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Direct insertion of a double-lumen tube (DLT) using a flexible fiberoptic bronchoscope (FOB) is an option for DLT intubation. The different properties of polyvinyl chloride and silicone DLTs may affect railroading differently, which is the difficult process of fiberoptic intubation. Therefore, we aimed to compare intubation using polyvinyl chloride and silicone DLTs over an FOB.Patients aged 19-75 years who required one-lung ventilation under general anesthesia were enrolled in this study. After induction of anesthesia, the anesthesiologist intubated the DLT using FOB. The primary outcome was the difficulty of railroading over the flexible FOB scaled into five grades (I, II-1, II-2, III, and IV). Additionally, the intubation time and mucosal damage were recorded.A total of 46 patients participated in this study, 23 each in the silicone and polyvinyl groups. The difficulty of railroading over the FOB was significantly different between the two groups (P0.001). In the silicone group, the grades of difficulty in railroading were limited to I and II-1; 20 patients (87%) presented no difficulty in advancing the tube. In contrast, in the polyvinyl group, 13 patients (57%) had scores of II-2 and III. Both the intubation time and mucosal damage were significantly better in the silicone group than in the polyvinyl group.Intubation using a silicone DLT over an FOB was easier and faster than that with a polyvinyl chloride DLT with lesser trauma around the glottis.

Frailty is important in diabetes management but its impact on the cardiovascular (CV) effectiveness of SGLT-2i and GLP-1 RA as used in routine care is unexplored. Using Medicare claims data, we identified three pairwise 1:1 propensity score (PS) matched cohorts of people with type 2 diabetes who initiated a SGLT-2i, a GLP-1 RA, or a DPP-4i between 04/2013-12/2018. The primary outcome was a composite of major adverse CV events (MACE) including acute myocardial infarction, ischemic stroke, hospitalization for heart failure, or all-cause mortality. We estimated hazard ratios (HR) and absolute rate differences (RD) per 1`000 person-years, with their 95% CI, in each PS-matched cohort by level of frailty, using a validated claims-based frailty index (3 strata: non-frail, 150 baseline covariates. We used the Wald test for homogeneity to assess treatment heterogeneity across strata. The HR for MACE associated with SGLT-2i vs. DPP4i (n=91`141 PS-matched pairs) was 0.82 (95% CI 0.72 to 0.93) in frail, 0.71 (0.67 to 0.75) in pre-frail, and 0.78 (0.71 to 0.86) in non-frail people (p for homogeneity=0.033) . The HR for MACE associated with GLP-1 RA vs. DPP4i (n=90`988 pairs) was 0.84 (0.76 to 0.93) in frail, 0.77 (95% CI 0.73 to 0.81) in pre-frail, and 0.82 (0.74 to 0.91) in non-frail people (p for h.=0.150) . The HR for MACE associated with SGLT-2i versus GLP-1 RA (n=67`067 pairs) was 0.87 (0.75 to 1.01) in frail, 0.93 (95% CI 0.87 to 1.01) in pre-frail, and 0.90 (0.79 to 1.03) in non-frail people (p for h.=0.692) . Compared to DPP-4i, the absolute benefit of either SGLT-2i or GLP-1 RA was largest in frail people [RD, -25.0 (-42.1 to -7.9) , p for h. Disclosure A.Kutz: Research Support; Novo Nordisk. C.Gopalakrishnan: None. D.H.Kim: None. E.Patorno: Research Support; Boehringer Ingelheim International GmbH, National Institutes of Health, Patient-Centered Outcomes Research Institute. Funding National Institute on Aging (K08AG055670)

The high prevalence of multiple chronic conditions (MCC), multimorbidity, and frailty may affect treatment and outcomes for older adults with cancer. The goal of this study was to use three conceptually distinct measures of morbidity to examine the association between these measures and mortality.Using Medicare claims data linked with the 2012-2016 Ohio Cancer Incidence Surveillance System we identified older adults with incident primary cancer sites of breast, colorectal, lung, or prostate (n = 29,140). We used claims data to identify their Elixhauser comorbidities, Multimorbidity-Weighted Index (MWI), and Claims Frailty Index (CFI) as measures of MCC, multimorbidity, and frailty, respectively. We used Cox proportional hazard models to examine the association between these measures and survival time since diagnosis.Lung cancer patients had the highest levels of MCC, multimorbidity, and frailty. There was a positive association between all three measures and a greater hazard of death after adjusting for age, sex (colorectal and lung only), and stage. Breast cancer patients with 5+ comorbidities had an adjusted hazard ratio (aHR) of 1.63 (95% confidence interval [CI]: 1.38, 1.93), and those with mild frailty had an aHR of 3.38 (95% CI; 2.12, 5.41). The C statistics for breast cancer were 0.79, 0.78, and 0.79 for the MCC, MWI, and CFI respectively. Similarly, lung cancer patients who were moderately or severely frail had an aHR of 1.82 (95% CI: 1.53, 2.18) while prostate cancer patients had an aHR of 3.39 (95% CI: 2.12, 5.41) and colorectal cancer patients had an aHR of 4.51 (95% CI: 3.23, 6.29). Model performance was nearly identical across the MCC, multimorbidity, and frailty models within cancer type. The models performed best for prostate and breast cancer, and notably worse for lung cancer. The frailty models showed the greatest separation in unadjusted survival curves.The MCC, multimorbidity, and frailty indices performed similarly well in predicting mortality among a large cohort of older cancer patients. However, there were notable differences by cancer type. This work highlights that although model performance is similar, frailty may serve as a clearer indicator in risk stratification of geriatric oncology patients than simple MCCs or multimorbidity.

Objective: Both SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1RA) demonstrated cardiovascular benefits in RCTs of patients with type 2 diabetes (T2D) generally Methods: Using Medicare data (4/2013-12/2016), we identified 90,094 1:1 propensity score-matched T2D patients ≥66 years initiating SGLT2i or GLP-1RA. Primary outcomes were major adverse cardiovascular events (MACE, i.e., myocardial infarction, stroke or cardiovascular death) and hospitalization for heart failure (HHF). Other outcomes included diabetic ketoacidosis (DKA), genital infections (GI), fractures, lower-limb amputations (LLA), acute kidney injury (AKI), severe urinary tract infections (UTI), and overall mortality. We estimated hazard ratios (HR) and rate differences (RD) per 1000 person-years, controlling for 140 baseline covariates. Results: Compared with GLP-1RA, SGLT2i initiators had similar MACE risk [HR (95% CI)=0.98 (0.87-1.10); RD (95% CI)= -0.38 (-2.48,1.72)] and reduced HHF risk [HR=0.68 (0.57-0.80)]; RD= -3.23 (-4.68,-1.77)], over a median follow up of approximately 6 months. They also had 0.7 [RD=0.72 (0.02, 1.41)] more DKA, 0.9 [RD=0.90 (0.10, 1.70)] more LLA, 57.1 [RD=57.08 (53.45, 60.70)] more GI, and 7.1 [RD=-7.05 (-10.27, -3.83)] fewer AKI events. Conclusions: Among older adults, SGLT2i had similar MACE risk, decreased HHF risk, and increased risk of DKA, LLA, and GI, vs. GLP-1RA.

The authors sought to assess the distribution and prognostic significance of habitual physical activity (HPA) in older adults undergoing transcatheter aortic valve replacement (TAVR).Low HPA is associated with mortality and disability in community-dwelling older adults. In the setting of TAVR, it is unclear whether low HPA is a risk factor for downstream morbidity or a byproduct of severe aortic stenosis that improves following its correction.Older adults undergoing TAVR in the prospective multicentre FRAILTY-AVR (Frailty in Aortic Valve Replacement) study were interviewed to quantify their HPA in kilocalories/week using a validated questionnaire at baseline and follow-up. The primary endpoint was all-cause mortality at 12 months.The cohort consisted of 755 patients with a median age of 84.0 years (interquartile range [IQR]: 80.0 to 87.0 years). At baseline, median HPA was 1,116 kcal/week (IQR: 227 to 2,715 kcal/week) with 73% of patients performing 150 min/week of moderate or vigorous HPA. Sedentary patients were more likely to be older, female, frail, cognitively impaired, depressed, and have multimorbidity, although they had similar left ventricular function and aortic stenosis severity. In the logistic regression model adjusting for these covariates, HPA was found to be associated with mortality at 12 months (odds ratio: 0.84/100 kcal; 95% confidence interval: 0.73 to 0.98). HPA was associated with longer length of stay, discharge to health care facilities, and disability. At 12 months, median HPA among survivors was 933 kcal/week (IQR: 0 to 2,334 kcal/week) with pre-existing frailty being independently predictive of worsening HPA following TAVR.Sedentary patients have a higher risk of mortality and functional decline following TAVR.

Frailty is a geriatric syndrome that diminishes the potential for functional recovery after a transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) procedure; however, its integration in clinical practice has been limited by a lack of consensus on how to measure it.This study sought to compare the incremental predictive value of 7 different frailty scales to predict poor outcomes following TAVR or SAVR.A prospective cohort of older adults undergoing TAVR or SAVR was assembled at 14 centers in 3 countries from 2012 to 2016. The following frailty scales were compared: Fried, Fried+, Rockwood, Short Physical Performance Battery, Bern, Columbia, and the Essential Frailty Toolset (EFT). Outcomes of interest were all-cause mortality and disability 1 year after the procedure.The cohort was composed of 1,020 patients with a median age of 82 years. Depending on the scale used, the prevalence of frailty ranged from 26% to 68%. Frailty as measured by the EFT was the strongest predictor of death at 1 year (adjusted odds ratio [OR]: 3.72; 95% confidence interval [CI]: 2.54 to 5.45) with a C-statistic improvement of 0.071 (p 0.001) and integrated discrimination improvement of 0.067 (p 0.001). Moreover, the EFT was the strongest predictor of worsening disability at 1 year (adjusted OR: 2.13; 95% CI: 1.57 to 2.87) and death at 30 days (adjusted OR: 3.29; 95% CI: 1.73 to 6.26).Frailty is a risk factor for death and disability following TAVR and SAVR. A brief 4-item scale encompassing lower-extremity weakness, cognitive impairment, anemia, and hypoalbuminemia outperformed other frailty scales and is recommended for use in this setting. (Frailty Assessment Before Cardiac SurgeryTranscatheter Interventions; NCT01845207).

Pyrosequencing is a method used to sequence DNA by detecting the pyrophosphate (PPi) group that is generated when a nucleotide is incorporated into the growing DNA strand in polymerase reaction. However, this method has an inherent difficulty in accurately deciphering the homopolymeric regions of the DNA templates. We report here the development of a method to solve this problem by using nucleotide reversible terminators. These nucleotide analogues are modified with a reversible chemical moiety capping the 3′-OH group to temporarily terminate the polymerase reaction. In this way, only one nucleotide is incorporated into the growing DNA strand even in homopolymeric regions. After detection of the PPi for sequence determination, the 3′-OH of the primer extension products is regenerated through different deprotection methods. Using an allyl or a 2-nitrobenzyl group as the reversible moiety to cap the 3′-OH of the four nucleotides, we have synthesized two sets of 3′- O -modified nucleotides, 3′- O -allyl-dNTPs and 3′- O -(2-nitrobenzyl)-dNTPs as reversible terminators for pyrosequencing. The capping moiety on the 3′-OH of the DNA extension product is efficiently removed after PPi detection by either a chemical method or photolysis. To sequence DNA, templates containing homopolymeric regions are immobilized on Sepharose beads, and then extension–signal detection–deprotection cycles are conducted by using the nucleotide reversible terminators on the DNA beads to unambiguously decipher the sequence of DNA templates. Our results establish that this reversible-terminator-pyrosequencing approach can be potentially developed into a powerful methodology to accurately determine DNA sequences.

We report microporous carbon nanosheets containing numerous redox active heteroatoms fabricated from exfoliated waste coffee grounds by simple heating with KOH for pseudocapacitive charge storage. We found that various heteroatom combinations in carbonaceous materials can be a redox host for lithium ion storage. The bio-inspired nanomaterials had unique characteristics, showing superior electrochemical performances as cathode for asymmetric pseudocapacitors.

Seven tetraploid watermelon lines developed by colchicine treatments were compared with their diploid counterpart for plant, flower, fruit, seed and qualitative characteristics. Tetraploid genotypes attained statistically higher vine thickness (8.04 mm), leaf area (298.9 cm2) and chlorophyll content (55.6) while internode length and chlorophyll fluorescence was similar to their corresponding diploid. Both pistillate and staminate flower organs (pedicel, anther, ovary, stigma, petals) were larger in tetraploid plants; however, the percent increase in flower components varied across the tetraploid lines. Fruit weight and total sugar content (∘Brix) in both ploidy fruits was similar. Rind thickness in fruits varied significantly and averaged 12.7 and 17.2 mm in diploid and tetraploid fruits, respectively. Tetraploid genotypes showed sterility, yielded lower number of seed per fruit (37.9), and tetraploid seed was larger and thicker than diploid seed. Overall β-carotene (0.89), lycopene (1.16), fructose (5.43%) and glucose (2.38%) contents were higher in tetraploid than diploid fruits.

DNA sequencing by synthesis (SBS) offers an approach for potential high-throughput sequencing applications. In this method, the ability of an incoming nucleotide to act as a reversible terminator for a DNA polymerase reaction is an important requirement to unambiguously determine the identity of the incorporated nucleotide before the next nucleotide is added. A free 3′-OH group on the terminal nucleotide of the primer is necessary for the DNA polymerase to incorporate an incoming nucleotide. Therefore, if the 3′-OH group of an incoming nucleotide is capped by a chemical moiety, it will cause the polymerase reaction to terminate after the nucleotide is incorporated into the DNA strand. If the capping group is subsequently removed to generate a free 3′-OH, the polymerase reaction will reinitialize. We report here the design and synthesis of a 3′-modified photocleavable fluorescent nucleotide, 3′- O -allyl-dUTP-PC-Bodipy-FL-510 (PC-Bodipy, photocleavable 4,4-difluoro-4-bora-3α,4α-diaza- s -indacene), as a reversible terminator for SBS. This nucleotide analogue contains an allyl moiety capping the 3′-OH group and a fluorophore Bodipy-FL-510 linked to the 5 position of the uracil through a photocleavable 2-nitrobenzyl linker. Here, we have shown that this nucleotide is a good substrate for a DNA polymerase. After the nucleotide was successfully incorporated into a growing DNA strand and the fluorophore was photocleaved, the allyl group was removed by using a Pd-catalyzed reaction to reinitiate the polymerase reaction, thereby establishing the feasibility of using such nucleotide analogues as reversible terminators for SBS.

We report four-color DNA sequencing by synthesis (SBS) on a chip, using four photocleavable fluorescent nucleotide analogues (dGTP-PC-Bodipy-FL-510, dUTP-PC-R6G, dATP-PC-ROX, and dCTP-PC-Bodipy-650) (PC, photocleavable; Bodipy, 4,4-difluoro-4-bora-3α,4α-diaza- s -indacene; ROX, 6-carboxy-X-rhodamine; R6G, 6-carboxyrhodamine-6G). Each nucleotide analogue consists of a different fluorophore attached to the 5 position of the pyrimidines and the 7 position of the purines through a photocleavable 2-nitrobenzyl linker. After verifying that these nucleotides could be successfully incorporated into a growing DNA strand in a solution-phase polymerase reaction and the fluorophore could be cleaved using laser irradiation (≈355 nm) in 10 sec, we then performed an SBS reaction on a chip that contains a self-priming DNA template covalently immobilized by using 1,3-dipolar azide-alkyne cycloaddition. The DNA template was produced by PCR, using an azido-labeled primer, and the self-priming moiety was attached to the immobilized DNA template by enzymatic ligation. Each cycle of SBS consists of the incorporation of the photocleavable fluorescent nucleotide into the DNA, detection of the fluorescent signal, and photocleavage of the fluorophore. The entire process was repeated to identify 12 continuous bases in the DNA template. These results demonstrate that photocleavable fluorescent nucleotide analogues can be incorporated accurately into a growing DNA strand during a polymerase reaction in solution and on a chip. Moreover, all four fluorophores can be detected and then efficiently cleaved using near-UV irradiation, thereby allowing continuous identification of the DNA template sequence. Optimization of the steps involved in this SBS approach will further increase the read-length.

Editorial Work-related musculoskeletal disorders (WMSDs) constitute a major component of occupational diseases (ODs), accounting for approximately 38.1% of all ODs in Europe [1] and approximately 70% of all compensated ODs in Korea [2]. According to a recent European Union report, WMSDs tend to be underreported and are tending to increase among women, young, and migrant workers. The costs for upper extremity WMSDs alone rage from 0.5 to 3.8% of gross national product [3]. In the United States, costs for compensation, wage loss, and production loss range from 45–54 billion US dollors [4]. Research to prevent these highly costly WMSDs is being conducted in various fields including epidemiology, physiology, ergonomics, biomechanics, molegular biology, and genetics and to tackle such issues as return to work, rehabilitation, policy and compensation. One of the most important avenues of communication for these research efforts is the Intenational Conference on Prevention of Work-related Musculoskeletal Disorders (PREMUS). There are 35 active scientific committees in the International Commission on Occupational Health, and the Musculoskeletal Disorder Committee has held an international conference every 3 years under the name of PREMUS. The most recent PREMUS conference was held in Busan, Korea on July 7–11, 2013. It was the first time that PREMUS was organized outside of North America or Europe. Attending pariticipants were 290 scholars from 30 conutries all over the world, including 11 Asian countries. Among the many papers presented at the conference, 10 describing the spectrum of WMSDs research around world were chosen to public in AOEM. The study by Nur Azmar et al. shows the prevalence and psychosocial risk factors for WMSDs among Malaysian

We present the genomic sequence of Legionella pneumophila , the bacterial agent of Legionnaires' disease, a potentially fatal pneumonia acquired from aerosolized contaminated fresh water. The genome includes a 45–kilobase pair element that can exist in chromosomal and episomal forms, selective expansions of important gene families, genes for unexpected metabolic pathways, and previously unknown candidate virulence determinants. We highlight the genes that may account for Legionella 's ability to survive in protozoa, mammalian macrophages, and inhospitable environmental niches and that may define new therapeutic targets.

This paper presents an inventory model for determining the ordering schedule in which the demand rate is changing linearly with time and the decay is assumed to be a constant rate of the on-hand inventory. Solutions of the model to test problems show that our heuristic model produces a better solution compared to other existing models in the literature.

Three pathologists evaluated a number of designated architectural features to assign grades to 41 cases of well- to moderately differentiated adenocarcinoma, and their opinions were compared. The consensus opinion was obtained and evaluated against objective measurements of glandular architecture that were obtained by morphometric techniques. The observers agreed on gland size, gland uniformity, and the number of glands per field in only 49%, 31%, and 39% of cases, respectively. There were significant differences in the Gleason grades assigned by observers. Paired matching of individual Gleason grades showed agreement among observers in 44% (18 of 41), 56% (23 of 41), and 75% (31 of 41) of cases, respectively. This level of interobserver disagreement occurred even though cases with predominant patterns were selected carefully and those with variable patterns were excluded. A direct relationship appears to exist between increasing Gleason grade and increasing glandular variability, and there is an inverse relationship between Gleason grade, gland lumen area, and the number of glandular nuclei, as assessed by a group of pathologists.

DNA sequencing by synthesis (SBS) on a solid surface during polymerase reaction can decipher many sequences in parallel. We report here a DNA sequencing method that is a hybrid between the Sanger dideoxynucleotide terminating reaction and SBS. In this approach, four nucleotides, modified as reversible terminators by capping the 3′-OH with a small reversible moiety so that they are still recognized by DNA polymerase as substrates, are combined with four cleavable fluorescent dideoxynucleotides to perform SBS. The ratio of the two sets of nucleotides is adjusted as the extension cycles proceed. Sequences are determined by the unique fluorescence emission of each fluorophore on the DNA products terminated by ddNTPs. On removing the 3′-OH capping group from the DNA products generated by incorporating the 3′- O -modified dNTPs and the fluorophore from the DNA products terminated with the ddNTPs, the polymerase reaction reinitiates to continue the sequence determination. By using an azidomethyl group as a chemically reversible capping moiety in the 3′- O -modified dNTPs, and an azido-based cleavable linker to attach the fluorophores to the ddNTPs, we synthesized four 3′- O -azidomethyl-dNTPs and four ddNTP-azidolinker-fluorophores for the hybrid SBS. After sequence determination by fluorescence imaging, the 3′- O -azidomethyl group and the fluorophore attached to the DNA extension product via the azidolinker are efficiently removed by using Tris(2-carboxyethyl)phosphine in aqueous solution that is compatible with DNA. Various DNA templates, including those with homopolymer regions, were accurately sequenced with a read length of >30 bases by using this hybrid SBS method on a chip and a four-color fluorescence scanner.

The goal of this study was to investigate the therapeutic potential of combining radiation therapy and cytotoxic RNase, ranpirnase (ONCONASE; ONC), in human lung tumor models in vitro and in vivo. As translational implications, the non-invasive monitoring response to individual therapy with ONC was also investigated to determine the underlying therapeutic mechanisms.A clonogenic survival assay was used to measure the effect of ONC and radiation on A549 human non-small cell lung carcinoma (NSCLC) cells. HE staining, TUNEL staining and caspase-3-antibody labeling were used for in vivo analysis of apoptosis. A growth-delay assay was applied to detect the therapeutic potential of ONC as a radiation sensitizer in vivo. ONC-induced changes in blood flow and biochemical metabolites were measured by various noninvasive dynamic contrast enhanced magnetic resonance imaging (DCE MRI), non-localized 1H magnetic resonance spectroscopy (MRS), and near-infrared spectroscopy (NIRS) methods.ONC at 5-10 microg/ml sensitized the radiation response of A549 tumor cells in vitro. Remarkable increases in ONC-induced apoptosis in vivo were observed in caspase-3 antibody labeling and TUNEL staining assays. ONC significantly increased the radiation-induced tumor growth delay of A549 tumors. It was observed, when using a DCE MRI method, that there were significant increases in K(trans) values at the rim of tumor regions at 1.5 h post-injection of ONC. When using non-localized 1H MRS, an approximately 20% decrease in lactate levels with ONC was found.ONC may be a new and promising drug in the treatment of NSCLC as a radiation therapy enhancer.

The completion of the Human Genome Project has increased the need for high-throughput DNA sequencing technologies aimed at uncovering the genomic contributions to diseases. The DNA sequencing by synthesis (SBS) approach has shown great promise as a new platform for deciphering the genome. Recently, much progress has been made on the fundamental sciences required to make SBS a viable sequencing technology. One of the unique features of this approach is that many of the steps required are compatible in a modular fashion allowing for the best solution at each stage to be effectively integrated. Recent advances include emulsion-PCR based DNA template preparation, the design and synthesis of novel reporter nucleotides and new surface attachment chemistries for DNA template. The integration of these advances will lead to the development of a high-throughput DNA sequencing system in the near future.

This paper presents a heuristic treatment of a stochastic inventory model for a two-echelon distribution system, in which one central warehouse stocks goods for distribution to retailers. An iterative algorithm is developed to find an optimal or near optimal inventory policy minimizing the total variable system cost per year. Numerical experience with 15 randomly generated problems shows that the algorithm converges rapidly. A numerical example is given to illustrate the savings in annual cost by the two-echelon inventory model compared to the situation where the suboptimal inventory policies are determined sequentially, from the retailer level to the central warehouse.

This paper presents a stochastic inventory model for situations in which, during a stockout period, a fraction β of the demand is backordered and the remaining fraction 1 – β is lost. The model is suggested by the customers' different reactions to a stockout condition: during the stockout period, some patient customers wait until their demand is satisfied, while other impatient or urgent customers cannot wait and have to fill their demand from another source. The cost of a backorder is assumed to be proportional to the length of time for which the backorder exists, and a fixed penalty cost is incurred per unit of lost demand. Based on a heuristic treatment of a lot-size reorder-point policy, a mathematical model representing the average annual cost of operating the inventory system is developed. The optimal operating policy variables minimizing the average annual cost can be calculated iteratively. At the extremes β = 1 and β = 0, the model presented reduces to the usual backorders and lost sales case, respectively.