Group versus conventional antenatal care for women.
Antenatal care is one of the key preventive health services used around the world. In most Western countries, antenatal care traditionally involves a schedule of one-to-one visits with a care provider. A different way of providing antenatal care involves use of a group model. 1. To compare the effects of group antenatal care versus conventional antenatal care on psychosocial, physiological, labour and birth outcomes for women and their babies.2. To compare the effects of group antenatal care versus conventional antenatal care on care provider satisfaction. We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 October 2014), contacted experts in the field and reviewed the reference lists of retrieved studies. All identified published, unpublished and ongoing randomised and quasi-randomised controlled trials comparing group antenatal care with conventional antenatal care were included. Cluster-randomised trials were eligible, and one has been included. Cross-over trials were not eligible. Two review authors independently assessed trials for inclusion and risk of bias and extracted data; all review authors checked data for accuracy. We included four studies (2350 women). The overall risk of bias for the included studies was assessed as acceptable in two studies and good in two studies. No statistically significant differences were observed between women who received group antenatal care and those given standard individual antenatal care for the primary outcome of preterm birth (risk ratio (RR) 0.75, 95% confidence interval (CI) 0.57 to 1.00; three trials; N = 1888). The proportion of low-birthweight (less than 2500 g) babies was similar between groups (RR 0.92, 95% CI 0.68 to 1.23; three trials; N = 1935). No group differences were noted for the primary outcomes small-for-gestational age (RR 0.92, 95% CI 0.68 to 1.24; two trials; N = 1473) and perinatal mortality (RR 0.63, 95% CI 0.32 to 1.25; three trials; N = 1943).Satisfaction was rated as high among women who were allocated to group antenatal care, but this outcome was measured in only one trial. In this trial, mean satisfaction with care in the group given antenatal care was almost five times greater than that reported by those allocated to standard care (mean difference 4.90, 95% CI 3.10 to 6.70; one study; N = 993). No differences in neonatal intensive care admission, initiation of breastfeeding or spontaneous vaginal birth were observed between groups. Several outcomes related to stress and depression were reported in one trial. No differences between groups were observed for any of these outcomes.No data were available on the effects of group antenatal care on care provider satisfaction.We used the GRADE (Grades of Recommendation, Assessment, Development and Evaluation) approach to assess evidence for seven prespecified outcomes; results ranged from low quality (perinatal mortality) to moderate quality (preterm birth, low birthweight, neonatal intensive care unit admission, breastfeeding initiation) to high quality (satisfaction with antenatal care, spontaneous vaginal birth). Available evidence suggests that group antenatal care is positively viewed by women and is associated with no adverse outcomes for them or for their babies. No differences in the rate of preterm birth were reported when women received group antenatal care. This review is limited because of the small numbers of studies and women, and because one study contributed 42% of the women. Most of the analyses are based on a single study. Additional research is required to determine whether group antenatal care is associated with significant benefit in terms of preterm birth or birthweight.


Substrate balances across colonic carcinomas in humans.
To investigate the utilization of nutrients by malignant tumors in humans, the balances of energy-yielding substrates and amino acids across colonic carcinomas were assessed in 17 patients during surgery. Blood samples were taken from an artery and the main tumor-draining vein, which was also used for determining tumor blood flow (direct venous outflow technique). Additionally, the substrate exchange by peripheral tissues was studied (femoral arteriovenous differences, venous occlusion plethysmography). Mean blood flow was greater in the carcinomas than in the leg tissues (43.2 versus 2.5 ml/100 ml/min; P < 0.001). There was a negative correlation between tumor blood flow and tumor weight (r = -0.87; P < 0.001). Glucose net uptake and lactate release by the malignancies exceeded the peripheral exchange rates 30- and 43-fold, respectively (mean values different at P < 0.001). The molar ratio of lactate output to glucose consumption was 0.78 in the tumors and 0.48 in the leg tissues (P < 0.05). Regarding free fatty acid and ketone body balances, no significant tumor-periphery differences were noted. The carcinomas utilized branched chain amino acids and serine, while alanine and, in particular, ammonia were released in large amounts. Net glutamine retention was not consistently observed. It is concluded that the energy metabolism of human colonic carcinomas relies predominantly on glucose, with fat-derived calories making no appreciable contribution. The impaired nutritive perfusion of malignant tumors appears to favor glycolysis and to limit both glucose oxidation and glutaminolysis. The present study has shown that the procedure chosen for the assessment of trans-tumor substrate flux rates is a workable and valid model for analyzing metabolic balances across human colonic cancers in vivo.


The breaking beads approach for photocleavage from solid support.
Photocleavage from polystyrene beads is a pivotal reaction for solid phase synthesis that relies on photolabile linkers. Photocleavage from intact porous polystyrene beads is not optimal because light cannot penetrate into the beads and the surface area exposed to irradiation is limited. Thus, hazardous, technically challenging and expensive setups are used for photocleavage from intact beads. We developed a new concept in which grinding the beads during or prior to irradiation is employed as an essential part of the photocleavage process. By grinding the beads we are exposing more surface area to the light source, hence, photocleavage can be performed even using a simple benchtop LED setup. This approach proved very efficient for photocleavage of various model compounds including fully protected oligosaccharides.


Plant Sar1 isoforms with near-identical protein sequences exhibit different localisations and effects on secretion.
In plants, differentiation of subdomains of the endoplasmic reticulum (ER) dedicated to protein export, the ER export sites (ERES), is influenced by the type of export-competent membrane cargo to be delivered to the Golgi. This raises a fundamental biological question: is the formation of transport intermediates at the ER for trafficking to the Golgi always regulated in the same manner? To test this, we followed the distribution and activity of two plant Sar1 isoforms. Sar1 is the small GTPase that regulates assembly of COPII (coat protein complex II) on carriers that transport secretory cargo from ER to Golgi. We show that, in contrast to a tobacco Sar1 isoform, the two Arabidopsis Sar1 GTPases were localised at ERES, independently of co-expression of Golgi-destined membrane cargo in tobacco cells. Although both isoforms labelled ERES, one was found to partition with the membrane fraction to a greater extent. The different distribution of fluorescent fusions of the two isoforms was influenced by the nature of an amino acid residue at the C-terminus of the protein, suggesting that the requirements for membrane association of the two GTPases are not equal. Furthermore, functional analyses based on the secretion of the bulk flow marker alpha-amylase indicated that over-expression of GTP-restricted mutants of the two isoforms caused different levels of ER export inhibition. These novel results indicate a functional heterogeneity among plant Sar1 isoforms.


Leprosy among the Limba: illness and healing in the context of world view.
The study analyzes the traditional beliefs and practices concerning leprosy of the Limba people of Sierra Leone. It shows that this dialectally diverse ethnic group has two views of leprosy and its cause, and two varieties of stigma associated with the disease. The Limba have abandoned their traditional treatments for leprosy in response to an effective leprosy control programme, but retained their traditional world view, including its definition of illness, which holds a person seriously ill only when he has severe pain or disability. Thus, they seek treatment from the programme, but often at a relatively advanced stage of the disease. The study shows that the Limba have reinterpreted the notion of 'germs' as introduced by medical workers, and that leprosy control workers have their own misunderstandings of Limba beliefs and practices. The study points the way to improved communication between leprosy workers and Limba patients by focusing on the points at which their views differ, and by identifying concepts within Limba world view that can be adapted by leprosy workers to help convey their message. The study emphasizes the importance of world view as a key to understanding patient attitudes and behaviour in developing countries, and to making valid cross-cultural comparisons, but notes that it can take years for an investigator to understand the world view of a particular culture. It argues that in short-term research projects there is an advantage to working with an anthropologist who has in-depth knowledge of the culture, but who may not be a specialist in medical anthropology.


Miniaturisation reduces contrast sensitivity and spatial resolving power in ants.
Vision is crucial for animals to find prey, locate conspecifics and navigate within cluttered landscapes. Animals need to discriminate objects against a visually noisy background. However, the ability to detect spatial information is limited by eye size. In insects, as individuals become smaller, the space available for the eyes reduces, which affects the number of ommatidia, the size of the lens and the downstream information-processing capabilities. The evolution of small body size in a lineage, known as miniaturisation, is common in insects. Here, using pattern electroretinography with vertical sinusoidal gratings as stimuli, we studied how miniaturisation affects spatial resolving power and contrast sensitivity in four diurnal ants that live in a similar environment but vary in their body and eye size. We found that ants with fewer and smaller ommatidial facets had lower spatial resolving power and contrast sensitivity. The spatial resolving power was maximum in the largest ant Myrmecia tarsata at 0.60 cycles deg-1 compared with that of the ant with smallest eyes Rhytidoponera inornata at 0.48 cycles deg-1 Maximum contrast sensitivity (minimum contrast threshold) in M. tarsata (2627 facets) was 15.51 (6.4% contrast detection threshold) at 0.1 cycles deg-1, while the smallest ant R. inornata (227 facets) had a maximum contrast sensitivity of 1.34 (74.1% contrast detection threshold) at 0.05 cycles deg-1 Miniaturisation thus dramatically decreases maximum contrast sensitivity and also reduces spatial resolution, which could have implications for visually guided behaviours. This is the first study to physiologically investigate contrast sensitivity in the context of insect allometry.


Splenic Artery Aneurysm (SAA) Rupture in Pregnancy: A Case Report of a Rare but Life-Threatening Obstetrical Complication.
This is the case of a 38 year-old Lebanese woman G2P1, history of previous cesarean section, presenting at 30+5 weeks of gestation with acute left-sided flank pain and a two-day history of chills and dysuria. In light of the clinical presentation, the patient was initially diagnosed with pyelonephritis and managed accordingly; however, her clinical status deteriorated with worsening hypotension and lethargy despite resuscitative measures and a normal abdominal ultrasound. Failure to revive the patient eventually led to a cardiac arrest for which a peri-mortem cesarean section was performed at bedside. Upon abdominal entry, an actively-bleeding ruptured splenic artery aneurysm (SAA) was identified, for which massive transfusion protocol was activated, and the patient was transferred to the operating room. The patient had a complicated postoperative course, the fetus was stillborn, and she was discharged home after 6 months of hospital stay. In view of the high mortality and morbidity associated with ruptured SAA in pregnancy, early recognition and prompt intervention are crucial for maternal and fetal benefit.


Risk of psychiatric disorders in patients with chronic insomnia and sedative-hypnotic prescription: a nationwide population-based follow-up study.
Previous epidemiological studies have established insomnia as a major risk factor for mood, anxiety, and substance use disorders. However, the associations between insomnia with sedative-hypnotic prescriptions and various psychiatric disorders have not been thoroughly examined. The current study involved evaluating the risk of psychiatric disorders, namely schizophrenia, mood, anxiety, somatoform, and substance-related disorders, over a 6-y follow-up period in three groups: patients with insomnia and sedative-hypnotic prescriptions (Inso-Hyp), those with insomnia and without sedative-hypnotic prescriptions (Inso-NonHyp), and those with neither insomnia nor sedative-hypnotic prescriptions (NonInso-NonHyp). We used a historical cohort study design to compare the risk of psychiatric disorders among the three groups. Data regarding these patients were derived from reimbursement claims recorded in Taiwan's National Health Insurance Research Database. Cox proportional hazards regression was used to compare the 6-y risk of subsequent psychiatric disorders among the Inso-Hyp, Inso-NonHyp, and NonInso-NonHyp groups. Compared with the Inso-NonHyp and NonInso-NonHyp group patients, the Inso-Hyp group patients exhibited a higher risk of psychiatric disorders, particularly bipolar disorders (adjusted hazard ratio [AHR]: 7.60; 95% confidence interval [CI]: 5.31-10.89 and AHR: 14.69; 95% CI: 11.11-19.43, respectively). Moreover, among the Inso-Hyp patient group, insomnia prescribed with benzodiazepine, a longer duration of sedative-hypnotic action, and higher doses of sedativehypnotics were significantly associated with a higher risk of depressive and anxiety disorders. The Inso-Hyp group exhibited a higher risk of developing psychiatric disorders than did the Inso-NonHyp and NonInso-NonHyp groups. The results regarding patients with insomnia and sedative-hypnotic prescriptions associated with the risk of psychiatric disorders can serve as a reference for care providers when managing sleep disturbances.


An on-chip small intestine-liver model for pharmacokinetic studies.
Testing of drug effects and cytotoxicity by using cultured cells has been widely performed as an alternative to animal testing. However, the estimation of pharmacokinetics by conventional cell-based assay methods is difficult because of the inability to evaluate multiorgan effects. An important challenge in the field is to mimic the organ-to-organ network in the human body by using a microfluidic network connecting small-scale tissues based on recently emerging MicroTAS (Micro Total Analysis Systems) technology for prediction of pharmacokinetics. Here, we describe an on-chip small intestine-liver coupled model for pharmacokinetic studies. To construct an in vitro pharmacokinetic model that appropriately models in vivo conditions, physiological parameters such as the structure of internal circulation, volume ratios of each organ, and blood flow ratio of the portal vein to the hepatic artery were mimicked using microfluidic networks. To demonstrate interactions between organs in vitro in pharmacokinetic studies, Caco-2, HepG2, and A549 cell cultures were used as organ models of the small intestine, liver, and lung, respectively, and connected to each other through a microporous membrane and microchannels to prepare a simple model of a physiological organ-to-organ network. The on-chip organ model assay using three types of substrate-epirubicine (EPI), irinotecan (CPT-11), and cyclophosphamide (CPA)-were conducted to model the effects of orally administered or biologically active anticancer drugs. The result suggested that the device can replicate physiological phenomena such as activity of the anticancer drugs on the target cells. This microfluidic device can thus be used as an in vitro organ model to predict the pharmacokinetics of drugs in the human body and may thus provide not only an alternative to animal testing but also a method of obtaining parameters for in silico models of physiologically based pharmacokinetics.


Why Ineffective Psychotherapies Appear to Work: A Taxonomy of Causes of Spurious Therapeutic Effectiveness.
The past 40 years have generated numerous insights regarding errors in human reasoning. Arguably, clinical practice is the domain of applied psychology in which acknowledging and mitigating these errors is most crucial. We address one such set of errors here, namely, the tendency of some psychologists and other mental health professionals to assume that they can rely on informal clinical observations to infer whether treatments are effective. We delineate four broad, underlying cognitive impediments to accurately evaluating improvement in psychotherapy-naive realism, confirmation bias, illusory causation, and the illusion of control. We then describe 26 causes of spurious therapeutic effectiveness (CSTEs), organized into a taxonomy of three overarching categories: (a) the perception of client change in its actual absence, (b) misinterpretations of actual client change stemming from extratherapeutic factors, and (c) misinterpretations of actual client change stemming from nonspecific treatment factors. These inferential errors can lead clinicians, clients, and researchers to misperceive useless or even harmful psychotherapies as effective. We (a) examine how methodological safeguards help to control for different CSTEs, (b) delineate fruitful directions for research on CSTEs, and (c) consider the implications of CSTEs for everyday clinical practice. An enhanced appreciation of the inferential problems posed by CSTEs may narrow the science-practice gap and foster a heightened appreciation of the need for the methodological safeguards afforded by evidence-based practice.


Validation of large-volume batch solar reactors for the treatment of rainwater in field trials in sub-Saharan Africa.
The efficiency of two large-volume batch solar reactors [Prototype I (140 L) and II (88 L)] in treating rainwater on-site in a local informal settlement and farming community was assessed. Untreated [Tank 1 and Tank 2-(First-flush)] and treated (Prototype I and II) tank water samples were routinely collected from each site and all the measured physico-chemical parameters (e.g. pH and turbidity, amongst others), anions (e.g. sulphate and chloride, amongst others) and cations (e.g. iron and lead, amongst others) were within national and international drinking water guidelines limits. Culture-based analysis indicated that Escherichia coli, total and faecal coliforms, enterococci and heterotrophic bacteria counts exceeded drinking water guideline limits in 61%, 100%, 45%, 24% and 100% of the untreated tank water samples collected from both sites. However, an 8 hour solar exposure treatment for both solar reactors was sufficient to reduce these indicator organisms to within national and international drinking water standards, with the exception of the heterotrophic bacteria which exceeded the drinking water standard limit in 43% of the samples treated with the Prototype I reactor (1 log reduction). Molecular viability analysis subsequently indicated that mean overall reductions of 75% and 74% were obtained for the analysed indicator organisms (E. coli and enterococci spp.) and opportunistic pathogens (Klebsiella spp., Legionella spp., Pseudomonas spp., Salmonella spp. and Cryptosporidium spp. oocysts) in the Prototype I and II solar reactors, respectively. The large-volume batch solar reactor prototypes could thus effectively provide four (88 L Prototype II) to seven (144 L Prototype I) people on a daily basis with the basic water requirement for human activities (20 L). Additionally, a generic Water Safety Plan was developed to aid practitioners in identifying risks and implement remedial actions in this type of installation in order to ensure the safety of the treated water.


Bioavailability and efficacy of a gap junction enhancer (PQ7) in a mouse mammary tumor model.
The loss of gap junctional intercellular communication is characteristic of neoplastic cells, suggesting that the restoration with a gap junction enhancer may be a new therapeutic treatment option with less detrimental effects than traditional antineoplastic drugs. A gap junction enhancer, 6-methoxy-8-[(2-furanylmethyl) amino]-4-methyl-5-(3-trifluoromethylphenyloxy) quinoline (PQ7), on the normal tissue was evaluated in healthy C57BL/6J mice in a systemic drug distribution study. Immunoblot analysis of the vital organs indicates a reduction in Cx43 expression in PQ7-treated animals with no observable change in morphology. Next the transgenic strain FVB/N-Tg(MMTV-PyVT) 634Mul/J (also known as PyVT) was used as a spontaneous mammary tumor mouse model to determine the biological and histological effects of PQ7 on tumorigenesis and metastasis at three stages of development: Pre tumor, Early tumor, and Late tumor formation. PQ7 was assessed to have a low toxicity through intraperitoneal administration, with the majority of the compound being detected in the heart, liver, and lungs six hours post injection. The treatment of tumor bearing animals with PQ7 had a 98% reduction in tumor growth, while also decreasing the total tumor burden compared to control mice during the Pre stage of development. PQ7 treatment increased Cx43 expression in the neoplastic tissue during Pre-tumor formation; however, this effect was not observed in Late stage tumor formation. This study shows that the gap junction enhancer, PQ7, has low toxicity to normal tissue in healthy C57BL/6J mice, while having clinical efficacy in the treatment of spontaneous mammary tumors of PyVT mice. Additionally, gap junctional intercellular communication and neoplastic cellular growth are shown to be inversely related, while treatment with PQ7 inhibits tumor growth through targeting gap junction expression.


Use of non-steroidal anti-inflammatory drugs and risk of death from COVID-19: an OpenSAFELY cohort analysis based on two cohorts.
To assess the association between routinely prescribed non-steroidal anti-inflammatory drugs (NSAIDs) and deaths from COVID-19 using OpenSAFELY, a secure analytical platform. We conducted two cohort studies from 1 March to 14 June 2020. Working on behalf of National Health Service England, we used routine clinical data in England linked to death data. In study 1, we identified people with an NSAID prescription in the last 3 years from the general population. In study 2, we identified people with rheumatoid arthritis/osteoarthritis. We defined exposure as current NSAID prescription within the 4 months before 1 March 2020. We used Cox regression to estimate HRs for COVID-19 related death in people currently prescribed NSAIDs, compared with those not currently prescribed NSAIDs, accounting for age, sex, comorbidities, other medications and geographical region. In study 1, we included 536 423 current NSAID users and 1 927 284 non-users in the general population. We observed no evidence of difference in risk of COVID-19 related death associated with current use (HR 0.96, 95% CI 0.80 to 1.14) in the multivariable-adjusted model. In study 2, we included 1 708 781 people with rheumatoid arthritis/osteoarthritis, of whom 175 495 (10%) were current NSAID users. In the multivariable-adjusted model, we observed a lower risk of COVID-19 related death (HR 0.78, 95% CI 0.64 to 0.94) associated with current use of NSAID versus non-use. We found no evidence of a harmful effect of routinely prescribed NSAIDs on COVID-19 related deaths. Risks of COVID-19 do not need to influence decisions about the routine therapeutic use of NSAIDs.


Quality assurance in diabetic retinal screening in South Africa.
Diabetic retinopathy (DR) is an important biomarker for microvascular disease and blindness. Digital fundus photography is a cost-effective way of screening for DR. Access to DR screening is difficult for many South Africans with diabetes. To perform external quality assurance (EQA) on graders registered in the Ophthalmological Society of South Africa DR screening programme. Graders registered on the South African (SA) Diabetic Register website were invited to participate in the study. The Scottish EQA software system was used to enable on-line grading of 100 retinal photographs. Expert National Health Service graders provided the consensus expert grading for the image set. Two hundred and sixty-one participants completed the EQA process, including nine ophthalmologists, 243 optometrists, and nine other graders. A wide range of outcomes were demonstrated, with a mean sensitivity of 0.905 (range 0.286 - 1.000) and mean specificity of 0.507 (0.000 - 0.935). The mean diagnostic odds ratio was calculated to be 12.3 (range 0.147 - 148.2). This is the first quality assurance study conducted with SA healthcare professionals. The outcomes are of interest to all stakeholders dealing with the diabetes epidemic. The disparity in grader performance indicates room for improvement. The results demonstrate a high referral rate to ophthalmology, suggesting that on average graders are performing safely, but with a high number of inappropriate referrals.


Contact patterns among high school students.
Face-to-face contacts between individuals contribute to shape social networks and play an important role in determining how infectious diseases can spread within a population. It is thus important to obtain accurate and reliable descriptions of human contact patterns occurring in various day-to-day life contexts. Recent technological advances and the development of wearable sensors able to sense proximity patterns have made it possible to gather data giving access to time-varying contact networks of individuals in specific environments. Here we present and analyze two such data sets describing with high temporal resolution the contact patterns of students in a high school. We define contact matrices describing the contact patterns between students of different classes and show the importance of the class structure. We take advantage of the fact that the two data sets were collected in the same setting during several days in two successive years to perform a longitudinal analysis on two very different timescales. We show the high stability of the contact patterns across days and across years: the statistical distributions of numbers and durations of contacts are the same in different periods, and we observe a very high similarity of the contact matrices measured in different days or different years. The rate of change of the contacts of each individual from one day to the next is also similar in different years. We discuss the interest of the present analysis and data sets for various fields, including in social sciences in order to better understand and model human behavior and interactions in different contexts, and in epidemiology in order to inform models describing the spread of infectious diseases and design targeted containment strategies.


Transformation of a high-dimensional color space for material classification.
Images in red-green-blue (RGB) color space need to be transformed to other color spaces for image processing or analysis. For example, the well-known hue-saturation-intensity (HSI) color space, which separates hue from saturation and intensity and is similar to the color perception of humans, can aid many computer vision applications. For high-dimensional images, such as multispectral or hyperspectral images, transformation images to a color space that can separate hue from saturation and intensity would be useful; however, the related works are limited. Some methods could interpret a set of high-dimensional images to hue, saturation, and intensity, but these methods need to reduce the dimension of original images to three images and then map them to the trichromatic color space of RGB. Generally, dimension reduction could cause loss or distortion of original data, and, therefore, the transformed color spaces could not be suitable for material classification in critical conditions. This paper describes a method that can transform high-dimensional images to a color space called hyper-hue-saturation-intensity (HHSI), which is analogous to HSI in high dimensions. The transformation does not need dimension reduction, and, therefore, it can preserve the original information. Experimental results indicate that the hyper-hue is independent of saturation and intensity and it is more suitable for material classification of proximal or remote sensing images captured in a natural environment where illumination usually cannot be controlled.


Transient ischaemic attacks mimicking focal motor seizures.
Limb shaking is an under-recognised form of transient ischaemic attack (TIA), which can easily be confused with focal motor seizures. However, it is important to distinguish limb shaking TIAs and focal seizures, as patients with this form of TIA almost invariably have severe carotid occlusive disease and are at high risk of stroke. A patient with limb shaking TIAs is presented in whom the diagnosis was missed.


Clinician adoption patterns and patient outcome results in use of evidence-based nursing plans of care.
Delivery of safe, effective and appropriate health care is an imperative facing health care organizations globally. While many initiatives have been launched in a number of countries to address this need from a medical perspective, a similar focus for generating evidence-based nursing knowledge has been missing. This paper reports on a collaborative evidence-based practice (EBP) research initiative that adds nursing knowledge into computerized care protocols. Here, a brief overview of the study's aims, purpose and methodology is presented as well as results of data analysis and lessons learned. The research team examined nurses' adoption patterns of EBP recommendations with respect to activity tolerance using four-month patient data collected from a pilot hospital. Study findings indicate a need for more focus on the system design and implementation process with the next rollout phase to promote evidence-based nursing practice.


Band selection method for subpixel target detection using only the target reflectance signature.
While offering powerful capabilities, the high dimensionality of hyperspectral images can make information extraction a challenge. For that reason, dimension reduction is a common data processing step. For the purpose of subpixel target detection, band selection is a dimension reduction method that can optimize results as well as reduce computation costs. However, existing band selection methods that are used for subpixel target detection require background spectral reflectance signatures to compare with the target signatures. These methods work well and offer a distinct advantage over other dimension reduction methods such as principal component analysis or nonnegative matrix factorization, but only when the background information is available. In this study, we developed a method that selected bands using only the target spectral reflectance signature. We tested this method using a utility prediction model, validated the results with real images, then cross-validated the results with simulated images that were associated with perfect truth data. We studied the detection statistics for a range of bands selected using this method and compared it to the results obtained from three other band selection methods. The motivation for developing this method was to be able to reduce the number of bands prior to collection when background information was not available. For an adaptive spectral imaging system with a tunable sensor, we would be able to optimize detection for a specific target and save data handling costs associated with transmitting, storing, and disseminating the data for information extraction. This method was also simple enough to be computed using a small on-board CPU, and modify the bands' selection criteria as the target changed.


Ethnicity and mental health treatment utilization by patients with personality disorders.
The authors examined the relationship between ethnicity and treatment utilization by individuals with personality disorders (PDs). Lifetime and prospectively determined rates and amounts of mental health treatments received were compared in over 500 White, African American, and Hispanic participants with PDs in a naturalistic longitudinal study. Minority, especially Hispanic, participants were significantly less likely than White participants to receive a range of outpatient and inpatient psychosocial treatments and psychotropic medications. This pattern was especially pronounced for minority participants with more severe PDs. A positive support alliance factor significantly predicted the amount of individual psychotherapy used by African American and Hispanic but not White participants, underscoring the importance of special attention to the treatment relationship with minority patients. These treatment use differences raise complex questions about treatment assessment and delivery, cultural biases of the current diagnostic system, and possible variation in PD manifestation across racial/ethnic groups. Future studies need to assess specific barriers to adequate and appropriate treatments for minority individuals with PDs.


Clinical and mutation analysis of 51 probands with anophthalmia and/or severe microphthalmia from a single center.
Clinical evaluation and mutation analysis was performed in 51 consecutive probands with severe eye malformations - anophthalmia and/or severe microphthalmia - seen in a single specialist ophthalmology center. The mutation analysis consisted of bidirectional sequencing of the coding regions of SOX2, OTX2, PAX6 (paired domain), STRA6, BMP4, SMOC1, FOXE3, and RAX, and genome-wide array-based copy number assessment. Fifteen (29.4%) of the 51 probands had likely causative mutations affecting SOX2 (9/51), OTX2 (5/51), and STRA6 (1/51). Of the cases with bilateral anophthalmia, 9/12 (75%) were found to be mutation positive. Three of these mutations were large genomic deletions encompassing SOX2 (one case) or OTX2 (two cases). Familial inheritance of three intragenic, plausibly pathogenic, and heterozygous mutations was observed. An unaffected carrier parent of an affected child with an identified OTX2 mutation confirmed the previously reported nonpenetrance for this disorder. Two families with SOX2 mutations demonstrated a parent and child both with significant but highly variable eye malformations. Heterozygous loss-of-function mutations in SOX2 and OTX2 are the most common genetic pathology associated with severe eye malformations and bi-allelic loss-of-function in STRA6 is confirmed as an emerging cause of nonsyndromal eye malformations.


Observations on the factors that control the generation of triiodothyronine from thyroxine in rat liver and the nature of the defect induced by fasting.
Studies were performed to explore the mechanism underlying the impaired generation of 125-I-3,5,3'-triiodothyronine (T3) from 125I-thyroxine (T4) (T3-neogenesis)) in preparations of liver from rats fasted for 48 h and the prevention of this effect by the feeding of glucose. T3-neogenesis in livers from fasted animals and those fed chow or glucose was assessed in various mixtures of crude microsomal fractions with either buffer or cytosols. T3-neogenesis was mediated by an enzyme present in the microsomal fraction whose activity was enhanced by cytosolic cofactor(s). In livers from animals fasted for 48 h, the supporting activity of cytosol was decreased, whereas the activity of the enzyme was unaffected. Administration of glucose as the sole nutritional source prevented the decrease in the supporting activity of hepatic cytosol that was regularly observed in the case of animals totally deprived of food. The diminished supporting activity for T3-neogenesis provided by liver cytosol from fasted animals was restored to normal by enrichment with either NADPH or GSH, but the two cofactors appeared to act at different loci. GSH stimulated T3-neogenesis in microsomes incubated in the absence of cytosol, i.e., in buffer, whereas NADPH did not. The stimulatory effect of both agents was blocked by the sulfhydryl oxidant, diamide, which also inhibited T3-neogenesis in mixtures of microsomes with cytosols. Taken together, these observations suggest that GSH acts directly on the enzyme in the crude microsomal fraction, whereas NADPH acts within the cytosol, possibly by increasing the concentration of GSH through the action of the enzyme glutathione reductase, for which NADPH is a cofactor. In this light, the decreased supporting activity of hepatic cytosol from starved animals appears to reflect, at least partly, a decreased concentration of one or both cofactors. The direct stimulation of enzyme activity by GSH, and the apparent lack of inhibition of unstimulated activity by diamide, suggests that the 5'-monodeiodinase for thyroxine that mediates T3-neogenesis may be a GSH transhydrogenase.


Activation of the c-myc p1 promoter in Burkitt's lymphoma by the hs3 immunoglobulin heavy-chain gene enhancer.
The expression of c-myc is deregulated in Burkitt's lymphoma by the translocation t(8;14). Most of the increased c-myc expression is from the P1 promoter, which is normally a minor promoter. How the P1 promoter is activated by the immunoglobulin heavy chain gene enhancers is not understood. We identified a YY1 site in the immunoglobulin heavy-chain gene HS3 enhancer, which increased c-myc P1 promoter activity, and a MARE site, which decreased c-myc P1 activity. Small Maf proteins bound to the MARE site both in vitro and in vivo, recruited histone deacetylase 2, and resulted in deacetylation of histones H3 and H4 at the c-myc promoter region. In contrast, YY1 recruited CBP and increased histone acetylation at the c-myc promoter. Rb interacts with YY1 to prevent DNA binding in normal B cells, but no significant interaction with YY1 was detected in Burkitt's cells, and binding of YY1 to the HS3 enhancer was observed by chromatin immunoprecipitaton. Increased expression of MafK and/or decreased expression of YY1 by silencing RNA downregulated endogenous c-myc mRNA levels and increased the sensitivity of the cells to doxorubicin. Mutation of the major active sites (nuclear factor-kappa B and YY1) in the enhancers prevented c-myc activation.


Monocyte-mediated lysis of acute myeloid leukemia cells in the presence of the bispecific antibody 251 x 22 (anti-CD33 x anti-CD64).
Immunotherapy using bispecific antibodies (BsAb) to direct immune effector cells toward target tumor cells has been shown to be effective in a number of studies. Several immune trigger molecules have been characterized. Among them, FcgammaRI appears to play an important role in antibody-dependent cellular cytotoxicity. It is expressed mainly on monocytes, macrophages, and neutrophils under certain clinical situations. The expression of FcgammaRI can be regulated by a variety of cytokines, primarily by IFN-gamma. Recent studies have shown that granulocyte-colony-stimulating factor (G-CSF) and granulocyte-macrophage-colony stimulating factor (GM-CSF) can increase the number of the FcgammaRI-positive monocytes, increase the expression of FcgammaRI on circulating neutrophils after in vivo infusion, and greatly enhance the cytotoxic activity of circulating neutrophils. CD33 is a glycoprotein expressed on the cell surface of mature monocytes, myeloid progenitor cells, and myeloid leukemic blasts, but not on the earliest hematopoietic progenitor cells and other normal tissues. Herein, we report the construction of a BsAb, 251 x 22, by conjugating an anti-CD33 mAb (mAb 251) to an anti-FcgammaRI mAb (mAb 22). The BsAb 251 x 22 is capable of enhancing the cytotoxicity of several leukemia cell lines by cytokine-activated monocytes. Our data also show that G-CSF- and GM-CSF-stimulated monocytes can mediate cytotoxicity of target leukemia cells comparable to that of IFN-gamma-stimulated monocytes. The expression of FcgammaRI on monocytes after 24-h in vitro incubation with G-CSF and GM-CSF was increased, although not significantly. Prolonged incubation of monocytes with G-CSF for 48 h significantly increased the FcgammaRI expression. Because humanized anti-CD33 and anti-FcgammaRI mAb are available, and because GM-CSF and G-CSF have been used widely for patients after chemotherapy to stimulate the recovery of myeloid hematopoiesis, additional clinical development of this project is feasible. A BsAb comprised of humanized anti-CD33 and anti-FcgammaRI could have clinical application in the treatment of myeloid leukemia, especially in the management of minimal residual disease.


Lymphedema following breast cancer: regions affected, severity of symptoms, and benefits of treatment from the patients' perspective.
Limited high-quality research has focused on the efficacy of lymphedema treatments and symptomatic relief. With that in mind, the authors conducted a cross-sectional survey to describe the presentation of breast cancer-related lymphedema, treatment modalities used, and perceived effectiveness. An electronic validated questionnaire to assess the presentation of lymphedema, severity of swelling and discomfort, number of modalities tried, and the benefits gained from treatment was completed by the Review and Survey Group of the Breast Cancer Network of Australia. Thirty-five percent of participants reported the presence of lymphedema, a majority of which reported it to be mild or moderate for magnitude of swelling and for discomfort. The correlation was weak between magnitude of swelling and discomfort. Compression, massage, and exercise were the most commonly used modalities in these patients. Notably, chest wall or breast lymphedema--about which research is lacking--was as common as hand lymphedema. Women experienced discomfort and physical changes, although the severity of the two was not related. Some benefit was reported for all modalities, but no particular modality was considered extremely helpful. Oncology nurses are ideally positioned to monitor women for early signs of swelling and to advise women on the range of treatments available.


Psychologists Are Open to Change, yet Wary of Rules.
Psychologists must change the way they conduct and report their research-this notion has been the topic of much debate in recent years. One article recently published in Psychological Science proposing six requirements for researchers concerning data collection and reporting practices as well as four guidelines for reviewers aimed at improving the publication process has recently received much attention (Simmons, Nelson, & Simonsohn, 2011). We surveyed 1,292 psychologists to address two questions: Do psychologists support these concrete changes to data collection, reporting, and publication practices, and if not, what are their reasons? Respondents also indicated the percentage of print and online journal space that should be dedicated to novel studies and direct replications as well as the percentage of published psychological research that they believed would be confirmed if direct replications were conducted. We found that psychologists are generally open to change. Five requirements for researchers and three guidelines for reviewers were supported as standards of good practice, whereas one requirement was even supported as a publication condition. Psychologists appear to be less in favor of mandatory conditions of publication than standards of good practice. We conclude that the proposal made by Simmons, Nelson & Simonsohn (2011) is a starting point for such standards.


Long-term isolation and recent range expansion from glacial refugia revealed for the endemic springtail Gomphiocephalus hodgsoni from Victoria Land, Antarctica.
We examined the phylogeography of the endemic Antarctic collembolan Gomphiocephalus hodgsoni using allozymes and mitochondrial DNA (mtDNA; COI) to determine if potentially limited dispersal and long-term habitat fragmentation have promoted regional genetic differentiation. Allozyme analyses showed that differentiation among 21 populations within the Ross Dependency was high (FST = 0.55) with two main groups each representing a distinct geographical region: (1) Ross Island and Beaufort Island; and (2) all continental sites. Ross Island populations showed low levels of differentiation (FST = 0.05) and no correlation with geographical distance, suggesting their derivation from a single glacial refuge. By contrast, continental regions revealed moderate levels of differentiation (FST = 0.27) and a strong correlation with geographical distance, indicating a much older history with several refugia likely. Two sympatric allozyme genotypes were found at three continental sites from Taylor Valley and were congruent with two mtDNA haplotypes, implying nonrandom breeding groups. Although haplotype sharing between one Ross Island site (Cape Bird) and one continental site (Granite Harbour) was identified, the clades showed mostly fragmented allopatric distributions. The extensive Pleistocene glaciations, in conjunction with limited dispersal opportunities, appear to have promoted isolation and divergence among the fragmented habitats. Furthermore, the McMurdo Sound appears to be an effective isolating barrier to dispersal. However, we suggest that the unaided dispersal capacity of G. hodgsoni is unlikely to account for the limited mixing of haplotypes across the McMurdo Sound and recent human- or bird-mediated dispersal is highly probable.


Effect of fish oil on ruminal biohydrogenation of C18 unsaturated fatty acids in steers fed grass or red clover silages.
Red clover and fish oil (FO) are known to alter ruminal lipid biohydrogenation leading to an increase in the polyunsaturated fatty acid (PUFA) and conjugated linoleic acid (CLA) content of ruminant-derived foods, respectively. The potential to exploit these beneficial effects were examined using eight Hereford × Friesian steers fitted with rumen and duodenal cannulae. Treatments consisted of grass silage or red clover silage fed at 90% of ad libitum intake and FO supplementation at 0, 10, 20 or 30 g/kg diet dry matter (DM). The experiment was conducted with two animals per FO level and treatments formed extra-period Latin squares. Flows of fatty acids at the duodenum were assessed using ytterbium acetate and chromium ethylene diamine tetra-acetic acid as indigestible markers. Intakes of DM were higher (P < 0.001) for red clover silage than grass silage (5.98 v. 5.09 kg/day). There was a linear interaction effect (P = 0.004) to FO with a reduction in DM intake in steers fed red clover silage supplemented with 30 g FO/kg diet DM. Apparent ruminal biohydrogenation of C18:2n-6 and C18:3n-3 were lower (P < 0.001) for red clover silage than grass silage (0.83 and 0.79 v. 0.87 and 0.87, respectively), whilst FO increased the extent of biohydrogenation on both diets. Ruminal biohydrogenation of C20:5n-3 and C22:6n-3 was extensive on both silage diets, averaging 0.94 and 0.97, respectively. Inclusion of FO in the diet enhanced the flow of total CLA leaving the rumen with an average across silages of 0.22, 0.31, 0.41 and 0.44 g/day for 0, 10, 20 or 30 g FO/kg, respectively, with a linear interaction effect between the two silages (P = 0.03). FO also showed a dose-dependent increase in the flow of trans-C18:1 intermediates at the duodenum from 4.6 to 15.0 g/day on grass silage and from 9.4 to 22.5 g/day for red clover silage. Concentrations of trans-C18:1 with double bonds from Δ4-16 in duodenal digesta were all elevated in response to FO in both diets, with trans-11 being the predominant isomer. FO inhibited the complete biohydrogenation of dietary PUFA on both diets, whilst red clover increased the flow of C18:2n-6 and C18:3n-3 compared with grass silage. In conclusion, supplementing red clover silage-based diets with FO represents a novel nutritional strategy for enhancing the concentrations of beneficial fatty acids in ruminant milk and meat.


Are there risk factors in alpine skiing? A controlled multicentre survey of 1278 skiers.
To analyse risk factors in alpine skiing. A controlled multicentre survey of injured and non-injured alpine skiers. One tertiary and two secondary trauma centres in Bern, Switzerland. All injured skiers admitted from November 2007 to April 2008 were analysed using a completed questionnaire incorporating 15 parameters. The same questionnaire was distributed to non-injured controls. Multiple logistic regression was performed. Patterns of combined risk factors were calculated by inference trees. A total of 782 patients and 496 controls were interviewed. Parameters that were significant for the patients were: high readiness for risk (p = 0.0365, OR 1.84, 95% CI 1.04 to 3.27); low readiness for speed (p = 0.0008, OR 0.29, 95% CI 0.14 to 0.60); no aggressive behaviour on slopes (p<0.0001, OR 0.19, 95% CI 0.09 to 0.37); new skiing equipment (p = 0.0228, OR 59, 95% CI 0.37 to 0.93); warm-up performed (p = 0.0015, OR 1.79, 95% CI 1.25 to 2.57); old snow compared with fresh snow (p = 0.0155, OR 0.31, 95% CI 0.12 to 0.80); old snow compared with artificial snow (p = 0.0037, OR 0.21, 95% CI 0.07 to 0.60); powder snow compared with slushy snow (p = 0.0035, OR 0.25, 95% CI 0.10 to 0.63); drug consumption (p = 0.0044, OR 5.92, 95% CI 1.74 to 20.11); and alcohol abstinence (p<0.0001, OR 0.14, 95% CI 0.05 to 0.34). Three groups at risk were detected: (1) warm-up 3-12 min, visual analogue scale (VAS)(speed) >4 and bad weather/visibility; (2) VAS(speed) 4-7, icy slopes and not wearing a helmet; (3) warm-up >12 min and new skiing equipment. Low speed, high readiness for risk, new skiing equipment, old and powder snow, and drug consumption are significant risk factors when skiing. Future work should aim to identify more precisely specific groups at risk and develop recommendations--for example, a snow weather index at valley stations.


Salvage esophagectomy for locoregional failure after chemoradiotherapy in patients with advanced esophageal cancer.
Definitive chemoradiotherapy is associated with high local treatment failure rates, and surgical resection may be an appropriate salvage therapy. However, the efficacy and safety of salvage esophagectomy have not been elucidated fully. The clinical outcomes of salvage esophagectomy for locoregional failure after chemoradiotherapy were assessed. Twelve patients who underwent salvage esophagectomy after chemoradiotherapy between January 2003 and November 2010 were included in this retrospective analysis. Baseline demographics and survivals of these patients were compared with 21 patients who did not receive salvage esophagectomy for locoregional failure only after chemoradiotherapy, identified from our own previous prospective trials. The median age was 62.5 years (range 50 to 69) and all patients had squamous cell carcinoma. The median radiation dose was 54.0 Gy (range 41.4 to 66.0) and the median interval between completion of chemoradiation and surgery was 8.0 months (range 2.0 to 32.9). There were no in-hospital deaths. Pulmonary complication was the most common postoperative morbidity (42%), and anastomotic leakage occurred in 1 patient (8%). With a median follow-up period of 29.3 months (range 5.8 to 73.0), the overall 3-year survival rate was 58%. Patients with early pathologic stage disease (T1/2 and N0) showed significantly prolonged survival (p=0.03) compared with those with advanced pathologic stage (T3/T4 or N1). Patients with salvage esophagectomy had prolonged event-free survival and overall survival compared with those patients with locoregional failure who received primary chemotherapy or boost radiotherapy (p<0.001). While salvage esophagectomy for locoregional failure after chemoradiotherapy should be employed with great caution, it appears to be a feasible and effective therapeutic option for highly selected patients, especially with early pathologic stage disease. Salvage esophagectomy can be recommended as the only current curative treatment option for patients with locoregional failure after chemoradiotherapy.


Transposition of a Ty3 GAG3-POL3 fusion mutant is limited by availability of capsid protein.
Ty3 encodes structural proteins in its upstream open reading frame (GAG3) and catalytic proteins in an overlapping open reading frame (POL3). As is the case for retroviruses, high levels of structural protein versus catalytic proteins are synthesized and we show here that catalytic proteins are derived from a GAG3-POL3 fusion polyprotein. To evaluate the relative contributions of structural and catalytic components of the Ty3 particle, we perturbed the balance of these proteins by fusing the GAG3 and POL3 frames. This fusion Ty3 was capable of complementing low levels of transposition of a donor Ty3 which contained only cis-acting sequences required for transposition. Examination of extracts of cells expressing the GAG3-POL3 fusion mutant showed that particle formation differed qualitatively and quantitatively from viruslike particle formation by wild-type Ty3. Suprisingly, expression of 238 codons of GAG3, encoding only capsid protein, complemented transposition and particle formation defects of the fusion mutant, showing that the limiting deficiency was in capsid, and not in nucleocapsid, function. In addition, protein containing the capsid domain expressed alone accumulated in the same particulate fraction as viruslike particles, showing that it was sufficient for particle formation. The activity of the Ty3 fusion mutant contrasts with the inviability of mutant retroviruses in which gag and pol frames were fused and argues that retrotransposons tolerate considerable variation in the nucleoprotein complexes that permit replication and integration.


Auxin promotes Arabidopsis root growth by modulating gibberellin response.
The growth of plant organs is influenced by a stream of the phytohormone auxin that flows from the shoot apex to the tip of the root. However, until now it has not been known how auxin regulates the cell proliferation and enlargement that characterizes organ growth. Here we show that auxin controls the growth of roots by modulating cellular responses to the phytohormone gibberellin (GA). GA promotes the growth of plants by opposing the effects of nuclear DELLA protein growth repressors, one of which is Arabidopsis RGA (for repressor of gal-3). GA opposes the action of several DELLA proteins by destabilizing them, reducing both the concentration of detectable DELLA proteins and their growth-restraining effects. We also show that auxin is necessary for GA-mediated control of root growth, and that attenuation of auxin transport or signalling delays the GA-induced disappearance of RGA from root cell nuclei. Our observations indicate that the shoot apex exerts long-distance control on the growth of plant organs through the effect of auxin on GA-mediated DELLA protein destabilization.


Prediction of bleeding risk in patients taking vitamin K antagonists using thrombin generation testing.
Until recently, vitamin K antagonists (VKAs) were the mainstay of oral anticoagulant treatment with bleeding as the most prevalent adverse effect. One to four percent of patients experience major bleeding episodes, while clinically relevant bleeding occurs in up to 20%. At this moment no laboratory assays are available to identify patients at risk for bleeding. With this study we aimed to investigate whether thrombin generation tests might identify a bleeding risk in patients taking VKAs. This prospective cohort study included 129 patients taking VKAs for more than three months. Calibrated automated thrombinography (CAT) was performed in whole blood, platelet rich and platelet poor plasma. Hematocrit, hemoglobin concentrations and the International Normalized Ratio (INR) were defined and coagulation factor levels were measured. Forty clinically relevant bleeding episodes were registered in 26 patients during follow-up. No differences were found in plasma CAT parameters or INR values. Bleeding was not associated with age, sex, hematocrit, hemoglobin levels or coagulation factor levels. In whole blood a significantly lower endogenous thrombin potential (ETP) and peak were found in patients with bleeding (median ETP: 182.5 versus 256.2 nM.min, p = 0.002; peak: 23.9 versus 39.1 nM, p = 0.029). Additionally, the area under the receiver operating curve (AUC ROC) was significantly associated with bleeding (ETP: 0.700, p = 0.002; peak: 0.642, p = 0.029). HAS-BLED scores were also significantly higher in bleeding patients (3 versus 2, p = 0.003), with an AUC ROC 0.682 (p = 0.004). In conclusion, bleeding in patients taking VKAs is associated with a decreased whole blood ETP and peak as well as with an increased HAS-BLED score.


Identification of genes that promote or antagonize somatic homolog pairing using a high-throughput FISH-based screen.
The pairing of homologous chromosomes is a fundamental feature of the meiotic cell. In addition, a number of species exhibit homolog pairing in nonmeiotic, somatic cells as well, with evidence for its impact on both gene regulation and double-strand break (DSB) repair. An extreme example of somatic pairing can be observed in Drosophila melanogaster, where homologous chromosomes remain aligned throughout most of development. However, our understanding of the mechanism of somatic homolog pairing remains unclear, as only a few genes have been implicated in this process. In this study, we introduce a novel high-throughput fluorescent in situ hybridization (FISH) technology that enabled us to conduct a genome-wide RNAi screen for factors involved in the robust somatic pairing observed in Drosophila. We identified both candidate "pairing promoting genes" and candidate "anti-pairing genes," providing evidence that pairing is a dynamic process that can be both enhanced and antagonized. Many of the genes found to be important for promoting pairing are highly enriched for functions associated with mitotic cell division, suggesting a genetic framework for a long-standing link between chromosome dynamics during mitosis and nuclear organization during interphase. In contrast, several of the candidate anti-pairing genes have known interphase functions associated with S-phase progression, DNA replication, and chromatin compaction, including several components of the condensin II complex. In combination with a variety of secondary assays, these results provide insights into the mechanism and dynamics of somatic pairing.


Paternal alcohol consumption, family transition and child development in a former Soviet country.
Although major societal changes have been observed in former Soviet countries, the child health consequences of these changes have rarely been studied. We examined the associations of paternal alcohol consumption and family transitions with cognitive ability and behaviour problems among healthy, early school-age Belarusian children. Our study is based on follow-up of children aged 6.5 years participating in a cluster-randomized trial of a breastfeeding promotion intervention. Paternal alcohol consumption was measured at follow-up and classified into three categories: at least weekly consumption of heavy (≥ 6 standard units per occasion), moderate (4-5 units per occasion), or light (≤ 3 units per occasion) or infrequent drinking. Family transition from birth to age 6.5 years was categorized into living stably with an intact family, having transitioned into a stepfamily, having transitioned into a single-parent family and living stably with a single-parent family. Mean differences in intelligence quotient (IQ) measured with the Wechsler Abbreviated Scales of Intelligence and in behaviour problems measured with the Strengths and Difficulties Questionnaire were compared according to paternal alcohol and family transition, after controlling for a wide range of confounding factors. Children whose fathers were moderate or heavy drinkers with at least weekly alcohol consumption showed 1.5-2.5 points lower mean IQ scores and greater behaviour problems (range 0.1-0.3 SD) compared with those whose fathers were light or infrequent drinkers. Compared with children from stable intact families, children who transitioned into stepfamilies had 1 point lower IQ and greater behaviour problems by 0.1-0.4 SD, and children from stable single-parent families or with transition into single-parent families showed no cognitive deficit but greater behaviour problems (range 0.1-0.3 SD). The sharp rise in both alcohol consumption and divorce/re-marriage rates in former Soviet countries may have negative consequences for cognitive and behavioural development in children.


β-(1,3)-Glucan derived from Candida albicans induces inflammatory cytokines from macrophages and lamina propria mononuclear cells derived from patients with Crohn's disease.
Recent research has highlighted the importance of interactions between commensal fungi and intestinal inflammation. However, there are few studies investigating whether commensal fungi contribute to inflammation in patients with Crohn's disease (CD). The aim of this study is to investigate reveal interactions between commensal fungi and host immune cells in CD. CD14-positive monocytes were isolated from peripheral blood mononuclear cells from healthy human volunteers and then differentiated in the presence of macrophage colony-stimulating factor (M-CSF) (referred to as M-macrophages, M-Mϕs) or M-CSF and interferon-γ (IFN-γ) (referred to as M-gamma macrophages, Mγ-Mϕs). Cytokine production by these in vitro differentiated macrophages in response to β-(1,3)-glucan was analyzed by flow cytometry. Expression of Dectin-1 was examined using flow cytometry, western blotting, and quantitative reverse transcription-polymerase chain reaction. Cytokine production by in vitro differentiated macrophages in response to β-(1,3)-glucan was measured in the presence of an anti-Dectin-1 receptor antagonist, anti-Syr, or an anti-Fas-1 antibody. Cytokine production by lamina propria mononuclear cells (LPMCs) derived from CD patients in response to β-(1,3)-glucan was also analyzed. Mγ-Mϕs produced a large amount of tumor necrosis factor-α (TNF-α) and interleukin-6 in response to β-(1,3)-glucan. Dectin-1 expression was significantly higher in Mγ-Mϕs than in M-Mϕs. The increase in TNF-α production by Mγ-Mϕs stimulated with glucan was reversed by blocking Dectin-1, Syr or Fas-1. LPMCs derived from CD patients stimulated with β-(1,3)-glucan produced significantly higher amount of TNF-α than LPMCs derived from UC patients. These results suggest that commensal fungal microbiota may contribute to the pathogenesis of CD by inducing macrophages-derived pro-inflammatory cytokines.


Complementary medicine, exercise, meditation, diet, and lifestyle modification for anxiety disorders: a review of current evidence.
Use of complementary medicines and therapies (CAM) and modification of lifestyle factors such as physical activity, exercise, and diet are being increasingly considered as potential therapeutic options for anxiety disorders. The objective of this metareview was to examine evidence across a broad range of CAM and lifestyle interventions in the treatment of anxiety disorders. In early 2012 we conducted a literature search of PubMed, Scopus, CINAHL, Web of Science, PsycInfo, and the Cochrane Library, for key studies, systematic reviews, and metaanalyses in the area. Our paper found that in respect to treatment of generalized anxiety or specific disorders, CAM evidence revealed current support for the herbal medicine Kava. One isolated study shows benefit for naturopathic medicine, whereas acupuncture, yoga, and Tai chi have tentative supportive evidence, which is hampered by overall poor methodology. The breadth of evidence does not support homeopathy for treating anxiety. Strong support exists for lifestyle modifications including adoption of moderate exercise and mindfulness meditation, whereas dietary improvement, avoidance of caffeine, alcohol, and nicotine offer encouraging preliminary data. In conclusion, certain lifestyle modifications and some CAMs may provide a beneficial role in the treatment of anxiety disorders.


Impact of sleep inertia on visual selective attention for rare targets and the influence of chronotype.
Sleep inertia is affected by circadian phase, with worse performance upon awakening from sleep during the biological night than biological day. Visual search/selective visual attention performance is known to be sensitive to sleep inertia and circadian phase. Individual differences exist in the circadian timing of habitual wake time, which may contribute to individual differences in sleep inertia. Because later chronotypes awaken at an earlier circadian phase, we hypothesized that later chronotypes would have worse visual search performance during sleep inertia than earlier chronotypes if awakened at habitual wake time. We analysed performance from 18 healthy participants [five females (22.1 ± 3.7 years; mean ± SD)] at ~1, 10, 20, 30, 40 and 60 min following electroencephalogram-verified awakening from an 8 h in-laboratory sleep opportunity. Cognitive throughput and reaction times of correct responses were impaired by sleep inertia and took ~10-30 min to improve after awakening. Regardless whether chronotype was defined by dim light melatonin onset or mid-sleep clock hour on free days, derived from the Munich ChronoType Questionnaire, the duration of sleep inertia for cognitive throughput and reaction times was longer for later chronotypes (n = 7) compared with earlier chronotypes (n = 7). Specifically, performance for earlier chronotypes showed significant improvement within ~10-20 min after awakening, whereas performance for later chronotypes took ~30 min or longer to show significant improvement (P < 0.05). Findings have implications for decision making immediately upon awakening from sleep, and are consistent with circadian theory suggesting that sleep inertia contributes to longer-lasting impairments in morning performance in later chronotypes.


Paternal and maternal lineages in Guinea-Bissau population.
The aim of the present work was to study the origin of paternal and maternal lineages in Guinea-Bissau population, inferred by phylogeographic analyses of mtDNA and Y chromosome defined haplogroups. To determine the male lineages present in Guinea-Bissau, 33 unrelated males were typed using a PCR-SNaPshot multiplex based method including 24 Y-SNPs, which characterize the main haplogroups in sub-Saharan Africa and Western Europe. In the same samples, 17 Y-STRs (included in the YFiler kit, Applied Biosystems) were additionally typed. The most frequent lineages observed were E1b1a (xE1b1a4,7)-M2 (68%) and E1a-M33 (15%). The European haplogroup R1b1-P25 was represented with a frequency of 12%. The two hypervariable mtDNA regions were sequenced in 79 unrelated individuals from Guinea-Bissau, and haplogroups were classified based on control region motifs using mtDNA manager. A high diversity of haplogroups was determined in our sample being the most frequent haplogroups characteristic of populations from sub-Saharan Africa, namely L2a1 (15%), L3d (13%), L2c (9%), L3e4 (9%), L0a1 (8%), L1b (6%) and L1c1 (6%). None of the typical European haplogroups (H, J and T) were found in the present sample of Guinea-Bissau. From our results, it is possible to confirm that Guinea-Bissau presents a typically West African profile, marked by a high frequency of the Y chromosome haplogroup E1b1a(xE1b1a4,7)-M2 and a high proportion of mtDNA lineages belonging to the sub-Saharan specific sub-clusters L1 to L3 (89%). A small European influx has been also detected, although restricted to the male lineages.


Hemagglutinin of influenza virus partitions into the nonraft domain of model membranes.
The HA of influenza virus is a paradigm for a transmembrane protein thought to be associated with membrane-rafts, liquid-ordered like nanodomains of the plasma membrane enriched in cholesterol, glycosphingolipids, and saturated phospholipids. Due to their submicron size in cells, rafts can not be visualized directly and raft-association of HA was hitherto analyzed by indirect methods. In this study, we have used GUVs and GPMVs, showing liquid disordered and liquid ordered domains, to directly visualize partition of HA by fluorescence microscopy. We show that HA is exclusively (GUVs) or predominantly (GPMVs) present in the liquid disordered domain, regardless of whether authentic HA or domains containing its raft targeting signals were reconstituted into model membranes. The preferential partition of HA into ld domains and the difference between lo partition in GUV and GPMV are discussed with respect to differences in packaging of lipids in membranes of model systems and living cells suggesting that physical properties of lipid domains in biological membranes are tightly regulated by protein-lipid interactions.


UniChip enables long-term recirculating unidirectional perfusion with gravity-driven flow for microphysiological systems.
Microphysiological systems, also known as body-on-a-chips, are promising "human surrogates" that may be used to evaluate potential human response to drugs in preclinical drug development. Various microfluidics-based platforms have been proposed to interconnect different organ models and provide perfusion in mimicking the blood circulation. We have previously developed a pumpless platform that combines gravity-driven fluid flow and a rocking motion to create reciprocating flow between reservoirs for recirculation. Such platform allows design of self-contained and highly integrated systems that are relatively easy and cost-effective to construct and maintain. To integrate vasculature and other shear stress-sensitive tissues (e.g. lung and kidney) into pumpless body-on-a-chips, we propose "UniChip" fluid network design, which transforms reciprocating flow input into unidirectional perfusion in the channel(s) of interest by utilizing supporting channels and passive valves. The design enables unidirectional organ perfusion with recirculation on the pumpless platform and provides an effective backflow-proof mechanism. To demonstrate principles of UniChip design, we created a demonstration chip with a single straight channel as a simple example of the organ perfusion network. A BiChip providing bidirectional perfusion was used for comparison. Computational and experimental fluid dynamic characterization of the UniChip confirmed continuous unidirectional flow in the perfusion channel and the backflow-proof mechanism. Vascular endothelial cells cultured on UniChips for 5 d showed changes matching cell responses to unidirectional laminar flows. Those include cell elongation and alignment to the flow direction, continuous network of VE-cadherin at cell borders, realignment of F-actin and suppressed cell proliferation. Cells on BiChips manifested distinct responses that are close to responses to oscillatory flows, where cells remain a polygonal shape with intermittent VE-cadherin networks and few F-actin realignment. These results demonstrate that microfluidic devices of UniChip design provide recirculating unidirectional perfusion suitable for long-term culture of shear stress-sensitive tissues. This is the first time a gravity-drive flow system has achieved continuous unidirectional perfusion with recirculation. The inherent backflow-proof mechanism allows hassle-free long-term operation of body-on-a-chips. Overall, our UniChip design provides a reliable and cost-effective solution for the integration of vasculature and other shear stress-sensitive tissues into pumpless recirculating body-on-a-chips, which can expedite the development and widespread application of moderately high-throughput, high-content microphysiological systems.


Monitoring the marketing, distribution, and use of Sprinkles micronutrient powders in rural western Kenya.
In 2007, the US Centers for Disease Control and Prevention partnered with local Kenyan institutions to implement the Nyando Integrated Child Health and Education Project, an effectiveness study that used social marketing and a community-based distribution program to promote the sale of Sprinkles and other health products. To describe monitoring of wholesale sales, household demand, promotional strategies, and perceived factors influencing Sprinkles sales among vendors. Ongoing quantitative and qualitative monitoring of Sprinkles sales began in May 2007 in 30 intervention villages. Data sources included baseline and follow-up cross-sectional surveys; office records of Sprinkles sales to vendors; biweekly household monitoring of Sprinkles use; and qualitative data collection, including vendor focus groups and key informant interviews. A total of 550 children aged 6 to 35 months were enrolled at baseline, and 451 were available at 12-month follow-up. During this period, nearly 160,000 sachets were sold wholesale to vendors, with variability in sales influenced by the social, political, and economic context. Vendors living closer to the wholesale office purchased more Sprinkles, so a second office was opened closer to remote vendors. On average, 33% of households purchased Sprinkles during household monitoring visits. Training sessions and community launches were important for community support and raising awareness about Sprinkles. Vendor incentives motivated vendors to sell Sprinkles, and consumer incentives promoted purchases. Sprinkles program monitoring in Kenya was critically important for understanding sales and distribution trends and vendor perceptions. Understanding these trends led to strategic changes to the intervention over time.


Distribution of beta-tectorin mRNA in the early posthatch and developing avian inner ear.
Expression of beta-tectorin mRNA in the inner ear of the embryonic and early posthatch (PH) chick was studied by in situ hybridisation. In the PH chick, beta-tectorin mRNA is expressed in the basilar papilla, in the clear and the cuboidal cells that lie either side of the papilla, in the striolar regions of the maculae, and in two small groups of cells lying adjacent to the midline in the cristae of the anterior and posterior ampullae. Expression of beta-tectorin is not observed in the lateral ampulla. In the sensory epithelia of the PH chick in which beta-tectorin mRNA is detected, expression is restricted to the supporting cell population. During development of the cochlear duct, beta-tectorin expression begins between embryonic (E) days 5 and 6. At E6, expression is observed throughout the length of the duct but is highest at the distal end. By E7, the pattern of expression is reversed and is highest at the proximal end of the cochlea, suggesting that a wave of high beta-tectorin expression passes disto-proximally along the papilla during E6 and E7. Expression of beta-tectorin mRNA is not detected in the homogene cells at any stage during the development of the cochlear duct, indicating that these cells do not synthesise one of the two major proteins of the avian tectorial membrane. The distribution of supporting cells expressing beta-tectorin mRNA in the different epithelia was compared with the distribution of sensory cells that have type B hair bundles, those with shaft links restricted to basal regions of their stereocilia, and sensory cells that have type A bundles, those with shaft links all over the entire surface of their stereocilia. Hair cells with type A hair bundles are never found in association with supporting cells expressing beta-tectorin. Although there is a correspondence in the basilar papilla and the maculae of the utriculus and lagena between the distribution of supporting cells expressing beta-tectorin mRNA and hair cells with type B bundles, this correlation does not generalise to the other sensory epithelia.


In silico modelling of pesticide aquatic toxicity.
Human activities have introduced tens of thousands of chemicals into water systems around the world which has significantly impacted water quality and aquatic ecosystems. The aim of this study was to develop an in silico QSAR model, capable of predicting the aquatic toxicity of pesticides in terms of a lethal dose (LD50) for fish without requiring the use of in vivo testing. A large data set of 230 diverse pesticides, including fungicides, herbicides and insecticides, with experimentally measured LD50 values was used to develop a predictive QSAR model. Each pesticide molecule was described using 62 calculated molecular descriptors. These descriptors were then related to the LD50 values via an Artificial Neural Network. Sensitivity analysis was used to select descriptors that best describe the model. The developed model included 13 molecular descriptors related to lipophilicity, hydrogen binding and polarity. Note the value of the predictive squared correlation coefficient (q(2)) for the final model was 0.748, demonstrating the model's predictability. In the domain of QSAR studies, a q(2) value above 0.5 renders a model to be predictive. The model could therefore be used to accurately screen a wide range of compounds without the need for actual compound synthesis and to prioritize potentially toxic compounds for further testing.


Correlation-induced synchronization of oscillations in olfactory bulb neurons.
Oscillations are a common feature of odor-evoked and spontaneous activity in the olfactory system in vivo and in vitro and are thought to play an important role in information processing and memory in a variety of brain areas. Theoretical and experimental studies have described several mechanisms by which oscillations can be generated and synchronized. Here, we investigate the hypothesis that correlated noisy inputs are able to generate synchronous oscillations in olfactory bulb mitral cells in vitro. We consider several alternative mechanisms and conclude that olfactory bulb synchronous oscillations are likely to arise because of the response of uncoupled oscillating neurons to aperiodic but correlated inputs. This mechanism has been described theoretically, but we provide the first experimental evidence that such a mechanism may underlie synchronization in real neurons. In physiological experiments, we show that this mechanism can generate gamma-band oscillations in populations of olfactory bulb mitral cells. This mechanism synchronizes oscillatory firing by using shared fast fluctuations in stochastic inputs across neurons, without requiring any synaptic or electrical coupling. We discuss the properties and limitations of synchronization by this mechanism and suggest that it may underlie fast oscillations in many brain areas.


Targeted disruption of the Huntington's disease gene results in embryonic lethality and behavioral and morphological changes in heterozygotes.
Huntington's disease (HD) is an incurable neuropsychiatric disease associated with CAG repeat expansion within a widely expressed gene that causes selective neuronal death. To understand its normal function, we have created a targeted disruption in exon 5 of Hdh (Hdhex5), the murine homolog of the HD gene. Homozygotes die before embryonic day 8.5, initiate gastrulation, but do not proceed to the formation of somites or to organogenesis. Mice heterozygous for the Hdhex5 mutation display increased motor activity and cognitive deficits. Neuropathological assessment of two heterozygous mice shows significant neuronal loss in the subthalamic nucleus. These studies show that the HD gene is essential for postimplantation development and that it may play an important role in normal functioning of the basal ganglia.


Lack of fructose-1,6-bisphosphatase in a range of higher plants that store starch.
The aim of this work was to discover whether fructose-1,6-bisphosphatase (FBPase) is present in higher-plant cells that synthesize storage starch. The following were examined: suspension cultures of soybean (Glycine max), tubers of potato (Solanum tuberosum), florets of cauliflower (Brassica oleracea), developing endosperm of maize and of sweet corn (Zea mays), roots of pea (Pisum sativum), and the developing embryos of round and wrinkled varieties of pea. Unfractionated extracts of each tissue readily converted fructose 1,6-bisphosphate to fructose 6-phosphate in assays for both plastidic and cytosolic FBPase. These conversions were not inhibited by 20 microM-fructose 2,6-bisphosphate. Except in extracts of pea embryos and sweet-corn endosperm, treatment with affinity-purified antibodies to pyrophosphate: fructose-6-phosphate 1-phosphotransferase reduced the above fructose 6-phosphate production to the rate found with boiled extracts. The antibody-resistant activity from sweet corn was slight. In immunoblot analyses, antibody to plastidic FBPase did not react positively with any protein in extracts of soybean cells, potato tuber, cauliflower florets, maize endosperm and pea roots. Positive reactions were found for extracts of embryos of both round and wrinkled varieties of peas and endosperm of sweet corn. For pea embryos, but not for sweet-corn endosperm, the Mr of the recognized protein corresponded to that of plastidic FBPase. It is argued that soybean cells, potato tuber, cauliflower florets, maize (var. White Horse Tooth) endosperm and pea roots lack significant activity of plastidic FBPase, but that this enzyme is present in developing embryos of pea. The data for sweet corn (var. Golden Bantam) are not decisive. It is also argued that, where FBPase is absent, carbon for starch synthesis does not enter the amyloplast as triose phosphate.


Circulating angiogenic factors in patients with thromboangiitis obliterans.
Thromboangiitis obliterans (TAO, also known as Buerger's disease) is a non-atherosclerotic inflammatory vascular disease that primarily affects arteries in the extremities of young adult smokers. Since the etiology of TAO is still unknown, therapeutic options are limited. Recent attempts in therapeutic angiogenesis have been promising. Therefore, the aim of our study was to evaluate angiogenic processes and factors including circulating progenitor cells in TAO. TAO patients with critical limb ischemia and age- and gender-matched nonsmokers and smokers without cardiovascular disease (n = 12 in each group) were enrolled in the study. Flow cytometric analysis of peripheral blood showed significantly decreased levels of circulating CD45(dim)CD34(+) progenitor cells in TAO patients and in smokers compared to nonsmokers. In contrast to both control groups, the proportion of CD45(dim)CD34(+) progenitor cells co-expressing VEGF receptor-2 (VEGFR2) was significantly elevated in TAO patients. Enzyme-linked immunosorbent assay (ELISA) of common angiogenic factors (such as VEGF) did not clearly point to pro- or antiangiogenic conditions in serum or plasma of TAO patients. Serum of TAO patients and controls was evaluated in proliferation, migration (scratch assay) and spheroid sprouting assays using human umbilical vein endothelial cells (HUVECs). Serum of TAO patients exhibited a diminished sprouting capacity of HUVECs compared to both control groups. Proliferation and migration of endothelial cells were impaired after treatment with serum of TAO patients. Levels of circulating progenitor cells were altered in TAO patients compared to healthy nonsmokers and smokers. Furthermore, serum of TAO patients exhibited an antiangiogenic activity (impaired endothelial cell sprouting, migration and proliferation) on endothelial cells, which may contribute to vascular pathology in this patient population.


First Report of Cylindrocarpon pauciseptatum Associated with Root Rot and Decline of Peach in Southern Italy (Apulia Region).
During a survey for the sanitary status of stone fruits in southern Italy (Apulia region), symptoms of low vigor, sparse foliage, and chlorosis of leaves, frequently leading to decline or death of the plants, were observed on 3- to 5-year-old peach trees (Prunus persica) cvs. Tardi Belle, Zee Lady, and O'Henry grafted on GF677. Brown-to-black discolorations of the wood were observed in cross-sections of the trunks just below the graft union. Samples were collected from May to June 2010 from two symptomatic orchards in Brindisi and Foggia provinces. Small pieces of brownish, vascular wood and necrotic root tissues were surface disinfested, placed onto potato dextrose agar (PDA), and incubated for 7 days at 25°C in the dark. Single-conidial isolates were subsequently grown on PDA at 25°C for 10 days. Fungal colonies were presumptively identified as members of the genus Cylindrocarpon on the basis of their morphological and conidial characteristics. On PDA, the isolates developed abundant mycelium, which gradually became yellowish or partially brownish. Macroconidia were predominantly three septate, straight and cylindrical with both ends broadly rounded. Chlamydospores and ovoidal microconidia were observed on synthetic nutrient-poor agar (1). Sequence of the ribosomal internal transcribed spacer (ITS) region was obtained using universal primers (ITS6-ITS4) and deposited in GenBank (Accession No. HE577846). This sequence revealed 100% genetic identity with a sequence from Cylindrocarpon pauciseptatum Schroers & Crous (Accession No. EF607090), a recently described species (3). In nature, several species of the genus Cylindrocarpon affect a large number of woody plants, mainly grapevine, olive, and stone fruits, in which they attack the root surface (2). To verify Koch's postulates, the roots of 20 3-month-old peach seedlings (GF305) were dipped for 30 min in a spore suspension of the fungus (1 × 108 conidia ml-1). Seedlings were then transplanted in an artificial soil mix and held under controlled conditions in a greenhouse at 24°C. Typical black-foot symptoms developed on 92% of the inoculated plants within 3 months, whereas the control plants, whose roots had been dipped in distilled water, remained healthy. C. pauciseptatum was reisolated from infected tissues and internal vascular lesions of 45% of the inoculated plants, but none of the plants used as controls, fulfilling Koch's postulates. To our knowledge, this is the first report of this pathogen on peach in the Apulia Region of Italy. Currently, C. pauciseptatum is limited to a few orchards where presumably it was introduced with infected propagating material from extra-regional nurseries. C. pauciseptatum has the potential to negatively affect the stone fruit industry in Italy including reducing nursery production and productivity and vigor of trees in orchards, or even rapid death of young trees. References: (1) W. Gams et al. CBS Course of Mycology. 4th ed. Centraalbureau voor Schimmelcultures, Baarn, the Netherlands, 1998. (2) M. E. S. Hernandez et al. Eur. J. Plant Pathol. 104:347, 1998. (3) H. J. Schroers et al. Mycol. Res. 112:82, 2008.


Immunoselected STRO-3+ mesenchymal precursor cells and restoration of the extracellular matrix of degenerate intervertebral discs.
Chronic low-back pain of discal origin is linked strongly to disc degeneration. Current nonsurgical treatments are palliative and fail to restore the disc extracellular matrix. In this study the authors examined the capacity of ovine mesenchymal precursor cells (MPCs) to restore the extracellular matrix of degenerate discs in an ovine model. Three adjacent lumbar discs of 24 adult male sheep were injected intradiscally with chondroitinase-ABC (cABC) to initiate disc degeneration. The remaining lumbar discs were used as normal controls. Three months after cABC injection, the L3-4 discs of all animals were injected with either a high dose (4 × 10(6) cells, in 12 sheep) or low dose (0.5 × 10(6) cells, in 12 sheep) of MPCs suspended in hyaluronic acid (HA). The adjacent L4-5 degenerate discs remained untreated; the L5-6 discs were injected with HA only. The animals were euthanized at 3 or 6 months after MPC injections (6 sheep from each group at each time point), and histological sections of the lumbar discs were prepared. Radiographs and MR images were obtained prior to cABC injection (baseline), 3 months after cABC injection (pretreatment), and just prior to necropsy (posttreatment). Injection of cABC decreased the disc height index (DHI) of target discs by 45%-50%, confirming degeneration. Some recovery in DHI was observed 6 months after treatment in all cABC-injected discs, but the DHI increased to within baseline control values only in the MPC-injected discs. This improvement was accompanied by a reduction in MRI degeneration scores. The histopathology scores observed at 3 months posttreatment for the high-dose MPC-injected discs and at 6 months posttreatment for the low-dose MPC-injected discs were significantly different from those of the noninjected and HA-injected discs (p <0.001) but not from the control disc scores. On the basis of the findings of this study, the authors conclude that the injection of MPCs into degenerate intervertebral discs can contribute to the regeneration of a new extracellular matrix.


Developmental control of cell cycle regulators: a fly's perspective.
During early development in many species, maternally supplied gene products permit the cell cycle to run at maximum velocity, subdividing the fertilized egg into smaller and smaller cells. As development proceeds, zygotic controls are activated that first limit divisions to defined spatial and temporal domains, coordinating them with morphogenesis, and then halt proliferation altogether, to allow cell differentiation. Analysis of the regulation of cyclin-dependent kinases (Cdks) in Drosophila has provided insights into how this embryonic program of cell proliferation is controlled at the molecular level and how it is linked to developmental cues. Recent studies have also begun to reveal how cell proliferation is controlled during the second phase of Drosophila development, which occurs in imaginal tissues. In contrast to their embryonic progenitors, imaginal cells proliferate with a cycle that requires cell growth and is linked to patterning processes controlled by secreted cell signaling molecules. The functions of these signaling molecules appear to be nearly as conserved between vertebrates and invertebrates as the cell cycle control apparatus itself, suggesting that the mechanisms that coordinate growth, patterning, and cell proliferation in developing tissues have ancient origins.


Outdoor Time is Not Associated with Metabolically Healthy Overweight and Obesity Phenotype in Canadian Children Aged 6-14 Years.
A large proportion of children living with obesity have favorable cardiometabolic profiles despite their adiposity levels, who are referred to as metabolically healthy overweight or obese (MHO). However, the contribution of active outdoor time to the MHO phenotype is unknown. The purpose of this study was to investigate the association between outdoor time and moderate-to-vigorous physical activity (MVPA) with the MHO phenotype. A cross-sectional analysis of overweight/obese children aged 6-14 (n = 386) from the Canadian Health Measures Survey was performed. Outdoor time was self-reported using five questions in relation to the school schedule to produce a computed score ranging from 0-25. MVPA was measured using accelerometers. The MHO phenotype was defined based on the absence of cardiometabolic risk factors: triglycerides, HDL-cholesterol, systolic and diastolic blood pressure, and glucose (MHO: 0 cardiometabolic risk factors). The proportion of children living with obesity with the MHO phenotype was 58.5%. No significant differences were observed between MHO and non-MHO according to outdoor time or MVPA (p > 0.05). Logistic regressions indicated that outdoor time was not significantly associated with the MHO phenotype (OR: 0.99, 95% CI = 0.92-1.06; p = 0.694), while MVPA was significantly associated with the MHO phenotype (OR: 1.41, 95% CI = 1.01-1.98; p = 0.047) after adjusting for confounders. We conclude that outdoor time is not associated with the MHO phenotype, even though Canadian children living with obesity are more likely to be MHO with greater amounts of MVPA, regardless of whether these activities are completed outdoors or not.


Multilayer model of photon diffusion in skin.
A diffusion model describing the propagation of photon flux in the epidermal, dermal, and subcutaneous tissue layers of the skin is presented. Assuming that the skin is illuminated by a collimated, finite-aperture source, we develop expressions relating photon flux density within the skin and intensities re-emitted from the skin surface to the optical properties of the individual layers. Model simulations show that the rate at which re-emitted intensities diminish with radial distance away from the source can provide information about absorption and scattering in underlying tissues. Re-emitted intensities measured from homogeneous and two-layer tissue phantoms compare favorably with model predictions. We demonstrate potential applications of the model by estimating the absorption (sigma a) and transport-corrected scattering (sigma's) coefficients of dermis and subcutis from intensities measured from intact skin and by predicting the magnitude of the optical-density variations measured by a photoplethysmograph.


Memory conformity and the perceived accuracy of self versus other.
Here, we demonstrate that the decision to conform to another person's memory involves a strategic trade-off that balances the accuracy of one's own memory against that of another person. We showed participants three household scenes, one for 30 s, one for 60 s, and one for 120 s. Half were told that they would encode each scene for half as long as their virtual partner, and half were told that they would encode each scene for twice as long as their virtual partner. On a subsequent two-alternative-forced choice (2AFC) memory test, the simulated answer of the partner (accurate, errant, or no response) was shown before participants responded. Conformity to the partner's responses was significantly enhanced for the 30-s versus the 60- and 120-s scenes. This pattern, however, was present only in the group who believed that they had encoded each scene for half as long as their partner, even though the short-duration scene had the lowest baseline 2AFC accuracy in both groups and was also subjectively rated as the least memorable by both groups. Our reliance on other people's memory is therefore dynamically and strategically adjusted according to knowledge of the conditions under which we and other people have acquired different memories.


Role of large Ca(2+)-activated K+ channels in regulation of mesangial contraction by nitroprusside and ANP.
The patch-clamp method, in conjunction with measurements of cell contraction, was employed to investigate activation by guanosine 3',5'-cyclic monophosphate (cGMP) and guanylyl cyclase-stimulating vasodilators of large Ca(2+)-activated K+ channels (BKCa) in human glomerular mesangial cells (MC). In cell-attached patches, with physiological NaCl bathing solutions, BKCa was activated transiently by nitroprusside [NP; a nitric oxide (NO) donor], atrial natriuretic peptide (ANP), and dibutyryl cGMP (DBcGMP), reaching peak responses between 10 and 60 s and decreasing to near baseline activity within the next 120 s. In the presence of LY-83583, a specific inhibitor of guanylyl cyclase, BKCa was activated on cell by DBcGMP but not by NP or ANP. In all cases, the increase in channel activity coincided with a decrease in channel amplitude, indicating that the membrane potential was approaching equilibrium potential as BKCa was activated. If membrane potential was maintained depolarized with 140 mM KCl in the bathing solution, DBcGMP induced a sustained activation of BKCa. In the continued presence of DBcGMP, BKCa was further activated when 100 nM angiotensin II (ANG II) was added to the bathing solution. Experiments were performed to determine the role of BKCa in the regulation by vasorelaxants of mesangial contraction measured as percent maximal and defined by reduction in length induced by replacing 135 mM bath NaCl with KCl. Contraction by ANG II (100 nM = 60.5%) was attenuated by NP (100 microM), ANP (1.0 microM), and DBcGMP (10 microM) in the absence, but not the presence, of iberiotoxin, a specific inhibitor of BKCa. These results indicate that guanylyl cyclase-stimulating vasorelaxants counteract ANG II-induced contraction of MC, in part, by repolarizing the membrane through activation of BKCa channels.


Intraocular pressure rise is predictive of vision improvement after intravitreal triamcinolone acetonide for diabetic macular oedema: a retrospective analysis of data from a randomised controlled trial.
Intravitreal triamcinolone acetonide (IVTA) is an effective treatment for recalcitrant diabetic macular oedema (DMO). It has been shown to improve vision with benefits persisting up to five years. The most common initial side effect of IVTA treatment is rise in intraocular pressure, occurring in approximately 50% of patients within the first 6 months of treatment. We evaluated whether there is a correlation between the development of intraocular pressure rise and improvement in vision. Analysis of individual data from 33 eyes of 33 participants treated with IVTA for DMO from a prospective, randomised, double-masked, placebo controlled trial. The degree of intraocular pressure (IOP) rise was correlated with improvement in best-corrected visual acuity (BCVA) at 1 and 6 months. The proportion of eyes gaining 5 or more logMAR letters was higher in eyes with greater IOP rise (p = 0.044). Better absolute improvement in BCVA at 6 months (p = 0.045) was also found in eyes with greater IOP rise. Regression analyses revealed a correlation between IOP rise of 10 or more mmHg and absolute BCVA improvement at 6 months (odds ratio 1.22, 95% confidence interval 1.01-1.48, p = 0.039), but not at 1 month. IOP rise and vision improvement appear to be correlated following IVTA for DMO, suggesting that the mechanisms that cause both may be linked. Clinical trials.gov NCT00167518, September 5, 2005.