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Terahertz (THz) imaging has long held promise for skin cancer detection but has been hampered by the lack of practical technological implementation. In this article, we introduce a technique for discriminating several skin pathologies using a coherent THz confocal system based on a THz quantum cascade laser. High resolution in vivo THz images (with diffraction limited to the order of 100 µm) of several different lesion types were acquired and compared against one another using the amplitude and phase values. Our system successfully separated pathologies using a combination of phase and amplitude information and their respective surface textures. The large scan field (50 × 40 mm) of the system allows macroscopic visualization of several skin lesions in a single frame. Utilizing THz imaging for dermatological assessment of skin lesions offers substantial additional diagnostic value for clinicians. THz images contain information complementary to the information contained in the conventional digital images.

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Patients treated for breast cancer are at risk of developing breast cancer-related lymphedema (BCRL). A significant proportion of patients treated for breast cancer are opting to undergo a contralateral prophylactic mastectomy (CPM). Currently, it remains unclear as to whether the relative volume change (RVC) equation may be used as an alternative to the weight adjusted change (WAC) equation to quantify BCRL in patients who undergo CPM. In order to simplify BCRL screening, our cohort of patients who underwent a CPM (n=310) was matched by BMI to a subset of patients who underwent unilateral breast surgery (n=310). Arm volume measurements were obtained via an optoelectronic perometer preoperatively, postoperatively, and in the follow-up setting every 6-12 months. The correlation of ipsilateral RVC and WAC values for those who underwent bilateral surgery was calculated (r=0.60). Contralateral WAC values for patients in both cohorts were compared, and there was no significant difference between the two distributions in variance (p=0.446). The RVC equation shows potential to be used to quantify ipsilateral postoperative arm volume changes for patients who undergo a CPM. However, a larger trial in which RVC and WAC values are prospectively assessed is needed.

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Breast cancer-related lymphedema (BCRL) affects more than one in five women treated for breast cancer, and women remain at lifelong risk. Screening for BCRL is recommended by several national and international organizations for women at risk of BCRL, and multiple methods of objective screening measurement exist. The goal of this study was to compare the use of perometry and bioimpedance spectroscopy (BIS) for early identification of BCRL in a cohort of 138 prospectivelyscreened patients. At each screening visit, a patient's relative volume change (RVC) from perometer measurements and change in L-Dex from baseline (ΔL-Dex) using BIS was calculated. There was a negligible correlation between RVC and ΔL-Dex (r=0.195). Multiple thresholds of BCRL were examined: RVC ≥5% and ≥10% as well as and ΔL-Dex ≥6.5 and ≥10. While some patients developed an elevated RVC and ΔL-Dex, many demonstrated elevations in only one threshold category. Moreover, the majority of patients with RVC ≥5%, ΔL-Dex ≥6.5, or ΔL-Dex ≥10 regressed to non-elevated measurements without intervention. These findings suggest a role for combining multiple screening methods for early identification of BCRL; furthermore, BCRL diagnosis must incorporate patient symptoms and clinical evaluation with objective measurements obtained from techniques such as perometry and bioimpedance spectroscopy.

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Emerging zoonotic infectious diseases pose a serious threat to global health. This is especially true in relation to the great apes, whose close phylogenetic relationship with humans results in a high potential for microorganism exchange. In this review, we show how studies of the microorganisms of wild great apes can lead to the discovery of novel pathogens of importance for humans. We also illustrate how these primates, living in their natural habitats, can serve as sentinels for outbreaks of human disease in regions with a high likelihood of disease emergence. Greater sampling efforts and improvements in sample preservation and diagnostic capacity are rapidly improving our understanding of the diversity and distribution of microorganisms in wild great apes. Linking non-invasive diagnostic data with observational health data from great apes habituated to human presence is a promising approach for the discovery of pathogens of high relevance for humans.

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The purpose of this paper is to implement current and novel research techniques in human energy budget estimations to give more accurate and efficient application of models by a variety of users. Using the COMFA model, the conditioning level of an individual is incorporated into overall energy budget predictions, giving more realistic estimations of the metabolism experienced at various fitness levels. Through the use of VO(2) reserve estimates, errors are found when an elite athlete is modelled as an unconditioned or a conditioned individual, giving budgets underpredicted significantly by -173 and -123 W m(-2), respectively. Such underprediction can result in critical errors regarding heat stress, particularly in highly motivated individuals; thus this revision is critical for athletic individuals. A further improvement in the COMFA model involves improved adaptation of clothing insulation (I (cl)), as well clothing non-uniformity, with changing air temperature (T (a)) and metabolic activity (M (act)). Equivalent T (a) values (for I (cl) estimation) are calculated in order to lower the I (cl) value with increasing M (act) at equal T (a). Furthermore, threshold T (a) values are calculated to predict the point at which an individual will change from a uniform I (cl) to a segmented I (cl) (full ensemble to shorts and a T-shirt). Lastly, improved relative velocity (v (r)) estimates were found with a refined equation accounting for the degree angle of wind to body movement. Differences between the original and improved v (r) equations increased with higher wind and activity speeds, and as the wind to body angle moved away from 90°. Under moderate microclimate conditions, and wind from behind a person, the convective heat loss and skin temperature estimates were 47 W m(-2) and 1.7°C higher when using the improved v (r) equation. These model revisions improve the applicability and usability of the COMFA energy budget model for subjects performing physical activity in outdoor environments. Application is possible for other similar energy budget models, and within various urban and rural environments.

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BACKGROUND/AIMS: Premature infants are born with incompletely vascularised retinas and are at a risk of developing retinopathy of prematurity (ROP). Rate of prenatal and postnatal body growth is important in the pathogenesis of ROP. The aim of this study was to develop a physiology-based rat model in order to study the effect of growth restriction and oxygen on early retinal vascular development. METHODS: Rat mothers were fed either a normal (18% casein) or low (9% casein) protein diet (to cause pup growth restriction) from the last week of gestation. After birth, mother and pups were placed in either room air or a specialised oxygen chamber that delivered a rapidly fluctuating hyperoxic oxygen profile. The oxygen profile was based on that from a premature infant who developed severe ROP. On day 14, retinas were dissected, flat-mounted and stained using biotinylated lectin. Images were captured by confocal microscopy. The avascular areas of the retinas were measured and compared. RESULTS: Growth restricted rat pups had significantly larger retinal avascular areas than 'normally grown' rat pups (Mann-Whitney U test, p<0.001). Growth restricted rat pups raised in fluctuating oxygen had significantly larger retinal avascular areas than growth restricted rat pups raised in room air (Mann-Whitney U test, p=0.001). CONCLUSIONS: The authors have developed a novel model for ROP that involves inducing both intrauterine and postnatal growth restriction and also exposes neonatal rat pups to fluctuating oxygen. This physiology-based model can be used to study the effects of growth, nutrition and oxygen on early retinal vascular development.

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The disposition and metabolism of prasugrel, a thienopyridine prodrug and a potent inhibitor of platelet aggregation in vivo, were investigated in mice, rats, and dogs. Prasugrel was rapidly absorbed and extensively metabolized. In the mouse and dog, maximum plasma concentration of radioactivity was observed in less than 1 h after an oral [14C]prasugrel dose. Most of the administered prasugrel dose was recovered in the faeces of rats and dogs (72% and 52-73%, respectively), and in mice urine (54%). Prasugrel is hydrolysed by esterases to a thiolactone, which is subsequently metabolized to thiol-containing metabolites. The main circulating thiol-containing metabolite in the three animal species is the pharmacologically active metabolite, R-138727. The thiol-containing metabolites are further metabolized by S-methylation and conjugation with cysteine.

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Replication of Barley stripe mosaic virus (BSMV), genus Hordeivirus, is thought to be associated with vesicles in proplastids and chloroplasts, but the molecular details of the process and identity of virus proteins involved in establishing the virus replication complexes are unknown. In addition, BSMV encodes a triple-gene block of movement proteins (TGBs) that putatively share functional roles with their counterparts in other hordei-, pomo- and pecluviruses, but detailed information on the intracellular locations of the individual TGBs is lacking. Here, the subcellular localizations of BSMV-encoded proteins TGB2 and gammab fused to green or red fluorescent proteins were examined in epidermal cells of Nicotiana benthamiana and barley (Hordeum vulgare 'Black Hulless'). The fusion proteins were expressed from a BSMV vector or under the control of the cauliflower mosaic virus 35S promoter. The subcellular localizations were studied by confocal laser-scanning microscopy (CLSM). CLSM studies showed that both proteins were recruited to chloroplasts in the presence of viral RNA and that virus RNA, coat protein and gammab protein were detected in plastid preparations from infected leaves. Electron microscope images of thin sections of virus-infected leaves revealed abnormal chloroplasts with cytoplasmic inclusions containing virus-like particles. In addition, cellular localizations of BSMV TGB2 suggest subtle differences in function between the hordei-like TGB2 proteins. The results indicate that TGB2 and gammab proteins play a previously unknown functional role at the site of virus replication.

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The contamination rate of phlebotomy tourniquets with meticillin-resistant Staphylococcus aureus (MRSA) was assessed, and it was determined whether this could be reduced by changes in practice or by the use of a physical barrier. Initially, the tourniquets of both preregistration house officers and phlebotomists were investigated, but as phlebotomists reported significantly more venepunctures daily, the trial continued solely with phlebotomists. Each day, the phlebotomists were supplied with a fresh sterile tourniquet, and after use, the tourniquets were swabbed and cultured. The rate of contamination with MRSA was 32 of 131 (25%) tourniquets. An audit of hand hygiene practice was undertaken and revealed that phlebotomists were performing hand decontamination inadequately between patients and wore wristwatches while working. Education comprising standard infection control methods to encourage good practice was given. After this, a polythene strip was used as a barrier by half of the phlebotomists during all venepunctures. Tourniquets were cultured and replaced daily as before. During this stage of the trial, the rates of contamination were 1 of 46 tourniquets (using a polythene strip) and 1 of 42 tourniquets (without using a polythene strip). In conclusion, phlebotomy tourniquets may be potential vectors for transferring bacteria, including MRSA. Contamination rates, and hence potential risk, can be reduced if hand decontamination is performed. This suggests that contamination of tourniquets is via phlebotomists' hands, not directly from patients' skin. Hand hygiene should be regarded as the most important method by which the spread of organisms can be reduced.

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Several putative phase I duloxetine metabolites, 4-hydroxy-, 5-hydroxy-, 6-hydroxy-, 5-hydroxy-6-methoxy-, 6-hydroxy-5-methoxy-, 5,6-dihydroxy-, and 4,6-dihydroxyduloxetine were synthesized, and their phase II metabolite as glucuronide or sulfate conjugates were also synthesized. Their in vitro binding activities were compared to that of parent compound duloxetine.

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The purpose of this study was to compare and evaluate the performance of electronic leaf wetness duration (LWD) sensors in measuring LWD in a cotton crop canopy when unpainted and painted sensors were used. LWD was measured with flat, printed-circuit wetness sensors, and the data were divided into two periods of 24 days: from 18 December 2001 to 10 January 2002, when the sensors were unpainted, and from 20 January to 13 February 2002, when the sensors were painted with white latex paint (two coats of paint). The data analysis included evaluating the coefficient of variation (CV%) among the six sensors for each day, and the relationship between the measured LWD (mean for the six sensors) and the number of hours with dew point depression under 2 degrees C, used as an indicator of dew presence. The results showed that the painting markedly reduced the CV% values. For the unpainted sensors the CV% was on average 67% against 9% for painted sensors. For the days without rainfall this reduction was greater. Comparing the sensor measurements to another estimator of LWD, in this case the number of hours with dew point depression under 2 degrees C, it was also observed that painting improved not only the precision of the sensors but also their sensitivity, because it increases the ability of the sensor to detect and measure the wetness promoted by small water droplets.

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Duloxetine is a potent and balanced dual inhibitor of serotonin and norepinephrine reuptake being investigated for the treatment of depression and urinary incontinence. The disposition of duloxetine was studied in four healthy human subjects after a single 20.2-mg (100.6 microCi) oral dose of [14C]duloxetine in an enteric-coated tablet. The mean total recovery of radioactivity (+/- S.E.M.) after 312 h was 90.5% (+/-0.4%) with 72.0% (+/-1.1%) excreted in the urine. Duloxetine was extensively metabolized to numerous metabolites primarily excreted into the urine in the conjugated form. The major biotransformation pathways for duloxetine involved oxidation of the naphthyl ring at either the 4-, 5-, or 6-positions followed by further oxidation, methylation, and/or conjugation. The major metabolites found in plasma were glucuronide conjugates of the following: 4-hydroxy duloxetine (M6), 6-hydroxy-5-methoxy duloxetine (M10), 4, 6-dihydroxy duloxetine (M9), and a sulfate conjugate of 5-hydroxy-6-methoxy duloxetine (M7). The major metabolites found in plasma were also found in the urine, but the urine contained many additional metabolites. In addition to duloxetine, 4-hydroxy duloxetine (M14) and an unidentified polar metabolite were observed in feces. Following [14C]duloxetine administration, Cmax was reached at a median of 6 h for both duloxetine and total radioactivity. Duloxetine accounted for less than 3% of the circulating radioactivity based on mean area under the curve values. The elimination half-life of total radioactivity (120 h) was substantially longer than that of duloxetine (10.3 h).

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The frequency by which resistant Pseudomonas aeruginosa strains could be selected was compared for two antibiotics, levofloxacin and ciprofloxacin. Seven distinct strains were cultured on plates containing 1x, 2x, 4x and 8x the minimum inhibitory concentration (MIC) of the antibiotic under investigation. Resistant mutants were more readily isolated by growth on culture plates that contained ciprofloxacin, and the resulting MIC of the resistant mutant was also more frequently increased. Time-kill studies on comparable strains where the MIC for both antibiotics had increased by at least fourfold showed no difference between the two agents.

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Landfarming is used to treat petroleum hydrocarbon-contaminated soils and a variety of waste streams from industrial operations. Wastes are applied to a soil surface and indigenous soil microorganisms utilize the hydrocarbons in the applied waste as a carbon source for metabolism, thereby biodegrading the applied material. Concerns have been expressed that abiotic losses, such as volatilization, play a significant role in hydrocarbon reduction within the soil. To assist in better defining atmospheric releases of total hydrocarbons from landfarms treating petroleum hydrocarbons, a flux gradient micrometeorological approach was developed and integrated with a custom-built total hydrocarbon detector, and a novel air sampling system and averaging algorithm. The micrometeorological technique offers unobtrusive spatially averaged real-time continuous measurements, thereby providing a time history of emissions. This provides opportunities to investigate mechanisms controlling emissions and to evaluate landfarm management strategies. The versatility of the technique is illustrated through measurements performed at a remote landfarm used to treat diesel fuel-contaminated soil in northern Ontario and during routine operations at two active refinery landfarms in southwestern Ontario.

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PURPOSE/OBJECTIVES: To provide key examples from the oncology literature related to chemotherapy dose/dose intensity to guide nurses in evidence-based decision making. DATA SOURCES: Published articles and abstracts of scientific findings and clinical trials. DATA SYNTHESIS: Understanding tumor biology and growth kinetics is essential in determining optimal approaches to cancer treatment and goal setting in cancer care. CONCLUSIONS: Therapeutic decision making ideally should be data driven. Dose and dose intensity can make a difference in therapeutic outcomes. Additional research with well-designed clinical trials, incorporating recent advances in cancer biology, is needed to define more distinctly the role of dose/dose intensity related to specific tumor types. IMPLICATIONS FOR NURSING PRACTICE: Establish therapeutic goals at initiation of therapy, and communicate them clearly with patients, families, and the rest of the healthcare team.

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Insulin-like growth factors (IFGs), IGF-I and IGF-II, present in mammalian milk, play an important role during gastrointestinal tract development. In this study we identified and localized the activities of the common intestinal proteolytic enzymes and investigated their degradation effect on IGFs. Results indicated that the enzymatic activities of chymotrypsin, trypsin, and elastase progressed from the lowest in the duodenum, to the highest in the midjejunum, and declined in the ileum. Chymotrypsin exhibited the greatest IGFs degradation activities in neonatal intestinal lumen followed by elastase. These data furnish a potential strategic design to supplement IGFs into milk formulas.

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Peptides have the potential to be potent pharmaceutical agents for the treatment of many central nervous system derived maladies. Unfortunately peptides are generally water-soluble compounds that will not enter the central nervous system, via passive diffusion, due to the existence of the blood-brain barrier. Peptides can also undergo metabolic deactivation by peptidases, thus further reducing their therapeutic benefits. In targeting peptides to the central nervous system consideration must be focused both on increasing bioavailability and enhancing brain uptake. To date multiple strategies have been examined with this focus. However, each strategy comes with its own complications and considerations. In this review we assess the strengths and weaknesses of many of the methods currently being examined to enhance peptide entry into the central nervous system.

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The present study reports the hematopoietic response to the exogenous administration of recombinant rhesus interleukin-3 (rrIL-3) or a combination of recombinant human granulocyte colony-stimulating factor (rhG-CSF)/erythropoietin (Epo)/thrombopoietin (Tpo) at two different stages of SIV infection: Early-stage (n = 6, CD4 + > 1000/microl and mild splenomegaly) and late-stage (n = 6, CD4 + < 500/microl, progressive hepatosplenomegaly and/or weight loss). SIV-infected animals exhibited significantly impaired bone marrow (BM) and peripheral blood (PB) responses to both rrIL-3 and rhG-CSF/Epo/Tpo administration, as compared to historic controls. In addition, compared to early-stage SIV-infected animals, late-stage SIV-infected macaques demonstrated a more marked dysfunction, as assessed by PB and BM CD34 + content and clonogenic progenitors (colony-forming unit). Neither rrIL-3 nor rhG-CSF/Epo/Tpo administration during either early-stage or late-stage SIV infection increased the viral load, as assessed by bDNA assay. These data suggest that hematopoietic reserve and the response to various cytokines is decreased even in early-stage SIV infection, with the hematopoietic dysfunction progressing in parallel to SIV infection.

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