INTRAMOLECULAR VIBRATIONAL ENERGY REDISTRIBUTION (IVR) IN SELECTED S1 LEVELS ABOVE 1000 cm−1 IN PARA-FLUOROTOLUENE.

With increasing vibrational wavenumber, the density of states of a molecule is expected to rise dramatically, especially so when low wavenumber torsions (internal rotations) are present, as in the case of textit{para}-fluorotoluene (textit{p}FT). This in turn is expected to lead to more opportunities for coupling between vibrational modes, which is the driving force for intramolecular vibrational energy redistribution (IVR). Previous studiesfootnote{C. J. Hammond, V. L. Ayles, D. E. Bergeron, K. L. Reid and T. G. Wright, textit{J. Chem. Phys.}, textbf{125}, 124308 (2006)}$^{,}$footnote{J. A. Davies, A. M. Green, A. M. Gardner, C. D. Withers, T. G. Wright and K. L. Reid, textit{Phys. Chem. Chem. Phys.}, textbf{16}, 430 (2014)} at higher energies have focussed on the two close lying vibrational levels at ~1200 cm$^{-1}$ in the S$_{1}$ electronic state of textit{p}FT which were assigned to two zero-order bright states (ZOBSs), whose characters predominantly involve C-CH$_{3}$ and C-F stretching modes. A surprising result of these studies was that the photoelectron spectra showed evidence that IVR is more extensive following excitation of the C-F mode than it is following excitation of the C-CH$_{3}$ mode, despite these levels being separated by only 35 cm$^{-1}$. This observation provides evidence that the IVR dynamics are mode-specific, which in turn may be a consequence of the IVR route being dependent on couplings to nearby states that are only available to the C-F mode. _x000d_ _x000d_ In this work, in order to further investigate this behaviour, we have employed resonance-enhanced multiphoton ionisation (REMPI) spectroscopy and zero-kinetic-energy (ZEKE) spectroscopy to probe S$_{1}$ levels above 1000 cm$^{-1}$ in textit{p}FT. Such ZEKE spectra have been recorded via a number of S$_{1}$ intermediate levels allowing the character and coupling between vibrations to be unravelled; the consequence of this coupling will be discussed with a view to understanding any IVR dynamics seen

Direct observation of vibrational energy dispersal via methyl torsions

Explicit evidence for the role of methyl rotor levels in promoting energy dispersal is reported. A set of coupled zero-order vibration/vibration-torsion (vibtor) levels in the S1 state of para-fluorotoluene (pFT) are investigated. Two-dimensional laser-induced fluorescence (2D-LIF) and two-dimensional zero-kinetic-energy (2D-ZEKE) spectra are reported, and the assignment of the main features in both sets of spectra reveals that the methyl torsion is instrumental in providing a route for coupling between vibrational levels of different symmetry classes. We find that there is very localized, and selective, dissipation of energy via doorway states, and that, in addition to an increase in the density of states, a critical role of the methyl group is a relaxation of symmetry constraints compared to direct vibrational coupling

Torsion and vibration-torsion levels of the S1 and ground cation electronic states of para-fluorotoluene

We investigate the low-energy transitions (0–570 cm-1) of the S1 state of para-fluorotoluene (pFT) using a combination of resonance-enhanced multiphoton ionization (REMPI) and zero-kinetic-energy (ZEKE) spectroscopy and quantum chemical calculations. By using various S1 states as intermediate levels, we obtain zero-kinetic-energy (ZEKE) spectra. The differing activity observed allows detailed assignments to be made of both the cation and S1 low-energy levels. The assignments are in line with the recently-published work on toluene from the Lawrance group [J. Chem. Phys. 143, 044313 (2015)], which considered vibration-torsion coupling in depth for the S1 state of toluene. In addition, we investigate whether two bands that occur in the range 390–420 cm-1 are the result of a Fermi resonance; we present evidence for weak coupling between various vibrations and torsions that contribute to this region. This work has led to the identification of a number of misassignments in the literature, and these are corrected

Vibration and vibration-torsion levels of the S1 state of para-fluorotoluene in the 580–830 cm-1 range: interactions and coincidences

A study of the vibration and vibration-torsion levels of para-fluorotoluene (pFT) in the 580–830 cm-1 region is presented, where a number of features are located whose identity is complicated by interactions and overlap. We examine this region with a view to ascertaining the assignments of the bands; in particular, identifying those that arise from interactions involving various zero-order states (ZOSs) involving both vibrations and torsions. Resonance-enhanced multiphoton ionization (REMPI) is employed to identify the wavenumbers of the relevant transitions and subsequently zero-kinetic-energy (ZEKE) spectra are recorded to assign the various eigenstates. In some cases, a set of ZEKE spectra are recorded across the wavenumber range of a REMPI feature, and we construct what we term a two-dimensional ZEKE (2D-ZEKE) spectrum, which allows the changing ZOS contributions to the eigenstates to be ascertained. Assignment of the observed bands is aided by quantum chemical calculations and all b1 and a2 symmetry vibrational wavenumbers are now determined in the S1 state and cation, as well as those of the D10 vibration. We also compare with the activity seen in the corresponding S1 ←S0 spectrum of para-difluorobenzene

Gambling and gaming in the United Kingdom during the COVID-19 lockdown

© 2022 The Authors. Published by MDPI. This is an open access article available under a Creative Commons licence. The published version can be accessed at the following link on the publisher’s website: https://doi.org/10.3390/covid2020007During the first UK national COVID-19 lockdown, there were fears that increased online gaming and gambling could negatively impact wellbeing. Using a cross-sectional retrospective change survey of 631 UK adult gamers and/or gamblers during the week the UK lockdown was partially lifted (June 2020), we investigated participation in gaming/gambling and relationships with problem gaming, problem gambling and wellbeing (using the following previously validated scales: the Internet Gaming Disorder Short Form; a short-form version of the Problem Gambling Severity Index; a short-form of the Warwick–Edinburgh Mental Well-Being Scale). Results indicated a near-doubling in gaming activity during lockdown and significant increases in problem gaming scores, but not in numbers of disordered gamers. Aggregate changes to gambling participation and problem gambling were negligible: decreases in offline and sports gambling were balanced by increases in online gambling. Wellbeing scores decreased during lockdown across the sample, particularly amongst women, and path analysis revealed moderate correlations between increases in problem gaming and gambling scores and reductions in wellbeing. We conclude that for some, maladaptive gaming/gambling coping strategies during the lockdown may have exacerbated its negative effects.This work was funded by the University of Plymouth School of Psychology. J.C., S.S., H.L., L.L.N. and J.L. were further supported by funding from GambleAware.Published onlin

Comprehensive Assessment of Sleep Duration, Insomnia and Brain Structure within the UK Biobank Cohort

STUDY OBJECTIVES: To assess for associations between sleeping more than or less than recommended by the National Sleep Foundation (NSF), and self-reported insomnia, with brain structure. METHODS: Data from the UK Biobank cohort were analysed (N between 9K and 32K, dependent on availability, aged 44 to 82 years). Sleep measures included self-reported adherence to NSF guidelines on sleep duration (sleeping between 7 and 9 hours per night), and self-reported difficulty falling or staying asleep (insomnia). Brain structural measures included global and regional cortical or subcortical morphometry (thickness, surface area, volume), global and tract-related white matter microstructure, brain age gap (difference between chronological age and age estimated from brain scan), and total volume of white matter lesions. RESULTS: Longer-than-recommended sleep duration was associated with lower overall grey and white matter volumes, lower global and regional cortical thickness and volume measures, higher brain age gap, higher volume of white matter lesions, higher mean diffusivity globally and in thalamic and association fibers, and lower volume of the hippocampus. Shorter-than-recommended sleep duration was related to higher global and cerebellar white matter volumes, lower global and regional cortical surface areas, and lower fractional anisotropy in projection fibers. Self-reported insomnia was associated with higher global grey and white matter volumes, and with higher volumes of the amygdala, hippocampus and putamen. CONCLUSIONS: Sleeping longer than recommended by the NSF is associated with a wide range of differences in brain structure, potentially indicative of poorer brain health. Sleeping less than recommended is distinctly associated with lower cortical surface areas. Future studies should assess the potential mechanisms of these differences and investigate long sleep duration as a putative marker of brain health

Pharmacodynamics of the Orotomides against Aspergillus fumigatus: New Opportunities for Treatment of Multidrug-Resistant Fungal Disease.

F901318 is an antifungal agent with a novel mechanism of action and potent activity against Aspergillus spp. An understanding of the pharmacodynamics (PD) of F901318 is required for selection of effective regimens for study in phase II and III clinical trials. Neutropenic murine and rabbit models of invasive pulmonary aspergillosis were used. The primary PD endpoint was serum galactomannan. The relationships between drug exposure and the impacts of dose fractionation on galactomannan, survival, and histopathology were determined. The results were benchmarked against a clinically relevant exposure of posaconazole. In the murine model, administration of a total daily dose of 24 mg/kg of body weight produced consistently better responses with increasingly fractionated regimens. The ratio of the minimum total plasma concentration/MIC (Cmin/MIC) was the PD index that best linked drug exposure with observed effect. An average Cmin (mg/liter) and Cmin/MIC of 0.3 and 9.1, respectively, resulted in antifungal effects equivalent to the effect of posaconazole at the upper boundary of its expected human exposures. This pattern was confirmed in a rabbit model, where Cmin and Cmin/MIC targets of 0.1 and 3.3, respectively, produced effects previously reported for expected human exposures of isavuconazole. These targets were independent of triazole susceptibility. The pattern of maximal effect evident with these drug exposure targets was also apparent when survival and histopathological clearance were used as study endpoints. F901318 exhibits time-dependent antifungal activity. The PD targets can now be used to select regimens for phase II and III clinical trials.IMPORTANCE Invasive fungal infections are common and often lethal. There are relatively few antifungal agents licensed for clinical use. Antifungal drug toxicity and the emergence of drug resistance make the treatment of these infections very challenging. F901318 is the first in a new class of antifungal agents called the orotomides. This class has a novel mechanism of action that involves the inhibition of the fungal enzyme dihydroorotate dehydrogenase. F901318 is being developed for clinical use. A deep understanding of the relationship between dosages, drug concentrations in the body, and the antifungal effect is fundamental to the identification of the regimens to administer to patients with invasive fungal infections. This study provides the necessary information to ensure that the right dose of F901318 is used the first time. Such an approach considerably reduces the risks in drug development programs and ensures that patients with few therapeutic options can receive potentially life-saving antifungal therapy at the earliest opportunity

Effects of symmetry, methyl groups and serendipity on intramolecular vibrational energy dispersal

We consider two key parameters that have been proposed to be important for vibrational energy delocalization, closely related to intramolecular vibrational redistribution (IVR), in molecules. These parameters are the symmetry of the molecule, and the presence of torsional (internal rotor) modes of a methyl group. We consider four para-disubstituted benzene molecules and examine their vibrational character. The molecules selected are para-difluorobenzene, para-chlorofluorobenzene, para-fluorotoluene, and para-xylene. This set of molecules allows the above parameters to be assessed in a systematic way. The probe we use is zero-electron-kinetic-energy (ZEKE) spectroscopy, which is employed in a resonant scheme, where the intermediate levels are selected vibrational levels of the S1 excited electronic state, with wavenumbers up to 1300 cm 1. We conclude that symmetry, and the presence of a methyl groups, do indeed have a profound effect on “restricted” IVR at low energies. This is underpinned by serendipitous coincidences in the energies of the levels, owing to small shifts in vibrational wavenumbers. Additionally, methyl groups play an important role in opening up new routes for coupling between vibrations of different symmetry, and this is critical in the transition to “statistical” IVR at lower energies for molecules that contain them. Further, the presence of two methyl groups in the symmetrically-substituted p-xylene causes more widespread IVR than does the single methyl group in the asymmetrically-substituted p-fluorotoluene