A compact 2.0 T superconducting magnet.

A compact 2.0 T superconducting magnet has been developed for use in photoelectron microscopy. The magnet was required to be compact and magnetically well shielded with low stray fields. Because the magnet is for use with a microscope, the working volume can be small. A small volume implies that the stored magnetic energy is low, and with low stray fields, it makes the magnet safe while operating and during quench events. The magnet is a cryogen free design that uses a diamond loaded vacuum grease for current lead encapsulation and cooling. To make as small a coil as possible, a new coil winding method was developed that does not require solder joints between pancake windings. We show that a low temperature Sn/Bi/Ag eutectic solder can be used for connecting the input leads in this application.

Vector Potential Photoelectron Microscopy Instrument Design.

This report covers the main aspects of designing a vector potential photoelectron microscope (VPPEM). While the VPPEM is straightforward in concept, there are several areas where the optimum configuration of the optics is not immediately obvious, and compromises must be made to make a practical instrument. This report summarizes our instrumental setups, and some basic design issues.

Enhanced efficacy in drug-resistant cancer cells through synergistic nanoparticle mediated delivery of cisplatin and decitabine.

There are several limitations with monodrug cancer therapy, including poor bioavailability, rapid clearance and drug resistance. Combination therapy addresses these by exploiting synergism between different drugs against cancer cells. In particular, the combination of epigenetic therapies with conventional chemotherapeutic agents can improve the initial tumour response and overcome acquired drug resistance. Co-encapsulation of multiple therapeutic agents into a single polymeric nanoparticle is one of the many approaches taken to enhance therapeutic effect and improve the pharmacokinetic profile. In this study, different types of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs), matrix and core-shell (CS), were investigated for simultaneous encapsulation of a demethylating drug, decitabine, and a potent anticancer agent, cisplatin. It was shown that by altering the configuration of the CS structure, the release profile could be tuned. In order to investigate whether this could enhance the anticancer effect compared to cisplatin, human ovarian carcinoma cell line (A2780) and its cisplatin resistant variant (A2780cis) were exposed to free cisplatin and the CS-NPs. A better response was obtained in both cell lines (11% and 51% viability of A2780 and A2780cis, respectively) using CS-NPs than cisplatin alone (27%, 82% viability of A2780 and A2780cis, respectively) or in combination with decitabine (22%, 96% viability of A2780 and A2780cis, respectively) at equivalent doses (10 µM).

Slow Acceptance of Universal Antiretroviral Therapy (ART) Among Mothers Enrolled in IMPAACT PROMISE Studies Across the Globe.

The PROMISE trial enrolled asymptomatic HIV-infected pregnant and postpartum women not eligible for antiretroviral treatment (ART) per local guidelines and randomly assigned proven antiretroviral strategies to assess relative efficacy for perinatal prevention plus maternal/infant safety and maternal health. The START study subsequently demonstrated clear benefit in initiating ART regardless of CD4 count. Active PROMISE participants were informed of results and women not receiving ART were strongly recommended to immediately initiate treatment to optimize their own health. We recorded their decision and the primary reason given for accepting or rejecting the universal ART offer after receiving the START information. One-third of participants did not initiate ART after the initial session, wanting more time to consider. Six sessions were required to attain 95% uptake. The slow uptake of universal ART highlights the need to prepare individuals and sensitize communities regarding the personal and population benefits of the "Treat All" strategy.

Ultrasound-activated microbubbles as a novel intracellular drug delivery system for urinary tract infection.

The development of new modalities for high-efficiency intracellular drug delivery is a priority for a number of disease areas. One such area is urinary tract infection (UTI), which is one of the most common infectious diseases globally and which imposes an immense economic and healthcare burden. Common uropathogenic bacteria have been shown to invade the urothelial wall during acute UTI, forming latent intracellular reservoirs that can evade antimicrobials and the immune response. This behaviour likely facilitates the high recurrence rates after oral antibiotic treatments, which are not able to penetrate the bladder wall and accumulate to an effective concentration. Meanwhile, oral antibiotics may also exacerbate antimicrobial resistance and cause systemic side effects. Using a human urothelial organoid model, we tested the ability of novel ultrasound-activated lipid microbubbles to deliver drugs into the cytoplasm of apical cells. The gas-filled lipid microbubbles were decorated with liposomes containing the non-cell-permeant antibiotic gentamicin and a fluorescent marker. The microbubble suspension was added to buffer at the apical surface of the bladder model before being exposed to ultrasound (1.1 MHz, 2.5 Mpa, 5500 cycles at 20 ms pulse duration) for 20 s. Our results show that ultrasound-activated intracellular delivery using microbubbles was over 16 times greater than the control group and twice that achieved by liposomes that were not associated with microbubbles. Moreover, no cell damage was detected. Together, our data show that ultrasound-activated microbubbles can safely deliver high concentrations of drugs into urothelial cells, and have the potential to be a more efficacious alternative to traditional oral antibiotic regimes for UTI. This modality of intracellular drug delivery may prove useful in other clinical indications, such as cancer and gene therapy, where such penetration would aid in treatment.

Development and validation of models to predict personal ventilation rate for air pollution research.

Air pollution intake represents the amount of pollution inhaled into the body and may be calculated by multiplying an individual's ventilation rate with the concentration of pollutant present in their breathing zone. Ventilation rate is difficult to measure directly, and methods for estimating ventilation rate (and intake) are lacking. Therefore, the goal of this work was to examine how well linear models using heart rate and other basic physiologic data can predict personal ventilation rate. We measured personal ventilation and heart rate among a panel of subjects (n = 36) while they conducted a series of specified routine tasks of varying exertion levels. From these data, 136 candidate models were identified using a series of variable transformation and selection algorithms. A second "free­living" validation study (n = 26) served as an independent validation dataset for these candidate models. The top­performing model, which included heart rate (Hr), resting heart rate (Hrest), age, sex, and hip circumference and interactions between sex with Hr, Hrest, age, and hip predicted ventilation rate (Ve) to within 11% and 33% for moderate (Ve = 45 L/min) and low (Ve = 15 L/min) intensity activities, respectively, based on the validation study. Many of the promising candidate models performed substantially worse under independent validation. Our results indicate that while measures of air pollution exposure and intake are highly correlated within tasks for a given individual, this correlation decreases substantially across tasks (i.e., as individuals go about a series of typical daily activities). This discordance between exposure and intake may influence exposure­response estimates in epidemiological studies. New air pollution studies should consider the trade­offs between the predictive ability of intake models and the error potentially introduced by not accounting for ventilation rate.

Differences among four meat goat breeds for doe fitness indicator traits in the southeastern United States.

Sustainable meat goat production begins with the identification and use of maternal breeds that demonstrate relatively enhanced levels of fitness under less-than-optimal conditions. The Myotonic goat is a heritage breed that is lacking in comparative assessment for female fitness. In this study, Boer ( = 73), Kiko ( = 115), Myotonic ( = 80), and Spanish ( = 114) meat goat does were compared for traits associated with health and reproduction. The herd was semi-intensively managed on humid subtropical pasture for 6 yr. The study included 838 doe-year matings and over 2,000 records for BW, fecal egg count (FEC), and packed cell volume (PCV). Body weights of Boer and Kiko does were heavier ( < 0.05) than for Spanish does, which, in turn, were heavier ( < 0.05) than for Myotonic does. In production does, FEC were lower ( < 0.05) for Myotonic does than for Boer does, whereas Kiko and Spanish does had intermediate FEC that differed ( < 0.05) from Myotonic and Boer does. Kiko, Myotonic, and Spanish does had greater ( < 0.05) PCV than Boer does. Doe age and physiological status also affected ( < 0.05) BW, FEC, and PCV. Annual kidding rates, weaning rates, doe retention rates, and kid crop weaned were greater ( < 0.05) for Kiko and Spanish does than for Boer does, whereas Myotonic does were intermediate and differed ( < 0.05) from the other 3 breeds. The results suggest that Kiko and Spanish does should be preferred over Boer and Myotonic does for sustainable meat goat doe performance under limited-input management conditions. Myotonic does maintained the lowest FEC among all doe breeds and warrant further evaluation as a genetic resource for controlling gastrointestinal parasitism.

Efficacy and safety of ultra rapid iron polymaltose infusion during general anaesthesia.

To assess the efficacy and safety of ultra rapid (15 minute) infusion of iron polymaltose to iron deficient patients during general anaesthesia, we performed a prospective, interventional non-randomised study on 99 adult patients with iron deficiency with or without anaemia presenting for surgery under general anaesthesia. Over 15 minutes during the maintenance phase of anaesthesia, patients were given iron polymaltose, 500 mg if not anaemic, or 1,000 mg if anaemic. Haemodynamic stability, immediate or delayed iron-related side-effects and efficacy at six weeks were assessed. The incidence of significant hypotension or the requirement for vasopressor was not different before, during or after the iron infusion. There were no serious intraoperative events (allergic reactions or skin staining). Mean (standard deviation, SD) haemoglobin rose from 121 (14) g/l preoperatively to 131 (12) g/l at six weeks (P <0.001). Mean (SD) ferritin rose from 17 (12) µg/l to 110 (83) µg/l by six weeks (P <0.001). At six weeks only four out of 64 contactable patients (6.25%) had a ferritin of <30 µg/l. The incidence of immediate or delayed side-effects was similar to patients undergoing outpatient iron polymaltose infusions and reflective of a post-surgical population. We conclude that up to 1,000 mg of iron polymaltose can be given over 15 minutes without significant haemodynamic compromise to selected patients undergoing general anaesthesia. Iron polymaltose administered in this way appears efficacious in treating iron deficiency.

Enhanced spatial resolution in vector potential photoelectron microscopy.

The spatial resolution of the vector potential photoelectron microscope is determined by the maximum size of the cyclotron orbits of the imaged electrons at the surface of a sample. It is straightforward to calculate the spatial resolution for any imaged electron energy given the magnetic field strength. However, in low-energy secondary photoelectron images from an aluminium-calcium metal matrix alloy, we find the apparent spatial resolution is significantly higher than expected. A possible explanation for the enhanced resolution is that the low-energy cyclotron orbits are distorted when passing from one area of work function to another and the image is dependent on the surface field distribution.

Anaphylaxis-induced hyperfibrinolysis in pregnancy.

Anaphylaxis during pregnancy is rare but life threatening to both mother and fetus. The anaesthetist may be unexpectedly faced with an obstructing airway, severe bronchospasm and cardiac arrest requiring perimortem caesarean delivery to relieve aortocaval compression. We present a case of anaphylaxis-induced hyperfibrinolysis, an infrequently discussed complication that could exacerbate postpartum haemorrhage and hamper resuscitative efforts.

Transcriptional activation of antioxidants may compensate for selenoprotein deficiencies in Amblyomma maculatum (Acari: Ixodidae) injected with selK- or selM-dsRNA.

The Gulf-Coast tick, Amblyomma maculatum, possesses an elaborate set of selenoproteins, which prevent the deleterious effects from oxidative stress that would otherwise occur during feeding. In the current work, we examined the role of selenoprotein K (SelK) and selenoprotein M (SelM) in feeding A. maculatum by bioinformatics, transcriptional gene expression, RNA interference and antioxidant assays. The transcriptional expression of SelK did not vary significantly in salivary glands or midguts throughout the bloodmeal. However, there was a 58-fold increase in transcript levels of SelM in tick midguts. Ticks injected with selK-dsRNA or selM-dsRNA did not reveal any observable differences in egg viability but oviposition was reduced. Surprisingly, salivary antioxidant activity was higher in selenoprotein knockouts compared with controls, which is probably the result of compensatory transcriptional expression of genes involved in combating reactive oxygen species. In fact, quantitative real-time PCR data suggest that the transcriptional expression of catalase increased in ticks injected with selM-double-stranded RNA. Additionally, the transcriptional expression of selN decreased ∼90% in both SelK/SelM knockdowns. These data indicate that SelK and SelM are salivary antioxidants but are not essential for tick survival or reproduction and are compensated by other antioxidant systems.

Spatial resolution in vector potential photoelectron microscopy.

The experimental spatial resolution of vector potential photoelectron microscopy is found to be much higher than expected because of the cancellation of one of the expected contributions to the point spread function. We present a new calculation of the spatial resolution with support from finite element ray tracing, and experimental results.

A case of pulmonary infiltrates in a patient with colon carcinoma.

A 31-year-old white male with a known history of colon carcinoma was referred to the Interventional Pulmonary service for right lower lobe infiltrates and mucous plugging on computed tomography with concern for pneumonia. Bronchoscopy was performed revealing a broad based mass completely obstructing the bronchus intermedius. It was possible to pass a probe into the right lower lobe, and subsequent photoablation and mechanical debulking revealed that the mass was arising near the origin of the superior basal segment of the right lower lobe (RB6) and could be resected. Pathology confirmed this was consistent with the patient's known primary colon carcinoma. The potential for endobronchial metastasis in patients with colorectal carcinoma should be investigated in those patients with new or worsening pulmonary symptoms and signs.

RNA interference-mediated depletion of N-ethylmaleimide sensitive fusion protein and synaptosomal associated protein of 25 kDa results in the inhibition of blood feeding of the Gulf Coast tick, Amblyomma maculatum.

The signalling pathways in tick salivary glands that control 'sialo-secretome' secretion at the tick-host interface remain elusive; however, this complex process is essential for successful feeding and manipulation of the host haemostatic response. Exocytosis of the sialo-secretome in the salivary glands requires a core of soluble N-ethylmaleimide-sensitive fusion (NSF) attachment proteins (SNAPs) and receptor proteins (SNAREs). SNAREs have been identified as the key components in regulating the sialo-secretome in the salivary gland cells. In this study, we utilized RNA interference to investigate the functional role of two Amblyomma maculatum SNARE complex proteins, AmNSF and AmSNAP-25, in the tick salivary glands during extended blood feeding on the vertebrate host. Knock-down of AmNSF and AmSNAP-25 resulted in death, impaired feeding on the host, lack of engorgement and inhibited oviposition in ticks. Depletion also led to important morphological changes in the collapse of the Golgi apparatus in the salivary gland cells. Our results imply a functional significance of AmNSF and AMSNAP-25 in prolonged tick feeding, and survival on the host. Further characterization of the factors that regulate exocytosis may lead to novel approaches to prevent tick-borne diseases.

Comparative stress responses to short transport and related events in Hereford and Brahman steers.

Three summer experiments compared responses to transportation-related events in 2- to 4-yr-old Brahman (Bos indicus) and Hereford (B. taurus) steers. In Exp. 1, steers were hauled round-trip (4 h) or fasted in holding pens. Transport transiently increased (P < 0.01) plasma cortisol and glucose concentrations, decreased (P < 0.05) plasma triglyceride concentrations, and increased total leukocyte counts. Blood constituents were not altered for steers fasting in holding pens. Treatment-day BW shrink was greater (P < 0.01) in transported steers than penned steers. Blood constituent responses were unaffected (P < 0.05) by subspecies. Hereford experienced greater (P < 0.05) transport-day BW shrink than Brahman across treatments. Steers in Exp. 2 were hauled to a new farm for a 1-wk relocation period or hauled round-trip an equal time (0.67 h) and returned to the home station. Both treatments similarly experienced transport-day BW shrink and increased (P < 0.01) plasma cortisol and glucose. Subspecies did not affect (P < 0.05) blood constituent responses to transport. Hereford experienced greater (P < 0.05) transport-day shrink than Brahman. Relocation did not elicit (P < 0.05) changes in blood profiles beyond the day of transport. In Exp. 3, steers were loaded and unloaded without transport, transported round-trip (1 h), or fasted in a holding pen for 3 h. Cortisol increased (P < 0.01) after transport and after loading/unloading. Leukocytes and glucose increased (P < 0.01) after the 1 h transport. Steers transported experienced greater treatment-day BW shrink than those fasted or loaded and unloaded (P < 0.01; -3.13 vs. -1.36 and -0.35 ± 0.76%, respectively). The subspecies did not vary (P < 0.05) for blood constituent responses or shrink in Exp. 3. Animal responses were not evident 24 h after treatments in each experiment. In summary, transport caused stress, but Brahman steers were not more sensitive than Herefords. Hereford steers were susceptible to greater transport BW shrink than Brahman under the summer conditions.

Carcass yield traits of kids from a complete diallel of Boer, Kiko, and Spanish meat goat breeds semi-intensively managed on humid subtropical pasture.

Bucklings (n = 275) from a complete diallel of Boer, Kiko, and Spanish meat goats were slaughtered at 7 mo of age (4 mo postweaning) to evaluate genetic effects on carcass yield. Breed of sire did not affect (P > 0.05) live, carcass, and primal weights. Conversely, breed of dam was a consistently significant source of variation for carcass weight traits. Kiko dams produced kids with heavier (P < 0.05) live, carcass, and primal weights than Boer dams. Weights from Spanish dams were intermediate to Boer and Kiko with the significance of differences varying by trait. Cold carcass dressing percent was affected (P < 0.01) by breeds of sire and dam. Boer sires decreased (P < 0.05) dressing percent compared with Kiko and Spanish sires. Dressing percent was also less (P < 0.01) from Boer dams than from Kiko dams; Spanish dams were intermediate and did not differ (P > 0.05) from Boer or Kiko. Subjective conformation scores for muscularity were affected (P < 0.01) by breeds of sire and dam. Boer-sired kids had better (P < 0.01) live scores than Kiko-sired kids. Progeny of Boer dams had better (P < 0.05) live scores than progeny of Spanish dams. Boer-sired kids also had better carcass scores (P < 0.05) than Kiko-sired and Spanish-sired kids. Breed differences for primal cut proportions were negligible. Proportional boneless meat yields did not vary (P > 0.05) by breeds of sire or dam. Direct effects of Boer were negative for carcass weight, dressing percent, and shoulder weight and positive for proportional leg weight. Direct effects of Kiko were positive for carcass weight and shoulder weight and negative for proportional leg weight. Direct effects of Spanish did not differ (P > 0.10) from 0 for any trait tested. Heterosis levels were similar among breed pairings. Heterosis was substantial (P ≤ 0.05) for live, carcass, and primal weights (5 to 9%) but not for dressing percent, proportional boneless meat yield, or primal weight proportions (<2%). Significant genetic variation was observed among goat breeds for carcass yield traits. Dam breed was more influential than sire breed. Boer germplasm was not superior to Kiko or Spanish germplasm for carcass yield when semi-intensively managed on humid, subtropical pasture. Results emphasize the importance of comparative breed evaluations to provide industry with reliable information on carcass yield among goat genotypes.

Vector potential photoelectron microscopy.

A new class of electron microscope has been developed for the chemical microanalysis of a wide range of real world samples using photoelectron spectroscopy. Highly structured, three-dimensional samples, such as fiber mats and fracture surfaces can be imaged, as well as insulators and magnetic materials. The new microscope uses the vector potential field from a solenoid magnet as a spatial reference for imaging. A prototype instrument has demonstrated imaging of uncoated silk, magnetic steel wool, and micron-sized single strand tungsten wires.

Birth to weaning kid traits from a complete diallel of Boer, Kiko, and Spanish meat goat breeds semi-intensively managed on humid subtropical pasture.

Boer, Kiko, and Spanish meat goats were semi-intensively managed in a complete 3-breed diallel mating scheme to evaluate genetic effects on preweaning kid performance. Over a 6-yr period, 1,547 kids were born in March and May with 1,173 kids raised by their dams to weaning at 3 mo of age. March-born kids were lighter (P < 0.01) at birth, but had greater (P < 0.01) preweaning ADG and survival rates and heavier (P < 0.01) weaning weights than May-born kids. For birth weight, the direct Boer effect was positive (P < 0.01) and direct effects were negative (P < 0.01) for Kiko and Spanish. The direct Kiko effect for preweaning ADG was positive (P < 0.05), whereas other direct breed effects for ADG and all direct effects for weaning weight did not differ from 0 (P > 0.10). Maternal Boer effects were negative (P < 0.01) for birth weight and weaning weight, whereas maternal Kiko effects were significantly (P < 0.05) positive for preweaning ADG and weaning weight. Maternal Spanish effect was positive (P < 0.05) for birth weight, but did not differ from 0 (P > 0.5) for preweaning ADG or weaning weight. Heterosis for birth weight was exhibited (P < 0.01) for each pair of breed crosses, but only between Boer and Kiko for ADG and weaning weight. Kiko and Spanish dams had greater (P < 0.01) preweaning kid survival rates than Boer dams, but the former 2 did not differ (P = 0.72). Significant genetic variation was observed between meat goat breeds for kid performance to weaning. Maternal breed effects were more influential than direct breed effects. Boer goats were not superior to Kiko or Spanish for preweaning kid performance when semi-intensively managed on humid, subtropical pasture. Kiko should be a preferred breed and to a lesser extent Spanish for enhancing birth to weaning kid performance. Findings of this study emphasize the importance of proper doe breed selection in achieving desired kid performance to weaning in meat goats.