, a tumor necrosis factor inhibitor.

Infliximab, a tumor necrosis factor (TNF) antagonist, is associated with tuberculosis (TB), but it is unknown whether this phenomenon is true of all TNF antagonists. We reviewed 25 cases of TB due to another TNF antagonist, etanercept, that were reported to the US Food and Drug Administration (FDA) between November 1998 and March 2002. Such cases are sometimes incomplete and are subject to underreporting.

Deaths among children less than two years of age receiving palivizumab: an analysis of comorbidities.

Background: Palivizumab (Synagis) is used for prophylaxis against respiratory syncytial virus infection among children at high risk for respiratory syncytial virus disease. A number of deaths after palivizumab use among children <2 years have been reported to the Food and Drug Administration. We assessed available information, including the extent to which preexisting medical conditions may have put these children at higher than normal risk of death.

Surveillance, epidemiology, and end results analysis of 2677 cases of uterine sarcoma 1989-1999.

Objectives: To determine the association of race with incidence, histology, treatment, and survival in women with uterine sarcoma during the period 1989-1999.

Methods: Uterine sarcomas were defined as leiomyosarcoma, carcinosarcoma, high-grade endometrial stromal sarcoma (HGESS), adenosarcoma, and sarcoma not otherwise specified (NOS). We used cases from Surveillance, Epidemiology, and End Results (SEER) program to compare uterine sarcoma among women >35 years of age.

Survival among women with borderline ovarian tumors and ovarian carcinoma: a population-based analysis.

Background: Serous and mucinous ovarian tumors of low malignant potential (LMP-S and LMP-M, respectively) are noninvasive tumors that portend excellent survival when confined to the ovary. Comparison of the survival for women with LMP tumors staged as distant with women who have carcinoma may have important implications for diagnostic terminology and clinical management.

Methods: The authors compared relative survival rates among patients diagnosed with ovarian tumors during the period 1988-1999 (with follow-up through 2000) by histologic type, disease stage, tumor grade (for carcinomas), and patient age, using data from the Surveillance, Epidemiology, and End Results Program.

Case reports of heart failure after therapy with a tumor necrosis factor antagonist.

Background: Etanercept and infliximab are U.S. Food and Drug Administration-approved tumor necrosis factor (TNF) antagonists.