Constraining the long-term evolution of the slip rate for a major extensional fault system in the central Aegean, Greece, using thermochronology

The brittle/ductile transition is a major rheologic boundary in the crust yet little is known about how or if rates of tectonic processes are influenced by this boundary. In this study we examine the slip history of the large-scale Naxos/Paros extensional fault system (NPEFS), Cyclades, Greece, by comparing published slip rates for the ductile crust with new thermochronological constraints on slip rates in the brittle regime. Based on apatite and zircon fission-track (AFT and ZFT) and (U–Th)/He dating we observe variable slip rates across the brittle/ductile transition on Naxos. ZFT and AFT ages range from 11.8 ± 0.8 to 9.7 ± 0.8 Ma and 11.2 ± 1.6 to 8.2 ± 1.2 Ma and (U–Th)/He zircon and apatite ages are between 10.4 ± 0.4 to 9.2 ± 0.3 Ma and 10.7 ± 1.0 to 8.9 ± 0.6 Ma, respectively. On Paros, ZFT and AFT ages range from 13.1 ± 1.4 Ma to 11.1 ± 1.0 Ma and 12.7 ± 2.8 Ma to 10.5 ± 2.0 Ma while the (U–Th)/He zircon ages are slightly younger between 8.3 ± 0.4 Ma and 9.8 ± 0.3 Ma. All ages consistently decrease northwards in the direction of hanging wall transport. Most of our new thermochronological results and associated thermal modeling more strongly support the scenario of an identical fault dip and a constant or slightly accelerating slip rate of 6–8 km Myr− 1 on the NPEFS across the brittle/ductile transition. Even the intrusion of a large granodiorite body into the narrowing fault zone at 12 Ma on Naxos does not seem to have affected the thermal structure of the area in a way that would significantly disturb the slip rate. The data also show that the NPEFS accomplished a minimum total offset of 50 km between 16 and 8 Ma

Understanding self-reported difficulties in decision-making by people with autism spectrum disorders.

Autobiographical accounts and a limited research literature suggest that adults with autism spectrum disorders can experience difficulties with decision-making. We examined whether some of the difficulties they describe correspond to quantifiable differences in decision-making when compared to adults in the general population. The participants (38 intellectually able adults with autism spectrum disorders and 40 neurotypical adults) were assessed on three tasks of decision-making (Iowa Gambling Task, Cambridge Gamble Task and Information Sampling Task), which quantified, respectively, decision-making performance and relative attention to negative and positive outcomes, speed and flexibility, and information sampling. As a caution, all analyses were repeated with a subset of participants ( nASD = 29 and nneurotypical = 39) who were not taking antidepressant or anxiolytic medication. Compared to the neurotypical participants, participants with autism spectrum disorders demonstrated slower decision-making on the Cambridge Gamble Task, and superior performance on the Iowa Gambling Task. When those taking the medications were excluded, participants with autism spectrum disorders also sampled more information. There were no other differences between the groups. These processing tendencies may contribute to the difficulties self-reported in some contexts; however, the results also highlight strengths in autism spectrum disorders, such as a more logical approach to, and care in, decision-making. The findings lead to recommendations for how adults with autism spectrum disorders may be better supported with decision-making.The research reported here was carried out by the first author (Lydia Vella, née Luke) as part of her PhD in the Department of Psychiatry, University of Cambridge, and was supported by a Pinsent Darwin Studentship in Mental Health; University of Cambridge Domestic Research Studentship; the Charles Slater Fund; and the Marmaduke Sheild Fund. IC was supported during the preparation of this paper by the National Institute of Health Research (NIHR) Collaboration for Applied Health Research and Care (CLAHRC) East of England at Cambridgeshire & Peterborough NHS Foundation Trust. We are grateful to all our funders for their support. The paper describes independent research and the views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health

Transcutaneous vagus nerve stimulation (t-VNS): A novel effective treatment for temper outbursts in adults with Prader-Willi Syndrome indicated by results from a non-blind study.

Temper outbursts are a severe problem for people with Prader-Willi Syndrome (PWS). Previous reports indicate that vagus nerve stimulation (VNS) may reduce maladaptive behaviour in neurodevelopmental disorders, including PWS. We systematically investigated the effectiveness of transcutaneous VNS (t-VNS) in PWS. Using a non-blind single case repeat measures modified ABA design, with participants as their own controls, t-VNS was evaluated in five individuals with PWS [three males; age 22-41 (M = 26.8)]. After a baseline phase, participants received four-hours of t-VNS daily for 12 months, followed by one month of daily t-VNS for two-hours. The primary outcome measure was the mean number of behavioural outbursts per day. Secondary outcomes included findings from behavioural questionnaires and both qualitative and goal attainment interviews. Four of the five participants who completed the study exhibited a statistically significant reduction in number and severity of temper outbursts after approximately nine months of daily four-hour t-VNS. Subsequent two-hour daily t-VNS was associated with increased outbursts for all participants, two reaching significance. Questionnaire and interview data supported these findings, the latter indicating potential mechanisms of action. No serious safety issues were reported. t-VNS is an effective, novel and safe intervention for chronic temper outbursts in PWS. We propose these changes are mediated through vagal projections and their effects both centrally and on the functioning of the parasympathetic nervous system. These findings challenge our present biopsychosocial understanding of such behaviours suggesting that there is a single major mechanism that is modifiable using t-VNS. This intervention is potentially generalizable across other clinical groups. Future research should address the lack of a sham condition in this study along with the prevalence of high drop out rates, and the potential effects of different stimulation intensities, frequencies and pulse widths

Echocardiographic assessment of pulmonary hypertension: a guideline protocol from the British Society of Echocardiography.

Pulmonary hypertension is defined as a mean arterial pressure of ≥25 mmHg as confirmed on right heart catheterisation. Traditionally, the pulmonary arterial systolic pressure has been estimated on echo by utilising the simplified Bernoulli equation from the peak tricuspid regurgitant velocity and adding this to an estimate of right atrial pressure. Previous studies have demonstrated a correlation between this estimate of pulmonary arterial systolic pressure and that obtained from invasive measurement across a cohort of patients. However, for an individual patient significant overestimation and underestimation can occur and the levels of agreement between the two is poor. Recent guidance has suggested that echocardiographic assessment of pulmonary hypertension should be limited to determining the probability of pulmonary hypertension being present rather than estimating the pulmonary artery pressure. In those patients in whom the presence of pulmonary hypertension requires confirmation, this should be done with right heart catheterisation when indicated. This guideline protocol from the British Society of Echocardiography aims to outline a practical approach to assessing the probability of pulmonary hypertension using echocardiography and should be used in conjunction with the previously published minimum dataset for a standard transthoracic echocardiogram

Long-term cognitive outcome in adult survivors of an early childhood posterior fossa brain tumour

Funder: Samantha Dickson Brain Tumour Trust; doi: http://dx.doi.org/10.13039/501100000394Abstract: Purpose: Posterior fossa brain tumours (PFT) and their treatment in young children are often associated with subsequent cognitive impairment. However, reported follow-up periods rarely exceed 10 years. This study reports very long-term cognitive consequences of surviving an early childhood PFT. Methods: 62 adult survivors of a PFT, ascertained from a national register, diagnosed before 5 years of age, and a sibling control, received a single IQ assessment an average of 32 years (range 18–53) after initial diagnosis, using the Weschler Abbreviated Scale of Intelligence. Regression models were fitted to survivor–sibling pair differences on verbal and performance IQ (VIQ and PIQ) scores to investigate whether increasing time between PFT diagnosis and follow-up IQ assessment contributed to survivor–sibling IQ differences. Results: At follow-up, survivors had, on average, VIQ 15 points and PIQ 19 points lower than their siblings. There was no significant effect of time since diagnosis on survivor–sibling VIQ difference. Survivors who received radiotherapy showed no significant effect of time since diagnosis on survivor–sibling PIQ difference. Survivors who did not receive radiotherapy demonstrated a trend for it to reduce. Conclusions: VIQ and PIQ deficits persist in adulthood, suggesting the effect of a fixed injury imposing on cognitive development, rather than an ongoing pathological process. Implications for cancer survivors: The findings will help parents and others supporting survivors of an early life PFT to identify and plan for possible cognitive outcomes, and highlight the importance of early interventions to optimize cognitive function during the developmental period

Microneurosurgical Anastomoses for Cerebral Ischemia [Contents]

From jacket: The purpose of this volume is to present a series of important papers on the rapidly growing surgical field of microneurosurgical anastomoses for cerebral ischemia. It includes papers on the indications and results of microneurosurgical bypass anastomoses; on the techniques used to study patients before and after surgery, including cerebral blood flow psychometic testing, etc.; and on the basic mechanisms of cerebral ischemia studies in animals. New ideas are suggested for techniques involving increased use of the occipital arteries and the development of vein, arterial, or prosthetic grafts in place of the STA (superficial temporal artery). Also discussed are the importance of measuring blood flow in the STA where possible, and the measurement of cerebral blood flow pre- and postoperatively to monitor the results. Psychometric studies are shown to be of importance pre- and postoperatively in addition to careful neurologic evaluation

CD36 Inhibitors Reduce Postprandial Hypertriglyceridemia and Protect against Diabetic Dyslipidemia and Atherosclerosis

CD36 is recognized as a lipid and fatty acid receptor and plays an important role in the metabolic syndrome and associated cardiac events. The pleiotropic activity and the multiple molecular associations of this scavenger receptor with membrane associated molecules in different cells and tissues have however questioned its potential as a therapeutic target. The present study shows that it is possible to identify low molecular weight chemicals that can block the CD36 binding and uptake functions. These inhibitors were able to reduce arterial lipid deposition, fatty acid intestinal transit, plasma concentration of triglycerides and glucose, to improve insulin sensitivity, glucose tolerance and to reduce the plasma concentration of HbAc1 in different and independent rodent models. Correlation between the anti-CD36 activity of these inhibitors and the known pathophysiological activity of this scavenger receptor in the development of atherosclerosis and diabetes were observed at pharmacological doses. Thus, CD36 might represent an attractive therapeutic target

Thromboxane biosynthesis in cancer patients and its inhibition by aspirin: a sub-study of the Add-Aspirin trial

BACKGROUND: Pre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases. METHODS: Urinary 11-dehydro-thromboxane B2 (U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values. RESULTS: In total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (~500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P < 0.001) independent of other baseline characteristics. Aspirin 100 mg daily decreased U-TXM similarly across all tumour types (median reductions: 77-82%). Aspirin 300 mg daily provided no additional suppression of U-TXM compared with 100 mg. CONCLUSIONS: Persistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin

The relationship between change in subjective outcome and change in disease: a potential paradox

Contains fulltext : 87756.pdf (publisher's version ) (Closed access)BACKGROUND: Response shift theory suggests that improvements in health lead patients to change their internal standards and re-assess former health states as worse than initially rated when using retrospective ratings via the then-test. The predictions of response shift theory can be illustrated using prospect theory, whereby a change in current health causes a change in reference frame. Therefore, if health deteriorates, the former health state will receive a better rating, whereas if it improves, the former health state will receive a worse rating. OBJECTIVE: To explore the predictions of response shift and prospect theory by relating subjective change to objective change. METHODS: Baseline and 3-month follow-up data from a cohort of rheumatoid arthritis patients (N = 197) starting on TNFalpha-blocking agents were used. Objective disease change was classified according to a disease-specific clinical outcome measure (DAS28). Visual analogue scales (VAS) for general health (GH) and pain were used as self-reported measures. Three months after starting on anti-TNFalpha, patients used the then-test to re-rate their baseline health with regard to general health and pain. Differences between then-test value and baseline values were calculated and tested between improved, non-improved and deteriorated patients by the Student t-test. RESULTS: At 3 months, 51 (25.9%) patients had good improvement in health, 83 (42.1%) had moderate improvement, and 63 (32.0%) had no improvement or deteriorated in health. All patients no matter whether they improved, did not improve, or even became worse rated their health as worse retrospectively. The difference between the then-test rating and the baseline value was similarly sized in all groups. CONCLUSION: More positive ratings of retrospective health are independent of disease change. This suggests that patients do not necessarily change their standards in line with their disease change, and therefore it is inappropriate to use the then-test to correct for such a change. If a then-test is used to correct for shifts in internal standards, it might lead to the paradoxical result that patients who do not improve or even deteriorate increase significantly on self-reported health and pain. An alternative explanation for differences in retrospective and prospective ratings of health is the implicit theory of change which is more successful in explaining our results than prospect theory.1 september 201