ONeSAMP 3.0: Estimation of Effective Population Size via SNP Data from One Population.

The genetic effective size (Ne) is arguably one of the most important characteristics of a population as it impacts the rate of loss of genetic diversity. Methods that estimate Ne are important in population and conservation genetic studies as they quantify the risk of a population being inbred or lacking genetic diversity. Yet there are very few methods that can estimate the Ne from data from a single population and without extensive information about the genetics of the population, such as a linkage map, or a reference genome of the species of interest. We present ONeSAMP 3.0, an algorithm for estimating Ne from single nucleotide polymorphism (SNP) data collected from a single population sample using Approximate Bayesian Computation and local linear regression. We demonstrate the utility of this approach using simulated Wright-Fisher populations, and empirical data from five endangered Channel Island fox (Urocyon littoralis) populations to evaluate the performance of ONeSAMP 3.0 compared to a commonly used Ne estimator. Our results show that ONeSAMP 3.0 is is broadly applicable to natural populations and is flexible enough that future versions could easily include summary statistics appropriate for a suite of biological and sampling conditions. ONeSAMP 3.0 is publicly available under the GNU license at https://github.com/AaronHong1024/ONeSAMP_3.

Pfp-fm: an accelerated FM-index.

FM-indexes are crucial data structures in DNA alignment, but searching with them usually takes at least one random access per character in the query pattern. Ferragina and Fischer [1] observed in 2007 that word-based indexes often use fewer random accesses than character-based indexes, and thus support faster searches. Since DNA lacks natural word-boundaries, however, it is necessary to parse it somehow before applying word-based FM-indexing. In 2022, Deng et al. [2] proposed parsing genomic data by induced suffix sorting, and showed that the resulting word-based FM-indexes support faster counting queries than standard FM-indexes when patterns are a few thousand characters or longer. In this paper we show that using prefix-free parsing-which takes parameters that let us tune the average length of the phrases-instead of induced suffix sorting, gives a significant speedup for patterns of only a few hundred characters. We implement our method and demonstrate it is between 3 and 18 times faster than competing methods on queries to GRCh38, and is consistently faster on queries made to 25,000, 50,000 and 100,000 SARS-CoV-2 genomes. Hence, it seems our method accelerates the performance of count over all state-of-the-art methods with a moderate increase in the memory. The source code for PFP - FM is available at https://github.com/AaronHong1024/afm .

PFP-FM: An Accelerated FM-index.

FM-indexes are a crucial data structure in DNA alignment, but searching with them usually takes at least one random access per character in the query pattern. Ferragina and Fischer [1] observed in 2007 that word-based indexes often use fewer random accesses than character-based indexes, and thus support faster searches. Since DNA lacks natural word-boundaries, however, it is necessary to parse it somehow before applying word-based FM-indexing. Last year, Deng et al. [2] proposed parsing genomic data by induced suffix sorting, and showed the resulting word-based FM-indexes support faster counting queries than standard FM-indexes when patterns are a few thousand characters or longer. In this paper we show that using prefix-free parsing-which takes parameters that let us tune the average length of the phrases-instead of induced suffix sorting, gives a significant speedup for patterns of only a few hundred characters. We implement our method and demonstrate it is between 3 and 18 times faster than competing methods on queries to GRCh38, and is consistently faster on queries made to 25,000, 50,000 and 100,000 SARS-CoV-2 genomes. Hence, it seems our method accelerates the performance of count over all state-of-the-art methods with a minor increase in the memory. The source code for PFP-FM is available at https://github.com/marco-oliva/afm.

Routine Preoperative Electrocardiograms in Patients at Low Risk for Cardiac Complications During Shockwave Lithotripsy: Are They Useful?

INTRODUCTION: Routine preoperative electrocardiogram (ECG) before shockwave lithotripsy (SWL) is frequently performed despite recommendations against its use in asymptomatic patients undergoing low-risk surgical procedures. This study assesses whether routine preoperative ECG before SWL is useful in patients at low risk for cardiac complications. MATERIALS AND METHODS: A retrospective study of SWL at our center (2003-2013) reviewed all cardiac-related preoperative cancellations, intraoperative complications, postoperative admissions, and emergency department presentations in patients at low risk for cardiac complications. Patients received SWL with sedation and continuous five-lead ECG monitoring. RESULTS: Of 30,892 referrals, preoperative ECG triggered 13 (0.04%) cancelations in low-risk patients (1 with new atrial fibrillation and 12 with ischemia/previous infarction). Of these patients, 1 had a subsequent abnormal cardiac work-up and 11 underwent uncomplicated SWL without cardiac intervention (2 had unknown history). Of 27,722 treatments, 5 (0.02%) were stopped prematurely in low-risk patients because of arrhythmia (3 had normal preoperative ECG, 1 had abnormal ECG, and 1 did not complete ECG). Three patients developed an arrhythmia with sedation and 2 patients were admitted postoperatively because of cardiac complications (1 for atrial fibrillation and 1 for hypertension), of whom all had normal preoperative ECG. No patients presented to our emergency department with cardiac complications after SWL. CONCLUSIONS: In patients at low risk for cardiac complications, preoperative ECG triggered very few cancellations and did not predict early termination of treatment or cardiac complications after SWL. These findings suggest that in low-risk patients, routine preoperative ECG has little effect on treatment or complication rate and should be omitted.

Perinatal phthalate and high-fat diet exposure induce sex-specific changes in adipocyte size and DNA methylation.

Environmental factors such as diet and endocrine-disrupting chemicals have individually been shown to mediate metabolic function. However, the underlying mechanism by which the combination disrupts adipocyte morphology and fat storage remains unknown. The current study evaluated early-life programming by diet and phthalate exposure. During gestation and lactation, pregnant Long-Evans hooded rat dams were fed either a control (C) or high-fat (HF) diet and were orally administered one of three phthalate dosages (0, 200 or 1000 µg/kg/day), yielding six groups of offspring: C-0, C-200, C-1000, HF-0, HF-200 and HF-1000. On postnatal day (PND) 90, gonadal fat pads were collected and analyzed for histology, gene expression and DNA methylation. Differences in body weight were observed only in males. Hematoxylin and eosin staining revealed larger adipocyte size in HF-0 vs. C-0 females. Exposure to 200 or 1000 µg/kg/day phthalates modulated diet-induced changes in adipose morphology. Compared to C-0 females, HF-0 females also had higher expression of the adipogenesis gene Wnt receptor, frizzled 1 (Fzd1) and the triglyceride cleaving enzyme lipoprotein lipase (Lpl). These increases in gene expression were accompanied by lower DNA methylation surrounding the transcription start sites of the two genes. Diet-driven effects were observed in unexposed females but not in phthalate-treated rats. Results suggest a sex-specific association between perinatal HF diet and body weight, adipocyte size and DNA methylation. Perinatal phthalate exposure appears to produce a phenotype that more closely resembles HF-fed animals.

A randomized-controlled trial of nabilone for the prevention of acute postoperative nausea and vomiting in elective surgery.

PURPOSE: Nabilone is a synthetic cannabinoid with properties that make it an appealing candidate as a postoperative nausea and vomiting (PONV) prophylactic adjunct. Nabilone has proven clinical utility in chemotherapy-related nausea and vomiting but has not been adequately tested for PONV. The purpose of this study was to evaluate the effectiveness of a single dose of nabilone for the prevention of PONV. METHODS: This was a pragmatic single-centre randomized-controlled trial comparing oral nabilone vs placebo for the prevention of PONV. Eligible patients scheduled for elective surgery under general anesthesia who had a preoperative risk of PONV greater than 60% received either nabilone 0.5 mg or placebo orally prior to surgery. As part of the pragmatic design, the study medication was given in addition to any other combination of antiemetic prophylaxis. The primary outcome was the incidence of PONV. Secondary outcomes included the effect on pain, speed of recovery, and drug side effects. RESULTS: Of the 340 patients randomized, 172 received nabilone and 168 received placebo. There was no difference in the incidence of PONV, which occurred in 20.9% in the nabilone group and 21.4% in the placebo group (relative risk, 0.98; 95% confidence interval, 0.89 to 1.11; P = 0.99). There were also no differences in pain scores, opioid consumption, or reported drug side effects. CONCLUSION: Oral nabilone 0.5 mg given as a single dose prior to surgery is ineffective in reducing PONV. This trial was registered at ClinicalTrials.gov, identifier: NCT02115529.

Effect of Medialization Thyroplasty on Glottic Airway Anatomy: Cadaver Model.

OBJECTIVES: The purpose of this study was to investigate the change in airway dimensions after medialization thyroplasty (MT) using a cadaveric model. Helical computerized tomography (CT) was performed before and after placement of a silastic block in human larynges to investigate the effect on airway anatomy at the level of the glottis. Tissue density (TD) of the medialized vocal fold (VF) was documented to understand the effect on tissue displacement. STUDY DESIGN: This is a cadaveric study. METHODS: Thirteen human cadaveric larynges underwent fine-cut CT scan before and after MT was performed using carved blocks in two sizes (small block and large block [LB]). Clientstream software was used to measure laryngeal dimensions: intraglottic volume (IGV), cross-sectional area (CSA), posterior-glottic diameter (PGD), VF density (in Hounsfield units [HUs]), and anterior-posterior diameter (APD). Eight sequential axial sections 0.625 mm cuts) at the level of the true VFs were analyzed. RESULTS: There was a significant decrease between the three conditions for IGV (P < 0.0001) and CSA (P < 0.0001). TD of the VF was increased after MT as indicated by HU increase (P = 0.0003). APD was not significantly changed. PGD was significantly different between the no block to LB placement (P = 0.0012). CONCLUSIONS: MT significantly changes the IGV and CSA at the level of the glottis. Density in the true VF was significantly increased. These findings have important implications for understanding volumetric effects of MT.

Electrophysiological stimulation (Tsui test) is feasible for epidural catheter positioning in adults with chronic back pain: a cohort study.

PURPOSE: Determining epidural catheter placement and accurately depositing corticosteroids at the site of the pathology in adults with chronic back pain can be challenging. Fluoroscopy is considered the standard of care for guiding epidural catheter positioning and subsequent injection in patients receiving epidural corticosteroids, but the technique has some limitations. We hypothesized that electrophysiological stimulation using the Tsui test is feasible for determining the appropriate epidural catheter position in adults with chronic back pain receiving epidural corticosteroids. METHODS: We conducted a prospective cohort study of 12 patients receiving epidural corticosteroid injections for chronic back pain. Anatomical landmarks and epidural needle positions were initially confirmed by fluoroscopy. Epidural catheter position was assessed according to sensory and motor responses, as described by Tsui et al. (Can J Anaesth 45: 640-644, 1998). The current was increased slowly from zero until muscle activity was visible or the current reached 10 mA. The catheter was then advanced until muscle responses occurred in the desired myotome. The test was deemed positive or negative according to the Tsui criteria. The anatomical level was confirmed by fluoroscopy prior to injection. RESULTS: Electrophysiological stimulation effectively established the appropriate epidural catheter position in 11 patients (92%). Epidural stimulation occurred at a mean (SD) threshold of 3.95 (3.35) mA. The kappa statistic between interventions was 0.65, indicating a substantial level of agreement. CONCLUSION: This study demonstrated that electrophysiological stimulation using the Tsui technique is feasible for epidural catheter positioning in adults with chronic back pain. It may optimize epidural steroid injection in this population.

Cricoid pressure provides incomplete esophageal occlusion associated with lateral deviation: a magnetic resonance imaging study.

BACKGROUND: Cricoid pressure is a routine component of rapid sequence induction and is designed to reduce the risk of reflux and its associated morbidity. Recent studies have raised questions regarding the efficacy of cricoid pressure in terms of changes in the pharyngeal and esophageal anatomy. OBJECTIVE: This current descriptive study was designed to observe the anatomical effect of cricoid pressure on the occlusion of esophageal lumen in conscious volunteers using magnetic resonance imaging (MRI). METHODS: We quantitatively assessed esophageal patency before and during application of cricoid pressure in 20 awake volunteers utilizing MRI. RESULTS: Target cricoid pressure was achieved in 16 of 20 individuals, corresponding to a mean percentage reduction in cricovertebral distance of 43% (range 25-80%). Cricoid pressure was applied incorrectly in 4 (20%) individuals as evidenced by no change in the cricovertebral distance. Incomplete esophageal occlusion was seen in 10 of 16, or 62.5% (95% confidence interval 35-85%) of individuals when appropriate cricoid pressure was applied. Incomplete esophageal occlusion was always associated with a lateral deviation of the esophagus. None of the 6 subjects with complete occlusion had esophageal deviation during the appropriate application of cricoid pressure. CONCLUSION: Effective application of cricoid pressure by an experienced operator frequently resulted in lateral deviation of the esophagus and incomplete occlusion of esophageal lumen. Reliance on cricoid pressure for esophageal occlusion requires further evaluation utilizing functional studies.

Central venous catheters and upper-extremity deep-vein thrombosis complicating immune heparin-induced thrombocytopenia.

Heparin-induced thrombocytopenia (HIT) is a transient antibody-mediated hypercoagulability state strongly associated with lower-limb deep-vein thrombosis (DVT). Whether HIT is additionally associated with upper-limb DVT--either with or without central venous catheter (CVC) use--is unknown. We therefore studied 260 patients with antibody-positive HIT to determine the influence of CVC use on frequency and localization of upper-extremity DVT in comparison with 2 non-HIT control populations (postoperative orthopedic surgery and intensive-care unit patients). Compared with the control populations, both upper- and lower-extremity DVTs were found to be associated with HIT. Upper-extremity DVTs occurred more frequently in HIT patients with a CVC (14 of 145 [9.7%]) versus none of 115 (0%) patients without a CVC (P =.000 35). All upper-extremity DVTs occurred at the CVC site (right, 12; left, 2; kappa = 1.0; P =.011). We conclude that a localizing vascular injury (CVC use) and a systemic hypercoagulability disorder (HIT) interact to explain upper-extremity DVT complicating HIT.