Perceived need for alcohol, drug, and mental health treatment.
To investigate determinants of perceived need for alcohol, drug, and mental (ADM) health treatment and differences in ADM treatment patterns between individuals with perceived need and those without. We used data from a nationally representative telephone survey of 9585 adults conducted in 1997-1998. Logistic regression was used to study the determinants of perceived need and the correlation between perceived need and any ADM treatment, specialty ADM treatment, appropriate care, and medication adherence. Just fewer than 37% of individuals with an ADM disorder perceived a need for treatment, while 4.6% of those without an ADM disorder perceived a need for treatment. Women, the young and middle aged, the better educated, those with greater emotional support, and those with greater psychiatric morbidity were more likely to perceive need for ADM services. Perceived need was strongly correlated with receiving ADM treatment, although almost 44% of individuals in ADM treatment did not perceive a need for treatment. Among individuals in ADM treatment, those with perceived need were significantly more likely to receive specialty ADM treatment, but not more likely to be treatment adherent, or to receive appropriate care. Substantial levels of unmet need are likely to persist as long as perceived levels of need remain low. Interventions targeting perceived need may hold promise for decreasing unmet need.


Comparison of high-resolution echo-planar spectroscopic imaging with conventional MR imaging of prostate tumors in mice.
High spectral and spatial resolution (HiSS) MRI of rodent tumors has previously been performed using conventional spectroscopic imaging to obtain images with improved contrast and anatomic detail. The work described here evaluates the use of much faster echo-planar spectroscopic imaging (EPSI) to acquire HiSS data from rodent tumor models of prostate cancer. A high-resolution EPSI pulse sequence was implemented on a 4.7 T Bruker scanner. Three-dimensional EPSI data were Fourier-transformed along the k-space and temporal (free-induction decay) axes to produce detailed water and fat spectra associated with each small image voxel. The data were used to generate images of spectral parameters, e.g. peak-height images for each small voxel. Two variants of EPSI were performed; gradient-echo or spin-echo excitation with EPSI readout. These imaging methods were tested in commonly used rodent prostate cancers, including seven mice implanted with non-metastatic AT2.1 (n=3) and metastatic AT3.1 (n=4) prostate tumors on the hind leg, and 10 mice implanted with LNCaP prostate cancers in situ. The peak-height images derived from EPSI datasets provide more detailed tumor anatomy, improved signal-to-noise and contrast-to-noise ratios compared with the gradient-echo or spin-echo images at all echo times. The results suggest that HiSS MRI data from small animal models of prostate cancer can be acquired using EPSI, and that this approach improves imaging of heterogeneous tissue and vascular environments inside the tumors compared with conventional MR techniques.


Psychological and behavioral predictors of body fat distribution: age and gender effects.
Abdominal fat has been shown to be associated with several adverse outcomes including diabetes, cardiovascular disease, and hypertension. Risk factors for abdominal fatness include genetic effects, age, and gender. Most recently, it has been hypothesized that psychological factors, as well as behavioral factors, may play a part in where fat is distributed. The purpose of this study was to assess the longitudinal predictive power of psychological variables (cynicism, anger, anxiety, and depression) measured in 1987 on waist-hip ratio (WHR) measured from 1992 to 1994 among different age and gender groups, as well as to test if alcohol consumption or smoking (measured in 1990) would mediate any of the relationships found. Data from the Swedish Adoption/Twin Study of Aging (n = 1392; average age: 58 years for middle-aged group and 74 years for older group; 58% female) were analyzed using a maximum-likelihood regression model where age, gender, and age by gender effects were assessed. Cynicism and anxiety predicted WHR in middle-aged subjects regardless of gender. Cynicism explained 2.5% of the variance in WHR and anxiety explained 1.7% of the variance in WHR. Anger predicted WHR in males regardless of age, explaining 4.0% of the variance; depression predicted WHR only in middle-aged females, explaining 2.0% of the variance. All analyses adjusted for body mass index, and neither alcohol consumption or smoking status mediated the relationships. These findings are suggestive with regard to the hypotheses that certain psychological states and behaviors may be associated with increased abdominal fatness.


Transgenic overexpression of the alpha-synuclein interacting protein synphilin-1 leads to behavioral and neuropathological alterations in mice.
Synphilin-1 has been identified as an interacting protein of alpha-synuclein, Parkin, and LRRK2, proteins which are mutated in familial forms of Parkinson disease (PD). Subsequently, synphilin-1 has also been shown to be an intrinsic component of Lewy bodies in sporadic PD. In order to elucidate the role of synphilin-1 in the pathogenesis of PD, we generated transgenic mice overexpressing wild-type and mutant (R621C) synphilin-1 driven by a mouse prion protein promoter. Transgenic expression of both wild-type and the R621C variant synphilin-1 resulted in increased dopamine levels of the nigrostriatal system in 3-month-old mice. Furthermore, we found pathological ubiquitin-positive inclusions in cerebellar sections and dark-cell degeneration of Purkinje cells. Both transgenic mouse lines showed significant reduction of motor skill learning and motor performance. These findings suggest a pathological role of overexpressed synphilin-1 in vivo and will help to further elucidate the mechanisms of protein aggregation and neuronal cell death.


Accelerated osteoblastic differentiation in patient-derived dental pulp stem cells carrying a gain-of-function mutation of TRPV4 associated with metatropic dysplasia.
Metatropic dysplasia (MD) is a congenital skeletal dysplasia characterized by severe platyspondyly and dumbbell-like long-bone deformities. These skeletal phenotypes are predominantly caused by autosomal dominant gain-of-function (GOF) mutations in transient receptor potential vanilloid 4 (TRPV4), which encodes a nonselective Ca2+-permeable cation channel. Previous studies have shown that constitutive TRPV4 channel activation leads to irregular chondrogenic proliferation and differentiation, and thus to the disorganized endochondral ossification seen in MD. Therefore, the present study investigated the role of TRPV4 in osteoblast differentiation and MD pathogenesis. Specifically, the behavior of osteoblasts differentiated from patient-derived dental pulp stem cells carrying a heterozygous single base TRPV4 mutation, c.1855C > T (p.L619F) was compared to that of osteoblasts differentiated from isogenic control cells (in which the mutation was corrected using the CRISPR/Cas9 system). The mutant osteoblasts exhibited enhanced calcification (indicated by intense Alizarin Red S staining), increased intracellular Ca2+ levels, strongly upregulated runt-related transcription factor 2 and osteocalcin expression, and increased expression and nuclear translocation of nuclear factor-activated T cell c1 (NFATc1) compared to control cells. These results suggest that the analyzed TRPV4 GOF mutation disrupts osteoblastic differentiation and induces MD-associated disorganized endochondral ossification by increasing Ca2+/NFATc1 pathway activity. Thus, inhibiting the NFATc1 pathway may be a promising potential therapeutic strategy to attenuate skeletal deformities in MD.


Histological confirmation of breast cancer registration and self-reporting in England and Wales: a cohort study within the UK Collaborative Trial of Ovarian Cancer Screening.
In research studies, accurate information of cancer diagnosis is crucial. In women with breast cancer (BC), we compare cancer registration (CR) in England/Wales and self-reporting with independent confirmation. In the UK Collaborative Trial of Ovarian Cancer Screening, notification of BC diagnosed between randomisation and 31 December 2009 was obtained through (1) CR (17 October 2011) and (2) self-reporting using postal-questionnaire. Breast cancer was confirmed using a detailed questionnaire (BC questionnaire BCQ) completed by the treating clinician (gold standard). Apparent sensitivity and positive-predictive value of CR/self-reporting vs BCQ were calculated. Of 1065 women with possible BC notification, diagnosis was confirmed in 932 (87.5%). A total of 3.1% (28 out of 918) of BC CR and 12.4% (128 out of 1032) of women with self-reported BC only had in-situ carcinoma on BCQ. Another 4.6% (43 out of 932) of BCQ-confirmed cancer did not have a BC registration, and 3.6% (34 out of 932) did not self-report BC. Apparent sensitivity of CR and self-reporting vs BCQ were 95.4 and 96.4%, respectively. Positive-predictive value of self-reporting (87.1%) was significantly lower than that of CR (96.8%). Women aged<65 were more likely to over report in-situ carcinoma as BC. Overall, 73 (6.8%) women would have been misclassified/missed if CR, and 167 (15.6%) if self-reporting data alone was used. This study confirms the reliability of BC registration in England/Wales and highlights the fact that 1 in 10 women self-reporting BC might only have in-situ breast carcinoma.


Development of an MRI biomarker sensitive to tetrameric visual arrestin 1 and its reduction via light-evoked translocation in vivo.
Rod tetrameric arrestin 1 (tet-ARR1), stored in the outer nuclear layer/inner segments in the dark, modulates photoreceptor synaptic activity; light exposure stimulates a reduction via translocation to the outer segments for terminating G-protein coupled phototransduction signaling. Here, we test the hypothesis that intraretinal spin-lattice relaxation rate in the rotating frame (1/T1ρ), an endogenous MRI contrast mechanism, has high potential for evaluating rod tet-ARR1 and its reduction via translocation. Dark- and light-exposed mice (null for the ARR1 gene, overexpressing ARR1, diabetic, or wild type with or without treatment with Mn2+, a calcium channel probe) were studied using 1/T1ρ MRI. Immunohistochemistry and single-cell recordings of the retinas were also performed. In wild-type mice with or without treatment with Mn2+, 1/T1ρ of avascular outer retina (64% to 72% depth) was significantly (P < 0.05) greater in the dark than in the light; a significant (P < 0.05) but opposite pattern was noted in the inner retina (<50% depth). Light-evoked outer retina Δ1/T1ρ was absent in ARR1-null mice and supernormal in overexpressing mice. In diabetic mice, the outer retinal Δ1/T1ρ pattern suggested normal dark-to-light tet-ARR1 translocation and chromophore content, conclusions confirmed ex vivo. Light-stimulated Δ1/T1ρ in inner retina was linked to changes in blood volume. Our data support 1/T1ρ MRI for noninvasively assessing rod tet-ARR1 and its reduction via protein translocation, which can be combined with other metrics of retinal function in vivo.


Mechanistic studies of the mRNA transcription cycle.
We have now completed an atomic crystallographic model of the 12-subunit yeast RNA polymerase II in elongation mode, with DNA and RNA in the active-centre cleft, and the NTP substrate at the growing end of the RNA. From these studies has emerged a detailed three-dimensional view of mRNA elongation. We have extended this structural analysis to a polymerase elongation complex bound by the transcript cleavage factor TFIIS (transcription factor IIS), which is required for polymerase escape from DNA arrest sites. A detailed model of this complex reveals a single tuneable active site for RNA polymerization and cleavage, and changes in the position of the RNA and polymerase domains, reflecting the dynamic nature of the elongation complex. An additional structure of a polymerase CTD (C-terminal domain) phosphopeptide bound by the 3'-RNA processing factor Pcf11 provides insights into the coupling of transcription elongation to mRNA processing. The structure of the CTD phosphatase Scp1 trapped in an intermediary enzymatic state explains CTD dephosphorylation during recycling of the polymerase. We also recently reported the first crystal structure of a Mediator subcomplex, which reveals an extended helical fold with a conserved hinge.


Structure of Co-2 × 2 nanoislands grown on Ag/Ge(111)-√3 × √3 surface studied by scanning tunneling microscopy.
We have found that Co-2 × 2 islands grown on an Ag/Ge(111)-√3 × √3 surface have hcp structure with the (11-20) orientation. The island evolution involves transformation of the unit cell shape from parallelogram into rectangular, which is accompanied by the island shape transformation from hexagonal into stripe-like. Identified are two crystallographic directions for the island growth, the pseudo-[0001] and the pseudo-[1-100]. We have observed the occurrence of a lateral shift between the topmost and the underlying bilayers in the case of the island growth along the pseudo-[0001] direction. In contrast, the topmost and the underlying bilayers are unshifted for the growth along the pseudo-[1-100] direction.


Factors affecting metal concentrations in the upper sediment layer of intertidal reedbeds along the river Scheldt.
Factors that play a role in determining metal accumulation in sediments of 26 intertidal marshes which are mainly vegetated by reed plants (Phragmites australis) were assessed along the Scheldt estuary (Belgium and The Netherlands). In the upper 20 cm sediment layer, several physico-chemical properties (clay, silt and sand content, organic matter, carbonate and chloride content, pH and conductivity) and aqua regia extractable metals (Cd, Cr, Cu, Ni, Pb, Zn) were determined. The sediments were significantly contaminated with trace metals. The Cd concentrations often exceeded the Flemish soil remediation thresholds for nature areas, whereas Cr, Cu and Zn levels indicated moderate contamination. Pb concentrations occasionally were high, whereas Ni concentrations leaned towards background values. Organic matter was the single most important predictor variable for total metal contents in regression models, except for Cr. Additional significant predictor variables were clay or chloride content, depending on the metal. Observed metal concentrations at sites within a range of a few km from specific point-sources of metals (e.g. shipyards, industrial areas with metallurgic activities, affluents, major motorways) were somewhat higher than predicted by the models, whereas they were lower than predicted at sites which are regularly subjected to flooding by water of high salinity. The ratio between observed and predicted concentrations seems to be a valuable tool for the identification of areas which are specifically impacted by point sources.


Initial preference for drinking goal in the treatment of alcohol problems: I. Baseline differences between abstinence and non-abstinence groups.
To compare baseline characteristics of clients initially preferring abstinence with those preferring non-abstinence at the screening stage of a randomized controlled trial of treatment for alcohol problems (UKATT) and to identify predictors of goal preference from client characteristics present before the preference was stated. From discussions with clients entering the trial (N = 742), screeners noted whether clients were aiming for abstinence 'probably yes' or 'probably no'. Differences between the two groups thus formed were explored by univariate comparisons among client characteristics recorded at baseline assessment and by logistic regression analysis with pre-existing characteristics as independent variables. Across all UKATT sites, 54.3% of clients expressed a preference for abstinence and 45.7% for non-abstinence. In univariate comparisons, clients preferring abstinence were significantly (P < 0.01) more likely to: (i) be female, (ii) be unemployed, (iii) report drinking more heavily but less frequently, (iv) have been detoxified in the 2 weeks prior to assessment, (v) report more alcohol problems, (vi) be in the action stage of change, (vii) report greater negative expectancies of drinking, (viii) report greater mental and physical ill-health, (ix) report less social support for drinking and (x) be more confident of their ability to resist heavy drinking in tempting situations. In the logistic regression model, the strongest predictors of goal preference were gender, drinking pattern, recent detoxification and social support for drinking. The implications of these findings for service delivery are best considered in conjunction with findings from a companion paper reporting treatment outcomes associated with each goal preference.


Forest cover mapping in post-Soviet Central Asia using multi-resolution remote sensing imagery.
Despite rapid advances and large-scale initiatives in forest mapping, reliable cross-border information about the status of forest resources in Central Asian countries is lacking. We produced consistent Central Asia forest cover (CAFC) maps based on a cost-efficient approach using multi-resolution satellite imagery from Landsat and MODIS during 2009-2011. The spectral-temporal metrics derived from 2009-2011 Landsat imagery (overall accuracy of 0.83) was used to predict sub-pixel forest cover on the MODIS scale for 2010. Accuracy assessment confirmed the validity of MODIS-based forest cover map with a normalized root-mean-square error of 0.63. A general paucity of forest resources in post-Soviet Central Asia was indicated, with 1.24% of the region covered by forest. In comparison to the CAFC map, a regional map derived from MODIS Vegetation Continuous Fields tended to underestimate forest cover, while the Global Forest Change product matched well. The Global Forest Resources Assessments, based on individual country reports, overestimated forest cover by 1.5 to 147 times, particularly in the more arid countries of Turkmenistan and Uzbekistan. Multi-resolution imagery contributes to regionalized assessment of forest cover in the world's drylands while developed CAFC maps (available at https://data.zef.de/ ) aim to facilitate decisions on biodiversity conservation and reforestation programs in Central Asia.


The effects of a single injection of dexamethasone-21-isonicotinate on the lymphocyte functions of dairy cows at two weeks post partum.
Dexamethasone is a potent therapeutic for treatment of the fatty liver syndrome or primary ketosis in post partum dairy cows. Reservations exist, however, among practitioners with respect to the risk of immunosuppression induced by corticosteroids. The aim of this study was to investigate the effect of a single injection of dexamethasone-21-isonicotinate on distinct immune functions of postpartum dairy cows because only scarce information is available on the effects of corticosteroid preparations when administered at a dosage and frequency for treatment of the fatty liver syndrome or primary ketosis. Sixteen Swedish red-pied dairy cows, between days 9 and 15 post partum, were allotted to either a control group (n = 8) or a treatment group (n = 8). The cows in the treatment group received a single intramuscular injection of a dexamethasone-21-isonicotinate suspension at a dosage of 0.02 mg/kg i.m. at the start of the experiment. White blood cell counts and selected lymphocyte functions (lymphocyte proliferation, expression of lymphocyte markers and the b2 and a4 chain of adhesion molecules belonging to the integrin family) and some parameters of the energy metabolism (glucose, insulin) were determined before the administration of corticosteroids (day 0) and subsequently at days 2, 4, 7 and 9 of the experiment. Changes in glucose and insulin were within the target range for treatment of the fatty liver syndrome or primary ketosis. Significant (P < 0.05) increases in the number of circulating white blood cells were observed in treated cows on the second day following treatment which was exclusively caused by an increase in the number of circulating neutrophils. Lymphocyte blastogenesis in response to ConA and the percentages of lymphocytes positive for CD2, CD4, CD8, CD49d and CD18 as well as the intensity of CD49d expression did not differ between the treatment and control groups. There was, however, a significant reduction (P < 0.01) in the intensity of CD18 expression on lymphocytes in the treated animals on the fourth day after treatment. In conclusion, a single administration of dexamethasone-21-isonicotinate in a dosage of 0.02 mg/kg i.m. at two weeks post partum in healthy cows had a significant but highly transient effect on CD18 expression on lymphocytes and the number of peripheral blood neutrophils, but did not affect lymphocyte blastogenesis or lymphocyte subpopulation patterns in peripheral blood.


Malignant pleural mesothelioma: predictors and staging.
Malignant pleural mesothelioma remains a rapidly fatal cancer with few effective therapies. Unusual anatomic features complicate determination of stage and prognosis for individual patients. Validation of staging criteria has been difficult given the rarity of the disease and the fact that only a minority of patients undergo surgical resection with pathological examination of their tumors. Thus, additional heuristic factors and algorithms have been taken into account by clinicians to estimate prognosis and inform discussion of appropriate management strategies or clinical research protocols with patients.


Protective factors for psychotic experiences amongst adolescents exposed to multiple forms of victimization.
Experiencing multiple types of victimization (poly-victimization) during adolescence is associated with the onset of psychotic experiences (such as hearing voices, having visions, or being extremely paranoid). However, many poly-victimized adolescents will not develop such subclinical phenomena and the factors that protect them are unknown. This study investigated whether individual, family, or community-level characteristics were associated with an absence of psychotic experiences amongst poly-victimized adolescents. Participants were from the Environmental Risk (E-Risk) Longitudinal Twin Study, a nationally-representative cohort of 2232 UK-born twins. Exposure to seven different types of victimization between ages 12-18 was ascertained using a modified version of the Juvenile Victimization Questionnaire at age 18. Adolescents were also interviewed about psychotic experiences at age 18. Protective factors were measured at ages 12 and 18. We found that exposure to poly-victimization during adolescence was associated with age-18 psychotic experiences (OR = 4.62, 95% CI 3.59-5.94, P < 0.001), but more than a third of the poly-victimized adolescents reported having no psychotic experiences (40.1%). Greater social support was found to be protective against adolescent psychotic experiences even amongst those exposed to poly-victimization. Engaging in physical activity and greater neighborhood social cohesion were also associated with a reduced likelihood of age-18 psychotic experiences in the whole sample, with non-significant trends in the poly-victimized group. Increasing social support and promoting physical activity appear to be important areas for future research into the development of preventive interventions targeting adolescent psychotic experiences. This adds further weight to calls to increase the promotion of these factors on a public health scale.


Envisioning Minimally Disruptive Opioid Use Disorder Care.
Most people who need and want treatment for opioid addiction cannot access it. Among those who do get treatment, only a fraction receive evidence-based, life-saving medications for opioid use disorder (MOUD). MOUD access is not simply a matter of needing more clinicians or expanding existing treatment capacity. Instead, many facets of our health systems and policies create unwarranted, inflexible, and punitive practices that create life-threatening barriers to care. In the USA, opioid use disorder care is maximally disruptive. Minimally disruptive medicine (MDM) is a framework that focuses on achieving patient goals while imposing the smallest possible burden on patients' lives. Using MDM framing, we highlight how current medical practices and policies worsen the burden of treatment and illness, compound life demands, and strain resources. We then offer suggestions for programmatic and policy changes that would reduce disruption to the lives of those seeking care, improve health care quality and delivery, begin to address disparities and inequities, and save lives.


Mps1 at kinetochores is essential for female mouse meiosis I.
In female meiosis, chromosome missegregations lead to the generation of aneuploid oocytes and can cause the development of trisomies or infertility. Because mammalian female meiosis I is error prone, the full functionality of control mechanisms, such as the spindle assembly checkpoint (SAC), has been put into question. The SAC monitors the correct orientation, microtubule occupancy and tension on proteinaceous structures named kinetochores. Although it has been shown previously that the SAC exists in meiosis I, where attachments are monopolar, the role of microtubule occupancy for silencing the SAC and the importance of certain essential SAC components, such as the kinase Mps1, are unknown in mammalian oocytes. Using a conditional loss-of-function approach, we address the role of Mps1 in meiotic progression and checkpoint control in meiosis I. Our data demonstrate that kinetochore localization of Mps1 is required for the proper timing of prometaphase and is essential for SAC control, chromosome alignment and aurora C localization in meiosis I. The absence of Mps1 from kinetochores severely impairs chromosome segregation in oocyte meiosis I and, therefore, fertility in mice. In addition, we settle a long-standing question in showing that kinetochore-microtubule attachments are present in prometaphase I at a time when most of the SAC protein Mad2 disappears from kinetochores.


Schismatothelinae spiders (Araneae, Mygalomorphae, Theraphosidae) from Colombia: four new species and an approach to their diversity.
The spider subfamily Schismatothelinae from Colombia is revised. One new species of Euthycaelus Simon 1889 and three new species of Schismatothele Karsch 1879 are named, as well as new geographical records provided. E. guane sp. nov. from Santander, S. hacaritama sp. nov. from Norte de Santander, S. olsoni sp. nov. from Norte de Santander and Táchira (Venezuela), and S. weinmanni sp. nov. from Cundinamarca are herein described, diagnosed and illustrated. Schismatothele is newly recorded from Colombia. Morphological aspects and diversity of the Ischnocolinae and Schismatothelinae from Colombia are discussed. An identification key to species of these subfamilies from Colombia is provided.


Bile bilirubin pigment analysis in disorders of bilirubin metabolism in early infancy.
Early and accurate diagnosis of Crigler-Najjar syndrome, which causes prolonged unconjugated hyperbilirubinaemia in infancy, is important, as orthotopic liver transplantation is the definitive treatment. To determine whether bilirubin pigment analysis of bile in infants with prolonged unconjugated hyperbilirubinaemia provides useful diagnostic information in the first 3 months of life. Retrospective review of patients with prolonged unconjugated hyperbilirubinaemia referred to the liver unit, Birmingham Children's Hospital, for the diagnosis of Crigler-Najjar syndrome. Bile bilirubin pigment composition was determined by high performance liquid chromatography. Initial diagnoses were made based on the result of bile bilirubin pigment composition. Final diagnoses were made after reviewing the clinical course, response to phenobarbitone, repeat bile bilirubin pigment composition analysis, and genetic studies. Between 1992 and 1999, nine infants aged less than 3 months of age with prolonged hyperbilirubinaemia underwent bile bilirubin pigment analyses. Based on these, two children were diagnosed with Crigler-Najjar syndrome (CNS) type 1, six with CNS type 2, and one with Gilbert's syndrome. Five children whose initial diagnosis was CNS type 2 had resolution of jaundice and normalisation of serum bilirubin after discontinuing phenobarbitone, and these cases were thought to be normal or to have Gilbert's syndrome. One of the initial cases of CNS type 1 responded to phenobarbitone with an 80% reduction in serum bilirubin consistent with CNS type 2. In all, the diagnoses of six cases needed to be reviewed. Early bile pigment analysis, performed during the first 3 months of life, often shows high levels of unconjugated bilirubin or bilirubin monoconjugates, leading to the incorrect diagnosis of both type 1 and type 2 Crigler-Najjar syndrome.


EUSTAR biobanking: recommendations for the collection, storage and distribution of biospecimens in scleroderma research.
The European League Against Rheumatism Scleroderma Trials and Research Group (EUSTAR) has established an online database with clinical data of currently more than 8200 patients with systemic sclerosis (SSc). In addition to clinical research, EUSTAR fosters biomolecular studies to develop novel biomarkers and therapies for SSc. High-quality biospecimens are the basis for successful biomolecular studies. The EUSTAR biobanking group has therefore developed recommendations to standardise the collection, storage and distribution of SSc biospecimens at EUSTAR centres. These recommendations consider the scientific challenges associated with biomolecular research in SSc and the organisational requirements of EUSTAR. They were approved by the EUSTAR executive committee as well as the EUSTAR board. Once they become effective, these recommendations will be the basis for international EUSTAR studies with large numbers of SSc biospecimens. These recommendations might also be followed by other SSc consortia to enable exchange of biosamples between different SSc initiatives and might serve as a template for biobanking initiatives in other rheumatic diseases.


Combinatorial Use of Chitosan Nanoparticles, Reversine, and Ionising Radiation on Breast Cancer Cells Associated with Mitosis Deregulation.
Breast cancer is the most commonly occurring cancer in women worldwide and the second most common cancer overall. The development of new therapies to treat this devastating malignancy is needed urgently. Nanoparticles are one class of nanomaterial with multiple applications in medicine, ranging from their use as drug delivery systems and the promotion of changes in cell morphology to the control of gene transcription. Nanoparticles made of the natural polymer chitosan are easy to produce, have a very low immunogenic profile, and diffuse easily into cells. One hallmark feature of cancer, including breast tumours, is the genome instability caused by defects in the spindle-assembly checkpoint (SAC), the molecular signalling mechanism that ensures the timely and high-fidelity transmission of the genetic material to an offspring. In recent years, the use of nanoparticles to treat cancer cells has gained momentum. This is in part because nanoparticles made of different materials can sensitise cancer cells to chemotherapy and radiotherapy. These advances prompted us to study the potential sensitising effect of chitosan-based nanoparticles on breast cancer cells treated with reversine, which is a small molecule inhibitor of Mps1 and Aurora B that induces premature exit from mitosis, aneuploidy, and cell death, before and after exposure of the cancer cells to X-ray irradiation. Our measurements of metabolic activity as an indicator of cell viability, DNA damage by alkaline comet assay, and immunofluorescence using anti-P-H3 as a mitotic biomarker indicate that chitosan nanoparticles elicit cellular responses that affect mitosis and cell viability and can sensitise breast cancer cells to X-ray radiation (2Gy). We also show that such a sensitisation effect is not caused by direct damage to the DNA by the nanoparticles. Taken together, our data indicates that chitosan nanoparticles have potential application for the treatment of breast cancer as adjunct to radiotherapy.


A Comparative Pharmacokinetics Study of the Anti-Parkinsonian Drug Pramipexole.
The present study aimed to compare pharmacokinetic parameters of two pramipexole 0.25 mg formulations in order to show bioequivalence. The study was conducted in a randomized, open-label, two-period, two-sequence, and crossover design, involving 23 healthy volunteers. One of the 0.25 mg formulations of pramipexole evaluated in the study was manufactured by PT Dexa Medica, Palembang, Indonesia, the other, used as the reference, by Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim am Rhein, Germany. All eligible subjects were required to fast before each drug administration period, which was separated by a one-week washout period. Pramipexole concentrations in plasma were assayed using a validated ultra performance liquid chromatography with mass spectrometry (UPLC-MS/MS) detector. The evaluated pharmacokinetic parameters included the area under the plasma concentration curve from time zero to the last observed measurable concentration (AUC0-t), the area under the plasma concentration curve extrapolated to infinite time (AUC0-∞), the maximum plasma concentration (Cmax), the time to reach Cmax (tmax), and the plasma concentration half-life (t1/2). To evaluate the bioequivalence of those two pramipexole formulations, 90% confidence intervals (CIs) for geometric mean ratios of both formulations were calculated for AUC and Cmax parameters, while tmax and t1/2 differences were analyzed on the non-transformed data using Wilcoxon matched-pairs and a Student's paired t-test, respectively. The 90% CIs for the geometric mean ratios of the two pramipexole formulations were 95.89% (90.73%-101.34%), 95.53% (89.75%-101.68%), and 92.11% (84.35%-100.58%) for AUC0-t, AUC0-∞, and Cmax, respectively. There were no statistically significant differences for tmax and t1/2 between the two pramipexole formulations. It is concluded that two pramipexole formulations in this study were bioequivalent.


Adverse food reactions in dogs and cats.
Adverse food reactions (AFR) are a common problem that may cause cutaneous and/or gastrointestinal signs in dogs and cats. They comprise food intolerance, food intoxication, and food allergy. Response to a dietary elimination trial and recurrence of signs during dietary provocation remain the centerpiece of diagnosis and management of dogs and cats with AFR. Response to an elimination trial is frequently observed in dogs and cats with chronic idiopathic enteropathies. However, only a fraction of them relapse after a dietary challenge. These animals may have mild to enteritis and/or colitis and benefit from various additional properties of the elimination diet.


The development of a clinical trial to determine if watchful waiting is an acceptable alternative to routine herniorrhaphy for patients with minimal or no hernia symptoms.
This article describes the development and implementation of a randomized clinical trial designed to answer the question: Is watchful waiting an acceptable alternative to operation for men with asymptomatic or minimally symptomatic inguinal hernias? A clinical trial has been designed to compare watchful waiting and operation for men with an asymptomatic or a relatively asymptomatic inguinal hernia. Men are randomized to watchful waiting or a standard open operation, the Lichtenstein tension-free hernia repair, and are followed for a minimum of 2 years. The target sample size of 753 patients was chosen so that the trial would have power sufficiently high to detect a clinically meaningful difference between treatment groups in either of the two primary outcomes as measured at 2 years: pain or discomfort interfering with normal activities and the physical component summary score of the SF-36 health-related quality-of-life survey. The study was begun in five centers located in both community and academic environments. At 18 months, a sixth site was added and at 28 months, after enrollment of 145 patients, one of the centers was terminated for reasons related to inadequate followup; all data from this center were deleted. As a routine measure, an independent experienced trial manager audited all clinical sites. Enrollment of patients began in January 2000 and will end on December 31, 2002. As of November 1, 2002, 637 patients had been randomized, 85% of the target enrollment. An additional 2,115 patients were screened but not randomized, yielding a recruitment rate of 23.1%. Analysis and publication of the results of the study will take place on completion of the minimum 2-year followup period for all patients. A trial to compare the outcomes of watchful waiting and operation for management of inguinal hernias in men is needed to provide data to surgeons and to patients that can aid in choice of treatment. A description of the design of such a trial is presented.


Ethical concerns with online direct-to-consumer pharmaceutical companies.
In recent years, online direct-to-consumer pharmaceutical companies have been created as an alternative method for individuals to get prescription medications. While these companies have noble aims to provide easier, more cost-effective access to medication, the fact that these companies both issue prescriptions (via entirely online medical reviews that can have no direct contact between physician and patient) as well as distribute and ship medications creates multiple ethical concerns. This paper aims to explore two in particular. First, this model creates conflicts of interest for the physicians hired by these companies to write prescriptions. Second, the lack of direct contact from physicians may be harmful to prospective patients. After analysing these issues, this paper argues that there ought to be further consideration for regulation and oversight for these companies.


Combining data assimilation and machine learning to build data-driven models for unknown long time dynamics-Applications in cardiovascular modeling.
We propose a method to discover differential equations describing the long-term dynamics of phenomena featuring a multiscale behavior in time, starting from measurements taken at the fast-scale. Our methodology is based on a synergetic combination of data assimilation (DA), used to estimate the parameters associated with the known fast-scale dynamics, and machine learning (ML), used to infer the laws underlying the slow-scale dynamics. Specifically, by exploiting the scale separation between the fast and the slow dynamics, we propose a decoupling of time scales that allows to drastically lower the computational burden. Then, we propose a ML algorithm that learns a parametric mathematical model from a collection of time series coming from the phenomenon to be modeled. Moreover, we study the interpretability of the data-driven models obtained within the black-box learning framework proposed in this paper. In particular, we show that every model can be rewritten in infinitely many different equivalent ways, thus making intrinsically ill-posed the problem of learning a parametric differential equation starting from time series. Hence, we propose a strategy that allows to select a unique representative model in each equivalence class, thus enhancing the interpretability of the results. We demonstrate the effectiveness and noise-robustness of the proposed methods through several test cases, in which we reconstruct several differential models starting from time series generated through the models themselves. Finally, we show the results obtained for a test case in the cardiovascular modeling context, which sheds light on a promising field of application of the proposed methods.


The Role of M2 Macrophages in the Progression of Chronic Kidney Disease following Acute Kidney Injury.
Acute kidney injury (AKI) is a major risk factor in the development of chronic kidney disease (CKD). However, the mechanisms linking AKI to CKD remain unclear. We examined the alteration of macrophage phenotypes during an extended recovery period following ischemia/reperfusion injury (IRI) and determine their roles in the development of fibrosis. The left renal pedicle of mice was clamped for 40 min. To deplete monocyte/macrophage, liposome clodronate was injected or CD11b-DTR and CD11c-DTR transgenic mice were used. Throughout the phase of IRI recovery, M2-phenotype macrophages made up the predominant macrophage subset. On day 28, renal fibrosis was clearly shown with increased type IV collagen and TGF-β. The depletion of macrophages induced by the liposome clodronate injection improved renal fibrosis with a reduction of kidney IL-6, type IV collagen, and TGF-β levels. Additionally, the adoptive transfer of the M2c macrophages partially reversed the beneficial effect of macrophage depletion, whereas the adoptive transfer of the M1 macrophages did not. M2 macrophages isolated from the kidneys during the recovery phase expressed 2.5 fold higher levels of TGF-β than the M1 macrophages. The injection of the diphtheria toxin into CD11b or CD11c-DTR transgenic mice resulted in lesser depletion or no change in M2 macrophages and had little impact on renal fibrosis. Although M2 macrophages are known to be indispensible for short-term recovery, they are thought to be main culprit in the development of renal fibrosis following IRI.


Peripheral Oxytocin Predicts Higher-Level Social Cognition in Men Regardless of Empathy Quotient.
Pharmaceutical oxytocin (OT) administration is being tested as a novel treatment for social deficits in various psychiatric populations. However, little is known about how naturally occurring variation in peripheral OT relates to differences in social cognition. This study investigates whether healthy individuals with very high or very low levels of empathy differ in endogenous OT and whether OT plasma levels can predict performance in a mentalizing task. 40 healthy men were included based upon their score above the 85th or below the 15th percentile of the empathy quotient inventory 1. Participants' abilities to interpret social information was assessed via the Social Detection Task 2. Plasma OT levels were analyzed using enzyme immunoassay. OT plasma levels predicted mentalizing performance for more ambiguous social scenes (i. e., difficult items) for all participants. We found no group differences in OT plasma levels between subjects with high and low empathy. These findings confirm a link between peripheral OT and the ability to read subtle nonverbal social cues in healthy individuals, which is independent of self-reported empathy.


Current management of the vascular subtype of Ehlers-Danlos syndrome.
Vascular Ehlers-Danlos syndrome (vEDS) is the most severe form of EDS, affecting the synthesis of type III collagen. It is notable for decreased life expectancy and morbidity, including spontaneous vessel rupture. The present review summarizes recent findings that have improved the ability to manage and delineate the natural history of vEDS. Recent EDS consortium guidelines for the diagnosis of vEDS have emerged and outlined clinical features and molecular diagnostic tools to help facilitate rapid diagnosis. Although medical interventions to help halt the disease progression remain limited, improved awareness of vEDS by patients and practitioners have resulted in increased average life expectancy. Early excitement with celiprolol has been tempered by a lack of high-quality studies. Likewise, the creation of multidisciplinary care teams and tertiary referral centers is helping improve outcomes. Unfortunately, there remain limitations in terms of the surgical management (including more advanced endovascular techniques) of these patients and the morbidity associated with these interventions. Although new consensus guidelines have emerged to facilitate the diagnosis of those with vEDS, there remain limitations in terms of interventions and medical therapy that can be provided for these patients. Life expectancy does appear to be improving however with increased awareness and coordinated multidisciplinary efforts among medical geneticists, general practitioners, and interventionalists alike.


Inhaled nitric oxide for premature infants with severe respiratory failure.
Inhaled nitric oxide is a controversial treatment for premature infants with severe respiratory failure. We conducted a multicenter, randomized, blinded, controlled trial to determine whether inhaled nitric oxide reduced the rate of death or bronchopulmonary dysplasia in such infants. We randomly assigned 420 neonates, born at less than 34 weeks of gestation, with a birth weight of 401 to 1500 g, and with respiratory failure more than four hours after treatment with surfactant to receive placebo (simulated flow) or inhaled nitric oxide (5 to 10 ppm). Infants with a response (an increase in the partial pressure of arterial oxygen of more than 10 mm Hg) were weaned according to protocol. Treatment with study gas was discontinued in infants who did not have a response. The rate of death or bronchopulmonary dysplasia was 80 percent in the nitric oxide group, as compared with 82 percent in the placebo group (relative risk, 0.97; 95 percent confidence interval, 0.86 to 1.06; P=0.52), and the rate of bronchopulmonary dysplasia was 60 percent versus 68 percent (relative risk, 0.90; 95 percent confidence interval, 0.75 to 1.08; P=0.26). There were no significant differences in the rates of severe intracranial hemorrhage or periventricular leukomalacia. Post hoc analyses suggest that rates of death and bronchopulmonary dysplasia are reduced for infants with a birth weight greater than 1000 g, whereas infants weighing 1000 g or less who are treated with inhaled nitric oxide have higher mortality and increased rates of severe intracranial hemorrhage. The use of inhaled nitric oxide in critically ill premature infants weighing less than 1500 g does not decrease the rates of death or bronchopulmonary dysplasia. Further trials are required to determine whether inhaled nitric oxide benefits infants with a birth weight of 1000 g or more.


Designing a successful HMD-based experience.
For entertainment applications, a successful virtual experience based on a head-mounted display (HMD) needs to overcome some or all of the following problems: entering a virtual world is a jarring experience, people do not naturally turn their heads or talk to each other while wearing an HMD, putting on the equipment is hard, and people do not realize when the experience is over. In the Electric Garden at SIGGRAPH 97, we presented the Mad Hatter's Tea Party, a shared virtual environment experienced by more than 1,500 SIGGRAPH attendees. We addressed these HMD-related problems with a combination of back story, see-through HMDs, virtual characters, continuity of real and virtual objects, and the layout of the physical and virtual environments.


Exploring the health-wealth nexus.
The causal links between health and economic resources have long concerned social scientists. We use four waves of data from the Panel Study of Income Dynamics (PSID) to analyze the impact of wealth upon an individual's health status. The difficulty in approaching this task that has bedeviled previous studies is that wealth may be endogenous; a priori, it is just as likely that changes in health affect wealth as vice versa. We argue that inheritance is a suitable instrument for the change in wealth, and implement a straightforward instrumental variables strategy to deal with this problem. Our results suggest that the causal relationship running from wealth to health may not be as strong as first appears. In the data, wealth exerts a positive and statistically significant effect on health status, but it is very small in magnitude. Instrumental variables estimation leaves the point estimate approximately the same, but renders it insignificantly different from zero. And even when the point estimate is increased by twice its standard error (S.E.), the quantitative effect is small. We conclude that the wealth-health connection is not driven by short run changes in wealth.


Rates of pelvic inflammatory disease and ectopic pregnancy in Australia, 2009-2014: ecological analysis of hospital data.
To analyse yearly rates of pelvic inflammatory disease (PID) and ectopic pregnancy (EP) diagnosed in hospital settings in Australia from 2009 to 2014. We calculated yearly PID and EP diagnosis rates in three states (Victoria, New South Wales, Queensland) for women aged 15-44 years using hospital admissions and emergency department (ED) attendance data, with population and live birth denominators. We stratified PID diagnoses as chlamydial-related or gonorrhoeal-related (Chlamydia trachomatis (CT)-related or Neisseria gonorrhoeae (NG)-related), acute, unspecified and chronic, and analysed variations by year, age and residential area using Poisson regression models. For PID, the rate of all admissions in 2014 was 63.3 per 100 000 women (95% CI 60.8 to 65.9) and of all presentations in EDs was 97.0 per 100 000 women (95% CI 93.9 to 100.2). Comparing 2014 with 2009, the rate of all PID admissions did not change, but the rate of all presentations in EDs increased (adjusted incidence rate ratio (aIRR) 1.34, 95% CI 1.24 to 1.45), and for admissions by PID category was higher for CT-related or NG-related PID (aIRR 1.73, 95% CI 1.31 to 2.28) and unspecified PID (aIRR 1.09, 95% CI 1.00 to 1.19), and lower for chronic PID (aIRR 0.84, 95% CI 0.74 to 0.95). For EP, in 2014 the rate of all admissions was 17.4 (95% CI 16.9 to 17.9) per 1000 live births and of all ED presentations was 15.6 (95% CI 15.1 to 16.1). Comparing 2014 with 2009, the rates of all EP admissions (aIRR 1.06, 95% CI 1.04 to 1.08) and rates in EDs (aIRR 1.24, 95% CI 1.18 to 1.31) were higher. PID and EP remain important causes of hospital admissions for female STI-associated complications. Hospital EDs care for more PID cases than inpatient departments, particularly for young women. Updated primary care data are needed to better understand PID epidemiology and healthcare usage.


Texture discrimination based on global feature alignments.
Three experiments are reported that examined the abilities of human observers to discriminate textures with identical distributions of orientation and spatial frequency. In Experiment 1, the stimuli consisted of low-pass filtered noise that was uniformly distributed and spatially isotropic. Observers were able to discriminate textures with identical image statistics when their frequencies were 1 cpd or less, but performance dropped off sharply for textures with higher frequencies. In Experiment 2, a novel procedure was employed with which it is possible to increase the high-frequency energy in the amplitude spectrum of a texture, while preserving the macroscopic alignments of its phase spectrum. The results reveal that this has little effect on performance, thus indicating that it is not spatial frequency per se that limits the abilities of observers to discriminate macroscopic texture patterns. When the phase spectra of these textures were randomly scrambled in Experiment 3, the frequency thresholds for discriminating textures reverted back to 1 cpd as was obtained in Experiment 1. These results provide strong evidence that human observers make use of two distinct procedures for discriminating patches of texture: One based on image statistics that is possible for all textures; and another based on macroscopic phase alignments that define features that are larger than 1°.


Use of treatment strategies in a moderated drinking program for women.
Little is known about the extent to which individuals participating in drinking reduction interventions use the drinking reduction strategies presented during treatment. In consideration of this issue, we advanced hypotheses about the impact of baseline drinking patterns on strategy use and the relationship of strategy use to drinking patterns over time. One hundred forty-four women who participated in a 10-week drinking reduction program were monitored over an 18-month posttreatment follow-up period. Results indicated that the frequency of baseline heavy drinking days and the frequency of baseline abstinent/light drinking days negatively predicted drinking reduction strategy use during treatment. Over the follow-up period, strategy use decreased; however, participants who received booster sessions had higher strategy use during the initial phase of follow-up. Although cross-lagged panel analysis revealed that strategy use during treatment predicted abstinent/light days at the 6-month follow-up assessment, this effect was moderated by baseline drinking patterns. These data indicated that the use of drinking reduction strategies is predictive of subsequent reduced drinking only in the early posttreatment period and only for baseline heavier drinkers. Future research is needed to further specify the interplay of strategy use and drinking outcomes and to develop interventions designed to encourage the continued use of strategies over extended periods of time.


Masturbation from judaism to victorianism.
This article demonstrates how masturbation, based on a misconception of Genesis 38:7-10, was judged harshly in both Judaism and Christianity, laying the foundation historically for social and religious hostility toward sex. Masturbation, known as the "secret sin," a threat to the human race, and an ontic evil, was condemned officially in 1054 by Pope Leo IX.From the medieval era to Victorianism there evolved new distortions of religion and science, so that masturbation was regarded as unnatural sex, murder, a diabolical practice, and the cause of two-thirds of all diseases and disorders including insanity, neurosis, and neurasthenia. Masturbation has historically served as the catalyst for social change in sexual attitudes.


Where and how breastfeeding promotion initiatives should focus its attention? A study from rural wardha.
In India, the practice of breastfeeding is almost universal, but initiation of breastfeeding is generally quite late and colostrum is discarded. Integrated Management of Neonatal and Childhood Illness (IMNCI) strategy recommended systematic assessment of breastfeeding and emphasized counseling of the mother on proper positioning and attachment of infant to the breast. To assess breastfeeding among mothers of below six months children in rural Wardha. The present cross-sectional study was undertaken in surrounding 23 villages of Kasturba Rural Health Training Center (KRHTC), Anji. Two Auxiliary Nurse Midwives (ANMs) trained in IMNCI paid house visits to 99 mothers during the study period and undertook the assessment of breastfeeding using IMNCI assessment form for young infants. Auxiliary Nurse Midwives observed and recorded the positioning and attachment of infant to the breast as per IMNCI guidelines. The data were entered and analyzed using Epi_Info (version 6.04d) software package. Most of the deliveries 94 (94.9%) took place in the healthcare facilities. Majority 61 (61.6%) newborn babies had received breastfeeding within half an hour. About half of the mothers had any of the feeding problems like feeding less than eight times in 24 h, giving any other food or drinks or is low weight for age. Significantly more mothers with feeding problems had problems in positioning and attachment of infant to the breast as compared with those mothers who did not have any feeding problems. In the settings, where practice of institutional delivery is high, the staff of healthcare facility should ensure education of the mothers regarding position and attachment of infant to the breast before discharge from the healthcare facility. At the village level, Village Health Nutrition Day (VHND) can be utilized for health education of future mothers and support for the breastfeeding mothers. The IMNCI assessment form for young infant should also include assessment of positioning of infant.


Relation between circulating angiotensin II type 1 receptor agonistic autoantibodies and soluble fms-like tyrosine kinase 1 in the pathogenesis of preeclampsia.
Placental and circulatory soluble fms-like tyrosine kinase 1 (sFlt1) has proven to be elevated in pregnant women with preeclampsia, a disease characterized by hypertension, proteinuria, and endothelial dysfunction. Recent studies also demonstrated an autoantibody against the angiotensin II type 1 (AT1) receptor (AT1-AA) in that disease. Both factors are discussed as key players in the etiology of preeclampsia. However, it has not yet been clarified whether these two circulating factors correlate and whether synergy determines the severity of pathology. AT1-AA was retrospectively determined by a bioassay and sFlt1 by an ELISA. Serum from second-trimester pregnancies with normal or abnormal uterine perfusion and in women at term with or without pregnancy pathology was analyzed. Most of the preeclamptic patients were characterized by high sFlt1 levels and the presence of AT1-AA, although the agonistic effects of the antibody did not correlate with the sFlt1 concentrations (P = 0.85). Although AT1-AA was also detected in second-trimester pregnancies evidencing abnormal uterine perfusion without later pathology, sFlt1 was not significantly elevated in these pregnancies, compared with those with normal uterine perfusion. However, whereas women with abnormal perfusion and later pregnancy pathology did not differ in AT1-AA, compared with those with normal outcome, sFlt1 was significantly increased. Again, the two factors did not correlate (P = 0.15). We conclude that AT1-AA bioactivity and sFlt1 concentrations do not correlate, are not mutually dependent, and are thus probably involved in distinct pathogenetic mechanisms. Both factors in combination may not be causative for the early impaired trophoblast invasion and pathological uterine perfusion.


Effects on subjective and objective alertness and sleep in response to evening light exposure in older subjects.
Evening bright light exposure is reported to ameliorate daytime sleepiness and age-related sleep complaints, and also delays the timing of circadian rhythms. We tested whether evening light exposure given to older adults with sleep-wake complaints would delay the timing of their circadian rhythms with respect to their sleep timing, thereby reducing evening sleepiness and improving subsequent sleep quality. We examined the impact of evening light exposure from two different light sources on subjective alertness, EEG activity during wakefulness, and sleep stages. Ten healthy older adults with sleep complaints (mean age=63.3 years; 6F) participated in a 13-day study. After three baseline days, circadian phase was assessed. On the evening of days 5-8 the subjects were exposed for 2h to either polychromatic blue-enriched white light or standard white fluorescent light, and on the following day circadian phase was re-assessed. Subjects were allowed to leave the laboratory during all but the two days when the circadian phase assessment took place. Evening assessments of subjective alertness, and wake and sleep EEG data were analyzed. Subjective alertness and wake EEG activity in the alpha range (9.75-11.25 Hz) were significantly higher during light exposures when compared to the pre-light exposure evening (p<0.05). The light exposures produced circadian phase shifts and significantly prolonged latency to rapid eye-movement (REM) sleep for both light groups (p<0.05). The increase in wake EEG alpha activity during the light exposures was negatively correlated with REM sleep duration (p<0.05). Evening light exposure could benefit older adults with early evening sleepiness, without negatively impacting the subsequent sleep episode.


Patient expectations did not predict outcome of drug and behavioral treatment of urgency urinary incontinence.
: This study aimed to determine whether expectations of treatment outcomes in women participating in a drug and behavioral treatment trial for urge urinary incontinence are related to patient factors, demographics, health-related locus of control, and treatment outcomes. : Baseline assessments included expectations (improvement in bladder condition, time to improvement in bladder condition, and duration of improvement) and the Medical Health Locus of Control (MHLC) scale. Outcomes were measured by the Patient Global Impression of Improvement scale (PGI-I) at the end of active treatment (10 weeks) and 8 months after trial start. : At baseline among 173 subjects, 114 (66%) believed their incontinence would get "very much better," 94 (55%) expected improvement by 1 month, and 111 (66%) expected improvement would last for the rest of their lives. There were no significant associations between baseline expectations or MHLC with the Patient Global Impression of Improvement scale at 10 weeks or 8 months. : Expectations of treatment outcome and MHLC did not predict eventual patient-reported treatment outcome in this sample of women with urge-predominant urinary incontinence participating in a trial of drug and behavioral therapy.


GPU-assisted high-resolution, real-time 3-D shape measurement.
This paper describes a Graphics Processing Unit (GPU)-assisted real-time three-dimensional shape measurement system. Our experiments demonstrated that the absolute coordinates calculation and rendering speed of a GPU is more than four times faster than that of a dual CPU workstation with the same graphics card. By implementing the GPU into our system, we realized simultaneous absolute coordinate acquisition, reconstruction and display at 30 frames per second with a resolution of approximately 266K points per frame. Moreover, a 2+1 phase-shifting algorithm was employed to alleviate the measurement error caused by motion. Applications of the system include medical imaging, manufacturing, entertainment, and security.


Comparison of results of thoracic radiography, cytologic evaluation of bronchoalveolar lavage fluid, and histologic evaluation of lung specimens in dogs with respiratory tract disease: 16 cases (1996-2000).
To compare results of thoracic radiography, cytologic evaluation of bronchoalveolar lavage (BAL) fluid, and histologic evaluation of biopsy and necropsy specimens in dogs with respiratory tract disease and to determine whether histologic evaluation provides important diagnostic information not attainable by the other methods. Retrospective study. 16 dogs. BAL fluid was classified as normal, neutrophilic, eosinophilic, mononuclear, mixed, neoplastic, or nondiagnostic. Radiographic abnormalities were classified as interstitial, bronchial, bronchointerstitial, or alveolar. Histologic lesions were classified as inflammatory, fibrotic, or neoplastic, and the predominant site of histologic lesions was classified as the alveoli, interstitium, or airway. The predominant radiographic location of lesions correlated with the histologic location in 8 dogs. Of 11 dogs with histologic evidence of inflammatory disease, 8 had inflammatory BAL fluid. Of the 2 dogs with histologic evidence of neoplasia, 1 had BAL fluid suggestive of neoplasia, and the other had BAL fluid consistent with septic purulent inflammation. Two dogs without any histologic abnormalities had mononuclear or nondiagnostic BAL fluid. Two dogs with histologic evidence of fibrosis had mononuclear or mixed inflammatory BAL fluid. Results suggest that although thoracic radiography, cytologic evaluation of BAL fluid, and histologic evaluation of lung specimens are complementary, each method has limitations in regard to how well results reflect the underlying disease process in dogs with respiratory tract disease. Lung biopsy should be considered in cases where results of radiography and cytology are nondiagnostic.


Evidence for heterogeneity in the 160/165 x 10(3) Mr glycoprotein components of desmosomes.
We have prepared both monoclonal and polyclonal antibody preparations directed against the 160/165 x 10(3) Mr glycoproteins (desmogleins) of bovine tongue epithelial desmosomes. The polyclonal antibody preparation recognizes desmosomes in a number of mouse tissues, e.g. mouse skin, heart, bladder and trachea, as determined by immunofluorescence microscopy. Furthermore, the polyclonal antibodies recognize polypeptide(s), present in the high salt, Triton-insoluble residues ('cytoskeleton preparations') of mouse skin, heart, bladder and trachea, which comigrate with the 160/165 x 10(3) Mr glycoproteins of bovine tongue epithelial desmosomes as determined by 'Western' immunoblotting. Conversely, the monoclonal 160/165 x 10(3) Mr antibody preparation recognizes desmosomes of stratified squamous epithelial tissues but not desmosomes in other tissue types. Moreover, whereas the monoclonal antibodies recognize 160/165 x 10(3) Mr polypeptides in mouse skin cell cytoskeletons they show no immunoreactivity with the cytoskeleton preparations of mouse bladder, trachea and heart following immunoblotting. These results suggest therefore that although there are conserved epitopes of the 160/165 x 10(3) Mr glycoproteins there are also epitopes of these molecules which vary from tissue to tissue. Double label immunofluorescence observations of cryostat sections of mouse skin using the monoclonal antibodies and antibodies directed against desmoplakin, a plaque component of desmosomes, reveal that the monoclonal antibodies do not recognize certain desmosomes in basal cells which are recognized by desmoplakin antibodies. Indeed, double label observations of cryostat sections of mouse skin using the monoclonal antibodies and human autoantibodies which react with hemidesmosomal components suggest that the monoclonal antibodies stain desmosomes located along the apical surfaces of basal cells but fail to recognize desmosomes along the lateral surfaces of these same cells.(ABSTRACT TRUNCATED AT 250 WORDS)


Expression of Filaggrin and its Degradation Products in Human Skin Following Erythemal Doses of Ultraviolet B Irradiation.
Epidermal filaggrin level is affected by ultraviolet B irradiation in animal and experimental models. This study examined the effect of ultraviolet B irradiation on epidermal filaggrin and natural moisturizing factors in vivo in healthy adults (n = 22). Participants were irradiated with 2 minimal erythema doses of ultraviolet B on the skin. Biopsies and tape strips were collected from skin irradiated 24 and 72 h earlier and from non-irradiated skin (control). Real-time quantitative PCR on skin biopsies showed significantly reduced profilaggrin mRNA expression 24 h after irradiation (mean relative mRNA expression ± standard deviation: control, 3.86 ± 2.06 vs. 24 h, 1.52 ± 0.640; p = 0.02; n = 8). Immunohistochemistry showed aberrant spatial distribution of filaggrin protein 72 h after irradiation (n = 3). High-pressure liquid chromatography of tape extracts showed no change in mean total natural moisturizing factor levels after irradiation, but mean trans-urocanic acid was significantly reduced, as expected (n = 8). In conclusion, erythemal doses of ultraviolet B exert acute effects on profilaggrin mRNA and filaggrin protein in human skin in vivo.


Evolutionary divergence of the necroptosis effector MLKL.
The pseudokinase, MLKL (mixed-lineage kinase domain-like), is the most terminal obligatory component of the necroptosis cell death pathway known. Phosphorylation of the MLKL pseudokinase domain by the protein kinase, receptor interacting protein kinase-3 (RIPK3), is known to be the key step in MLKL activation. This phosphorylation event is believed to trigger a molecular switch, leading to exposure of the N-terminal four-helix bundle (4HB) domain of MLKL, its oligomerization, membrane translocation and ultimately cell death. To examine how well this process is evolutionarily conserved, we analysed the function of MLKL orthologues. Surprisingly, and unlike their mouse, horse and frog counterparts, human, chicken and stickleback 4HB domains were unable to induce cell death when expressed in murine fibroblasts. Forced dimerization of the human MLKL 4HB domain overcame this defect and triggered cell death in human and mouse cell lines. Furthermore, recombinant proteins from mouse, frog, human and chicken MLKL, all of which contained a 4HB domain, permeabilized liposomes, and were most effective on those designed to mimic plasma membrane composition. These studies demonstrate that the membrane-permeabilization function of the 4HB domain is evolutionarily conserved, but reveal that execution of necroptotic death by it relies on additional factors that are poorly conserved even among closely related species.


Multiple admissions for alcohol withdrawal.
The objective was to identify risk factors for multiple admissions for alcohol withdrawal syndrome (AWS) in patients admitted to a general medicine service. A retrospective study was performed examining records of patients admitted for AWS between January 1, 2006 and December 31, 2008 to an academic tertiary referral hospital. Patients with a single admission were compared to patients with multiple admissions with respect to demographic and clinical variables. Three hundred and twenty-two patients accounted for 788 admissions. Of the 322 patients, 142 (44%) had multiple admissions. Compared to patients with a single admission, patients with multiple admissions were more likely to have a high school education or less (p=0.0071), a higher Charlson comorbidity index score (p=0.0010), a positive urine drug screen for non-alcohol drug (p=0.0002), psychiatric comorbidity (p=0.0303) and a higher CIWA-Ar maximum total score (p<0.0001). In patients with AWS, we identified demographic and clinical variables associated with multiple admissions to a general medicine service. Our results indicate areas for a targeted multidisciplinary and multispecialty approach at initial intervention, which is especially important given the high rates of recidivism in this patient population.


Tracking and compensation of respiration pattern by an automatic compensation system.
This study aimed to determine the feasibility of using an ultrasound image tracking algorithm (UITA) combined with a respiration compensating system (RCS) to track and compensate the respiration pattern of the diaphragm in real time. Diaphragm motions and various respiration patterns were tracked and captured in volunteers using our previously developed UITA (Kuo et al., J Xray Sci Technol, 2016:875). A diaphragm phantom was placed on a respiration simulation system (RSS) that received signals with different respiration patterns to simulate actual human respiration signals. The RSS was mounted on the RCS, which is 180 cm long and driven by inputting a compensating signal to a linear actuator underneath with and without using a phase-lead compensator (PLC) (Chuang et al., J Xray Sci Technol, 2015:503). The target displacement was calculated automatically by the UITA and compensated by the RCS. The phantom displacements were observed using a fluoroscopic imaging system on the linear accelerator at the Department of Radiation Oncology, Taipei Medical University Hospital, and the results were also compared with the displacements measured by the UITA and the RSS for correlation verification. In addition, the compensating effect was analyzed after activating the RCS. The experimental results indicate a significant correlation between the UITA-calculated and actual displacements, with a correlation coefficient of up to 91% for the simulated respiration patterns. After activating the RCS, the obtained compensating effect was more than 65%, and even up to 85% if a PLC was used. Moreover, the compensation of 10 extreme respiration patterns of diaphragm was improved significantly through the use of a PLC, with a peak compensating rate of 88.92% being achieved. Finally, compensation effects ranging from 52% to 74% were obtained in 10 human volunteers. This study combined ultrasound imaging tracking technology with the RCS to offset the respiration-induced diaphragm displacement and compensate the various respiration patterns, even including those with baseline-shift phenomenon in real time with the aid of a noninvasive ultrasound imaging system.


Guanabenz repurposed as an antiparasitic with activity against acute and latent toxoplasmosis.
Toxoplasma gondii is a protozoan parasite that persists as a chronic infection. Toxoplasma evades immunity by forming tissue cysts, which reactivate to cause life-threatening disease during immune suppression. There is an urgent need to identify drugs capable of targeting these latent tissue cysts, which tend to form in the brain. We previously showed that translational control is critical during infections with both replicative and latent forms of Toxoplasma. Here we report that guanabenz, an FDA-approved drug that interferes with translational control, has antiparasitic activity against replicative stages of Toxoplasma and the related apicomplexan parasite Plasmodium falciparum (a malaria agent). We also found that inhibition of translational control interfered with tissue cyst biology in vitro. Toxoplasma bradyzoites present in these abnormal cysts were diminished and misconfigured, surrounded by empty space not seen in normal cysts. These findings prompted analysis of the efficacy of guanabenz in vivo by using established mouse models of acute and chronic toxoplasmosis. In addition to protecting mice from lethal doses of Toxoplasma, guanabenz has a remarkable ability to reduce the number of brain cysts in chronically infected mice. Our findings suggest that guanabenz can be repurposed into an effective antiparasitic with a unique ability to reduce tissue cysts in the brain.


Shake Table Testing of an Elevator System in a Full-Scale Five-Story Building.
This paper investigates the seismic performance of a functional traction elevator as part of a full-scale five-story building shake table test program. The test building was subjected to a suite of earthquake input motions of increasing intensity, first while the building was isolated at its base, and subsequently while it was fixed to the shake table platen. In addition, low-amplitude white noise base excitation tests were conducted while the elevator system was placed in three different configurations, namely, by varying the vertical location of its cabin and counterweight, to study the acceleration amplifications of the elevator components due to dynamic excitations. During the earthquake tests, detailed observation of the physical damage and operability of the elevator as well as its measured response are reported. Although the cabin and counterweight sustained large accelerations due to impact during these tests, the use of well-restrained guide shoes demonstrated its effectiveness in preventing the cabin and counterweight from derailment during high-intensity earthquake shaking. However, differential displacements induced by the building imposed undesirable distortion of the elevator components and their surrounding support structure, which caused damage and inoperability of the elevator doors. It is recommended that these aspects be explicitly considered in elevator seismic design.


Estimating the immediate impact of the COVID-19 shock on parental attachment to the labor market and the double bind of mothers.
I examine the impact of the COVID-19 shock on parents' labor supply during the initial stages of the pandemic. Using difference-in-difference estimation and monthly panel data from the Current Population Survey (CPS), I compare labor market attachment, non-work activity, hours worked, and earnings and wages of those in areas with early school closures and stay-in-place orders with those in areas with delayed or no pandemic closures. While there was no immediate impact on detachment or unemployment, mothers with jobs in early closure states were 68.8 percent more likely than mothers in late closure states to have a job but not be working as a result of early shutdowns. There was no effect on working fathers or working women without school age children. Mothers who continued working increased their work hours relative to comparable fathers; this effect, however, appears entirely driven by a reduction in fathers' hours worked. Overall, the pandemic appears to have induced a unique immediate juggling act for working parents of school age children. Mothers took a week of leave from formal work; fathers working fulltime, for example, reduced their hours worked by 0.53 hours over the week. While experiences were different for mothers and fathers, each are vulnerable to scarring and stunted opportunities for career growth and advancement due to the pandemic.


The molecular structure of the surface of water-ethanol mixtures.
Mixtures of water and alcohol exhibit an excess surface concentration of alcohol as a result of the amphiphilic nature of the alcohol molecule, which has important consequences for the physico-chemical properties of water-alcohol mixtures. Here we use a combination of intensity vibrational sum-frequency generation (VSFG) spectroscopy, heterodyne-detected VSFG (HD-VSFG), and core-level photoelectron spectroscopy (PES) to investigate the molecular properties of water-ethanol mixtures at the air-liquid interface. We find that increasing the ethanol concentration up to a molar fraction (MF) of 0.1 leads to a steep increase of the surface density of the ethanol molecules, and an increased ordering of the ethanol molecules at the surface. When the ethanol concentration is further increased, the surface density of ethanol remains more or less constant, while the orientation of the ethanol molecules becomes increasingly disordered. The used techniques of PES and VSFG provide complementary information on the density and orientation of ethanol molecules at the surface of water, thus providing new information on the molecular-scale properties of the surface of water-alcohol mixtures over a wide range of compositions. This information is invaluable in understanding the chemical and physical properties of water-alcohol mixtures.


Anechoic stripe size influences accuracy of FAST examination interpretation.
Accurate and precise interpretations of Focused Assessment with Sonography for Trauma (FAST) findings are important factors in managing trauma patients. The objectives were to analyze the influence of anechoic stripe (AS) size on interpretation accuracy by emergency physicians (EPs) and to assess the precision of FAST examination interpretation as a function of EP FAST experience. A prospective comparison study of FAST examination interpretation by 11 emergency medicine faculty (FAC), nine community attending EPs (ATT), and nine senior emergency medicine residents (RES) was conducted; these physicians were then divided into more experienced and less experienced cohorts to assess precision. Participants interpreted video recordings of the four standard views from five FAST examinations (20 total video clips); each examination contained views with various AS sizes. Accuracy of FAST examination interpretation was calculated for each group stratified by size of AS. Precision (reproducibility) of FAST examination interpretation was assessed by calculating kappa values. With large, moderate, or no AS, no significant differences in accuracy were found between groups. For small AS, significant differences in accuracy were found between the ATT and RES groups and between the combined FAC + ATT group and the RES group. Kappa was good to excellent when the nth and the (n + 1)th experienced physicians in the more experienced cohort were compared. kappa values reflected that the more experienced cohort was more precise than the less experienced cohort. AS size visible on FAST examinations and EP experience level with FAST examination interpretation exerted a significant influence on the interpretation accuracy of videotaped FAST examinations. In addition, precision was enhanced by increased EP experience with FAST.


Anthocyanins: natural colorants with health-promoting properties.
Anthocyanins are flavonoids in fruits and vegetables that render them vivid red to blue. To date, there have been more than 635 anthocyanins identified in nature, featuring six common aglycones and various types of glycosylations and acylations. Dietary consumption of anthocyanins is high compared to other flavonoids, owing to their wide distribution in plant materials. Based upon many cell-line studies, animal models, and human clinical trials, it has been suggested that anthocyanins possess anti-inflammatory and anti-carcinogenic activity, cardiovascular disease prevention, obesity control, and diabetes alleviation properties, all of which are more or less associated with their potent antioxidant property. Evidence suggests that absorption of anthocyanins occurs in the stomach and small intestine. Epithelial tissue uptake seems to be highly efficient, yet transportation into circulation, tissue distribution, and urine excretion are very limited. The bioactivity of bioavailable anthocyanins should be a focus of future research regarding their putative health-promoting effects.


Paid advertising for AIDS prevention--would the ends justify the means?
An examination by the Centers for Disease Control and the Research Triangle Institute concluded that "hard-to-reach" populations could be reached with AIDS prevention messages through the broadcast and print media and that a study should be undertaken to assess whether paid placement of these messages could have an effect on HIV-related behaviors. The recommended target population for a study of paid advertising would be sexually active 18-24-year-old black urban dwellers. Its behavioral objectives would include abstinence and safer sex practices. For any evaluation of a paid advertising campaign to be valid, there would have to be extensive audience profiling, research into the development of the message, pretesting of the message, and involvement of the community. The proposed study would include measurement of various "dosage" levels of paid advertising, use of a no-intervention comparison group, and a novel data collection technique. Although a specific target group and specific messages would be involved, the evaluation would make a substantial contribution to resolving the broader issue of whether and how mass media should be used directly or indirectly to change or reinforce health-related behaviors.


Nematode-induced endoreduplication in plant host cells: why and how?
Plant-parasitic root-knot and cyst nematodes have acquired the ability to induce remarkable changes in host cells during the formation of feeding sites. Root-knot nematodes induce several multinucleate giant cells inside a gall whereas cyst nematodes provoke the formation of a multinucleate syncytium. Both strategies impinge on the deregulation of the cell cycle, involving a major role for endoreduplication. This review will first describe the current knowledge on the control of normal and aberrant cell cycles. Thereafter, we will focus on the role of both cell-cycle routes in the transformation process of root cells into large and highly differentiated feeding sites as induced by the phytoparasitic root-knot and cyst nematodes.


[Intracoronary, human autologous stem cell transplantation for myocardial regeneration following myocardial infarction].
The regenerative potential of human autologous adult stem cells on myocardial regeneration and neovascularisation after myocardial infarction may contribute to healing of the infarction area. But no clinical application has previously been reported. We here describe for the first time the results of this method applied in a patient who had sustained an acute myocardial infarction. 14 hours after the onset of left precordial pain a 46-year-old man was admitted to our hospital for interventional diagnosis and treatment. Coronary angiography demonstrated occlusion of the anterior descending branch of the left coronary artery with transmural infarction. This was treated by percutaneous transluminal catheter angioplasty and stent placement. Mononuclear bone marrow cells of the patient were prepared and 6 days after infaction 1,2 infinity 107 cells were transplanted at low pressure via a percutaneous transluminal catheter placed in the infarct-related artery. Before and 10 weeks after this procedure left ventricular function, infarct size, ventricular geometry and myocardial perfusion were measured by (201)thallium SPECT both at rest and on exercise, together with bull's-eye analysis, dobutamine stress echocardiography, right heart catheterisation and radionuclide ventriculography. At 10 weeks after the stem cell transplantation the transmural infarct area had been reduced from 24.6 % to 15.7 % of left ventricular circumference, while ejection fraction, cardiac index and stroke volume had increased by 20-30 %. On exercise the end diastolic volume had decreased by 30 % and there was a comparable fall in left ventricular filling pressure (mean pulmonary capillary pressure). These results for the first time demonstrate that selective intracoronary transplantation of human autologous adult stem cells is possible under clinical conditions and that it can lead to regeneration of the myocardial scar after transmural infarction. The therapeutic effects may be ascribed to stem cell-associated myocardial regeneration and neovascularisation.


Adherence to Antiretroviral Therapy (ART) in Yaoundé-Cameroon: Association with Opportunistic Infections, Depression, ART Regimen and Side Effects.
Following global efforts to increase antiretroviral therapy (ART) access in Sub-Saharan Africa, ART coverage among HIV-infected Cameroonians increased from 0% in 2003 to 22% in 2014. However, the success of current HIV treatment programs depends not only on access to ART, but also on retention in care and good treatment adherence. This is necessary to achieve viral suppression, prevent virologic failure, and reduce viral transmission and HIV/AIDS-related deaths. Previous studies in Cameroon showed poor adherence, treatment interruption, and loss to follow-up among HIV+ subjects on ART, but the factors that influence ART adherence are not well known. In the current cross-sectional study, patient/self-reported questionnaires and pharmacy medication refill data were used to quantify ART adherence and determine the factors associated with increased risk of non-adherence among HIV-infected Cameroonians. We demonstrated that drug side-effects, low CD4 cell counts and higher viral loads are associated with increased risk of non-adherence, and compared to females, males were more likely to forego ART because of side effects (p<0.05). Univariate logistic regression analysis demonstrated that subjects with opportunistic infections (on antibiotics) had 2.42-times higher odds of having been non-adherent (p<0.001). Multivariable analysis controlling for ART regimen, age, gender, and education showed that subjects with opportunistic infections had 3.1-times higher odds of having been non-adherent (p<0.0003), with significantly longer periods of non-adherence, compared to subjects without opportunistic infections (p = 0.02). We further showed that compared to younger subjects (≤40 years), older subjects (>40 years) were less likely to be non-adherent (p<0.01) and had shorter non-adherent periods (p<0.0001). The presence of depression symptoms correlated with non-adherence to ART during antibiotic treatment (r = 0.53, p = 0.04), and was associated with lower CD4 cell counts (p = 0.04) and longer non-adherent periods (p = 0.04). Change in ART regimen was significantly associated with increased likelihood of non-adherence and increased duration of the non-adherence period. Addressing these underlying risk factors could improve ART adherence, retention in care and treatment outcomes for HIV/AIDS patients in Cameroon.


Accuracy of an automatic patient-positioning system based on the correlation of two edge images in radiotherapy.
We have clinically evaluated the accuracy of an automatic patient-positioning system based on the image correlation of two edge images in radiotherapy. Ninety-six head & neck images from eight patients undergoing proton therapy were compared with a digitally reconstructed radiograph (DRR) of planning CT. Two edge images, a reference image and a test image, were extracted by applying a Canny edge detector algorithm to a DRR and a 2D X-ray image, respectively, of each patient before positioning. In a simulation using a humanoid phantom, performed to verify the effectiveness of the proposed method, no registration errors were observed for given ranges of rotation, pitch, and translation in the x, y, and z directions. For real patients, however, there were discrepancies between the automatic positioning method and manual positioning by physicians or technicians. Using edged head coronal- and sagittal-view images, the average differences in registration between these two methods for the x, y, and z directions were 0.11 cm, 0.09 cm and 0.11 cm, respectively, whereas the maximum discrepancies were 0.34 cm, 0.38 cm, and 0.50 cm, respectively. For rotation and pitch, the average registration errors were 0.95° and 1.00°, respectively, and the maximum errors were 3.6° and 2.3°, respectively. The proposed automatic patient-positioning system based on edge image comparison was relatively accurate for head and neck patients. However, image deformation during treatment may render the automatic method less accurate, since the test image many differ significantly from the reference image.


Assessing macroinvertebrate biodiversity in freshwater ecosystems: advances and challenges in DNA-based approaches.
Assessing the biodiversity of macroinvertebrate fauna in freshwater ecosystems is an essential component of both basic ecological inquiry and applied ecological assessments. Aspects of taxonomic diversity and composition in freshwater communities are widely used to quantify water quality and measure the efficacy of remediation and restoration efforts. The accuracy and precision of biodiversity assessments based on standard morphological identifications are often limited by taxonomic resolution and sample size. Morphologically based identifications are laborious and costly, significantly constraining the sample sizes that can be processed. We suggest that the development of an assay platform based on DNA signatures will increase the precision and ease of quantifying biodiversity in freshwater ecosystems. Advances in this area will be particularly relevant for benthic and planktonic invertebrates, which are often monitored by regulatory agencies. Adopting a genetic assessment platform will alleviate some of the current limitations to biodiversity assessment strategies. We discuss the benefits and challenges associated with DNA-based assessments and the methods that are currently available. As recent advances in microarray and next-generation sequencing technologies will facilitate a transition to DNA-based assessment approaches, future research efforts should focus on methods for data collection, assay platform development, establishing linkages between DNA signatures and well-resolved taxonomies, and bioinformatics.


Maturation of ureter-bladder connection in mice is controlled by LAR family receptor protein tyrosine phosphatases.
Congenital anomalies affecting the ureter-bladder junction are frequent in newborns and are often associated with other developmental defects. However, the molecular and morphological processes underlying these malformations are still poorly defined. In this study, we identified the leukocyte antigen-related (LAR) family protein tyrosine phosphatase, receptor type, S and F (Ptprs and Ptprf [also known as Lar], respectively), as crucially important for distal ureter maturation and craniofacial morphogenesis in the mouse. Embryos lacking both Ptprs and Ptprf displayed severe urogenital malformations, characterized by hydroureter and ureterocele, and craniofacial defects such as cleft palate, micrognathia, and exencephaly. The detailed analysis of distal ureter maturation, the process by which the ureter is displaced toward its final position in the bladder wall, leads us to propose a revised model of ureter maturation in normal embryos. This process was deficient in embryos lacking Ptprs and Ptprf as a result of a marked reduction in intrinsic programmed cell death, thereby causing urogenital system malformations. In cell culture, Ptprs bound and negatively regulated the phosphorylation and signaling of the Ret receptor tyrosine kinase, whereas Ptprs-induced apoptosis was inhibited by Ret expression. Together, these results suggest that ureter positioning is controlled by the opposing actions of Ret and LAR family phosphatases regulating apoptosis-mediated tissue morphogenesis.


Etiological Theories of Adolescent Idiopathic Scoliosis: Past and Present.
Adolescent idiopathic scoliosis is one of the most common spinal deformities, yet its cause is unknown. Various theories look to biomechanical, neuromuscular, genetic, and environmental origins, yet our understanding of scoliosis etiology is still limited. Determining the cause of a disease is crucial to developing the most effective treatment. Associations made with scoliosis do not necessarily point to causality, and it is difficult to determine whether said associations are primary (playing a role in development) or secondary (develop as a result of scoliosis). Scoliosis is a complex condition with highly variable expression, even among family members, and likely has many causes. These causes could be similar among homogenous groups of AIS patients, or they could be individual. Here, we review the most prevalent theories of scoliosis etiology and recent trends in research.


ABC3 Part II: a review of the new criteria for evaluating cervical cytology in England.
The new Achievable Standards, Benchmarks for Reporting, and Criteria for Evaluating Cervical Cytopathology, 3rd edn (ABC3) includes radical changes in the criteria for evaluating cervical cytology. First, they include a new mission statement 'the objective of cervical screening is to reduce cervical cancer incidence and mortality by screening with a high sensitivity for the detection of CIN2 or worse, whilst maintaining a high specificity'. Second, the original four performance measurement criteria where laboratories were examined further if they were below the 10th or above the 90th percentile has been changed to three and laboratories are only mandatorily examined if they fall below the 5th or above the 95th percentile. The old criteria related to the percentage of samples that were inadequate, the percentage of all adequate samples reported as moderate dyskaryosis or worse (equivalent to high-grade squamous intraepithelial lesion or cancer), the percentage of adequate samples reported as mild dyskaryosis or borderline (equivalent to low-grade squamous intraepithelial lesion or atypical squamous/glandular cells) and the positive predictive value. The new criteria are percentage of inadequate samples, positive predictive value and a new measure termed referral value. These changes mean that far fewer laboratories will require mandatory examination. Third, a raft of optional performance measures have been introduced to help laboratories examine their annual statistical return to the Department of Health in comparison with other laboratories. These measures have been designed to produce a more uniform national programme, and to help laboratories decide whether they are maximizing the benefit of screening while minimizing the harm, which is the goal of all screening programmes. This review examines in detail the new criteria and explains in more detail some of the thinking behind them.


Comprehensive characterization of T-DNA integration induced chromosomal rearrangement in a birch T-DNA mutant.
Integration of T-DNA into plant genomes via Agrobacterium may interrupt gene structure and generate numerous mutants. The T-DNA caused mutants are valuable materials for understanding T-DNA integration model in plant research. T-DNA integration in plants is complex and still largely unknown. In this work, we reported that multiple T-DNA fragments caused chromosomal translocation and deletion in a birch (Betula platyphylla × B. pendula) T-DNA mutant yl. We performed PacBio genome resequencing for yl and the result revealed that two ends of a T-DNA can be integrated into plant genome independently because the two ends can be linked to different chromosomes and cause chromosomal translocation. We also found that these T-DNA were connected into tandem fragment regardless of direction before integrating into plant genome. In addition, the integration of T-DNA in yl genome also caused several chromosomal fragments deletion. We then summarized three cases for T-DNA integration model in the yl genome. (1) A T-DNA fragment is linked to the two ends of a double-stranded break (DSB); (2) Only one end of a T-DNA fragment is linked to a DSB; (3) A T-DNA fragment is linked to the ends of different DSBs. All the observations in the yl genome supported the DSB repair model. In this study, we showed a comprehensive genome analysis of a T-DNA mutant and provide a new insight into T-DNA integration in plants. These findings would be helpful for the analysis of T-DNA mutants with special phenotypes.


Colonization of the female genital tract with Staphylococcus saprophyticus.
The prevalence of colonization by Staphylococcus saprophyticus of the urogenital tracts of 276 women from an outpatient gynecology practice was determined by using selective and enrichment culture techniques. Nineteen subjects (6.9%) were found to be colonized by S. saprophyticus. The rectum was the most frequent site of colonization and was responsible for 40% of the isolates; this was followed in decreasing order by the urethra, urine, and cervix. Women colonized by S. saprophyticus were more likely to have experienced a urinary tract infection in the previous 12 months (P = 0.058; odds ratio, 2.844; 95% confidence interval, 1.054 to 7.671). Patients colonized by S. saprophyticus tended to have had their menstrual periods more recently (P = 0.066), experienced sexual intercourse more recently (P = 0.168), and had a recent or concurrent diagnosis of vaginal candidiasis (P = 0.111; odds ratio, 2.393; 95% confidence interval, 0.877 to 6.528). A seasonal variation in colonization was observed, with colonization most likely occurring during the summer and fall. Follow-up for an average of 6.75 months failed to document any colonized woman progressing to symptomatic urinary tract infection. In addition, 21 women colonized by non-S. saprophyticus, novobiocin-resistant, coagulase-negative staphylococci were identified and characterized.