Method Comparison for Simulating Non-Gaussian Beams and Diffraction for Precision Interferometry.

In the context of simulating precision laser interferometers, we use several examples to compare two wavefront decomposition methods-the Mode Expansion Method (MEM) and the Gaussian Beam Decomposition (GBD) method-for their precision and applicability. To assess the performance of these methods, we define different types of errors and study their properties. We specify how the two methods can be fairly compared and based on that, compare the quality of the MEM and GBD through several examples. Here, we test cases for which analytic results are available, i.e., non-clipped circular and general astigmatic Gaussian beams, as well as clipped circular Gaussian beams, in the near, far, and extremely far fields of millions of kilometers occurring in space-gravitational wave detectors. Additionally, we compare the methods for aberrated wavefronts and their interaction with optical components by testing reflections from differently curved mirrors. We find that both methods can generally be used for decomposing non-Gaussian beams. However, which method is more accurate depends on the optical system and simulation settings. In the given examples, the MEM more accurately describes non-clipped Gaussian beams, whereas for clipped Gaussian beams and the interaction with surfaces, the GBD is more precise.

Quantum Euler Relation for Local Measurements.

In classical thermodynamics the Euler relation is an expression for the internal energy as a sum of the products of canonical pairs of extensive and intensive variables. For quantum systems the situation is more intricate, since one has to account for the effects of the measurement back action. To this end, we derive a quantum analog of the Euler relation, which is governed by the information retrieved by local quantum measurements. The validity of the relation is demonstrated for the collective dissipation model, where we find that thermodynamic behavior is exhibited in the weak-coupling regime.

Neuromodulation and Devices in Trigeminal Neuralgia.

PREMISE: Trigeminal neuralgia is a severe facial pain disorder that has been studied for decades. Classical trigeminal neuralgia (CTN) is either idiopathic or caused by neurovascular compression. The related painful trigeminal neuropathies are often secondary to other causes, such as multiple sclerosis or trauma. PROBLEM: Therapies for trigeminal neuralgia and neuropathy have often been pharmacologic or surgical. Pharmacologic therapies are not effective in some cases and often cause side effects, some substantial. Surgery can have comorbidity (such as anesthesia dolorosa, or painful differentiation of the affected nerve distribution) and also is not always effective. There is a desire, as in all chronic conditions, to find effective treatments with minimal morbidity and side effects. POTENTIAL SOLUTIONS: We review several devices including neuromodulation, ranging in invasiveness, for treatment of trigeminal neuralgia and neuropathy. We review existing data on sphenopalatine ganglion blocks, transcranial magnetic stimulation, transcortical direct stimulation, deep brain stimulation, spinal cord stimulation, peripheral nerve stimulation, and transcutaneous electrical stimulation for CTN and pain trigeminal neuropathies. We also offer hope for further research in this area with the goal of discovering a device that can provide treatment for many with few side effects and minimal morbidity.

High school principals' resources, knowledge, and practices regarding the returning student with concussion.

OBJECTIVE: To determine high school principals' self-reported resources, knowledge, and practices regarding the management of students returning to school following concussion. STUDY DESIGN: A cross-sectional survey of public high school principals in the state of Ohio assessed respondent and school demographics, respondent concussion training, school resources, and monitoring and accommodation practices for students with concussion. RESULTS: Of the 695 eligible high school principals, 465 (66.9%) completed the survey. Over one-third of principals (37.2%) had some form of concussion training in the past year. Those with training were more likely to promote training of other school faculty (57.4% vs 30.6%, P < .001). Principals were asked to identify school personnel who are designated as case managers for students with concussion. Schools without a designated case manager were less likely to have an athletic trainer (P < .001) and had fewer students (median 424.5 vs 599) than schools with a case manager. Principals could list at least 1 faculty designee who communicates with health professionals more often for student-athletes than for nonathletes (P < .001). Most principals were willing to provide students with short-term academic accommodations, but 30.1% required a health professional's note prior to making any academic changes. Only 32% of principals reported providing families with a written academic plan following concussion. CONCLUSIONS: Schools differ in their resources and management strategies for students returning to school after concussion. Understanding these differences can help health professionals to overcome potential barriers in managing their school-aged patients with concussion.

Theoretical study on stable small clusters of oxalic acid with ammonia and water.

Thermodynamically stable small clusters of oxalic acid (CO2H)2, ammonia (NH3), and water (H2O) are studied through quantum chemical calculations. The (CO2H)2-NH3 core system with up to three waters of hydration was examined by B3LYP density functional theory and MP2 molecular orbital theory with the aug-cc-pVDZ basis set. The (CO2H)2-NH3 core complexes are observed to hydrogen bond strongly and should be found in appreciably significant concentrations in the atmosphere. Subsequent hydration of the (CO2H)2-NH3 core, however, is found to be somewhat prohibitive under ambient conditions. Relative populations of the examined clusters are predicted and the binding patterns detailed. Atmospheric implications related to new particle formations are discussed.

Theoretical study of the hydrogen abstraction of substituted phenols by nitrogen dioxide as a source of HONO.

The mild yet promiscuous reactions of nitrogen dioxide (NO2) and phenolic derivatives to produce nitrous acid (HONO) have been explored with density functional theory calculations. The reaction is found to occur via four distinct pathways with both proton coupled electron transfer (PCET) and hydrogen atom transfer (HAT) mechanisms available. While the parent reaction with phenol may not be significant in the gas phase, electron donating groups in the ortho and para positions facilitate the reduction of nitrogen dioxide by electronically stabilizing the product phenoxy radical. Hydrogen bonding groups in the ortho position may additionally stabilize the nascent resonantly stabilized radical product, thus enhancing the reaction. Catechol (ortho-hydroxy phenol) has a predicted overall free energy change ΔG(0) = -0.8 kcal mol(-1) and electronic activation energy Ea = 7.0 kcal mol(-1). Free amines at the ortho and para positions have ΔG(0) = -3.8 and -1.5 kcal mol(-1); Ea = 2.3 and 2.1 kcal mol(-1), respectively. The results indicate that the hydrogen abstraction reactions of these substituted phenols by NO2 are fast and spontaneous. Hammett constants produce a linear correlation with bond dissociation energy (BDE) demonstrating that the BDE is the main parameter controlling the dark abstraction reaction. The implications for atmospheric chemistry and ground-level nitrous acid production are discussed.

Cavity-mediated long-range interactions in levitated optomechanics.

The ability to engineer cavity-mediated interactions has emerged as a powerful tool for the generation of non-local correlations and the investigation of non-equilibrium phenomena in many-body systems. Levitated optomechanical systems have recently entered the multiparticle regime, which promises the use of arrays of strongly coupled massive oscillators to explore complex interacting systems and sensing. Here we demonstrate programmable cavity-mediated interactions between nanoparticles in vacuum by combining advances in multiparticle optical levitation and cavity-based quantum control. The interaction is mediated by photons scattered by spatially separated particles in a cavity, resulting in strong coupling that is long-range in nature. We investigate the scaling of the interaction strength with cavity detuning and interparticle separation and demonstrate the tunability of interactions between different mechanical modes. Our work will enable the exploration of many-body effects in nanoparticle arrays with programmable cavity-mediated interactions, generating entanglement of motion, and the use of interacting particle arrays for optomechanical sensing.

Comparing Migraine Headache Index vs. Monthly Migraine Days Following Nerve Deactivation for Headache: A Systematic Review and Meta-Analysis.

BACKGROUND: Nerve deactivation surgery for the treatment of migraine has quickly evolved over the last two decades. Studies typically report changes in migraine frequency (attacks/month), attack duration, attack intensity, and their composite score, the migraine headache index (MHI), as primary outcomes. However, the neurology literature predominantly reports migraine prophylaxis outcomes as change in monthly migraine days (MMD). Therefore, the goal of this study is to foster common communication between plastic surgeons and neurologists by assessing the effect of nerve deactivation surgery on monthly migraine days (MMD) and motivating future studies to include MMD in their reported outcomes. METHODS: An updated literature search was performed according to the PRISMA guidelines. The National Library of Medicine (PubMed), Scopus, and EMBASE were systematically searched for relevant articles. Data was extracted and analyzed from studies which met the inclusion criteria. RESULTS: A total of 19 studies were included. There was a significant overall reduction in monthly migraine days (mean difference [MD] 14.11, 95% CI 10.95 to 17.27; I2 = 92%), total migraine attacks per month (MD 8.65, 95% CI 7.84 to 9.46, I2 = 90%), migraine headache index (MD 76.59, 95% CI 60.85 to 92.32; I2 = 98%), migraine attack intensity (MD 3.84, 95% CI 3.35 to 4.33; I2 = 98%), and migraine attack duration (MD 11.80, 95% CI 6.44 to 17.16; I2 = 99%) at follow-up (range 6-38 months). CONCLUSIONS: This study demonstrates the efficacy of nerve deactivation surgery on the outcomes used in both the PRS and neurology literature.

Theoretical study on the structure and stabilities of molecular clusters of oxalic acid with water.

The importance of aerosols to humankind is well-known, playing an integral role in determining Earth's climate and influencing human health. Despite this fact, much remains unknown about the initial events of nucleation. In this work, the molecular properties of common organic atmospheric pollutant oxalic acid and its gas phase interactions with water have been thoroughly examined. Local minima single-point energies for the monomer conformations were calculated at the B3LYP and MP2 level of theory with both 6-311++G(d,p) and aug-cc-pVDZ basis sets and are compared with previous works. Optimized geometries, relative energies, and free energy changes for the stable clusters of oxalic acid conformers with up to six waters were then obtained from B3LYP calculations with 6-31+G(d) and 6-311++G(d,p) basis sets. Initially, cooperative binding is predicted to be the most important factor in nucleation, but as the clusters grow, dipole cancellations are found to play a pivotal role. The clusters of oxalic acid hydrated purely with water tend to produce extremely stable and neutral core systems. Free energies of formation and atmospheric implications are discussed.

Differential effects of the translocator protein 18 kDa (TSPO) ligand etifoxine and the benzodiazepine alprazolam on startle response to predictable threat in a NPU-threat task after acute and short-term treatment.

RATIONALE: Benzodiazepines have been extensively investigated in experimental settings especially after single administration, which mostly revealed effects on unpredictable threat (U-threat) rather than predictable threat (P-threat). Given the need for pharmacological alternatives with a preferable side-effect profile and to better represent clinical conditions, research should cover also other anxiolytics and longer application times. OBJECTIVES: The present study compared the acute and short-term effects of the translocator protein 18 kDa (TSPO) ligand etifoxine and the benzodiazepine alprazolam on P-threat and U-threat while controlling for sedation. METHODS: Sixty healthy male volunteers, aged between 18 and 55 years, were randomly assigned to receive a daily dose of either 150 mg etifoxine, 1.5 mg alprazolam, or placebo for 5 days. On days 1 and 5 of intake, they performed a NPU-threat task including neutral (N), predictable (P), and unpredictable (U) conditions, while startle responsivity and self-reports were studied. Sedative effects were assessed using a continuous performance test. RESULTS: Neither alprazolam nor etifoxine affected startle responsivity to U-threat on any of the testing days. While etifoxine reduced the startle response to P-threat on day 1 of treatment for transformed data, a contrary effect of alprazolam was found for raw values. No effects on self-reports and no evidence of sedation could be observed for either drug. CONCLUSIONS: None of the anxiolytic substances had an impact on startle potentiation to U-threat even after several days of intake. The effects of the anxiolytics on startle responsivity to P-threat as well as implications for future studies are discussed.

Dissociation of endocrine responses to the Trier Social Stress Test in Virtual Reality (VR-TSST) by the benzodiazepine alprazolam and the translocator protein 18 kDa (TSPO) ligand etifoxine.

BACKGROUND: Activity of the two major stress systems, the hypothalamic-pituitary-adrenal (HPA) and the sympathetic-adrenal-medullary (SAM) axis, has already been shown to be modulated by different compounds that bind to the central benzodiazepine receptor. Less is known about ligands that modulate the peripheral benzodiazepine receptor - meanwhile known as the translocator protein 18 kDa (TSPO) - which constitute promising candidates in the search of novel anxiolytics. To close this gap, the present study compared the effects of the benzodiazepine alprazolam and the TSPO ligand etifoxine on responses of the HPA and SAM axes to the Trier Social Stress Test, a standardized paradigm to induce acute psychosocial stress in humans, performed in Virtual Reality (VR-TSST). METHODS: Sixty healthy males, aged between 18 and 55 years, were randomly assigned to receive either a daily dose of 1.5 mg alprazolam, 150 mg etifoxine, or placebo over five days. On the last day of intake, they were exposed to the VR-TSST. We assessed changes of salivary cortisol, allopregnanolone, (nor-) epinephrine in serum, TSPO expression in platelets as well as heart rate (HR), skin conductance level (SCL) and self-reports in response to the stress task. Repeated measures ANOVAs were conducted to examine treatment effects on these stress response variables during the course of VR-TSST. RESULTS: The response of salivary cortisol to the VR-TSST was significantly blunted in participants pre-treated with alprazolam but was not affected by etifoxine. While levels of allopregnanolone, epinephrine and norepinephrine increased in response to stress, TSPO expression decreased. None of those endocrine stress markers was affected by the active treatments, whereas TSPO expression increased after etifoxine administration over all study days. There were no effects of the two anxiolytics on HR, SCL or any self-report measurement. CONCLUSION: The current study confirmed the attenuating effects of benzodiazepines on stress-induced HPA axis activity but did not reveal a comparable effect of the TSPO ligand etifoxine. The long-term consequences of a pharmacologically blunted response of the HPA axis to an acute stressor should be further elucidated. Due to the missing effects of etifoxine on stress-related parameters in our sample of healthy subjects, it might be concluded that the therapeutic effects of this TSPO ligand are restricted to stronger or pathological stress responses, respectively.

Flash pyrolysis of ethyl, n-propyl, and isopropyl iodides as monitored by supersonic expansion vacuum ultraviolet photoionization time-of-flight mass spectrometry.

The thermal decomposition of ethyl and propyl iodides, along with select isotopomers, up to 1300 K was performed by flash pyrolysis with a 20-100 mus time scale. The pyrolysis was followed by supersonic expansion to isolate the reactive intermediates and initial products, and detection was accomplished by vacuum ultraviolet single photon ionization time-of-flight mass spectrometry (VUV-SPI-TOFMS). The products monitored, such as CH(3), CH(3)I, C(2)H(5), C(2)H(4), HI, I, C(3)H(7), C(3)H(6), and I(2), provide for the simultaneous and direct observation of molecular elimination and bond fission pathways in ethyl and propyl iodides. In the pyrolysis of ethyl iodide, both C-I bond fission and HI molecular elimination pathways are competitive at the elevated temperatures, with C-I bond fission being preferred; at temperatures >or=1000 K, the ethyl radical products further dissociate to ethene + H atoms. In the pyrolysis of isopropyl iodide, both HI molecular elimination and C-I bond fission are observed and the molecular elimination channel is more important at all the elevated temperatures; the isopropyl radicals produced in the C-I fission channel undergo further decomposition to propene + H at temperatures >or=850 K. In contrast, bond fission is found to dominate the n-propyl iodide pyrolysis; at temperatures >or=950 K the n-propyl radicals produced decompose into methyl radical + ethene and propene + H atom. Isotopomer experiments characterize the extent of surface reactions and verify that the HI molecular eliminations in ethyl and propyl iodides proceed by a C1, C2 elimination mechanism (the 1,2 intramolecular elimination).

High-Throughput Method of Whole-Brain Sectioning, Using the Tape-Transfer Technique.

Cryostat sectioning is a popular but labor-intensive method for preparing histological brain sections. We have developed a modification of the commercially available CryoJane tape collection method that significantly improves the ease of collection and the final quality of the tissue sections. The key modification involves an array of UVLEDs to achieve uniform polymerization of the glass slide and robust adhesion between the section and slide. This report presents system components and detailed procedural steps, and provides examples of end results; that is, 20 µm mouse brain sections that have been successfully processed for routine Nissl, myelin staining, DAB histochemistry, and fluorescence. The method is also suitable for larger brains, such as rat and monkey.

The Diagnosis and Management of Concussion in Children and Adolescents.

BACKGROUND: Concussion is a complex brain injury that results in more than 100,000 emergency department visits for school-aged children each year in the United States. All 50 US states have passed concussion legislation designed to promote safety in youth sports. Most of these laws require medical clearance by a licensed health care provider before returning to sport, which may have contributed to an increase in pediatric subspecialty referrals, particularly referrals to the child neurologist. METHODS: We reviewed the literature on pediatric concussion. RESULTS: This review summarizes the current knowledge and recommendations for concussion diagnosis and management in children and adolescents, athletes and nonathletes. It highlights concussion epidemiology, pathophysiology, advances in neuroimaging, and potential health risks including second impact syndrome and chronic traumatic encephalopathy. It also underscores clinical areas where evidence is lacking. CONCLUSIONS: The diagnosis and management of concussion requires specific considerations in children. Further concussion research must be done to minimize injury risk and to optimize medical care for this common problem.

How common is attention-deficit/hyperactivity disorder? Incidence in a population-based birth cohort in Rochester, Minn.

CONTEXT: The frequency of occurrence of attention-deficit/hyperactivity disorder (AD/HD) is in dispute. This uncertainty has contributed to the concern that too many children in the United States are being treated with stimulant medication. OBJECTIVES: To determine the cumulative incidence of AD/HD in a population-based birth cohort and to estimate the prevalence of pharmacologic treatment for children who fulfill research criteria for AD/HD. DESIGN: Population-based birth cohort study. SETTING AND SUBJECTS: All children born between 1976 and 1982 in Rochester, Minn, who remained in the community after age 5 years (N = 5718). MAIN OUTCOME MEASURES: Medical and school records were reviewed for clinical diagnoses of AD/HD and supporting documentation (symptoms consistent with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition criteria and positive results for AD/HD-related questionnaires). Research-identified cases were defined as: (1) "definite" AD/HD (clinical diagnosis and at least one type of supporting documentation); (2) "probable" AD/HD (clinical diagnosis but no supporting documentation or no clinical diagnosis but both types of supporting documentation); (3) "questionable" AD/HD (no clinical diagnosis, but at least one type of supporting documentation); and (4) "not AD/HD" (all other subjects). Information about pharmacologic treatment for AD/HD was abstracted for all subjects. RESULTS: The highest estimate of the cumulative incidence at age 19 years (with 95% confidence interval) of AD/HD (definite plus probable plus questionable AD/HD) was 16.0% (14.7-17.3). The lowest estimate (definite AD/HD only) was 7.4% (6.5-8.4). Prevalence of treatment with stimulant medication was 86.5% for definite AD/HD, 40.0% for probable AD/HD, 6.6% for questionable AD/HD, and 0.2% for not AD/HD. CONCLUSIONS: These results provide insight into the apparent discrepancies in estimates of the occurrence of AD/HD, with less stringent criteria resulting in higher cumulative incidence. Children who met the most stringent criteria for AD/HD were most likely to receive pharmacologic treatment.

A low-cost technique to cryo-protect and freeze rodent brains, precisely aligned to stereotaxic coordinates for whole-brain cryosectioning.

A major challenge in the histological sectioning of brain tissue is achieving accurate alignment in the standard coronal, horizontal, or sagittal planes. Correct alignment is desirable for ease of subsequent analysis and is a prerequisite for computational registration and algorithm-based quantification of experimental data. We have developed a simple and low-cost technique for whole-brain cryosectioning of rodent brains that reliably results in a precise alignment of stereotactic coordinates. The system utilises a 3-D printed model of a mouse brain to create a tailored cavity that is used to align and support the brain during freezing. The alignment of the frozen block is achieved in relation to the fixed edge of the mold. The system also allows for two brains to be frozen and sectioned simultaneously. System components, procedural steps, and examples of the end results are presented.

Synthesis and cancer stem cell-based activity of substituted 5-morpholino-7H-thieno[3,2-b]pyran-7-ones designed as next generation PI3K inhibitors.

Dysregulation of the phosphatidylinositol-3-kinase (PI3K) pathway in a wide range of tumors has made PI3K a consensus target to inhibit as illustrated by more than 15 inhibitors now in clinical trials. Our previous work, built on the early pioneering multikinase inhibitor LY294002, resulted in the only PI3K vascular-targeted PI3K inhibitor prodrug, SF1126, which has now completed Phase I clinical trials. This inhibitor has properties that impart more in vivo activity than should be warranted by its enzymatic potency, which in general is much lower than other clinical stage PI3K inhibitors. We embarked on the exploration of scaffolds that retained such properties while simultaneously exhibiting an increased potency toward PI3K. This work resulted in the discovery of the 5-morpholino-7H-thieno[3,2-b]pyran-7-one system as the foundation of a new compound class of potential PI3K inhibitors having improved potency toward PI3K. The synthesis and cancer stem cell-based activity of these compounds are reported herein.

Semimembranosus tendinopathy: one cause of chronic posteromedial knee pain.

CONTEXT: Semimembranosus tendinopathy (SMT) is an uncommon cause of chronic knee pain that is rarely described in the medical literature and may be underdiagnosed or inadequately treated owing to a lack of understanding of the condition. EVIDENCE ACQUISITION: A search of the entire PubMed (MEDLINE) database using the terms knee pain semimembranosus and knee tendinitis semimembranosus, returned only 5 references about SMT-4 case series and 1 case report-and several relevant anatomical or imaging references. RESULTS: The incidence of SMT is unknown in the athletic population and is probably more common in older patients. The usual presentation for SMT is aching posteromedial knee pain. Physical examination can usually localize the area of tenderness to the distal semimembranosus tendon or its insertion on the medial proximal tibia. In unclear cases, bone scan, magnetic resonance imaging, or ultrasound may distinguish SMT from other causes of posteromedial knee pain. Treatment should begin with relative rest, ice, nonsteroidal anti-inflammatory drugs, and rehabilitative exercise. In the minority of cases that persist greater than 3 months, a corticosteroid injection at the tendon insertion site may be effective. Surgery to reroute and reattach the tendon is rarely needed but may be effective. CONCLUSION: SMT is an uncommon cause of knee pain, but timely diagnosis can lead to effective treatments.

Antitumor efficacy and molecular mechanism of TLK58747, a novel DNA-alkylating prodrug.

BACKGROUND: DNA-damaging agents are widely used for the treatment of human malignancies. Agents containing the multifunctional alkylating moiety tetrakis(2-chloroethyl)phosphorodiamidic acid are currently under development as cancer therapeutics. MATERIALS AND METHODS: TLK58747, a phophorodiamidate-based prodrug, was tested in vivo for antitumor efficacy and safety. The in vitro responses of tumor cells to TLK58747 were examined by cytotoxicity assays, cell cycle analysis, immunoblots and microscopy. RESULTS: TLK58747 was efficacious in xenograft models of human breast, pancreas, and prostate cancer, as well as in leukemia and glioma. It caused less bone marrow suppression in rats than did cyclophosphamide. In vitro, TLK58747 inhibited the growth of a wide variety of cancer cells and activated the DNA damage-response pathway, leading to G(2)/M cell cycle arrest and subsequent premature senescence or apoptosis. CONCLUSION: TLK58747 is a promising new alkylating agent with broad antitumor activity and superior safety that warrants further development.

Mechanistic study of thermal decomposition of isoprene (2-methyl-1,3-butadiene) using flash pyrolysis supersonic jet VUV photoionization mass spectrometry.

The thermal decomposition of isoprene up to 1400 K was performed by flash pyrolysis with an approximately 100 mus time scale. This pyrolysis was followed by supersonic expansion to isolate the reactive intermediates and initial products, and detection was accomplished by vacuum ultraviolet single photon ionization time-of-flight mass spectrometry (VUV-SPI-TOFMS) at lambda = 118.2 nm. Products CH(3), C(2)H(4), C(3)H(3), C(3)H(4), C(4)H(4), C(4)H(5), C(5)H(6), C(5)H(7), and C(6)H(6) were directly observed and provide mechanistic insights to the isoprene pyrolysis. At temperatures >or= approximately 1200 K, the molecular elimination of ethene to form C(3)H(4) and sigma bond homolysis producing C(4)H(5) and CH(3) radicals are competitive reaction pathways. The molecular elimination of acetylene to form C(3)H(6) was minimal and direct C(2)-C(3) sigma bond homolysis was not observed. The C(3)H(3) radicals are also observed, as a result of hydrogen loss of C(3)H(4) by pyrolysis or hydrogen abstraction by the CH(3) radical from C(3)H(4). Above approximately 1250 K, production of C(6)H(6) was observed and identified as the combination product of the C(3)H(3) radicals.