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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. 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. 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. 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.

Disturbed sleep is one of the most common complaints following traumatic brain injury (TBI) and worsens morbidity and long-term sequelae. Further, sleep and TBI share neurophysiologic underpinnings with direct relevance to recovery from TBI. As such, disturbed sleep and clinical sleep disorders represent modifiable treatment targets to improve outcomes in TBI. This paper presents key findings from a national working group on sleep and TBI, with a specific focus on the testing and development of sleep-related therapeutic interventions for mild TBI (mTBI). First, mTBI and sleep physiology are briefly reviewed. Next, essential empirical and clinical questions and knowledge gaps are addressed. Finally, actionable recommendations are offered to guide active and efficient collaboration between academic, industry, and governmental stakeholders.

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. The performance of state‐of‐the‐art bi‐concave 2D focusing diamond X‐ray lenses produced via laser‐ablation and improved via a polishing process is reported.

One man's genome Next-generation sequencing technologies are revolutionizing human genomics, promising to yield draft genomes cheaply and quickly. One such technology has now been used to analyse much of the genetic code of a single individual — who happens to be James D. Watson. The procedure, which involves no cloning of the genomic DNA, makes use of the latest 454 parallel sequencing instrument. The sequence cost less than US$1 million (and a mere two months) to produce, compared to the approximately US$100 million reported for sequencing Craig Venter's genome by traditional methods. Still a major undertaking, but another step towards the goal of 'personalized genomes' and 'personalized medicine'. The DNA sequence of a diploid genome of a single individual, James D. Watson, sequenced to 7.4-fold redundancy in two months using massively parallel sequencing in picolitre-size reaction vessels is reported. The association of genetic variation with disease and drug response, and improvements in nucleic acid technologies, have given great optimism for the impact of ‘genomic medicine’. However, the formidable size of the diploid human genome 1 , approximately 6 gigabases, has prevented the routine application of sequencing methods to deciphering complete individual human genomes. To realize the full potential of genomics for human health, this limitation must be overcome. Here we report the DNA sequence of a diploid genome of a single individual, James D. Watson, sequenced to 7.4-fold redundancy in two months using massively parallel sequencing in picolitre-size reaction vessels. This sequence was completed in two months at approximately one-hundredth of the cost of traditional capillary electrophoresis methods. Comparison of the sequence to the reference genome led to the identification of 3.3 million single nucleotide polymorphisms, of which 10,654 cause amino-acid substitution within the coding sequence. In addition, we accurately identified small-scale (2–40,000 base pair (bp)) insertion and deletion polymorphism as well as copy number variation resulting in the large-scale gain and loss of chromosomal segments ranging from 26,000 to 1.5 million base pairs. Overall, these results agree well with recent results of sequencing of a single individual 2 by traditional methods. However, in addition to being faster and significantly less expensive, this sequencing technology avoids the arbitrary loss of genomic sequences inherent in random shotgun sequencing by bacterial cloning because it amplifies DNA in a cell-free system. As a result, we further demonstrate the acquisition of novel human sequence, including novel genes not previously identified by traditional genomic sequencing. This is the first genome sequenced by next-generation technologies. Therefore it is a pilot for the future challenges of ‘personalized genome sequencing’.

This review discusses the methodology of the standardized on-the-road driving test and standard operation procedures to conduct the test and analyze the data. The on-the-road driving test has proven to be a sensitive and reliable method to examine driving ability after administration of central nervous system (CNS) drugs. The test is performed on a public highway in normal traffic. Subjects are instructed to drive with a steady lateral position and constant speed. Its primary parameter, the standard deviation of lateral position (SDLP), ie, an index of 'weaving', is a stable measure of driving performance with high test-retest reliability. SDLP differences from placebo are dose-dependent, and do not depend on the subject's baseline driving skills (placebo SDLP). It is important that standard operation procedures are applied to conduct the test and analyze the data in order to allow comparisons between studies from different sites.

Suvorexant (MK-4305) is an orexin receptor antagonist shown to be efficacious for insomnia over 3 months. We aimed to assess its clinical profile during and after 1 year of treatment. We did a randomised, placebo-controlled, parallel-group trial at 106 investigational centres in the Americas, Australia, Europe, and South Africa from December, 2009, to August, 2011. Patients aged 18 years or older with primary insomnia by DSM-IV-TR criteria were assigned using a computer-generated randomised allocation schedule to receive nightly suvorexant (40 mg for patients younger than 65 years, 30 mg for patients aged 65 years or older) or placebo at a 2:1 ratio for 1 year with a subsequent 2-month randomised discontinuation phase in which patients on suvorexant either continued suvorexant or were abruptly switched to placebo while patients on placebo remained on placebo. Treatment assignment was masked from patients and investigators. The primary objective was to assess the safety and tolerability of suvorexant for up to 1 year. Secondary objectives were to assess the efficacy of suvorexant for improving patient-reported subjective total sleep time (sTST) and time to sleep onset (sTSO) over the first month of treatment. Efficacy endpoints over the first month were assessed with a mixed model with terms for baseline value of the response variable, age, sex, region, treatment, time, and treatment by time interaction. This trial is registered with ClinicalTrials.gov, number NCT01021813. 322 (62%) of 522 patients randomly assigned to receive suvorexant and 162 (63%) of 259 assigned to receive placebo completed the 1-year phase. Over 1 year, 362 (69%) of 521 patients treated with suvorexant experienced any adverse events compared with 164 (64%) of 258 treated with placebo. Serious adverse events were recorded in 27 patients (5%) who received suvorexant and 17 (7%) who received placebo. The most common adverse event, somnolence, was reported for 69 patients (13%) who received suvorexant and seven (3%) who received placebo. At month 1, suvorexant (517 patients in the efficacy population) showed greater efficacy than placebo (254 in the efficacy population) in improving sTST (38·7 min vs 16·0 min; difference 22·7, 95% CI 16·4 to 29·0; p<0·0001) and sTSO (–18·0 min vs −8·4 min, difference −9·5, −14·6 to −4·5; p=0·0002). Our findings show that suvorexant was generally safe and well tolerated over 1 year of nightly treatment in patients with insomnia, with efficacy noted for subjective measures of sleep onset and maintenance. Merck & Co Inc.

Narcolepsy is a rare and chronic hypersomnolence disorder characterized by excessive daytime sleepiness, disrupted nighttime sleep, sleep paralysis, and hypnagogic hallucinations and occurs with or without cataplexy. Orexin neuron loss has been implicated in the underlying pathophysiology of narcolepsy type 1 through dysregulation of sleep/wake patterns and rapid eye movement sleep. γ-Aminobutyric acid (GABA) has been shown to play a role in modulation of orexin neuronal activity during transitions from wakefulness to sleep. γ-Hydroxybutyrate (GHB), an endogenous analog of GABA, has demonstrated therapeutic benefit in treatment of narcolepsy through early investigations, but use has historically been limited owing to existing stigma related to illicit use and abuse risk. Initial regulatory approval of its sodium salt derivative, sodium oxybate (SXB), for cataplexy in patients with narcolepsy occurred in 2002, and additional formulations have been developed. The efficacy and safety of SXB in narcolepsy have been supported by decades of clinical use and research. This review discusses the history and clinical application of GHB and its SXB derivatives in the treatment of individuals with narcolepsy, including clinical safety and effect on sleep.

Hyperarousal is a key component in all modern etiological models of insomnia disorder. Overall patterns in the literature suggest that over-active neurobiological and psychological systems contribute to difficulty sleeping. Even so, mixed results regarding the specific mechanisms linking hyperarousal to sleep disturbance limit current etiological conceptualizations. Similar basal arousal profiles between individuals with high vs low risk for insomnia in the absence of stress exposure suggest that dysregulated stress \"response\" rather than general hyperarousal may be a more pertinent marker of risk. In this report, we discuss evidence for hyperarousal in insomnia and explore the role of sleep reactivity. A trait characteristic, sleep reactivity is the degree to which stress disrupts sleep, manifesting as difficulty falling and staying asleep. Premorbid sleep reactivity has been shown to identify individuals at risk for future insomnia disorder, such as highly reactive sleepers (whose sleep systems are sensitive to stress) who are at elevated disease risk. Research points to genetics, family history of insomnia, gender, and environmental stress as factors that influence sleep reactivity. Importantly, stress-related cognitive-emotional reactivity (e.g., rumination, worry) may exploit the vulnerability of a highly reactive sleep system. We propose that sleep reactivity and cognitive-emotional reactivity may share a bidirectional relationship, conferring an insalubrious environment for sleep in response to stress. Future research on sleep reactivity is needed to identify its neurobiology, characterize its relationship with cognitive-emotional reactivity, and explore the potential clinical utility of sleep reactivity in treatment planning.

Potential-based integral equations are being explored to develop numerical methods that avoid low frequency breakdown issues and are better suited to couple to quantum physics computations. Important classes of quantum electrodynamics problems are typically formulated in the radiation gauge, leading to interest in efficient numerical solutions able to be performed directly in this gauge. This work presents time domain integral equations for penetrable regions that are developed in the radiation gauge. An appropriate marching-on-in-time discretization scheme is developed that fully conforms to the spatial and temporal Sobolev space properties of the integral equations. It is shown that following this approach leads to a discrete system with improved stability properties that produces accurate results down to very low frequencies. The accuracy and stability of this formulation at low frequencies are shown through numerical results.