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This study tests the utility of convolutional neural networks as a postprocessing framework for improving the National Center for Environmental Prediction's Global Forecast System's integrated vapor transport forecast field in the Eastern Pacific and western United States. Integrated vapor transport is the characteristic field of atmospheric rivers, which provide over 65% of yearly precipitation at some western U.S. locations. The method reduces full‐field root‐mean‐square error (RMSE) at forecast leads from 3 hr to seven days (9–17% reduction), while increasing correlation between observations and predictions (0.5–12% increase). This represents an approximately one‐ to two‐day lead time improvement in RMSE. Decomposing RMSE shows that random error and conditional biases are predominantly reduced. Systematic error is reduced up to five‐day forecast lead, but accounts for a smaller portion of RMSE. This work demonstrates convolutional neural networks potential to improve forecast skill out to seven days for precipitation events affecting the western United States. Machine learning methods are data‐driven algorithms that improve by examining massive amounts of existing data. We explore the utility of a computer‐vision machine learning technique to reduce error in numerical weather forecasts of the characteristic field for atmospheric rivers (ARs). ARs are long narrow corridors of anomalous vapor transport capable of providing both beneficial and hazardous precipitation. Therefore, accurately forecasting AR events is extremely important from a water supply and flood protection standpoint. We show significant forecast improvements by applying machine learning postprocessing for lead times ranging from 3 hr to seven days, making the predictions more valuable to stakeholders affected by AR events. The GFS forecast field of integrated vapor transport is used for a convolutional neural network‐based forecast postprocessing methodThe machine learning algorithm reduces the full‐field root‐mean‐square error and improves the correlation with ground truthAn error deconstruction shows that the dominant improvements come from the reduction of random error and conditional biases

Arid regions are often characterized by exceptionally high rates of fluvial sediment transport, but the processes responsible for this apparent connection between climate and sediment transport remain unclear. We examined decades of continuous flow records and suspended sediment concentrations from 71 rivers across the United States by comparing the suspended sediment rating curve behavior, quantified using power law coefficients and exponents, to an aridity index. Results indicate that higher aridity correlates with both greater overall suspended sediment concentration and lower sensitivity of concentration to changes in discharge, demonstrating that rivers in arid locations on average have greater suspended sediment transport efficiency across most discharges, and achieve high transport rates at a relatively lower discharge than rivers in temperate climates. Furthermore, based on additional analyses of the Normalized Difference Vegetation Index, specific suspended sediment yield, and a hydrograph flashiness index, we attribute the relationships between sediment transport and climate primarily to differences in vegetation density, precipitation, and runoff, variables that all influence both sediment supply and riverbed grain sorting. Finally, we note that the observed contrasts in sediment transport behavior likely represent climate‐driven differences in the magnitude and frequency of sediment supply rather than annual suspended sediment load, which does not depend significantly on climate. This study highlights a critical connection between multiple interrelated climatic factors and sediment transport, an important finding for future hazard mitigation in a changing climate with rapidly shifting vegetation patterns and hydrology. There is a wide variation in the appearance and behavior of rivers throughout the world, which often relates to how rivers move sediment. For example, the degree of erosion and sediment deposition following large floods does not depend solely on the size of the flood but also on the amount of sediment it contains. To this point, some evidence suggests that rivers in dry climates carry larger volumes of sediment at a given flow than rivers in temperate climates, but this connection has not been sufficiently explored on a large scale. We addressed this scientific gap by examining how sediment concentrations in rivers respond to changes in flow. Our results from dozens of rivers across the United States indicate that streams in more arid climates often carry higher concentrations of sediment at a given flow rate than their temperate counterparts, especially during smaller flood events. This behavior may relate to differences in vegetation density and rainfall patterns, as both of these climate‐dependent factors influence the quantity of sediment entering streams and the organization of sediment on the streambed. These findings reveal an important link between climate and sediment transport, which is important to consider as we prepare for future climate change. Flow records and suspended sediment data from 71 rivers in the US reveal a significant relationship between aridity and sediment transportIn arid climates, suspended sediment concentration is on average higher and less sensitive to changes in discharge than in humid climatesClimate‐dependent factors like vegetation density and runoff variability likely explain observed differences in sediment transport behavior Flow records and suspended sediment data from 71 rivers in the US reveal a significant relationship between aridity and sediment transport In arid climates, suspended sediment concentration is on average higher and less sensitive to changes in discharge than in humid climates Climate‐dependent factors like vegetation density and runoff variability likely explain observed differences in sediment transport behavior

The Test of Memory Malingering (TOMM) is a commonly utilized performance validity test currently recommended for pediatric use with children as young as 5 years of age. Yet, a small sample of children struggles to pass the TOMM due to true cognitive difficulties. The systematic search and review identified the reported cases of false positive and overall failing TOMM performance in children. The goal of this project was to increase the understanding of the cognitive constructs and minimum cognitive abilities necessary for children to pass the TOMM. The secondary goal was to use the existing data to suggest clinical guidelines related to use of the TOMM with children. A comprehensive search of PubMed/MEDLINE, EMBASE, Web of Science, and PsycINFO was conducted, returning an initial 12,052 results. After duplicate articles were removed, 10,583 remained; 61 were evaluated for eligibility and 22 were included as our final sample. Results suggested that false positives were observed in children with low IQ, memory issues, complex medical presentation, and younger children. Without relevant, quality validation and normative studies, the TOMM should not be used clinically with young children or children suspected of having significant cognitive issues. Failing performance on the TOMM does not necessarily indicate poor effort or invalidate the neuropsychological profile. Instead, it may be reflective of other factors, particularly in children below age 6, children with lower intellectual abilities (especially FSIQ ≤ 75), children with multiple diagnoses, or children with more severe neurological diagnoses. Clinical recommendations are also discussed.

Acute upper gastrointestinal bleed (AUGIB) is one of the most common medical emergencies in the UK, with roughly one presentation every 6 min. Despite advances in therapeutics and endoscopy provision, mortality following AUGIB over the last two decades has remained high, with over 9,000 deaths annually in the UK; consequently, several national bodies have published UK-relevant guidelines. Despite this, the 2015 UK National Confidential Enquiry into Patient Outcome and Death in AUGIB highlighted variations in practice, raised concerns regarding suboptimal patient care and released a series of recommendations. This review paper incorporates the latest available evidence and UK-relevant guidelines to summarise the optimal pre-endoscopic, endoscopic, and post-endoscopic approach to and management of non-variceal and variceal AUGIB that will be of practical value to both general physicians and gastroenterologists.

Background:Malreduction of the syndesmosis can lead to increased peak pressures and subsequent arthritis. The purpose of this study was to evaluate the initial syndesmotic reduction and radiographic maintenance when using a knotless suture button fixation device for treatment of syndesmotic injury.Methods:A retrospective chart and radiographic review was performed to identify patients who underwent open reduction internal fixation of ankle syndesmosis ruptures treated with a knotless, suture button fixation system. Radiographic measurements included medial clear space, tibiofibular overlap, tibiofibular clear space, and the distance between buttons. Fifty-six patients underwent repair of an ankle fracture with syndesmotic rupture over a 3-year period, with a mean follow-up of 160.9 days.Results:The tibiofibular clear space and tibiofibular overlap significantly improved from pre- to first postoperative, but also demonstrated some loss of fixation at final follow-up (P < .001). The distance between the buttons increased on average 1.1 mm from immediate postoperative to final follow-up, demonstrating some postoperative creep and loss of fixation in the system. A low complication rate and need for a revision operation was found in our patient cohort. Some loss of reduction did occur postoperatively, although this did not correlate to adverse patient outcomes.Conclusion:Syndesmotic stabilization, using a knotless suture button fixation device demonstrated adequate initial syndesmotic reduction, but also exhibited an increase in the tibiofibular clear space and tibiofibular overlap, relative to initial postfixation position, at short-term follow-up.Level of Evidence:Level IV, retrospective case series.

The authors report on the establishment of the nation's first Organ Procurement Organization–based organ recovery facility with a goal of increasing efficiencies, reducing costs, and reducing procurement surgeon travel.

In this retrospective study, the authors demonstrate that biopsy‐proven transplant glomerulopathy in renal transplant recipients is associated with immune responses to self‐antigens Collagen‐IV and fibronectin.

Early conversion from tacrolimus to a regimen combining everolimus with low‐exposure tacrolimus improves renal function at two years post‐liver transplantation. See editorial by Bhat and Charlton on page 1633.

In a prospective, multicenter, open‐label study, de novoliver transplant patients were randomized at day 30±5 to (i) everolimus initiation with tacrolimus elimination (TAC Elimination) (ii) everolimus initiation with reduced‐exposure tacrolimus (EVR+Reduced TAC) or (iii) standard‐exposure tacrolimus (TAC Control). Randomization to TAC Elimination was terminated prematurely due to a higher rate of treated biopsy‐proven acute rejection (tBPAR). EVR+Reduced TAC was noninferior to TAC Control for the primary efficacy endpoint (tBPAR, graft loss or death at 12 months posttransplantation): 6.7% versus 9.7% (−3.0%; 95% CI −8.7, 2.6%; p<0.001 for noninferiority [12% margin]). tBPAR occurred in 2.9% of EVR+Reduced TAC patients versus 7.0% of TAC Controls (p = 0.035). The change in adjusted estimated GFR from randomization to month 12 was superior with EVR+Reduced TAC versus TAC Control (difference 8.50 mL/min/1.73 m2, 97.5% CI 3.74, 13.27 mL/min/1.73 m2, p<0.001 for superiority). Drug discontinuation for adverse events occurred in 25.7% of EVR+Reduced TAC and 14.1% of TAC Controls (relative risk 1.82, 95% CI 1.25, 2.66). Relative risk of serious infections between the EVR+Reduced TAC group versus TAC Controls was 1.76 (95% CI 1.03, 3.00). Everolimus facilitates early tacrolimus minimization with comparable efficacy and superior renal function, compared to a standard tacrolimus exposure regimen 12 months after liver transplantation.

Hepatitis C virus (HCV) recurrence with accelerated fibrosis following orthotopic liver transplantation (OLT) is a universal phenomenon. To evaluate mechanisms contributing to HCV induced allograft fibrosis/cirrhosis, we investigated HCV‐specific CD4+Th17 cells and their induction in OLT recipients with recurrence utilizing 51 HCV+ OLT recipients, 15 healthy controls and 9 HCV‐ OLT recipients. Frequency of HCV specific CD4+ Tcells secreting IFN‐γ, IL‐17 and IL‐10 was analyzed by ELISpot. Serum cytokines and chemokines were analyzed by LUMINEX. Recipients with recurrent HCV induced allograft inflammation and fibrosis/cirrhosis demonstrated a significant increase in frequency of HCV specific CD4+Th17 cells. Increased pro‐inflammatory mediators (IL‐17, IL‐1β, IL‐6, IL‐8 and MCP‐1), decreased IFN‐γ, and increased IL‐4, IL‐5 and IL‐10 levels were identified. OLT recipients with allograft inflammation and fibrosis/cirrhosis demonstrated increased frequency of Foxp3+ regulatory T cells (Tregs) that inhibited HCV specific CD4+Th1 but not Th17 cells. This suggests that recurrent HCV infection in OLT recipients induces an inflammatory milieu characterized by increased IL‐6, IL‐1β and decreased IFN‐γ which facilitates induction of HCV specific CD4+Th17 cells. These cells are resistant to suppression by Tregs and may mediate an inflammatory cascade leading to cirrhosis in OLT recipients following HCV recurrence.

T-cell activation up-regulates CD30 resulting in an increase in serum soluble CD30 (sCD30). CD4 T cells, a major source for sCD30, play a significant role in the pathogenesis of rejection. In this study, sCD30 was measured pre- and posttransplant in mouse islet allograft models and human islet allograft recipients. sCD30 was measured by ELISA in diabetic C57BL6, CD4Knockout (KO) and CD8KO islet allograft recipients. sCD30 increased significantly prior to rejection (1.8 ± 1 days) in 80 of allograft recipients. Sensitization with donor splenocytes, or a second graft, further increased sCD30 (282.5 ± 53.5 for the rejecting first graft vs. 374.6 ± 129 for the rejecting second graft) prior to rejection suggesting memory CD4 T cells contribute to sCD30. CD4KO failed to reject islet allograft and did not demonstrate sCD30 increase. CD8KO showed elevated (227 ± 107) sCD30 (1 day) prior to rejection. High pretransplant sCD30 (>20 Uml) correlated with poor outcome in human islet allograft recipients. Further, increase in sCD30 posttransplant preceded (3-4 months) loss of islet function. We conclude that sCD30 is released from activated CD4 T cells prior to islet allograft rejection and monitoring sCD30 can be a valuable adjunct in the follow-up of islet transplant recipients.

Recurrent hepatitis C infection (HCV) following liver transplantation causes accelerated allograft cirrhosis. Here we characterized HCV-specific immunity in adult liver transplant recipients (n 74) with and without allograft cirrhosis. Patients were divided into hepatic inflammationno cirrhosis (METAVIR scores 0-2, HIN) and hepatic cirrhosis (score 3-4, HFC). As control, 20 normal subjects and 10 non-HCV liver transplant patients were included. Twenty-five different serum cytokines were analyzed using LUMINEX. Frequency of T-cells specific to HCV-derived proteins (NS3, NS4, NS5, Core) was characterized using ELISPOT immunoassays. There was no difference in clinical characteristics between HIN (n 49) and HFC (n 25) groups. HIN group had high serum IFN-? and IL-12 while HFC demonstrated elevated IL-4, IL-5 and IL-10 (p < 0.01). HCV (NS3, NS4, NS5, Core)-specific IFN-?-producing CD4T-cells were elevated in the HIN group whereas the HFC patients showed predominance of HCV-specific IL-5 and IL-10-producing CD4T-cells. Conclusions: Lack of HCV-specific Th1-type T-cell immunity is observed in liver transplant recipients with advanced allograft cirrhosis.

Islet transplantation is a treatment option for type I diabetic patients. Preservation of human pancreata prior to islet isolation using two-layer method with perfluorocarbon (PFC) and University of Wisconsin solution (UW) results in twofold increase in islet yields. The objective of this study was to determine the mechanism by which islets undergo apoptosis and determine PFC's effects on this process. Gene array analysis was used to analyze the expression of pro- and anti-apoptotic genes in islets isolated from pancreata preserved under varying conditions. A 12-fold increase in the expression of inhibitor of apoptosis (IAP) and survivin was observed in islets isolated from pancreata preserved in PFC. This was accompanied by decreased expression of BAD (3.7-fold), BAX (2.7-fold) and caspases (5.2-fold). Levels of activated caspase-9 (77.98%), caspase-2 (61.5%), caspase-3 (68.3%) and caspase-8 (37.2%) were also reduced. ‘Rescue’ of pancreata after storage (12 h) in UW by preservation using PFC also resulted in a down-regulation of pro-apoptotic genes and inhibition of caspase activation. Apoptosis observed in islets from all groups was mainly mitochondria-dependent, mediated by change in redox potential initiated by hypoxia. We demonstrate that reduction in hypoxia of pancreata preserved using PFC leads to significant up-regulation of anti-apoptotic and inhibition of pro-apoptotic genes.

A program was established within our regional procurement organization to permit evaluation of altruistic living donors (LD) interested in nondirected kidney or liver segment donation prior to transplant center referral.

Molecular dynamics (MD) simulations were performed to investigate odd−even chain length dependencies in the wetting properties of self-assembled monolayers (SAMs) of n-alkanethiols [CH3(CH2)n-1SH] on gold by water and hexadecane. Experimentally, the contact angle of hexadecane on the SAMs depends on whether n is odd or even, while contact angles for water show no odd−even dependence. Our MD simulations of this system included a microscopic droplet of either 256 water molecules or 60 hexadecane molecules localized on an n-alkanethiolate SAM on gold with either an even or odd chain length. Contact angles calculated for these nanoscopic droplets were consistent with experimentally observed macroscopic trends in wettability, namely, that hexadecane is sensitive to structural differences between odd- and even-chained SAMs while water is not. Structural properties for the SAMs (including features such as chain tilt, chain twist, and terminal methyl group tilt) were calculated during the MD simulations and used to generate IR spectra of these films that compared favorably with experimental spectra. MD simulations of SAMs in contact with slabs of water and hexadecane revealed that the effects of these solvents on the structure of the SAM was restricted to the chain terminus and had no effect on the inner structure of the SAM. The density profiles for water and hexadecane on the SAMs were different in that water displayed a significant depletion in its density at the liquid/SAM interface from its bulk value, while no such depletion occurred for hexadecane. This difference in contact may explain the lack of an odd−even variation in the wetting characteristics of water on these surfaces, because the water molecules are positioned further away from the surface and, therefore, are not sensitive to the structural differences in the average orientations for the terminal methyl groups in odd- and even-chained SAMs. In contrast, the differences in the wetting properties of hexadecane on the odd- and even-chained SAMs may reflect the closer proximity of these molecules to the SAM surface and a resulting greater sensitivity to the differences in the terminal methyl group orientations in the SAMs. SAM−solvent interaction energies were calculated during the MD simulations, yielding interaction energies that differed on the even- and odd-chained surfaces by ~10% for hexadecane and negligibly for water, in accord with estimates using experimental wetting results.

To better understand clathrate hydrate mechanisms, nuclear magnetic resonance (NMR) and viscosity measurements were employed to investigate tetrahydrofuran (THF) hydrate formation and dissociation processes. In NMR experiments, the proton spin lattice relaxation time (T1) of THF in deuterium oxide (D2O) was measured as the sample was cooled from room temperature down to the hydrate formation region. The D2O structural change around THF during this process was examined by monitoring the rotational activation energy of THF, which can be obtained from the slope of ln(1/T1) vs 1/T. No evidence of hydrate precursor formation in the hydrate region was found. T1 measurements of THF under constant subcooling temperature indicate that THF hydration shells do not undergo much structural rearrangement during induction. The T1 of THF was also measured as the sample was warmed back to room temperature after hydrate dissociation. T1 values of THF after hydrate dissociation were consistently smaller than those before hydrate formation and never returned to original values. It was proposed that this difference in T1 after hydrate dissociation indicates that the THF−D2O solution is more microscopically homogeneous than before hydrate formation. In viscosity experiments, a Champion Technologies hydrate rocking cell (CTHRC) was used to probe the residual viscosity phenomenon after Green Canyon (GC) gas hydrate as well as THF hydrate dissociation. The residual viscosity reported in the literature was observed after GC hydrate dissociation but not after THF hydrate dissociation. Because GC hydrate behavior involves significant amounts of gas mass transfer while THF hydrate does not, one might conclude that the residual viscosity observed after GC hydrate dissociation was likely caused by the supersaturated gas concentration and its general effect on solvent viscosity, not necessarily by a clathrate water structure lingering from the solid.

The Perturbed-Chain SAFT (PC-SAFT) equation of state is applied to model phase equilibria and the thermodynamic properties of ethers and esters. A systematic study of these two homologous series is conducted, and the performance of two different approaches for including the dipolar interactions in the equation of state is evaluated. Although both Polar PC−SAFT [dipolar contribution due to Jog and Chapman, Mol. Phys. 1999, 97, 307−319] and PC−SAFT + Fischer [dipolar contribution by Saager and Fischer, Mol. Simul. 1991, 6, 27−49] yield similar results for the considered systems, the parameters of Polar PC−SAFT are more physically meaningful than those of PC−SAFT + Fischer. Consequently, Polar PC−SAFT is considered to be more suitable for extrapolations, and for application to components that have multiple polar groups in the chain.

Dipolar interactions, which traditionally have been very difficult to model or predict accurately, have a significant effect on the phase behavior of a plethora of systems of industrial importance such as mixtures containing ketones, aldehydes, ethers, and esters as well as polar polymers, copolymers, and a variety of biochemicals. Jog and Chapman proposed a model that accurately predicts the properties of chainlike molecules with single or multiple dipolar sites (Jog, P. K.; Chapman, W. G. Mol. Phys. 1999, 97, 307). In a more recent paper (Jog, P. K.; Sauer, S. G.; Blaesing, J.; Chapman, W. G. Ind. Eng. Chem. Res. 2001, 40, 4641), this theory was extended to mixtures of polar fluids. We continue the analysis and application of the method here in a parametric study using ketones and further demonstrate the ability of the model to accurately predict phase behavior for polar mixtures by applying the method to mixtures of alkanes and ketones of varying lengths. The ketone parameters are very well behaved in that they are smooth functions of molecular weight. The model is able to capture the physics of the phase behavior of a variety of alkane and ketone mixtures, including those of a diketone and alkane mixture. We utilize both the perturbed-chain and Chen−Krewlewski approaches to the dispersion term for the SAFT model, which demonstrates the inclusiveness of the polar term independent of the dispersion term. A comparison with UNIFAC shows the advantage of our polar chain theory for modeling systems containing molecules with multiple dipolar groups.

Repopulation of clonogenic tumor cells appears to increase during fractionated radiation treatment and is recognized as an important factor affecting local control. Given the longer intervals between cycles and longer total duration of treatment, the impact of repopulation is likely to be greater after chemotherapy. We assessed tumor cell repopulation with the proliferative marker Ki-67 in 21 patients with ovarian carcinoma who received initial chemotherapy. Paraffin slides were evaluated from the diagnostic biopsy and from tumor obtained at debulking surgery after chemotherapy. Immunohistochemistry using the MIB-1 antibody was performed on the paired samples and analyzed with a digital imaging device linked to a color camera mounted on a transmitted-light microscope. The ratio of Ki-67 positive to all nuclei was used as a proliferative index and compared for pre- and postchemotherapy specimens. All patients received platinum-based chemotherapy and most showed a response to treatment. The median duration between last chemotherapy and debulking surgery was 33 days (range, 22–50 days). Four (19%) of 21 patients showed an increased proliferative index after chemotherapy, and the remainder showed a decrease (n = 12) or no significant change (n = 5). Our results did not suggest an increase in proliferation of tumor cells after this type of chemotherapy in the majority of patients with ovarian cancer. Cytometry Part A 51A:1–6, 2003. © 2002 Wiley-Liss, Inc.

In this work we relate agglomeration in a polyethylene reactor to the solid−liquid phase transition of the polymer. The model assumes that the polyethylene dissolution temperature in the carrier [or the solid−liquid equilibrium (SLE) temperature of the polymer at the reactor conditions] correlates with, and is representative of, the onset of agglomeration in slurry reactors. We use the statistical associating fluid theory (SAFT) model for the liquid phase to study the effect of various carriers, polymer molecular weight, polymer crystallinity, and the effect of excess monomer on the SLE behavior of polyethylene. It is seen that the polyethylene−carrier SLE temperature correlates well with the onset of agglomeration for the carriers considered in this study.

The statistical associating fluid theory (SAFT) is used to model liquid−liquid-phase equilibria in solutions of linear low-density polyethylene (LLDPE) with hexane, heptane, and octane. The effect of temperature, pressure, polymer concentration, and polymer molecular weight on phase separation is studied. Finally, the effect of polydispersity on cloud point is also considered. SAFT results are compared with experimental data by de Loos et al. (Fluid Phase Equilib. 1996, 117, 40). SAFT can model the phase behavior of the polymer in different solvents at various state conditions with a single adjustable parameter. For a monodisperse polymer in hexane, the critical polymer concentration is linear with respect to the reciprocal of the square root of molecular weight. Calculations with a polydisperse polymer show that the cloud-point curve for a polydisperse polymer differs qualitatively from that of a monodisperse polymer at low polymer concentration. As the polymer concentration is decreased below the critical polymer concentration, the cloud-point pressures decrease for a monodisperse polymer. SAFT predicts that the cloud-point pressures for a polydisperse polymer continue to increase in qualitative agreement with experimental data. Thus, SAFT can be used to predict the phase behavior of LLDPE in different hydrocarbon solvents.

We propose an algorithm for calculating phase equilibria of polydisperse polymer systems using the SAFT equation of state. The algorithm is formally exact and the computation time is independent of the number of pseudocomponents used to represent the polymer molecular weight distribution. The algorithm is based on the assumptions that the discrete pseudocomponents have the same segment size, the chain length is directly proportional to the molecular weight, and the binary interaction parameter kij between the discrete pseudocomponents is zero. The basic version of the algorithm assumes that the dispersion energy parameter (u⁰/k) is the same for all the pseudocomponents and the binary interaction parameter kij is the same between all the pseudocomponents and the solvent. The algorithm is then generalized to the case where the dispersion energy parameter (u⁰/k) is different for each pseudocomponent and the polymer/solvent binary interaction parameter is different for each pseudocomponent. Distinctive features of the phase diagrams of polydisperse systems are illustrated by calculating the cloud point and shadow point curves of polyethylene solutions in ethylene using the algorithm proposed in this work.

Phase behavior is strongly affected by dipolar interactions in a wide range of systems including those containing ketones, aldehydes, ethers, and esters. Multiple polar sites are present in various polar copolymers as well as in polyethers and polyesters. Although theories have been developed for nearly spherical polar molecules and for nonpolar chain molecules, accounting simultaneously for a single multipolar interaction and molecular shape has remained an unsolved problem of statistical-mechanics-based perturbation theory (Gray, C. G.; Gubbins, K. E. Theory of Molecular Fluids I; Clarendon Press:  Oxford, U.K., 1984. Walsh, J. M.; Gang, J.; Donohue, M. D. Fluid Phase Equilib. 1991, 65, 209). Accurate accounting for the effect of multiple polar sites in nonspherical molecules has been well beyond expectation. In recent work, we solved part of this problem by showing how to accurately predict the properties of chainlike molecules with single or multiple dipolar sites (Jog, P. K.; Chapman, W. G. Mol. Phys. 1999, 97, 307−319). Although we cast this result in terms of the original SAFT equation of state (Chapman, W. G.; Gubbins, K. E.; Jackson, G. Mol. Phys. 1988, 65, 1057−1079. Chapman, W. G. Ph.D. Dissertation, Cornell University, Ithaca, NY, 1988. Chapman, W. G.; Gubbins, K. E.; Jackson, G.; Radosz, M. Ind. Eng. Chem. Res. 1990, 29, 1709−1721), the approach is applicable to other accurate chain fluid equations of state. In this paper, we (a) demonstrate the differences between our approach and previous models, (b) extend our theory to mixtures of polar fluids, and (c) compare our results with experimental data to demonstrate the predictive capabilities of the new theory.

Objectives.The aim of this study was to determine whether there have been any significant changes in the demographics and perioperative care of FIGO stage IA2/IB1cervical cancer over the past 16 years and, if so, to quantify them.

Damage to cellular DNA is believed to determine the antiproliferative properties of platinum (Pt) drugs. This study characterized DNA damage by oxaliplatin, a diaminocyclohexane Pt drug with clinical antitumor activity. Compared with cisplatin, oxaliplatin formed significantly fewer Pt-DNA adducts (e.g., 0.86+/-0.04 versus 1.36+/- 0.01 adducts/10(6) base pairs/10 microM drug/1 h, respectively, in CEM cells, P<.01). Oxaliplatin was found to induce potentially lethal bifunctional lesions, such as interstrand DNA cross-links (ISC) and DNA-protein cross-links (DPC) in CEM cells. As with total adducts, however, oxaliplatin produced fewer (P<.05) bifunctional lesions than did cisplatin: 0.7+/-0.2 and 1.8+/-0.3 ISC and 0.8+/-0.1 and 1.5+/-0.3 DPC/10(6) base pairs/10 microM drug, respectively, after a 4-h treatment. Extended postincubation (up to 12 h) did not compensate the lower DPC and ISC levels by oxaliplatin. ISC and DPC determinations in isolated CEM nuclei unequivocally verified that oxaliplatin is inherently less able than cisplatin to form these lesions. Reactivation of drug-treated plasmids, observed in four cell lines, suggests that oxaliplatin adducts are repaired with similar kinetics as cisplatin adducts. Oxaliplatin, however, was more efficient than cisplatin per equal number of DNA adducts in inhibiting DNA chain elongation ( approximately 7-fold in CEM cells). Despite lower DNA reactivity, oxaliplatin exhibited similar or greater cytotoxicity in several other human tumor cell lines (50% growth inhibition in CEM cells at 1.1/1.2 microM, respectively). The results demonstrate that oxaliplatin-induced DNA lesions, including ISC and DPC, are likely to contribute to the drug's biological properties. However, oxaliplatin requires fewer DNA lesions than does cisplatin to achieve cell growth inhibition.

Objectives.The aim of this study was to assess the prognostic significance of local tumor factors in predicting lymph node metastases and/or recurrence in early adenocarcinoma of the cervix.

Oxaliplatin is a clinical anticancer drug with a pharmacological profile distinct from that of cisplatin. Our studies compared site- and region-specificity of lesions induced by oxaliplatin and cisplatin in naked and intracellular DNA, respectively. Oxaliplatin adducts in naked Simian virus 40 (SV40 DNA) were mapped by repetitive primer extension. The sites of oxaliplatin adducts were nearly identical to the sites of cisplatin adducts and were focused in G clusters and GNG motifs probably reflecting intrastrand cross-links. Although alkaline agarose electrophoresis of specific SV40 fragments showed that oxaliplatin formed interstrand cross-links, the levels of this lesion type were low. Drug-induced lesions in discrete loci of cellular DNA were assessed by the polymerase chain reaction stop assay in human tumor A2780 cells. Oxaliplatin at 200 microM induced approximately 1300, approximately 1500, approximately 800, and approximately 300 lesions/10(6) bp in the human beta-globin, c-myc, and HPRT genes and in mitochondrial DNA, respectively. Cisplatin formed two to six times more lesions in the same regions. For both drugs, lesion frequencies seem to parallel the density of drug-binding motifs in the nuclear regions, whereas mitochondrial DNA was disproportionately less affected. Despite less potent induction of DNA lesions, oxaliplatin was more cytotoxic than cisplatin against A2780 cells. Because our findings clearly demonstrate that oxaliplatin forms covalent adducts with a similar sequence- and region-specificity to that of cisplatin, other properties of oxaliplatin adducts, factors other than DNA binding, or both determine the unique features of the mechanism of action of oxaliplatin.

To obtain additional information on the effectiveness of recurrent selection for specific combining ability in maize (Zea maysL.), we evaluated seven cycles of selection for combining ability with the single‐cross tester F44 ✕ F6. Grain yield, lodging resistance, and low ear height were the main selection criteria. Seed of the selected population from each cycle was stored and later evaluated for combining ability with the original tester, F44 ✕ F6, and with an unrelated synthetic. The evaluation with F44 ✕ F6 indicated that the seven cycles of selection resulted in 18% more grain yield, 9% lower ear height, and 35% less lodging. Performance was similar when the same selected populations were crossed with an unrelated synthetic. This suggests that gains for all traits resulted from increasing the frequency of genes with additive effects. These results and others previously reported for inbred testers suggest that narrow‐base testers are effective for improving general as well as specific combining ability, and that it is possible to change such testers in a recurrent selection program with little loss in accumulated improvement.

Standing eddy fluxes of geopotential are derived from Northern Hemisphere conventional and satellite data. Vertical and meridional wave guide behaviour is clearly evident for planetary-scale wave disturbances in the extratropical winter troposphere and stratosphere. In accordance with zonal harmonic perturbation model studies (steady-state and linearized) of forced planetary wave propagation, the observed standing wave geopotential flux patterns are characterized by a marked dependence on zonal wavenumber and the basic state transmission properties (refractive index squared). Transports for the middle and upper stratosphere are based on satellite measurements of thermal radiation and represent the first quantitative analysis at these levels of two-dimensional wave guide effects associated with individual zonal wave disturbances for a quiescent stratospheric winter period.

To determine the relationship between the expression of epidermal growth factor receptor (EGFR) and the presence or type of human papillomavirus (HPV) in cervical squamous intraepithelial lesions (SIL), paired colposcopically directed cervical biopsies were obtained from 88 patients referred for abnormal Papanicolaou smears. One biopsy was formalin-fixed and processed for conventional light microscopy, and the other was immediately frozen. A portion of the frozen tissue was used for Southern blot HPV DNA hybridization and a portion for immunohistochemical studies for EGFR using a monoclonal antibody. Forty-seven cases were SIL and 41 were normal. In 41 (87) of the cases of SIL and in eight (20) of the normal cases, HPV DNA was detected. Of the SIL cases, HPV 16 was the most frequently detected type, being present in 12 (25), followed by 10(21) types 31 or 35, nine (19) types 52 or 56, five (11) uncharacterized types, three (6) type 18, and two (4) multiple types. Regardless of histology, EGFR was detected in all cases. In normal cases, EGFR expression was detected in the basal cells only and in SIL in abnormal proliferating parabasal cells such that it correlated with the grade of SIL. When stratified by grade of SIL, no differential expression of EGFR was seen in cases where HPV was detected; in contrast, in cases where no HPV was detected, no differential expression was seen between cases of different HPV type. Thus, EGFR is expressed by all proliferating squamous epithelial cells and as such correlates with the grade of SIL. The lack of correlation between EGFR expression and the presence or type of HPV suggests that EGF and its receptor are not mediators of the action of HPV in SIL.

Adult wild-trapped opossums were infected with Leishmania donovani (Khartoum strain, WR 378) and evaluated as an animal model of visceral leishmaniasis. All infected opossums died within 32 days. Loss of body fat, hepatomegaly, and petechiae of skin and abdominal musculature were seen at necropsy. Microscopically, numerous amastigote-laden macrophages were seen in histologic sections of liver, spleen, and lymph nodes; fewer parasite-laden macrophages were in the bronchial-associated lymphoid tissues and renal glomeruli. Hematological findings included thrombocytopenia (terminal), neutropenia, and lymphopenia. Blood lymphocyte blastogenesis in response to concanavalin A and phytohemagglutinin was decreased markedly at day 24 post-infection (PI). Serum antibodies (1:40 dilution) to promastigotes of L. donovani were detected in five of eight infected opossums tested on days 10 and 24 PI. Total bilirubin concentrations and alanine aminotransferase and aspartate aminotransferase activities were increased after day 25 PI. Activated partial thromboplastin times and one-stage prothrombin times were prolonged before death. Concurrently, factors V, VIII, and XII activities were decreased.

Visceral leishmaniasis developed in eight owl monkeys (Aotus trivirgatus) after intravenous inoculation with a Khartoum strain (WR378) of Leishmania donovani. Six monkeys died within 93 days, and two monkeys recovered from the disease. Clinically, signs were weight loss, anemia, and hepatosplenomegaly. Hematologic findings included anemia, granulocytopenia, thrombocytopenia, and lymphocytosis. Analysis of serum or plasma revealed hyperbilirubinemia, azotemia, hyperglobulinemia, hypoalbuminemia, and altered hemostasis. All monkeys developed positive antibody titers to promastigotes of L. donovani and had increases in immunoglobulins M and subsequently G. Liver, spleen, bone marrow, and lymph nodes were the principal organs containing numerous parasitized macrophages. The owl monkey was highly susceptible to L. donovani infection and should be a useful animal model for the study of visceral leishmaniasis.

A new theory for intramolecular hydrogen bonding of flexible hard chain molecules in the absence of intermolecular association is presented. The theory predicts the change in thermodynamic properties due to intramolecular association and the fraction of nonbonded chains. Comparisons with molecular simulation results are presented to demonstrate the accuracy of the theory. By considering the limit of complete association, an accurate equation of state of cyclic molecules is obtained.

In this paper we review recent molecular simulation results for the bridge function and cavity correlation function of the Lennard-Jones and soft-sphere fluids. We demonstrate that closures similar to the Percus Yevick (PY) closure are poor at short range and should only he valid for repulsive fluids, Finally, by comparing with our simulation results for the Lennard-Jones bridge function, we show how to rescale the Lennard-Jones bridge function so that it can be approximated with the bridge function for a repulsive fluid.

Excimer laser photolysis in combination with time-resolved IR laser absorption detection of OH radicals has been used to study O3/OH(v = 0)/HO2 chain reaction kinetics at 298 K, (i.e., OH + O3 %@mt;sys@%%@mv;-5.90q@%%@st;c;1q@%%@ital@%k%@rsf@%%@sb@%1%@sbx@%%@ov@%→%@stx@%%@mvx@%%@mx@% HO2 + O2 and HO2 + O3 %@mt;sys@%%@mv;-5.90q@%%@st;c;1q@%%@ital@%k%@rsf@%%@sb@%2%@sbx@%%@ov@%→%@stx@%%@mvx@%%@mx@% OH + 2O2). From time-resolved detection of OH radicals with high-resolution near IR laser absorption methods, the chain induction kinetics have been measured at up to an order of magnitude higher ozone concentrations ([O3] ≤ 10¹⁷ molecules/cm³) than accessible in previous studies. This greater dynamic range permits the full evolution of the chain induction, propagation, and termination process to be temporally isolated and measured in real time. An exact solution for time-dependent OH evolution under pseudo- first-order chain reaction conditions is presented, which correctly predicts new kinetic signatures not included in previous OH + O3 kinetic analyses. Specifically, the solutions predict an initial exponential loss (chain “induction”) of the OH radical to a steady-state level ([OH]ss), with this fast initial decay determined by the sum of both chain rate constants, kind = k1 + k2. By monitoring the chain induction feature, this sum of the rate constants is determined to be kind = 8.4(8) × 10^-14 cm³ molecule^-1 s^-1 for room temperature reagents. This is significantly higher than the values currently recommended for use in atmospheric models, but in excellent agreement with previous results from Ravishankara et al. [J. Chem. Phys. 1979, 70, 984].

Abstract We compared results using Neoral versus Sandimmune, each in combination with steroid and azathioprine immunosuppression, in primary liver transplantation recipients. There were 15 patients in each group with similar demographic distributions. Intravenous cyclosporine was stopped at 4.3 ± 1.9 days in the Neoral group vs 7.8 ± 4.9 days in the Sandimmune group (P &lt; 0.025). Cyclosporine levels in the first 10 days were higher (mean 306 ng/ml vs 231 ng/ml) in the Neoral group than the Sandimmune group (P &lt; 0.05). The Neoral dose was less than the Sandimmune dose (mean 5.5 ng/kg per day vs 7.9 ng/kg per day) to achieve these levels in that time period (P &lt; 0.05). Two patients (13 %) experienced three episodes of biopsy-proven rejection in the Neoral group compared to nine patients (60 %) with 12 episodes of rejection in the Sandimmune group (P &lt; 0.025). Incidences of neurological and renal complications were similar between the groups. Infections requiring treatment were also similar. Liver function, renal function, and marrow function, evaluated at days 7, 14, 21, 28, and 2, 4, 6, and 12 months post-transplant, were not different between the groups. In summary, shorter use of intravenous cyclosporine and quicker stabilization of trough cyclosporine levels was achieved with Neoral than with Sandimmune. In the early posttransplant period, higher levels with lower doses were achieved with Neoral than with Sandimmune. In our experience, the incidence of rejection was lower with Neoral than with Sandimmune. There were similar lengths of hospitalization, mortality, adverse events, retransplantation, and similar liver, renal, and marrow function up to 1 year posttransplantation. Because of this experience, we continued to use Neoral in a total of 59 primary liver transplant recipients. We have not used intravenous cyclosporine in the last 44 patients. Follow-up was a mean of 11.4 months, ranging from 1 to 27 months. The incidence of rejection was 24 % in these 59 patients compared to our historical experience of 70 % using Sandimmune.