Tropical savannas are characterized by high primary productivity and high fire frequency, such that much of the carbon captured by vegetation is rapidly returned to the atmosphere. Hence, there have ...been suggestions that management‐driven reductions in savanna fire frequency and/or severity could significantly reduce greenhouse gas emissions and sequester carbon in tree biomass. However, a key knowledge gap is the extent to which savanna tree biomass will respond to modest shifts in fire regimes due to plausible, large‐scale management interventions. Here, we: (1) characterize relationships between the frequency and severity of fires and key demographic rates of savanna trees, based on long‐term observations in vegetation monitoring plots across northern Australia; (2) use these relationships to develop a process‐explicit demographic model describing the effects of fire on savanna tree populations; and (3) use the demographic model to address the question: to what extent is it feasible, through the strategic application of prescribed burning, to increase tree biomass in Australian tropical savannas? Our long‐term tree monitoring dataset included observations of 12,344 tagged trees in 236 plots, monitored for between 3 and 24 years. Analysis of this dataset showed that frequent high‐severity fires significantly reduced savanna tree recruitment, survival, and growth. Our demographic model suggested that: (1) despite the negative effects of frequent high‐severity fires on demographic rates, savanna tree biomass appears to be suppressed by only a relatively small amount by contemporary fire regimes, characterized by a mix of low‐ to high‐severity fires; and (2) plausible, management‐driven reductions in the frequency of high‐severity fires are likely to lead to increases in tree biomass of about 11.0 t DM ha−1 (95% CI: −1.2–20.8) over a century. Accounting for this increase in carbon storage could generate significant carbon credits, worth, on average, three times those generated annually by current greenhouse gas (methane and nitrous oxide) abatement projects, and has the potential to significantly increase the economic viability of fire/carbon projects, thereby promoting ecologically sustainable management of tropical savannas in Australia and elsewhere. This growing industry has the potential to bring much‐needed economic activity to savanna landscapes, without compromising important natural and cultural values.
Killed whole-cell oral cholera vaccines (kOCVs) are becoming a standard cholera control and prevention tool. However, vaccine efficacy and direct effectiveness estimates have varied, with differences ...in study design, location, follow-up duration, and vaccine composition posing challenges for public health decision making. We did a systematic review and meta-analysis to generate average estimates of kOCV efficacy and direct effectiveness from the available literature.
For this systematic review and meta-analysis, we searched PubMed, Embase, Scopus, and the Cochrane Review Library on July 9, 2016, and ISI Web of Science on July 11, 2016, for randomised controlled trials and observational studies that reported estimates of direct protection against medically attended confirmed cholera conferred by kOCVs. We included studies published on any date in English, Spanish, French, or Chinese. We extracted from the published reports the primary efficacy and effectiveness estimates from each study and also estimates according to number of vaccine doses, duration, and age group. The main study outcome was average efficacy and direct effectiveness of two kOCV doses, which we estimated with random-effect models. This study is registered with PROSPERO, number CRD42016048232.
Seven trials (with 695 patients with cholera) and six observational studies (217 patients with cholera) met the inclusion criteria, with an average two-dose efficacy of 58% (95% CI 42–69, I2=58%) and effectiveness of 76% (62–85, I2=0). Average two-dose efficacy in children younger than 5 years (30% 95% CI 15–42, I2=0%) was lower than in those 5 years or older (64% 58–70, I2=0%; p<0·0001). Two-dose efficacy estimates of kOCV were similar during the first 2 years after vaccination, with estimates of 56% (95% CI 42–66, I2=45%) in the first year and 59% (49–67, I2=0) in the second year. The efficacy reduced to 39% (13 to 57, I2=48%) in the third year, and 26% (−46 to 63, I2=74%) in the fourth year.
Two kOCV doses provide protection against cholera for at least 3 years. One kOCV dose provides at least short-term protection, which has important implications for outbreak management. kOCVs are effective tools for cholera control.
The Bill & Melinda Gates Foundation.
We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic ...cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 × 10−8; multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Women with a mutation in BRCA1 or BRCA2 have a high risk of developing breast cancer and of contralateral cancer after the initial diagnosis of breast cancer. Tamoxifen protects against contralateral ...breast cancer in the general population, but whether it protects against contralateral breast cancer in BRCA1 or BRCA2 mutation carriers is not known.
We compared 209 women with bilateral breast cancer and BRCA1 or BRCA2 mutation (bilateral-disease cases), with 384 women with unilateral disease and BRCA1 or BRCA2 mutation (controls) in a matched case-control study. Age and age at diagnosis of breast cancer (range 24–74 years) were much the same in bilateral-disease cases and controls, and both groups had been followed up for the same time for a second primary breast cancer. History of tamoxifen use for first breast cancer was obtained by interview, or by self-administered questionnaire.
The multivariate odds ratio for contralateral breast cancer associated with tamoxifen use was 0–50 (95% Cl 0·28–0·89). Tamoxifen protected against contralateral breast cancer for carriers of BRCA1 mutations (odds ratio 0·38, 95% Cl 0·19–0·74) and for those with BRCA2 mutations (0·63, 0·20–1·50). In women who used tamoxifen for 2–4 years, the risk of contralateral breast cancer was reduced by 75%. A reduction in risk of contralateral cancer was also seen with oophorectomy (0·42, 0·22–0·83) and with chemotherapy (0·40, 0·26–0·60).
Tamoxifen use reduces the risk of contralateral breast cancer in women with pathogenic mutations in the BRCA1 or BRCA2 gene. The protective effect of tamoxifen seems independent of that of oophorectomy.
We conducted a genome-wide association study of pancreatic cancer in 3,851 affected individuals (cases) and 3,934 unaffected controls drawn from 12 prospective cohort studies and 8 case-control ...studies. Based on a logistic regression model for genotype trend effect that was adjusted for study, age, sex, self-described ancestry and five principal components, we identified eight SNPs that map to three loci on chromosomes 13q22.1, 1q32.1 and 5p15.33. Two correlated SNPs, rs9543325 (P = 3.27 × 10−11, per-allele odds ratio (OR) 1.26, 95% CI 1.18-1.35) and rs9564966 (P = 5.86 × 10−8, per-allele OR 1.21, 95% CI 1.13-1.30), map to a nongenic region on chromosome 13q22.1. Five SNPs on 1q32.1 map to NR5A2, and the strongest signal was at rs3790844 (P = 2.45 × 10−10, per-allele OR 0.77, 95% CI 0.71-0.84). A single SNP, rs401681 (P = 3.66 × 10−7, per-allele OR 1.19, 95% CI 1.11-1.27), maps to the CLPTM1L-TERT locus on 5p15.33, which is associated with multiple cancers. Our study has identified common susceptibility loci for pancreatic cancer that warrant follow-up studies.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Pathogenic variants in the chromatin organizer CTCF were previously reported in seven individuals with a neurodevelopmental disorder (NDD).
Through international collaboration we collected data from ...39 subjects with variants in CTCF. We performed transcriptome analysis on RNA from blood samples and utilized Drosophila melanogaster to investigate the impact of Ctcf dosage alteration on nervous system development and function.
The individuals in our cohort carried 2 deletions, 8 likely gene-disruptive, 2 splice-site, and 20 different missense variants, most of them de novo. Two cases were familial. The associated phenotype was of variable severity extending from mild developmental delay or normal IQ to severe intellectual disability. Feeding difficulties and behavioral abnormalities were common, and variable other findings including growth restriction and cardiac defects were observed. RNA-sequencing in five individuals identified 3828 deregulated genes enriched for known NDD genes and biological processes such as transcriptional regulation. Ctcf dosage alteration in Drosophila resulted in impaired gross neurological functioning and learning and memory deficits.
We significantly broaden the mutational and clinical spectrum ofCTCF-associated NDDs. Our data shed light onto the functional role of CTCF by identifying deregulated genes and show that Ctcf alterations result in nervous system defects in Drosophila.
Summary
The Australian Government has sanctioned development of greenhouse gas emissions (GHG) abatement methodologies to meet international emissions reduction obligations. Savanna burning emissions ...abatement methodologies have been available since 2012, and there are currently 72 registered projects covering approximately 32 million ha. Abatement to date has exceeded 4 million tonnes of carbon dioxide equivalent (CO2‐e) principally through the application of low intensity early dry season fire management to reduce the amount of biomass combusted in higher intensity late dry season (LDS) fires. Savanna burning projects can only be conducted on areas with eligible fire‐prone vegetation fuel types where implementing the improved fire management regime is considered ecologically appropriate. This study assesses the suitability of including tall Acacia shrublands (‘Pindan’) as a new eligible fuel type. These shrublands make up 12% (~2 million ha) of the Kimberley region, Western Australia, where, on average, 32% is fire affected annually, mostly in the LDS. A standard assessment protocol was applied to describe vegetation fuel type structural and pyrolysis characteristics. We show that Pindan (i) can be identified and mapped as a unique tall Acacia shrubland vegetation fuel type, (ii) characterised by a significantly greater shrubby fuel load biomass, and (iii) the conservation status of which would benefit from imposition of strategic prescribed burning programme. Savanna burning projects in the Pindan fuel type could potentially abate up to 24.43 t.CO2‐e/km2 per year, generating significant income and employment opportunities for predominantly Indigenous land managers in the region.
Background: Women with breast cancer and a BRCA mutation have a high risk of developing a contralateral breast cancer. It is generally believed that the two cancers represent
independent events. ...However, the extent of concordance between the first and second tumors with respect to hormone receptor
expression and other pathologic features is unknown.
Purpose: To determine the degree of concordance of estrogen receptor (ER) status, tumor grade, and histology in tumors from
women with bilateral breast cancer and a BRCA mutation.
Subjects and Methods: Women with a history of bilateral invasive breast cancers were selected from an international registry
of women with BRCA1 or BRCA2 mutations. Medical records were reviewed to document the characteristics of each cancer and the treatments received.
Results: Data were available for 286 women with bilateral breast cancer and a BRCA mutation (211 BRCA1 ; 75 BRCA2 ). The mean interval between first and second tumor was 5.1 years. The two tumors were concordant more often than expected
for ER status ( P < 0.0001) and for grade ( P < 0.0001), but not for histology ( P = 0.55). The ER status of the first tumor was highly predictive of the ER status of the second tumor (odds ratio, 8.7; 95%
confidence interval, 3.5-21.5; P < 0.0001). Neither age, menopausal status, oophorectomy nor tamoxifen use was predictive of the ER status of the second tumor.
Conclusions: There is strong concordance in ER status and tumor grade between independent primary breast tumors in women with
a BRCA mutation. The excess concordance may be due to common risk factors, genetic variation, or the existence of a preneoplastic
lesion that is common to both tumors.
PDF
