Search

Monkeypox, a zoonotic infection caused by an orthopoxvirus, is endemic in parts of Africa. On August 4, 2022, the U.S. Department of Health and Human Services declared the U.S. monkeypox outbreak, which began on May 17, to be a public health emergency (1,2). After detection of the first U.S. monkeypox case), CDC and health departments implemented enhanced monkeypox case detection and reporting. Among 2,891 cases reported in the United States through July 22 by 43 states, Puerto Rico, and the District of Columbia (DC), CDC received case report forms for 1,195 (41%) cases by July 27. Among these, 99% of cases were among men; among men with available information, 94% reported male-to-male sexual or close intimate contact during the 3 weeks before symptom onset. Among the 88% of cases with available data, 41% were among non-Hispanic White (White) persons, 28% among Hispanic or Latino (Hispanic) persons, and 26% among non-Hispanic Black or African American (Black) persons. Forty-two percent of persons with monkeypox with available data did not report the typical prodrome as their first symptom, and 46% reported one or more genital lesions during their illness; 41% had HIV infection. Data suggest that widespread community transmission of monkeypox has disproportionately affected gay, bisexual, and other men who have sex with men and racial and ethnic minority groups. Compared with historical reports of monkeypox in areas with endemic disease, currently reported outbreak-associated cases are less likely to have a prodrome and more likely to have genital involvement. CDC and other federal, state, and local agencies have implemented response efforts to expand testing, treatment, and vaccination. Public health efforts should prioritize gay, bisexual, and other men who have sex with men, who are currently disproportionately affected, for prevention and testing, while addressing equity, minimizing stigma, and maintaining vigilance for transmission in other populations. Clinicians should test patients with rash consistent with monkeypox

Objectives: Although many people who are incarcerated have risk factors for hepatitis A virus (HAV) infection, the proportion of hepatitis A cases among people with a recent incarceration is unknown. We examined the relationship between recent incarceration and HAV infection during community-based, person-to-person outbreaks to inform public health recommendations. Methods: The Centers for Disease Control and Prevention surveyed health departments in 33 jurisdictions reporting person-to-person HAV outbreaks during 2016-2020 on the number of outbreak-associated cases, HAV-infected people recently incarcerated, and HAV-associated hospitalizations and deaths. Results: Twenty-five health departments reported 18 327 outbreak-associated hepatitis A cases during January 11, 2016–January 24, 2020. In total, 2093 (11.4%) HAV-infected people had been recently incarcerated. Of those with complete data, 1402 of 1462 (95.9%) had been held in a local jail, and 1513 of 1896 (79.8.%) disclosed hepatitis A risk factors. Eighteen jurisdictions reported incarceration timing relative to the exposure period. Of 9707 cases in these jurisdictions, 991 (10.2%) were among recently incarcerated people; 451 of 688 (65.6%) people with complete data had been incarcerated during all (n = 55) or part (n = 396) of their exposure period. Conclusions: Correctional facilities are important settings for reaching people with risk factors for HAV infection and can also be venues where transmission occurs. Providing HAV vaccination to incarcerated people, particularly people housed in jails, can be an effective component of community-wide outbreak response.

BackgroundCytomegalovirus (CMV) infection continues to negatively affect outcomes for solid organ transplant recipients, despite the advent of strategies for preemptive surveillance and prophylaxis. The impact is especially great for CMV seronegative recipients of donor seropositive organs, who typically lack the ability to control CMV infection at the time of transplantation.MethodsWe reviewed episodes of CMV DNAemia in a modern cohort of kidney transplant recipients over a 3-year period at a high-volume transplant center to investigate the frequency of DNAemia during antiviral prophylaxis.ResultsDespite receipt of antiviral prophylaxis per current guidelines, 75 cases of CMV DNAemia were observed in the first 100days after transplantation. For high risk patients, median time to DNAemia was 75days after transplantation, and the majority of patients had experienced dose-reduction of valganciclovir due to renal insufficiency. Review of CMV seropositive intermediate risk patients demonstrated DNAemia occurring earlier after transplantation compared with high risk patients with a median time of 64days (P=.029). The impact of valganciclovir dose adjustment was less notable in the intermediate risk group.ConclusionsGuidelines recommend beginning routine surveillance for CMV after the completion of antiviral prophylaxis. Our findings suggest that closer monitoring may be beneficial, especially for high risk patients at risk for DNAemia. Patients requiring dose adjustment of valganciclovir due to renal insufficiency may be at increased risk for CMV DNAemia. Improved methods for CMV prophylaxis and evaluation of immunologic risk for CMV DNAemia and disease are needed to improve patient outcomes after kidney transplantation.

When optimizing chimeric antigen receptor (CAR) therapy in terms of efficacy, safety, and broadening its application to new malignancies, there are two main clusters of topics to be addressed: the CAR design and the choice of transfected cells. The former focuses on the CAR construct itself. The utilized transmembrane and intracellular domains determine the signaling pathways induced by antigen binding and thereby the cell-specific effector functions triggered. The main part of this review summarizes our understanding of common signaling domains employed in CARs, their interactions among another, and their effects on different cell types. It will, moreover, highlight several less common extracellular and intracellular domains that might permit unique new opportunities. Different antibody-based extracellular antigen-binding domains have been pursued and optimized to strike a balance between specificity, affinity, and toxicity, but these have been reviewed elsewhere. The second cluster of topics is about the cellular vessels expressing the CAR. It is essential to understand the specific attributes of each cell type influencing anti-tumor efficacy, persistence, and safety, and how CAR cells crosstalk with each other and bystander cells. The first part of this review focuses on the progress achieved in adopting different leukocytes for CAR therapy.

In this short communication, we investigated the synthesis and mixing of porphyrin and pyridine functionalized copolymers as a proof of concept for a velcro-like interaction. A functionalized porphyrin monomer with one polymerizable side chain was synthesized following a rational synthetic pathway. Subsequent copolymerization and careful removal of residual free porphyrin led to poly(n-butyl acrylate-co-5,10,15-triphenyl-20-(3-vinylphenyl)porphyrin). The immobilized porphyrin was transformed into the corresponding zinc(II) complex, which is capable of the coordinative binding of one pyridine moiety. Complete metallation was proven by absorption spectroscopy. 4-Vinylpyridine was immobilized by copolymerization with n-butyl acrylate, too. Via controlled radical polymerization conditions, the molecular weight of poly(n-butyl acrylate-co-4-vinylpyridine) was limited to one tenth of the molecular weight of the porphyrin containing copolymer. This large difference in the molecular weight easily allowed identifying the polymers in the mixture of both. With the help of diffusion ordered nuclear magnetic resonance spectroscopy, the complete and temperature-stable precipitation of the porphyrin containing copolymer was observed, proving the expected attractive interaction and supramolecular network formation.

The prevalence of pain has been reported to be >60–70% among patients with advanced and end-stage kidney disease. Although the underlying etiologies of pain may vary, pain per se has been linked to lower quality of life and depression. The latter is of great concern given its known association with reduced survival among patients with end-stage kidney disease. We herein discuss and update the management of pain in patients with chronic kidney disease with and without requirement for renal replacement therapy with the focus on optimizing pain control while minimizing therapy-induced complications.

4518 Background: Neoadjuvant cisplatin-based chemotherapy (CT) prior to radical cystectomy (RC) improves overall survival (OS) in MIBC, but about half of pts are cisplatin-unfit or refuse it. Neoadjuvant immune checkpoint inhibitors can induce high pathologic complete response rate (ypT0N0). The combination of anti-PD-1 (N) and anti-KIR (L) is hypothesized to be safe and have significant activity based on the complementary and possibly synergistic roles in regulating adaptive and innate immune response in MIBC. Methods: This is a phase Ib multi-institutional trial in pts with localized MIBC treated with 2 neoadjuvant doses (4 weeks apart) of N alone (480 mg) in cohort 1 or N (480 mg) + L (240 mg) in cohort 2 prior to RC without adjuvant therapy (NCT03532451). Cohorts were enrolled sequentially and were not randomized. Key eligibility criteria included stage cT2-4aN0-1M0, ≥20% tumor content at TURBT and cisplatin-ineligibility (Galsky criteria) or refusal. Primary endpoint was safety manifested as rate of ≥G3 treatment related adverse events (TRAE) assessed in each cohort with CTCAE v5.0. Key secondary endpoints included the % of pts who had RC > 6 weeks after last neoadjuvant dose due to TRAE, CD8+ T cell density at RC, ypT0N0 and < ypT2N0 rates, CD8+ T cell density change between TURBT and RC, recurrence-free survival (RFS) and biomarkers in tumor tissue, blood and urine. Results: Among 43 pts enrolled (13 cohort 1, 30 cohort 2), median age was 75 (51-89), 67% were men, all had PS ECOG 0-1. Pts were cisplatin-ineligible due to impaired renal function (47%) and hearing loss (37%), while 14 % refused cisplatin. At baseline, 37 pts had cT2 stage, 2 had cN1 and 3 cNx. In cohort 1 and 2, 13 and 29 pts, respectively, completed intended neoadjuvant treatment, and 41/43 underwent RC (12/13 cohort 1, 29/30 cohort 2). One pt progressed to metastatic disease prior to RC (cohort 1) and 1 withdrew consent prior to being treated (cohort 2). Additionally, 1 patient was found to have cervical cancer at RC. Median time from last neoadjuvant dose to RC was 27 (95%CI: 24-29) days. There was no RC delayed > 6 weeks from treatment completion due to TRAE. G3 TRAEs occurred in 0% with N and 6.7% (90%CI 1.2-19.5%) in N+L (1: arthralgia, 1: gout, 2: hip pain) that all resolved. No G4/5 TRAEs occurred. Of 40 pts with MIBC and RC, ypT0N0 rates for N and N+L were 8% and 18%, while < ypT2N0 rates were 17% and 29%, respectively. Data on RFS and OS, and biomarker data were not yet mature. Conclusions: Neoadjuvant N alone and N+L combination prior to RC were safe, feasible and well tolerated in cisplatin-ineligible pts with MIBC, but ypT0N0 rates were unexpectedly low, especially with N alone. Two phase 3 trials (NCT03661320; NCT04209114) are evaluating the peri-operative role of N + chemotherapy +/- Linrodostat in cisplatin-fit and N +/- Bempeg in cisplatin unfit patients and are also assessing biomarkers. Clinical trial information: NCT03532451.

Anthropogenic disturbances to habitats influence the fitness of individual animals, the abundance of their populations, and the composition of their communities. Wetlands in particular are frequently degraded and destroyed, impacting the animals that inhabit these important ecosystems. The creation of wetlands during and following sand extraction processes is inevitable, and thus, sand quarries have the potential to support aquatic animals. To determine how amphibians utilise these wetlands, I conducted nocturnal call surveys at wetlands within the Kables Sands quarry, New South Wales, Australia, and within surrounding reference wetlands, and quantified levels of developmental instability (DI) as a proxy for fitness. Whilst quarry and reference wetlands were largely similar in terms of environmental characteristics, quarry wetlands consistently harboured more amphibian species and individuals. Using unsigned asymmetry as a measure of DI, frogs from the quarry sites exhibited significantly lower levels of DI compared to reference wetlands, indicating that quarry wetlands may be comparatively higher quality. Levels of DI within quarry wetlands also compared favourably to data from healthy frog populations extracted from the literature. Further enhancing the suitability of quarry wetlands would require minimal effort, with potentially significant increases in local and regional biodiversity. Documenting species presence and quantifying individual fitness by measuring limb lengths is an economically and logistically feasible method to assess the health of quarry wetlands. Overall, the methods outlined here provide a powerful, yet simple, tool to assess the overall health and suitability of quarry wetlands that could be easily adopted at quarries throughout the world.

Electrodialysis (ED) is an advancing seawater sample processing tool that enables the separation of analytes from the often interfering salt matrix. In this study, we present the evaluation of a laboratory scale ED system for both dissolved organic matter (DOM) and target pollutant analysis of seawater. The developed sample processing protocol yields reproducible data and was found to be robust towards moderate changes in sample composition. At the final salinity of 0.1, the average recovery of DOM in the form of dissolved organic carbon, nitrogen and phosphorus (DOC, DON and DOP) was 44, 53 and 89%, respectively. DOM loss occurred mainly in the late stage of the ED process. When investigating specific ED processing parameters, it was discovered that the initial sample salinity does not influence DOM recovery. The final salinity, by contrast, is a dominant influence factor on DOM recovery. Furthermore, DOC and DOP recoveries could be improved by 8% by refining the electrical current in the ED cell. Surprisingly, adjustments of the sample pH did not lead to any improvements in DOM recovery. The experiments with target analytes showed that the recovery of individual molecules is determined by their n-octanol water partition coefficients logKow. High recoveries > 80% were achieved for compounds with medium logKow of −1 to 3. Hydrophobic compounds with logKow > 3 were lost through surface adsorption to the system walls and tubing. Small, polar and charged compounds with logKow

New applications such as renewable energy sources demand reliable operating lifetimes beyond 15 years. To validate the robustness of power semiconductors, it is paramount to investigate the effects and interactions of various failure and degradation mechanisms. In particular, the degradation of power semiconductors under application relevant stress test conditions until their end-of-life is of interest. The difficulties with such application relevant end-of-life testing is that test systems are very complex and costly. In addition, it is difficult to protect the devices under test sufficiently for post failure analysis without interfering too much with the operation itself. This paper presents a modular test system that can be configured to apply different operating scenarios and apply application relevant stress to the devices under test. Within the presented system, numerous safety features have been implemented to minimize the damage to a failed device under test so that it may undergo further analysis. By making applications relevant stress testing feasible and capable of end-of-life testing, we hope to contribute to making future power electronic system more reliable.

A systematic study is reported of the photochemical properties of the multi-azobenzene compounds bis[4-(phenylazo)phenyl]amine (BPAPA) and tris[4-(phenylazo)phenyl]amine (TPAPA) compared to the parent molecule 4-aminoazobenzene (AAB). The bis- and tris-azobenzenes were synthesised by a variant of the Ullmann reaction and exist in their stable all-E forms at room temperature. Striking changes in the spectral positions and intensities of their first ππ* absorption bands compared to AAB reveal strong electronic coupling between the AB units. The nature of the excited states was explored by quantum chemical calculations at the approximate coupled-cluster (CC2) level. Upon UV/VIS irradiation, the molecules isomerise to the Z-isomer (AAB), ZE- and ZZ-isomers (BPAPA), and ZEE-, ZZE- and ZZZ-isomers (TPAPA), respectively. The photoswitching behaviours were investigated by UV/VIS and NMR spectroscopies. All individual isomers were detected by one-dimensional (1D) (1)H NMR spectroscopy (BPAPA) and two-dimensional (2D) HSQC NMR spectroscopy (TPAPA). A kinetic analysis provided the isomer-specific thermal lifetimes. The variance of the thermal lifetimes demonstrates a dependence of the Z-E isomerisation on the chromophore size and number of AB units.

TPS5098Background: Germline DNA repair gene mutations are present in ~10% of patients with metastatic prostate cancer (mPC) irrespective of age at diagnosis or family history, and have potential pr...

OBJECTIVE: To test the feasibility of automated lateral cephalometric radiograph (LCR) superimposition using an image fitting algorithm. MATERIALS AND METHODS: Using radiopaque markers, we identified seven cephalometric landmarks on three dry skulls, took digital LCRs on each in several rotated positions, and used a custom software program (XRay3D) to automatically superimpose each rotated image on the initial image using an anterior cranial base reference. We measured superimposition error at each landmark and adjusted image brightness levels to simulate potential fitting error due to exposure variation. RESULTS: The greatest mean error for 24 image rotation trials of less than 10° was less than 0.5 mm. Rotations of 10° or more were not reliably superimposed. Errors of 0.2–1.6 mm occurred for ±10% brightness but increased exponentially with further brightness alteration. CONCLUSION: Automated superimposition of LCRs, using this fitting technique, has great potential when rotation is less than 10° and brightness variation is less than 10%.

ObjectiveSurgical manipulation of lung cancers may increase circulating tumor cells and contribute to metastatic recurrence after resection. Cyclooxygenase 2 is overexpressed in most non–small cell lung cancer and upregulates the cell adhesion receptor CD44. Our goal was to examine the effects of perioperative cyclooxygenase blockade on the metastatic potential of circulating tumor cells, CD44 expression, and adhesion of cancer cells to extracellular matrix.MethodsHuman non–small cell lung cancer cells (A549) were injected through the lateral tail vein in an in vivo murine model of tumor metastasis with three random treatment groups: no treatment, perioperative selective cyclooxygenase 2 inhibition (celecoxib) only, and continuous celecoxib. Lung metastases were assessed at 6 weeks by a blinded observer. For in vitro experiments, cells were treated with celecoxib, and expression of CD44 was determined by Western blotting. Extracellular matrix adhesion was assessed by Matrigel (BD Labware, Bedford, Mass) assay.ResultsIn vivo lung metastases were significantly decreased relative to control by both perioperative and continuous celecoxib (P = .0135). There was no significant difference in number of metastases between continuous and perioperative treatment groups. In vitro adhesion to the extracellular matrix was significantly inhibited by celecoxib in a dose-dependent manner (P < .01). A549 cells expressed high levels of CD44, upregulated by interleukin 1β and downregulated by celecoxib.ConclusionCelecoxib significantly reduced establishment of metastases by circulating tumor cells in a murine model. It also inhibited CD44 expression and extracellular matrix adhesion in vitro. Perioperative modulation of cyclooxygenase 2 may be a novel strategy to minimize metastases from circulating tumor cells during this high-risk period.

Background We reviewed our experience with adult living lobar lung transplant (LL) recipients to assess whether size and shape mismatch of the donor organ to the recipient pre-disposes to the development of pleural space problems (PSP). Methods Eighty-seven LL were performed on 84 adult recipients from 1993 through 2003. Seventy-six patients had cystic fibrosis. Patient records were examined for PSP, defined as air leak or bronchopleural fistula for more than 7 days; pneumothorax, loculated pleural effusions, or empyema in 68 patients for which complete data were available. Results There were 24 PSP identified for an overall incidence of 35%. The most common PSP was air leak/bronchopleural fistula, accounting for 38% of PSP. The second most common PSP was loculated pleural effusion (21% of PSP). Empyema was uncommon (2 patients, 3% of total patients) in our series of patients despite the large population of cystic fibrosis patients. In 4 of these patients, computed tomography-guided drainage was used for loculated effusions after chest tube removal. Three LL patients underwent surgery for persistent air leak and required muscle flap repair. One of these required subsequent omental transfer. Two LL patients required decortication for empyema. Many patients with PSP could be managed without further surgical intervention (14/24 patients). Donor-recipient height mismatch was not significantly different between PSP and non-PSP patients ( p = 0.53). Conclusions The incidence of PSP in LL recipients is similar to that reported in the literature on cadaveric transplant recipients. The relatively small lobe in the potentially contaminated chest cavity of cystic fibrosis recipients does not significantly pre-dispose to development of empyema despite immunosuppression. Many PSP can be managed non-operatively, although early aggressive intervention for large air leaks and judicious chest tube management are essential for a good outcome.

Objectives Cyclooxygenase-2 plays a role in growth, apoptosis, angiogenesis, and metastasis in lung cancer. Inhibition of cyclooxygenase-2 with celecoxib has been shown to inhibit tumor growth. We evaluated the effect of increasing doses of celecoxib in a murine model of human lung cancer. Methods Human lung adenocarcinoma cells (A549) were implanted in the left lung upper lobe of mice with severe combined immunodeficiency syndrome. Mice were randomly assigned to 4 groups at implantation (n = 10 per group): control, 125 mg/kg chow, 500 mg/kg chow, 1000 mg/kg chow. After 3 weeks, mice were killed, and a blinded observer measured total tumor volume. The dose effect of celecoxib was examined in vitro by studying cell proliferation, expression of cyclooxygenase-2 (mRNA and protein), and production of prostaglandin E 2 in unstimulated and interleukin 1β-stimulated cells. Results All 40 mice survived for 3 weeks with no observed toxicities. Total tumor volume was inhibited in each celecoxib group ( P = .0038, Welch analysis of variance): 206.7 ± 119.5 mm 3 (control group), 41.4 ± 54.0 mm 3 (low-dose group), 34.5 ± 39.3 mm 3 (medium-dose group), and 27.3 ± 53.6 mm 3 (high-dose group). In vitro celecoxib was effective at inhibiting production of prostaglandin E 2 , even in stimulated cells, although little effect was seen on cyclooxygenase-2 protein levels. Inhibition of proliferation was evident only at doses that exceeded those used in the animal model. Conclusion Inhibition of cyclooxygenase-2 with low-dose celecoxib restricted the growth of lung cancer in this model. This might be mediated by prostaglandin E 2 . Higher doses of celecoxib afforded no additional benefit. Chronic therapy with low-dose cyclooxygenase-2 inhibition has the potential to influence tumor progression in non-small cell lung cancer.

A series of radiolabeled cyclic arginine-glycine-aspartic acid (RGD) peptide ligands for cell adhesion molecule integrin alpha v beta 3-targeted tumor angiogenesis targeting are being developed in our laboratory. In this study, this effort continues by applying a positron emitter 64Cu-labeled PEGylated dimeric RGD peptide radiotracer 64Cu-DOTA-PEG-E[c(RGDyK)]2 for lung cancer imaging. The PEGylated RGD peptide indicated integrin alpha v beta 3 avidity, but the PEGylation reduced the receptor binding affinity of this ligand compared to the unmodified RGD dimer. The radiotracer revealed rapid blood clearance and predominant renal clearance route. The minimum nonspecific activity accumulation in normal lung tissue and heart rendered high-quality orthotopic lung cancer tumor images, enabling clear demarcation of both the primary tumor at the upper lobe of the left lung, as well as metastases in the mediastinum, contralateral lung, and diaphragm. As a comparison, fluorodeoxyglucose (FDG) scans on the same mice were only able to identify the primary tumor, with the metastatic lesions masked by intense cardiac uptake and high lung background. 64Cu-DOTA-PEG-E[c(RGDyK)]2 is an excellent position emission tomography (PET) tracer for integrin-positive tumor imaging. Further studies to improve the receptor binding affinity of the tracer and subsequently to increase the magnitude of tumor uptake without comprising the favorable in vivo kinetics are currently in progress.

Ozonation of industrial and sewage sludge is a suitable process for minimizing the sludge production of activated sludge processes. The ozonation has the advantage for complete oxidation of volatile suspended solids (VSS) of combining partial sludge oxidation with subsequent biological oxidation. This paper describes the evaluation of two full-scale sewage sludge ozonation investigations for subsequent aerobic stabilisation as well as for subsequent anaerobic stabilisation compared to different sludge treatment processes. For both the anaerobic and aerobic application, sludge liquefying by release of 110 and 160 mg COD per g total suspended solids (TSS) has been reached at specific ozone consumption of 0.03 and 0.06 kg O3 per kg TSS, respectively. The subsequent biological treatment has reached a mass reduction of 20-35% for the aerobic and 19% for the anaerobic stabilisation. For both applications the specific ozone consumption was about 0.05 kg O3 per kg TSS to be treated. A comparison with mechanical and thermo-chemical sludge mass reduction methods shows that the mass reduction potential of ozonation is presently higher. Even though costs for sludge ozonation are higher compared to other methods, the optimisation potential for cost reduction of sludge ozonation is obvious from the results presented in this paper.

Before the early 1980s, patient and allograft survival for solid organ transplant recipients was dismal. By 1983, the first calcineurin blocker, cyclosporine (Sandimmun), had been introduced, and outcomes were dramatically improved. However, cyclosporine macroemulsion had suboptimal pharmacokinetics, significant drug interactions, and several adverse effects, including nephrotoxicity, neurotoxicity, hyperlipidemia, and hypertension. Recent advances with cyclosporine include the introduction of modified dosage formulations: Neoral, a microemulsion, and several generic microemulsion products. The potent second-generation calcineurin blocker tacrolimus (Prograf) was introduced in 1994 and has become the drug of choice for several types of transplant recipients. Although tacrolimus has improved pharmacokinetics and therapeutic drugmonitoring parameters, it has adverse effects such as nephrotoxicity, neurotoxicity, and diabetes. Thus, current immunosuppressive regimens implementing calcineurin blockers often involve additional immunosuppressive agents to “spare” the use of these agents, minimizing their adverse effects. This article reviews the mechanisms of action, pharmacokinetics, clinical use, therapeutic drug monitoring, drug interactions, adverse effects, and dosing of cyclosporine and tacrolimus in solid organ transplant recipients.

Since the early 1980s, the combination of cyclosporine, azathioprine, and prednisone has been the mainstay tripledrug immunosuppressive regimen used in transplantation. However, advances in drug research, design, and development have allowed for the introduction of new agents that have greatly increased the number of immunosuppressive agents available for use in transplant recipients. Particularly, the newer antiproliferative immunosuppressive drugs (agents that directly inhibit the proliferation of T and B lymphocytes) have had an important impact on patient outcomes posttransplant. These agents are mycophenolate mofetil and sirolimus.

A total of 42 storm-water overland-flow samples were collected from four sampling sites (a highway off-ramp, a gas station, and a low- and high-traffic-volume parking lot). For each sample, the suspended-sediment and water phases were separated and analyzed for 16 polycyclic aromatic hydrocarbons (PAHs). The gas station site produced the highest total PAH loading (2.24 g/yr/m2), followed by the high-traffic-volume parking lot (5.56 X 10-2 g/yr/m2), the highway off-ramp (5.20 × 10-2 g/yr/m2), and the low-traffic-volume parking lot (3.23 × 10-2 g/yr/m2). In several samples, one or more PAHs were detected in the aqueous phase at concentrations above its aqueous solubility. This result suggests the presence of colloidal-size particles capable of sorbing PAHs to an appreciable extent, or the presence of an oil-and-grease microemulsion. Based on rainfall and PAH data from seven discrete storm events, PAH concentrations were usually highest during the “first flush” of storm-water runoff and tapered off rapidly as time progressed. It is apparent from these analyses that storm-water runoff from parking lots, highways, and gas stations is a significant source of PAHs to the environment. Because some of the PAHs are carcinogens or suspected carcinogens, best management practices such as oil/grit separators should be implemented at “hot spots” in urban areas to mitigate potential PAH pollution.

Bioreactors are broadly applied in biotechnology and wastewater treatments. The so-called advanced bioreactor systems should be optimised in a more compact, more efficient and more effective form. One method of optimisation is the improvement of the solid-liquid interface of the sludge flocs and the mass transfer rate of gas and nutrients in the liquid. This could be obtained by the intake of ultrasound in the bioreactor at a frequency of 25 kHz and a power input of 0.3 Wl-1. An increase in the biological activity of the process investigated with alternating ultrasound as well as a decrease without ultrasound were measured.

Mycophenolate mofetil (MMF) is the morpholinoethylester prodrug of mycophenolic acid, an agent which inhibits the proliferation of B and T lymphocytes through the noncompetitive, reversible inhibition of inosine monophosphate dehydrogenase, itself a key enzyme in the de novo synthetic pathway of guanosine nucleotides. Currently, MMF is approved for the prevention of acute renal allograft rejection when used in combination with cyclosporin and corticosteroids. Several studies have also demonstrated that this drug is useful in the treatment of refractory rejection in renal, heart and liver transplant recipients.

Effluents from both cells of a two-cell anaerobic lagoon system treating flushed swine waste were loaded into two types of constructed wetlands [submerged flow (SF) and free water surface (FWS)]. The wetlands were planted to Scirpus lacustris (Bulrush), Juncus Effusus (Soft Rush), and Saggitaria latifolia (Arrowhead). Passing anaerobic lagoon effluents through the constructed wetlands resulted in the following average reductions in water quality parameters: BOD5, 18 to 50%; NH3-N, 17 to 41%; TSS, 34 to 48%; total phosphorus, 15 to 30%. Effluents from the lagoons were too concentrated to achieve wetland effluent criteria suggested by the Natural Resource Conservation Service. This study showed that the Rational Method for sizing constructed wetlands to treat anaerobic swine lagoon wastewaters to achieve a wetland effluent criteria

Experimental results relating to the hydrodynamic behaviour of an impinging-stream reactor are presented and discussed. The parameters varied were the gas flow rate and the liquid flow rate while the quantities measured were the gas holdup, the mean bubble diameter and the absolute bubble velocity in the main reactor tube. From these quantities, the internal gas recirculation rate and the gas flow ratio have been determined. The internal gas recirculation rate is important in evaluating the mass-transfer performance of the impinging-stream reactor.

The objectives of this study were to determine effective vegetation species that had the ability and efficiency to improve the effluent quality of an existing wastewater wetland treatment system. Channels were constructed down the length of one cell of the existing wetland trough and planted with the selected plant materials, which included bullrushes (Scirpus validus) and arrowhead (Sagitarria latifolia). Removal efficiencies for BOD5, total suspended solids (TSS), and ammonia‐nitrogen were monitored and shown to be influenced more significantly by hydraulic retention times than the presence of introduced vegetation. However, when retention times were adequate, removal efficiencies did reach similar levels as those documented by other researchers using these plant species.

Results from laboratory coagulation-settling experiments using five coagulants (one inorganic salt and four organic polymers) on four dilute wastewaters (fresh manure from swine, poultry, and cattle and effluent from a swine anaerobic digester) are presented to provide chemical coagulation data for designing treatment facilities for livestock and poultry. Adjustment of pH alone was generally ineffective in promoting coagulation on all wastewaters. Values of pH above nine were effective for swine wastewater. Ferric chloride removed 60 to 70% of the volatile solids (VS) for cattle and swine at concentrations of 300 to 450 mg/L, but was less effective on poultry wastewater. Addition of organic polymers with iron salt did not improve coagulation from swine wastewater. Synthetic polymers and chitosan were excellent coagulants for all manure wastewaters but not for digester effluent. Based upon the effective concentrations to remove suspended solids from the flush waters of a 1,000-head swine finishing unit, synthetic polymers are the most cost-effective chemical coagulant, while chitosan is the least cost-effective.

OBJECTIVE: To estimate possible differences in skeletal asymmetry between patients with skeletal Class I and skeletal Class II relationships. MATERIALS AND METHODS: Cone beam computed tomography (CBCT) images were examined from 70 consecutive patients who presented for orthodontic care and fit the inclusion criteria. Asymmetry was quantified using an asymmetry index developed by Katsumata et al. Anatomic landmarks were defined and reference planes were established to determine the asymmetry of the landmarks using a constructed coordinate plane system. Thirty randomly selected patients were reanalyzed to assess the reliability of the method. RESULTS: Statistical analysis did not find any significant relationship between asymmetry and A-P skeletal relationship for any of the landmarks. Asymmetry index scores were reproducible within a certain range of agreement for each landmark. CONCLUSIONS: Based on this study, the discrepant jaw growth resulting in a Class II skeletal pattern results in no more skeletal asymmetry than Class I skeletal patterns.

Advanced oxidation processes (AOPs) received increasing interest in both science and practice of water and wastewater treatment during the last few decades due to their potential of conversion of anthropogenic and biorecalcitrant organic pollutants to biodegradable compounds together with potential of disinfection, decolorization, and deodorization. A prerequisite for safe application of AOPs is the avoidance and minimization of by-product formation and therefore each particular application needs feasibility and validation studies in laboratory and pilot scale before application. Due to the complex character of free radical chemistry which is always involved in AOPs, this chapter aims at summarizing the science and practice of different AOPs from fundamentals via mechanistic aspects of reaction competition, a guide in selecting a suitable AOP, some reactor design criteria, useful process combinations with other non-AOPs, and a compilation of different applications in industrial and domestic wastewater treatment as well as drinking water treatment since the boundaries between drinking water and wastewater treatment have begun to fade. The AOPs treated hereinafter among others are ozone based, photochemical, and homogeneous/heterogeneous catalytic processes.

Mice infected with the parasite Mesocestoides corti develop hypergammaglobulinemia, hepatomegaly, and splenomegaly. The immune response to M. corti infection is directed, in part, at molecules secreted by the organism. Two of these molecules have been shown to be hsp70 and hsp60 homologues. In this study it was found that incubation of splenocytes from infected animals with M. corti-secreted molecules or the isolated M. corti hsp70 results in the expansion of an unusual cell type with the morphology of large granular lymphocytes. The cell lines express Thy-1, CD4 (low), and CD45RB but lack TCR alpha beta, TCR gamma delta, CD3, CD8, and slg. The lack of a TCR suggested NK cells, but no cytolytic activity could be detected. In addition, the cell lines constitutively produce IL-6 and can be induced to express IL-2, but not IL-4, IL-5, or IFN-gamma. Given the phenotype of these cells, it is possible that they represent T lineage precursors or some type of effector cells. Notably, CD3- CD4+ cells appear to be expanded in the spleens and livers of M. corti-infected animals, suggesting an important role in infection. Moreover, the selective growth of this cell type with M. corti hsp70 suggests that the outgrowth and in vivo expansion of these cells may be related to the stress response of the parasite.

Two hundred and one rural wells were sampled in eight agricultural areas of Missouri. Samples were analyzed for 25 pesticides and nitrate. Forty-three percent of the wells sampled had at least one pesticide detection. Thirteen percent of the wells had at least one detection ≧ 1 ppb and these concentrations were confirmed. Only one well exceeded U.S. EPA Health Advisory levels. Twenty-two percent of the wells exceeded the U.S. EPA Drinking Water Standard for nitrate. Pesticide detections were most strongly correlated to well depth. Nitrate levels were primarily related to well depth, well construction methods, and well siting.

V kappa gene family usage was determined in the resident in vivo-activated plasma cells of individual diseased MRL mice by using in situ hybridization. In this way, the entire autoimmune repertoire could be analyzed. Autoantibody levels and extent of glomerulonephritis were also measured, so that the severity of disease could be assessed. It was found that V kappa expression was highly variable from mouse to mouse. Some animals displayed a V kappa family repertoire similar to mitogen-stimulated cells and consistent with the size of the families. These animals tended to have lower disease indices. Other animals, which had higher disease indices, displayed considerable over- or underutilization of individual V kappa families. However, no particular V kappa families were repeatedly biased in their expression, as was found at the VH level with J558. Importantly, in the 10% of animals that expressed VH J558 exclusively, four or more V kappa families were expressed and multiple antiself specificities were produced. The data are most consistent with a number of J558 genes being expanded in a variety of self-specificities. However, because only VH J558 is expressed in these sicker animals, nonspecific polyclonal activation is highly unlikely. These results underscore the continuing evolution of the autoimmune repertoire, with considerable diversity at early stages followed by a highly selected repertoire in which a potential role for nonspecific polyclonal activation is virtually excluded.

Two hundred twenty six rural wells in Missouri were tested for N03-N. Nineteen percent exceeded Environmental Protection Agency (EPA) drinking water standards. Nitrate concentrations were most strongly related to well depth. Well construction, depth to aquifer and well age had lesser influence. Distance from well to livestock was a poor predictor of nitrate pollution.

Long-term use of both zidovudine (AZT) and stavudine (d4T) is associated with lipoatrophy, but it occurs possibly through different mechanisms.Surgical biopsy specimens of subcutaneous adipose tissue were obtained from 18 human immunodeficiency virus type 1 (HIV-1)-infected lipoatrophic patients (the LA+ group) who were treated with either zidovudine (the AZT+LA+ group; n = 10) or stavudine (the d4T+LA+ group; n = 8) and from 10 nonlipoatrophic HIV-1-infected patients (the LA- group) who received antiretroviral therapy. Mitochondrial DNA (mtDNA) copy numbers, gene expression, and immunohistochemistry data were analyzed.mtDNA copy numbers were significantly reduced in the LA+ group, compared with the LA- group, and in the d4T+LA+ group, compared with the AZT+LA+ group. The ratio of mtDNA-encoded cytochrome COX3 to nuclear DNA-encoded COX4 expression was significantly lower in the LA+ group than in the LA- group. Compared with the LA- group, the LA+ group had significantly lower expression of genes involved in adipogenesis (SREBP1c and CEBPB), lipid (fatty acid synthase), and glucose (GLUT4) metabolism. Expression of genes involved in mitochondrial biogenesis (PGC1B), apoptosis (FAS), inflammation (IL1B), oxidative stress (PCNA and SOD1), and lamin B was significantly higher in the LA+ group than in the LA- group. The d4T+LA+ group had significantly lower expression of genes involved in mitochondrial biogenesis (POLG1), energy metabolism (the COX3/COX4 ratio), adipogenesis (SREBP1c and CEBPA), perilipin, and hexokinase than did the AZT+LA+ group. There were 7-fold more macrophages in adipose tissue specimens obtained from patients in the LA+ group, compared with the LA- group.Lipoatrophy is characterized by mtDNA depletion, inflammation, and signs of apoptosis. Changes were more profound in the d4T+LA+ group than in the AZT+LA+ group.

Effluents from both cells of a two-cell anaerobic lagoon system treating flushed swine waste from the University of Missouri Swine Farm were treated in parallel constructed wetlands — submerged flow (SF) and free water surface (FWS). Reductions in magnesium, ammonium, and total phosphorus ion concentrations in the wetlands were measured and used to calculate ion activity products (IAP) for struvite and compared to struvite solubility products (Ksp). Comparison of IAPs with Ksps indicated that the wetlands reduced the potential for struvite formation by 54 to 70%. The reductions were largely due to ammonium losses from the wetlands.