ADHD 24/7:Circadian clock genes, chronotherapy and sleep/wake cycle insufficiencies in ADHD

Objectives: The current paper addresses the evidence for circadian clock characteristics associated with attention-deficit hyperactivity disorder (ADHD), and possible therapeutic approaches based on chronomodulation through bright light (BL) therapy. Methods: We review the data reported in ADHD on genetic risk factors for phase-delayed circadian rhythms and on the role of photic input in circadian re-alignment. Results: Single nucleotide polymorphisms in circadian genes were recently associated with core ADHD symptoms, increased evening-orientation and frequent sleep problems. Additionally, alterations in exposure and response to photic input may underlie circadian problems in ADHD. BL therapy was shown to be effective for re-alignment of circadian physiology toward morningness, reducing sleep disturbances and bringing overall improvement in ADHD symptoms. The susceptibility of the circadian system to phase shift by timed BL exposure may have broad cost-effective potential implications for the treatment of ADHD. Conclusions: We conclude that further research of circadian function in ADHD should focus on detection of genetic markers (e.g., using human skin fibroblasts) and development of BL-based therapeutic interventions

Acute enlargement and subsequent rupture of an abdominal aortic aneurysm in a patient receiving chemotherapy for pancreatic carcinoma

AbstractWe report a case of ruptured abdominal aortic aneurysm (AAA) in a patient receiving chemotherapy for pancreatic cancer. We reviewed the literature on the effects of corticosteroids and chemotherapy on aaa formation and discuss possible mechanisms for drug action to promote aneurysm expansion and rupture. If cancer and AAA coincide and curative chemotherapy is possible, a potential impact of chemotherapy on AAA expansion should be considered. (J Vasc Surg 2000;32:197-200.

Influence of Surface Tension and Evaporation on Melt Dynamics of Aluminum Alloys for Laser Powder Bed Fusion

One of the most important factors during Laser Powder Bed Fusion is a robust and stable process to generate reproducibly dense and crack-free components with the same homogenous and fine-grained microstructure. Among other factors, surface tension influences the robustness of this process. Three aluminum alloys were investigated by means of 3D laser printing with respect to their ability to form lightweight and high-performance structures. The alloys include two Al-Cr based alloys (Zicromal®: Al-Cr-Zr-Mn, Scancromal®: Al-Cr-Sc-Zr) and an Al-Mg based alloy (Scalmalloy®: Al-Mg-Sc-Mn-Zr). The surface tensions of their liquid melts were measured by means of the oscillating droplet method in electromagnetic levitation. Scalmalloy® exhibited a surface tension that was by 3-8% smaller than the other two alloys, over a temperature range of 500 K above their liquidus temperature; the evaporation analysis showed that Scancromal® exhibits significantly less evaporation compared to the other two alloys by an order of magnitude. During the Laser Powder Bed Fusion process, Scalmalloy® presented the most unstable melt dynamics, and Scancromal® appeared to be more robust and stable with less weld spatters and negligible dust deposition, as evidence from the high-speed video observations. The results support the idea that surface tension and evaporation are potentially crucial factors influencing the melt dynamics and also demonstrate the capability of additive manufacturing that produces customized aluminum alloys for aerospace applications

Microstructure Evolution of a New Precipitation-Strengthened Fe–Al–Ni–Ti Alloy down to Atomic Scale

Ferritic materials consisting of a disordered matrix and a significant volume fraction of ordered intermetallic precipitates have recently gained attention due to their favorable properties regarding high-temperature applicability. Alloys strengthened by Heusler-type precipitates turned out to show promising properties at elevated temperatures, e.g., creep resistance. The present work aims at developing a fundamental understanding of the microstructure of an alloy with a nominal composition of 60Fe–20Al–10Ni–10Ti (in at. %). In order to determine the microstructural evolution, prevailing phases and corresponding phase transformation temperatures are investigated. Differential thermal analysis, high-temperature X-ray diffraction, and special heat treatments were performed. The final microstructures are characterized by means of scanning and transmission electron microscopy along with hardness measurements. Atom probe tomography conducted on alloys of selected heat-treated conditions allows for evaluating the chemical composition and spatial arrangement of the constituent phases. All investigated sample conditions showed microstructures consisting of two phases with crystal structures A2 and L21. The L21 precipitates grew within a continuous A2 matrix. Due to a rather small lattice mismatch, matrix–precipitate interfaces are either coherent or semicoherent depending on the cooling condition after heat treatment

BIOTINYLATED AND CHELATED POLY-L-LYSINE AS EFFECTOR FOR PRETARGETING IN CANCER THERAPY AND IMAGING

Objective: The aim of this study was to synthesise and evaluate polylysine-based effectors for pretargeted radioimmunotherapy and imaging. These molecules can readily be size-modified and charge-modified to decrease the renal uptake of radioactivity, which is often a major problem for small radiolabeled molecules. Several chelators and biotin molecules (for antibody-streptavidin-binding in vivo) are also easily incorporated into one structure because of the polylysine.Methods: The effectors were synthesised using poly-L-lysine, NHS-LC-biotin, CHX-A''-DTPA or p-SCN-Bn-DOTA and succinic anhydride. They were characterised, labelled with 213Bi for targeted α therapy, 68Ga for PET and 111In for SPECT, and evaluated in vitro. A kidney uptake study was performed as well with two different-sized 213Bi-labeled effectors, to evaluate how the difference in size affects the renal filtration.Results: Radiochemical purities between 97.4±0.6 % and 99.6±0.1 % and decay-corrected yields of 80.2±2.4 % after purification were achieved with the radiolabeled molecules, as well as a specific activity of 7.6 × 103GBq/µmol. The avidin binding capacity was 94.4±1.9%. The kidney uptake study demonstrated a reduction of renal absorbed dose by 80% when modifying the molecular size and charge.Conclusion: The synthesised polylysine-based effectors show potential for further in vivo evaluation in pretargeted radioimmunotherapy and imaging

Effects of Transcranial Direct Current Stimulation on Information Processing Speed, Working Memory, Attention, and Social Cognition in Multiple Sclerosis

Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Cognitive impairment occurs in 40–65% of patients and could drastically affect their quality of life. Deficits could involve general cognition (e.g., attention and working memory) as well as social cognition. Transcranial direct current stimulation (tDCS), is a novel brain stimulation technique that has been assessed in the context of several neuropsychiatric symptoms, including those described in the context of MS. However, very rare trials have assessed tDCS effects on general cognition in MS, and none has tackled social cognition. The aim of this work was to assess tDCS effects on general and social cognition in MS. Eleven right-handed patients with MS received two blocks (bifrontal tDCS and sham, 2 mA, 20 min, anode/cathode over left/right prefrontal cortex) of 5 daily stimulations separated by a 3-week washout interval. Working memory and attention were, respectively, measured using N-Back Test (0-Back, 1-Back, and 2-Back) and Symbol Digit Modalities Test (SDMT) at the first and fifth day of each block and 1 week later. Social cognition was evaluated using Faux Pas Test and Eyes Test at baseline and 1 week after each block. Interestingly, accuracy of 1-Back test improved following sham but not active bifrontal tDCS. Therefore, active bifrontal tDCS could have impaired working memory via cathodal stimulation of the right prefrontal cortex. No significant tDCS effects were observed on social cognitive measures and SDMT. Admitting the small sample size and the learning (practice) effect that might arise from the repetitive administration of each task, the current results should be considered as preliminary and further investigations in larger patient samples are needed to gain a closer understanding of tDCS effects on cognition in MS

The influence of instrumental line shape degradation on NDACC gas retrievals: Total column and profile

We simulated instrumental line shape (ILS) degradations with respect to typical types of misalignment, and compared their influence on each NDACC (Network for Detection of Atmospheric Composition Change) gas. The sensitivities of the total column, the root mean square (rms) of the fitting residual, the total random uncertainty, the total systematic uncertainty, the total uncertainty, degrees of freedom for signal (DOFs), and the profile with respect to different levels of ILS degradation for all current standard NDACC gases, i.e. O3, HNO3, HCl, HF, ClONO2, CH4, CO, N2O, C2H6, and HCN, were investigated. The influence of an imperfect ILS on NDACC gases’ retrieval was assessed, and the consistency under different meteorological conditions and solar zenith angles (SZAs) were examined. The study concluded that the influence of ILS degradation can be approximated by the linear sum of individual modulation efficiency (ME) amplitude influence and phase error (PE) influence. The PE influence is of secondary importance compared with the ME amplitude. Generally, the stratospheric gases are more sensitive to ILS degradation than the tropospheric gases, and the positive ME influence is larger than the negative ME. For a typical ILS degradation (10 %), the total columns of stratospheric gases O3, HNO3, HCl, HF, and ClONO2 changed by 1.9, 0.7, 4, 3, and 23 %, respectively, while the columns of tropospheric gases CH4, CO, N2O, C2H6, and HCN changed by 0.04, 2.1, 0.2, 1.1, and 0.75 %, respectively. In order to suppress the fractional difference in the total column for ClONO2 and other NDACC gases within 10 and 1 %, respectively, the maximum positive ME degradations for O3, HNO3, HCl, HF, ClONO2, CO, C2H6, and HCN should be less than 6, 15, 5, 5, 5, 5, 9, and 13 %, respectively; the maximum negative ME degradations for O3, HCl, and HF should be less than 6, 12, and 12 %, respectively; the influence of ILS degradation on CH4 and N2O can be regarded as being negligible

TRIM Simulations Tool for μ+\mu^+ Stopping Fraction in Hydrostatic Pressure Cells

For quantum systems or materials, a common procedure for probing their behaviour is to tune electronic/magnetic properties using external parameters, e.g. temperature, magnetic field or pressure. Pressure application as an external stimuli is a widely used tool, where the sample in question is inserted into a pressure cell providing a hydrostatic pressure condition. Such device causes some practical problems when using in Muon Spin Rotation/Relaxation ($\mu^+$SR) experiments as a large proportion of the muons will be implanted in the pressure cell rather than in the sample, resulting in a higher background signal. This issue gets further amplified when the temperature dependent response from the sample is much smaller than that of the pressure cell,which may cause the sample response to be lost in the background and cause difficulties in aligning the sample within the beam. To tackle this issue, we have used pySRIM to construct a practical and helpful simulation tool for calculating muon stopping fractions, specifically for the pressure cell setup at the $\mu$E1 beamline using the GPD spectrometer at the Paul Scherrer Institute, with the use of TRIM simulations. The program is used to estimate the number of muon stopping in both the sample and the pressure cell at a given momentum. The simulation tool is programmed into a GUI, making it accessible to user to approximate prior to their experiments at GPD what fractions will belong to the sample and the pressure cell in their fitting procedure.Comment: 8 Pages, 3 Figures, Conference proceedings for 15th international conference on muon spin rotation, relaxation and resonanc

Transcranial Direct Current Stimulation (tDCS) for Depression during Pregnancy: Scientific Evidence and What Is Being Said in the Media - A Systematic Review

Major depression is the most frequent morbidity in pregnancy. The first-line therapies, psychopharmacologic treatment and psychotherapy, are either insufficient or may cause severe or teratogenic adverse events. As a result of its local limitation to the patient's brain, transcranial direct current stimulation (tDCS) could potentially be an ideal treatment for pregnant women with depression. A literature search was conducted in medical databases, globally published newspapers, search engines, and clinical trial registers to collect all articles on tDCS for the treatment of depression during pregnancy. The aim of this review was to investigate the scientific evidence of tDCS use for depression during pregnancy and to compare these results with the textual and emotional perception in the media as interventions during pregnancy are under particular surveillance. We detected 13 medical articles dealing with tDCS for depression in pregnancy. Overall, the scientific evidence as well as articles in the media for tDCS in pregnancy are sparse, but promising. Further studies are required in this specifically vulnerable population of pregnant women to generate evidence. It is likely that public interest will increase when the results of a pilot study in Canada are published