Anaesthetic neuroprotection in the setting of traumatic brain injury (TBI) remains unproved and is based upon the results in preclinical experiments. Here, we sought to synthesise the results in ...rodent models of TBI, and to evaluate the effects of publication bias, experimental manipulation, and poor study quality on the effect estimates.
After a systematic review, we used pairwise meta-analysis to estimate the effect of anaesthetics, opioids, and sedative–hypnotics on neurological outcome, and network meta-analysis to compare their relative efficacy. We sought evidence of bias related to selective publication, experimental manipulation, and study quality.
Sixteen studies, involving 32 comparisons, were included (546 animals). The treatment improved the neurological outcomes by 35%; 95% confidence interval: 26–44%; P<0.001. The statistical heterogeneity was small (12%), but the 95% prediction interval for the estimate was wide (15–56%). The statistical power was low: 61% (90% confidence interval: 22–86%). The small sample size in the studies was a serious shortcoming reducing the statistical heterogeneity and obscuring differences in outcome between drugs and between experimental conditions.
Anaesthetics do provide neuroprotection in rodent models of TBI. The effect-size estimates do not appear to be exaggerated by selective publication, experimental manipulation, or study design. The main shortcoming of the included studies were small sample sizes leading to low power and imprecision, which precluded the network meta-analysis from providing a meaningful ranking for efficacy amongst the drugs. Reliable preclinical investigations of neuroprotection by anaesthetics will require larger sample sizes.
Wildfire is an important disturbance agent in Canada's boreal forest. Optical remotely sensed imagery (e.g., Landsat TM/ETM+), is well suited for capturing horizontally distributed forest conditions, ...structure, and change, while Light Detection and Ranging (LIDAR) data are more appropriate for capturing vertically distributed elements of forest structure and change. The integration of optical remotely sensed imagery and LIDAR data provides improved opportunities to characterize post-fire conditions. The objective of this study is to compare changes in forest structure, as measured with a discrete return profiling LIDAR, to post-fire conditions, as measured with remotely sensed data. Our research is focused on a boreal forest fire that occurred in May 2002 in Alberta, Canada. The Normalized Burn Ratio (NBR), the differenced NBR (dNBR), and the relative dNBR (RdNBR) were calculated from two dates of Landsat data (August 2001 and September 2002). Forest structural attributes were derived from two spatially coincident discrete return LIDAR profiles acquired in September 1997 and 2002 respectively. Image segmentation was used to produce homogeneous spatial patches analogous to forest stands, with analysis conducted at this patch level.
In this study area, which was relatively homogenous and dominated by open forest, no statistically significant relationships were found between pre-fire forest structure and post-fire conditions (
r
<
0.5;
p
>
0.05). Post-fire forest structure and absolute and relative changes in forest structure were strongly correlated to post-fire conditions (
r ranging from −
0.507 to 0.712;
p
<
0.0001). Measures of vegetation fill (VF) (LIDAR capture of cross-sectional vegetation amount), post-fire and absolute change in crown closure (CC), and relative change in average canopy height, were most useful for characterizing post-fire conditions. Forest structural attributes generated from the post-fire LIDAR data were most strongly correlated to post-fire NBR, while dNBR and RdNBR had stronger correlations with absolute and relative changes in the forest structural attributes. Absolute and relative changes in VF and changes in CC had the strongest positive correlations with respect to dNBR and RdNBR, ranging from 0.514 to 0.715 (
p
<
0.05). Measures of average inter-tree distance and volume were not strongly correlated to post-fire NBR, dNBR, or RdNBR. No marked differences were found in the strength or significance of correlations between post-fire structure and the post-fire NBR, dNBR, RdNBR, indicating that for the conditions present in this study area all three burn severity indices captured post-fire conditions in a similar manner. Finally, the relationship between post-fire forest structure and post-fire condition was strongest for dense forests (>
60% crown closure) compared to open (26–60%) and sparse forests (10–25%). Forest structure information provided by LIDAR is useful for characterizing post-fire conditions and burn induced structural change, and will complement other attributes such as vegetation type and moisture, topography, and long-term weather patterns, all of which will also influence variations in post-fire conditions.
Background Data from several studies indicate that children of mothers who smoked during pregnancy may be at a risk of overweight compared with children of non-smoking mothers. The size of this ...relation, however, is unclear, as is the age at which it becomes detectable. Methods Prospective data for 34 866 children enrolled in the US Collaborative Perinatal Project were analysed to examine maternal pregnancy smoking in relation to weight, height, and body mass index (BMI) in offspring at ages 1, 3, 4, 7, and 8 years. Results Compared with offspring of non-smokers, children of smokers had (i) weight that was lower at birth but then quickly equalled or exceeded that of non-smokers, (ii) consistently decreased height, and (iii) increased risk of overweight, particularly in girls. For example, at age 7 years, the adjusted odds ratio of BMI ≥85th percentile in boys of mothers who smoked on an average ≥20 cigarettes per day while pregnant was 1.22 (95% confidence interval 1.03–1.46), and in girls it was 1.30 (1.08–1.56). Conclusions In these data, maternal smoking during pregnancy was associated with a modest increase in risk of overweight in children before the age of 8 years.
DDT (bis4-chlorophenyl-1,1,1-trichloroethane) is a persistent insecticide that was used worldwide from the mid 1940s until its ban in the USA and other countries in the 1970s. When a global ban on ...DDT was proposed in 2001, several countries in sub-Saharan Africa claimed that DDT was still needed as a cheap and effective means for vector control. Although DDT is generally not toxic to human beings and was banned mainly for ecological reasons, subsequent research has shown that exposure to DDT at amounts that would be needed in malaria control might cause preterm birth and early weaning, abrogating the benefit of reducing infant mortality from malaria. Historically, DDT has had mixed success in Africa; only the countries that are able to find and devote substantial resources towards malaria control have made major advances. DDT might be useful in controlling malaria, but the evidence of its adverse effects on human health needs appropriate research on whether it achieves a favourable balance of risk versus benefit.
Purpose
The molecular mechanism of breast and/or ovarian cancer susceptibility remains unclear in the majority of patients. While germline mutations in the regulatory non-coding regions of
BRCA1
and
...BRCA2
genes have been described, screening has generally been limited to coding regions. The aim of this study was to evaluate the contribution of
BRCA1/2
non-coding variants.
Methods
Four
BRCA1/2
non-coding regions were screened using high-resolution melting analysis/Sanger sequencing or next-generation sequencing on DNA extracted from index cases with breast and ovarian cancer predisposition (3926 for
BRCA1
and 3910 for
BRCA2
). The impact of a set of variants on
BRCA1/2
gene regulation was evaluated by site-directed mutagenesis, transfection, followed by Luciferase gene reporter assay.
Results
We identified a total of 117 variants and tested twelve
BRCA1
and 8
BRCA2
variants mapping to promoter and intronic regions. We highlighted two neighboring
BRCA1
promoter variants (c.-130del; c.-125C > T) and one
BRCA2
promoter variants (c.-296C > T) inhibiting significantly the promoter activity. In the functional assays, a regulating region within the intron 12 was found with the same enhancing impact as within the intron 2. Furthermore, the variants c.81-3980A > G and c.4186-2022C > T suppress the positive effect of the introns 2 and 12, respectively, on the
BRCA1
promoter activity. We also found some variants inducing the promoter activities.
Conclusion
In this study, we highlighted some variants among many, modulating negatively the promoter activity of
BRCA1
or
2
and thus having a potential impact on the risk of developing cancer. This selection makes it possible to conduct future validation studies on a limited number of variants.
Breastfed infants in the United States have lower rates of morbidity, especially from infectious disease, but there are few contemporary studies in the developed world of the effect of breastfeeding ...on postneonatal mortality. We evaluated the effect of breastfeeding on postneonatal mortality in United States using 1988 National Maternal and Infant Health Survey (NMIHS) data.
Nationally representative samples of 1204 infants who died between 28 days and 1 year from causes other than congenital anomaly or malignant tumor (cases of postneonatal death) and 7740 children who were still alive at 1 year (controls) were included. We calculated overall and cause-specific odds ratios for ever/never breastfeeding among all children, conducted race and birth weight-specific analyses, and looked for duration-response effects.
Overall, children who were ever breastfed had 0.79 (95% confidence interval CI: 0.67-0.93) times the risk of never breastfed children for dying in the postneonatal period. Longer breastfeeding was associated with lower risk. Odds ratios by cause of death varied from 0.59 (95% CI: 0.38-0.94) for injuries to 0.84 (95% CI: 0.67-1.05) for sudden infant death syndrome.
Breastfeeding is associated with a reduction in risk for postneonatal death. This large data set allowed robust estimates and control of confounding, but the effects of breast milk and breastfeeding cannot be separated completely from other characteristics of the mother and child. Assuming causality, however, promoting breastfeeding has the potential to save or delay approximately 720 postneonatal deaths in the United States each year.
Recent advances in basic science have greatly expanded our understanding of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR), the chloride and bicarbonate channel that is encoded ...by the gene, which is mutated in patients with CF. We review the structure, function, biosynthetic processing, and intracellular trafficking of CFTR and discuss the five classes of mutations and their impact on the CF phenotype. The therapeutic discussion is focused on the significant progress toward CFTR mutation-specific therapies. We review the results of encouraging clinical trials examining orally administered therapeutics, including agents that promote read-through of class I mutations (premature termination codons); correctors, which overcome the CFTR misfolding that characterizes the common class II mutation F508del; and potentiators, which enhance the function of class III or IV mutated CFTR at the plasma membrane. Long-term outcomes from successful mutation-specific treatments could finally answer the question that has been lingering since and even before the CFTR gene discovery: Will therapies that specifically restore CFTR-mediated chloride secretion slow or arrest the deleterious cascade of events leading to chronic infection, bronchiectasis, and end-stage lung disease?
The field of population genetics is rapidly moving into population genomics as the quantity of data generated by high‐throughput sequencing platforms increases. In this study, we used ...restriction‐site‐associated DNA sequencing (RADSeq) to recover genomewide genotypes from 70 white‐beaked (Lagenorhynchus albirostris) and 43 Atlantic white‐sided dolphins (L. acutus) gathered throughout their north‐east Atlantic distribution range. Both species are at a high risk of being negatively affected by climate change. Here, we provide a resource of 38 240 RAD‐tags and 52 981 nuclear SNPs shared between both species. We have estimated overall higher levels of nucleotide diversity in white‐sided (π = 0.0492 ± 0.0006%) than in white‐beaked dolphins (π = 0.0300 ± 0.0004%). White‐sided dolphins sampled in the Faroe Islands, belonging to two pods (N = 7 and N = 11), showed similar levels of diversity (π = 0.0317 ± 0.0007% and 0.0267 ± 0.0006%, respectively) compared to unrelated individuals of the same species sampled elsewhere (e.g. π = 0.0285 ± 0.0007% for 11 Scottish individuals). No evidence of higher levels of kinship within pods can be derived from our analyses. When identifying the most likely number of genetic clusters among our sample set, we obtained an estimate of two to four clusters, corresponding to both species and possibly, two further clusters within each species. A higher diversity and lower population structuring was encountered in white‐sided dolphins from the north‐east Atlantic, in line with their preference for pelagic waters, as opposed to white‐beaked dolphins that have a more patchy distribution, mainly across continental shelves.
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