Preliminary evidence of psychological improvements and increased maternal-fetal attachment associated with a mindfulness sleep programme: secondary analysis of uncontrolled data in 11 pregnant women with insomnia disorder.

Treating insomnia during pregnancy improves sleep and depressed mood. However, given well-established links between poor sleep and a broad spectrum of adverse maternal outcomes, the benefits of insomnia care may reach beyond sleep and depression. The present study evaluated the preliminary efficacy of 'Perinatal Understanding of Mindful Awareness for Sleep' (PUMAS)-a mindfulness sleep programme tailored to pregnancy that combines behavioural sleep strategies and meditation-for enhancing everyday mindfulness and maternal-fetal attachment, as well as for alleviating anxiety, repetitive thinking, and sleep-related daytime impairment. We conducted a secondary analysis of a single-arm proof-of-concept trial of 11 pregnant women with fifth edition of the Diagnostic and Statistical Manual of Mental Disorders diagnosed insomnia disorder who completed PUMAS (six sessions), which was delivered in an individual format via telemedicine video. Pre- and post-treatment outcomes included the Cognitive and Affective Mindfulness Scale-Revised (CAMS-R), Maternal-Fetal Attachment Scale (MFAS), Generalised Anxiety Disorder seven-item survey (GAD-7), Perseverative Thinking Questionnaire (PTQ), Daytime Insomnia Symptoms Response Scale (DISRS), and the Patient-Reported Outcomes Measurement Information System Sleep-Related Impairment Scale (PROMIS-SRI). Symptom changes were evaluated with paired-samples t tests. Results showed PUMAS patients reported large increases in CAMS-R (Cohen's dz = 1.81) and medium-large increases in MFAS scores (Cohen's dz = 0.73). Moreover, PUMAS patients reported large reductions in scores on the GAD-7 (Cohen's dz = 1.09), PTQ (Cohen's dz = 1.26), DISRS (Cohen's dz = 1.38), and PROMIS-SRI (Cohen's dz = 1.53). Preliminary evidence suggests that a mindfulness-based perinatal sleep programme may benefit several domains of maternal wellbeing beyond sleep and depression. PUMAS substantially enhanced patient ratings of everyday mindfulness and maternal-fetal attachment, while reporting alleviations in anxiety, perseverative thinking, insomnia-focused rumination, and sleep-related daytime impairment.

Tilting refractive x-ray lenses for fine-tuning of their focal length.

In this work, we measure and model tilted x-ray refractive lenses to investigate their effects on an x-ray beam. The modelling is benchmarked against at-wavelength metrology obtained with x-ray speckle vector tracking experiments (XSVT) at the BM05 beamline at the ESRF-EBS light source, showing very good agreement. This validation permits us to explore possible applications of tilted x-ray lenses in optical design. We conclude that while tilting 2D lenses does not seem interesting from the point of view of aberration-free focusing, tilting 1D lenses around their focusing direction can be used for smoothly fine-tuning their focal length. We demonstrate experimentally this continuous change in the apparent lens radius of curvature R: a reduction up to a factor of two and beyond is achieved and possible applications in beamline optical design are proposed.

Pre-pandemic sleep reactivity prospectively predicts distress during the COVID-19 pandemic: The protective effect of insomnia treatment.

The COVID-19 pandemic is a rare stressor that has precipitated an accompanying mental health crisis. Prospective studies traversing the pandemic's onset can elucidate how pre-existing disease vulnerabilities augured risk for later stress-related morbidity. We examined how pre-pandemic sleep reactivity predicted maladaptive stress reactions and depressive symptoms in response to, and during, the pandemic. This study is a secondary analysis of a randomised controlled trial from 2016 to 2017 comparing digital cognitive behavioural therapy for insomnia (dCBT-I) against sleep education (N = 208). Thus, we also assessed whether dCBT-I moderated the association between pre-pandemic sleep reactivity and pandemic-related distress. Pre-pandemic sleep reactivity was measured at baseline using the Ford Insomnia Response to Stress Test. In April 2020, participants were recontacted to report pandemic-related distress (stress reactions and depression). Controlling for the treatment condition and the degree of COVID-19 impact, higher pre-pandemic sleep reactivity predicted more stress reactions (ß = 0.13, ± 0.07 SE, p = 0.045) and depression (ß = 0.22, ± 0.07 SE, p = 0.001) during the pandemic. Further, the odds of reporting clinically significant stress reactions and depression during the pandemic were over twice as high in those with high pre-pandemic sleep reactivity. Notably, receiving dCBT-I in 2016-2017 mitigated the relationship between pre-pandemic sleep reactivity and later stress reactions (but not depression). Pre-pandemic sleep reactivity predicted psychological distress 3-4 years later during the COVID-19 pandemic, and dCBT-I attenuated its association with stress reactions, specifically. Sleep reactivity may inform prevention and treatment efforts by identifying individuals at risk of impairment following stressful events.

Polished diamond X-ray lenses.

High-quality bi-concave 2D focusing diamond X-ray lenses of apex-radius R = 100 µm produced via laser-ablation and improved via mechanical polishing are presented here. Both for polished and unpolished individual lenses and for stacks of ten lenses, the remaining figure errors determined using X-ray speckle tracking are shown and these results are compared with those of commercial R = 50 µm beryllium lenses that have similar focusing strength and physical aperture. For two stacks of ten diamond lenses (polished and unpolished) and a stack of eleven beryllium lenses, this paper presents measured 2D beam profiles out of focus and wire scans to obtain the beam size in the focal plane. These results are complemented with small-angle X-ray scattering (SAXS) measurements of a polished and an unpolished diamond lens. Again, this is compared with the SAXS of a beryllium lens. The polished X-ray lenses show similar figure errors to commercially available beryllium lenses. While the beam size in the focal plane is comparable to that of the beryllium lenses, the SAXS signal of the polished diamond lenses is considerably lower.

ID23-2: an automated and high-performance microfocus beamline for macromolecular crystallography at the ESRF. Corrigendum.

A revised version of Table 2 of Nanao et al. [J. Synchrotron Rad. (2022). 29, 581-590] is provided.

ID23-2: an automated and high-performance microfocus beamline for macromolecular crystallography at the ESRF.

ID23-2 is a fixed-energy (14.2 keV) microfocus beamline at the European Synchrotron Radiation Facility (ESRF) dedicated to macromolecular crystallography. The optics and sample environment have recently been redesigned and rebuilt to take full advantage of the upgrade of the ESRF to the fourth generation Extremely Brilliant Source (ESRF-EBS). The upgraded beamline now makes use of two sets of compound refractive lenses and multilayer mirrors to obtain a highly intense (>1013 photons s-1) focused microbeam (minimum size 1.5 µm × 3 µm full width at half-maximum). The sample environment now includes a FLEX-HCD sample changer/storage system, as well as a state-of-the-art MD3Up high-precision multi-axis diffractometer. Automatic data reduction and analysis are also provided for more advanced protocols such as synchrotron serial crystallographic experiments.

Examining Patient Feedback and the Role of Cognitive Arousal in Treatment Non-response to Digital Cognitive-behavioral Therapy for Insomnia during Pregnancy.

OBJECTIVE: Insomnia affects over half of pregnant and postpartum women. Early evidence indicates that cognitive-behavioral therapy for insomnia (CBTI) improves maternal sleep and mood. However, standard CBTI may be less efficacious in perinatal women than the broader insomnia population. This study sought to identify patient characteristics in a perinatal sample associated with poor response to CBTI, and characterize patient feedback to identify areas of insomnia therapy to tailor for the perinatal experience. PARTICIPANTS: Secondary analysis of 46 pregnant women with insomnia symptoms who were treated with digital CBTI in a randomized controlled trial. METHODS: We assessed insomnia, cognitive arousal, and depression before and after prenatal treatment, then 6 weeks postpartum. Patients provided feedback on digital CBTI. RESULTS: Residual cognitive arousal after treatment was the most robust factor associated with treatment non-response. Critically, CBTI responders and non-responders differed on no other sociodemographic or pretreatment metrics. After childbirth, short sleep (<6 hrs/night) was associated with maternal reports of poor infant sleep quality. Patient feedback indicated that most patients preferred online treatment to in-person treatment. Although women described digital CBTI as convenient and helpful, many patients indicated that insomnia therapy would be improved if it addressed sleep challenges unique to pregnancy and postpartum. Patients requested education on maternal and infant sleep, flexibility in behavioral sleep strategies, and guidance to manage infant sleep. CONCLUSIONS: Modifying insomnia therapy to better alleviate refractory cognitive arousal and address the changing needs of women as they progress through pregnancy and early parenting may increase efficacy for perinatal insomnia.Name: Insomnia and Rumination in Late Pregnancy and the Risk for Postpartum DepressionURL: clinicaltrials.govRegistration: NCT03596879.

Insomnia Complaints and Perceived Immune Fitness in Young Adults with and without Self-Reported Impaired Wound Healing.

Background and Objectives: Adequate sleep and an effective immune system are both essential to maintain a good health status. The current study aimed to determine the nature of insomnia complaints and perceived immune fitness among Dutch young adults with and without self-reported impaired wound healing. Materials and Methods: A total of (n = 2033) Dutch students (83.8% women) completed an online survey. Perceived immune fitness was assessed with a single-item scale and insomnia complaints with the SLEEP-50 insomnia subscale. The sample comprised a control group without self-reported impaired wound healing (n = 1622), a wound infection (WI) group (n = 69), a slow healing wounds (SHW) group (n = 250), and a COMBI group that experienced both WI and SHW (n = 92). Results: Comparisons with the control group revealed that individuals of the SHW and COMBI groups reported significantly poorer perceived immune functioning, increased insomnia complaints and daytime fatigue, and poorer sleep quality. Conclusions: Individuals with self-reported impaired wound healing have a poorer perceived immune functioning, increased insomnia complaints, daytime fatigue, and poorer sleep quality.

Simultaneous determination of six antibiotics in human serum by high-performance liquid chromatography with UV detection.

Antibiotics are widely used in intensive care patients to treat severe infections. To avoid bacterial resistance or toxic side effects, the determination of serum concentration of ABs is advisable. Therefore, in this study, we developed and validated a simple and fast high-performance liquid chromatography method with UV detection for the simultaneous determination of four ß-lactam ABs (meropenem, imipenem, ceftazidime, and piperacillin) and two coadministered substances (cilastatin and tazobactam) in human serum. Sample preparation required a simple protein precipitation by methanol. The separation of the ABs occurred within a timeframe of 17 min. For this purpose, we used a Kinetex F5 column with a linear gradient of acetonitrile and phosphate buffer (pH 6.9). The UV detector recorded two separate chromatograms at 220 and 295 nm simultaneously. Validation has demonstrated that the method is linear, accurate, and precise within the clinically relevant range for each substance.

Modelling phase imperfections in compound refractive lenses.

A framework based on physical optics for simulating the effect of imperfect compound refractive lenses (CRLs) upon an X-ray beam is described, taking into account measured phase errors obtained from at-wavelength metrology. A CRL stack is modelled, with increasing complexity, as a single thin phase element, then as a more realistic compound element including absorption and thickness effects, and finally adding realistic optical imperfections to the CRL. Coherent and partially coherent simulations using Synchrotron Radiation Workshop (SRW) are used to evaluate the different models, the effects of the phase errors and to check the validity of the design equations and suitability of the figures of merit.

X-ray optics and beam characterization using random modulation: theory.

X-ray near-field speckle-based phase-sensing approaches provide efficient means of characterizing optical elements. Presented here is a theoretical review of several of these speckle methods within the framework of optical characterization, and a generalization of the concept is provided. As is also demonstrated experimentally in a parallel paper [Berujon, Cojocaru, Piault, Celestre, Roth, Barrett & Ziegler (2020), J. Synchrotron Rad. 27, (this issue)], the methods theoretically developed here can be applied to different beams and optics and within a variety of situations where at-wavelength metrology is desired. By understanding the differences between the various processing methods, it is possible to find and implement the most suitable approach for each metrology scenario.

X-ray optics and beam characterization using random modulation: experiments.

A parallel paper [Berujon, Cojocaru, Piault, Celestre, Roth, Barrett & Ziegler (2020), J. Synchrotron Rad. 27, 284-292] reviewed theoretically some of the available processing schemes for X-ray wavefront sensing based on random modulation. Shown here are experimental applications of the technique for characterizing both refractive and reflective optical components. These fast and accurate X-ray at-wavelength metrology methods can assist the manufacture of X-ray optics that transport X-ray beams with a minimum amount of wavefront distortion. It is also recalled how such methods can facilitate online optimization of active optics.

Diffraction properties of a strongly bent diamond crystal used as a dispersive spectrometer for XFEL pulses.

Self-amplified spontaneous emission (SASE) enables X-ray free-electron lasers (XFELs) to generate hard X-ray pulses of sub-100 fs duration. However, due to the stochastic nature of SASE, the energy spectrum fluctuates from pulse to pulse. Many experiments that employ XFEL radiation require the resolution of the spectrum of each pulse. The work presented here investigates the capacity of a thin strongly bent diamond crystal to resolve the energy spectra of hard X-ray SASE pulses by studying its diffraction properties. Rocking curves of the symmetric C*(440) reflection have been measured for different bending radii. The experimental data match the theoretical modelling based on the Takagi-Taupin equations of dynamical diffraction. A uniform strain gradient has proven to be a valid model of strain deformations in the crystal.

Efficacy of digital CBT for insomnia to reduce depression across demographic groups: a randomized trial.

BACKGROUND: Insomnia and depression are highly comorbid and mutually exacerbate clinical trajectories and outcomes. Cognitive behavioral therapy for insomnia (CBT-I) effectively reduces both insomnia and depression severity, and can be delivered digitally. This could substantially increase the accessibility to CBT-I, which could reduce the health disparities related to insomnia; however, the efficacy of digital CBT-I (dCBT-I) across a range of demographic groups has not yet been adequately examined. This randomized placebo-controlled trial examined the efficacy of dCBT-I in reducing both insomnia and depression across a wide range of demographic groups. METHODS: Of 1358 individuals with insomnia randomized, a final sample of 358 were retained in the dCBT-I condition and 300 in the online sleep education condition. Severity of insomnia and depression was examined as a dependent variable. Race, socioeconomic status (SES; household income and education), gender, and age were also tested as independent moderators of treatment effects. RESULTS: The dCBT-I condition yielded greater reductions in both insomnia and depression severity than sleep education, with significantly higher rates of remission following treatment. Demographic variables (i.e. income, race, sex, age, education) were not significant moderators of the treatment effects, suggesting that dCBT-I is comparably efficacious across a wide range of demographic groups. Furthermore, while differences in attrition were found based on SES, attrition did not differ between white and black participants. CONCLUSIONS: Results provide evidence that the wide dissemination of dCBT-I may effectively target both insomnia and comorbid depression across a wide spectrum of the population.

Zolpidem and Gender: Are Women Really At Risk?

BACKGROUND: In 2013 the Food and Drug Administration (FDA) claimed the existence of new data showing women to be at risk for excessive daytime sedation and impaired driving proficiency following bedtime doses of zolpidem. The putative explanation was the reduced metabolic clearance of zolpidem and higher morning blood concentrations in women compared to men. The FDA acted to reduce the recommended dosage for women down to 50% of the dose for men. No other regulatory agency worldwide has taken similar action. METHODS: Gender effects on zolpidem pharmacokinetics, pharmacodynamics, adverse effects, clinical efficacy, and driving performance were evaluated through a further analysis of data from a previous study, together with a literature review. RESULTS: Women had on average 35% lower apparent clearance of zolpidem than men (236 vs 364 mL/min, P < 0.001). This difference was not explained by body weight. In some laboratory studies, women had greater functional impairment than men taking the same dose, but in all studies active drug was not distinguishable from placebo at 8 hours after oral dosage. On-the-road driving studies likewise showed no evidence of driving impairment in men or women at 8 hours after 10 mg of oral immediate-release zolpidem. No clinical trial demonstrated a gender-related difference in clinical efficacy or adverse reactions, and there was no evidence of a particular risk to women. CONCLUSIONS: Dosage reduction in women is not supported by available scientific evidence, and may in fact lead to underdosing and the consequent hazard of inadequately treated insomnia.

Orexin receptor antagonists for the treatment of insomnia and potential treatment of other neuropsychiatric indications.

In this review, we outline the role of orexin receptor antagonists in disorders of sleep/wake and other potential neuropsychiatric conditions, with a focus on suvorexant, which is currently the only approved agent in this class. The efficacy of suvorexant was established in Phase 2-3 trials with treatment durations ranging from 1 to 12 months in patients with insomnia. Suvorexant is effective at improving sleep assessed by patient self-report and by polysomnography, with generally little effect on underlying sleep architecture. The main side-effect is next day somnolence. With the growing realization of the important connections between sleep and other disorders, studies are ongoing to explore this novel mechanism in other disorders such as Alzheimer's disease and depression.

Relation between ambulatory actigraphy and laboratory polysomnography in insomnia practice and research.

Actigraphy is increasingly used in practice and research studies because of its relative low cost and decreased subject burden. How multiple nights of at-home actigraphy compare to one independent night of in-laboratory polysomnography (PSG) has not been examined in people with insomnia. Using event markers (MARK) to set time in bed (TIB) compared to automatic program analysis (AUTO) has not been systematically evaluated. Subjects (n = 30) meeting DSM-5 criteria for insomnia and in-laboratory PSG sleep efficiency (SE) of <85% were studied. Subjects were free of psychiatric, sleep or circadian disorders, other chronic conditions and medications that effect sleep. Subjects had an in-laboratory PSG, then were sent home for 7 nights with Philips Actiwatch Spectrum Plus. Data were analysed using Philips Actiware version 6. Using the mean of seven nights, TIB, total sleep time (TST), SE, sleep-onset latency (SOL) and wake after sleep onset (WASO) were examined. Compared to PSG, AUTO showed longer TIB and TST and less WASO. MARK only differed from PSG with decreased WASO. Differences between the PSG night and the following night at home were found, with better sleep on the first night home. Actigraphy in people with insomnia over seven nights is a valid indicator of sleep compared to an independent in-laboratory PSG. Event markers increased the validity of actigraphy, showing no difference in TIB, TST, SE and SOL. AUTO was representative of SE and SOL. Increased SE and TST without increased TIB suggests possible compensatory sleep the first at night home after in-laboratory PSG.

Efficacy of SM-1 in a transient insomnia model.

OBJECTIVES: The objectives of this study were primarily to assess the efficacy and safety of SM-1 in a circadian challenge model of transient insomnia and secondarily, to assess the contribution of diphenhydramine to the combination. METHODS: Randomized, double-blind, placebo-controlled three-way cross-over study with a 5-hr phase advance. Subjects were 39 healthy adults reporting a history of transient insomnia. All treatments (SM-1, SM-1 without diphenhydramine, or placebo) were administered to all subjects in a randomly assigned sequence, with at least 1 week between treatments. The primary endpoint was total sleep time (TST) determined by polysomnography. Secondary endpoints included wakefulness after sleep onset (WASO), latency to persistent sleep, number of awakenings (NAW), subjective TST (sTST) and sleep latency (sSL), TST, and NAW by quarters of the night and sleep quality. Safety endpoints included adverse events, Karolinska Sleepiness Scale digit symbol substitution test, and subject-reported alertness level. RESULTS: SM-1 provided an increase of 126.7 min in TST over placebo (p < .001). WASO, sTST, sleep quality, and sSL also showed significant improvement. Diphenhydramine demonstrated a significant (p = .014) contribution of 43.7 min to TST. SM-1 was well-tolerated with type and frequency of adverse events comparable with placebo, and no residual sleepiness upon awakening after 8 hr. CONCLUSIONS: SM-1 provided a robust and statistically significant increase in TST compared with placebo in a circadian model of transient insomnia, without evidence of next-day impairment. Diphenhydramine contributed to the effect.

Pharmacodynamic and pharmacokinetic profile of SM-1, a triple-drug combination to increase total sleep time.

OBJECTIVE: The primary objective was to characterize the pharmacokinetics and pharmacodynamics of SM-1 after administration of a single oral dose to healthy volunteers in a placebo-controlled double-blind trial of daytime sedation. Secondary objectives were to determine the onset, duration, and offset of the sedative effects using subjective and objective measures of sedation. Safety and tolerability of SM-1 were also investigated. METHODS: Males and females 18-45 years of age received SM-1, a combination drug product comprised of diphenhydramine, zolpidem (delayed release), and lorazepam (delayed release). The pharmacokinetic profile of each drug was determined from blood samples. Sedative effects were assessed by visual analog scale, digit symbol substitution test, memory test, and quantitative electroencephalography. RESULTS: Similar number and severity of adverse events were observed following administration of SM-1 and placebo. Onset of sedation, as determined by subjective, performance, and electroencephalography measures, occurred 0.5-1 hr postdose, lasting about 7-7.5 hr. Plasma concentration curves for the two delayed-release components were altered compared with published data for unmodified drugs. Exposure values obtained with the combination product were in good agreement with published values of the drugs given individually. CONCLUSIONS: SM-1 was well tolerated and has pharmacologic activity starting within an hour of ingestion, lasting approximately 7-8 hr. Sedative activity was seen with subjective, psychomotor, and electroencephalography assays.

Pulse-resolved intensity measurements at a hard X-ray FEL using semi-transparent diamond detectors.

Solid-state ionization chambers are presented based on thin diamond crystals that allow pulse-resolved intensity measurements at a hard X-ray free-electron laser (FEL), up to the 4.5 MHz repetition rate that will become available at the European XFEL. Due to the small X-ray absorption of diamond the thin detectors are semi-transparent which eases their use as non-invasive monitoring devices in the beam. FELs are characterized by strong pulse-to-pulse intensity fluctuations due to the self-amplified spontaneous emission (SASE) process and in many experiments it is mandatory to monitor the intensity of each individual pulse. Two diamond detectors with different electrode materials, beryllium and graphite, were tested as intensity monitors at the XCS endstation of the Linac Coherent Light Source (LCLS) using the pink SASE beam at 9 keV. The performance is compared with LCLS standard monitors that detect X-rays backscattered from thin SiN foils placed in the beam. The graphite detector can also be used as a beam position monitor although with rather coarse resolution.