Is the disease risk and penetrance in Leber hereditary optic neuropathy actually low?

Pedigree analysis showed that a large proportion of Leber hereditary optic neuropathy (LHON) family members who carry a mitochondrial risk variant never lose vision. Mitochondrial haplotype appears to be a major factor influencing the risk of vision loss from LHON. Mitochondrial variants, including m.14484T>C and m.11778G>A, have been added to gene arrays, and thus many patients and research participants are tested for LHON mutations. Analysis of the UK Biobank and Australian cohort studies found more than 1 in 1,000 people in the general population carry either the m.14484T>C or the m.11778G>A LHON variant. None of the subset of carriers examined had visual acuity at 20/200 or worse, suggesting a very low penetrance of LHON. Haplogroup analysis of m.14484T>C carriers showed a high rate of haplogroup U subclades, previously shown to have low penetrance in pedigrees. Penetrance calculations of the general population are lower than pedigree calculations, most likely because of modifier genetic factors. This Matters Arising Response paper addresses the Watson et al. (2022) Matters Arising paper, published concurrently in The American Journal of Human Genetics.

Establishing risk of vision loss in Leber hereditary optic neuropathy.

We conducted an updated epidemiological study of Leber hereditary optic neuropathy (LHON) in Australia by using registry data to establish the risk of vision loss among different LHON mutations, sex, age at onset, and mitochondrial haplogroup. We identified 96 genetically unrelated LHON pedigrees, including 56 unpublished pedigrees, and updated 40 previously known pedigrees, comprising 620 affected individuals and 4,948 asymptomatic carriers. The minimum prevalence of vision loss due to LHON in Australia in 2020 was one in 68,403 individuals. Although our data confirm some well-established features of LHON, the overall risk of vision loss among those with a LHON mutation was lower than reported previously-17.5% for males and 5.4% for females. Our findings confirm that women, older adults, and younger children are also at risk. Furthermore, we observed a higher incidence of vision loss in children of affected mothers as well as in children of unaffected women with at least one affected brother. Finally, we confirmed our previous report showing a generational fall in prevalence of vision loss among Australian men. Higher reported rates of vision loss in males with a LHON mutation are not supported by our work and other epidemiologic studies. Accurate knowledge of risk is essential for genetic counseling of individuals with LHON mutations. This knowledge could also inform the detection and validation of potential biomarkers and has implications for clinical trials of treatments aimed at preventing vision loss in LHON because an overestimated risk may lead to an underpowered study or a false claim of efficacy.

The mitochondrial genome of the diploid oat Avena longiglumis.

BACKGROUND: Avena longiglumis Durieu (2n = 2x = 14) is a wild relative of cultivated oat (Avena sativa, 2n = 6x = 42) with good agronomic and nutritional traits. The plant mitochondrial genome has a complex organization and carries genetic traits of value in exploiting genetic resources, not least male sterility alleles used to generate F1 hybrid seeds. Therefore, we aim to complement the chromosomal-level nuclear and chloroplast genome assemblies of A. longiglumis with the complete assembly of the mitochondrial genome (mitogenome) based on Illumina and ONT long reads, comparing its structure with Poaceae species. RESULTS: The complete mitochondrial genome of A. longiglumis can be represented by one master circular genome being 548,445 bp long with a GC content of 44.05%. It can be represented by linear or circular DNA molecules (isoforms or contigs), with multiple alternative configurations mediated by long (4,100-31,235 bp) and medium (144-792 bp) size repeats. Thirty-five unique protein-coding genes, three unique rRNA genes, and 11 unique tRNA genes are identified. The mitogenome is rich in duplications (up to 233 kb long) and multiple tandem or simple sequence repeats, together accounting for more than 42.5% of the total length. We identify homologous sequences between the mitochondrial, plastid and nuclear genomes, including the exchange of eight plastid-derived tRNA genes, and nuclear-derived retroelement fragments. At least 85% of the mitogenome is duplicated in the A. longiglumis nuclear genome. We identify 269 RNA editing sites in mitochondrial protein-coding genes including stop codons truncating ccmFC transcripts. CONCLUSIONS: Comparative analysis with Poaceae species reveals the dynamic and ongoing evolutionary changes in mitochondrial genome structure and gene content. The complete mitochondrial genome of A. longiglumis completes the last link of the oat reference genome and lays the foundation for oat breeding and exploiting the biodiversity in the genus.

Genome-wide expansion and reorganization during grass evolution: from 30 Mb chromosomes in rice and Brachypodium to 550 Mb in Avena.

BACKGROUND: The BOP (Bambusoideae, Oryzoideae, and Pooideae) clade of the Poaceae has a common ancestor, with similarities to the genomes of rice, Oryza sativa (2n = 24; genome size 389 Mb) and Brachypodium, Brachypodium distachyon (2n = 10; 271 Mb). We exploit chromosome-scale genome assemblies to show the nature of genomic expansion, structural variation, and chromosomal rearrangements from rice and Brachypodium, to diploids in the tribe Aveneae (e.g., Avena longiglumis, 2n = 2x = 14; 3,961 Mb assembled to 3,850 Mb in chromosomes). RESULTS: Most of the Avena chromosome arms show relatively uniform expansion over the 10-fold to 15-fold genome-size increase. Apart from non-coding sequence diversification and accumulation around the centromeres, blocks of genes are not interspersed with blocks of repeats, even in subterminal regions. As in the tribe Triticeae, blocks of conserved synteny are seen between the analyzed species with chromosome fusion, fission, and nesting (insertion) events showing deep evolutionary conservation of chromosome structure during genomic expansion. Unexpectedly, the terminal gene-rich chromosomal segments (representing about 50 Mb) show translocations between chromosomes during speciation, with homogenization of genome-specific repetitive elements within the tribe Aveneae. Newly-formed intergenomic translocations of similar extent are found in the hexaploid A. sativa. CONCLUSIONS: The study provides insight into evolutionary mechanisms and speciation in the BOP clade, which is valuable for measurement of biodiversity, development of a clade-wide pangenome, and exploitation of genomic diversity through breeding programs in Poaceae.

US regulations to curb alleged cancer causes are ineffectual and compromised by scientific, constitutional and ethical violations.

The 1958 Delaney amendment to the Federal Food Drug and Cosmetics Act prohibited food additives causing cancer in animals by appropriate tests. Regulators responded by adopting chronic lifetime cancer tests in rodents, soon challenged as inappropriate, for they led to very inconsistent results depending on the subjective choice of animals, test design and conduct, and interpretive assumptions. Presently, decades of discussions and trials have come to conclude it is impossible to translate chronic animal data into verifiable prospects of cancer hazards and risks in humans. Such conclusion poses an existential crisis for official agencies in the US and abroad, which for some 65 years have used animal tests to justify massive regulations of alleged human cancer hazards, with aggregated costs of $trillions and without provable evidence of public health advantages. This article addresses suitable remedies for the US and potentially worldwide, by critically exploring the practices of regulatory agencies vis-á-vis essential criteria for validating scientific evidence. According to this analysis, regulations of alleged cancer hazards and risks have been and continue to be structured around arbitrary default assumptions at odds with basic scientific and legal tests of reliable evidence. Such practices raise a manifold ethical predicament for being incompatible with basic premises of the US Constitution, and with the ensuing public expectations of testable truth and transparency from government agencies. Potential remedies in the US include amendments to the US Administrative Procedures Act, preferably requiring agencies to justify regulations compliant with the Daubert opinion of the Daubert ruling of the US Supreme Court, which codifies the criteria defining reliable scientific evidence. International reverberations are bound to follow what remedial actions may be taken in the US, the origin of current world regulatory procedures to control alleged cancer causing agents.

The ambivalence toward neuropsychology in dementia research, diagnosis, and drug development: Myths and misconceptions.

Clinical assessment remains the gold standard for diagnosing dementia, monitoring progression, and conducting clinical research. Biomarkers hold promise for targeted therapeutic approaches, selection of participants in clinical trials, and direct physiological efficacy readouts. However, the anchoring of biomarker research to clinical symptomatology is often based on short and insensitive cognitive screening. This gives the impression that cognitive symptoms occur relatively late and that their progression in the early stages of the disease is slow. A thorough cognitive assessment is a powerful tool and has a key role in the accurate and early diagnosis of dementia. It is very different from the cognitive testing usually seen in biomarker research and drug development. Yet the distinction between these approaches is unclear to many. This paper highlights the misconceptions around cognitive research in dementia and suggests a way forward to facilitate biomarker and drug development through the improved utility of cognitive assessment tools.

Why a clinical trial is as good as its outcome measure: A framework for the selection and use of cognitive outcome measures for clinical trials of Alzheimer's disease.

A crucial aspect of any clinical trial is using the right outcome measure to assess treatment efficacy. Compared to the rapidly evolved understanding and measurement of pathophysiology in preclinical and early symptomatic stages of Alzheimer's disease (AD), relatively less progress has been made in the evolution of clinical outcome assessments (COAs) for those stages. The current paper aims to provide a benchmark for the design and evaluation of COAs for use in early AD trials. We discuss lessons learned on capturing cognitive changes in predementia stages of AD, including challenges when validating novel COAs for those early stages and necessary evidence for their implementation in clinical trials. Moving forward, we propose a multi-step framework to advance the use of more effective COAs to assess clinically meaningful changes in early AD, which will hopefully contribute to the much-needed consensus around more appropriate outcome measures to assess clinical efficacy of putative treatments. HIGHLIGHTS: We discuss lessons learned on capturing cognitive changes in predementia stages of AD. We propose a framework for the design and evaluation of performance based cognitive tests for use in early AD trials. We provide recommendations to facilitate the implementation of more effective cognitive outcome measures in AD trials.

Health risks from radioactive particles on Cumbrian beaches near the Sellafield nuclear site.

A monitoring programme, in place since 2006, continues to recover radioactive particles (<2 mm diameter) and larger objects from the beaches of West Cumbria. The potential risks to members of the public using the beaches are mainly related to prolonged skin contact with or the inadvertent ingestion of small particles. Most particles are classified as either 'beta-rich' or 'alpha-rich' and are detected as a result of their caesium-137 or americium-241 content. Beta-rich particles generally also contain strontium-90, with90Sr:137Cs ratios of up to about 1:1, but typically <0.1:1. Alpha-rich particles contain plutonium isotopes, with Pu:241Amαratios usually around 0.5-0.6:1. 'Beta-rich' particles have the greatest potential to cause localised skin damage if held in stationary contact with the skin for prolonged periods. However, it is concluded that only particles of >106Bq of137Cs, with high90Sr:137Cs ratios, would pose a significant risk of causing acute skin ulceration. No particles of this level of activity have been found. Inadvertent ingestion of a particle will result in the absorption to blood of a small proportion of the radionuclide content of the particle. The subsequent retention of radionuclides in body organs and tissues presents a potential risk of the development of cancer. For 'beta-rich' particles with typical activities (mean 2 × 104Bq137Cs, Sr:Cs ratio of 0.1:1), the estimated committed effective doses are about 30µSv for adults and about 40µSv for 1 year old infants, with lower values for 'alpha-rich' particles of typical activities. The corresponding estimates of lifetime cancer incidence following ingestion for both particle types are of the order of 10-6for adults and up to 10-5for infants. These estimates are subject to substantial uncertainties but provide an indication of the low risks to members of the public.

Effective doses and risks from medical diagnostic x-ray examinations for male and female patients from childhood to old age.

The consideration of risks from medical diagnostic x-ray examinations and their justification commonly relies on estimates of effective dose, although the quantity is actually a health-detriment-weighted summation of organ/tissue-absorbed doses rather than a measure of risk. In its 2007 Recommendations, the International Commission on Radiological Protection (ICRP) defines effective dose in relation to a nominal value of stochastic detriment following low-level exposure of 5.7 × 10-2Sv-1, as an average over both sexes, all ages, and two fixed composite populations (Asian and Euro-American). Effective dose represents the overall (whole-body) dose received by a person from a particular exposure, which can be used for the purposes of radiological protection as set out by ICRP, but it does not provide a measure that is specific to the characteristics of the exposed individual. However, the cancer incidence risk models used by ICRP can be used to provide estimates of risk separately for males and females, as a function of age-at-exposure, and for the two composite populations. Here, these organ/tissue-specific risk models are applied to estimates of organ/tissue-specific absorbed doses from a range of diagnostic procedures to derive lifetime excess cancer incidence risk estimates; the degree of heterogeneity in the distribution of absorbed doses between organs/tissues will depend on the procedure. Depending on the organs/tissues exposed, risks are generally higher in females and notably higher for younger ages-at-exposure. Comparing lifetime cancer incidence risks per Sv effective dose from the different procedures shows that overall risks are higher by about a factor of two to three for the youngest age-at-exposure group, 0-9 yr, than for 30-39 yr adults, and lower by a similar factor for an age-at-exposure of 60-69 yr. Taking into account these differences in risk per Sv, and noting the substantial uncertainties associated with risk estimates, effective dose as currently formulated provides a reasonable basis for assessing the potential risks from medical diagnostic examinations.

Feasibility study of a novel digital health platform for patients undergoing transcatheter aortic valve replacement.

INTRODUCTION: Despite abundant evidence indicating that digital health solutions improve outcomes in chronic medical conditions, there are few validated solutions for acute surgical episodes. Transcatheter aortic valve replacement (TAVR) is a less invasive alternative to open surgery that is becoming more prevalent. We assessed the feasibility of ManageMySurgery (MMS), a smartphone application that combines patient education and outcomes tracking for patients undergoing TAVR procedures. METHODS: MMS was offered to patients receiving TAVR at an academic health center. Pre- and postoperatively, patients completed app-based tasks and reported clinical results using validated NYHA and KCCQ-12 surveys. Additionally, users reported levels of satisfaction with the digital platform. RESULTS: Sixty-nine patients were invited to use MMS, of which 43 (62%) downloaded and used the platform. The median age of patients was 77 years and 66.7% were male. The platform was accessed at an average of 2.6 times per user, with 79.1% of patients logging in one to three times. On average, 5.2 frequently asked questions were viewed. Of the 37 patients who completed the feedback survey (86%), 73.0% said it was helpful in preparation for surgery and 86.5% would recommend MMS to others. DISCUSSION: It is possible to utilize a digital health platform to guide patients undergoing TAVR through their interventional journey. Additional research is warranted to assess whether digital patient navigation tools provide an added benefit over traditional perioperative care alone, in terms of long-term patient engagement and outcomes.

Ultraviolet-C Photoresponsivity Using Fabricated TiO2 Thin Films and Transimpedance-Amplifier-Based Test Setup.

We report on fabricated titanium dioxide (TiO2) thin films along with a transimpedance amplifier (TIA) test setup as a photoconductivity detector (sensor) in the ultraviolet-C (UV-C) wavelength region, particularly at 260 nm. TiO2 thin films deposited on high-resistivity undoped silicon-substrate at thicknesses of 100, 500, and 1000 nm exhibited photoresponsivities of 81.6, 55.6, and 19.6 mA/W, respectively, at 30 V bias voltage. Despite improvements in the crystallinity of the thicker films, the decrease in photocurrent, photoconductivity, photoconductance, and photoresponsivity in thicker films is attributed to an increased number of defects. Varying the thickness of the film can, however, be leveraged to control the wavelength response of the detector. Future development of a chip-based portable UV-C detector using TiO2 thin films will open new opportunities for a wide range of applications.

Genome Assembly and Analysis of the Flavonoid and Phenylpropanoid Biosynthetic Pathways in Fingerroot Ginger (Boesenbergia rotunda).

Boesenbergia rotunda (Zingiberaceae), is a high-value culinary and ethno-medicinal plant of Southeast Asia. The rhizomes of this herb have a high flavanone and chalcone content. Here we report the genome analysis of B. rotunda together with a complete genome sequence as a hybrid assembly. B. rotunda has an estimated genome size of 2.4 Gb which is assembled as 27,491 contigs with an N50 size of 12.386 Mb. The highly heterozygous genome encodes 71,072 protein-coding genes and has a 72% repeat content, with class I TEs occupying ~67% of the assembled genome. Fluorescence in situ hybridization of the 18 chromosome pairs at the metaphase showed six sites of 45S rDNA and two sites of 5S rDNA. An SSR analysis identified 238,441 gSSRs and 4604 EST-SSRs with 49 SSR markers common among related species. Genome-wide methylation percentages ranged from 73% CpG, 36% CHG and 34% CHH in the leaf to 53% CpG, 18% CHG and 25% CHH in the embryogenic callus. Panduratin A biosynthetic unigenes were most highly expressed in the watery callus. B rotunda has a relatively large genome with a high heterozygosity and TE content. This assembly and data (PRJNA71294) comprise a source for further research on the functional genomics of B. rotunda, the evolution of the ginger plant family and the potential genetic selection or improvement of gingers.

Intrathecal Morphine for Analgesia in Minimally Invasive Cardiac Surgery: A Randomized, Placebo-controlled, Double-blinded Clinical Trial.

BACKGROUND: Intrathecal morphine decreases postoperative pain in standard cardiac surgery. Its safety and effectiveness have not been adequately evaluated in minimally invasive cardiac surgery. The authors hypothesized that intrathecal morphine would decrease postoperative morphine consumption after minimally invasive cardiac surgery. METHODS: In this randomized, placebo-controlled, double-blinded clinical trial, patients undergoing robotic totally endoscopic coronary artery bypass received either intrathecal morphine (5 mcg/kg) or intrathecal saline before surgery. The primary outcome was postoperative morphine equivalent consumption in the first 24 h after surgery; secondary outcomes included pain scores, side effects, and patient satisfaction. Pain was assessed via visual analog scale at 1, 2, 6, 12, 24, and 48 h after intensive care unit arrival. Opioid-related side effects (nausea/vomiting, pruritus, urinary retention, respiratory depression) were assessed daily. Patient satisfaction was evaluated with the Revised American Pain Society Outcome Questionnaire. RESULTS: Seventy-nine patients were randomized to receive intrathecal morphine (n = 37) or intrathecal placebo (n = 42), with 70 analyzed (morphine 33, placebo 37). Intrathecal morphine patients required significantly less median (25th to 75th percentile) morphine equivalents compared to placebo during first postoperative 24 h (28 [16 to 46] mg vs. 59 [41 to 79] mg; difference, -28 [95% CI, -40 to -18]; P < 0.001) and second postoperative 24 h (0 [0 to 2] mg vs. 5 [0 to 6] mg; difference, -3.3 [95% CI, -5 to 0]; P < 0.001), exhibited significantly lower visual analog scale pain scores at rest and cough at all postoperative timepoints (overall treatment effect, -4.1 [95% CI, -4.9 to -3.3] and -4.7 [95% CI, -5.5 to -3.9], respectively; P < 0.001), and percent time in severe pain (10 [0 to 40] vs. 40 [20 to 70]; P = 0.003) during the postoperative period. Mild nausea was more common in the intrathecal morphine group (36% vs. 8%; P = 0.004). CONCLUSIONS: When given before induction of anesthesia for totally endoscopic coronary artery bypass, intrathecal morphine decreases use of postoperative opioids and produces significant postoperative analgesia for 48 h.

Bone Mineral Density Differences Across Female Olympic Lifters, Power Lifters, and Soccer Players.

ABSTRACT: Jeon, W, Harrison, JM, Stanforth, PR, and Griffin, L. Bone mineral density differences across female Olympic lifters, power lifters, and soccer players. J Strength Cond Res 35(3): 638-643, 2021-Athletic training improves bone mineral density (BMD) through repeated mechanical loading. The location, intensity, and direction of applied mechanical pressure play an important role in determining BMD, making some sports more advantageous at improving BMD at specific regions. Thirty-seven (10 power lifters [PL], 8 Olympic lifters [OL], 8 soccer players [SP], and 11 recreationally active [RA]) women participated in a cross-sectional study. We measured lumbar spine (L1-L4), femoral neck, total-body BMD, and overall body composition (total fat mass, lean mass, percent body fat) with dual-energy x-ray absorptiometry. All athletic groups had greater total BMD than RA (p = 0.01 [PL]; p < 0.001 [OL]; p = 0.01 [SP]). Olympic lifters had the highest total BMD than all other athletic groups. Olympic lifters had the significantly greater total BMD than PL (p = 0.018), but there was no difference in total BMD between PL and SP. As compared with RA, OL showed greater BMD at both the total lumbar spine (p = 0.002) and the femoral neck (p = 0.007), whereas PL showed greater BMD only for the total lumbar spine (p = 0.019) and SP showed greater BMD only for the femoral neck (p = 0.002). Olympic-style lifting includes both high-impact and odd-impact loading modalities that are associated with the highest BMD at both the lumbar spine and femoral neck.

Methane oxidation in anoxic lake water stimulated by nitrate and sulfate addition.

Methanotrophic bacteria play a key role in limiting methane emissions from lakes. It is generally assumed that methanotrophic bacteria are mostly active at the oxic-anoxic transition zone in stratified lakes, where they use oxygen to oxidize methane. Here, we describe a methanotroph of the genera Methylobacter that is performing high-rate (up to 72 µM day-1 ) methane oxidation in the anoxic hypolimnion of the temperate Lacamas Lake (Washington, USA), stimulated by both nitrate and sulfate addition. Oxic and anoxic incubations both showed active methane oxidation by a Methylobacter species, with anoxic rates being threefold higher. In anoxic incubations, Methylobacter cell numbers increased almost two orders of magnitude within 3 days, suggesting that this specific Methylobacter species is a facultative anaerobe with a rapid response capability. Genomic analysis revealed adaptations to oxygen-limitation as well as pathways for mixed-acid fermentation and H2 production. The denitrification pathway was incomplete, lacking the genes narG/napA and nosZ, allowing only for methane oxidation coupled to nitrite-reduction. Our data suggest that Methylobacter can be an important driver of the conversion of methane in oxygen-limited lake systems and potentially use alternative electron acceptors or fermentation to remain active under oxygen-depleted conditions.

Comparative chloroplast genome analyses of Avena: insights into evolutionary dynamics and phylogeny.

BACKGROUND: Oat (Avena sativa L.) is a recognized health-food, and the contributions of its different candidate A-genome progenitor species remain inconclusive. Here, we report chloroplast genome sequences of eleven Avena species, to examine the plastome evolutionary dynamics and analyze phylogenetic relationships between oat and its congeneric wild related species. RESULTS: The chloroplast genomes of eleven Avena species (size range of 135,889-135,998 bp) share quadripartite structure, comprising of a large single copy (LSC; 80,014-80,132 bp), a small single copy (SSC; 12,575-12,679 bp) and a pair of inverted repeats (IRs; 21,603-21,614 bp). The plastomes contain 131 genes including 84 protein-coding genes, eight ribosomal RNAs and 39 transfer RNAs. The nucleotide sequence diversities (Pi values) range from 0.0036 (rps19) to 0.0093 (rpl32) for ten most polymorphic genes and from 0.0084 (psbH-petB) to 0.0240 (petG-trnW-CCA) for ten most polymorphic intergenic regions. Gene selective pressure analysis shows that all protein-coding genes have been under purifying selection. The adjacent position relationships between tandem repeats, insertions/deletions and single nucleotide polymorphisms support the evolutionary importance of tandem repeats in causing plastome mutations in Avena. Phylogenomic analyses, based on the complete plastome sequences and the LSC intermolecular recombination sequences, support the monophyly of Avena with two clades in the genus. CONCLUSIONS: Diversification of Avena plastomes is explained by the presence of highly diverse genes and intergenic regions, LSC intermolecular recombination, and the co-occurrence of tandem repeat and indels or single nucleotide polymorphisms. The study demonstrates that the A-genome diploid-polyploid lineage maintains two subclades derived from different maternal ancestors, with A. longiglumis as the first diverging species in clade I. These genome resources will be helpful in elucidating the chloroplast genome structure, understanding the evolutionary dynamics at genus Avena and family Poaceae levels, and are potentially useful to exploit plastome variation in making hybrids for plant breeding.

Strong, Nonresonant Radiation Enhances Cis-Trans Photoisomerization of Stilbene in Solution.

Previously, it has been demonstrated that external electric fields may be used to exert control over chemical reactivity. In this study, the impact of a strong, nonresonant IR field (1064 nm) on the photoisomerization of cis-stilbene is investigated in cyclohexane solution. The design of a suitable reaction vessel for characterization of this effect is presented. The electric field supplied by the pulsed, near-IR radiation (εl = 4.5 × 107 V/cm) enhances the cis → trans photoisomerization yield at the red edge of the absorption spectrum (wavelengths between 337 and 340 nm). Within the microliter focal volume, up to 75% of all cis-stilbene molecules undergo isomerization to trans-stilbene in the strong electric-field environment, indicating a significant increase relative to the 35% yield of trans-stilbene under field-free conditions. This result correlates with a 1-3% enhancement in the trans-stilbene concentration throughout the bulk solution. Theoretical analysis suggests that the observed change is the result of dynamic Stark shifting of the ground and first excited states, leading to a significant redshift in cis-stilbene's absorption spectrum. The predicted increase in the absorption cross section in this range of excitation wavelengths is qualitatively consistent with the experimental increase in trans-stilbene production.

The Physical Activity Wearables in the Police Force (PAW-Force) study: acceptability and impact.

BACKGROUND: Policing is a highly stressful and increasingly sedentary occupation. The study aim was to assess the acceptability and impact of a mobile health (mHealth) technology intervention (Fitbit® activity monitor and 'Bupa Boost' smartphone app) to promote physical activity (PA) and reduce sedentary time in the police force. METHODS: Single-group, pre-post, mixed methods pilot study. Police officers and staff (n = 180) were recruited from two police forces in South West England. Participants used the technology for 12 weeks (an 'individual' then 'social' phase) followed by 5 months of optional use. Data sources included Fitbit®-recorded objective step count, questionnaire surveys and semi-structured interviews (n = 32). Outcome assessment points were baseline (week 0), mid-intervention (week 6), post-intervention (week 12) and follow-up (month 8). Paired t-tests were used to investigate changes in quantitative outcomes. Qualitative analysis involved framework and thematic analysis. RESULTS: Changes in mean daily step count were non-significant (p > 0.05), but self-reported PA increased in the short term (e.g. + 465.4 MET-minutes/week total PA baseline to week 12, p = 0.011) and longer term (e.g. + 420.5 MET-minutes/week moderate-to-vigorous PA baseline to month 8, p = 0.024). The greatest impact on behaviour was perceived by less active officers and staff. There were no significant changes in sedentary time; the qualitative findings highlighted the importance of context and external influences on behaviour. There were no statistically significant changes (all p-values > 0.05) in any secondary outcomes (physical and mental health-related quality of life, perceived stress and perceived productivity), with the exception of an improvement in mental health-related quality of life (SF-12 mental component score + 1.75 points, p = 0.020) from baseline to month 8. Engagement with and perceived acceptability of the intervention was high overall, but a small number of participants reported negative physical (skin irritation) and psychological (feelings of guilt and anxiety) consequences of technology use. Individual app features (such as goal-setting and self-monitoring) were generally preferred to social components (social comparison, competitions and support). CONCLUSIONS: mHealth technology is an acceptable and potentially impactful intervention for increasing PA in the police force. The intervention was less useful for reducing sedentary time and the impact on secondary outcomes is unclear. TRIAL REGISTRATION: NCT03169179 (registered 30th May 2017).

Nonresonant Photons Catalyze Photodissociation of Phenol.

Phenol represents an ideal polyatomic system for demonstrating photon catalysis because of its large polarizability, well-characterized excited-state potential energy surfaces, and nonadiabatic dissociation dynamics. A nonresonant IR pulse (1064 nm) supplies a strong electric field (4 × 107 V/cm) during the photolysis of isolated phenol (C6H5OH) molecules to yield C6H5O + H near two known energetic thresholds: the S1/S2 conical intersection and the S1 - S0 origin. H-atom speed distributions show marked changes in the relative contributions of dissociative pathways in both cases, compared to the absence of the nonresonant IR pulse. Results indicate that nonresonant photons lower the activation barrier for some pathways relative to others by dynamically Stark shifting the excited-state potential energy surfaces rather than aligning molecules in the strong electric field. Theoretical calculations offer support for the experimental interpretation.