Correspondence between the reaction force minimum and the onset of abrupt variations of the kinetic and potential energies in bond dissociation and formation.

CONTEXT: We demonstrate that the minimum of the reaction force curve of a diatomic or polyatomic molecule undergoing bond dissociation is significant in several respects. As has been pointed out in the past, it is the point at which the force opposing dissociation is strongest. It marks the boundary between the primarily structural stage of a bond dissociation (stretching) and the transition region between the stretched bond and independent atoms. We now show that the reaction force minimum is also where the kinetic and potential energy curves tend to change direction abruptly. At this point, the total energy E(R) has increased by about 27% of the dissociation energy, for both diatomic and polyatomic molecules. METHODS: Dissociation curves are analyzed at the UHF/daug-cc-pV5Z level of theory using Gaussian 16.

Radial Behavior of Electrostatic Potentials of Atoms and Ions Revisited: Isotropy and Anisotropy.

In this paper we revisit earlier work relating to monoatomic atoms and ions published by pioneers in the area of electrostatic potentials. We include plots of the radial distributions of the electrostatic potentials for spherically symmetric atoms and cations, and for singly, doubly and triply negative anions. For atoms with anisotropy in their densities and electrostatic potentials, such as the halonium cations, it is shown how the molecular surface approach for plotting electrostatic potentials complements that achieved by directional radial distributions.

Puppy Socialisation Experiences in Relation to Age and COVID-19 Lockdown Restrictions in the UK and ROI.

Limited socialisation can contribute to the development of undesirable dog behaviours. The COVID-19 lockdown potentially limited socialisation opportunities, which may negatively impact the future behaviour of puppies raised during lockdown. Data were gathered from longitudinal study participants in the United Kingdom/Republic of Ireland via multiple questionnaires between May 2016 and November 2022. The impact of age and lockdown phase (pre-, during, and post-) on the types of socialisation experiences of 8-to-19-week-old puppies and the recency of socialisation experiences of approximately 6-month-old puppies were examined. Puppies under 19-weeks had significantly more types of socialisation experiences (from a predefined list) as they aged, and pre-lockdown compared to post-lockdown, but not between other lockdown phases. Most 6-month-old puppies had met a new adult or dog outside the household, a familiar dog, and/or a child within the last 1-7 days, and this was similar between lockdown phases. During lockdown, 6-month-old puppies experienced longer periods between meeting a new adult in their home. Puppies were hypothesised to have had fewer experiences during lockdown, but this was not found. However, the quantity and quality of these experiences may have been affected. Future research within this longitudinal study will explore relationships between the timing and type of experiences had by puppies and their subsequent behaviour.

The Formation of σ-Hole Bonds: A Physical Interpretation.

This paper discusses two quite different computational experiments relating to the formation of σ-hole bonds A···B. The first involves looking at the complex at equilibrium and finding the contour X of the electronic density which allows the iso-density envelopes of A and B to be nearly touching. This contour increases, becoming closer to the nuclei, as the strength of the interaction increases. The second experiment involves allowing A and B to approach each other, with the aim of finding the distance at which their 0.001 a.u. iso-density envelopes are nearly merging into one envelope. What is found in the second experiment may be somewhat surprising, in that the ratio of the distance between interacting atoms at this nearly merging point-divided by the sum of the van der Waals radii of these atoms-covers a narrow range, typically between 1.2 and 1.3. It is intriguing to note that for the dataset presented, approaching molecules attracted to each other appear to do so unknowing of the strength of their ultimate interaction. This second experiment also supports the notion that one should expect favorable interactions, in some instances, to have close contacts significantly greater than the sums of the van der Waals radii.

Anisotropies in electronic densities and electrostatic potentials of Halonium Ions: focus on Chlorine, Bromine and Iodine.

CONTEXT: Why are the halonium cations so effective in forming strongly-bound complexes? We directed our research to address this question and we present electrostatic potential data for the valence-state halogen atoms X and halonium cations X+, where X = Cl, Br, I. The electron densities and electrostatic potentials of the halonium cations show considerably greater anisotropy than do the valence state halogens. The distances from the electrostatic potential surface maxima to the halogen nuclei are about 0.5 Å smaller than the distances from the electrostatic potential surface minima to the nuclei, giving the halonium cations each a more disk-like shape than the corresponding neutral valence state halogens. Their surface electrostatic potentials are totally consistent with the directionalities of halonium cations in complexes and the strengths of their interactions. To add perspective to this brief report, we have included calculations of the isotropic cation K+ and noble gas Kr. METHODS: The calculations of the electrostatic potentials of the valence states of the halogen atoms Cl, Br and I and the halonium cations Cl+, Br+ and I+, as well as K+ and Kr, on 0.001 au contours of their electronic densities were carried out with Gaussian O9 and the Wave Function Analysis - Surface Analysis Suite (WFA-SAS) at the M06-2X/6-31 + G(d,p) and M06-2X/3-21G* levels.

Probing intramolecular interactions using molecular electrostatic potentials: changing electron density contours to unveil both attractive and repulsive interactions.

We focus on intramolecular interactions, using the electrostatic potential plotted on iso-density surfaces to lead the way. We show that plotting the electrostatic potential on varying iso-density envelopes much closer to the nuclei than the commonly used 0.001 a.u. contour can reveal the driving forces for such interactions, whether they be stabilizing or destabilizing. Our approach involves optimizing the structures of molecules exhibiting intramolecular interactions and then finding the contour of the electronic density which allows the interacting atoms to be separated; we call this the nearly-touching contour. The electrostatic potential allows then to identify the intramolecular interactions as either attractive or repulsive. The discussed 1,5- and 1,6-intramolecular interactions in o-bromophenol and o-nitrophenol are attractive, while the interactions between terminal methyl hydrogens in diethyl disulfides (as shown recently) and those between the closest hydrogens in planar biphenyl and phenanthrene are clearly repulsive in nature. For the attractive 1,4-interactions in trinitromethane and chlorotrinitromethane, and the 1,3-S⋯N and the 1,4-Si⋯N interactions in the ClH2Si(CH2)nNH2 series, the lack of (3,-1) bond critical points has often been cited as reason to not identify such interactions as attractive in nature. Here, by looking at the nearly-touching contours we see that bond critical points are neither necessary nor sufficient for attractive interactions, as others have pointed out, and in some instances also pointing to repulsive interactions, as the examples of planar biphenyl and phenanthrene discussed in this work show.

GenPup-M: A novel validated owner-reported clinical metrology instrument for detecting early mobility changes in dogs.

OBJECTIVE: To use a previously validated veterinary clinical examination sheet, Liverpool Osteoarthritis in Dogs (LOAD) questionnaire, combined with kinetic and kinematic gait analysis in dogs with/without mobility problems to demonstrate the capacity of a novel clinical metrology instrument ("GenPup-M") to detect canine mobility impairments. DESIGN: Quantitative study. ANIMALS: 62 dogs (31 with mobility impairments and 31 without mobility impairments). PROCEDURE: The dogs' clinical history was obtained from owners and all dogs underwent a validated orthopaedic clinical examination. Mobility impairments were diagnosed in the mobility impaired group based on clinical history and orthopaedic examination. Owners were asked to complete GenPup-M along with a previously validated mobility questionnaire (Liverpool Osteoarthritis in Dogs (LOAD)) to identify construct validity. As a test of criterion validity, the correlation between instrument scores and the overall clinical examination scores, along with force-platform obtained peak vertical forces (PVF) were calculated. GenPup-M underwent internal consistency and factor analysis. Spatiotemporal parameters were calculated for dogs with/without mobility impairments to define the gait differences between these two groups. RESULTS: Principal Component Analysis identified GenPup-M had two components with Eigenvalues >1 ("stiffness/ease of movement" and "willingness to be active/exercise"). Cronbach's α was used to test internal consistency of GenPup-M and was found to be "good" (0.87). There was a strong, positive correlation between GenPup-M and LOAD responses (r2 = 0.69, p<0.001) highlighting construct validity. Criterion validity was also shown when comparing GenPup-M to clinical examination scores (r2 = 0.74, p<0.001) and PVF (r2 = 0.43, p<0.001). Quantitative canine gait analysis showed that there were statistically significant differences between peak vertical forces (PVF) of mobility impaired and non-mobility impaired dogs (p<0.05). Analyses of PVF showed that non-mobility impaired dogs more evenly distributed their weight across all thoracic and pelvic limbs when compared to mobility impaired dogs. There were also consistent findings that mobility impaired dogs moved slower than non-mobility impaired dogs. CONCLUSION AND CLINICAL RELEVANCE: GenPup-M is a clinical metrology instrument (CMI) that can be completed by dog owners to detect all mobility impairments, including those that are early in onset, indicating the versatility of GenPup-M to assess dogs with and without mobility impairments. Results of the study found that GenPup-M positively correlated with all three objective measures of canine mobility and consequently showed criterion and construct validity. Owner-reported CMIs such as GenPup-M allow non-invasive scoring systems which veterinary surgeons and owners can use to allow communication and longitudinal assessment of a dog's mobility. It is anticipated that GenPup-M will be used by owners at yearly vaccinations/health checks, allowing identification of any subtle mobility changes, and enabling early intervention.

"It's Like Living with a Sassy Teenager!": A Mixed-Methods Analysis of Owners' Comments about Dogs between the Ages of 12 Weeks and 2 Years.

Owners' understanding of dog behaviour influences dog welfare. This study aimed to investigate owners' experiences of living with dogs and perceptions of dog behaviour/behaviour change. Data from an ongoing UK/ROI longitudinal study of dogs were used. Open-ended survey data (n = 3577 comments, n = 1808 dogs) when dogs were 12/16 weeks (data combined), 6, 12, 18 and 24 months were analysed to cover the dog's puppyhood/adolescence. To evaluate the usefulness of open-ended survey questions, both quantitative textual and qualitative thematic analyses were employed. Textual analysis identified an overall positive sentiment at all timepoints; the proportion of positive: negative sentiments increased with the dog's age. Words related to 'love' were the most frequent descriptors at all but the first timepoint, when 'bite' was the most frequent descriptor. Qualitative analysis helped to identify that owners attribute dog behaviour to 'Dog's biology', 'Personality/deliberate action' and 'External influences'. Analysis of open-ended survey responses helped to identify changes in perception over time. When dogs were young, owners described problematic behaviours as 'mischievous', unintentional and context-specific. Similar behaviours shown by older dogs were seen as 'deliberate'. Both positive and negative experiences of dog ownership were identified. However, as not all respondents answered open-ended questions, the generalisability of our findings is limited.

Intramolecular Repulsion Visible Through the Electrostatic Potential in Disulfides: Analysis via Varying Iso-density Envelopes.

For a series of diethyl disulfide conformations, the nearly touching contours of the electrostatic potential plotted on iso-density molecular surfaces allow the assessment of intramolecular repulsion. The electrostatic potential is plotted on varying iso-density envelopes to find the nearly touching contours for which (a) the surface electrostatic potential does not show overlap between atoms or functional groups and (b) the typical features are visible (σ-hole, lone pair, hydrogen VS,max). When these nearly touching contours X are closer to the nuclei, the more electron density is excluded from the iso-density envelopes and the smaller are the volumes corresponding to these envelopes. Both the contours X and the corresponding volumes are found to correlate with relative conformational energy, reflecting the degree of intramolecular repulsion present in the various diethyl disulfides. Quantitative estimates of intramolecular repulsion can be made based on relationships between the nearly touching contour X vs relative energy and volume (of the nearly touching contour X) vs relative energy, obtained for series of diethyl disulfide conformers. These relations were used to analyze intramolecular repulsion in a set of disulfides broader than diethyl disulfide conformers. We have shown that the approach of varying electronic density contours can be used in the study of repulsive intramolecular interactions, hereby extending earlier work involving attractive intermolecular interactions.

The Effects of a Non-crossed-linked Hyaluronic Acid Gel on the Aging Signs of the Face versus Normal Saline: A Randomized, Double-blind, Placebo-controlled, Split-faced Study.

Background: Skin bio-revitalization improves skin quality globally; it permits the rejuvenation of the skin by increasing hydration and by reconstructing an optimal physiological environment for the skin cells together with a micro-filling effect. Objective: To assess the comparative efficacy of a non-cross-linked hyaluronic acid (NCHA) preparation (M-HA®10, FILLMED Laboratories, France) on fine lines reduction and on skin hydration, radiance and mechanical properties, after three sessions of multiple intradermal injections, active versus placebo, on the face of subjects presenting aging signs. Methods: Thirty healthy subjects received filler injections on one side and a control solution (saline) on the contralateral side of the face. Fine lines depth, skin hydration, and mechanical properties were evaluated using instrumental methods. Skin radiance, cheek fold and crow's feet were scored clinically. In addition, Investigator and subject satisfaction rates were evaluated by the Global Aesthetic Improvement Scale and a subject self-assessment questionnaire. Results: Ten days after the last multi-injection session, the following significant results were observed compared to the control: a reduction of both crow's feet wrinkle depth (in the 110 to 1000µm range, -10% for NCHA and +7% for control) and clinical scoring of cheek wrinkles, and increases in skin radiance and hydration (+35%) and also skin firmness (+27%). The Investigator found that NCHA either improved or much improved the aesthetic aspect on 82% of subjects whereas no improvement was found on the saline side. Subjects found that NCHA significantly reduced wrinkles and increased both skin firmness and elasticity. Conclusion: Intradermal injection of NCHA can improve the quality of facial skin with aging signs by reducing fine wrinkles and improving hydration, firmness and radiance.

Dichloromethane replacement: towards greener chromatography via Kirkwood-Buff integrals.

Dichloromethane (DCM) is a useful and advantageous solvent used in pharmaceutical development due to its low cost, miscibility with other organic solvents, high volatility, and ability to solubilize drug molecules of variable polarities and functionalities. Despite this favourable behaviour, efforts to identify safer and more sustainable alternatives to hazardous, halogenated solvents is imperative to the expansion of green chemistry. In this work, bio-derived esters tert-butyl acetate, sec-butyl acetate, ethyl isobutyrate, and methyl pivalate are experimentally identified as safe and sustainable alternatives to directly replace DCM within thin-layer chromatography (TLC) in the analysis of small, common drug molecules. To elucidate the intermolecular interactions influencing retardation factors (Rf) a statistical thermodynamic framework, which quantifies the driving molecular interactions that yield empirical TLC measurements, is presented. Within this framework, we are able to deduce Rf dependence on polar eluent concentration, in the presence of a low-polar mediating solvent, between the stationary and mobile phases. The strength of competitive analyte-eluent (and analyte-solvent interactions) are quantified through Kirkwood-Buff integrals (KBIs); resulting KBI terms at the dilute eluent limit provide a theoretical foundation for the observed suitability of alternative green solvents for the replacement of dichloromethane in TLC.

Introducing a Puppy to Existing Household Cat(s): Mixed Method Analysis.

Although cats and dogs can live amicably, inter-species conflict can result in poor welfare. Species introduction can impact the development of the cat-dog relationship. This study aimed to identify factors associated with owner reported 'only desirable' puppy behaviour (defined as the puppy being uninterested, ignored the cat and/or interacted in a calm way) following introduction to existing household cats, and to explore perceptions of the emerging cat-dog relationship. Owner-reported data collected as part of a longitudinal study of canine health and behaviour were used. Of 4678 puppies, 26.7% lived with at least one cat. Of the 1211 puppies who had been introduced to the household cat at the time of survey completion, playing (58.9%), being overexuberant or over-excited (56.6%), and chasing (48.6%) were the most common behaviours displayed towards cats. 'Only desirable' behaviours were shown by 7.3% of puppies. Multivariable logistic regression showed early (puppies aged <12 weeks), gradual introductions and living in a multi-dog household increased the odds of 'only desirable' behaviours. Qualitative analysis revealed two styles of introductions­owner-led and pet-led. Owners who led introductions anticipated amicable relationships between pets, whilst owners who let pets introduce themselves did not. Early, gradual, owner-led introductions of puppies to household cats should be encouraged.

Accessing veterinary healthcare during the COVID-19 pandemic: A mixed-methods analysis of UK and Republic of Ireland dog owners' concerns and experiences.

BACKGROUND: This study explored dog owners' concerns and experiences related to accessing veterinary healthcare during the COVID-19 pandemic. METHODS: Data were obtained through two cross-sectional owner-completed surveys conducted in May (first nationwide lockdown) and October 2020 and owner-completed diaries (April-November 2020). Diaries and relevant open-ended survey questions were analysed qualitatively to identify themes. Survey responses concerning veterinary healthcare access were summarised and compared using chi-square tests. RESULTS: During the initial months of the pandemic, veterinary healthcare availability worried 32.4% (n = 1431/4922) of respondents. However, between 23 March and 4 November 2020, 99.5% (n = 1794/1843) of those needing to contact a veterinarian managed to do so. Delays/cancellations of procedures affected 28.0% (n = 82/293) of dogs that owners planned to neuter and 34.2% (n = 460/1346) of dogs that owners intended to vaccinate. Qualitative themes included COVID-19 safety precautions, availability of veterinary healthcare and the veterinarian-client relationship. CONCLUSION: Veterinary healthcare availability concerned many owners during the COVID-19 pandemic. Access to veterinary healthcare for emergencies remained largely available, but prophylactic treatments were delayed for some dogs.

Interpreting the variations in the kinetic and potential energies in the formation of a covalent bond.

We address the long-standing controversy as to the physical origin of covalent bonding, whether it involves a lowering of the potential energy or a lowering of the kinetic energy. We conclude that both of these do occur and contribute to the formation of the bond. The analysis is in terms of the virial theorem and the variations in the potential energy and the kinetic energy as the atoms approach each other. At large separations, the change in kinetic energy relative to the separated atoms is negative and stabilizing, while the corresponding potential energy change is positive and destabilizing. However, as the atoms approach their equilibrium separation, these rapidly reverse; the kinetic energy increases and the potential energy decreases, so that at equilibrium the net kinetic energy is positive and the net potential energy negative. At equilibrium, the bonding is due solely to the potential energy and is electrostatic.

Impact of Changes in Time Left Alone on Separation-Related Behaviour in UK Pet Dogs.

Separation-related behaviours (SRBs), including but not limited to vocalisation, pacing, destruction and toileting, occur in the absence of human company. As well as being problematic for the dogs' owners, such behaviours indicate that the dogs' emotional state is compromised. As part of the COVID-19 pandemic, time spent alone decreased considerably for many pet dogs, leading to concerns about the development of SRBs when dogs are left alone more again. The main aim of this study was to test the hypothesis that dogs whose time left alone decreased most (compared to a February 2020 pre-COVID baseline) would be at greatest risk of developing new signs of SRB when time left alone increased again. To achieve this aim, we utilised survey data gathered from dog owners between 4th May and 3rd July 2020, during the first COVID-19 'lockdown' period in the United Kingdom (UK), and a follow-up survey of the same dog-owner cohort, completed when restrictions had eased between 10th October and 2nd November 2020. Individual dogs fluctuated considerably in whether they showed signs of SRB or not across the study period (n = 1807). Overall, the prevalence of SRB in the population decreased from 22.1% to 17.2%, as did the time dogs were left alone for between February and October 2020. However, 9.9% of dogs had developed new signs of SRB by the follow-up survey in October 2020, with dogs whose leaving hours decreased most during lockdown restrictions being at increased risk of developing SRBs. These findings have implications for our understanding of the etiology of SRB, by showing a link between changes in owner routine and SRB risk.

Transdermal Buprenorphine for Pain Management Following a Neck of Femur Fracture.

INTRODUCTION: Pain management in patients with hip fractures can be challenging. Poor pain control is associated with reduced mobility and increased morbidity. Inadequate analgesia in patients with dementia is a concern. After using several different alternatives, transdermal buprenorphine was chosen as a standardised approach for analgesia in patients with fragility fracture in our hospital. There is limited evidence on the use of buprenorphine in this population. Our aim was to investigate the safety and effectiveness of transdermal buprenorphine in patients with hip fractures. METHODS: A review of consecutive patients presenting with a hip fracture from June 2018 to December 2018 was conducted using medical records. Our primary outcome was the incidence of complications as a consequence of transdermal buprenorphine. Our secondary outcome was adequate analgesia measured by reviewing the requirement for analgesia during the first week following the patient's admission. Analgesia demands were considered adequate if patients required less than 20 mg of oral morphine in total during the first week following injury. RESULTS: In total, 148 patients presented with a hip fracture during the study period. 128 patients had documented evidence of buprenorphine patch application. Complete data was available for the primary outcome of complications in all cases. Data was available for the secondary outcome in 124 patients. Buprenorphine was discontinued in 24 patients (19%), most commonly due to due to concerns about contribution to hypoactive delirium (9%), and when strong analgesia was no longer required (4%). There were no severe complications. Adequate analgesia was achieved using this regime in 68% patients. 38 patients (32%) required more than 20 mg of oral morphine sulphate solution in the first week post-admission. CONCLUSION: This series suggests that transdermal buprenorphine is safe and effective in the management of pain following a neck of femur fragility fracture.

Age of sexual maturity and factors associated with neutering dogs in the UK and the Republic of Ireland.

BACKGROUND: Surgical neutering of dogs is common, however the average age that dogs reach sexual maturity, are neutered, and dog owners' attitudes to neutering in the UK and the Republic of Ireland have not been explored in a longitudinal study. METHODS: Owner-reported data on the timing of the first oestrus, timing of neutering and the reasons given for neutering dogs by 12 and 15 months of age were summarised. Factors associated with neutering at 15 months and factors associated with intention to neuter were quantified using multivariable logistic regression. RESULTS: At 15 months of age, 90.0% (n = 207/230) of unneutered females had had their first oestrus. By 7, 9, 12 and 15 months of age, 22.1% (n = 131/593), 32.2% (197/593), 45.4% (n = 269/593) and 59.9% (n = 352/593) of dogs were neutered, respectively. Breed purity, dog's source, owners' intentions to neuter and the number of dogs in the household were associated with neuter status at age 15 months. Dog's sex, Kennel Club registration, dog's source, dogs intended to be working dogs and previous dog ownership were associated with intentions to neuter. Preventing puppies was the most common reason for neutering. CONCLUSION: Understanding factors that shape owners' intentions to neuter can inform owner-vet discussions regarding whether to neuter a dog and the optimal age for doing so.

Are HOMO-LUMO gaps reliable indicators of explosive impact sensitivity?

A high priority in designing and evaluating proposed explosives is to minimize sensitivity, i.e., vulnerability to unintended detonation due to an accidental stimulus, such as impact. In order to establish a capability for predicting impact sensitivity, there have been numerous attempts to correlate it with some molecular or crystal property or properties. One common approach has been to relate impact sensitivity to the difference between the energies of the highest-occupied and lowest-unoccupied molecular orbitals of the explosive molecule, the "HOMO-LUMO gap." In the present study, we tested this approach for a series of twelve explosive nitroaromatics, using four different computational methods. We found that the HOMO-LUMO gap does not appear to be a reliable indicator of relative impact sensitivity. Since detonation initiation involves a series of steps, all of which influence sensitivity; it seems more realistic to try to identify fundamental factors and general trends related to sensitivity ‒ an approach that has already had some success ‒ rather than to seek correlations with one or two specific properties.

The π-hole revisited.

It follows from the Schrödinger equation that the forces operating within molecules and molecular complexes are Coulombic, which necessarily entails both electrostatics and polarization. A common and important class of molecular complexes is due to π-holes. These are molecular regions of low electronic density that are perpendicular to planar portions of the molecular frameworks. π-Holes often have positive electrostatic potentials associated with them, which result in mutually polarizing attractive forces with negative sites such as lone pairs, π electrons or anions. In many molecules, π-holes correspond to a flattening of the electronic density surface but in benzene derivatives and in polyazines the π-holes are craters above and below the rings. The interaction energies of π-hole complexes can be expressed quite well in terms of regression relationships that account for both the electrostatics and the polarization. There is a marked gradation in the interaction energies, from quite weak (about -2 kcal mol-1) to relatively strong (about -40 kcal mol-1). Gradations are also evident in the ratios of the intermolecular separations to the sums of the respective van der Waals radii and in the gradual transition of the π-hole atoms from trigonal to quasi-tetrahedral configurations. These trends are consistent with the concept that chemical interactions form a continuum, from very weak to very strong.