The Role of the Right Posterior Parietal Cortex in Letter Migration between Words

When briefly presented with pairs of words, skilled readers can sometimes report words with migrated letters (e.g., they report hunt when presented with the words hint and hurt). These letter migration phenomena have been often used to investigate factors that influence reading such as letter position coding. However, the neural basis of letter migration is poorly understood. Previous evidence has implicated the right posterior parietal cortex (PPC) in processing visuospatial attributes and lexical properties during word reading. The aim of this study was to assess this putative role by combining an inhibitory TMS protocol with a letter migration paradigm, which was designed to examine the contributions of visuospatial attributes and lexical factors. Temporary interference with the right PPC led to three specific effects on letter migration. First, the number of letter migrations was significantly increased only in the group with active stimulation (vs. a sham stimulation group or a control group without stimulation), and there was no significant effect on other error types. Second, this effect occurred only when letter migration could result in a meaningful word (migration vs. control context). Third, the effect of active stimulation on the number of letter migrations was lateralized to target words presented on the left. Our study thus demonstrates that the right PPC plays a specific and causal role in the phenomenon of letter migration. The nature of this role cannot be explained solely in terms of visuospatial attention, rather it involves an interplay between visuospatial attentional and word reading-specific factors.

Correlation between serum total globulins and gamma globulins and their use to diagnose failure of passive transfer in foals.

Various assays have been used as an aid to diagnose failure of passive transfer (FPT) of immunoglobulins in neonatal foals, but often lack sensitivity as screening tests, or are time consuming to perform and impractical as confirmatory tests. The aim of the present study was to evaluate whether measurement of serum total globulins (TG; i.e. total protein minus albumin) can be used to estimate the electrophoretic gamma globulin (EGG) fraction in hospitalised neonatal foals with suspected FPT. Sample data from 56 foals were evaluated retrospectively. The coefficient of rank correlation was 0.84. The area under the curve of ROC analysis was 0.887, 0.922 and 0.930 for EGG concentrations <2 g/L, < 4 g/L and <8 g/L, respectively. Cut-offs for TG achieved ≥90% sensitivity for detecting EGG <2 g/L, < 4 g/L and <8 g/L, with negative predictive values of >97% and >94%, using prevalence of 15% and 30%, respectively. These results suggest that measurement of TG can be used as a guide to predicting EGG, provided that appropriate cut-off values are selected, and this technique could be a useful initial screening test for FPT in foals.

Revisiting the Nd-142 deficits in the 1.48 Ga Khariar alkaline rocks, India

The 146Sm–142Nd system plays a central role in tracing the silicate differentiation of the Earth prior to 4.1 Ga. After this time, given its initial abundance, the 146Sm can be considered to be extinct. Upadhyay et al. (2009) reported unexpected negative 142Nd anomalies in 1.48 Ga rocks of the Khariar nepheline syenite complex (India) and inferred that an early enriched, low-Sm/Nd reservoir must have contributed to the mantle source rocks of the Khariar complex. As 146Sm had been effectively extinct for about 2.6 billion years before the crystallisation of the Khariar samples, this Nd signature should have remained isolated from the convective mantle for at least that long. It was thus suggested that the source rock of Khariar samples had been sequestered in the lithospheric root of the Indian craton. Using a different chemical separation method, and a different Thermal Ionization Mass Spectrometry (TIMS) analysis protocol, the present study attempted to replicate these negative 142Nd anomalies, but none were found. To determine which data set is correct, we investigated three possible sources of bias between them: imperfect cancellation of Faraday collector efficiencies during multidynamic TIMS analysis, rapid sample fractionation between the sequential measurement of 146Nd/144Nd and 142Nd/144Nd, and non-exponential law behaviour resulting from so-called “domain mixing.” Incomplete cancellation of collector efficiencies was found unlikely to cause resolvable biases at the estimated level of variation among collector efficiencies. Even in the case of highly variable efficiency and resolvable biases, there is no reason to suspect that they would reproducibly affect only four rocks out of 10 analysed by Upadhyay et al. (2009). Although domain mixing may explain apparent “reverse” fractionation trends observed in some TIMS analyses, it cannot be the cause of the apparent negative anomalies in the study of Upadhyay et al. (2009). It was determined that rapid mass fractionation during the course of a multidynamic TIMS analysis can bias all measured Nd ratios. After applying an approximate correction for this effect, only one rock from Upadhyay et al. (2009) retained an apparent negative 142Nd anomaly. This, in conjunction with our new, anomaly-free data set measured at fractionation rates too low to cause bias, leads to the conclusion that the anomalies reported by Upadhyay et al. (2009) are a subtle and reproducible analytical artefact. The absence of negative 142Nd anomalies in these rocks relaxes the need for a mechanism (other than crust formation) that can isolate a Nd reservoir from the convective mantle for billions of years.

Novel heating/cooling stage designed for fluid inclusion microthermometry of large stalagmite sections

Liquid–vapour homogenisation temperatures of fluid inclusions in stalagmites are used for quantitative temperature reconstructions in paleoclimate research. Specifically for this application, we have developed a novel heating/cooling stage that can be operated with large stalagmite sections of up to 17 × 35 mm2 to simplify and improve the chronological reconstruction of paleotemperature time-series. The stage is designed for use of an oil immersion objective and a high-NA condenser front lens to obtain high-resolution images for bubble radius measurements. The temperature accuracy of the stage is better than ± 0.1 °C with a precision (reproducibility) of ± 0.02 °C.

S-nitroso albumin enhances bone formation in a rabbit calvaria model.

Nitric oxide (NO) is a mediator involved in bone regeneration. We therefore examined the effect of the novel NO donor, S-nitroso human serum albumin (S-NO-HSA) on bone formation in a rabbit calvaria augmentation model. Circular grooves (8 mm diameter, two per animal) were created by a trephine drill in the cortical bone of 40 rabbits and titanium caps were placed on the rabbit calvaria bone filled with a collagen sponge soaked with either 100 μL S-NO-HSA (5%, 20%) or human albumin (5%, 20%). After 4 weeks the titanium hemispheres were subjected to histological and histomorphometric analysis. Bone formation and the volume of the residual collagen sponge were evaluated. S-NO-HSA treatment groups had a significantly higher volume of newly formed bone underneath the titanium hemispheres compared to the albumin control groups (5%: 15.5 ± 4.0% versus 10.6 ± 2.9%; P < 0.05; 20%: 14.0 ± 4.6% versus 6.0 ± 3.8%; P < 0.01). The volume of residual collagen sponge was also significantly lower in the S-NO-HSA groups compared to the control groups (5%: 0.4 ± 0.5% versus 2.6 ± 2.4%; P < 0.05 and 20%: 1.5 ± 2.7% versus 13.0 ± 18.7%; P < 0.01). This study demonstrates for the first time that S-NO-HSA promotes bone formation by slow NO release. Additionally, S-NO-HSA increases collagen sponge degradation.

Risk of falls and bleeding in elderly patients with acute venous thromboembolism.

OBJECTIVE Whether or not a high risk of falls increases the risk of bleeding in patients receiving anticoagulants remains a matter of debate. METHODS We conducted a prospective cohort study involving 991 patients ≥ 65 years of age who received anticoagulants for acute venous thromboembolism (VTE) at nine Swiss hospitals between September 2009 and September 2012. The study outcomes were as follows: the time to a first major episode of bleeding; and clinically relevant nonmajor bleeding. We determined the associations between the risk of falls and the time to a first episode of bleeding using competing risk regression, accounting for death as a competing event. We adjusted for known bleeding risk factors and anticoagulation as a time-varying covariate. RESULTS Four hundred fifty-eight of 991 patients (46%) were at high risk of falls. The mean duration of follow-up was 16.7 months. Patients at high risk of falls had a higher incidence of major bleeding (9.6 vs. 6.6 events/100 patient-years; P = 0.05) and a significantly higher incidence of clinically relevant nonmajor bleeding (16.7 vs. 8.3 events/100 patient-years; P < 0.001) than patients at low risk of falls. After adjustment, a high risk of falls was associated with clinically relevant nonmajor bleeding [subhazard ratio (SHR) = 1.74, 95% confidence interval (CI) = 1.23-2.46], but not with major bleeding (SHR = 1.24, 95% CI = 0.83-1.86). CONCLUSION In elderly patients who receive anticoagulants because of VTE, a high risk of falls is significantly associated with clinically relevant nonmajor bleeding, but not with major bleeding. Whether or not a high risk of falls is a reason against providing anticoagulation beyond 3 months should be based on patient preferences and the risk of VTE recurrence.

Cloning, sequencing and partial functional characterization of the 5' region of the human p75 tumor necrosis factor receptor-encoding gene (TNF-R)

A 1887-bp region at the 5' flank of the human p75 tumor necrosis factor receptor (p75 TNF-R)-encoding gene was found to be active in driving expression of the luc (luciferase-encoding) reporter gene, suggesting that it contains the promoter for the receptor. Rather unexpectedly, a 1827-bp region at the 3' end of the first intron of the p75 TNF-R gene also displayed promoter activity. This activity may be artefactual, reflecting only the presence of an enhancer in this region; yet it also raises the possibility that p75 TNF-R is controlled by more than one promoter and that it encodes various forms of the receptor, or even other proteins. We present here the nucleotide sequences of the 5' flanking and intron regions. Possible implications for the transcriptional regulation of the p75 TNF-R gene are discussed.

Quantifying uncertainty on Pareto fronts with Gaussian process conditional simulations

Multi-objective optimization algorithms aim at finding Pareto-optimal solutions. Recovering Pareto fronts or Pareto sets from a limited number of function evaluations are challenging problems. A popular approach in the case of expensive-to-evaluate functions is to appeal to metamodels. Kriging has been shown efficient as a base for sequential multi-objective optimization, notably through infill sampling criteria balancing exploitation and exploration such as the Expected Hypervolume Improvement. Here we consider Kriging metamodels not only for selecting new points, but as a tool for estimating the whole Pareto front and quantifying how much uncertainty remains on it at any stage of Kriging-based multi-objective optimization algorithms. Our approach relies on the Gaussian process interpretation of Kriging, and bases upon conditional simulations. Using concepts from random set theory, we propose to adapt the Vorob’ev expectation and deviation to capture the variability of the set of non-dominated points. Numerical experiments illustrate the potential of the proposed workflow, and it is shown on examples how Gaussian process simulations and the estimated Vorob’ev deviation can be used to monitor the ability of Kriging-based multi-objective optimization algorithms to accurately learn the Pareto front.

State of the art: Reproduction and pregnancy in rheumatic diseases

Throughout the last decade, increasing awareness has been raised on issues related to reproduction in rheumatic diseases including basic research to clarify the important role of estrogens in the etiology and pathophysiology of immune/inflammatory diseases. Sub- or infertility is a heterogeneous condition that can be related to immunological mechanisms, to pregnancy loss, to disease burden, to therapy, and to choices in regard to family size. Progress in reproductive medicine has made it possible for more patients with rheumatic disease to have children. Active disease in women with rheumatoid arthritis (RA) affects their children's birth weight and may have long-term effects on their future health status. Pregnancy complications as preeclampsia and intrauterine growth restriction are still increased in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS), however, biomarkers can monitor adverse events, and several new therapies may improve outcomes. Pregnancies in women with APS remain a challenge, and better therapies for the obstetric APS are needed. New prospective studies indicate improved outcomes for pregnancies in women with rare diseases like systemic sclerosis and vasculitis. TNF inhibitors hold promise for maintaining remission in rheumatological patients and may be continued at least in the first half of pregnancy. Pre-conceptional counseling and interdisciplinary management of pregnancies are essential for ensuring optimal pregnancy outcomes.

Pro Judaeis : riflessioni e documenti

[von] Corrado Guidetti

Predicting Psychotherapy Dropouts: A Multilevel Approach

The role of therapeutic processes in predicting premature termination of psychotherapy has been a particular focus of recent research. The purpose of this study was to contrast outpatients who completed therapy and those who dropped out with respect to their self-reported in-session experiences of self-esteem, mastery, clarification and the therapeutic alliance. The 296 patients with mixed disorders were treated with an integrative form of cognitive–behavioural therapy without pre-determined time limit (M = 20.2 sessions). Multilevel analyses indicated that patients who did not completetreatment reported, on average, lower levels of self-esteem, mastery and clarification and lower ratings of their therapeutic alliance in treatment in contrast to patients who completed therapy. Patient-reported change in self-esteem experiences over the course of treatment turned out to be the strongest predictor of dropout from psychotherapy or successful completion. When dropout occurred before the average treatment length was reached, patients reported fewer clarifying experiences as early as the first session and their ratings of the therapeutic alliance were characterized by an absence of positive development. Both of these aspects seem to be involved in patients' decisions to leave treatment early. The findings underscore the importance of the therapeutic process in understanding the mechanisms behind treatment dropout. Copyright © 2014 John Wiley & Sons, Ltd.

Prenatal management of monoamniotic twin pregnancies

OBJECTIVE To evaluate antenatal surveillance strategies and the optimal timing of delivery for monoamniotic twin pregnancies. METHODS Obstetric and perinatal outcomes were retrospectively retrieved for 193 monoamniotic twin pregnancies. Fetal and neonatal outcomes were compared between fetuses followed in an inpatient setting and those undergoing intensive outpatient follow-up from 26 to 28 weeks of gestation until planned cesarean delivery between 32 and 35 weeks of gestation. The risk of fetal death was compared with the risk of neonatal complications. RESULTS Fetal deaths occurred in 18.1% of fetuses (70/386). Two hundred ninety-five neonates from 153 pregnancies were born alive after 23 weeks of gestation. There were 17 neonatal deaths (5.8%), five of whom had major congenital anomalies. The prospective risk of a nonrespiratory neonatal complication was lower than the prospective risk of fetal death after 32 4/7 weeks of gestation (95% confidence interval 32 0/7-33 4/7). The incidence of death or a nonrespiratory neonatal complication was not significantly different between fetuses managed as outpatients (14/106 [13.2%]) or inpatients (15/142 [10.5%]; P=.55). Our statistical power to detect a difference in outcomes between these groups was low. CONCLUSIONS The in utero risk of a monoamniotic twin fetus exceeds the risk of a postnatal nonrespiratory complication at 32 4/7 weeks of gestation. If close fetal surveillance is instituted after 26-28 weeks of gestation and delivery takes place at approximately 33 weeks of gestation, the risk of fetal or neonatal death is low, no matter the surveillance setting. LEVEL OF EVIDENCE II.