Identification of a common variant in the lipoprotein lipase gene in a large Utah kindred ascertained for coronary heart disease: the -93G/D9N variant predisposes to low HDL-C/high triglycerides

Defects in the lipoprotein lipase (LPL) gene are associated with dyslipidemia in the general population. Several rare mutations in the gene, as well as two common coding region polymorphisms, D9N and N291S, exhibit deleterious effects on circulating lipid levels. Using a linkage-based approach, we have identified a large Utah kindred segregating the D9N variant in the LPL gene. The kindred was ascertained for premature coronary heart disease and was expanded based on familial dyslipidemia. A genomic scan identified a region of linkage including LPL, and mutation screening identified the segregating variant. In the kindred, the variant shows high penetrance for a hypoalphalipoproteinemia phenotype, but is also associated with hypertriglyceridemia and elevated insulin levels. The strength of linkage was dependent on the combination of phenotype definition and model parameters, favoring the use of a MOD score approach. Most other studies of LPL have proceeded by mutation screening of randomly chosen individuals or selected affected probands; this is the first example identifying a segregating LPL mutation using direct linkage.     

A Web-based compendium of clinical questions and medical evidence to educate internal medicine residents.

The authors designed an electronic database of clinical questions (CQs) and medical evidence and implemented it in 2001-02 at Duke University Medical Center and the Veterans Administration Medical Center in Durham, North Carolina. This Web-based data collection system is called the Critical Appraisal Resource (CAR) and is still in operation. This report is of ten months of the system's operation. During their medicine ward rotations, residents entered CQs into the CAR; they also entered Medline reference links and validated article summaries. Residents' utilization of the CAR database, Medline, and other electronic resources was prospectively measured. In addition, residents were prospectively surveyed regarding the impact of each question and associated reference on medical decision making for individual patients. Over ten months, residents entered 625 patient-based CQs into the CAR and were able to obtain useful information from the medical literature on 82% of the CQs they searched. The two most prevalent CQ types were therapy and diagnosis questions (53% and 22%). Sixty percent of the therapy articles considered useful were reports of randomized controlled trials. Residents obtained 77% of their useful data from Medline. They reported that obtaining useful data altered patient management 47% of the time. Residents used the CAR as a resource, searching the database for information 1,035 times over the study period. In summary, the use of an evidence-based critical appraisal resource led residents to engage the medical literature on behalf of their patients and influenced approximately half of their patient-care decisions. Residents benefited from questions previously searched by other residents, allowing them to address a wider spectrum of CQs during ward rotations.     

UK food and nutrition security during and after the COVID‐19 pandemic

The COVID‐19 pandemic is a major shock to society in terms of health and economy that is affecting both UK and global food and nutrition security. It is adding to the ‘perfect storm’ of threats to society from climate change, biodiversity loss and ecosystem degradation, at a time of considerable change, rising nationalism and breakdown in international collaboration. In the UK, the situation is further complicated due to Brexit. The UK COVID‐19 Food and Nutrition Security project, lasting one year, is funded by the Economic and Social Research Council and is assessing the ongoing impact of COVID‐19 on the four pillars of food and nutrition security: access, availability, utilisation and stability. It examines the food system, how it is responding, and potential knock on effects on the UK’s food and nutrition security, both in terms of the cascading risks from the pandemic and other threats. The study provides an opportunity to place the initial lessons being learnt from the on‐going responses to the pandemic in respect of food and nutrition security in the context of other long‐term challenges such as climate change and biodiversity loss.     

Margaret Sanger: birth control's successful revolutionary.

The year 1979 marked the centennial of Margaret Sanger, birth control pioneer. Sanger worked to secure two new human rights: the right to decide whether to have a child and the right of a child to be wanted. Beginning in 1873, antipornography crusader Anthony Comstock lobbied through Congress and the state legislatures laws forbidding the distribution of contraceptive devices and even information. He equated these with erotic postcards as "obscene, lewd, lascivious, filthy, indecent and disgusting." Sanger's strategy was to challenge the Comstock laws in the courts. She studied birth control methods abroad and published a pamphlet, Family Limitation, in 1914. It was the first modern marriage manual; it was also illegal. The publicity her trial generated was immense and highly sympathetic. The government dropped its case when it saw it could only make her a martyr. An obstetrical nurse, Sanger had seen the plight of factory women in the poorest sections of New York City. In order to provide the medical advice and supplies women clamored for, Sanger opened the first U.S. birth control clinic, in Brooklyn in 1916. The New York City Vice Squad raided and closed it, and jailed Sanger. Margaret Sanger underwent other trials, raids, and harassments, but each time won additional public support for her organization--Planned Parenthood--and her cause.     

Development of a Pacifier for Low-Birth-Weight Infants' Nonnutritive Sucking

Nonnutritive sucking can provide low-birth-weight infants with an opportunity to organize their behavior, an important component of developmental care. A pacifier specifically designed for low-birth-weight infants facilitates their nonnutritive sucking to more fully meet their needs. The research and development of a pacifier for low-birth-weight infants incorporated a naturalistic approach and used the best model, the infant thumb, in the design. Clinical trials with infants randomized to control and experimental groups were conducted to compare the prototype pacifier to a commercially available pacifier. Observations using the Anderson Behavioral State Scale demonstrated that infants using the prototype pacifier more often were found to be in an alert state. This pacifier may contribute to infants' state organization for optimum feeding and could be a component in developmental care planning.     

Genomewide profiling of copy‐number alteration in monoclonal gammopathy of undetermined significance

Monoclonal gammopathy of undetermined significance (MGUS) is a benign condition with an approximate 1% annual risk of symptomatic plasma cell disorder development, mostly to multiple myeloma (MM). We performed genomewide screening of copy‐number alterations (CNAs) in 90 MGUS and 33 MM patients using high‐density DNA microarrays. We identified CNAs in a smaller proportion of MGUS (65.6%) than in MM (100.0%, P = 1.31 × 10^?5) and showed median number of CNAs is lower in MGUS (3, range 0–22) than in MM (13, range 4–38, P = 1.82 × 10^?10). In the MGUS cohort, the most frequent losses were located at 1p (5.6%), 6q (6.7%), 13q (30.0%), 14q (14.4%), 16q (8.9%), 21q (5.6%), and gains at 1q (23.3%), 2p (6.7%), 6p (13.3%), and Xq (7.8%). Hyperdiploidy was detected in 38.9% of MGUS cases, and the most frequent whole chromosome gains were 3 (25.6%), 5 (23.3%), 9 (37.8%), 15 (23.3%), and 19 (32.2%). We also identified CNAs such as 1p, 6q, 8p, 12p, 13q, 16q losses, 1q gain and hypodiploidy, which are potentially associated with an adverse prognosis in MGUS. In summary, we showed that MGUS is similar to MM in that it is a genetically heterogeneous disorder, but overall cytogenetic instability is lower than in MM, which confirms that genetic abnormalities play important role in monoclonal gammopathies.     

Identification of a novel t(7;14) translocation in multiple myeloma resulting in overexpression of EGFR

IGH translocations in myeloma are a primary event and determine the prognostic outcome of a patient. These events are characterized by FISH and classical cytogenetics, but in a small proportion of samples a translocation involving the IGH locus can be detected but the partner chromosome cannot be identified. These cases are usually genetically complex and are the result of cryptic events that cannot be discerned at the resolution of FISH. Here we analyzed a sample with an unidentified translocation partner using a targeted capture and massively parallel sequencing. We identified the partner chromosome as a t(7;14) with the breakpoint upstream of EGFR. This sample over‐expresses the target oncogene, EGFR. This case represents a rare and novel translocation in myeloma, from which a targeted personalized treatment, in the form of EGFR inhibitors, which are commonly used in other cancer types, could be used. © 2013 Wiley Periodicals, Inc.