Modelling the impact of prescribed global warming on runoff from headwater catchments of the Irrawaddy River and their implications for the water level regime of Loktak Lake, northeast India

Climate change is likely to have major implications for wetland ecosystems, which will include altered water level regimes due to modifications in local and catchment hydrology. However, substantial uncertainty exists in the precise impacts of climate change on wetlands due in part to uncertainty in GCM projections. This paper explores the impacts of climate change upon river discharge within three sub-catchments of Loktak Lake, an internationally important wetland in northeast India. This is achieved by running pattern-scaled GCM output through distributed hydrological models (developed using MIKE SHE) of each sub-catchment. The impacts of climate change upon water levels within Loktak Lake are subsequently investigated using a water balance model. Two groups of climate change scenarios are investigated. Group 1 uses results from seven different GCMs for an increase in global mean temperature of 2 A degrees C, the purported threshold of ''dangerous'' climate change, whilst Group 2 is based on results from the HadCM3 GCM for increases in global mean temperature between 1 A degrees C and 6 A degrees C. Results from the Group 1 scenarios show varying responses between the three sub-catchments. The majority of scenario-sub-catchment combinations (13 out of 21) indicate increases in discharge which vary from < 1% to 42% although, in some cases, discharge decreases by as much as 20%. Six of the GCMs suggest overall increases in river flow to Loktak Lake (2-27%) whilst the other results in a modest (6%) decline. In contrast, the Group 2 scenarios lead to an almost linear increase in total river flow to Loktak Lake with increasing temperature (up to 27% for 6 A degrees C), although two sub-catchments experience reductions in mean discharge for the smallest temperature increases. In all but one Group 1 scenario, and all the Group 2 scenarios, Loktak Lake water levels are higher, regularly reaching the top of a downstream hydropower barrage that impounds the lake and necessitating the release of water for barrage structural stability. Although elevated water levels may permit enhanced abstraction for irrigation and domestic uses, future increases in hydropower generation are limited by existing infrastructure. The higher water levels are likely to exacerbate existing ecological deterioration within the lake as well as enhancing problems of flooding of lakeside communities

BAFF and MyD88 signals promote a lupuslike disease independent of T cells

Systemic lupus erythernatosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies. However, the underlying cause of disease appears to relate to defects in T cell tolerance or T cell help to 13 cells. Transgenic (Tg) mice over-expressing the cytokine 13 cell-activating factor of the tumor necrosis factor family (BAFF) develop an autoimmune disorder similar to SLE and show impaired B cell tolerance and altered T cell differentiation. We generated BAFF Tg mice that were completely deficient in T cells, and, surprisingly, these mice developed an SLE-like disease indistinguishable from that of BAFF Tg mice. Autoimmunity in BAFF Tg mice did, however, require 13 cell-intrinsic signals through the Toll-like receptor (TLR)-associated signaling adaptor MyD88, which controlled the production of proinflammatory autoantibody isotypes. TLR7/9 activation strongly up-regulated expression of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), which is a receptor for BAFF involved in 13 cell responses to T cell-independent antigens. Moreover, BAFF enhanced TLR7/9 expression on 13 cells and TLR-mediated production of autoantibodies. Therefore, autoirnmunity in BAFF Tg mice results from altered 13 cell tolerance, but requires TLR signaling and is independent of T cell help. It is possible that SLE patients with elevated levels of BAFF show a similar basis for disease

Approaches towards expression profiling the response to treatment

Over the past 8 years there has been a wealth of breast cancer gene expression studies. The majority of these studies have focused upon characterising a tumour at presentation, before treatment, rather than looking at the effects of treatment on the tumour. More recently, a number of groups have moved from predicting prognosis based upon long-term follow-up to alternative approaches of using expression profiling to measure the effect of treatment on breast tumours and potentially predict response to therapy using either post-treatment samples or both pre-treatment and post-treatment samples. Whilst this provides great potential to further our understanding of the mode of action of treatments and to more accurately select which patients will benefit from a particular treatment, serious issues of experimental design must be considered

Multiplex Detection and SNP Genotyping in a Single Fluorescence Channel

Probe-based PCR is widely used for SNP (single nucleotide polymorphism) genotyping and pathogen nucleic acid detection due to its simplicity, sensitivity and cost-effectiveness. However, the multiplex capability of hydrolysis probe-based PCR is normally limited to one target (pathogen or allele) per fluorescence channel. Current fluorescence PCR machines typically have 4–6 channels. We present a strategy permitting the multiplex detection of multiple targets in a single detection channel. The technique is named Multiplex Probe Amplification (MPA). Polymorphisms of the CYP2C9 gene (cytochrome P450, family 2, subfamily C, polypeptide 9, CYP2C9*2) and human papillomavirus sequences HPV16, 18, 31, 52 and 59 were chosen as model targets for testing MPA. The allele status of the CYP2C9*2 determined by MPA was entirely concordant with the reference TaqMan® SNP Genotyping Assays. The four HPV strain sequences could be independently detected in a single fluorescence detection channel. The results validate the multiplex capacity, the simplicity and accuracy of MPA for SNP genotyping and multiplex detection using different probes labeled with the same fluorophore. The technique offers a new way to multiplex in a single detection channel of a closed-tube PCR

Hidden Yangian symmetry in sigma model on squashed sphere

We discuss a hidden symmetry of a two-dimensional sigma model on a squashed S^3. The SU(2) current can be improved so that it can be regarded as a flat connection. Then we can obtain an infinite number of conserved non-local charges and show the Yangian algebra by directly checking the Serre relation. This symmetry is also deduced from the coset structure of the squashed sphere. The same argument is applicable to the warped AdS_3 spaces via double Wick rotations.Comment: 11 pages, 1 figure, typos corrected, references adde

Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder

Background Recurrent microdeletions and microduplications of w555 kb at 16p11.2 confer susceptibility to autism spectrum disorder (ASD) in up to 1% of ASD patients. No physical or behavioural features have been identified that distinguish these individuals as having a distinct ASD subtype, but clinical data are limited. Methods We report five autistic probands identified by microarray analysis with copy number variation (CNV) of 16p11.2 (three deletions, two duplications). Each patient was assessed for ASD and dysmorphic features. We also describe a deletion positive 26-month-old female who has developmental delay (DD) and autistic features. Results Proband 1 (female with ASD, de novo deletion) is not dysmorphic. Proband 2 (male with autism, de novo deletion) and proband 3 and his brother (males with autism, inherited deletions) are dysmorphic, but the two probands do not resemble one another. The mother of proband 3 has mild mental retardation (MR), minor dysmorphism and meets the criteria for ASD. Proband 4 (dysmorphic autistic male, de novo duplication) had a congenital diaphragmatic hernia. Proband 5 (nondysmorphic ASD female with a duplication) has two apparently healthy duplication positive relatives. Probands 1 and 2 have deletion negative siblings with ASD and Asperger syndrome, respectively. Proband 6 (a female with DD and an inherited duplication) is dysmorphic, but has oligohydramnios sequence. Conclusions The phenotypic spectrum associated with CNV at 16p11.2 includes ASD, MR/DD and/or possibly other primary psychiatric disorders. Compared with the microduplications, the reciprocal microdeletions are more likely to be penetrant and to be associated with nonspecific major or minor dysmorphism. There are deletion positive ASD probands with a less severe phenotype than deletion negative ASD siblings underscoring the significant phenotypic heterogeneity.published_or_final_versio

Socioeconomic differentials in the immediate mortality effects of the national Irish smoking ban

This article has been made available through the Brunel Open Access Publishing Fund.Background: Consistent evidence has demonstrated that smoking ban policies save lives, but impacts on health inequalities are uncertain as few studies have assessed post-ban effects by socioeconomic status (SES) and findings have been inconsistent. The aim of this study was to assess the effects of the national Irish smoking ban on ischemic heart disease (IHD), stroke, and chronic obstructive pulmonary disease (COPD) mortality by discrete and composite SES indicators to determine impacts on inequalities. Methods: Census data were used to assign frequencies of structural and material SES indicators to 34 local authorities across Ireland with a 2000–2010 study period. Discrete indicators were jointly analysed through principal component analysis to generate a composite index, with sensitivity analyses conducted by varying the included indicators. Poisson regression with interrupted time-series analysis was conducted to examine monthly age and gender-standardised mortality rates in the Irish population, ages ≥35 years, stratified by tertiles of SES indicators. All models were adjusted for time trend, season, influenza, and smoking prevalence. Results: Post-ban mortality reductions by structural SES indicators were concentrated in the most deprived tertile for all causes of death, while reductions by material SES indicators were more equitable across SES tertiles. The composite indices mirrored the results of the discrete indicators, demonstrating that post-ban mortality decreases were either greater or similar in the most deprived when compared to the least deprived for all causes of death. Conclusions: Overall findings indicated that the national Irish smoking ban reduced inequalities in smoking-related mortality. Due to the higher rates of smoking-related mortality in the most deprived group, even equitable reductions across SES tertiles resulted in decreases in inequalities. The choice of SES indicator was influential in the measurement of effects, underscoring that a differentiated analytical approach aided in understanding the complexities in which structural and material factors influence mortality

Assessment of the impact of the scanner-related factors on brain morphometry analysis with Brainvisa.

BACKGROUND: Brain morphometry is extensively used in cross-sectional studies. However, the difference in the estimated values of the morphometric measures between patients and healthy subjects may be small and hence overshadowed by the scanner-related variability, especially with multicentre and longitudinal studies. It is important therefore to investigate the variability and reliability of morphometric measurements between different scanners and different sessions of the same scanner. METHODS: We assessed the variability and reliability for the grey matter, white matter, cerebrospinal fluid and cerebral hemisphere volumes as well as the global sulcal index, sulcal surface and mean geodesic depth using Brainvisa. We used datasets obtained across multiple MR scanners at 1.5 T and 3 T from the same groups of 13 and 11 healthy volunteers, respectively. For each morphometric measure, we conducted ANOVA analysis and verified whether the estimated values were significantly different across different scanners or different sessions of the same scanner. The between-centre and between-visit reliabilities were estimated from their contribution to the total variance, using a random-effects ANOVA model. To estimate the main processes responsible for low reliability, the results of brain segmentation were compared to those obtained using FAST within FSL. RESULTS: In a considerable number of cases, the main effects of both centre and visit factors were found to be significant. Moreover, both between-centre and between-visit reliabilities ranged from poor to excellent for most morphometric measures. A comparison between segmentation using Brainvisa and FAST revealed that FAST improved the reliabilities for most cases, suggesting that morphometry could benefit from improving the bias correction. However, the results were still significantly different across different scanners or different visits. CONCLUSIONS: Our results confirm that for morphometry analysis with the current version of Brainvisa using data from multicentre or longitudinal studies, the scanner-related variability must be taken into account and where possible should be corrected for. We also suggest providing some flexibility to Brainvisa for a step-by-step analysis of the robustness of this package in terms of reproducibility of the results by allowing the bias corrected images to be imported from other packages and bias correction step be skipped, for example.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are