Early last glacial maximum in the southern Central Andes reveals northward shift of the westerlies at similar to 39 ka

The latitudinal position of the southern westerlies has been suggested to be a key parameter for the climate on Earth. According to the general notion, the southern westerlies were shifted equatorward during the global Last Glacial Maximum (LGM: ~24–18 ka), resulting in reduced deep ocean ventilation, accumulation of old dissolved carbon, and low atmospheric CO2 concentrations. In order to test this notion, we applied surface exposure dating on moraines in the southern Central Andes, where glacial mass balances are particularly sensitive to changes in precipitation, i.e. to the latitudinal position of the westerlies. Our results provide robust evidence that the maximum glaciation occurred already at ~39 ka, significantly predating the global LGM. This questions the role of the westerlies for atmospheric CO2, and it highlights our limited understanding of the forcings of atmospheric circulation.

Accuracy of Preoperative Endoscopic Ultrasound (EUS) to Distinguish Between Early and Locally Advanced Esophageal Cancer in Daily Clinical Practice

Introduction: Preoperative chemoradiotherapy is generally recommended for locally advanced esophageal cancer (clinical stage T3 or T4 or nodal positive disease) but not for early cancer (clinical stage T0 to T2, N0). EUS has been described as the most accurate method to distinguish between early and locally advanced stage in several studies. Recently however, the high accuracy of EUS (90% or higher) was questioned by some investigators. This raises the issue whether the results of studies focused on EUS accuracy may be directly translated into daily clinical practice. Aim & Methods: The aim of this retrospective analysis was to assess the accuracy of preoperative EUS to distinguish between early and locally advanced esophageal cancer in daily clinical practice outside a study setting. EUS was performed by several investigators, including trainees in one university hospital. For this purpose, EUS reports and patient files (medical and surgical) including histological reports of 300 consecutive pts with esophageal tumors were reviewed. In pts with adenocarcinoma or squamous cell cancer and surgical resection without previous radio-/chemotherapy, EUS tumor staging was compared with histological diagnosis. Results: Out of the 300 consecutive pts with esophageal tumor and EUS 102 pts had esophageal surgery after EUS-staging without any radio-/chemotherapy. In 93 pts oesophageal cancer was confirmed, whereas 9 had other tumors. The mean age was 65 years (range 27-89), sex ratio female:male was 1:3.2. To distinguish between early and late tumor stage, the accuracy was 85%. The sensitivity and specificity for early cancer was 59%, and 93%, respectively. The diagnostic accuracy for local tumor spread was 90%, 90%, 68%, 69%, 89% for pT0, pT1, pT2, pT3 and pT4 lesions, respectively. The overall accuracy for T-stage was 74%. For pN-positive staging the accuracy of EUS was 73%. Conclusion: In daily clinical practice, the accuracy of EUS in assessing esophageal tumor staging is lower than in specific studies focusing on EUS accuracy. Mainly early esophageal cancer stages were overstaged. Thus, the implementation of recommendations for diagnostic work-up of esophageal cancer patients resulting from highly specific studies should consider the appropriate clinical setting.

The independent role of prenatal and postnatal exposure to active and passive smoking on the development of early wheeze in children.

Maternal smoking during pregnancy increases childhood asthma risk, but health effects in children of nonsmoking mothers passively exposed to tobacco smoke during pregnancy are unclear. We examined the association of maternal passive smoking during pregnancy and wheeze in children aged ≤2 years.Individual data of 27 993 mother-child pairs from 15 European birth cohorts were combined in pooled analyses taking into consideration potential confounders.Children with maternal exposure to passive smoking during pregnancy and no other smoking exposure were more likely to develop wheeze up to the age of 2 years (OR 1.11, 95% CI 1.03-1.20) compared with unexposed children. Risk of wheeze was further increased by children's postnatal passive smoke exposure in addition to their mothers' passive exposure during pregnancy (OR 1.29, 95% CI 1.19-1.40) and highest in children with both sources of passive exposure and mothers who smoked actively during pregnancy (OR 1.73, 95% CI 1.59-1.88). Risk of wheeze associated with tobacco smoke exposure was higher in children with an allergic versus nonallergic family history.Maternal passive smoking exposure during pregnancy is an independent risk factor for wheeze in children up to the age of 2 years. Pregnant females should avoid active and passive exposure to tobacco smoke for the benefit of their children's health.

The Influence of PRP on Early Bone Formation in Membrane Protected Defects. A Histological and Histomorphometric Study in the Rabbit Calvaria

Platelet rich plasma (PRP) has been proposed to be a useful adjunct to bone grafting.

Early osseointegration to hydrophilic and hydrophobic implant surfaces in humans

To evaluate the rate and degree of osseointegration at chemically modified moderately rough, hydrophilic (SLActive) and moderately rough, hydrophobic (SLA) implant surfaces during early phases of healing in a human model.

Slc15a4, a gene required for pDC sensing of TLR ligands, is required to control persistent viral infection

Plasmacytoid dendritic cells (pDCs) are the major producers of type I IFN in response to viral infection and have been shown to direct both innate and adaptive immune responses in vitro. However, in vivo evidence for their role in viral infection is lacking. We evaluated the contribution of pDCs to acute and chronic virus infection using the feeble mouse model of pDC functional deficiency. We have previously demonstrated that feeble mice have a defect in TLR ligand sensing. Although pDCs were found to influence early cytokine secretion, they were not required for control of viremia in the acute phase of the infection. However, T cell priming was deficient in the absence of functional pDCs and the virus-specific immune response was hampered. Ultimately, infection persisted in feeble mice. We conclude that pDCs are likely required for efficient T cell priming and subsequent viral clearance. Our data suggest that reduced pDC functionality may lead to chronic infection.

Treatment of adolescents with early-onset schizophrenia spectrum disorders: in search of a rational, evidence-informed approach

Purpose of review: We aimed to review literature on the efficacy and tolerability of psychosocial and psychopharmacological interventions in youth with early-onset schizophrenia spectrum disorders (EOS). A rationale for pragmatic psychopharmacology in EOS, including dosing, switching and adverse effect monitoring and management, is provided. Recent findings: Three randomized controlled trials (RCTs) over the last 8 years demonstrated benefits of psychosocial interventions (i.e. psychoeducation, cognitive remediation, cognitive behavioural therapy) for EOS without clear advantages of one psychosocial treatment over another. Six large, placebo-controlled, short-term RCTs over the last 4 years demonstrated that aripiprazole, olanzapine, paliperidone, quetiapine and risperidone, but not ziprasidone, were superior to placebo. Except for clozapine's superiority in treatment-refractory EOS, efficacy appeared similar across studied first-generation and second-generation antipsychotics, but tolerability varied greatly across individual agents. Summary: Antipsychotics are efficacious in the treatment of EOS. Given the lack of efficacy differences between antipsychotics (except for clozapine for treatment-refractory EOS), we propose that tolerability considerations need to guide choice of antipsychotics. Further and longer-term efficacy and effectiveness studies are urgently needed that should also explore pharmacologic and nonpharmacologic augmentation strategies.

The development and evaluation of a computer-based program to test and to teach the recognition of facial affect

Autism is a chronic pervasive neurodevelopmental disorder characterized by the early onset of social and communicative impairments as well as restricted, ritualized, stereotypic behavior. The endophenotype of autism includes neuropsychological deficits, for instance a lack of "Theory of Mind" and problems recognizing facial affect. In this study, we report the development and evaluation of a computer-based program to teach and test the ability to identify basic facially expressed emotions. 10 adolescent or adult subjects with high-functioning autism or Asperger-syndrome were included in the investigation. A priori the facial affect recognition test had shown good psychometric properties in a normative sample (internal consistency: rtt=.91-.95; retest reliability: rtt=.89-.92). In a prepost design, one half of the sample was randomly assigned to receive computer treatment while the other half of the sample served as control group. The training was conducted for five weeks, consisting of two hours training a week. The trained individuals improved significantly on the affect recognition task, but not on any other measure. Results support the usefulness of the program to teach the detection of facial affect. However, the improvement found is limited to a circumscribed area of social-communicative function and generalization is not ensured.

Alterations of white matter integrity related to the season of birth in schizophrenia: a DTI study

In schizophrenia there is a consistent epidemiological finding of a birth excess in winter and spring. Season of birth is thought to act as a proxy indicator for harmful environmental factors during foetal maturation. There is evidence that prenatal exposure to harmful environmental factors may trigger pathologic processes in the neurodevelopment, which subsequently increase the risk of schizophrenia. Since brain white matter alterations have repeatedly been found in schizophrenia, the objective of this study was to investigate whether white matter integrity was related to the season of birth in patients with schizophrenia. Thirty-four patients with schizophrenia and 33 healthy controls underwent diffusion tensor imaging. Differences in the fractional anisotropy maps of schizophrenia patients and healthy controls born in different seasons were analysed with tract-based spatial statistics. A significant main effect of season of birth and an interaction of group and season of birth showed that patients born in summer had significantly lower fractional anisotropy in widespread white matter regions than those born in the remainder of the year. Additionally, later age of schizophrenia onset was found in patients born in winter months. The current findings indicate a relationship of season of birth and white matter alterations in schizophrenia and consequently support the neurodevelopmental hypothesis of early pathological mechanisms in schizophrenia.

Long-term outcome of the unrestricted use of everolimus-eluting stents compared to sirolimus-eluting stents and paclitaxel-eluting stents in diabetic patients: The Bern–Rotterdam diabetes cohort study

BACKGROUND Newer generation everolimus-eluting stents (EES) improve clinical outcome compared to early generation sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES). We investigated whether the advantage in safety and efficacy also holds among the high-risk population of diabetic patients during long-term follow-up. METHODS Between 2002 and 2009, a total of 1963 consecutive diabetic patients treated with the unrestricted use of EES (n=804), SES (n=612) and PES (n=547) were followed throughout three years for the occurrence of cardiac events at two academic institutions. The primary end point was the occurrence of definite stent thrombosis. RESULTS The primary outcome occurred in 1.0% of EES, 3.7% of SES and 3.8% of PES treated patients ([EES vs. SES] adjusted HR=0.58, 95% CI 0.39-0.88; [EES vs. PES] adjusted HR=0.29, 95% CI 0.13-0.67). Similarly, patients treated with EES had a lower risk of target-lesion revascularization (TLR) compared to patients treated with SES and PES ([EES vs. SES], 5.6% vs. 11.5%, adjusted HR=0.68, 95% CI: 0.55-0.83; [EES vs. PES], 5.6% vs. 11.3%, adjusted HR=0.51, 95% CI: 0.33-0.77). There were no differences in other safety end points, such as all-cause mortality, cardiac mortality, myocardial infarction (MI) and MACE. CONCLUSION In diabetic patients, the unrestricted use of EES appears to be associated with improved outcomes, specifically a significant decrease in the need for TLR and ST compared to early generation SES and PES throughout 3-year follow-up.