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Hotspots that form above upwelling plumes of hot material from the deep mantle typically leave narrow trails of volcanic seamounts as a tectonic plate moves over their location. These seamount trails are excellent recorders of Earth’s deep processes and allow us to untangle ancient mantle plume motions. During ascent it is likely that mantle plumes are pushed away from their vertical upwelling trajectories by mantle convection forces. It has been proposed that a large-scale lateral displacement, termed the mantle wind, existed in the Pacific between about 80 and 50 million years ago, and shifted the Hawaiian mantle plume southwards by about 15° of latitude. Here we use 40 Ar/ 39 Ar age dating and palaeomagnetic inclination data from four seamounts associated with the Louisville hotspot in the South Pacific Ocean to show that this hotspot has been relatively stable in terms of its location. Specifically, the Louisville hotspot—the southern hemisphere counterpart of Hawai’i—has remained within 3–5° of its present-day latitude of about 51° S between 70 and 50 million years ago. Although we cannot exclude a more significant southward motion before that time, we suggest that the Louisville and Hawaiian hotspots are moving independently, and not as part of a large-scale mantle wind in the Pacific. The mantle plume beneath Hawai’i shifted southwards by about 15° between 80 and 50 million years ago. Palaeomagnetic inclination data from four South Pacific seamounts along with Ar/Ar dating reveal that by contrast the Louisville hotspot—Hawai’i’s southern hemisphere counterpart—remained within 3° of its present latitude between 70 and 50 million years ago.

Introduction/BackgroundEndometrial cancer (EC) is the most common gynaecologic malignancy in Europe. A hereditary background by germline mutations in the DNA mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) as part of Lynch syndrome (LS) is expected in 2–4% of all EC. For women with LS, the lifetime risk of developing EC is up to 60%, which is higher than colorectal cancer risk. EC is considered a sentinel cancer of women with LS, making its proper diagnostic workup key in the detection of LS and prevention of other cancers. Detection of affected women by Amsterdam II, revised Bethesda criteria has low sensitivity. Up to 30% of EC are MMR deficient (MMRd) which is caused in part by germline mutations.MethodologyWe analysed 231 consecutive EC patients treated at Kliniken Essen-Mitte. MMR was either assessed on paraffin-embedded tumour slides by immunohistochemistry (IHC), PCR based microsatellite analysis or both. In case of MLH1 ± PMS2 deficiency or microsatellite instability additional methylation analysis was performed. Amsterdam II, revised Bethesda criteria and PREMM5 Model were used to detect patients with a familial history at risk for LS.ResultsMMR diagnostic was successfully performed in 213 patients (110-IHC, 69-PCR, and 34-both). MMRd was detected in 45 patients (21.2%). We observed no discordant results between IHC and PCR. Methylation analysis was performed in 75,5% (n=34) of MMRd EC resulting in the identification of 12 patients at risk for LS. The Amsterdam II and Bethesda criteria identified none of these patients. The PREMM5Model proposed further investigation in seven of these patients. Genetic testing was performed in five patients and revealed two mutation carriers.ConclusionGeneral MMRd assessment is a feasible strategy to improve the detection of LS in patients presenting with endometrial cancer as an additional measure to familial history.DisclosureNP has nothing to disclose. BA received fees/honoraria (e.g. lectures, advisory boards) from Roche, Amgen, Astra Zeneca, Tesaro, Clovis, Celgene, and non-financial support (e.g. travel grant) from Roche, PharmaMar, Tesaro outside the submitted work. AdB received honoraria for advisory boards outside the submitted work from Roche, Clovis, Astra Zeneca, Tesaro, Pfizer, Pharmar, Biocad and Genmab.PH received: Honoraria: Astra Zeneca, Roche, Sotio, Tesaro, Stryker, ASCO, Zai Lab, MSD Advisory Board: Astra Zeneca, Roche, Tesaro, Lilly, Clovis, Immunogen, MSD/Merck; Research funding (Inst): Astra Zeneca, Roche, GSK, Boehringer Ingelheim, Medac, DFG, European Union, DKH, Tesaro, Genmab.SP has nothing to disclose.KR has nothing to disclose. FH has received Advisory board: Roche, Tesaro, Honoraria: AstraZeneca, Roche, Tesaro, Clovis, travel/accommodation expenses: PharmaMar; Tesaro.TB has reported research grant from Amgen, travel expenses from Amgen and Roche as well as advisory board membership for Tesaro. BSM has nothing to disclose. SS has received fees/honoraria (e.g. lectures, advisory boards) Tesaro, Astra Zeneca, Roche and travel grant from Tesaro outside the submitted work. SH has nothing to disclose.SE has nothing to disclose. AT has nothing to disclose.

Over the past few decades, there has been increasing interest in the study of social impairment in schizophrenia. However, the concept of social functioning has been poorly defined in the literature. This article highlights the global and multi-factorial nature of social functioning and reviews the theoretical determinants of social dysfunction in schizophrenia. Emphasis is placed on outlining the social cognitive deficits that may occur. The study of social cognition appears particularly promising in elucidating our understanding of the development of social impairment in schizophrenia and has the potential to improve current psychosocial interventions. However, continued advances depend upon the existence of reliable and well-validated measures of social functioning and social cognition. A selection of measures are reviewed in this article in an attempt to highlight the importance of assessing multiple aspects of social functioning in schizophrenia and to assist researchers in the selection of appropriate measures. Future efforts should be directed towards the continued validation of social functioning and social cognitive measures and their adaptation for use in at-risk and early psychosis populations.

Verbal memory impairment is a core feature in schizophrenia even at early stages of the disease, but its etiopathogenesis is not fully understood. The -ε4 is the main genetic risk factor for late-onset Alzheimer's disease. Our primary goal was to ascertain whether -ε4 status had a pleiotropic effect in early stages of the illness. A total of 86 first-episode psychosis (FEP) outpatients and 39 healthy volunteers were recruited. Demographic and clinical data, genotyping, and a neuropsychological test battery including the California Verbal Learning Test - second edition (CVLT-II) were administered and assessed at study entry and at 1-year follow-up. Data were analyzed using mixed-model repeated measures, where the dependent variable was verbal memory indexed by California Verbal Learning Test (CVLT) Trials 1-5 total recall score. FEP- -ε4 carriers and FEP- -ε4 noncarriers had similar symptom severity, clinical outcomes, premorbid and current intelligence quotient, and exposure to antipsychotics. There was a main effect of group on CVLT 1-5 (FEP =43.30 vs control =58.25; [1, 119.7]=42.97; <0.001) as well as an -ε4 by group by time ( [4, 116.2]=2.73, =0.033) interaction with only FEP- -ε4 carriers showing improved verbal memory at follow-up. Our study is the first to report improvement in verbal memory in persons afflicted by FEP who are -ε4 carriers and replicates the prominent verbal memory deficits present in FEP. Our work provides further evidence pointing to an antagonistic pleiotropic effect of -ε4 in neuropsychiatric disorders. Our results merit further research into antagonistic pleiotropic effects in schizophrenia.

Nature Geoscience 5, 911–917 (2012); published online 25 November 2012. In the print version of this Article originally published, the present address for Toshitsugu Yamazaki was erroneously omitted. It is as follows: Atmosphere and Ocean Research Institute, The University of Tokyo, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8564, Japan.

Background Small-bowel obstruction is a frequent disorder in emergency medicine and represents a major burden for patients and health care systems worldwide. Within the past years, progress has been made regarding the management of small-bowel obstructions, including the use of contrast agent swallow as a tool in the decision-making process. Objectives This is a prospective controlled study investigating the central role of contrast agent swallow in the diagnostic and treatment algorithm for small-bowel obstruction at a university department of surgery. Endpoints were the correct identification of patients who needed operative treatment and the accuracy of a conservative treatment decision including the analysis of dropout from this routine algorithm. Methods We performed a single-center analysis of 181 consecutive patients diagnosed with a small-bowel obstruction based on clinical, radiologic, and sonographic findings. Patients with clinical signs of strangulation or peritonitis underwent immediate surgery (group 1). Patients without signs of peritonitis and incomplete stop in the initial abdominal plain film were considered eligible for Gastrografin® challenge (group 2). Results Seventy-six of the 181 patients (42.0%) underwent immediate surgery. A Gastrografin® challenge was initialized in 105 of the 181 patients (58.0%). Twenty of these 105 patients (19.1%) with persisting or progressive symptoms and absence of contrast agent in the colon after 12 and 24 h subsequently underwent surgery. Here, a segmental bowel resection was necessary in 6 of these 20 patients (30.0%). In 16 out of 20 patients (80.0%) who failed the Gastrografin® challenge, a corresponding correlate in terms of a strangulation was detected intraoperatively. The Gastrografin® challenge had a specificity of 96% and a sensitivity of 100%; accuracy to predict the need for exploration was 96%. Conclusion A straightforward algorithm based mainly on contrast agent swallow for patients with small-bowel obstructions enabled a timely and very accurate differentiation between patients qualifying for conservative and operative treatment.

Objective: Factor analytic studies of the Positive and Negative Syndrome Scale (PANSS) have consistently isolated a factor that is frequently labeled as ‘cognitive’. The present study sought to further explore the factor by examining the relationships between 4 versions of the cognitive factor and a set of neuropsychological tests. Method: Thirty-seven inpatients diagnosed with schizophrenia or schizoaffective disorder were assessed with the PANSS and neuropsychological measures. Results: Verbal intelligence and verbal memory were found to be most closely associated with cognitive factor scores. A global rating of illness severity showed greater relationships to cognitive variables than any cognitive factor. Conclusions: The PANSS cognitive factor may reflect verbal ability and memory, but is not sufficiently comprehensive to be considered as a replacement for direct assessment of cognitive functioning.

Background: Verbal memory impairment is a core feature in schizophrenia even at early stages of the disease, but its etiopathogenesis is not fully understood. The APOE-[epsilon]4 is the main genetic risk factor for late-onset Alzheimer's disease. Our primary goal was to ascertain whether APOE-[epsilon]4 status had a pleiotropic effect in early stages of the illness. Participants and methods: A total of 86 first-episode psychosis (FEP) outpatients and 39 healthy volunteers were recruited. Demographic and clinical data, APOE genotyping, and a neuropsychological test battery including the California Verbal Learning Test--second edition (CVLT-II) were administered and assessed at study entry and at 1-year follow-up. Data were analyzed using mixed-model repeated measures, where the dependent variable was verbal memory indexed by California Verbal Learning Test (CVLT) Trials 1-5 total recall score. Results: FEP-APOE-[epsilon]4 carriers and FEP-APOE-[epsilon]4 noncarriers had similar symptom severity, clinical outcomes, premorbid and current intelligence quotient, and exposure to antipsychotics. There was a main effect of group on CVLT 1-5 (FEP =43.30 vs control =58.25; F[1, 119.7]=42.97; P<0.001) as well as an APOE-[epsilon]4 by group by time (F[4, 116.2]=2.73, P=0.033) interaction with only FEP-APOE-[epsilon]4 carriers showing improved verbal memory at follow-up. Conclusion: Our study is the first to report improvement in verbal memory in persons afflicted by FEP who are APOE-[epsilon]4 carriers and replicates the prominent verbal memory deficits present in FEP. Our work provides further evidence pointing to an antagonistic pleiotropic effect of APOE-[epsilon]4 in neuropsychiatric disorders. Our results merit further research into antagonistic pleiotropic effects in schizophrenia. Keywords: APOE, verbal memory, antagonistic pleiotropy, first-episode psychosis, schizophrenia

This study examined the reliability and validity of a brief, face-valid self-report measure designed to assess subjective judgments of functioning. The Patient Perception of Functioning Scale (PPFS) is a 6-item scale with ratings for both community functioning and cognition. Sixty-eight subjects with psychotic disorders were recruited to complete the PPFS on 2 occasions and to complete a battery of neurocognitive tests. Objective ratings of overall illness severity (Clinical Global Impression), illness severity (Global Assessment of Functioning), and functioning (Social and Occupational Functioning Assessment Scale and Role Functioning Scale) were also obtained. The internal consistency and test-retest correlation coefficients revealed that the PPFS possesses good reliability characteristics. The PPFS did not show relationships to demographic, historical, or illness-related variables such as diagnosis or length of illness. The PPFS did show significant associations with several dimensions of community functioning. However, no significant associations were found with neurocognitive measures or clinical status. In populations with psychotic disorders, self-reported ratings of community function and cognition may converge less with objective cognitive measures than with objective ratings of everyday functioning. Several factors inherent to self-report methodology may have contributed to the poor convergent validity results. Theoretical underpinnings and operationalization of the underlying constructs of some neuropsychological instruments may not closely match how patients conceptualize those constructs.