Body mass index has risen more steeply in tall than in short 3-year olds: serial cross-sectional surveys 1988-2003

Objective: To monitor the changing relationship between body mass index ( BMI) and height in young children.Design: Annual cross-sectional surveys using health-visitor-collected routine data 1988 - 2003.Setting: Wirral, England.Participants: Fifty thousand four hundred and fifty-five children ( 49% female) each measured once at the age of 3 years.Main outcome measures: Weight, height and derived BMI ( weight/height(2)) adjusted for age and sex ( British 1990 revised reference) using standard deviation scores.Results: From 1988 to 2003, mean BMI increased by 0.7 kg/m(2), whereas mean height fell by 0.5 cm. Over the same period, the weight - height correlation rose from 0.59 to 0.71 ( P < 0.0001) owing to BMI increasing faster in the taller than the shorter children. Among the shortest 10% of children, mean BMI rose by 0.12 ( 95% confidence interval: - 0.05 - 0.28) kg/m(2) as against 1.38 ( 1.19 - 1.56) kg/m(2) among the tallest 10%, a 12-fold difference. Adjustment for age, sex, seasonality, birth-weight and deprivation did not alter the findings.Conclusions: Among 3-year-old children in Wirral, where BMI has been rising for 16 years, the largest increase in BMI has occurred in the tallest children, whereas in the shortest BMI has hardly changed. Tall stature has, therefore, become important for child obesity. It suggests a drive to increasing adiposity in young children that involves both growth and appetite, with fast growing and hungrier children now more exposed to the 'obesogenic' environment

Body mass index has a curvilinear relationship with the percentage of body fat among children

<p>Abstract</p> <p>Background</p> <p>Body Mass Index (BMI), which is defined as the ratio between weight (in kg) and height (in m²), is often used in clinical practice as well as in large scale epidemiological studies to classify subjects as underweight, normal weight, overweight or obese. Although BMI does not directly measure the percentage of Body Fat (BF%), it is widely applied because it is strongly related with BF%, it is easy to measure and it is an important predictor of mortality. Among children, age and sex-specific reference values of BMI, known as percentiles, are used. However, it is not clear how strong the relationship between BMI and BF% is among children and whether the association is linear. We performed a cross-sectional study aiming at evaluating the strength and shape of the relationship between BMI and BF% among school-aged children aged 6-12 years.</p> <p>Findings</p> <p>The study was conducted on a sample of 361 football-playing male children aged 6 to 12 years in Rome, Italy. Age, weight, height and skinfold thickness were collected. BF% was estimated using 4 skinfold equations whereas BMI was converted into BMI-for-age z-score. The relationship between these variables was examined using linear regression analyses. Mean BMI was 18.2 (± 2.8), whereas BF% was influenced by the skinfold equation used, with mean values ranging from 15.6% to 23.0%. A curvilinear relationship between BMI-for-age zscore and BF % was found, with the regression line being convex. The association between BMI-for-age zscore and BF% was stronger among overweight/obese children than among normal/underweight children. This curvilinear pattern was evident in all 4 skinfold equations used.</p> <p>Conclusions</p> <p>The association between BMI-for-age zscore and BF% is not linear among male children aged 6-12 years and it is stronger among overweight and obese subjects than among normal and underweight subjects. In this age group, BMI is a valid index of adiposity only among overweight and obese subjects.</p

Farms, pipes, streams and reforestation : reasoning about structured parallel processes using types and hylomorphisms

The increasing importance of parallelism has motivated the creation of better abstractions for writing parallel software, including structured parallelism using nested algorithmic skeletons. Such approaches provide high-level abstractions that avoid common problems, such as race conditions, and often allow strong cost models to be defined. However, choosing a combination of algorithmic skeletons that yields good parallel speedups for a program on some specific parallel architecture remains a difficult task. In order to achieve this, it is necessary to simultaneously reason both about the costs of different parallel structures and about the semantic equivalences between them. This paper presents a new type-based mechanism that enables strong static reasoning about these properties. We exploit well-known properties of a very general recursion pattern, hylomorphisms, and give a denotational semantics for structured parallel processes in terms of these hylomorphisms. Using our approach, it is possible to determine formally whether it is possible to introduce a desired parallel structure into a program without altering its functional behaviour, and also to choose a version of that parallel structure that minimises some given cost model.Postprin

Estrogen as therapy for breast cancer

High-dose estrogen was generally considered the endocrine therapy of choice for postmenopausal women with breast cancer prior to the introduction of tamoxifen. Subsequently, the use of estrogen was largely abandoned. Recent clinical trial data have shown clinically meaningful efficacy for high-dose estrogen even in patients with extensive prior endocrine therapy. Preclinical research has demonstrated that the estrogen dose-response curve for breast cancer cells can be shifted by modification of the estrogen environment. Clinical and laboratory data together provide the basis for developing testable hypotheses of management strategies, with the potential of increasing the value of endocrine therapy in women with breast cancer

Improved annotation of 3' untranslated regions and complex loci by combination of strand-specific direct RNA sequencing, RNA-seq and ESTs

The reference annotations made for a genome sequence provide the framework for all subsequent analyses of the genome. Correct annotation is particularly important when interpreting the results of RNA-seq experiments where short sequence reads are mapped against the genome and assigned to genes according to the annotation. Inconsistencies in annotations between the reference and the experimental system can lead to incorrect interpretation of the effect on RNA expression of an experimental treatment or mutation in the system under study. Until recently, the genome-wide annotation of 3-prime untranslated regions received less attention than coding regions and the delineation of intron/exon boundaries. In this paper, data produced for samples in Human, Chicken and A. thaliana by the novel single-molecule, strand-specific, Direct RNA Sequencing technology from Helicos Biosciences which locates 3-prime polyadenylation sites to within +/- 2 nt, were combined with archival EST and RNA-Seq data. Nine examples are illustrated where this combination of data allowed: (1) gene and 3-prime UTR re-annotation (including extension of one 3-prime UTR by 5.9 kb); (2) disentangling of gene expression in complex regions; (3) clearer interpretation of small RNA expression and (4) identification of novel genes. While the specific examples displayed here may become obsolete as genome sequences and their annotations are refined, the principles laid out in this paper will be of general use both to those annotating genomes and those seeking to interpret existing publically available annotations in the context of their own experimental dataComment: 44 pages, 9 figure

Swab pooling enables rapid expansion of high-throughput capacity for SARS-CoV-2 community testing

Background: The challenges of rapid upscaling of testing capacity were a major lesson from the COVID-19 pandemic response. The need for process adjustments in high-throughput testing laboratories made sample pooling a challenging option to implement. / Objective: This study aimed to evaluate whether pooling samples at source (swab pooling) was as effective as qRT-PCR testing of individuals in identifying cases of SARS-CoV-2 in real-world community testing conditions using the same high-throughput pipeline. / Methods: Two cohorts of 10 (Pool10: 1,030 participants and 103 pools) and 6 (Pool6: 1,284 participants and 214 pools) samples per pool were tested for concordance, sensitivity, specificity, and Ct value differences with individual testing as reference. Results: Swab pooling allowed unmodified application of an existing high-throughput SARS-Cov-2 testing pipeline with only marginal loss of accuracy. For Pool10, concordance was 98.1% (95% Confidence interval: 93.3–99.8%), sensitivity was 95.7% (85.5–99.5%), and specificity was 100.0% (93.6–100.0%). For Pool6, concordance was 97.2% (94.0–99.0%), sensitivity was 97.5% (93.7–99.3%), and specificity was 96.4% (87.7–99.6%). Differences of outcomes measure between pool size were not significant. Most positive individual samples, which were not detected in pools, had very low viral concentration. If only individual samples with a viral concentration > 400 copies/ml (i.e. Ct value < 30) were considered positive, the overall sensitivity of pooling increased to 99.5%. / Conclusion: The study demonstrated high sensitivity and specificity by swab pooling and the immediate capability of high-throughput laboratories to implement this method making it an option in planning of rapid upscaling of laboratory capacity for future pandemics

Surfactant status and respiratory outcome in premature infants receiving late surfactant treatment.

BACKGROUND:Many premature infants with respiratory failure are deficient in surfactant, but the relationship to occurrence of bronchopulmonary dysplasia (BPD) is uncertain. METHODS:Tracheal aspirates were collected from 209 treated and control infants enrolled at 7-14 days in the Trial of Late Surfactant. The content of phospholipid, surfactant protein B, and total protein were determined in large aggregate (active) surfactant. RESULTS:At 24 h, surfactant treatment transiently increased surfactant protein B content (70%, p &lt; 0.01), but did not affect recovered airway surfactant or total protein/phospholipid. The level of recovered surfactant during dosing was directly associated with content of surfactant protein B (r = 0.50, p &lt; 0.00001) and inversely related to total protein (r = 0.39, p &lt; 0.0001). For all infants, occurrence of BPD was associated with lower levels of recovered large aggregate surfactant, higher protein content, and lower SP-B levels. Tracheal aspirates with lower amounts of recovered surfactant had an increased proportion of small vesicle (inactive) surfactant. CONCLUSIONS:We conclude that many intubated premature infants are deficient in active surfactant, in part due to increased intra-alveolar metabolism, low SP-B content, and protein inhibition, and that the severity of this deficit is predictive of BPD. Late surfactant treatment at the frequency used did not provide a sustained increase in airway surfactant

Use of Short Tandem Repeat Sequences to Study Mycobacterium leprae in Leprosy Patients in Malawi and India

Molecular typing has provided an important tool for studies of many pathogens. Such methods could be particularly useful in studies of leprosy, given the many outstanding questions about the pathogenesis and epidemiology of this disease. The approach is particularly difficult with leprosy, however, because of the genetic homogeneity of M. leprae and our inability to culture it. This paper describes molecular epidemiological studies carried out on leprosy patients in Malawi and in India, using short tandem repeat sequences (STRS) as markers of M. leprae strains. It reveals evidence for continuous changes in these markers within individual patients over time, and for selection of different STRS-defined strains between different tissues (skin and nerve) in the same patient. Comparisons between patients collected under different circumstances reveal the uses and limitations of the approach—STRS analysis may in some circumstances provide a means to trace short transmission chains, but it does not provide a robust tool for distinguishing between relapse and reinfection. This encourages further work to identify genetic markers with different stability characteristics for incorporation into epidemiological studies of leprosy

Efficacy and tolerability of high dose "ethinylestradiol" in post-menopausal advanced breast cancer patients heavily pre-treated with endocrine agents

BACKGROUND: High dose estrogens (HDEs) were frequently used as endocrine agents prior to the introduction of tamoxifen which carries fewer side effects. Due to the development of resistance to available endocrine agents in almost all women with metastatic breast cancer, interest has renewed in the use of HDEs as yet another endocrine option that may have activity. We report our experience with one of the HDEs ("ethinylestradiol" 1 mg daily) in advanced breast cancer (locally advanced and metastatic) in post-menopausal women who had progressed on multiple endocrine agents. PATIENTS AND METHODS: According to a database of advanced breast cancer patients seen in our Unit since 1998, those who had complete set of information and fulfilled the following criteria were studied: (1) patients in whom further endocrine therapy was deemed appropriate i.e., patients who have had clinical benefit with previous endocrine agents or were not fit or unwilling to receive chemotherapy in the presence of potentially life-threatening visceral metastases; (2) disease was assessable by UICC criteria; (3) were treated with "ethinylestradiol" until they were withdrawn from treatment due to adverse events or disease progression. RESULTS: Twelve patients with a median age of 75.1 years (49.1 – 85 years) were identified. Majority (N = 8) had bony disease. They had ethinylestradiol as 3(rd )to 7(th )line endocrine therapy. One patient (8%) came off treatment early due to hepato-renal syndrome. Clinical benefit (objective response or durable stable disease for ≥ 6 months) was seen in 4 patients (33.3%) with a median duration of response of 10+ (7–36) months. The time to treatment failure was 4 (0.5–36) months. CONCLUSION: Yet unreported, high dose "ethinylestradiol" is another viable therapeutic strategy in heavily pre-treated patients when further endocrine therapy is deemed appropriate. Although it tends to carry more side effects, they may not be comparable to those of other HDEs (such as diethylstilbestrol) or chemotherapy

Using the RDP Classifier to Predict Taxonomic Novelty and Reduce the Search Space for Finding Novel Organisms

BACKGROUND: Currently, the naïve Bayesian classifier provided by the Ribosomal Database Project (RDP) is one of the most widely used tools to classify 16S rRNA sequences, mainly collected from environmental samples. We show that RDP has 97+% assignment accuracy and is fast for 250 bp and longer reads when the read originates from a taxon known to the database. Because most environmental samples will contain organisms from taxa whose 16S rRNA genes have not been previously sequenced, we aim to benchmark how well the RDP classifier and other competing methods can discriminate these novel taxa from known taxa. PRINCIPAL FINDINGS: Because each fragment is assigned a score (containing likelihood or confidence information such as the boostrap score in the RDP classifier), we "train" a threshold to discriminate between novel and known organisms and observe its performance on a test set. The threshold that we determine tends to be conservative (low sensitivity but high specificity) for naïve Bayesian methods. Nonetheless, our method performs better with the RDP classifier than the other methods tested, measured by the f-measure and the area-under-the-curve on the receiver operating characteristic of the test set. By constraining the database to well-represented genera, sensitivity improves 3-15%. Finally, we show that the detector is a good predictor to determine novel abundant taxa (especially for finer levels of taxonomy where novelty is more likely to be present). CONCLUSIONS: We conclude that selecting a read-length appropriate RDP bootstrap score can significantly reduce the search space for identifying novel genera and higher levels in taxonomy. In addition, having a well-represented database significantly improves performance while having genera that are "highly" similar does not make a significant improvement. On a real dataset from an Amazon Terra Preta soil sample, we show that the detector can predict (or correlates to) whether novel sequences will be assigned to new taxa when the RDP database "doubles" in the future