Is total pancreatectomy as feasible, safe, efficacious, and cost-effective as pancreaticoduodenectomy? A single center, prospective, observational study.

Science.gov (United States)

Casadei, Riccardo; Ricci, Claudio; Taffurelli, Giovanni; Guariniello, Anna; Di Gioia, Anthony; Di Marco, Mariacristina; Pagano, Nico; Serra, Carla; Calculli, Lucia; Santini, Donatella; Minni, Francesco

2016-09-01

Total pancreatectomy is actually considered a viable option in selected patients even if large comparative studies between partial versus total pancreatectomy are not currently available. Our aim was to evaluate whether total pancreatectomy can be considered as feasible, safe, efficacious, and cost-effective as pancreaticoduodenectomy. A single center, prospective, observational trial, regarding postoperative outcomes, long-term results, and cost-effectiveness, in a tertiary referral center was conducted, comparing consecutive patients who underwent elective total pancreatectomy and/or pancreaticoduodenectomy. Seventy-three consecutive elective total pancreatectomies and 184 pancreaticoduodenectomies were compared. There were no significant differences regarding postoperative outcomes and overall survival. The quality of life, evaluated in 119 patients according to the EQ-5D-5L questionnaire, showed that there were no significant differences regarding the five items considered. The mean EQ-5D-5L score was similar in the two procedures (total pancreatectomy = 0.872, range 0.345-1.000; pancreaticoduodenectomy = 0.832, range 0.393-1.000; P = 0.320). The impact of diabetes according to the Problem Areas in Diabetes (PAID) questionnaire did not show any significant differences except for question 13 (total pancreatectomy = 0.60; pancreaticoduodenectomy = 0.19; P = 0.022). The cost-effectiveness analysis suggested that the quality-adjusted life year was not significantly different between the two procedures (total pancreatectomy = 0.910, range 0.345-1.000; pancreaticoduodenectomy = 0.910, range -0.393-1.000; P = 0.320). From this study, it seems reasonable to suggest that total pancreatectomy can be considered as safe, feasible, and efficacious as PD and acceptable in terms of cost-effectiveness.

Direct cost comparison of totally endoscopic versus open ear surgery.

Science.gov (United States)

Patel, N; Mohammadi, A; Jufas, N

2018-02-01

Totally endoscopic ear surgery is a relatively new method for managing chronic ear disease. This study aimed to test the null hypothesis that open and endoscopic approaches have similar direct costs for the management of attic cholesteatoma, from an Australian private hospital setting. A retrospective direct cost comparison of totally endoscopic ear surgery and traditional canal wall up mastoidectomy for the management of attic cholesteatoma in a private tertiary setting was undertaken. Indirect and future costs were excluded. A direct cost comparison of anaesthetic setup and resources, operative setup and resources, and surgical time was performed between the two techniques. Totally endoscopic ear surgery has a mean direct cost reduction of AUD$2978.89 per operation from the hospital perspective, when compared to canal wall up mastoidectomy. Totally endoscopic ear surgery is more cost-effective, from an Australian private hospital perspective, than canal wall up mastoidectomy for attic cholesteatoma.

Effects of the Length of Stay on the Cost of Total Knee and Total Hip Arthroplasty from 2002 to 2013.

Science.gov (United States)

Molloy, Ilda B; Martin, Brook I; Moschetti, Wayne E; Jevsevar, David S

2017-03-01

Utilization of total knee and hip arthroplasty has greatly increased in the past decade in the United States; these are among the most expensive procedures in patients with Medicare. Advances in surgical techniques, anesthesia, and care pathways decrease hospital length of stay. We examined how trends in hospital cost were altered by decreases in length of stay. Procedure, demographic, and economic data were collected on 6.4 million admissions for total knee arthroplasty and 2.8 million admissions for total hip arthroplasty from 2002 to 2013 using the National (Nationwide) Inpatient Sample, a component of the Healthcare Cost and Utilization Project. Trends in mean hospital costs and their association with length of stay were estimated using inflation-adjusted, survey-weighted generalized linear regression models, controlling for patient demographic characteristics and comorbidity. From 2002 to 2013, the length of stay decreased from a mean time of 4.06 to 2.97 days for total knee arthroplasty and from 4.06 to 2.75 days for total hip arthroplasty. During the same time period, the mean hospital cost for total knee arthroplasty increased from $14,988 (95% confidence interval [CI], $14,927 to $15,049) in 2002 to $22,837 (95% CI, $22,765 to $22,910) in 2013 (an overall increase of $7,849 or 52.4%). The mean hospital cost for total hip arthroplasty increased from $15,792 (95% CI, $15,706 to $15,878) in 2002 to $23,650 (95% CI, $23,544 to $23,755) in 2013 (an increase of $7,858 or 49.8%). If length of stay were set at the 2002 mean, the growth in cost for total knee arthroplasty would have been 70.8% instead of 52.4% as observed, and the growth in cost for total hip arthroplasty would have been 67.4% instead of 49.8% as observed. Hospital costs for joint replacement increased from 2002 to 2013, but were attenuated by reducing inpatient length of stay. With demographic characteristics showing an upward trend in the utilization of joint arthroplasty, including a shift

Managing the total cost of risk exposures through risk mapping techniques

International Nuclear Information System (INIS)

Unione, A.J.; Rode, D.M.

1998-01-01

In a competitive power market, power producers are exposed to an increasingly broad spectrum of financial risks. The cumulative impact of these financial risks is known collectively as the Total of Cost of Risk. The concept of Total of Cost of Risk presents the business reality of a company's exposure to potentially devastating financial consequences in an integrated and useful way. In this way, a strategy of managing Total Cost of Risk in the most cost effective way can become a means of ensuring long term business health and security. This paper will examine the use of risk mapping as a tool for visually understanding Total Cost of Risk, thus creating an enhanced situational awareness and an integrated basis for risk management decision. The evaluation process, available through the use of risk maps allows the power producers to pro-actively implement prudent business decisions concerning the design, operation and maintenance of power plants. Risk mapping is thus a means for harmonizing operational objectives, such as improved plant reliability, with corporate strategies and goals in terms of an effective risk management program

Half a decade of mini-pool nucleic acid testing: Cost-effective way for improving blood safety in India

Directory of Open Access Journals (Sweden)

Shivaram Chandrashekar

2014-01-01

Full Text Available Background and Objectives: It is well established that Nucleic acid testing (NAT reduces window phase of transfusion transmissible infections (TTI and helps improve blood safety. NAT testing can be done individually or in pools. The objectives of this study were to determine the utility, feasibility and cost effectiveness of an in-house minipool-NAT(MP-NAT. Materials and Methods: Blood donors were screened by history, tested by ELISA and sero-negative samples were subjected to an in-house NAT by using reverse transcriptase-polymerase chain reaction (RT-PCR. Testing was done in mini-pools of size eight (8. Positive pools were repeated with individual samples. Results: During the study period of Oct 2005-Sept 2010 (5 years all blood donors (n=53729 were screened by ELISA. Of which 469 (0.87% were positive for HIV-1, HBV or HCV. Sero-negative samples (n=53260 were screened by in-house MP-NAT. HIV-NAT yield was 1/53260 (n=1 and HBV NAT yield (n=2 was 1/26630. Conclusion: NAT yield was lower than other India studies possibly due to the lower sero-reactivity amongst our donors. Nevertheless it intercepted 9 lives including the components prepared. The in-house assay met our objective of improving blood safety at nominal cost and showed that it is feasible to set up small molecular biology units in medium-large sized blood banks and deliver blood within 24-48 hours. The utility of NAT (NAT yield will vary based on the donor population, the type of serological test used, the nature of kit employed and the sensitivity of NAT test used. The limitations of our in-house MP-NAT consisted of stringent sample preparation requirements, with labor and time involved. The benefits of our MP-NAT were that it acted as a second level of check for ELISA tests, was relatively inexpensive compared to ID-NAT and did not need sophisticated equipment.

Total Cost of Ownership and Cost-to-Serve

DEFF Research Database (Denmark)

Zachariassen, Frederik

2007-01-01

Artiklen reviewer den eksisterende litteratur vedrørende økonomistyringsværktøjerne Total Cost of Ownership (TCO) og Cost-to-Serve (CtS). Herefter kortlægges det, hvordan TCO og CtS bidrager til en identificering af direkte omkostninger såvel som indirekte omkostninger henholdsvis up-stream og down...

Total generating costs: coal and nuclear plants

International Nuclear Information System (INIS)

1979-02-01

The study was confined to single and multi-unit coal- and nuclear-fueled electric-generating stations. The stations are composed of 1200-MWe PWRs; 1200-MWe BWRs; 800-and 1200-MWe High-Sulfur Coal units, and 800- and 1200-MWe Low-Sulfur Coal units. The total generating cost estimates were developed for commercial operation dates of 1985 and 1990; for 5 and 8% escalation rates, for 10 and 12% discount rates; and, for capacity factors of 50, 60, 70, and 80%. The report describes the methodology for obtaining annualized capital costs, levelized coal and nuclear fuel costs, levelized operation and maintenance costs, and the resulting total generating costs for each type of station. The costs are applicable to a hypothetical Middletwon site in the Northeastern United States. Plant descriptions with general design parameters are included. The report also reprints for convenience, summaries of capital cost by account type developed in the previous commercial electric-power cost studies. Appropriate references are given for additional detailed information. Sufficient detail is given to allow the reader to develop total generating costs for other cases or conditions

A Rapid and Cost-Effective Method for DNA Extraction from Archival Herbarium Specimens.

Science.gov (United States)

Krinitsina, A A; Sizova, T V; Zaika, M A; Speranskaya, A S; Sukhorukov, A P

2015-11-01

Here we report a rapid and cost-effective method for the extraction of total DNA from herbarium specimens up to 50-90-year-old. The method takes about 2 h, uses AMPure XP magnetic beads diluted by PEG-8000- containing buffer, and does not require use of traditional volatile components like chloroform, phenol, and liquid nitrogen. It yields up to 4 µg of total nucleic acid with high purity from about 30 mg of dry material. The quality of the extracted DNA was tested by PCR amplification of 5S rRNA and rbcL genes (nuclear and chloroplast DNA markers) and compared against the traditional chloroform/isoamyl alcohol method. Our results demonstrate that the use of the magnetic beads is crucial for extraction of DNA suitable for subsequent PCR from herbarium samples due to the decreasing inhibitor concentrations, reducing short fragments of degraded DNA, and increasing median DNA fragment sizes.

Controlling costs without compromising quality: paying hospitals for total knee replacement.

Science.gov (United States)

Pine, Michael; Fry, Donald E; Jones, Barbara L; Meimban, Roger J; Pine, Gregory J

2010-10-01

Unit costs of health services are substantially higher in the United States than in any other developed country in the world, without a correspondingly healthier population. An alternative payment structure, especially for high volume, high cost episodes of care (eg, total knee replacement), is needed to reward high quality care and reduce costs. The National Inpatient Sample of administrative claims data was used to measure risk-adjusted mortality, postoperative length-of-stay, costs of routine care, adverse outcome rates, and excess costs of adverse outcomes for total knee replacements performed between 2002 and 2005. Empirically identified inefficient and ineffective hospitals were then removed to create a reference group of high-performance hospitals. Predictive models for outcomes and costs were recalibrated to the reference hospitals and used to compute risk-adjusted outcomes and costs for all hospitals. Per case predicted costs were computed and compared with observed costs. Of the 688 hospitals with acceptable data, 62 failed to meet effectiveness criteria and 210 were identified as inefficient. The remaining 416 high-performance hospitals had 13.4% fewer risk-adjusted adverse outcomes (4.56%-3.95%; P costs ($12,773-$11,512; P costs. A payment system based on the demonstrated performance of effective, efficient hospitals can produce sizable cost savings without jeopardizing quality. In this study, 96% of total excess hospital costs resulted from higher routine costs at inefficient hospitals, whereas only 4% was associated with ineffective care.

Costs, health effects and cost-effectiveness of alcohol and tobacco control strategies in Estonia.

NARCIS (Netherlands)

Lai, T.; Habicht, J.; Reinap, M.; Chisholm, D.; Baltussen, R.M.P.M.

2007-01-01

OBJECTIVE: To assess the population-level costs, effects and cost-effectiveness of different alcohol and tobacco control strategies in Estonia. DESIGN: A WHO cost-effectiveness modelling framework was used to estimate the total costs and effects of interventions. Costs were assessed in Estonian

Cost-Effective Mobile-Based Healthcare System for Managing Total Joint Arthroplasty Follow-Up.

Science.gov (United States)

Bitsaki, Marina; Koutras, George; Heep, Hansjoerg; Koutras, Christos

2017-01-01

Long-term follow-up care after total joint arthroplasty is essential to evaluate hip and knee arthroplasty outcomes, to provide information to physicians and improve arthroplasty performance, and to improve patients' health condition. In this paper, we aim to improve the communication between arthroplasty patients and physicians and to reduce the cost of follow-up controls based on mobile application technologies and cloud computing. We propose a mobile-based healthcare system that provides cost-effective follow-up controls for primary arthroplasty patients through questions about symptoms in the replaced joint, questionnaires (WOMAC and SF-36v2) and the radiological examination of knee or hip joint. We also perform a cost analysis for a set of 423 patients that were treated in the University Clinic for Orthopedics in Essen-Werden. The estimation of healthcare costs shows significant cost savings (a reduction of 63.67% for readmission rate 5%) in both the University Clinic for Orthopedics in Essen-Werden and the state of North Rhine-Westphalia when the mobile-based healthcare system is applied. We propose a mHealth system to reduce the cost of follow-up assessments of arthroplasty patients through evaluation of diagnosis, self-monitoring, and regular review of their health status.

Cost-identification analysis of total laryngectomy: an itemized approach to hospital costs.

Science.gov (United States)

Dedhia, Raj C; Smith, Kenneth J; Weissfeld, Joel L; Saul, Melissa I; Lee, Steve C; Myers, Eugene N; Johnson, Jonas T

2011-02-01

To understand the contribution of intraoperative and postoperative hospital costs to total hospital costs, examine the costs associated with specific hospital services in the postoperative period, and recognize the impact of patient factors on hospital costs. Case series with chart review. Large tertiary care teaching hospital system. Using the Pittsburgh Head and Neck Organ-Specific Database, 119 patients were identified as having total laryngectomy with bilateral selective neck dissection and primary closure from 1999 to 2009. Cost data were obtained for 112 patients. Costs include fixed and variable costs, adjusted to 2010 US dollars using the Consumer Price Index. Mean total hospital costs were $29,563 (range, $10,915 to $120,345). Operating room costs averaged 24% of total hospital costs, whereas room charges, respiratory therapy, laboratory, pharmacy, and radiology accounted for 38%, 14%, 8%, 7%, and 3%, respectively. Median length of stay was 9 days (range, 6-43), and median Charlson comorbidity index score was 8 (2-16). Patients with ≥1 day in the intensive care unit had significantly higher hospital costs ($46,831 vs $24,601, P cost differences with stratification based on previous radiation therapy ($27,598 vs $29,915 with no prior radiation, P = .62) or hospital readmission within 30 days ($29,483 vs $29,609 without readmission, P = .97). This is one of few studies in surgery and the first in otolaryngology to analyze hospital costs for a relatively standardized procedure. Further work will include cost analysis from multiple centers with investigation of global cost drivers.

Enhanced anti-HIV-1 activity of G-quadruplexes comprising locked nucleic acids and intercalating nucleic acids

DEFF Research Database (Denmark)

Pedersen, Erik Bjerregaard; Nielsen, Jakob Toudahl; Nielsen, Claus

2011-01-01

Two G-quadruplex forming sequences, 50-TGGGAG and the 17-mer sequence T30177, which exhibit anti-HIV-1 activity on cell lines, were modified using either locked nucleic acids (LNA) or via insertions of (R)-1-O-(pyren-1-ylmethyl)glycerol (intercalating nucleic acid, INA) or (R)-1-O-[4-(1......-pyrenylethynyl)phenylmethyl]glycerol (twisted intercalating nucleic acid, TINA). Incorporation of LNA or INA/TINA monomers provide as much as 8-fold improvement of anti-HIV-1 activity. We demonstrate for the first time a detailed analysis of the effect the incorporation of INA/TINA monomers in quadruplex forming...

Effect of Body Mass Index and Psychosocial Traits on Total Knee Replacement Costs in Patients with Osteoarthritis.

Science.gov (United States)

Waimann, Christian A; Fernandez-Mazarambroz, Rodrigo J; Cantor, Scott B; Lopez-Olivo, Maria A; Barbo, Andrea G; Landon, Glenn C; Siff, Sherwin J; Lin, Heather; Suarez-Almazor, Maria E

2016-08-01

Clinical and psychosocial attributes are associated with clinical outcomes after total knee replacement (TKR) surgery in patients with osteoarthritis (OA), but their relationship with TKR-related costs is less clear. Our objective was to evaluate the effect of clinical and psychosocial attributes on TKR costs. We conducted a 6-month prospective cohort study of patients with knee OA who underwent TKR. We examined baseline demographic, clinical [body mass index (BMI) and comorbidities], and psychosocial attributes (social support, locus of control, coping, depression, anxiety, stress, and self-efficacy); baseline and 6-month OA clinical outcomes [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and function]; and 6-month direct and indirect TKR-related costs. Multiple regression was performed to identify determinants of TKR-related costs. We included 212 patients; 66% were women, 71% were white, and the mean age was 65.2 years. The mean baseline WOMAC pain score was 55 (SD 19) and WOMAC function score was 54 (SD 20). Mean total TKR-related costs were US$30,831 (SD $9893). Multivariate regression analyses showed that increasing BMI and anxiety levels and decreasing levels of positive social interactions were associated with increased costs. A lower cost scenario with a lower range of normal BMI (19.5), highest positive social interaction, and no anxiety predicted TKR costs to be $22,247. Predicted costs in obese patients (BMI 36) with lowest positive social interaction and highest anxiety were $58,447. Increased baseline BMI, anxiety, and poor social support lead to higher TKR-related costs in patients with knee OA. Preoperative interventions targeting these factors may reduce TKR-related costs, and therefore be cost-effective.

Nucleic Acid-Based Nanoconstructs

Science.gov (United States)

Focuses on the design, synthesis, characterization, and development of spherical nucleic acid constructs as effective nanotherapeutic, single-entity agents for the treatment of glioblastoma multiforme and prostate cancers.

Cost-Effectiveness of Reverse Total Shoulder Arthroplasty Versus Arthroscopic Rotator Cuff Repair for Symptomatic Large and Massive Rotator Cuff Tears.

Science.gov (United States)

Makhni, Eric C; Swart, Eric; Steinhaus, Michael E; Mather, Richard C; Levine, William N; Bach, Bernard R; Romeo, Anthony A; Verma, Nikhil N

2016-09-01

To compare the cost-effectiveness within the United States health care system of arthroscopic rotator cuff repair versus reverse total shoulder arthroplasty in patients with symptomatic large and massive rotator cuff tears without cuff-tear arthropathy. An expected-value decision analysis was constructed comparing the costs and outcomes of patients undergoing arthroscopic rotator cuff repair and reverse total shoulder arthroplasty for large and massive rotator cuff tears (and excluding cases of cuff-tear arthropathy). Comprehensive literature search provided input data to extrapolate costs and health utility states for these outcomes. The primary outcome assessed was that of incremental cost-effectiveness ratio (ICER) of reverse total shoulder arthroplasty versus rotator cuff repair. For the base case, both arthroscopic rotator cuff repair and reverse total shoulder were superior to nonoperative care, with an ICER of $15,500/quality-adjusted life year (QALY) and $37,400/QALY, respectively. Arthroscopic rotator cuff repair was dominant over primary reverse total shoulder arthroplasty, with lower costs and slightly improved clinical outcomes. Arthroscopic rotator cuff repair was the preferred strategy as long as the lifetime progression rate from retear to end-stage cuff-tear arthropathy was less than 89%. However, when the model was modified to account for worse outcomes when reverse shoulder arthroplasty was performed after a failed attempted rotator cuff repair, primary reverse total shoulder had superior outcomes with an ICER of $90,000/QALY. Arthroscopic rotator cuff repair-despite high rates of tendon retearing-for patients with large and massive rotator cuff tears may be a more cost-effective initial treatment strategy when compared with primary reverse total shoulder arthroplasty and when assuming no detrimental impact of previous surgery on outcomes after arthroplasty. Clinical judgment should still be prioritized when formulating treatment plans for these

Total cost of ownership: Getting past the 10% solution

International Nuclear Information System (INIS)

Anderson, R.F.

1996-01-01

As the refining industry strives to succeed in a more-competitive world, some fresh ideas are needed to counter the headlines of plant closings, layoffs, and corporate restructurings. Other industries facing the same pressures have discovered opportunities to reduce cost in a more human and effective manner by using some tools borrowed from the Total Quality process to enhance the procurement process. Experience suggests that the purchase cost is a small fraction of the actual cost of a commodity and is often dwarfed by hidden costs. Discovering and eliminating the hidden costs of variation, nonoptimal operations, and poorly aligned vendor relations is vital to economic survival. The purpose of this paper is to suggest some fresh approaches to vendor-customer relations that can dramatically reduce undesired costs

Simple Approaches to Minimally-Instrumented, Microfluidic-Based Point-of-Care Nucleic Acid Amplification Tests

Science.gov (United States)

Mauk, Michael G.; Song, Jinzhao; Liu, Changchun; Bau, Haim H.

2018-01-01

Designs and applications of microfluidics-based devices for molecular diagnostics (Nucleic Acid Amplification Tests, NAATs) in infectious disease testing are reviewed, with emphasis on minimally instrumented, point-of-care (POC) tests for resource-limited settings. Microfluidic cartridges (‘chips’) that combine solid-phase nucleic acid extraction; isothermal enzymatic nucleic acid amplification; pre-stored, paraffin-encapsulated lyophilized reagents; and real-time or endpoint optical detection are described. These chips can be used with a companion module for separating plasma from blood through a combined sedimentation-filtration effect. Three reporter types: Fluorescence, colorimetric dyes, and bioluminescence; and a new paradigm for end-point detection based on a diffusion-reaction column are compared. Multiplexing (parallel amplification and detection of multiple targets) is demonstrated. Low-cost detection and added functionality (data analysis, control, communication) can be realized using a cellphone platform with the chip. Some related and similar-purposed approaches by others are surveyed. PMID:29495424

Simple Approaches to Minimally-Instrumented, Microfluidic-Based Point-of-Care Nucleic Acid Amplification Tests

Directory of Open Access Journals (Sweden)

Michael G. Mauk

2018-02-01

Full Text Available Designs and applications of microfluidics-based devices for molecular diagnostics (Nucleic Acid Amplification Tests, NAATs in infectious disease testing are reviewed, with emphasis on minimally instrumented, point-of-care (POC tests for resource-limited settings. Microfluidic cartridges (‘chips’ that combine solid-phase nucleic acid extraction; isothermal enzymatic nucleic acid amplification; pre-stored, paraffin-encapsulated lyophilized reagents; and real-time or endpoint optical detection are described. These chips can be used with a companion module for separating plasma from blood through a combined sedimentation-filtration effect. Three reporter types: Fluorescence, colorimetric dyes, and bioluminescence; and a new paradigm for end-point detection based on a diffusion-reaction column are compared. Multiplexing (parallel amplification and detection of multiple targets is demonstrated. Low-cost detection and added functionality (data analysis, control, communication can be realized using a cellphone platform with the chip. Some related and similar-purposed approaches by others are surveyed.

Possibilities for prognostication of radiation injury in rats by leucocyte nucleic acid levels

International Nuclear Information System (INIS)

Minkova, M.; Pantev, T.

1988-01-01

The possibilities to prognosticate acute radiation injury by the changes in the amount of nucleic acids in the leucocytes was studied. Experiments were carried out on male Wistar albino rats, gamma-irradiated with nonlethal and sublethal doses of 0.5, 2 and 4 Gy and lethal dose of 8 Gy (LD 90/30 ). The nucleic acid content and the total leucocyte count were determined at definite intervals on days 1-30. The changes in the nucleic acids in nonlethally and sublethally irradiated animals had phase nature, with a clear-cut abortive increase in their amount on days 7-10. In lethally irradiated animals the phase character of the changes was lost and the abortive peak disappeared. By reducing the effectiveness of the lethal radiation dose survival of the population increased from 10-75% through physical and from 10-70% - through chemical protection. The nucleic acid dynamics showed features typical for an injury with possible survival - appearance of abortive peak and resumption of their normal values. It is assumed that determination of leucocyte nucleic acid content may be used for early prognostication of radiation injury, as it allows keen differentiation of the lethal from nonlethal outcome of radiation sickness. The absence of abortive peak (over 50%) by day 14 post-irradiation is a poor prognostic sign

Cost-Effectiveness Analysis of Total Hip Arthroplasty Performed by a Canadian Short-Stay Surgical Team in Ecuador.

Science.gov (United States)

Schlegelmilch, Michael; Rashiq, Saifee; Moreau, Barbara; Jarrín, Patricia; Tran, Bach; Chuck, Anderson

2017-01-01

Few charitable overseas surgical missions produce cost-effectiveness analyses of their work. We compared the pre- and postoperative health status for 157 total hip arthroplasty (THA) patients operated on from 2007 to 2011 attended by an annual Canadian orthopedic mission to Ecuador to determine the quality-adjusted life years (QALYs) gained. The costs of each mission are known. The cost per surgery was divided by the average lifetime QALYs gained to estimate an incremental cost-effectiveness ratio (ICER) in Canadian dollars per QALY. The average lifetime QALYs (95% CI) gained were 1.46 (1.4-1.5), 2.5 (2.4-2.6), and 2.9 (2.7-3.1) for unilateral, bilateral, and staged (two THAs in different years) operations, respectively. The ICERs were $4,442 for unilateral, $2,939 for bilateral, and $4392 for staged procedures. Seventy percent of the mission budget was spent on the transport and accommodation of volunteers. THA by a Canadian short-stay surgical team was highly cost-effective, according to criteria from the National Institute for Health and Care Excellence and the World Health Organization. We encourage other international missions to provide similar cost-effectiveness data to enable better comparison between mission types and between mission and nonmission care.

Universal nucleic acids sample preparation method for cells, spores and their mixture

Science.gov (United States)

Bavykin, Sergei [Darien, IL

2011-01-18

The present invention relates to a method for extracting nucleic acids from biological samples. More specifically the invention relates to a universal method for extracting nucleic acids from unidentified biological samples. An advantage of the presently invented method is its ability to effectively and efficiently extract nucleic acids from a variety of different cell types including but not limited to prokaryotic or eukaryotic cells and/or recalcitrant organisms (i.e. spores). Unlike prior art methods which are focused on extracting nucleic acids from vegetative cell or spores, the present invention effectively extracts nucleic acids from spores, multiple cell types or mixtures thereof using a single method. Important that the invented method has demonstrated an ability to extract nucleic acids from spores and vegetative bacterial cells with similar levels effectiveness. The invented method employs a multi-step protocol which erodes the cell structure of the biological sample, isolates, labels, fragments nucleic acids and purifies labeled samples from the excess of dye.

Total medical costs of treating femoral neck fracture patients with hemi- or total hip arthroplasty: a cost analysis of a multicenter prospective study

NARCIS (Netherlands)

P.T.P.W. Burgers (Paul); M. Hoogendoorn (Martine); E.A.C. Van Woensel; R.W. Poolman (Rudolf); M. Bhandari (Mohit); P. Patka (Peter); E.M.M. van Lieshout (Esther)

2016-01-01

textabstractSummary: The aim of this study was to determine the total medical costs for treating displaced femoral neck fractures with hemi- or total hip arthroplasty in fit elderly patients. The mean total costs per patient at 2 years of follow-up were €26,399. These results contribute to cost

New nucleic acid testing devices to diagnose infectious diseases in resource-limited settings.

Science.gov (United States)

Maffert, P; Reverchon, S; Nasser, W; Rozand, C; Abaibou, H

2017-10-01

Point-of-care diagnosis based on nucleic acid testing aims to incorporate all the analytical steps, from sample preparation to nucleic acid amplification and detection, in a single device. This device needs to provide a low-cost, robust, sensitive, specific, and easily readable analysis. Microfluidics has great potential for handling small volumes of fluids on a single platform. Microfluidic technology has recently been applied to paper, which is already used in low-cost lateral flow tests. Nucleic acid extraction from a biological specimen usually requires cell filtration and lysis on specific membranes, while affinity matrices, such as chitosan or polydiacetylene, are well suited to concentrating nucleic acids for subsequent amplification. Access to electricity is often difficult in resource-limited areas, so the amplification step needs to be equipment-free. Consequently, the reaction has to be isothermal to alleviate the need for a thermocycler. LAMP, NASBA, HDA, and RPA are examples of the technologies available. Nucleic acid detection techniques are currently based on fluorescence, colorimetry, or chemiluminescence. For point-of-care diagnostics, the results should be readable with the naked eye. Nowadays, interpretation and communication of results to health professionals could rely on a smartphone, used as a telemedicine device. The major challenge of creating an "all-in-one" diagnostic test involves the design of an optimal solution and a sequence for each analytical step, as well as combining the execution of all these steps on a single device. This review provides an overview of available materials and technologies which seem to be adapted to point-of-care nucleic acid-based diagnosis, in low-resource areas.

Nucleic acid purification from plants, animals and microbes in under 30 seconds.

Directory of Open Access Journals (Sweden)

Yiping Zou

2017-11-01

Full Text Available Nucleic acid amplification is a powerful molecular biology tool, although its use outside the modern laboratory environment is limited due to the relatively cumbersome methods required to extract nucleic acids from biological samples. To address this issue, we investigated a variety of materials for their suitability for nucleic acid capture and purification. We report here that untreated cellulose-based paper can rapidly capture nucleic acids within seconds and retain them during a single washing step, while contaminants present in complex biological samples are quickly removed. Building on this knowledge, we have successfully created an equipment-free nucleic acid extraction dipstick methodology that can obtain amplification-ready DNA and RNA from plants, animals, and microbes from difficult biological samples such as blood and leaves from adult trees in less than 30 seconds. The simplicity and speed of this method as well as the low cost and availability of suitable materials (e.g., common paper towelling, means that nucleic acid extraction is now more accessible and affordable for researchers and the broader community. Furthermore, when combined with recent advancements in isothermal amplification and naked eye DNA visualization techniques, the dipstick extraction technology makes performing molecular diagnostic assays achievable in limited resource settings including university and high school classrooms, field-based environments, and developing countries.

Economics of human performance and systems total ownership cost.

Science.gov (United States)

Onkham, Wilawan; Karwowski, Waldemar; Ahram, Tareq Z

2012-01-01

Financial costs of investing in people is associated with training, acquisition, recruiting, and resolving human errors have a significant impact on increased total ownership costs. These costs can also affect the exaggerate budgets and delayed schedules. The study of human performance economical assessment in the system acquisition process enhances the visibility of hidden cost drivers which support program management informed decisions. This paper presents the literature review of human total ownership cost (HTOC) and cost impacts on overall system performance. Economic value assessment models such as cost benefit analysis, risk-cost tradeoff analysis, expected value of utility function analysis (EV), growth readiness matrix, multi-attribute utility technique, and multi-regressions model were introduced to reflect the HTOC and human performance-technology tradeoffs in terms of the dollar value. The human total ownership regression model introduces to address the influencing human performance cost component measurement. Results from this study will increase understanding of relevant cost drivers in the system acquisition process over the long term.

Optimized methods for total nucleic acid extraction and quantification of the bat white-nose syndrome fungus, Pseudogymnoascus destructans, from swab and environmental samples.

Science.gov (United States)

Verant, Michelle L; Bohuski, Elizabeth A; Lorch, Jeffery M; Blehert, David S

2016-03-01

The continued spread of white-nose syndrome and its impacts on hibernating bat populations across North America has prompted nationwide surveillance efforts and the need for high-throughput, noninvasive diagnostic tools. Quantitative real-time polymerase chain reaction (qPCR) analysis has been increasingly used for detection of the causative fungus, Pseudogymnoascus destructans, in both bat- and environment-associated samples and provides a tool for quantification of fungal DNA useful for research and monitoring purposes. However, precise quantification of nucleic acid from P. destructans is dependent on effective and standardized methods for extracting nucleic acid from various relevant sample types. We describe optimized methodologies for extracting fungal nucleic acids from sediment, guano, and swab-based samples using commercial kits together with a combination of chemical, enzymatic, and mechanical modifications. Additionally, we define modifications to a previously published intergenic spacer-based qPCR test for P. destructans to refine quantification capabilities of this assay. © 2016 The Author(s).

Optimized methods for total nucleic acid extraction and quantification of the bat white-nose syndrome fungus, Pseudogymnoascus destructans, from swab and environmental samples

Science.gov (United States)

Verant, Michelle; Bohuski, Elizabeth A.; Lorch, Jeffrey M.; Blehert, David

2016-01-01

The continued spread of white-nose syndrome and its impacts on hibernating bat populations across North America has prompted nationwide surveillance efforts and the need for high-throughput, noninvasive diagnostic tools. Quantitative real-time polymerase chain reaction (qPCR) analysis has been increasingly used for detection of the causative fungus, Pseudogymnoascus destructans, in both bat- and environment-associated samples and provides a tool for quantification of fungal DNA useful for research and monitoring purposes. However, precise quantification of nucleic acid fromP. destructans is dependent on effective and standardized methods for extracting nucleic acid from various relevant sample types. We describe optimized methodologies for extracting fungal nucleic acids from sediment, guano, and swab-based samples using commercial kits together with a combination of chemical, enzymatic, and mechanical modifications. Additionally, we define modifications to a previously published intergenic spacer–based qPCR test for P. destructans to refine quantification capabilities of this assay.

Peptide Nucleic Acids

DEFF Research Database (Denmark)

2003-01-01

A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

Peptide Nucleic Acids

DEFF Research Database (Denmark)

1998-01-01

A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

Peptide Nucleic Acids

DEFF Research Database (Denmark)

2004-01-01

A novel class of compounds known as peptide nucleic acids, bind complementary DNA and RNA strands, and generally do so more strongly than the corresponding DNA or RNA strands while exhibiting increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from...

Can a Costly Intervention Be Cost-effective?

Science.gov (United States)

Foster, E. Michael; Jones, Damon

2009-01-01

Objectives To examine the cost-effectiveness of the Fast Track intervention, a multi-year, multi-component intervention designed to reduce violence among at-risk children. A previous report documented the favorable effect of intervention on the highest-risk group of ninth-graders diagnosed with conduct disorder, as well as self-reported delinquency. The current report addressed the cost-effectiveness of the intervention for these measures of program impact. Design Costs of the intervention were estimated using program budgets. Incremental cost-effectiveness ratios were computed to determine the cost per unit of improvement in the 3 outcomes measured in the 10th year of the study. Results Examination of the total sample showed that the intervention was not cost-effective at likely levels of policymakers' willingness to pay for the key outcomes. Subsequent analysis of those most at risk, however, showed that the intervention likely was cost-effective given specified willingness-to-pay criteria. Conclusions Results indicate that the intervention is cost-effective for the children at highest risk. From a policy standpoint, this finding is encouraging because such children are likely to generate higher costs for society over their lifetimes. However, substantial barriers to cost-effectiveness remain, such as the ability to effectively identify and recruit such higher-risk children in future implementations. PMID:17088509

Locked nucleic acid

DEFF Research Database (Denmark)

Jepsen, Jan Stenvang; Sørensen, Mads D; Wengel, Jesper

2004-01-01

Locked nucleic acid (LNA) is a class of nucleic acid analogs possessing very high affinity and excellent specificity toward complementary DNA and RNA, and LNA oligonucleotides have been applied as antisense molecules both in vitro and in vivo. In this review, we briefly describe the basic...

Electricity-free, sequential nucleic acid and protein isolation.

Science.gov (United States)

Pawlowski, David R; Karalus, Richard J

2012-05-15

Traditional and emerging pathogens such as Enterohemorrhagic Escherichia coli (EHEC), Yersinia pestis, or prion-based diseases are of significant concern for governments, industries and medical professionals worldwide. For example, EHECs, combined with Shigella, are responsible for the deaths of approximately 325,000 children each year and are particularly prevalent in the developing world where laboratory-based identification, common in the United States, is unavailable (1). The development and distribution of low cost, field-based, point-of-care tools to aid in the rapid identification and/or diagnosis of pathogens or disease markers could dramatically alter disease progression and patient prognosis. We have developed a tool to isolate nucleic acids and proteins from a sample by solid-phase extraction (SPE) without electricity or associated laboratory equipment (2). The isolated macromolecules can be used for diagnosis either in a forward lab or using field-based point-of-care platforms. Importantly, this method provides for the direct comparison of nucleic acid and protein data from an un-split sample, offering a confidence through corroboration of genomic and proteomic analysis. Our isolation tool utilizes the industry standard for solid-phase nucleic acid isolation, the BOOM technology, which isolates nucleic acids from a chaotropic salt solution, usually guanidine isothiocyanate, through binding to silica-based particles or filters (3). CUBRC's proprietary solid-phase extraction chemistry is used to purify protein from chaotropic salt solutions, in this case, from the waste or flow-thru following nucleic acid isolation(4). By packaging well-characterized chemistries into a small, inexpensive and simple platform, we have generated a portable system for nucleic acid and protein extraction that can be performed under a variety of conditions. The isolated nucleic acids are stable and can be transported to a position where power is available for PCR amplification

Double-Stranded Peptide Nucleic Acids

DEFF Research Database (Denmark)

2001-01-01

A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker.......A novel class of compounds, known as peptide nucleic acids, form double-stranded structures with one another and with ssDNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

Nucleic Acid Aptamers Against Biotoxins: A New Paradigm Toward the Treatment and Diagnostic Approach

DEFF Research Database (Denmark)

Lauridsen, Lasse Holm; Veedu, Rakesh N.

2012-01-01

Nucleic acid aptamers are short single-stranded DNA or RNA oligonucleotides that can bind to their targets with very high affinity and specificity, and are generally selected by a process referred to as systematic evolution of ligands by exponential enrichment. Conventional antibody-based therape......Nucleic acid aptamers are short single-stranded DNA or RNA oligonucleotides that can bind to their targets with very high affinity and specificity, and are generally selected by a process referred to as systematic evolution of ligands by exponential enrichment. Conventional antibody......-based therapeutic and diagnostic approach currently employed against biotoxins pose major limitations such as the requirement of a live animal for the in vivo enrichment of the antibody species, decreased stability, high production cost, and side effects. Aptamer technology is a viable alternative that can be used...

Molecular Structure of Nucleic Acids

Indian Academy of Sciences (India)

Molecular Structure of Nucleic Acids. A Structure for Deoxyribose Nucleic Acid. J. D. Watson and F. H. C. Crick. Medical Research Council Unit for the Study of the Molecular Structure of Biological. Systems, Cavendish Laboratory, Cambridge. April 2. We wish to suggest a structure for the salt of deoxyribose nucleic acid ...

Quantitative thermodynamic predication of interactions between nucleic acid and non-nucleic acid species using Microsoft excel.

Science.gov (United States)

Zou, Jiaqi; Li, Na

2013-09-01

Proper design of nucleic acid sequences is crucial for many applications. We have previously established a thermodynamics-based quantitative model to help design aptamer-based nucleic acid probes by predicting equilibrium concentrations of all interacting species. To facilitate customization of this thermodynamic model for different applications, here we present a generic and easy-to-use platform to implement the algorithm of the model with Microsoft(®) Excel formulas and VBA (Visual Basic for Applications) macros. Two Excel spreadsheets have been developed: one for the applications involving only nucleic acid species, the other for the applications involving both nucleic acid and non-nucleic acid species. The spreadsheets take the nucleic acid sequences and the initial concentrations of all species as input, guide the user to retrieve the necessary thermodynamic constants, and finally calculate equilibrium concentrations for all species in various bound and unbound conformations. The validity of both spreadsheets has been verified by comparing the modeling results with the experimental results on nucleic acid sequences reported in the literature. This Excel-based platform described here will allow biomedical researchers to rationalize the sequence design of nucleic acid probes using the thermodynamics-based modeling even without relevant theoretical and computational skills. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Effect of gamma rays on nucleic acids content (RNA and DNA) of the cotton leaf worm Spodoptera Littoralis (BOISD). Vol. 4

International Nuclear Information System (INIS)

Sallam, H.A.; El-Shall, S.A.; Sobeiha, A.K.; El-Bamby, M.A.

1996-01-01

Full grown pupae of the cotton leaf worm Spodoptera Littoralis (Boisd) were exposed to exposed to sub sterilizing doses of 100, 200 and 300 Gy gamma radiation. The changes in nucleic acids content (RNA and DNA) of irradiated pupae, after 24 hours from irradiation, and also in 3 days old adults resulting from irradiated pupae were investigated. The total nucleic acids content in either pupae or adults was progressively reduced as the dose was increased. The reduction of both RNA and DNA in females was greater than in males. DNA was more radiosensitive than RNA. The destructive action of irradiation on nucleic acids was more pronounced in adult stage. Irradiation increased the RNA/DNA ratio than control at all treatments for female pupae at 200 Gy. 2 tabs

Effect of gamma rays on nucleic acids content (RNA and DNA) of the cotton leaf worm Spodoptera Littoralis (BOISD). Vol. 4.

Energy Technology Data Exchange (ETDEWEB)

Sallam, H A; El-Shall, S A [Biological Applications Department, Nuclear Research Center, Atomic Energy Authority, Cairo (Egypt); Sobeiha, A K; El-Bamby, M A [Plant Protection Department, Faculty of Agriculture, Ain Shams University, Cairo (Egypt)

1996-03-01

Full grown pupae of the cotton leaf worm Spodoptera Littoralis (Boisd) were exposed to exposed to sub sterilizing doses of 100, 200 and 300 Gy gamma radiation. The changes in nucleic acids content (RNA and DNA) of irradiated pupae, after 24 hours from irradiation, and also in 3 days old adults resulting from irradiated pupae were investigated. The total nucleic acids content in either pupae or adults was progressively reduced as the dose was increased. The reduction of both RNA and DNA in females was greater than in males. DNA was more radiosensitive than RNA. The destructive action of irradiation on nucleic acids was more pronounced in adult stage. Irradiation increased the RNA/DNA ratio than control at all treatments for female pupae at 200 Gy. 2 tabs.

Miniaturized isothermal nucleic acid amplification, a review.

Science.gov (United States)

Asiello, Peter J; Baeumner, Antje J

2011-04-21

Micro-Total Analysis Systems (µTAS) for use in on-site rapid detection of DNA or RNA are increasingly being developed. Here, amplification of the target sequence is key to increasing sensitivity, enabling single-cell and few-copy nucleic acid detection. The several advantages to miniaturizing amplification reactions and coupling them with sample preparation and detection on the same chip are well known and include fewer manual steps, preventing contamination, and significantly reducing the volume of expensive reagents. To-date, the majority of miniaturized systems for nucleic acid analysis have used the polymerase chain reaction (PCR) for amplification and those systems are covered in previous reviews. This review provides a thorough overview of miniaturized analysis systems using alternatives to PCR, specifically isothermal amplification reactions. With no need for thermal cycling, isothermal microsystems can be designed to be simple and low-energy consuming and therefore may outperform PCR in portable, battery-operated detection systems in the future. The main isothermal methods as miniaturized systems reviewed here include nucleic acid sequence-based amplification (NASBA), loop-mediated isothermal amplification (LAMP), helicase-dependent amplification (HDA), rolling circle amplification (RCA), and strand displacement amplification (SDA). Also, important design criteria for the miniaturized devices are discussed. Finally, the potential of miniaturization of some new isothermal methods such as the exponential amplification reaction (EXPAR), isothermal and chimeric primer-initiated amplification of nucleic acids (ICANs), signal-mediated amplification of RNA technology (SMART) and others is presented.

Seven-year cost-effectiveness of ProDisc-C total disc replacement: results from investigational device exemption and post-approval studies.

Science.gov (United States)

Radcliff, Kris; Lerner, Jason; Yang, Chao; Bernard, Thierry; Zigler, Jack E

2016-05-01

OBJECTIVE The purpose of this study was to evaluate the 7-year cost-effectiveness of cervical total disc replacement (CTDR) versus anterior cervical discectomy and fusion (ACDF) for the treatment of patients with single-level symptomatic degenerative disc disease. A change in the spending trajectory for spine care is to be achieved, in part, through the selection of interventions that have been proven effective yet cost less than other options. This analysis complements and builds upon findings from other cost-effectiveness evaluations of CTDR through the use of long-term, patient-level data from a randomized study. METHODS This was a 7-year health economic evaluation comparing CTDR versus ACDF from the US commercial payer perspective. Prospectively collected health care resource utilization and treatment effects (quality-adjusted life years [QALYs]) were obtained from individual patient-level adverse event reports and SF-36 data, respectively, from the randomized, multicenter ProDisc-C total disc replacement investigational device exemption (IDE) study and post-approval study. Statistical distributions for unit costs were derived from a commercial claims database and applied using Monte Carlo simulation. Patient-level costs and effects were modeled via multivariate probabilistic analysis. Confidence intervals for 7-year costs, effects, and net monetary benefit (NMB) were obtained using the nonparametric percentile method from results of 10,000 bootstrap simulations. The robustness of results was assessed through scenario analysis and within a parametric regression model controlling for baseline variables. RESULTS Seven-year follow-up data were available for more than 70% of the 209 randomized patients. In the base-case analysis, CTDR resulted in mean per-patient cost savings of $12,789 (95% CI $5362-$20,856) and per-patient QALY gains of 0.16 (95% CI -0.073 to 0.39) compared with ACDF over 7 years. CTDR was more effective and less costly in 90.8% of probabilistic

Impact Of Health Care Delivery System Innovations On Total Cost Of Care.

Science.gov (United States)

Smith, Kevin W; Bir, Anupa; Freeman, Nikki L B; Koethe, Benjamin C; Cohen, Julia; Day, Timothy J

2017-03-01

Using delivery system innovations to advance health care reform continues to be of widespread interest. However, it is difficult to generalize about the success of specific types of innovations, since they have been examined in only a few studies. To gain a broader perspective, we analyzed the results of forty-three ambulatory care programs funded by the first round of the Center for Medicare and Medicaid Innovation's Health Care Innovations Awards. The innovations' impacts on total cost of care were estimated by independent evaluators using multivariable difference-in-differences models. Through the first two years, most of the innovations did not show a significant effect on total cost of care. Using meta-regression, we assessed the effects on costs of five common components of these innovations. Innovations that used health information technology or community health workers achieved the greatest cost savings. Savings were also relatively large in programs that targeted clinically fragile patients-clinically complex populations at risk for disease progression. While the magnitude of these effects was often substantial, none achieved conventional levels of significance in our analyses. Meta-analyses of a larger number of delivery system innovations are needed to more clearly establish their potential for patient care cost savings. Project HOPE—The People-to-People Health Foundation, Inc.

Cost-effectiveness Analysis for Technology Acquisition.

Science.gov (United States)

Chakravarty, A; Naware, S S

2008-01-01

In a developing country with limited resources, it is important to utilize the total cost visibility approach over the entire life-cycle of the technology and then analyse alternative options for acquiring technology. The present study analysed cost-effectiveness of an "In-house" magnetic resonance imaging (MRI) scan facility of a large service hospital against outsourcing possibilities. Cost per unit scan was calculated by operating costing method and break-even volume was calculated. Then life-cycle cost analysis was performed to enable total cost visibility of the MRI scan in both "In-house" and "outsourcing of facility" configuration. Finally, cost-effectiveness analysis was performed to identify the more acceptable decision option. Total cost for performing unit MRI scan was found to be Rs 3,875 for scans without contrast and Rs 4,129 with contrast. On life-cycle cost analysis, net present value (NPV) of the "In-house" configuration was found to be Rs-(4,09,06,265) while that of "outsourcing of facility" configuration was Rs-(5,70,23,315). Subsequently, cost-effectiveness analysis across eight Figures of Merit showed the "In-house" facility to be the more acceptable option for the system. Every decision for acquiring high-end technology must be subjected to life-cycle cost analysis.

Cleaving Double-Stranded DNA with Peptide Nucleic Acids

DEFF Research Database (Denmark)

1997-01-01

Peptide nucleic acids and analogues of peptide nucleic acids are used to form duplex, triplex, and other structures with nucleic acids and to modify nucleic acids. The peptide nucleic acids and analogues thereof also are used to modulate protein activity through, for example, transcription arrest......, transcription initiation, and site specific cleavage of nucleic acids....

Identifying a base in a nucleic acid

Science.gov (United States)

Fodor, Stephen P. A.; Lipshutz, Robert J.; Huang, Xiaohua

2005-02-08

Devices and techniques for hybridization of nucleic acids and for determining the sequence of nucleic acids. Arrays of nucleic acids are formed by techniques, preferably high resolution, light-directed techniques. Positions of hybridization of a target nucleic acid are determined by, e.g., epifluorescence microscopy. Devices and techniques are proposed to determine the sequence of a target nucleic acid more efficiently and more quickly through such synthesis and detection techniques.

Zero risk tolerance costs lives: loss of transplantable organs due to human immunodeficiency virus nucleic acid testing of potential donors.

Science.gov (United States)

Shafer, Teresa J; Schkade, David; Schkade, Lawrence; Geier, Steven S; Orlowski, Jeffrey P; Klintmalm, Goran

2011-09-01

Patients' deaths due to the organ donor shortage make it imperative that every suitable organ be transplanted. False-positive results of tests for infection with the human immunodeficiency virus (HIV) result in lost organs. A survey of US organ procurement organizations collected the numbers of donors and ruled-out potential donors who had a positive result on an HIV test from January 1,2006, to October 31, 2008. Sixty-two percent of US organ procurement organizations participated. Of the 12397 donor/nondonor cases, 56 (0.45%) had an initial positive result on an HIV antibody or HIV nucleic acid test, and only 8 (14.3%) of those were confirmed positive. Of the false-positive results, 50% were from HIV antibody tests and 50% were from HIV nucleic acid tests. Organs are a scarce, finite, and perishable resource. Use of HIV antibody testing has produced a remarkably safe track record of avoiding HIV transmission, with 22 years of nonoccurrence between transmissions. Because false positives occur with any test, including the HIV Ab test, adding nucleic acid testing to the standard donor testing panel doubles the number of false-positive HIV test results and thus the number of medically suitable donors lost. The required HIV antibody test is 99.99% effective in preventing transmission of the HIV virus. Adding the HIV nucleic acid test to routine organ donor screening could result in as many as 761 to 1551 unnecessary deaths of patients between HIV transmission events because medically suitable organs are wasted.

Intensive care unit drug costs in the context of total hospital drug expenditures with suggestions for targeted cost containment efforts.

Science.gov (United States)

Altawalbeh, Shoroq M; Saul, Melissa I; Seybert, Amy L; Thorpe, Joshua M; Kane-Gill, Sandra L

2018-04-01

To assess costs of intensive care unit (ICU) related pharmacotherapy relative to hospital drug expenditures, and to identify potential targets for cost-effectiveness investigations. We offer the unique advantage of comparing ICU drug costs with previously published data a decade earlier to describe changes over time. Financial transactions for all ICU patients during fiscal years (FY) 2009-2012 were retrieved from the hospital's data repository. ICU drug costs were evaluated for each FY. ICU departments' charges were also retrieved and calculated as percentages of total ICU charges. Albumin, prismasate (dialysate), voriconazole, factor VII and alteplase denoted the highest percentages of ICU drug costs. ICU drug costs contributed to an average of 31% (SD 1.0%) of the hospital's total drug costs. ICU drug costs per patient day increased by 5.8% yearly versus 7.8% yearly for non-ICU drugs. This rate was higher for ICU drugs costs at 12% a decade previous. Pharmacy charges contributed to 17.7% of the total ICU charges. Growth rates of costs per year have declined but still drug expenditures in the ICU are consistently a significant driver in this resource intensive environment with a high impact on hospital drug expenditures. Copyright © 2017 Elsevier Inc. All rights reserved.

Peptide Nucleic Acids (PNA)

DEFF Research Database (Denmark)

2002-01-01

A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

Peptide Nucleic Acid Synthons

DEFF Research Database (Denmark)

2004-01-01

A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

Nucleic acid-based diagnostics for infectious diseases in public health affairs.

Science.gov (United States)

Yu, Albert Cheung-Hoi; Vatcher, Greg; Yue, Xin; Dong, Yan; Li, Mao Hua; Tam, Patrick H K; Tsang, Parker Y L; Wong, April K Y; Hui, Michael H K; Yang, Bin; Tang, Hao; Lau, Lok-Ting

2012-06-01

Infectious diseases, mostly caused by bacteria and viruses but also a result of fungal and parasitic infection, have been one of the most important public health concerns throughout human history. The first step in combating these pathogens is to get a timely and accurate diagnosis at an affordable cost. Many kinds of diagnostics have been developed, such as pathogen culture, biochemical tests and serological tests, to help detect and fight against the causative agents of diseases. However, these diagnostic tests are generally unsatisfactory because they are not particularly sensitive and specific and are unable to deliver speedy results. Nucleic acid-based diagnostics, detecting pathogens through the identification of their genomic sequences, have shown promise to overcome the above limitations and become more widely adopted in clinical tests. Here we review some of the most popular nucleic acid-based diagnostics and focus on their adaptability and applicability to routine clinical usage. We also compare and contrast the characteristics of different types of nucleic acid-based diagnostics.

The Cost of Joint Replacement: Comparing Two Approaches to Evaluating Costs of Total Hip and Knee Arthroplasty.

Science.gov (United States)

Palsis, John A; Brehmer, Thomas S; Pellegrini, Vincent D; Drew, Jacob M; Sachs, Barton L

2018-02-21

In an era of mandatory bundled payments for total joint replacement, accurate analysis of the cost of procedures is essential for orthopaedic surgeons and their institutions to maintain viable practices. The purpose of this study was to compare traditional accounting and time-driven activity-based costing (TDABC) methods for estimating the total costs of total hip and knee arthroplasty care cycles. We calculated the overall costs of elective primary total hip and total knee replacement care cycles at our academic medical center using traditional and TDABC accounting methods. We compared the methods with respect to the overall costs of hip and knee replacement and the costs for each major cost category. The traditional accounting method resulted in higher cost estimates. The total cost per hip replacement was $22,076 (2014 USD) using traditional accounting and was $12,957 using TDABC. The total cost per knee replacement was $29,488 using traditional accounting and was $16,981 using TDABC. With respect to cost categories, estimates using traditional accounting were greater for hip and knee replacement, respectively, by $3,432 and $5,486 for personnel, by $3,398 and $3,664 for space and equipment, and by $2,289 and $3,357 for indirect costs. Implants and consumables were derived from the actual hospital purchase price; accordingly, both methods produced equivalent results. Substantial cost differences exist between accounting methods. The focus of TDABC only on resources used directly by the patient contrasts with the allocation of all operating costs, including all indirect costs and unused capacity, with traditional accounting. We expect that the true costs of hip and knee replacement care cycles are likely somewhere between estimates derived from traditional accounting methods and TDABC. TDABC offers patient-level granular cost information that better serves in the redesign of care pathways and may lead to more strategic resource-allocation decisions to optimize

Cost per case or total cost? The potential of prevention of hand injuries in young children – Retrospective and prospective studies

Directory of Open Access Journals (Sweden)

Carlsson Katarina

2008-07-01

Full Text Available Abstract Background Health-care costs for hand and forearm injuries in young children are poorly documented. We examined costs in 533 children injured years 1996–2003. Methods Health-care costs and costs for lost productivity were retrospectively calculated in children from three catchment areas in Sweden. Seven case categories corresponding to alternative prevention strategies were constructed. Results Over time, diminishing number of ward days reduced the health-care cost per case. Among children, the cost of lost productivity due to parental leave was 14 percent of total cost. Fingertip injuries had low median costs but high total costs due to their frequency. Complex injuries by machine or rifle had high costs per case, and despite a low number of cases, total cost was high. Type of injury, surgery and physiotherapy sessions were associated with variations in health-care cost. Low age and ethnic background had a significant effect on number of ward days. Conclusion The costs per hand injury for children were lower compared to adults due to both lower health-care costs and to the fact that parents had comparatively short periods of absence from work. Frequent simple fingertip injuries and rare complex injuries induce high costs for society. Such costs should be related to costs for prevention of these injuries.

A general approach to total repair cost limit replacement policies

Directory of Open Access Journals (Sweden)

F. Beichelt

2014-01-01

Full Text Available A common replacement policy for technical systems consists in replacing a system by a new one after its economic lifetime, i.e. at that moment when its long-run maintenance cost rate is minimal. However, the strict application of the economic lifetime does not take into account the individual deviations of maintenance cost rates of single systems from the average cost development. Hence, Beichet proposed the total repair cost limit replacement policy: the system is replaced by a new one as soon as its total repair cost reaches or exceeds a given level. He modelled the repair cost development by functions of the Wiener process with drift. Here the same policy is considered under the assumption that the one-dimensional probability distribution of the process describing the repair cost development is given. In the examples analysed, applying the total repair cost limit replacement policy instead of the economic life-time leads to cost savings of between 4% and 30%. Finally, it is illustrated how to include the reliability aspect into the policy.

A decision-making framework for total ownership cost management of complex systems: A Delphi study

Science.gov (United States)

King, Russel J.

This qualitative study, using a modified Delphi method, was conducted to develop a decision-making framework for the total ownership cost management of complex systems in the aerospace industry. The primary focus of total ownership cost is to look beyond the purchase price when evaluating complex system life cycle alternatives. A thorough literature review and the opinions of a group of qualified experts resulted in a compilation of total ownership cost best practices, cost drivers, key performance factors, applicable assessment methods, practitioner credentials and potential barriers to effective implementation. The expert panel provided responses to the study questions using a 5-point Likert-type scale. Data were analyzed and provided to the panel members for review and discussion with the intent to achieve group consensus. As a result of the study, the experts agreed that a total ownership cost analysis should (a) be as simple as possible using historical data; (b) establish cost targets, metrics, and penalties early in the program; (c) monitor the targets throughout the product lifecycle and revise them as applicable historical data becomes available; and (d) directly link total ownership cost elements with other success factors during program development. The resultant study framework provides the business leader with incentives and methods to develop and implement strategies for controlling and reducing total ownership cost over the entire product life cycle when balancing cost, schedule, and performance decisions.

Nucleic Acid-Based Approaches for Detection of Viral Hepatitis

Science.gov (United States)

Behzadi, Payam; Ranjbar, Reza; Alavian, Seyed Moayed

2014-01-01

Context: To determining suitable nucleic acid diagnostics for individual viral hepatitis agent, an extensive search using related keywords was done in major medical library and data were collected, categorized, and summarized in different sections. Results: Various types of molecular biology tools can be used to detect and quantify viral genomic elements and analyze the sequences. These molecular assays are proper technologies for rapidly detecting viral agents with high accuracy, high sensitivity, and high specificity. Nonetheless, the application of each diagnostic method is completely dependent on viral agent. Conclusions: Despite rapidity, automation, accuracy, cost-effectiveness, high sensitivity, and high specificity of molecular techniques, each type of molecular technology has its own advantages and disadvantages. PMID:25789132

Implementation of antimicrobial peptides for sample preparation prior to nucleic acid amplification in point-of-care settings.

Science.gov (United States)

Krõlov, Katrin; Uusna, Julia; Grellier, Tiia; Andresen, Liis; Jevtuševskaja, Jekaterina; Tulp, Indrek; Langel, Ülo

2017-12-01

A variety of sample preparation techniques are used prior to nucleic acid amplification. However, their efficiency is not always sufficient and nucleic acid purification remains the preferred method for template preparation. Purification is difficult and costly to apply in point-of-care (POC) settings and there is a strong need for more robust, rapid, and efficient biological sample preparation techniques in molecular diagnostics. Here, the authors applied antimicrobial peptides (AMPs) for urine sample preparation prior to isothermal loop-mediated amplification (LAMP). AMPs bind to many microorganisms such as bacteria, fungi, protozoa and viruses causing disruption of their membrane integrity and facilitate nucleic acid release. The authors show that incubation of E. coli with antimicrobial peptide cecropin P1 for 5 min had a significant effect on the availability of template DNA compared with untreated or even heat treated samples resulting in up to six times increase of the amplification efficiency. These results show that AMPs treatment is a very efficient sample preparation technique that is suitable for application prior to nucleic acid amplification directly within biological samples. Furthermore, the entire process of AMPs treatment was performed at room temperature for 5 min thereby making it a good candidate for use in POC applications.

Histidine-Containing Peptide Nucleic Acids

DEFF Research Database (Denmark)

2000-01-01

Peptide nucleic acids containing histidine moieties are provided. These compounds have applications including diagnostics, research and potential therapeutics.......Peptide nucleic acids containing histidine moieties are provided. These compounds have applications including diagnostics, research and potential therapeutics....

A Cost-Effectiveness Analysis of Reverse Total Shoulder Arthroplasty versus Hemiarthroplasty for the Management of Complex Proximal Humeral Fractures in the Elderly.

Science.gov (United States)

Osterhoff, Georg; O'Hara, Nathan N; D'Cruz, Jennifer; Sprague, Sheila A; Bansback, Nick; Evaniew, Nathan; Slobogean, Gerard P

2017-03-01

There is ongoing debate regarding the optimal surgical treatment of complex proximal humeral fractures in elderly patients. To evaluate the cost-effectiveness of reverse total shoulder arthroplasty (RTSA) compared with hemiarthroplasty (HA) in the management of complex proximal humeral fractures, using a cost-utility analysis. On the basis of data from published literature, a cost-utility analysis was conducted using decision tree and Markov modeling. A single-payer perspective, with a willingness-to-pay (WTP) threshold of Can$50,000 (Canadian dollars), and a lifetime time horizon were used. The incremental cost-effectiveness ratio (ICER) was used as the study's primary outcome measure. In comparison with HA, the incremental cost per quality-adjusted life-year gained for RTSA was Can$13,679. One-way sensitivity analysis revealed the model to be sensitive to the RTSA implant cost and the RTSA procedural cost. The ICER of Can$13,679 is well below the WTP threshold of Can$50,000, and probabilistic sensitivity analysis demonstrated that 92.6% of model simulations favored RTSA. Our economic analysis found that RTSA for the treatment of complex proximal humeral fractures in the elderly is the preferred economic strategy when compared with HA. The ICER of RTSA is well below standard WTP thresholds, and its estimate of cost-effectiveness is similar to other highly successful orthopedic strategies such as total hip arthroplasty for the treatment of hip arthritis. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Cost-effectiveness of antibiotic prophylaxis for dental patients with prosthetic joints: Comparisons of antibiotic regimens for patients with total hip arthroplasty.

Science.gov (United States)

Skaar, Daniel D; Park, Taehwan; Swiontkowski, Marc F; Kuntz, Karen M

2015-11-01

Clinician uncertainty concerning the need for antibiotic prophylaxis to prevent prosthetic joint infection (PJI) after undergoing dental procedures persists. Improved understanding of the potential clinical and economic risks and benefits of antibiotic prophylaxis will help inform the debate and facilitate the continuing evolution of clinical management guidelines for dental patients with prosthetic joints. The authors developed a Markov decision model to compare the lifetime cost-effectiveness of alternative antibiotic prophylaxis strategies for dental patients aged 65 years who had undergone total hip arthroplasty (THA). On the basis of the authors' interpretation of previous recommendations from the American Dental Association and American Academy of Orthopaedic Surgeons, they compared the following strategies: no prophylaxis, prophylaxis for the first 2 years after arthroplasty, and lifetime prophylaxis. A strategy of foregoing antibiotic prophylaxis before dental visits was cost-effective and resulted in lower lifetime accumulated costs ($11,909) and higher accumulated quality-adjusted life years (QALYs) (12.375) when compared with alternative prophylaxis strategies. The results of Markov decision modeling indicated that a no-antibiotic prophylaxis strategy was cost-effective for dental patients who had undergone THA. These results support the findings of case-control studies and the conclusions of an American Dental Association Council on Scientific Affairs report that questioned general recommendations for antibiotic prophylaxis before dental procedures. The results of cost-effectiveness decision modeling support the contention that routine antibiotic prophylaxis for dental patients with total joint arthroplasty should be reconsidered. Copyright © 2015 American Dental Association. Published by Elsevier Inc. All rights reserved.

Archive of Samples for Long-Term Preservation of RNA and Other Nucleic Acids

Science.gov (United States)

2016-05-15

workflow can be developed for large scale blood collection , transport , and long-term archiving without the use of costly and unreliable cold chain...management, using commercially available biopreservation products. For the development of the automated workflow we have chosen Biomatrica’s commercially...This ambient workflow can be developed for large scale blood collection, transport and long-term nucleic acid archiving without the use of costly

Knee Joint Distraction Compared to Total Knee Arthroplasty for Treatment of End Stage Osteoarthritis: Simulating Long-Term Outcomes and Cost-Effectiveness.

Science.gov (United States)

van der Woude, J A D; Nair, S C; Custers, R J H; van Laar, J M; Kuchuck, N O; Lafeber, F P J G; Welsing, P M J

2016-01-01

In end-stage knee osteoarthritis the treatment of choice is total knee arthroplasty (TKA). An alternative treatment is knee joint distraction (KJD), suggested to postpone TKA. Several studies reported significant and prolonged clinical improvement of KJD. To make an appropriate decision regarding the position of this treatment, a cost-effectiveness and cost-utility analysis from healthcare perspective for different age and gender categories was performed. A treatment strategy starting with TKA and a strategy starting with KJD for patients of different age and gender was simulated. To extrapolate outcomes to long-term health and economic outcomes a Markov (Health state) model was used. The number of surgeries, QALYs, and treatment costs per strategy were calculated. Costs-effectiveness is expressed using the cost-effectiveness plane and cost-effectiveness acceptability curves. Starting with KJD the number of knee replacing procedures could be reduced, most clearly in the younger age categories; especially revision surgery. This resulted in the KJD strategy being dominant (more effective with cost-savings) in about 80% of simulations (with only inferiority in about 1%) in these age categories when compared to TKA. At a willingness to pay of 20.000 Euro per QALY gained, the probability of starting with KJD to be cost-effective compared to starting with a TKA was already found to be over 75% for all age categories and over 90-95% for the younger age categories. A treatment strategy starting with knee joint distraction for knee osteoarthritis has a large potential for being a cost-effective intervention, especially for the relatively young patient.

Cost-effectivness analysis of total thyroidectomy vs radioiodine for Graves disease

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Prokić Anđelka

2013-01-01

Full Text Available Among the patients suffering from hyperthyroidism 60-80% have Graves' disease. The initial therapy of Graves's disease are antithyroid drugs. If the remission is not achieved after 12-18 months, the patients should be directed to surgical treatment or to the therapy with radioactive iodine. The aim of this study was to compare cost/effectiveness ratios for radioactive iodine and total thyroidectomy. The analysis was made using Markov model, from the perspective of Republic Fund for Health Insurance in Serbia. Duration of one cycle in the model is six months, and the time horizon is 30 years. Monte Carlo simulation was performed for 1000 virtual patients as well as the analysis of sensitivity with the variation of parameters ± 50%. For total thyroidectomy the insurance should provide 138.389,72 RSD / 57, 83 QALY i.e. 2.393,04 dinars for one quality-adjusted life year, and for radioactive iodine the insurance should provide 110.043,64 RSD / 57,82 QALY i.e. 1.903,37 dinars for one quality-adjusted life year. This economic analysis showed that radioactive iodine has better ratio of costs to clinical effectiveness as opposed to total thyroidectomy.

Animal board invited review: Dairy cow lameness expenditures, losses and total cost.

Science.gov (United States)

Dolecheck, K; Bewley, J

2018-03-20

Lameness is one of the most costly dairy cow diseases, yet adoption of lameness prevention strategies remains low. Low lameness prevention adoption might be attributable to a lack of understanding regarding total lameness costs. In this review, we evaluated the contribution of different expenditures and losses to total lameness costs. Evaluated expenditures included labor for treatment, therapeutic supplies, lameness detection and lameness control and prevention. Evaluated losses included non-saleable milk, reduced milk production, reduced reproductive performance, increased animal death, increased animal culling, disease interrelationships, lameness recurrence and reduced animal welfare. The previous literature on total lameness cost estimates was also summarized. The reviewed studies indicated that previous estimates of total lameness costs are variable and inconsistent in the expenditures and losses they include. Many of the identified expenditure and loss categories require further research to accurately include in total lameness cost estimates. Future research should focus on identifying costs associated with specific lameness conditions, differing lameness severity levels, and differing stages of lactation at onset of lameness to provide better total lameness cost estimates that can be useful for decision making at both the herd and individual cow level.

Association of Hospital Costs With Complications Following Total Gastrectomy for Gastric Adenocarcinoma.

Science.gov (United States)

Selby, Luke V; Gennarelli, Renee L; Schnorr, Geoffrey C; Solomon, Stephen B; Schattner, Mark A; Elkin, Elena B; Bach, Peter B; Strong, Vivian E

2017-10-01

Postoperative complications are associated with increased hospital costs following major surgery, but the mechanism by which they increase cost and the categories of care that drive this increase are poorly described. To describe the association of postoperative complications with hospital costs following total gastrectomy for gastric adenocarcinoma. This retrospective analysis of a prospectively collected gastric cancer surgery database at a single National Cancer Institute-designated comprehensive cancer center included all patients undergoing curative-intent total gastrectomy for gastric adenocarcinoma between January 2009 and December 2012 and was conducted in 2015 and 2016. Ninety-day normalized postoperative costs. Hospital accounting system costs were normalized to reflect Medicare reimbursement levels using the ratio of hospital costs to Medicare reimbursement and categorized into major cost categories. Differences between costs in Medicare proportional dollars (MP $) can be interpreted as the amount that would be reimbursed to an average hospital by Medicare if it paid differentially based on types and extent of postoperative complications. In total, 120 patients underwent curative-intent total gastrectomy for stage I through III gastric adenocarcinoma between 2009 and 2012. Of these, 79 patients (65.8%) were men, and the median (interquartile range) age was 64 (52-70) years. The 51 patients (42.5%) who underwent an uncomplicated total gastrectomy had a mean (SD) normalized cost of MP $12 330 (MP $2500), predominantly owing to the cost of surgical care (mean [SD] cost, MP $6830 [MP $1600]). The 34 patients (28.3%) who had a major complication had a mean (SD) normalized cost of MP $37 700 (MP $28 090). Surgical care was more expensive in these patients (mean [SD] cost, MP $8970 [MP $2750]) but was a smaller contributor to total cost (24%) owing to increased costs from room and board (mean [SD] cost, MP $11 940 [MP $8820]), consultations (mean [SD

Real-time electrochemical monitoring of isothermal helicase-dependent amplification of nucleic acids.

Science.gov (United States)

Kivlehan, Francine; Mavré, François; Talini, Luc; Limoges, Benoît; Marchal, Damien

2011-09-21

We described an electrochemical method to monitor in real-time the isothermal helicase-dependent amplification of nucleic acids. The principle of detection is simple and well-adapted to the development of portable, easy-to-use and inexpensive nucleic acids detection technologies. It consists of monitoring a decrease in the electrochemical current response of a reporter DNA intercalating redox probe during the isothermal DNA amplification. The method offers the possibility to quantitatively analyze target nucleic acids in less than one hour at a single constant temperature, and to perform at the end of the isothermal amplification a DNA melt curve analysis for differentiating between specific and non-specific amplifications. To illustrate the potentialities of this approach for the development of a simple, robust and low-cost instrument with high throughput capability, the method was validated with an electrochemical system capable of monitoring up to 48 real-time isothermal HDA reactions simultaneously in a disposable microplate consisting of 48-electrochemical microwells. Results obtained with this approach are comparable to that obtained with a well-established but more sophisticated and expensive fluorescence-based method. This makes for a promising alternative detection method not only for real-time isothermal helicase-dependent amplification of nucleic acid, but also for other isothermal DNA amplification strategies.

Optimizing the specificity of nucleic acid hybridization.

Science.gov (United States)

Zhang, David Yu; Chen, Sherry Xi; Yin, Peng

2012-01-22

The specific hybridization of complementary sequences is an essential property of nucleic acids, enabling diverse biological and biotechnological reactions and functions. However, the specificity of nucleic acid hybridization is compromised for long strands, except near the melting temperature. Here, we analytically derived the thermodynamic properties of a hybridization probe that would enable near-optimal single-base discrimination and perform robustly across diverse temperature, salt and concentration conditions. We rationally designed 'toehold exchange' probes that approximate these properties, and comprehensively tested them against five different DNA targets and 55 spurious analogues with energetically representative single-base changes (replacements, deletions and insertions). These probes produced discrimination factors between 3 and 100+ (median, 26). Without retuning, our probes function robustly from 10 °C to 37 °C, from 1 mM Mg(2+) to 47 mM Mg(2+), and with nucleic acid concentrations from 1 nM to 5 µM. Experiments with RNA also showed effective single-base change discrimination.

Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids

Directory of Open Access Journals (Sweden)

Joana R. Viola

2013-01-01

Full Text Available Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment mostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with chemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied. As an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst avoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease, discusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic intervention with nucleic acids. We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma therapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already clinical application of nucleic acids in melanoma are discussed.

Immunotherapeutic effect of BCG-polysaccharide nucleic acid powder on Mycobacterium tuberculosis-infected mice using microneedle patches.

Science.gov (United States)

Yan, Qinying; Liu, Houming; Cheng, Zhigang; Xue, Yun; Cheng, Zhide; Dai, Xuyong; Shan, Wanshui; Chen, Fan

2017-11-01

Polysaccharide nucleic acid fractions of bacillus Calmette-Guérin, termed BCG-PSN, have traditionally been used as immunomodulators in the treatment of dermatitis and allergic diseases. While the sales of injectable BCG-PSN have shown steady growth in recent years, no reports of using BCG-PSN powder or its immunotherapeutic effects exist. Here, BCG-PSN powder was applied directly to the skin to evaluate the immunotherapeutic effects on mice infected with Mycobacterium tuberculosis (MTB). In total, 34 μg of BCG-PSN powder could be loaded into a microneedle patch (MNP). Mice receiving BCG-PSN powder delivered via MNP exhibited significantly increased IFN-γ and TNF-α production in peripheral blood CD4 + T cells and improved pathological changes in their lungs and spleens compared to control group mice. The immunotherapeutic effect of BCG-PSN powder delivered via MNP was better than that delivered via intramuscular injection to some extent. Furthermore, MNPs eliminate the side effects of syringes, and this study demonstrated that BCG-PSN can be clinically administrated in powder form.

Histidine-lysine peptides as carriers of nucleic acids.

Science.gov (United States)

Leng, Qixin; Goldgeier, Lisa; Zhu, Jingsong; Cambell, Patricia; Ambulos, Nicholas; Mixson, A James

2007-03-01

With their biodegradability and diversity of permutations, peptides have significant potential as carriers of nucleic acids. This review will focus on the sequence and branching patterns of peptide carriers composed primarily of histidines and lysines. While lysines within peptides are important for binding to the negatively charged phosphates, histidines are critical for endosomal lysis enabling nucleic acids to reach the cytosol. Histidine-lysine (HK) polymers by either covalent or ionic bonds with liposomes augment transfection compared to liposome carriers alone. More recently, we have examined peptides as sole carriers of nucleic acids because of their intrinsic advantages compared to the bipartite HK/liposome carriers. With a protocol change and addition of a histidine-rich tail, HK peptides as sole carriers were more effective than liposomes alone in several cell lines. While four-branched polymers with a primary repeating sequence pattern of -HHK- were more effective as carriers of plasmids, eight-branched polymers with a sequence pattern of -HHHK- were more effective as carriers of siRNA. Compared to polyethylenimine, HK carriers of siRNA and plasmids had reduced toxicity. When injected intravenously, HK polymers in complex with plasmids encoding antiangiogenic proteins significantly decreased tumor growth. Furthermore, modification of HK polymers with polyethylene glycol and vascular-specific ligands increased specificity of the polyplex to the tumor by more than 40-fold. Together with further development and insight on the structure of HK polyplexes, HK peptides may prove to be useful as carriers of different forms of nucleic acids both in vitro and in vivo.

Total cost of ownership of CHP SOFC systems: Effect of installation context

International Nuclear Information System (INIS)

Arduino, Francesco; Santarelli, Massimo

2016-01-01

Solid oxide fuel cells (SOFC) are one of the most interesting between the emerging technologies for energy production. Although some information about the production cost of these devices are already known, their operational cost has not been studied yet with sufficient accuracy. This paper presents a life cycle cost (LCC) analysis of CHP (combined heat and power) SOFC systems performed in hospitals located in various cities of the US and one in Italy. In this study the strong effects of the installation context will be analyzed using a customized use phase model for each location. The cost effectiveness of these devices has been proved without credits in Mondovi (IT), New York (NY) and Minneapolis (MN) where the payback time goes from 10 to 7 years. Considering the credits, it is possible to obtain economic feasibility also in Chicago (IL) and reduce the payback for other cities to values from 4 to 6 years. In other cities like Phoenix (AZ) and Houston (TX) the payback can’t be reached in any case. The life cycle impact assessment analysis has shown how, even in the cities with cleaner electricity grid, there is a reduction in the emissions of both greenhouse gases and pollutants. - Highlights: •Life cycle cost analysis has been performed for CHP SOFC systems. •The strong effects of the installation context have been analyzed. •Economic feasibility has been proven in new york, Minneapolis and Mondovi. •Economic feasibility can’t be reached in phoenix and Houston. •SOFC always provide a reduction in the emissions of greenhouse gases and pollutant.

[Preliminary analysis of total cost and life quality for elder patients with femoral neck fracture].

Science.gov (United States)

Liu, Haonan; He, Liang; Zhang, Guilin; Gong, Xiaofeng; Li, Ning

2015-09-01

To analyze the total cost and life quality of the femoral neck fracture patients who received different surgery and supplement comprehensive data of osteoporotic fracture. One hundred and five patients above 60-year old who were diagnosed femoral neck fracture and received operation in Department of Orthopedics ＆ Traumatology, Beijing Jishuitan Hospital were admitted into our study from August 2013 to December. According to the type of surgery there were 52 and 53 cases in internal fixation (IF) group and hemiarthroplasty (HA) group respectively. At first we collected the medical expense of the patients before and during hospitalization. And then the 1-year medical and non-medical expenses were collected by the cost diary ever 3 months after discharge. At the last follow-up we evaluated the life quality by the EuroQol-5 Dimensions (EQ-5D) and calculated the total cost. Outcome All the patients completed the operation successfully. No nonunion or delayed union cases in IF group, and no cases received revision surgery in both groups. The total average cost was 59 584.9 yuan including 79.1% medical cost and 20.9% non-medical cost. The primary treatment cost accounts for 84.1% of the medical cost. The cost for home care accounts for 90.7% of the non-medical care. The total and medical cost of IF group just account for 40.3% and 38.5% of the HA group and the non-medical showed no significant difference between the 2 groups (P>0.05). In addition the data of life quality and walking capability also showed no significant difference. The main cost for the femoral neck fracture is medical expense in 1-year follow-up. Both surgeries can provide satisfactory outcome, however IF may be more cost-effective compared to the HA because of the less total cost.

The total lifetime health cost savings of smoking cessation to society

DEFF Research Database (Denmark)

Rasmussen, Gitte Susanne; Prescott, Eva; Sørensen, Thorkild I A

2005-01-01

Smoking cessation has major immediate and long-term health benefits. However, ex-smokers' total lifetime health costs and continuing smokers' costs remain uncompared, and hence the economic savings of smoking cessation to society have not been determined.......Smoking cessation has major immediate and long-term health benefits. However, ex-smokers' total lifetime health costs and continuing smokers' costs remain uncompared, and hence the economic savings of smoking cessation to society have not been determined....

Cost-Effectiveness of Five Commonly Used Prosthesis Brands for Total Knee Replacement in the UK: A Study Using the NJR Dataset.

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Mark Pennington

Full Text Available There is a lack of evidence on the effectiveness or cost-effectiveness of alternative brands of prosthesis for total knee replacement (TKR. We compared patient-reported outcomes, revision rates, and costs, and estimated the relative cost-effectiveness of five frequently used cemented brands of unconstrained prostheses with fixed bearings (PFC Sigma, AGC Biomet, Nexgen, Genesis 2, and Triathlon.We used data from three national databases for patients who had a TKR between 2003 and 2012, to estimate the effect of prosthesis brand on post-operative quality of life (QOL (EQ-5D-3L in 53 126 patients at six months. We compared TKR revision rates by brand over 10 years for 239 945 patients. We used a fully probabilistic Markov model to estimate lifetime costs and quality-adjusted life years (QALYs, incremental cost effectiveness ratios (ICERs, and the probability that each prosthesis brand is the most cost effective at alternative thresholds of willingness-to-pay for a QALY gain.Revision rates were lowest with the Nexgen and PFC Sigma (2.5% after 10 years in 70-year-old women. Average lifetime costs were lowest with the AGC Biomet (£9 538; mean post-operative QOL was highest with the Nexgen, which was the most cost-effective brand across all patient subgroups. For example, for 70-year-old men and women, the ICERs for the Nexgen compared to the AGC Biomet were £2 300 per QALY. At realistic cost per QALY thresholds (£10 000 to £30 000, the probabilities that the Nexgen is the most cost-effective brand are about 98%. These results were robust to alternative modelling assumptions.AGC Biomet prostheses are the least costly cemented unconstrained fixed brand for TKR but Nexgen prostheses lead to improved patient outcomes, at low additional cost. These results suggest that Nexgen should be considered as a first choice prosthesis for patients with osteoarthritis who require a TKR.

Artificial Specific Binders Directly Recovered from Chemically Modified Nucleic Acid Libraries

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Yuuya Kasahara

2012-01-01

Full Text Available Specific binders comprised of nucleic acids, that is, RNA/DNA aptamers, are attractive functional biopolymers owing to their potential broad application in medicine, food hygiene, environmental analysis, and biological research. Despite the large number of reports on selection of natural DNA/RNA aptamers, there are not many examples of direct screening of chemically modified nucleic acid aptamers. This is because of (i the inferior efficiency and accuracy of polymerase reactions involving transcription/reverse-transcription of modified nucleotides compared with those of natural nucleotides, (ii technical difficulties and additional time and effort required when using modified nucleic acid libraries, and (iii ambiguous efficacies of chemical modifications in binding properties until recently; in contrast, the effects of chemical modifications on biostability are well studied using various nucleotide analogs. Although reports on the direct screening of a modified nucleic acid library remain in the minority, chemical modifications would be essential when further functional expansion of nucleic acid aptamers, in particular for medical and biological uses, is considered. This paper focuses on enzymatic production of chemically modified nucleic acids and their application to random screenings. In addition, recent advances and possible future research are also described.

Artificial specific binders directly recovered from chemically modified nucleic acid libraries.

Science.gov (United States)

Kasahara, Yuuya; Kuwahara, Masayasu

2012-01-01

Specific binders comprised of nucleic acids, that is, RNA/DNA aptamers, are attractive functional biopolymers owing to their potential broad application in medicine, food hygiene, environmental analysis, and biological research. Despite the large number of reports on selection of natural DNA/RNA aptamers, there are not many examples of direct screening of chemically modified nucleic acid aptamers. This is because of (i) the inferior efficiency and accuracy of polymerase reactions involving transcription/reverse-transcription of modified nucleotides compared with those of natural nucleotides, (ii) technical difficulties and additional time and effort required when using modified nucleic acid libraries, and (iii) ambiguous efficacies of chemical modifications in binding properties until recently; in contrast, the effects of chemical modifications on biostability are well studied using various nucleotide analogs. Although reports on the direct screening of a modified nucleic acid library remain in the minority, chemical modifications would be essential when further functional expansion of nucleic acid aptamers, in particular for medical and biological uses, is considered. This paper focuses on enzymatic production of chemically modified nucleic acids and their application to random screenings. In addition, recent advances and possible future research are also described.

Internal Logistics System Selection with Total Cost of Ownership Analysis

Science.gov (United States)

Araújo, Inês; Pimentel, Carina; Godina, Radu; Matias, João C. O.

2017-06-01

In this paper a methodology was followed in order to support the decision-making of one industrial unit regarding its internal logistics system. The addressed factory was facing issues with their internal logistics approach. Some alternatives were pointed out and a proper total cost of ownership (TCO) analysis was developed. This analysis was taken in order to demonstrate the more cost-effective solution for the internal logistics system. This tool is more and more valued by the companies, due to their willing to reduce the costs that are associated with the way of doing business. Despite the proposal of the best choice for the internal logistics system of the enterprise, this study also intends to present some conclusions about the match between the nature of the industrial unit and the logistics systems that best fit the requirements of those.

FTA Cards for Preservation of Nucleic Acids for Molecular Assays: A Review on the Use of Cytologic/Tissue Samples.

Science.gov (United States)

da Cunha Santos, Gilda

2018-03-01

- Traditional methods for storing histologic and cytologic specimens for future use in molecular assays have consisted of either snap-freezing with cryopreservation or formalin-fixing, paraffin-embedding the samples. Although snap-freezing with cryopreservation is recommended for better preservation of nucleic acids, the infrastructure and space required for archiving impose challenges for high-volume pathology laboratories. Cost-effective, long-term storage at room temperature; relatively easy shipment; and standardized handling can be achieved with formalin-fixed, paraffin-embedded samples, but formalin fixation induces fragmentation and chemical modification of nucleic acids. Advances in next-generation sequencing platforms, coupled with an increase in diagnostic, prognostic, and predictive molecular biomarkers have created a demand for high-quality nucleic acids. To address issues of the quality of nucleic acid and logistics in sample acquisition, alternatives for specimen preservation and long-term storage have been described and include novel universal tissue fixatives, stabilizers, and technologies. - To collect, retrieve, and review information from studies describing the use of nucleic acids recovered from cytologic/tissue specimens stored on Flinders Technology Associates (FTA, GE Whatman, Maidstone, Kent, United Kingdom) cards for downstream molecular applications. - An electronic literature search in the PubMed (National Center for Biotechnology Information, Bethesda, Maryland) database allowed the selection of manuscripts addressing the use of FTA cards for storage of cytologic samples for molecular analysis. Only articles published in English were retrieved. - The use of FTA cards is a versatile method for fostering multicenter, international collaborations and clinical trials that require centralized testing, long-distance shipment, and high-quality nucleic acids for molecular techniques. Studies with controlled temperature are required to test the

Use of Nucleic Acid Analogs for the Study of Nucleic Acid Interactions

Directory of Open Access Journals (Sweden)

Shu-ichi Nakano

2011-01-01

Full Text Available Unnatural nucleosides have been explored to expand the properties and the applications of oligonucleotides. This paper briefly summarizes nucleic acid analogs in which the base is modified or replaced by an unnatural stacking group for the study of nucleic acid interactions. We also describe the nucleoside analogs of a base pair-mimic structure that we have examined. Although the base pair-mimic nucleosides possess a simplified stacking moiety of a phenyl or naphthyl group, they can be used as a structural analog of Watson-Crick base pairs. Remarkably, they can adopt two different conformations responding to their interaction energies, and one of them is the stacking conformation of the nonpolar aromatic group causing the site-selective flipping of the opposite base in a DNA double helix. The base pair-mimic nucleosides can be used to study the mechanism responsible for the base stacking and the flipping of bases out of a nucleic acid duplex.

Method of Identifying a Base in a Nucleic Acid

Science.gov (United States)

Fodor, Stephen P. A.; Lipshutz, Robert J.; Huang, Xiaohua

1999-01-01

Devices and techniques for hybridization of nucleic acids and for determining the sequence of nucleic acids. Arrays of nucleic acids are formed by techniques, preferably high resolution, light-directed techniques. Positions of hybridization of a target nucleic acid are determined by, e.g., epifluorescence microscopy. Devices and techniques are proposed to determine the sequence of a target nucleic acid more efficiently and more quickly through such synthesis and detection techniques.

Nucleic acid detection based on the use of microbeads: a review

International Nuclear Information System (INIS)

Rödiger, Stefan; Liebsch, Claudia; Schmidt, Carsten; Schierack, Peter; Lehmann, Werner; Resch-Genger, Ute; Schedler, Uwe

2014-01-01

Microbead-based technologies represent elegant and versatile approaches for highly parallelized quantitative multiparameter assays. They also form the basis of various techniques for detection and quantification of nucleic acids and proteins. Nucleic acid-based methods include hybridization assays, solid-phase PCR, sequencing, and trapping assays. Microbead assays have been improved in the past decades and are now important tools in routine and point-of-care diagnostics as well as in life science. Its advances include low costs, low workload, high speed and high-throughput automation. The potential of microbead-based assays therefore is apparent, and commercial applications can be found in the detection and discrimination of single nucleotide polymorphism, of pathogens, and in trapping assays. This review provides an overview on microbead-based platforms for biosensing with a main focus on nucleic acid detection (including amplification strategies and on selected probe systems using fluorescent labeling). Specific sections cover chemical properties of microbeads, the coupling of targets onto solid surfaces, microbead probe systems (mainly oligonucleotide probes), microbead detection schemes (with subsections on suspension arrays, microfluidic devices, and immobilized microbeads), quantification of nucleic acids, PCR in solution and the detection of amplicons, and methods for solid-phase amplification. We discuss selected trends such as microbead-coupled amplification, heterogeneous and homogenous DNA hybridization assays, real-time assays, melting curve analysis, and digital microbead assays. We finally discuss the relevance and trends of the methods in terms of high-level multiplexed analysis and their potential in diagnosis and personalized medicine. (author)

Detection of nucleic acid sequences by invader-directed cleavage

Science.gov (United States)

Brow, Mary Ann D.; Hall, Jeff Steven Grotelueschen; Lyamichev, Victor; Olive, David Michael; Prudent, James Robert

1999-01-01

The present invention relates to means for the detection and characterization of nucleic acid sequences, as well as variations in nucleic acid sequences. The present invention also relates to methods for forming a nucleic acid cleavage structure on a target sequence and cleaving the nucleic acid cleavage structure in a site-specific manner. The 5' nuclease activity of a variety of enzymes is used to cleave the target-dependent cleavage structure, thereby indicating the presence of specific nucleic acid sequences or specific variations thereof. The present invention further relates to methods and devices for the separation of nucleic acid molecules based by charge.

Comparative evaluation of three commercial systems for nucleic acid extraction from urine specimens.

Science.gov (United States)

Tang, Yi-Wei; Sefers, Susan E; Li, Haijing; Kohn, Debra J; Procop, Gary W

2005-09-01

A nucleic acid extraction system that can handle small numbers of specimens with a short test turnaround time and short hands-on time is desirable for emergent testing. We performed a comparative validation on three systems: the MagNA Pure compact system (Compact), the NucliSens miniMAG extraction instrument (miniMAG), and the BioRobot EZ1 system (EZ1). A total of 75 urine specimens submitted for polyomavirus BK virus detection were used. The human beta-actin gene was detected on 75 (100%), 75 (100%), and 72 (96%) nucleic acid extracts prepared by the miniMAG, EZ1, and Compact, respectively. The miniMAG produced the highest quantity of nucleic acids and the best precision among the three systems. The agreement rate was 100% for BKV detection on nucleic acid extracts prepared by the three extraction systems. When a full panel of specimens was run, the hands-on time and test turnaround time were 105.7 and 121.1 min for miniMAG, 6.1 and 22.6 min for EZ1, and 7.4 and 33.7 min for Compact, respectively. The EZ1 and Compact systems processed automatic nucleic acid extraction properly, providing a good solution to the need for sporadic but emergent specimen detection. The miniMAG yielded the highest quantity of nucleic acids, suggesting that this system would be the best for specimens containing a low number of microorganisms of interest.

Colorimetric Nucleic Acid Detection on Paper Microchip Using Loop Mediated Isothermal Amplification and Crystal Violet Dye.

Science.gov (United States)

Roy, Sharmili; Mohd-Naim, Noor Faizah; Safavieh, Mohammadali; Ahmed, Minhaz Uddin

2017-11-22

Nucleic acid detection is of paramount importance in monitoring of microbial pathogens in food safety and infectious disease diagnostic applications. To address these challenges, a rapid, cost-effective label-free technique for nucleic acid detection with minimal instrumentations is highly desired. Here, we present paper microchip to detect and quantify nucleic acid using colorimetric sensing modality. The extracted DNA from food samples of meat as well as microbial pathogens was amplified utilizing loop-mediated isothermal amplification (LAMP). LAMP amplicon was then detected and quantified on a paper microchip fabricated in a cellulose paper and a small wax chamber utilizing crystal violet dye. The affinity of crystal violet dye toward dsDNA and positive signal were identified by changing the color from colorless to purple. Using this method, detection of Sus scrofa (porcine) and Bacillus subtilis (bacteria) DNA was possible at concentrations as low as 1 pg/μL (3.43 × 10 -1 copies/μL) and 10 pg/μL (2.2 × 10 3 copies/μL), respectively. This strategy can be adapted for detection of other DNA samples, with potential for development of a new breed of simple and inexpensive paper microchip at the point-of-need.

BIOPHYSICAL PROPERTIES OF NUCLEIC ACIDS AT SURFACES RELEVANT TO MICROARRAY PERFORMANCE.

Science.gov (United States)

Rao, Archana N; Grainger, David W

2014-04-01

Both clinical and analytical metrics produced by microarray-based assay technology have recognized problems in reproducibility, reliability and analytical sensitivity. These issues are often attributed to poor understanding and control of nucleic acid behaviors and properties at solid-liquid interfaces. Nucleic acid hybridization, central to DNA and RNA microarray formats, depends on the properties and behaviors of single strand (ss) nucleic acids (e.g., probe oligomeric DNA) bound to surfaces. ssDNA's persistence length, radius of gyration, electrostatics, conformations on different surfaces and under various assay conditions, its chain flexibility and curvature, charging effects in ionic solutions, and fluorescent labeling all influence its physical chemistry and hybridization under assay conditions. Nucleic acid (e.g., both RNA and DNA) target interactions with immobilized ssDNA strands are highly impacted by these biophysical states. Furthermore, the kinetics, thermodynamics, and enthalpic and entropic contributions to DNA hybridization reflect global probe/target structures and interaction dynamics. Here we review several biophysical issues relevant to oligomeric nucleic acid molecular behaviors at surfaces and their influences on duplex formation that influence microarray assay performance. Correlation of biophysical aspects of single and double-stranded nucleic acids with their complexes in bulk solution is common. Such analysis at surfaces is not commonly reported, despite its importance to microarray assays. We seek to provide further insight into nucleic acid-surface challenges facing microarray diagnostic formats that have hindered their clinical adoption and compromise their research quality and value as genomics tools.

BIOPHYSICAL PROPERTIES OF NUCLEIC ACIDS AT SURFACES RELEVANT TO MICROARRAY PERFORMANCE

Science.gov (United States)

Rao, Archana N.; Grainger, David W.

2014-01-01

Both clinical and analytical metrics produced by microarray-based assay technology have recognized problems in reproducibility, reliability and analytical sensitivity. These issues are often attributed to poor understanding and control of nucleic acid behaviors and properties at solid-liquid interfaces. Nucleic acid hybridization, central to DNA and RNA microarray formats, depends on the properties and behaviors of single strand (ss) nucleic acids (e.g., probe oligomeric DNA) bound to surfaces. ssDNA’s persistence length, radius of gyration, electrostatics, conformations on different surfaces and under various assay conditions, its chain flexibility and curvature, charging effects in ionic solutions, and fluorescent labeling all influence its physical chemistry and hybridization under assay conditions. Nucleic acid (e.g., both RNA and DNA) target interactions with immobilized ssDNA strands are highly impacted by these biophysical states. Furthermore, the kinetics, thermodynamics, and enthalpic and entropic contributions to DNA hybridization reflect global probe/target structures and interaction dynamics. Here we review several biophysical issues relevant to oligomeric nucleic acid molecular behaviors at surfaces and their influences on duplex formation that influence microarray assay performance. Correlation of biophysical aspects of single and double-stranded nucleic acids with their complexes in bulk solution is common. Such analysis at surfaces is not commonly reported, despite its importance to microarray assays. We seek to provide further insight into nucleic acid-surface challenges facing microarray diagnostic formats that have hindered their clinical adoption and compromise their research quality and value as genomics tools. PMID:24765522

Triptycene: A Nucleic Acid Three-Way Junction Binder Scaffold

Science.gov (United States)

Yoon, Ina

Nucleic acids play a critical role in many biological processes such as gene regulation and replication. The development of small molecules that modulate nucleic acids with sequence or structure specificity would provide new strategies for regulating disease states at the nucleic acid level. However, this remains challenging mainly because of the nonspecific interactions between nucleic acids and small molecules. Three-way junctions are critical structural elements of nucleic acids. They are present in many important targets such as trinucleotide repeat junctions related to Huntington's disease, a temperature sensor sigma32 in E. coli, Dengue virus, and HIV. Triptycene-derived small molecules have been shown to bind to nucleic acid three-way junctions, resulting from their shape complementary. To develop a better understanding of designing molecules for targeting different junctions, a rapid screening of triptycene-based small molecules is needed. We envisioned that the installation of a linker at C9 position of the bicyclic core would allow for a rapid solid phase diversification. To achieve this aim, we synthesized 9-substituted triptycene scaffolds by using two different synthetic routes. The first synthetic route installed the linker from the amidation reaction between carboxylic acid at C9 position of the triptycene and an amine linker, beta-alanine ethyl ester. This new 9-substituted triptycene scaffold was then attached to a 2-chlorotrityl chloride resin for solid-phase diversification. This enabled a rapid diversification and an easy purification of mono-, di-, and tri-peptide triptycene derivatives. The binding affinities of these compounds were investigated towards a (CAG)˙(CTG) trinucleotide repeat junction. In the modified second synthetic route, we utilized a combined Heck coupling/benzyne Diels-Alder strategy. This improved synthetic strategy reduced the number of steps and total reaction times, increased the overall yield, improved solubilities of

Integrated sample-to-detection chip for nucleic acid test assays.

Science.gov (United States)

Prakash, R; Pabbaraju, K; Wong, S; Tellier, R; Kaler, K V I S

2016-06-01

Nucleic acid based diagnostic techniques are routinely used for the detection of infectious agents. Most of these assays rely on nucleic acid extraction platforms for the extraction and purification of nucleic acids and a separate real-time PCR platform for quantitative nucleic acid amplification tests (NATs). Several microfluidic lab on chip (LOC) technologies have been developed, where mechanical and chemical methods are used for the extraction and purification of nucleic acids. Microfluidic technologies have also been effectively utilized for chip based real-time PCR assays. However, there are few examples of microfluidic systems which have successfully integrated these two key processes. In this study, we have implemented an electro-actuation based LOC micro-device that leverages multi-frequency actuation of samples and reagents droplets for chip based nucleic acid extraction and real-time, reverse transcription (RT) PCR (qRT-PCR) amplification from clinical samples. Our prototype micro-device combines chemical lysis with electric field assisted isolation of nucleic acid in a four channel parallel processing scheme. Furthermore, a four channel parallel qRT-PCR amplification and detection assay is integrated to deliver the sample-to-detection NAT chip. The NAT chip combines dielectrophoresis and electrostatic/electrowetting actuation methods with resistive micro-heaters and temperature sensors to perform chip based integrated NATs. The two chip modules have been validated using different panels of clinical samples and their performance compared with standard platforms. This study has established that our integrated NAT chip system has a sensitivity and specificity comparable to that of the standard platforms while providing up to 10 fold reduction in sample/reagent volumes.

Cost-effectiveness of cervical total disc replacement vs fusion for the treatment of 2-level symptomatic degenerative disc disease.

Science.gov (United States)

Ament, Jared D; Yang, Zhuo; Nunley, Pierce; Stone, Marcus B; Kim, Kee D

2014-12-01

Cervical total disc replacement (CTDR) was developed to treat cervical spondylosis, while preserving motion. While anterior cervical discectomy and fusion (ACDF) has been the standard of care for 2-level disease, a randomized clinical trial (RCT) suggested similar outcomes. Cost-effectiveness of this intervention has never been elucidated. To determine the cost-effectiveness of CTDR compared with ACDF. Data were derived from an RCT that followed up 330 patients over 24 months. The original RCT consisted of multi-institutional data including private and academic institutions. Using linear regression for the current study, health states were constructed based on the stratification of the Neck Disability Index and a visual analog scale. Data from the 12-item Short-Form Health Survey questionnaires were transformed into utilities values using the SF-6D mapping algorithm. Costs were calculated by extracting Diagnosis-Related Group codes from institutional billing data and then applying 2012 Medicare reimbursement rates. The costs of complications and return-to-work data were also calculated. A Markov model was built to evaluate quality-adjusted life-years (QALYs) for both treatment groups. The model adopted a third-party payer perspective and applied a 3% annual discount rate. Patients included in the original RCT had to be diagnosed as having radiculopathy or myeloradiculopathy at 2 contiguous levels from C3-C7 that was unresponsive to conservative treatment for at least 6 weeks or demonstrated progressive symptoms. Incremental cost-effectiveness ratio of CTDR compared with ACDF. A strong correlation (R2 = 0.6864; P sensitivity analysis, the incremental cost-effectiveness ratio value stays below the threshold of $50,000 per QALY in most scenarios (range, -$58,194 to $147,862 per QALY). The incremental cost-effectiveness ratio of CTDR compared with traditional ACDF is lower than the commonly accepted threshold of $50,000 per QALY. This remains true with varying input

Process Improvement Project Using Tranexamic Acid Is Cost-Effective in Reducing Blood Loss and Transfusions After Total Hip and Total Knee Arthroplasty.

Science.gov (United States)

Demos, Harry A; Lin, Zilan X; Barfield, William R; Wilson, Sylvia H; Robertson, Dawn C; Pellegrini, Vincent D

2017-08-01

Tranexamic acid (TXA) has been associated with decreased blood loss and transfusion after total hip arthroplasty (THA) and total knee arthroplasty (TKA). The purpose of this study was to examine both transfusion utilization and the economic impact of a Process Improvement Project implementing TXA for THA and TKA. After standardization of TXA administration in THA and TKA patients, retrospective data were compared from 12 consecutive months before (group A, n = 336 procedures) and after (group B, n = 436 procedures) project initiation. TXA administration increased with project implementation (group A = 3.57%, group B = 86.01%) and was associated with reductions in perioperative hemoglobin decrement (20.2%), patients transfused (45%), and number of units transfused per patient (61.9%). Cost savings were notable per patient ($128) and annually program wide ($55,884) with the primary THA subgroup contributing the most to the savings. No increase in adverse effects was observed. Standardized administration of TXA is an effective and economically favorable blood-reduction strategy for patients undergoing elective THA or TKA. Although reduction in transfusions with TXA may be greater after TKA, the economic and clinical impact of transfusion reduction is more substantial in THA patients. Copyright © 2017 Elsevier Inc. All rights reserved.

System for portable nucleic acid testing in low resource settings

Science.gov (United States)

Lu, Hsiang-Wei; Roskos, Kristina; Hickerson, Anna I.; Carey, Thomas; Niemz, Angelika

2013-03-01

Our overall goal is to enable timely diagnosis of infectious diseases through nucleic acid testing at the point-of-care and in low resource settings, via a compact system that integrates nucleic acid sample preparation, isothermal DNA amplification, and nucleic acid lateral flow (NALF) detection. We herein present an interim milestone, the design of the amplification and detection subsystem, and the characterization of thermal and fluidic control and assay execution within this system. Using an earlier prototype of the amplification and detection unit, comprised of a disposable cartridge containing flexible pouches, passive valves, and electrolysis-driven pumps, in conjunction with a small heater, we have demonstrated successful execution of an established and clinically validated isothermal loop-mediated amplification (LAMP) reaction targeting Mycobacterium tuberculosis (M.tb) DNA, coupled to NALF detection. The refined design presented herein incorporates miniaturized and integrated electrolytic pumps, novel passive valves, overall design changes to facilitate integration with an upstream sample preparation unit, and a refined instrument design that automates pumping, heating, and timing. Nucleic acid amplification occurs in a two-layer pouch that facilitates fluid handling and appropriate thermal control. The disposable cartridge is manufactured using low-cost and scalable techniques and forms a closed system to prevent workplace contamination by amplicons. In a parallel effort, we are developing a sample preparation unit based on similar design principles, which performs mechanical lysis of mycobacteria and DNA extraction from liquefied and disinfected sputum. Our next step is to combine sample preparation, amplification, and detection in a final integrated cartridge and device, to enable fully automated sample-in to answer-out diagnosis of active tuberculosis in primary care facilities of low-resource and high-burden countries.

[Total knee and hip prosthesis: variables associated with costs].

Science.gov (United States)

Herrera-Espiñeira, Carmen; Escobar, Antonio; Navarro-Espigares, José Luis; Castillo, Juan de Dios Lunadel; García-Pérez, Lidia; Godoy-Montijano, Amparo

2013-01-01

The elevated prevalence of osteoarthritis in Western countries, the high costs of hip and knee arthroplasty, and the wide variations in the clinical practice have generated considerable interest in comparing the associated costs before and after surgery. To determine the influence of a number of variables on the costs of total knee and hip arthroplasty surgery during the hospital stay and during the one-year post-discharge. A prospective multi-center study was performed in 15 hospitals from three Spanish regions. Relationships between the independent variables and the costs of hospital stay and postdischarge follow-up were analyzed by using multilevel models in which the "hospital" variable was used to group cases. Independent variables were: age, sex, body mass index, preoperative quality of life (SF-12, EQ-5 and Womac questionnaires), surgery (hip/knee), Charlson Index, general and local complications, number of beds and economic-institutional dependency of the hospital, the autonomous region to which it belongs, and the presence of a caregiver. The cost of hospital stay, excluding the cost of the prosthesis, was 4,734 Euros, and the post-discharge cost was 554 Euros. With regard to hospital stay costs, the variance among hospitals explained 44-46% of the total variance among the patients. With regard to the post-discharge costs, the variability among hospitals explained 7-9% of the variance among the patients. There is considerable potential for reducing the hospital stay costs of these patients, given that more than 44% of the observed variability was not determined by the clinical conditions of the patients but rather by the behavior of the hospitals.

Procedure for estimating permanent total enclosure costs

Energy Technology Data Exchange (ETDEWEB)

Lukey, M.E.; Prasad, C.; Toothman, D.A.; Kaplan, N.

1999-07-01

Industries that use add-on control devices must adequately capture emissions before delivering them to the control device. One way to capture emissions is to use permanent total enclosures (PTEs). By definition, an enclosure which meets the US Environmental Protection Agency's five-point criteria is a PTE and has a capture efficiency of 100%. Since costs play an important role in regulatory development, in selection of control equipment, and in control technology evaluations for permitting purposes, EPA has developed a Control Cost Manual for estimating costs of various items of control equipment. EPA's Manual does not contain any methodology for estimating PTE costs. In order to assist environmental regulators and potential users of PTEs, a methodology for estimating PTE costs was developed under contract with EPA, by Pacific Environmental Services, Inc. (PES) and is the subject of this paper. The methodology for estimating PTE costs follows the approach used for other control devices in the Manual. It includes procedures for sizing various components of a PTE and for estimating capital as well as annual costs. It contains verification procedures for demonstrating compliance with EPA's five-point criteria. In addition, procedures are included to determine compliance with Occupational Safety and Health Administration (OSHA) standards. Meeting these standards is an important factor in properly designing PTEs. The methodology is encoded in Microsoft Exel spreadsheets to facilitate cost estimation and PTE verification. Examples are given throughout the methodology development and in the spreadsheets to illustrate the PTE design, verification, and cost estimation procedures.

Procedure for estimating permanent total enclosure costs

Energy Technology Data Exchange (ETDEWEB)

Lukey, M E; Prasad, C; Toothman, D A; Kaplan, N

1999-07-01

Industries that use add-on control devices must adequately capture emissions before delivering them to the control device. One way to capture emissions is to use permanent total enclosures (PTEs). By definition, an enclosure which meets the US Environmental Protection Agency's five-point criteria is a PTE and has a capture efficiency of 100%. Since costs play an important role in regulatory development, in selection of control equipment, and in control technology evaluations for permitting purposes, EPA has developed a Control Cost Manual for estimating costs of various items of control equipment. EPA's Manual does not contain any methodology for estimating PTE costs. In order to assist environmental regulators and potential users of PTEs, a methodology for estimating PTE costs was developed under contract with EPA, by Pacific Environmental Services, Inc. (PES) and is the subject of this paper. The methodology for estimating PTE costs follows the approach used for other control devices in the Manual. It includes procedures for sizing various components of a PTE and for estimating capital as well as annual costs. It contains verification procedures for demonstrating compliance with EPA's five-point criteria. In addition, procedures are included to determine compliance with Occupational Safety and Health Administration (OSHA) standards. Meeting these standards is an important factor in properly designing PTEs. The methodology is encoded in Microsoft Exel spreadsheets to facilitate cost estimation and PTE verification. Examples are given throughout the methodology development and in the spreadsheets to illustrate the PTE design, verification, and cost estimation procedures.

Synthetic Procedures for Peptide Nucleic Acids

DEFF Research Database (Denmark)

2004-01-01

A novel class of compounds, known as peptide nucleic acids, bind complementary ssDNA and RNA strands more strongly than a corresponding DNA. The peptide nucleic acids generally comprise ligands such as naturally occurring DNA bases attached to a peptide backbone through a suitable linker....

Time-based analysis of total cost of patient episodes: a case study of hip replacement.

Science.gov (United States)

Peltokorpi, Antti; Kujala, Jaakko

2006-01-01

Healthcare in the public and private sectors is facing increasing pressure to become more cost-effective. Time-based competition and work-in-progress have been used successfully to measure and improve the efficiency of industrial manufacturing. Seeks to address this issue. Presents a framework for time based management of the total cost of a patient episode and apply it to the six sigma DMAIC-process development approach. The framework is used to analyse hip replacement patient episodes in Päijät-Häme Hospital District in Finland, which has a catchment area of 210,000 inhabitants and performs an average of 230 hip replacements per year. The work-in-progress concept is applicable to healthcare--notably that the DMAIC-process development approach can be used to analyse the total cost of patient episodes. Concludes that a framework, which combines the patient-in-process and the DMAIC development approach, can be used not only to analyse the total cost of patient episode but also to improve patient process efficiency. Presents a framework that combines patient-in-process and DMAIC-process development approaches, which can be used to analyse the total cost of a patient episode in order to improve patient process efficiency.

Continuously tunable nucleic acid hybridization probes.

Science.gov (United States)

Wu, Lucia R; Wang, Juexiao Sherry; Fang, John Z; Evans, Emily R; Pinto, Alessandro; Pekker, Irena; Boykin, Richard; Ngouenet, Celine; Webster, Philippa J; Beechem, Joseph; Zhang, David Yu

2015-12-01

In silico-designed nucleic acid probes and primers often do not achieve favorable specificity and sensitivity tradeoffs on the first try, and iterative empirical sequence-based optimization is needed, particularly in multiplexed assays. We present a novel, on-the-fly method of tuning probe affinity and selectivity by adjusting the stoichiometry of auxiliary species, which allows for independent and decoupled adjustment of the hybridization yield for different probes in multiplexed assays. Using this method, we achieved near-continuous tuning of probe effective free energy. To demonstrate our approach, we enforced uniform capture efficiency of 31 DNA molecules (GC content, 0-100%), maximized the signal difference for 11 pairs of single-nucleotide variants and performed tunable hybrid capture of mRNA from total RNA. Using the Nanostring nCounter platform, we applied stoichiometric tuning to simultaneously adjust yields for a 24-plex assay, and we show multiplexed quantitation of RNA sequences and variants from formalin-fixed, paraffin-embedded samples.

Variation in the cost of care for primary total knee arthroplasties.

Science.gov (United States)

Haas, Derek A; Kaplan, Robert S

2017-03-01

The study examined the cost variation across 29 high-volume US hospitals and their affiliated orthopaedic surgeons for delivering a primary total knee arthroplasty without major complicating conditions. The hospitals had similar patient demographics, and more than 80% of them had statistically-similar Medicare risk-adjusted readmission and complication rates. Hospital and physician personnel costs were calculated using time-driven activity-based costing. Consumable supply costs, such as the prosthetic implant, were calculated using purchase prices, and postacute care costs were measured using either internal costs or external claims as reported by each hospital. Despite having similar patient demographics and readmission and complication rates, the average cost of care for total knee arthroplasty across the hospitals varied by a factor of about 2 to 1. Even after adjusting for differences in internal labor cost rates, the hospital at the 90th percentile of cost spent about twice as much as the one at the 10th percentile of cost. The large variation in costs among sites suggests major and multiple opportunities to transfer knowledge about process and productivity improvements that lower costs while simultaneously maintaining or improving outcomes.

Nucleic Acid-based Detection of Bacterial Pathogens Using Integrated Microfluidic Platform Systems

Directory of Open Access Journals (Sweden)

Carl A. Batt

2009-05-01

Full Text Available The advent of nucleic acid-based pathogen detection methods offers increased sensitivity and specificity over traditional microbiological techniques, driving the development of portable, integrated biosensors. The miniaturization and automation of integrated detection systems presents a significant advantage for rapid, portable field-based testing. In this review, we highlight current developments and directions in nucleic acid-based micro total analysis systems for the detection of bacterial pathogens. Recent progress in the miniaturization of microfluidic processing steps for cell capture, DNA extraction and purification, polymerase chain reaction, and product detection are detailed. Discussions include strategies and challenges for implementation of an integrated portable platform.

Hybridization and sequencing of nucleic acids using base pair mismatches

Science.gov (United States)

Fodor, Stephen P. A.; Lipshutz, Robert J.; Huang, Xiaohua

2001-01-01

Devices and techniques for hybridization of nucleic acids and for determining the sequence of nucleic acids. Arrays of nucleic acids are formed by techniques, preferably high resolution, light-directed techniques. Positions of hybridization of a target nucleic acid are determined by, e.g., epifluorescence microscopy. Devices and techniques are proposed to determine the sequence of a target nucleic acid more efficiently and more quickly through such synthesis and detection techniques.

Probe kit for identifying a base in a nucleic acid

Science.gov (United States)

Fodor, Stephen P. A.; Lipshutz, Robert J.; Huang, Xiaohua

2001-01-01

Devices and techniques for hybridization of nucleic acids and for determining the sequence of nucleic acids. Arrays of nucleic acids are formed by techniques, preferably high resolution, light-directed techniques. Positions of hybridization of a target nucleic acid are determined by, e.g., epifluorescence microscopy. Devices and techniques are proposed to determine the sequence of a target nucleic acid more efficiently and more quickly through such synthesis and detection techniques.

Multiplexed microfluidic approach for nucleic acid enrichment

Science.gov (United States)

VanderNoot, Victoria A.; Langevin, Stanley Alan; Bent, Zachary; Renzi, Ronald F.; Ferko, Scott M.; Van De Vreugde, James L.; Lane, Todd; Patel, Kamlesh; Branda, Steven

2016-04-26

A system for enhancing a nucleic acid sample may include a one pump, a denaturing chamber; a microfluidic hydroxyapatite chromatography device configured for performing hydroxyapatite chromatography on the nucleic acid sample, a sample collector, and tubing connecting the pump with the denaturing chamber, the hydroxyapatite chromatography device and the sample collector such that the pump may be used to move the nucleic acid sample from the denaturing chamber to the hydroxyapatite chromatography device and then to the sample collector.

Lateral flow devices for nucleic acid analysis exploiting quantum dots as reporters

Energy Technology Data Exchange (ETDEWEB)

Sapountzi, Eleni A.; Tragoulias, Sotirios S.; Kalogianni, Despina P. [Department of Chemistry, University of Patras, GR-26504 Patras (Greece); Ioannou, Penelope C. [Department of Chemistry, University of Athens, GR-15771 Athens (Greece); Christopoulos, Theodore K., E-mail: tchrist@upatras.gr [Department of Chemistry, University of Patras, GR-26504 Patras (Greece); Institute of Chemical Engineering and High Temperature Processes, Foundation of Research and Technology Hellas, GR-26504 Patras (Greece)

2015-03-15

Highlights: • Dipstick tests for DNA hybridization assays and genotyping of single-nucleotide polymorphisms. • Use of quantum dots as reporters. • Visual detection without the need for expensive instrumentation. • Simplicity and low-cost of the assays. - Abstract: There is a growing interest in the development of biosensors in the form of simple lateral flow devices that enable visual detection of nucleic acid sequences while eliminating several steps required for pipetting, incubation and washing out the excess of reactants. In this work, we present the first dipstick-type nucleic acid biosensors based on quantum dots (QDs) as reporters. The biosensors enable sequence confirmation of the target DNA by hybridization and simple visual detection of the emitted fluorescence under a UV lamp. The ‘diagnostic’ membrane of the biosensor contains a test zone (TZ) and a control zone (CZ). The CZ always fluoresces in order to confirm the proper function of the biosensor. Fluorescence is emitted from the TZ, only when the specific nucleic acid sequence is present. We have developed two general types of QD-based nucleic acid biosensors, namely, Type I and Type II, in which the TZ consists of either immobilized streptavidin (Type I) or immobilized oligodeoxynucleotides (Type II). The control zone consists of immobilized biotinylated albumin. No purification steps are required prior to the application of the DNA sample on the strip. The QD-based nucleic acid biosensors performed accurately and reproducibly when applied to (a) the visual detection of PCR amplification products and (b) visual genotyping of single nucleotide polymorphisms (SNPs) in human genomic DNA from clinical samples. As low as 1.5 fmol of double-stranded DNA were clearly detected by naked eye and the dynamic range extended to 200 fmol. The %CV were estimated to be 4.3–8.2.

Effectiveness and cost-effectiveness of antidepressants in primary care: a multiple treatment comparison meta-analysis and cost-effectiveness model.

Directory of Open Access Journals (Sweden)

Joakim Ramsberg

Full Text Available OBJECTIVE: To determine effectiveness and cost-effectiveness over a one-year time horizon of pharmacological first line treatment in primary care for patients with moderate to severe depression. DESIGN: A multiple treatment comparison meta-analysis was employed to determine the relative efficacy in terms of remission of 10 antidepressants (citalopram, duloxetine escitalopram, fluoxetine, fluvoxamine mirtazapine, paroxetine, reboxetine, sertraline and venlafaxine. The estimated remission rates were then applied in a decision-analytic model in order to estimate costs and quality of life with different treatments at one year. DATA SOURCES: Meta-analyses of remission rates from randomised controlled trials, and cost and quality-of-life data from published sources. RESULTS: The most favourable pharmacological treatment in terms of remission was escitalopram with an 8- to 12-week probability of remission of 0.47. Despite a high acquisition cost, this clinical effectiveness translated into escitalopram being both more effective and having a lower total cost than all other comparators from a societal perspective. From a healthcare perspective, the cost per QALY of escitalopram was €3732 compared with venlafaxine. CONCLUSION: Of the investigated antidepressants, escitalopram has the highest probability of remission and is the most effective and cost-effective pharmacological treatment in a primary care setting, when evaluated over a one year time-horizon. Small differences in remission rates may be important when assessing costs and cost-effectiveness of antidepressants.

The cost effectiveness of intracyctoplasmic sperm injection (ICSI).

Science.gov (United States)

Hollingsworth, Bruce; Harris, Anthony; Mortimer, Duncan

2007-12-01

To estimate the incremental cost effectiveness of ICSI, and total costs for the population of Australia. Treatment effects for three patient groups were drawn from a published systematic review and meta-analysis of trials comparing fertilisation outcomes for ICSI. Incremental costs derived from resource-based costing of ICSI and existing practice comparators for each patient group. Incremental cost per live birth for patients unsuited to IVF is estimated between A$8,500 and 13,400. For the subnormal semen indication, cost per live birth could be as low as A$3,600, but in the worst case scenario, there would just be additional incremental costs of A$600 per procedure. Multiplying out the additional costs of ICSI over the relevant target populations in Australia gives potential total financial implications of over A$31 million per annum. While there are additional benefits from ICSI procedure, particularly for those with subnormal sperm, the additional cost for the health care system is substantial.

How do high cost-sharing policies for physician care affect total care costs among people with chronic disease?

Science.gov (United States)

Xin, Haichang; Harman, Jeffrey S; Yang, Zhou

2014-01-01

This study examines whether high cost-sharing in physician care is associated with a differential impact on total care costs by health status. Total care includes physician care, emergency room (ER) visits and inpatient care. Since high cost-sharing policies can reduce needed care as well as unneeded care use, it raises the concern whether these policies are a good strategy for controlling costs among chronically ill patients. This study used the 2007 Medical Expenditure Panel Survey data with a cross-sectional study design. Difference in difference (DID), instrumental variable technique, two-part model, and bootstrap technique were employed to analyze cost data. Chronically ill individuals' probability of reducing any overall care costs was significantly less than healthier individuals (beta = 2.18, p = 0.04), while the integrated DID estimator from split results indicated that going from low cost-sharing to high cost-sharing significantly reduced costs by $12,853.23 more for sick people than for healthy people (95% CI: -$17,582.86, -$8,123.60). This greater cost reduction in total care among sick people likely resulted from greater cost reduction in physician care, and may have come at the expense of jeopardizing health outcomes by depriving patients of needed care. Thus, these policies would be inappropriate in the short run, and unlikely in the long run to control health plans costs among chronically ill individuals. A generous benefit design with low cost-sharing policies in physician care or primary care is recommended for both health plans and chronically ill individuals, to save costs and protect these enrollees' health status.

Cost of Radiotherapy Versus NSAID Administration for Prevention of Heterotopic Ossification After Total Hip Arthroplasty

International Nuclear Information System (INIS)

Strauss, Jonathan B.; Chen, Sea S.; Shah, Anand P.; Coon, Alan B.; Dickler, Adam

2008-01-01

Purpose: Heterotopic ossification (HO), or abnormal bone formation, is a common sequela of total hip arthroplasty. This abnormal bone can impair joint function and must be surgically removed to restore mobility. HO can be prevented by postoperative nonsteroidal anti-inflammatory drug (NSAID) use or radiotherapy (RT). NSAIDs are associated with multiple toxicities, including gastrointestinal bleeding. Although RT has been shown to be more efficacious than NSAIDs at preventing HO, its cost-effectiveness has been questioned. Methods and Materials: We performed an analysis of the cost of postoperative RT to the hip compared with NSAID administration, taking into account the costs of surgery for HO formation, treatment-induced morbidity, and productivity loss from missed work. The costs of RT, surgical revision, and treatment of gastrointestinal bleeding were estimated using the 2007 Medicare Fee Schedule and inpatient diagnosis-related group codes. The cost of lost wages was estimated using the 2006 median salary data from the U.S. Census Bureau. Results: The cost of administering RT was estimated at $899 vs. $20 for NSAID use. After accounting for the additional costs associated with revision total hip arthroplasty and gastrointestinal bleeding, the corresponding estimated costs were $1,208 vs. $930. Conclusion: If the costs associated with treatment failure and treatment-induced morbidity are considered, the cost of NSAIDs approaches that of RT. Other NSAID morbidities and quality-of-life differences that are difficult to quantify add to the cost of NSAIDs. These considerations have led us to recommend RT as the preferred modality for use in prophylaxis against HO after total hip arthroplasty, even when the cost is considered

A multi-perspective cost-effectiveness analysis comparing rivaroxaban with enoxaparin sodium for thromboprophylaxis after total hip and knee replacement in the German healthcare setting

Directory of Open Access Journals (Sweden)

Zindel Sonja

2012-07-01

Full Text Available Abstract Background Patients undergoing major orthopaedic surgery (MOS, such as total hip (THR or total knee replacement (TKR, are at high risk of developing venous thromboembolism (VTE. For thromboembolism prophylaxis, the oral anticoagulant rivaroxaban has recently been included in the German diagnosis related group (DRG system. However, the cost-effectiveness of rivaroxaban is still unclear from both the German statutory health insurance (SHI and the German hospital perspective. Objectives To assess the cost-effectiveness of rivaroxaban from the German statutory health insurance (SHI perspective and to analyse financial incentives from the German hospital perspective. Methods Based on data from the RECORD trials and German cost data, a decision tree was built. The model was run for two settings (THR and TKR and two perspectives (SHI and hospital per setting. Results Prophylaxis with rivaroxaban reduces VTE events (0.02 events per person treated after TKR; 0.007 after THR compared with enoxaparin. From the SHI perspective, prophylaxis with rivaroxaban after TKR is cost saving (€27.3 saving per patient treated. However, the cost-effectiveness after THR (€17.8 cost per person remains unclear because of stochastic uncertainty. From the hospital perspective, for given DRGs, the hospital profit will decrease through the use of rivaroxaban by €20.6 (TKR and €31.8 (THR per case respectively. Conclusions Based on our findings, including rivaroxaban for reimbursement in the German DRG system seems reasonable. Yet, adequate incentives for German hospitals to use rivaroxaban are still lacking.

Does the high nucleic acid content of individual bacterial cells allow us to discriminate between active cells and inactive cells in aquatic systems?

Science.gov (United States)

Lebaron, P; Servais, P; Agogué, H; Courties, C; Joux, F

2001-04-01

The nucleic acid contents of individual bacterial cells as determined with three different nucleic acid-specific fluorescent dyes (SYBR I, SYBR II, and SYTO 13) and flow cytometry were compared for different seawater samples. Similar fluorescence patterns were observed, and bacteria with high apparent nucleic acid contents (HNA) could be discriminated from bacteria with low nucleic acid contents (LNA). The best discrimination between HNA and LNA cells was found when cells were stained with SYBR II. Bacteria in different water samples collected from seven freshwater, brackish water, and seawater ecosystems were prelabeled with tritiated leucine and then stained with SYBR II. After labeling and staining, HNA, LNA, and total cells were sorted by flow cytometry, and the specific activity of each cellular category was determined from leucine incorporation rates. The HNA cells were responsible for most of the total bacterial production, and the specific activities of cells in the HNA population varied between samples by a factor of seven. We suggest that nucleic acid content alone can be a better indicator of the fraction of growing cells than total counts and that this approach should be combined with other fluorescent physiological probes to improve detection of the most active cells in aquatic systems.

Nucleic acid drugs: a novel approach

African Journals Online (AJOL)

Administrator

Nucleic acid base sequence of proteins plays a crucial role in the expression of gene. The gene is responsible for the synthesis of proteins and these proteins, which are synthesized, are responsible for the biological process and also for dreadful diseases as well. Once if the nucleic acid sequence is altered, we would be ...

Soybean phytase and nucleic acid encoding the same

OpenAIRE

1999-01-01

Isolated soybean phytase polypeptides and isolated nucleic acids encoding soybean phytases are provided. The invention is also directed to nucleic acid expression constructs, vectors, and host cells comprising the isolated soybean phytase nucleic acids, as well as methods for producing recombinant and non-recombinant purified soybean phytase. The invention also relates to transgenic plants expressing the soybean phytase, particularly expression under seed-specific expression control elements.

Strategies for reducing implant costs in the revision total knee arthroplasty episode of care.

Science.gov (United States)

Elbuluk, Ameer M; Old, Andrew B; Bosco, Joseph A; Schwarzkopf, Ran; Iorio, Richard

2017-12-01

Implant price has been identified as a significant contributing factor to high costs associated with revision total knee arthroplasty (rTKA). The goal of this study is to analyze the cost of implants used in rTKAs and to compare this pricing with 2 alternative pricing models. Using our institutional database, we identified 52 patients from January 1, 2014 to December 31, 2014. Average cost of components for each case was calculated and compared to the total hospital cost for that admission. Costs for an all-component revision were then compared to a proposed "direct to hospital" (DTH) standardized pricing model and a fixed price revision option. Potential savings were calculated from these figures. On average, 28% of the total hospital cost was spent on implants for rTKA. The average cost for revision of all components was $13,640 and ranged from $3000 to $28,000. On average, this represented 32.7% of the total hospital cost. Direct to hospital implant pricing could potentially save approximately $7000 per rTKA, and the fixed pricing model could provide a further $1000 reduction per rTKA-potentially saving $8000 per case on implants alone. Alternative implant pricing models could help lower the total cost of rTKA, which would allow hospitals to achieve significant cost containment.

Peptide nucleic acid (PNA) antisense effects in Escherichia coli

DEFF Research Database (Denmark)

Good, L; Nielsen, P E

1999-01-01

Antisense peptide nucleic acid (PNA) can be used to control cell growth, gene expression and growth phenotypes in the bacteria Escherichia coli. PNAs targeted to the RNA components of the ribosome can inhibit translation and cell growth, and PNAs targeted to mRNA can limit gene expression with gene...... and sequence specificity. In an E. coli cell extract, efficient inhibition is observed when using PNA concentrations in the nanomolar range, whereas micromolar concentrations are required for inhibition in growing cells. A mutant strain of E. coli that is more permeable to antibiotics also is more susceptible...... to antisense PNAs than the wild type. This chapter details methods for testing the antisense activities of PNA in E. coli. As an example of the specific antisense inhibition possible, we show the effects of an anti-beta-galactosidase PNA in comparison to control PNAs. With improvements in cell uptake...

Assessment for Melting Temperature Measurement of Nucleic Acid by HRM.

Science.gov (United States)

Wang, Jing; Pan, Xiaoming; Liang, Xingguo

2016-01-01

High resolution melting (HRM), with a high sensitivity to distinguish the nucleic acid species with small variations, has been widely applied in the mutation scanning, methylation analysis, and genotyping. For the aim of extending HRM for the evaluation of thermal stability of nucleic acid secondary structures on sequence dependence, we investigated effects of the dye of EvaGreen, metal ions, and impurities (such as dNTPs) on melting temperature ( T m ) measurement by HRM. The accuracy of HRM was assessed as compared with UV melting method, and little difference between the two methods was found when the DNA T m was higher than 40°C. Both insufficiency and excessiveness of EvaGreen were found to give rise to a little bit higher T m , showing that the proportion of dye should be considered for precise T m measurement of nucleic acids. Finally, HRM method was also successfully used to measure T m s of DNA triplex, hairpin, and RNA duplex. In conclusion, HRM can be applied in the evaluation of thermal stability of nucleic acid (DNA or RNA) or secondary structural elements (even when dNTPs are present).

Nucleic Acid Templated Reactions for Chemical Biology.

Science.gov (United States)

Di Pisa, Margherita; Seitz, Oliver

2017-06-21

Nucleic acid directed bioorthogonal reactions offer the fascinating opportunity to unveil and redirect a plethora of intracellular mechanisms. Nano- to picomolar amounts of specific RNA molecules serve as templates and catalyze the selective formation of molecules that 1) exert biological effects, or 2) provide measurable signals for RNA detection. Turnover of reactants on the template is a valuable asset when concentrations of RNA templates are low. The idea is to use RNA-templated reactions to fully control the biodistribution of drugs and to push the detection limits of DNA or RNA analytes to extraordinary sensitivities. Herein we review recent and instructive examples of conditional synthesis or release of compounds for in cellulo protein interference and intracellular nucleic acid imaging. © 2017 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Recent advances in delivery of drug-nucleic acid combinations for cancer treatment.

Science.gov (United States)

Li, Jing; Wang, Yan; Zhu, Yu; Oupický, David

2013-12-10

Cancer treatment that uses a combination of approaches with the ability to affect multiple disease pathways has been proven highly effective in the treatment of many cancers. Combination therapy can include multiple chemotherapeutics or combinations of chemotherapeutics with other treatment modalities like surgery or radiation. However, despite the widespread clinical use of combination therapies, relatively little attention has been given to the potential of modern nanocarrier delivery methods, like liposomes, micelles, and nanoparticles, to enhance the efficacy of combination treatments. This lack of knowledge is particularly notable in the limited success of vectors for the delivery of combinations of nucleic acids with traditional small molecule drugs. The delivery of drug-nucleic acid combinations is particularly challenging due to differences in the physicochemical properties of the two types of agents. This review discusses recent advances in the development of delivery methods using combinations of small molecule drugs and nucleic acid therapeutics to treat cancer. This review primarily focuses on the rationale used for selecting appropriate drug-nucleic acid combinations as well as progress in the development of nanocarriers suitable for simultaneous delivery of drug-nucleic acid combinations. Copyright © 2013 Elsevier B.V. All rights reserved.

Clinical evaluation based on cost-effectiveness

International Nuclear Information System (INIS)

Inoue, Takehiro; Inoue, Toshihiko

1998-01-01

We carried out two Phase III clinical trials using high dose rate (HDR) remote afterloading brachytherapy unit. We evaluated the clinical results based not only on the medical but also the economical standpoint. The first trial is the Phase III trial for cervical cancer treated with HDR or medium dose rate (MDR) intracavitary radiotherapy. The second one is the Phase III trial for tongue cancer treated with HDR or low dose rate (LDR) interstitial radiation. For cervical cancer, the survival rate of patients treated with HDR brachytherapy is the some as for LDR brachytherapy. The average total cost of treatment for the HDR group was 1.47 million yen, while that for the MDR group was 1.58 million yen. The average total admission days was 63. For tongue cancer, the local control rate of the HDR group is almost the same as that of the LDR groups. The average total cost for the HDR group was 780 thousand yen, and that for the LDR group was 830 thousand yen. The average total admission days was 34. According to the cost-effectiveness, HDR brachytherapy for cervical cancer has the same result as MDR, and HDR brachytherapy for tongue cancer has the same result as LDR. However, HDR can be treated without admission for patients who live near the hospital. HDR can be applied for these patients with less expense. We must be aware of not only the medical results but also the cost-effectiveness. (author)

Effects of ultraviolet and visible radiation on nucleic acids and proteins

International Nuclear Information System (INIS)

Loeber, G.

1977-01-01

Three possible photochemical reaction mechanisms have been discussed which might cause changes in biological materials: 1) Photoreactions induced in that constituents of cell substrates absorbing UV-light by themselves, i.e. heteroaromatic moieties of nucleic acids and proteins. 2) Photoreactions induced in that constituents not belonging to the natural biological system and absorbing UV-light, i.e. furocoumarins or cancer producing hydrocarbons. 3) Photoreactions induced in that proper sensitizer molecules absorbing UV-light or visible light. The latter type of photoreactions consumes molecular oxygen but does not consume sensitizer molecules (photodynamic action). Examples have been given for the three possibilities concerning photochemistry of nucleic acids and proteins. Damages of biopolymers were discussed with respect to their biological consequences. Photodynamic changes in the blood system might be caused either after addition of sensitizers to blood or by sensitizers which are constituents of blood itself, i.e. porphytines. (author)

Near-infrared optical imaging of nucleic acid nanocarriers in vivo.

Science.gov (United States)

Rome, Claire; Gravier, Julien; Morille, Marie; Divita, Gilles; Bolcato-Bellemin, Anne-Laure; Josserand, Véronique; Coll, Jean-Luc

2013-01-01

Noninvasive, real-time optical imaging methods are well suited to follow the in vivo distribution of nucleic acid nanocarriers, their dissociation, and the resulting gene expression or inhibition. Indeed, most small animal imaging devices perform bioluminescence and fluorescence measurements without moving the animal, allowing a simple, rapid, and cost-effective method of investigation of several parameters at a time, in longitudinal experiments that can last for days or weeks.Here we help the reader in choosing adapted near-infrared (NIR) fluorophores or pairs of fluorophores for Förster resonance energy transfer assays, imaging of reporter genes, as well as nanocarriers for in vivo gene and siRNA delivery. In addition, we present the labeling methods of these macromolecules and of their payload and the protocols to detect them using bioluminescence and NIR fluorescence imaging in mice.

Identification of nucleic acid binding sites on translin-associated factor X (TRAX protein.

Directory of Open Access Journals (Sweden)

Gagan Deep Gupta

Full Text Available Translin and TRAX proteins play roles in very important cellular processes such as DNA recombination, spatial and temporal expression of mRNA, and in siRNA processing. Translin forms a homomeric nucleic acid binding complex and binds to ssDNA and RNA. However, a mutant translin construct that forms homomeric complex lacking nucleic acid binding activity is able to form fully active heteromeric translin-TRAX complex when co-expressed with TRAX. A substantial progress has been made in identifying translin sites that mediate its binding activity, while TRAX was thought not to bind DNA or RNA on its own. We here for the first time demonstrate nucleic acid binding to TRAX by crosslinking radiolabeled ssDNA to heteromeric translin-TRAX complex using UV-laser. The TRAX and translin, photochemically crosslinked with ssDNA, were individually detected on SDS-PAGE. We mutated two motifs in TRAX and translin, designated B2 and B3, to help define the nucleic acid binding sites in the TRAX sequence. The most pronounced effect was observed in the mutants of B3 motif that impaired nucleic acid binding activity of the heteromeric complexes. We suggest that both translin and TRAX are binding competent and contribute to the nucleic acid binding activity.

Identification of Nucleic Acid Binding Sites on Translin-Associated Factor X (TRAX) Protein

Science.gov (United States)

Gupta, Gagan Deep; Kumar, Vinay

2012-01-01

Translin and TRAX proteins play roles in very important cellular processes such as DNA recombination, spatial and temporal expression of mRNA, and in siRNA processing. Translin forms a homomeric nucleic acid binding complex and binds to ssDNA and RNA. However, a mutant translin construct that forms homomeric complex lacking nucleic acid binding activity is able to form fully active heteromeric translin-TRAX complex when co-expressed with TRAX. A substantial progress has been made in identifying translin sites that mediate its binding activity, while TRAX was thought not to bind DNA or RNA on its own. We here for the first time demonstrate nucleic acid binding to TRAX by crosslinking radiolabeled ssDNA to heteromeric translin-TRAX complex using UV-laser. The TRAX and translin, photochemically crosslinked with ssDNA, were individually detected on SDS-PAGE. We mutated two motifs in TRAX and translin, designated B2 and B3, to help define the nucleic acid binding sites in the TRAX sequence. The most pronounced effect was observed in the mutants of B3 motif that impaired nucleic acid binding activity of the heteromeric complexes. We suggest that both translin and TRAX are binding competent and contribute to the nucleic acid binding activity. PMID:22427937

Resource use and costs associated with opioid-induced constipation following total hip or total knee replacement surgery

Directory of Open Access Journals (Sweden)

Wittbrodt ET

2018-05-01

Full Text Available Eric T Wittbrodt,1 Tong J Gan,2 Catherine Datto,1 Charles McLeskey,1 Meenal Sinha3 1US Medical Affairs, AstraZeneca, Wilmington, DE, USA; 2Department of Anesthesiology, Stony Brook Medicine, Stony Brook, NY, USA; 3Premier Applied Sciences, Premier, Inc., Charlotte, NC, USA Purpose: Constipation is a well-known complication of surgery that can be exacerbated by opioid analgesics. This study evaluated resource utilization and costs associated with opioid-induced constipation (OIC. Patients and methods: This retrospective, observational, and propensity-matched cohort study utilized the Premier Healthcare Database. The study included adults ≥18 years of age undergoing total hip or total knee replacement as inpatients who received an opioid analgesic and were discharged between January 1, 2012, and June 30, 2015. Diagnosis codes identified patients with OIC who were then matched 1:1 to patients without OIC. Generalized linear and logistic regression models were used to compare inpatient resource utilization, total hospital costs, inpatient mortality, and 30-day all-cause readmissions and emergency department visits. Results: Of 788,448 eligible patients, 40,891 (5.2% had OIC. Covariates were well balanced between matched patients with and without OIC (n=40,890 each. In adjusted analyses, patients with OIC had longer hospital lengths of stay (3.6 versus 3.3 days; p<0.001, higher total hospital costs (US$17,479 versus US$16,265; p<0.001, greater risk of intensive care unit admission (odds ratio [OR]=1.12, 95% CI: 1.01–1.24, and increased likelihood of 30-day hospital readmissions (OR=1.16, 95% CI: 1.11–1.22 and emergency department visits (OR=1.38, 95% CI: 1.07–1.79 than patients without OIC. No statistically significant difference was found with inpatient mortality (OR=0.89, 95% CI: 0.59–1.35. Conclusion: OIC was associated with greater resource utilization and hospital costs for patients undergoing primarily elective total hip or total knee

Nucleic acid protocols: Extraction and optimization

Directory of Open Access Journals (Sweden)

Saeed El-Ashram

2016-12-01

Full Text Available Yield and quality are fundamental features for any researchers during nucleic acid extraction. Here, we describe a simplified, semi-unified, effective, and toxic material free protocol for extracting DNA and RNA from different prokaryotic and eukaryotic sources exploiting the physical and chemical properties of nucleic acids. Furthermore, this protocol showed that DNA and RNA are under triple protection (i.e. EDTA, SDS and NaCl during lysis step, and this environment is improper for RNase to have DNA liberated of RNA and even for DNase to degrade the DNA. Therefore, the complete removal of RNA under RNase influence is achieved when RNase is added after DNA extraction, which gives optimal quality with any protocols. Similarly, DNA contamination in an isolated RNA is degraded by DNase to obtain high-quality RNA. Our protocol is the protocol of choice in terms of simplicity, recovery time, environmental safety, amount, purity, PCR and RT-PCR applicability.

Cost-Effectiveness of Alternative Blood-Screening Strategies for West Nile Virus in the United States.

Directory of Open Access Journals (Sweden)

2006-01-01

Full Text Available BACKGROUND: West Nile virus (WNV is endemic in the US, varying seasonally and by geographic region. WNV can be transmitted by blood transfusion, and mandatory screening of blood for WNV was recently introduced throughout the US. Guidelines for selecting cost-effective strategies for screening blood for WNV do not exist. METHODS AND FINDINGS: We conducted a cost-effectiveness analysis for screening blood for WNV using a computer-based mathematical model, and using data from prospective studies, retrospective studies, and published literature. For three geographic areas with varying WNV-transmission intensity and length of transmission season, the model was used to estimate lifetime costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios associated with alternative screening strategies in a target population of blood-transfusion recipients. We compared the status quo (baseline screening using a donor questionnaire to several strategies which differed by nucleic acid testing of either pooled or individual samples, universal versus targeted screening of donations designated for immunocompromised patients, and seasonal versus year-long screening. In low-transmission areas with short WNV seasons, screening by questionnaire alone was the most cost-effective strategy. In areas with high levels of WNV transmission, seasonal screening of individual samples and restricting screening to blood donations designated for immunocompromised recipients was the most cost-effective strategy. Seasonal screening of the entire recipient pool added minimal clinical benefit, with incremental cost-effectiveness ratios exceeding US$1.7 million per quality-adjusted life-year gained. Year-round screening offered no additional benefit compared to seasonal screening in any of the transmission settings. CONCLUSIONS: In areas with high levels of WNV transmission, seasonal screening of individual samples and restricting screening to blood donations

Cost-effectiveness of alternative blood-screening strategies for West Nile Virus in the United States.

Directory of Open Access Journals (Sweden)

Caroline T Korves

2006-02-01

Full Text Available West Nile virus (WNV is endemic in the US, varying seasonally and by geographic region. WNV can be transmitted by blood transfusion, and mandatory screening of blood for WNV was recently introduced throughout the US. Guidelines for selecting cost-effective strategies for screening blood for WNV do not exist.We conducted a cost-effectiveness analysis for screening blood for WNV using a computer-based mathematical model, and using data from prospective studies, retrospective studies, and published literature. For three geographic areas with varying WNV-transmission intensity and length of transmission season, the model was used to estimate lifetime costs, quality-adjusted life expectancy, and incremental cost-effectiveness ratios associated with alternative screening strategies in a target population of blood-transfusion recipients. We compared the status quo (baseline screening using a donor questionnaire to several strategies which differed by nucleic acid testing of either pooled or individual samples, universal versus targeted screening of donations designated for immunocompromised patients, and seasonal versus year-long screening. In low-transmission areas with short WNV seasons, screening by questionnaire alone was the most cost-effective strategy. In areas with high levels of WNV transmission, seasonal screening of individual samples and restricting screening to blood donations designated for immunocompromised recipients was the most cost-effective strategy. Seasonal screening of the entire recipient pool added minimal clinical benefit, with incremental cost-effectiveness ratios exceeding USD 1.7 million per quality-adjusted life-year gained. Year-round screening offered no additional benefit compared to seasonal screening in any of the transmission settings.In areas with high levels of WNV transmission, seasonal screening of individual samples and restricting screening to blood donations designated for immunocompromised recipients is cost

Comparative analysis of three different of extraction protocols of total nucleic acids of squash (Cucurbita moschata) for the diagnosis from geminivirus

International Nuclear Information System (INIS)

Hernandez Jimenez, Eduardo

2008-01-01

The geminivirus constitute an important group of plant pathogens, characterized by an unusual morphology of the viral particle and its DNA. They have a paired icosahedral cover and a small circular genome of DNA simple band that is replicated, by DNA double band, in the nucleus of the infected cell of the plant. Many researchers have focused on the development and optimization of protocols for obtaining DNA or RNA of interest, because of rapid advances in molecular biology during the second half of the XX century and the beginning of XXI century, and to that the extraction and purification of nucleic acids is the first step mainly of the procedures in this area. The objective is to compare, by means of molecular techniques, the DNA purification in squash from different ways of storage and extraction protocols of total nucleic acids of the plant, in order to improve the quality and amount of genetic matters whereupon the detection and characterization of geminivirus are realised. Three methods were compared: i. Dellaporta and collaborators (1983), ii.- Doyle and Doyle (1990) and iii.- Jose and Usha (2000). The operation of the three methods scaled downward (15 milligrams of leaf tissue) and two ways of storage were evaluated: 1.- tubes with silica gel (SG, a desiccant) and 2.- frozen to -70 degrees Celsius. The method of Jose and Usha (2000) presented technical difficulties that not permitted to scale downward, for which it should work with the purification from a gram of foliar tissue. The integrity of the total DNA was verified superior in the material stored to -70 degrees celsius for all the methods, by means of electrophoresis in gels of agarose, besides that the protocol of Dellaporta et al. (1983) tends to enrich the RNA. The readings were similar for the methods of Dellaporta et al. (1983) and Doyle and Doyle (1993), this was evidenced upon quantifying the total DNA and that is extracted at least a 30% more of DNA from material in the desiccant with respect

Self-reported Function, Health Resource Use, and Total Health Care Costs Among Medicare Beneficiaries With Glaucoma.

Science.gov (United States)

Prager, Alisa J; Liebmann, Jeffrey M; Cioffi, George A; Blumberg, Dana M

2016-04-01

The effect of glaucoma on nonglaucomatous medical conditions and resultant secondary health care costs is not well understood. To assess self-reported medical conditions, the use of medical services, and total health care costs among Medicare beneficiaries with glaucoma. Longitudinal observational study of 72,587 Medicare beneficiaries in the general community using the Medicare Current Beneficiary Survey (2004-2009). Coding to extract data started in January 2015, and analyses were performed between May and July 2015. Self-reported health, the use of health care services, adjusted mean annual total health care costs per person, and adjusted mean annual nonoutpatient costs per person. Participants were 72,587 Medicare beneficiaries 65 years or older with (n = 4441) and without (n = 68,146) a glaucoma diagnosis in the year before collection of survey data. Their mean age was 76.9 years, and 43.2% were male. Patients with glaucoma who responded to survey questions on visual disability were stratified into those with (n = 1748) and without (n = 2639) self-reported visual disability. Medicare beneficiaries with glaucoma had higher adjusted odds of inpatient hospitalizations (odds ratio [OR], 1.27; 95% CI, 1.17-1.39; P total health care costs and $2599 (95% CI, $1985-$3212; P total and nonoutpatient medical costs. Perception of vision loss among patients with glaucoma may be associated with depression, falls, and difficulty walking. Reducing the prevalence and severity of glaucoma may result in improvements in associated nonglaucomatous medical conditions and resultant reduction in health care costs.

[Comparison of two nucleic acid extraction methods for norovirus in oysters].

Science.gov (United States)

Yuan, Qiao; Li, Hui; Deng, Xiaoling; Mo, Yanling; Fang, Ling; Ke, Changwen

2013-04-01

To explore a convenient and effective method for norovirus nucleic acid extraction from oysters suitable for long-term viral surveillance. Two methods, namely method A (glycine washing and polyethylene glycol precipitation of the virus followed by silica gel centrifugal column) and method B (protease K digestion followed by application of paramagnetic silicon) were compared for their performance in norovirus nucleic acid extraction from oysters. Real-time RT-PCR was used to detect norovirus in naturally infected oysters and in oysters with induced infection. The two methods yielded comparable positive detection rates for the samples, but the recovery rate of the virus was higher with method B than with method A. Method B is a more convenient and rapid method for norovirus nucleic acid extraction from oysters and suitable for long-term surveillance of norovirus.

Nucleic acid-functionalized transition metal nanosheets for biosensing applications.

Science.gov (United States)

Mo, Liuting; Li, Juan; Liu, Qiaoling; Qiu, Liping; Tan, Weihong

2017-03-15

In clinical diagnostics, as well as food and environmental safety practices, biosensors are powerful tools for monitoring biological or biochemical processes. Two-dimensional (2D) transition metal nanomaterials, including transition metal chalcogenides (TMCs) and transition metal oxides (TMOs), are receiving growing interest for their use in biosensing applications based on such unique properties as high surface area and fluorescence quenching abilities. Meanwhile, nucleic acid probes based on Watson-Crick base-pairing rules are also being widely applied in biosensing based on their excellent recognition capability. In particular, the emergence of functional nucleic acids in the 1980s, especially aptamers, has substantially extended the recognition capability of nucleic acids to various targets, ranging from small organic molecules and metal ions to proteins and cells. Based on π-π stacking interaction between transition metal nanosheets and nucleic acids, biosensing systems can be easily assembled. Therefore, the combination of 2D transition metal nanomaterials and nucleic acids brings intriguing opportunities in bioanalysis and biomedicine. In this review, we summarize recent advances of nucleic acid-functionalized transition metal nanosheets in biosensing applications. The structure and properties of 2D transition metal nanomaterials are first discussed, emphasizing the interaction between transition metal nanosheets and nucleic acids. Then, the applications of nucleic acid-functionalized transition metal nanosheet-based biosensors are discussed in the context of different signal transducing mechanisms, including optical and electrochemical approaches. Finally, we provide our perspectives on the current challenges and opportunities in this promising field. Copyright © 2016 Elsevier B.V. All rights reserved.

Cost-effectiveness of hysteroscopy screening for infertile women.

Science.gov (United States)

Kasius, Jenneke C; Eijkemans, René J C; Mol, Ben W J; Fauser, Bart C J M; Fatemi, Human M; Broekmans, Frank J M

2013-06-01

This study assessed the cost-effectiveness of office hysteroscopy screening prior to IVF. Therefore, the cost-effectiveness of two distinct strategies - hysteroscopy after two failed IVF cycles (Failedhyst) and routine hysteroscopy prior to IVF (Routinehyst) - was compared with the reference strategy of no hysteroscopy (Nohyst). When present, intrauterine pathology was treated during hysteroscopy. Two models were constructed and evaluated in a decision analysis. In model I, all patients had an increase in pregnancy rate after screening hysteroscopy prior to IVF; in model II, only patients with intrauterine pathology would benefit. For each strategy, the total costs and live birth rates after a total of three IVF cycles were assessed. For model I (all patients benefit from hysteroscopy), Routinehyst was always cost-effective compared with Nohyst or Failedhyst. For the Routinehyst strategy, a monetary profit would be obtained in the case where hysteroscopy would increase the live birth rate after IVF by ≥ 2.8%. In model II (only patients with pathology benefit from hysteroscopy), Routinehyst also dominated Failedhyst. However, hysteroscopy performance resulted in considerable costs. In conclusion, the application of a routine hysteroscopy prior to IVF could be cost-effective. However, randomized trials confirming the effectiveness of hysteroscopy are needed. Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Study of the effects of radiation of nucleic acids and related compounds. Progress report, August 15, 1975--August 14, 1976

International Nuclear Information System (INIS)

Wang, S.Y.

1976-04-01

Ionizing radiation produces genetic effects in biological systems. Since genetic effects are usually the result of modifications of DNA or sometimes of RNA, interest is being centered on the chemical and physical nature of radiation-induced lesions to nucleic acids and their components. These investigations have revealed the enormous complexity of chemical events and the possible degradation of nucleic acids by strand breakage. Therefore, work in the ionization radiation of nucleic acids has proceeded along a dual course. On the one hand, molecular changes have been characterized for a number of primary radiation products. On the other hand, strand breakage has been investigated intensively as a direct primary event. Both of these aspects were emphasized in our research last year. We succeeded in improving the synthesis of 5-hydroxy-methyl thymine (α-TOOH). α-TOOH was found to be much more effective than cis-5,6-dihydro-6-hydroperoxy-5-hydroxy thymine (6-TOOH) in the inactivation of transforming DNA of H. influenzae cells although α-TOOH is much less reactive chemically than 6-TOOH. 6-TOOH causes inactivation and acts as an inhibitor of DNA synthesis in mammalian cells. In addition, evidence may indicate that 6-TOOH does not induce strand breaks directly in DNA although we showed that 6-TOOH is a clastogenic compound

Total life-cycle cost analysis of conventional and alternative fueled vehicles

International Nuclear Information System (INIS)

Cardullo, M.W.

1993-01-01

Total Life-Cycle Cost (TLCC) Analysis can indicate whether paying higher capital costs for advanced technology with low operating and/or environmental costs is advantageous over paying lower capital costs for conventional technology with higher operating and/or environmental costs. While minimizing total life-cycle cost is an important consideration, the consumer often identifies non-cost-related benefits or drawbacks that make more expensive options appear more attractive. The consumer is also likely to heavily weigh initial capital costs while giving limited consideration to operating and/or societal costs, whereas policy-makers considering external costs, such as those resulting from environmental impacts, may reach significantly different conclusions about which technologies are most advantageous to society. This paper summarizes a TLCC model which was developed to facilitate consideration of the various factors involved in both individual and societal policy decision making. The model was developed as part of a US Department of Energy Contract and has been revised to reflect changes necessary to make the model more realistic. The model considers capital, operating, salvage, and environmental costs for cars, vans, and buses using conventional and alternative fuels. The model has been developed to operate on an IBM or compatible personal computer platform using the commercial spreadsheet program MicroSoft Excell reg-sign Version 4 for Windows reg-sign and can be easily kept current because its modular structure allows straightforward access to embedded data sets for review and update

Total life cycle cost model for electric power stations

International Nuclear Information System (INIS)

Cardullo, M.W.

1995-01-01

The Total Life Cycle Cost (TLCC) model for electric power stations was developed to provide a technology screening model. The TLCC analysis involves normalizing cost estimates with respect to performance standards and financial assumptions and preparing a profile of all costs over the service life of the power station. These costs when levelized present a value in terms of a utility electricity rate. Comparison of cost and the pricing of the electricity for a utility shows if a valid project exists. Cost components include both internal and external costs. Internal costs are direct costs associated with the purchase, and operation of the power station and include initial capital costs, operating and maintenance costs. External costs result from societal and/or environmental impacts that are external to the marketplace and can include air quality impacts due to emissions, infrastructure costs, and other impacts. The cost stream is summed (current dollars) or discounted (constant dollars) to some base year to yield a overall TLCC of each power station technology on a common basis. While minimizing life cycle cost is an important consideration, it may not always be a preferred method for some utilities who may prefer minimizing capital costs. Such consideration does not always result in technology penetration in a marketplace such as the utility sector. Under various regulatory climates, the utility is likely to heavily weigh initial capital costs while giving limited consideration to other costs such as societal costs. Policy makers considering external costs, such as those resulting from environmental impacts, may reach significantly different conclusions about which technologies are most advantageous to society. The TLCC analysis model for power stations was developed to facilitate consideration of all perspectives

A Single Electrochemical Probe Used for Analysis of Multiple Nucleic Acid Sequences

Science.gov (United States)

Mills, Dawn M.; Calvo-Marzal, Percy; Pinzon, Jeffer M.; Armas, Stephanie; Kolpashchikov, Dmitry M.; Chumbimuni-Torres, Karin Y.

2017-01-01

Electrochemical hybridization sensors have been explored extensively for analysis of specific nucleic acids. However, commercialization of the platform is hindered by the need for attachment of separate oligonucleotide probes complementary to a RNA or DNA target to an electrode’s surface. Here we demonstrate that a single probe can be used to analyze several nucleic acid targets with high selectivity and low cost. The universal electrochemical four-way junction (4J)-forming (UE4J) sensor consists of a universal DNA stem-loop (USL) probe attached to the electrode’s surface and two adaptor strands (m and f) which hybridize to the USL probe and the analyte to form a 4J associate. The m adaptor strand was conjugated with a methylene blue redox marker for signal ON sensing and monitored using square wave voltammetry. We demonstrated that a single sensor can be used for detection of several different DNA/RNA sequences and can be regenerated in 30 seconds by a simple water rinse. The UE4J sensor enables a high selectivity by recognition of a single base substitution, even at room temperature. The UE4J sensor opens a venue for a re-useable universal platform that can be adopted at low cost for the analysis of DNA or RNA targets. PMID:29371782

Time-driven Activity-based Cost of Fast-Track Total Hip and Knee Arthroplasty

DEFF Research Database (Denmark)

Andreasen, Signe E; Holm, Henriette B; Jørgensen, Mira

2017-01-01

this between 2 departments with different logistical set-ups. METHODS: Prospective data collection was analyzed using the time-driven activity-based costing method (TDABC) on time consumed by different staff members involved in patient treatment in the perioperative period of fast-track THA and TKA in 2 Danish...... orthopedic departments with standardized fast-track settings, but different logistical set-ups. RESULTS: Length of stay was median 2 days in both departments. TDABC revealed minor differences in the perioperative settings between departments, but the total cost excluding the prosthesis was similar at USD......-track methodology, the result could be a more cost-effective pathway altogether. As THA and TKA are potentially costly procedures and the numbers are increasing in an economical limited environment, the aim of this study is to present baseline detailed economical calculations of fast-track THA and TKA and compare...

Prevention of low back pain in the military cluster randomized trial: effects of brief psychosocial education on total and low back pain-related health care costs.

Science.gov (United States)

Childs, John D; Wu, Samuel S; Teyhen, Deydre S; Robinson, Michael E; George, Steven Z

2014-04-01

Effective strategies for preventing low back pain (LBP) have remained elusive, despite annual direct health care costs exceeding $85 billion dollars annually. In our recently completed Prevention of Low Back Pain in the Military (POLM) trial, a brief psychosocial education program (PSEP) that reduced fear and threat of LBP reduced the incidence of health care-seeking for LBP. The purpose of this cost analysis was to determine if soldiers who received psychosocial education experienced lower health care costs compared with soldiers who did not receive psychosocial education. The POLM trial was a cluster randomized trial with four intervention arms and a 2-year follow-up. Consecutive subjects (n=4,295) entering a 16-week training program at Fort Sam Houston, TX, to become a combat medic in the U.S. Army were considered for participation. In addition to an assigned exercise program, soldiers were cluster randomized to receive or not receive a brief psychosocial education program delivered in a group setting. The Military Health System Management Analysis and Reporting Tool was used to extract total and LBP-related health care costs associated with LBP incidence over a 2-year follow-up period. After adjusting for postrandomization differences between the groups, the median total LBP-related health care costs for soldiers who received PSEP and incurred LBP-related costs during the 2-year follow-up period were $26 per soldier lower than for those who did not receive PSEP ($60 vs. $86, respectively, p=.034). The adjusted median total health care costs for soldiers who received PSEP and incurred at least some health care costs during the 2-year follow-up period were estimated at $2 per soldier lower than for those who did not receive PSEP ($2,439 vs. $2,441, respectively, p=.242). The results from this analysis demonstrate that a brief psychosocial education program was only marginally effective in reducing LBP-related health care costs and was not effective in reducing

Bio-Orthogonal Mediated Nucleic Acid Transfection of Cells via Cell Surface Engineering.

Science.gov (United States)

O'Brien, Paul J; Elahipanah, Sina; Rogozhnikov, Dmitry; Yousaf, Muhammad N

2017-05-24

The efficient delivery of foreign nucleic acids (transfection) into cells is a critical tool for fundamental biomedical research and a pillar of several biotechnology industries. There are currently three main strategies for transfection including reagent, instrument, and viral based methods. Each technology has significantly advanced cell transfection; however, reagent based methods have captured the majority of the transfection market due to their relatively low cost and ease of use. This general method relies on the efficient packaging of a reagent with nucleic acids to form a stable complex that is subsequently associated and delivered to cells via nonspecific electrostatic targeting. Reagent transfection methods generally use various polyamine cationic type molecules to condense with negatively charged nucleic acids into a highly positively charged complex, which is subsequently delivered to negatively charged cells in culture for association, internalization, release, and expression. Although this appears to be a straightforward procedure, there are several major issues including toxicity, low efficiency, sorting of viable transfected from nontransfected cells, and limited scope of transfectable cell types. Herein, we report a new strategy (SnapFect) for nucleic acid transfection to cells that does not rely on electrostatic interactions but instead uses an integrated approach combining bio-orthogonal liposome fusion, click chemistry, and cell surface engineering. We show that a target cell population is rapidly and efficiently engineered to present a bio-orthogonal functional group on its cell surface through nanoparticle liposome delivery and fusion. A complementary bio-orthogonal nucleic acid complex is then formed and delivered to which chemoselective click chemistry induced transfection occurs to the primed cell. This new strategy requires minimal time, steps, and reagents and leads to superior transfection results for a broad range of cell types

Extraction of total nucleic acid based on silica-coated magnetic particles for RT-qPCR detection of plant RNA virus/viroid.

Science.gov (United States)

Sun, Ning; Deng, Congliang; Zhao, Xiaoli; Zhou, Qi; Ge, Guanglu; Liu, Yi; Yan, Wenlong; Xia, Qiang

2014-02-01

In this study, a nucleic acid extraction method based on silica-coated magnetic particles (SMPs) and RT-qPCR assay was developed to detect Arabis mosaic virus (ArMV), Lily symptomless virus (LSV), Hop stunt viroid (HSVd) and grape yellow speckle viroid 1 (GYSVd-1). The amplification sequences of RT-qPCR were reversely transcribed in vitro as RNA standard templates. The standard curves covered six or seven orders of magnitude with a detection limit of 100 copies per each assay. Extraction efficiency of the SMPs method was evaluated by recovering spiked ssRNAs from plant samples and compared to two commercial kits (TRIzol and RNeasy Plant mini kit). Results showed that the recovery rate of SMPs method was comparable to the commercial kits when spiked ssRNAs were extracted from lily leaves, whereas it was two or three times higher than commercial kits when spiked ssRNAs were extracted from grapevine leaves. SMPs method was also used to extract viral nucleic acid from15 ArMV-positive lily leaf samples and 15 LSV-positive lily leaf samples. SMPs method did not show statistically significant difference from other methods on detecting ArMV, but LSV. The SMPs method has the same level of virus load as the TRIzol, and its mean virus load of was 0.5log10 lower than the RNeasy Plant mini kit. Nucleic acid was extracted from 19 grapevine-leaf samples with SMPs and the two commercial kits and subsequently screened for HSVd and GYSVd-1 by RT-qPCR. Regardless of HSVd or GYSVd-1, SMPs method outperforms other methods on both positive rate and the viroid load. In conclusion, SMPs method was able to efficiently extract the nucleic acid of RNA viruses or viroids, especially grapevine viroids, from lily-leaf or grapevine-leaf samples for RT-qPCR detection. Copyright © 2013 Elsevier B.V. All rights reserved.

Episode of Care Payments in Total Joint Arthroplasty and Cost Minimization Strategies.

Science.gov (United States)

Nwachukwu, Benedict U; O'Donnell, Evan; McLawhorn, Alexander S; Cross, Michael B

2016-02-01

Total joint arthroplasty (TJA) is receiving significant attention in the US health care system for cost containment strategies. Specifically, payer organizations have embraced and are implementing bundled payment schemes in TJA. Consequently, hospitals and providers involved in the TJA care cycle have sought to adapt to the new financial pressures imposed by episode of care payment models by analyzing what components of the total "event" of a TJA are most essential to achieve a good outcome after TJA. As part of this review, we analyze and discuss a health economic study by Snow et al. As part of their study, the authors aimed to understand the association between preoperative physical therapy (PT) and post-acute care resource utilization, and its effect on the total cost of care during total joint arthroplasty. The purpose of this current review therefore is to (1) describe and analyze the findings presented by Snow et al. and (2) provide a framework for analyzing and critiquing economic analyses in orthopedic surgery. The study under review, while having important strengths, has several notable limitations that are important to keep in mind when making policy and coverage decisions. We support cautious interpretation and application of study results, and we encourage maintained attention to economic analysis in orthopedics as well as continued care path redesign to maximize value for patients and health care providers.

Single-stranded nucleic acids promote SAMHD1 complex formation.

Science.gov (United States)

Tüngler, Victoria; Staroske, Wolfgang; Kind, Barbara; Dobrick, Manuela; Kretschmer, Stefanie; Schmidt, Franziska; Krug, Claudia; Lorenz, Mike; Chara, Osvaldo; Schwille, Petra; Lee-Kirsch, Min Ae

2013-06-01

SAM domain and HD domain-containing protein 1 (SAMHD1) is a dGTP-dependent triphosphohydrolase that degrades deoxyribonucleoside triphosphates (dNTPs) thereby limiting the intracellular dNTP pool. Mutations in SAMHD1 cause Aicardi-Goutières syndrome (AGS), an inflammatory encephalopathy that mimics congenital viral infection and that phenotypically overlaps with the autoimmune disease systemic lupus erythematosus. Both disorders are characterized by activation of the antiviral cytokine interferon-α initiated by immune recognition of self nucleic acids. Here we provide first direct evidence that SAMHD1 associates with endogenous nucleic acids in situ. Using fluorescence cross-correlation spectroscopy, we demonstrate that SAMHD1 specifically interacts with ssRNA and ssDNA and establish that nucleic acid-binding and formation of SAMHD1 complexes are mutually dependent. Interaction with nucleic acids and complex formation do not require the SAM domain, but are dependent on the HD domain and the C-terminal region of SAMHD1. We finally demonstrate that mutations associated with AGS exhibit both impaired nucleic acid-binding and complex formation implicating that interaction with nucleic acids is an integral aspect of SAMHD1 function.

Converting Mosquito Surveillance to Arbovirus Surveillance with Honey-Baited Nucleic Acid Preservation Cards.

Science.gov (United States)

Flies, Emily J; Toi, Cheryl; Weinstein, Philip; Doggett, Stephen L; Williams, Craig R

2015-07-01

Spatially and temporally accurate information about infectious mosquito distribution allows for pre-emptive public health interventions that can reduce the burden of mosquito-borne infections on human populations. However, the labile nature of arboviruses, the low prevalence of infection in mosquitoes, the expensive labor costs for mosquito identification and sorting, and the specialized equipment required for arbovirus testing can obstruct arbovirus surveillance efforts. The recently developed techniques of testing mosquito expectorate using honey-baited nucleic acid preservation cards or sugar bait stations allows a sensitive method of testing for infectious, rather than infected, mosquito vectors. Here we report the results from the first large-scale incorporation of honey-baited cards into an existing mosquito surveillance program. During 4 months of the peak virus season (January-April, 2014) for a total of 577 trap nights, we set CO2-baited encephalitis vector survey (EVS) light traps at 88 locations in South Australia. The collection container for the EVS trap was modified to allow for the placement of a honey-baited nucleic acid preservation card (FTA™ card) inside. After collection, mosquitoes were maintained in a humid environment and allowed access to the cards for 1 week. Cards were then analyzed for common endemic Australian arboviruses using a nested RT-PCR. Eighteen virus detections, including 11 Ross River virus, four Barmah Forest virus, and three Stratford virus (not previously reported from South Australia) were obtained. Our findings suggest that adding FTA cards to an existing mosquito surveillance program is a rapid and efficient way of detecting infectious mosquitoes with high spatial resolution.

Retail clinic utilization associated with lower total cost of care.

Science.gov (United States)

Sussman, Andrew; Dunham, Lisette; Snower, Kristen; Hu, Min; Matlin, Olga S; Shrank, William H; Choudhry, Niteesh K; Brennan, Troyen

2013-04-01

To better understand the impact of retail clinic use on a patient's annual total cost of care. A propensity score matched-pair, cohort design was used to analyze healthcare spending patterns among CVS Caremark employees in the year following a visit to a MinuteClinic, the retail clinics inside CVS pharmacies. De-identified medical and pharmacy claims for CVS Caremark employees and their dependents who received care at a retail clinic between June 1, 2009, and May 31, 2010, were matched to those of subjects who received care elsewhere. High-dimensional propensity score and greedy matching techniques were used to create a 1-to-1 matched cohort that was analyzed using generalized linear regression models. Individuals using a retail clinic had a lower total cost of care (-$262; 95% confidence interval, -$510 to -$31; P = .025) in the year following their clinic visit than individuals who received care in other settings. This savings was primarily due to lower medical expenses at physicians' offices ($77 savings, P = .008) and hospital inpatient care ($121 savings, P = .049). The 6022 retail clinic users also had 142 (12%) fewer emergency department visits (P = .01), though this was not related to significant cost savings. This study found that retail clinic use was associated with lower overall total cost of care compared with that at alternative sites. Savings may extend beyond the retail clinic visit itself to other types of medical utilization.

NaVirCept - Nucleic Acid-Based Anti-Viral Project

International Nuclear Information System (INIS)

Stephen, E. R.; Wong, J.; Van Loon, D.

2007-01-01

Vaccines are generally considered to be the most effective countermeasures to bacterial and viral diseases, however, licensed vaccines against many disease agents are either not available or their efficacies have not been demonstrated. Vaccines are generally agent specific in terms of treatment spectrum and are subject to defeat through natural mutation or through directed efforts. With respect to viral therapeutics, one of the major limitations associated with antiviral drugs is acquired drug resistance caused by antigenic shift or drift. A number of next-generation prophylactic and/or therapeutic measures are on the horizon. Of these, nucleic acid-based drugs are showing great antiviral potential. These drugs elicit long-lasting, broad spectrum protective immune responses, especially to respiratory viral pathogens. The Nucleic Acid-Based Antiviral (NaVirCept) project provides the opportunity to demonstrate the effectiveness of novel medical countermeasures against military-significant endemic and other viral threat agents. This project expands existing DRDC drug delivery capability development, in the form of proprietary liposome intellectual property, by coupling it with leading-edge nucleic acid-based technology to deliver effective medical countermeasures that will protect deployed personnel and the warfighter against a spectrum of viral disease agents. The technology pathway will offer a means to combat emerging viral diseases or modified threat agents such as the bird flu or reconstructed Spanish flu without going down the laborious, time-consuming and expensive paths to develop countermeasures for each new and/or emerging viral disease organism.(author)

Determining the total cost of reverse supply chain operations for original equipment manufacturers

DEFF Research Database (Denmark)

Larsen, Samuel Brüning; Jacobsen, Peter

2014-01-01

When original equipment manufacturers (OEM) examine whether or not to invest in a reverse supply chain (RSC), managers need insight into not only the cost savings and new revenue streams the RSC enables, but also the total cost of the RSC itself. Using case study research the study examines what...... cost parameters constitute the total cost (TC) of the RSC. The specific RSC that the study seeks the TC for consists of 1) end-product refurbishing, 2) component refurbishing, and 3) sales of used materials back to original suppliers or independent recyclers for materials recycling....

Patterns of pharmacotherapy and health care utilization and costs prior to total hip or total knee replacement in patients with osteoarthritis.

Science.gov (United States)

Berger, Ariel; Bozic, Kevin; Stacey, Brett; Edelsberg, John; Sadosky, Alesia; Oster, Gerry

2011-08-01

To examine patterns of pharmacotherapy and health care utilization and costs prior to total knee replacement (TKR) or total hip replacement (THR) in patients with osteoarthritis (OA). Using a large US health insurance claims database, we identified all patients with OA who were ages ≥40 years and had undergone TKR or THR between January 1, 2006 and December 31, 2007. Patients with care utilization and costs over the 2-year period preceding surgery. A total of 16,527 patients met all study entry criteria. Their mean ± SD age was 56.6 ± 6.1 years, and 56% of them were women. In the 2 years preceding surgery, 55% of patients received prescription nonsteroidal antiinflammatory drugs, 58% received opioids, and 50% received injections of corticosteroids. The numbers of patients receiving these drugs increased steadily during the presurgery period. The mean ± SD total health care costs in the 2 years preceding surgery were $19,466 ± 29,869, of which outpatient care, inpatient care, and pharmacotherapy represented 45%, 20%, and 20%, respectively. Costs increased from $2,094 in the eighth calendar quarter prior to surgery to $3,100 in the final quarter. Patients with OA who undergo THR or TKR have relatively high levels of use of pain-related pharmacotherapy and high total health care costs in the 2-year period preceding surgery. Levels of utilization and cost increase as the date of surgery approaches. Copyright © 2011 by the American College of Rheumatology.

Early assessment of the likely cost-effectiveness of a new technology: A Markov model with probabilistic sensitivity analysis of computer-assisted total knee replacement.

Science.gov (United States)

Dong, Hengjin; Buxton, Martin

2006-01-01

The objective of this study is to apply a Markov model to compare cost-effectiveness of total knee replacement (TKR) using computer-assisted surgery (CAS) with that of TKR using a conventional manual method in the absence of formal clinical trial evidence. A structured search was carried out to identify evidence relating to the clinical outcome, cost, and effectiveness of TKR. Nine Markov states were identified based on the progress of the disease after TKR. Effectiveness was expressed by quality-adjusted life years (QALYs). The simulation was carried out initially for 120 cycles of a month each, starting with 1,000 TKRs. A discount rate of 3.5 percent was used for both cost and effectiveness in the incremental cost-effectiveness analysis. Then, a probabilistic sensitivity analysis was carried out using a Monte Carlo approach with 10,000 iterations. Computer-assisted TKR was a long-term cost-effective technology, but the QALYs gained were small. After the first 2 years, the incremental cost per QALY of computer-assisted TKR was dominant because of cheaper and more QALYs. The incremental cost-effectiveness ratio (ICER) was sensitive to the "effect of CAS," to the CAS extra cost, and to the utility of the state "Normal health after primary TKR," but it was not sensitive to utilities of other Markov states. Both probabilistic and deterministic analyses produced similar cumulative serious or minor complication rates and complex or simple revision rates. They also produced similar ICERs. Compared with conventional TKR, computer-assisted TKR is a cost-saving technology in the long-term and may offer small additional QALYs. The "effect of CAS" is to reduce revision rates and complications through more accurate and precise alignment, and although the conclusions from the model, even when allowing for a full probabilistic analysis of uncertainty, are clear, the "effect of CAS" on the rate of revisions awaits long-term clinical evidence.

Spherical Nucleic Acids as Intracellular Agents for Nucleic Acid Based Therapeutics

Science.gov (United States)

Hao, Liangliang

Recent functional discoveries on the noncoding sequences of human genome and transcriptome could lead to revolutionary treatment modalities because the noncoding RNAs (ncRNAs) can be applied as therapeutic agents to manipulate disease-causing genes. To date few nucleic acid-based therapeutics have been translated into the clinic due to challenges in the delivery of the oligonucleotide agents in an effective, cell specific, and non-toxic fashion. Unmodified oligonucleotide agents are destroyed rapidly in biological fluids by enzymatic degradation and have difficulty crossing the plasma membrane without the aid of transfection reagents, which often cause inflammatory, cytotoxic, or immunogenic side effects. Spherical nucleic acids (SNAs), nanoparticles consisting of densely organized and highly oriented oligonucleotides, pose one possible solution to circumventing these problems in both the antisense and RNA interference (RNAi) pathways. The unique three dimensional architecture of SNAs protects the bioactive oligonucleotides from unspecific degradation during delivery and supports their targeting of class A scavenger receptors and endocytosis via a lipid-raft-dependent, caveolae-mediated pathway. Owing to their unique structure, SNAs are able to cross cell membranes and regulate target genes expression as a single entity, without triggering the cellular innate immune response. Herein, my thesis has focused on understanding the interactions between SNAs and cellular components and developing SNA-based nanostructures to improve therapeutic capabilities. Specifically, I developed a novel SNA-based, nanoscale agent for delivery of therapeutic oligonucleotides to manipulate microRNAs (miRNAs), the endogenous post-transcriptional gene regulators. I investigated the role of SNAs involving miRNAs in anti-cancer or anti-inflammation responses in cells and in in vivo murine disease models via systemic injection. Furthermore, I explored using different strategies to construct

Cost and cost-effectiveness of smear-positive tuberculosis treatment by Health Extension Workers in Southern Ethiopia: a community randomized trial.

Directory of Open Access Journals (Sweden)

Daniel G Datiko

Full Text Available UNLABELLED: Treatments by HEWs in the health posts and general health workers at health facility were compared along a community-randomized trial. Costs were analysed from societal perspective in 2007 in US $ using standard methods. We prospectively enrolled smear positive patients, and calculated cost-effectiveness as the cost per patient successfully treated. The total cost for each successfully treated smear-positive patient was higher in health facility ($158.9 compared with community ($61.7. Community-based treatment reduced the total, patient and caregiver cost by 61.2%, 68.1% and 79.8%, respectively. Involving HEWs added a total cost of $8.80 (14.3% of total cost on health service per patient treated in the community. CONCLUSIONS/SIGNIFICANCE: Community-based treatment by HEWs costs only 39% of what treatment by general health workers costs for similar outcomes. Involving HEWs in TB treatment is a cost effective treatment alternative to the health service, to the patients and the family. There is an economic and public health reason to consider involving HEWs in TB treatment in Ethiopia. However, community-based treatment requires initial investment to start its implementation, training and supervision. TRIAL REGISTRATION: ClinicalTrials.gov NCT00803322.

Accelerated digestion of nucleic acids by pepsin from the stomach of chicken.

Science.gov (United States)

Liu, Y; Zhang, Y; Guo, H; Wu, W; Dong, P; Liang, X

2016-10-01

Nucleic acids have become an important nutritional supplement in poultry feed; however, the digestion of nucleic acids in poultry is unclear. The objective of this study was to investigate the digestion of nucleic acids by chicken pepsin in vitro. The extracted pepsinogen from the stomach of the chicken was purified to homogeneity. Upon activation at pH 2.0, chicken pepsinogen was converted to its active form. Nucleic acids, including λ-DNA, salmon sperm DNA and single-strand DNA (ssDNA), can be used as substrates and digested into short-chain oligonucleotides by pepsin. Interestingly, the digestion of the nucleic acids was inhibited when pepsin was treated by alkaline solution (pH 8.0) or pepstatin A. Also, the digestion of the nucleic acids was not affected by the addition of haemoglobin or bovine serum albumin. The results suggested that nucleic acids could be digested by chicken pepsin. Thus pepsin may have a role in digesting nucleic acids in vivo. Nucleic acids added to poultry fed may be digested, starting from the stomach.

Selenium Derivatization of Nucleic Acids for Phase and Structure Determination in Nucleic Acid X-ray Crystallography

Directory of Open Access Journals (Sweden)

Zhen Huang

2008-03-01

Full Text Available Selenium derivatization (via selenomethionine of proteins for crystal structure determination via MAD phasing has revolutionized protein X-ray crystallography. It is estimated that over two thirds of all new crystal structures of proteins have been determined via Se-Met derivatization. Similarly, selenium functionalities have also been successfully incorporated into nucleic acids to facilitate their structure studies and it has been proved that this Se-derivatization has advantages over halogen strategy, which was usually used as a traditional method in this field. This review reports the development of site-specific selenium derivatization of nucleic acids for phase determination since the year of 2001 (mainly focus on the 2’-position of the ribose. All the synthesis of 2’-SeMe modified phosphoramidite building blocks (U, C, T, A, G and the according oligonucleotides are included. In addition, several structures of selenium contained nucleic acid are also described in this paper.

Non-enzymatic Polymerization of Nucleic Acids from Monomers

DEFF Research Database (Denmark)

Dörr, Mark; Löffler, Philipp M. G.; Monnard, Pierre-Alain

2012-01-01

synthesis of long nucleic acid polymers or to sequence-specifically amplify nucleic acid polymers, respectively. Starting from molecular requirements, details of the polymerization mechanisms and strategies are first presented and then compared. Finally, we discuss the relevance of these strategies...

Pressure relieving support surfaces (PRESSURE) trial: cost effectiveness analysis.

Science.gov (United States)

Iglesias, Cynthia; Nixon, Jane; Cranny, Gillian; Nelson, E Andrea; Hawkins, Kim; Phillips, Angela; Torgerson, David; Mason, Su; Cullum, Nicky

2006-06-17

To assess the cost effectiveness of alternating pressure mattresses compared with alternating pressure overlays for the prevention of pressure ulcers in patients admitted to hospital. Cost effectiveness analysis carried out alongside the pressure relieving support surfaces (PRESSURE) trial; a multicentre UK based pragmatic randomised controlled trial. 11 hospitals in six UK NHS trusts. Intention to treat population comprising 1971 participants. Kaplan Meier estimates of restricted mean time to development of pressure ulcers and total costs for treatment in hospital. Alternating pressure mattresses were associated with lower overall costs (283.6 pounds sterling per patient on average, 95% confidence interval--377.59 pounds sterling to 976.79 pounds sterling) mainly due to reduced length of stay in hospital, and greater benefits (a delay in time to ulceration of 10.64 days on average,--24.40 to 3.09). The differences in health benefits and total costs for hospital stay between alternating pressure mattresses and alternating pressure overlays were not statistically significant; however, a cost effectiveness acceptability curve indicated that on average alternating pressure mattresses compared with alternating pressure overlays were associated with an 80% probability of being cost saving. Alternating pressure mattresses for the prevention of pressure ulcers are more likely to be cost effective and are more acceptable to patients than alternating pressure overlays.

Pre-fracture individual characteristics associated with high total health care costs after hip fracture.

Science.gov (United States)

Schousboe, J T; Paudel, M L; Taylor, B C; Kats, A M; Virnig, B A; Dowd, B E; Langsetmo, L; Ensrud, K E

2017-03-01

Older women with pre-fracture slow walk speed, high body mass index, and/or a high level of multimorbidity have significantly higher health care costs after hip fracture compared to those without those characteristics. Studies to investigate if targeted health care interventions for these individuals can reduce hip fracture costs are warranted. The aim of this study is to estimate the associations of individual pre-fracture characteristics with total health care costs after hip fracture, using Study of Osteoporotic Fractures (SOF) cohort data linked to Medicare claims. Our study population was 738 women age 70 and older enrolled in Medicare Fee for Service (FFS) who experienced an incident hip fracture between January 1, 1992 and December 31, 2009. We assessed pre-fracture individual characteristics at SOF study visits and estimated costs of hospitalizations, skilled nursing facility and inpatient rehabilitation stays, home health care visits, and outpatient utilization from Medicare FFS claims. We used generalized linear models to estimate the associations of predictor variables with total health care costs (2010 US dollars) after hip fracture. Median total health care costs for 1 year after hip fracture were $35,536 (inter-quartile range $24,830 to $50,903). Multivariable-adjusted total health care costs for 1 year after hip fracture were 14 % higher ($5256, 95 % CI $156 to $10,356) in those with walk speed total health care costs after hip fracture in older women. Studies to investigate if targeted health care interventions for these individuals can reduce the costs of hip fractures are warranted.

Hybrid Cloud Computing Architecture Optimization by Total Cost of Ownership Criterion

Directory of Open Access Journals (Sweden)

Elena Valeryevna Makarenko

2014-12-01

Full Text Available Achieving the goals of information security is a key factor in the decision to outsource information technology and, in particular, to decide on the migration of organizational data, applications, and other resources to the infrastructure, based on cloud computing. And the key issue in the selection of optimal architecture and the subsequent migration of business applications and data to the cloud organization information environment is the question of the total cost of ownership of IT infrastructure. This paper focuses on solving the problem of minimizing the total cost of ownership cloud.

Selected topics in photochemistry of nucleic acids. Recent results and perspectives

International Nuclear Information System (INIS)

Loeber, G.; Kittler, L.

1977-01-01

Recent results on the following photoreactions of nucleic acids are reported: photochemistry of aza-bases and minor bases, formation of photoproducts of the non-cyclobutane type, formations of furocoumarin-pyrimidine photoadducts, fluorescence of dye-nucleic acid complexes and their role in chromosomal fluorescence staining, and mechanisms of the photochemical reaction. Results are discussed with respect to: (i) photobiological relevance of light-induced defects in nucleic acids; (ii) possibilities of achieving higher selectivity of light-induced defects in nucleic acids; (iii) the use of nucleic acid photochemistry to analyze genetic material. An extensive bibliography is included. (author)

The isolation of nucleic acids from fixed, paraffin-embedded tissues-which methods are useful when?

DEFF Research Database (Denmark)

Gilbert, M Thomas P; Haselkorn, Tamara; Bunce, Michael

2007-01-01

. Cross-linking not only complicates isolation of nucleic acid but also introduces polymerase "blocks" during PCR. A wide variety of methods exists for the recovery of DNA and RNA from archival tissues, and although a number of previous studies have qualitatively compared the relative merits....... These include methods of pre-treating the samples prior to extraction, extraction and nucleic acid purification methods themselves, and a post-extraction enzymatic repair technique. We find that although many of the published methods have distinct positive effects on some characteristics of the nucleic acids...

Cost-Effectiveness of the Freeze-All Policy.

Science.gov (United States)

Roque, Matheus; Valle, Marcello; Guimarães, Fernando; Sampaio, Marcos; Geber, Selmo

2015-08-01

To evaluate the cost-effectiveness of freeze-all cycles when compared to fresh embryo transfer. This was an observational study with a cost-effectiveness analysis. The analysis consisted of 530 intracytoplasmic sperm injection (ICSI) cycles in a private center in Brazil between January 2012 and December 2013. A total of 530 intracytoplasmic sperm injection (ICSI) cycles - 351 fresh embryo transfers and 179 freeze-all cycles - with a gonadotropin-releasing hormone (GnRH) antagonist protocol and day 3 embryo transfers. The pregnancy rate was 31.1% in the fresh group and 39.7% in the freeze-all group. We performed two scenario analyses for costs. In scenario 1, we included those costs associated with the ICSI cycle (monitoring during controlled ovarian stimulation [COS], oocyte retrieval, embryo transfer, IVF laboratory, and medical costs), embryo cryopreservation of supernumerary embryos, hormone measurements during COS and endometrial priming, medication use (during COS, endometrial priming, and luteal phase support), ultrasound scan for frozen- thawed embryo transfer (FET), obstetric ultrasounds, and miscarriage. The total cost (in USD) per pregnancy was statistically lower in the freeze-all cycles (19,156.73 ± 1,732.99) when compared to the fresh cycles (23,059.72 ± 2,347.02). Even in Scenario 2, when charging all of the patients in the freeze-all group for cryopreservation (regardless of supernumerary embryos) and for FET, the fresh cycles had a statistically significant increase in treatment costs per ongoing pregnancy. The results presented in this study suggest that the freeze-all policy is a cost-effective strategy when compared to fresh embryo transfer.

Cost effectiveness of teratology counseling - the Motherisk experience.

Science.gov (United States)

Koren, Gideon; Bozzo, Pina

2014-01-01

While the benefits of evidence-based counseling to large numbers of women and physicians are intuitively evident, there is an urgent need to document that teratology counseling, in addition to improving the quality of life of women and families, also leads to cost saving. The objective of the present study was to calculate the cost effectiveness of the Motherisk Program, a large teratology information and counseling service at The Hospital for Sick Children and the University of Toronto. We analyzed data from the Motherisk Program on its 2012 activities in two domains: 1) Calculation of cost-saving in preventing unjustified pregnancy terminations; and 2) prevention of major birth defects. Cost of pregnancy termination and lifelong cost of specific birth defects were identified from primary literature and prorated for cost of living for the year 2013. Prevention of 255 pregnancy terminations per year led to cost savings of $516,630. The total estimated number of major malformations prevented by Motherisk counseling in 2012 was 8.41 cases at a total estimated cost of $9,032,492. With an estimated minimum annual prevention of 8 major malformations, and numerous unnecessary terminations of otherwise- wanted pregnancies, a cost saving of $10 million can be calculated. In 2013 the operating budget of Motherisk counseling totaled $640,000. Even based on the narrow range of activities for which we calculated cost, this service is highly cost- effective. Because most teratology counseling services are operating in a very similar method to Motherisk, it is fair to assume that these results, although dependent on the size of the service, are generalizable to other countries.

Molecular polarization potential maps of the nucleic acid bases

International Nuclear Information System (INIS)

Alkorta, I.; Perez, J.J.

1996-01-01

Ab initio calculations at the SCF level were carried out to compute the polarization potential map NM of the nucleic acid bases: cytosine, thymine, uracil, adedine, and guanine. For this purpose, the Dunning's 9s5p basis set contracted to a split-valence, was selected to perform the calculations. The molecular polarization potential (MPP) at each point was evaluated by the difference between the interaction energy of the molecule with a unit point charge and the molecular electrostatic potential (MEP) at that point. MEPS and MPPS for the different molecules were computed with a density of 5 points/Angstrom 2 on the van der Waals surface of each molecule, defined using the van der Waals radii. Due to the symmetry of the molecules, only half the points were computed. The total number of points calculated was 558 for cytosine, 621 for thymine, 526 for uracil, 666 for adenine, and 699 for guanine. The results of these calculations are analyzed in terms of their implications on the molecular interactions between pairs of nucleic acid bases. 23 refs., 5 figs., 1 tab

MEANS AND METHODS FOR CLONING NUCLEIC ACID SEQUENCES

NARCIS (Netherlands)

Geertsma, Eric Robin; Poolman, Berend

2008-01-01

The invention provides means and methods for efficiently cloning nucleic acid sequences of interest in micro-organisms that are less amenable to conventional nucleic acid manipulations, as compared to, for instance, E.coli. The present invention enables high-throughput cloning (and, preferably,

Peptide Nucleic Acids Having Amino Acid Side Chains

DEFF Research Database (Denmark)

1998-01-01

A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than the corresponding DNA or RNA strands, and exhibit increased sequence specificity and solubility. The peptide nucleic acids comprise ligands selected from a group consisting...

Accuracy assessment of the linear Poisson-Boltzmann equation and reparametrization of the OBC generalized Born model for nucleic acids and nucleic acid-protein complexes.

Science.gov (United States)

Fogolari, Federico; Corazza, Alessandra; Esposito, Gennaro

2015-04-05

The generalized Born model in the Onufriev, Bashford, and Case (Onufriev et al., Proteins: Struct Funct Genet 2004, 55, 383) implementation has emerged as one of the best compromises between accuracy and speed of computation. For simulations of nucleic acids, however, a number of issues should be addressed: (1) the generalized Born model is based on a linear model and the linearization of the reference Poisson-Boltmann equation may be questioned for highly charged systems as nucleic acids; (2) although much attention has been given to potentials, solvation forces could be much less sensitive to linearization than the potentials; and (3) the accuracy of the Onufriev-Bashford-Case (OBC) model for nucleic acids depends on fine tuning of parameters. Here, we show that the linearization of the Poisson Boltzmann equation has mild effects on computed forces, and that with optimal choice of the OBC model parameters, solvation forces, essential for molecular dynamics simulations, agree well with those computed using the reference Poisson-Boltzmann model. © 2015 Wiley Periodicals, Inc.

Novel Biochip Platform for Nucleic Acid Analysis

Directory of Open Access Journals (Sweden)

Juan J. Diaz-Mochon

2012-06-01

Full Text Available This manuscript describes the use of a novel biochip platform for the rapid analysis/identification of nucleic acids, including DNA and microRNAs, with very high specificity. This approach combines a unique dynamic chemistry approach for nucleic acid testing and analysis developed by DestiNA Genomics with the STMicroelectronics In-Check platform, which comprises two microfluidic optimized and independent PCR reaction chambers, and a sequential microarray area for nucleic acid capture and identification by fluorescence. With its compact bench-top “footprint” requiring only a single technician to operate, the biochip system promises to transform and expand routine clinical diagnostic testing and screening for genetic diseases, cancers, drug toxicology and heart disease, as well as employment in the emerging companion diagnostics market.

Peptide Nucleic Acids Having 2,6-Diaminopurine Nucleobases

DEFF Research Database (Denmark)

2003-01-01

A novel class of compounds, known as peptide nucleic acids, bind complementary DNA and RNA strands more strongly than a corresponding DNA strand, and exhibit increased sequence specificity and binding affinity. The peptide nucleic acids of the invention comprise ligands selected from a group...

EGVII endoglucanase and nucleic acids encoding the same

Science.gov (United States)

Dunn-Coleman, Nigel [Los Gatos, CA; Goedegebuur, Frits [Vlaardingen, NL; Ward, Michael [San Francisco, CA; Yao, Jian [Sunnyvale, CA

2009-05-05

The present invention provides an endoglucanase nucleic acid sequence, designated egl7, and the corresponding EGVII amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding EGVII, recombinant EGVII proteins and methods for producing the same.

Dimethyl adipimidate/Thin film Sample processing (DTS); A simple, low-cost, and versatile nucleic acid extraction assay for downstream analysis.

Science.gov (United States)

Shin, Yong; Lim, Swee Yin; Lee, Tae Yoon; Park, Mi Kyoung

2015-09-15

Sample processing, especially that involving nucleic acid extraction, is a prerequisite step for the isolation of high quantities of relatively pure DNA for downstream analyses in many life science and biomedical engineering studies. However, existing methods still have major problems, including labor-intensive time-consuming methods and high costs, as well as requirements for a centrifuge and the complex fabrication of filters and membranes. Here, we first report a versatile Dimethyl adipimidate/Thin film based Sample processing (DTS) procedure without the limitations of existing methods. This procedure is useful for the extraction of DNA from a variety of sources, including 6 eukaryotic cells, 6 bacteria cells, and 2 body fluids in a single step. Specifically, the DTS procedure does not require a centrifuge and has improved time efficiency (30 min), affordability, and sensitivity in downstream analysis. We validated the DTS procedure for the extraction of DNA from human body fluids, as well as confirmed that the quality and quantity of the extracted DNA were sufficient to allow robust detection of genetic and epigenetic biomarkers in downstream analysis.

Minimizing total costs of forest roads with computer-aided design ...

Indian Academy of Sciences (India)

imum total road costs, while conforming to design specifications, environmental ..... quality, and enhancing fish and wildlife habitat, an appropriate design ..... Soil, Water and Timber Management: Forest Engineering Solutions in Response to.

Comparative cost analyses: total flow vs other power conversion systems for the Salton Sea Geothermal Resource

Energy Technology Data Exchange (ETDEWEB)

Wright, G.W.

1978-09-18

Cost studies were done for Total Flow, double flash, and multistage flash binary systems for electric Energy production from the Salton Sea Geothermal Resource. The purpose was to provide the Department of energy's Division of Geothermal Energy with information by which to judge whether to continue development of the Total Flow system. Results indicate that the Total Flow and double flash systems have capital costs of $1,135 and $1,026 /kW with energy costs of 40.9 and 39.7 mills/kW h respectively. The Total Flow and double flash systems are not distinguishable on a cost basis alone; the multistage flash binary system, with capital cost of $1,343 /kW and energy cost of 46.9 mills/kW h, is significantly more expensive. If oil savings are considered in the total analysis, the Total Flow system could save 30% more oil than the double flash system, $3.5 billion at 1978 oil prices.

Assembly of barcode-like nucleic acid nanostructures.

Science.gov (United States)

Wang, Pengfei; Tian, Cheng; Li, Xiang; Mao, Chengde

2014-10-15

Barcode-like (BC) nanopatterns from programmed self-assembly of nucleic acids (DNA and RNA) are reported. BC nanostructures are generated by the introduction of open spaces at selected sites to an otherwise closely packed, plain, rectangle nucleic acid nanostructure. This strategy is applied to nanostructures assembled from both origami approach and single stranded tile approach. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Nucleic acid-binding glycoproteins which solubilize nucleic acids in dilute acid: re-examination of the Ustilago maydis glycoproteins

Energy Technology Data Exchange (ETDEWEB)

Unrau, P.; Champ, D.R.; Young, J.L.; Grant, C.E.

1980-01-01

Holloman reported the isolation from Ustilago maydis of a glycoprotein which prevented the precipitation of nucleic acids in cold 5% trichloroacetic acid. Two glycoprotein fractions from U. maydis with this nucleic acid-solubilizing activity were isolated in our laboratory using improved purification procedures. The activity was not due to nuclease contamination. The glycoproteins are distinguished by: their ability to bind to concanavalin A-Sepharose; their differential binding to double- and single-stranded deoxyribonucleic acid, and to ribonucleic acid; their molecular weights (46,000 and 69,000); and the relative amounts present in growing versus nongrowing cells. Both fractions required sulfhydryl-reducing conditions for optimal yields, specific activity, and stability. Nucleic acid binding was cooperative, the minimum number of glycoproteins required to make a native T7 DNA molecule soluble in dilute acid being estimated at 2 and 15, respectively.

How rebates, copayments, and administration costs affect the cost-effectiveness of osteoporosis therapies.

Science.gov (United States)

Ferko, Nicole C; Borisova, Natalie; Airia, Parisa; Grima, Daniel T; Thompson, Melissa F

2012-11-01

Because of rising drug expenditures, cost considerations have become essential, necessitating the requirement for cost-effectiveness analyses for managed care organizations (MCOs). The study objective is to examine the impact of various drug-cost components, in addition to wholesale acquisition cost (WAC), on the cost-effectiveness of osteoporosis therapies. A Markov model of osteoporosis was used to exemplify different drug cost scenarios. We examined the effect of varying rebates for oral bisphosphonates--risedronate and ibandronate--as well as considering the impact of varying copayments and administration costs for intravenous zoledronate. The population modeled was 1,000 American women, > or = 50 years with osteoporosis. Patients were followed for 1 year to reflect an annual budget review of formularies by MCOs. The cost of therapy was based on an adjusted WAC, and is referred to as net drug cost. The total annual cost incurred by an MCO for each drug regimen was calculated using the net drug cost and fracture cost. We estimated cost on a quality adjusted life year (QALY) basis. When considering different rebates, results for risedronate versus ibandronate vary from cost-savings (i.e., costs less and more effective) to approximately $70,000 per QALY. With no risedronate rebate, an ibandronate rebate of approximately 65% is required before cost per QALY surpasses $50,000. With rebates greater than 25% for risedronate, irrespective of ibandronate rebates, results become cost-saving. Results also showed the magnitude of cost savings to the MCO varied by as much as 65% when considering no administration cost and the highest coinsurance rate for zoledronate. Our study showed that cost-effectiveness varies considerably when factors in addition to the WAC are considered. This paper provides recommendations for pharmaceutical manufacturers and MCOs when developing and interpreting such analyses.

Evaluation of the Total Cost of Ownership of Fuel Cell-Powered Material Handling Equipment

Energy Technology Data Exchange (ETDEWEB)

Ramsden, T.

2013-04-01

This report discusses an analysis of the total cost of ownership of fuel cell-powered and traditional battery-powered material handling equipment (MHE, or more typically 'forklifts'). A number of fuel cell MHE deployments have received funding support from the federal government. Using data from these government co-funded deployments, DOE's National Renewable Energy Laboratory (NREL) has been evaluating the performance of fuel cells in material handling applications. NREL has assessed the total cost of ownership of fuel cell MHE and compared it to the cost of ownership of traditional battery-powered MHE. As part of its cost of ownership assessment, NREL looked at a range of costs associated with MHE operation, including the capital costs of battery and fuel cell systems, the cost of supporting infrastructure, maintenance costs, warehouse space costs, and labor costs. Considering all these costs, NREL found that fuel cell MHE can have a lower overall cost of ownership than comparable battery-powered MHE.

Functional outcome and cost-effectiveness of pulsed electromagnetic fields in the treatment of acute scaphoid fractures: a cost-utility analysis.

Science.gov (United States)

Hannemann, Pascal F W; Essers, Brigitte A B; Schots, Judith P M; Dullaert, Koen; Poeze, Martijn; Brink, Peter R G

2015-04-11

Physical forces have been widely used to stimulate bone growth in fracture repair. Addition of bone growth stimulation to the conservative treatment regime is more costly than standard health care. However, it might lead to cost-savings due to a reduction of the total amount of working days lost. This economic evaluation was performed to assess the cost-effectiveness of Pulsed Electromagnetic Fields (PEMF) compared to standard health care in the treatment of acute scaphoid fractures. An economic evaluation was carried out from a societal perspective, alongside a double-blind, randomized, placebo-controlled, multicenter trial involving five centres in The Netherlands. One hundred and two patients with a clinically and radiographically proven fracture of the scaphoid were included in the study and randomly allocated to either active bone growth stimulation or standard health care, using a placebo. All costs (medical costs and costs due to productivity loss) were measured during one year follow up. Functional outcome and general health related quality of life were assessed by the EuroQol-5D and PRWHE (patient rated wrist and hand evaluation) questionnaires. Utility scores were derived from the EuroQol-5D. The average total number of working days lost was lower in the active PEMF group (9.82 days) compared to the placebo group (12.91 days) (p = 0.651). Total medical costs of the intervention group (€1594) were significantly higher compared to the standard health care (€875). The total amount of mean QALY's (quality-adjusted life year) for the active PEMF group was 0.84 and 0.85 for the control group. The cost-effectiveness plane shows that the majority of all cost-effectiveness ratios fall into the quadrant where PEMF is not only less effective in terms of QALY's but also more costly. This study demonstrates that the desired effects in terms of cost-effectiveness are not met. When comparing the effects of PEMF to standard health care in terms of QALY's, PEMF

Dioxaphosphorinane-constrained nucleic Acid dinucleotides as tools for structural tuning of nucleic acids.

Science.gov (United States)

Catana, Dan-Andrei; Renard, Brice-Loïc; Maturano, Marie; Payrastre, Corinne; Tarrat, Nathalie; Escudier, Jean-Marc

2012-01-01

We describe a rational approach devoted to modulate the sugar-phosphate backbone geometry of nucleic acids. Constraints were generated by connecting one oxygen of the phosphate group to a carbon of the sugar moiety. The so-called dioxaphosphorinane rings were introduced at key positions along the sugar-phosphate backbone allowing the control of the six-torsion angles α to ζ defining the polymer structure. The syntheses of all the members of the D-CNA family are described, and we emphasize the effect on secondary structure stabilization of a couple of diastereoisomers of α,β-D-CNA exhibiting wether B-type canonical values or not.

Dioxaphosphorinane-Constrained Nucleic Acid Dinucleotides as Tools for Structural Tuning of Nucleic Acids

Directory of Open Access Journals (Sweden)

Dan-Andrei Catana

2012-01-01

Full Text Available We describe a rational approach devoted to modulate the sugar-phosphate backbone geometry of nucleic acids. Constraints were generated by connecting one oxygen of the phosphate group to a carbon of the sugar moiety. The so-called dioxaphosphorinane rings were introduced at key positions along the sugar-phosphate backbone allowing the control of the six-torsion angles α to ζ defining the polymer structure. The syntheses of all the members of the D-CNA family are described, and we emphasize the effect on secondary structure stabilization of a couple of diastereoisomers of α,β-D-CNA exhibiting wether B-type canonical values or not.

Autoradiographic studies on nucleic acid synthesis of human gastric cancer cells, 2. Effects of 5-Fluorouracil on nucleic acid synthesis of cancer cells

Energy Technology Data Exchange (ETDEWEB)

Inoue, K [Kobe Univ. (Japan). School of Medicine

1982-03-01

Changes in nucleic acid synthesis of gastric cancer cells by oral administration of 5-fluorouracil (5-FU) were evaluated autoradiographically. 1) Average /sup 3/H-thymidine labeling index (TLI) in the administered group (31.8%, n = 13) was a significantly high value compared with that of the control group (22.4%, n = 21). This result is considered to show that the pharmacological effects of 5-FU appeared on the cancer cells by the clinical administration of 5-FU. 2) Increase in TLI of the administered group was also found in the advanced stages. However, the degree of its increase seemed to be higher in the early stages. 3) Average /sup 3/H-uridine labeling index (89.9%) was not different from that (92.7%) of control group.

Cost-Effective Control of Infectious Disease Outbreaks Accounting for Societal Reaction.

Science.gov (United States)

Fast, Shannon M; González, Marta C; Markuzon, Natasha

2015-01-01

Studies of cost-effective disease prevention have typically focused on the tradeoff between the cost of disease transmission and the cost of applying control measures. We present a novel approach that also accounts for the cost of social disruptions resulting from the spread of disease. These disruptions, which we call social response, can include heightened anxiety, strain on healthcare infrastructure, economic losses, or violence. The spread of disease and social response are simulated under several different intervention strategies. The modeled social response depends upon the perceived risk of the disease, the extent of disease spread, and the media involvement. Using Monte Carlo simulation, we estimate the total number of infections and total social response for each strategy. We then identify the strategy that minimizes the expected total cost of the disease, which includes the cost of the disease itself, the cost of control measures, and the cost of social response. The model-based simulations suggest that the least-cost disease control strategy depends upon the perceived risk of the disease, as well as media intervention. The most cost-effective solution for diseases with low perceived risk was to implement moderate control measures. For diseases with higher perceived severity, such as SARS or Ebola, the most cost-effective strategy shifted toward intervening earlier in the outbreak, with greater resources. When intervention elicited increased media involvement, it remained important to control high severity diseases quickly. For moderate severity diseases, however, it became most cost-effective to implement no intervention and allow the disease to run its course. Our simulation results imply that, when diseases are perceived as severe, the costs of social response have a significant influence on selecting the most cost-effective strategy.

Cost-Effective Control of Infectious Disease Outbreaks Accounting for Societal Reaction.

Directory of Open Access Journals (Sweden)

Shannon M Fast

Full Text Available Studies of cost-effective disease prevention have typically focused on the tradeoff between the cost of disease transmission and the cost of applying control measures. We present a novel approach that also accounts for the cost of social disruptions resulting from the spread of disease. These disruptions, which we call social response, can include heightened anxiety, strain on healthcare infrastructure, economic losses, or violence.The spread of disease and social response are simulated under several different intervention strategies. The modeled social response depends upon the perceived risk of the disease, the extent of disease spread, and the media involvement. Using Monte Carlo simulation, we estimate the total number of infections and total social response for each strategy. We then identify the strategy that minimizes the expected total cost of the disease, which includes the cost of the disease itself, the cost of control measures, and the cost of social response.The model-based simulations suggest that the least-cost disease control strategy depends upon the perceived risk of the disease, as well as media intervention. The most cost-effective solution for diseases with low perceived risk was to implement moderate control measures. For diseases with higher perceived severity, such as SARS or Ebola, the most cost-effective strategy shifted toward intervening earlier in the outbreak, with greater resources. When intervention elicited increased media involvement, it remained important to control high severity diseases quickly. For moderate severity diseases, however, it became most cost-effective to implement no intervention and allow the disease to run its course. Our simulation results imply that, when diseases are perceived as severe, the costs of social response have a significant influence on selecting the most cost-effective strategy.

Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment.

Directory of Open Access Journals (Sweden)

Smita Nayak

Full Text Available Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women.Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA, and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through $800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs; and incremental cost-effectiveness ratios (ICERs in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed.Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days. When assuming alendronate costs of $400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from $714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of $50,000/QALY at all alendronate costs evaluated.Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost

Controlling Healthcare Costs: Just Cost Effectiveness or "Just" Cost Effectiveness?

Science.gov (United States)

Fleck, Leonard M

2018-04-01

Meeting healthcare needs is a matter of social justice. Healthcare needs are virtually limitless; however, resources, such as money, for meeting those needs, are limited. How then should we (just and caring citizens and policymakers in such a society) decide which needs must be met as a matter of justice with those limited resources? One reasonable response would be that we should use cost effectiveness as our primary criterion for making those choices. This article argues instead that cost-effectiveness considerations must be constrained by considerations of healthcare justice. The goal of this article will be to provide a preliminary account of how we might distinguish just from unjust or insufficiently just applications of cost-effectiveness analysis to some healthcare rationing problems; specifically, problems related to extraordinarily expensive targeted cancer therapies. Unconstrained compassionate appeals for resources for the medically least well-off cancer patients will be neither just nor cost effective.

Costs and cost-effectiveness of periviable care.

Science.gov (United States)

Caughey, Aaron B; Burchfield, David J

2014-02-01

With increasing concerns regarding rapidly expanding healthcare costs, cost-effectiveness analysis allows assessment of whether marginal gains from new technology are worth the increased costs. Particular methodologic issues related to cost and cost-effectiveness analysis in the area of neonatal and periviable care include how costs are estimated, such as the use of charges and whether long-term costs are included; the challenges of measuring utilities; and whether to use a maternal, neonatal, or dual perspective in such analyses. A number of studies over the past three decades have examined the costs and the cost-effectiveness of neonatal and periviable care. Broadly, while neonatal care is costly, it is also cost effective as it produces both life-years and quality-adjusted life-years (QALYs). However, as the gestational age of the neonate decreases, the costs increase and the cost-effectiveness threshold is harder to achieve. In the periviable range of gestational age (22-24 weeks of gestation), whether the care is cost effective is questionable and is dependent on the perspective. Understanding the methodology and salient issues of cost-effectiveness analysis is critical for researchers, editors, and clinicians to accurately interpret results of the growing body of cost-effectiveness studies related to the care of periviable pregnancies and neonates. Copyright © 2014 Elsevier Inc. All rights reserved.

Reduction of Total Ownership Costs (R-TOC) Best Practices Guide

National Research Council Canada - National Science Library

Reed, Danny

2003-01-01

The purpose of the Reduction of Total Ownership Costs (R-TOC) program is to achieve readiness improvements in weapon systems by improving the reliability of the systems or the efficiency of the processes used to support...

evaluation of total annual costs of heat exchanger networks using

African Journals Online (AJOL)

user

after solving the first problem using RPA based heat integration gave a minimum total annual cost (TAC) of $237, ... mathematical programming and non-RPA based Hint software. ... The concept of pinch analysis evolved over the years.

[Incremental cost effectiveness of multifocal cataract surgery].

Science.gov (United States)

Pagel, N; Dick, H B; Krummenauer, F

2007-02-01

Supplementation of cataract patients with multifocal intraocular lenses involves an additional financial investment when compared to the corresponding monofocal supplementation, which usually is not funded by German health care insurers. In the context of recent resource allocation discussions, however, the cost effectiveness of multifocal cataract surgery could become an important rationale. Therefore an evidence-based estimation of its cost effectiveness was carried out. Three independent meta-analyses were implemented to estimate the gain in uncorrected near visual acuity and best corrected visual acuity (vision lines) as well as the predictability (fraction of patients without need for reading aids) of multifocal supplementation. Study reports published between 1995 and 2004 (English or German language) were screened for appropriate key words. Meta effects in visual gain and predictability were estimated by means and standard deviations of the reported effect measures. Cost data were estimated by German DRG rates and individual lens costs; the cost effectiveness of multifocal cataract surgery was then computed in terms of its marginal cost effectiveness ratio (MCER) for each clinical benefit endpoint; the incremental costs of multifocal versus monofocal cataract surgery were further estimated by means of their respective incremental cost effectiveness ratio (ICER). An independent meta-analysis estimated the complication profiles to be expected after monofocal and multifocal cataract surgery in order to evaluate expectable complication-associated additional costs of both procedures; the marginal and incremental cost effectiveness estimates were adjusted accordingly. A sensitivity analysis comprised cost variations of +/- 10 % and utility variations alongside the meta effect estimate's 95 % confidence intervals. Total direct costs from the health care insurer's perspective were estimated 3363 euro, associated with a visual meta benefit in best corrected visual

Nucleic acid and nucleotide-mediated synthesis of inorganic nanoparticles

Science.gov (United States)

Berti, Lorenzo; Burley, Glenn A.

2008-02-01

Since the advent of practical methods for achieving DNA metallization, the use of nucleic acids as templates for the synthesis of inorganic nanoparticles (NPs) has become an active area of study. It is now widely recognized that nucleic acids have the ability to control the growth and morphology of inorganic NPs. These biopolymers are particularly appealing as templating agents as their ease of synthesis in conjunction with the possibility of screening nucleotide composition, sequence and length, provides the means to modulate the physico-chemical properties of the resulting NPs. Several synthetic procedures leading to NPs with interesting photophysical properties as well as studies aimed at rationalizing the mechanism of nucleic acid-templated NP synthesis are now being reported. This progress article will outline the current understanding of the nucleic acid-templated process and provides an up to date reference in this nascent field.

One window-period donation in two years of individual donor-nucleic acid test screening for hepatitis B, hepatitis C and human immunodeficiency virus

Directory of Open Access Journals (Sweden)

Jose Eduardo Levi

2013-06-01

Full Text Available Objective: To describe general data on nucleic acid/serology testing and report the first hepatitis B-nucleic acid testing yield case of an immunized donor in Brazil. Methods: A total of 24,441 donations collected in 2010 and 2011 were submitted to individual nucleic acid testing for hepatitis B, hepatitis C and human immunodeficiency virus using the TaqMan® MPX kit (Roche on the Cobas s201 platform, in addition to routine screening for serological markers. Nucleic acid testing-reactive donations were further evaluated by real-time polymerase chain reaction using Cobas AmpliPrep/Cobas TaqMan hepatitis B virus, hepatitis C virus and human immunodeficiency virus tests. Results: Thirty-two donations were reactive by nucleic acid testing, 31 were also serologically reactive and one first-time donor was identified as having hepatitis B in the window period. Follow-up samples showed increasing titers of anti-HBs rising from 19 UI/mL in the index donation to 109 IU/mL seven months later attributable to his vaccination history. Curiously, this donor was never reactive for HbsAg nor for anti-HBc. In the yield donation, he was concomitantly reactive for syphilis (enzyme immunoassay and fluorescent treponemal antibody-absorption; venereal disease research laboratory non-reactive. Overall, six donors (0.02% were characterized as occult hepatitis B. A total of 35% of the confirmed (recombinant immunoblot assay positive hepatitis C donations were nucleic acid testing non-reactive and no human immunodeficiency virus "elite controller" was identified. Conclusion: The yield rate (1:24,441; 95% confidence interval: 1:9,537 - 1:89,717 contrasts to the North American rate (1:410,540 donations and strongly advocates the adoption of nucleic acid testing for hepatitis B in Brazil despite the increasing rate of anti-HBs reactive subjects due to the successful immunization program.

The value-based medicine comparative effectiveness and cost-effectiveness of penetrating keratoplasty for keratoconus.

Science.gov (United States)

Roe, Richard H; Lass, Jonathan H; Brown, Gary C; Brown, Melissa M

2008-10-01

To perform a base case, comparative effectiveness, and cost-effectiveness (cost-utility) analysis of penetrating keratoplasty for patients with severe keratoconus. Visual acuity data were obtained from a large, retrospective multicenter study in which patients with keratoconus with less than 20/40 best corrected visual acuity and/or the inability to wear contact lenses underwent penetrating keratoplasty, with an average follow-up of 2.1 years. The results were combined with other retrospective studies investigating complication rates of penetrating keratoplasty. The data were then incorporated into a cost-utility model using patient preference-based, time trade-off utilities, computer-based decision analysis, and a net present value model to account for the time value of outcomes and money. The comparative effectiveness of the intervention is expressed in quality-of-life gain and QALYs (quality-adjusted life-years), and the cost-effectiveness results are expressed in the outcome of $/QALY (dollars spent per QALY). Penetrating keratoplasty in 1 eye for patients with severe keratoconus results in a comparative effectiveness (value gain) of 16.5% improvement in quality of life every day over the 44-year life expectancy of the average patient with severe keratoconus. Discounting the total value gain of 5.36 QALYs at a 3% annual discount rate yields 3.05 QALYs gained. The incremental cost for penetrating keratoplasty, including all complications, is $5934 ($5913 discounted at 3% per year). Thus, the incremental cost-utility (discounted at 3% annually) for this intervention is $5913/3.05 QALYs = $1942/QALY. If both eyes undergo corneal transplant, the total discounted value gain is 30% and the overall cost-utility is $2003. Surgery on the second eye confers a total discounted value gain of 2.5 QALYs, yielding a quality-of-life gain of 11.6% and a discounted cost-utility of $2238/QALY. Penetrating keratoplasty for patients with severe keratoconus seems to be a

Cost-effectiveness of total hip and knee replacements for the Australian population with osteoarthritis: discrete-event simulation model.

Directory of Open Access Journals (Sweden)

Hideki Higashi

Full Text Available BACKGROUND: Osteoarthritis constitutes a major musculoskeletal burden for the aged Australians. Hip and knee replacement surgeries are effective interventions once all conservative therapies to manage the symptoms have been exhausted. This study aims to evaluate the cost-effectiveness of hip and knee replacements in Australia. To our best knowledge, the study is the first attempt to account for the dual nature of hip and knee osteoarthritis in modelling the severities of right and left joints separately. METHODOLOGY/PRINCIPAL FINDINGS: We developed a discrete-event simulation model that follows up the individuals with osteoarthritis over their lifetimes. The model defines separate attributes for right and left joints and accounts for several repeat replacements. The Australian population with osteoarthritis who were 40 years of age or older in 2003 were followed up until extinct. Intervention effects were modelled by means of disability-adjusted life-years (DALYs averted. Both hip and knee replacements are highly cost effective (AUD 5,000 per DALY and AUD 12,000 per DALY respectively under an AUD 50,000/DALY threshold level. The exclusion of cost offsets, and inclusion of future unrelated health care costs in extended years of life, did not change the findings that the interventions are cost-effective (AUD 17,000 per DALY and AUD 26,000 per DALY respectively. However, there was a substantial difference between hip and knee replacements where surgeries administered for hips were more cost-effective than for knees. CONCLUSIONS/SIGNIFICANCE: Both hip and knee replacements are cost-effective interventions to improve the quality of life of people with osteoarthritis. It was also shown that the dual nature of hip and knee OA should be taken into account to provide more accurate estimation on the cost-effectiveness of hip and knee replacements.

Cost-effectiveness of implant-supported mandibular removable partial dentures.

Science.gov (United States)

Jensen, Charlotte; Ross, Jamila; Feenstra, Talitha L; Raghoebar, Gerry M; Speksnijder, Caroline; Meijer, Henny J A; Cune, Marco S

2017-05-01

The aim of this study was to conduct a cost-effectiveness analysis comparing conventional removable partial dentures (RPDs) and implant-supported RPDs (ISRPDs) treatment in patients with an edentulous maxilla and a bilateral free-ending situation in the mandible. Thirty subjects were included. A new RPD was made and implant support was provided 3 months later. Treatment costs (opportunity costs and costs based on tariffs) were calculated. Treatment effect was expressed by means of the Dutch Oral Health Impact Profile questionnaire (OHIP-NL49), a chewing ability test (Mixing Ability Index, MAI) and a short-form health survey measuring perceived general health (SF-36), which was subsequently converted into quality-adjusted-life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was the primary outcome measure of cost-effectiveness, comparing both treatment strategies. The mean total opportunity costs were €981 (95% CI €971-€991) for the RPD treatment and €2.480 (95% CI €2.461-€2.500) for the ISRPD treatment. The total costs derived from the national tariff structure were €850 for the RPD treatment and €2.610 for the ISRPD treatment. The ICER for OHIP-NL49 and MAI using the opportunity costs was €80 and €786, respectively. When using the tariff structure, corresponding ICERs were €94 and €921. The effect of supporting an RPD with implants when expressed in QALYs was negligible; hence an ICER was not determined. It is concluded that depending on the choice of outcome measure and monetary threshold, supporting an RPD with implants is cost-effective when payers are willing to pay more than €80 per OHIP point gained. Per MAI point gained, an additional €786 has to be invested. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Costs of diarrheal disease and the cost-effectiveness of a rotavirus vaccination program in kyrgyzstan.

Science.gov (United States)

Flem, Elmira T; Latipov, Renat; Nurmatov, Zuridin S; Xue, Yiting; Kasymbekova, Kaliya T; Rheingans, Richard D

2009-11-01

We examined the cost-effectiveness of a rotavirus immunization program in Kyrgyzstan, a country eligible for vaccine funding from the GAVI Alliance. We estimated the burden of rotavirus disease and its economic consequences by using national and international data. A cost-effectiveness analysis was conducted from government and societal perspectives, along with a range of 1-way sensitivity analyses. Rotavirus-related hospitalizations and outpatient visits cost US$580,864 annually, of which $421,658 (73%) is direct medical costs and $159,206 (27%) is nonmedical and indirect costs. With 95% coverage, vaccination could prevent 75% of rotavirus-related hospitalizations and deaths and 56% of outpatient visits and could avert $386,193 (66%) in total costs annually. The medical break-even price at which averted direct medical costs equal vaccination costs is $0.65/dose; the societal break-even price is $1.14/dose for a 2-dose regimen. At the current GAVI Alliance-subsidized vaccine price of $0.60/course, rotavirus vaccination is cost-saving for the government. Vaccination is cost-effective at a vaccine price $9.41/dose, according to the cost-effectiveness standard set by the 2002 World Health Report. Addition of rotavirus vaccines to childhood immunization in Kyrgyzstan could substantially reduce disease burden and associated costs. Vaccination would be cost-effective from the national perspective at a vaccine price $9.41 per dose.

Noninvasive Hemoglobin Monitoring: A Rapid, Reliable, and Cost-Effective Method Following Total Joint Replacement.

Science.gov (United States)

Martin, J Ryan; Camp, Christopher L; Stitz, Amber; Young, Ernest Y; Abdel, Matthew P; Taunton, Michael J; Trousdale, Robert T

2016-03-02

Noninvasive hemoglobin (nHgb) monitoring was initially introduced in the intensive care setting as a means of rapidly assessing Hgb values without performing a blood draw. We conducted a prospective analysis to compare reliability, cost, and patient preference between nHgb monitoring and invasive Hgb (iHgb) monitoring performed via a traditional blood draw. We enrolled 100 consecutive patients undergoing primary or revision total hip or total knee arthroplasty. On postoperative day 1, nHgb and iHgb values were obtained within thirty minutes of one another. iHgb and nHgb values, cost, patient satisfaction, and the duration of time required to obtain each reading were recorded. The concordance correlation coefficient (CCC) was utilized to evaluate the agreement of the two Hgb measurement methods. Paired t tests and Wilcoxon signed-rank tests were utilized to compare mean Hgb values, time, and pain for all readings. The mean Hgb values did not differ significantly between the two measurement methods: the mean iHgb value (and standard deviation) was 11.3 ± 1.4 g/dL (range, 8.2 to 14.3 g/dL), and the mean nHgb value was 11.5 ± 1.8 g/dL (range, 7.0 to 16.0 g/dL) (p = 0.11). The CCC between the two Hgb methods was 0.69. One hundred percent of the patients with an nHgb value of ≥ 10.5 g/dL had an iHgb value of >8.0 g/dL. The mean time to obtain an Hgb value was 0.9 minute for the nHgb method and 51.1 minutes for the iHgb method (p measurement, resulting in a savings of $26 per Hgb assessment when the noninvasive method is used. Noninvasive Hgb monitoring was found to be more efficient, less expensive, and preferred by patients compared with iHgb monitoring. Providers could consider screening total joint arthroplasty patients with nHgb monitoring and only order iHgb measurement if the nHgb value is protocol had been applied to the first blood draw in our 100 patients, approximately $2000 would have been saved. Extrapolated to the U.S. total joint arthroplasty practice

Using value-based total cost of ownership (TCO) measures to inform subsystem trade-offs

Science.gov (United States)

Radziwill, Nicole M.; DuPlain, Ronald F.

2010-07-01

Total Cost of Ownership (TCO) is a metric from management accounting that helps expose both the direct and indirect costs of a business decision. However, TCO can sometimes be too simplistic for "make vs. buy" decisions (or even choosing between competing design alternatives) when value and extensibility are more critical than total cost. A three-dimensional value-based TCO, which was developed to clarify product decisions for an observatory prior to Final Design Review (FDR), will be presented in this session. This value-based approach incorporates priority of requirements, satisfiability of requirements, and cost, and can be easily applied in any environment.

The cost of preventing undernutrition: cost, cost-efficiency and cost-effectiveness of three cash-based interventions on nutrition outcomes in Dadu, Pakistan.

Science.gov (United States)

Trenouth, Lani; Colbourn, Timothy; Fenn, Bridget; Pietzsch, Silke; Myatt, Mark; Puett, Chloe

2018-07-01

Cash-based interventions (CBIs) increasingly are being used to deliver humanitarian assistance and there is growing interest in the cost-effectiveness of cash transfers for preventing undernutrition in emergency contexts. The objectives of this study were to assess the costs, cost-efficiency and cost-effectiveness in achieving nutrition outcomes of three CBIs in southern Pakistan: a 'double cash' (DC) transfer, a 'standard cash' (SC) transfer and a 'fresh food voucher' (FFV) transfer. Cash and FFVs were provided to poor households with children aged 6-48 months for 6 months in 2015. The SC and FFV interventions provided $14 monthly and the DC provided $28 monthly. Cost data were collected via institutional accounting records, interviews, programme observation, document review and household survey. Cost-effectiveness was assessed as cost per case of wasting, stunting and disability-adjusted life year (DALY) averted. Beneficiary costs were higher for the cash groups than the voucher group. Net total cost transfer ratios (TCTRs) were estimated as 1.82 for DC, 2.82 for SC and 2.73 for FFV. Yet, despite the higher operational costs, the FFV TCTR was lower than the SC TCTR when incorporating the participation cost to households, demonstrating the relevance of including beneficiary costs in cost-efficiency estimations. The DC intervention achieved a reduction in wasting, at $4865 per case averted; neither the SC nor the FFV interventions reduced wasting. The cost per case of stunting averted was $1290 for DC, $882 for SC and $883 for FFV. The cost per DALY averted was $641 for DC, $434 for SC and $563 for FFV without discounting or age weighting. These interventions are highly cost-effective by international thresholds. While it is debatable whether these resource requirements represent a feasible or sustainable investment given low health expenditures in Pakistan, these findings may provide justification for continuing Pakistan's investment in national social safety

Integrated Microfluidic Nucleic Acid Isolation, Isothermal Amplification, and Amplicon Quantification

Directory of Open Access Journals (Sweden)

Michael G. Mauk

2015-10-01

Full Text Available Microfluidic components and systems for rapid (<60 min, low-cost, convenient, field-deployable sequence-specific nucleic acid-based amplification tests (NAATs are described. A microfluidic point-of-care (POC diagnostics test to quantify HIV viral load from blood samples serves as a representative and instructive example to discuss the technical issues and capabilities of “lab on a chip” NAAT devices. A portable, miniaturized POC NAAT with performance comparable to conventional PCR (polymerase-chain reaction-based tests in clinical laboratories can be realized with a disposable, palm-sized, plastic microfluidic chip in which: (1 nucleic acids (NAs are extracted from relatively large (~mL volume sample lysates using an embedded porous silica glass fiber or cellulose binding phase (“membrane” to capture sample NAs in a flow-through, filtration mode; (2 NAs captured on the membrane are isothermally (~65 °C amplified; (3 amplicon production is monitored by real-time fluorescence detection, such as with a smartphone CCD camera serving as a low-cost detector; and (4 paraffin-encapsulated, lyophilized reagents for temperature-activated release are pre-stored in the chip. Limits of Detection (LOD better than 103 virons/sample can be achieved. A modified chip with conduits hosting a diffusion-mode amplification process provides a simple visual indicator to readily quantify sample NA template. In addition, a companion microfluidic device for extracting plasma from whole blood without a centrifuge, generating cell-free plasma for chip-based molecular diagnostics, is described. Extensions to a myriad of related applications including, for example, food testing, cancer screening, and insect genotyping are briefly surveyed.

Nucleic acids in circulation

Indian Academy of Sciences (India)

Elevated blood levels of extracellular nucleic acids have been reported in various disease conditions; such as ageing and age-related degenerative disorders, cancer; acute and chronic inflammatory conditions, severe trauma and autoimmune disorders. In addition to genomic DNA and nucleosomes, mitochondrial DNA is ...

En differentieret tilgang til total cost of ownership (TCO)

DEFF Research Database (Denmark)

Zachariassen, Frederik

2010-01-01

Økonomistyring er en nødvendig brik i forsøget på at kunne styre dele af eller hele forsyningskæden, og til dette bruges diverse økonomistyringsværktøjer. Denne artikel omhandler økonomistyringsværktøjet 'total cost of ownership', og hvordan dette kan bruges til at forbedre samarbejdet med...

Quantitative nucleic features are effective for discrimination of intraductal proliferative lesions of the breast

Directory of Open Access Journals (Sweden)

Masatoshi Yamada

2016-01-01

Full Text Available Background: Intraductal proliferative lesions (IDPLs of the breast are recognized as a risk factor for subsequent invasive carcinoma development. Although opportunities for IDPL diagnosis have increased, these lesions are difficult to diagnose correctly, especially atypical ductal hyperplasia (ADH and low-grade ductal carcinoma in situ (LG-DCIS. In order to define the difference between these lesions, many molecular pathological approaches have been performed. However, still we do not have a molecular marker and objective histological index about IDPLs of the breast. Methods: We generated full digital pathology archives from 175 female IDPL patients, including usual ductal hyperplasia (UDH, ADH, LG-DCIS, intermediate-grade (IM-DCIS, and high-grade (HG-DCIS. After total 2,035,807 nucleic segmentations were extracted, we evaluated nuclear features using step-wise linear discriminant analysis (LDA and a support vector machine. Results: High diagnostic accuracy (81.8–99.3% was achieved between pathologists' diagnoses and two-group LDA predictions from nucleic features for IDPL discrimination. Grouping of nuclear features as size and shape-related or intranuclear texture-related revealed that the latter group was more important when distinguishing between normal duct, UDH, ADH, and LG-DCIS. However, these two groups were equally important when discriminating between LG-DCIS and HG-DCIS. The Mahalanobis distances between each group showed that the smallest distance values occurred between LG-DCIS and IM-DCIS and between ADH and Normal. On the other hand, the distance value between ADH and LG-DCIS was larger than this distance. Conclusions: In this study, we have presented a practical and useful digital pathological method that incorporates nuclear morphological and textural features for IDPL prediction. We expect that this novel algorithm is used for the automated diagnosis assisting system for breast cancer.

Quantitative nucleic features are effective for discrimination of intraductal proliferative lesions of the breast

Science.gov (United States)

Yamada, Masatoshi; Saito, Akira; Yamamoto, Yoichiro; Cosatto, Eric; Kurata, Atsushi; Nagao, Toshitaka; Tateishi, Ayako; Kuroda, Masahiko

2016-01-01

Background: Intraductal proliferative lesions (IDPLs) of the breast are recognized as a risk factor for subsequent invasive carcinoma development. Although opportunities for IDPL diagnosis have increased, these lesions are difficult to diagnose correctly, especially atypical ductal hyperplasia (ADH) and low-grade ductal carcinoma in situ (LG-DCIS). In order to define the difference between these lesions, many molecular pathological approaches have been performed. However, still we do not have a molecular marker and objective histological index about IDPLs of the breast. Methods: We generated full digital pathology archives from 175 female IDPL patients, including usual ductal hyperplasia (UDH), ADH, LG-DCIS, intermediate-grade (IM)-DCIS, and high-grade (HG)-DCIS. After total 2,035,807 nucleic segmentations were extracted, we evaluated nuclear features using step-wise linear discriminant analysis (LDA) and a support vector machine. Results: High diagnostic accuracy (81.8–99.3%) was achieved between pathologists’ diagnoses and two-group LDA predictions from nucleic features for IDPL discrimination. Grouping of nuclear features as size and shape-related or intranuclear texture-related revealed that the latter group was more important when distinguishing between normal duct, UDH, ADH, and LG-DCIS. However, these two groups were equally important when discriminating between LG-DCIS and HG-DCIS. The Mahalanobis distances between each group showed that the smallest distance values occurred between LG-DCIS and IM-DCIS and between ADH and Normal. On the other hand, the distance value between ADH and LG-DCIS was larger than this distance. Conclusions: In this study, we have presented a practical and useful digital pathological method that incorporates nuclear morphological and textural features for IDPL prediction. We expect that this novel algorithm is used for the automated diagnosis assisting system for breast cancer. PMID:26955499

A pilot study to evaluate the cost-effectiveness of ondansetron and granisetron in fractionated total body irradiation

Energy Technology Data Exchange (ETDEWEB)

Gibbs, S.J.; Cassoni, A.M. [Middlesex Hospital, London (United Kingdom)

1996-11-01

The duration of the antiemetic effect of granisetron was examined in a pilot study of patients (n = 26) undergoing a standard emetogenic stimulus in the form of total body irradiation fractionated over 3-4 days, in a randomized comparison with twice-daily ondansetron. A single intravenous dose of granisetron at the onset of therapy was effective over the entire follow-up period in 50% (6/12) of patients, compared with 77% (10/13) prescribed twice-daily oral ondansetron for 3 or 4 days. The response rate within the first 24 hours from the start of irradiation was 67% (8/12) for granisetron and 77% (10/13) for ondansetron. Granisetron and ondansetron was therefore of similar efficacy within the first 24-hour period, but granisetron was less efficaceous more than 24 hours after the onset of therapy. Patients who required a second dose of granisetron did so at intervals of 12, 42, 47 and 48 hours following the first fraction of radiotherapy. The cost per patient in this study was 48 for granisetron and {sub 1}54 for ondanestron, but the dose scheduling we used cannot be recommended in view of the lower effectiveness of granisetron. (author).

A pilot study to evaluate the cost-effectiveness of ondansetron and granisetron in fractionated total body irradiation

International Nuclear Information System (INIS)

Gibbs, S.J.; Cassoni, A.M.

1996-01-01

The duration of the antiemetic effect of granisetron was examined in a pilot study of patients (n = 26) undergoing a standard emetogenic stimulus in the form of total body irradiation fractionated over 3-4 days, in a randomized comparison with twice-daily ondansetron. A single intravenous dose of granisetron at the onset of therapy was effective over the entire follow-up period in 50% (6/12) of patients, compared with 77% (10/13) prescribed twice-daily oral ondansetron for 3 or 4 days. The response rate within the first 24 hours from the start of irradiation was 67% (8/12) for granisetron and 77% (10/13) for ondansetron. Granisetron and ondansetron was therefore of similar efficacy within the first 24-hour period, but granisetron was less efficaceous more than 24 hours after the onset of therapy. Patients who required a second dose of granisetron did so at intervals of 12, 42, 47 and 48 hours following the first fraction of radiotherapy. The cost per patient in this study was 48 for granisetron and 1 54 for ondanestron, but the dose scheduling we used cannot be recommended in view of the lower effectiveness of granisetron. (author)

RNA:DNA Ratio and Other Nucleic Acid Derived Indices in Marine Ecology

Directory of Open Access Journals (Sweden)

Luis Chícharo

2008-08-01

Full Text Available Some of most used indicators in marine ecology are nucleic acid-derived indices. They can be divided by target levels in three groups: 1 at the organism level as ecophysiologic indicators, indicators such as RNA:DNA ratios, DNA:dry weight and RNA:protein, 2 at the population level, indicators such as growth rate, starvation incidence or fisheries impact indicators, and 3 at the community level, indicators such as trophic interactions, exergy indices and prey identification. The nucleic acids derived indices, especially RNA:DNA ratio, have been applied with success as indicators of nutritional condition, well been and growth in marine organisms. They are also useful as indicators of natural or anthropogenic impacts in marine population and communities, such as upwelling or dredge fisheries, respectively. They can help in understanding important issues of marine ecology such as trophic interactions in marine environment, fish and invertebrate recruitment failure and biodiversity changes, without laborious work of counting, measuring and identification of small marine organisms. Besides the objective of integrate nucleic acid derived indices across levels of organization, the paper will also include a general characterization of most used nucleic acid derived indices in marine ecology and also advantages and limitations of them. We can conclude that using indicators, such RNA:DNA ratios and other nucleic acids derived indices concomitantly with organism and ecosystems measures of responses to climate change (distribution, abundance, activity, metabolic rate, survival will allow for the development of more rigorous and realistic predictions of the effects of anthropogenic climate change on marine systems.

The Relationship between Cost Leadership Strategy, Total Quality Management Applications and Financial Performance

Directory of Open Access Journals (Sweden)

Ali KURT

2016-03-01

Full Text Available Firms need to implement some competition strategies and total quality management applications to overcome the fierce competition among others. The purpose of this study is to show the relationship between cost leadership strategy, total quality management applications and firms’ financial performance with literature review and empirical analysis. 449 questionnaires were conducted to the managers of 142 big firms. The data gathered was assessed with AMOS. As a result, the relationship between cost leadership strategy, total quality management applications and firms’ financial performance has been gathered. In addition, the relationship between TQM applications and financial performance has also been gathered.

Nucleic acid-induced antiviral immunity in invertebrates: an evolutionary perspective.

Science.gov (United States)

Wang, Pei-Hui; Weng, Shao-Ping; He, Jian-Guo

2015-02-01

Nucleic acids derived from viral pathogens are typical pathogen associated molecular patterns (PAMPs). In mammals, the recognition of viral nucleic acids by pattern recognition receptors (PRRs), which include Toll-like receptors (TLRs) and retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), induces the release of inflammatory cytokines and type I interferons (IFNs) through the activation of nuclear factor κB (NF-κB) and interferon regulatory factor (IRF) 3/7 pathways, triggering the host antiviral state. However, whether nucleic acids can induce similar antiviral immunity in invertebrates remains ambiguous. Several studies have reported that nucleic acid mimics, especially dsRNA mimic poly(I:C), can strongly induce non-specific antiviral immune responses in insects, shrimp, and oyster. This behavior shows multiple similarities to the hallmarks of mammalian IFN responses. In this review, we highlight the current understanding of nucleic acid-induced antiviral immunity in invertebrates. We also discuss the potential recognition and regulatory mechanisms that confer non-specific antiviral immunity on invertebrate hosts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Photochemical reactions of nucleic acids and their constituents of photobiological relevance

International Nuclear Information System (INIS)

Saito, I.; Sugiyama, H.; Matsuura, T.

1983-01-01

A review is given of the papers published from 1977 to May 1983 on the UV-induced photochemical reactions of nucleic acids and their constituents of photobiological relevance where the structures of photoproducts have been fully characterized. Among the topics discussed are photoadditions relevant to nucleic acid-protein photocrosslinking, photoreactions with psoralens and nucleic acids and photochemical reactions of polynucleotides. (U.K.)

Extending total parenteral nutrition hang time in the neonatal intensive care unit: is it safe and cost effective?

Science.gov (United States)

Balegar V, Kiran Kumar; Azeem, Mohammad Irfan; Spence, Kaye; Badawi, Nadia

2013-01-01

To investigate the effects of prolonging hang time of total parenteral nutrition (TPN) fluid on central line-associated blood stream infection (CLABSI), TPN-related cost and nursing workload. A before-after observational study comparing the practice of hanging TPN bags for 48 h (6 February 2009-5 February 2010) versus 24 h (6 February 2008-5 February 2009) in a tertiary neonatal intensive care unit was conducted. The main outcome measures were CLABSI, TPN-related expenses and nursing workload. One hundred thirty-six infants received 24-h TPN bags and 124 received 48-h TPN bags. Median (inter-quartile range) gestation (37 weeks (33,39) vs. 36 weeks (33,39)), mean (±standard deviation) admission weight of 2442 g (±101) versus 2476 g (±104) and TPN duration (9.7 days (±12.7) vs. 9.9 days (±13.4)) were similar (P > 0.05) between the 24- and 48-h TPN groups. There was no increase in CLABSI with longer hang time (0.8 vs. 0.4 per 1000 line days in the 24-h vs. 48-h group; P < 0.05). Annual cost saving using 48-h TPN was AUD 97,603.00. By using 48-h TPN, 68.3% of nurses indicated that their workload decreased and 80.5% indicated that time spent changing TPN reduced. Extending TPN hang time from 24 to 48 h did not alter CLABSI rate and was associated with a reduced TPN-related cost and perceived nursing workload. Larger randomised controlled trials are needed to more clearly delineate these effects. © 2012 The Authors. Journal of Paediatrics and Child Health © 2012 Paediatrics and Child Health Division (Royal Australasian College of Physicians).

Geometric properties of nucleic acids with potential for autobuilding

International Nuclear Information System (INIS)

Gruene, Tim; Sheldrick, George M.

2011-01-01

Algorithms and geometrical properties are described for the automated building of nucleic acids in experimental electron density. Medium- to high-resolution X-ray structures of DNA and RNA molecules were investigated to find geometric properties useful for automated model building in crystallographic electron-density maps. We describe a simple method, starting from a list of electron-density ‘blobs’, for identifying backbone phosphates and nucleic acid bases based on properties of the local electron-density distribution. This knowledge should be useful for the automated building of nucleic acid models into electron-density maps. We show that the distances and angles involving C1′ and the P atoms, using the pseudo-torsion angles η' and θ' that describe the …P—C1′—P—C1′… chain, provide a promising basis for building the nucleic acid polymer. These quantities show reasonably narrow distributions with asymmetry that should allow the direction of the phosphate backbone to be established

Cost-effectiveness analysis of sandhill crane habitat management

Science.gov (United States)

Kessler, Andrew C.; Merchant, James W.; Shultz, Steven D.; Allen, Craig R.

2013-01-01

Invasive species often threaten native wildlife populations and strain the budgets of agencies charged with wildlife management. We demonstrate the potential of cost-effectiveness analysis to improve the efficiency and value of efforts to enhance sandhill crane (Grus canadensis) roosting habitat. We focus on the central Platte River in Nebraska (USA), a region of international ecological importance for migrating avian species including sandhill cranes. Cost-effectiveness analysis is a valuation process designed to compare alternative actions based on the cost of achieving a pre-determined objective. We estimated costs for removal of invasive vegetation using geographic information system simulations and calculated benefits as the increase in area of sandhill crane roosting habitat. We generated cost effectiveness values for removing invasive vegetation on 7 land parcels and for the entire central Platte River to compare the cost-effectiveness of management at specific sites and for the central Platte River landscape. Median cost effectiveness values for the 7 land parcels evaluated suggest that costs for creating 1 additional hectare of sandhill crane roosting habitat totaled US $1,595. By contrast, we found that creating an additional hectare of sandhill crane roosting habitat could cost as much as US $12,010 for some areas in the central Platte River, indicating substantial cost savings can be achieved by using a cost effectiveness analysis to target specific land parcels for management. Cost-effectiveness analysis, used in conjunction with geographic information systems, can provide decision-makers with a new tool for identifying the most economically efficient allocation of resources to achieve habitat management goals.

Total hip arthroplasty revision due to infection: a cost analysis approach.

Science.gov (United States)

Klouche, S; Sariali, E; Mamoudy, P

2010-04-01

The treatment of total hip arthroplasty (THA) infections is long and costly. However,the number of studies in the literature analysing the real cost of THA revision in relation to their etiology, including infection, is limited. The aim of this retrospective study was to determine the cost of revision of infected THA and to compare these costs to those of primary THA and revision of non-infected THA. We performed a retrospective cost analysis for the year 2006 using an identical analytic accounting system in each hospital department (according to internal criteria) based on allotment of direct costs and receipts for each department. From January to December 2006, 424 primary THA, 57 non-infected THA revisions and 40 THA revisions due to infection were performed. The different cost areas of the patient's treatment were identified.This included preoperative medical work-up, medicosurgical management during hospital stay,a second stay in an orthopedic rehabilitation hospital (ORH) and post-hospitalisation antibiotic therapy after revision due to infection, as well as home-based hospitalisation (HH) costs, if this was the selected alternative option. We used the national health insurance fee schedule found in the "Common classification of medical procedures" and the "General nomenclature of professional procedures" applicable in France since September 1, 2005. Hospital costs included direct costs (hospital overhead costs) and indirect costs, (medical, surgical, technical settings and net general service expenses). The calculation of HH costs and ORH costs were based on the average daily charge of these departments. The cost of primary THA was used as the reference.We then compared our surgical costs with those found for the corresponding comparable hospital stay groups (Groupes homogènes de séjour). The average hospital stay (AHS) was 7.5 +/- 1.8 days for primary THA, 8.9 +/- 2.2 days for non-infected revisions and 30.6 +/- 14.9 days for revisions due to infection

Evaluation of three automated nucleic acid extraction systems for identification of respiratory viruses in clinical specimens by multiplex real-time PCR.

Science.gov (United States)

Kim, Yoonjung; Han, Mi-Soon; Kim, Juwon; Kwon, Aerin; Lee, Kyung-A

2014-01-01

A total of 84 nasopharyngeal swab specimens were collected from 84 patients. Viral nucleic acid was extracted by three automated extraction systems: QIAcube (Qiagen, Germany), EZ1 Advanced XL (Qiagen), and MICROLAB Nimbus IVD (Hamilton, USA). Fourteen RNA viruses and two DNA viruses were detected using the Anyplex II RV16 Detection kit (Seegene, Republic of Korea). The EZ1 Advanced XL system demonstrated the best analytical sensitivity for all the three viral strains. The nucleic acids extracted by EZ1 Advanced XL showed higher positive rates for virus detection than the others. Meanwhile, the MICROLAB Nimbus IVD system was comprised of fully automated steps from nucleic extraction to PCR setup function that could reduce human errors. For the nucleic acids recovered from nasopharyngeal swab specimens, the QIAcube system showed the fewest false negative results and the best concordance rate, and it may be more suitable for detecting various viruses including RNA and DNA virus strains. Each system showed different sensitivity and specificity for detection of certain viral pathogens and demonstrated different characteristics such as turnaround time and sample capacity. Therefore, these factors should be considered when new nucleic acid extraction systems are introduced to the laboratory.

Nucleic Acid Therapy: from humble beginnings a dynamic technology

CSIR Research Space (South Africa)

Millroy, L

2011-02-01

Full Text Available The term “nucleic acid therapy” encompasses a wide range of technologies for the treatment of a range of plant and animal ailments. As the name implies, it makes use of nucleic acid (either DNA or RNA) as a therapeutic agent. There are six branches...

Ionizing radiation induced attachment reactions of nucleic acids and their components

International Nuclear Information System (INIS)

Myers, L.S. Jr.

1975-01-01

An extensive bibliographic review is given of experimental and theoretical data on radiation-induced attachment reactions of nucleic acids and their components. Mechanisms of these reactions are reviewed. The reactions with water, formate, and alcohols, with amines and other small molecules, and with radiation sensitizers and nucleic acid-nucleic acid reactions are discussed. Studies of the reaction mechanisms show that many of the reactions occur by radical-molecule reactions, but radical-radical reactions also occur. Radiation modifiers become attached to nucleic acids in vitro and in vivo and there are indications that attachment may be necessary for the action of some sensitizers. (U.S.)

Supplier managed inventory in the OEM supply chain : the impact of relationship types on total costs and cost distribution

NARCIS (Netherlands)

Nyen, van P.L.M.; Bertrand, J.W.M.; Ooijen, van H.P.G.; Vandaele, N.J.

2009-01-01

We investigate the impact of four variants of supplier managed inventory on total costs and cost distribution in a capital goods supply chain consisting of a parts supplier who delivers parts to an original equipment manufacturer’s assembly plant. The four supplier managed inventory variants differ

[Cost-Effectiveness and Cost-Utility Analyses of Antireflux Medicine].

Science.gov (United States)

Gockel, Ines; Lange, Undine Gabriele; Schürmann, Olaf; Jansen-Winkeln, Boris; Sibbel, Rainer; Lyros, Orestis; von Dercks, Nikolaus

2018-04-12

Laparoscopic antireflux surgery and medical therapy with proton pump inhibitors are gold standards of gastroesophageal reflux treatment. On account of limited resources and increasing healthcare needs and costs, in this analysis, not only optimal medical results, but also superiority in health economics of these 2 methods are evaluated. We performed an electronic literature survey in MEDLINE, PubMed, Cochrane Library, ISRCTN (International Standard Randomization Controlled Trial Number) as well as in the NHS Economic Evaluation Database, including studies published until 1/2017. Only studies considering the effect size of QALY (Quality-Adjusted Life Years) (with respect to different quality of life-scores) as primary outcome comparing laparoscopic fundoplication and medical therapy were included. Criteria of comparison were ICER (Incremental Cost-Effectiveness Ratio) and ICUR (Incremental Cost-Utility Ratio). Superiority of the respective treatment option for each publication was worked out. In total, 18 comparative studies were identified in the current literature with respect to above-mentioned search terms, qualifying for the defined inclusion criteria. Six studies were finally selected for analyses. Out of 6 publications, 3 showed superiority of laparoscopic fundoplication over long-term medical management based on current cost-effectiveness data. Limitations were related to different time intervals, levels of evidence of studies and underlying resources/costs of analyses, healthcare systems and applied quality of life instruments. Future prospective, randomized trials should examine this comparison in greater detail. Additionally, there is a large potential for further research in the health economics assessment of early diagnosis and prevention measures of reflux disease and Barrett's esophagus/carcinoma. © Georg Thieme Verlag KG Stuttgart · New York.

Biological activity and biotechnological aspects of locked nucleic acids

DEFF Research Database (Denmark)

Lundin, Karin E; Højland, Torben; Hansen, Bo

2013-01-01

Locked nucleic acid (LNA) is one of the most promising new nucleic acid analogues that has been produced under the past two decades. In this chapter, we have tried to cover many of the different areas, where this molecule has been used to improve the function of synthetic oligonucleotides (ONs). ...

Permanent magnet design for magnetic heat pumps using total cost minimization

Science.gov (United States)

Teyber, R.; Trevizoli, P. V.; Christiaanse, T. V.; Govindappa, P.; Niknia, I.; Rowe, A.

2017-11-01

The active magnetic regenerator (AMR) is an attractive technology for efficient heat pumps and cooling systems. The costs associated with a permanent magnet for near room temperature applications are a central issue which must be solved for broad market implementation. To address this problem, we present a permanent magnet topology optimization to minimize the total cost of cooling using a thermoeconomic cost-rate balance coupled with an AMR model. A genetic algorithm identifies cost-minimizing magnet topologies. For a fixed temperature span of 15 K and 4.2 kg of gadolinium, the optimal magnet configuration provides 3.3 kW of cooling power with a second law efficiency (ηII) of 0.33 using 16.3 kg of permanent magnet material.

Clustered Regularly Interspaced Short Palindromic Repeats/Cas9 Triggered Isothermal Amplification for Site-Specific Nucleic Acid Detection.

Science.gov (United States)

Huang, Mengqi; Zhou, Xiaoming; Wang, Huiying; Xing, Da

2018-02-06

A novel CRISPR/Cas9 triggered isothermal exponential amplification reaction (CAS-EXPAR) strategy based on CRISPR/Cas9 cleavage and nicking endonuclease (NEase) mediated nucleic acids amplification was developed for rapid and site-specific nucleic acid detection. CAS-EXPAR was primed by the target DNA fragment produced by cleavage of CRISPR/Cas9, and the amplification reaction performed cyclically to generate a large number of DNA replicates which were detected using a real-time fluorescence monitoring method. This strategy that combines the advantages of CRISPR/Cas9 and exponential amplification showed high specificity as well as rapid amplification kinetics. Unlike conventional nucleic acids amplification reactions, CAS-EXPAR does not require exogenous primers, which often cause target-independent amplification. Instead, primers are first generated by Cas9/sgRNA directed site-specific cleavage of target and accumulated during the reaction. It was demonstrated this strategy gave a detection limit of 0.82 amol and showed excellent specificity in discriminating single-base mismatch. Moreover, the applicability of this method to detect DNA methylation and L. monocytogenes total RNA was also verified. Therefore, CAS-EXPAR may provide a new paradigm for efficient nucleic acid amplification and hold the potential for molecular diagnostic applications.

Analysis of the total system life cycle cost for the Civilian Radioactive Waste Management Program: executive summary

International Nuclear Information System (INIS)

1985-04-01

The total-system life-cycle cost (TSLCC) analysis for the Department of Energy's Civilian Radioactive Waste Management Progrram is an ongoing activity that helps determine whether the revenue-producing mechanism established by the Nuclear Waste Policy Act of 1982 is sufficient to cover the cost of the program. This report is an input into the third evaluation of the adequacy of the fee. The total-system cost for the reference waste-management program in this analysis is estimated to be 24 to 30 billion (1984) dollars. For the sensitivity cases studied in this report, the costs could be as high as 35 billion dollars and as low as 21 billion dollars. Because factors like repository location, the quantity of waste generated, transportation-cask technology, and repository startup dates exert substantial impacts on total-system costs, there are several tradeoffs between these factors, and these tradeoffs can greatly influence the total cost of the program. The total-system cost for the reference program described in this report is higher by 3 to 5 billion dollars, or 15 to 20%, than the cost for the reference program of the TSLCC analysis of April 1984. More than two-thirds of this increase is in the cost of repository construction and operation. These repository costs have increased because of changing design concepts, different assumptions about the effort required to perform the necessary activities, and a change in the source data on which the earlier analysis was based. Development and evaluation costs have similarly increased because of a net addition to the work content. Transportation costs have increased because of different assumptions about repository locations and several characteristics of the transportation system. It is expected that the estimates of total-system costs will continue to change in response to both an evolving program strategy and better definition of the work required to achieve the program objectives

Prediction of molecular alignment of nucleic acids in aligned media

International Nuclear Information System (INIS)

Wu Bin; Petersen, Michael; Girard, Frederic; Tessari, Marco; Wijmenga, Sybren S.

2006-01-01

We demonstrate - using the data base of all deposited DNA and RNA structures aligned in Pf1-medium and RDC refined - that for nucleic acids in a Pf1-medium the electrostatic alignment tensor can be predicted reliably and accurately via a simple and fast calculation based on the gyration tensor spanned out by the phosphodiester atoms. The rhombicity is well predicted over its full range from 0 to 0.66, while the alignment tensor orientation is predicted correctly for rhombicities up to ca. 0.4, for larger rhombicities it appears to deviate somewhat more than expected based on structural noise and measurement error. This simple analytical approach is based on the Debye-Huckel approximation for the electrostatic interaction potential, valid at distances sufficiently far away from a poly-ionic charged surface, a condition naturally enforced when the charge of alignment medium and solute are of equal sign, as for nucleic acids in a Pf1-phage medium. For the usual salt strengths and nucleic acid sizes, the Debye-Huckel screening length is smaller than the nucleic acid size, but large enough for the collective of Debye-Huckel spheres to encompass the whole molecule. The molecular alignment is then purely electrostatic, but it's functional form is under these conditions similar to that for steric alignment. The proposed analytical expression allows for very fast calculation of the alignment tensor and hence RDCs from the conformation of the nucleic acid molecule. This information provides opportunities for improved structure determination of nucleic acids, including better assessment of dynamics in (multi-domain) nucleic acids and the possibility to incorporate alignment tensor prediction from shape directly into the structure calculation process. The procedures are incorporated into MATLAB scripts, which are available on request

BIOPHYSICAL PROPERTIES OF NUCLEIC ACIDS AT SURFACES RELEVANT TO MICROARRAY PERFORMANCE

OpenAIRE

Rao, Archana N.; Grainger, David W.

2014-01-01

Both clinical and analytical metrics produced by microarray-based assay technology have recognized problems in reproducibility, reliability and analytical sensitivity. These issues are often attributed to poor understanding and control of nucleic acid behaviors and properties at solid-liquid interfaces. Nucleic acid hybridization, central to DNA and RNA microarray formats, depends on the properties and behaviors of single strand (ss) nucleic acids (e.g., probe oligomeric DNA) bound to surface...

The role of immunostimulatory nucleic acids in septic shock

Science.gov (United States)

Bleiblo, Farag; Michael, Paul; Brabant, Danielle; Ramana, Chilakamarti V; Tai, TC; Saleh, Mazen; Parrillo, Joseph E; Kumar, Anand; Kumar, Aseem

2012-01-01

Sepsis and its associated syndromes represent the systemic host response to severe infection and is manifested by varying degrees of hypotension, coagulopathy, and multiorgan dysfunction. Despite great efforts being made to understand this condition and designing therapies to treat sepsis, mortality rates are still high in septic patients. Characterization of the complex molecular signaling networks between the various components of host-pathogen interactions, highlights the difficulty in identifying a single driving force responsible for sepsis. Although triggering the inflammatory response is generally considered as protective against pathogenic threats, the interplay between the signaling pathways that are induced or suppressed during sepsis may harm the host. Numerous surveillance mechanisms have evolved to discriminate self from foreign agents and accordingly provoke an effective cellular response to target the pathogens. Nucleic acids are not only an essential genetic component, but sensing their molecular signature is also an important quality control mechanism which has evolved to maintain the integrity of the human genome. Evidence that has accumulated recently indicated that distinct pattern recognition receptors sense nucleic acids released from infectious organisms or from damaged host cells, resulting in the modulation of intracellular signalling cascades. Immunoreceptor-mediated detection of these nucleic acids induces antigen-specific immunity, secretion of proinflammatory cytokines and reactive oxygen/nitrogen species and thus are implicated in a range of diseases including septic shock. PMID:22328944

A novel universal real-time PCR system using the attached universal duplex probes for quantitative analysis of nucleic acids

Directory of Open Access Journals (Sweden)

Wilson Zoe A

2008-06-01

Full Text Available Abstract Background Real-time PCR techniques are being widely used for nucleic acids analysis, but one limitation of current frequently employed real-time PCR is the high cost of the labeled probe for each target molecule. Results We describe a real-time PCR technique employing attached universal duplex probes (AUDP, which has the advantage of generating fluorescence by probe hydrolysis and strand displacement over current real-time PCR methods. AUDP involves one set of universal duplex probes in which the 5' end of the fluorescent probe (FP and a complementary quenching probe (QP lie in close proximity so that fluorescence can be quenched. The PCR primer pair with attached universal template (UT and the FP are identical to the UT sequence. We have shown that the AUDP technique can be used for detecting multiple target DNA sequences in both simplex and duplex real-time PCR assays for gene expression analysis, genotype identification, and genetically modified organism (GMO quantification with comparable sensitivity, reproducibility, and repeatability with other real-time PCR methods. Conclusion The results from GMO quantification, gene expression analysis, genotype identification, and GMO quantification using AUDP real-time PCR assays indicate that the AUDP real-time PCR technique has been successfully applied in nucleic acids analysis, and the developed AUDP real-time PCR technique will offer an alternative way for nucleic acid analysis with high efficiency, reliability, and flexibility at low cost.

evaluation of total annual costs of heat exchanger networks using

African Journals Online (AJOL)

This study presents pinch analysis of some heat exchanger networks (HENs) problems using Hint integration (HINT) software. Three examples reported to have been solved using different approaches by various researchers to obtain the least possible total annual cost (TAC) were solved using the Hint software. In this work ...

Cost-effectiveness of osteo-odonto keratoprosthesis in Singapore.

Science.gov (United States)

Dong, Di; Tan, Anna; Mehta, Jodhbir S; Tan, Donald; Finkelstein, Eric Andrew

2014-01-01

To determine the long-term cost-effectiveness of osteo-odonto keratoprosthesis (OOKP) relative to no treatment among patients with end-stage corneal and ocular surface diseases in Singapore. Cost-effectiveness analysis based on data from a retrospective cohort study. From a health system perspective, we calculated the incremental cost-effectiveness ratio of OOKP treatment relative to no treatment over a 30-year horizon, based on data from a cohort of 23 patients who underwent OOKP surgery between 2004 and 2009 at Singapore National Eye Centre. Preoperative and postoperative vision-related quality-of-life values were estimated from patients' visual outcomes and were used to calculate the gain in quality-adjusted life years (QALYs) resulting from OOKP treatment. Unsubsidized costs for surgery, consultations, examinations, medications, follow-up visits, and treatments for complications were retrieved from patients' bills to estimate the total costs associated with OOKP treatment. Sensitivity analyses were conducted to test the robustness of the model. Over a 30-year period, OOKP treatment, compared with no treatment, improved QALYs by 3.991 among patients with end-stage corneal and ocular surface diseases at an additional cost of S$67 840 (US$55 150), resulting in an incremental cost-effectiveness ratio of S$17 000/QALY (US$13 820/QALY). Based on commonly cited cost-effectiveness benchmarks, the OOKP is a cost-effective treatment for patients with end-stage corneal and ocular surface diseases. Copyright © 2014 Elsevier Inc. All rights reserved.

"Clickable" LNA/DNA probes for fluorescence sensing of nucleic acids and autoimmune antibodies

DEFF Research Database (Denmark)

Jørgensen, Anna S; Gupta, Pankaj; Wengel, Jesper

2013-01-01

Herein we describe fluorescent oligonucleotides prepared by click chemistry between novel alkyne-modified locked nucleic acid (LNA) strands and a series of fluorescent azides for homogeneous (all-in-solution) detection of nucleic acids and autoimmune antibodies.......Herein we describe fluorescent oligonucleotides prepared by click chemistry between novel alkyne-modified locked nucleic acid (LNA) strands and a series of fluorescent azides for homogeneous (all-in-solution) detection of nucleic acids and autoimmune antibodies....

Total cost estimates for large-scale wind scenarios in UK

International Nuclear Information System (INIS)

Dale, Lewis; Milborrow, David; Slark, Richard; Strbac, Goran

2004-01-01

The recent UK Energy White Paper suggested that the Government should aim to secure 20% of electricity from renewable sources by 2020. A number of estimates of the extra cost of such a commitment have been made, but these have not necessarily included all the relevant cost components. This analysis sets out to identify these and to calculate the extra cost to the electricity consumer, assuming all the renewable electricity is sourced from wind energy. This enables one of the more controversial issues--the implications of wind intermittency--to be addressed. The basis of the assumptions associated with generating costs, extra balancing costs and distribution and transmission system reinforcement costs are all clearly identified and the total costs of a '20% wind' scenario are compared with a scenario where a similar amount of energy is generated by gas-fired plant. This enables the extra costs of the renewables scenario to be determined. The central estimate of the extra costs to electricity consumers is just over 0.3 p/kW h in current prices (around 5% extra on average domestic unit prices). Sensitivity analyses examine the implications of differing assumptions. The extra cost would rise if the capital costs of wind generation fall slower than anticipated, but would fall if gas prices rise more rapidly than has been assumed, or if wind plant are more productive. Even if it is assumed that wind has no capacity displacement value, the added cost to the electricity consumer rises by less than 0.1 p/kW h. It is concluded that there does not appear to be any technical reason why a substantial proportion of the country's electricity requirements could not be delivered by wind

Direct hospital costs of total laparoscopic hysterectomy compared with fast-track open hysterectomy at a tertiary hospital: a retrospective case-controlled study.

Science.gov (United States)

Rhou, Yoon J J; Pather, Selvan; Loadsman, John A; Campbell, Neil; Philp, Shannon; Carter, Jonathan

2015-12-01

To assess the direct intraoperative and postoperative costs in women undergoing total laparoscopic hysterectomy and fast-track open hysterectomy. A retrospective review of the direct hospital-related costs in a matched cohort of women undergoing total laparoscopic hysterectomy (TLH) and fast-track open hysterectomy (FTOH) at a tertiary hospital. All costs were calculated, including the cost of advanced high-energy laparoscopic devices. The effect of the learning curve on cost in laparoscopic hysterectomy was also assessed, as was the hospital case-weighted cost, which was compared with the actual cost. Fifty women were included in each arm of the study. TLH had a higher intraoperative cost, but a lower postoperative cost than FTOH (AUD$3877 vs AUD$2776 P funding model in our hospital is inaccurate when compared to directly calculated hospital costs. © 2013 The Authors ANZJOG © 2013 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

The adoption of total cost of ownership for sourcing decisions - a structural equations analysis

NARCIS (Netherlands)

Wouters, Marc; Anderson, James C.; Wynstra, Finn

2005-01-01

This study investigates the adoption of total cost of ownership (TCO) analysis to improve sourcing decisions. TCO can be seen as an application of activity based costing (ABC) that quantifies the costs that are involved in acquiring and using purchased goods or services. TCO supports purchasing

Cost-effectiveness analysis of the introduction of rotavirus vaccine in Iran.

Science.gov (United States)

Javanbakht, Mehdi; Moradi-Lakeh, Maziar; Yaghoubi, Mohsen; Esteghamati, Abdoulreza; Mansour Ghanaie, Roxana; Mahmoudi, Sussan; Shamshiri, Ahmad-Reza; Zahraei, Seyed Mohsen; Baxter, Louise; Shakerian, Sareh; Chaudhri, Irtaza; Fleming, Jessica A; Munier, Aline; Baradaran, Hamid R

2015-05-07

Although the mortality from diarrheal diseases has been decreasing dramatically in Iran, it still represents an important proportion of disease burden in children Rotavirus vaccines are among the most effective strategies against diarrheal diseases in specific epidemiological conditions. This study aimed to evaluate the cost-effectiveness of the introduction of rotavirus vaccine (3 doses of pentavalent RotaTeq (RV5)) in Iran, from the viewpoints of Iran's health system and society. The TRIVAC decision support model was used to calculate total incremental costs, life years (LYs) gained, and disability-adjusted life years (DALYs) averted due to the vaccination program. Necessary input data were collected from the most valid accessible sources as well as a systematic review and meta-analysis on epidemiological studies. We used WHO guidelines to estimate vaccination cost. An annual discount rate of 3% was considered for both health gain and costs. A deterministic sensitivity analysis was performed for testing the robustness of the models results. Our results indicated that total DALYs potentially lost due to rotavirus diarrhea within 10 years would be 138,161, of which 76,591 could be prevented by rotavirus vaccine. The total vaccination cost for 10 cohorts was estimated to be US$ 499.91 million. Also, US$ 470.61 million would be saved because of preventing outpatient visits and inpatient admissions (cost-saving from the society perspective). We estimated a cost per DALY averted of US$ 2868 for RV5 vaccination, which corresponds to a highly cost-effective strategy from the government perspective. In the sensitivity analysis, all scenarios tested were still cost-saving or highly cost-effective from the society perspective, except in the least favorable scenario and low vaccine efficacy and disease incidence scenario. Based on the findings, introduction of rotavirus vaccine is a highly cost-effective strategy from the government perspective. Introducing the vaccine to

An integer batch scheduling model considering learning, forgetting, and deterioration effects for a single machine to minimize total inventory holding cost

Science.gov (United States)

Yusriski, R.; Sukoyo; Samadhi, T. M. A. A.; Halim, A. H.

2018-03-01

This research deals with a single machine batch scheduling model considering the influenced of learning, forgetting, and machine deterioration effects. The objective of the model is to minimize total inventory holding cost, and the decision variables are the number of batches (N), batch sizes (Q[i], i = 1, 2, .., N) and the sequence of processing the resulting batches. The parts to be processed are received at the right time and the right quantities, and all completed parts must be delivered at a common due date. We propose a heuristic procedure based on the Lagrange method to solve the problem. The effectiveness of the procedure is evaluated by comparing the resulting solution to the optimal solution obtained from the enumeration procedure using the integer composition technique and shows that the average effectiveness is 94%.

Low-Cost 3D Printers Enable High-Quality and Automated Sample Preparation and Molecular Detection.

Directory of Open Access Journals (Sweden)

Kamfai Chan

Full Text Available Most molecular diagnostic assays require upfront sample preparation steps to isolate the target's nucleic acids, followed by its amplification and detection using various nucleic acid amplification techniques. Because molecular diagnostic methods are generally rather difficult to perform manually without highly trained users, automated and integrated systems are highly desirable but too costly for use at point-of-care or low-resource settings. Here, we showcase the development of a low-cost and rapid nucleic acid isolation and amplification platform by modifying entry-level 3D printers that cost between $400 and $750. Our modifications consisted of replacing the extruder with a tip-comb attachment that houses magnets to conduct magnetic particle-based nucleic acid extraction. We then programmed the 3D printer to conduct motions that can perform high-quality extraction protocols. Up to 12 samples can be processed simultaneously in under 13 minutes and the efficiency of nucleic acid isolation matches well against gold-standard spin-column-based extraction technology. Additionally, we used the 3D printer's heated bed to supply heat to perform water bath-based polymerase chain reactions (PCRs. Using another attachment to hold PCR tubes, the 3D printer was programmed to automate the process of shuttling PCR tubes between water baths. By eliminating the temperature ramping needed in most commercial thermal cyclers, the run time of a 35-cycle PCR protocol was shortened by 33%. This article demonstrates that for applications in resource-limited settings, expensive nucleic acid extraction devices and thermal cyclers that are used in many central laboratories can be potentially replaced by a device modified from inexpensive entry-level 3D printers.

Low-Cost 3D Printers Enable High-Quality and Automated Sample Preparation and Molecular Detection

Science.gov (United States)

Chan, Kamfai; Coen, Mauricio; Hardick, Justin; Gaydos, Charlotte A.; Wong, Kah-Yat; Smith, Clayton; Wilson, Scott A.; Vayugundla, Siva Praneeth; Wong, Season

2016-01-01

Most molecular diagnostic assays require upfront sample preparation steps to isolate the target’s nucleic acids, followed by its amplification and detection using various nucleic acid amplification techniques. Because molecular diagnostic methods are generally rather difficult to perform manually without highly trained users, automated and integrated systems are highly desirable but too costly for use at point-of-care or low-resource settings. Here, we showcase the development of a low-cost and rapid nucleic acid isolation and amplification platform by modifying entry-level 3D printers that cost between $400 and $750. Our modifications consisted of replacing the extruder with a tip-comb attachment that houses magnets to conduct magnetic particle-based nucleic acid extraction. We then programmed the 3D printer to conduct motions that can perform high-quality extraction protocols. Up to 12 samples can be processed simultaneously in under 13 minutes and the efficiency of nucleic acid isolation matches well against gold-standard spin-column-based extraction technology. Additionally, we used the 3D printer’s heated bed to supply heat to perform water bath-based polymerase chain reactions (PCRs). Using another attachment to hold PCR tubes, the 3D printer was programmed to automate the process of shuttling PCR tubes between water baths. By eliminating the temperature ramping needed in most commercial thermal cyclers, the run time of a 35-cycle PCR protocol was shortened by 33%. This article demonstrates that for applications in resource-limited settings, expensive nucleic acid extraction devices and thermal cyclers that are used in many central laboratories can be potentially replaced by a device modified from inexpensive entry-level 3D printers. PMID:27362424

[Cost effectiveness in treatment of acute myeloid leukemia].

Science.gov (United States)

Nordmann, P; Schaffner, A; Dazzi, H

2000-12-23

Although the rise in health costs is a widely debated issue, in Switzerland it was until recently taken for granted that patients are given the best available treatment regardless of cost. An example of a disease requiring costly treatment is acute myelogenous leukaemia (AML). To relate cost to benefit we calculated expenditure per life years gained. To assess costs we determined the real cost of treatment up to total remission, followed by consolidation or withdrawal of treatment or death. For survival time exceeding the 2-year observation period we used data from recent literature. The average cost of treatment ranges up to 107,592 Swiss francs (CHF). In 1997 we treated 23 leukaemia patients at Zurich University Hospital and gained a total of 210 life years. This represents an average cost of CHF 11,741 per life year gained. Chief cost items were therapy and personnel costs for nursing staff, followed by hotel business and personnel costs for doctors and diagnosis. Our results for AML treatment are far removed from the $61,500 ranging up to $166,000 discussed in the literature as the "critical" QALY (quality adjusted life years) value. This is the first time the actual costs of AML therapy have been shown for a Swiss cohort. Despite high initial treatment costs and success only in a limited number of patients, the expenditure per QALY is surprisingly low and shows clearly the effectiveness of apparently costly acute medicine.

Solving nucleic acid structures by molecular replacement: examples from group II intron studies

International Nuclear Information System (INIS)

Marcia, Marco; Humphris-Narayanan, Elisabeth; Keating, Kevin S.; Somarowthu, Srinivas; Rajashankar, Kanagalaghatta; Pyle, Anna Marie

2013-01-01

Strategies for phasing nucleic acid structures by molecular replacement, using both experimental and de novo designed models, are discussed. Structured RNA molecules are key players in ensuring cellular viability. It is now emerging that, like proteins, the functions of many nucleic acids are dictated by their tertiary folds. At the same time, the number of known crystal structures of nucleic acids is also increasing rapidly. In this context, molecular replacement will become an increasingly useful technique for phasing nucleic acid crystallographic data in the near future. Here, strategies to select, create and refine molecular-replacement search models for nucleic acids are discussed. Using examples taken primarily from research on group II introns, it is shown that nucleic acids are amenable to different and potentially more flexible and sophisticated molecular-replacement searches than proteins. These observations specifically aim to encourage future crystallographic studies on the newly discovered repertoire of noncoding transcripts

Primary vs Conversion Total Hip Arthroplasty: A Cost Analysis

Science.gov (United States)

Chin, Garwin; Wright, David J.; Snir, Nimrod; Schwarzkopf, Ran

2018-01-01

Introduction Increasing hip fracture incidence in the United States is leading to higher occurrences of conversion total hip arthroplasty (THA) for failed surgical treatment of the hip. In spite of studies showing higher complication rates in conversion THA, the Centers for Medicare and Medicaid services currently bundles conversion and primary THA under the same diagnosis-related group. We examined the cost of treatment of conversion THA compared with primary THA. Our hypothesis is that conversion THA will have higher cost and resource use than primary THA. Methods Fifty-one consecutive conversion THA patients (Current Procedure Terminology code 27132) and 105 matched primary THA patients (Current Procedure Terminology code 27130) were included in this study. The natural log-transformed costs for conversion and primary THA were compared using regression analysis. Age, gender, body mass index, American Society of Anesthesiologist, Charlson comorbidity score, and smoker status were controlled in the analysis. Conversion THA subgroups formed based on etiology were compared using analysis of variance analysis. Results Conversion and primary THAs were determined to be significantly different (P conversion THA has significantly greater cost and resource use than primary THA. In order to prevent disincentives for treating these complex surgical patients, reclassification of conversion THA is needed, as they do not fit together with primary THA. PMID:26387923

Effects of cost metric on cost-effectiveness of protected-area network design in urban landscapes.

Science.gov (United States)

Burkhalter, J C; Lockwood, J L; Maslo, B; Fenn, K H; Leu, K

2016-04-01

A common goal in conservation planning is to acquire areas that are critical to realizing biodiversity goals in the most cost-effective manner. The way monetary acquisition costs are represented in such planning is an understudied but vital component to realizing cost efficiencies. We sought to design a protected-area network within a forested urban region that would protect 17 birds of conservation concern. We compared the total costs and spatial structure of the optimal protected-area networks produced using three acquisition-cost surrogates (area, agricultural land value, and tax-assessed land value). Using the tax-assessed land values there was a 73% and 78% cost savings relative to networks derived using area or agricultural land value, respectively. This cost reduction was due to the considerable heterogeneity in acquisition costs revealed in tax-assessed land values, especially for small land parcels, and the corresponding ability of the optimization algorithm to identify lower-cost parcels for inclusion that had equal value to our target species. Tax-assessed land values also reflected the strong spatial differences in acquisition costs (US$0.33/m(2)-$55/m(2)) and thus allowed the algorithm to avoid inclusion of high-cost parcels when possible. Our results add to a nascent but growing literature that suggests conservation planners must consider the cost surrogate they use when designing protected-area networks. We suggest that choosing cost surrogates that capture spatial- and size-dependent heterogeneity in acquisition costs may be relevant to establishing protected areas in urbanizing ecosystems. © 2015 Society for Conservation Biology.

Polymerase chain reaction system using magnetic beads for analyzing a sample that includes nucleic acid

Science.gov (United States)

Nasarabadi, Shanavaz [Livermore, CA

2011-01-11

A polymerase chain reaction system for analyzing a sample containing nucleic acid includes providing magnetic beads; providing a flow channel having a polymerase chain reaction chamber, a pre polymerase chain reaction magnet position adjacent the polymerase chain reaction chamber, and a post pre polymerase magnet position adjacent the polymerase chain reaction chamber. The nucleic acid is bound to the magnetic beads. The magnetic beads with the nucleic acid flow to the pre polymerase chain reaction magnet position in the flow channel. The magnetic beads and the nucleic acid are washed with ethanol. The nucleic acid in the polymerase chain reaction chamber is amplified. The magnetic beads and the nucleic acid are separated into a waste stream containing the magnetic beads and a post polymerase chain reaction mix containing the nucleic acid. The reaction mix containing the nucleic acid flows to an analysis unit in the channel for analysis.

Mapping photothermally induced gene expression in living cells and tissues by nanorod-locked nucleic acid complexes.

Science.gov (United States)

Riahi, Reza; Wang, Shue; Long, Min; Li, Na; Chiou, Pei-Yu; Zhang, Donna D; Wong, Pak Kin

2014-04-22

The photothermal effect of plasmonic nanostructures has numerous applications, such as cancer therapy, photonic gene circuit, large cargo delivery, and nanostructure-enhanced laser tweezers. The photothermal operation can also induce unwanted physical and biochemical effects, which potentially alter the cell behaviors. However, there is a lack of techniques for characterizing the dynamic cell responses near the site of photothermal operation with high spatiotemporal resolution. In this work, we show that the incorporation of locked nucleic acid probes with gold nanorods allows photothermal manipulation and real-time monitoring of gene expression near the area of irradiation in living cells and animal tissues. The multimodal gold nanorod serves as an endocytic delivery reagent to transport the probes into the cells, a fluorescence quencher and a binding competitor to detect intracellular mRNA, and a plasmonic photothermal transducer to induce cell ablation. We demonstrate the ability of the gold nanorod-locked nucleic acid complex for detecting the spatiotemporal gene expression in viable cells and tissues and inducing photothermal ablation of single cells. Using the gold nanorod-locked nucleic acid complex, we systematically characterize the dynamic cellular heat shock responses near the site of photothermal operation. The gold nanorod-locked nucleic acid complex enables mapping of intracellular gene expressions and analyzes the photothermal effects of nanostructures toward various biomedical applications.

Nucleic acid metabolism in hemopoietic tissues of polycythemic rats during long-term fractionated irradiation

International Nuclear Information System (INIS)

Mushkacheva, G.S.; Murzina, L.D.

1980-01-01

A study was made of the effect of long-term fractionated exposure with a daily dose of 50 R on the nucleic acid metabolism in hemopoietic tissues (bone marrow and spleen) of rats with erythropoiesis selectively inhibited by posttransfusion polycythemia. The comparison of present and previously obtained results enables us to conclude that the pathways of changes in the nucleic acid metabolism, which is responsible for hemopoiesis compensation during long-term exposure, are, in the main, similar for both white and red compartments of hemopoiesis

Novel (Phenylethynyl)pyrene-LNA Constructs for Fluorescence SNP Sensing in Polymorphic Nucleic Acid Targets

DEFF Research Database (Denmark)

Astakhova, Irina Kira; Samokhina, Evgeniya; Babu, B Ravindra

2012-01-01

We describe fluorescent oligonucleotide probes labeled with novel (phenylethynyl)pyrene dyes attached to locked nucleic acids. Furthermore, we prove the utility of these probes for the effective detection of single-nucleotide polymorphisms in natural nucleic acids. High-affinity hybridization......DNA and RNA gene fragments. Target sequences were obtained by analysis of 200 clinical samples from patients currently receiving anti-HIV/AIDS combination therapy at the Russian Federal AIDS Center. Using these fluorescent oligonucleotides, we were able to detect the target mutation despite all the challenges...

Cost of post-operative intravenous iron therapy in total lower limb arthroplasty: a retrospective, matched cohort study

Science.gov (United States)

Muñoz, Manuel; Gómez-Ramírez, Susana; Martín-Montañez, Elisa; Naveira, Enrique; Seara, Javier; Pavía, José

2014-01-01

Background Requirements for allogeneic red cell transfusion after total lower limb arthroplasty are still high (20–50%), and post-operative intravenous iron has been shown to reduce transfusion requirements for this surgery. We performed a cost analysis to ascertain whether this alternative is also likely to be cost-effective. Materials and methods Data from 182 matched-pairs of total lower limb arthroplasty patients, managed with a restrictive transfusion protocol and without (control group) or with post-operative intravenous iron (iron group), were retrospectively reviewed. Acquisition and administration costs of iron (iron sucrose or ferric carboxymaltose) and allogeneic red cell concentrates, haemoglobin measurements, and prolonged stay in hospital were used for blood management cost analysis. Results Patients in the iron group received 600 mg intravenous iron, without clinically relevant incidents, and had a lower allogeneic transfusion rate (11.5% vs 26.4% for the iron and control groups, respectively; p=0.001). The reduction in transfusion rate was more pronounced in anaemic patients (17% vs 40%; p=0.015) than in non-anaemic ones (9.6% vs 21.2%; p=0.011). There were no differences with respect to post-operative infection rate. Patients receiving allogeneic transfusion stayed in hospital longer (+1.9 days [95% CI: 1.2–2.6]). As intravenous iron reduces the allogeneic transfusion rate, both iron formulations were cost-neutral in the different cost scenarios (−25.5 to 62.1 €/patient for iron sucrose, and −51.1 to 64.4 €/patient for ferric carboxymaltose). Discussion In patients presenting with or without pre-operative anaemia, post-operative intravenous iron after total lower limb arthroplasty seems to be safe and is associated with reduced transfusion rates, without incremental costs. For anaemic patients, its efficacy could be increased by associating some other blood-saving method. PMID:24120595

Study Of The Fuel Cycle Effect To The Electricity Generating Cost

International Nuclear Information System (INIS)

Salimy, D. H.

1998-01-01

The nuclear fuel cycle cost contributes relatively small fraction to the total nuclear power generation cost, I.e. about 15 to 30%, compared to the fuel cost in the coal-generated electricity (40-60%). Or in the oil-generated electricity (70-80%). This situation will give effect that the future generation cost is much less sensitive to the changes in the fuel prince than in the case of fossil fuel power plants. The study has shown that by assuming a 100% increase in the natural uranium price, the total nuclear fuel cycle cost would increase only by about 27% and in turn it contributes about 29% increase to the total nuclear fuel cycle cost. As a result, it contributes only 4 to 8% increase in the nuclear energy generation cost. As a comparison, if the same situation should occur to fossil fuel plants, the assumed fuel price increase would have increased the electricity generating cost by about 40-65% for coal-fired plants, and about 70-85% for oil-fired plants. This study also has assesses the economic aspects of the electricity generating cots for nuclear power plant (NPP) and the coal power plant. For an NPP the most affecting factor is the investment cost, while for the coal power plant, the major factor influencing the total cost is the price/cost of the fuel

Gene Targeting and Expression Modulation by Peptide Nucleic Acids (PNA)

DEFF Research Database (Denmark)

Nielsen, Peter E

2010-01-01

Peptide nucleic acids (PNA) are artificial structural mimics of nucleic acids capable of sequence specific hybridization to both RNA and DNA. Thus they have obvious potential as gene targeting agents for drug discovery approaches. An overview with emphasis on recent progress on RNA "interference...

Field Effect Sensors for Nucleic Acid Detection: Recent Advances and Future Perspectives

Directory of Open Access Journals (Sweden)

Bruno Veigas

2015-05-01

Full Text Available In the last decade the use of field-effect-based devices has become a basic structural element in a new generation of biosensors that allow label-free DNA analysis. In particular, ion sensitive field effect transistors (FET are the basis for the development of radical new approaches for the specific detection and characterization of DNA due to FETs’ greater signal-to-noise ratio, fast measurement capabilities, and possibility to be included in portable instrumentation. Reliable molecular characterization of DNA and/or RNA is vital for disease diagnostics and to follow up alterations in gene expression profiles. FET biosensors may become a relevant tool for molecular diagnostics and at point-of-care. The development of these devices and strategies should be carefully designed, as biomolecular recognition and detection events must occur within the Debye length. This limitation is sometimes considered to be fundamental for FET devices and considerable efforts have been made to develop better architectures. Herein we review the use of field effect sensors for nucleic acid detection strategies—from production and functionalization to integration in molecular diagnostics platforms, with special focus on those that have made their way into the diagnostics lab.

Costs and cost effectiveness of different strategies for chlamydia screening and partner notification: an economic and mathematical modelling study.

Science.gov (United States)

Turner, Katy; Adams, Elisabeth; Grant, Arabella; Macleod, John; Bell, Gill; Clarke, Jan; Horner, Paddy

2011-01-04

To compare the cost, cost effectiveness, and sex equity of different intervention strategies within the English National Chlamydia Screening Programme. To develop a tool for calculating cost effectiveness of chlamydia control programmes at a local, national, or international level. An economic and mathematical modelling study with cost effectiveness analysis. Costs were restricted to those of screening and partner notification from the perspective of the NHS and excluded patient costs, the costs of reinfection, and costs of complications arising from initial infection. England. Population Individuals eligible for the National Chlamydia Screening Programme. Cost effectiveness of National Chlamydia Screening Programme in 2008-9 (as cost per individual tested, cost per positive diagnosis, total cost of screening, number screened, number infected, sex ratio of those tested and treated). Comparison of baseline programme with two different interventions-(i) increased coverage of primary screening in men and (ii) increased efficacy of partner notification. In 2008-9 screening was estimated to cost about £46.3m in total and £506 per infection treated. Provision for partner notification within the screening programme cost between £9 and £27 per index case, excluding treatment and testing. The model results suggest that increasing male screening coverage from 8% (baseline value) to 24% (to match female coverage) would cost an extra £22.9m and increase the cost per infection treated to £528. In contrast, increasing partner notification efficacy from 0.4 (baseline value) to 0.8 partners per index case would cost an extra £3.3m and would reduce the cost per infection diagnosed to £449. Increasing screening coverage to 24% in men would cost over six times as much as increasing partner notification to 0.8 but only treat twice as many additional infections. In the English National Chlamydia Screening Programme increasing the effectiveness of partner notification is likely

PET in tumor imaging: research only or a cost effective clinical tool?

International Nuclear Information System (INIS)

Wahl, R.L.

1997-01-01

PET imaging has for many years been a versatile tool for non-invasive imaging of neuro-physiology and, indeed, whole body physiology. Quantitative PET imaging of trace amounts of radioactivity is scientifically elegant and can be very complex. This lecture focuses on whether and where this test is clinically useful. Because of the research tradition, PET imaging has been perceived as an 'expensive' test, as it costs more per scan than CT and MRI scans at most institutions. Such a superficial analysis is incorrect, however, as it is increasingly recognized that imaging costs, which in some circumstances will be increased by the use of PET, are only a relatively small component of patient care costs. Thus, PET may raise imaging costs and the number of imaging procedures in some settings, though PET may reduce imaging test numbers in other settings. However, the analysis must focus on the total costs of patient management. Analyses focused on total patient care costs, including cost of hospitalization and cost surgery as well as imaging costs, have shown that PET can substantially reduce total patient care costs in several settings. This is achieved by providing a more accurate diagnosis, and thus having fewer instances of an incorrect diagnosis resulting in subsequent inappropriate surgery or investigations. Several institutions have shown scenarios in which PET for tumor imaging is cost effective. While the specific results of the analyses vary based on disease prevalence and cost input values for each procedure, as well as the projected performance of PET, the similar results showing total care cost savings in the management of several common cancers, strongly supports the rational for the use of PET in cancer management. In addition, promising clinical results are forthcoming in several other illnesses, suggesting PET will have broader utility than these uses, alone. Thus, while PET is an 'expensive' imaging procedure and has considerable utility as a research

Histogram analysis parameters of dynamic contrast-enhanced magnetic resonance imaging can predict histopathological findings including proliferation potential, cellularity, and nucleic areas in head and neck squamous cell carcinoma.

Science.gov (United States)

Surov, Alexey; Meyer, Hans Jonas; Leifels, Leonard; Höhn, Anne-Kathrin; Richter, Cindy; Winter, Karsten

2018-04-20

Our purpose was to analyze possible associations between histogram analysis parameters of dynamic contrast-enhanced magnetic resonance imaging DCE MRI and histopathological findings like proliferation index, cell count and nucleic areas in head and neck squamous cell carcinoma (HNSCC). 30 patients (mean age 57.0 years) with primary HNSCC were included in the study. In every case, histogram analysis parameters of K trans , V e , and K ep were estimated using a mathlab based software. Tumor proliferation index, cell count, and nucleic areas were estimated on Ki 67 antigen stained specimens. Spearman's non-parametric rank sum correlation coefficients were calculated between DCE and different histopathological parameters. KI 67 correlated with K trans min ( p = -0.386, P = 0.043) and s K trans skewness ( p = 0.382, P = 0.045), V e min ( p = -0.473, P = 0.011), Ve entropy ( p = 0.424, P = 0.025), and K ep entropy ( p = 0.464, P = 0.013). Cell count correlated with K trans kurtosis ( p = 0.40, P = 0.034), V e entropy ( p = 0.475, P = 0.011). Total nucleic area correlated with V e max ( p = 0.386, P = 0.042) and V e entropy ( p = 0.411, P = 0.030). In G1/2 tumors, only K trans entropy correlated well with total ( P =0.78, P =0.013) and average nucleic areas ( p = 0.655, P = 0.006). In G3 tumors, KI 67 correlated with Ve min ( p = -0.552, P = 0.022) and V e entropy ( p = 0.524, P = 0.031). Ve max correlated with total nucleic area ( p = 0.483, P = 0.049). Kep max correlated with total area ( p = -0.51, P = 0.037), and K ep entropy with KI 67 ( p = 0.567, P = 0.018). We concluded that histogram-based parameters skewness, kurtosis and entropy of K trans , V e , and K ep can be used as markers for proliferation activity, cellularity and nucleic content in HNSCC. Tumor grading influences significantly associations between perfusion and histopathological parameters.

Epidural analgesia during labour, routinely or on request: a cost-effectiveness analysis.

Science.gov (United States)

Bonouvrié, Kimberley; van den Bosch, Anouk; Roumen, Frans J M E; van Kuijk, Sander M; Nijhuis, Jan G; Evers, Silvia M A A; Wassen, Martine M L H

2016-12-01

To assess the cost-effectiveness of routine labour epidural analgesia (EA), from a societal perspective, as compared with labour analgesia on request. Women delivering of a singleton in cephalic presentation beyond 36+0 weeks' gestation were randomly allocated to routine labour EA or analgesia on request in one university and one non-university teaching hospital in the Netherlands. Costs included all medical, non-medical and indirect costs from randomisation to 6 weeks postpartum. Effectiveness was defined as a non-operative, spontaneous vaginal delivery without EA-related maternal adverse effects. Incremental cost-effectiveness ratio (ICER) was defined as the ratio of the difference in costs and the difference in effectiveness between both groups. Data were analysed according to intention to treat and divided into a base case analysis and a sensitivity analysis. Total delivery costs in the routine EA group (n=233) were higher than in the labour on request group (n=255) (difference -€ 322, 95% CI -€ 60 to € 355) due to more medication costs (including EA), a longer stay in the labour ward, and more operations including caesarean sections. Total postpartum hospital costs in the routine EA group were lower (difference -€ 344, 95% CI -€ 1338 to € 621) mainly due to less neonatal admissions (difference -€ 472, 95% CI -€ 1297 to € 331), whereas total postpartum home and others costs were comparable (difference -€ 20, 95% CI -€ 267 to € 248, and -€ 1, 95% CI -€ 67 to € 284, respectively). As a result, the overall mean costs per woman were comparable between the routine EA group and the analgesia on request group (€ 8.708 and € 8.710, respectively, mean difference -€ 2, 95% CI -€ 1.012 to € 916). Routine labour EA resulted in more deliveries with maternal adverse effects, nevertheless the ICER remained low (€ 8; bootstrap 95% CI -€ 6.120 to € 8.659). The cost-effectiveness acceptability curve indicated a low probability that

Nucleic acids for the rational design of reaction circuits.

Science.gov (United States)

Padirac, Adrien; Fujii, Teruo; Rondelez, Yannick

2013-08-01

Nucleic acid-based circuits are rationally designed in vitro assemblies that can perform complex preencoded programs. They can be used to mimic in silico computations. Recent works emphasized the modularity and robustness of these circuits, which allow their scaling-up. Another new development has led to dynamic, time-responsive systems that can display emergent behaviors like oscillations. These are closely related to biological architectures and provide an in vitro model of in vivo information processing. Nucleic acid circuits have already been used to handle various processes for technological or biotechnological purposes. Future applications of these chemical smart systems will benefit from the rapidly growing ability to design, construct, and model nucleic acid circuits of increasing size. Copyright © 2012 Elsevier Ltd. All rights reserved.

Time-driven activity based costing of total knee replacement surgery at a London teaching hospital.

Science.gov (United States)

Chen, Alvin; Sabharwal, Sanjeeve; Akhtar, Kashif; Makaram, Navnit; Gupte, Chinmay M

2015-12-01

The aim of this study was to conduct a time-driven activity based costing (TDABC) analysis of the clinical pathway for total knee replacement (TKR) and to determine where the major cost drivers lay. The in-patient pathway was prospectively mapped utilising a TDABC model, following 20 TKRs. The mean age for these patients was 73.4 years. All patients were ASA grade I or II and their mean BMI was 30.4. The 14 varus knees had a mean deformity of 5.32° and the six valgus knee had a mean deformity of 10.83°. Timings were prospectively collected as each patient was followed through the TKR pathway. Pre-operative costs including pre-assessment and joint school were £ 163. Total staff costs for admission and the operating theatre were £ 658. Consumables cost for the operating theatre were £ 1862. The average length of stay was 5.25 days at a total cost of £ 910. Trust overheads contributed £ 1651. The overall institutional cost of a 'noncomplex' TKR in patients without substantial medical co-morbidities was estimated to be £ 5422, representing a profit of £ 1065 based on a best practice tariff of £ 6487. The major cost drivers in the TKR pathway were determined to be theatre consumables, corporate overheads, overall ward cost and operating theatre staffing costs. Appropriate discounting of implant costs, reduction in length of stay by adopting an enhanced recovery programme and control of corporate overheads through the use of elective orthopaedic treatment centres are proposed approaches for reducing the overall cost of treatment. Copyright © 2015 Elsevier B.V. All rights reserved.

12 CFR Appendix K to Part 226 - Total Annual Loan Cost Rate Computations for Reverse Mortgage Transactions

Science.gov (United States)

2010-01-01

... Appendix K to Part 226—Total Annual Loan Cost Rate Computations for Reverse Mortgage Transactions (a... loan cost rate for various transactions, as well as instructions, explanations, and examples for.... (2) Term of the transaction. For purposes of total annual loan cost disclosures, the term of a...

THE VARIATION OF NUCLEIC ACIDS CONTENT AFTER SIMAZIN TREATMENT ON VICIA SATIVA L.

Directory of Open Access Journals (Sweden)

Odeta Grama-Tiganasu

2005-08-01

Full Text Available Simazin has in certain conditions stimulatory effects on nucleic acids biosynthese. The biosyntese and mitotic division stimulation sugest the possibility to use simazin like growing and germination stimulator.

Preliminary estimates of the total-system cost for the restructured program: An addendum to the May 1989 analysis of the total-system life cycle cost for the Civilian Radioactive Waste Management Program

International Nuclear Information System (INIS)

1990-12-01

The total-system life-cycle cost (TSLCC) analysis for the Department of Energy's (DOE) Civilian Radioactive Waste Management Program is an ongoing activity that helps determine whether the revenue-producing mechanism established by the Nuclear Waste Policy Act of 1982 - a fee levied on electricity generated and sold by commercial nuclear power plants - is sufficient to cover the cost of the program. This report provides cost estimates for the sixth annual evaluation of the adequacy of the fee. The costs contained in this report represent a preliminary analysis of the cost impacts associated with the Secretary of Energy's Report to Congress on Reassessment of the Civilian Radioactive Waste Management Program issued in November 1989. The major elements of the restructured program announced in this report which pertain to the program's life-cycle costs are: a prioritization of the scientific investigations program at the Yucca Mountain candidate site to focus on identification of potentially adverse conditions, a delay in the start of repository operations until 2010, the start of limited waste acceptance at the monitored retrievable storage (MRS) facility in 1998, and the start of waste acceptance at the full-capability MRS facility in 2,000. Based on the restructured program, the total-system cost for the system with a repository at the candidate site at Yucca Mountain in Nevada, a facility for monitored retrievable storage (MRS), and a transportation system is estimated at $26 billion (expressed in constant 1988 dollars). In the event that a second repository is required and is authorized by the Congress, the total-system cost is estimated at $34 to $35 billion, depending on the quantity of spent fuel and high-level waste (HLW) requiring disposal. 17 figs., 17 tabs

BGL6 beta-glucosidase and nucleic acids encoding the same

Science.gov (United States)

Dunn-Coleman, Nigel [Los Gatos, CA; Ward, Michael [San Francisco, CA

2009-09-01

The present invention provides a novel .beta.-glucosidase nucleic acid sequence, designated bgl6, and the corresponding BGL6 amino acid sequence. The invention also provides expression vectors and host cells comprising a nucleic acid sequence encoding BGL6, recombinant BGL6 proteins and methods for producing the same.

Calcium ions effectively enhance the effect of antisense peptide nucleic acids conjugated to cationic tat and oligoarginine peptides

DEFF Research Database (Denmark)

Shiraishi, Takehiko; Pankratova, Stanislava; Nielsen, Peter E

2005-01-01

Cell-penetrating peptides have been widely used to improve cellular delivery of a variety of proteins and antisense agents. However, recent studies indicate that such cationic peptides are predominantly entering cells via an endosomal pathway. We now show that the nuclear antisense effect in He......La cells of a variety of peptide nucleic acid (PNA) peptide conjugates is significantly enhanced by addition of 6 mM Ca(2+) (as well as by the lysosomotrophic agent chloroquine). In particular, the antisense activities of Tat(48-60) and heptaarginine-conjugated PNAs were increased 44-fold and 8.5-fold......, respectively. Evidence is presented that the mechanism involves endosomal release. The present results show that Ca(2+) can be used as an effective enhancer for in vitro cellular delivery of cationic peptide-conjugated PNA oligomers, and also emphasize the significance of the endosomal escape route...

Total inpatient treatment costs in patients with severe burns: towards a more accurate reimbursement model.

Science.gov (United States)

Mehra, Tarun; Koljonen, Virve; Seifert, Burkhardt; Volbracht, Jörk; Giovanoli, Pietro; Plock, Jan; Moos, Rudolf Maria

2015-01-01

Reimbursement systems have difficulties depicting the actual cost of burn treatment, leaving care providers with a significant financial burden. Our aim was to establish a simple and accurate reimbursement model compatible with prospective payment systems. A total of 370 966 electronic medical records of patients discharged in 2012 to 2013 from Swiss university hospitals were reviewed. A total of 828 cases of burns including 109 cases of severe burns were retained. Costs, revenues and earnings for severe and nonsevere burns were analysed and a linear regression model predicting total inpatient treatment costs was established. The median total costs per case for severe burns was tenfold higher than for nonsevere burns (179 949 CHF [167 353 EUR] vs 11 312 CHF [10 520 EUR], interquartile ranges 96 782-328 618 CHF vs 4 874-27 783 CHF, p <0.001). The median of earnings per case for nonsevere burns was 588 CHF (547 EUR) (interquartile range -6 720 - 5 354 CHF) whereas severe burns incurred a large financial loss to care providers, with median earnings of -33 178 CHF (30 856 EUR) (interquartile range -95 533 - 23 662 CHF). Differences were highly significant (p <0.001). Our linear regression model predicting total costs per case with length of stay (LOS) as independent variable had an adjusted R2 of 0.67 (p <0.001 for LOS). Severe burns are systematically underfunded within the Swiss reimbursement system. Flat-rate DRG-based refunds poorly reflect the actual treatment costs. In conclusion, we suggest a reimbursement model based on a per diem rate for treatment of severe burns.

The effects of utility DSM programs on electricity costs and prices

Energy Technology Data Exchange (ETDEWEB)

Hirst, E.

1991-11-01

More and more US utilities are running more and larger demand-side management (DSM) programs. Assessing the cost-effectiveness of these programs raises difficult questions for utilities and their regulators. Should these programs aim to minimize the total cost of providing electric-energy services or should they minimize the price of electricity? This study offers quantitative estimates on the tradeoffs between total costs and electricity prices. This study uses a dynamic model to assess the effects of energy-efficiency programs on utility revenues, total resource costs, electricity prices, and electricity consumption for the period 1990 to 2010. These DSM programs are assessed under alternative scenarios. In these cases, fossil-fuel prices, load growth, the amount of excess capacity the utility has in 1990, planned retirements of power plants, the financial treatment of DSM programs, and the costs of energy- efficient programs vary. These analyses are conducted for three utilities: a ``base`` that is typical of US utilities; a ``surplus`` utility that has excess capacity, few planned retirements, and slow growth in fossil-fuel prices and incomes; and a ``deficit`` utility that has little excess capacity, many planned retirements, and rapid growth in fossil-fuel prices and incomes. 28 refs.

Nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs.

Science.gov (United States)

Huang, Wei; Chen, Liqing; Kang, Lin; Jin, Mingji; Sun, Ping; Xin, Xin; Gao, Zhonggao; Bae, You Han

2017-06-01

Anticancer therapy has always been a vital challenge for the development of nanomedicine. Repeated single therapeutic agent may lead to undesirable and severe side effects, unbearable toxicity and multidrug resistance due to complex nature of tumor. Nanomedicine-based combination anticancer therapy can synergistically improve antitumor outcomes through multiple-target therapy, decreasing the dose of each therapeutic agent and reducing side effects. There are versatile combinational anticancer strategies such as chemotherapeutic combination, nucleic acid-based co-delivery, intrinsic sensitive and extrinsic stimulus combinational patterns. Based on these combination strategies, various nanocarriers and drug delivery systems were engineered to carry out the efficient co-delivery of combined therapeutic agents for combination anticancer therapy. This review focused on illustrating nanomedicine-based combination anticancer therapy between nucleic acids and small-molecular drugs for synergistically improving anticancer efficacy. Copyright © 2017 Elsevier B.V. All rights reserved.

Costs and cost-effectiveness of training traditional birth attendants to reduce neonatal mortality in the Lufwanyama Neonatal Survival study (LUNESP).

Science.gov (United States)

Sabin, Lora L; Knapp, Anna B; MacLeod, William B; Phiri-Mazala, Grace; Kasimba, Joshua; Hamer, Davidson H; Gill, Christopher J

2012-01-01

The Lufwanyama Neonatal Survival Project ("LUNESP") was a cluster randomized, controlled trial that showed that training traditional birth attendants (TBAs) to perform interventions targeting birth asphyxia, hypothermia, and neonatal sepsis reduced all-cause neonatal mortality by 45%. This companion analysis was undertaken to analyze intervention costs and cost-effectiveness, and factors that might improve cost-effectiveness. We calculated LUNESP's financial and economic costs and the economic cost of implementation for a forecasted ten-year program (2011-2020). In each case, we calculated the incremental cost per death avoided and disability-adjusted life years (DALYs) averted in real 2011 US dollars. The forecasted 10-year program analysis included a base case as well as 'conservative' and 'optimistic' scenarios. Uncertainty was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. The estimated financial and economic costs of LUNESP were $118,574 and $127,756, respectively, or $49,469 and $53,550 per year. Fixed costs accounted for nearly 90% of total costs. For the 10-year program, discounted total and annual program costs were $256,455 and $26,834 respectively; for the base case, optimistic, and conservative scenarios, the estimated cost per death avoided was $1,866, $591, and $3,024, and cost per DALY averted was $74, $24, and $120, respectively. Outcomes were robust to variations in local costs, but sensitive to variations in intervention effect size, number of births attended by TBAs, and the extent of foreign consultants' participation. Based on established guidelines, the strategy of using trained TBAs to reduce neonatal mortality was 'highly cost effective'. We strongly recommend consideration of this approach for other remote rural populations with limited access to health care.

Management of End-Stage Ankle Arthritis: Cost-Utility Analysis Using Direct and Indirect Costs.

Science.gov (United States)

Nwachukwu, Benedict U; McLawhorn, Alexander S; Simon, Matthew S; Hamid, Kamran S; Demetracopoulos, Constantine A; Deland, Jonathan T; Ellis, Scott J

2015-07-15

Total ankle replacement and ankle fusion are costly but clinically effective treatments for ankle arthritis. Prior cost-effectiveness analyses for the management of ankle arthritis have been limited by a lack of consideration of indirect costs and nonoperative management. The purpose of this study was to compare the cost-effectiveness of operative and nonoperative treatments for ankle arthritis with inclusion of direct and indirect costs in the analysis. Markov model analysis was conducted from a health-systems perspective with use of direct costs and from a societal perspective with use of direct and indirect costs. Costs were derived from the 2012 Nationwide Inpatient Sample (NIS) and expressed in 2013 U.S. dollars; effectiveness was expressed in quality-adjusted life years (QALYs). Model transition probabilities were derived from the available literature. The principal outcome measure was the incremental cost-effectiveness ratio (ICER). In the direct-cost analysis for the base case, total ankle replacement was associated with an ICER of $14,500/QALY compared with nonoperative management. When indirect costs were included, total ankle replacement was both more effective and resulted in $5900 and $800 in lifetime cost savings compared with the lifetime costs following nonoperative management and ankle fusion, respectively. At a $100,000/QALY threshold, surgical management of ankle arthritis was preferred for patients younger than ninety-six years and total ankle replacement was increasingly more cost-effective in younger patients. Total ankle replacement, ankle fusion, and nonoperative management were the preferred strategy in 83%, 12%, and 5% of the analyses, respectively; however, our model was sensitive to patient age, the direct costs of total ankle replacement, the failure rate of total ankle replacement, and the probability of arthritis after ankle fusion. Compared with nonoperative treatment for the management of end-stage ankle arthritis, total ankle

Hepatitis B virus X protein (HBx)-induced abnormalities of nucleic acid metabolism revealed by (1)H-NMR-based metabonomics.

Science.gov (United States)

Dan Yue; Zhang, Yuwei; Cheng, Liuliu; Ma, Jinhu; Xi, Yufeng; Yang, Liping; Su, Chao; Shao, Bin; Huang, Anliang; Xiang, Rong; Cheng, Ping

2016-04-14

Hepatitis B virus X protein (HBx) plays an important role in HBV-related hepatocarcinogenesis; however, mechanisms underlying HBx-mediated carcinogenesis remain unclear. In this study, an NMR-based metabolomics approach was applied to systematically investigate the effects of HBx on cell metabolism. EdU incorporation assay was conducted to examine the effects of HBx on DNA synthesis, an important feature of nucleic acid metabolism. The results revealed that HBx disrupted metabolism of glucose, lipids, and amino acids, especially nucleic acids. To understand the potential mechanism of HBx-induced abnormalities of nucleic acid metabolism, gene expression profiles of HepG2 cells expressing HBx were investigated. The results showed that 29 genes involved in DNA damage and DNA repair were differentially expressed in HBx-expressing HepG2 cells. HBx-induced DNA damage was further demonstrated by karyotyping, comet assay, Western blotting, immunofluorescence and immunohistochemistry analyses. Many studies have previously reported that DNA damage can induce abnormalities of nucleic acid metabolism. Thus, our results implied that HBx initially induces DNA damage, and then disrupts nucleic acid metabolism, which in turn blocks DNA repair and induces the occurrence of hepatocellular carcinoma (HCC). These findings further contribute to our understanding of the occurrence of HCC.

Label-free direct surface-enhanced Raman scattering (SERS) of nucleic acids (Conference Presentation)

Science.gov (United States)

Guerrini, Luca; Morla-Folch, Judit; Gisbert-Quilis, Patricia; Xie, Hainan; Alvarez-Puebla, Ramon

2016-03-01

Recently, plasmonic-based biosensing has experienced an unprecedented level of attention, with a particular focus on the nucleic acid detection, offering efficient solutions to engineer simple, fast, highly sensitive sensing platforms while overcoming important limitations of PCR and microarray techniques. In the broad field of plasmonics, surface-enhanced Raman scattering (SERS) spectroscopy has arisen as a powerful analytical tool for detection and structural characterization of biomolecules. Today applications of SERS to nucleic acid analysis largely rely on indirect strategies, which have been demonstrated very effective for pure sensing purposes but completely dismiss the exquisite structural information provided by the direct acquisition of the biomolecular vibrational fingerprint. Contrarily, direct label-free SERS of nucleic acid shows an outstanding potential in terms of chemical-specific information which, however, remained largely unexpressed mainly because of the inherent poor spectral reproducibility and/or limited sensitivity. To address these limitations, we developed a fast and affordable high-throughput screening direct SERS method for gaining detailed genomic information on nucleic acids (DNA and RNA) and for the characterization and quantitative recognition of DNA interactions with exogenous agents. The simple strategy relies on the electrostatic adhesion of DNA/RNA onto positively-charged silver colloids that promotes the nanoparticle aggregation into stable clusters yielding intense and reproducible SERS spectra at picogram level (i.e. the analysis can be performed without the necessity of amplification steps thus providing realistic direct information of the nucleic acid in its native state). We anticipate this method to gain a vast impact and set of applications in different fields, including medical diagnostics, genomic screening, drug discovery, forensic science and even molecular electronics.

Consumer-Operated Service Programs: monetary and donated costs and cost-effectiveness.

Science.gov (United States)

Yates, Brian T; Mannix, Danyelle; Freed, Michael C; Campbell, Jean; Johnsen, Matthew; Jones, Kristine; Blyler, Crystal R

2011-01-01

Examine cost differences between Consumer Operated Service Programs (COSPs) as possibly determined by a) size of program, b) use of volunteers and other donated resources, c) cost-of-living differences between program locales, d) COSP model applied, and e) delivery system used to implement the COSP model. As part of a larger evaluation of COSP, data on operating costs, enrollments, and mobilization of donated resources were collected for eight programs representing three COSP models (drop-in centers, mutual support, and education/advocacy training). Because the 8 programs were operated in geographically diverse areas of the US, costs were examined with and without adjustment for differences in local cost of living. Because some COSPs use volunteers and other donated resources, costs were measured with and without these resources being monetized. Scale of operation also was considered as a mediating variable for differences in program costs. Cost per visit, cost per consumer per quarter, and total program cost were calculated separately for funds spent and for resources donated for each COSP. Differences between COSPs in cost per consumer and cost per visit seem better explained by economies of scale and delivery system used than by cost-of-living differences between program locations or COSP model. Given others' findings that different COSP models produce little variation in service effectiveness, minimize service costs by maximizing scale of operation while using a delivery system that allows staff and facilities resources to be increased or decreased quickly to match number of consumers seeking services.

Cost-effectiveness of heat and moisture exchangers compared to usual care for pulmonary rehabilitation after total laryngectomy in Poland

NARCIS (Netherlands)

Retèl, Valesca P.; van den Boer, Cindy; Steuten, Lotte M. G.; Okła, Sławomir; Hilgers, Frans J.; van den Brekel, Michiel W.

2015-01-01

The beneficial physical and psychosocial effects of heat and moisture exchangers (HMEs) for pulmonary rehabilitation of laryngectomy patients are well evidenced. However, cost-effectiveness in terms of costs per additional quality-adjusted life years (QALYs) has not yet been investigated. Therefore,

Associations between preoperative physical therapy and post-acute care utilization patterns and cost in total joint replacement.

Science.gov (United States)

Snow, Richard; Granata, Jaymes; Ruhil, Anirudh V S; Vogel, Karen; McShane, Michael; Wasielewski, Ray

2014-10-01

Health-care costs following acute hospital care have been identified as a major contributor to regional variation in Medicare spending. This study investigated the associations of preoperative physical therapy and post-acute care resource use and its effect on the total cost of care during primary hip or knee arthroplasty. Historical claims data were analyzed using the Centers for Medicare & Medicaid Services Limited Data Set files for Diagnosis Related Group 470. Analysis included descriptive statistics of patient demographic characteristics, comorbidities, procedures, and post-acute care utilization patterns, which included skilled nursing facility, home health agency, or inpatient rehabilitation facility, during the ninety-day period after a surgical hospitalization. To evaluate the associations, we used bivariate and multivariate techniques focused on post-acute care use and total episode-of-care costs. The Limited Data Set provided 4733 index hip or knee replacement cases for analysis within the thirty-nine-county Medicare hospital referral cluster. Post-acute care utilization was a significant variable in the total cost of care for the ninety-day episode. Overall, 77.0% of patients used post-acute care services after surgery. Post-acute care utilization decreased if preoperative physical therapy was used, with only 54.2% of the preoperative physical therapy cohort using post-acute care services. However, 79.7% of the non-preoperative physical therapy cohort used post-acute care services. After adjusting for demographic characteristics and comorbidities, the use of preoperative physical therapy was associated with a significant 29% reduction in post-acute care use, including an $871 reduction of episode payment driven largely by a reduction in payments for skilled nursing facility ($1093), home health agency ($527), and inpatient rehabilitation ($172). The use of preoperative physical therapy was associated with a 29% decrease in the use of any post-acute care

Preservation of Biospecimens at Ambient Temperature: Special Focus on Nucleic Acids and Opportunities for the Biobanking Community.

Science.gov (United States)

Muller, Rolf; Betsou, Fay; Barnes, Michael G; Harding, Keith; Bonnet, Jacques; Kofanova, Olga; Crowe, John H

2016-04-01

Several approaches to the preservation of biological materials at ambient temperature and the relative impact on sample stability and degradation are reviewed, with a focus on nucleic acids. This appraisal is undertaken within the framework of biobank risk, quality management systems, and accreditation, with a view to assessing how best to apply ambient temperature sample storage to ensure stability, reduce costs, improve handling logistics, and increase the efficiency of biobank procedures.

Analysis of the total system life cycle cost for the Civilian Radioactive Waste Management Program

International Nuclear Information System (INIS)

1989-05-01

The total-system life-cycle cost (TSLCC) analysis for the Department of Energy's (DOE) Civilian Radioactive Waste Management Program is an ongoing activity that helps determine whether the revenue-producing mechanism established by the Nuclear Waste Policy Act of 1982 -- a fee levied on electricity generated in commercial nuclear power plants -- is sufficient to cover the cost of the program. This report provides cost estimates for the sixth annual evaluation of the adequacy of the fee and is consistent with the program strategy and plans contained in the DOE's Draft 1988 Mission Plan Amendment. The total-system cost for the system with a repository at Yucca Mountain, Nevada, a facility for monitored retrievable storage (MRS), and a transportation system is estimated at $24 billion (expressed in constant 1988 dollars). In the event that a second repository is required and is authorized by the Congress, the total-system cost is estimated at $31 to $33 billion, depending on the quantity of spent fuel to be disposed of. The $7 billion cost savings for the single-repository system in comparison with the two-repository system is due to the elimination of $3 billion for second-repository development and $7 billion for the second-repository facility. These savings are offset by $2 billion in additional costs at the first repository and $1 billion in combined higher costs for the MRS facility and transportation. 55 refs., 2 figs., 24 tabs

Cost and cost-effectiveness analysis of a community mobilisation intervention to reduce intimate partner violence in Kampala, Uganda.

Science.gov (United States)

Michaels-Igbokwe, Christine; Abramsky, Tanya; Devries, Karen; Michau, Lori; Musuya, Tina; Watts, Charlotte

2016-02-29

Intimate partner violence (IPV) poses a major public health concern. To date there are few rigorous economic evaluations of interventions aimed at preventing IPV in low-income settings. This study provides a cost and cost effectiveness analysis of SASA!, a community mobilisation intervention to change social norms and prevent IPV. An economic evaluation alongside a cluster randomised controlled trial. Both financial and economic costs were collected retrospectively from the provider's perspective to generate total and unit cost estimates over four years of intervention programming. Univariate sensitivity analysis is conducted to estimate the impact of uncertainty in cost and outcome measures on results. The total cost of developing the SASA! Activist Kit is estimated as US$138,598. Total intervention costs over four years are estimated as US$553,252. The annual cost of supporting 351 activists to conduct SASA! activities was approximately US$389 per activist and the average cost per person reached in intervention communities was US$21 over the full course of the intervention, or US$5 annually. The primary trial outcome was past year experience of physical IPV with an estimated 1201 cases averted (90% CI: 97-2307 cases averted). The estimated cost per case of past year IPV averted was US$460. This study provides the first economic evaluation of a community mobilisation intervention aimed at preventing IPV. SASA! unit costs compare favourably with gender transformative interventions and support services for survivors of IPV. ClinicalTrials.gov # NCT00790959.

[Blood Test Patterns for Blood Donors after Nucleic Acid Detection in the Blood Center].

Science.gov (United States)

Men, Shou-Shan; Lv, Lian-Zhi; Chen, Yuan-Feng; Han, Chun-Hua; Liu, Hong-Yu; Yan, Yan

2017-12-01

To investigate the blood test patterns for blood donors after nucleic acid detection in blood center. The collected blood samples after voluntary blood donors first were detected by conventional ELISA, then 31981 negative samples were detected via HBV/HCV/HIV combined nucleic acid test of 6 mixed samples(22716 cases) or single samples(9265 cases) by means of Roche cobas s201 instrument. The combined detection method as follows: the blood samples were assayed by conventional nucleic acid test of 6 mixed samples, at same time, 6 mixed samples were treated with polyethylene glycol precipitation method to concentrate the virus, then the nucleic acid test of blood samples was performed; the single detection method as follows: firstly the conventional nucleic acid test of single sample was performed, then the positive reactive samples after re-examination were 6-fold diluted to simulate the nucleic acid test of 6-mixed samples. The positive rate of positive samples detected by combined nucleic acid test, positive samples detected by nucleic acid test of mixed virus concentration and positive samples detected by single nucleic acid test was statistically analyzed. In addition, for HBV + persons the serological test yet should be performed. In 22 716 samples detected by nucleic acid test of 6 mixed samples (MP-6-NAT) , 9 cases were HBV + (0.40‰, 9/22716); at same time, the detection of same samples by nucleic acid test of mixed sample virus concentration showed 29 cases of HBV + (1.28‰, 29/22716). In 9265 samples detected by single nucleic acid test(ID-NAT) 12 cases showed HBV + (1.30‰, 12/9265), meanwhile the detection of these 12 samples with HBV + by 6-fold dilution for virus concentration found only 4 samples with HBV + . In serological qualified samples, ID-NAT unqualified rate was 1.28‰, which was higher than that of MP-6-NAT(0.4‰) (χ 2 =8.11, P0.05). In 41 samples with HBsAg - HBV DNA + detected by ELISA, 36 samples were confirmed to be occult HBV

Total cost of ownership in the services sector: A case study

NARCIS (Netherlands)

K. Hurkens (Krisje); W. van der Valk (Wendy); J.Y.F. Wynstra (Finn)

2006-01-01

textabstractFew detailed studies exist of the trade-offs to be made when developing a comprehensive, strategically focused total cost of ownership (TCO) model. Moreover, most studies of TCO have been conducted in manufacturing firms, with little or no TCO research directed toward service

Ion-pair chromatography of nucleic acid derivatives

International Nuclear Information System (INIS)

Perrone, P.A.; Brown, P.R.

1985-01-01

Little work has been done on the ion-pair chromatography of nucleic acid constituents, although there is a great potential for the use of this technique in the field. Since the classic work in 1949, nucleotides, as well as nucleosides and bases, have been separated by ion-exchange chromatography. However, ion exchange is a difficult mode and most researchers prefer the use of reversed-phase whenever possible. Although reversed-phase is now the method of choice, ionic compounds like nucleotides and some of the more polar bases are not adequately retained by many systems of this type. In addition, it is difficult to analyze simultaneously members of all three classes of nucleic acid compounds (bases, nucleosides, and nucleotides) using a reversed-phase system, even with gradient elution. Ion pairing can be a useful technique because, theoretically, the separation of nonionic bases and nucleosides along with the ionic nucleotides can be achieved. Additionally, each group of compounds may be separated isocratically. In this chapter, they will discuss ion-pair chromatography as applied to nucleic acid constituents. The current theories, advantages and disadvantages, a limited number of applications, and potential for future work are presented

Methods of introducing nucleic acids into cellular DNA

Energy Technology Data Exchange (ETDEWEB)

Lajoie, Marc J.; Gregg, Christopher J.; Mosberg, Joshua A.; Church, George M.

2017-06-27

A method of introducing a nucleic acid sequence into a cell is provided where the cell has impaired or inhibited or disrupted DnaG primase activity or impaired or inhibited or disrupted DnaB helicase activity, or larger or increased gaps or distance between Okazaki fragments or lowered or reduced frequency of Okazaki fragment initiation, or the cell has increased single stranded DNA (ssDNA) on the lagging strand of the replication fork including transforming the cell through recombination with a nucleic acid oligomer.

Study of the radiation effects on nucleic acids and related compounds. Annual progress report, August 15, 1974--August 14, 1975

International Nuclear Information System (INIS)

Wang, S.Y.

1975-01-01

Interest is being centered on the chemical and physical nature of radiation-induced lesions to nucleic acids and their components. These investigations have revealed the enormous complexity of chemical events in these systems and the possible degradation of nucleic acids by strand breakage. Therefore, work in the ionizing radiation of DNA and its components has proceeded along a dual course. For chemical studies, our prime concern is the stepwise isolation and identification of the radiation products of derivatives of pyrimidines and the study of the actual mechanisms of their formation. For biological studies, H. influenzae cells, the Chinese hamster V79B-1 cell line, and the Dunn osteosarcoma lung colony system were used. During the last year, the method of synthesis of 5-hydroperoxymethyluracil (T/sub α/OOH) was greatly improved. Large-scale preparation of 5-hydroxy-6-hydroperoxy-5,6-dihydrothymine (T 6 OOH) were carried out in order to study the action of T 6 OOH on neighboring bases, glycosidic bond-breakage, cell mutagenesis, chromosomal aberrations, and possible synergistic effects on x radiation. These results allow one to relate radiobiological effects with radiation chemical changes in DNA

Synergistic Combination of Unquenching and Plasmonic Fluorescence Enhancement in Fluorogenic Nucleic Acid Hybridization Probes.

Science.gov (United States)

Vietz, Carolin; Lalkens, Birka; Acuna, Guillermo P; Tinnefeld, Philip

2017-10-11

Fluorogenic nucleic acid hybridization probes are widely used for detecting and quantifying nucleic acids. The achieved sensitivity strongly depends on the contrast between a quenched closed form and an unquenched opened form with liberated fluorescence. So far, this contrast was improved by improving the quenching efficiency of the closed form. In this study, we modularly combine these probes with optical antennas used for plasmonic fluorescence enhancement and study the effect of the nanophotonic structure on the fluorescence of the quenched and the opened form. As quenched fluorescent dyes are usually enhanced more by fluorescence enhancement, a detrimental reduction of the contrast between closed and opened form was anticipated. In contrast, we could achieve a surprising increase of the contrast with full additivity of quenching of the dark form and fluorescence enhancement of the bright form. Using single-molecule experiments, we demonstrate that the additivity of the two mechanisms depends on the perfect quenching in the quenched form, and we delineate the rules for new nucleic acid probes for enhanced contrast and absolute brightness. Fluorogenic hybridization probes optimized not only for quenching but also for the brightness of the open form might find application in nucleic acid assays with PCR avoiding detection schemes.

Clarithromycin, trimethoprim, and penicillin and oxidative nucleic acid modifications in humans

DEFF Research Database (Denmark)

Larsen, Emil List; Cejvanovic, Vanja; Kjaer, Laura Kofoed

2017-01-01

, phenoxymethylpenicillin (penicillin V), or placebo. Oxidative modifications were measured as 24-h urinary excretion of 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), and plasma levels of malondialdehyde before and after treatment as a measurement of DNA oxidation, RNA oxidation.......7% (95% CI: 5.8–37.6%), but did not influence urinary excretion of 8-oxoGuo. Penicillin V did not influence urinary excretion of 8-oxodG or 8-oxoGuo. None of the antibiotic drugs influenced plasma levels of malondialdehyde. Conclusion Clarithromycin significantly increases oxidative nucleic acid...... modifications. Increased oxidative modifications might explain some of clarithromycin's known adverse reactions. Trimethoprim significantly lowers DNA oxidation but not RNA oxidation. Penicillin V had no effect on oxidative nucleic acid modifications....

The Cost-Effectiveness of School-Based Eating Disorder Screening

Science.gov (United States)

Austin, S. Bryn; LeAnn Noh, H.; Jiang, Yushan; Sonneville, Kendrin R.

2014-01-01

Objectives. We aimed to assess the value of school-based eating disorder (ED) screening for a hypothetical cohort of US public school students. Methods. We used a decision-analytic microsimulation model to model the effectiveness (life-years with ED and quality-adjusted life-years [QALYs]), total direct costs, and cost-effectiveness (cost per QALY gained) of screening relative to current practice. Results. The screening strategy cost $2260 (95% confidence interval [CI] = $1892, $2668) per student and resulted in a per capita gain of 0.25 fewer life-years with ED (95% CI = 0.21, 0.30) and 0.04 QALYs (95% CI = 0.03, 0.05) relative to current practice. The base case cost-effectiveness of the intervention was $9041 per life-year with ED avoided (95% CI = $6617, $12 344) and $56 500 per QALY gained (95% CI = $38 805, $71 250). Conclusions. At willingness-to-pay thresholds of $50 000 and $100 000 per QALY gained, school-based ED screening is 41% and 100% likely to be cost-effective, respectively. The cost-effectiveness of ED screening is comparable to many other accepted pediatric health interventions, including hypertension screening. PMID:25033131

Study of the radiation effects on nucleic acids and related compounds. Progress report, August 15, 1976--November 14, 1977

International Nuclear Information System (INIS)

Wang, S.Y.

1977-08-01

The effects of ionizing radiation on nucleic acids and components were studied in vitro. Our approach involves four levels of operation and progress is being made at each stage. First, procedures were established to separate and purify three reactive radiation products from thymidine. Second, improved methods of synthesizing trans-glycols of pyrimidines were developed, and a new method for the stereospecific synthesis of cis-glycol of pyrimidines was realized. Thirdly, the Ames Salmonella test was used to determine the mutagenicity of the radiation products and the reactive ones from thymine and thymidine were found to be highly mutagenic. Therefore, all radiation products should be considered potential human health hazards and should be screened when they can be purified and synthesized. In the fourth stage, the reaction of each nucleic-acid base with Cu ++ and cis-5,6-dihydro-6-hydroperoxy-5-hydroxythymine (6-TOOH) was studied in order to further our understanding of the molecular mechanisms of radiation mutagenesis. The presence of Cu ++ was shown to be necessary for the effective mutagenic activity of 6-TOOH in the H. influenzae transformation assay. These findings provide fundamental information about the possible health hazards of ionizing radiation and will be useful in designing methods to protect against and repair radiation damage, which may be mutagenic and carcinogenic

Digital Microfluidics for Nucleic Acid Amplification

Directory of Open Access Journals (Sweden)

Beatriz Coelho

2017-06-01

Full Text Available Digital Microfluidics (DMF has emerged as a disruptive methodology for the control and manipulation of low volume droplets. In DMF, each droplet acts as a single reactor, which allows for extensive multiparallelization of biological and chemical reactions at a much smaller scale. DMF devices open entirely new and promising pathways for multiplex analysis and reaction occurring in a miniaturized format, thus allowing for healthcare decentralization from major laboratories to point-of-care with accurate, robust and inexpensive molecular diagnostics. Here, we shall focus on DMF platforms specifically designed for nucleic acid amplification, which is key for molecular diagnostics of several diseases and conditions, from pathogen identification to cancer mutations detection. Particular attention will be given to the device architecture, materials and nucleic acid amplification applications in validated settings.

Costs and cost-effectiveness of training traditional birth attendants to reduce neonatal mortality in the Lufwanyama Neonatal Survival study (LUNESP.

Directory of Open Access Journals (Sweden)

Lora L Sabin

Full Text Available The Lufwanyama Neonatal Survival Project ("LUNESP" was a cluster randomized, controlled trial that showed that training traditional birth attendants (TBAs to perform interventions targeting birth asphyxia, hypothermia, and neonatal sepsis reduced all-cause neonatal mortality by 45%. This companion analysis was undertaken to analyze intervention costs and cost-effectiveness, and factors that might improve cost-effectiveness.We calculated LUNESP's financial and economic costs and the economic cost of implementation for a forecasted ten-year program (2011-2020. In each case, we calculated the incremental cost per death avoided and disability-adjusted life years (DALYs averted in real 2011 US dollars. The forecasted 10-year program analysis included a base case as well as 'conservative' and 'optimistic' scenarios. Uncertainty was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. The estimated financial and economic costs of LUNESP were $118,574 and $127,756, respectively, or $49,469 and $53,550 per year. Fixed costs accounted for nearly 90% of total costs. For the 10-year program, discounted total and annual program costs were $256,455 and $26,834 respectively; for the base case, optimistic, and conservative scenarios, the estimated cost per death avoided was $1,866, $591, and $3,024, and cost per DALY averted was $74, $24, and $120, respectively. Outcomes were robust to variations in local costs, but sensitive to variations in intervention effect size, number of births attended by TBAs, and the extent of foreign consultants' participation.Based on established guidelines, the strategy of using trained TBAs to reduce neonatal mortality was 'highly cost effective'. We strongly recommend consideration of this approach for other remote rural populations with limited access to health care.

Nucleic Acid Extraction from Synthetic Mars Analog Soils for in situ Life Detection.

Science.gov (United States)

Mojarro, Angel; Ruvkun, Gary; Zuber, Maria T; Carr, Christopher E

2017-08-01

Biological informational polymers such as nucleic acids have the potential to provide unambiguous evidence of life beyond Earth. To this end, we are developing an automated in situ life-detection instrument that integrates nucleic acid extraction and nanopore sequencing: the Search for Extra-Terrestrial Genomes (SETG) instrument. Our goal is to isolate and determine the sequence of nucleic acids from extant or preserved life on Mars, if, for example, there is common ancestry to life on Mars and Earth. As is true of metagenomic analysis of terrestrial environmental samples, the SETG instrument must isolate nucleic acids from crude samples and then determine the DNA sequence of the unknown nucleic acids. Our initial DNA extraction experiments resulted in low to undetectable amounts of DNA due to soil chemistry-dependent soil-DNA interactions, namely adsorption to mineral surfaces, binding to divalent/trivalent cations, destruction by iron redox cycling, and acidic conditions. Subsequently, we developed soil-specific extraction protocols that increase DNA yields through a combination of desalting, utilization of competitive binders, and promotion of anaerobic conditions. Our results suggest that a combination of desalting and utilizing competitive binders may establish a "universal" nucleic acid extraction protocol suitable for analyzing samples from diverse soils on Mars. Key Words: Life-detection instruments-Nucleic acids-Mars-Panspermia. Astrobiology 17, 747-760.

Higher cost of implementing Xpert(®) MTB/RIF in Ugandan peripheral settings: implications for cost-effectiveness.

Science.gov (United States)

Hsiang, E; Little, K M; Haguma, P; Hanrahan, C F; Katamba, A; Cattamanchi, A; Davis, J L; Vassall, A; Dowdy, D

2016-09-01

Initial cost-effectiveness evaluations of Xpert(®) MTB/RIF for tuberculosis (TB) diagnosis have not fully accounted for the realities of implementation in peripheral settings. To evaluate costs and diagnostic outcomes of Xpert testing implemented at various health care levels in Uganda. We collected empirical cost data from five health centers utilizing Xpert for TB diagnosis, using an ingredients approach. We reviewed laboratory and patient records to assess outcomes at these sites and10 sites without Xpert. We also estimated incremental cost-effectiveness of Xpert testing; our primary outcome was the incremental cost of Xpert testing per newly detected TB case. The mean unit cost of an Xpert test was US$21 based on a mean monthly volume of 54 tests per site, although unit cost varied widely (US$16-58) and was primarily determined by testing volume. Total diagnostic costs were 2.4-fold higher in Xpert clinics than in non-Xpert clinics; however, Xpert only increased diagnoses by 12%. The diagnostic costs of Xpert averaged US$119 per newly detected TB case, but were as high as US$885 at the center with the lowest volume of tests. Xpert testing can detect TB cases at reasonable cost, but may double diagnostic budgets for relatively small gains, with cost-effectiveness deteriorating with lower testing volumes.

Programming the Assembly of Unnatural Materials with Nucleic Acids

Science.gov (United States)

Mirkin, Chad

Nature directs the assembly of enormously complex and highly functional materials through an encoded class of biomolecules, nucleic acids. The establishment of a similarly programmable code for the construction of synthetic, unnatural materials would allow researchers to impart functionality by precisely positioning all material components. Although it is exceedingly difficult to control the complex interactions between atomic and molecular species in such a manner, interactions between nanoscale components can be directed through the ligands attached to their surface. Our group has shown that nucleic acids can be used as highly programmable surface ligands to control the spacing and symmetry of nanoparticle building blocks in structurally sophisticated and functional materials. These nucleic acids function as programmable ``bonds'' between nanoparticle ``atoms,'' analogous to a nanoscale genetic code for assembling materials. The sequence and length tunability of nucleic acid bonds has allowed us to define a powerful set of design rules for the construction of nanoparticle superlattices with more than 30 unique lattice symmetries, tunable defect structures and interparticle spacings, and several well-defined crystal habits. Further, the nature of the nucleic acid bond enables an additional level of structural control: temporal regulation of dynamic material response to external biomolecular and chemical stimuli. This control allows for the reversible transformation between thermodynamic states with different crystal symmetries, particle stoichiometries, thermal stabilities, and interparticle spacings on demand. Notably, our unique genetic approach affords functional nanoparticle architectures that, among many other applications, can be used to systematically explore and manipulate optoelectronic material properties, such as tunable interparticle plasmonic interactions, microstructure-directed energy emission, and coupled plasmonic and photonic modes.

A DNA origami nanorobot controlled by nucleic acid hybridization.

Science.gov (United States)

Torelli, Emanuela; Marini, Monica; Palmano, Sabrina; Piantanida, Luca; Polano, Cesare; Scarpellini, Alice; Lazzarino, Marco; Firrao, Giuseppe

2014-07-23

A prototype for a DNA origami nanorobot is designed, produced, and tested. The cylindrical nanorobot (diameter of 14 nm and length of 48 nm) with a switchable flap, is able to respond to an external stimulus and reacts by a physical switch from a disarmed to an armed configuration able to deliver a cellular compatible message. In the tested design the robot weapon is a nucleic acid fully contained in the inner of the tube and linked to a single point of the internal face of the flap. Upon actuation the nanorobot moves the flap extracting the nucleic acid that assembles into a hemin/G-quadruplex horseradish peroxidase mimicking DNAzyme catalyzing a colorimetric reaction or chemiluminescence generation. The actuation switch is triggered by an external nucleic acid (target) that interacts with a complementary nucleic acid that is beard externally by the nanorobot (probe). Hybridization of probe and target produces a localized structural change that results in flap opening. The flap movement is studied on a two-dimensional prototype origami using Förster resonance energy transfer and is shown to be triggered by a variety of targets, including natural RNAs. The nanorobot has potential for in vivo biosensing and intelligent delivery of biological activators. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A DNA origami nanorobot controlled by nucleic acid hybridization

KAUST Repository

Torelli, Emanuela

2014-03-20

A prototype for a DNA origami nanorobot is designed, produced, and tested. The cylindrical nanorobot (diameter of 14 nm and length of 48 nm) with a switchable flap, is able to respond to an external stimulus and reacts by a physical switch from a disarmed to an armed configuration able to deliver a cellular compatible message. In the tested design the robot weapon is a nucleic acid fully contained in the inner of the tube and linked to a single point of the internal face of the flap. Upon actuation the nanorobot moves the flap extracting the nucleic acid that assembles into a hemin/G-quadruplex horseradish peroxidase mimicking DNAzyme catalyzing a colorimetric reaction or chemiluminescence generation. The actuation switch is triggered by an external nucleic acid (target) that interacts with a complementary nucleic acid that is beard externally by the nanorobot (probe). Hybridization of probe and target produces a localized structural change that results in flap opening. The flap movement is studied on a two-dimensional prototype origami using Förster resonance energy transfer and is shown to be triggered by a variety of targets, including natural RNAs. The nanorobot has potential for in vivo biosensing and intelligent delivery of biological activators. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

BIGNASim: a NoSQL database structure and analysis portal for nucleic acids simulation data.

Science.gov (United States)

Hospital, Adam; Andrio, Pau; Cugnasco, Cesare; Codo, Laia; Becerra, Yolanda; Dans, Pablo D; Battistini, Federica; Torres, Jordi; Goñi, Ramón; Orozco, Modesto; Gelpí, Josep Ll

2016-01-04

Molecular dynamics simulation (MD) is, just behind genomics, the bioinformatics tool that generates the largest amounts of data, and that is using the largest amount of CPU time in supercomputing centres. MD trajectories are obtained after months of calculations, analysed in situ, and in practice forgotten. Several projects to generate stable trajectory databases have been developed for proteins, but no equivalence exists in the nucleic acids world. We present here a novel database system to store MD trajectories and analyses of nucleic acids. The initial data set available consists mainly of the benchmark of the new molecular dynamics force-field, parmBSC1. It contains 156 simulations, with over 120 μs of total simulation time. A deposition protocol is available to accept the submission of new trajectory data. The database is based on the combination of two NoSQL engines, Cassandra for storing trajectories and MongoDB to store analysis results and simulation metadata. The analyses available include backbone geometries, helical analysis, NMR observables and a variety of mechanical analyses. Individual trajectories and combined meta-trajectories can be downloaded from the portal. The system is accessible through http://mmb.irbbarcelona.org/BIGNASim/. Supplementary Material is also available on-line at http://mmb.irbbarcelona.org/BIGNASim/SuppMaterial/. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

Cost-utility analysis comparing radioactive iodine, anti-thyroid drugs and total thyroidectomy for primary treatment of Graves' disease.

Science.gov (United States)

Donovan, Peter J; McLeod, Donald S A; Little, Richard; Gordon, Louisa

2016-12-01

Little data is in existence about the most cost-effective primary treatment for Graves' disease. We performed a cost-utility analysis comparing radioactive iodine (RAI), anti-thyroid drugs (ATD) and total thyroidectomy (TT) as first-line therapy for Graves' disease in England and Australia. We used a Markov model to compare lifetime costs and benefits (quality-adjusted life-years (QALYs)). The model included efficacy, rates of relapse and major complications associated with each treatment, and alternative second-line therapies. Model parameters were obtained from published literature. One-way sensitivity analyses were conducted. Costs were presented in 2015£ or Australian Dollars (AUD). RAI was the least expensive therapy in both England (£5425; QALYs 34.73) and Australia (AUD5601; 30.97 QALYs). In base case results, in both countries, ATD was a cost-effective alternative to RAI (£16 866; 35.17 QALYs; incremental cost-effectiveness ratio (ICER) £26 279 per QALY gained England; AUD8924; 31.37 QALYs; ICER AUD9687 per QALY gained Australia), while RAI dominated TT (£7115; QALYs 33.93 England; AUD15 668; 30.25 QALYs Australia). In sensitivity analysis, base case results were stable to changes in most cost, transition probabilities and health-relative quality-of-life (HRQoL) weights; however, in England, the results were sensitive to changes in the HRQoL weights of hypothyroidism and euthyroidism on ATD. In this analysis, RAI is the least expensive choice for first-line treatment strategy for Graves' disease. In England and Australia, ATD is likely to be a cost-effective alternative, while TT is unlikely to be cost-effective. Further research into HRQoL in Graves' disease could improve the quality of future studies. © 2016 European Society of Endocrinology.

The total lifetime costs of smoking

DEFF Research Database (Denmark)

Rasmussen, S.R.; Prescott, E.; Sørensen, T.I.A.

2004-01-01

Net costs of smoking in a lifetime perspective and, hence, the economic interests in antismoking policies have been questioned. It has been proposed that the health-related costs of smoking are balanced by smaller expenditure due to shorter life expectancy.......Net costs of smoking in a lifetime perspective and, hence, the economic interests in antismoking policies have been questioned. It has been proposed that the health-related costs of smoking are balanced by smaller expenditure due to shorter life expectancy....

Molecular modeling of nucleic Acid structure: electrostatics and solvation.

Science.gov (United States)

Bergonzo, Christina; Galindo-Murillo, Rodrigo; Cheatham, Thomas E

2014-12-19

This unit presents an overview of computer simulation techniques as applied to nucleic acid systems, ranging from simple in vacuo molecular modeling techniques to more complete all-atom molecular dynamics treatments that include an explicit representation of the environment. The third in a series of four units, this unit focuses on critical issues in solvation and the treatment of electrostatics. UNITS 7.5 & 7.8 introduced the modeling of nucleic acid structure at the molecular level. This included a discussion of how to generate an initial model, how to evaluate the utility or reliability of a given model, and ultimately how to manipulate this model to better understand its structure, dynamics, and interactions. Subject to an appropriate representation of the energy, such as a specifically parameterized empirical force field, the techniques of minimization and Monte Carlo simulation, as well as molecular dynamics (MD) methods, were introduced as a way of sampling conformational space for a better understanding of the relevance of a given model. This discussion highlighted the major limitations with modeling in general. When sampling conformational space effectively, difficult issues are encountered, such as multiple minima or conformational sampling problems, and accurately representing the underlying energy of interaction. In order to provide a realistic model of the underlying energetics for nucleic acids in their native environments, it is crucial to include some representation of solvation (by water) and also to properly treat the electrostatic interactions. These subjects are discussed in detail in this unit. Copyright © 2014 John Wiley & Sons, Inc.

The effects of utility DSM programs on electricity costs and prices

Energy Technology Data Exchange (ETDEWEB)

Hirst, E.

1991-11-01

More and more US utilities are running more and larger demand-side management (DSM) programs. Assessing the cost-effectiveness of these programs raises difficult questions for utilities and their regulators. Should these programs aim to minimize the total cost of providing electric-energy services or should they minimize the price of electricity This study offers quantitative estimates on the tradeoffs between total costs and electricity prices. This study uses a dynamic model to assess the effects of energy-efficiency programs on utility revenues, total resource costs, electricity prices, and electricity consumption for the period 1990 to 2010. These DSM programs are assessed under alternative scenarios. In these cases, fossil-fuel prices, load growth, the amount of excess capacity the utility has in 1990, planned retirements of power plants, the financial treatment of DSM programs, and the costs of energy- efficient programs vary. These analyses are conducted for three utilities: a base'' that is typical of US utilities; a surplus'' utility that has excess capacity, few planned retirements, and slow growth in fossil-fuel prices and incomes; and a deficit'' utility that has little excess capacity, many planned retirements, and rapid growth in fossil-fuel prices and incomes. 28 refs.

Cost effectiveness of adopted quality requirements in hospital laboratories.

Science.gov (United States)

Hamza, Alneil; Ahmed-Abakur, Eltayib; Abugroun, Elsir; Bakhit, Siham; Holi, Mohamed

2013-01-01

The present study was designed in quasi-experiment to assess adoption of the essential clauses of particular clinical laboratory quality management requirements based on international organization for standardization (ISO 15189) in hospital laboratories and to evaluate the cost effectiveness of compliance to ISO 15189. The quality management intervention based on ISO 15189 was conceded through three phases; pre - intervention phase, Intervention phase and Post-intervention phase. In pre-intervention phase the compliance to ISO 15189 was 49% for study group vs. 47% for control group with P value 0.48, while the post intervention results displayed 54% vs. 79% for study group and control group respectively in compliance to ISO 15189 and statistically significant difference (P value 0.00) with effect size (Cohen's d) of (0.00) in pre-intervention phase and (0.99) in post - intervention phase. The annual average cost per-test for the study group and control group was 1.80 ± 0.25 vs. 1.97 ± 0.39, respectively with P value 0.39 whereas the post-intervention results showed that the annual average total costs per-test for study group and control group was 1.57 ± 0.23 vs 2.08 ± 0.38, P value 0.019 respectively, with cost-effectiveness ratio of (0.88) in pre -intervention phase and (0.52) in post-intervention phase. The planned adoption of quality management requirements (QMS) in clinical laboratories had great effect to increase the compliance percent with quality management system requirement, raise the average total cost effectiveness, and improve the analytical process capability of the testing procedure.

Sodium sulphite inhibition of potato and cherry polyphenolics in nucleic acid extraction for virus detection by RT-PCR.

Science.gov (United States)

Singh, R P; Nie, X; Singh, M; Coffin, R; Duplessis, P

2002-01-01

Phenolic compounds from plant tissues inhibit reverse transcription-polymerase chain reaction (RT-PCR). Multiple-step protocols using several additives to inhibit polyphenolic compounds during nucleic acid extraction are common, but time consuming and laborious. The current research highlights that the inclusion of 0.65 to 0.70% of sodium sulphite in the extraction buffer minimizes the pigmentation of nucleic acid extracts and improves the RT-PCR detection of Potato virus Y (PVY) and Potato leafroll virus (PLRV) in potato (Solanum tuberosum) tubers and Prune dwarf virus (PDV) and Prunus necrotic ringspot virus (PNRSV) in leaves and bark in the sweet cherry (Prunus avium) tree. Substituting sodium sulphite in the nucleic acid extraction buffer eliminated the use of proteinase K during extraction. Reagents phosphate buffered saline (PBS)-Tween 20 and polyvinylpyrrolidone (PVP) were also no longer required during RT or PCR phase. The resultant nucleic acid extracts were suitable for both duplex and multiplex RT-PCR. This simple and less expensive nucleic acid extraction protocol has proved very effective for potato cv. Russet Norkotah, which contains a high amount of polyphenolics. Comparing commercially available RNA extraction kits (Catrimox and RNeasy), the sodium sulphite based extraction protocol yielded two to three times higher amounts of RNA, while maintaining comparable virus detection by RT-PCR. The sodium sulphite based extraction protocol was equally effective in potato tubers, and in leaves and bark from the cherry tree.

Developing nucleic acid-based electrical detection systems

Directory of Open Access Journals (Sweden)

Gabig-Ciminska Magdalena

2006-03-01

Full Text Available Abstract Development of nucleic acid-based detection systems is the main focus of many research groups and high technology companies. The enormous work done in this field is particularly due to the broad versatility and variety of these sensing devices. From optical to electrical systems, from label-dependent to label-free approaches, from single to multi-analyte and array formats, this wide range of possibilities makes the research field very diversified and competitive. New challenges and requirements for an ideal detector suitable for nucleic acid analysis include high sensitivity and high specificity protocol that can be completed in a relatively short time offering at the same time low detection limit. Moreover, systems that can be miniaturized and automated present a significant advantage over conventional technology, especially if detection is needed in the field. Electrical system technology for nucleic acid-based detection is an enabling mode for making miniaturized to micro- and nanometer scale bio-monitoring devices via the fusion of modern micro- and nanofabrication technology and molecular biotechnology. The electrical biosensors that rely on the conversion of the Watson-Crick base-pair recognition event into a useful electrical signal are advancing rapidly, and recently are receiving much attention as a valuable tool for microbial pathogen detection. Pathogens may pose a serious threat to humans, animal and plants, thus their detection and analysis is a significant element of public health. Although different conventional methods for detection of pathogenic microorganisms and their toxins exist and are currently being applied, improvements of molecular-based detection methodologies have changed these traditional detection techniques and introduced a new era of rapid, miniaturized and automated electrical chip detection technologies into pathogen identification sector. In this review some developments and current directions in

Cost-effectiveness of Crohn’s disease post-operative care

Science.gov (United States)

Wright, Emily K; Kamm, Michael A; Dr Cruz, Peter; Hamilton, Amy L; Ritchie, Kathryn J; Bell, Sally J; Brown, Steven J; Connell, William R; Desmond, Paul V; Liew, Danny

2016-01-01

AIM: To define the cost-effectiveness of strategies, including endoscopy and immunosuppression, to prevent endoscopic recurrence of Crohn’s disease following intestinal resection. METHODS: In the “POCER” study patients undergoing intestinal resection were treated with post-operative drug therapy. Two thirds were randomized to active care (6 mo colonoscopy and drug intensification for endoscopic recurrence) and one third to drug therapy without early endoscopy. Colonoscopy at 18 mo and faecal calprotectin (FC) measurement were used to assess disease recurrence. Administrative data, chart review and patient questionnaires were collected prospectively over 18 mo. RESULTS: Sixty patients (active care n = 43, standard care n = 17) were included from one health service. Median total health care cost was $6440 per patient. Active care cost $4824 more than standard care over 18 mo. Medication accounted for 78% of total cost, of which 90% was for adalimumab. Median health care cost was higher for those with endoscopic recurrence compared to those in remission [$26347 (IQR 25045-27485) vs $2729 (IQR 1182-5215), P cost by $1010 per patient over 18 mo. Active care was associated with 18% decreased endoscopic recurrence, costing $861 for each recurrence prevented. CONCLUSION: Post-operative management strategies are associated with high cost, primarily medication related. Calprotectin use reduces costs. The long term cost-benefit of these strategies remains to be evaluated. PMID:27076772

Theoretical and methodological aspects of assessing economic effectiveness of nuclear power plant construction using cost-benefit analysis

International Nuclear Information System (INIS)

Moravcik, A.

1984-01-01

The cost benefit of investments is devided into social and economic benefits. The postulates are discussed for the assessment of the cost benefit of capital costs of nuclear power plants. The relations are given for total cost benefit of capital costs expressed by the total profit rate of capital costs, and the absolute effectiveness exoressed by the socio-economic benefit of capital costs. The absolute cost benefit of capital costs is characterized by several complex indexes. Comparable capital cost benefit is used for assessing the effectiveness of interchangeable variants of solution. The minimum calculated costs serve as the criterion for selecting the optimal variant. (E.S.)

Cost, affordability and cost-effectiveness of strategies to control tuberculosis in countries with high HIV prevalence

Directory of Open Access Journals (Sweden)

Williams Brian G

2005-12-01

Full Text Available Abstract Background The HIV epidemic has caused a dramatic increase in tuberculosis (TB in East and southern Africa. Several strategies have the potential to reduce the burden of TB in high HIV prevalence settings, and cost and cost-effectiveness analyses can help to prioritize them when budget constraints exist. However, published cost and cost-effectiveness studies are limited. Methods Our objective was to compare the cost, affordability and cost-effectiveness of seven strategies for reducing the burden of TB in countries with high HIV prevalence. A compartmental difference equation model of TB and HIV and recent cost data were used to assess the costs (year 2003 US$ prices and effects (TB cases averted, deaths averted, DALYs gained of these strategies in Kenya during the period 2004–2023. Results The three lowest cost and most cost-effective strategies were improving TB cure rates, improving TB case detection rates, and improving both together. The incremental cost of combined improvements to case detection and cure was below US$15 million per year (7.5% of year 2000 government health expenditure; the mean cost per DALY gained of these three strategies ranged from US$18 to US$34. Antiretroviral therapy (ART had the highest incremental costs, which by 2007 could be as large as total government health expenditures in year 2000. ART could also gain more DALYs than the other strategies, at a cost per DALY gained of around US$260 to US$530. Both the costs and effects of treatment for latent tuberculosis infection (TLTI for HIV+ individuals were low; the cost per DALY gained ranged from about US$85 to US$370. Averting one HIV infection for less than US$250 would be as cost-effective as improving TB case detection and cure rates to WHO target levels. Conclusion To reduce the burden of TB in high HIV prevalence settings, the immediate goal should be to increase TB case detection rates and, to the extent possible, improve TB cure rates, preferably

Effectiveness of autologous transfusion system in primary total hip and knee arthroplasty.

LENUS (Irish Health Repository)

Schneider, Marco M

2014-01-01

Autologous transfusion has become a cost-efficient and useful option in the treatment of patients with high blood loss following major orthopaedic surgery. However, the effectiveness of autologous transfusion in total joint replacement remains controversial.

Hepatitis C Treatment Regimens Are Cost-Effective: But Compared With What?

Science.gov (United States)

Mattingly, T Joseph; Slejko, Julia F; Mullins, C Daniel

2017-11-01

Numerous economic models have been published evaluating treatment of chronic hepatitis C virus (HCV) infection, but none provide a comprehensive comparison among new antiviral agents. Evaluate the cost-effectiveness of all recommended therapies for treatment of genotypes 1 and 4 chronic HCV. Using data from clinical trials, observational analyses, and drug pricing databases, Markov decision models were developed for HCV genotypes 1 and 4 to compare all recommended drugs from the perspective of the third-party payer over a 5-, 10-, and 50-year time horizon. A probabilistic sensitivity analysis (PSA) was conducted by assigning distributions for clinical cure, age entering the model, costs for each health state, and quality-adjusted life years (QALYs) for each health state in a Monte Carlo simulation of 10 000 repetitions of the model. In the lifetime model for genotype 1, effects ranged from 18.08 to 18.40 QALYs and total costs ranged from $88 107 to $184 636. The lifetime model of genotype 4 treatments had a range of effects from 18.23 to 18.43 QALYs and total costs ranging from $87 063 to $127 637. Grazoprevir/elbasvir was the optimal strategy followed by velpatasvir/sofosbuvir as the second-best strategy in most simulations for both genotypes 1 and 4, with drug costs and efficacy of grazoprevir/elbasvir as the primary model drivers. Grazoprevir/elbasvir was cost-effective compared with all strategies for genotypes 1 and 4. Effects for all strategies were similar with cost of drug in the initial year driving the results.

Cost-effectiveness of hydrotherapy versus land-based therapy in patients with musculoskeletal disorders in Singapore.

Science.gov (United States)

Teng, Monica; Zhou, Hui Jun; Lin, Liang; Lim, Pang Hung; Yeo, Doreen; Goh, Suzanne; Tjan, Soon Yin; Lim, Boon Peng

2018-03-09

The study evaluated the cost-effectiveness of hydrotherapy versus land-based therapy in patients with musculoskeletal disorders (MSDs) in Singapore. A decision-analytic model was constructed to compare the cost-effectiveness of hydrotherapy to land-based therapy over 3 months from societal perspective. Target population comprised patients with low back pain (LBP), osteoarthritis (OA), rheumatoid arthritis (RA), total hip replacement (THR) and total knee replacement (TKR). Subgroup analyses were carried out to determine the cost-effectiveness of hydrotherapy in individual MSDs. Relative treatment effects were obtained through a systematic review of published data. Compared to land-based therapy, hydrotherapy was associated with an incremental cost-effectiveness ratio (ICER) of SGD 27 471 per quality-adjusted life-year (QALY) gained, which was below the willingness-to-pay threshold of SGD 70 000 per QALY (one gross domestic product per capita in Singapore in 2015). For the respective MSDs, hydrotherapy were dominant (more effective and less costly) in THR and TKR, cost-effective for LBP and RA, and not cost-effective for OA. Treatment adherence and cost of hydrotherapy were key drivers to the ICER values. Hydrotherapy was a cost-effective rehabilitation compared to land-based therapy for a population with MSDs in Singapore. However, the benefit of hydrotherapy was not observed in patients with OA.

Study of nucleic acids variations in children in nearest areas to the Chernobyl accident

International Nuclear Information System (INIS)

Morera, L.; Navarro, I.; Proenza, E.; Estrada, L.

1996-01-01

The technique used to determine the nucleic acids concentration of leucocytes in peripheral blood is simple, quick and reproducible. Mathematical patterns for small doses have been achieved by means of this technique, which is also useful as biochemical indicator for evaluating exposure to ionizing radiations. The following information is the result of a research in 445 children from 43 locations that suffered, in different degrees, the effect of this accident. Children were grouped taking into account different degrees of superficial pollution for Cs-137 of original places. Groups were built as follows: G-1, 165 children from 20 superficially polluted places between 0-37 KBq/m 2 ; G-2, 135 children from 15 locations with a level of superficial pollution higher than 37 KBq/m 2 and lower than 185 KBq/m 2 ; G-3, 85 children from 7 locations with a pollution degree higher than 296 KBq/m 2 and G-4, 60 children from a place with a non-determined superficial pollution. Values within the interval 1,29 - 4,89 mg/100 ml of blood samples taken from healthy children in group G-1 were considered as normal. The increase in dose led neither to a decrease in nucleic acids medium value, nor to a meaningful growth in the number of cases with nucleic acids figures under rank considered normal. On the other hand, thyroid hyperplasia did not lead either to an increase in medium values of nucleic acids or to an increase in the number of cases with nucleic acids figures over intervals considered as normal. (authors). 10 refs., 2 tabs

Bearing Procurement Analysis Method by Total Cost of Ownership Analysis and Reliability Prediction

Science.gov (United States)

Trusaji, Wildan; Akbar, Muhammad; Sukoyo; Irianto, Dradjad

2018-03-01

In making bearing procurement analysis, price and its reliability must be considered as decision criteria, since price determines the direct cost as acquisition cost and reliability of bearing determine the indirect cost such as maintenance cost. Despite the indirect cost is hard to identify and measured, it has high contribution to overall cost that will be incurred. So, the indirect cost of reliability must be considered when making bearing procurement analysis. This paper tries to explain bearing evaluation method with the total cost of ownership analysis to consider price and maintenance cost as decision criteria. Furthermore, since there is a lack of failure data when bearing evaluation phase is conducted, reliability prediction method is used to predict bearing reliability from its dynamic load rating parameter. With this method, bearing with a higher price but has higher reliability is preferable for long-term planning. But for short-term planning the cheaper one but has lower reliability is preferable. This contextuality can give rise to conflict between stakeholders. Thus, the planning horizon needs to be agreed by all stakeholder before making a procurement decision.

A METHOD OF THE MINIMIZING OF THE TOTAL ACQUISITIONS COST WITH THE INCREASING VARIABLE DEMAND

Directory of Open Access Journals (Sweden)

ELEONORA IONELA FOCȘAN

2015-12-01

Full Text Available Over time, mankind has tried to find different ways of costs reduction. This subject which we are facing more often nowadays, has been detailed studied, without reaching a general model, and also efficient, regarding the costs reduction. Costs reduction entails a number of benefits over the entity, the most important being: increase revenue and default to the profit, increase productivity, a higher level of services / products offered to clients, and last but not least, the risk mitigation of the economic deficit. Therefore, each entity search different modes to obtain most benefits, for the company to succeed in a competitive market. This article supports the companies, trying to make known a new way of minimizing the total cost of acquisitions, by presenting some hypotheses about the increasing variable demand, proving them, and development of formulas for reducing the costs. The hypotheses presented in the model described below, can be maximally exploited to obtain new models of reducing the total cost, according to the modes of the purchase of entities which approach it.

Cost and cost effectiveness of vaginal progesterone gel in reducing preterm birth: an economic analysis of the PREGNANT trial.

Science.gov (United States)

Pizzi, Laura T; Seligman, Neil S; Baxter, Jason K; Jutkowitz, Eric; Berghella, Vincenzo

2014-05-01

Preterm birth (PTB) is a costly public health problem in the USA. The PREGNANT trial tested the efficacy of vaginal progesterone (VP) 8 % gel in reducing the likelihood of PTB among women with a short cervix. We calculated the costs and cost effectiveness of VP gel versus placebo using decision analytic models informed by PREGNANT patient-level data. PREGNANT enrolled 459 pregnant women with a cervical length of 10-20 mm and randomized them to either VP 8 % gel or placebo. We used a cost model to estimate the total cost of treatment per mother and a cost-effectiveness model to estimate the cost per PTB averted with VP gel versus placebo. Patient-level trial data informed model inputs and included PTB rates in low- and high-risk women in each study group at <28 weeks gestation, 28-31, 32-36, and ≥37 weeks. Cost assumptions were based on 2010 US healthcare services reimbursements. The cost model was validated against patient-level data. Sensitivity analyses were used to test the robustness of the cost-effectiveness model. The estimated cost per mother was $US23,079 for VP gel and $US36,436 for placebo. The cost-effectiveness model showed savings of $US24,071 per PTB averted with VP gel. VP gel realized cost savings and cost effectiveness in 79 % of simulations. Based on findings from PREGNANT, VP gel was associated with cost savings and cost effectiveness compared with placebo. Future trials designed to include cost metrics are needed to better understand the value of VP.

Delivery Systems for In Vivo use of Nucleic Acid Drugs

Directory of Open Access Journals (Sweden)

Resende R.R

2007-01-01

Full Text Available The notorious biotechnological advance of the last few decades has allowed the development of experimental methods for understanding molecular mechanisms of genes and new therapeutic approaches. Gene therapy is maturing into a viable, practical method with the potential to cure a variety of human illnesses. Some nucleic-acid-based drugs are now available for controlling the progression of genetic diseases by inhibiting gene expression or the activity of their gene products. New therapeutic strategies employ a wide range of molecular tools such as bacterial plasmids containing transgenic inserts, RNA interference aptamers. A nucleic-acid based constitution confers a lower immunogenic potential and as result of the high stringency selection of large molecular variety, these drugs have high affi nity and selectivity for their targets. However, nucleic acids have poor biostability thus requiring chemical modifications and delivery systems to maintain their activity and ease their cellular internalization. This review discusses some of the mechanisms of action and the application of therapies based on nucleic acids such as aptamers and RNA interference as well as platforms for cellular uptake and intracellular delivery of therapeutic oligonucleotides and their trade-offs.

Nucleic acid helix structure determination from NMR proton chemical shifts

Energy Technology Data Exchange (ETDEWEB)

Werf, Ramon M. van der; Tessari, Marco; Wijmenga, Sybren S., E-mail: S.Wijmenga@science.ru.nl [Radboud University Nijmegen, Department of Biophysical Chemistry, Institute of Molecules and Materials (Netherlands)

2013-06-15

We present a method for de novo derivation of the three-dimensional helix structure of nucleic acids using non-exchangeable proton chemical shifts as sole source of experimental restraints. The method is called chemical shift de novo structure derivation protocol employing singular value decomposition (CHEOPS) and uses iterative singular value decomposition to optimize the structure in helix parameter space. The correct performance of CHEOPS and its range of application are established via an extensive set of structure derivations using either simulated or experimental chemical shifts as input. The simulated input data are used to assess in a defined manner the effect of errors or limitations in the input data on the derived structures. We find that the RNA helix parameters can be determined with high accuracy. We finally demonstrate via three deposited RNA structures that experimental proton chemical shifts suffice to derive RNA helix structures with high precision and accuracy. CHEOPS provides, subject to further development, new directions for high-resolution NMR structure determination of nucleic acids.

Nanoparticulate systems for nucleic acid delivery

NARCIS (Netherlands)

Varkouhi, A.K.

2011-01-01

Development of carrier systems with controllable physicochemical and delivery properties has opened up the possibility of nanomedicines containing nucleic acids. In the last decades, much effort has been dedicated to two exciting approaches in biomedicine, namely gene and RNA interference

A locked nucleic Acid-based nanocrawler

DEFF Research Database (Denmark)

Astakhova, I Kira; Pasternak, Karol; Campbell, Meghan A

2013-01-01

Herein we introduce a novel fluorescent LNA/DNA machine, a nanocrawler, which reversibly moves along a directionally polar complementary road controlled by affinity-enhancing locked nucleic acid (LNA) monomers and additional regulatory strands. Polyaromatic hydrocarbon (PAH) dyes attached to 2...

Localization of Bovine Papillomavirus Nucleic Acid in Equine Sarcoids.

Science.gov (United States)

Gaynor, A M; Zhu, K W; Dela Cruz, F N; Affolter, V K; Pesavento, P A

2016-05-01

Bovine papillomaviruses (BPV1/BPV2) have long been associated with equine sarcoids; deciphering their contribution has been difficult due to their ubiquitous presence on skin and in the environment, as well as the lack of decent techniques to interrogate their role in pathogenesis. We have developed and characterized an in situ hybridization (ISH) assay that uses a pool of probes complementary to portions of the E5, E6, and E7 genes. This assay is highly sensitive for direct visualization of viral transcript and nucleic acid in routinely processed histopathologic samples. We demonstrate here the visualization of BPV nucleic acid in 18 of 18 equine sarcoids, whereas no detectable viral DNA was present in 15 of 15 nonsarcoid controls by this technique. In nearly 90% (16/18) of the sarcoids, 50% or more of the fibroblastic cell nuclei distributed throughout the neoplasm had detectable hybridization. In the remaining 2 cases, fewer than half of the fibroblastic cells contained detectable hybridization, but viral nucleic acid was also detected in epithelial cells of the sebaceous glands, hair follicles and epidermis. A sensitive ISH assay is an indispensable addition to the molecular methods used to detect viral nucleic acid in tissue. We have used this technique to determine the specific cellular localization and distribution of BPV in a subset of equine sarcoids. © The Author(s) 2015.

Efforts to Support Consumer Enrollment Decisions Using Total Cost Estimators: Lessons from the Affordable Care Act’s Marketplaces.

Science.gov (United States)

Giovannelli, Justin; Curran, Emily

2017-02-01

Issue: Policymakers have sought to improve the shopping experience on the Affordable Care Act’s marketplaces by offering decision support tools that help consumers better understand and compare their health plan options. Cost estimators are one such tool. They are designed to provide consumers a personalized estimate of the total cost--premium, minus subsidy, plus cost-sharing--of their coverage options. Cost estimators were available in most states by the start of the fourth open enrollment period. Goal: To understand the experiences of marketplaces that offer a total cost estimator and the interests and concerns of policymakers from states that are not using them. Methods: Structured interviews with marketplace officials, consumer enrollment assisters, technology vendors, and subject matter experts; analysis of the total cost estimators available on the marketplaces as of October 2016. Key findings and conclusions: Informants strongly supported marketplace adoption of a total cost estimator. Marketplaces that offer an estimator faced a range of design choices and varied significantly in their approaches to resolving them. Interviews suggested a clear need for additional consumer testing and data analysis of tool usage and for sustained outreach to enrollment assisters to encourage greater use of the estimators.

Benefits of using customized instrumentation in total knee arthroplasty: results from an activity-based costing model.

Science.gov (United States)

Tibesku, Carsten O; Hofer, Pamela; Portegies, Wesley; Ruys, C J M; Fennema, Peter

2013-03-01

The growing demand for total knee arthroplasty (TKA) associated with the efforts to contain healthcare expenditure by advanced economies necessitates the use of economically effective technologies in TKA. The present analysis based on activity-based costing (ABC) model was carried out to estimate the economic value of patient-matched instrumentation (PMI) compared to standard surgical instrumentation in TKA. The costs of the two approaches, PMI and standard instrumentation in TKA, were determined by the use of ABC which measures the cost of a particular procedure by determining the activities involved and adding the cost of each activity. Improvement in productivity due to increased operating room (OR) turn-around times was determined and potential additional revenue to the hospital by the efficient utilization of gained OR time was estimated. Increased efficiency in the usage of OR and utilization of surgical trays were noted with patient-specific approach. Potential revenues to the hospital were estimated with the use of PMI by efficient utilization of time saved in OR. Additional revenues of 78,240 per year were estimated considering utilization of gained OR time to perform surgeries other than TKA. The analysis suggests that use of PMI in TKA is economically effective when compared to standard instrumentation.

Nucleic Acid Extraction from Synthetic Mars Analog Soils for in situ Life Detection

Science.gov (United States)

Mojarro, Angel; Ruvkun, Gary; Zuber, Maria T.; Carr, Christopher E.

2017-08-01

Biological informational polymers such as nucleic acids have the potential to provide unambiguous evidence of life beyond Earth. To this end, we are developing an automated in situ life-detection instrument that integrates nucleic acid extraction and nanopore sequencing: the Search for Extra-Terrestrial Genomes (SETG) instrument. Our goal is to isolate and determine the sequence of nucleic acids from extant or preserved life on Mars, if, for example, there is common ancestry to life on Mars and Earth. As is true of metagenomic analysis of terrestrial environmental samples, the SETG instrument must isolate nucleic acids from crude samples and then determine the DNA sequence of the unknown nucleic acids. Our initial DNA extraction experiments resulted in low to undetectable amounts of DNA due to soil chemistry-dependent soil-DNA interactions, namely adsorption to mineral surfaces, binding to divalent/trivalent cations, destruction by iron redox cycling, and acidic conditions. Subsequently, we developed soil-specific extraction protocols that increase DNA yields through a combination of desalting, utilization of competitive binders, and promotion of anaerobic conditions. Our results suggest that a combination of desalting and utilizing competitive binders may establish a "universal" nucleic acid extraction protocol suitable for analyzing samples from diverse soils on Mars.

Scaffolding along Nucleic Acid Duplexes Using 2'-Amino-Locked Nucleic Acids

DEFF Research Database (Denmark)

Astakhova, I Kira; Wengel, Jesper

2014-01-01

-LNA nucleotides. By application of different chemical reactions, modification of 2'-amino-LNA scaffolds can be efficiently performed in high yields and with various tags, postsynthetically or during the automated oligonucleotide synthesis. The choice of a synthetic method for scaffolding along 2'-amino-LNA mainly....../DNA probes bind nucleic acid targets with advantages of high affinity and specificity. Thus, molecular motion of nanodevices and programmable self-assembly of chemically modified LNA/DNA nanomaterials can be followed by bright fluorescence signaling from the functionalized LNA units. Another appealing aspect...

Effect of prospective reimbursement on nursing home costs.

Science.gov (United States)

Coburn, A F; Fortinsky, R; McGuire, C; McDonald, T P

1993-04-01

This study evaluates the effect of Maine's Medicaid nursing home prospective payment system on nursing home costs and access to care for public patients. The implementation of a facility-specific prospective payment system for nursing homes provided the opportunity for longitudinal study of the effect of that system. Data sources included audited Medicaid nursing home cost reports, quality-of-care data from state facility survey and licensure files, and facility case-mix information from random, stratified samples of homes and residents. Data were obtained for six years (1979-1985) covering the three-year period before and after implementation of the prospective payment system. This study used a pre-post, longitudinal analytical design in which interrupted, time-series regression models were estimated to test the effects of prospective payment and other factors, e.g., facility characteristics, nursing home market factors, facility case mix, and quality of care, on nursing home costs. Prospective payment contributed to an estimated $3.03 decrease in total variable costs in the third year from what would have been expected under the previous retrospective cost-based payment system. Responsiveness to payment system efficiency incentives declined over the study period, however, indicating a growing problem in achieving further cost reductions. Some evidence suggested that cost reductions might have reduced access for public patients. Study findings are consistent with the results of other studies that have demonstrated the effectiveness of prospective payment systems in restraining nursing home costs. Potential policy trade-offs among cost containment, access, and quality assurance deserve further consideration, particularly by researchers and policymakers designing the new generation of case mix-based and other nursing home payment systems.

Changes in Energy Cost and Total External Work of Muscles in Elite Race Walkers Walking at Different Speeds

Directory of Open Access Journals (Sweden)

Chwała Wiesław

2014-12-01

Full Text Available The aim of the study was to assess energy cost and total external work (total energy depending on the speed of race walking. Another objective was to determine the contribution of external work to total energy cost of walking at technical, threshold and racing speed in elite competitive race walkers.

Design of polymer motifs for nucleic acid recognition and assembly stabilization

Science.gov (United States)

Zhou, Zhun

This dissertation describes the synthesis and assembly of bio-functional polymers and the applications of these polymers to drug encapsulation, delivery, and multivalent biomimetic macromolecular recognition between synthetic polymer and nucleic acids. The main content is divided into three parts: (1) polyacidic domains as strongly stabilizing design elements for aqueous phase polyacrylate diblock assembly; (2) small molecule/polymer recognition triggered macromolecular assembly and drug encapsulation; (3) trizaine derivatized polymer as a novel class of "bifacial polymer nucleic acid" (bPoNA) and applications of bPoNA to nanoparticle loading of DNA/RNA, silencing delivery as well as control of aptamer function. Through the studies in part (1) and part (2), it was demonstrated that well-designed polymer motifs are not only able to enhance assemblies driven by non-specific hydrophobic effect, but are also able to direct assemblies based on specific recognitions. In part (3) of this dissertation, this concept was further extended by the design of polyacrylate polymers that are capable of discrete and robust hybridization with nucleic acids. This surprising finding demonstrated both fundamental and practical applications. Overall, these studies provided insights into the rational design elements for improving the bio-functions of synthetic polymers, and significantly expanded the scope of biological applications in which polymers synthesized via controlled radical polymerization may play a role.

Novel fluorescent nanoparticles for ultrasensitive identification of nucleic acids by optical methods

DEFF Research Database (Denmark)

Mulberg, Mads Westergaard; Taskova, Maria; Thomsen, Rasmus P.

2017-01-01

For decades, the detection of nucleic acids and their interactions at low abundances has been a challenging task. Present nucleic acid diagnostics are primarily based on enzymatic reactions including sequencing, polymerase-chain reaction and microarrays. However, the use of enzymatic amplificatio...

A cost-effectiveness analysis of a multimedia learning education program for stoma patients.

Science.gov (United States)

Lo, Shu-Fen; Wang, Yun-Tung; Wu, Li-Yue; Hsu, Mei-Yu; Chang, Shu-Chuan; Hayter, Mark

2010-07-01

The purpose of this study was to compare the costs and effectiveness of enterostomal education using a multimedia learning education program (MLEP) and a conventional education service program (CESP). Multimedia health education programs not only provide patients with useful information in the absence of health professionals, but can also augment information provided in traditional clinical practice. However, the literature on the cost-effectiveness of different approaches to stoma education is limited. This study used a randomised experimental design. A total of 54 stoma patients were randomly assigned to MLEP or CESP nursing care with a follow-up of one week. Effectiveness measures were knowledge of self-care (KSC), attitude of self-care (ASC) and behavior of self-care (BSC). The costs measures for each patient were: health care costs, MLEP cost and family costs. Subjects in the MLEP group demonstrated significantly better outcomes in the effectiveness measures of KSC, ASC and BSC. Additionally, the total social costs for each MLEP patient and CESP patient were US$7396·90 and US$8570·54, respectively. The cost-effectiveness ratios in these two groups showed that the MLEP model was better than the CESP model after one intervention cycle. In addition, the Incremental Cost Effectiveness Ratio was -20·99. This research provides useful information for those who would like to improve the self-care capacity of stoma patients. Due to the better cost-effectiveness ratio of MLEP, hospital policy-makers may consider these results when choosing to allocate resources and develop care and educational interventions. This study provides a cost effective way of addressing stoma care in the post-operative period that could be usefully transferred to stoma care settings internationally. © 2009 The Authors. Journal compilation © 2009 Blackwell Publishing Ltd.

Nucleic acid compositions and the encoding proteins

Science.gov (United States)

Preston, III, James F.; Chow, Virginia; Nong, Guang; Rice, John D.; St. John, Franz J.

2014-09-02

The subject invention provides at least one nucleic acid sequence encoding an aldouronate-utilization regulon isolated from Paenibacillus sp. strain JDR-2, a bacterium which efficiently utilizes xylan and metabolizes aldouronates (methylglucuronoxylosaccharides). The subject invention also provides a means for providing a coordinately regulated process in which xylan depolymerization and product assimilation are coupled in Paenibacillus sp. strain JDR-2 to provide a favorable system for the conversion of lignocellulosic biomass to biobased products. Additionally, the nucleic acid sequences encoding the aldouronate-utilization regulon can be used to transform other bacteria to form organisms capable of producing a desired product (e.g., ethanol, 1-butanol, acetoin, 2,3-butanediol, 1,3-propanediol, succinate, lactate, acetate, malate or alanine) from lignocellulosic biomass.

Cost-effectiveness of pharmacotherapy to reduce obesity.

Directory of Open Access Journals (Sweden)

J Lennert Veerman

Full Text Available AIMS: Obesity causes a high disease burden in Australia and across the world. We aimed to analyse the cost-effectiveness of weight reduction with pharmacotherapy in Australia, and to assess its potential to reduce the disease burden due to excess body weight. METHODS: We constructed a multi-state life-table based Markov model in Excel in which body weight influences the incidence of stroke, ischemic heart disease, hypertensive heart disease, diabetes mellitus, osteoarthritis, post-menopausal breast cancer, colon cancer, endometrial cancer and kidney cancer. We use data on effectiveness identified from PubMed searches, on mortality from Australian Bureau of Statistics, on disease costs from the Australian Institute of Health and Welfare, and on drug costs from the Department of Health and Ageing. We evaluate 1-year pharmacological interventions with sibutramine and orlistat targeting obese Australian adults free of obesity-related disease. We use a lifetime horizon for costs and health outcomes and a health sector perspective for costs. Incremental Cost-Effectiveness Ratios (ICERs below A$50 000 per Disability Adjusted Life Year (DALY averted are considered good value for money. RESULTS: The ICERs are A$130 000/DALY (95% uncertainty interval [UI] 93 000-180 000 for sibutramine and A$230 000/DALY (170 000-340 000 for orlistat. The interventions reduce the body weight-related disease burden at the population level by 0.2% and 0.1%, respectively. Modest weight loss during the interventions, rapid post-intervention weight regain and low adherence limit the health benefits. CONCLUSIONS: Treatment with sibutramine or orlistat is not cost-effective from an Australian health sector perspective and has a negligible impact on the total body weight-related disease burden.

Cost effective reductions in the agricultural load of nitrogen to the Baltic Sea

Energy Technology Data Exchange (ETDEWEB)

Elofsson, K.

1997-11-01

To restore the health of the Baltic Sea, the Helsinki Commission, HELCOM, suggests that the nitrogen load should be reduced by 50%. The agricultural sector accounts for about 1/3 of the total load of nitrogen to the Baltic Sea, while point sources account for about 1/4. The remaining load reaches the Baltic as atmospheric deposition. The purpose of this study is to calculate cost effective reductions in the agricultural load of nitrogen to the Baltic Sea coastal waters. The Baltic Sea drainage basin is divided into 17 regions, which differ with respect to costs, leaching and nitrogen retention. For each region, cost functions are estimated for 11 nitrogen abatement measures in the agricultural sector. It is difficult to find reliable data on both costs and biological parameters for all regions included, and several assumptions are made to obtain the cost functions. In this paper the total cost of a 50% reduction of the nitrogen load from arable land is estimated to 11,700 million SEK per year. A decrease in the use of fertilizer nitrogen is the most important measure in a cost effective policy. Other measures included in the cost effective solution are changes in land-use and in manure management practices. If, instead, each country is required to reduce its load by 50%, the total cost will increase by nearly 60%. Three out of nine countries around the Baltic Sea would gain from separate reduction targets, while all others lose by such a policy. The results are sensitive to assumptions about the biological parameters and the shape of the cost functions for reductions in chemical fertilizer. 75 refs, 3 figs, 11 tabs

Cost-effectiveness of surgical interventions for the management of osteoarthritis: a systematic review of the literature.

Science.gov (United States)

Kamaruzaman, Hanin; Kinghorn, Philip; Oppong, Raymond

2017-05-10

The primary purpose of this study is to assess the existing evidence on the cost-effectiveness of surgical interventions for the management of knee and hip osteoarthritis by systematically reviewing published economic evaluation studies. A systematic review was conducted for the period 2004 to 2016. Electronic databases were searched to identify both trial and model based economic evaluation studies that evaluated surgical interventions for knee and hip osteoarthritis. A total of 23 studies met the inclusion criteria and an assessment of these studies showed that total knee arthroplasty (TKA), and total hip arthroplasty (THA) showed evidence of cost-effectiveness and improvement in quality of life of the patients when compared to non-operative and non-surgical procedures. On the other hand, even though delaying TKA and THA may lead to some cost savings in the short-run, the results from the study showed that this was not a cost-effective option. TKA and THA are cost-effective and should be recommended for the management of patients with end stage/severe knee and hip OA. However, there needs to be additional studies to assess the cost-effectiveness of other surgical interventions in order for definite conclusions to be reached.

Analysis of the total system life cycle cost for the Civilian Radioactive Waste Management Program: Volume 2, Supporting information

International Nuclear Information System (INIS)

1987-06-01

This report provides cost estimates for the fifth evaluation of the adequacy of the fee and is consistent with the program strategy and plans. The total-system cost for the reference cases in the improved-performance system is estimated at $32.1 to $38.2 billion (expressed in constant 1986 collars) over the entire life of the system, or $1.5 to $1.6 billion more than that of the authorized system (i.e., the system without an MRS facility). The current estimate of the total-system cost for the reference cases in the improved-performance system is $3.8 to $5.4 billion higher than the estimate for the same system in the 1986 TSLCC analysis. In the case with the maximum increase, nearly all of the higher cost is due to a $5.2-billion increase in the costs of development and evaluation (D and E); all other system costs are essentially unchanged. The cost difference between the improved-performance system and the authorized system is smaller than the difference estimated in last year's TSLCC analysis. Volume 2 presents the detailed results for the 1987 analysis of the total-system life cycle cost (TSLCC). It consists of four sections: Section A presents the yearly flows of waste between waste-management facilities for the 12 aggregate logistics cases that were studied; Section B presents the annual total-system costs for each of the 30 TSLCC cases by major cost category; Section C presents the annual costs for the disposal of 16,000 canisters of defense high-level waste (DHLW) by major cost category for each of the 30 TSLCC cases; and Section D presents a summary of the cost-allocation factors that were calculated to determine the defense waste share of the total-system costs

Cost Analysis of Total Joint Arthroplasty Readmissions in a Bundled Payment Care Improvement Initiative.

Science.gov (United States)

Clair, Andrew J; Evangelista, Perry J; Lajam, Claudette M; Slover, James D; Bosco, Joseph A; Iorio, Richard

2016-09-01

The Bundled Payment for Care Improvement (BPCI) Initiative is a Centers for Medicare and Medicaid Services program designed to promote coordinated and efficient care. This study seeks to report costs of readmissions within a 90-day episode of care for BPCI Initiative patients receiving total knee arthroplasty (TKA) or total hip arthroplasty (THA). From January 2013 through December 2013, 1 urban, tertiary, academic orthopedic hospital admitted 664 patients undergoing either primary TKA or THA through the BPCI Initiative. All patients readmitted to our hospital or an outside hospital within 90-days from the index episode were identified. The diagnosis and cost for each readmission were analyzed. Eighty readmissions in 69 of 664 patients (10%) were identified within 90-days. There were 53 readmissions (45 patients) after THA and 27 readmissions (24 patients) after TKA. Surgical complications accounted for 54% of THA readmissions and 44% of TKA readmissions. These complications had an average cost of $36,038 (range, $6375-$60,137) for THA and $38,953 (range, $4790-$104,794) for TKA. Eliminating the TKA outlier of greater than $100,000 yields an average cost of $27,979. Medical complications of THA and TKA had an average cost of $22,775 (range, $5678-$82,940) for THA and $24,183 (range, $3306-$186,069) for TKA. Eliminating the TKA outlier of greater than $100,000 yields an average cost of $11,682. Hospital readmissions after THA and TKA are common and costly. Identifying the causes for readmission and assessing the cost will guide quality improvement efforts. Copyright © 2016 Elsevier Inc. All rights reserved.

An integrated portable hand-held analyser for real-time isothermal nucleic acid amplification

International Nuclear Information System (INIS)

Smith, Matthew C.; Steimle, George; Ivanov, Stan; Holly, Mark; Fries, David P.

2007-01-01

A compact hand-held heated fluorometric instrument for performing real-time isothermal nucleic acid amplification and detection is described. The optoelectronic instrument combines a Printed Circuit Board/Micro Electro Mechanical Systems (PCB/MEMS) reaction detection/chamber containing an integrated resistive heater with attached miniature LED light source and photo-detector and a disposable glass waveguide capillary to enable a mini-fluorometer. The fluorometer is fabricated and assembled in planar geometry, rolled into a tubular format and packaged with custom control electronics to form the hand-held reactor. Positive or negative results for each reaction are displayed to the user using an LED interface. Reaction data is stored in FLASH memory for retrieval via an in-built USB connection. Operating on one disposable 3 V lithium battery >12, 60 min reactions can be performed. Maximum dimensions of the system are 150 mm (h) x 48 mm (d) x 40 mm (w), the total instrument weight (with battery) is 140 g. The system produces comparable results to laboratory instrumentation when performing a real-time nucleic acid sequence-based amplification (NASBA) reaction, and also displayed comparable precision, accuracy and resolution to laboratory-based real-time nucleic acid amplification instrumentation. A good linear response (R 2 = 0.948) to fluorescein gradients ranging from 0.5 to 10 μM was also obtained from the instrument indicating that it may be utilized for other fluorometric assays. This instrument enables an inexpensive, compact approach to in-field genetic screening, providing results comparable to laboratory equipment with rapid user feedback as to the status of the reaction

An integrated portable hand-held analyser for real-time isothermal nucleic acid amplification

Energy Technology Data Exchange (ETDEWEB)

Smith, Matthew C. [College of Marine Science, University of South Florida, St Petersburg, FL (United States)], E-mail: msmith@marine.usf.edu; Steimle, George; Ivanov, Stan; Holly, Mark; Fries, David P. [College of Marine Science, University of South Florida, St Petersburg, FL (United States)

2007-08-29

A compact hand-held heated fluorometric instrument for performing real-time isothermal nucleic acid amplification and detection is described. The optoelectronic instrument combines a Printed Circuit Board/Micro Electro Mechanical Systems (PCB/MEMS) reaction detection/chamber containing an integrated resistive heater with attached miniature LED light source and photo-detector and a disposable glass waveguide capillary to enable a mini-fluorometer. The fluorometer is fabricated and assembled in planar geometry, rolled into a tubular format and packaged with custom control electronics to form the hand-held reactor. Positive or negative results for each reaction are displayed to the user using an LED interface. Reaction data is stored in FLASH memory for retrieval via an in-built USB connection. Operating on one disposable 3 V lithium battery >12, 60 min reactions can be performed. Maximum dimensions of the system are 150 mm (h) x 48 mm (d) x 40 mm (w), the total instrument weight (with battery) is 140 g. The system produces comparable results to laboratory instrumentation when performing a real-time nucleic acid sequence-based amplification (NASBA) reaction, and also displayed comparable precision, accuracy and resolution to laboratory-based real-time nucleic acid amplification instrumentation. A good linear response (R{sup 2} = 0.948) to fluorescein gradients ranging from 0.5 to 10 {mu}M was also obtained from the instrument indicating that it may be utilized for other fluorometric assays. This instrument enables an inexpensive, compact approach to in-field genetic screening, providing results comparable to laboratory equipment with rapid user feedback as to the status of the reaction.

Linking the spare parts management with the total costs of ownership: An agenda for future research

Directory of Open Access Journals (Sweden)

Orlando Duran

2016-12-01

Full Text Available Purpose: This manuscript explores the link between Spare Parts Management and Total Costs of Ownership or Life Cycle Costs (LCC. Design/methodology/approach: First, this work enumerates the different managerial decisions instances in spare parts management that are present during the life cycle of a physical asset. Second, we analyse how those decision instances could affect the TCO of a physical asset (from the economic point of view. Finally, we propose a conceptual framework for incorporating the spare parts management into a TCO model. Findings: The recent literature lacks discussions on the integration of spare parts management with the Total Costs of Ownership (TCO. Based in an extensive literature revision we can declare that the computation of costs related to spare parts management has been neglected by TCO models. Originality/value: The contribution of this paper is twofold. First, a literature review and identification of a series of spare parts management decision instances and its relationship with TCOs is presented in this paper. Second, a conceptual framework is suggested for linking those decisions instances to a total cost of ownership perspective. Some research questions and future research challenges are presented at the end of this work.

Linking the spare parts management with the total costs of ownership: An agenda for future research

International Nuclear Information System (INIS)

Duran, O.; Roda, I.; Macchi, M.

2016-01-01

Purpose: This manuscript explores the link between Spare Parts Management and Total Costs of Ownership or Life Cycle Costs (LCC). Design/methodology/approach: First, this work enumerates the different managerial decisions instances in spare parts management that are present during the life cycle of a physical asset. Second, we analyse how those decision instances could affect the TCO of a physical asset (from the economic point of view). Finally, we propose a conceptual framework for incorporating the spare parts management into a TCO model. Findings: The recent literature lacks discussions on the integration of spare parts management with the Total Costs of Ownership (TCO). Based in an extensive literature revision we can declare that the computation of costs related to spare parts management has been neglected by TCO models. Originality/value: The contribution of this paper is twofold. First, a literature review and identification of a series of spare parts management decision instances and its relationship with TCOs is presented in this paper. Second, a conceptual framework is suggested for linking those decisions instances to a total cost of ownership perspective. Some research questions and future research challenges are presented at the end of this work.

Linking the spare parts management with the total costs of ownership: An agenda for future research

Energy Technology Data Exchange (ETDEWEB)

Duran, O.; Roda, I.; Macchi, M.

2016-07-01

Purpose: This manuscript explores the link between Spare Parts Management and Total Costs of Ownership or Life Cycle Costs (LCC). Design/methodology/approach: First, this work enumerates the different managerial decisions instances in spare parts management that are present during the life cycle of a physical asset. Second, we analyse how those decision instances could affect the TCO of a physical asset (from the economic point of view). Finally, we propose a conceptual framework for incorporating the spare parts management into a TCO model. Findings: The recent literature lacks discussions on the integration of spare parts management with the Total Costs of Ownership (TCO). Based in an extensive literature revision we can declare that the computation of costs related to spare parts management has been neglected by TCO models. Originality/value: The contribution of this paper is twofold. First, a literature review and identification of a series of spare parts management decision instances and its relationship with TCOs is presented in this paper. Second, a conceptual framework is suggested for linking those decisions instances to a total cost of ownership perspective. Some research questions and future research challenges are presented at the end of this work.

The true costs of participatory sanitation: Evidence from community-led total sanitation studies in Ghana and Ethiopia.

Science.gov (United States)

Crocker, Jonny; Saywell, Darren; Shields, Katherine F; Kolsky, Pete; Bartram, Jamie

2017-12-01

Evidence on sanitation and hygiene program costs is used for many purposes. The few studies that report costs use top-down costing methods that are inaccurate and inappropriate. Community-led total sanitation (CLTS) is a participatory behavior-change approach that presents difficulties for cost analysis. We used implementation tracking and bottom-up, activity-based costing to assess the process, program costs, and local investments for four CLTS interventions in Ghana and Ethiopia. Data collection included implementation checklists, surveys, and financial records review. Financial costs and value-of-time spent on CLTS by different actors were assessed. Results are disaggregated by intervention, cost category, actor, geographic area, and project month. The average household size was 4.0 people in Ghana, and 5.8 people in Ethiopia. The program cost of CLTS was $30.34-$81.56 per household targeted in Ghana, and $14.15-$19.21 in Ethiopia. Most program costs were from training for three of four interventions. Local investments ranged from $7.93-$22.36 per household targeted in Ghana, and $2.35-$3.41 in Ethiopia. This is the first study to present comprehensive, disaggregated costs of a sanitation and hygiene behavior-change intervention. The findings can be used to inform policy and finance decisions, plan program scale-up, perform cost-effectiveness and benefit studies, and compare different interventions. The costing method is applicable to other public health behavior-change programs. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Cost-Effectiveness Analysis of Isavuconazole vs. Voriconazole as First-Line Treatment for Invasive Aspergillosis.

Science.gov (United States)

Harrington, Rachel; Lee, Edward; Yang, Hongbo; Wei, Jin; Messali, Andrew; Azie, Nkechi; Wu, Eric Q; Spalding, James

2017-01-01

Invasive aspergillosis (IA) is associated with a significant clinical and economic burden. The phase III SECURE trial demonstrated non-inferiority in clinical efficacy between isavuconazole and voriconazole. No studies have evaluated the cost-effectiveness of isavuconazole compared to voriconazole. The objective of this study was to evaluate the costs and cost-effectiveness of isavuconazole vs. voriconazole for the first-line treatment of IA from the US hospital perspective. An economic model was developed to assess the costs and cost-effectiveness of isavuconazole vs. voriconazole in hospitalized patients with IA. The time horizon was the duration of hospitalization. Length of stay for the initial admission, incidence of readmission, clinical response, overall survival rates, and experience of adverse events (AEs) came from the SECURE trial. Unit costs were from the literature. Total costs per patient were estimated, composed of drug costs, costs of AEs, and costs of hospitalizations. Incremental costs per death avoided and per additional clinical responders were reported. Deterministic and probabilistic sensitivity analyses (DSA and PSA) were conducted. Base case analysis showed that isavuconazole was associated with a $7418 lower total cost per patient than voriconazole. In both incremental costs per death avoided and incremental costs per additional clinical responder, isavuconazole dominated voriconazole. Results were robust in sensitivity analysis. Isavuconazole was cost saving and dominant vs. voriconazole in most DSA. In PSA, isavuconazole was cost saving in 80.2% of the simulations and cost-effective in 82.0% of the simulations at the $50,000 willingness to pay threshold per additional outcome. Isavuconazole is a cost-effective option for the treatment of IA among hospitalized patients. Astellas Pharma Global Development, Inc.

Blood Transfusion During Total Ankle Arthroplasty Is Associated With Increased In-Hospital Complications and Costs.

Science.gov (United States)

Ewing, Michael A; Huntley, Samuel R; Baker, Dustin K; Smith, Kenneth S; Hudson, Parke W; McGwin, Gerald; Ponce, Brent A; Johnson, Michael D

2018-04-01

Total ankle arthroplasty (TAA) is an increasingly used, effective treatment for end-stage ankle arthritis. Although numerous studies have associated blood transfusion with complications following hip and knee arthroplasty, its effects following TAA are largely unknown. This study uses data from a large, nationally representative database to estimate the association between blood transfusion and inpatient complications and hospital costs following TAA. Using the Nationwide Inpatient Sample (NIS) database from 2004 to 2014, 25 412 patients who underwent TAA were identified, with 286 (1.1%) receiving a blood transfusion. Univariate analysis assessed patient and hospital factors associated with blood transfusion following TAA. Patients requiring blood transfusion were more likely to be female, African American, Medicare recipients, and treated in nonteaching hospitals. Average length of stay for patients following transfusion was 3.0 days longer, while average inpatient cost was increased by approximately 50%. Patients who received blood transfusion were significantly more likely to suffer from congestive heart failure, peripheral vascular disease, hypothyroidism, coagulation disorder, or anemia. Acute renal failure was significantly more common among patients receiving blood transfusion ( P < .001). Blood transfusions following TAA are infrequent and are associated with multiple medical comorbidities, increased complications, longer hospital stays, and increased overall cost. Level III: Retrospective, comparative study.

Costs and Cost-Effectiveness of Plasmodium vivax Control.

Science.gov (United States)

White, Michael T; Yeung, Shunmay; Patouillard, Edith; Cibulskis, Richard

2016-12-28

The continued success of efforts to reduce the global malaria burden will require sustained funding for interventions specifically targeting Plasmodium vivax The optimal use of limited financial resources necessitates cost and cost-effectiveness analyses of strategies for diagnosing and treating P. vivax and vector control tools. Herein, we review the existing published evidence on the costs and cost-effectiveness of interventions for controlling P. vivax, identifying nine studies focused on diagnosis and treatment and seven studies focused on vector control. Although many of the results from the much more extensive P. falciparum literature can be applied to P. vivax, it is not always possible to extrapolate results from P. falciparum-specific cost-effectiveness analyses. Notably, there is a need for additional studies to evaluate the potential cost-effectiveness of radical cure with primaquine for the prevention of P. vivax relapses with glucose-6-phosphate dehydrogenase testing. © The American Society of Tropical Medicine and Hygiene.

Cost-effectiveness of telemonitoring of diabetic foot ulcer patients

DEFF Research Database (Denmark)

Fasterholdt, Iben; Gerstrøm, Marie; Rasmussen, Benjamin Schnack Brandt

2016-01-01

This study compared the cost-effectiveness of telemonitoring with standard monitoring for patients with diabetic foot ulcers. The economic evaluation was nested within a pragmatic randomised controlled trial. A total of 374 patients were randomised to either telemonitoring or standard monitoring...

Effects of nucleic acid local structure and magnesium ions on minus-strand transfer mediated by the nucleic acid chaperone activity of HIV-1 nucleocapsid protein

OpenAIRE

Wu, Tiyun; Heilman-Miller, Susan L.; Levin, Judith G.

2007-01-01

HIV-1 nucleocapsid protein (NC) is a nucleic acid chaperone, which is required for highly specific and efficient reverse transcription. Here, we demonstrate that local structure of acceptor RNA at a potential nucleation site, rather than overall thermodynamic stability, is a critical determinant for the minus-strand transfer step (annealing of acceptor RNA to (−) strong-stop DNA followed by reverse transcriptase (RT)-catalyzed DNA extension). In our system, destabilization of a stem-loop stru...

Cost-effectiveness of the SEN-concept: Specialized Emergency Nurses (SEN treating ankle/foot injuries

Directory of Open Access Journals (Sweden)

van Tulder Maurits W

2007-10-01

Full Text Available Abstract Background Emergency Departments (EDs are confronted with progressive overcrowding. As a consequence, the workload for ED physicians increases and waiting times go up with the risk of unnecessary complications and patient dissatisfaction. To cope with these problems, Specialized Emergency Nurses (SENs, regular ED-nurses receiving a short, injury-specific course, were trained to assess and treat minor injuries according to a specific protocol. Methods An economic evaluation was conducted alongside a randomized controlled trial comparing House Officers (HOs and SENs in their assessment of ankle and foot injuries. Cost prices were established for all parts of healthcare utilization involved. Total costs of health care utilization were computed per patient in both groups. Cost-effectiveness was investigated by comparing the difference in total cost between groups with the difference in sensitivity and specificity between groups in diagnosing fractures and severe sprains. Finally, cost-effectiveness ratios were calculated and presented on a cost-effectiveness plane. Results No significant differences were seen between treatment groups for any of the health care resources assessed. However, the waiting times for both first assessment by a treatment officer and time spent waiting between hearing the diagnosis and final treatment were significantly longer in the HO group. There was no statistically significant difference in costs between groups. The total costs were € 186 (SD € 623 for patients in the SEN group and € 153 (SD € 529 for patients in the HO group. The difference in total costs was € 33 (95% CI: – € 84 to € 155. The incremental cost-effectiveness ratio was € 27 for a reduction of one missed diagnosis and € 18 for a reduction of one false negative. Conclusion Considering the benefits of the SEN-concept in terms of decreased workload for the ED physicians, increased patient satisfaction and decreased waiting times

Functional and oncologic outcomes after excision of the total femur in primary bone tumors: Results with a low cost total femur prosthesis

Directory of Open Access Journals (Sweden)

Ajay Puri

2012-01-01

Full Text Available Background: The extent of tumor may necessitate resection of the complete femur rarely to achieve adequate oncologic clearance in bone sarcomas. We present our experience with reconstruction in such cases using an indigenously manufactured, low-cost, total femoral prosthesis (TFP. We assessed the complications of the procedure, the oncologic and functional outcomes, and implant survival. Materials and Methods: Eight patients (four males and four females with a mean age of 32 years, operated between December 2003 and June 2009, had a TFP implanted. The diagnosis included osteogenic sarcoma (5, Ewing′s sarcoma (1, and chondrosarcoma (2. Mean followup was 33 months (9-72 months for all and 40 months (24-72 months in survivors. They were evaluated by Musculoskeletal Tumor Society score, implant survival as well as patient survival. Results: There was one local recurrence and five of seven patients are currently alive at the time of last followup. The Musculoskeletal Tumor Society score for patients ranged from 21 to 25 with a mean of 24 (80%. The implant survival was 88% at 5 years with only one TFP needing removal because of infection. Conclusions: A TFP in appropriately indicated patients with malignant bone tumors is oncologically safe. A locally manufactured, cost-effective implant provided consistent and predictable results after excision of the total femur with good functional outcomes.

Integrated and Person-Centered Care for Community-Living Older Adults: A Cost-Effectiveness Study.

Science.gov (United States)

Uittenbroek, Ronald J; van Asselt, Antoinette D I; Spoorenberg, Sophie L W; Kremer, Hubertus P H; Wynia, Klaske; Reijneveld, Sijmen A

2018-03-24

To assess the cost-effectiveness of Embrace, an integrated primary care service for older adults. Care and support claims from health care insurers, long-term care administration, and municipalities for enrolled older adults between 2011 and 2013. A total of 1,456 older adults, listed with 15 general practitioners practices in the Netherlands, were stratified into risk profiles ("Robust," "Frail," and "Complex care needs") and randomized to Embrace or care-as-usual groups. Incremental costs were calculated per quality-adjusted life year, per day able to age in place, and per percentage point risk profile improvement. Total average costs were higher for Embrace compared to care-as-usual. Differences in health-associated outcomes were small and not statistically significant. Probabilities that Embrace is cost-effective were below 80 percent, except for "risk profile improvements" within risk profile "Complex care needs." Complete case analysis resulted in smaller differences in total average costs across conditions and differences in health-associated outcomes remained small. According to current standards, Embrace is not considered cost effective after 12 months. However, it could be considered worthwhile in terms of "risk profile improvements" for older adults with "Complex care needs," if society is willing to invest substantially. © Health Research and Educational Trust.

Logic gates and antisense DNA devices operating on a translator nucleic Acid scaffold.

Science.gov (United States)

Shlyahovsky, Bella; Li, Yang; Lioubashevski, Oleg; Elbaz, Johann; Willner, Itamar

2009-07-28

A series of logic gates, "AND", "OR", and "XOR", are designed using a DNA scaffold that includes four "footholds" on which the logic operations are activated. Two of the footholds represent input-recognition strands, and these are blocked by complementary nucleic acids, whereas the other two footholds are blocked by nucleic acids that include the horseradish peroxidase (HRP)-mimicking DNAzyme sequence. The logic gates are activated by either nucleic acid inputs that hybridize to the respective "footholds", or by low-molecular-weight inputs (adenosine monophosphate or cocaine) that yield the respective aptamer-substrate complexes. This results in the respective translocation of the blocking nucleic acids to the footholds carrying the HRP-mimicking DNAzyme sequence, and the concomitant release of the respective DNAzyme. The released product-strands then self-assemble into the hemin/G-quadruplex-HRP-mimicking DNAzyme that biocatalyzes the formation of a colored product and provides an output signal for the different logic gates. The principle of the logic operation is, then, implemented as a possible paradigm for future nanomedicine. The nucleic acid inputs that bind to the blocked footholds result in the translocation of the blocking nucleic acids to the respective footholds carrying the antithrombin aptamer. The released aptamer inhibits, then, the hydrolytic activity of thrombin. The system demonstrates the regulation of a biocatalytic reaction by a translator system activated on a DNA scaffold.

Structure, stability and behaviour of nucleic acids in ionic liquids

Science.gov (United States)

Tateishi-Karimata, Hisae; Sugimoto, Naoki

2014-01-01

Nucleic acids have become a powerful tool in nanotechnology because of their conformational polymorphism. However, lack of a medium in which nucleic acid structures exhibit long-term stability has been a bottleneck. Ionic liquids (ILs) are potential solvents in the nanotechnology field. Hydrated ILs, such as choline dihydrogen phosphate (choline dhp) and deep eutectic solvent (DES) prepared from choline chloride and urea, are ‘green’ solvents that ensure long-term stability of biomolecules. An understanding of the behaviour of nucleic acids in hydrated ILs is necessary for developing DNA materials. We here review current knowledge about the structures and stabilities of nucleic acids in choline dhp and DES. Interestingly, in choline dhp, A–T base pairs are more stable than G–C base pairs, the reverse of the situation in buffered NaCl solution. Moreover, DNA triplex formation is markedly stabilized in hydrated ILs compared with aqueous solution. In choline dhp, the stability of Hoogsteen base pairs is comparable to that of Watson–Crick base pairs. Moreover, the parallel form of the G-quadruplex is stabilized in DES compared with aqueous solution. The behaviours of various DNA molecules in ILs detailed here should be useful for designing oligonucleotides for the development of nanomaterials and nanodevices. PMID:25013178

Analyses of Blood Bank Efficiency, Cost-Effectiveness and Quality

Science.gov (United States)

Lam, Hwai-Tai Chen

In view of the increasing costs of hospital care, it is essential to investigate methods to improve the labor efficiency and the cost-effectiveness of the hospital technical core in order to control costs while maintaining the quality of care. This study was conducted to develop indices to measure efficiency, cost-effectiveness, and the quality of blood banks; to identify factors associated with efficiency, cost-effectiveness, and quality; and to generate strategies to improve blood bank labor efficiency and cost-effectiveness. Indices developed in this study for labor efficiency and cost-effectiveness were not affected by patient case mix and illness severity. Factors that were associated with labor efficiency were identified as managerial styles, and organizational designs that balance workload and labor resources. Medical directors' managerial involvement was not associated with labor efficiency, but their continuing education and specialty in blood bank were found to reduce the performance of unnecessary tests. Surprisingly, performing unnecessary tests had no association with labor efficiency. This suggested the existence of labor slack in blood banks. Cost -effectiveness was associated with workers' benefits, wages, and the production of high-end transfusion products by hospital-based donor rooms. Quality indices used in this study included autologous transfusion rates, platelet transfusion rates, and the check points available in an error-control system. Because the autologous transfusion rate was related to patient case mix, severity of illness, and possible inappropriate transfusion, it was not recommended to be used for quality index. Platelet-pheresis transfusion rates were associated with the transfusion preferences of the blood bank medical directors. The total number of check points in an error -control system was negatively associated with government ownership and workers' experience. Recommendations for improving labor efficiency and cost-effectiveness

Application of locked nucleic acid-based probes in fluorescence in situ hybridization

DEFF Research Database (Denmark)

Fontenete, Sílvia; Carvalho, Daniel R; Guimarães, Nuno

2016-01-01

of nucleic acid mimics used as mixmers in LNA-based probes strongly influence the efficiency of detection. LNA probes with 10 to 15 mers showed the highest efficiency. Additionally, the combination of 2′-OMe RNA with LNA allowed an increase on the fluorescence intensities of the probes. Overall......Fluorescence in situ hybridization (FISH) employing nucleic acid mimics as probes is becoming an emerging molecular tool in the microbiology area for the detection and visualization of microorganisms. However, the impact that locked nucleic acid (LNA) and 2′-O-methyl (2′-OMe) RNA modifications have...

Cost-Effectiveness and Cost-Utility Analysis of Ingenol Mebutate Versus Diclofenac 3% and Imiquimod 5% in the Treatment of Actinic Keratosis in Spain.

Science.gov (United States)

Elías, I; Ortega-Joaquín, N; de la Cueva, P; Del Pozo, L J; Moreno-Ramírez, D; Boada, A; Aguilar, M; Mirada, A; Mosquera, E; Gibbons, C; Oyagüez, I

2016-01-01

To perform a cost-effectiveness and cost-utility analysis of ingenol mebutate in the treatment of actinic keratosis in Spain. We used an adapted Markov model to simulate outcomes in a cohort of patients (mean age, 73 years) with actinic keratosis over a 5-year period. The comparators were diclofenac 3% and imiquimod 5%. The analysis was performed from the perspective of the Spanish National Health System based on direct costs (2015 retail price plus value added tax less the mandatory discount). A panel of experts estimated resources, taking unit costs from national databases. An annual discount rate of 3% was applied. Deterministic and probabilistic sensitivity analyses were performed. The effectiveness of ingenol mebutate-with 0.192 and 0.129 more clearances gained in treatments for face and scalp lesions and trunk and extremity lesions, respectively-was superior to diclofenac's. The total costs of treatment with ingenol mebutate were lower at € 551.50 (face and scalp) and € 622.27 (trunk and extremities) than the respective costs with diclofenac (€ 849.11 and € 844.93). The incremental cost-effectiveness and cost-utility ratios showed that ingenol mebutate was a dominant strategy vs diclofenac. Ingenol mebutate also proved to be more effective than imiquimod, based on 0.535 and 0.503 additional clearances, and total costs of € 551.50 and € 527.89 for the two drugs, respectively. The resulting incremental cost-effectiveness ratio was € 728.64 per clearance gained with ingenol mebutate vs imiquimod. Ingenol mebutate was a dominant treatment option vs diclofenac and was efficient vs imiquimod (i.e., more effective at a higher cost, achieving an incremental cost-utility ratio of<€30000/quality-adjusted life-years). Copyright © 2016 AEDV. Published by Elsevier España, S.L.U. All rights reserved.

Optimizing scoring function of protein-nucleic acid interactions with both affinity and specificity.

Directory of Open Access Journals (Sweden)

Zhiqiang Yan

Full Text Available Protein-nucleic acid (protein-DNA and protein-RNA recognition is fundamental to the regulation of gene expression. Determination of the structures of the protein-nucleic acid recognition and insight into their interactions at molecular level are vital to understanding the regulation function. Recently, quantitative computational approach has been becoming an alternative of experimental technique for predicting the structures and interactions of biomolecular recognition. However, the progress of protein-nucleic acid structure prediction, especially protein-RNA, is far behind that of the protein-ligand and protein-protein structure predictions due to the lack of reliable and accurate scoring function for quantifying the protein-nucleic acid interactions. In this work, we developed an accurate scoring function (named as SPA-PN, SPecificity and Affinity of the Protein-Nucleic acid interactions for protein-nucleic acid interactions by incorporating both the specificity and affinity into the optimization strategy. Specificity and affinity are two requirements of highly efficient and specific biomolecular recognition. Previous quantitative descriptions of the biomolecular interactions considered the affinity, but often ignored the specificity owing to the challenge of specificity quantification. We applied our concept of intrinsic specificity to connect the conventional specificity, which circumvents the challenge of specificity quantification. In addition to the affinity optimization, we incorporated the quantified intrinsic specificity into the optimization strategy of SPA-PN. The testing results and comparisons with other scoring functions validated that SPA-PN performs well on both the prediction of binding affinity and identification of native conformation. In terms of its performance, SPA-PN can be widely used to predict the protein-nucleic acid structures and quantify their interactions.

Survivin mRNA antagonists using locked nucleic acid, potential for molecular cancer therapy

DEFF Research Database (Denmark)

Fisker, Niels; Westergaard, Majken; Hansen, Henrik Frydenlund

2007-01-01

We have investigated the effects of different locked nucleic acid modified antisense mRNA antagonists against Survivin in a prostate cancer model. These mRNA antagonists were found to be potent inhibitors of Survivin expression at low nanomolar concentrations. Additionally there was a pronounced ...

Leveraging Real-World Evidence in Disease-Management Decision-Making with a Total Cost of Care Estimator.

Science.gov (United States)

Nguyen, Thanh-Nghia; Trocio, Jeffrey; Kowal, Stacey; Ferrufino, Cheryl P; Munakata, Julie; South, Dell

2016-12-01

Health management is becoming increasingly complex, given a range of care options and the need to balance costs and quality. The ability to measure and understand drivers of costs is critical for healthcare organizations to effectively manage their patient populations. Healthcare decision makers can leverage real-world evidence to explore the value of disease-management interventions in shifting total cost trends. To develop a real-world, evidence-based estimator that examines the impact of disease-management interventions on the total cost of care (TCoC) for a patient population with nonvalvular atrial fibrillation (NVAF). Data were collected from a patient-level real-world evidence data set that uses the IMS PharMetrics Health Plan Claims Database. Pharmacy and medical claims for patients meeting the inclusion or exclusion criteria were combined in longitudinal cohorts with a 180-day preindex and 360-day follow-up period. Descriptive statistics, such as mean and median patient costs and event rates, were derived from a real-world evidence analysis and were used to populate the base-case estimates within the TCoC estimator, an exploratory economic model that was designed to estimate the potential impact of several disease-management activities on the TCoC for a patient population with NVAF. Using Microsoft Excel, the estimator is designed to compare current direct costs of medical care to projected costs by varying assumptions on the impact of disease-management activities and applying the associated changes in cost trends to the affected populations. Disease-management levers are derived from literature-based concepts affecting costs along the NVAF disease continuum. The use of the estimator supports analyses across 4 US geographic regions, age, cost types, and care settings during 1 year. All patients included in the study were continuously enrolled in their health plan (within the IMS PharMetrics Health Plan Claims Database) between July 1, 2010, and June 30

Cost, cost-efficiency and cost-effectiveness of integrated family planning and HIV services.

Science.gov (United States)

Shade, Starley B; Kevany, Sebastian; Onono, Maricianah; Ochieng, George; Steinfeld, Rachel L; Grossman, Daniel; Newmann, Sara J; Blat, Cinthia; Bukusi, Elizabeth A; Cohen, Craig R

2013-10-01

To evaluate costs, cost-efficiency and cost-effectiveness of integration of family planning into HIV services. Integration of family planning services into HIV care and treatment clinics. A cluster-randomized trial. Twelve health facilities in Nyanza, Kenya were randomized to integrate family planning into HIV care and treatment; six health facilities were randomized to (nonintegrated) standard-of-care with separately delivered family planning and HIV services. We assessed costs, cost-efficiency (cost per additional use of more effective family planning), and cost-effectiveness (cost per pregnancy averted) associated with the first year of integration of family planning into HIV care. More effective family planning methods included oral and injectable contraceptives, subdermal implants, intrauterine device, and female and male sterilization. We collected cost data through interviews with study staff and review of financial records to determine costs of service integration. Integration of services was associated with an average marginal cost of $841 per site and $48 per female patient. Average overall and marginal costs of integration were associated with personnel costs [initial ($1003 vs. $872) and refresher ($498 vs. $330) training, mentoring ($1175 vs. $902) and supervision ($1694 vs. $1636)], with fewer resources required for other fixed ($18 vs. $0) and recurring expenses ($471 vs. $287). Integration was associated with a marginal cost of $65 for each additional use of more effective family planning and $1368 for each pregnancy averted. Integration of family planning and HIV services is feasible, inexpensive to implement, and cost-efficient in the Kenyan setting, and thus supports current Kenyan integration policy.

Cell-free nucleic acids as noninvasive biomarkers for colorectal cancer detection

KAUST Repository

Mansour, Hicham

2014-01-01

Cell-free nucleic acids (CFNA) have been reported by several authors in blood, stool, and urine of patients with colorectal cancer (CRC). These genetic biomarkers can be an indication of neoplastic colorectal epithelial cells, and can thus potentially be used as noninvasive tests for the detection of the disease in CRC patients and monitor their staging, without the need to use heavier and invasive tools. In a number of test-trials, these genetic tests have shown the advantage of non-invasiveness, making them well accepted by most of the patients, without major side effects. They have also shown a promising sensitivity and specificity in the detection of malignant and premalignant neoplasms. Moreover, costs for performing such tests are very low. Several studies reported and confirmed the proof of the principle for these genetic tests for screening, diagnosis, and prognosis; the main challenge of translating this approach from research to clinical laboratory is the validation from large and long-term randomized trials to prove sustainable high sensitivity and specificity. In this paper, we present a review on the noninvasive genetics biomarkers for CRC detection described in the literature and the challenges that can be encountered for validation processes.

Cell-free nucleic acids as noninvasive biomarkers for colorectal cancer detection

KAUST Repository

Mansour, Hicham

2014-08-27

Cell-free nucleic acids (CFNA) have been reported by several authors in blood, stool, and urine of patients with colorectal cancer (CRC). These genetic biomarkers can be an indication of neoplastic colorectal epithelial cells, and can thus potentially be used as noninvasive tests for the detection of the disease in CRC patients and monitor their staging, without the need to use heavier and invasive tools. In a number of test-trials, these genetic tests have shown the advantage of non-invasiveness, making them well accepted by most of the patients, without major side effects. They have also shown a promising sensitivity and specificity in the detection of malignant and premalignant neoplasms. Moreover, costs for performing such tests are very low. Several studies reported and confirmed the proof of the principle for these genetic tests for screening, diagnosis, and prognosis; the main challenge of translating this approach from research to clinical laboratory is the validation from large and long-term randomized trials to prove sustainable high sensitivity and specificity. In this paper, we present a review on the noninvasive genetics biomarkers for CRC detection described in the literature and the challenges that can be encountered for validation processes.

Cleavage and protection of locked nucleic acid-modified DNA by restriction endonucleases

DEFF Research Database (Denmark)

Crouzier, Lucile; Dubois, Camille; Wengel, Jesper

2012-01-01

Locked nucleic acid (LNA) is one of the most prominent nucleic acid analogues reported so far. We herein for the first time report cleavage by restriction endonuclease of LNA-modified DNA oligonucleotides. The experiments revealed that RsaI is an efficient enzyme capable of recognizing and cleaving...

Bis-Pyrene-Modified Unlocked Nucleic Acids: Synthesis, Hybridization Studies, and Fluorescent Properties

Czech Academy of Sciences Publication Activity Database

Perlíková, Pavla; Ejlersen, M.; Langkjaer, N.; Wengel, J.

2014-01-01

Roč. 9, č. 9 (2014), s. 2120-2127 ISSN 1860-7179 Grant - others:European Research Council(XE) FP7-268776 Institutional support: RVO:61388963 Keywords : fluorescence * nucleic acid hybridization * oligonucleotides * pyrenes * unlocked nucleic acids Subject RIV: CC - Organic Chemistry Impact factor: 2.968, year: 2014

Cost effectiveness of fine needle aspiration cytology for breast masses

African Journals Online (AJOL)

The total cost for FNAC and histopathology as well as cost saving between FNAC and histopathology for the 110 patients were calculated. Result: The total cost for FNAC procedure and cytological evaluation of each smear was one thousand, seven hundred naira (N1,700.00 = US$11). The total cost for open surgical ...

Cost effectiveness and budget impact of natalizumab in patients with relapsing multiple sclerosis.

Science.gov (United States)

Chiao, Evelyn; Meyer, Kellie

2009-06-01

Disease-modifying therapy (DMT) is the largest single-cost item that contributes to the total per-patient cost of multiple sclerosis (MS), a disabling disorder of the central nervous system. Natalizumab is the most recent DMT to be approved for the treatment of relapsing MS and may be an attractive alternative to interferon beta and glatiramer acetate (GA). To determine from the perspective of a United States payer (1) the incremental cost effectiveness of natalizumab compared with other DMTs and (2) the budgetary impact of utilization of natalizumab for the treatment of relapsing MS. A combined cost effectiveness and budget impact model was developed. Model inputs were drug acquisition costs (wholesale acquisition cost), costs of drug administration and monitoring, costs of treating relapses, anticipated reduction in relapse rates after 2 years of therapy, and estimated market utilization of natalizumab. Outcomes included total 2-year costs of therapy per patient, costs per relapse avoided for each treatment, and overall 2-year costs to the health plan and per member per month (PMPM) costs. Drug acquisition costs are in 2008 US dollars, and all other costs were inflated to 2008 US dollars when necessary. Univariate sensitivity analyses were performed to determine the model inputs with the greatest influence on the cost per relapse avoided for natalizumab. The overall 2-year cost of therapy per patient was $72,120 for natalizumab, $56,790 for intramuscular (IM) interferon beta-1a (IFNbeta-1a), $56,773 for IFNbeta-1b, $57,180 for GA, and $58,538 for subcutaneous (SC) IFNbeta-1a. The cost per relapse avoided was lowest for natalizumab at $56,594, followed by $87,791 for IFNbeta-1b, $93,306 for IM IFNbeta-1a, $96,178 for SC IFNbeta-1a, and $103,665 for GA. The incremental cost-effectiveness ratios of natalizumab relative to IM IFNbeta-1a, IFNbeta-1b, GA, and SC IFNbeta-1a were $23,029, $24,452, $20,671, and $20,403 per additional relapse avoided, respectively. An

Assessing the cost-effectiveness of electric vehicles in European countries using integrated modeling

International Nuclear Information System (INIS)

Seixas, J.; Simões, S.; Dias, L.; Kanudia, A.; Fortes, P.; Gargiulo, M.

2015-01-01

Electric vehicles (EVs) are considered alternatives to internal combustion engines due to their energy efficiency and contribution to CO 2 mitigation. The adoption of EVs depends on consumer preferences, including cost, social status and driving habits, although it is agreed that current and expected costs play a major role. We use a partial equilibrium model that minimizes total energy system costs to assess whether EVs can be a cost-effective option for the consumers of each EU27 member state up to 2050, focusing on the impact of different vehicle investment costs and CO 2 mitigation targets. We found that for an EU-wide greenhouse gas emission reduction cap of 40% and 70% by 2050 vis-à-vis 1990 emissions, battery electric vehicles (BEVs) are cost-effective in the EU only by 2030 and only if their costs are 30% lower than currently expected. At the EU level, vehicle costs and the capability to deliver both short- and long-distance mobility are the main drivers of BEV deployment. Other drivers include each state’s national mobility patterns and the cost-effectiveness of alternative mitigation options, both in the transport sector, such as plug-in hybrid electric vehicles (PHEVs) or biofuels, and in other sectors, such as renewable electricity. - Highlights: • Electric vehicles were assessed through the minimization of the total energy systems costs. • EU climate policy targets could act as a major driver for PHEV adoption. • Battery EV is an option before 2030 if costs will drop by 30% from expected costs. • EV deployment varies per country depending on each energy system configuration. • Incentives at the country level should consider specific cost-effectiveness factors

Cost-effectiveness analysis of different embryo transfer strategies in England.

Science.gov (United States)

Dixon, S; Faghih Nasiri, F; Ledger, W L; Lenton, E A; Duenas, A; Sutcliffe, P; Chilcott, J B

2008-05-01

The objective of this study was to assess the cost-effectiveness of different embryo transfer strategies for a single cycle when two embryos are available, and taking the NHS cost perspective. Cost-effectiveness model. Five in vitro fertilisation (IVF) centres in England between 2003/04 and 2004/05. Women with two embryos available for transfer in three age groups (Costs and adverse outcomes are estimated up to 5 years after the birth. Incremental cost per live birth was calculated for different embryo transfer strategies and for three separate age groups: less than 30, 30-35 and 36-39 years. Premature birth, neonatal intensive care unit admissions and days, cerebral palsy and incremental cost-effectiveness ratios. Single fresh embryo transfer (SET) plus frozen single embryo transfer (fzSET) is the more costly in terms of IVF costs, but the lower rates of multiple births mean that in terms of total costs, it is less costly than double embryo transfer (DET). Adverse events increase when moving from SET to SET+fzSET to DET. The probability of SET+fzSET being cost-effective decreases with age. When SET is included in the analysis, SET+fzSET no longer becomes a cost-effective option at any threshold value for all age groups studied. The analyses show that the choice of embryo transfer strategy is a function of four factors: the age of the mother, the relevance of the SET option, the value placed on a live birth and the relative importance placed on adverse outcomes. For each patient group, the choice of strategy is a trade-off between the value placed on a live birth and cost.

The cost of post-operative shed blood salvage after total knee arthroplasty: an analysis of 1,093 consecutive procedures

Science.gov (United States)

Muñoz, Manuel; Ariza, Daniel; Campos, Arturo; Martín-Montañez, Elisa; Pavía, José

2013-01-01

Background Requirements for allogeneic red cell transfusion after total knee arthroplasty are still high (20–50%), and salvage and reinfusion of unwashed, filtered post-operative shed blood is an established method for reducing transfusion requirements following this operation. We performed a cost analysis to ascertain whether this alternative is likely to be cost-effective. Materials and methods Data from 1,093 consecutive primary total knee arthroplasties, managed with (reinfusion group, n=763) or without reinfusion of unwashed salvaged blood (control group, n=330), were retrospectively reviewed. The costs of low-vacuum drains, shed blood collection canisters (Bellovac ABT®, Wellspect HealthCare and ConstaVac CBC II®, Stryker), shed blood reinfusion, acquisition and transfusion of allogeneic red cell concentrate, haemoglobin measurements, and prolonged length of hospital stay were used for the blood management cost analysis. Results Patients in the reinfusion group received 152±64 mL of red blood cells from postoperatively salvaged blood, without clinically relevant incidents, and showed a lower allogeneic transfusion rate (24.5% vs 8.5%, for the control and reinfusion groups, respectively; p =0.001). There were no differences in post-operative infection rates. Patients receiving allogeneic transfusions stayed in hospital longer (+1.9 days [95% CI: 1.2 to 2.6]). As reinfusion of unwashed salvaged blood reduced the allogeneic transfusion rate, both reinfusion systems may provide net savings in different cost scenarios (€ 4.6 to € 106/patient for Bellovac ABT, and € −51.9 to € 49.9/patient for ConstaVac CBCII). Discussion Return of unwashed salvaged blood after total knee arthroplasty seems to save costs in patients with pre-operative haemoglobin between 12 and 15 g/dL. It is not cost-saving in patients with a pre-operative haemoglobin >15 g/dL, whereas in those with a pre-operative haemoglobin cost-saving, its efficacy could be increased by

Use of predefined biochemical admission profiles does not reduce the number of tests or total cost

DEFF Research Database (Denmark)

Pareek, Manan; Haidl, Felix; Folkestad, Lars

2014-01-01

The objective of this pilot study was to evaluate whether the use of predefined biochemical profiles as an alternative to individually ordered blood tests by the treating physicians resulted in fewer tests or a lower total cost.......The objective of this pilot study was to evaluate whether the use of predefined biochemical profiles as an alternative to individually ordered blood tests by the treating physicians resulted in fewer tests or a lower total cost....

A cost-effectiveness and cost-utility analysis of radiosurgery vs. resection for single-brain metastases

International Nuclear Information System (INIS)

Mehta, Minesh; Noyes, William; Craig, Bruce; Lamond, John; Auchter, Richard; French, Molly; Johnson, Mark; Levin, Allan; Badie, Behnam; Robbins, Ian; Kinsella, Timothy

1997-01-01

Purpose: The median survival of well-selected patients with single-brain metastases treated with whole-brain irradiation and resection or radiosurgery is comparable, although a randomized trial of these two modalities has not been performed. In this era of cost containment, it is imperative that health-care professionals make fiscally prudent decisions. The present environment necessitates a critical appraisal of apparently equi-efficacious therapeutic modalities, and it is within this context that we present a comparison of the actual costs of resection and radiosurgery for brain metastases. Methods and Materials: Survival and quality of life outcome data for radiation alone or with surgery were obtained from two randomized trials, and radiosurgical results were obtained from a multiinstitutional analysis that specifically evaluated patients meeting surgical criteria. Only linear accelerator radiosurgery data were considered. Cost analysis was performed from a societal view point, and the following parameters were evaluated: actual cost, cost ratios, cost effectiveness, incremental cost effectiveness, cost utility, incremental cost utility, and national cost burden. The computerized billing records for all patients undergoing resection or radiosurgery for single-brain metastases from January 1989 to July 1994 were reviewed. A total of 46 resections and 135 radiosurgery procedures were performed. During the same time period, 454 patients underwent whole-brain radiation alone. An analysis of the entire bill was performed for each procedure, and each itemized cost was assigned a proportionate figure. The relative cost ratios of resection and radiosurgery were compared using the Wilcoxon rank sum test. Cost effectiveness of each modality, defined as the cost per year of median survival, was evaluated. Incremental cost effectiveness, defined as the additional cost per year of incremental gain in median survival, compared to the next least expensive modality, was also

The Relationship between Cost Leadership Strategy, Total Quality Management Applications and Financial Performance

OpenAIRE

Ali KURT; Cemal ZEHİR

2016-01-01

Firms need to implement some competition strategies and total quality management applications to overcome the fierce competition among others. The purpose of this study is to show the relationship between cost leadership strategy, total quality management applications and firms’ financial performance with literature review and empirical analysis. 449 questionnaires were conducted to the managers of 142 big firms. The data gathered was assessed with AMOS. As a result, the relationship between ...

Probing the mechanical properties, conformational changes, and interactions of nucleic acids with magnetic tweezers.

Science.gov (United States)

Kriegel, Franziska; Ermann, Niklas; Lipfert, Jan

2017-01-01

Nucleic acids are central to the storage and transmission of genetic information. Mechanical properties, along with their sequence, both enable and fundamentally constrain the biological functions of DNA and RNA. For small deformations from the equilibrium conformations, nucleic acids are well described by an isotropic elastic rod model. However, external forces and torsional strains can induce conformational changes, giving rise to a complex force-torque phase diagram. This review focuses on magnetic tweezers as a powerful tool to precisely determine both the elastic parameters and conformational transitions of nucleic acids under external forces and torques at the single-molecule level. We review several variations of magnetic tweezers, in particular conventional magnetic tweezers, freely orbiting magnetic tweezers and magnetic torque tweezers, and discuss their characteristic capabilities. We then describe the elastic rod model for DNA and RNA and discuss conformational changes induced by mechanical stress. The focus lies on the responses to torque and twist, which are crucial in the mechanics and interactions of nucleic acids and can directly be measured using magnetic tweezers. We conclude by highlighting several recent studies of nucleic acid-protein and nucleic acid-small-molecule interactions as further applications of magnetic tweezers and give an outlook of some exciting developments to come. Copyright © 2016. Published by Elsevier Inc.

What is known about the cost-effectiveness of orphan drugs? Evidence from cost-utility analyses.

Science.gov (United States)

Picavet, E; Cassiman, D; Simoens, S

2015-06-01

In times of financial and economic hardship, governments are looking to contain pharmaceutical expenditure by focusing on cost-effective drugs. Because of their high prices and difficulties in demonstrating effectiveness in small patient populations, orphan drugs are often perceived as not able to meet traditional reimbursement threshold value for money. The aim of this study was to provide an overview of the available evidence on the cost-effectiveness of orphan drugs. All orphan drugs listed as authorized on the website of the European Medicines Agency on 21 November 2013 were included in the analysis. Cost-utility analyses (CUAs) were identified by searching the Tufts Medical Center Cost-Effectiveness Analysis Registry and Embase. For each CUA, a number of variables were collected. The search identified 23 articles on the Tufts registry and 167 articles on Embase. The final analysis included 45 CUAs and 61 incremental cost-utility ratios (ICURs) for 19 orphan drugs. Of all ICURS, 16·3% were related to dominant drugs (i.e. more effective and less expensive than the comparator), 70·5% were related to drugs that are more effective, but at a higher cost, and 13·1% were related to dominated drugs (i.e. less effective and more expensive than the comparator). The median overall ICUR was €40 242 per quality-adjusted life year (QALY) with a minimum ICUR of €6311/QALY and a maximum ICUR of €974,917/QALY. This study demonstrates that orphan drugs can meet traditional reimbursement thresholds. Considering a threshold of £30,000/QALY, in this study, ten (52·6%) of a total of 19 orphan drugs for which data were available meet the threshold. As much as fifteen orphan drugs (78·9%) are eligible for reimbursement if a threshold of €80,000/QALY is considered. © 2015 John Wiley & Sons Ltd.

Molecular structure and interactions of nucleic acid components in nanoparticles: ab initio calculations

International Nuclear Information System (INIS)

Rubin, Yu.V.; Belous, L.F.

2012-01-01

Self-associates of nucleic acid components (stacking trimers and tetramers of the base pairs of nucleic acids) and short fragments of nucleic acids are nanoparticles (linear sizes of these particles are more than 10 A). Modern quantum-mechanical methods and softwares allow one to perform ab initio calculations of the systems consisting of 150-200 atoms with enough large basis sets (for example, 6-31G * ). The aim of this work is to reveal the peculiarities of molecular and electronic structures, as well as the energy features of nanoparticles of nucleic acid components. We had carried out ab initio calculations of the molecular structure and interactions in the stacking dimer, trimer, and tetramer of nucleic base pairs and in the stacking (TpG)(ApC) dimer and (TpGpC) (ApCpG) trimer of nucleotides, which are small DNA fragments. The performed calculations of molecular structures of dimers and trimers of nucleotide pairs showed that the interplanar distance in the structures studied is equal to 3.2 A on average, and the helical angle in a trimer is approximately equal to 30 o : The distance between phosphor atoms in neighboring chains is 13.1 A. For dimers and trimers under study, we calculated the horizontal interaction energies. The analysis of interplanar distances and angles between nucleic bases and their pairs in the calculated short oligomers of nucleic acid base pairs (stacking dimer, trimer, and tetramer) has been carried out. Studies of interactions in the calculated short oligomers showed a considerable role of the cross interaction in the stabilization of the structures. The contribution of cross interactions to the horizontal interactions grows with the length of an oligomer. Nanoparticle components get electric charges in nanoparticles. Longwave low-intensity bands can appear in the electron spectra of nanoparticles.

Moving toward rapid and low-cost point-of-care molecular diagnostics with a repurposed 3D printer and RPA.

Science.gov (United States)

Chan, Kamfai; Wong, Pui-Yan; Parikh, Chaitanya; Wong, Season

2018-03-15

Traditionally, the majority of nucleic acid amplification-based molecular diagnostic tests are done in centralized settings. In recent years, point-of-care tests have been developed for use in low-resource settings away from central laboratories. While most experts agree that point-of-care molecular tests are greatly needed, their availability as cost-effective and easy-to-operate tests remains an unmet goal. In this article, we discuss our efforts to develop a recombinase polymerase amplification reaction-based test that will meet these criteria. First, we describe our efforts in repurposing a low-cost 3D printer as a platform that can carry out medium-throughput, rapid, and high-performing nucleic acid extraction. Next, we address how these purified templates can be rapidly amplified and analyzed using the 3D printer's heated bed or the deconstructed, low-cost thermal cycler we have developed. In both approaches, real-time isothermal amplification and detection of template DNA or RNA can be accomplished using a low-cost portable detector or smartphone camera. Last, we demonstrate the capability of our technologies using foodborne pathogens and the Zika virus. Our low-cost approach does not employ complicated and high-cost components, making it suitable for resource-limited settings. When integrated and commercialized, it will offer simple sample-to-answer molecular diagnostics. Copyright © 2018 Elsevier Inc. All rights reserved.

Non-viral Nucleic Acid Delivery Strategies to the Central Nervous System

Directory of Open Access Journals (Sweden)

James-Kevin Tan

2016-11-01

Full Text Available With an increased prevalence and understanding of central nervous system injuries and neurological disorders, nucleic acid therapies are gaining promise as a way to regenerate lost neurons or halt disease progression. While more viral vectors have been used clinically as tools for gene delivery, non-viral vectors are gaining interest due to lower safety concerns and the ability to deliver all types of nucleic acids. Nevertheless, there are still a number of barriers to nucleic acid delivery. In this focused review, we explore the in vivo challenges hindering non-viral nucleic acid delivery to the central nervous system and the strategies and vehicles used to overcome them. Advantages and disadvantages of different routes of administration including: systemic injection, cerebrospinal fluid injection, intraparenchymal injection, and peripheral administration are discussed. Non-viral vehicles and treatment strategies that have overcome delivery barriers and demonstrated in vivo gene transfer to the central nervous system are presented. These approaches can be used as guidelines in developing synthetic gene delivery vectors for central nervous system applications and will ultimately bring non-viral vectors closer to clinical application.

Nucleic acid polymeric properties and electrostatics: Directly comparing theory and simulation with experiment.

Science.gov (United States)

Sim, Adelene Y L

2016-06-01

Nucleic acids are biopolymers that carry genetic information and are also involved in various gene regulation functions such as gene silencing and protein translation. Because of their negatively charged backbones, nucleic acids are polyelectrolytes. To adequately understand nucleic acid folding and function, we need to properly describe its i) polymer/polyelectrolyte properties and ii) associating ion atmosphere. While various theories and simulation models have been developed to describe nucleic acids and the ions around them, many of these theories/simulations have not been well evaluated due to complexities in comparison with experiment. In this review, I discuss some recent experiments that have been strategically designed for straightforward comparison with theories and simulation models. Such data serve as excellent benchmarks to identify limitations in prevailing theories and simulation parameters. Copyright © 2015 Elsevier B.V. All rights reserved.

Cost-effectiveness of tiotropium versus salmeterol: the POET-COPD trial.

Science.gov (United States)

Hoogendoorn, Martine; Al, Maiwenn J; Beeh, Kai-Michael; Bowles, David; Graf von der Schulenburg, J Matthias; Lungershausen, Juliane; Monz, Brigitta U; Schmidt, Hendrik; Vogelmeier, Claus; Rutten-van Mölken, Maureen P M H

2013-03-01

The aim of this study was to perform a 1-yr trial-based cost-effectiveness analysis (CEA) of tiotropium versus salmeterol followed by a 5-yr model-based CEA. The within-trial CEA, including 7,250 patients with moderate to very severe chronic obstructive pulmonary disease (COPD), was performed alongside the 1-yr international randomised controlled Prevention of Exacerbations with Tiotropium (POET)-COPD trial comparing tiotropium with salmeterol regarding the effect on exacerbations. Main end-points of the trial-based analysis were costs, number of exacerbations and exacerbation days. The model-based analysis was conducted to extrapolate results to 5 yrs and to calculate quality-adjusted life years (QALYs). 1-yr costs per patient from the German statutory health insurance (SHI) perspective and the societal perspective were €126 (95% uncertainty interval (UI) €55-195) and €170 (95% UI €77-260) higher for tiotropium, respectively. The annual number of exacerbations was 0.064 (95% UI 0.010-0.118) lower for tiotropium, leading to a reduction in exacerbation-related costs of €87 (95% UI €19-157). The incremental cost-effectiveness ratio was €1,961 per exacerbation avoided from the SHI perspective and €2,647 from the societal perspective. In the model-based analyses, the 5-yr costs per QALY were €3,488 from the SHI perspective and €8,141 from the societal perspective. Tiotropium reduced exacerbations and exacerbation-related costs, but increased total costs. Tiotropium can be considered cost-effective as the resulting cost-effectiveness ratios were below commonly accepted willingness-to-pay thresholds.

Cost-effectiveness analysis of mammography and clinical breast examination strategies

Science.gov (United States)

Ahern, Charlotte Hsieh; Shen, Yu

2009-01-01

Purpose Breast cancer screening by mammography and clinical breast exam are commonly used for early tumor detection. Previous cost-effectiveness studies considered mammography alone or did not account for all relevant costs. In this study, we assessed the cost-effectiveness of screening schedules recommended by three major cancer organizations and compared them with alternative strategies. We considered costs of screening examinations, subsequent work-up, biopsy, and treatment interventions after diagnosis. Methods We used a microsimulation model to generate women’s life histories, and assessed screening and treatment impacts on survival. Using statistical models, we accounted for age-specific incidence, preclinical disease duration, and age-specific sensitivity and specificity for each screening modality. The outcomes of interest were quality-adjusted life years (QALYs) saved and total costs with a 3% annual discount rate. Incremental cost-effectiveness ratios were used to compare strategies. Sensitivity analyses were performed by varying some of the assumptions. Results Compared to guidelines from the National Cancer Institute and the U.S. Preventive Services Task Force, alternative strategies were more efficient. Mammography and clinical breast exam in alternating years from ages 40 to 79 was a cost-effective alternative compared to the guidelines, costing $35,500 per QALY saved compared with no screening. The American Cancer Society guideline was the most effective and the most expensive, costing over $680,000 for an added QALY compared to the above alternative. Conclusion Screening strategies with lower costs and benefits comparable to those currently recommended should be considered for implementation in practice and for future guidelines. PMID:19258473

The value of confirmatory testing in early infant HIV diagnosis programmes in South Africa: A cost-effectiveness analysis.

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Lorna Dunning

2017-11-01

Full Text Available The specificity of nucleic acid amplification tests (NAATs used for early infant diagnosis (EID of HIV infection is <100%, leading some HIV-uninfected infants to be incorrectly identified as HIV-infected. The World Health Organization recommends that infants undergo a second NAAT to confirm any positive test result, but implementation is limited. Our objective was to determine the impact and cost-effectiveness of confirmatory HIV testing for EID programmes in South Africa.Using the Cost-effectiveness of Preventing AIDS Complications (CEPAC-Pediatric model, we simulated EID testing at age 6 weeks for HIV-exposed infants without and with confirmatory testing. We assumed a NAAT cost of US$25, NAAT specificity of 99.6%, NAAT sensitivity of 100% for infants infected in pregnancy or at least 4 weeks prior to testing, and a mother-to-child transmission (MTCT rate at 12 months of 4.9%; we simulated guideline-concordant rates of testing uptake, result return, and antiretroviral therapy (ART initiation (100%. After diagnosis, infants were linked to and retained in care for 10 years (false-positive or lifelong (true-positive. All parameters were varied widely in sensitivity analyses. Outcomes included number of infants with false-positive diagnoses linked to ART per 1,000 ART initiations, life expectancy (LE, in years and per-person lifetime HIV-related healthcare costs. Both without and with confirmatory testing, LE was 26.2 years for HIV-infected infants and 61.4 years for all HIV-exposed infants; clinical outcomes for truly infected infants did not differ by strategy. Without confirmatory testing, 128/1,000 ART initiations were false-positive diagnoses; with confirmatory testing, 1/1,000 ART initiations were false-positive diagnoses. Because confirmatory testing averted costly HIV care and ART in truly HIV-uninfected infants, it was cost-saving: total cost US$1,790/infant tested, compared to US$1,830/infant tested without confirmatory testing

Highly simplified lateral flow-based nucleic acid sample preparation and passive fluid flow control

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Cary, Robert E.

2015-12-08

Highly simplified lateral flow chromatographic nucleic acid sample preparation methods, devices, and integrated systems are provided for the efficient concentration of trace samples and the removal of nucleic acid amplification inhibitors. Methods for capturing and reducing inhibitors of nucleic acid amplification reactions, such as humic acid, using polyvinylpyrrolidone treated elements of the lateral flow device are also provided. Further provided are passive fluid control methods and systems for use in lateral flow assays.

Highly simplified lateral flow-based nucleic acid sample preparation and passive fluid flow control

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Cary, Robert B.

2018-04-17

Highly simplified lateral flow chromatographic nucleic acid sample preparation methods, devices, and integrated systems are provided for the efficient concentration of trace samples and the removal of nucleic acid amplification inhibitors. Methods for capturing and reducing inhibitors of nucleic acid amplification reactions, such as humic acid, using polyvinylpyrrolidone treated elements of the lateral flow device are also provided. Further provided are passive fluid control methods and systems for use in lateral flow assays.

Cation–Anion Interactions within the Nucleic Acid Ion Atmosphere Revealed by Ion Counting

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Gebala, Magdalena; Giambasu, George M.; Lipfert, Jan; Bisaria, Namita; Bonilla, Steve; Li, Guangchao; York, Darrin M.; Herschlag, Daniel

2016-01-01

The ion atmosphere is a critical structural, dynamic, and energetic component of nucleic acids that profoundly affects their interactions with proteins and ligands. Experimental methods that “count” the number of ions thermodynamically associated with the ion atmosphere allow dissection of energetic properties of the ion atmosphere, and thus provide direct comparison to theoretical results. Previous experiments have focused primarily on the cations that are attracted to nucleic acid polyanions, but have also showed that anions are excluded from the ion atmosphere. Herein, we have systematically explored the properties of anion exclusion, testing the zeroth-order model that anions of different identity are equally excluded due to electrostatic repulsion. Using a series of monovalent salts, we find, surprisingly, that the extent of anion exclusion and cation inclusion significantly depends on salt identity. The differences are prominent at higher concentrations and mirror trends in mean activity coefficients of the electrolyte solutions. Salts with lower activity coefficients exhibit greater accumulation of both cations and anions within the ion atmosphere, strongly suggesting that cation–anion correlation effects are present in the ion atmosphere and need to be accounted for to understand electrostatic interactions of nucleic acids. To test whether the effects of cation–anion correlations extend to nucleic acid kinetics and thermodynamics, we followed the folding of P4–P6, a domain of the Tetrahymena group I ribozyme, via single-molecule fluorescence resonance energy transfer in solutions with different salts. Solutions of identical concentration but lower activity gave slower and less favorable folding. Our results reveal hitherto unknown properties of the ion atmosphere and suggest possible roles of oriented ion pairs or anion-bridged cations in the ion atmosphere for electrolyte solutions of salts with reduced activity. Consideration of these new

Are labour-intensive efforts to prevent pressure ulcers cost-effective?

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Mathiesen, Anne Sofie Mølbak; Nørgaard, Kamilla; Andersen, Marie Frederikke Bruun; Møller, Klaus Meyer; Ehlers, Lars Holger

2013-10-01

Pressure ulcers are a major problem in Danish healthcare with a prevalence of 13-43% among hospitalized patients. The associated costs to the Danish Health Care Sector are estimated to be €174.5 million annually. In 2010, The Danish Society for Patient Safety introduced the Pressure Ulcer Bundle (PUB) in order to reduce hospital-acquired pressure ulcers by a minimum of 50% in five hospitals. The PUB consists of evidence-based preventive initiatives implemented by ward staff using the Model for Improvement. To investigate the cost-effectiveness of labour-intensive efforts to reduce pressure ulcers in the Danish Health Care Sector, comparing the PUB with standard care. A decision analytic model was constructed to assess the costs and consequences of hospital-acquired pressure ulcers during an average hospital admission in Denmark. The model inputs were based on a systematic review of clinical efficacy data combined with local cost and effectiveness data from the Thy-Mors Hospital, Denmark. A probabilistic sensitivity analysis (PSA) was conducted to assess the uncertainty. Prevention of hospital-acquired pressure ulcers by implementing labour-intensive effects according to the PUB was cost-saving and resulted in an improved effect compared to standard care. The incremental cost of the PUB was -€38.62. The incremental effects were a reduction of 9.3% prevented pressure ulcers and 0.47% prevented deaths. The PSAs confirmed the incremental cost-effectiveness ratio (ICER)'s dominance for both prevented pressure ulcers and saved lives with the PUB. This study shows that labour-intensive efforts to reduce pressure ulcers on hospital wards can be cost-effective and lead to savings in total costs of hospital and social care. The data included in the study regarding costs and effects of the PUB in Denmark were based on preliminary findings from a pilot study at Thy-Mors Hospital and literature.

Sequence Design for a Test Tube of Interacting Nucleic Acid Strands.

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Wolfe, Brian R; Pierce, Niles A

2015-10-16

We describe an algorithm for designing the equilibrium base-pairing properties of a test tube of interacting nucleic acid strands. A target test tube is specified as a set of desired "on-target" complexes, each with a target secondary structure and target concentration, and a set of undesired "off-target" complexes, each with vanishing target concentration. Sequence design is performed by optimizing the test tube ensemble defect, corresponding to the concentration of incorrectly paired nucleotides at equilibrium evaluated over the ensemble of the test tube. To reduce the computational cost of accepting or rejecting mutations to a random initial sequence, the structural ensemble of each on-target complex is hierarchically decomposed into a tree of conditional subensembles, yielding a forest of decomposition trees. Candidate sequences are evaluated efficiently at the leaf level of the decomposition forest by estimating the test tube ensemble defect from conditional physical properties calculated over the leaf subensembles. As optimized subsequences are merged toward the root level of the forest, any emergent defects are eliminated via ensemble redecomposition and sequence reoptimization. After successfully merging subsequences to the root level, the exact test tube ensemble defect is calculated for the first time, explicitly checking for the effect of the previously neglected off-target complexes. Any off-target complexes that form at appreciable concentration are hierarchically decomposed, added to the decomposition forest, and actively destabilized during subsequent forest reoptimization. For target test tubes representative of design challenges in the molecular programming and synthetic biology communities, our test tube design algorithm typically succeeds in achieving a normalized test tube ensemble defect ≤1% at a design cost within an order of magnitude of the cost of test tube analysis.

The effect of maternal substance abuse on the cost of neonatal care.

Science.gov (United States)

Norton, E C; Zarkin, G A; Calingaert, B; Bradley, C J