Birth defects interstate data exchange: a battle worth fighting?

BACKGROUND: Regardless of where infants and children are delivered, diagnosed, or treated, an important aspect of population-based birth defects surveillance is ensuring the inclusion of children with birth defects in the catchment area. However, little is known as to how the lack of interstate birth defects data exchange affects program surveillance, monitoring, prevention, and referral activities. The study objectives were to determine the status of interstate birth defects data exchange agreements and to quantify statewide data on resident births occurring in nonresident states. METHODS: In 2004, surveys were distributed to all population-based birth defects programs in the United States to determine: 1) the types of interstate birth defects data exchange agreements that exist among birth defects programs, 2) perceived barriers in establishing exchange agreements, and 3) the extent to which out-of-state births affect a program's catchment area. The National Center for Health Statistics (NCHS) data for 2002 on live birth residency were used to determine the actual frequency of out-of-state live birth occurrence. RESULTS: Of the 52 states and territories that were surveyed, 65% (n = 34) responded. Approximately 21% (n = 7) of those that responded had an interstate data exchange agreement that allowed sharing of birth defects data with another state or a facility within another state. Approximately 53% (n = 18) of responding states indicated plans to develop an interstate birth defects data exchange agreement with other states, hospitals, or both. The NCHS data showed that the actual percentage of resident out-of-state live births ranged from 0.16 to 11.51. NCHS data also reveal that 78% of states would be able to capture >75% of their out-of-state births by sharing data on out-of-state births with the three neighboring states ranking highest in terms of such occurrences. CONCLUSIONS: Few states have interstate birth defects data exchange agreements, though all states have resident births occurring out of state. While suggestive, data beyond residency of live births are needed to quantify the degree to which the objectives of state-based birth defects programs are compromised. Resources exist to guide programs in establishing interstate data exchange agreements. Efforts to establish such agreements with only a few neighboring states could be a large step toward improving birth defects surveillance on a state, regional, and national level.     

Strengthening the Reporting of Observational Studies in Epidemiology (STROBE): explanation and elaboration

Much medical research is observational. The reporting of observational studies is often of insufficient quality. Poor reporting hampers the assessment of the strengths and weaknesses of a study and the generalisability of its results. Taking into account empirical evidence and theoretical considerations, a group of methodologists, researchers, and editors developed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) recommendations to improve the quality of reporting of observational studies. The STROBE Statement consists of a checklist of 22 items, which relate to the title, abstract, introduction, methods, results and discussion sections of articles. Eighteen items are common to cohort studies, case-control studies and cross-sectional studies and four are specific to each of the three study designs. The STROBE Statement provides guidance to authors about how to improve the reporting of observational studies and facilitates critical appraisal and interpretation of studies by reviewers, journal editors and readers. This explanatory and elaboration document is intended to enhance the use, understanding, and dissemination of the STROBE Statement. The meaning and rationale for each checklist item are presented. For each item, one or several published examples and, where possible, references to relevant empirical studies and methodological literature are provided. Examples of useful flow diagrams are also included. The STROBE Statement, this document, and the associated Web site (http://www.strobe-statement.org/) should be helpful resources to improve reporting of observational research.     

Mechanism of Cross-talk between H2B Ubiquitination and H3 Methylation by Dot1L

1. Download high-res image (196KB)
2. Download full-size image

     

IQCELL: A platform for predicting the effect of gene perturbations on developmental trajectories using single-cell RNA-seq data

The increasing availability of single-cell RNA-sequencing (scRNA-seq) data from various developmental systems provides the opportunity to infer gene regulatory networks (GRNs) directly from data. Herein we describe IQCELL, a platform to infer, simulate, and study executable logical GRNs directly from scRNA-seq data. Such executable GRNs allow simulation of fundamental hypotheses governing developmental programs and help accelerate the design of strategies to control stem cell fate. We first describe the architecture of IQCELL. Next, we apply IQCELL to scRNA-seq datasets from early mouse T-cell and red blood cell development, and show that the platform can infer overall over 74% of causal gene interactions previously reported from decades of research. We will also show that dynamic simulations of the generated GRN qualitatively recapitulate the effects of known gene perturbations. Finally, we implement an IQCELL gene selection pipeline that allows us to identify candidate genes, without prior knowledge. We demonstrate that GRN simulations based on the inferred set yield results similar to the original curated lists. In summary, the IQCELL platform offers a versatile tool to infer, simulate, and study executable GRNs in dynamic biological systems.     

Stereotactic radiotherapy for brain oligometastases

Brain metastases, the most common metastases in adults, will develop in up to 40% of cancer patients, accounting for more than one-half of all intracranial tumors. They are most associated with breast and lung cancer, melanoma and, less frequently, colorectal and kidney carcinoma.Magnetic resonance imaging (MRI) is the gold standard for diagnosis. For the treatment plan, computed tomography (CT ) images are co-registered and fused with a gadolinium-enhanced T1-weighted MRI where tumor volume and organs at risk are contoured. Alternatively, plain and contrast-enhanced CT scans are co-registered. Single-fraction stereotactic radiotherapy (SRT ) is used to treat patients with good performance status and up to 4 lesions with a diameter of 30 mm or less that are distant from crucial brain function areas. Fractionated SRT (2–5 fractions) is used for larger lesions, in eloquent areas or in proximity to crucial or surgically inaccessible areas and to reduce treatment-related neurotoxicity. The single-fraction SRT dose, which depends on tumor diameter, impacts local control. Fractionated SRT may encompass different schedules. No randomized trial data compared the safety and efficacy of single and multiple fractions. Both single-fraction and fractionated SRT provide satisfactory local control rates, tolerance, a low risk of transient acute adverse events and of radiation necrosis the incidence of which correlated with the irradiated brain volume.     

Radiobiology of stereotactic radiotherapy

This paper focuses on the radiobiological mechanisms underlying the effects of stereotactic radiotherapy (SRT ) which, despite SRT expansion, have not yet been fully elucidated. Some authors postulated that radiobiology principles, as applied to conventional fractionations (5R: reoxygenation, repair, repopulation, redistribution, radioresistence), suffice in themselves to account for the excellent clinical results of SRT; others argued that the role of the 5R was limited. Recent preclinical data showed that hypofractionated ablative treatments altered the microenvironment, thus determining cell death either directly or indirectly. Furthermore, dead tumor cells released quantities of antigens, which stimulated antitumor immunity, thus reducing the risk of relapse and metastasis. Better understanding of the radiobiological mechanisms underlying response to high-dose radiation treatment is essential for predicting its short- and long-term effects on the tumor and surrounding healthy tissues and, consequently, for improving its related therapeutic index.     

Determination of a HIV protease inhibitor (DMP 450) in animal and human plasma by solid-phase extraction and high-performance liquid chromatography

Extraction of DMP 450 from plasma was performed with C₂ solid-phase extraction columns, using 0.1 M ammonium acetate in 90% methanol to elute DMP 450. The extraction recovery over the range of 10 to 10 000 ng/ml averaged 81.0, 96.2, 77.4, 95.2 and 68.0% from rat, dog, monkey, chimpanzee (25–10 000 ng/ml) and human plasma, respectively. HPLC analysis was carried out with a C₁₈ column and a mobile phase of acetonitrile, methanol and 30 mM potassium phosphate (pH 3), the composition dependent on the type of plasma being analyzed, and monitored at a wavelength of 229 nm. Intra-day and inter-day coefficients of variation were less than 9.9 and 12.9%, respectively. Absolute differences were less than 11.5%.     

Changes in white oak (Quercus alba) phytochemistry in response to periodical cicadas: Before,during, and after an emergence

Periodical cicadas have mass emergences once every 13 or 17 years. Plants may need to upregulate defense production in response to an emergence. Defense production is energetically expensive, so plants may downregulate their production after periodical cicada populations dissipate. We examined the defensive responses in leaves, branches, and roots of a common host, white oak (Quercus alba), prior to, during, and after a 17‐year periodical cicada (Magicicada spp.) emergence in western Pennsylvania, United States. During the emergence, total tannins and condensed tannins increased in foliar tissue, while simultaneously decreasing in root tissue compared to the prior and subsequent years. Non‐structural carbohydrates were low prior to the mass emergence but were re‐allocated to belowground storage during the emergence year and dropped thereafter. In the year after the emergence, there was a relaxation of foliar defenses, and root defenses returned to pre‐emergence concentrations. We also tested for differences in damaged and undamaged branches on the same tree during (2019) and the year after the emergence (2020). Both damaged and undamaged branches had significantly greater chemical defenses (polyphenols, total tannins, and condensed tannins) during the emergence than in the following year when there was no emergence. We propose that re‐allocation of resources may help maximize oak tree fitness by moving resources away from areas that are not in immediate threat to areas that are under immediate threat. Changes in aboveground and belowground phytochemistry in response to periodical cicada mass emergences may help us better understand which resource re‐allocation strategies are used by plants to minimize the effects of insect emergencies.     

Resistance to Acarapis woodi by honey bees (Hymenoptera: Apidae): divergent selection and evaluation of selection progress

Two generations of honey bees, Apis mellifera L., selected for resistance to tracheal mites, Acarapis woodi (Rennie), were produced from a foundation stock. The mite resistant lines had significantly low mite abundances and prevalences in each selected generation. The high mite-resistant lines of the first selected generation showed resistance equal to that of bees that had undergone natural selection from tracheal mite infestations for 3 yr in New York. Additionally, the high mite-resistant lines of the second selected generation and Buckfast bees had significantly lower mite abundances and prevalences than honey bees from control colonies which had never been exposed to tracheal mite infestation in Ontario. These results corroborate studies that have shown that honey bees possess genetic components for tracheal mite resistance that can be readily enhanced in a breeding program. The two methods used for evaluating relative resistance of honey bees to tracheal mites, a short-term bioassay and evaluation in field colonies, were positively correlated (rs = 0.64, P < 0.001).