Development of a model-based clinical sepsis biomarker for critically ill patients

Sepsis occurs frequently in the intensive care unit (ICU) and is a leading cause of admission, mortality, and cost. Treatment guidelines recommend early intervention, however positive blood culture results may take up to 48 h. Insulin sensitivity (S_I) is known to decrease with worsening condition and could thus be used to aid diagnosis. Some glycemic control protocols are able to accurately identify insulin sensitivity in real-time.Hourly model-based insulin sensitivity S_I values were calculated from glycemic control data of 36 patients with sepsis. The hourly S_I is compared to the hourly sepsis score (ss) for these patients (ss = 0-4 for increasing severity). A multivariate clinical biomarker was also developed to maximize the discrimination between different ss groups. Receiver operator characteristic (ROC) curves for severe sepsis (ss ≥ 2) are created for both S_I and the multivariate clinical biomarker.Insulin sensitivity as a sepsis biomarker for diagnosis of severe sepsis achieves a 50% sensitivity, 76% specificity, 4.8% positive predictive value (PPV), and 98.3% negative predictive value (NPV) at an S_I cut-off value of 0.00013 L/mU/min. Multivariate clinical biomarker combining S_I, temperature, heart rate, respiratory rate, blood pressure, and their respective hourly rates of change achieves 73% sensitivity, 80% specificity, 8.4% PPV, and 99.2% NPV. Thus, the multivariate clinical biomarker provides an effective real-time negative predictive diagnostic for severe sepsis. Examination of both inter- and intra-patient statistical distribution of this biomarker and sepsis score shows potential avenues to improve the positive predictive value.     

Effects of the resting time associated with the number of trials on the total and individual finger forces in a maximum grasping task

The repetitive and excessive workload accompanying grip strength- or hand-intensive tasks are often considered to be common causes of work-related upper limb musculoskeletal disorders. For this reason, numerous experimental studies have been performed on maximum grip strength. However, due to an absence of standard guidelines, researchers have adopted different resting times and number of trials suited for their particular research purposes. The effects of resting time and the number of trials on the maximum total grip strength and individual finger forces of 24 participants over 20 trials were investigated. Results showed that the total grip strength and individual finger strengths differed significantly according to the resting time and the number of trials (p < 0.05). Overall, grip strength tended to increase with a reduction in resting time (% reduction: 7.8%, 9.1%, 11.1%, and 13.0% for 3 min, 2 min, 1 min, and 30 s resting time, respectively) as well as with an increase in the number of trials (% reduction: 8%, 10%, 13%, and 16% for 5th, 10th, 15th, and 20th trials). The effects of resting time and the number of trials also showed statistically significant effects on individual finger forces. Regression equations of total grip strength and finger forces with resting time and number of trials were established. These equations were then applied to formulate guidelines for appropriate resting times in experiments based on the number of trials and acceptable reductions in grip strength. Data from this and future studies regarding decreasing grip strength and the contribution of each finger are expected to form the groundwork for ergonomic hand tool design and development.     

Impact of glucocorticoids on insulin resistance in the critically ill

Glucocorticoids (GCs) have been shown to reduce insulin sensitivity in healthy individuals. Widely used in critical care to treat a variety of inflammatory and allergic disorders, they may inadvertently exacerbate stress-hyperglycaemia. This research uses model-based methods to quantify the reduction in insulin sensitivity from GCs in critically ill patients, and thus their impact on glycaemic control. A model-based measure of insulin sensitivity (S_I) was used to quantify changes between two matched cohorts of 40 intensive care unit (ICU) patients. Patients in one cohort received GC treatment, while patients in the control cohort did not. All patients were admitted to the Christchurch hospital ICU between 2005 and 2007 and spent at least 24 h on the SPRINT glycaemic control protocol.A 31% reduction in whole-cohort median insulin sensitivity was seen between the control cohort and patients receiving glucocorticoids with a median dose equivalent to 200 mg/d of hydrocortisone per patient. Comparing percentile patients as a surrogate for matched patients, reductions in median insulin sensitivity of 20%, 25%, and 21% were observed for the 25th-, 50th- and 75th-percentile patients, respectively. These cohort and percentile patient reductions are less than or equivalent to the 30-62% reductions reported in healthy subjects especially when considering the fact that the GC doses in this study are 1.3-4.0 times larger than those in studies of healthy subjects. This reduced suppression of insulin sensitivity in critically ill patients could be a result of saturation due to already increased levels of catecholamines and cortisol common in critically illness. Virtual trial simulation showed that reductions in insulin sensitivity of 20-30% associated with glucocorticoid treatment in the ICU have limited impact on glycaemic control levels within the context of the SPRINT protocol.     

Physical activity levels among adult computer users

As computer use becomes prevalent at work and in leisure pursuits it presents a potential barrier to regular physical activity. However an individual’s confidence in overcoming such barriers may moderate the relationship between computer use and physical activity levels. This study examined the associations among computer use, self-efficacy in overcoming barriers to exercise, and physical activity levels among adult computer users. Participants (N = 615) were recruited through national email and newsletters announcements, and completed standardized self-report questionnaires online. Computer use was not associated with meeting physical activity guidelines (adjusted odds ratio, AOR = 0.63-1.00, n.s.). Among leisure computer users, the moderate efficacy group (AOR = 3.72, 95% CI = 1.59-8.69) and the high efficacy group (AOR = 5.31, 95% CI = 2.37-11.91) had higher odds of meeting physical activity guidelines compared to the low efficacy group. Among the work related computer users, the high efficacy group (AOR = 2.83, 95% CI = 1.18-6.77) had higher odds of meeting physical activity guidelines than the low efficacy group. These results suggest that barriers posed by high levels of computer use are surmountable. Efforts to increase efficacy in overcoming barriers to exercise may be more practical and have a greater impact on physical activity levels than trying to decrease computer use among adults.     

Mapping and mining interictal pathological gamma (30-100 Hz) oscillations with clinical intracranial EEG in patients with epilepsy

Localizing an epileptic network is essential for guiding neurosurgery and antiepileptic medical devices as well as elucidating mechanisms that may explain seizure-generation and epilepsy. There is increasing evidence that pathological oscillations may be specific to diseased networks in patients with epilepsy and that these oscillations may be a key biomarker for generating and indentifying epileptic networks. We present a semi-automated method that detects, maps, and mines pathological gamma (30-100 Hz) oscillations (PGOs) in human epileptic brain to possibly localize epileptic networks. We apply the method to standard clinical iEEG (<100 Hz) with interictal PGOs and seizures from six patients with medically refractory epilepsy. We demonstrate that electrodes with consistent PGO discharges do not always coincide with clinically determined seizure onset zone (SOZ) electrodes but at times PGO-dense electrodes include secondary seizure-areas (SS) or even areas without seizures (NS). In 4/5 patients with epilepsy surgery, we observe poor (Engel Class 4) postsurgical outcomes and identify more PGO-activity in SS or NS than in SOZ. Additional studies are needed to further clarify the role of PGOs in epileptic brain.     

A hybrid semi-automatic method for liver segmentation based on level-set methods using multiple seed points

The present study developed a hybrid semi-automatic method to extract the liver from abdominal computerized tomography (CT) images. The proposed hybrid method consists of a customized fast-marching level-set method for detection of an optimal initial liver region from multiple seed points selected by the user and a threshold-based level-set method for extraction of the actual liver region based on the initial liver region. The performance of the hybrid method was compared with those of the 2D region growing method implemented in OsiriX using abdominal CT datasets of 15 patients. The hybrid method showed a significantly higher accuracy in liver extraction (similarity index, SI = 97.6 ± 0.5%; false positive error, FPE = 2.2 ± 0.7%; false negative error, FNE = 2.5 ± 0.8%; average symmetric surface distance, ASD = 1.4 ± 0.5 mm) than the 2D (SI = 94.0 ± 1.9%; FPE = 5.3 ± 1.1%; FNE = 6.5 ± 3.7%; ASD = 6.7 ± 3.8 mm) region growing method. The total liver extraction time per CT dataset of the hybrid method (77 ± 10 s) is significantly less than the 2D region growing method (575 ± 136 s). The interaction time per CT dataset between the user and a computer of the hybrid method (28 ± 4 s) is significantly shorter than the 2D region growing method (484 ± 126 s). The proposed hybrid method was found preferred for liver segmentation in preoperative virtual liver surgery planning.     

An ultra-sensitive chemiluminescence immunosensor of carcinoembryonic antigen using HRP-functionalized mesoporous silica nanoparticles as labels

A novel chemiluminescence immunosensor using horseradish peroxidase (HRP)-functionalized mesoporous silica nanoparticles (MSN) as labels was developed, which increases the sensitivity of the chemiluminescence immunoassay. The enzyme-functionalized MSN were fabricated by simultaneous coimmobilization of HRP and the carcinoembryonic antigen antibody (anti-CEA) onto the surface of MSN using 3-aminopropyltriethoxysilane (APTES) as the linkage. Because the large surface area of MSN carriers increased the amount of HRP bound per sandwiched immunoreaction, the conjugates provided a much higher signal and increased sensitivity. This is an improvement over the traditional sandwich immunoassay which often has one or two enzyme molecules per antibody. This approach was successfully demonstrated as a simple, cost-effective, specific, and potent method to detect CEA in practical samples. The analysis showed a linear response within the range of 0.1-40 ng/mL (r = 0.9912). The relative standard deviation (RSD) for 11 parallel measurements of 20 ng/mL CEA was 3.9%. The sensitivity of the immunosensor using MSN-HRP-Ab2 as labels was about 10-fold higher than that of traditional labels. These labels for immunosensors may provide many potential applications for detection of different biomolecules.     

All-terrain vehicle use in agriculture: Exposure to whole body vibration and mechanical shock

Whole body vibration (WBV) and mechanical shock were measured in 12 New Zealand farmers during their daily use of all-terrain vehicles (ATVs). As per the International Organization for Standardization (ISO) guidelines for WBV exposure, frequencies between 0 and 100 Hz were recorded via a seat-pad tri-axial accelerometer during 20 min of ATV use. The farmers were also surveyed to estimate seasonal variation in daily ATV usage as well as 7-day and 12-month prevalence of spinal pain. Frequency-weighted vibration exposure and total riding time were calculated to determine the daily vibration dose value (VDV). The daily VDV of 16.6 m/s^1.75 was in excess of the 9.1 m/s^1.75 action limit set by ISO guidelines suggesting an increased risk of low back injury from such exposure. However, the mean shock factor R, representing cumulative adverse health effects, was 0.31 indicating that these farmers were not exposed to excessive doses of mechanical shock. Extrapolation of daily VDV data to estimated seasonal variations of farmers in ATV riding time demonstrated that all participants would exceed the ISO recommended maximum permissible limits during the spring lambing season, as compared to lower exposures calculated for summer, autumn and winter. Low back pain was the most commonly reported complaint for both 7 day (50%) and 12 month prevalence (67%), followed by the neck (17% and 42%) and the upper back (17% and 25%) respectively. The results demonstrate high levels of vibration exposure within New Zealand farmers and practical recommendations are needed to reduce their exposure to WBV.     

Estimating the age and structure of forests in a multi-ownership landscape of western Oregon,U.S.A.

Forests of the Pacific Northwest region of the U.S.A. are part of an ongoing political debate that focuses on the trade-offs between commodity and non-commodity values. A key issue in this debate is the location and extent of closed canopy mature and old-growth forest remaining in the region. Remote sensing can play a major part in locating mature and old-growth forests, but. several challenges must be overcome to do so with acceptable accuracy. Conifer forests of the region have high leaf area indices. Thus, most incident solar energy is absorbed, making these forests difficult targets for discrimination of classes. Additionally, spectral characteristics can be affected more by the effects of steep topography than condition of the closed canopy forest.

Experimenting with a number of techniques, we estimated and mapped forest age and structure in 1988 over a 1 237 482 ha area on the west side of the Oregon Cascade Range with an overall accuracy of 82 per cent. Unsupervised classification enabled several forest classes to be defined in terms of per cent cover: open (0-30 per cent), semi-open (30-85 per cent), closed mix (> 85 per cent, of which at least 10 percent is comprised of non-conifer species), and closed conifer (> 85 per cent, of which less than 10 per cent is non-conifer). These classes represented nearly distinct spectral groups. Within the closed canopy conifer class, between two and three age and structural classes could be distinguished using regression analysis (e.g., young, mature, and old-growth). Defining more classes seriously degraded map accuracies. The Tasseled Cap wetness index was not sensitive to topography, and yielded more accurate results in closed canopy conifer stands than Tasseled Cap brightness or greenness, even when regression models using these indices were based on solar incidence angle stratification.

The multi-ownership study area consisted of 76 per cent forestland. Of the total forestland, 70 per cent was closed canopy conifer, with 42 per cent being in a mature or old-growth state. Forests administered by the USD1 Bureau of Land Management (BLM) and the USDA Forest Service, but protected by congressional and administrative mandates from harvest, were 10 per cent of the total forestland. Of the protected category, only 60 per cent was mature and old-growth forest, Unprotected BLM and Forest Service lands accounted for 53 per cent of the forestland in this study (8 and 45 per cent, respectively). Of the unprotected category, the BLM had 63 per cent, and the Forest Service had 49 per cent, respectively, of their holdings in a pre-canopy closure and young conifer condition. Thirty-five per cent of the forestland was privately owned, and consisted of 73 per cent pre-canopy closure and young conifer forest stands. Of all mature and old-growth forest, 22 per cent was found on private land, 7 per cent on unprotected BLM land, 55 per cent on unprotected Forest Service land, and 15 per cent on protected land.     

Segmentation and detection of breast cancer in mammograms combining wavelet analysis and genetic algorithm

In Brazil, the National Cancer Institute (INCA) reports more than 50,000 new cases of the disease, with risk of 51 cases per 100,000 women. Radiographic images obtained from mammography equipments are one of the most frequently used techniques for helping in early diagnosis. Due to factors related to cost and professional experience, in the last two decades computer systems to support detection (Computer-Aided Detection – CADe) and diagnosis (Computer-Aided Diagnosis – CADx) have been developed in order to assist experts in detection of abnormalities in their initial stages. Despite the large number of researches on CADe and CADx systems, there is still a need for improved computerized methods. Nowadays, there is a growing concern with the sensitivity and reliability of abnormalities diagnosis in both views of breast mammographic images, namely cranio-caudal (CC) and medio-lateral oblique (MLO). This paper presents a set of computational tools to aid segmentation and detection of mammograms that contained mass or masses in CC and MLO views. An artifact removal algorithm is first implemented followed by an image denoising and gray-level enhancement method based on wavelet transform and Wiener filter. Finally, a method for detection and segmentation of masses using multiple thresholding, wavelet transform and genetic algorithm is employed in mammograms which were randomly selected from the Digital Database for Screening Mammography (DDSM). The developed computer method was quantitatively evaluated using the area overlap metric (AOM). The mean ± standard deviation value of AOM for the proposed method was 79.2 ± 8%. The experiments demonstrate that the proposed method has a strong potential to be used as the basis for mammogram mass segmentation in CC and MLO views. Another important aspect is that the method overcomes the limitation of analyzing only CC and MLO views.     

Copper oxide nanoparticle sensors for hydrogen cyanide detection: Unprecedented selectivity and sensitivity

In the current work, CuO nanoparticles were synthesized in a facile way, and characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, and thermogravimetry. Using these CuO nanoparticles, CuO functionalized QCM resonators were fabricated and explored for HCN sensing. The sensing properties were studied by a sensor characterization system coupled with a mass spectrometer. The sensor response to HCN (+347 Hz) was found to be in an opposite direction as compared with other common volatile substances (ether: −1230 Hz; water: −1815 Hz; n-hexane: −2100 Hz; benzene: −3410 Hz; acetic acid: −4840 Hz; ethanol: −6270 Hz), offering excellent selectivity for HCN detection. In addition, the sensitivity (15.1 Hz/μg) was very high, and the response (30 s) and recovery (750 s) were very fast. A sensing mechanism was proposed based on experimental results, in which a surface redox reaction occurs between CuO and Cu₂O on the nanoparticle reversibly upon contact with HCN and air, respectively. The current results would provide an exciting alternative to fast, sensitive and selective detection of trace HCN, which would be of particular benefit in the area of public security and environmental applications.     

Potentiometric urea biosensor based on urease immobilized by an electrosynthesized poly(o-phenylenediamine) film with buffering capability

A simple and novel potentiometric biosensor for urea detection was prepared by employing an electrosynthesized polymer with buffering capability. It was obtained by deposition of a weighed amount of urease (Ur) at a glassy carbon (GC) electrode followed by immobilization by an electrosynthesized poly-o-phenylenediamine (PPD) film. An unconventional “upside-down” (UD) geometry was employed for the electrochemical cell. The response of GC/Ur/PPD sensor is linear with urea concentration in the range 10 μM to 1 mM (15 mV/mM, R² = 0.9999) due to buffering capability of PPD film, which represents a novel role of electrosynthesized polymers in their application to biosensors. At higher concentrations, the more common Nernstian response (28 mV/decade, R² = 0.9987) is observed. The sensor exhibits a sufficient sensitivity for practical determinations, rapid response and long term stability.     

A glucose oxidase immobilization platform for glucose biosensor using ZnO hollow nanospheres

A good route (template-directed synthetic route) for the fabrication of ZnO hollow nanospheres (ZnO-HNSPs) was proposed. ZnO hollow nanosphere is a wonderful platform to immobilize glucose oxidase for glucose biosensor owing to the high specific surface area and high isoelectric point (IEP). Along with nafion and glucose oxidase (GOD), a glucose sensor was designed. Nafion/ZnO-HNSPs/GOD/GCE displays higher catalytic activity toward the glucose oxidation than Nafion/ZnO nano-Flowers/GOD/GCE. Linear response was obtained over a concentration range from 5.0 × 10⁻³ mM to 13.15 mM with a detection limit of 1.0 μM (S/N = 3), and the sensitivity was 65.82 μA/(mM cm²). Satisfyingly, the Nafion/ZnO-HNSPs/GOD/GCE could effectively avoid the interferences from the common interfering species such as uric acid (UA), ascorbic acid (AA), dopamine (DA) and fructose. The Nafion/ZnO-HNSPs/GOD modified electrode allows high sensitivity, excellently selective, stable, and fast amperometric sensing of glucose and thus is promising for the future development of glucose sensors.     

Correlation between cell growth rate and glucose consumption determined by electrochemical monitoring

The electrochemical monitoring of glucose consumption is relevant for cell biology studies because of its wide detection range, high sensitivity and easy implementation. Whereas the glucose consumption and cell growth rate can be tightly correlated, they should also be cell population density dependent. In this work, we fabricated high sensitive enzyme electrodes for accurate monitoring of glucose consumption of cells in different growth stages. The performance of the fabricated device was firstly evaluated by cyclic voltammetry (CV) with p-benzoquinone (PBQ) as redox mediator, showing a linear response over a wide detection range (0.3-60 mM), a high sensitivity (1.61 ± 0.10 μA mM⁻¹ mm⁻² (n = 5)) and a low detection limit (80 μM). Then, daily glucose consumptions of NIH 3T3 cells in 24-well plates were determined for a period of 7 days. The results could be compared to the cell population growth curve, showing a close correlation but different behavior. We found that the increase of the glucose consumption took place prior the cell number increase but the glucose consumption per cell decreases linearly in the exponential growth stage of cells.     

Sensitive amperometric determination of chemical oxygen demand using Ti/Sb-SnO2/PbO2 composite electrode

A novel Ti/Sb-SnO₂/PbO₂ composite electrode was fabricated for COD determination. The new electrode configuration improved the sensitivity of the amperometric method apparently. Effects of common experimental parameters, such as applied potential, pH and concentration of the electrolyte on its analytical performance were investigated. A linear range of 0.5-200 mg L⁻¹ COD and a detection limit (a signal-to-noise ratio of 3) of 0.3 mg L⁻¹ were achieved under optimized conditions. The experiments for detecting COD in model samples and real samples were carried out to evaluate the electrode's performance. The obtained results were in good agreement with those determined by the standard dichromate method, with a relative error less than 12%.     

Low-power subthreshold to above threshold level shifters in 90 nm and 65 nm process

In this paper we present low power level shifters in the 90 nm (general purpose) and 65 nm (low power) technology nodes capable of converting subthreshold voltage signals to above threshold voltage signals. The level shifters make use of the MTCMOS design technique which gives more design flexibility, especially in low power systems. Post layout simulations indicate static power consumption down to 1 nW and 83 pW in the 90 nm and 65 nm process respectively. Energy consumption per transition is recorded to be below 30 fJ in both processes, orders of magnitude lower then other published level shifter implementations. Propagation delay is found to be as low as 32 ns for subthreshold logic high input signals of 180 mV. The functionality of the level shifters is verified across process-, mismatch- and temperature variations between −40 °C and 150 °C. Minimum input voltage attainable while maintaining robust operation is found to be around 180 mV at operational frequencies above 1 MHz in the 90 nm process, and 350 mV at operational frequencies above 500 kHz in the 65 nm process. The level shifters employ an enable/disable feature, allowing for power saving when the level shifter is not in use.     

An improved maximally redundant signed digit adder

Signed digit (SD) number systems support digit-parallel carry-free addition, where the sum digits absorb the possible signed carries in {−1, 0, 1}. Radix-2^h maximally redundant SD (MRSD) number systems are particularly attractive. The reason is that, with the minimal (h + 1) bits per SD, maximum range is achieved. There are speculative MRSD adders that trade increased area and power for higher speed, via simultaneous computation of three sum digits, while anticipating one of the possible signed carries. However, the nonspeculative approach that uses carry-save two’s complement encoding for intermediate sum digits, has proved to be more efficient.In this paper, we examine three previous nonspeculative MRSD adders and offer an improved design with significant savings in latency, area consumption and power dissipation. The enhanced performance is mainly due to the elimination of sign extension of the signed carries. The latter leads to a sum matrix of positively and negatively weighted bits that normally complicate the use of standard adder cells. However, with inverted encoding of negatively weighted bits, we manage to efficiently use such cells. The claimed performance measures are supported by 0.13 μm CMOS technology synthesis.     

Facile synthesis of NiO nanoflowers and their electrocatalytic performance

In this paper, hierarchically structured NiO nanoflowers were facile synthesized by incorporating a convenient solution process with a subsequent thermal treating process. Their catalytic activity was then electrochemically investigated in detail. The NiO nanoflower modified biosensor exhibits excellent sensing performance for the determination of l-ascorbic acid with a response time less than 8 s, linear range between 0.005 and 3.5 mM, and sensitivity as 220.4 μA mM⁻¹ cm⁻². Besides, a high selectivity towards the oxidation of AA in the presence of dopamine (DA) and nitrite was also observed at their maximum physiological concentrations. The good analytical performance, long-term stability, low cost and straightforward fabrication process made the NiO nanomaterials promising for the development of effective electrochemical sensors for a wide range of potential applications in medicine, biotechnology and environmental chemistry.     

Design and performances of a mid-infrared CH4 detection device with novel three-channel-based LS-FTF self-adaptive denoising structure

A novel mid-infrared (MIR) CH₄ concentration detection device using three-channel-based least-square fast transverse filtering (LS-FTF) self-adaptive denoising structure was proposed. By introducing an additional noise-channel besides the traditional detection-channel and reference-channel, the noises can be well removed using the LS-FTF denoising algorithm. The detection procedure was described, and the key modules including the optical part and electrical part were designed and fabricated. Thorough experiments performed for the fabricated device show that the absolute detection error is less than 5%, and by quantifying the detected voltage using software, the minimum detection level is 8 ppm and the detection sensitivity is 9 ppm within the detection range of 8-1000 ppm. The measured maximum response time is less than 10 s, and the absolute detection error with temperature-compensation is less than 5%. The proposed three-channel-based LS-FTF denoising structure can also be adapted to other similar detection systems for noise elimination.