Meningococcal genetic variation mechanisms viewed through comparative analysis of Serogroup C strain FAM18

Copyright @ 2007 Public Library of ScienceThe bacterium Neisseria meningitidis is commonly found harmlessly colonising the mucosal surfaces of the human nasopharynx. Occasionally strains can invade host tissues causing septicaemia and meningitis, making the bacterium a major cause of morbidity and mortality in both the developed and developing world. The species is known to be diverse in many ways, as a product of its natural transformability and of a range of recombination and mutation-based systems. Previous work on pathogenic Neisseria has identified several mechanisms for the generation of diversity of surface structures, including phase variation based on slippage-like mechanisms and sequence conversion of expressed genes using information from silent loci. Comparison of the genome sequences of two N. meningitidis strains, serogroup B MC58 and serogroup A Z2491, suggested further mechanisms of variation, including C-terminal exchange in specific genes and enhanced localised recombination and variation related to repeat arrays. We have sequenced the genome of N. meningitidis strain FAM18, a representative of the ST-11/ET-37 complex, providing the first genome sequence for the disease-causing serogroup C meningococci; it has 1,976 predicted genes, of which 60 do not have orthologues in the previously sequenced serogroup A or B strains. Through genome comparison with Z2491 and MC58 we have further characterised specific mechanisms of genetic variation in N. meningitidis, describing specialised loci for generation of cell surface protein variants and measuring the association between noncoding repeat arrays and sequence variation in flanking genes. Here we provide a detailed view of novel genetic diversification mechanisms in N. meningitidis. Our analysis provides evidence for the hypothesis that the noncoding repeat arrays in neisserial genomes (neisserial intergenic mosaic elements) provide a crucial mechanism for the generation of surface antigen variants. Such variation will have an impact on the interaction with the host tissues, and understanding these mechanisms is important to aid our understanding of the intimate and complex relationship between the human nasopharynx and the meningococcus.This work was supported by the Wellcome Trust through the Beowulf Genomics Initiative

Giant Anharmonic Phonon Scattering in PbTe

Understanding the microscopic processes affecting the bulk thermal conductivity is crucial to develop more efficient thermoelectric materials. PbTe is currently one of the leading thermoelectric materials, largely thanks to its low thermal conductivity. However, the origin of this low thermal conductivity in a simple rocksalt structure has so far been elusive. Using a combination of inelastic neutron scattering measurements and first-principles computations of the phonons, we identify a strong anharmonic coupling between the ferroelectric transverse optic (TO) mode and the longitudinal acoustic (LA) modes in PbTe. This interaction extends over a large portion of reciprocal space, and directly affects the heat-carrying LA phonons. The LA-TO anharmonic coupling is likely to play a central role in explaining the low thermal conductivity of PbTe. The present results provide a microscopic picture of why many good thermoelectric materials are found near a lattice instability of the ferroelectric type

Variation in use of surveillance colonoscopy among colorectal cancer survivors in the United States

<p>Abstract</p> <p>Background</p> <p>Clinical practice guidelines recommend colonoscopies at regular intervals for colorectal cancer (CRC) survivors. Using data from a large, multi-regional, population-based cohort, we describe the rate of surveillance colonoscopy and its association with geographic, sociodemographic, clinical, and health services characteristics.</p> <p>Methods</p> <p>We studied CRC survivors enrolled in the Cancer Care Outcomes Research and Surveillance (CanCORS) study. Eligible survivors were diagnosed between 2003 and 2005, had curative surgery for CRC, and were alive without recurrences 14 months after surgery with curative intent. Data came from patient interviews and medical record abstraction. We used a multivariate logit model to identify predictors of colonoscopy use.</p> <p>Results</p> <p>Despite guidelines recommending surveillance, only 49% of the 1423 eligible survivors received a colonoscopy within 14 months after surgery. We observed large regional differences (38% to 57%) across regions. Survivors who received screening colonoscopy were more likely to: have colon cancer than rectal cancer (OR = 1.41, 95% CI: 1.05-1.90); have visited a primary care physician (OR = 1.44, 95% CI: 1.14-1.82); and received adjuvant chemotherapy (OR = 1.75, 95% CI: 1.27-2.41). Compared to survivors with no comorbidities, survivors with moderate or severe comorbidities were less likely to receive surveillance colonoscopy (OR = 0.69, 95% CI: 0.49-0.98 and OR = 0.44, 95% CI: 0.29-0.66, respectively).</p> <p>Conclusions</p> <p>Despite guidelines, more than half of CRC survivors did not receive surveillance colonoscopy within 14 months of surgery, with substantial variation by site of care. The association of primary care visits and adjuvant chemotherapy use suggests that access to care following surgery affects cancer surveillance.</p

Consensus recommendations for clinical assessment tools for the diagnosis of posterior cortical atrophy syndrome from the Atypical AD PIA of ISTAART

INTRODUCTION: Delay in diagnosis of posterior cortical atrophy (PCA) syndrome is common, and the lack of familiarity with assessment tools for identifying visual cortical dysfunction is a contributing factor. We propose recommendations for the approach to the evaluation of PCA clinical features during the office visit, the neuropsychological evaluation, and the research setting. A recommended screening battery for eye clinics is also proposed. METHODS: Recommendations were developed using results from a web-based survey of members of Alzheimer's Association International Society to Advance Alzheimer's Research and Treatment (ISTAART) Atypical Alzheimer's Disease Professional Interest Area (PIA), literature review, and consensus by the PCA assessment working party of the Atypical Alzheimer's Disease PIA. RESULTS: Survey results revealed robust agreement for assessment tool preferences for PCA features, and many respondents indicated that they reserve assessment tools for use only when PCA is suspected. For some PCA features, curated tools were preferred over validated battery tools, particularly for the office visit. Consensus recommendations superseded survey preferences for two core cognitive features within the 2017 PCA diagnostic criteria. DISCUSSION: These consensus recommendations provide an evaluation framework for PCA clinical features and can facilitate timely and accurate recognition and diagnosis of PCA. Broader use of these tools should be sought, and development and validation of novel PCA clinical outcome assessments are needed to improve our understanding of atypical AD and other dementias and support the inclusion of those with PCA in treatment trials

Health status, use of healthcare, and socio-economic implications of cancer survivorship in Portugal : results from the fourth national health survey

Health status, use of healthcare, and socio-economic implications of cancer survivorship in Portugal: results from the Fourth National Health SurveyUnderstanding the morbidity and socio-economic implications of cancer survivorship is essential for a comprehensive management of oncological diseases. We compared cancer survivors (CS) with the general population regarding health status, use of healthcare resources and socio-economic condition. We analyzed data from a representative sample of the Portuguese population aged a parts per thousand yen15 years (n = 35,229). We defined three groups of CS, according to the time since diagnosis and the latest cancer treatment: CS 1 diagnosis within 12 months of interview; CS 2 diagnosis more than 12 months before and treatment in the previous 12 months; CS 3 diagnosis and treatment more than 12 months before. These were compared with the general population, adjusting for differences in sex, age, and place of residence. The prevalence of CS was 2.2 % (CS 1: 0.2 %; CS 2: 0.9 %, CS 3: 1.1 %). Self-perceived health status was worse among CS and short-time incapacity more frequent among CS 1 and CS 2. Health expenses were higher in the early stages of survivorship. Lower household income and financial difficulties were more frequent in CS 1 and CS 3 men, respectively. This study confirmed the higher consumption of healthcare resources and worse financial situation among CS. Our study provides valuable information for understanding the global impact of cancer survivorship.The authors thank the National Health Systems Observatory (Observatorio Nacional de Saude), National Institute of Health Dr. Ricardo Jorge (INSA), Ministry of Health and the National Institute of Statistics (INE) for providing the data (Ministerio da Saude, Instituto Nacional de Saude Dr. Ricardo Jorge; IP, Departamento de Epidemiologia/Instituto Nacional de Estatistica: Inquerito Nacional de Saude 2005/2006). Luis Pacheco-Figueiredo received a grant from the Fundacao para a Ciencia e a Tecnologia (SFRH/SINTD/60124/2009)

Thermoelectric performance of n-type Mg2Ge

Magnesium-based thermoelectric materials (Mg2X, X = Si, Ge, Sn) have received considerable attention due to their availability, low toxicity, and reasonably good thermoelectric performance. The synthesis of these materials with high purity is challenging, however, due to the reactive nature and high vapour pressure of magnesium. In the current study, high purity single phase n-type Mg2Ge has been fabricated through a one-step reaction of MgH2 and elemental Ge, using spark plasma sintering (SPS) to reduce the formation of magnesium oxides due to the liberation of hydrogen. We have found that Bi has a very limited solubility in Mg2Ge and results in the precipitation of Mg2Bi3. Bismuth doping increases the electrical conductivity of Mg2Ge up to its solubility limit, beyond which the variation is minimal. The main improvement in the thermoelectric performance is originated from the significant phonon scattering achieved by the Mg2Bi3 precipitates located mainly at grain boundaries. This reduces the lattice thermal conductivity by ~50% and increases the maximum zT for n-type Mg2Ge to 0.32, compared to previously reported maximum value of 0.2 for Sb-doped Mg2Ge

Narrow safety range of intraoperative rectal irradiation exposure volume for avoiding bleeding after seed implant brachytherapy

<p>Abstract</p> <p>Background & Purpose</p> <p>Rectal toxicity is less common after ¹²⁵I seed implant brachytherapy for prostate cancer, and intraoperative rectal dose-volume constraints (the constraint) is still undetermined in pioneering studies. As our constraint failed to prevent grade 2 or 3 rectal bleeding (bled-pts) in 5.1% of patients, we retrospectively explored another constraint for the prevention of rectal bleeding.</p> <p>Materials and methods</p> <p>The study population consisted of 197 patients treated with the brachytherapy as monotherapy using real-time intraoperative transrectal ultrasound (US)-guided treatment at a prescribed dose of 145 Gy. Post-implant dosimetry was performed on Day 1 and Day 30 after implantation using computed tomography (CT) imaging. Rectal bleeding toxicity was classified by CTC-AE ver. 3.0 during a mean 29-month (range, 12-48 months) period after implantation. The differences in rV100s were compared among intraoperative, Day 1 and Day 30 dosimetry, and between that of patients with grade 2 or 3 rectal bleeding (the bled-pts) and of the others (the spared-pts). All patients were divided into groups based on provisional rV100s that were increased stepwise in 0.1-cc increments from 0 to 1.0 cc. The difference in the ratios of the bled-pts to the spared-pts was tested by chi-square tests, and their odds ratios were calculated (bled-OR). All statistical analyses were performed by <it>t</it>-tests.</p> <p>Results</p> <p>The mean values of rV100us, rV100CT_1, and rV100CT_30 were 0.31 ± 0.43, 0.22 ± 0.36, and 0.59 ± 0.68 cc, respectively. These values temporarily decreased (p = 0.020) on Day 1 and increased (p = 0.000) on Day 30. There was no significant difference in rV100s between the bled-pts and spared-pts at any time of dosimetry. The maximum bled-OR was identified among patients with an rV100us value above 0.1 cc (p = 0.025; OR = 7.8; 95% CI, 1.4-145.8); an rV100CT_1 value above 0.3 cc (p = 0.014; OR = 16.2; 95% CI, 3.9-110.7), and an rV100CT_30 value above 0.5 cc (p = 0.019; OR = 6.3; 95% CI, 1.5-42.3).</p> <p>Conclusion</p> <p>By retrospective analysis exploring rV100 as intraoperative rectal dose-volume thresholds in ¹²⁵I seed implant brachytherapy for prostate cancer, it is proved that rV100 should be less than 0.1 cc for preventing rectal bleeding.</p

Insulin utilizes the PI 3-kinase pathway to inhibit SP-A gene expression in lung epithelial cells

BACKGROUND: It has been proposed that high insulin levels may cause delayed lung development in the fetuses of diabetic mothers. A key event in lung development is the production of adequate amounts of pulmonary surfactant. Insulin inhibits the expression of surfactant protein A (SP-A), the major surfactant-associated protein, in lung epithelial cells. In the present study, we investigated the signal transduction pathways involved in insulin inhibition of SP-A gene expression. METHODS: H441 cells, a human lung adenocarcinoma cell line, or human fetal lung explants were incubated with or without insulin. Transcription run-on assays were used to determine SP-A gene transcription rates. Northern blot analysis was used to examine the effect of various signal transduction inhibitors on SP-A gene expression. Immunoblot analysis was used to evaluate the levels and phosphorylation states of signal transduction protein kinases. RESULTS: Insulin decreased SP-A gene transcription in human lung epithelial cells within 1 hour. Insulin did not affect p44/42 mitogen-activated protein kinase (MAPK) phosphorylation and the insulin inhibition of SP-A mRNA levels was not affected by PD98059, an inhibitor of the p44/42 MAPK pathway. In contrast, insulin increased p70 S6 kinase Thr389 phosphorylation within 15 minutes. Wortmannin or LY294002, both inhibitors of phosphatidylinositol 3-kinase (PI 3-kinase), or rapamycin, an inhibitor of the activation of p70 S6 kinase, a downstream effector in the PI 3-kinase pathway, abolished or attenuated the insulin-induced inhibition of SP-A mRNA levels. CONCLUSION: Insulin inhibition of SP-A gene expression in lung epithelial cells probably occurs via the rapamycin-sensitive PI 3-kinase signaling pathway

Facilitative parenting and children's social, emotional and behavioural adjustment

Facilitative parenting (FP) supports the development of children’s social and emotional competence and effective peer relationships. Previous research has shown that FP discriminates between children bullied by peers from children who are not bullied, according to reports of teachers. This study investigates the association between FP and children’s social, emotional and behavioral problems, over and above the association with dysfunctional parenting (DP). 215 parents of children aged 5–11 years completed questionnaires about parenting and child behavior, and children and teachers completed measures of child bullying victimization. As predicted, FP accounted for variance in teacher reports of children’s bullying victimization as well as parent reports of children’s social and emotional problems and prosocial behavior better than that accounted for by DP. However for children’s reports of peer victimization the whole-scale DP was a better predictor than FP. Contrary to predictions, FP accounted for variance in conduct problems and hyperactivity better than DP. When analyses were replicated substituting subscales of dysfunctional and FP, a sub-set of FP subscales including Warmth, Supports Friendships, Not Conflicting, Child Communicates and Coaches were correlated with low levels of problems on a broad range of children’s adjustment problems. Parent–child conflict accounted for unique variance in children’s peer victimization (teacher report), peer problems, depression, emotional problems, conduct problems and hyperactivity. The potential relevance of FP as a protective factor for children against a wide range of adjustment problems is discussed

Magnetoelectric interaction and transport behaviours in magnetic nanocomposite thermoelectric materials

How to suppress the performance deterioration of thermoelectric materials in the intrinsic excitation region remains a key challenge. The magnetic transition of permanent magnet nanoparticles from ferromagnetism to paramagnetism provides an effective approach to finding the solution to this challenge. Here, we have designed and prepared magnetic nanocomposite thermoelectric materials consisting of BaFe12O19 nanoparticles and Ba0.3In0.3Co4Sb12 matrix. It was found that the electrical transport behaviours of the nanocomposites are controlled by the magnetic transition of BaFe12O19 nanoparticles from ferromagnetism to paramagnetism. BaFe12O19 nanoparticles trap electrons below the Curie temperature (TC) and release the trapped electrons above the TC, playing an ‘electron repository’ role in maintaining high figure of merit ZT. BaFe12O19 nanoparticles produce two types of magnetoelectric effect—electron spiral motion and magnon-drag thermopower—as well as enhancing phonon scattering. Our work demonstrates that the performance deterioration of thermoelectric materials in the intrinsic excitation region can be suppressed through the magnetic transition of permanent magnet nanoparticles