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Sleep apnea is the manifestation of key "endotypic traits" including greater pharyngeal collapsibility, reduced dilator muscle compensation and elevated chemoreflex loop gain.We investigate how endotypic traits vary with obesity, age, sex, and race/ethnicity to influence sleep apnea disease severity (apnea-hypopnea index, AHI).Endotypic traits were estimated from polysomnography in a diverse community-based cohort study (Multi-Ethnic Study of Atherosclerosis, N=1971, age: 54-93yr). Regression models assessed associations between each exposure (continuous variables per 2SD) and endotypic traits (per SD) or AHI (events/h), independent of other exposures. Generalizability was assessed in two independent cohorts.Greater AHI was associated with obesity (+19 events/h per 11 kg/m2 [2SD]), male sex (+13 events/h v. female), older age (+7 events/h per 20 yr), and Chinese ancestry (+5 events/h v. White, nb. obesity adjusted). Obesity-related increase in AHI was best explained by elevated collapsibility (+0∙40 SD) and greater loop gain (+0∙38 SD; percentage mediated=26[95% CI: 20-32] %). Male-related increase in AHI was explained by elevated collapsibility (+0∙86 SD) and reduced compensation (-0∙40 SD; percentage mediated=57[50-66] %). Age-related AHI increase was explained by elevated collapsibility (+0∙37 SD) and greater loop gain (+0∙15 SD; percentage mediated=48[34-63] %). Increased AHI with Chinese ancestry was explained by collapsibility (+0∙57 SD; percentage mediated=87[57-100] %). Black race was associated reduced collapsibility (-0∙30 SD) and elevated loop gain (+0∙29 SD). Similar patterns were observed in the other cohorts.Different subgroups exhibit different underlying pathophysiological pathways to sleep apnea, highlighting the variability in mechanisms that could be targeted for intervention.

Data on the prevalence of sleep-disordered breathing (SDB) in people with HIV are limited. Moreover, whether the associations between SDB and age or BMI differ by HIV status is unknown.Is SDB more prevalent in men with HIV than those without HIV, and do the predictors of SDB differ between the two groups?Home polysomnography was used in the Multicenter AIDS Cohort Study to assess SDB prevalence in men with (n = 466; 92% virologically suppressed) and without (n = 370) HIV. SDB was defined using the oxygen desaturation index (ODI) and the apnea-hypopnea index (AHI), using four definitions: ≥ 5 events/h based on an ODI with a 3% (ODISDB prevalence was similar in men with and without HIV using the ODISDB prevalence was high overall but greater in men with than without HIV using the ODI

BACKGROUND AND AIM Existing interventions promoting positive airway pressure (PAP) adherence focus only on the diagnosed individual, despite the fact that partners are often the most impacted by obstructive sleep apnea (OSA), and are delivered mostly by health professionals, with limited success. The goal of this work is to develop a prototype of OurSleepKit, a couple-focused mobile health (mHealth) tool to coach mutual engagement and promote adherence to PAP treatment. METHODS We used an iterative participatory approach working with future end users of OurSleepKit to support the development of this prototype. We conducted a total of 14 semi-structured in-depth open-ended dyadic interviews with OSA patients and their partners. Phase 1 of the development was to inform key functions of an engaging tool. Phase 2 focused on developing functions to engage positive conversation in the dyad and obtained feedback for this initial prototype. RESULTS The OurSleepKit prototype was developed and demonstrated high acceptability and engagement. Three key functions included periodic assessments based on developmental stages of PAP treatment, a Coaching Board which provides customized and dynamically updated support content - primarily brief story-telling videos featuring real-life couples' experiences - and timely tailored prompts (for action, learning, and conversation) through push notifications in the evening to facilitate positive conversation in the dyad and offer in-the-moment support for PAP use. CONCLUSIONS Going beyond the traditional and prevailing view of PAP use as an individual phenomenon, OurSleepKit is a novel mHealth intervention engaging both the patient and partner holding great promise to promote PAP adherence.

Examine the associations of sleep measures with kidney function changes over time among individuals from a community-based study.The sample includes 1657 participants (287 with chronic kidney disease [CKD]) in the Multi-Ethnic Study of Atherosclerosis Sleep Cohort (mean age: 57.7 years, male: 46.0%). We examined associations between a large set of sleep variables (polysomnography, actigraphy, and questionnaires) and cardiovascular disease risk factors and changes in estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio over approximately 5 years using high-dimensional regression. We investigated the modifying effect of sleep on the associations between cardiovascular disease risk factors and kidney function.Sleep metrics predicted kidney function decline only among individuals with baseline CKD. Among this group, eGFR decline was associated with decreased stage N3 sleep (0.32 mL/min/1.73 mReduced deep sleep, daytime napping, increased wake bouts, delayed sleep rhythms, and overnight hypoxemia are associated with longitudinal kidney function decline, with effects most apparent in individuals with CKD. Deep sleep, napping, and sleep timing modified the association between hemoglobin A1C and kidney function.

Orally disintegrating tablets are an emerging trend in novel drug delivery system and have received ever increasing demand during the last few decades. Orally disintegrating tablets ODTs are the dosage form which will disintegrate in mouth within seconds without need of water. This type of property in dosage form can be attained by addition of different varieties of excipients. But the number of fillers/binders/disintegrant which can be used for ODT formulations is limited because these bulk excipients have to fulfill special requirements, such as being soluble in water, pleasant taste, mouth feel, sweetness, and rapid dispersibility. In recent years drug formulation scientists have recognized that single component excipients do not always provide the requisite performance to allow certain active pharmaceutical ingredients to be formulated or manufactured adequately. New combinations of existing excipients are an interesting option for improving excipient functionality now a day. In excipients mannitol is used as diluents but now a day’s modified mannitol is available which give extensive flow, compression and rapid dispersibility to the tablet e.g. like Orocell, Mannogem EZ, and Pearlitol SD 200. The current review article is prepared to have a look over the recent development in excipient technology and the approaches involved in development of such excipients. It emphasizes on the different examples of functionality added materialsalso called as multifunctional co processed excipients available in market such as Ludiflash, Pharmburst, and F- MELT.

Artificial Intelligence (AI) focuses in producing intelligent modeling, which helps in imagining knowledge, cracking problems and decision making. In the year 1943, the first work which is now recognized as AI was done by Warren McCulloch and Walter pits. Previously, Artificial Intelligence was only limited to the field of engineering, but recently, AI plays an important role in various fields of pharmacy like drug discovery, drug delivery formulation development, marketing, management, marketing, quality assurance, hospital pharmacy etc. In drug discovery and drug delivery formulation development, various Artificial Neural Networks (ANNs) like Deep Neural Networks (DNNs) or Recurrent Neural Networks (RNNs) are being employed. Several implementations of drug discovery have currently been analyzed and supported the power of the technology in quantitative structure-property relationship (QSPR) or quantitative structure-activity relationship (QSAR). In addition, de novo design promotes the invention of significantly newer drug molecules with regard to desired/optimal qualities. Now the robots are using in the various medical procedures as they are more trustworthy for doctors, as they are more advanced in their work, as they can do any task within the short time period and effectively than humans. This is concluded that AI is the new evolving field in every sector, even in pharmacy, and it need more development for updating the current scenario as well as for new researches.

Bacteria are associated with the human body and colonize the gut, skin, and mucous membranes. These associations can be either symbiotic or pathogenic. In either case, bacteria derive more benefit from their host. The ability of bacteria to enter and survive within the human body can be exploited for human benefit. They can be used as a vehicle for delivering or producing bioactive molecules, such as toxins and lytic enzymes, and eventually for killing tumor cells. Clostridium and Salmonella have been shown to infect and survive within the human body, including in tumors. There is a need to develop genetic circuits, which enable bacterial cells to carry out the following activities: (i) escape the human immune system, (ii) invade tumors, (iii) multiply within the tumorous cells, (iv) produce toxins via quorum sensing at low cell densities, and (v) express suicide genes to undergo cell death or cell lysis after the tumor has been lysed. Thus, bacteria have the potential to be exploited as anticancer agents.

Since ancient times, agriculture has been one of the chief factors in the advancement of many nations. Also, it has been a huge contributor to the GDP (Gross Domestic Product). But the farmers and the small-scale retailers are still unaware of the demand and supply of the commodities in mandis. Ultimately, they are compelled to use the repetitive pattern of crops. Through knowledge of the intra-mandi prices for seasonal crops is necessary to gain the desired profit. Price trends in several Gujarat markets were investigated for Ajwain and Isabgol (Psyllium Husk) in order to forecast price volatility and problems that produce mandi-level projections, enhancing its usefulness. Given that medicinal crops have various medical and culinary uses, boosting their productivity could increase farmers' profits in comparison to typical pattern crops. So, the aim of this study is to evaluate the optimum preferred crop conditions for important commodities like Isabgol, Ajwain, Fenugreek, Mint and Raw turmeric with respect to profit. A data from the past decade was screened to observe the variation in prices of the crops along with production analysis. Also, it was validated statistically by various statical measures like Standard Deviation, Mean and Coefficient of Variation. We examined intra-mandi prices and found that prices fluctuate over the whole peak season, with notable fluctuations in modal prices among several mandis. To demonstrate the variations in pricing reported for certain mandis on specific days, we've given a few instances. A low standard deviation implies that the commodities price is clustered around the mean, whereas a large standard deviation shows that the commodities price is more dispersed. Price volatility is the discrepancy between what is anticipated and what occurs.

ObjectiveTo determine if the sensitivity of the lateral flow test is dependent on the viral load and on the location of swabbing in the respiratory tract in children.DesignPhase 1: Routinely performed reverse transcriptase PCR (RT-PCR) using nose and throat (NT) swabs or endotracheal (ET) aspirates were compared with Innova lateral flow tests (LFTs) using anterior nasal (AN) swabs. Phase 2: RT-PCR-positive children underwent paired AN RT-PCR and LFT and/or paired AN RT-PCR and buccal LFT.SettingTertiary paediatric hospitals.PatientsChildren under the age of 18 years. Phase 1: undergoing routine testing, phase 2: known SARS-CoV-2 positive.ResultsPhase 1: 435 paired swabs taken in 431 asymptomatic patients resulted in 8 positive RT-PCRs, 9 PCR test failures and 418 negative RT-PCRs from NT or ET swabs. The test performance of AN LFT demonstrated sensitivity: 25% (4%–59%), specificity: 100% (99%–100%), positive predictive value (PPV): 100% (18%–100%) and negative predictive value (NPV): 99% (97%–99%).Phase 2: 14 AN RT-PCR-positive results demonstrated a sensitivity of 77% (50%–92%) of LFTs performed on AN swabs. 15/16 paired buccal LFT swabs were negative.ConclusionThe NPV, PPV and specificity of LFTs are excellent. The sensitivity of LFTs compared with RT-PCR is good when the samples are colocated but may be reduced when the LFT swab is taken from the AN. Buccal swabs are not appropriate for LFT testing. Careful consideration of the swabbing reason, the tolerance of the child and the requirements for test processing (eg, rapidity of results) should be undertaken within hospital settings.Trial registration numberNCT04629157.

To assess vision in pseudophakic eyes with Fuchs' endothelial corneal dystrophy (FECD) before the onset of clinically detectable corneal edema.Cross-sectional study.Sixty-one otherwise healthy pseudophakic eyes of 38 subjects with FECD (without clinically detectable edema) and 17 otherwise healthy pseudophakic eyes of 9 subjects with normal corneas. Subjects underwent clinical examination to determine the morphologic distribution of guttae (severity grading). Standardized best-corrected high-contract and low-contrast (photopic and mesopic) visual acuity (HCVA, LCVA) and straylight were measured. Scheimpflug tomography posterior elevation and pachymetry maps were interpreted for 3 tomographic features of subclinical edema: loss of regular isopachs, displacement of the thinnest point of the cornea, and presence of posterior surface depression.In FECD without tomographic features of edema (ie, normal tomography patterns), HCVA, LCVA, and straylight did not differ from that of eyes with normal corneas (P ≥ .09); these eyes encompassed the full range of severity grading of guttae. In FECD with all 3 tomographic features of edema, the same parameters were worse compared with eyes with normal corneas (P ≤ .02). In FECD with 1 or 2 tomographic abnormalities, mesopic LCVA (P = .04) and straylight (P = .003) were worse compared with eyes with normal corneas.Impairment of vision was associated with the presence of tomographic edema in eyes with FECD. When tomography patterns were normal in FECD (ie, guttae were present without tomographic edema), visual acuity and straylight were normal, and therefore corneal surgical intervention would not typically be indicated to improve vision.

To determine the root causes of patient safety events in a high-volume intravitreal injection clinic and to assess the effect of interventions to reduce the rate of events.Quality improvement study.All cases of intravitreal injection in a designated injection clinic between January 1, 2016, and December 31, 2019.The injection clinic model involved an injecting physician, who usually differed from a prescribing physician. The procedural injection area was also physically separate from the retina outpatient clinic. A root cause analysis was used to determine the factors that contributed to possible patient safety events in an institutional quality improvement project. Specific interventions were implemented to address each specific root cause. The rates of patient safety events (never events and near misses), whether associated with patient harm or not, were compared before and after the intervention.Frequency (%) of patient-safety-related intravitreal injection events before (January 1, 2016, to December 31, 2018) and after (January 1, 2019, to December 31, 2019) intervention.The root cause analysis included complex treatment plans that could be difficult to interpret, insufficient time to adequately review the designated treatment plans, and the risk of human error given the pace and volume of scheduled injections. Quality improvement strategies included revising the standardized treatment plan documentation template, scheduling block time for injecting physicians to review treatment plans within 24 hours of the injection clinic, and requiring agreement between dual, independent, site, and medication verifications of the treatment plan by the injecting physician and an allied health coordinator before site marking. The rate of events was 0.1% (28 in 27 400, or 9.3 events per year) before intervention and decreased to 0.01% (1 in 9375, or 1 event per year) after intervention (P = 0.01). Most events were classified as near misses, and there were no instances of patient harm.A high level of patient safety can be achieved in a complex, high-volume intravitreal injection practice by recognizing potential safety issues and root causes and implementing relevant quality improvements. Although most events were near misses and no patients were harmed, reducing near misses can reduce the likelihood of harm associated with never events.

Somatic mutations in the nucleophosmin (NPM1) gene occur in approximately 30% of de novo acute myeloid leukemias (AML), and are relatively enriched in normal karyotype (NK) AMLs. Earlier World Health Organization (WHO) classification schema recognized NPM1-mutated AMLs as a unique subtype of AML, while the latest WHO and International Consensus Classification (ICC) now consider NPM1 mutations as AML-defining, albeit at different blast count thresholds. NPM1 mutational load correlates closely with disease status, particularly in the post-therapy setting, and therefore high sensitivity-based methods for detection of the mutant allele have proven useful for minimal/measurable residual disease (MRD) monitoring. MRD status has been conventionally measured by either multiparameter flow cytometry (MFC) and/or molecular diagnostic techniques, although recent data suggest that MFC data may be potentially more challenging to interpret in this AML subtype. Of note, MRD status does not predict patient outcome in all cases, and therefore a deeper understanding of the biological significance of MRD may be required. Recent studies have confirmed that NPM1-mutated cells rely on overexpression of HOX/MEIS1, which is dependent on the presence of the aberrant cytoplasmic localization of mutant NPM1 protein (NPM1c); this biology may explain the promising response to novel agents, including menin inhibitors and second-generation XPO1 inhibitors. In this review, these and other recent developments around NPM1-mutated AML, in addition to open questions warranting further investigation, will be discussed.

INTRODUCTION: Previous studies have linked sleep to risk of diabetes and obesity, at least partially via alterations in food intake. Diabetes and obesity are common among Hispanics/Latinos, and studies are needed to better clarify the role of sleep in health among this group. Utilizing the revised TFEQ-R-18, this study will examine whether eating behaviors such as cognitive restraint, emotional eating and uncontrolled eating are related to self-reported sleep experiences. Specifically, we hypothesized that poor eating habits would be associated with (1) more insomnia symptoms, (2) overall worse sleep quality, (3) increased daytime sleepiness, and (4) shorter sleep duration. METHODS: Data were collected from N=100 adults (age 18–60, 47% female) of Mexican descent in the city of Nogales, AZ (34% not born in the US). Surveys were presented in English or Spanish. Eating Patterns were assessed with the Three-Factor Eating Questionnaire (TFEQ), which resulted in a total score and subscales for “cognitive restraint,” “uncontrolled eating, “and “emotional eating.” Insomnia was assessed with the use of the Insomnia Severity Index (ISI), Sleepiness with the use of the Epworth Sleepiness Scale (ESS), Sleep quality with the use of the Pittsburgh Sleep Quality Index (PSQI), and weekday and weekend sleep duration with the use of the Sleep Timing Questionnaire (STQ). Covariates included: age, sex, Body Mass Index (BMI), education and immigrant status. RESULTS: Overall TFEQ score (problematic eating) was positively associated with greater insomnia, poorer sleep quality, more sleepiness, and less weekend (but not weekday) sleep. Mean TFEQ score in the sample was 18.7 (range 0–51). In adjusted analyses, every point on the TFEQ was associated with 0.6 ISI points, 0.8 PSQI points, 0.5 ESS points, and 1.1 minutes of less weekend sleep duration. Regarding subscale scores, relationships were generally seen between sleep and emotional eating and unrestricted eating, and not cognitive restraint. CONCLUSIONS: Greater insomnia, poorer sleep quality, increased daytime sleepiness and decreased weekend sleep duration were associated with eating patterns at the US Mexico border, particularly in the area of unrestricted eating and emotional eating. This suggests possible mechanisms linking sleep and obesity in Hispanic/Latinos.

Background An unmet medical need remains for an effective dengue tetravalent vaccine that can be administered irrespective of previous dengue exposure. TAK-003, a dengue tetravalent vaccine, has demonstrated efficacy in an ongoing phase 3 trial in children and adolescents living in dengue-endemic areas, with an acceptable safety profile in both dengue-naive and dengue-exposed individuals. Methods Safety findings are presented herein from an integrated analysis of data for healthy 4–60-year-olds from two phase 2 and three phase 3 double-blind, placebo-controlled clinical trials of TAK-003 (TAK-003, n = 14 627; placebo, n = 7167). Safety evaluation included analyses of postinjection reactogenicity, unsolicited adverse events (AEs), serious AEs (SAEs), and deaths. Subgroup analyses were performed by age group, baseline serostatus, and gender. Results The most common local and systemic AEs were injection site pain (43% for TAK-003 and 26% for placebo) and headache (34% and 30%, respectively). Injection site AEs were mostly mild and resolved within 1–3 days. Unsolicited AEs and AEs leading to discontinuation occurred with similar frequency across both groups, while SAEs were fewer for TAK-003 recipients (6% vs 8% for placebo). Four of the 5 vaccine-related SAEs (which included hypersensitivity, dengue fever, and dengue hemorrhagic fever) occurred in the placebo group. No deaths were considered vaccine-related. Subgroup analyses showed no differences in safety by baseline serostatus or by gender, albeit analysis by age indicated greater local reactogenicity rates for adolescents (46% for TAK-003 and 28% for placebo) and adults (56% and 19%, respectively) than for children (37% and 25%, respectively). Conclusions No important safety risks were identified, and TAK-003 was well tolerated irrespective of age, gender, or baseline dengue serostatus in recipients aged 4–60 years.

Despite having a higher prevalence and severity of obstructive sleep apnea (OSA), African Americans have lower adherence to continuous positive airway pressure (CPAP) compared to other groups. Information regarding challenges faced by African Americans prescribed CPAP are lacking.To determine the barriers and facilitators to optimal management of OSA with CPAP among African Americans and to understand the role bed partners may play.We conducted semi-structured in-depth interviews via video conferencing with African American patients of an urban safety-net health care system with OSA prescribed CPAP and their bed partners. Recruitment continued until theoretical saturation was achieved. Verbatim transcripts were analyzed using the principles of thematic analysis.15 patients (12 women) diagnosed with OSA and prescribed CPAP a mean 2.6 years prior along with 15 bed partners (3 women) were individually interviewed. Four themes emerged regarding impediments to CPAP use: 1) inadequate education and support, 2) CPAP maintenance and hygiene, 3) inconvenient design of CPAP interfaces, and 4) impediment to intimacy. Four themes emerged as facilitators to CPAP use: 1) provider and technical support, 2) properly fitted CPAP masks, 3) active support from partner and family, and 4) experiencing positive results from CPAP.African American patients with OSA and their bed partners identified several unique barriers and facilitators to CPAP use. Active involvement by bed partners was considered by both patients and partners as helpful in improving CPAP adherence. Interventions to improve OSA outcomes in this population should focus on patients and their bed partners.

The goal of this study was to compare outcomes of Descemet stripping endothelial keratoplasty (DSEK) in eyes with glaucoma and abnormal anatomy to eyes with Fuchs endothelial corneal dystrophy (FECD).In a retrospective interventional series of all cases of DSEK between April 1, 2006, and November 30, 2015, recipient diagnosis, preoperative glaucoma status, concurrent surgical procedures, and graft outcomes were recorded. Graft survival, risk of rejection, and subsequent glaucoma surgery were estimated by using Kaplan-Meier analysis with risk factors determined by proportional hazard models.Of 703 DSEKs in 666 eyes (509 subjects), the main recipient diagnoses were FECD (n = 496), pseudophakic corneal edema (n = 112), and failed graft (n = 83). Glaucoma was present in 150 cases before DSEK. Overall graft survival was 85%, 75%, and 71% at 5, 10, and 12 years, respectively, and for FECD without glaucoma was 95%, 89%, and 87% at 5, 10, and 12 years, respectively. Independent risk factors for graft failure included recipient diagnoses of pseudophakic corneal edema (HR = 8.3, P0.001), failed graft (HR = 6.4, P0.001), and preoperative medical glaucoma (HR = 7.1, P0.001) or surgical glaucoma (HR = 12.3, P0.001). Preoperative glaucoma treated by previous surgery resulted in graft survival of 28% at 10 years. Preoperative glaucoma was associated with an increased risk of graft rejection (HR = 6.8, P0.001) and subsequent glaucoma surgery (HR17.4, P0.001).Preoperative glaucoma increases the risk of graft failure, graft rejection, and needing subsequent glaucoma surgery in the first decade after DSEK. With previous glaucoma surgery, DSEK graft survival was more favorable compared with published reports of Descemet membrane endothelial keratoplasty.

Sanskrit character and number documents have a lot of errors. Correcting those errors using conventional spell-checking approaches breaks down due to the limited vocabulary. This is because of high inflexions of Sanskrit, where words are dynamically formed by Sandhi rules, Samasa rules, Taddhita affixes, etc. Therefore, correcting OCR documents require huge efforts. Here, we can present different machine learning approaches and various ways to improve features for ameliorating the error corrections in Sanskrit documents. Simulation of Sanskrit dictionary for synthesizing off-the-shelf dictionary can be done. Most of the proposed methods can also work for general Sanskrit word corrections and Hindi word corrections. Handwriting recognition in Indic scripts, like Devanagari, is very challenging due to the subtitles in the scripts, variations in rendering and the cursive nature of the handwriting. Lack of public handwriting datasets in Indic scripts has long stymied the development of offline handwritten word recognizers and made comparison across different methods a tedious task in the field. In this paper, a new handwritten word dataset will be released for Devanagari, IIIT-HW-Dev to alleviate some of these issues. This process is required for successful training of deep learning architecture, availability of huge amounts of training data is crucial, as any typical architecture contains millions of parameters. A new method for the classification of freeman chain code using four-connectivity and eight-connectivity events with deep learning approach is presented. Application of CNN LeNet-5 is found to be suitable to get results in this cases as the numbers are formed with curved lines In contrast with the existing FCC event data analysis techniques, sampled grey images of the existing events are not used, but image files of the three-phase PQ event data are analysed by taking the advantage of the success of the deep learning approach on imagefile-classification. Therefore, the novelty of the proposed approach is that image files of the voltage waveforms of the three phases of the power grid are classified. It is shown that the test data can be classified with 100% accuracy. The proposed work is believed to serve the needs of the future smart grid applications, which are fast and taking automatic countermeasures against potential PQ events.

Rationale: Prior work suggests that Black persons have more severe obstructive sleep apnea (OSA) upon clinical presentation. However, the extent to which this may reflect differences in symptoms or...

Introduction: Suboptimal sleep health is highly prevalent and multiple dimensions of poor sleep have been identified as obesity predictors. Prior sleep interventions have not demonstrated a convincing effect on reducing obesity but this may be due to focusing on a single sleep dimension. The Transdiagnostic Intervention for Sleep and Circadian Dysfunction (TranS-C) is an efficacious, individually tailored behavioral intervention aimed at improving multiple dimensions of sleep. However, TranS-C has not been tested in adults with excess weight and suboptimal sleep health. Purpose: This single group, pre-test, post-test pilot study conducted in adults with excess weight and suboptimal sleep health examined the feasibility and impact of a remotely delivered, 8-week TranS-C intervention on a composite sleep health score and individual sleep health dimensions. Methods: The six dimensions of sleep addressed in TranS-C were regularity, satisfaction, alertness, timing, efficiency, and duration. Pre- and post-intervention individual sleep dimensions were assessed using validated questionnaires and Fitbit-derived accelerometry data, with values dichotomized into ‘good’ or ‘poor’ for each sleep dimension. A composite sleep health score was calculated as the count of the ‘good’ individual dimensions (possible range 0-6). Effect sizes were calculated as standardized within-subject mean differences ( d ) to describe the intervention effect on the composite score and individual dimensions. We conducted post-intervention semi-structured interviews and used thematic analysis to analyze the qualitative data. Results: Participants (N = 7) were mostly female (71.4%) and white (71.4%) with a mean age of 41.0 ± 17.2 years and mean body mass index of 33.2 ± 3.8 kg/m 2 . Mean composite sleep health score pre-TranS-C was 3.6 ± 1.3 (range 2-5) compared to a mean post-TranS-C composite sleep health score of 4.7 ± 0.8 (range 4-6) ( d = 1.27). Improvements were seen in all individual dimensions except timing with effect sizes ranging from 0.38 to 1.46. During the semi-structured interviews, participants stated that they found the intervention to be informative, liked receiving the sessions remotely, and thought it improved their sleep. However, participants mentioned that some of the modules were not very helpful because information was repetitive or the information did not apply to them, and they suggested that the intervention be delivered in fewer sessions. Conclusions: TranS-C was acceptable for participants with overweight or obesity and suboptimal sleep health and had a large, positive effect on the composite sleep health score. Future refinement of the intervention will include reducing the number of sessions by identifying the most relevant modules and eliminating repetitive information. Continued refinement of the intervention will focus on the content addressing the timing dimension of sleep.

Study objectivesAlthough the importance of upper airway assessment in the consideration of obstructive sleep apnea (OSA) is recognized, there are current limitations in our approach to assessment.MethodsWe convened a group of experts in upper airway neuromuscular physiology and anatomy, sleep apnea endophenotypes, novel therapeutics and sleep epidemiology to summarize existing literature and delineate future opportunities to utilize and incorporate innovative and less invasive techniques focused on upper airway neuromuscular physiology to assess and manage OSA.ResultsIn OSA, genioglossus electromyogram (EMG) activity is reduced during sleep onset with higher levels observed during wakefulness compared to controls. Surface EMG recordings are limited due to distance from the actual muscle and while needle EMG offers more direct assessment, this approach is more invasive. Novel alternatives overcoming these limitations to assess upper airway neuromuscular physiology in OSA may therefore prove beneficial. Specifically, such an approach would facilitate identification of upstream prognostic biomarkers of OSA clinical trajectory and offer more informative mechanistic data. Novel approaches to neuromuscular assessment in OSA would enhance phenotyping to predict better tolerance to positive airway pressure therapy and set the stage to target neuromuscular function and upper airway anatomy. A quantifiable and repeatable neuromuscular physiologic metric has potential to facilitate a precision medicine strategy and personalize treatment, including measuring treatment response to neurophysiologic-focused interventions including hypoglossal nerve stimulation (HGNS), myofunctional therapy and neuromuscular electrical stimulation. A key area for future investigation is whether observed neuromuscular changes can identify patients at future risk of OSA, facilitating early intervention or prevention strategies.ConclusionsOverall, recognizing the critical contributions of abnormalities of upper airway neuromuscular function to the pathophysiology of OSA, it may be important to find accurate and reproducible neurophysiological assessments to address existing knowledge gaps in OSA assessment and management.

PURPOSE Therapy-related acute myeloid leukemias (t-AML) are a heterogenous group of aggressive neoplasms that arise following exposure to cytotoxic chemotherapy and/or ionizing radiation. Many therapy-related myeloid neoplasms (t-MN) are associated with distinct chromosomal aberrations and/or TP53 alterations, but little is known about the clinicopathologic and molecular features of normal karyotype t-AML (NK-t-AML) and whether this t-MN subtype is distinctly different from NK de novo AML (NK-dn-AML). METHODS This multi-institutional study by the Bone Marrow Pathology Group retrospectively evaluated clinicopathologic and molecular characteristics of 335 patients with NK-AML, comprising 105 t-AML and 230 dn-AML cases. RESULTS Patients with t-AML compared with dn-AML exhibit significantly shorter overall survival (OS; median months: 17.6 v 44.2; P < .0001) and relapse-free survival (RFS; median months: 9.1 v 19.2; P = .0018). Frequency of NPM1, FLT3, KRAS, and GATA2 mutations were significantly different in NK-t-AML compared with NK-dn-AML ( NPM1 35% v 49%; P = .0493; FLT3 23% v 36%; P = 0494; KRAS 12% v 5%; P = .0465; GATA2 9% v 2% P = .0105), while TP53 mutations were rare. Patients with t-AML more often stratified into intermediate or adverse 2017 ELN genetic risk groups. Favorable ELN risk predicted favorable OS (hazard ratio [HR], 0.4056; 95% CI, 0 to 0.866; P = .020) and RFS (HR, 0.355; 95% CI, 0 to 0.746; P = .006). Among all patients with NK-AML, stem-cell transplant and favorable ELN risk both significantly affected RFS, while therapy-relatedness and age had a borderline significant impact on OS (HR, 1.355; 95% CI, 0.975 to 1.882; P = .070). CONCLUSION To our knowledge, this is the largest study to date to comprehensively evaluate NK-t-AML and provides a framework that may inform our understanding of NK-t-AML disease biology and could potentially help guide therapeutic management and improved disease classification in t-MNs that lack cytogenetic aberrations.