Ustekinumab Pharmacokinetics and Exposure Response in a Phase 3 Randomized Trial of Patients With Ulcerative Colitis.

BACKGROUND & AIMS: The efficacy of antibody-based therapeutics depends on their pharmacokinetics. The pharmacokinetic and exposure response profiles of ustekinumab, a monoclonal antibody against interleukin 12/interleukin 23, are known in patients with Crohn's disease, yet there are few data from patients with ulcerative colitis. We characterized ustekinumab's pharmacokinetics, exposure response, and optimal serum concentrations in patients with ulcerative colitis. METHODS: We collected data from 2 phase 3 trials (1 induction and 1 maintenance), in which patients with moderate to severe ulcerative colitis received an intravenous induction dose of ustekinumab (130 mg, n = 320; or approximately 6 mg/kg, n = 322). Responders were assigned randomly to groups that received subcutaneous maintenance ustekinumab (90 mg) every 8 weeks (n = 176) or 12 weeks (n = 172), or placebo (n = 175). We evaluated the association between ustekinumab concentration and efficacy, serum based on clinical effects (Mayo score), histologic features, and inflammation (measurement of C-reactive protein, fecal calprotectin, and fecal lactoferrin), as well as safety (infections, serious infections, and serious adverse events), during induction and maintenance therapy. Optimal serum concentrations of ustekinumab were identified using receiver operating characteristic curve analyses. RESULTS: In patients with ulcerative colitis, dose-proportional serum concentrations of ustekinumab, unaffected by prior biologic or concomitant immunomodulator therapy, reached steady state by the second maintenance dose; the median trough concentration for dosing every 8 weeks was approximately 3-fold that of dosing every 12 weeks. Serum concentrations were associated with clinical and histologic features of efficacy and normalization of inflammation markers. The week-8 concentration threshold for induction of response was 3.7 µg/mL. A steady-state trough serum concentration of 1.3 µg/mL or higher was associated with a higher rate of clinical remission compared with patients who had lower serum concentrations. Serum concentrations of ustekinumab were not associated with infections, serious infections, or serious adverse events. CONCLUSIONS: In an analysis of data from 2 phase 3 trials of patients with ulcerative colitis, we found that serum concentrations of ustekinumab were proportional to dose, unaffected by prior biologic or concomitant immunomodulator therapies, associated with clinical and histologic efficacy and markers of inflammation, and were not associated with safety events at doses evaluated. Ustekinumab pharmacokinetics are consistent between patients with Crohn's disease vs ulcerative colitis.

A sexual health quality improvement program (SHIMMER) triples chlamydia and gonorrhoea testing rates among young people attending Aboriginal primary health care services in Australia.

BACKGROUND: In Australia, chlamydia is the most commonly notifiable infection and over the past ten years chlamydia and gonorrhoea notification rates have increased. Aboriginal compared with non-Aboriginal Australians have the highest notifications rates of chlamydia and gonorrhoea. Regular testing of young people for chlamydia and gonorrhoea is a key prevention strategy to identify asymptomatic infections early, provide treatment and safe sex education. This study evaluated if a sexual health quality improvement program (QIP) known as SHIMMER could increase chlamydia and gonorrhoea testing among young people attending four Aboriginal primary health care services in regional areas of New South Wales, Australia. METHODS: We calculated the proportion of 15-29 year olds tested and tested positivity for chlamydia and gonorrhoea in a 12-month before period (March 2010-February 2011) compared with a 12-month QIP period (March 2012-February 2013). Logistic regression was used to assess the difference in the proportion tested for chlamydia and gonorrhoea between study periods by gender, age group, Aboriginal status and Aboriginal primary health service. Odds ratios (OR) and their 95 % confidence intervals (CIs) were calculated with significance at p < 0.05. RESULTS: In the before period, 9 % of the 1881 individuals were tested for chlamydia, compared to 22 % of the 2259 individuals in the QIP period (OR): 1.43, 95 % CI: 1.22-1.67). From the before period to the QIP period, increases were observed in females (13 % to 25 %, OR: 1.32, 95 % CI: 1.10-1.59) and males (3 % to 17 %, OR: 1.85, 95 % CI: 1.36-2.52). The highest testing rate in the QIP period was in 15-19 year old females (16 % to 29 %, OR: 1.02, 95 % CI: 0.75-1.37), yet the greatest increase was in 20-24 year olds males (3 % to 19 %, OR: 1.65, 95 % CI: 1.01-2.69). Similar increases were seen in gonorrhoea testing. Overall, there were 70 (11 %) chlamydia diagnoses, increasing from 24 in the before to 46 in the QIP period. Overall, 4 (0.7 %) gonorrhoea tests were positive. CONCLUSIONS: The QIP used in SHIMMER almost tripled chlamydia and gonorrhoea testing in young people and found more than twice as many chlamydia infections. The QIP could be used by other primary health care centres to increase testing among young people.

Incidence and predictors of annual chlamydia testing among 15-29 year olds attending Aboriginal primary health care services in New South Wales, Australia.

BACKGROUND: For the past two decades, chlamydia has been the most commonly notified infectious disease among young people (15-29 year olds) in Australia, the United States of America and the United Kingdom and rates have increased annually in these three countries. In Australia, rates of chlamydia are three times higher in Aboriginal compared with non-Aboriginal people. Australian sexually transmissible infection guidelines recommend annual chlamydia testing for 15-29 year old females and males. This analysis will examine the incidence and predictors of annual chlamydia testing in 15-29 year olds attending four Aboriginal Community Controlled Health Services (ACCHS) in Australia. METHODS: From 2009-2011, attendance and chlamydia testing data were extracted from the patient system to calculate the number and proportion of 15-29 year olds that were tested for chlamydia and that tested positive for chlamydia by gender (male, female), age-group (15-19, 20-24, 25-29 years), Aboriginal status (Aboriginal, non-Aboriginal people) and by the four ACCHSs sites (1, 2, 3 and 4). A cohort was created to calculate the incidence rate per 100 person-years (PY) and predictors of an annual chlamydia test (a test within 12-months of a previous test/visit) by the above factors using Cox regression. Unadjusted and adjusted hazard ratios (AHR) and their 95 % confidence intervals (CIs) and p-values were calculated with significance at p < 0.05. RESULTS: From 2009-2011, there were 2896 individuals who attended the four ACCHSs. Overall , 17 % (22 % of females and 10 % of males) were tested for chlamydia and 9 % tested positive (8 % of females and 14 % of males). The median time to an annual chlamydia test was 10.7 months. The cohort included 2318 individuals. Overall the incidence rate of an annual chlamydia test was 9.1 per 100 PY (11.6 in females and 5.8 in males). Predictors of an annual chlamydia test were being female (AHR: 1.7, 95 % CI: 1.2-2.2, p < 0.01), being 15-19 years old (AHR: 1.6, 95 % CI: 1.1-2.3, p < 0.01) and attending ACCHS site 2 (AHR: 3.8, 95 % CI: 1.8-8.0, p < 0.01). CONCLUSIONS: This analysis highlights that opportunistic STI testing strategies are needed to increase annual chlamydia testing in young people; especially males.

Tissue Culture Innovations for Propagation and Conservation of Myrteae-A Globally Important Myrtaceae Tribe.

Myrteae is the most species-rich tribe in the Myrtaceae family, represented by a range of socioeconomically and ecologically significant species. Many of these species, including commercially relevant ones, have become increasingly threatened in the wild, and now require conservation actions. Tissue culture presents an appropriate in vitro tool to facilitate medium-term and long-term wild germplasm conservation, as well as for commercial propagation to maintain desirable traits of commercial cultivars. So far, tissue culture has not been extensively achieved for Myrteae. Here, tissue culture for Eugenia, one of the most species-rich genera in Myrteae, is reviewed, giving directions for other related Myrteae. This review also focuses on ex situ conservation of Australian Myrteae, including using seed banking and field banking. Despite some progress, challenges to conserve these species remain, mostly due to the increasing threats in the wild and limited research. Research into in vitro methods (tissue culture and cryopreservation) is paramount given that at least some of the species are 'non-orthodox'. There is an urgent need to develop long-term in vitro conservation for capturing the remaining germplasm of threatened Myrteae.

Haploinsufficiency of the Parkinson's disease gene synaptojanin1 is associated with abnormal responses to psychomotor stimulants and mesolimbic dopamine signaling.

The synaptojanin-1 (SYNJ1) gene is known to be important for dopamine-related disorders. Recent evidence has demonstrated that Synj1 deficient mice (Synj1 +/-) have impairments in dopaminergic synaptic vesicular recycling. However, less is known about how Synj1 deficits affect the mesolimbic system, reward processing, and motivated behavior. To examine the role of the Synj1 gene in motivated behavior, we subjected male and female Synj1 +/- and Synj1 +/+ mice to a battery of behavioral tests evaluating hedonic responses, effortful responding, and responses to psychomotor stimulants. We observed that Synj1 +/- mice exhibit few differences in reward processing and motivated behavior, with normal hedonic responses and motivated responding for sucrose. However, male but not female Synj1 +/- demonstrated an attenuated conditioned place preference for cocaine that could not be attributed to deficits in spatial memory. To further understand the dopamine signaling underlying the attenuated response to cocaine in these mutant mice, we recorded nucleus accumbens dopamine in response to cocaine and observed that Synj1 +/- male and female mice took longer to reach peak dopamine release following experimenter-administered cocaine. However, female mice also showed slower decay in accumbens dopamine that appear to be linked to differences in cocaine-induced DAT responses. These findings demonstrate that SYNJ1 deficiencies result in abnormal mesolimbic DA signaling which has not previously been demonstrated. Our work also highlights the need to develop targeted therapeutics capable of restoring deficits in DAT function, which may be effective for reversing the pathologies associated with Synj1 mutations.

Diaphragm electrical activity during weaning of nasal high-flow therapy in preterm infants.

OBJECTIVE: To determine whether electrical activity of the diaphragm (Edi) changes with weaning nasal high-flow (HF) therapy in preterm infants according to a standardised protocol. DESIGN: Prospective observational cohort study. SETTING: Neonatal intensive care unit. PATIENTS: Preterm infants born at <32 weeks gestation, receiving nasal HF as part of routine clinical care. INTERVENTIONS: Infants recruited to the study had their HF weaned according to set clinical criteria. Edi was measured using a modified gastric feeding tube serially from baseline (pre-wean) to 24-hours post-wean. MAIN OUTCOME MEASURES: Change in Edi from baseline was measured at four time points up to 24 hours after weaning. Minimum Edi during expiration, maximum Edi during inspiration and amplitude of the Edi signal (Edidelta) were measured. Clinical parameters (heart rate, respiratory rate and fraction of inspired oxygen) were also recorded. RESULTS: Forty preterm infants were recruited at a mean corrected gestational age of 31.6 (±2.7) weeks. Data from 156 weaning steps were analysed, 91% of which were successful. Edi did not change significantly from baseline during flow reduction steps, but a significant increase in diaphragm activity was observed when discontinuing HF (median increase in Edidelta immediately post-discontinuation 1.7 µV (95% CI: 0.6 to 3.0)) and at 24 hours 1.9 µV (95% CI: 0.7 to 3.8)). No significant difference in diaphragm activity was observed between successful and unsuccessful weaning steps. CONCLUSIONS: A protocolised approach to weaning has a high probability of success. Edi does not change with reducing HF rate, but significantly increases with discontinuation of HF from 2 L/min.

The use of mentoring for knowledge translation by allied health: a scoping review.

OBJECTIVE: To describe how allied health professionals have used mentoring as a knowledge translation strategy to inform practice. INTRODUCTION: Mentoring has been reported to be used by nursing and medicine as a knowledge translation strategy. It is not known if allied health professionals have also used mentoring to improve their use of research in practice, or what the key mentoring characteristics are that guide its application in allied health settings. Improved understanding of the barriers and facilitators to mentoring in allied health settings may be used to guide the design of future mentoring programs to assist knowledge translation. INCLUSION CRITERIA: Eligible studies must have included allied health professionals, and used the concept of mentoring to support knowledge translation in the context of healthcare. Primary empirical and synthesized studies were eligible. METHODS: An a-priori protocol was followed to complete a search of six databases (MEDLINE [OVID], EMBASE [OVID], CINAHL [EBSCO], PsycInfo [OVID], PDQ-Evidence ( www.pdq-evidence.org ), and Cochrane on the 9 March 2021. Screening for eligibility was conducted by two authors at the title and abstract stage and the full text stage. Selection criteria and the data extraction tool were established prior to the search. Findings are presented in narrative and tabular formats. RESULTS: A total of 2053 studies met the inclusion criteria for screening and nine were determined to be eligible for inclusion. Mentoring has been used by allied health professionals to improve the translation of interventional research evidence by clinicians, and to establish clinician skills and knowledge relating to knowledge translation processes. Mentoring was predominantly used as part of a multifaceted knowledge translation strategy alongside educational strategies. Mentoring characteristics such as structure, context, goals, resourcing and dosage varied depending on the context of translation. The specific barriers reported to using mentoring were varied, whereas the facilitators to mentoring were primarily related to the mentor's approach and expertise. The impact of mentoring was primarily measured through the mentee's experience of mentoring. CONCLUSIONS: Allied health professionals have used mentoring as a knowledge translation strategy to enhance the use of research evidence in their practice and to learn the process of knowledge translation. Mentoring is mostly used in conjunction with other strategies in practice, such as education. The limited number of identified barriers and facilitators to using mentoring as a knowledge translation strategy supports the need for future research to deepen our understanding about the mentoring process.

Stress reveals a specific behavioral phenotype for opioid abuse susceptibility.

Susceptibility to stress has long been considered important for the development of substance use disorders. Nonetheless, behavioral and physiological responses to stress are highly variable, making it difficult to identify the individuals who are most likely to abuse drugs. In the present study, we employed a comprehensive battery of tests for negative valence behaviors and nociception to identify individuals predisposed to opioid seeking following oral opioid self-administration. Furthermore, we examined how this profile was affected by a history of stress. We observed that mice receiving foot shock stress failed to exhibit a preference for sucrose, showed increased immobility in the forced swim task, and exhibited mechanical hypersensitivity when compared to controls. When considering these behaviors in light of future fentanyl-seeking responses, we observed that heightened mechanical sensitivity corresponded to higher opioid preference in mice with a history of stress, but not controls. Moreover, we were surprised to discover that paradoxically high sucrose preferences predicted fentanyl preference in shock mice, while signs of anhedonia predicted fentanyl preference in controls. Taken together, these results indicate that stress can act as a physiological modulator, shifting profiles of opioid abuse susceptibility depending on an individual's history.

A diencephalic circuit in rats for opioid analgesia but not positive reinforcement.

Mu opioid receptor (MOR) agonists are potent analgesics, but also cause sedation, respiratory depression, and addiction risk. The epithalamic lateral habenula (LHb) signals aversive states including pain, and here we found that it is a potent site for MOR-agonist analgesia-like responses in rats. Importantly, LHb MOR activation is not reinforcing in the absence of noxious input. The LHb receives excitatory inputs from multiple sites including the ventral tegmental area, lateral hypothalamus, entopeduncular nucleus, and the lateral preoptic area of the hypothalamus (LPO). Here we report that LHb-projecting glutamatergic LPO neurons are excited by noxious stimulation and are preferentially inhibited by MOR selective agonists. Critically, optogenetic stimulation of LHb-projecting LPO neurons produces an aversive state that is relieved by LHb MOR activation, and optogenetic inhibition of LHb-projecting LPO neurons relieves the aversiveness of ongoing pain.

Tissue culture tools for selenium hyperaccumulator Neptunia amplexicaulis for development in phytoextraction.

Neptunia amplexicaulis is an herbaceous legume endemic to the Richmond area in central Queensland, Australia and is one of the strongest known Selenium hyperaccumulators on earth, showing significant potential to be utilised in Se phytoextraction applications. Here a protocol was established for in vitro micropropagation of Se hyperaccumulator N. amplexicaulis using nodal segments from in vitro-germinated seedlings. Shoot multiplication was achieved on Murashige and Skoog (MS) basal media supplemented with various concentrations of 6-Benzylaminopurine (BA) (1.0, 2.0, 3.0 mg L-1) alone or in combination with low levels of Naphthaleneacetic acid (NAA) (0.1, 0.2, 0.3 mg L-1), with 2.0 mg L-1 BA + 0.2 mg L-1 NAA found to be most effective. Elongated shoots were rooted in vitro using NAA, with highest root induction rate of 30% observed at 0.2 mg L-1 NAA. About 95% of the in vitro rooted shoots survived acclimatization. Clonally propagated plantlets were dosed with selenate/selenite solution and assessed for Se tissue concentrations using Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES) and found to retain their ability to hyperaccumulate. The protocol developed for this study has potential to be optimised for generating clonal plants of N. amplexicaulis for use in research and phytoextraction industry applications.

Central compartment dissection in thyroid papillary carcinoma.

BACKGROUND: Systematic elective paratracheal dissection for papillary thyroid carcinoma is controversial. OBJECTIVE: This study aims to analyze the pattern of locoregional recurrence (LRR) to determine the potential benefit of elective paratracheal dissection and to identify prognostic factors influencing locoregional control and disease specific survival. METHODS: A cohort of 342 patients who underwent a total thyroidectomy with or without neck dissection for a papillary thyroid carcinoma was retrospectively reviewed. Clinicopathological variables predicting for survival and control were examined. RESULTS: All patients underwent total thyroidectomy and 84 underwent neck dissection as primary treatment. Sixty-six patients underwent a central compartment neck dissection. Twenty-eight (8.2%) patients developed LRR, of which 12 did not undergo neck dissection at initial surgery. The majority of neck recurrences were found in the lateral neck. Two patients (0.7%) without a paratracheal dissection done initially recurred only in the central compartment. On univariable analysis significant pathological predictors of locoregional control included tumor size, extrathyroidal extension (ETE), lymphovascular invasion and pathological lymph node status. Only ETE was a significant adverse prognostic variable for disease specific survival. On regression analysis, ETE and lymphovascular invasion were the only significant independent predictors of LRR. Paratracheal dissection did neither influence LRR nor central compartment control when adjusted for the effect of other variables. CONCLUSIONS: Strong conclusions are difficult to draw without a comparable group, but these results suggest that the absolute benefit of elective paratracheal dissection is small.

Optically controllable photonic structures with zero absorption.

We show the possibility to periodically modulate the refractive index in a homogeneous resonant atomic medium in space or/and time while simultaneously keeping vanishing absorption or gain. Such modulation is based on periodic resonant enhancement of the refractive index, controlled by an external optical field, and opens the way to produce coherently controllable photonic structures. We suggest the possible implementation of the proposed scheme in rare-earth doped crystals with excited state absorption.

pMAT: An open-source software suite for the analysis of fiber photometry data.

The combined development of new technologies for neuronal recordings and the development of novel sensors for recording both cellular activity and neurotransmitter binding has ushered in a new era for the field of neuroscience. Among these new technologies is fiber photometry, a technique wherein an implanted fiber optic is used to record signals from genetically encoded fluorescent sensors in bulk tissue. Fiber photometry has been widely adapted due to its cost-effectiveness, ability to examine the activity of neurons with specific anatomical or genetic identities, and the ability to use these highly modular systems to record from one or more sensors or brain sites in both superficial and deep-brain structures. Despite these many benefits, one major hurdle for laboratories adopting this technique is the steep learning curve associated with the analysis of fiber photometry data. This has been further complicated by a lack of standardization in analysis pipelines. In the present communication, we present pMAT, a 'photometry modular analysis tool' that allows users to accomplish common analysis routines through the use of a graphical user interface. This tool can be deployed in MATLAB and edited by more advanced users, but is also available as an independently deployable, open-source application.

Cryopreservation of Woody Crops: The Avocado Case.

Recent development and implementation of crop cryopreservation protocols has increased the capacity to maintain recalcitrant seeded germplasm collections via cryopreserved in vitro material. To preserve the greatest possible plant genetic resources globally for future food security and breeding programs, it is essential to integrate in situ and ex situ conservation methods into a cohesive conservation plan. In vitro storage using tissue culture and cryopreservation techniques offers promising complementary tools that can be used to promote this approach. These techniques can be employed for crops difficult or impossible to maintain in seed banks for long-term conservation. This includes woody perennial plants, recalcitrant seed crops or crops with no seeds at all and vegetatively or clonally propagated crops where seeds are not true-to-type. Many of the world's most important crops for food, nutrition and livelihoods, are vegetatively propagated or have recalcitrant seeds. This review will look at ex situ conservation, namely field repositories and in vitro storage for some of these economically important crops, focusing on conservation strategies for avocado. To date, cultivar-specific multiplication protocols have been established for maintaining multiple avocado cultivars in tissue culture. Cryopreservation of avocado somatic embryos and somatic embryogenesis have been successful. In addition, a shoot-tip cryopreservation protocol has been developed for cryo-storage and regeneration of true-to-type clonal avocado plants.

Mentoring for knowledge translation in allied health: a scoping review protocol.

OBJECTIVE: The primary objective of this review is to identify how allied health staff have used mentoring as a knowledge translation strategy to support practice change. Secondary objectives include identifying barriers and enablers to using mentoring as a knowledge translation strategy, and the methods used to evaluate the strategy. INTRODUCTION: Mentoring provides professional support and guidance while attending to the learning needs of the individual. Mentoring has been described in previous knowledge synthesis reviews as a strategy for nursing and medicine practitioners to improve capability and capacity to participate in knowledge translation to create practice change. To the authors' knowledge, a synthesis of the use of mentoring as a knowledge translation strategy by allied health staff has not been reported. INCLUSION CRITERIA: This scoping review will consider all studies that describe the use of mentoring with allied health staff to support practice change as directed by research evidence. The scoping review will not investigate the use of mentoring to increase the conduct of research in a clinical setting, nor will studies be included if the majority of participants are students. METHODS: A three-step search strategy will be undertaken. Two independent authors will screen articles and perform data extraction. The results will be presented in a narrative Summary of Findings, alongside a presentation of the data in diagrammatic or tabular form. The findings will inform future use of mentoring as a knowledge translation strategy in a regional health service.

A pharmacokinetic evaluation of five H(1) antagonists after an oral and intravenous microdose to human subjects.

AIMS: To evaluate the pharmacokinetics (PK) of five H(1) receptor antagonists in human volunteers after a single oral and intravenous (i.v.) microdose (0.1 mg). METHODS: Five H(1) receptor antagonists, namely NBI-1, NBI-2, NBI-3, NBI-4 and diphenhydramine, were administered to human volunteers as a single 0.1-mg oral and i.v. dose. Blood samples were collected up to 48 h, and the parent compound in the plasma extract was quantified by high-performance liquid chromatography and accelerator mass spectroscopy. RESULTS: The median clearance (CL), apparent volume of distribution (V(d)) and apparent terminal elimination half-life (t(1/2)) of diphenhydramine after an i.v. microdose were 24.7 l h(-1), 302 l and 9.3 h, and the oral C(max) and AUC(0-infinity) were 0.195 ng ml(-1) and 1.52 ng h ml(-1), respectively. These data were consistent with previously published diphenhydramine data at 500 times the microdose. The rank order of oral bioavailability of the five compounds was as follows: NBI-2 > NBI-1 > NBI-3 > diphenhydramine > NBI-4, whereas the rank order for CL was NBI-4 > diphenhydramine > NBI-1 > NBI-3 > NBI-2. CONCLUSIONS: Human microdosing provided estimates of clinical PK of four structurally related compounds, which were deemed useful for compound selection.

Making reliable decisions in the study of wildlife diseases: using hypothesis tests, statistical power, and observed effects.

The increasing importance of wildlife diseases in conservation efforts places an additional importance on research study design, data analysis, and interpretation. In this paper, we explore the design and analysis of wildlife disease data with regard to hypothesis testing, statistical power, sample sizes, the relative costs of type I versus type II errors, and effect size. To illustrate these ideas, we conducted a literature review of the Journal of Wildlife Diseases (JWD), ran computer simulations that estimate type II error rates for statistical techniques commonly used in JWD, and reanalyzed previously published data on disease prevalence. Many studies published in JWD used chi-squared analysis on prevalence data, but only 19% reported estimates of the observed effect size. Furthermore, 10% of studies had pooled sample sizes < or =40, and many had potentially high costs of type II relative to type I errors. Our computer simulations suggest that many articles published in JWD lack sufficient statistical power, and this, coupled with our findings that many studies often ignore high costs of type II errors, argues for increased attention to statistical power. Finally, our data reanalysis shows how the presentation of observed effect sizes could allow a better assessment of the biologic significance of findings reported in JWD. We conclude with some general guidelines to assist wildlife disease researchers in the design of future studies and the statistical analysis of their data.

A systematic review of the amount and timing of light in association with objective and subjective sleep outcomes in community-dwelling adults.

Light is considered the dominant environmental cue, or zeitgeber, influencing the sleep-wake cycle. Despite recognizing the importance of light for our well-being, less is known about the specific conditions under which light is optimally associated with better sleep. Therefore, a systematic review was conducted to examine the association between the amount and timing of light exposure in relation to sleep outcomes in healthy, community-dwelling adults. A systematic search was conducted of four databases from database inception to June 2016. In total, 45 studies met the review eligibility criteria with generally high study quality excepting for the specification of eligibility criteria and the justification of sample size. The majority of studies involved experimental manipulation of light (n = 32) vs observational designs (n = 13). Broad trends emerged suggesting that (1) bright light (>1000 lux) has positive implications for objectively assessed sleep outcomes compared to dim (<100 lux) and moderate light (100-1000 lux) and (2) bright light (>1000 lux) has positive implications for subjectively assessed sleep outcomes compared to moderate light (100-1000 lux). Effects due to the amount of light are moderated by the timing of light exposure such that, for objectively assessed sleep outcomes, brighter morning and evening light exposure are consistent with a shift in the timing of the sleep period to earlier and later in the day, respectively. For subjectively assessed sleep outcomes, brighter light delivered in the morning was associated with self-reported sleep improvements and brighter evening light exposure was associated with worse self-reported sleep.

Directional coherent light via intensity-induced sideband emission.

We introduce a unique technique for generating directional coherent emissions that could be utilized to create coherent sources in a wide range of frequencies from the extreme ultraviolet (XUV) to the deep infrared. This is accomplished without population inversion by pumping a two-level system with a far-detuned strong optical field that induces the splitting of the two-level system. A nonlinear process of four-wave mixing then occurs across the split system, driving coherent emission at sidebands both red- and blue-detuned from the pump frequency, and propagates both forward and backward along the pump beam path. We observed this phenomenon in dense rubidium vapor along both the D1 and D2 transitions. The sideband emission exhibits a short pulse duration (<1 ns) with threshold-like behavior dependent on both the pump intensity and Rb vapor density. This technique offers a new capability for manipulating the emission frequency simply through intensity-induced atomic modulation that can be scaled to most frequency regimes using various atomic/molecular ensembles and pump energies.