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Background: Dalteparin is often used for prophylaxis or treatment of venous thromboembolism during pregnancy, yet there is no laboratory test to accurately reflect its clinical activity. Thromboelastography is a point-of-care monitor of whole blood coagulation. The aim of this study was to determine if serial doses of dalteparin added in vitro to whole blood samples from term, pregnant women are detectable as changes in thromboelastography parameters.Methods: Thirty healthy parturients presenting for elective caesarean section were recruited. Dalteparin was added to whole blood samples to yield final concentrations of 0 (control), 0.05, 0.25, 0.5, 0.75 and 1.0U/mL anti-Xa activity. Thromboelastography tracings were obtained for all six samples using the standard kaolin protocol.Results: Significant differences were noted in median thromboelastography r time, k time, alpha angle and maximal amplitude between non-anticoagulated (⩽0.05U/mL) and samples ⩾0.5U/mL (P<0.05). The r time and k time presented with the highest sensitivities of 97.5 and 84.0, respectively.Conclusion: This pilot study provides proof-of-concept that thromboelastography can discriminate differences in blood anticoagulated with varying doses of dalteparin in a dose-dependent manner. This suggests that thromboelastography may be a feasible monitor of anticoagulation in the presence of dalteparin in maternal whole blood and may potentially translate to a point-of-care test that can be used to determine real-time coagulation status in patients. [ABSTRACT FROM AUTHOR]

Abstract: Biomass bales often need to be aggregated (collected into groups and transported) to a field-edge stack or a temporary storage before utilization. Several logistics scenarios for aggregation involving equipment and aggregation strategies were modeled and evaluated. Cumulative Euclidean distance criteria evaluated the various aggregation scenarios. Application of a single-bale loader that aggregated bales individually was considered as the “control” scenario with which others were compared. A computer simulation program developed determined bale coordinates in ideal and random layouts that evaluated aggregation scenarios. Simulation results exhibited a “diamond pattern” of bales on ideal layout and a “random pattern” emerged when ≥10% variation was introduced. Statistical analysis revealed that the effect of field shape, swath width, biomass yield, and randomness on bale layout did not affect aggregation logistics, while area and number of bales handled had significant effects. Number of bales handled in the direct method significantly influenced the efficiency. Self-loading bale picker with minimum distance path (MDP, 80%) and parallel transport of loader and truck with MDP (78%) were ranked the highest, and single-bale central grouping the lowest (29%) among 19 methods studied. The MDP was found significantly more efficient (4%–16%) than the baler path. Simplistic methods, namely a direct triple-bale loader with MDP (64%–66%), or a loader and truck handling six bales running parallel with MDP (75%–82%) were highly efficient. Great savings on cumulative distances that directly influence time, fuel, and cost were realized when the number of bales handled was increased or additional equipment was utilized. [Copyright &y& Elsevier]

• White matter tracts that overlap with the thalamus and the putamen (hub+ tracts) have a lower degree of lesional and non-lesional tissue injury than white matter tracts that do not overlap or pass through these structures (hub- tracts), suggesting a protective role of the hubs against MS pathology. • Disease in both hub+ and hub- tracts was associated with measures of disability, however, disease in hub- tracts, retained slightly stronger correlation coefficients. • Our data points to the role of disease location in relation to hubs as guidance for treatment personalization, considering more aggressive approaches for patients presenting with MRI changes in hub- tracks. The thalamus and the putamen are highly connected hubs implicated in multiple sclerosis (MS) pathology. It remains unclear if white matter (WM) tracts, which pass through them, have a different susceptibility to MS pathology, and if so, if their impact on disability predominates over that exerted by disease in other WM tracts. We hypothesized that WM tracts connected to and passing through these hubs (subsequently termed hub+ tracts) would be more susceptible to MS-related pathology than tracts that do not pass through them (hub- tracts) due to retrograde and anterograde distant degeneration. Thus, we compared the lesion load and neurite orientation dispersion and density imaging (NODDI) derived metrics between hub+ and hub- tracts and assessed the relationship between these MRI metrics and those of physical impairment. Eighteen patients (mean age of 45.5 years, 12 females) had 3 Tesla MRI consisting of T1-weighted and T2-weighted Fluid Attenuated Inversion Recovery (FLAIR), and NODDI from which the orientation dispersion index (ODI), neurite density index (NDI), and isotropic volume fraction (IVF) were derived. Forty-nine WM tracts, i.e., 12 hub+ and 37 hub- tracts, were segmented out. Exploratory analyses of the differences in lesion burden, whole tract and normal appearing WM (NAWM) NODDI metrics were carried out between the two types of tracts using a Mann-Whitney U test. Correlations with physical impairment, quantified using the expanded disability status scale (EDSS) and timed 25-foot walk (T25FW) test were assessed using Spearman correlation analyses. Hub- tracts had larger T1- (p <0.001) and T2-lesion (p <0.001) volumes; lower ODI (p <0.001), NDI (p <0.001) and higher IVF (p = 0.020) in comparison to hub+ tracts. Measures of tissue injury in hub+ tracts correlated with those of clinical disability, though less strongly than in hub- tracts. Contrary to our hypothesis, our exploratory pilot study results suggest that WM tracts that overlap with the thalamus and the putamen have a lower degree of lesional and non-lesional tissue injury, suggesting a protective role of the hubs against MS pathology or a higher degree of vulnerability of those not passing through hub stations. We also show a weaker association between disability impairment and hub+ pathology, compared to that in hub- tracts. Our findings point to a potential role of disease location in relation to hubs as guidance for treatment personalization in MS [ABSTRACT FROM AUTHOR]

The rate of ribosome synthesis is proportional to the rate of cell proliferation; thus, transcription of rRNA by RNA polymerase I (Pol I) is an important target for the regulation of this process. Most previous investigations into mechanisms that regulate the rate of ribosome synthesis have focused on the initiation step of transcription by Pol I; however, recent studies in yeast and mammals have identified factors that influence transcription elongation by Pol l. The RNA polymerase-associated factor 1 complex (Paf1C) is a transcription elongation factor with known roles in Pol II transcription. We previously identified a role for Paf1C in transcription elongation by Pol l. In this study, genetic interactions between genes for Paf1C and Poll subunits confirm this conclusion. In vitro studies demonstrate that purified Paf1C directly increases the rate of transcription elongation by Pol I. Finally, we show that Paf1C function is required for efficient control of Pol I transcription in response to target of rapamycin (TOR) signaling or amino acid limitation. These studies demonstrate that Paf1C plays an important direct role in cellular control of rRNA expression. [ABSTRACT FROM AUTHOR]

Gamma scintigraphy is a well established imaging modality, which in equine practice is predominantly used in the investigation of lameness and suspected musculoskeletal problems. Whilst there is a growing literature on the indications for scintigraphy in the horse, there has been little emphasis so far on identifying the validity of scintigraphy as a diagnostic test. In particular, to what extent can the results of a scintigraphic examination be trusted? In this opinionated review the current indications for skeletal scintigraphy in the horse are considered and its validity as a diagnostic test reviewed. It is concluded that in the majority of published studies, inherent biases in study design make it difficult to assess accurately the validity of skeletal scintigraphy in the horse. Further well designed, prospective studies are required to assess the validity of skeletal scintigraphy as a diagnostic tool, particularly in horses with subtle alterations in radiopharmaceutical uptake. [ABSTRACT FROM AUTHOR]

Gamma scintigraphy is an established imaging modality in the horse and is principally utilised to investigate skeletal disease using bone-seeking radiopharmaceuticals. However, depending on the radiopharmaceutical and imaging sequence, scintigraphy can be used to investigate disease in virtually any organ system. In this article the indications and validity of scintigraphy as a clinical diagnostic tool to investigate non-skeletal disease in the horse are reviewed. These indications include: investigation of dental disease, identification of inflammatory foci, vascular lesions, muscle and tendon pathology, assessment of physiological function of the lungs, gastrointestinal tract and other organs. Some of the techniques described for use in the horse have not been validated fully and as a result non-skeletal scintigraphy requires further investigation and validation using well-designed prospective studies. Such information can be used by clinicians to make informed decisions regarding the clinical and economic issues associated with a specific scintigraphic technique and may help when interpreting the results. [ABSTRACT FROM AUTHOR]

Colic remains a significant problem in the horse in terms of welfare and economics; in some equine populations it is the single most common cause of death. Many causes of colic are cited in the equestrian and veterinary literature but little scientific evidence exists to substantiate these theories. Recent epidemiological investigations have confirmed that colic is complex and multi-factorial in nature. Studies have identified a number of factors that are associated with increased risk of colic including parasite burden, certain feed types, recent change in feeding practices, stabling, lack of access to pasture and water, increasing exercise and transport. These findings are reviewed together with examples of management practices that may be altered to reduce the incidence of specific types of colic. This is an opinionated, not a systematic, review focusing on those areas that are considered most relevant to the practitioner. [ABSTRACT FROM AUTHOR]

The NifU protein is a homodimer that is proposed to provide a molecular scaffold for the assembly of [Fe-S] clusters uniquely destined for the maturation of the nitrogenase catalytic components. There are three domains contained within NifU, with the N-terminal domain exhibiting a high degree of primary sequence similarity to a related family of [Fe-S] cluster biosynthetic scaffolds designated IseU. The C-terminal domain of NifU exhibits sequence similarity to a second family of proposed [Fe-S] cluster biosynthetic scaffolds designated Nfu. Genetic experiments described here involving amino acid substitutions within the N-terminal and C-terminal domains of NifU indicate that both domains can separately participate in nitrogenase-specific [Fe-S] cluster formation, although the N-terminal domain appears to have the dominant function. These in vivo experiments were supported by in vitro [Fe-S] cluster assembly and transfer experiments involving the activation of an apo-form of the nitrogenase Fe protein. [ABSTRACT FROM AUTHOR]

Objective: This study was undertaken to evaluate the effects on hemostatic factors of a low-dose preparation of levonorgestrel and ethinyl estradiol in a 12-cycle study.Study Design: Thirty healthy women began taking 100 microg levonorgestrel and 20 microg ethinyl estradiol on the first day of the menstrual cycle, continued to take the preparation for the next 21 days, and then took placebo for 7 days. Mean changes in prothrombin time, partial thromboplastin time, and levels of factors VII and X, antithrombin, plasminogen, fibrinogen, protein S, thrombin-antithrombin complexes, and D-dimer were analyzed at baseline and at cycles 3, 6, and 12 with paired Student t tests.Results: Factor X, plasminogen antigen and activity, and D-dimer levels were significantly increased (P Conclusion: The effects on hemostatic factors in healthy women of a monophasic preparation of 100 microg levonorgestrel and 20 microg ethinyl estradiol were similar to those of other low-dose oral contraceptives. [ABSTRACT FROM AUTHOR]

The efficacy and safety of a low-dose 21-day combination oral contraceptive containing 100 microg levonorgestrel and 20 microg ethinyl estradiol were evaluated in an open-label, multicenter trial. A total of 1708 subjects with regular menstrual cycles (27,011 cycles) were evaluated. The oral contraceptive was administered once a day for 21 days, followed by 7 days of placebo for a complete cycle. During 26,554 cycles evaluated for efficacy, 18 pregnancies occurred (Pearl index of 0.88); 6 of these events were attributable to subject noncompliance. After 30 cycles of exposure the cumulative rate of withdrawal as a result of accidental pregnancy was 1.9%. Breakthrough bleeding (with or without spotting) occurred in 12.9% of the cycles and spotting alone occurred in 10.1% of the cycles. The 2 most common adverse events cited as reasons for discontinuation were headache (2% of subjects) and metrorrhagia (2%). One serious event led to withdrawal of a subject. Overall, the results of this study demonstrate that the monophasic regimen of 100 microg levonorgestrel and 20 microg ethinyl estradiol offers effective contraception, acceptable cycle control, and a good tolerability profile. [ABSTRACT FROM AUTHOR]

Objective: Our purpose was to evaluate the efficacy and safety of 3 dosages of Esclim, delivering 0.025 mg, 0.050 mg, or 0.100 mg 17beta-estradiol per 24 hours, in the treatment of moderate to severe vasomotor symptoms.Study Design: In this double-blind, placebo-controlled, parallel-group, multicenter trial, 196 highly symptomatic menopausal women received 12 weeks of continuous unopposed treatment with 1 of the 3 dosages of Esclim or a matching placebo patch.Results: The reduction in frequency of moderate to severe vasomotor symptoms was statistically significant compared with placebo (P <.05) from week 2 onward in the Esclim 50 and 100 groups and from week 3 onward in the Esclim 25 group. Symptom severity was also reduced. Estrogen-related adverse events, particularly metrorrhagia and endometrial hyperplasia, were less frequent in the Esclim 25 group than in the higher-dosage groups.Conclusion: All 3 dosages of Esclim were effective in the treatment of vasomotor symptoms. The efficacy and safety of Esclim 25 indicate a good risk-benefit ratio. [ABSTRACT FROM AUTHOR]

Focuses on the effects of 1,25-dihydroxyvitamin D3 and analogue, 1,25-dihydroxy-16ene-vitamin D3, on T helper subsets type 1 (Th1) or type 2 (Th2) that have distinctive functional characteristics in humans. Th1 and Th2 secretions; Sterol; Spontaneous autoimmunity.

Harvested hay or biomass are traditionally baled for better handling and they are transported to the outlet for final utilization. For better management of bale logistics, producers often aggregate bales into stacks so that bale-hauling equipment can haul multiple bales for improved efficiency. Objectives of this research include simulation of bale collection logistics after forming subfield stacks, evaluation of location effects of bale stack and field outlet, the number of stacks, transported bales/trip, and other field parameters on logistics distances (aggregation, transportation, and total). The software ‘R’ performed the simulation, statistical analysis, and data visualization. Formation of bale stacks decoupled aggregation and transportation components. Stacks formation thus allows for aggregation and transportation to be performed at different times. Increasing the number of subfield stacks and the number of transported bales/trip significantly reduced the total logistics distances. The order for the best bale stack and outlet locations was: middle, near middle, mid-edge along the length, mid-edge along the width, and finally, corners. Except for swath and windrow variation, the studied field variables had a highly significant influence on the logistics distances. Increased bales/trip (≥6) reduced the variations of outlet locations. Locating the field outlet at or near the center of the field along with an appropriate number of square subfields with stacks at the middle, and increased bales/trip will be the most efficient infield logistics strategy. [ABSTRACT FROM AUTHOR]

Industrial beets are an emerging feedstock for biofuel and bioproducts industry in the US. Milling of industrial beets is the primary step in front end processing for ethanol production. Milled beets undergo color change during juice extraction. A custom designed computer vision system for measurement of milled beet color kinetics, consisting of a digital camera, custom-designed non-reflective enclosure, and color calibration method was developed in the present study. Beet samples of five different total soluble solids (TSS) contents were prepared by washing with cold water for color kinetics measurement. An artificial neural network model was used for converting the red, green, and blue (RGB) values of the acquired sample images to L * a * b * values. Seven color parameters ( L * , a * , b * , hue, chroma, browning index ( BI ), and total color change (Δ E )) were analyzed. Page, user-defined polynomial, and fractional conversion models gave better fits for the experimental data with color parameters than the zeroth order, first order, exponential, and Peleg kinetic models. Of the color parameters studied, L * (Page R 2 > 0.99, user-defined polynomial R 2 > 0.97, and fractional R 2 > 0.93) and Δ E (Page R 2 > 0.98, user-defined polynomial R 2 > 0.94, and fractional R 2 > 0.85) gave the best description for the color change kinetics of milled beets. Developed TSS prediction models from the color measurements based on Page model constant, k p with color parameter, L * gave good prediction ( R 2 = 0.99), also did the simple linear model based on direct color values ( R 2 = 0.98). Measurement and mathematical modeling of milled industrial beets color kinetics will serve as important quality assessment tool in processing the beets for various renewable fuel and products applications. [ABSTRACT FROM AUTHOR]

Post-translational histone modifications play important roles in regulating gene expression programs, which in turn determine cell fate and lineage commitment during development. One such modification is histone ubiquitination, which primarily targets histone H2A and H2B. Although ubiquitination of H2A and H2B has been generally linked to gene silencing and gene activation, respectively, the functions of histone ubiquitination during eukaryote development are not well understood. Here, we identified USP12 and USP46 as histone H2A and H2B deubiquitinases that regulate Xenopus development. USP12 and USP46 prefer nucleosomal substrates and deubiquitinate both histone H2A and H2B in vitro and in vivo. WDR48, a WD40 repeat-containing protein, interacts with USP12 and USP46 and is required for the histone deubiquitination activity. Overexpression of either gene leads to gastrulation defects without affecting mesodermal cell fate, whereas knockdown of USP12 in Xenopus embryos results in reduction of a subset of mesodermal genes at gastrula stages. Immunohistochemical staining and chromatin immunoprecipitation assays revealed that USP12 regulates histone deubiquitination in the mesoderm and at specific gene promoters during Xenopus development. Taken together, this study identifies USP12 and USP46 as histone deubiquitinases for H2A and H2B and reveals that USP12 regulates Xenopus development during gastrula stages. [ABSTRACT FROM AUTHOR]

Summary: We discuss our surgical philosophy concerning the subtle interplay between the size of the surgical margin taken and the resultant morbidity from ablative oncological procedures, which is ever more evident in the treatment of head and neck malignancy. The extent of tissue resection is determined by the “trade off” between cancer control and the perioperative, functional and aesthetic morbidity and mortality of the surgery. We also discuss our dilemmas concerning recent minimally invasive endoscopic microsurgical techniques for the trans-oral laser removal or co-ablation of aero-digestive tract tumours, which result in a minimal surgical margin of oncological clearance. By a process of inductive argument as to the nature of the surgical margin, we consider whether the risks of taking a lesser margin with adjuvant therapy is justified by the attendant gain in reduced surgical morbidity and the possible costs in tumour control. [Copyright &y& Elsevier]

Summary: We investigated the association between genetic polymorphisms in GPX1 gene amongst patients who had index squamous cell carcinoma (SCCHN) and a second primary tumour (SPT) after a primary SCCHN in a case-control study. GPX1 genotypes were determined for 61 patients with SPT and for 259 control subjects by a PCR technique using a fluorescent-labelled primer. Analysis was by an ABI automated fluorescent sequencer. The associations between specific genotypes and the development of SPT were examined by logistic regression. A significant difference was found between the control group and the SPT cases in allele frequencies of GPX1 ALA∗6 and ALA∗7 (p trend =0.04). These results suggest that polymorphisms in the GPX1 gene may be a marker for SPT development and further studies are indicated. [Copyright &y& Elsevier]

Squamous cell carcinoma (SCC) of the oral tongue is characterized by a high propensity for cervical nodal metastasis, which affects the probability of regional control and survival. Until now, elective treatment of the clinically negative neck in early lesions (T1–2) of the oral tongue cancer remains controversial. This study attempted to identify predictive factor(s) for cervical nodal metastasis and treatment outcomes in patients with early stage SCC of the oral tongue treated primarily by surgery. Fifty patients with previously untreated Stage I/II primary tongue carcinomas with available archival specimens treated at the Royal Marsden Hospital between 1981 and 1998 were reviewed. Clinico-pathological features including age, gender, alcohol and tobacco consumption, tumour location, histological grade, tumour-stromal border, growth pattern, tumour thickness, and clinical stage were evaluated and the correlations with cervical metastases and outcome analysis were determined. The overall occult nodal metastatic rate was 40% (20/50). Tumour thickness exceeding 5 mm was statistically significantly correlated with cervical metastases (P=0.003; relative risk=2.429). No statistical correlation was observed between other clinico-pathological parameters and nodal metastasis. With a median follow-up of 98 months, 5-year actuarial overall, disease-specific (DSS), and relapse-free survival were 65.71, 67.77, and 68.18%, respectively. Univariate analysis for DSS showed poorer outcomes for patients with age >60 years (P=0.0423) and tumour thickness >5 mm (P=0.0067). The effect of tumour thickness was maintained (P=0.005) on multivariate analysis. The present study indicates that the thickness of primary tumour has a strong predictive value for occult cervical metastasis and poor outcomes in patients with Stage I/II oral tongue SCC. Thus, elective neck treatment (surgery or irradiation) is indicated for tumours exceeding 5 mm thickness. [Copyright &y& Elsevier]

We reviewed patients treated at The Royal Marsden Hospital for mucosal malignant melanoma of the head and neck between 1945 and 1996. The analysis included 89 patients, and this study is the largest so far reported from a single institution in the literature. The overall 5-year survival rate for the patient population was 23% (95% confidence interval: 14–33) and the 10-year survival rate was 12% (6–21%). The only significant predictor of survival was the tumour stage at presentation. Radical local excision was the only treatment that provided a chance of cure. Adding radiotherapy to surgery in tumours that could be radically excised did not confer any statistically significant advantage in reducing local recurrence or improving survival. [Copyright &y& Elsevier]

Infield bale aggregation is essential for bale removal and preparing the field for subsequent crops, which can be more efficiently performed using the modern automatic bale picker (ABP) that supports multiple bales/trip (BPT) than commonly used tractors. But the energy involved in the bale aggregation logistics using ABP has not been thoroughly evaluated. Therefore, the energy involved in the bale aggregation, in terms of fuel consumption, was studied for different logistic scenarios using a tractor (control) and ABP through a user-developed simulation program in R. Different variables such as field areas (8 to 259 ha), biomass yields (3–40 Mg ha − 1), four outlet locations, and five equipment speeds (6.6–10.5 km h − 1) using realistic equipment turning paths were used in the simulation. The Nebraska Tractor Test general method and fuel efficiency method were considered for the fuel consumption calculations. Fuel consumption for the ABP (8–259 ha) with 8 BPT on an average decreased by 72 % and 53 % compared to a tractor with 1 and 2 BPT, respectively, based on logistics distance and equipment operation. Field area, biomass yield, and BPT were the most influential variables affecting logistics distance; while, field area, biomass yield, BPT, and equipment speed affecting the operation time and fuel quantity. Convenient prediction models (multi-variate nonlinear) for logistics distance, operation time, and fuel quantity, using the influential field variables, produced very good fits ( R 2 ≥ 0.98). Overall, an ABP with a capacity of 8 BPT, split which can also handle 11 BPT, is recommended considering the logistics energy. • Bale aggregation with tractor and automatic bale picker (ABP) were simulated using R. • Field area, biomass yield, and bales/trip (BPT) were influential variables for modeling. • ABP with 8 BPT greatly decreased the logistics distance and fuel compared to tractor. • Multi-variate models predicted logistics distances, operation time, and fuel quantity. [ABSTRACT FROM AUTHOR]