Interhemispheric white matter integrity in young people with bipolar disorder and at high genetic risk

White matter (WM) impairments have been reported in patients with bipolar disorder (BD) and those at high familial risk of developing BD. However, the distribution of these impairments has not been well characterized. Few studies have examined WM integrity in young people early in the course of illness and in individuals at familial risk who have not yet passed the peak age of onset. WM integrity was examined in 63 BD subjects, 150 high-risk (HR) individuals and 111 participants with no family history of mental illness (CON). All subjects were aged 12 to 30 years. This young BD group had significantly lower fractional anisotropy within the genu of the corpus callosum (CC) compared with the CON and HR groups. Moreover, the abnormality in the genu of the CC was also present in HR participants with recurrent major depressive disorder (MDD) (n = 16) compared with CON participants. Our findings provide important validation of interhemispheric abnormalities in BD patients. The novel finding in HR subjects with recurrent MDD – a group at particular risk of future hypo/manic episodes – suggests that this may potentially represent a trait marker for BD, though this will need to be confirmed in longitudinal follow-up studies

The airtightness and air leakage characteristics of new UK holiday homes

It is estimated that in the UK, 200,000 residents live in park and holiday homes all year round, the majority of which are elderly and on low incomes. As these homes are often thermally inefficient and leaky, these residents are some of the most susceptible in society to fuel poverty. Despite this, there is a dearth of empirical data available on the in situ fabric performance of these homes. This paper presents the results obtained from undertaking a series of pressurisation tests and leakage identification on new build holiday homes. While the sample size reported is small, the results indicate almost a factor of two variation in the airtightness performance of the homes. In spite of this, all of the homes achieved an air permeability significantly lower than the default value incorporated within the industry standard Energy Efficiency Rating Calculator, suggesting that a much lower figure may be more appropriate. The results also suggest that the use of the air permeability metric within the Calculator potentially biases the performance of holiday homes due to their particular form factor, and that this bias could be mitigated against by adopting the air leakage metric within any future revisions to the Calculator

Relevance and quality of climate planning for large and medium-sized cities of the Tropics

In the last seven years, the number of plans with climate measures for tropical cities has increased 2.3 times compared to the previous seven years as a result of the initiatives of central and local governments, multi-bilateral development aid and development banks. The plans matter in achieving the 11th United Nations’ Sustainable development goal. Therefore, the objective of this chapter is to ascertain the relevance and quality of climate planning in large and medium-sized cities in the Tropics. The chapter proposes and applies the QCPI-Quality of Climate Plans Index, consisting of 10 indicators (characterization of climate, number, quantification, relevance, potential impact, cost, funding sources, timetable and responsibility of measures, implementation monitoring and reporting). It is revealed that 338 tropical cities currently have a local development, emergency, master, mitigation, adaptation, risk reduction plan or a resilience or smart city strategy. These tools were unquestionably more common in large cities, especially in OCDE and BRICS countries, while they were rare in Developing Countries. Local development plans (Municipal development, general, comprehensive) were the most common in medium-sized cities, along with those with the lowest quality, while stand-alone strategies and plans (resilience, mitigation, sustainable, adaptation), applied mostly in big cities, present much higher quality

Hypofractionated radiotherapy has the potential for second cancer reduction

<p>Abstract</p> <p>Background and Purpose</p> <p>A model for carcinoma and sarcoma induction was used to study the dependence of carcinogenesis after radiotherapy on fractionation.</p> <p>Materials and methods</p> <p>A cancer induction model for radiotherapy doses including fractionation was used to model carcinoma and sarcoma induction after a radiation treatment. For different fractionation schemes the dose response relationships were obtained. Tumor induction was studied as a function of dose per fraction.</p> <p>Results</p> <p>If it is assumed that the tumor is treated up to the same biologically equivalent dose it was found that large dose fractions could decrease second cancer induction. The risk decreases approximately linear with increasing fraction size and is more pronounced for sarcoma induction. Carcinoma induction decreases by around 10% per 1 Gy increase in fraction dose. Sarcoma risk is decreased by about 15% per 1 Gy increase in fractionation. It is also found that tissue which is irradiated using large dose fractions to dose levels lower than 10% of the target dose potentially develop less sarcomas when compared to tissues irradiated to all dose levels. This is not observed for carcinoma induction.</p> <p>Conclusions</p> <p>It was found that carcinoma as well as sarcoma risk decreases with increasing fractionation dose. The reduction of sarcoma risk is even more pronounced than carcinoma risk. Hypofractionation is potentially beneficial with regard to second cancer induction.</p

The SINS trial: A randomised controlled trial of excisional surgery versus imiquimod 5% cream for nodular and superficial basal cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Basal cell carcinoma is the commonest human cancer. Despite increasing incidence it remains poorly researched. While not life threatening it can cause significant cosmetic disfigurement. Imiquimod, a cream which enhances the body's immune response, may help deal with the number of cases that occur in low-risk sites, especially when good cosmetic results and home use without surgery are needed.</p> <p>This study aims 1. To compare excisional surgery with imiquimod cream for nodular or superficial basal cell carcinoma in low risk sites, with respect to 3 year clinical clearance, cost-effectiveness and cosmetic results. 2. To ascertain if certain phenotypic features and gene polymorphisms predict tumour responsiveness to treatment.</p> <p>Methods/Design</p> <p>Five hundred participants with low risk nodular or superficial basal cell carcinoma will be recruited from hospitals to this multi-centre, randomised, parallel group, controlled phase III trial. Treatment in the imiquimod group is for 6 weeks for superficial basal cell carcinoma and 12 weeks for nodular basal cell carcinoma. Both treatment groups are followed up in clinic for 3 years. Primary outcome variable: the proportion of participants with clinical evidence of success (no recurrence) at 3 years. The primary outcome will be compared between the two treatment groups. Secondary outcomes include: i) clinical success at 1, 2 and 5 years, ii) time to first recurrence, iii) cosmetic appearance of lesion site after treatment, iv) level of pain, and v) cost-effectiveness. Safety and tolerability data will also be reported.</p> <p>Discussion</p> <p>This study protocol describes a pragmatic randomised controlled trial which it is hoped will address the above uncertainties. Three-year results will be available towards the end of 2010.</p> <p>Trial registration</p> <p>Meta-register: NCT00066872, Eudract No. 2004-004506-24, ISRCTN48755084.</p

Subclinical Hypothyroidism after Radioiodine Exposure: Ukrainian–American Cohort Study of Thyroid Cancer and Other Thyroid Diseases after the Chornobyl Accident (1998–2000)

BackgroundHypothyroidism is the most common thyroid abnormality in patients treated with high doses of iodine-131 (131I). Data on risk of hypothyroidism from low to moderate 131I thyroid doses are limited and inconsistent.ObjectiveThis study was conducted to quantify the risk of hypothyroidism prevalence in relation to 131I doses received because of the Chornobyl accident.MethodsThis is a cross-sectional (1998-2000) screening study of thyroid diseases in a cohort of 11,853 individuals &lt; 18 years of age at the time of the accident, with individual thyroid radioactivity measurements taken within 2 months of the accident. We measured thyroid-stimulating hormone (TSH), free thyroxine, and antibodies to thyroid peroxidase (ATPO) in serum.ResultsMean age at examination of the analysis cohort was 21.6 years (range, 12.2-32.5 years), with 49% females. Mean 131I thyroid dose was 0.79 Gy (range, 0-40.7 Gy). There were 719 cases with hypothyroidism (TSH &gt; 4 mIU/L), including 14 with overt hypothyroidism. We found a significant, small association between (131)I thyroid doses and prevalent hypothyroidism, with the excess odds ratio (EOR) per gray of 0.10 (95% confidence interval, 0.03-0.21). EOR per gray was higher in individuals with ATPO &lt; or = 60 U/mL compared with individuals with ATPO &gt; 60 U/mL (p &lt; 0.001).ConclusionsThis is the first study to find a significant relationship between prevalence of hypothyroidism and individual (131)I thyroid doses due to environmental exposure. The radiation increase in hypothyroidism was small (10% per Gy) and limited largely to subclinical hypothyroidism. Prospective data are needed to evaluate the dynamics of radiation-related hypothyroidism and clarify the role of antithyroid antibodies

A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita

© The Author(s). 2018Background: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment. Results: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle. Conclusions: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.Peer reviewedFinal Published versio

Autoimmune and autoinflammatory mechanisms in uveitis

The eye, as currently viewed, is neither immunologically ignorant nor sequestered from the systemic environment. The eye utilises distinct immunoregulatory mechanisms to preserve tissue and cellular function in the face of immune-mediated insult; clinically, inflammation following such an insult is termed uveitis. The intra-ocular inflammation in uveitis may be clinically obvious as a result of infection (e.g. toxoplasma, herpes), but in the main infection, if any, remains covert. We now recognise that healthy tissues including the retina have regulatory mechanisms imparted by control of myeloid cells through receptors (e.g. CD200R) and soluble inhibitory factors (e.g. alpha-MSH), regulation of the blood retinal barrier, and active immune surveillance. Once homoeostasis has been disrupted and inflammation ensues, the mechanisms to regulate inflammation, including T cell apoptosis, generation of Treg cells, and myeloid cell suppression in situ, are less successful. Why inflammation becomes persistent remains unknown, but extrapolating from animal models, possibilities include differential trafficking of T cells from the retina, residency of CD8(+) T cells, and alterations of myeloid cell phenotype and function. Translating lessons learned from animal models to humans has been helped by system biology approaches and informatics, which suggest that diseased animals and people share similar changes in T cell phenotypes and monocyte function to date. Together the data infer a possible cryptic infectious drive in uveitis that unlocks and drives persistent autoimmune responses, or promotes further innate immune responses. Thus there may be many mechanisms in common with those observed in autoinflammatory disorders

Back from a Predicted Climatic Extinction of an Island Endemic: A Future for the Corsican Nuthatch

The Corsican Nuthatch (Sitta whiteheadi) is red-listed as vulnerable to extinction by the IUCN because of its endemism, reduced population size, and recent decline. A further cause is the fragmentation and loss of its spatially-restricted favourite habitat, the Corsican pine (Pinus nigra laricio) forest. In this study, we aimed at estimating the potential impact of climate change on the distribution of the Corsican Nuthatch using species distribution models. Because this species has a strong trophic association with the Corsican and Maritime pines (P. nigra laricio and P. pinaster), we first modelled the current and future potential distribution of both pine species in order to use them as habitat variables when modelling the nuthatch distribution. However, the Corsican pine has suffered large distribution losses in the past centuries due to the development of anthropogenic activities, and is now restricted to mountainous woodland. As a consequence, its realized niche is likely significantly smaller than its fundamental niche, so that a projection of the current distribution under future climatic conditions would produce misleading results. To obtain a predicted pine distribution at closest to the geographic projection of the fundamental niche, we used available information on the current pine distribution associated to information on the persistence of isolated natural pine coppices. While common thresholds (maximizing the sum of sensitivity and specificity) predicted a potential large loss of the Corsican Nuthatch distribution by 2100, the use of more appropriate thresholds aiming at getting closer to the fundamental distribution of the Corsican pine predicted that 98% of the current presence points should remain potentially suitable for the nuthatch and its range could be 10% larger in the future. The habitat of the endemic Corsican Nuthatch is therefore more likely threatened by an increasing frequency and intensity of wildfires or anthropogenic activities than by climate change

Genomic Instability Is Associated with Natural Life Span Variation in Saccharomyces cerevisiae

Increasing genomic instability is associated with aging in eukaryotes, but the connection between genomic instability and natural variation in life span is unknown. We have quantified chronological life span and loss-of-heterozygosity (LOH) in 11 natural isolates of Saccharomyces cerevisiae. We show that genomic instability increases and mitotic asymmetry breaks down during chronological aging. The age-dependent increase of genomic instability generally lags behind the drop of viability and this delay accounts for ∼50% of the observed natural variation of replicative life span in these yeast isolates. We conclude that the abilities of yeast strains to tolerate genomic instability co-vary with their replicative life spans. To the best of our knowledge, this is the first quantitative evidence that demonstrates a link between genomic instability and natural variation in life span