Search

SummaryWhat is known and objective Paritaprevir/ritonavir/ombitasvir+dasabuvir (PrOD) is a direct-acting antiviral (DAA) approved for the treatment of chronic hepatitis C virus. We report on a probable interaction between PrOD with ribavirin and warfarin. Case description Two weeks after the start of PrOD with ribavirin, the patient's international normalized ratio (INR) became subtherapeutic. Eleven weeks into therapy and following a 125% total increase in the weekly warfarin dose, therapeutic INR was achieved. Thirteen days after DAA therapy was completed and discontinued, the patient's INR became critically supratherapeutic. What is new and conclusion Patients on PrOD plus ribavirin with warfarin should have INR followed closely upon initiation and discontinuation of therapy due to a probable drug interaction.

Background Prescribing for patients taking multiple medicines (i.e. polypharmacy) is challenging for general practitioners (GPs). Limited evidence suggests that the integration of pharmacists into the general practice team could improve the management of these patients. The aim of this study is to develop and test an intervention involving pharmacists, working within GP practices, to optimise prescribing in Ireland, which has a mixed public and private primary healthcare system. Methods This non-randomised pilot study will use a mixed-methods approach. Four general practices will be purposively sampled and recruited. A pharmacist will join the practice team for 6 months. They will participate in the management of repeat prescribing and undertake medication reviews (which will address high-risk prescribing and potentially inappropriate prescribing, deprescribing and cost-effective and generic prescribing) with adult patients. Pharmacists will also provide prescribing advice regarding the use of preferred drugs, undertake clinical audits, join practice team meetings and facilitate practice-based education. Throughout the 6-month intervention period, anonymised practice-level medication (e.g. medication changes) and cost data will be collected. A nested Patient Reported Outcome Measure (PROM) study will be undertaken during months 4 and 5 of the 6-month intervention period to explore the impact of the intervention in older adults (aged ≥ 65 years). For this, a sub-set of 50 patients aged ≥ 65 years with significant polypharmacy (≥ 10 repeat medicines) will be recruited from each practice and invited to a medication review with the pharmacist. PROMs and healthcare utilisation data will be collected using patient questionnaires, and a 6-week follow-up review conducted. Acceptability of the intervention will be explored using pre- and post-intervention semi-structured interviews with key stakeholders. Quantitative and qualitative data analysis will be undertaken and an economic evaluation conducted. Discussion This non-randomised pilot study will provide evidence regarding the feasibility and potential effectiveness of general practice-based pharmacists in Ireland and provide data on whether a randomised controlled trial of this intervention is indicated. It will also provide a deeper understanding as to how a pharmacist working as part of the general practice team will affect organisational processes and professional relationships in a mixed public and private primary healthcare system.

Maintaining adequate nutrient intake during space flight is important not only to meet nutrient needs of astronauts but also to help counteract negative effects of space flight on the human body. Beyond these functions, food also provides psychosocial benefits throughout a mission. Dietary intake data from multiple space programs, including the Space Shuttle and the International Space Station, are discussed. These data arise from medical monitoring of dietary intake and crew health, as well as from research protocols designed to assess the role of diet in counteracting bone loss and other health concerns. Ground- based studies are conducted to better understand some of the negative issues related to space flight. Examples of ground-based studies are extended-duration bed rest studies, vitamin D supplementation studies in Antarctica during 6-month winterovers, and 10- to 14-day saturation diving missions on the floor of the ocean. The use of weighed food records, diet diaries, barcodes and food-frequency questionnaires to assess nutritional intake of space crewmembers is described. Provision of food and nutrients in space flight is important for many body systems including the cardiovascular, musculoskeletal, endocrine, and immune systems. Key areas of concern during long-duration space flight include loss of body mass, bone and muscle loss, radiation exposure and oxidative damage, nutrient intake during spacewalks (extravehicular activity), depletion of nutrient stores, and inadequate dietary intake. Initial experimental research studies using food and nutrition as a countermeasure to aid in mitigating these concerns are underway. Beyond their importance for the few individuals leaving the planet, these studies have significant implications for those remaining on Earth.

Animal models and human studies suggest that osteocytes regulate the skeleton's response to mechanical unloading in part by an increase in sclerostin. However, few studies have reported changes in serum sclerostin in humans exposed to reduced mechanical loading.We determined changes in serum sclerostin and bone turnover markers in healthy adult men undergoing controlled bed rest.Seven healthy adult men (31 ± 3 yr old) underwent 90 d of 6° head down tilt bed rest at the University of Texas Medical Branch Institute for Translational Sciences-Clinical Research Center.Serum sclerostin, PTH, vitamin D, bone resorption and formation markers, urinary calcium and phosphorus excretion, and 24-h pooled urinary markers of bone resorption were evaluated before bed rest [baseline (BL)] and at bed rest d 28 (BR-28), d 60 (BR-60), and d 90 (BR-90). Bone mineral density was measured at BL, BR-60, and 5 d after the end of the study (BR+5). Data are reported as mean ± SD.Consistent with prior reports, bone mineral density declined significantly (1-2% per month) at weight-bearing skeletal sites. Serum sclerostin was elevated above BL at BR-28 (+29 ± 20%; P = 0.003) and BR-60 (+42 ± 31%; P0.001), with a lesser increase at BR-90 (+22 ± 21%; P = 0.07). Serum PTH levels were reduced at BR-28 (-17 ± 16%; P = 0.02) and BR-60 (-24 ± 14%; P = 0.03) and remained lower than BL at BR-90 (-21 ± 21%; P = 0.14), but did not reach statistical significance. Serum bone turnover markers were unchanged; however, urinary bone resorption markers and calcium were significantly elevated at all time points after bed rest (P0.01).In healthy men subjected to controlled bed rest for 90 d, serum sclerostin increased, with a peak at 60, whereas serum PTH declined, and urinary calcium and bone resorption markers increased.

Using the finite element software Abaqus, the present study utilized explicit flaw modeling techniques to compute nozzle corner crack stress intensity factors for a range of semi-elliptical and sawcut cracks in a nozzle and semi-elliptical cracks in a flat plate. Additionally, a weight function method (WFM) for a semi-elliptical crack in a flat plate was evaluated. Stress intensity factors were computed for a number of loading conditions. A transient thermal stress analysis was performed for the nozzle explicit flaw models and discussed. Results of this study indicate that stress intensity factors at the bisecting position of the elliptical crack front from the flat plate model agree well with the analogous nozzle crack bisector position results and WFM solution.Copyright © 2015 by ASME

Received 17 January 2003; revised 27 March 2003; accepted 8 April 2003 Background: Our aim was to explore the use of concurrent chemoradiotherapy in the management of patients with squamous cell carcinoma of the head and neck from an occult primary (HNCOP). Patients and methods: From 1991 to 2000, 25 patients with T0N2M0 or T0N3M0 HNCOP were entered into five sequential phase II clinical trials. Chemoradiotherapy consisted of a split course of radiotherapy with concurrent 5-fluorouracil and hydroxyurea either alone or with cisplatin, or paclitaxel. Two of the five protocols incorporated induction chemotherapy. Results: Nodal stage was N2a in five patients (20%), N2b in 13 (52%), N2c in one (4%) and N3 in six (24%). Twenty-two patients (88%) underwent neck dissection; 14 of 22 patients underwent neck dissection before initiating protocol therapy. Total radiation doses of 55–75 Gy (median 60 Gy) were delivered; radiation fields included the potential sites of mucosal primaries and the neck bilaterally. Selected patients received a radiation boost to the involved neck. With a median follow-up of 3.9 years, three patients have progressed (one local, two distant) and seven patients have died. Deaths were due to disease progression (three) or unrelated causes (four). No metachronous primaries developed. The 5-year progression-free and overall survival was 87% and 75%, respectively. Conclusion: Combined-modality treatment with intensive chemoradiotherapy results in excellent disease control and long-term survival for patients with N2–N3 HNCOP and compares favorably with traditional

Structured Abstract Objectives To determine minimal dose levels required for local inhibition of orthodontic relapse by recombinant OPG protein (OPG-Fc), while also determining effects of injected OPG-Fc on alveolar bone and long bone. Setting and Sample Population The Department of Orthodontics and Pediatric Dentistry at the University of Michigan. Eighteen male Sprague Dawley rats. Materials & Methods Maxillary molars were moved with nickel–titanium springs and then allowed to relapse in Sprague Dawley rats. Upon appliance removal, animals were injected with a single dose of 1.0 mg/kg OPG-Fc, 0.1 mg/kg OPG-Fc, or phosphate-buffered saline (vehicle) just distal to the molar teeth. Tooth movement measurements were made from stone casts, which were scanned and digitally measured. Alveolar tissues were examined by histology. Micro-computed tomography was used to quantify changes in alveolar and femur bone. Results Local injection of OPG-Fc inhibited molar but not incisor relapse, when compared to vehicle-injected animals. No significant differences in alveolar or femur bone were seen between the three treatment groups after 24 days of relapse. Conclusions Our results demonstrate that a single local injection of OPG-Fc effectively inhibits orthodontic relapse, with minimal systemic bone metabolic effects. Our results also show that a single injection of OPG-Fc will influence tooth movement only in teeth close to the injection site. These findings indicate that OPG-Fc has potential as a safe and effective pharmacological means to locally control osteoclasts, for uses such as maintaining anchorage during orthodontic tooth movement and preventing orthodontic relapse in humans.

Animal studies were done using an in vivo dog model to examine the possible mechanism for the esophageal adverse events reported with alendronate sodium tablets. These studies showed that under low pH conditions alendronate sodium can cause esophageal irritation. No esophageal irritation occurred at pH 3.5 or higher where the drug exists primarily as the sodium salt. The animal studies also showed that alendronate sodium can exacerbate preexisting esophageal damage. Exposure of the esophageal mucosa for a prolonged period to alendronate sodium tablet can also cause mild esophageal irritation. These findings suggest that the esophageal irritation in patients taking Fosamax can be from prolonged contact with the tablet, reflux of acidic gastric contents with alendronate sodium, and exacerbation of preexisting esophageal damage. The findings also suggest that other bisphosphonates can cause esophageal injury under similar conditions.

The Senegalese grasshopper, Oedaleus senegalensis (Krauss) (Orthoptera: Acrididae), is a major grasshopper pest of subsistence crops in the West African Sahel. In northern Mali, O. senegalensis spends the dry season in the egg stage in the soil and eclosion is triggered by the first rains which usually occur in May and June. Satellite imagery potentially enables rainfall, and hense O. senegalensis eclosion, to be monitored over much wider areas than those possible for ground-based observers. In 1990 and 1991, rain-gauge networks were set up at Mourdiah, northern Mali, and for each storm event, rainfall and Meteosat infra-red data were collected. The coldest convection clouds (< -70°C) produced rain 93.1% (n = 15) of the time, whereas warmer cloud (>- 10°C) produced rain only once (n = 61). The relationship between minimum cloud temperature and log transformed rainfall data was negative and highly significant (P < 0.0005). The maximum rain-gauge separation for reliable point measurements of rainfall was 8 km. Simulated rainfall experiments showed that O. senegalensis eclosion is influenced both by soil type and by the quantity of water added to the soil. A grasshopper survey after the first rain in 1994 showed that 8 mm of rain was sufficient to cause eclosion 9 days later. The implications of these results for improved O. senegalensis control are discussed.

The new Basolan AS process for wool dyeing is described. The process restricts the deterioration of wool properties that occurs as a result of dyeing. This is achieved through a reduction in the extent to which wool is permanently set during dyeing. Two options are available to the dyer involving the addition of antisetting chemicals to the wool dyebath. Processing and product benefits can be obtained for wool dyed as loose fibre, top, yarn (package or hank) and woven fabric.

The results obtained during a wake-vortex test conducted in the NASA Ames Research Center 80- by 120-ft Wind Tunnel are described. The wind-tunnel test is part of an FA A and NASA program to study the characteristics of lift-generate d vortices in order to safely increase airport capacity for subsonic transports. Data was first obtained to confirm that measurements in the 80- by 120-ft Wind Tunnel are in agreement with those taken in the 40- by 80-ft Wind Tunnel during the test program of the 1970s. Measurements are then presented on the maximum rolling moment induced on following models of various sizes when they encounter the vortex wakes shed by several configurations of a subsonic transport. Finally, measurements are presented of the lift and rolling moment induced on various following models, and of the down wash, as a function of span wise distance in the wake. The wing spans of the followers vary from 0.085 to 1.022 times the span of the wakegenerating model.

We report on the sol–gel deposition and characterization of high-quality, epitaxial films of PbZr.52Ti.48O3 (PZT) on (001)Si substrates, with a thickness range of 400 A to 1 μm. The epitaxial growth of PZT on (001)Si is achieved using a thin template layer of SrTiO3, grown by molecular-beam epitaxy. The sol–gel PZT films have a typical surface roughness of 5 A and exhibit well defined reflective high-energy electron diffraction patterns characteristic of smooth, epitaxial films. Using high-resolution transmission electron microscopy and double-crystal x-ray diffraction, we find that the PZT films are oriented with the c axis normal to the (001)Si plane and with the a axis lying along 〈110〉Si direction. Finally, we measure the electromechanical coupling coefficients and the surface acoustic wave velocities for our films as a function of thickness and compare our experimental data to previously published theoretical values for this system.

Nitrate concentrations and nitrate loads throughout the River Frome catchment (Dorset) are compared for the periods 1970-71 and 1984-86. Nitrate concentrations and loads have increased at every site, the increase in mean nitrate concentrations varying from 31% to 123%. These increases in nitrate concentrations are related to changes in land use and fertiliser applications and also to an increase in sewage effluent entering the river.

ObjectiveTo test the effectiveness of a complex intervention designed, within a theoretical framework, to improve outcomes for patients with coronary heart disease.DesignCluster randomised controlled multicentre trial.SettingGeneral practices in Northern Ireland and the Republic of Ireland, regions with different healthcare systems.Participants903 patients with established coronary heart disease registered with one of 48 practices.InterventionTailored care plans for practices (practice based training in prescribing and behaviour change, administrative support, quarterly newsletter), and tailored care plans for patients (motivational interviewing, goal identification, and target setting for lifestyle change) with reviews every four months at the practices. Control practices provided usual care.Main outcome measuresThe proportion of patients at 18 month follow-up above target levels for blood pressure and total cholesterol concentration, and those admitted to hospital, and changes in physical and mental health status (SF-12).ResultsAt baseline the numbers (proportions) of patients above the recommended limits were: systolic blood pressure greater than 140 mm Hg (305/899; 33.9%, 95% confidence interval 30.8% to 33.9%), diastolic blood pressure greater than 90 mm Hg (111/901; 12.3%, 10.2% to 14.5%), and total cholesterol concentration greater than 5 mmol/l (188/860; 20.8%, 19.1% to 24.6%). At the 18 month follow-up there were no significant differences between intervention and control groups in the numbers (proportions) of patients above the recommended limits: systolic blood pressure, intervention 98/360 (27.2%) v control, 133/405 (32.8%), odds ratio 1.51 (95% confidence interval 0.99 to 2.30; P=0.06); diastolic blood pressure, intervention 32/360 (8.9%) v control, 40/405 (9.9%), 1.40 (0.75 to 2.64; P=0.29); and total cholesterol concentration, intervention 52/342 (15.2%) v control, 64/391 (16.4%), 1.13 (0.63 to 2.03; P=0.65). The number of patients admitted to hospital over the 18 month study period significantly decreased in the intervention group compared with the control group: 107/415 (25.8%) v 148/435 (34.0%), 1.56 (1.53 to 2.60; P=0.03).ConclusionsAdmissions to hospital were significantly reduced after an intensive 18 month intervention to improve outcomes for patients with coronary heart disease, but no other clinical benefits were shown, possibly because of a ceiling effect related to improved management of the disease.

We report results from a study designed to explore the utility of artificial gravity (AG) as a countermeasure to bone loss induced by microgravity simulation. After baseline testing, 15 male subjects underwent 21 days of 6° head-down bed rest to simulate the deconditioning associated with spaceflight. Eight of the subjects underwent 1 h of centrifugation (AG; 1 Gzat the heart, 2.5 Gzat the feet) each day for 21 days, whereas seven of the subjects served as untreated controls (Con). Blood and urine were collected before, during, and after bed rest for bone marker determinations. Bone mineral density (BMD) and bone mineral content (BMC) were determined by dual-energy X-ray absorptiometry and peripheral quantitative computerized tomography before and after bed rest. Urinary excretion of bone resorption markers increased during bed rest, but the AG and Con groups did not differ significantly. The same was true for serum C-telopeptide. During bed rest, bone alkaline phosphatase (ALP) and total ALP tended to be lower in the AG group ( P = 0.08, P = 0.09). Neither BMC nor BMD changed significantly from the pre-bed rest period in AG or Con groups, and the two groups were not significantly different. However, when AG and Con data were combined, there was a significant ( P < 0.05) effect of time for whole body total BMC and total hip and trochanter BMD. These data failed to demonstrate efficacy of this AG prescription to prevent the changes in bone metabolism observed during 3 wk of bed rest.

In efficient agricultural systems high production and high quality is expected throughout the year, but spatial and seasonal variation of biophysical variables can have a significant impact on the yield and quality of production. The yield and quality component of a forage field was monitored using statistical and Geographical Information System (GIS) techniques. The display of yield and forage quality in a spatial context proved to be very useful to the farmer since it allowed him to determine where in the field he obtained the best and worst production and whether such performance was consistent over the entire growing season. GIS is considered a new management tool that allows the spatial evaluation and presentation of production information in a new and innovative manner. Examples are provided to assist farmers in production accounting, to determine cause and effect relationships between management and production, to forecast production and to modify management to account for differences within the field.

The ability of the egg parasitoid, Trichogramma minutum Riley, to suppress outbreak populations of the spruce budworm, Choristoneura fumiferana (Clemens), was studied annually near Hearst, Ont., from 1982 through 1986. Timing of broadcast parasitoid-releases was linked to spruce budworm moth emergence and oviposition. These phenological relationships were predicted from a regression based on larval development at least 2 weeks before expected emergence; this allowed sufficient time to regulate (program) parasitoid emergence during mass-rearing. Emergence of caged spruce budworm adults was used to monitor moth eclosion in the field. Pheromone traps provided daily information on the activity of male moths and helped to synchronize the parasitoid releases with spruce budworm oviposition. Information on parasitoid activity was obtained from sentinel (laboratory-reared) and naturally occurring spruce budworm egg masses. A curvilinear relationship between the rate of parasitoid release and parasitism of sentinel egg masses was developed. Two parasitoid releases, 1 week apart, early in the oviposition period of spruce budworm, significantly increased parasitism of host eggs by 14–83% and reduced larval populations correspondingly from 42 to 82%. Single releases were less effective and increased parasitism by 0.3–52% (single ground release, 1986). Two parasitoid releases, combined with a spring application of Bacillus thuringiensis Berliner to larval populations, was the most effective strategy and resulted in 83% egg parasitism and 93% larval reduction. Release rates greater than 12–16 × 106 ♀ ♀ T. minutum per hectare were not warranted based on impact and costs. The effects of release timing, weather, host density, and parasitoid quality on the future successful use of T. minutum are discussed.

Two systems for releasing the egg parasitoid, Trichogramma minutum Riley, from ground level in forest stands are described: (1) a gridded point-source release using parasitized host eggs attached to cards, and (2) a hand-held leafblower distributing parasitized eggs in bulk. Neither technique affected the emergence of the parasitoids released. Parasitoids emerging from eggs released in bulk had a similar sex ratio, longevity, and fecundity to those not released. Both methods of ground release achieved uniform parasitoid distribution and resulted in levels of parasitism similar to those achieved with aerial releases. Parasitism was greater in the mid- to upper canopy of trees than in the lower canopy. The difficulties associated with each technique and its comparative usefulness in experimental and operational programs are discussed.

Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed candidate multiplexed assays that may potentially be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the ability to improve our nation's capability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect food and agricultural resources with a diagnostic test which could enhance the nation's capabilities for early detection of a foreign animal disease. In FY2005 with funding from the DHS, LLNL developed the first version (Version 1.0) of a multiplexed (MUX) nucleic-acid-based RT-PCR assay that included signatures for foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases (FADs) of swine, Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease Virus (SVDV), and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus [BPSV], Orf of sheep, and Pseudocowpox). In FY06, LLNL has developed Bovine and Porcine species-specific panel which included existing signatures from Version 1.0 panel as well as new signatures. The MUX RT-PCR porcine assay for detection of FMDV includes the FADs, VESV and SVD in addition to vesicular stomatitis virus (VSV) and porcine reproductive and respiratory syndrome (PRRS). LLNL has also developed a MUX RT-PCR bovine assay for detection of FMDV with rule out tests for the two bovine FADs malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis virus (VSV), bovine viral diarrhea virus (BVDV), infectious bovine rhinotracheitus virus (BHV-1), bluetongue virus (BTV), and the Parapox viruses (which are of two bovine types) bovine papular stomatitis virus (BPSV) and psuedocowpox (PCP). A timeline for this development is presented in Table 1. The development of the Version 1.0 panel for FMDV rule-out and the most current efforts aimed to designed species specific panels has spanned over 2 1/2 years with multiple collaborative partnerships. This document provides a summary of the development, testing and performance data at OIE Stage 1 Feasibility into Stage 2 Assay Development and Standardization1 (see Table 2), gathered as of June 30th, 2007 for the porcine and bovine MUX assay panels. We present an overview of the identification and selection of candidate genetic signatures, the assay development process, and preliminary performance data for each of the individual signatures as characterized in the multiplexed format for the porcine and bovine panels. The Stage 1 Feasibility data of the multiplexed panels is presented in this report also includes relevant data acquired from the Version 1.0 panel as supporting information where appropriate. In contrast to last years effort, the development of the bovine and porcine panels is pending additional work to complete analytical characterization of FMDV, VESV, SVD, RPV and MCF. The signature screening process and final panel composition impacts this effort. The unique challenge presented this year was having strict predecessor limitations in completing characterization, where efforts at LLNL must precede efforts at PIADC, such challenges were alleviated in the 2006 reporting by having characterization data from the interlaboratory comparison and at Plum Island under AgDDAP project. We will present an addendum at a later date with additional data on the characterization of the porcine and bovine multiplex assays when that data is available. As a summary report, this document does not provide the details of signature generation, evaluation, and testing, nor does it provide specific methods and materials used. This information has been provided in the separate 488 page Supplementary Materials document.

In September 2004, the Nuclear Regulatory Commission (NRC) issued Generic Letter GL2004-02 “Potential Impact of Debris Blockage on Emergency Recirculation during Design Basis Accidents at Pressurized-Water Reactors” to address Generic Safety Issue 191 (GSI-191) “Assessment of debris accumulation on PWR sump performance.” [1] GL2004-02 requested pressurized water reactor (PWR) licensees to perform a “downstream effects” evaluation of their emergency core cooling (ECCS) and containment spray systems (CSS). GL2004-02 also gave guidance on what analysis had to be completed in order to resolve GSI-191. These evaluations included a wear and plugging assessment of all ECCS and CSS components, including valves. During preliminary “downstream effects” analysis of a plant, it was determined that the positions of ECCS throttle valves could be such that the flow clearances through the valves would be too small to meet the criteria developed for component plugging or wear assessment. This suggested that a modification to the system needs to be made which allows the throttle valves to be more fully opened. In order to allow the throttle valves to be opened more fully, additional hydraulic resistance (i.e. pressure drop at the design flow rate) was added at another location. Several orifice designs were considered to provide the needed resistance. Since the required additional pressure drop was a substantial fraction of the total pressure drop, special design features of the orifice were necessary to preclude system instabilities due to cavitation, degassing and flow swirl. The purpose of this paper is to present a method for assessing the effectiveness of a multi-stage orifice that can be placed in the system to provide the required resistance, thus permitting the throttle valves to be used more efficiently. The paper presents the design aspects of the multi-stage breakdown orifice, CFD modeling used to select the design, and the system condition testing results.Copyright © 2007 by ASME

Multilayered optical filters have been formed using layer-by-layer self-assembly processes. Unlike conventional vapor deposition coating techniques, molecular-level self-assembly is an aqueous solution-based process that is performed at room temperature and pressure. This allows the incorporation of a wider range of possible materials, including polymers, oxide and other nanoclusters, and other molecules. We review the general filter deposition method and give generalized results for nominal substrate materials.

During spaceflight, skeletal unloading results in loss of bone mineral density (BMD). This occurs primarily in the spine and lower body regions. This loss of skeletal mass could prove hazardous to astronauts on flights of long duration. In this study, intense resistance exercise was used to test whether a training regimen would prevent the loss of BMD that accompanies disuse. Nine subjects (5 men, 4 women) participated in a supine maximal resistance exercise training program during 17 wk of horizontal bed rest. These subjects were compared with 18 control subjects (13 men, 5 women) who followed the same bed rest protocol without exercise. Determination of treatment effect was based on measures of BMD, bone metabolism markers, and calcium balance obtained before, during, and after bed rest. Exercisers and controls had significantly ( P < 0.05) different means, represented by the respective following percent changes: lumbar spine BMD, +3% vs. −1%; total hip BMD, +1% vs. −3%; calcaneus BMD, +1% vs. −9%; pelvis BMD, −0.5% vs. −3%; total body BMD, 0% vs. −1%; bone-specific alkaline phosphatase, +64% vs. 0%; alkaline phosphatase, +31% vs. +5%; osteocalcin, +43% vs. +10%; 1,25 dihydroxyvitamin D, +12% vs. −15%; parathyroid hormone intact molecule, +18% vs. −25%; and serum and ionized calcium, −1% vs. +1%. The difference in net calcium balance was also significant (+21 mg/day vs. −199 mg/day, exercise vs. control). The gastrocnemius and soleus muscle volumes decreased significantly in the exercise group, but the loss was significantly less than observed in the control group. The results indicate that resistance exercise had a positive treatment effect and thus might be useful as a countermeasure to prevent the deleterious skeletal changes associated with long-duration spaceflight.

Background. Leptin, the protein product of the ob gene, is produced by the adipocyte and seems to function as a link between adiposity, satiety, and activity. Leptin has also been found to be necessary for pubertal development, conception, and pregnancy in mice, and is increased in prepubertal children, independent of adiposity, suggesting a role in childhood growth and development. This study investigated 100 mother/newborn pairs to determine the role of leptin in neonatal development. Placental tissue was assayed for leptin mRNA to evaluate it as a source of leptin production in utero. Methods. One hundred mother/newborn pairs were enrolled in this study. Radioimmunoassay was performed for leptin on maternal venous and newborn cord blood. Leptin concentrations were measured in 43 children in Tanner stages 1 and 2 as a control group. Placental tissue was obtained from five mothers and assayed for leptin mRNA by reverse transcription/polymerase chain reaction (RT/PCR). Human placental cell lines JAR and JEG-3 were also assayed for leptin mRNA expression. Results. Leptin was present in all newborns studied at a mean concentration of 8.8 ng/mL (±9.6 standard deviations). Leptin concentrations in cord blood correlated with newborn weight (r = .51), body mass index (BMI) (r = .48), and arm fat (r = .42). There was no correlation between leptin and insulin. When statistically covarying for adiposity for newborns and Tanner stages 1 and 2 children, newborns had greater concentrations of leptin (mean, 10.57 ng/mL) than children (mean, 3.04 ng/mL). Leptin was present in all mothers at a mean value of 28.8 ng/mL (±22.2 standard deviations). Leptin concentration correlated with prepregnancy BMI (r = .56), BMI at time of delivery (r = .74), and arm fat (r = .73). Maternal leptin correlated with serum insulin (r = .49). There was no correlation between maternal and newborn leptin concentrations. Thirteen percent of newborns had higher leptin concentrations than their mothers. Placental tissue from five separate placentas expressed leptin mRNA at comparable or greater levels than adipose tissue. Two human trophoblastic placental cell lines, JAR and JEG-3, also expressed leptin mRNA. Conclusions. The correlation between leptin and adiposity found in children and adults was also found in newborns. Serum leptin concentrations in newborns were increased more than three-fold compared with children in Tanner stages 1 and 2 when controlling for adiposity, suggesting that leptin concentrations in the newborn are not explained by adiposity alone. Maternal leptin concentrations correlated with measures of adiposity at delivery but did not correlate with newborn adiposity or leptin. Leptin mRNA was expressed both in placental tissue and in two human placental cell lines. These data suggest that leptin has a role in intrauterine and neonatal development and that the placenta provides a source of leptin for the growing fetus.

Oedaleus senegalensis (Krauss) (Acrididae: Oedipodinae) is a serious grasshopper pest in the Sahel. This species passes the dry season as eggs in the soil and emergence is triggered by the onset of rain in May/June Satellite imagery enables the monitoring of rainfall over much wider areas than those possible by ground-based observers. Although this has been investigated for some areas of the Sahel, any relationship between cloud temperature and the rainfall measured at the surface has never been quantified for Mali. Such rainfall information will lead to more effective identification of areas where grasshopper hatching may occur and enable ground control teams to target such areas more efficiently than at present. The results of a four-year field investigation into the use of satellite imagery to assess rainfall in Mali are presented, as well as the findings of an investigation into the influence of rainfall on eclosion. The effects of rain-gauge spacing for reliable point measurements of rainfall are discussed, and a possible relationship between cloud temperature and the amount of rain received at the surface is presented. Implications for improved pest control are summarised.

F oregut cysLs are uncommon anomalies that form during embryologic development. These cysts can result in respiratory symptoms in children but in adults are usually a.symptomatic and discovered incidentally. Malignant transformation is rare. To the authors’ knowledge. only two cases are reported in the literature [I, 21. We present a case of adenocarcinoma arising within a foregut cyst detected with positron emission tomography.

The large, low speed wind tunnel at NASA-Ames has been used to study the characteristics of lift-generated vortices involved in the definition of aircraft-separation criteria, in order to enhance airport capacity without compromising safety. Attention is given to the potential hazard caused by the vortex wake of several configurations of a subsonic transport. Measured downwash distributions in the wake of three different wake-generator configurations are obtained by means of a vortex-lattice method, in order to predict the lift and rolling moment on several models of wake-following aircraft.

The recent debate in the Emergency Medicine Journal about the clinical effects of infusion equipment dead space1 highlights the need for care and attention to detail when administering medication in accordance with the latest evidence for its use. Our paediatric analgesia protocols stated that for severe pain, opiate analgesia was to be used, preferably parenterally. The usage of intranasal diamorphine was common, but anecdotally the effects were not as great as expected given the research evidence. …

In addition to their traditional role in counseling about contraception and sterilization, psychiatrists are becoming increasingly involved in decisions surrounding in vitro fertilization, surrogate motherhood, and artificial insemination. The medical-legal and ethical ramifications of these issues are other significant areas involving the psychiatrist. Exploration of feelings and fears about reproduction can benefit from psychiatric involvement for successful outcomes.

The purpose of this study was to evaluate the ability of pulsed Doppler ultrasonography to predict brain blood flow by comparing measurements made in basal cerebral arteries using a pulsed Doppler system with measurements of brain blood flow using radioactive microspheres in lambs. We measured the instantaneous maximum velocity during peak systole and end diastole and the mean velocity over the pulse cycle in basal cerebral arteries, calculated Pourcelot's index of resistance and Gosling's pulsatility index, and used regression analysis to compare the pulsed Doppler measurements with brain blood flow measured with radioactive microspheres. Pulsed Doppler measurements of the peak systolic, end diastolic, and mean flow velocity in basal cerebral arteries were directly related to brain blood flow. In contrast, no linear relationship was detected between the resistance or pulsatility indices and brain blood flow measured by microspheres (p greater than 0.14). Prediction of brain blood flow for individual subjects lacks the quantitative precision necessary for use as a clinical tool. However, the direct relationship between brain blood flow and the peak systolic, end diastolic, and mean flow velocities in basal cerebral arteries supports the use of these measurements in clinical research for the qualitative assessment of change in brain blood flow.

An auctioneer is described in whom focal dystonia of the jaw developed as an occupational symptom, occurring solely and predictably when he commenced his selling ''patter'' and resolving quickly on stopping. He responded well to treatment with intramuscular botulinus toxin.

Ketamine hydrochloride alone was an effective analgesic in the Mongolian gerbil. In 28 young adult animals of both sexes (bodyweight 45-68 g) intramuscular injection of 44 mg/kg produced analgesia in about 83 seconds. Deep surgical anaesthesia could be readily achieved in about 12 min from start when methoxyflurane was administered by nasal cone 5 min after ketamine injection, and the surgical level was maintained arbitrarily for about 40 min during part of which laparotomy was performed. Induction of deep anaesthesia was smooth and recovery occurred uneventfully. The combination of ketamine and methoxyflurane allowed effective control of both the depth and duration of anaesthesia. Recovery time was about 77 min. Sex differences generally were slight.

Aztreonam was administered as a single, 2-g intravenous dose to 25 patients with noninflamed meninges and to 9 patients with inflamed meninges. It was well tolerated and was detected in the cerebrospinal fluid at the initial sampling period at 1 h after the end of infusion. Aztreonam levels in the cerebrospinal fluid of patients with inflamed meninges were four times higher than those recorded for the same time period in patients with noninflamed meninges. Aztreonam concentrations in cerebrospinal fluid in the presence of normal and inflamed meninges exceeded the inhibitory and bactericidal concentrations for most gram-negative bacteria. Thus, a multiple-dose treatment regimen with 2-g intravenous doses every 6 h appears to be appropriate for clinical trials of aztreonam for the treatment of gram-negative bacillary meningitis which is caused by susceptible organisms.

We have shown that a Ga1−xAlxAs/GaAs heterostructure can be used as a sensitive tunable detector of mm-wave/sub-mm-wave radiation. The mechanism for detection requires the application of a magnetic field varying from approximately 0.2T at 94GHz (3.2mm wavelength) to 6.2T at 2500GHz (119μm wavelength). The responsivity and N.E.P. at 3.2mm have been roughly estimated at 200V/W and 5×10−11W/✓Hz respectively. The speed of such a detector could be several orders of magnitude greater than comparable InSb detectors.

This study examined the influence of insects (mosquitoes and oestrids) on the distribution, microhabitat choice, and behavior of a population of mountain caribou. The study was conducted in the Burwash area of southwestern Yukon Territory during the summers of 1982 and 1983. Mosquito density, the presence or absence of oestrids, and the distribution, microhabitat use, and insect-avoidance behavior of the caribou were observed. Seasonal activity budgets for caribou were calculated. Mosquitoes became active in mid-June. Activity decreased with altitude, and at the highest altitudes (2000 m) the number of mosquitoes was negligible. Snow patches and exposed windy ridges had fewer mosquitoes than did open tundra. The oestrid season began in late June and lasted until early August. Oestrids were widespread throughout the study area and were present in all microhabitats. Caribou reduced harassment by mosquitoes by their altitudinal movements and use of microhabitat. Oestrids influenced activity budgets of caribou, acting to decrease feeding and resting time and to increase the time spent standing and moving.

Damage caused by Empoasca fabae (Harris) and Philaenus spumarius (L.), caged on second and third alfalfa harvests, was additive. Numbers of E. fabae were linearly correlated negatively with plant height, leaf area, and percentage protein, and positively with percentage chlorosis. Perceptible stunting and yellowing occurred with mean infestations per stem of 0.09 E. fabae and 0.6 P. spumarius nymphs. P. spumarius adults reduced plant height only at infestations of 0.3/stem, while 0.6 nymph/stem also reduced dry weight. E. fabae reduced protein at 0.11/stem and dry weight and leaf area at higher populations of 0.17/stem. None of these parameters was affected on subsequent regrowths. Lygus lineolaris (P. de B.) could not be maintained on pre-bloom alfalfa and was not considered a pest. Adelphocoris lineolatus (Goeze) reduced protein at levels of 0.01 bug/stem and dry weight at 0.06 bug/stem but results were confounded by high mortality. Field populations of all these species were reduced by the second cutting but redeveloped on the regrowth. Although applications of dimethoate (200 g AI/ha) and dimethoate (200 g AI/ha) plus endosulphan (280 g AI/ha) were effective in reducing populations of E. fabae, Acyrthosiphon pisum (Harris), A. lineolatus, and Hypera postica (Gyllenhal), insecticides were cost-effective on only one field. This field had 1.9 E. fabae/sweep and a 3% loss in protein resulted. Plant height, density, dry weight, protein content, and overwintering survival were not significantly affected at harvest in other fields. With the exception of E. fabae, the sum of the maximum field populations, each expressed as a fraction of its threshold, did not reach 50% of an economic threshold.

The yield in cultures of bone marrow aspirations or biopsies was determined in 50 patients with acquired immunodeficiency syndrome. Most patients were febrile and had no identifiable source of infection. Concurrent stool, urine, and blood samples were also cultured. The bone marrow aspiration and biopsy procedures produced no complications and enabled a microbiological diagnosis to be made in 42% of the cases. Granuloma formation was not seen in any of the infected bone marrow specimens despite the fact that mycobacteria were seen in abundance in some. Bone marrow culture is a valuable low-morbidity invasive procedure in the evaluation of febrile patients with acquired immunodeficiency syndrome.

We have shown that a Ga 1-x Al x As/GaAs heterostructure can be used as a sensitive tunable detector of mm-wave/submm-wave radiation. The mechanism for detection requires the application of a magnetic field varying from approximately 0.2T at 94GHz (3.2mm wavelength) to 6.2T at 2500GHz (119μm wavelength). The speed of such a detector could be several orders of magnitude greater than comparable InSb detectors.

The purpose of this project was to investigate the effects of high rates of dopamine infusion on cardiac output and regional blood flow in the lamb. We studied eight unanesthetized newborn lambs (mean age 7 +/- 2 days) during a 15-min baseline period and while infusing dopamine at 5-, 20-, 80-, and 160 micrograms/kg/min. We measured cardiac output and mean aortic, pulmonary arterial and left atrial pressures, and organ blood flow using radionuclide-labeled microspheres at each rate of dopamine infusion. Cardiac output increased significantly with increasing rates of infusion up to 80 micrograms/kg/min but decreased at 160 micrograms/kg/min. Aortic, pulmonary arterial, and left atrial pressures increased at rates of infusion above 5 micrograms/kg/min. Blood flow to all organs was unchanged at the 5 micrograms/kg/min rate of infusion of dopamine while blood flow to the brain and heart increased at the 80 micrograms/kg/min rate of infusion and blood flow to the gut and kidney decreased. We conclude that dopamine is an effective inotropic agent in the newborn lamb but that an inotropic:afterload mismatch exists at high infusion rates. Despite an increase in cardiac output at low rates of infusion, dopamine did not selectively vasodilate the vascular bed of any organs tested. Furthermore, at high rates of infusion dopamine actually impaired blood flow to the gut and kidney.

A simple procedure is described of catheterizing the left ventricle of the anaesthetized rat.

Thirty patients were treated for colonization or for skin and soft tissue infections caused by methicillin-resistant Staphylococcus aureus. Three treatment regimens were evaluated, each progressively more aggressive. Our regimen was 750 mg of ciprofloxacin twice daily for 5 days, the second regimen was 750 mg of ciprofloxacin twice daily for 10 to 14 days, and the final regimen was 750 mg of ciprofloxacin twice daily plus 300 mg of rifampin twice daily for 21 days. It appears that ciprofloxacin alone produced an initial eradication rate in at least one site in 50% of the patients, regardless of whether the treatment was for 5 or up to 14 days. All of the patients with eradication became recolonized within 1 week posttherapy. When rifampin was combined with ciprofloxacin, the eradication rate was 100% when the isolates were susceptible to both agents, and these patients remained free of methicillin-resistant S. aureus at 1-week and 1-month follow-ups.