404 research outputs found

    A global digital image correlation enhanced full-field bulge test method

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    The miniature bulge test is a known method for characterizing the full stress-strain response of freestanding thin films. However, some discrepancies between quantitative results in the literature may be attributed to erroneous assumptions on the bulge shape. In this research, a specialized global Digital Image Correlation technique is developed that circumvents the need for bulge shape assumptions by correlating directly high-resolution profilometry maps of bulged membranes to yield full-field continuous displacement maps, from which local strain maps can be computed. Additionally, local curvature maps are also derived

    Conversion of daily pegvisomant to weekly pegvisomant combined with long-acting somatostatin analogs, in controlled acromegaly patients

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    The efficacy of combined treatment in active acromegaly with both long-acting somatostatin analogs (SRIF) and pegvisomant (PEG-V) has been well established. The aim was to describe the PEG-V dose reductions after the conversion from daily PEG-V to combination treatment. To clarify the individual beneficial and adverse effects, in two acromegaly patients, who only normalized their insulin like growth factor (IGF-I) levels with high-dose pegvisomant therapy. We present two cases of a 31 and 44 years old male with gigantism and acromegaly that were controlled subsequently by surgery, radiotherapy, SRIF analogs and daily PEG-V treatment. They were converted to combined treatment of monthly SSA and (twice) weekly PEG-V. High dose SSA treatment was added while the PEG-V dose was decreased during carful monitoring of the IGF-I. After switching from PEG-V monotherapy to SRIF analogs plus pegvisomant combination therapy IGF-I remained normal. However, the necessary PEG-V dose, to normalize IGF-I differed significantly between these two patients. One patient needed twice weekly 100 mg, the second needed 60 mg once weekly on top of their monthly lanreotide Autosolution injections of 120 mg. The weekly dose reduction was 80 and 150 mg. After the introducing of lanreotide, fasting glucose and glycosylated haemoglobin concentrations increased. Diabetic medication had to be introduced or increased. No changes in liver tests or in pituitary adenoma size were observed. In these two patients, PEG-V in combination with long-acting SRIF analogs was as effective as PEG-V monotherapy in normalizing IGF-I levels, although significant dose-reductions in PEG-V could be achieved. However, there seems to be a wide variation in the reduction of PEG-V dose, which can be obtained after conversion to combined treatment

    In active acromegaly, IGF1 bioactivity is related to soluble Klotho levels and quality of life

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    The value of measuring IGF1 bioactivity in active acromegaly is unknown. Soluble Klotho (S-Klotho) level is elevated in active acromegaly and it has been suggested that S-Klotho can inhibit activation of the IGF1 receptor (IGF1R). A cross-sectional study was carried out in 15 patients with active acromegaly based on clinical presentation, unsuppressed GH during an oral glucose tolerance test, and elevated total IGF1 levels (>+2 s.d.). Total IGF1 was measured by immunoassay, IGF1 bioactivity by the IGF1R kinase receptor activation assay and S-Klotho by an ELISA. Quality of Life (QoL) was assessed by Acromegaly QoL (AcroQoL) Questionnaire and Short-Form-36 Health Survey Questionnaire (SF-36). Out of 15 patients, nine had IGF1 bioactivity values within the reference range. S-Klotho was higher in active acromegaly compared with controls. Age-adjusted S-Klotho was significantly related to IGF1 bioactivity (r=0.75, P=0.002) and to total IGF1 (r=0.62, P=0.02). IGF1 bioactivity and total IGF1 were inversely related to the physical component summary of the SF-36 (r=−0.78, P=0.002 vs r=−0.60, P=0.03). Moreover, IGF1 bioactivity, but not total IGF1, was significantly inversely related to the physical dimension of the AcroQoL Questionnaire (r=−0.60, P=0.02 vs r=−0.37, P=0.19). In contrast to total IGF1, IGF1 bioactivity was within the reference range in a considerable number of subjects with active acromegaly. Elevated S-Klotho levels may have reduced IGF1 bioactivity. Moreover, IGF1 bioactivity was more strongly related to physical measures of QoL than total IGF1, suggesting that IGF1 bioactivity may better reflect physical limitations perceived in active acromegaly

    Modeling the evolution space of breakage fusion bridge cycles with a stochastic folding process

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    Breakage-Fusion-Bridge cycles in cancer arise when a broken segment of DNA is duplicated and an end from each copy joined together. This structure then 'unfolds' into a new piece of palindromic DNA. This is one mechanism responsible for the localised amplicons observed in cancer genome data. The process has parallels with paper folding sequences that arise when a piece of paper is folded several times and then unfolded. Here we adapt such methods to study the breakage-fusion-bridge structures in detail. We firstly consider discrete representations of this space with 2-d trees to demonstrate that there are 2^(n(n-1)/2) qualitatively distinct evolutions involving n breakage-fusion-bridge cycles. Secondly we consider the stochastic nature of the fold positions, to determine evolution likelihoods, and also describe how amplicons become localised. Finally we highlight these methods by inferring the evolution of breakage-fusion-bridge cycles with data from primary tissue cancer samples

    Celio (\u2705), Orkand (\u2707) Named Up and Coming Leaders

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    BackgroundAlthough auditory verbal hallucinations (AVH) are a core symptom of schizophrenia, they also occur in non-psychotic individuals, in the absence of other psychotic, affective, cognitive and negative symptoms. AVH have been hypothesized to result from deviant integration of inferior frontal, parahippocampal and superior temporal brain areas. However, a direct link between dysfunctional connectivity and AVH has not yet been established. To determine whether hallucinations are indeed related to aberrant connectivity, AVH should be studied in isolation, for example in non-psychotic individuals with AVH.MethodResting-state connectivity was investigated in 25 non-psychotic subjects with AVH and 25 matched control subjects using seed regression analysis with the (1) left and (2) right inferior frontal, (3) left and (4) right superior temporal and (5) left parahippocampal areas as the seed regions. To correct for cardiorespiratory (CR) pulsatility rhythms in the functional magnetic resonance imaging (fMRI) data, heartbeat and respiration were monitored during scanning and the fMRI data were corrected for these rhythms using the image-based method for retrospective correction of physiological motion effects RETROICOR.ResultsIn comparison with the control group, non-psychotic individuals with AVH showed increased connectivity between the left and the right superior temporal regions and also between the left parahippocampal region and the left inferior frontal gyrus. Moreover, this group did not show a negative correlation between the left superior temporal region and the right inferior frontal region, as was observed in the healthy control group.ConclusionsAberrant connectivity of frontal, parahippocampal and superior temporal brain areas can be specifically related to the predisposition to hallucinate in the auditory domain.</jats:sec

    Non-invasive brain stimulation in schizophrenia:hallucinations and negative symptoms

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    BACKGROUND: New approaches are needed in the treatment of characteristic symptoms of schizophrenia such as hallucinations and negative symptoms. Non-invasive brain stimulation can make a useful contribution.&lt;br/&gt; AIM: To discuss the published evidence regarding efficacy and safety of repetitive transcranial magnetic stimulation (rtms) and transcranial direct current stimulation (tdcs) when used in the treatment of auditory verbal hallucinations and negative symptoms.&lt;br/&gt; METHOD: We review and discuss recent meta-analyses and we analyse relevant factors.&lt;br/&gt; RESULTS: On average, when compared to sham-stimulation, rtms was found to have a significant effect on hallucinations and negative symptoms. Nevertheless, the results of some studies were variable and some studies did not report any improvement. There are indications that some factors such as age and distance between scalp and cortex may influence efficiency. There were only a few studies relating to the use of tdcs and none of these reported a clear effect.&lt;br/&gt; CONCLUSION: There is reasonable evidence that rtms is an efficient treatment for hallucinations and negative symptoms, although some variable results have been reported. There is insufficient evidence for conclusions to be drawn about the efficacy of tdcs for the treatment of hallucinations and negative symptoms. However, both simulation methods are safe and largely without side-effects.</p

    Combining eye and hand in search is suboptimal

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    When performing everyday tasks, we often move our eyes and hand together: we look where we are reaching in order to better guide the hand. This coordinated pattern with the eye leading the hand is presumably optimal behaviour. But eyes and hands can move to different locations if they are involved in different tasks. To find out whether this leads to optimal performance, we studied the combination of visual and haptic search. We asked ten participants to perform a combined visual and haptic search for a target that was present in both modalities and compared their search times to those on visual only and haptic only search tasks. Without distractors, search times were faster for visual search than for haptic search. With many visual distractors, search times were longer for visual than for haptic search. For the combined search, performance was poorer than the optimal strategy whereby each modality searched a different part of the display. The results are consistent with several alternative accounts, for instance with vision and touch searching independently at the same time

    Gaze–mouse coordinated movements and dependency with coordination demands in tracing.

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    Eye movements have been shown to lead hand movements in tracing tasks where subjects have to move their fingers along a predefined trace. The question remained, whether the leading relationship was similar when tracing with a pointing device, such as a mouse; more importantly, whether tasks that required more or less gaze–mouse coordination would introduce variation in this pattern of behaviour, in terms of both spatial and temporal leading of gaze position to mouse movement. A three-level gaze–mouse coordination demand paradigm was developed to address these questions. A substantial dataset of 1350 trials was collected and analysed. The linear correlation of gaze–mouse movements, the statistical distribution of the lead time, as well as the lead distance between gaze and mouse cursor positions were all considered, and we proposed a new method to quantify lead time in gaze–mouse coordination. The results supported and extended previous empirical findings that gaze often led mouse movements. We found that the gaze–mouse coordination demands of the task were positively correlated to the gaze lead, both spatially and temporally. However, the mouse movements were synchronised with or led gaze in the simple straight line condition, which demanded the least gaze–mouse coordination
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