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Study Objectives: Epiglottic collapse can obstruct the airway in obstructive sleep apnea (OSA) patients in an anteroposterior (E-ap) or lateral direction (E-lat). The present study investigates the concept that lateral or concentric pharyngeal collapse patterns may remodel the epiglottis and predispose it to lateral collapse. To do so, we hypothesized that the presence of-any form of laterally directed pharyngeal collapse, e.g., oropharyngeal lateral wall collapse (OLW) or complete concentric collapse of the soft palate (CCCp), is associated with increased odds for having concurrent lateral epiglottic collapse., Methods: We analyzed 582 OSA patients from our drug-induced sleep endoscopy (DISE) cohort. Site of collapse was scored by a single scorer using the VOTE criteria, with epiglottic collapse patients reviewed by 2 additional independent scorers. Logistic regression evaluated the association between presence of laterally directed pharyngeal collapse and the presence of lateral epiglottic collapse., Results: The overall prevalence of E-lat was 2.6% (n=15). The presence of any form of laterally directed pharyngeal collapse was associated with 4-fold increased odds (4.4 [1.5-12.6], p=0.006) of having concurrent lateral epiglottic collapse. Further, the specific presence of either complete OLW collapse or CCCp was associated with an odds ratio of 3.4 [1.2-9.6] and 8.6 [2.2-33.5], respectively of having concurrent lateral epiglottic collapse., Conclusions: Greater prevalence of severe laterally directed pharyngeal collapse, in the form of either CCCp or OLW collapse in patients with E-lat supports the concept that laterally and concentric pharyngeal collapse patterns may shape the epiglottis and thereby contribute to the pathogenesis of lateral epiglottic collapse., (© 2024 American Academy of Sleep Medicine.)

Background: Obstructive sleep apnea is associated with increased blood pressure (BP). Obstructive sleep apnea treatment reduces BP with substantial variability, not explained by the apnea-hypopnea index, partly due to inadequate characterization of obstructive sleep apnea's physiological consequences, such as oxygen desaturation, cardiac autonomic response, and suboptimal treatment efficacy. We sought to examine whether a high baseline heart rate response (ΔHR), a marker of high cardiovascular risk in obstructive sleep apnea, predicts a larger reduction in post-treatment systolic BP (SBP). Furthermore, we aimed to assess the extent to which a reduction in SBP is explained by a treatment-related reduction in hypoxic burden (HB)., Methods: ΔHR and HB were measured from pretreatment and posttreatment polygraphy, followed by a 24-hour BP assessment in 168 participants treated with continuous positive airway pressure or nocturnal supplemental oxygen from the HeartBEAT study (Heart Biomarker Evaluation in Apnea Treatment). Multiple linear regression models assessed whether high versus mid (reference) ΔHR predicted a larger reduction in SBP (primary outcome) and whether there was an association between treatment-related reductions in SBP and HB., Results: A high versus mid ΔHR predicted improvement in SBP (adjusted estimate, 5.8 [95% CI, 1.0-10.5] mm Hg). Independently, a greater treatment-related reduction in HB was significantly associated with larger reductions in SBP (4.2 [95% CI, 0.9-7.5] mm Hg per 2 SD treatment-related reduction in HB). Participants with substantial versus minimal treatment-related reductions in HB had a 6.5 (95% CI, 2.5-10.4) mm Hg drop in SBP., Conclusions: A high ΔHR predicted a more favorable BP response to therapy. Furthermore, the magnitude of the reduction in BP was partly explained by a greater reduction in HB., Competing Interests: Disclosures A. Azarbarzin receives grant support from Somnifix and serves as a consultant for Somnifix, Respicardia, Eli Lilly, and Apnimed; Apnimed is a developing pharmacological treatment for obstructive sleep apnea. A. Azarbarzin’s interests were reviewed by Brigham and Women’s Hospital and Mass General Brigham in accordance with their institutional policies. S. Sands receives personal fees as a consultant for Nox Medical, Apnimed, Merck, and Inspire outside the submitted work, and he has received grant support from Apnimed, Prosomnus, and Dynaflex. A. Wellman works as a consultant for Apnimed, Somnifix, Inspire, and Nox Medical. He has received grants from Somnifix and Regeneron. He has a financial interest in Apnimed, a company developing pharmacological therapies for sleep apnea. His interests were reviewed and are managed by Brigham and Women’s Hospital and Partners HealthCare in accordance with their conflict of interest policies. C. Schmickl reports income from consulting for Verily outside the submitted work. A. Malhotra is funded by the National Institutes of Health. He reports income related to medical education from Livanova, Eli Lilly, Jazz, and Zoll. ResMed provided a philanthropic donation to University of California San Diego. S. Redline received consulting fees from Eli Lilly, Inc, and Jazz Pharma and has consulted for Apnimed, Inc. D.J. Gottlieb has served on scientific advisory boards for Signifier Medical Technologies, Inc, and Wesper, Inc, and as a consultant to Powell-Mansfield, Inc, and Apnimed, Inc, and has received research support from ResMed, Inc. The other authors report no conflicts.

Rationale: The physiological factors modulating the severity of snoring have not been adequately described. Airway collapse or obstruction is generally the leading determinant of snore sound generation; however, we suspect that ventilatory drive is of equal importance. Objective: To determine the relationship between airway obstruction and ventilatory drive on snore loudness. Methods: In 40 patients with suspected or diagnosed obstructive sleep apnea (1-98 events/hr), airflow was recorded via a pneumotachometer attached to an oronasal mask, ventilatory drive was recorded using calibrated intraesophageal diaphragm electromyography, and snore loudness was recorded using a calibrated microphone attached over the trachea. "Obstruction" was taken as the ratio of ventilation to ventilatory drive and termed flow:drive, i.e., actual ventilation as a percentage of intended ventilation. Lower values reflect increased flow resistance. Using 165,063 breaths, mixed model analysis (quadratic regression) quantified snore loudness as a function of obstruction, ventilatory drive, and the presence of extreme obstruction (i.e., apneic occlusion). Results: In the presence of obstruction (flow:drive = 50%, i.e., doubled resistance), snore loudness increased markedly with increased drive (+3.4 [95% confidence interval, 3.3-3.5] dB per standard deviation [SD] change in ventilatory drive). However, the effect of drive was profoundly attenuated without obstruction (at flow:drive = 100%: +0.23 [0.08-0.39] dB per SD change in drive). Similarly, snore loudness increased with increasing obstruction exclusively in the presence of increased drive (at drive = 200% of eupnea: +2.1 [2.0-2.2] dB per SD change in obstruction; at eupneic drive: +0.14 [-0.08 to 0.28] dB per SD change). Further, snore loudness decreased substantially with extreme obstruction, defined as flow:drive <20% (-9.9 [-3.3 to -6.6] dB vs. unobstructed eupneic breathing). Conclusions: This study highlights that ventilatory drive, and not simply pharyngeal obstruction, modulates snore loudness. This new framework for characterizing the severity of snoring helps better understand the physiology of snoring and is important for the development of technologies that use snore sounds to characterize sleep-disordered breathing.

Rationale: Recent studies have shown that sleep apnea-specific intermittent hypoxemia quantified by the hypoxic burden (HB) predicted cardiovascular disease (CVD)-related mortality in community-based and clinical cohorts. Calculation of HB is based on manual scoring of hypopneas and apneas, which is time-consuming and prone to interscorer variability. Objective: To validate a novel method to quantify the HB that is based on automatically scored desaturations. Methods: The sample included 5,655 middle-aged or older adults from the Sleep Heart Health Study (52.8% women; age, 63.2 ± 11.3 yr). The original HB method was based on a subject-specific search window obtained from an ensemble average of oxygen saturation signals (as measured by pulse oximetry) and synchronized with respect to the termination of scored respiratory events. In this study, however, the search window was obtained from ensemble average of oxygen saturation signals that synchronized with respect to the minimum of all automatically identified desaturations (⩾2% and other thresholds, including 3% and 4%, in sensitivity analyses). The time interval between the two maxima around the minimum saturation was defined as the search window. The oximetry-derived HB (HB Oxi ) was defined as the total area under all desaturation curves (restricted by the search window) divided by the total sleep time. Logistic and Cox regression models assessed the adjusted odds ratio (aOR)/hazard ratio of excessive daytime sleepiness (EDS), hypertension (HTN), and CVD mortality per 1-standard deviation increase in HB Oxi after adjusting for several covariates and confounders. Results: The Spearman's rank correlation between HB (median [interquartile range], 34.4 [18.4-59.8] % min/h) and HB Oxi (median [interquartile range], 34.5 [21.6-53.8] % min/h) was 0.81 ( P  < 0.001). Similar to HB, HB Oxi was significantly associated with EDS (aOR [95% confidence interval (CI)], 1.17 [1.09-1.26] per standard deviation), HTN (aOR [95% CI], 1.13 [1.05-1.21]), and CVD mortality (adjusted hazard ratio [95% CI], 1.15 [1.01-1.30]) in fully adjusted models. Conclusions: The HB Oxi was highly correlated with the HB based on manually scored apneas and hypopneas and was associated with EDS, HTN, and CVD mortality with similar effect sizes as previously reported. This method could be incorporated into wearable technology that accurately records oxygen saturation signals.

Rationale: Obstructive sleep apnea is characterized by frequent reductions in ventilation, leading to oxygen desaturations and/or arousals. Objectives: In this study, association of hypoxic burden with incident cardiovascular disease (CVD) was examined and compared with that of "ventilatory burden" and "arousal burden." Finally, we assessed the extent to which the ventilatory burden, visceral obesity, and lung function explain variations in hypoxic burden. Methods: Hypoxic, ventilatory, and arousal burdens were measured from baseline polysomnograms in the Multi-Ethnic Study of Atherosclerosis (MESA) and the Osteoporotic Fractures in Men (MrOS) studies. Ventilatory burden was defined as event-specific area under ventilation signal (mean normalized, area under the mean), and arousal burden was defined as the normalized cumulative duration of all arousals. The adjusted hazard ratios for incident CVD and mortality were calculated. Exploratory analyses quantified contributions to hypoxic burden of ventilatory burden, baseline oxygen saturation as measured by pulse oximetry, visceral obesity, and spirometry parameters. Measurements and Main Results: Hypoxic and ventilatory burdens were significantly associated with incident CVD (adjusted hazard ratio [95% confidence interval] per 1 SD increase in hypoxic burden: MESA, 1.45 [1.14, 1.84]; MrOS, 1.13 [1.02, 1.26]; ventilatory burden: MESA, 1.38 [1.11, 1.72]; MrOS, 1.12 [1.01, 1.25]), whereas arousal burden was not. Similar associations with mortality were also observed. Finally, 78% of variation in hypoxic burden was explained by ventilatory burden, whereas other factors explained only <2% of variation. Conclusions: Hypoxic and ventilatory burden predicted CVD morbidity and mortality in two population-based studies. Hypoxic burden is minimally affected by measures of adiposity and captures the risk attributable to ventilatory burden of obstructive sleep apnea rather than a tendency to desaturate.

Rationale: A low respiratory arousal threshold is a key endotype responsible for obstructive sleep apnea (OSA) pathogenesis. Pimavanserin is an antiserotoninergic capable of suppressing CO 2 -mediated arousals without affecting the respiratory motor response in animal models, and thus it holds potential for increasing the arousal threshold in OSA and subsequently reducing OSA severity. Objectives: We measured the effect of pimavanserin on arousal threshold (primary outcome), OSA severity, arousal index, and other OSA endotypes (secondary outcomes). Methods: A total of 18 OSA participants were studied in a randomized, double-blind, crossover study. Patients received a single dose of placebo or pimavanserin 34 mg 4 hours before in-lab polysomnography. Airflow was measured with an oronasal mask attached to a pneumotachograph, and ventilatory drive was recorded with an intraesophageal electromyography catheter. Results are presented as mean or median changes (Δ) and 95% confidence intervals (CIs). Results: Pimavanserin did not increase the arousal threshold, nor did it decrease OSA severity or arousal index. It, however, prolonged total sleep time (Δ[confidence interval (CI)], 39.5 [95%CI, -1.2 to 80.1] min). In an exploratory analysis, a subgroup of seven patients who had a 10% or more increase in arousal threshold on pimavanserin exhibited a decrease in AHI 4 (hypopneas associated with 4% desaturation) (Δ[CI], 5.6 [95%CI, 3.6-11.1] events/h) and hypoxic burden (Δ[CI], 22.3 [95%CI, 6.6-32.3] %min/h). Conclusions: A single dose of pimavanserin did not have a significant effect on arousal threshold or OSA severity. However, in a post hoc analysis, a subset of patients who exhibited an increase in arousal threshold on pimavanserin showed a small decrease in OSA severity. Thus, if the arousal threshold could be increased with pimavanserin, perhaps with longer dosing to reach higher drug blood concentrations, then the desired effect on OSA severity might be achievable. Clinical trial registered with ClinicalTrials.gov (NCT04538755).

Rationale: Randomized controlled trials of continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) have not demonstrated protection against adverse cardiovascular outcomes. Recently, observational studies revealed that OSA-related cardiovascular risk is concentrated in patients with an elevated pulse rate response to respiratory events (ΔHR). Objectives: Here, in this post hoc analysis of a prospective clinical trial, we test the hypothesis that a greater pretreatment ΔHR is associated with greater CPAP-related protection against adverse cardiovascular outcomes. Methods: ΔHR was measured from baseline polysomnography of the RICCADSA (Randomized Intervention with CPAP in CAD and OSA) randomized controlled trial (patients with coronary artery disease [CAD] and OSA [apnea-hypopnea index ⩾ 15 events/h] with Epworth Sleepiness Scale score < 10; n CPAP : n control  = 113:113; male, 85%; age, 66 ± 8 [mean ± SD] yr). The primary outcome was a composite of repeat revascularization, myocardial infarction, stroke, and cardiovascular mortality. Multivariable Cox regression assessed whether the effect of CPAP was moderated by ΔHR (treatment-by-ΔHR interaction). Measurements and Main Results: The CPAP-related reduction in risk increased progressively with increasing pretreatment ΔHR (interaction hazard ratio [95% confidence interval], 0.49 [0.27 to 0.90] per SD increase in ΔHR; P  < 0.05). This means that in patients with a ΔHR of 1 SD above the mean (i.e., 10 beats/min), CPAP was estimated to reduce cardiovascular risk by 59% (6% to 82%) ( P  < 0.05), but no significant risk reduction was estimated in patients with a mean ΔHR (6 beats/min; CPAP risk reduction, 16% [-53% to 54%]; P  = 0.6). Conclusions: The protective effect of CPAP in patients with CAD and OSA without excessive sleepiness was modified by the ΔHR. Specifically, patients with higher ΔHR exhibit greater cardiovascular benefit from CPAP therapy.

Rationale: Mouth breathing increases upper airway collapsibility, leading to decreased efficacy of obstructive sleep apnea (OSA) treatments. We hypothesized that the use of mandibular advancement devices (MAD) increases mouth breathing, and thus, using an adhesive mouthpiece (AMT) to prevent mouth breathing in combination with MAD can improve the treatment efficacy. Objectives: To evaluate the efficacy of MAD + AMT in comparison with MAD alone. Methods: A prospective crossover pilot study was designed to test this hypothesis. Briefly, adult participants with an apnea-hypopnea index (AHI) between 10 and 50 events/h at the screening visit were randomized to no treatment (baseline), MAD treatment, AMT treatment, and MAD + AMT treatment. As a primary analysis, absolute AHI was compared between MAD and MAD + AMT arms. Secondary analyses included quantifying the percent change in AHI, percentage of complete (AHI < 5 events/h) and incomplete (5-10 events/h) responders, and the efficacy of AMT alone in comparison with other treatment arms. Results: A total of 21 participants were included (baseline AHI = 24.3 ± 9.9 events/h). The median AHI (interquartile range) in the MAD and MAD + AMT arms were 10.5 (5.4-19.6) events/h and 5.6 (2.2-11.7) events/h ( P  = 0.02), respectively. A total of 76% of individuals achieved an AHI of <10 events/h in the MAD + AMT arm versus 43% in the MAD arm ( P  < 0.01). Finally, the observed effect was similar in moderate to severe OSA (AHI ⩾ 15 events/h) in terms of absolute reduction and treatment responders, and AMT alone did not significantly reduce the AHI compared with baseline. Conclusions: A combination of an adhesive mouthpiece and MAD is a more effective therapy than MAD alone. These findings may help improve clinical decision making in sleep apnea.

Study Objectives: Obstructive sleep apnea has major health consequences but is challenging to treat. For many therapies, efficacy is determined by the severity of underlying pharyngeal collapsibility, yet there is no accepted clinical means to measure it. Here, we provide insight into which polysomnographic surrogate measures of collapsibility are valid, applicable across the population, and predictive of therapeutic outcomes., Methods: Seven promising polysomnography-derived surrogate collapsibility candidates were evaluated: Vpassive (flow at eupneic ventilatory drive), Vmin (ventilation at nadir drive), event depth (depth of the average respiratory event), oxygen desaturation slope and mean oxygen desaturation (events-related averages), Fhypopneas (fraction of events scored as hypopneas), and apnea index. Evaluation included (1) validation by comparison to physiological gold-standard collapsibility values (critical closing pressure, Pcrit), (2) capacity to detect increased collapsibility with older age, male sex, and obesity in a large community-based cohort (Multi-Ethnic Study of Atherosclerosis, MESA), and (3) prediction of treatment efficacy (oral appliances and pharmacological pharyngeal muscle stimulation using atomoxetine-plus-oxybutynin)., Results: Pcrit was significantly correlated with Vmin (r = -0.54), event depth (r = 0.49), Vpassive (r = -0.38), Fhypopneas (r = -0.46), and apnea index (r = -0.46; all p < .01) but not others. All measures detected greater collapsibility with male sex, age, and obesity, except Fhypopneas and apnea index which were not associated with obesity. Fhypopneas and apnea index were associated with oral appliance and atomoxetine-plus-oxybutynin efficacy (both p < .05)., Conclusions: Among several candidates, event depth, Fhypopneas, and apnea index were identified as preferred pharyngeal collapsibility surrogates for use in the clinical arena., (© The Author(s) 2022. Published by Oxford University Press on behalf of Sleep Research Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Rationale: REM sleep is associated with reduced ventilation and greater obstructive sleep apnea (OSA) severity than non-REM (nREM) sleep for reasons that have not been fully elucidated. Objectives: Here, we use direct physiological measurements to determine whether the pharyngeal compromise in REM sleep OSA is most consistent with 1 ) withdrawal of neural ventilatory drive or 2 ) deficits in pharyngeal pathophysiology per se (i.e., increased collapsibility and decreased muscle responsiveness ). Methods: Sixty-three participants with OSA completed sleep studies with gold standard measurements of ventilatory "drive" (calibrated intraesophageal diaphragm EMG), ventilation (oronasal "ventilation"), and genioglossus EMG activity. Drive withdrawal was assessed by examining these measurements at nadir drive (first decile of drive within a stage). Pharyngeal physiology was assessed by examining collapsibility (lowered ventilation at eupneic drive) and responsiveness (ventilation-drive slope). Mixed-model analysis compared REM sleep with nREM sleep; sensitivity analysis examined phasic REM sleep. Measurements and Main Results: REM sleep (⩾10 min) was obtained in 25 patients. Compared with drive in nREM sleep, drive in REM sleep dipped to markedly lower nadir values (first decile, estimate [95% confidence interval], -21.8% [-31.2% to -12.4%] of eupnea; P  < 0.0001), with an accompanying reduction in ventilation (-25.8% [-31.8% to -19.8%] of eupnea; P  < 0.0001). However, there was no effect of REM sleep on collapsibility (ventilation at eupneic drive), baseline genioglossus EMG activity, or responsiveness. REM sleep was associated with increased OSA severity (+10.1 [1.8 to 19.8] events/h), but this association was not present after adjusting for nadir drive (+4.3 [-4.2 to 14.6] events/h). Drive withdrawal was exacerbated in phasic REM sleep. Conclusions: In patients with OSA, the pharyngeal compromise characteristic of REM sleep appears to be predominantly explained by ventilatory drive withdrawal rather than by preferential decrements in muscle activity or responsiveness. Preventing drive withdrawal may be the leading target for REM sleep OSA.

CO 2 adsorption and activation on a catalyst are key elementary steps for CO 2 conversion to various valuable products. In the present computational study, we screened different Cu-ZrO 2 interface structures and analyzed the influence of the interface structure on CO 2 binding strength using density functional theory calculations. Our results demonstrate that a Cu nanorod favors one position on both tetragonal and monoclinic ZrO 2 surfaces, where the bottom Cu atoms are placed close to the lattice oxygens. In agreement with previous calculations, we find that CO 2 prefers a bent bidentate configuration at the Cu-ZrO 2 interface and the molecule is clearly activated being negatively charged. Straining of the Cu nanorod influences CO 2 adsorption energy but does not change the preferred nanorod position on zirconia. Altogether, our results highlight that CO 2 adsorption and activation depend sensitively on the chemical composition and atomic structure of the interface used in the calculations. This structure sensitivity may potentially impact further catalytic steps and the overall computed reactivity profile.

Background: Nurses caring for intensive care patients diagnosed with an aneurysmal subarachnoid hemorrhage (aSAH) conduct frequent neurological assessments and vital signs over an extended period during which patients are at risk of vasospasm. The frequency of assessments can negatively impact sleep, resulting in altered thought processes and mood, including delirium. There are 2 types of sleep during the night: non-rapid eye movement (non-REM) sleep and REM sleep (also called stage R). Non-REM sleep is subdivided into 3 stages: stage N1, stage N2, and stage N3. These 4 stages of sleep are referred to as sleep architecture., Objective: The aim of this study was to explore patterns of sleep in patients with aSAH over time during hospitalization., Methods: Sleep data of stages and cycles were collected with use of a Fitbit activity tracker in this pilot, exploratory research study. Demographic data included age and gender. Six English-speaking patients, diagnosed with an aneurysmal SAH, confirmed by diagnostic angiogram, were followed in neuro-intensive care unit (ICU), neuro-step-down, neuroscience unit, and inpatient rehabilitation., Results: There were a total of 226 sleep events. A sleep event encompassed a recorded start and end time on a single date. Each event included several sleep cycles. Each sleep cycle consisted of wakefulness, light sleep, deep sleep, and REM sleep. In 79 sleep events, light and deep sleep did add up to more than 4 hours; only 38 sleep events indicated more than 90 minutes of REM/night; 61 events showed the cycle of light-deep-light-REM cycles; 80 events showed 3 to 5 REM periods/night; and only 46 events demonstrated that the early-morning REM cycle was the longest. The average number of REM cycles increased from ICU (n = 4.6) to rehabilitation (n = 6.5). The percentage of days with sleep cycles also increased from ICU to rehabilitation (42 to 64)., Discussion: "Normal" sleep patterns are disrupted in aSAH patients throughout their hospitalization. Data in this study revealed that the patients do sleep; however, it is rarely organized. Patients were not always able to progress through the expected sleep cycle of light to deep to light to REM. Hospitalized aSAH patients do engage in REM sleep, but its pattern is abnormal. Staff should strategize on minimizing interruptions, clustering care, and minimizing sounds. Nurses should advocate for the frequency of assessments and vital signs based on hospital/unit policy and individual patient needs., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Demonstrated herein are the preparation and crystallographic characterization of the family of fcc silver nanoclusters from Nichol's cube to Rubik's cube and beyond via ligand-control (thiolates and phosphines in this case). The basic building block is our previously reported fcc cluster [Ag 14 (SPhF 2 ) 12 (PPh 3 ) 8 ] (1). The metal frameworks of [Ag 38 (SPhF 2 ) 26 (PR' 3 ) 8 ] (2 2 ) and [Ag 63 (SPhF 2 ) 36 (PR' 3 ) 8 ] + (2 3 ), where HSPhF 2 = 3,4-difluorothiophenol and R' = alkyl/aryl, are composed of 2 × 2 = 4 and 2 × 2 × 2 = 8 metal cubes of 1, respectively. All serial clusters share similar surface structural features. The thiolate ligands cap the six faces and the 12 edges of the cube (or half cube) while the phosphine ligands are terminally bonded to its eight corners. On the basis of the analysis of the crystal structures of 1, 2 2 , and 2 3 , we predict the next "cube of cubes" to be Ag 172 (SR) 72 (PR' 3 ) 8 ] (3 3 ), in the evolution of growth of this cluster sequence.

An intermetallic nanocluster containing 44 metal atoms, Au24Ag20(2-SPy)4(PhC≡C)20Cl2, was successfully synthesized and structurally characterized by single-crystal analysis and density funtional theory computations. The 44 metal atoms in the cluster are arranged as a concentric three-shell Au12@Ag20@Au12 Keplerate structure having a high symmetry. For the first time, the co-presence of three different types of anionic ligands (i.e., phenylalkynyl, 2-pyridylthiolate, and chloride) was revealed on the surface of metal nanoclusters. Similar to thiolates, alkynyls bind linearly to surface Au atoms using their σ-bonds, leading to the formation of two types of surface staple units (PhC≡C-Au-L, L = PhC≡C(-) or 2-pyridylthiolate) on the cluster. The co-presence of three different surface ligands allows the site-specific surface and functional modification of the cluster. The lability of PhC≡C(-) ligands on the cluster was demonstrated, making it possible to keep the metal core intact while removing partial surface capping. Moreover, it was found that ligand exchange on the cluster occurs easily to offer various derivatives with the same metal core but different surface functionality and thus different solubility.

Aim: Research exploring alcohol consumption patterns and behaviour change among older adults is relatively scarce, often necessitating reliance on international evidence. To understand the degree to which findings may be generalizable across countries, this review compares recent epidemiological evidence from developed countries on the prevalence of abstention and potentially problematic alcohol consumption in older adults., Methods: Medline, EMBASE, Web of Science and PsychInfo were searched for English language publications, identifying 21 peer-reviewed publications and six reports, including data from 17 national surveys and 10 general practice and community samples published since 2000., Results: Of the developed countries for which data are available on adults aged over 50 years, rates of past 12-month abstention and former drinking are lowest in England and Finland, and highest in Korea and the USA. The prevalence of binge drinking varies widely between studies, whilst rates of alcohol dependence are broadly similar., Conclusions: Older adults in developed countries report different rates of abstention and alcohol consumption. This places obvious limitations on the extrapolation of results from specific research findings and policy strategies to other countries., (© The Author 2014. Medical Council on Alcohol and Oxford University Press. All rights reserved.)

The electronic structure of two recently crystallographically solved, thiolate-phosphine protected silver clusters Ag14 and Ag16 are analyzed via density functional theory (DFT) and their optical excitations are analyzed from time-dependent DFT perturbation theory. Both clusters can be characterized as having the S(2) free-electron configuration in the metal core, which is the first time such a configuration is confirmed for structurally known ligand-protected noble metal clusters. However, their different core shapes and ligand layer induce significantly different optical spectra. Performance of gradient-corrected DFT functionals is discussed and it is shown that the asymptotically correct Leeuwen-Baerends LB94 functional reproduces the optical spectrum of Ag14 in a good agreement with experiment. Choice of the functional becomes important for clusters where the optical transitions are dominated by the electron-rich ligand layer.

Selenolate protected, stable and atomically precise, hollow silver cluster was synthesized using solid state as well as solution state routes. The optical absorption spectrum shows multiple and sharp features similar to the thiolated Ag44 cluster, Ag44(SR)30 whose experimental structure was reported recently. High-resolution electrospray ionization mass spectrometry (HRESI MS) shows well-defined molecular ion features with two, three, and four ions with isotopic resolution, due to Ag44(SePh)30. Additional characterization with diverse tools confirmed the composition. The closed-shell 18 electron superatom electronic structure, analogous to Ag44(SR)30 stabilizes the dodecahedral cage with a large HOMO-LUMO gap of 0.71 eV. The time-dependent density functional theory (TDDFT) prediction of the optical absorption spectrum, assuming the Ag44(SR)30 structure, matches the experimental data, confirming the structure.

We report a simple synthesis of silver:glutathione (Ag:SG) clusters using a cyclic reduction under oxidative conditions. Two syntheses are described which lead to solutions containing well-defined Ag31(SG)19 and Ag15(SG)11 clusters that have been characterized by mass spectrometry. The optical properties of silver:glutathione (Ag:SG) cluster solutions have been investigated experimentally. In particular, the solution containing Ag15(SG)11 clusters shows a bright and photostable emission. For Ag31(SG)19 and Ag15(SG)11 clusters, the comparison of experimental findings with DFT and TDDFT calculations allowed us to reveal the structural and electronic properties of such low nuclearity liganded silver clusters.

Gas phase reactivity observed in an ion trap was used to produce silver clusters protected with thioglycolic acid. Fragmentation pathways as well as optical properties were explored experimentally and theoretically. Sequential losses of SCH2 and CO2 in the ion trap lead to redox reactions with charge transfers between the metal part and the carboxylate and thiolate groups. This allows us to control the number of electrons in the metallic subunit and thus optical properties of the complexes. The presented formation process can be used as a prototype for tuning optical and chemical properties of ligated metal clusters by varying the number of confined electrons within the metallic subunit.

Noble metal nanoparticles stabilized by organic ligands are important for applications in assembly, site-specific bioconjugate labelling and sensing, drug delivery and medical therapy, molecular recognition and molecular electronics, and catalysis. Here we report crystal structures and theoretical analysis of three Ag44(SR)30 and three Au12Ag32(SR)30 intermetallic nanoclusters stabilized with fluorinated arylthiols (SR=SPhF, SPhF2 or SPhCF3). The nanocluster forms a Keplerate solid of concentric icosahedral and dodecahedral atom shells, protected by six Ag2(SR)5 units. Positive counterions in the crystal indicate a high negative charge of 4(-) per nanoparticle, and density functional theory calculations explain the stability as an 18-electron superatom shell closure in the metal core. Highly featured optical absorption spectra in the ultraviolet-visible region are analysed using time-dependent density functional perturbation theory. This work forms a basis for further understanding, engineering and controlling of stability as well as electronic and optical properties of these novel nanomaterials.

We focus on the functional role of small silver clusters in model hybrid systems involving peptides in the context of a new generation of nanostructured materials for biosensing. The optical properties of hybrids in the gas phase and at support will be addressed with the aim to bridge fundamental and application aspects. We show that extension and enhancement of absorption of peptides can be achieved by small silver clusters due to the interaction of intense intracluster excitations with the π-π* excitations of chromophoric aminoacids. Moreover, we demonstrate that the binding of a peptide to a supported silver cluster can be detected by the optical fingerprint. This illustrates that supported silver clusters can serve as building blocks for biosensing materials. Moreover, the clusters can be used simultaneously to immobilize biomolecules and to increase the sensitivity of detection, thus replacing the standard use of organic dyes and providing label-free detection. Complementary to that, we show that protected silver clusters containing a cluster core and a shell liganded by thiolates exhibit absorption properties with intense transitions in the visible regime which are also suitable for biosensing applications.

Introduction and Aims: Unhealthy lifestyle behaviours can cluster to produce more detrimental overall health consequences than expected with a simple additive effect. This study aims to expand current knowledge of the nature and strength of the relationship between two such health behaviours, alcohol and diet, through analysis of household expenditure on food and drink from a nationally representative UK sample., Design and Methods: Data from the Expenditure and Food Survey for 2005-2006 was used to analyse expenditure on alcohol and diet for 3146 UK households. The classification of a food as healthy or unhealthy was determined using dietary advice provided by the Food Standards Agency. Alcohol expenditure was disaggregated into spending in pubs, bars, clubs and restaurants (on-trade expenditure) and spending in off-licenses and supermarkets (off-trade expenditure). Analyses were stratified according to household disposable income quintile and household beverage preference., Results: As household expenditure on alcohol increases, spending on both healthy and unhealthy food decreases. Higher income households spend proportionately more on on-trade alcohol and healthy food than lower income households, and less on unhealthy food. Off-trade alcohol expenditure does not differ significantly according to household income. Households that prefer to purchase wine have healthier expenditure patterns than those that prefer to buy beer or spirits, even after controlling for income., Discussion and Conclusions: Low-income households and those that purchase more beer or spirits than wine could be targeted for health promotion interventions to reduce their risk of negative health outcomes from the clustering of alcohol consumption and unhealthy diet., (© 2011 Australasian Professional Society on Alcohol and other Drugs.)

An increasing number of care homes in the UK now provide placements for students undertaking pre-registration nursing programmes, enabling them to develop knowledge and skills in the continuing care of older people. In this article the authors describe an initiative to support nursing staff working in care homes and prepare them for their role in student education. The impetus for the initiative came from student feedback and evaluation of their placement experiences. These suggested that staff in some care homes were not fully prepared to help meet students' learning needs. Students' concerns about the quality of care in some homes also made clear the need for a forum in which the evidence base for practice in continuing care settings could be discussed and debated. The initiative combined the development of new roles with regular opportunities to share information and feedback.

A total of 701 adults living in the USA or Western Europe who had symptoms of allergic respiratory disease were skin prick tested with extracts prepared from eight basidiomycetes species and four Fungi Imperfecti species. In these subjects, the presence of asthma, rhinitis, or both was determined by questionnaire. Overall, 178/701 (25.4%) of the participants reacted to at least one basidiomycete extract. There was no difference in the prevalence of reactivity detected in the USA and Europe (P < 0.005); however, the prevalence of reactors in individual centers from both areas varied significantly. Psilocybe cubensis was the most potent allergen source in both the USA (12.3% reacted) and Europe (16.0%). Pleurotus ostreatus was second overall (10.6%) and in the USA (10.7%), and third in Europe (10.3%). Pisolithus tinctorius and Coprinus quadrifidus produced the least potent allergens, with only 5.4% of the population reacting. There was a significant relationship (P < 0.005) between basidiospore reactivity and the presence of atopy, asthma, and asthma and rhinitis. Basidiospore reactivity was not associated with the presence of rhinitis alone (P = 0.312). These results suggest that basidiomycetes are important sources of aeroallergens in geographically disparate regions and may be particularly important in patients with asthma.