Variation in Dialysis Facility Referral for Kidney Transplantation Among Patients With End-Stage Renal Disease in Georgia.
Dialysis facilities in the United States are required to educate patients with end-stage renal disease about all treatment options, including kidney transplantation. Patients receiving dialysis typically require a referral for kidney transplant evaluation at a transplant center from a dialysis facility to start the transplantation process, but the proportion of patients referred for transplantation is unknown. To describe variation in dialysis facility-level referral for kidney transplant evaluation and factors associated with referral among patients initiating dialysis in Georgia, the US state with the lowest kidney transplantation rates. Examination of United States Renal Data System data from a cohort of 15,279 incident, adult (18-69 years) patients with end-stage renal disease from 308 Georgia dialysis facilities from January 2005 to September 2011, followed up through September 2012, linked to kidney transplant referral data collected from adult transplant centers in Georgia in the same period. Referral for kidney transplant evaluation within 1 year of starting dialysis at any of the 3 Georgia transplant centers was the primary outcome; placement on the deceased donor waiting list was also examined. The median within-facility percentage of patients referred within 1 year of starting dialysis was 24.4% (interquartile range, 16.7%-33.3%) and varied from 0% to 75.0%. Facilities in the lowest tertile of referral (<19.2%) were more likely to treat patients living in high-poverty neighborhoods (absolute difference, 21.8% [95% CI, 14.1%-29.4%]), had a higher patient to social worker ratio (difference, 22.5 [95% CI, 9.7-35.2]), and were more likely nonprofit (difference, 17.6% [95% CI, 7.7%-27.4%]) compared with facilities in the highest tertile of referral (>31.3%). In multivariable, multilevel analyses, factors associated with lower referral for transplantation, such as older age, white race, and nonprofit facility status, were not always consistent with the factors associated with lower waitlisting. In Georgia overall, a limited proportion of patients treated with dialysis were referred for kidney transplant evaluation between 2005 and 2011, but there was substantial variability in referral among facilities. Variables associated with referral were not always associated with waitlisting, suggesting that different factors may account for disparities in referral.


National cross sectional survey to determine whether the decision to delivery interval is critical in emergency caesarean section.
To examine the association between decision to delivery interval and maternal and baby outcomes. National cross sectional survey. Maternity units in England and Wales. SUBJECTS REVIEWED: 17 780 singleton births (99% of all births) delivered by emergency caesarean section in England and Wales between 1 May 2000 and 31 July 2000. Association between decision to delivery interval and baby outcomes (Apgar scores of < 7 and < 4 at five minutes and stillbirth) and maternal outcomes (requirement for special care additional to routine care after caesarean section and where care was provided). Compared with babies delivered within 15 minutes, there was no difference in maternal or baby outcome for decision to delivery interval between 16 and 75 minutes. After 75 minutes, however, there was a significantly higher odds of a five minute Apgar score of < 7 (odds ratio 1.7, 95% confidence interval 1.2 to 2.4), and 50% increase in odds of special care additional to routine care for mothers. A decision to delivery interval of 30 minutes is not an absolute threshold for influencing baby outcome. Decision to delivery intervals of more than 75 minutes are associated with poorer maternal and baby outcomes and should be avoided.


Impact of Cognitive Dysfunction on Survival in Patients With and Without Statin Use Following Carotid Endarterectomy.
Early cognitive dysfunction (eCD) is a subtle form of neurological injury observed in ∼25% of carotid endarterectomy (CEA) patients. Statin use is associated with a lower incidence of eCD in asymptomatic patients having CEA. To determine whether eCD status is associated with worse long-term survival in patients taking and not taking statins. This is a post hoc analysis of a prospective observational study of 585 CEA patients. Patients were evaluated with a battery of neuropsychometric tests before and after surgery. Survival was compared for patients with and without eCD stratifying by statin use. At enrollment, 366 patients were on statins and 219 were not. Survival was assessed by using Kaplan-Meier methods and multivariable Cox proportional hazards models. Age ≥75 years (P = .003), diabetes mellitus (P < .001), cardiac disease (P = .02), and statin use (P = .014) are significantly associated with survival univariately (P < .05) by use of the log-rank test. By Cox proportional hazards model, eCD status and survival adjusting for univariate factors within statin and nonstatin use groups suggested a significant effect by association of eCD on survival within patients not taking statin (hazard ratio, 1.61; 95% confidence interval, 1.09-2.40; P = .018), and no significant effect of eCD on survival within patients taking statin (hazard ratio, 0.98; 95% confidence interval, 0.59-1.66; P = .95). eCD is associated with shorter survival in patients not taking statins. This finding validates eCD as an important neurological outcome and suggests that eCD is a surrogate measure for overall health, comorbidity, and vulnerability to neurological insult. aHR, adjusted hazards ratiosCEA, carotid endarterectomyCI, confidence intervalDM, diabetes mellituseCD, early cognitive dysfunctionNDI, National Death IndexNLR, neutrophil/lymphocyte ratioSD, standard deviationSEM, standard error of the mean.


Ethnobiology of the Nilgiri hills, India.
The Nilgiri is a popular massif towering high in the Western Ghats in South India with an altitude of 2623 m. Nature has been magnanimous in bestowing Nilgiri district with rich evergreen temperate to tropical forests. A high degree of biodiversity, marked by varied flora and fauna of good therapeutic potential as well as the varied number of indigenous groups of people in this area, makes it very popular among herbalists. The district has six anthropologically well defined ethnic groups namely Todas, Kotas, Kurumbas, Irulas, Paniyas and Kattunayakas living here possibly since 1200 B.C. The present review highlights the ethnobiological profile of six indigenous populations and their dependence on ambient flora and fauna for traditional health care needs. It has been observed that about 2700 therapeutically potent plant species are available in this hill station of which almost all have come from local medicine. Some have been explored scientifically. However, about 150 plant species are still to be explored for their therapeutic potential. The ethnography, phytochemical and therapeutic uses as well as the anthropological perspectives of the local medicines have been discussed in this review.


Gold therapy in women planning pregnancy: outcomes in one center.
To review the experience and outcome of pregnancies in women taking gold while planning pregnancy. We undertook a chart review of patients attending for gold injection and monitoring between January 1992 and April 2006. For women who became pregnant while being followed taking gold therapy, we extracted demographic, treatment, and disease activity data, information regarding pregnancy complications, outcome, and postpartum course. For details missing from the clinic records, patients were interviewed by the clinic nurse. Fourteen women experienced 20 pregnancies while being followed in the gold monitoring clinic. Mean age at the time of conception was 34.5 years (range 24-41), disease duration 8.5 years (1-16). Rheumatoid factor was positive in 9 of 14 women. Duration taking gold prior to conception was < 12 months in 7 pregnancies, 13-24 months in 4, 25-34 months in 2, and 2-10 years in 7 pregnancies. Four women continued taking gold until delivery. The rest of the women discontinued gold when they knew they were pregnant, with the exception of one who held her gold 4 weeks prior to conception. There were 5 spontaneous abortions in the first trimester; included were 2 spontaneous abortions in a woman with known Robertsonian chromosomal translocation. Sixteen babies were healthy including a pair of twins. One baby was born with weakness of one extraocular muscle requiring surgery; one had blocked tear ducts at birth. Rheumatoid arthritis (RA) flared during 3/15 completed pregnancies and postpartum and post-spontaneous abortion in 18/20 pregnancies. Our clinic experience and the published literature support the current practice that in patients with RA, gold may still be considered a treatment option in women planning pregnancy.


Journal Writing by Families of Critically Ill Patients: An Integrative Review.
Families experience high levels of stress during a loved one's critical illness. To provide an overview of current evidence on the use of journal writing as a coping mechanism for family members during a loved one's critical illness in a neonatal, pediatric, or adult intensive care unit. Five databases (MEDLINE, PsycINFO, CINAHL, APA PsycArticles, and Health Source: Nursing/Academic Edition) were searched to identify studies examining the benefits of journal writing for family members of critically ill patients. Eight eligible studies reported data from 426 relatives of critically ill patients. Regarding quality assessment, the quantitative studies met 73.1% of relevant quality criteria, whereas qualitative studies met 81.3%. Mixed-methods studies met 82.4% of quantitative and 55% of qualitative criteria. Various key themes were identified: communication and understanding, connection to the patient, emotional expression, creating something meaningful, and the importance of pictures and staff entries. Overall, writing in a diary seems to be beneficial for reducing psychological distress and posttraumatic stress disorder, but none of the studies found that it significantly decreased anxiety or depression. The findings of this review suggest that having family members of critically ill patients write in a diary is a simple and cost-effective intervention that may improve their psychological outcomes. Critical care nurses are in a position to educate families about the potential benefits of writing in a diary. Future research would be valuable regarding the benefits of using a diary and an optimal approach for doing so in this population.


Gestational and lactational exposure to low-dose bisphenol A increases Th17 cells in mice offspring.
Increasing evidence demonstrates that perinatal exposure to Bisphenol A (BPA) can cause immune disorders throughout the life span. However, the biological basis for these immune disorders is poorly understood and the effects of exposure to BPA on Th17 development are unknown. The present study sought to characterize alterations of Th17 cells in childhood and adulthood following gestational and lactational exposure to environmentally relevant low-dose of BPA and the underlying mechanisms. Pregnant dams were exposed to BPA (10, 100 or 1000nM) via drinking water from gestational day (GD) 0 to postnatal day (PND) 21. At PNDs 21 and 42, offspring mice were anesthetized, blood was obtained for cytokine assay and spleens were collected for Th17 cell frequency and RORγt mRNA expression analysis. Perinatal exposure to low-dose BPA resulted in a dose-dependent and gender-specific persistent rise in Th17 cells accompanied by an increase of RORγt mRNA expression in the offsprings. The contents of major Th17 cell-derived cytokines (IL-17 and IL-21) and those essential for Th17 cell differentiation (IL-6 and IL-23) were also increased compared to those in controls. These changes were more pronounced in female than in male offsprings. However, perinatal exposure to low-dose BPA had little effect on serum TGF-β, another key regulator for Th17 cell development. Our results suggest that gestational and lactational exposure to a low-dose of BPA can affect Th17 cell development via an action on its transcription factor and the regulatory cytokines. These findings provide novel insight into sustained immune disorders by BPA exposure during development.


Expression of neuronal nitric oxide synthase corresponds to regions of selective vulnerability to hypoxia-ischaemia in the developing rat brain.
Nitric oxide (NO) has been implicated in the pathogenesis of brain injury from hypoxia-ischaemia. In the brain, the enzyme responsible for NO synthesis is neuronal nitric oxide synthase (nNOS). Using in situ hybridization, immunohistochemistry and NADPH diaphorase histochemistry, we examined the spatial and temporal expression of nNOS during development of the rat brain to determine whether the expression of nNOS delineates the areas of the brain that are selectively vulnerable to hypoxic-ischaemia injury. The expression of nNOS was localized to discrete areas of the brain. nNOS could be detected in the developing forebrain in the 10-day-old embryo (E10). From E14 to E18, the highest level of expression was in the cortical plate, where the majority of neurons were positive. However, this expression diminished with time; in the adult there were only a few nNOS-positive neurones in the deep layers of the cortex. Expression of nNOS was not detected prenatally in the basal ganglia. There was transient high-level expression during the first postnatal week. Thereafter, the basal ganglia exhibited the adult pattern of expression. Expression of nNOS could be detected in the hippocampus at E16. This expression remained constant with regional localization in layers CA1 and CA3 in the adult. Similarly, nNOS expression in the developing cerebellum was observed only after birth. From the first day after birth (P1) to P6, expression was limited to the molecular cell layer. As the cerebellum matured, nNOS expression could be detected in the inner granular layer. By P21, the adult distribution of nNOS expression was observed. All regions expressing nNOS mRNA also demonstrated nNOS protein expression and NADPH diaphorase catalytic activity. Our results demonstrate that nNOS expression in the developing brain correlates with regions of selective vulnerability to hypoxic-ischaemic injury, and, therefore, supports a role for NO in hypoxic-ischaemic injury in the developing brain.


A long interspersed (LINE) DNA exhibiting polymorphic patterns in human genomes.
Several human DNAs digested with Kpn I restriction endonuclease released a 0.6-kilobase (kb) segment that varied in its intensity among human samples. A recombinant DNA clone (N6.4) of these 0.6-kb Kpn I segments was isolated and used to probe the genomic content and restriction cleavage pattern of homologous sequences. The hybridization patterns revealed a previously undescribed, moderately repetitive long interspersed (LINE) sequence family, which we have termed L2Hs (second LINE family in Homo sapiens). This LINE family exhibits both quantitative and qualitative polymorphisms in the human population. The content of L2Hs sequences in human genomes varies over a 5-fold range. Relative to the value for a human placental DNA, sequences homologous to the L2Hs family occur in lower amounts in gorilla DNA (approximately 20%) and even less in DNA from chimpanzees and other primates (less than 1%). Thus, the L2Hs sequences appear to have emerged only recently as a moderately repetitive sequence family in primate evolution. The observed restriction fragment length polymorphism of the L2Hs family members may reflect patterns of sequence rearrangements, amplifications, and/or deletions in human genomes.


Establishing Cohorts to Generate the Evidence Base to Reduce the Burden of Breast Cancer in Sub-Saharan Africa: Results From a Feasibility Study in Kenya.
By 2025, Kenya is estimated to experience a two-thirds increase in the incidence of breast cancer. Local research is necessary to generate evidence to inform policy, public health, and medical practice. There have been no longitudinal cohort studies in sub-Saharan Africa of women with and without breast cancer. Our aim is to assess the feasibility of conducting cohort studies in Kenya that consider clinical characteristics, socioeconomic factors, and self-care behaviors. We initiated a short-term follow-up cohort study of women with and without a diagnosis of breast cancer with baseline face-to-face data collection and one follow-up interview (at approximately 3 months by telephone). We developed tailored instruments to capture demographics, socioeconomic factors, breast cancer risk, ability to identify breast cancer symptoms, treatments received for breast cancer, and quality of life of survivors. We recruited 800 women between the ages of 20 and 60 years and successfully collected baseline data. Completeness of the data was high for demographic variables, but there was a larger proportion of missing information for specific variables required for assessing breast cancer risk. Respondents were able to complete standardized instruments to assess breast cancer knowledge among those without breast cancer and identification of symptoms among survivors. We were able to successfully contact approximately 80% of the participants for follow-up. This short-term follow-up study provides evidence that women can be successfully tracked and contacted for follow-up in the Kenyan setting and offers lessons to establish future longitudinal cohorts to identify approaches to improve breast cancer outcomes.


Antiangiogenesis and medical therapy failure in intracranial atherosclerosis.
Intracranial atherosclerotic disease (ICAD) is one of the most common causes of stroke worldwide and the one with the worst prognosis. In this study, we assessed the hypothesis that the balance of circulating pro- and antiangiogenic factors plays a role in the evolution of the disease and can be used as a potential marker for the disease course and a target for treatment. Seventy-four patients with severe ICAD were enrolled in this prospective observational study, medically optimized, and followed for 6 months. Thirteen pro- and eight antiangiogenic factors were measured in the participants' serum using a sandwich multiplex ELISA. Angiogenic profiles were calculated using principal component analysis. We tested the association between angiogenic profiles and recurring cerebrovascular events despite intensive medical therapy, disability at 6 months after enrollment, and angiographic neovascularization in patients who failed medical treatment and underwent indirect revascularization surgery. There is a strong association between a functionally antiangiogenic profile and recurrent stroke or TIA in patients with ICAD (OR = 7.2, CI 2.4-34.4). Multivariable regression analysis showed that this antiangiogenic profile was also associated with poor functional status after 6 months (p = 0.002), independent from other clinical features such as history of previous stroke, diabetes, and age. In patients who failed medical management and underwent indirect revascularization surgery, high endostatin and angiostatin levels were also associated with low angiographic neovascularization (p = 0.02). The results of this study point to the striking importance of antiangiogenesis as a determinant of ICAD patient prognosis and suggest a possible new target for therapy.


Temporal heterogeneity increases with spatial heterogeneity in ecological communities.
Heterogeneity is increasingly recognized as a foundational characteristic of ecological systems. Under global change, understanding temporal community heterogeneity is necessary for predicting the stability of ecosystem functions and services. Indeed, spatial heterogeneity is commonly used in alternative stable state theory as a predictor of temporal heterogeneity and therefore an early indicator of regime shifts. To evaluate whether spatial heterogeneity in species composition is predictive of temporal heterogeneity in ecological communities, we analyzed 68 community data sets spanning freshwater and terrestrial systems where measures of species abundance were replicated over space and time. Of the 68 data sets, 55 (81%) had a weak to strongly positive relationship between spatial and temporal heterogeneity, while in the remaining communities the relationship was weak to strongly negative (19%). Based on a mixed model analysis, we found a significant but weak overall positive relationship between spatial and temporal heterogeneity across all data sets combined, and within aquatic and terrestrial data sets separately. In addition, lifespan and successional stage were negatively and positively related to temporal heterogeneity, respectively. We conclude that spatial heterogeneity may be a predictor of temporal heterogeneity in ecological communities, and that this relationship may be a general property of many terrestrial and aquatic communities.


B cell-activating factor belonging to the TNF family (BAFF)-R is the principal BAFF receptor facilitating BAFF costimulation of circulating T and B cells.
BAFF (B cell-activating factor belonging to the TNF family) is a cell survival and maturation factor for B cells, and overproduction of BAFF is associated with systemic autoimmune disease. BAFF binds to three receptors, BAFF-R, transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), and B cell maturation Ag (BCMA). Using specific mAbs, BAFF-R was found to be the predominant BAFF receptor expressed on peripheral B cells, in both humans and mice, and antagonist mAbs to BAFF-R blocked BAFF-mediated costimulation of anti- micro responses. The other BAFF receptors showed a much more restricted expression pattern, suggestive of specialized roles. BCMA was expressed by germinal center B cells, while TACI was expressed predominantly by splenic transitional type 2 and marginal zone B cells, as well as activated B cells, but was notably absent from germinal center B cells. BAFF was also an effective costimulator for T cells, and this costimulation occurs entirely through BAFF-R. BAFF-R, but not TACI or BCMA, was expressed on activated/memory subsets of T cells, and T cells from BAFF-R mutant A/WySnJ mice failed to respond to BAFF costimulation. Thus, BAFF-R is important not only for splenic B cell maturation, but is the major mediator of BAFF-dependent costimulatory responses in peripheral B and T cells.


Predicting quality of life impairment in chronic schizophrenia from cognitive variables.
The aim of this study was to see whether and how cognition deficit predicts quality of life impairments in schizophrenia patients. The Computerized Cambridge Automated Neuropsychological Test Battery, the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q) and the Quality of Life Scale (QLS) were used to assess 62 patients with chronic schizophrenia. Step-wise multiple regression analysis was used in order to determine cognitive variables that would predict the scores of each Q-LES-Q and QLS domain scores. Regression analysis revealed a significant association of the cognitive deficits with both general and domain-specific quality of life impairment measured with Q-LES-Q and QLS. Deficits in executive functions, visual sustained attention, memory and motor skills have been found to be valid predictors both before and after controlling for the severity of symptoms, emotional distress, side effects, age, education, and illness duration. This study suggests that deficits in executive functioning, attention, memory and motor skills substantially contributes to predicting impairments across a wide range of HRQL domains, and, consequently, to quality of life appraisal in schizophrenia. Cognitive predictors cannot be attributed to illness-related and background variables. It can be concluded that, when aiming at the improvement of quality of life in schizophrenia patients, cognitive functioning should be targeted.


Quantitative trait mapping of plant architecture in two BC1F2 populations of Sorghum Bicolor × S. halepense and comparisons to two other sorghum populations.
Comparing populations derived, respectively, from polyploid Sorghum halepense and its progenitors improved knowledge of plant architecture and showed that S. halepense harbors genetic novelty of potential value for sorghum improvement Vegetative growth and the timing of the vegetative-to-reproductive transition are critical to a plant's fitness, directly and indirectly determining when and how a plant lives, grows and reproduces. We describe quantitative trait analysis of plant height and flowering time in the naturally occurring tetraploid Sorghum halepense, using two novel BC1F2 populations totaling 246 genotypes derived from backcrossing two tetraploid Sorghum bicolor x S. halepense F1 plants to a tetraploidized S. bicolor. Phenotyping for two years each in Bogart, GA and Salina, KS allowed us to dissect variance into narrow-sense genetic (QTLs) and environmental components. In crosses with a common S. bicolor BTx623 parent, comparison of QTLs in S. halepense, its rhizomatous progenitor S. propinquum and S. bicolor race guinea which is highly divergent from BTx623 permit inferences of loci at which new alleles have been associated with improvement of elite sorghums. The relative abundance of QTLs unique to the S. halepense populations may reflect its polyploidy and subsequent 'diploidization' processes often associated with the formation of genetic novelty, a possibility further supported by a high level of QTL polymorphism within sibling lines derived from a common S. halepense parent. An intriguing hypothesis for further investigation is that polyploidy of S. halepense following 96 million years of abstinence, coupled with natural selection during its spread to diverse environments across six continents, may provide a rich collection of novel alleles that offer potential opportunities for sorghum improvement.


Parents bereaved by infant death: PTSD symptoms up to 18 years after the loss.
Losing an infant or fetus late in pregnancy, during birth or in the first year of life is a potentially traumatic event for parents. However, little is known about the factors contributing to chronic posttraumatic stress reactions in this population. The present study examined chronic posttraumatic stress disorder (PTSD) symptoms and potential correlates in 634 mothers and fathers up to 18 years (M=3.4 years) after the death of their infant. Members of a private national support organization for parents bereaved by infant death were contacted and asked to participate in the study. Participants filled out a questionnaire package including measures of PTSD (the Harvard Trauma Questionnaire), coping (the Coping Style Questionnaire), perceived social support (the Crisis Support Scale) and attachment (the Revised Adult Attachment Scale). Associations between variables were examined through the use of analyses of variance, correlation analyses and a regression analysis. We found an estimated PTSD prevalence of 12.3%. Type of loss (pre-, peri- or postnatal) did not have any effect on PTSD severity, but lower gestational age was associated with more symptoms. Time since the loss, female sex, attachment avoidance, attachment anxiety, emotion-focused coping, rational coping, feeling let down and social support satisfaction accounted for 42% of the variance in PTSD severity. The study highlights the long-term impact of infant loss and points to attachment, coping and social support as important contributors to the development and maintenance of posttraumatic stress symptoms.


Genotyping-by-sequencing (GBS), an ultimate marker-assisted selection (MAS) tool to accelerate plant breeding.
Marker-assisted selection (MAS) refers to the use of molecular markers to assist phenotypic selections in crop improvement. Several types of molecular markers, such as single nucleotide polymorphism (SNP), have been identified and effectively used in plant breeding. The application of next-generation sequencing (NGS) technologies has led to remarkable advances in whole genome sequencing, which provides ultra-throughput sequences to revolutionize plant genotyping and breeding. To further broaden NGS usages to large crop genomes such as maize and wheat, genotyping-by-sequencing (GBS) has been developed and applied in sequencing multiplexed samples that combine molecular marker discovery and genotyping. GBS is a novel application of NGS protocols for discovering and genotyping SNPs in crop genomes and populations. The GBS approach includes the digestion of genomic DNA with restriction enzymes followed by the ligation of barcode adapter, PCR amplification and sequencing of the amplified DNA pool on a single lane of flow cells. Bioinformatic pipelines are needed to analyze and interpret GBS datasets. As an ultimate MAS tool and a cost-effective technique, GBS has been successfully used in implementing genome-wide association study (GWAS), genomic diversity study, genetic linkage analysis, molecular marker discovery and genomic selection under a large scale of plant breeding programs.


Paranasal sinus mucosal regeneration: the effect of topical retinoic acid.
Paranasal sinus mucosa may suffer morphological and functional alterations as a result of surgical trauma. Mucosal stripping typically yields regenerated mucosa characterized by fibrosis, inflammatory infiltrate, and dysmorphic or absent cilia. The aim of this study was to determine the effect of topical retinoic acid (vitamin A) on regeneration of paranasal sinus mucosa. Both maxillary sinuses of 12 New Zealand white rabbits were surgically opened and stripped of mucosa. Six rabbits received 0.01% topical retinoic acid gel treatment to the stripped left maxillary sinus (low concentration group). The remaining six rabbits received 0.025% topical retinoic acid gel to the stripped left maxillary sinus (high concentration group). The stripped right maxillary sinus of all 12 rabbits served as the operated, untreated control to reflect the normal healing process. Six other animals served as unoperated controls. The sinus mucosa was examined by light microscopy after 14 days. Untreated regenerated mucosa showed expected changes of submucosal gland loss, basal lamina and lamina propria fibrosis, cellular atypia, and loss of cilia. Topical retinoic acid treatment appeared to result in better mucosal regeneration marked by less cellular atypia and fibrosis. Although the regenerated mucosa was still grossly abnormal, the degree of ciliary loss and cellular derangement was reduced. The lower-concentration retinoic acid group had more favorable morphology than the higher-concentration retinoic acid group, and both were improved when compared with no treatment. In a rabbit model, topical vitamin A in the form of retinoic acid gel appears to enhance regeneration of ciliated paranasal sinus mucosa. This preliminary study suggests that topical retinoids may have applicability in promoting sinus wound healing.


A comparative biomarker study of 514 matched cases of male and female breast cancer reveals gender-specific biological differences.
Male breast cancer remains understudied despite evidence of rising incidence. Using a co-ordinated multi-centre approach, we present the first large scale biomarker study to define and compare hormone receptor profiles and survival between male and female invasive breast cancer. We defined and compared hormone receptor profiles and survival between 251 male and 263 female breast cancers matched for grade, age, and lymph node status. Tissue microarrays were immunostained for ERα, ERβ1, -2, -5, PR, PRA, PRB and AR, augmented by HER2, CK5/6, 14, 18 and 19 to assist typing. Hierarchical clustering determined differential nature of influences between genders. Luminal A was the most common phenotype in both sexes. Luminal B and HER2 were not seen in males. Basal phenotype was infrequent in both. No differences in overall survival at 5 or 10 years were observed between genders. Notably, AR-positive luminal A male breast cancer had improved overall survival over female breast cancer at 5 (P = 0.01, HR = 0.39, 95% CI = 0.26-0.87) but not 10 years (P = 0.29, HR = 0.75, 95% CI = 0.46-1.26) and both 5 (P = 0.04, HR = 0.37, 95% CI = 0.07-0.97) and 10 years (P = 0.04, HR = 0.43, 95% CI = 0.12-0.97) in the unselected group. Hierarchical clustering revealed common clusters between genders including total PR-PRA-PRB and ERβ1/2 clusters. A striking feature was the occurrence of ERα on distinct clusters between genders. In female breast cancer, ERα clustered with PR and its isoforms; in male breast cancer, ERα clustered with ERβ isoforms and AR. Our data supports the hypothesis that breast cancer is biologically different in males and females suggesting implications for clinical management. With the incidence of male breast cancer increasing this provides impetus for further study.


A genome-wide association study implicates the APOE locus in nonpathological cognitive ageing.
Cognitive decline is a feared aspect of growing old. It is a major contributor to lower quality of life and loss of independence in old age. We investigated the genetic contribution to individual differences in nonpathological cognitive ageing in five cohorts of older adults. We undertook a genome-wide association analysis using 549 692 single-nucleotide polymorphisms (SNPs) in 3511 unrelated adults in the Cognitive Ageing Genetics in England and Scotland (CAGES) project. These individuals have detailed longitudinal cognitive data from which phenotypes measuring each individual's cognitive changes were constructed. One SNP--rs2075650, located in TOMM40 (translocase of the outer mitochondrial membrane 40 homolog)--had a genome-wide significant association with cognitive ageing (P=2.5 × 10(-8)). This result was replicated in a meta-analysis of three independent Swedish cohorts (P=2.41 × 10(-6)). An Apolipoprotein E (APOE) haplotype (adjacent to TOMM40), previously associated with cognitive ageing, had a significant effect on cognitive ageing in the CAGES sample (P=2.18 × 10(-8); females, P=1.66 × 10(-11); males, P=0.01). Fine SNP mapping of the TOMM40/APOE region identified both APOE (rs429358; P=3.66 × 10(-11)) and TOMM40 (rs11556505; P=2.45 × 10(-8)) as loci that were associated with cognitive ageing. Imputation and conditional analyses in the discovery and replication cohorts strongly suggest that this effect is due to APOE (rs429358). Functional genomic analysis indicated that SNPs in the TOMM40/APOE region have a functional, regulatory non-protein-coding effect. The APOE region is significantly associated with nonpathological cognitive ageing. The identity and mechanism of one or multiple causal variants remain unclear.


Do people use the shortest path? An empirical test of Wardrop's first principle.
Most recent route choice models, following either the random utility maximization or rule-based paradigm, require explicit enumeration of feasible routes. The quality of model estimation and prediction is sensitive to the appropriateness of the consideration set. However, few empirical studies of revealed route characteristics have been reported in the literature. This study evaluates the widely applied shortest path assumption by evaluating routes followed by residents of the Minneapolis-St. Paul metropolitan area. Accurate Global Positioning System (GPS) and Geographic Information System (GIS) data were employed to reveal routes people used over an eight to thirteen week period. Most people did not choose the shortest path. Using three weeks of that data, we find that current route choice set generation algorithms do not reveal the majority of paths that individuals took. Findings from this study may guide future efforts in building better route choice models.


Theoretical study on the mechanism and stereochemistry of the cinchona-thiourea organocatalytic hydrophosphonylation of an α-ketoester.
The mechanism and stereochemistry of the hydrophosphonylation of an α-ketoester with dimethylphosphonate (DMHP) catalyzed by a thiourea-cinchona organocatalyst have been studied by the ONIOM method. The calculations show that the catalytic cycle is a three-step process, including the deprotonation of DMHP, C-P bond formation via nucleophilic addition and proton transfer with the regeneration of the catalyst. The deprotonation of DMHP mediated by the basicity of the quinuclidine nitrogen atom is the rate-determining step for the entire reaction. The activation of the α-ketoester by the thiourea or protonated cinchona moiety of the bifunctional catalyst is comparatively investigated, and the former is energy-preferred. AIM combined with NBO analysis indicate that the multiple hydrogen bonds play essential roles in activating substrates, facilitating charge transfer and stabilizing transition states and intermediates. The stereochemistry of the reaction is controlled by the C-P bond formation step and originated from the chiral induction of the multiple hydrogen-bonding interactions. The bulkier substituent groups on the chiral scaffold of the catalyst may increase rigidity of the catalyst and the asymmetric induction to the substrates. The calculations predict that alkyl substituted α-ketoesters might also be converted to chiral α-hydroxyl phosphonates with high enantioselectivity.


Parent and child cigarette use: a longitudinal, multigenerational study.
Using longitudinal data from the multigenerational Youth Development Study (YDS), this article documents how parents' long-term smoking trajectories are associated with adolescent children's likelihood of smoking. Prospective data from the parents (from age 14-38 years) enable unique comparisons of the parents' and children's smoking behavior, as well as that of siblings. Smoking trajectories are constructed using latent class analysis for the original YDS cohort (n = 1010). Multigenerational longitudinal data from 214 parents and 314 offspring ages 11 years and older are then analyzed by using logistic regression with cluster-corrected SEs. Four latent smoking trajectories emerged among the original cohort: stable nonsmokers (54%), early-onset light smokers who quit/reduce (16%), late-onset persistent smokers (14%), and early-onset persistent heavy smokers (16%). Although 8% of children of stable nonsmokers smoked in the last year, the other groups' children had much higher percentages, ranging from 23% to 29%. Multivariate logistic regression models confirm that these significant differences were robust to the inclusion of myriad child- and parent-level measures (for which child age and grade point average [GPA] are significant predictors). Older sibling smoking, however, mediated the link between parental heavy smoking and child smoking. Even in an era of declining rates of teenage cigarette use in the United States, children of current and former smokers face an elevated risk of smoking. Prevention efforts to weaken intergenerational associations should consider parents' long-term cigarette use, as well as the smoking behavior of older siblings in the household.


Effect of size (mis)matching in clinical double-lung transplantation.
Current United Network for Organ Sharing policy requires listing lung transplant recipients with an acceptable donor weight range, but lung size is a function of height, age, sex, and race. Frequently, lung transplant recipients are underweight, which results in a large discrepancy between donor and recipient weights. We reviewed our experience with size discrepancy between donors (D) and recipients (R) of 49 double-lung transplant (DLTX) procedures since July 1990. Pneumoreduction procedures were performed in 11 recipients of lungs judged to be too large at the time of DLTX (right middle lobectomy, 2; lingulectomy, 2; both, 6; right middle lobectomy and bilateral apical resections, 1). Predicted forced vital capacity (FVC) and total lung capacity (TLC) of donors and recipients were calculated. Donors were larger than recipients in general (D:R height = 1.02; D:R weight = 1.46), and, as a result, recipient-predicted lung volumes were smaller than donor-predicted lung volumes (D:R FVC = 1.1; D:R TLC = 1.1). Recipients undergoing pneumoreduction procedures had a significantly greater size discrepancy between donors and recipients; thus, both the ratio of D:R and the difference between D and R predicted FVC and TLC were significantly greater among recipients who underwent pneumoreduction, compared with nonreduced recipients. For recipients in the pneumoreduction group, predicted FVC and TLC were recalculated, with a proportionate amount subtracted based on the number of pulmonary segments removed. When the "corrected" FVC and TLC of the donors were compared with recipient-predicted FVC and TLC, there was no longer any significant difference between reduced and non-reduced groups, which implies that visual estimate of size mismatch at surgery is an accurate measure of size discrepancy. Post-DLTX spirometry showed identical improvement in FVC in patients who had pneumoreduction and those who did not, and survival at 6 months was identical in both groups. We conclude that pneumoreduction had no adverse effect on survival or post-DLTX spirometry, allowing safe use of larger donors in small recipients. Also, because lung size is more a function of height than weight, this study challenges the United Network for Organ Sharing practice of listing recipients with an acceptable donor weight range.


The population biology of fungal invasions.
Fungal invasions are increasingly recognized as a significant component of global changes, threatening ecosystem health and damaging food production. Invasive fungi also provide excellent models to evaluate the generality of results based on other eukaryotes. We first consider here the reasons why fungal invasions have long been overlooked: they tend to be inconspicuous, and inappropriate methods have been used for species recognition. We then review the information available on the patterns and mechanisms of fungal invasions. We examine the biological features underlying invasion success of certain fungal species. We review population structure analyses, revealing native source populations and strengths of bottlenecks. We highlight the documented ecological and evolutionary changes in invaded regions, including adaptation to temperature, increased virulence, hybridization, shifts to clonality and association with novel hosts. We discuss how the huge census size of most fungi allows adaptation even in bottlenecked, clonal invaders. We also present new analyses of the invasion of the anther-smut pathogen on white campion in North America, as a case study illustrating how an accurate knowledge of species limits and phylogeography of fungal populations can be used to decipher the origin of invasions. This case study shows that successful invasions can occur even when life history traits are particularly unfavourable to long-distance dispersal and even with a strong bottleneck. We conclude that fungal invasions are valuable models to contribute to our view of biological invasions, in particular by providing insights into the traits as well as ecological and evolutionary processes allowing successful introductions.


Depression and playfulness in fathers and young infants: A matched design comparison study.
Depression in fathers in the postnatal period is associated with an increased risk of some adverse child developmental outcomes. One possible mechanism for the familial transmission of risk is through the negative effects of depression on parenting and the parent-child relationship. So far, evidence indicates that depressed fathers tend to be more withdrawn in their early interactions. However, the interaction dimensions studied to date may not be able to detect and accurately classify unique features of father-infant play - including physically stimulating and highly rousing episodes of play. Hence, in this matched design comparison study, we set out to examine, for the first time, links between diagnosed paternal depression in the postnatal period and playfulness in father-infant interactions. Fathers and their infants were assessed when the infants were 3 months old. Paternal depression was diagnosed using a structured psychiatric interview. Currently depressed (n = 19) and non-depressed (n = 19) fathers were individually matched on age and education. Fathers were filmed playing with their children. Four dimensions were coded for paternal playfulness during free-play: physicality, playful excitation, tactile stimulation and active engagement. Depressed fathers, compared to non-depressed fathers, engaged in fewer episodes of playful excitation (mean scores: 0.71 vs.2.53, p = 0.005), less gentle touch (mean time: 38.57 vs. 53.37, p = 0.015) and less active engagement (mean scores: 2.29 vs 3.24, p = 0.044). When controlling for infant fretfulness, the findings remained largely unchanged. The sample size was small and the sample was limited to mostly white, well-educated fathers. Playful paternal behaviours as early as 3 months differ between fathers with and without depression. These changes may help in understanding children's risk in relation to paternal psychopathology and could be a target for future family interventions.


Classification of Semantic Paraphasias: Optimization of a Word Embedding Model.
In clinical assessment of people with aphasia, impairment in the ability to recall and produce words for objects (anomia) is assessed using a confrontation naming task, where a target stimulus is viewed and a corresponding label is spoken by the participant. Vector space word embedding models have had inital results in assessing semantic similarity of target-production pairs in order to automate scoring of this task; however, the resulting models are also highly dependent upon training parameters. To select an optimal family of models, we fit a beta regression model to the distribution of performance metrics on a set of 2,880 grid search models and evaluate the resultant first- and second-order effects to explore how parameterization affects model performance. Comparing to SimLex-999, we show that clinical data can be used in an evaluation task with comparable optimal parameter settings as standard NLP evaluation datasets.


The generalized transducing Salmonella bacteriophage ES18: complete genome sequence and DNA packaging strategy.
The generalized transducing double-stranded DNA bacteriophage ES18 has an icosahedral head and a long noncontractile tail, and it infects both rough and smooth Salmonella enterica strains. We report here the complete 46,900-bp genome nucleotide sequence and provide an analysis of the sequence. Its 79 genes and their organization clearly show that ES18 is a member of the lambda-like (lambdoid) phage group; however, it contains a novel set of genes that program assembly of the virion head. Most of its integration-excision, immunity, Nin region, and lysis genes are nearly identical to those of the short-tailed Salmonella phage P22, while other early genes are nearly identical to Escherichia coli phages lambda and HK97, S. enterica phage ST64T, or a Shigella flexneri prophage. Some of the ES18 late genes are novel, while others are most closely related to phages HK97, lambda, or N15. Thus, the ES18 genome is mosaically related to other lambdoid phages, as is typical for all group members. Analysis of virion DNA showed that it is circularly permuted and about 10% terminally redundant and that initiation of DNA packaging series occurs across an approximately 1-kbp region rather than at a precise location on the genome. This supports a model in which ES18 terminase can move substantial distances along the DNA between recognition and cleavage of DNA destined to be packaged. Bioinformatic analysis of large terminase subunits shows that the different functional classes of phage-encoded terminases can usually be predicted from their amino acid sequence.


Improving patient handover between teams using a business improvement model: PDSA cycle.
Medical admission units are continuously under pressure to move patients off the unit to outlying medical wards and allow for new admissions. In a typical district general hospital, doctors working in these medical wards reported that, on average, three patients each week arrived from the medical admission unit before any handover was received, and a further two patients arrived without any handover at all. A quality improvement project was therefore conducted using a 'Plan, Do, Study, Act' cycle model for improvement to address this issue. P - Plan: as there was no framework to support doctors with handover, a series of standard handover procedures were designed. D - Do: the procedures were disseminated to all staff, and championed by key stakeholders, including the clinical director and matron of the medical admission unit. S - STUDY: Measurements were repeated 3 months later and showed no change in the primary end points. A - ACT: The post take ward round sheet was redesigned, creating a checkbox for a medical admission unit doctor to document that handover had occurred. Nursing staff were prohibited from moving the patient off the ward until this had been completed. This later evolved into a separate handover sheet. Six months later, a repeat study revealed that only one patient each week was arriving before or without a verbal handover. Using a 'Plan, Do, Study, Act' business improvement tool helped to improve patient care.


Computerised systematic secondary prevention in ischaemic heart disease: a study in one practice.
One of the most effective interventions that the primary health care team can make is that of secondary prevention in ischaemic heart disease (IHD). There is still a need to improve the uptake of effective interventions such as aspirin and statins in these patients. General Practice in the UK is 95% computerised, but many functions are under-utilised. In the majority of cases primary care clinicians use the keyboard rather than mouse for data entry. Methods of data entry using the keyboard or CHUI (Character User Interface) can be cumbersome and time consuming. This can limit data collection and its assimilation for patient care. The object of this study was to assess the feasibility and effectiveness of a new software programme, which provides computerised support to primary care staff in their preventive care of IHD patients. To demonstrate that a systematic computer facilitated secondary prevention programme for IHD was effective, feasible, and acceptable to patients and improved patient care. Evidence-based guidelines and intervention levels for secondary prevention of IHD were agreed at practice level and embedded in the software. Patients aged 80 and under were identified by the use of Read codes and repeat prescribing. The nurse-run programme consisted of a detailed review of electronic and written records and then the clinical review of 141 patients. At follow-up patients were issued with a questionnaire to assess their satisfaction with the process. From a general practice computer search for ischaemic heart disease Read Code (G3) and/or nitrate prescription an initial cohort of 242 patients was established. 90 were excluded on clinical grounds (not IHD, deceased, over-riding other clinical problems), and eleven patients could not be recruited (eight declined and three had moved away). The final cohort consisted of 141 patients, of whom 101 patients suffered angina, 67 had a previous history of myocardial infarction, and 28 had had coronary artery bypass grafting. Hypertension had been diagnosed in 80 and hyperlipidaemia in 43. As a result of the study new diagnoses included: hyperlipidaemia where statins were indicated (38), congestive cardiac failure requiring treatment with ACE (Angiotensin Converting Enzyme) inhibitors (2) and carotid bruits requiring referral (4). In addition diabetes was diagnosed in three patients. The programme proved acceptable to patients, doctors and practice staff; follow-up continues. The use of this methodology, in a single practice, has improved the care of patients well beyond that achieved with established template-based secondary prevention programmes. The outcome has been measured in terms of increased diagnosis and active management of hyperlipidaemia and other risk factors.


Computation of high-resolution SAR distributions in a head due to a radiating dipole antenna representing a hand-held mobile phone.
SAR distributions in a healthy female adult head as a result of a radiating vertical dipole antenna (frequency 915 MHz) representing a hand-held mobile phone have been computed for three different resolutions: 2 mm, 1 mm and 0.4 mm. The extremely high resolution of 0.4 mm was obtained with our quasistatic zooming technique, which is briefly described in this paper. For an effectively transmitted power of 0.25 W, the maximum averaged SAR values in both cubic- and arbitrary-shaped volumes are, respectively, about 1.72 and 2.55 W kg(-1) for 1 g and 0.98 and 1.73 W kg(-1) for 10 g of tissue. These numbers do not vary much (<8%) for the different resolutions, indicating that SAR computations at a resolution of 2 mm are sufficiently accurate to describe the large-scale distribution. However, considering the detailed SAR pattern in the head, large differences may occur if high-resolution computations are performed rather than low-resolution ones. These deviations are caused by both increased modelling accuracy and improved anatomical description in higher resolution simulations. For example, the SAR profile across a boundary between tissues with high dielectric contrast is much more accurately described at higher resolutions. Furthermore, low-resolution dielectric geometries may suffer from loss of anatomical detail, which greatly affects small-scale SAR distributions. Thus. for strongly inhomogeneous regions high-resolution SAR modelling is an absolute necessity.


An alternative splice form of Mdm2 induces p53-independent cell growth and tumorigenesis.
The Mdm2 gene is amplified in approximately one-third of human sarcomas and overexpressed in a variety of other human cancers. Mdm2 functions as an oncoprotein, in part, by acting as a negative regulator of the p53 tumor suppressor protein. Multiple spliced forms of Mdm2 transcripts have been observed in human tumors; however, the contribution of these variant transcripts to tumorigenesis is unknown. In this report, we isolate alternative splice forms of Mdm2 transcripts from sarcomas that spontaneously arise in Mdm2-overexpressing mice, including Mdm2-b, the splice form most commonly observed in human cancers. Transduction of Mdm2-b into a variety of cell types reveals that Mdm2-b promotes p53-independent cell growth, inhibits apoptosis, and up-regulates the RelA subunit of NFkappaB. Furthermore, expression of Mdm2-b induces tumor formation in transgenic mice. These results identify a p53-independent role for Mdm2 and determine that an alternate spliced form of Mdm2 can contribute to formation of cancer via a p53-independent mechanism. These findings also provide a rationale for the poorer prognosis of those patients presenting with tumors harboring multiple Mdm2 transcripts.


Target-specific expression of presynaptic NMDA receptors in neocortical microcircuits.
Traditionally, NMDA receptors are located postsynaptically; yet, putatively presynaptic NMDA receptors (preNMDARs) have been reported. Although implicated in controlling synaptic plasticity, their function is not well understood and their expression patterns are debated. We demonstrate that, in layer 5 of developing mouse visual cortex, preNMDARs specifically control synaptic transmission at pyramidal cell inputs to other pyramidal cells and to Martinotti cells, while leaving those to basket cells unaffected. We also reveal a type of interneuron that mediates ascending inhibition. In agreement with synapse-specific expression, we find preNMDAR-mediated calcium signals in a subset of pyramidal cell terminals. A tuned network model predicts that preNMDARs specifically reroute information flow in local circuits during high-frequency firing, in particular by impacting frequency-dependent disynaptic inhibition mediated by Martinotti cells, a finding that we experimentally verify. We conclude that postsynaptic cell type determines presynaptic terminal molecular identity and that preNMDARs govern information processing in neocortical columns.


Seasonal variations in incidence and maternal-fetal outcomes of gestational diabetes.
To determine whether the neonatal and delivery outcomes of gestational diabetes vary seasonally in the context of a relatively cool temperate climate. A retrospect cohort of 23 735 women consecutively delivering singleton, live-born term infants in a single tertiary obstetrics centre in the UK (2004-2008) was identified. A total of 985 (4.1%) met the diagnostic criteria for gestational diabetes. Additive dynamic regression models, adjusted for maternal age, BMI, parity and ethnicity, were used to compare gestational diabetes incidence and outcomes over annual cycles. Outcomes included: random plasma glucose at booking; gestational diabetes diagnosis; birth weight centile; and delivery mode. The incidence of gestational diabetes varied by 30% from peak incidence (October births) to lowest incidence (March births; P=0.031). Ambient temperature at time of testing (28 weeks) was strongly positively associated with diagnosis (P<0.001). Significant seasonal variation was evident in birth weight in gestational diabetes-affected pregnancies (average 54th centile June to September; average 60th centile December to March; P=0.027). Emergency Caesarean rates also showed significant seasonal variation of up to 50% (P=0.038), which was closely temporally correlated with increased birth weights. There is substantial seasonal variation in gestational diabetes incidence and maternal-fetal outcomes, even in a relatively cool temperate climate. The highest average birth weight and greatest risk of emergency Caesarean delivery occurs in women delivering during the spring months. Recognizing seasonal variation in neonatal and delivery outcomes provides new opportunity for individualizing approaches to managing gestational diabetes.


The role of sleep and dreams in long-COVID.
Recent investigations show that many people affected by SARS-CoV2 (COVID-19) report persistent symptoms 2-3 months from the onset of the infection. Here, we report the Italian findings from the second International COVID-19 Sleep Study survey, aiming to investigate sleep and dream alterations in participants with post-acute symptoms, and identify the best determinants of these alterations among patients with long-COVID. Data from 383 participants who have had COVID-19 were collected through a web-survey (May-November 2021). Descriptive analyses were performed to outline the sociodemographic characteristics of long-COVID (N = 270, with at least two long-lasting symptoms) and short-COVID (N = 113, with none or one long-lasting symptom) participants. They were then compared concerning sleep and dream measures. We performed multiple linear regressions considering as dependent variables sleep and dream parameters discriminating the long-COVID group. Age, gender, work status, financial burden, COVID-19 severity and the level of care were significantly different between long-COVID and short-COVID subjects. The long-COVID group showed greater sleep alterations (sleep quality, daytime sleepiness, sleep inertia, naps, insomnia, sleep apnea, nightmares) compared with the short-COVID group. We also found that the number of long-COVID symptoms, psychological factors and age were the best explanatory variables of sleep and oneiric alterations. Our findings highlight that sleep alterations are part of the clinical presentation of the long-COVID syndrome. Moreover, psychological status and the number of post-acute symptoms should be considered as state-like variables modulating the sleep problems in long-COVID individuals. Finally, according to previous investigations, oneiric alterations are confirmed as a reliable mental health index.


Plasma alkylresorcinol concentrations, biomarkers of whole-grain wheat and rye intake, in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.
Whole-grain intake has been reported to be associated with a lower risk of several lifestyle-related diseases such as type 2 diabetes, CVD and some types of cancers. As measurement errors in self-reported whole-grain intake assessments can be substantial, dietary biomarkers are relevant to be used as complementary tools for dietary intake assessment. Alkylresorcinols (AR) are phenolic lipids found almost exclusively in whole-grain wheat and rye products among the commonly consumed foods and are considered as valid biomarkers of the intake of these products. In the present study, we analysed the plasma concentrations of five AR homologues in 2845 participants from ten European countries from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition. High concentrations of plasma total AR were found in participants from Scandinavia and Central Europe and lower concentrations in those from the Mediterranean countries. The geometric mean plasma total AR concentrations were between 35 and 41 nmol/l in samples drawn from fasting participants in the Central European and Scandinavian countries and below 23 nmol/l in those of participants from the Mediterranean countries. The whole-grain source (wheat or rye) could be determined using the ratio of two of the homologues. The main source was wheat in Greece, Italy, the Netherlands and the UK, whereas rye was also consumed in considerable amounts in Germany, Denmark and Sweden. The present study demonstrates a considerable variation in the plasma concentrations of total AR and concentrations of AR homologues across ten European countries, reflecting both quantitative and qualitative differences in the intake of whole-grain wheat and rye.


IL-1beta and IL-6 excite neurons and suppress nicotinic and noradrenergic neurotransmission in guinea pig enteric nervous system.
Conventional intracellular microelectrodes and injection of biocytin were used to study the actions of IL-1beta and IL-6 on electrical and synaptic behavior in morphologically identified guinea pig small intestinal submucous neurons. Exposure to nanomolar concentrations of either IL-1beta or IL-6 stimulated neuronal excitability. The excitatory action consisted of depolarization of the membrane potential, decreased membrane conductance, and increased discharge of action potentials. Excitatory action of IL-1beta was suppressed by the natural IL-1beta human receptor antagonist. Electrical stimulation of sympathetic postganglionic axons evoked inhibitory postsynaptic potentials (IPSPs), and stimulation of cholinergic axons evoked nicotinic fast excitatory postsynaptic potentials (EPSPs). Both kinds of synaptic potentials occurred in neurons with uniaxonal morphology believed to be secretomotor neurons. Either IL-1beta or IL-6 suppressed the noradrenergic IPSPs and the fast EPSPs, and the two acted synergistically when applied in combination. Suppression of the IPSP resulted from presynaptic inhibition of the release of norepinephrine from sympathetic nerves. The results suggest that the presence of either or both inflammatory cytokines will release the sympathetic brake from secretomotor neurons to the intestinal crypts and from nicotinic synapses in the integrative microcircuits, where norepinephrine is known to have a presynaptic inhibitory action. This, in concert with excitation of secretomotor neurons, may lead to neurogenic secretory diarrhea.


Automated perimetry. American Academy of Ophthalmology.
Automated perimetry is one product of the computer revolution that has had a dramatic impact on the practice of ophthalmology, affecting the quality of both the perimetric test (perimetric technique) and the interpretation of the test results. Before automation, the quality of visual field technique in many practices was poor, partly because perimetrists lacked the volume of patients requiring the test to provide training sufficient to maintain a high level of experience and expertise. At first, automated perimetry was developed simply to make available to all practitioners visual field testing that was nearly as good as the most skilled manual perimetry. The data provided by first-generation automated perimeters lacked the accuracy, sensitivity, and reproducibility obtainable from a highly skilled manual perimetrist. As automated perimeters evolved, perimetric techniques and the software that analyzes data for clinical significance were improved. The use of automated perimetry to evaluate routinely various visual disorders that require testing of the visual field has increased significantly. Statistical analysis of the test results aids interpretation, both to determine if the field is abnormal and if there is change in the field from one occasion to another, especially in the context of glaucoma. The test is excellent; it is now standardized, with better test algorithms, and in many cases it achieves better results than the best manual perimetrist. However, attention to detail and skill in administering the automated test are still essential. The future will hold further improvements. Nevertheless, as each manufacturer enhances computerized perimetry, it may become more difficult to compare the test results among instruments or even between two test algorithms on the same instrument. In addition, clinical knowledge and experience will still be necessary to reach accurate diagnostic conclusions.


Comparing Robot Controller Optimization Methods on Evolvable Morphologies.
In this paper we compare Bayesian Optimization, Differential Evolution, and an Evolution Strategy, employed as a gait learning algorithm in modular robots. The motivational scenario is the joint evolution of morphologies and controllers, where 'newborn' robots also undergo a learning process to optimize their inherited controllers (without changing their bodies). This context raises the question: How do gait learning algorithms compare when applied to various morphologies that are not known in advance (thus need to be treated without priors)? To answer this question, we use a test suite of twenty different robot morphologies to evaluate our gait learners and compare their efficiency, efficacy, and sensitivity to morphological differences. The results indicate that Bayesian Optimization and Differential Evolution deliver the same solution quality (walking speed for the robot) with fewer evaluations than the Evolution Strategy. Furthermore, the Evolution Strategy is more sensitive for morphological differences (its efficacy varies more between different morphologies) and is more subject to luck (repeated runs on the same morphology show greater variance in the outcomes).


Use of theory in computer-based interventions to reduce alcohol use among adolescents and young adults: a systematic review.
Alcohol use and binge drinking among adolescents and young adults remain frequent causes of preventable injuries, disease, and death, and there has been growing attention to computer-based modes of intervention delivery to prevent/reduce alcohol use. Research suggests that health interventions grounded in established theory are more effective than those with no theoretical basis. The goal of this study was to conduct a literature review of computer-based interventions (CBIs) designed to address alcohol use among adolescents and young adults (aged 12-21 years) and examine the extent to which CBIs use theories of behavior change in their development and evaluations. This study also provides an update on extant CBIs addressing alcohol use among youth and their effectiveness. Between November and December of 2014, a literature review of CBIs aimed at preventing or reducing alcohol in PsychINFO, PubMed, and Google Scholar was conducted. The use of theory in each CBI was examined using a modified version of the classification system developed by Painter et al. (Ann Behav Med 35:358-362, 2008). The search yielded 600 unique articles, 500 were excluded because they did not meet the inclusion criteria. The 100 remaining articles were retained for analyses. Many articles were written about a single intervention; thus, the search revealed a total of 42 unique CBIs. In examining the use of theory, 22 CBIs (52 %) explicitly named one or more theoretical frameworks. Primary theories mentioned were social cognitive theory, transtheoretical model, theory of planned behavior and reasoned action, and health belief model. Less than half (48 %), did not use theory, but mentioned either use of a theoretical construct (such as self-efficacy) or an intervention technique (e.g., manipulating social norms). Only a few articles provided detailed information about how the theory was applied to the CBI; the vast majority included little to no information. Given the importance of theory in guiding interventions, greater emphasis on the selection and application of theory is needed. The classification system used in this review offers a guiding framework for reporting how theory based principles can be applied to computer based interventions.


The developmental, dimensional and diagnostic interview (3di): a novel computerized assessment for autism spectrum disorders.
Autism is a diagnostic spectrum of variable severity, with significant comorbidity. No existing standardized interview measures autistic features dimensionally. The authors aimed to develop a parental autism interview that could be administered to unselected clinical and general population samples that measures both symptom intensity and comorbidity across the full range of the autistic spectrum. A computerized procedure was devised for administration by trained interviewers that generates symptom and diagnostic profiles for both autism and non-autistic conditions. Test-retest reliability and interrater reliability were assessed in unselected clinical (n = 50) and nonclinical (n = 30) populations. Concurrent validity (n = 120), discriminant validity (n = 120), and criterion validity (n = 29) were evaluated in autistic spectrum and non-autistic patients. Test-retest and interrater reliabilities were excellent (most intraclass correlation coefficients > 0.9). Concurrent validity (agreement with independent clinician formulation) was very good (mean kappa = 0.74). Criterion validity, a comparison with the Autism Diagnostic Interview, was excellent. Discrimination between autistic spectrum versus non-autistic subjects was almost perfect (sensitivity 1.0; specificity > 0.97). The Developmental, Dimensional and Diagnostic Interview (3di) provides an efficient and accurate means of assessing, in dimensional terms, the presence of autistic symptoms in both clinical and normal populations. It offers novel opportunities for those engaged in research and clinical practice.


Pathways through relapses and deaths of children with acute lymphoblastic leukemia: role of allogeneic stem-cell transplantation in Nordic data.
Our focus was on patients with pediatric acute lymphoblastic leukemia (ALL) who experienced relapse or died without becoming transplantation candidates. The purpose was to outline measures needed to improve the outcome. We analyzed our population-based 20-year data on 3,385 Nordic children with ALL treated on Nordic Society for Pediatric Hematology and Oncology ALL protocols, and described the flow of these patients through relapses, remissions, and deaths as a result of toxicity, demonstrating where major patient losses occurred. In total, 854 patients (25%) had a first and 274 patients (8%) had a second ALL relapse. P for survival after the first relapse was .35 +/- .02. The induction mortality (2.2%, primary; 10.3%, first relapse; 26.3%, second relapse) and remission mortality (1%, first complete remission [1CR]; 19%, second CR [2CR]) were significant; transplantation-related mortality (TRM) only represented 15% (69 of 459) of the deaths as a result of toxicity. Of the 766 patients entering 2CR, 29% underwent transplantation (P for survival, .46 +/- .04), whereas 71% continued receiving chemotherapy (P for survival, .39 +/- .02). Children with stem-cell transplantation indications in 2CR, if they did not undergo transplantation, generally died or had a second relapse. The patient groups that underwent transplantation in 1CR (n = 84), 2CR (n = 220), and > or = 3CR (n = 62) represented different risk profiles. Those with allogeneic stem-cell transplantation (allo-SCT) in > or = 3CR (P for survival, .37 +/- .07) had an ALL and first relapse with favorable features. Major patient losses occurred through mortality as a result of toxicity and resistant disease during the pathways before allo-SCT. After relapse, more patients were lost to mortality as a result of toxicity during conventional chemotherapy compared with TRM. After second relapse, the chance for rescue by allo-SCT in 3CR was minimal. The question of whether transplantation is recommended after ALL relapse should be carefully addressed, and more efficient relapse protocols should be launched.


The role of diet- and host-related factors in nutrient bioavailability and thus in nutrient-based dietary requirement estimates.
To convert physiological requirements into dietary requirements, adjustments are needed for some nutrients that take into account certain diet- and host-related factors specific to a country or region. Nutrients whose requirements should be adjusted in this way include calcium, magnesium, iron, zinc, protein, folate, vitamin A, and carotenoids. The diet-related factors that must be considered depend on the nature of the habitual diet and may include the chemical form of the nutrient and the nature of the dietary matrix, interactions between nutrients and/or organic components, and food preparation and processing practices within the country or region. The host-related factors can be further subdivided into intestinal and systemic factors. Reductions in the secretion of hydrochloric acid, gastric acid, and/or intrinsic factor, together with alterations in the permeability of the intestinal mucosa, are all examples of intestinal factors that can markedly influence the absorption of certain nutrients, but that are often ignored when setting dietary requirements. Systemic factors that should also be considered include nutrient status of the host, age, sex, ethnicity, genotype, and physiological state (e.g., pregnancy or lactation), and chronic and acute infectious disease states. Algorithms can estimate the bioavailability of iron, zinc, protein, folate, vitamin A, and carotenoids, although their accuracy is limited by the complex interactions among the absorption modifiers in the whole diet. For calcium and magnesium, the amount available for absorption is still estimated from their major food sources in the habitual diet. Currently, there are often large differences in the adjustments employed to convert physiological requirements to dietary requirements, even among countries consuming diets of similar patterns.


Elevated levels of protein-bound p-hydroxyphenylacetaldehyde, an amino-acid-derived aldehyde generated by myeloperoxidase, are present in human fatty streaks, intermediate lesions and advanced atherosclerotic lesions.
Reactive aldehydes might have a pivotal role in the pathogenesis of atherosclerosis by covalently modifying low-density lipoprotein (LDL). However, the identities of the aldehyde adducts that form on LDL in vivo are not yet clearly established. We previously demonstrated that the haem protein myeloperoxidase oxidizes proteins in the human artery wall. We also have shown that p-hydroxyphenylacetaldehyde (pHA), the aldehyde that forms when myeloperoxidase oxidizes L-tyrosine, covalently modifies the N(epsilon)-lysine residues of proteins. The resulting Schiff base can be quantified as N(epsilon)-[2-(p-hydroxyphenyl)ethyl]lysine (pHA-lysine) after reduction with NaCNBH(3). Here we demonstrate that pHA-lysine is a marker for LDL that has been modified by myeloperoxidase, and that water-soluble, but not lipid-soluble, antioxidants inhibit the modification of LDL protein. To determine whether myeloperoxidase-generated aldehydes might modify LDL in vivo, we used a combination of isotope-dilution GC-MS to quantify pHA-lysine in aortic tissues at various stages of lesion evolution. We also analysed LDL isolated from atherosclerotic aortic tissue. Comparison of normal and atherosclerotic aortic tissue demonstrated a significant elevation (more than 10-fold) of the reduced Schiff base adduct in fatty streaks, intermediate lesions and advanced lesions compared with normal aortic tissue. Moreover, the level of pHA-lysine in LDL recovered from atherosclerotic aortic intima was 200-fold that in plasma LDL of healthy donors. These results indicate that pHA-lysine, a specific covalent modification of LDL, is generated in human atherosclerotic vascular tissue. They also raise the possibility that reactive aldehydes generated by myeloperoxidase have a role in converting LDL into an atherogenic lipoprotein.


Multi-attribute health status classification systems. Health Utilities Index.
In this article, multi-attribute approaches to the assessment of health status are reviewed with a special focus on 2 recently developed systems, the Health Utilities Index (HUI) Mark II and Mark III systems. The Mark II system consists of 7 attributes: sensation, mobility, emotion, cognition, self-care, pain and fertility. The Mark III system contains 8 attributes: vision, hearing, speech, ambulation, dexterity, emotion, cognition and pain. Each attribute consists of multiple levels of functioning. A combination of levels across the attributes constitutes a health state. The HUI systems are deliberately focused on the fundamental core attributes of health status, and on the capacity of individuals to function with respect to these attributes. Thus, the measure obtained constitutes a pure description of health status, uncontaminated by differential opportunity or preference. Multi-attribute systems provide a compact but comprehensive framework for describing health status for use in population health and programme evaluation studies. An important advantage of such systems is their ability to simultaneously provide detail on an attribute-by-attribute basis and to capture combinations of deficits among attributes. An additional advantage is their compatibility with multi-attribute preference functions, which provide a method for computing a summary health-related quality-of-life score for each health state.


Reducing hole transporter use and increasing perovskite solar cell stability with dual-role polystyrene microgel particles.
Perovskite solar cells (PSCs) are a disruptive technology that continues to attract considerable attention due to their remarkable and sustained power conversion efficiency increase. Improving PSC stability and reducing expensive hole transport material (HTM) usage are two aspects that are gaining increased attention. In a new approach, we investigate the ability of insulating polystyrene microgel particles (MGs) to increase PSC stability and replace the majority of the HTM phase. MGs are sub-micrometre crosslinked polymer particles that swell in a good solvent. The MGs were prepared using a scalable emulsion polymerisation method. Mixed HTM/MG dispersions were subsequently spin-coated onto PSCs and formed composite HTM-MG layers. The HTMs employed were poly(triaryl amine) (PTAA), poly(3-hexylthiophene) (P3HT) and Spiro-MeOTAD (Spiro). The MGs formed mechanically robust composite HTMs with PTAA and P3HT. In contrast, Spiro-MG composites contained micro-cracks due the inability of the relatively small Spiro molecules to interdigitate. The efficiencies for the PSCs containing PTAA-MG and P3HT-MG decreased by only ∼20% compared to control PSCs despite PTAA and P3HT being the minority phases. They occupied only ∼35 vol% of the composite HTMs. An unexpected finding from the study was that the MGs dispersed well within the PTAA matrix. This morphology aided strong quenching of the CH3NH3PbI3-xClx fluorescence. In addition, the open circuit voltages for the PSCs prepared using P3HT-MG increased by ∼170 mV compared to control PSCs. To demonstrate their versatility the MGs were also used to encapsulate P3HT-based PSCs. Solar cell stability data for the latter as well as those for PSCs containing composite HTM-MG were both far superior compared to data measured for a control PSC. Since MGs can reduce conjugated polymer use and increase stability they have good potential as dual-role PSC additives.


Allergies and Asthma: Do Atopic Disorders Result from Inadequate Immune Homeostasis arising from Infant Gut Dysbiosis?
Our global hypothesis is that atopic conditions and asthma develop because an individual's immune system is not able to appropriately resolve inflammation resulting from allergen exposures. We propose that the failure to appropriately down-regulate inflammation and produce a toleragenic state results primarily from less robust immune homeostatic processes rather than from a tendency to over-respond to allergenic stimuli. An individual with lower immune homeostatic capacity is unable to rapidly and completely terminate, on average over time, immune responses to innocuous allergens, increasing risk of allergic disease. A lack of robust homeostasis also increases the risk of other inflammatory conditions, such as prolonged respiratory viral infections and obesity, leading to the common co-occurrence of these conditions. Further, we posit that the development of vigorous immune homeostatic mechanisms is an evolutionary adaptation strongly influenced by both 1) exposure to a diverse maternal microbiota through the prenatal period, labor and delivery, and, 2) an orderly assemblage process of the infant's gut microbiota ecosystem shaped by breastfeeding and early exposure to a wide variety of ingested foods and environmental microbes. This early succession of microbial communities together with early allergen exposures orchestrate the development of an immune system with a robust ability to optimally control inflammatory responses and a lowered risk for atopic disorders.


Novel Therapeutic Agent against Platelet Activation In Vitro and Arterial Thrombosis In Vivo by Morin Hydrate.
Morin hydrate, a bioactive flavonoid, has been proven to prevent inflammation and apoptosis of cells. Flavonoids can reduce the risk of cardiovascular diseases, in which platelet activation plays a major role. This study investigated the effect of morin hydrate on platelet activation in vitro and in vivo. Morin hydrate markedly inhibited platelet aggregation stimulated by collagen in human platelets but not that stimulated by other agonists. In collagen-activated platelets, morin hydrate inhibited adenosine triphosphate (ATP) release; intracellular Ca2+ mobilization; P-selectin expression; and phosphorylation of phospholipase Cγ2 (PLCγ2), protein kinase C (PKC), and Akt. In mitogen-activated protein kinase (MAPK) activation, morin hydrate evidently diminished ERK2 or JNK1 activation, except for p38 MAPK. Additionally, morin hydrate markedly reduced the OH· signals in platelet suspensions but not in the cell-free system (Fenton reaction solution). Moreover, morin hydrate substantially increased the occlusion time of thrombotic platelet plug formation but had no effect on bleeding time in mice. In conclusion, morin hydrate crucially inhibits platelet activation through inhibition of the PLCγ2⁻PKC cascade and subsequent suppression of Akt and MAPK activation, thereby ultimately inhibiting platelet aggregation. Therefore, this paper suggests that morin hydrate constitutes a novel and potential natural therapeutic product for preventing or treating thromboembolic disorders.


Contrasting effects of phosphatidylinositol 4,5-bisphosphate on cloned TMEM16A and TMEM16B channels.
Ca2+ -activated Cl- channels (CaCCs) are gated open by a rise in intracellular Ca2+ concentration ([Ca2+ ]i ), typically provoked by activation of Gq -protein coupled receptors (Gq PCR). Gq PCR activation initiates depletion of plasmalemmal phosphatidylinositol 4,5-bisphosphate (PIP2 ). Here, we determined whether PIP2 acts as a signalling lipid for CaCCs coded by the TMEM16A and TMEM16B genes. Patch-clamp electrophysiology, in conjunction with genetically encoded systems to control cellular PIP2 content, was used to define the mechanism of action of PIP2 on TMEM16A and TMEM16B channels. A water-soluble PIP2 analogue (diC8-PIP2 ) activated TMEM16A channels by up to fivefold and inhibited TMEM16B by ~0.2-fold. The effects of diC8-PIP2 on TMEM16A currents were especially pronounced at low [Ca2+ ]i . In contrast, diC8-PIP2 modulation of TMEM16B channels did not vary over a broad [Ca2+ ]i range but was only detectable at highly depolarized membrane potentials. Modulation of TMEM16A and TMEM16B currents was due to changes in channel gating, while single channel conductance was unaltered. Co-expression of TMEM16A or TMEM16B with a Danio rerio voltage-sensitive phosphatase (DrVSP), which degrades PIP2 , led to reduction and enhancement of TMEM16A and TMEM16B currents respectively. These effects were abolished by an inactivating mutation in DrVSP and antagonized by simultaneous co-expression of a phosphatidylinositol-4-phosphate 5-kinase that catalyses PIP2 formation. PIP2 acts as a modifier of TMEM16A and TMEM16B channel gating. Drugs interacting with PIP2 signalling may affect TMEM16A and TMEM16B channel gating and have potential uses in basic science and implications for therapy.


Prescription drug claims following a traumatic spinal cord injury for older adults: a retrospective population-based study in Ontario, Canada.
Retrospective cohort study. The objectives for this study were to examine the prevalence of polypharmacy for people with traumatic spinal cord injury (SCI) following injury and to determine risk factors. Ontario, Canada METHODS: We used provincial-level administrative health services data of publicly funded healthcare encounters housed at the Institute for Clinical Evaluative Sciences, Toronto, Ontario. We examined prescription medications dispensed over a 1 year period post injury for persons 66+ years with an index traumatic SCI between 2004 and 2014. Polypharmacy was defined as being on 10 or more drug classes. Descriptive and analytical statistics were conducted. Relative risks and 95% confidence limits for factors related to polypharmacy were calculated using a robust Poisson multivariate regression model. We identified 418 cases of persons with traumatic SCI during the observation window. A total of 233 patients (56%) were taking at least 10 drug classes in the year following discharge from care for traumatic SCI. The mean number of drug classes taken post injury was 11 (SD = 6). Continuity of care was significantly associated with polypharmacy, with a higher continuity of care (having at least 75% of visits with the same doctor) reducing the risk of polypharmacy. The most common drugs prescribed were laxatives, opioids and cardiovascular-related drugs. Findings suggest that polypharmacy is extensive among older adults with traumatic SCI. Persons with better continuity of care are less likely to have polypharmacy compared to those with less continuity. This project was funded by a Connaught New Investigator Award (University of Toronto), and the Craig H. Neilsen Foundation Psychosocial Research Pilot Grant (Grant #441259).


Photolytic degradation of sulfamethoxazole and trimethoprim using UV-A, UV-C and vacuum-UV (VUV).
The photolytic degradation of the non-degradable pharmaceuticals sulfamethoxazole (SMX) and trimethoprim (TMP) in an aqueous solution was investigated using three kinds of low-pressure mercury lamp UV-A (352 nm), UV-C (254 nm), and vacuum-UV (VUV, 185 nm and 254 nm). The degradation rates were highly dependent on the target compounds as well as the UV sources. No degradation of the target compounds was observed using UV-A treatment, because there was no overlap between the UV-A emission spectrum and absorption spectrum of the target compounds. On the other hand, UVC and VUV revealed higher reactivity. The results also indicated that SMX had a greater potential to react photochemically than TMP. Among the UV sources, VUV was the most effective process for the degradation of target compounds. Furthermore, the addition of oxidants such as hydrogen peroxide (H2O2) and sodium persulfate (Na2S2O8) to the reaction system improved the overall degradation rate significantly.The experimental results for the VUV-irradiated samples with the addition of methanol as a hydroxyl radical scavenger revealed that hydroxyl radicals contribute significantly to the elimination of the target compound. Overall, the degradation rate of the target compounds was in the order: VUV = UV-C > UV-A for sulfamethoxazole and VUV/H2O2 > VUV/ Na2S2O8 > VUV >UV-C >UV-A for trimethoprim.


Top-emitting organic light-emitting diodes.
We review top-emitting organic light-emitting diodes (OLEDs), which are beneficial for lighting and display applications, where non-transparent substrates are used. The optical effects of the microcavity structure as well as the loss mechanisms are discussed. Outcoupling techniques and the work on white top-emitting OLEDs are summarized. We discuss the power dissipation spectra for a monochrome and a white top-emitting OLED and give quantitative reports on the loss channels. Furthermore, the development of inverted top-emitting OLEDs is described.


The magnitude and severity of abortion-related morbidity in settings with limited access to abortion services: a systematic review and meta-regression.
Defining and accurately measuring abortion-related morbidity is important for understanding the spectrum of risk associated with unsafe abortion and for assessing the impact of changes in abortion-related policy and practices. This systematic review aims to estimate the magnitude and severity of complications associated with abortion in areas where access to abortion is limited, with a particular focus on potentially life-threatening complications. A previous systematic review covering the literature up to 2010 was updated with studies identified through a systematic search of Medline, Embase, Popline and two WHO regional databases until July 2016. Studies from settings where access to abortion is limited were included if they quantified the percentage of abortion-related hospital admissions that had any of the following complications: mortality, a near-miss event, haemorrhage, sepsis, injury and anaemia. We calculated summary measures of the percentage of abortion-related hospital admissions with each complication by conducting meta-analysis and explored whether these have changed over time. Based on data collected between 1988 and 2014 from 70 studies from 28 countries, we estimate that at least 9% of abortion-related hospital admissions have a near-miss event and approximately 1.5% ends in a death. Haemorrhage was the most common complication reported; the pooled percentage of abortion-related hospital admissions with severe haemorrhage was 23%, with around 9% having near-miss haemorrhage reported. There was strong evidence for between-study heterogeneity across most outcomes. In spite of the challenges on how near miss morbidity has been defined and measured in the included studies, our results suggest that a substantial percentage of abortion-related hospital admissions have potentially life-threatening complications. Estimates that are more reliable will only be obtained with increased use of standard definitions such as the WHO near-miss criteria and/or better reporting of clinical criteria applied in studies.


Prevalence of pain in the orofacial regions in patients visiting general dentists in the Northwest Practice-based REsearch Collaborative in Evidence-based DENTistry research network.
This study aimed to measure prevalence of pain in the orofacial regions and determine association with demographics, treatment history, and oral health conditions in dental patients visiting clinics in the Northwest Practice-based REsearch Collaborative in Evidence-based DENTistry (PRECEDENT) research network. Data were recorded in a survey with systematic random sampling of patients (n = 1,668, 18 to 93 years old, 56% female) visiting 100 general dentists in the Northwest PRECEDENT research network. Prevalence ratios (PR) of orofacial pain by each variable were estimated by generalized estimating equations for Poisson regression. The prevalence of orofacial pain during the past year was 16.1% (95% confidence interval [CI], 13.4-18.9), of which the most prevalent pain locations were dentoalveolar (9.1%; 95% CI, 7.0-11.2) and musculoligamentous tissues (6.6%; 95% CI, 4.5-8.7). Other locations included soft tissues (0.5%; 95% CI, 0.2-0.8) and nonspecific areas (0.6%; 95% CI, 0.2-1.0). The prevalence of dentoalveolar but not musculoligamentous pain decreased with age. When comparing the 18- to 29-year-old patients, dentoalveolar pain decreased significantly in 45- to 64-year-old patients (PR, 0.59; 95% CI, 0.4-0.9) and in those 65 years or older (PR, 0.5; 95% CI, 0.3-0.9). Sex significantly affected the prevalence of musculoligamentous but not dentoalveolar pain. Women (PR, 3.2; 95% CI, 2.0-5.1) were more likely to have musculoligamentous pain. The prevalence of dentoalveolar and musculoligamentous pain did not vary significantly by ethnicity. Dentoalveolar pain was reported more frequently in patients who did not receive dental maintenance (PR, 2.9; 95% CI, 2.1-4.2) and those visiting community-based public health clinics (PR, 2.2; 95% CI, 1.2-3.7). One in 6 patients visiting a general dentist had experienced orofacial pain during the past year. Dentoalveolar and musculoligamentous pains were the most prevalent types of pain. Pain in the muscles and temporomandibular joints was reported as frequently as that in the teeth and surrounding tissues in patients visiting general dentists. Although the dental curriculum is concentrated on the diagnosis and management of pain and related conditions from teeth and surrounding tissues, it is imperative to include the training for other types of orofacial pain, particularly those from temporomandibular joint and musculoligamentous tissues.


No increased risk of herpes zoster found in cirrhotic patients: a nationwide population-based study in Taiwan.
The association between liver cirrhosis (LC) and herpes zoster has rarely been studied. We investigated the hypothesis that LC, known as an immunodeficiency disease, may increase the risk of herpes zoster using a national health insurance database in Taiwan. The study cohort included cirrhotic patients between 1998 and 2005 (n = 4667), and a ratio of 1:5 randomly sampled age- and gender-matched control patients (n = 23,335). All subjects were followed up for 5 years from the date of cohort entry to identify whether or not they had developed herpes zoster. Cox proportional-hazard regressions were performed to evaluate 5-year herpes zoster-free survival rates. Of all patients, 523 patients developed herpes zoster during the 5-year follow-up period, among whom 82 were LC patients and 441 were in the comparison cohort. The adjusted hazard ratio (AHR) of herpes zoster in patients with LC was not higher (AHR: 0.77, 95% confidence interval: 0.59-1.01, p = 0.06) than that of the controls during the 5-year follow-up. No increased risk of herpes zoster was found in LC patients after stratification by age, gender, urbanization level, income, geographic region, and all comorbidities. This large nationwide population-based cohort study suggests that there is no increased risk for herpes zoster among people who have LC compared to a matching population.


Function and distribution of three types of rectifying channel in rat spinal root myelinated axons.
1. The nature, distribution and function of rectifying channels in rat spinal root myelinated axons has been assessed with selective blocking agents and a variety of intracellular and extracellular recording techniques. 2. The electrotonic responses of roots poisoned with tetrodotoxin (TTX) to constant current pulses had fast (rise time much less than 1 ms) and slow components, which were interpreted in terms of Barrett & Barrett's (1982) revised cable model for myelinated nerve. Depolarization evoked a rapid outward rectification (time constant, tau approximately 0.5 ms), selectively blocked by 4-aminopyridine (4AP, 1 mM), and a slow outward rectification (tau approximately 15 ms), selectively blocked by tetraethylammonium (TEA, 1 mM) or Ba2+ (0.5 mM). Hyperpolarization evoked an even slower inward rectification, selectively blocked by Cs+ (3 mM) but not by Ba2+. 3. From the different effects of the blocking agents on the fast and slow components of electrotonus, it was deduced (a) that the inward rectification is a property of the internodal axon, (b) that the slow outward rectifier is present at the nodes, and probably the internodes as well, and (c) that the 4AP-sensitive channels have a minor nodal and a major internodal representation. 4. TEA and Ba2+ reduced the accommodation of roots and fibres not poisoned with TTX to long current pulses, whereas 4AP facilitated short bursts of impulses in response to a single brief stimulus. 5. TEA and Ba2+ also abolished a late hyperpolarizing after-potential (peaking at 20-80 ms), while 4AP enhanced the depolarizing after-potential in normal fibres, and abolished an early hyperpolarizing after-potential (peaking at 1-3 ms) in depolarized fibres. Corresponding to the later after-potentials were post-spike changes in excitability and conduction velocity, which were affected similarly by the blocking agents. Cs+ increased the post-tetanic depression attributable to electrogenic hyperpolarization. 6. The physiological roles of the three different rectifying conductances are discussed. It is also argued that the prominent ohmic 'leak conductance', usually ascribed to the nodal axon, must arise in an extracellular pathway in series with the rectifying internodal axon.