Structural dynamics around a hydrogen bond: Investigating the effect of hydrogen bond strengths on the excited state dynamics of carboxylic acid dimers.

The photochemical dynamics of the acetic acid and trifluoro-acetic acid dimers in hexane are studied using time-resolved infrared absorption spectroscopy and ab initio electronic structure calculations. The different hydrogen bond strengths of the two systems lead to changes in the character of the accessed excited states and in the timescales of the initial structural rearrangement that define the early time dynamics following UV excitation. The much stronger hydrogen bonding in the acetic acid dimer stabilizes the system against dissociation. Ground state recovery is mediated by a structural buckling around the hydrogen bond itself with no evidence for excited state proton transfer processes that are usually considered to drive ultrafast relaxation processes in hydrogen bonded systems. The buckling of the ring leads to relaxation through two conical intersections and the eventual reformation of the electronic and vibrational ground states on a few picosecond timescale. In trifluoro-acetic acid, the weaker hydrogen bonding interaction means that the dimer dissociates under similar irradiation conditions. The surrounding solvent cage restricts the full separation of the monomer components, meaning that the dimer is reformed and returns to the ground state structure via a similar buckled structure but over a much longer, ∼100 ps, timescale.

Publisher's Note: Hydrogen Bonds in Excited State Proton Transfer [Phys. Rev. Lett. 117, 163002 (2016)].

This corrects the article DOI: 10.1103/PhysRevLett.117.163002.

Hydrogen Bonds in Excited State Proton Transfer.

Hydrogen bonding interactions between biological chromophores and their surrounding protein and solvent environment significantly affect the photochemical pathways of the chromophore and its biological function. A common first step in the dynamics of these systems is excited state proton transfer between the noncovalently bound molecules, which stabilizes the system against dissociation and principally alters relaxation pathways. Despite such fundamental importance, studying excited state proton transfer across a hydrogen bond has proven difficult, leaving uncertainties about the mechanism. Through time-resolved photoelectron imaging measurements, we demonstrate how the addition of a single hydrogen bond and the opening of an excited state proton transfer channel dramatically changes the outcome of a photochemical reaction, from rapid dissociation in the isolated chromophore to efficient stabilization and ground state recovery in the hydrogen bonded case, and uncover the mechanism of excited state proton transfer at a hydrogen bond, which follows sequential hydrogen and charge transfer processes.

Quantum dynamics study of the competing ultrafast intersystem crossing and internal conversion in the "channel 3" region of benzene.

Time-resolved photoelectron spectroscopy can obtain detailed information about the dynamics of a chemical process on the femtosecond timescale. The resulting signal from such detailed experiments is often difficult to analyze and therefore theoretical calculations are important in providing support. In this paper we continue our work on the competing pathways in the photophysics and photochemistry of benzene after excitation into the "channel 3" region [R. S. Minns, D. S. N. Parker, T. J. Penfold, G. A. Worth, and H. H. Fielding, Phys. Chem. Chem. Phys. 12, 15607 (2010)] with details of the calculations shown previously, building on a vibronic coupling Hamiltonian [T. J. Penfold and G. A. Worth, J. Chem. Phys. 131, 064303 (2009)] to include the triplet manifold. New experimental data are also presented suggesting that an oscillatory signal is due to a hot band excitation. The experiments show that signals are obtained from three regions of the potential surfaces, three open channels, which are assigned with the help of simulations showing that following excitation into vibrationally excited-states of S(1) the wavepacket not only crosses through the prefulvenoid conical intersection back to the singlet ground state, but also undergoes ultrafast intersystem crossing to low lying triplet states. The model is, however, not detailed enough to capture the full details of the oscillatory signal due to the hot band.

Ultrafast dynamics through conical intersections and intramolecular vibrational energy redistribution in styrene.

We report a femtosecond time-resolved photoelectron spectroscopy (TRPES) investigation of internal conversion in the first two excited singlet electronic states of styrene. We find that radiationless decay through an S(1)/S(0) conical intersection occurs on a timescale of ∼4 ps following direct excitation to S(1) with 0.6 eV excess energy, but that the same process is significantly slower (∼20 ps) if it follows internal conversion from S(2) to S(1) after excitation to S(2) with 0.3 eV excess energy (0.9 eV excess energy in S(1)).

Competing ultrafast intersystem crossing and internal conversion in the "channel 3" region of benzene.

We report new, detailed, femtosecond time-resolved photoelectron spectroscopy experiments and calculations investigating the competition between ultrafast internal conversion and ultrafast intersystem crossing in electronically and vibrationally excited benzene at the onset of "channel 3". Using different probe energies to record the total photoelectron yield as a function of pump-probe delay we are able to confirm that S(1), T(1) and T(2) electronic states are involved in the excited state dynamics. Time-resolved photoelectron spectroscopy measurements then allow us to unravel the evolution of the S(1), T(1) and T(2) components of the excited state population and, together with complementary quantum chemistry and quantum dynamics calculations, support our earlier proposal that ultrafast intersystem crossing competes with internal conversion (Chem. Phys. Lett., 2009, 469, 43).

Non-accidental head injury: a consequence of deprivation?

BACKGROUND: Non-accidental head injury (NAHI) is a significant personal and public health problem, with considerable mortality and morbidity. The evidence base for risk factors specific for NAHI is limited due to difficulties with case definition and study design. The risk factors associated with NAHI in infants was evaluated in this study, and the extent to which indices of deprivation influence this health problem was addressed. METHODS: A 10-year prospective study was conducted in Scotland involving all paediatric hospitals and other general hospital departments admitting children. Subjects were children ≤2 years of age, with a diagnosis of "suspected NAHI". Socioeconomic characteristics of the index cases were compared to the general population, using the Scottish Index of Multiple Deprivation (SIMD) 2006. RESULTS: There were highly significant differences (p<0.001) between the SIMD rank scores of the NAHI cases and scores for the whole Scottish population. For the cohort, SIMD ranks ranged from 34 to 6253 (median 1210; mean 1577) compared to the population range of 1-6505 (median and mean=3253). Similar differences were found for each of the component domains of income, employment, health, education, crime and housing (p<0.001). In contrast, the scores for "geographic access" (to essential service) were higher than for the whole population (p<0.001), indicating that the deprivation was not due to lack of local services. CONCLUSION: In Scotland, children who present with suspected NAHI originate predominantly from the most deprived areas of the community. Public health and intervention strategies should be focused in these areas.

Development of a new photoelectron spectroscopy instrument combining an electrospray ion source and photoelectron imaging.

A new apparatus has been constructed that combines electrospray ionization with a quadrupole mass filter, hexapole ion trap, and velocity-map imaging. The purpose is to record photoelectron images of isolated chromophore anions. To demonstrate the capability of our instrument we have recorded the photodetachment spectra of isolated deprotonated phenol and indole anions. To our knowledge, this is the first time that the photodetachment energy of the deprotonated indole anion has been recorded.

Comparison of morphine concentration-time profiles following intravenous and intranasal diamorphine in children.

BACKGROUND: Current best practice for treating acute severe pain in children is to administer intravenous or intranasal opioid. Intranasal diamorphine offers less traumatic analgesia than the potentially difficult and distressing intravenous route. However, there has been no direct comparison of intranasal and intravenous diamorphine nor are there pharmacokinetic data for intranasal diamorphine in children. OBJECTIVE: To compare plasma morphine concentration-time profiles following intranasal and intravenous diamorphine administration. DESIGN: Observational. SETTING: A&E department in a city-centre paediatric teaching hospital. PATIENTS: Children, aged 3-13 years, with isolated limb fracture. INTERVENTIONS: An intravenous catheter was sited and baseline blood taken. The first 12 children received intravenous diamorphine (0.1 mg/kg), and the subsequent 12 intranasal diamorphine (0.1 mg/kg) in 0.2 ml sterile water drops. Subsequent samples were taken at 2, 5, 10, 20, 30 and 60 min. MEASUREMENTS: Plasma morphine radioimmunoassay. RESULTS: Peak plasma morphine concentrations were higher (median 109 vs 36 nmol/l), and occurred earlier (median 2 vs 10 min), with greater area under the curve (3761 vs 1794 nmol/l/h) following intravenous compared to intranasal diamorphine (all p<0.001, Mann-Whitney U test). Higher plasma concentrations at 60 min (47 vs 32 nmol/l) were also observed following intravenous diamorphine (p = 0.01, Mann-Whitney U test). CONCLUSIONS: Our evidence supports the wider use of diamorphine administration by nasal drops in children, as it shows that adequate plasma levels of morphine are usually achieved. However, we demonstrated significantly attenuated and delayed peak plasma morphine levels with lower levels at 1 h with intranasal compared with intravenous diamorphine.

Modulating effect of apolipoprotein E polymorphisms on secondary brain insult and outcome after childhood brain trauma.

OBJECTIVE: The aim of this study was to determine the relationship between apolipoprotein E (APO E) alleles, the amount of cerebral perfusion pressure (CPP) insult and outcome in children after brain trauma. MATERIALS AND METHODS: In a prospective two-centre case-control study, the APO E genotypes of 65 critically ill children admitted after brain trauma were correlated with age-related CPP insult quantification, conscious state at the time of discharge from intensive care and global outcome at 6 months post-injury. One hundred sixty healthy age- and sex-matched children were genotyped as controls. RESULTS: The CPP insult level among the e4 carriers with poor outcome was significantly less than the non-e4 carriers (p=0.03). Homozygotic e3 patients with good recovery did so despite having suffered nearly 26 times more CPP insult than those who were not e3 homzygous (p=0.02). CONCLUSION: Different APO E alleles may potentially affect cerebral ischaemic tolerance differently in children after brain trauma.

Low frequency pressure waves of possible autonomic origin in severely head-injured children.

BACKGROUND: Useful information (both clinical and pathophysiological) which may be extracted from intracranial pressure (ICP) recordings include: (1) the mean level of ICP (and CPP), (2) cerebrovascular autoregulation status, (3) the intracranial pulse pressure (the pulse wave index, ICPpp/ICPm) or the pressure-volume compensatory reserve index (RAP) and (4) the presence of any abnormal ICP waveform. This paper describes a slow frequency ICP waveform in children with TBI and postulates the pathophysiological basis and whether it contains clinically useful detail. METHODS: Children admitted to the Regional Head Injury Service in Edinburgh with TBI have continuously monitored ICP, MAP, CPP, and other physiological data (stored at a 1-min resolution). Slow frequency waveforms were noted, prompting a review of the stored monitoring from all cases over a 10 year period. FINDINGS: Episodic slow pressure waves were detected in 11 of 122 severely head-injured (HI) children. The waveforms were detected in children of all ages (1.6-15 years) in the ICP signal, which were in phase with similar fluctuations in the MAP, CPP, and HR signals. Their mean periodicity was 1 per 7 min (range 1 per 5-10 min), with a mean ICP pulse wave amplitude of 5.45 mmHg (range 4-7.5), and mean MAP pulse wave amplitude (pulse pressure) of 10.4 mmHg (range 4-15 mmHg). The duration was variable (range approx 2 h to 4.5 days). They were detected in the preterminal phase after serious HI, as well as in those children who made an independent recovery (GOS 4/5). The waves were not related to the mean levels of ICP, CPP, MAP, temperature or the state of cerebrovascular autoregulation. CONCLUSIONS: We postulate that these previously unreported slow waveforms may reflect the very low frequency (VLF) and ultra low frequency (ULF; < or = 1 per 5 min) components of heart rate and arterial blood pressure variability.

Are head injury guidelines changing the outcome of head injured children? A regional investigation.

BACKGROUND: Secondary pathophysiological CPP insult is related to outcome after head injury, and improved management would be expected to reduce secondary brain insult. Paediatric head injury management guidelines have been published in recent years, by SIGN (2000), RCPCH (2001), NICE (June 2003), and jointly by Critical/Intensive Care Societies (C/ICS July 2003). We investigated whether outcome of children's head injury (and total burden of secondary CPP insult) has changed (1) annually; (2) before and after the introduction of any HI guidelines, and (3) following other service changes. METHODS: Seventy-six children (aged 1-14 years with severe HI) were admitted to the Edinburgh Regional Head Injury Service between 1989 and 2006, and dichotomised at various time points and compared in terms of: demographic factors, intracranial pressure (ICP), cerebral perfusion pressure (CPP) insults [e.g. age-banded pressure-time index (PTI)], and Glasgow Outcome Scale (GOS) score (assessed at 6 months post injury). FINDINGS: When dichotomised around the SIGN guidelines, there were no statistically significant differences between the two group's demography or in primary brain injury, but the outcomes were different (p = 0.03), with 6 vs 4 GOS1 (died), 2 vs 4 GOS3 (severely disabled), 5 vs 16 GOS4 (moderately disabled) and 23 vs 14 GOS5 (good recovery), when comparing before and after year 2000. GOS4 was significantly different (chi-square = 7.99, p < 0.007). There was a (non-significant) trend for the later years to have longer insult durations of ICP, hypertension, CPP, hypoxia, pyrexia, tachycardia and bradycardia, greater PTI for both CPP and ICP, and more CPP insults (p = 0.003). There was, however, significantly less CPP insult (p = 0.030) after the introduction of the more management-oriented C/ICS guidelines. CONCLUSIONS: The most recent paediatric HI guidelines appear to have reduced the burden of secondary insult, but more time is required to determine if this will be reflected in improved outcomes.

Are hip protectors correctly positioned in use?

There are many designs of hip protectors ranging from small elliptical shaped hard shell designs to large circular soft pads. They are held in position usually by being contained in a close fitting pocket on a garment that patients wear all the time they are at risk of sustaining a fracture of the hip if they fall onto the area of the greater trochanter (GT). It is important for the function of the hip protector that the pad element is positioned over the GT when the subject falls onto a surface such as the floor so as to provide the maximal protection by reducing the large forces transmitted to the femoral neck that lead to the fracture of the bone. In this study, anatomical measurements show where the GT is relevant to the centre of the hip protector, and position and movement studies have shown that generally the hard shell design of the hip protector lies posterior and proximal to the GT both for erect and flexed positions of the hip. The position of the GT relevant to the anterior superior iliac crest was established using ultrasound examinations on control and patients admitted with a fracture of the hip due to a fall. The diagonal surface distance for the three groups of test subjects was approximately 12 cm and a template was developed that could be used to locate the GT. A 'zone' of GT position and movement has been established relative to the anterior superior iliac crest, and designers of garments should ensure that this zone is within the area of protection provided by their hip protector pad design.

Preserving coherence in Rydberg quantum bits.

The effectiveness of decoherence suppression schemes is explored using quantum bits (qubits) stored in Li np Rydberg states. Following laser excitation, pulsed electric fields coherently control the electronic spin-orbit coupling, facilitating qubit creation, manipulation, and measurement. Spin-orbit coupling creates an approximate decoherence-free subspace for extending qubit storage times. However, sequences of fast NOT operations are found to be substantially more effective for preserving coherence.

Critical thresholds of intracranial pressure and cerebral perfusion pressure related to age in paediatric head injury.

BACKGROUND: The principal strategy for managing head injury is to reduce the frequency and severity of secondary brain insults from intracranial pressure (ICP) and cerebral perfusion pressure (CPP), and hence improve outcome. Precise critical threshold levels have not been determined in head injured children. OBJECTIVE: To create a novel pressure-time index (PTI) measuring both duration and amplitude of insult, and then employ it to determine critical insult thresholds of ICP and CPP in children. METHODS: Prospective, observational, physiologically based study from Edinburgh and Newcastle, using patient monitored blood pressure, ICP, and CPP time series data. The PTI for ICP and CPP for 81 children, using theoretical values derived from physiological norms, was varied systematically to derive critical insult thresholds which delineate Glasgow outcome scale categories. RESULTS: The PTI for CPP had a very high predictive value for outcome (receiver operating characteristic analyses: area under curve = 0.957 and 0.890 for mortality and favourable outcome, respectively) and was more predictive than for ICP. Initial physiological values most accurately predicted favourable outcome. The CPP critical threshold values determined for children aged 2-6, 7-10, and 11-15 years were 48, 54, and 58 mm Hg. respectively. CONCLUSIONS: The PTI is the first substantive paediatric index of total ICP and CPP following head injury. The insult thresholds generated are identical to age related physiological values. Management guidelines for paediatric head injuries should take account of these CPP thresholds to titrate appropriate pressor therapy.

The role of gait analysis in the management of the knee.

Gait analysis has been used as an investigative tool for locomotion disorders since the early 20th century when it was done using time-lapsed photography. Since the advent of video and advances in strain gauge technology and fast data-handling devices coupled with computers, many of the movements and forces acting on and around the knee can now be measured with a high degree of accuracy. The magnitude and position of the force in 3-dimensional space can be accurately determined relative to the anatomy of the knee, consequently the clinician can assess and evaluate the forces and movements of the structures around and within the knee. This information can help the clinician predict and monitor post-surgery changes to the anatomy of the knee, and the forces and movements on these structures.

Inner calvarial erosion from traumatic subdural haematoma in infancy.

CASE REPORT: This is a report of a case of a subdural haematoma in infancy of possible non-accidental aetiology with raised pericerebral pressure, which we postulate has eroded the inner table of the cranial bones and resulted in leakage of marrow precursor cells into the extradural space. RESULT: Subdural tapping via the fontanelle has created a channel allowing subsequent ingress of nucleated red cell precursors into the subdural space. This addition to the subdural collection has prolonged its course necessitating subduro-peritoneal shunting.

Which paediatric head injured patients might benefit from decompression? Thresholds of ICP and CPP in the first six hours.

Severe head injury in childhood continues to be associated with considerable mortality and morbidity. Early surgical decompression may be beneficial and the objective of this study was to examine the relationship between age-related thresholds of mean intracranial pressure (ICP) and cerebral perfusion pressure (CPP) over the first 6 hours and age outcome in paediatric head injury patients. A total of 209 head injured children admitted to five UK hospitals were studied. Patients aged 2 to 16 years were included if they had a minimum of six hours of invasive pressure monitoring. Mean values of ICP and CPP over this period were calculated and compared to those with independent (good recovery and moderate disability) and poor outcome (severe disability, and death) for different age groups. There were 148 children with independent outcome (92 good recovery, 56 moderately disabled), and 61 with poor outcome (30 severely disabled, 31 deaths). There was a significant difference between those with independent compared to poor outcome in relation to ICP (p < 0.001) and CPP (p < 0.001). Patients were divided into three groups according to age. The sensitivity of ICP and CPP in predicting outcome was similar for all groups but the specificity differed between groups. At a CPP of 50 mmHg the specificity varied between the age groups (2 to 6 years: 0.47, 7 to 10 years: 0.28 and 11 to 16 years: 0.10) and similarly for an ICP of 25 mmHg (2 to 6 years: 0.53, 7 to 10 years: 0.44 and 11 to 16 years: 0.38). Younger children may be able to tolerate lower perfusion pressures and still have an independent outcome. Our threshold values for young children are likely to be important in the identification of patients who might benefit from new treatments such as surgical decompression.