Precision in-cylinder H2O vapor absorption thermometry and the associated uncertainties.

Water vapor absorption spectroscopy was used to measure crank-angle resolved temperature in an internal combustion engine for two intake pressures and a range of intake temperatures from 323 to 423 K. Measurements were acquired throughout the full engine cycle, for both motored and fired operating conditions. The methodology to convert absorbance measurements to processed temperatures up to values of 650 K are detailed in this work. The sensitivity of the processed temperature to the processing parameters was analyzed and quantified. The precision of the sampled mean with 95% confidence uncertainty bounds was 0.5%, and a comparison of the temperature estimates using the band shape thermometry technique was compared to both fast-response thermocouple measurements as well as a trapped-mass thermodynamic model.

A phase II clinical trial of weekly paclitaxel and carboplatin in combination with panitumumab in metastatic triple negative breast cancer.

PURPOSE: Women with metastatic triple negative breast cancer (TNBC) can have a poor prognosis with treatment limited to cytotoxic chemotherapy. The identification of effective therapies that may limit exposure to cytotoxic chemotherapy and lead to prolonged survival is an unmet medical need. We tested an inhibitor of the epidermal growth factor receptor, panitumumab in combination with chemotherapy. METHODS: We conducted a single arm clinical trial in women with metastatic or locally advanced TNBC to paclitaxel 80 mg/m2 and carboplatin AUC of 2 on days 1, 8, and 15 and panitumumab 6 mg/kg on days 1 and 15 for a cycle length of 28 days. The objectives were to evaluate the response rate and safety of the combination in comparison to historical controls. RESULTS: Fourteen patients with TNBC were enrolled with a median age of 53 years. The majority of women were African American (64.3%) with visceral metastasis (64.2%). Hematologic toxicities, particularly neutropenia and thrombocytopenia, were a major cause of missed chemotherapy and delayed treatment in this study. The overall response rate (complete and partial response) of the 13 evaluable patients was 46%. The median time to best response was 2.4 months and the median time to disease progression was 3.6 months. We were able to perform the PAM50 analysis on tumors from 7 of our subjects. All the samples tested clustered within the basal-like subtype. CONCLUSIONS: In our experience the response rate of carboplatin, paclitaxel and panitumumab was consistent with other reports of response for cytotoxic chemotherapy in metastatic TNBC.

The role of connexin36 gap junctions in modulating the hypnotic effects of isoflurane and propofol in mice.

Gap junction blockade is a possible mechanism by which general anaesthetic drugs cause unconsciousness. We measured the sensitivity of connexin36 knockout mice to the hypnotic effects of isoflurane and propofol. The experimental endpoint was recovery of the righting reflex of the anaesthetised animals during 0.2% step-reductions in isoflurane concentration, or following intraperitoneal injection of propofol (100 mg.kg(-1) ). Connexin36 knockout animals were more sensitive to the hypnotic effects of isoflurane than 'normal' wild-type animals. The half maximal effective concentration (EC50) for recovery of righting reflex was 0.37% for connexin36 knockout vs 0.49% for wild-type animals (p < 0.001). For propofol, connnexin36 knockout animals showed more rapid loss of righting reflex than wild-type animals (mean (SD) 2.8 (0.13) vs 3.8 (0.27) min); and young (< 60 days) connexin36 knockout animals remained anaesthetised for longer than young wild-type mice (47.2 (2.9) vs 30.5 (1.7) min; p < 0.00001). These findings suggest that the hypnotic effects of anaesthetic drugs may be moderately enhanced by gap junction blockade.

Simple and inexpensive method of wood pellets macro-porosity measurement.

A novel simplified stereometric measurement method for determining the macro-porosity of wood pellets through geometrical approach was successfully developed and tested. The irregular ends of pellets of circular cross-section were sanded flat so that their geometry becomes cylinder and their volumes evaluated using mensuration formula. Such formed cylindrical pellets were loose or tap filled to selected volumes to evaluate the macro-porosity and the constant specific weight. The method was extended to evaluate actual wood pellets properties. Overall macro-porosity of actual wood pellets was determined as 41.0+/-2.5% and 35.5+/-2.7%, mean bulk density as 670+/-29 kg m(-3) and 731+/-31 kg m(-3), and classified as "Class-3:Medium" and "Class-3&4:Medium to Low" for loose and tapped fills, respectively. Hausner ratio and Carr's compressibility index classify wood pellets as "freely flowing." The developed stereometric method can be used as a handy inexpensive laboratory procedure to estimate the macro-porosity of different types and makes of wood pellets and other similar packaged materials.

Permeability of wood pellets in the presence of fines.

Broken pellets and fines are produced when pellets are handled. The resistance to air flow was measured for clean pellets and for pellets mixed with 1-20% broken pellets (fines). A pellet diameter was 6mm. The lengths ranged from 6 to 12 mm. Clean pellets were defined as particles that remained on a 4mm screen. A typical sieve analysis showed 30% of the mass of particles that passed through the 4mm screen was smaller than 1mm. The airflow rates used in the experiment ranged from 0.004 to 0.357 ms(-1). The corresponding pressure drop ranged from 1.9 to 271 Pam(-1) for clean pellets, from 4.8 to 1100 Pam(-1) for 10% fines content, and from 7.9 to 1800 Pam(-1) for 20% fines content. Coefficients of Hukill and Ives' equation were estimated for clean pellets and a multiplier was defined to calculate pressure drop for pellets mixed with fines.

Methicillin-resistant Staphylococcus aureus (MRSA) in municipal wastewater: an uncharted threat?

AIMS: (i) To cultivate methicillin-resistant Staphylococcus aureus (MRSA) from a full-scale wastewater treatment plant (WWTP), (ii) To characterize the indigenous MRSA-flora, (iii) To investigate how the treatment process affects clonal distribution and (iv) To examine the genetic relation between MRSA from wastewater and clinical MRSA. METHODS: Wastewater samples were collected during 2 months at four key sites in the WWTP. MRSA isolates were characterized using spa typing, antibiograms, SSCmec typing and detection of Panton-Valentine leukocidin (PVL). CONCLUSIONS: MRSA could be isolated on all sampling occasions, but only from inlet and activated sludge. The number of isolates and diversity of MRSA were reduced by the treatment process, but there are indications that the process was selected for strains with more extensive antibiotic resistance and PVL+ strains. The wastewater MRSA-flora had a close genetic relationship to clinical isolates, most likely reflecting carriage in the community. SIGNIFICANCE AND IMPACT OF THE STUDY: This study shows that MRSA survives in wastewater and that the WWTP may be a potential reservoir for MRSA.

Adjuvant gemcitabine and concurrent radiation for patients with resected pancreatic cancer: a phase II study.

The safety and efficacy of gemcitabine and concurrent radiation to the upper abdomen followed by weekly gemcitabine in patients with resected pancreatic cancer was determined. Patients with resected adenocarcinoma of the pancreas were treated with intravenous gemcitabine administered twice-weekly (40 mg m(-2)) for 5 weeks concurrent with upper abdominal radiation (50.4 Gy in 5(1/2) weeks). At the completion of the chemoradiation, patients without disease progression were given gemcitabine (1000 mg m(-2)) weekly for two cycles. Each cycle consisted of 3 weeks of treatment followed by 1 week without treatment. Forty-seven patients were entered, 46 of whom are included in this analysis. Characteristics: median age 61 years (range 35-79); 24 females (58%); 73% stage T3/T4; and 70% lymph node positive. Grade III/IV gastrointestinal or haematologic toxicities were infrequent. The median survival was 18.3 months, while the median time to disease recurrence was 10.3 months. Twenty-four percent of patients were alive at 3 years. Only six of 34 patients with progression experienced local regional relapse as a component of the first site of failure. These results confirm the feasibility of delivering adjuvant concurrent gemcitabine and radiation to the upper abdomen. This strategy produced good local regional tumour control.

MHC gene configuration variation in geographically disparate populations of California sea lions (Zalophus californianus).

Major histocompatibility complex (MHC) class II DRB genotypes were examined in two geographically isolated populations of California sea lions (Zalophus californianus) (Gulf of California and California coastal Pacific Ocean). Genomic DNA from 227 California sea lions was examined using eight sequence-specific primer (SSP) pairs flanking the putative peptide-binding site. A total of 40 different Zaca-DRB genotype configurations were identified among the 227 individuals. Using SSP-PCR, significant differences were found between coastal California and Gulf of California Zalophus populations in numbers of DRB sequences per individual and configuration of sequences within individuals. Additionally, unique local patterns of MHC diversity were identified among the Midriff Island animals. These population differences are consistent with either ecologically distinct patterns of selection pressures and/or geographical isolation. The consequences of these partitioned MHC configurations at the population level are as yet unknown; however, the worldwide increase in emerging marine diseases lends urgency to their examination.

Seasonal prevalence and intensity of hookworms (Uncinaria spp.) in California sea lion (Zalophus californianus) pups born in 2002 on San Miguel Island, California.

Intestines of California sea lion (Zalophus californianus) pups (n= 204), born in 2002 on San Miguel Island, California, were examined for hookworms (Uncinaria spp.) as part of a seasonal mortality study from June through December 2002 and January 2003. The investigation was planned to coincide with most of the previously established hookworm infection period of the pups. Prevalence of hookworms in dead pups was 100% for each month of the study. The geometric mean intensity of infections per month was: 94.03 (n=30) for June, 629.09 (n=50) for July, 319.90 (n=31) for August, 159.90 (n=30) for October, 109.03 (n=30) for November, 37.84 (n=24) for December 2002 and 11.05 (n=9) for January 2003. In addition to the temporal pattern, the infection intensity was higher for pups in good condition and for male pups. An inter-year comparison of hookworm counts from dead pups collected in July of 1996, 2000, and 2002 also demonstrated higher intensity in pups in better condition but sex-differences in intensity were inconsistent across years. The inter-year comparison also demonstrated higher intensities in dead pups collected from portions of the rookery with sandy substrate versus rocky substrate. No annual differences in intensity were found after adjusting for substrate and condition.

Observations in 2001 on hookworms ( Uncinaria spp.) in otariid pinnipeds.

Uncinaria spp. were recovered from the milk of California sea lions ( Zalophus californianus) collected from the: (1) teats of a cow just after parturition (one parasitic third-stage larva, L(3)), (2) stomach of her nursing pup (two L(3)), and (3) stomach of a dead pup about 2 days old (one L(3), one headless, probably L(3), and four L(4)) on San Miguel Island, California in May 2001. This, in addition to earlier research, indicates transmammary transmission of hookworms in this host. Uncinaria spp. were found in dead northern fur seals ( Callorhinus ursinus) in the: (1) intestines of 2 of 75 pups (either one or two adult specimens in each infected pup) and (2) ventral abdominal blubber of 3 of 78 subadult males (one to seven L(3) in each infected seal) on St. Paul Island (SPI), Alaska in July and August 2001. These findings verify the low current prevalence of Uncinariaspp. in fur seals on SPI. Rectal fecal samples taken from 50 live Steller sea lion ( Eumetopias jubatus) pups, about 1 month old, on Rogue Reef in Curry County, Oregon in July 2001, were all negative for the eggs of Uncinaria spp. The apparent zero infection rate in these pups is possibly because the rocky terrain of this rookery is not suitable for hookworm transmission.

Current prevalence of adult Uncinaria spp. in northern fur seal (Callorhinus ursinus) and California sea lion (Zalophus californianus) pups on San Miguel Island, California, with notes on the biology of these hookworms.

A prevalence survey for hookworms (Uncinaria spp.) was done in northern fur seal (Callorhinus ursinus) and California sea lion (Zalophus californianus) pups on San Miguel Island, CA, in 2000. Intestines of dead pups were examined for adult hookworms in July. These parasites were found in 95% of 20 fur seal pups and 100% of 31 sea lion pups. The number of hookworms varied from 4 to 2142 (mean = 760) in fur seal pups and from 20 to 2634 (mean = 612) in sea lion pups. A direct relationship was evident between body condition and number of hookworms in the pups; that is, pups in poor condition had fewer hookworms than those in good condition. There was a decline in the number of hookworms in sea lion pups in 2000 compared to collections in 1996. Eggs of Uncinaria spp. were found in rectal feces (collected in late September and early October) of none of 35 (0%) live fur seal pups and 41 of 48 (85%) live sea lion pups. Packed cell volume values, determined for most of the same live pups, were essentially normal for C. ursinus but were much lower than normal for most Z. californianus. Hookworm larvae were not found in blubber of fur seal and sea lion pups or in rookery sand in July. Rookery sand, positive for live hookworm larvae when put in a refrigerator, was negative at removal 2.5 years later. The average number of eggs in utero of female hookworms was 285 for three specimens from a fur seal pup and 281 from three specimens from a sea lion pup. One hookworm larva was recovered from milk stripped from the teats of a stranded Z. californianus female at The Marine Mammal Center, Sausalito, CA.

Molecular and morphometric evidence for separate species of Uncinaria (Nematoda: Ancylostomatidae) in California sea lions and northern fur seals: hypothesis testing supplants verification.

California sea lions (Zalophus californianus) and northern fur seals (Callorhinus ursinus) are each believed to host distinct hookworm species (Uncinaria spp.). However, a recent morphometric analysis suggested that a single species parasitizes multiple pinniped hosts, and that the observed differences are host-induced. To explore the systematics of these hookworms and test these competing hypotheses, we obtained nucleotide sequences of nuclear ribosomal DNA (D2/D3 28S, D18/D19 28S, and internal transcribed spacer [ITS] regions) from 20 individual hookworms parasitizing California sea lion and northern fur seal pups where their breeding grounds are sympatric. Five individuals from an allopatric population of California sea lions were also sampled for ITS-1 and D18/D19 28S sequences. The 28S D2/D3 sequences showed no diagnostic differences among hookworms sampled from individual sea lions and fur seals, whereas the 28S D18/D19 sequences had one derived (apomorphic) character demarcating hookworms from northern fur seals. ITS sequences were variable for 7 characters, with 4 derived (apomorphic) states in ITS-1 demarcating hookworms from California sea lions. Multivariate analysis of morphometric data also revealed significant differences between nematodes representing these 2 host-associated lineages. These results indicate that these hookworms represent 2 species that are not distributed indiscriminately between these host species, but instead exhibit host fidelity, evolving independently with each respective host species. This evolutionary approach to analyzing sequence data for species delimitation is contrasted with similarity-based methods that have been applied to numerous diagnostic studies of nematode parasites.

Comparative biology of Uncinaria spp. in the California sea lion (Zalophus californianus) and the northern fur seal (Callorhinus ursinus) in California.

Studies on several aspects of the life cycle of hookworms (Uncinaria spp.) in the California sea lion (Zalophus californianus) and northern fur seal (Callorhinus ursinus) were conducted on material collected on San Miguel Island (SMI), California and at The Marine Mammal Center, Sausalito, California in 1997, 1998, and 1999. Examination of Z. californianus intestines for adult hookworms and feces for eggs revealed that longevity of these parasites in pups is about 6-8 mo, and infections are probably not present in older sea lions. Parasitic third-stage larvae (L3) were recovered from the ventral abdominal tissue of Z. californianus, suggesting transmammary transmission. Callorhinus ursinus pups had no hookworm eggs in their feces or adult worms (except for 1 probable contaminant) in their intestines in the fall and early winter, revealing that adult Uncinaria spp. are spontaneously lost at <3 mo of age of the pups. Sand samples from rookeries, used by both Z. californianus and C. ursinus, on SMI were negative for free-living, L3 in summer months but positive in fall and winter months, indicating seasonality occurred.

Uncinariasis in northern fur seal and California sea lion pups from California.

Northern fur seal (Callorhinus ursinus) (n = 25) and California sea lion (Zalophus californianus) (n = 53) pups, found dead on rookeries on San Miguel Island (California, USA), were examined for adult Uncinaria spp. Prevalence of these nematodes was 96% in fur seal pups and 100% in sea lion pups. Mean intensity of Uncinaria spp. per infected pup was 643 in fur seals and 1,284 in sea lions. Eggs of Uncinaria spp. from dead sea lion pups underwent embryonation in an incubator; development to the free-living third stage larva occurred within the egg. This study provided some specific information on hookworm infections in northern fur seal and California sea lion pups on San Miguel Island. High prevalence rate of Uncinaria spp. in both species of pinnipeds was documented and much higher numbers (2X) of hookworms were present in sea lion than fur seal pups.

Simultaneous chemoradiation in the treatment of advanced head and neck cancer.

Fifty-eight patients with either advanced or unresectable squamous cell carcinoma of the head and neck were randomly selected to receive either twice daily radiation alone or twice daily radiation plus concomitant chemotherapy with cisplatin and fluorouracil (5-fluorouracil). There was no advantage in survival or time to progression with the addition of chemotherapy to twice daily radiation for patients with advanced resectable cancers. In the group of patients with unresectable cancers, however, there was a statistically significant advantage to the addition of chemotherapy, both in terms of disease-free survival and date to progression.

A double-blind comparison between a new multidose powder inhaler (Turbuhaler) and metered dose inhaler in children with asthma.

Turbuhaler is a ready-loaded multiple dose inhaler which does not require co-ordination between release of dose and inhalation. 57 children with asthma participated in this clinical trial to compare the clinical effect and acceptance of terbutaline sulphate via Turbuhaler with that of metered dose inhaler (MDI). The trial consisted of two parts. In the first part of the study, which made use of a double-blind cross-over design, the clinical effect and number of treatment occasions with Turbuhaler were compared with those of MDI. In the second part, which was open, all patients were treated with Turbuhaler for 2 weeks. At the end of this period the patients were asked to make a subjective assessment of effect and to state their preference. There was no difference in clinical effect and number of treatment occasions between Turbuhaler and MDI. A majority of the patients thought Turbuhaler had the best effect and was easy to use.

Effects of inhaled N-acetylcysteine in combination with terbutaline.

The additional effect of N-acetylcysteine in combination with inhaled terbutaline was studied in a controlled randomized double-blind cross-over study of one week periods in 22 patients with stable reversible chronic obstructive pulmonary disease. The patients improved clinically, more during the period with acetylcysteine in combination with terbutaline, than during the period with placebo/terbutaline. The differences were particularly noticeable on the parameters 'difficulties in raising sputum' and 'number of coughs'. Seventeen of 22 patients felt greater improvement during the period with acetylcysteine. Also a small improvement in FEV1 was found by addition of acetylcysteine. No side-effects of acetylcysteine were reported in this combination.

Monolayer culture of human endometrium: methods of culture and identification of cell types.

Monolayer cultures can be established from human endometrial tissue after enzymatic dispersal into isolated glands or single cells. Three cell types that have distinct morphology by light and electron microscopy are observed in the resulting primary cultures. One cell type, an elongated spindle cell, is similar in appearance to fibroblasts derived from other tissues. A second cell type forms colonies of tightly cohesive cells, ranging in shape from oval to polygonal. These cells have typical organelles and junctional complexes characteristic of epithelial cells from the endometrium. The third cell type assumes a pavement-like appearance composed of polygonal cells when viewed by phase contrast microscopy, but lacks distinctive ultrastructural features of epithelial cells. These cells in culture resemble the endometrial stromal cell, the predominant cell type of the human endometrium in vivo. The epithelial cell does not survive subculturing but the other two cell types can be passaged through several generations and can be stored in liquid nitrogen and subsequently returned to culture.

Morphology and growth potential of stromal cell cultures derived from human endometrium.

Propagable cell cultures derived from human endometrial tissue were determined to contain cells predominantly of stromal cell origin based on their morphologic resemblance to endometrial stromal cells. These features included nexi, solitary cilia, and predecidual cytology. In addition to morphology the cell cultures retained a normal karyotype and responded to steroid hormones as evidenced by cellular aggregation. The stromal cells were evaluated for a variety of characteristics associated with transformed cells and seemed to be biologically normal without neoplastic phenotypes. Growth potential of the stromal cell cultures was also characterized in normal maintenance medium, in nutritionally depleted medium with reduced levels of calcium or serum, and in medium with increased levels of serum. The prolonged survival of the stromal cells in vitro coupled with the retention of in vivo characteristics and an absence of neoplastic phenotype provides a human cell system that is amenable to a variety of long-term experimental analyses.