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Background: Idiopathic hypersomnia is a debilitating sleep disorder; however, little is known about the clinical presentation of patients receiving this diagnosis. Methods: A retrospective cohort study of IBM® MarketScan® claims (January 2014 to September 2019) was conducted. Analysis cohorts included adults ≥18 years of age from the MarketScan population and a subset newly diagnosed with idiopathic hypersomnia. Diagnosis required ≥2 idiopathic hypersomnia claims separated by ≥1 and ≤180 days, and continuous enrollment ≥12 months before the diagnosis date. Descriptive statistics were reported for diagnosing medical specialties, objective sleep laboratory testing utilization, and comorbidities in the 12 months prior to diagnosis. Results: From the general MarketScan cohort (N = 32,948,986), 4980 patients (0.015%) were newly diagnosed with idiopathic hypersomnia (mean age, 42.7 years; 66.9% female). The most common diagnosing medical specialties were pulmonary medicine (23.3%), neurology (14.4%), and internal medicine (11.4%). Only 44.4% of patients received objective sleep laboratory testing during the 12 months prior to diagnosis. The most common comorbidities were sleep apnea (49.5%), mood disorders (32.1%), depressive and anxiety disorders (31.0%, 30.7%, respectively), hyperlipidemia (30.1%), headache/migraine (23.9%), diabetes or use of diabetes/obesity medication (19.8%), hypertension (15.0%), and history of cardiovascular disease (14.3%). Conclusions: These results suggest that idiopathic hypersomnia is diagnosed by multiple medical specialists, and less than half of clinicians utilize proximate sleep laboratory testing prior to patient diagnosis in real-world settings. Furthermore, patients commonly have cardiovascular, metabolic, and psychiatric comorbidities. Healthcare providers should consider these comorbidities and cardiometabolic risks when evaluating treatment options for idiopathic hypersomnia.

Ongoing observing projects like the James Webb Space Telescope and future missions offer the chance to characterize Earth-like exoplanetary atmospheres. Thereby, M dwarfs are preferred targets for transit observations, for example, due to their favorable planet–star contrast ratio. However, the radiation and particle environment of these cool stars could be far more extreme than what we know from the Sun. Thus, knowing the stellar radiation and particle environment and its possible influence on detectable biosignatures—in particular, signs of life like ozone and methane—is crucial to understanding upcoming transit spectra. In this study, with the help of our unique model suite INCREASE, we investigate the impact of a strong stellar energetic particle event on the atmospheric ionization, neutral and ion chemistry, and atmospheric biosignatures of TRAPPIST-1e. Therefore, transit spectra for six scenarios are simulated. We find that a Carrington-like event drastically increases atmospheric ionization and induces substantial changes in ion chemistry and spectral transmission features: all scenarios show high event-induced amounts of nitrogen dioxide (i.e., at 6.2 μ m), a reduction of the atmospheric transit depth in all water bands (i.e., at 5.5–7.0 μ m), a decrease of the methane bands (i.e., at 3.0–3.5 μ m), and depletion of ozone (i.e., at ∼9.6 μ m). Therefore, it is essential to include high-energy particle effects to correctly assign biosignature signals from, e.g., ozone and methane. We further show that the nitric acid feature at 11.0–12.0 μ m, discussed as a proxy for stellar particle contamination, is absent in wet-dead atmospheres.

Abstract Background Tonsillectomy is a commonly performed procedure in Canada. The rate of occult malignancy is rare in adult and pediatric populations. At present, no guidelines exist surrounding the need for routine histopathological evaluation of tonsil specimens when no malignancy is suspected. Methods We sent a confidential online survey to active members of the Canadian Society of Otolaryngology – Head and Neck Surgery (CSO-HNS) about their current tonsillectomy practice and beliefs surrounding the need for routine histopathological evaluation of tonsillectomy specimens when no malignancy is suspected. We used Opinio survey software for data collection and descriptive statistics. Results 95 participants completed our survey (response rate 19.3%). Most participants reported performing both adult and pediatric tonsillectomies. When no malignancy is suspected, participant responses were split between whether they send tonsil specimens in pediatrics only (4.2%), in adults only (31.6%), or not sending specimens (29.5%). Half of the participants reported that routinely sending specimens to rule out occult malignancy is an institutional policy. Approximately 75% of participants were in favour of removing this practice in both the pediatric and adult populations. Conclusion Eliminating the practice of automatically sending tonsil specimens for histopathological evaluation when no malignancy is suspected was supported by the majority of study participants. This is in keeping with Choosing Wisely, a campaign designed to facilitate conversations about unnecessary medical tests and procedures. Institutional change is likely required in order to alter this practice. Graphical Abstract

Whole genome sequencing data are increasingly becoming routinely available but generating actionable insights is challenging. Here, the authors describe Pathogenwatch, a web tool for genomic surveillance of S. Typhi, and demonstrate its use for antimicrobial resistance assignment and strain risk assessment.

Abstract Background Antimicrobial-resistant (AMR) Neisseria gonorrhoeae is an urgent threat to public health, as strains resistant to at least one of the two last-line antibiotics used in empiric therapy of gonorrhoea, ceftriaxone and azithromycin, have spread internationally. Whole genome sequencing (WGS) data can be used to identify new AMR clones and transmission networks and inform the development of point-of-care tests for antimicrobial susceptibility, novel antimicrobials and vaccines. Community-driven tools that provide an easy access to and analysis of genomic and epidemiological data is the way forward for public health surveillance. Methods Here we present a public health-focussed scheme for genomic epidemiology of N. gonorrhoeae at Pathogenwatch ( https://pathogen.watch/ngonorrhoeae ). An international advisory group of experts in epidemiology, public health, genetics and genomics of N. gonorrhoeae was convened to inform on the utility of current and future analytics in the platform. We implement backwards compatibility with MLST, NG-MAST and NG-STAR typing schemes as well as an exhaustive library of genetic AMR determinants linked to a genotypic prediction of resistance to eight antibiotics. A collection of over 12,000 N. gonorrhoeae genome sequences from public archives has been quality-checked, assembled and made public together with available metadata for contextualization. Results AMR prediction from genome data revealed specificity values over 99% for azithromycin, ciprofloxacin and ceftriaxone and sensitivity values around 99% for benzylpenicillin and tetracycline. A case study using the Pathogenwatch collection of N. gonorrhoeae public genomes showed the global expansion of an azithromycin-resistant lineage carrying a mosaic mtr over at least the last 10 years, emphasising the power of Pathogenwatch to explore and evaluate genomic epidemiology questions of public health concern. Conclusions The N. gonorrhoeae scheme in Pathogenwatch provides customised bioinformatic pipelines guided by expert opinion that can be adapted to public health agencies and departments with little expertise in bioinformatics and lower-resourced settings with internet connection but limited computational infrastructure. The advisory group will assess and identify ongoing public health needs in the field of gonorrhoea, particularly regarding gonococcal AMR, in order to further enhance utility with modified or new analytic methods.

Abstract Background Patient reported outcome measurements (PROMs) are emerging as an important component of patient management in the cancer setting, providing broad perspectives on patients’ quality of life and experience. The use of PROMs is, however, generally limited to the context of randomised control trials, as healthcare services are challenged to sustain high quality of care whilst facing increasing demand and financial shortfalls. We performed a systematic review of the literature to identify any oncological benefit of using PROMs and investigate the wider impact on patient experience, in cancers of the pelvic abdominal cavity specifically. Methods A systematic review of the literature was conducted using MEDLINE (Pubmed) and Ovid Gateway (Embase and Ovid) until April 2020. Studies investigating the oncological outcomes of PROMs were deemed suitable for inclusion. Results A total of 21 studies were included from 2167 screened articles. Various domains of quality of life (QoL) were identified as potential prognosticators for oncologic outcomes in cancers of the pelvic abdominal cavity, independent of other clinicopathological features of disease: 3 studies identified global QoL as a prognostic factor, 6 studies identified physical and role functioning, and 2 studies highlighted fatigue. In addition to improved outcomes, a number of included studies also reported that the use of PROMs enhanced both patient-clinician communication and patient satisfaction with care in the clinical setting. Conclusions This review highlights the necessity of routine collection of PROMs within the pelvic abdominal cancer setting to improve patient quality of life and outcomes.

CubeSats are being increasingly specified and utilized for demanding astronomical and Earth observation missions where precise pointing and stability are critical requirements. Such precision is difficult to achieve in the case of CubeSats, mainly because of their small moment of inertia, this means that even small disturbance torques, such as those due to a residual magnetic moment are an issue and have a significant effect on the attitude of nanosatellites, when a high degree of stability is required. Also, hardware limitations in terms of power, weight and size, make the task more challenging. Recently, a PhD research program has been undertaken at the University of Surrey, to investigate the magnetic characteristics of CubeSats, it has been found that the disturbances may be mitigated by good engineering practice, in terms of reducing the use of permeable materials and minimizing current-loop area. This paper discusses the dominant source nanosatellites disturbances and presents a survey and a short description of magnetic cleanliness techniques to minimize the effect of the residual magnetic field. It is mainly intended to supply a guide for CubeSat community to design future CubeSats with improved attitude stability. We present then our findings to date of a new technique of the residual magnetic dipole determination for CubeSats and Nanosatellites. This method is performed by implementing a network of eight miniature 3-axis magnetometers on the spacecraft. These are used to determine the strength, the direction and the center of the magnetic dipole of the spacecraft dynamically in-orbit and in real-time. This technique will contribute to reduce the effect of magnetic disturbances and improve the stability of CubeSats. A software model and a hardware prototype using eight magnetometers controlled via a Raspberry-Pi were developed and successfully tested with the boom payload of the Alsat-1N CubeSat and a magnetic air coil developed for validation purposes.

Objective: Focused echocardiography during peri-shock pause (PSP) can prognosticate and detect reversible causes in cardiac arrest but minimising interruptions to chest compressions improves outcome. The COACH-RED protocol was adapted from the COACHED protocol to systematically incorporate echocardiography into rhythm check without prolonging PSP beyond the recommended 10 s. The primary objective of this study was to test the feasibility of emergency nurses learning to perform all roles in the COACH-RED protocol. PSP duration and change in participant confidence were secondary outcomes. Methods: After an initial two-hour workshop, five ALS-trained nurses were assessed for the correct use of COACH-RED protocol, without critical error, in three simulated cardiac arrest scenarios of four cycles each. Assessments were repeated on days 7 and 35. On day 35, three COACHED scenarios were also assessed for comparison. Participant roles per scenario and cardiac rhythm per cycle were randomised. Participants completed questionnaires on their confidence levels. Sessions were videotaped for accurate measurement of PSP duration and results tabulated for simple comparison. Statistical analysis was not performed due to small sample size. Results: There were no critical errors, two minor team-leading errors and two minor echosonography errors. Minor errors occurred in separate scenarios resulting in a 100% pass rate overall by predetermined criteria. Echocardiographic recordings were 100% adequate. Overall median PSP was 9.35 s for COACH-RED and 6.94 s for COACHED. Sub-group analysis of COACH-RED revealed median PSP 10.80 s in shockable rhythms and 8.74 s (∼2 s less) in non-shockable rhythms. Mean participant confidence in performing COACH-RED improved from 1.6 to 4.6, on a 5-point scale. Conclusion: The COACH-RED protocol can be effectively performed by ALS-trained nurses, in all roles of this protocol, including echocardiography, in a simulated environment, after a single training session. Using this protocol, focused echocardiography does not prolong PSP beyond 10 s.

Abstract Background Patients who have undergone treatment for head and neck cancer are at risk for neck lymphedema, which can severely affect quality of life. Liposuction has been used successfully in cancer patients who suffer from post-treatment limb lymphedema. The purpose of our study was to review the outcomes of head and neck cancer patients at our center who have undergone submental liposuction for post-treatment lymphedema and compare their subsequent results with a control group. Methods All head and neck cancer patients at an oncology center in tertiary hospital setting who complained to their attending surgeon or radiation oncologist regarding cervical lymphedema secondary to head and neck cancer treatment, and had been disease-free for a minimum of one year, with no previous facial plastic surgical procedures were eligible for inclusion into the study. Study design was a non-blinded randomized controlled trial. Twenty patients were randomized into a treatment arm (underwent submental liposuction n = 10) and control arm (n = 10). Both groups of patients completed two surveys (Modified Blepharoplasty Outcome Evaluation and the validated Derriford Appearance Scale) on initial office visit after consenting for the trial. The treatment group then completed the surveys 6 months post-operatively while the control group filled the surveys 6 months after the initial assessment but had no intervention. Mann-Whitney U tests were performed to compare the responses of those that did and did not receive liposuction. Results Our study demonstrated a statistically significant improvement in patients’ self-perception of appearance and statistically significant subjective scoring of appearance following submental liposuction. Conclusions Submental liposuction is an effective and safe procedure to improves the quality of life for head and neck cancer patients suffering from post-treatment lymphedema.

Microcombustion attracts interest with its promise of energy dense power generation for electronics. Yet, challenges remain to develop this technology further. Thermal management of heat losses is a known hurdle. Simultaneously, non-uniformities in heat release within the reaction regions also affect the device performance. Therefore a combination of thermal management strategies are necessary for further performance enhancements. Here, a bench top platinum nanoparticle based microcombustion reactor, coupled with thermoelectric generators is used. Methanol-air mixtures achieve room temperature ignition within a catalytic cartridge. In the current study, the reactor design is modified to incorporate two traditional thermal management strategies. By limiting enthalpic losses through the exhaust and reactor sides, using multi-pass preheating channels and heat recirculation, expected improvements are achieved. The combined strategies doubled the power output to 1.01 W when compared to the previous design. Furthermore, a preliminary study of catalyst distribution is presented to mitigate non-uniform catalytic activity within the substrate. To do this, tailored distribution of catalyst particles was investigated. This investigation shows a proof-of-concept to achieve localized control, thus management, over heat generation within substrates. By optimizing heat generation, a highly refined combustion-based portable power devices can be envisioned.

Category: Trauma, Ankle, Ankle Arthritis Introduction/Purpose: Ankle fractures in complicated diabetic patients (i.e. presence of neuropathy, nephropathy, or peripheral vascular disease) have significantly increased rates of complications with markedly worse functional outcomes. Current management advocates for operative intervention due to high rates of fracture reduction loss and Charcot arthropathy in those treated nonoperatively. Tibiotalocalcaneal (TTC) nails have been reported in the literature as a salvage option when initial ankle stabilization has failed. We hypothesize that the minimally invasive, robust construct that primary TTC fixation with an intramedullary nail offers will result in high rates of limb salvage, acceptable rates of complications, and nominal loss of function. Thus, the purpose of this study was to evaluate the outcomes of primary TTC intramedullary nailing for definitive treatment of neuropathic ankle fractures. Methods: This was an IRB approved retrospective study of 27 complicated diabetic patients who underwent TTC nailing of their ankle fracture as a primary treatment without formal joint preparation. The study was undertaken at an urban Level 1 trauma center. Complicated diabetes was defined as having one or more of the following formal diagnoses: neuropathy (20 patients), nephropathy (4), PVD (3). Mean clinical follow up was 888 days (range 21-2843 days). Patients were screened for associated risk factors such as open fracture, neuropathy, nicotine and alcohol abuse, obesity and elevated Hba1c. Data was also collected on surgical complications such as superficial and deep infection, wound dehiscence, amputation, revision fixation, hardware failure, malunion, nonunion. Outcomes were measured in length of hospital stay, loss of ambulatory level, and time to death. Results: The mean age was 66 (32-92) years with an average BMI of 38 (21-68). Six of 27 fractures were open and 20 of 27 patients were neuropathic. Mean hemoglobin A1C was 7.4 (5.5-13). Average hospital stay was 6 days (0-22). The average patient was fully weight bearing at 6 weeks (1-17). Two patients underwent removal of hardware, due to pain and proximal screw failure respectively. One patient required formal arthrodesis. There were no malunions, symptomatic nonunions, or instances of Charcot arthropathy. Two patients underwent repeat debridement for infection, resulting in antibiotic nail placement and above knee amputation respectively. A total of eight patients had died by final follow up (mean 1048 days) from index procedure. Overall, mean ambulatory status was maintained. Conclusion: Primary tibiotalocalcaneal nailing is a viable alternative to previously described methods of fixation of complicated diabetic ankle fractures. With high limb salvage rates, early weight bearing, maintained ambulatory status and low rates of return to the operating room, our technique can be considered an applicable approach to increase overall survivability of threatened limbs and lives with acceptably low complications.

PurposeTo validate prognostic factors and determine the impact of obesity, hypertension, smoking and diabetes mellitus (DM) on risk of recurrence after surgery in patients with localized renal cell carcinoma (RCC).Materials and methodsWe performed a retrospective cohort study among patients that underwent partial or radical nephrectomy at Weill Cornell Medicine for RCC and collected preoperative information on RCC risk factors, as well as pathological data. Cases were reviewed for radiographic evidence of RCC recurrence. A Cox proportional-hazards model was developed to determine the contribution of RCC risk factors to recurrence risk. Disease-free survival and overall survival were analyzed using the Kaplan-Meier method and log-rank test.ResultsWe identified 873 patients who underwent surgery for RCC between the years 2000-2015. In total 115 patients (13.2%) experienced a disease recurrence after a median follow up of 4.9 years. In multivariate analysis, increasing pathological T-stage (HR 1.429, 95% CI 1.265-1.614) and Nuclear grade (HR 2.376, 95% CI 1.734-3.255) were independently associated with RCC recurrence. In patients with T1-2 tumors, DM was identified as an additional independent risk factor for RCC recurrence (HR 2.744, 95% CI 1.343-5.605). Patients with DM had a significantly shorter median disease-free survival (1.5 years versus 2.6 years, p = 0.004), as well as median overall survival (4.1 years, versus 5.8 years, pConclusionsWe validated high pathological T-stage and nuclear grade as independent risk factors for RCC recurrence following nephrectomy. DM is associated with an increased risk of recurrence among patients with early stage disease.

BackgroundContact with the healthcare system represents an opportunity for individuals who discontinue statins to re‐initiate treatment. To help identify opportunities for healthcare providers to emphasize the risk‐lowering benefits accrued through restarting statins, we determined the types of healthcare utilization associated with statin re‐initiation among patients with history of a myocardial infarction. Methods and ResultsMedicare beneficiaries with a statin pharmacy fill claim within 30 days of hospital discharge for a myocardial infarction in 2007 to 2012 (n=158 795) were followed for 182 days postdischarge to identify treatment discontinuation, defined as 60 continuous days without statins (n=24 461). Re‐initiation was defined as a statin fill within 365 days of the discontinuation date (n=13 136). Using a case‐crossover study design and each beneficiary as their own control, healthcare utilization during 0 to 14 days before statin re‐initiation (case period) was compared with healthcare utilization 30 to 44 days before statin re‐initiation (control period). The mean age of beneficiaries was 75.4 years; 52.8% were women and 81.9% were white. For routine healthcare utilization, the odds ratio (95% confidence interval) for statin re‐initiation associated with lipid panel testing was 2.65 (1.93–3.65), outpatient primary care was 1.31 (1.23–1.40), and outpatient cardiologist care was 1.38 (1.28–1.50). For acute healthcare utilization, the odds ratio (95% confidence interval) for statin re‐initiation associated with emergency department visits was 1.77 (1.31–2.40), coronary heart disease (CHD) hospitalizations was 3.16 (2.41–4.14) and non–coronary heart disease hospitalizations was 1.73 (1.49–2.01). ConclusionsThe weaker association of routine versus acute healthcare utilization with statin re‐initiation suggests missed opportunities to reinforce the importance of statin therapy for secondary prevention.

Turning genes on and off is essential for development and homeostasis, yet little is known about the sequence and causal role of chromatin state changes during the repression of active genes. This is surprising, as defective gene silencing underlies developmental abnormalities and disease. Here we delineate the sequence and functional contribution of transcriptional repression mechanisms at high temporal resolution. Inducible entry of the NuRD-interacting transcriptional regulator Ikaros into mouse pre-B cell nuclei triggered immediate binding to target gene promoters. Rapid RNAP2 eviction, transcriptional shutdown, nucleosome invasion, and reduced transcriptional activator binding required chromatin remodeling by NuRD-associated Mi2beta/CHD4, but were independent of HDAC activity. Histone deacetylation occurred after transcriptional repression. Nevertheless, HDAC activity contributed to stable gene silencing. Hence, high resolution mapping of transcriptional repression reveals complex and interdependent mechanisms that underpin rapid transitions between transcriptional states, and elucidates the temporal order, functional role and mechanistic separation of NuRD-associated enzymatic activities.

The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/.

We investigate whether the Trap-Neuter-Return (TNR) program can be effectively used to control the population of free-roaming cats in Florida's Lee County. We do this by estimating the number of cats that must be spayed/neutered in order to keep the population from increasing.