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Toll-like receptors (TLR) are an evolutionarily-conserved family of pattern recognition receptors that are a key component of innate immune responses. To understand if leukocytes from tuatara (Sphenodon punctatus), an evolutionarily distinct reptile species, expressed TLR, we isolated blood leukocytes from tuatara and analysed their ability to respond to known TLR2, TLR3, TLR4, and TLR7/8 agonists. We found that all tuatara could respond to these agonists but that responses were significantly greater in leukocytes isolated in summer compared to winter. Additionally, these impaired innate responses correlated with a reduction in monocytes during winter. The finding that tuatara have impaired innate responses during winter has important implications for conservation and in particular, for the relocation of animals.

The authors describe lessons learned from a limited-duration experiential learning component of a Master’s level course. The course is open to Master’s in Business and Master’s in Public Administration students and explores the relationships between government and business. A complete discussion of the Master’s in Business and Master’s in Public Administration students is presented, with emphasis on advance planning and integration of a limited-duration field trip experience into the academic component of the course.

We compared the microbial community composition in soils from the Brazilian Amazon with two contrasting histories; anthrosols and their adjacent non-anthrosol soils of the same mineralogy. The anthrosols, also known as the Amazonian Dark Earths or terra preta, were managed by the indigenous pre-Colombian Indians between 500 and 8,700 years before present and are characterized by unusually high cation exchange capacity, phosphorus (P), and calcium (Ca) contents, and soil carbon pools that contain a high proportion of incompletely combusted biomass as biochar or black carbon (BC). We sampled paired anthrosol and unmodified soils from four locations in the Manaus, Brazil, region that differed in their current land use and soil type. Community DNA was extracted from sampled soils and characterized by use of denaturing gradient gel electrophoresis (DGGE) and terminal restriction fragment length polymorphism. DNA bands of interest from Bacteria and Archaea DGGE gels were cloned and sequenced. In cluster analyses of the DNA fingerprints, microbial communities from the anthrosols grouped together regardless of current land use or soil type and were distinct from those in their respective, paired adjacent soils. For the Archaea, the anthrosol communities diverged from the adjacent soils by over 90%. A greater overall richness was observed for Bacteria sequences as compared with those of the Archaea. Most of the sequences obtained were novel and matched those in databases at less than 98% similarity. Several sequences obtained only from the anthrosols grouped at 93% similarity with the Verrucomicrobia, a genus commonly found in rice paddies in the tropics. Sequences closely related to Proteobacteria and Cyanobacteria sp. were recovered only from adjacent soil samples. Sequences related to Pseudomonas, Acidobacteria, and Flexibacter sp. were recovered from both anthrosols and adjacent soils. The strong similarities among the microbial communities present in the anthrosols for both the Bacteria and Archaea suggests that the microbial community composition in these soils is controlled more strongly by their historical soil management than by soil type or current land use. The anthrosols had consistently higher concentrations of incompletely combusted organic black carbon material (BC), higher soil pH, and higher concentrations of P and Ca compared to their respective adjacent soils. Such characteristics may help to explain the longevity and distinctiveness of the anthrosols in the Amazonian landscape and guide us in recreating soils with sustained high fertility in otherwise nutrient-poor soils in modern times.

All existing transistors are based on the use of semiconductor junctions formed by introducing dopant atoms into the semiconductor material. As the distance between junctions in modern devices drops below 10 nm, extraordinarily high doping concentration gradients become necessary. Because of the laws of diffusion and the statistical nature of the distribution of the doping atoms, such junctions represent an increasingly difficult fabrication challenge for the semiconductor industry. Here, we propose and demonstrate a new type of transistor in which there are no junctions and no doping concentration gradients. These devices have full CMOS functionality and are made using silicon nanowires. They have near-ideal subthreshold slope, extremely low leakage currents, and less degradation of mobility with gate voltage and temperature than classical transistors.

We have assessed the utility of a single-copy nuclear locus and mitochondrial DNA (mtDNA) in a phylogeographic study of the New Zealand stick insect Niveaphasma annulata (Hutton). We amplified sequences from the mitochondrial cytochrome oxidase subunit I (COI) gene and the single-copy nuclear gene elongation factor-1alpha (EF1alpha) from 97 individuals. Allelic phase at the EF1alpha locus was determined using Denaturing Gradient Gel Electrophoresis. Phylogenetic analyses showed broad congruence between the geographic distribution of three major COI clades and EF1alpha alleles, which suggested that the phylogenetic patterns reflect population history rather than lineage sorting. However, the geographic boundaries of these clades were not always in exact agreement between the two loci. Our data indicate that Niveaphasma annulata was most likely separated into a number of refugia during Pleistocene glacial advances. Subsequent to glacial retreat these refugial populations have expanded and now form a number of zones of secondary contact. We contrast these patterns with those observed from other New Zealand taxa. Our study offers compelling evidence for the use of nuclear genes alongside mtDNA for future phylogeographic studies.

Liquid-crystalline compounds containing germanium atoms were synthesised and assessed for liquid-crystalline properties. These new compounds generally possess smectic C phases, and many also possess nematic, smectic A and higher order smectic phases. The germanium-containing liquid crystals were incorporated into smectic C mixtures. These mixtures tend to exhibit little change in smectic C* layer thickness over temperature. This characteristic is associated with de Vries smectic A materials, but measurements show that, although they have high smectic C stability, the materials' smectic cone angles are small. Measurement of smectic cone angle versus temperature of an exemplar material and its analogues containing carbon and silicon in place of the germanium, all show small cone angles which fall smoothly and extrapolate to zero as the smectic C* to smectic A transition is approached. These measurements largely explain the observed small layer changes and establish that the materials are not first-order de ...

A typical writing assignment in upper level required courses is a term paper. However many economics majors, particularly those in business schools, need to develop skill at writing shorter pieces. In this paper I describe numerous examples of shorter writing assignments that I have incorporated into an Intermediate Microeconomic Theory course. The assignments include such activities as comparison of competing theories; non-traditional applications of theory; book reviews; and explorations of the nuances of the standard consumer choice model. In addition to describing the details of the various assignments, the paper presents both student and instructor assessment of them.

Microbial community composition was examined in two soil types, Anthrosols and adjacent soils, sampled from three locations in the Brazilian Amazon. The Anthrosols, also known as Amazonian dark earths, are highly fertile soils that are a legacy of pre-Columbian settlement. Both Anthrosols and adjacent soils are derived from the same parent material and subject to the same environmental conditions, including rainfall and temperature; however, the Anthrosols contain high levels of charcoal-like black carbon from which they derive their dark color. The Anthrosols typically have higher cation exchange capacity, higher pH, and higher phosphorus and calcium contents. We used culture media prepared from soil extracts to isolate bacteria unique to the two soil types and then sequenced their 16S rRNA genes to determine their phylogenetic placement. Higher numbers of culturable bacteria, by over two orders of magnitude at the deepest sampling depths, were counted in the Anthrosols. Sequences of bacteria isolated on soil extract media yielded five possible new bacterial families. Also, a higher number of families in the bacteria were represented by isolates from the deeper soil depths in the Anthrosols. Higher bacterial populations and a greater diversity of isolates were found in all of the Anthrosols, to a depth of up to 1 m, compared to adjacent soils located within 50-500 m of their associated Anthrosols. Compared to standard culture media, soil extract media revealed diverse soil microbial populations adapted to the unique biochemistry and physiological ecology of these Anthrosols.

Prevention of bacterial colonization and consequent biofilm formation remains a major challenge in implantable medical devices. Implant-associated infections are not only a major cause of implant failures but also their conventional treatment with antibiotics brings further complications due to the escalation in multidrug resistance to a variety of bacterial species. Owing to their unique properties, antimicrobial peptides (AMPs) have gained significant attention as effective agents to combat colonization of microorganisms. These peptides have been shown to exhibit a wide spectrum of activities with specificity to a target cell while having a low tendency for developing bacterial resistance. Engineering biomaterial surfaces that feature AMP properties, therefore, offer a promising approach to prevent implant infections. Here, we engineered a chimeric peptide with bifunctionality that both forms a robust solid-surface coating while presenting antimicrobial property. The individual domains of the chimeric peptides were evaluated for their solid-binding kinetics to titanium substrate as well as for their antimicrobial properties in solution. The antimicrobial efficacy of the chimeric peptide on the implant material was evaluated in vitro against infection by a variety of bacteria, including Streptococcus mutans, Staphylococcus. epidermidis, and Escherichia coli, which are commonly found in oral and orthopedic implant related surgeries. Our results demonstrate significant improvement in reducing bacterial colonization onto titanium surfaces below the detectable limit. Engineered chimeric peptides with freely displayed antimicrobial domains could be a potential solution for developing infection-free surfaces by engineering implant interfaces with highly reduced bacterial colonization property.

The domain architecture of a large RNA can help explain and/or predict folding, function, biogenesis and evolution. We offer a formal and general definition of an RNA domain and use that definition to experimentally characterize the rRNA of the ribosomal small subunit. Here the rRNA comprising a domain is compact, with a self-contained system of molecular interactions. A given rRNA helix or stem-loop must be allocated uniquely to a single domain. Local changes such as mutations can give domain-wide effects. Helices within a domain have interdependent orientations, stabilities and interactions. With these criteria we identify a core domain (domain A) of small subunit rRNA. Domain A acts as a hub, linking the four peripheral domains and imposing orientational and positional restraints on the other domains. Experimental characterization of isolated domain A, and mutations and truncations of it, by methods including selective 2′OH acylation analyzed by primer extension and circular dichroism spectroscopy are consistent with our architectural model. The results support the utility of the concept of an RNA domain. Domain A, which exhibits structural similarity to tRNA, appears to be an essential core of the small ribosomal subunit.

Body composition assessment is an integral feature of elite sport as optimization facilitates successful performance. This study aims to refine the use of B-mode ultrasound in the assessment of athlete body composition by determining suitable sites for measurement. 67 elite athletes recruited from the Human Performance Laboratory, University College Cork, Ireland, underwent dual measurement of body composition. Subcutaneous adipose tissue thickness at 7 anatomical sites were measured using ultrasound and compared to percentage body fat values determined using Dual-Energy X-ray Absorptiometry. Multiple linear regressions were performed and an equation to predict percentage body fat was derived. The present study found subcutaneous adipose tissue depths at the triceps, biceps, anterior thigh and supraspinale sites correlated significantly with percentage body fat by X-ray absorptiometry (all p

Examination of cytochrome-b DNA sequences from specimens of Notiosorex crawfordi, the desert shrew, indicate that within this taxon there are at least 3 major subdivisions reflecting levels of variation more typical of species rather than subspecies. One of these cytochrome-b haplotypes was recently described as a previously unrecognized species; however, that paper was limited to the description of a species level name. We provide additional insight into subdivisions in N. crawfordi. One DNA haplotype is distributed in Texas, New Mexico, and eastern Arizona, a second haplotype in Arizona and Sonora, Mexico, and the third haplotype in Baja California, Mexico. Nucleotide sequences obtained from intron 7 of the nuclear gene, beta fibrinogen, support the conclusions that 2 of the haplotypes occur sympatrically in southeastern Arizona and are not hybridizing with each other.

A carbon budget was calculated for Tompkins County, NY, a semi-rural upstate county with a population density of 78 pp/km 2 . The costs and potential for several carbon mitigation options were analyzed in four categories: terrestrial C sequestration, local power generation, transportation, and energy end-use efficiency. This study outlines a methodology for conducting this type of local-scale analysis, including sources and calculations adaptable to different localities. Effective carbon mitigation strategies for this county based on costs/Mg C and maximum potential include reforestation of abandoned agricultural lands, biomass production for residential heating and co-firing in coal power plants, changes in personal behavior related to transportation (e.g., public transportation), installation of residential energy efficient products such as programmable thermostats or compact fluorescent light bulbs, and development of local wind power. The total county emissions are about 340 Gg C/year, with biomass sequestration rates of 121 Gg C/year. The potential for mitigation, assuming full market penetration, amounts to about 234 Gg C/year (69%), with 100 Gg C/year (29%) at no net cost to the consumer. The development of local-scale C mitigation plans based on this sort of model of analysis is feasible and would be useful for guiding investments in climate change prevention.

Black Carbon (BC) may significantly affect nutrient retention and play a key role in a wide range of biogeochemical processes in soils, especially for nutrient cycling. Anthrosols from the Brazilian Amazon (ages between 600 and 8700 yr BP) with high contents of biomassderived BC had greater potential cation exchange capacity (CEC measured at pH 7) per unit organic C than adjacent soils with low BC contents.Synchrotron-based near edge X-ray absorption fine structure (NEXAFS) spectroscopy coupled with scanning transmission X-ray microscopy (STXM) techniques explained the source of the higher surface charge of BC compared with non-BC by mapping crosssectional areas of BC particles with diameters of 10 to 50 mm for C forms. The largest cross-sectional areas consisted of highly aromatic or only slightly oxidized organic C most likely originating from the BC itself with a characteristic peak at 286.1 eV, which could not be found in humic substance extracts, bacteria or fungi. Oxidation significantly increased from the core of BC particles to their surfaces as shown by the ratio of carboxyl-C/aromatic-C. Spotted and non-continuous distribution patterns of highly oxidized C functional groups with distinctly different chemical signatures on BC particle surfaces (peak shift at 286.1 eV to a higher energy of 286.7 eV) indicated that non-BC may be adsorbed on the surfaces of BC particles creating highly oxidized surface. As a consequence of both oxidation of the BC particles themselves and adsorption of organic matter to BC surfaces, the charge density (potential CEC per unit surface area) was greater in BC-rich Anthrosols than adjacent soils. Additionally, a high specific surface area was attributable to the presence of BC, which may contribute to the high CEC found in soils that are rich in BC.

This paper examines the presence of spontaneous imitation within the social interactions of young people with developmental delay and their adult carers. There have been only a handful of observational studies examining imitation in this population, despite the relevance of such work to contemporary theoretical debates about imitation and the potential that imitation holds as an intervention for promoting communicative skills. The play of eight young people and 13 adult carers over 10 sessions at an after-school club was videotaped and analysed for the presence and impact of spontaneous imitative bouts. Results showed that, in the majority of cases, it was adults who initiated imitative bouts and that the young people generally did not reciprocate such acts. However, even such brief instances of adult imitation were sufficient to increase the children's subsequent smiles and speech vocalizations, as well as the adults' own use of smiling, eye contact, and speech vocalizations. These findings confirm that these young people are sensitive to imitation. The implications for designing interventions that promote communicative exchanges in young people with developmental delay are discussed. Copyright © 2006 John Wiley & Sons, Ltd.

Inter- and intra-specific variations in cytochrome b (Cytb) sequence were assessed in 22 specimens of Sorex palustris Richardson, 1828 and 6 specimens of Sorex bendirii (Merriam, 1884) from 20 locations in western North America. Phylogenetic analyses revealed three distinct clades: Boreal (S. p. palustris), Cordilleran (S. p. brooksi, S. p. navigator), and Coastal (S. b. palmeri, S. b. bendirii). Sequence divergence between the Boreal and the Coastal–Cordilleran lineages was 6.9%, while the divergence between the Coastal and the Cordilleran clades was 3.1%. Sorex palustris brooksi, a subspecies endemic to Vancouver Island, showed minor divergence from mainland samples of S. p. navigator. The results suggest that S. palustris may consist of two species: a boreal eastern form (S. palustris) and a Cordilleran form (S. navigator). The taxonomic validity of S. p. brooksi is unresolved. Distribution of the three clades are consistent with vicariance and isolation in coastal, Cordilleran, and eastern refugia in the Late Pliocene or Pleistocene. The Vancouver Island subspecies S. p. brooksi is probably derived from postglacial colonization in the Late Pleistocene.

Pichia caribbica sp. nov. (type strain DBVPG 4519, NRRL Y-27274, CBS 9966) is described as the ascosporic state of Candida fermentati, and Candida guilliermondii var. carpophila (type strain DBVPG 7739, NRRL Y-17905, CBS 5256) is elevated to species status as Candida carpophila comb. nov. These new taxa, which are indistinguishable on the basis of conventional taxonomic criteria, differ from one another and from Pichia guilliermondii by low DNA base sequence relatedness, different electrophoretic karyotypes, and nucleotide divergence in domains D1/D2 of 26S rDNA. Pichia caribbica produces one, rarely two, saturn-shaped ascospores in persistent asci. On the basis of molecular criteria, C. carpophila comb. nov., C. fukuyamaensis, and C. xestobii are conspecific, with the name C. carpophila having taxonomic priority.

To explore the community integration of individuals who had suffered a Traumatic Brain Injury (TBI) and compare this to members of the general public.An independent groups design explored differences in three groups' levels of community integration. These groups consisted of ten survivors of TBI, ten male and ten female controls and were measured using The Community Integration Measure (CIM). All participants were resident in Northern Ireland (NI). The brain injured participants were drawn from a Belfast-based social skills programme.Mann-Whitney U tests showed a statistically significant difference between female controls and brain-injured individuals (U = 26.50, N(1) = 10, N(2) = 10, p = 0.037, one-tailed).Females were more integrated into their communities than males, who were, in turn, more integrated than brain injured individuals. It would appear that brain injury survivors are doubly disadvantaged. Their gender (mainly male), and the injury itself, conspire to reduce their integration within the wider community.

Motor problems following stroke may be compounded by visual inattention. Limb Activation Training (LAT), originally developed for rehabilitation of unilateral visual neglect, may also contribute to...

Summary: Purpose: When seizures do not respond to medications, video-EEG monitoring is the best available diagnostic tool and is the principal activity of epilepsy centers. The purpose of this study was to analyze the eventual disposition of patients who undergo video-EEG monitoring at a typical referral epilepsy center. Methods: We reviewed the diagnoses and dispositions of all patients (adults and children) who underwent inpatient video-EEG monitoring (≥24 h) at our center (University of South Florida–Tampa General Hospital) over a 1-year period (2002). Results: In total, 251 inpatient video-EEG monitoring sessions were performed. Nonepileptic seizures were diagnosed in 75 (30%); 58 (23%) were found to be surgical candidates; seven were implanted with the vagus nerve stimulator. In 47 (19%) patients, seizures were recorded, and the diagnosis of epilepsy was confirmed and clarified (symptomatic/cryptogenic generalized epilepsy, seven; localization-related epilepsy, 35; idiopathic generalized epilepsy, five). Conclusions: The eventual outcome of video-EEG monitoring is diverse. The largest groups, as expected, are psychogenic nonepileptic seizures (30%), and surgery (23%).

To establish patients' perception of the effect of sport on rehabilitation.Single investigator telephone questionnaire survey.Spinal Cord Injuries Unit, Musgrave Park Hospital, Belfast, Northern Ireland, UK.A telephone questionnaire was administered to patients admitted over a 12-month period. Information on patient demographics, sports participation before and after injury and patients' perception of the impact of sports on rehabilitation was recorded.In all, 33 (84.6%) of the 39 patients could be contacted and all completed the questionnaire. Of the respondents 27 (81.8%) had a diagnosis of spinal cord injury. Six (18.2%) were female and 20 (60.6%) were below 45 years.A total of 15 (45.5%) patients previously participated in regular sporting activity. At least 24 (72.7%) tried one sport during admission. In all, 14 reported taking part in regular sporting activity after discharge, although 23 expressed a desire to do so. Of those 60% who had regularly exercised continued to do so and 27% of those who reported no regular sport, before injury, commenced regular active exercise. A general benefit of sporting activity was recognised by 78.8% and a rehabilitation benefit by 69.7%. Self-reported benefits included increase in fitness, quality of life, confidence and social contact.A high proportion of patients perceived sporting activity as beneficial. Patients exercising before injury were more likely to exercise after injury. All inpatients were introduced to sport by staff, emphasising the importance of this rehabilitation opportunity in planning in-patient care.

Structure-activity studies were performed on the alpha(1A)-adrenoceptor (AR) selective agonist N-[5-(1H-imidazol-4-yl)-5,6,7,8-tetrahydro-1-naphthalenyl]methanesulfonamide (4). Compounds were evaluated for binding activity at the alpha(1A), alpha(1b), alpha(1d), alpha(2a), and alpha(2B) subtypes. Functional activity in tissues containing the alpha(1A) (rabbit urethra), alpha(1B) (rat spleen), alpha(1D) (rat aorta), and alpha(2A) (rat prostatic vas deferens) was also evaluated. A dog in vivo model simultaneously measuring intraurethral pressure (IUP) and mean arterial pressure (MAP) was used to assess the uroselectivity of the compounds. Many of the compounds that were highly selective in vitro for the alpha(1A)-AR subtype were also more uroselective in vivo for increasing IUP over MAP than the nonselective alpha(1)-agonists phenylpropanolamine (PPA) (1) and ST-1059 (2, the active metabolite of midodrine), supporting the hypothesis that greater alpha(1A) selectivity would reduce cardiovascular side effects. However, the data also support a prominent role of the alpha(1A)-AR subtype in the control of MAP.

The morphometric oxygen diffusive conductance ( D p ) of the placenta provides a measure of the efficiency of oxygen transfer between the mother and the developing fetus. Any change in the D p may point towards possible adaptation in the light of altered oxygen transfer. Placentae from normal ( n =40) and small for gestational age SGA ( n =24) pregnancies were analysed using stereological techniques. Each placenta was uniform randomly sampled and tissue samples processed to wax infiltration and embedding using conventional histological preparatory methods. A combination of stereological techniques and physiological constants were used to estimate the partial conductances across the five major tissue compartments involved in oxygen transfer. There was a significant reduction in both fetal birthweight and placental weight in the SGA group when compared with controls. A decrease in both chorionic ( S cv ) and fetal capillary ( S fc ) surface area was also observed in SGA placentae when compared with controls ( P >0.001). Villous membrane harmonic thickness ( T vm ) was reduced in the SGA placentae (2.33 μm) when compared with controls (2.67 μm P =0.019). This resulted in a reduction in the minimum D p in SGA placentae when compared with controls ( P =0.023). Adjusting for fetal weight resulted in no difference in the specific diffusive conductance. Changes in T vm in SGA placentae combined with changes in basic surface areas were insufficient to maintain overall D p values comparable with control placentae.

The aim of present study was to characterize the in vitro and in vivo pharmacological effects of YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole), a soluble guanylate cyclase activator, on corpus cavernosal smooth muscle and penile erectile activity. YC-1 relaxed phenylephrine precontracted cavernosal smooth muscle (EC(50)=4.4 microM) and this effect was partially antagonized by 1H-[1,2,4]oxadiazole [4,3-a]quinoxalin-1-one (ODQ). ODQ is a selective soluble guanylate cyclase inhibitor that completely blocked the relaxation induced by sodium nitroprusside, suggesting that YC-1 binds to soluble guanylate cyclase at a different site from nitric oxide (NO). Both YC-1 and sodium nitroprusside, but not sildenafil (1-100 microM) caused concentration-dependent increases in cyclic GMP levels in cultured rabbit cavernosal smooth muscle cells and produced synergistic effects. Intraperitoneal administration of YC-1 (10 micromol/kg) evoked penile erection in rats with 70% incidence. More importantly, YC-1 was able to significantly augment the pro-erectile effects of a suboptimal dose of apomorphine. These results suggest that the soluble guanylate cyclase activator YC-1 increases cyclic GMP levels, leading to relaxation of cavernosal smooth muscle. These biochemical events may be related to the pro-erectile properties of YC-1 in vivo.

The society expects males and females to adopt, believe in, and fulfill specific gender roles and stereotypes that have been established. Generally, males are expected to be strong, independent, and athletic, whereas females are expected to be quiet, obedient, attractive and nurturers. Society demands compliance to the enforced gender order. When these gender norms are violated, it is common for labels to be given, questions to be asked, and people to be ridiculed. Over the past few centuries, gender roles of men and women have started to change greatly in our society, and especially in the world of sports. Also, female athletes are beginning to establish themselves in the sports world. With the change in gender roles in our society, many female athletes have started to view themselves in a different manner. Even though women athletes have become more prominent in society, many wonder how these women feel about the evolution of gender roles, and how they have affected the perceptions of women athletes. In recent years, there has been a significant shift from advocating for ‘gender equity in sport’ towards using ‘sport for gender equity and personal development’. DOI: 10.5901/jesr.2014.v4n7p25

BACKGROUND: In 2012, using a genome-wide association study (GWAS) of UCSF Adult Glioma Study patients and replication in patients from the Mayo Clinic, TCGA and GliomaSE, we showed that a SNP in SSBP2 on chromosome 5 was associated with survival of glioblastoma (GBM) patients who received standard of care (SOC). Since then we have examined 41 SNPs that were potentially associated with survival after glioma diagnosis based on our preliminary results or published results of others. METHODS: The data set consisted of 401 patients with grade 2 or grade 3 astrocytic, oligodendroglial, or mixed oligoastrocytic tumors and 339 GBM patients not included in the previous GWAS. RESULTS: The SSBP2 minor allele was again associated with poorer survival among GBM patients who received SOC, but interestingly with improved survival among Grade 2 and Grade 3 patients. SNPs in another region of chromosome 5 were associated with GBM survival irrespective of whether or not the patients had SOC. Several other SNPs were significantly (p < 0.05) associated with survival of GBM or lower grade glioma. The results are currently being replicated in a similar sized group of patients from the Mayo Clinic. CONCLUSIONS: Inherited germline variation may influence glioma survival. SECONDARY CATEGORY: n/a.

Purpose: We describe and compare the usefulness of 3 minimally invasive dog urethral function models to demonstrate the efficacy potential of α1 agonists for stress urinary incontinence. From this overall composite dataset the efficacy profiles of the α1A selective agonist A-61603 and the active metabolite of midodrine ST-1059 were specifically compared.Materials and Methods: Isoflurane anesthetized multiparous female beagle dogs were used in all studies. Intraurethral pressure was measured using a 7Fr balloon catheter. Profilometry was performed using an 8Fr Millar transducer catheter. Bladder pressure required to produce leakage in response to external abdominal ballottements of increasing intensity was measured using a 5Fr transurethral catheter. Agonist responses were measured before and after increasing cumulative intravenous doses of each compound in each test.Results: Agonist induced increases in maximal urethral closure and leak point pressure strongly correlated in linear fashion (R2 = 0.94), as ...

Background: The purpose of this study was to further delineate the outcome of arthroscopically assisted anterior cruciate ligament reconstruction in 125 patients who had previously been followed for two to five years. One of the original 125 patients was excluded from the present study because of insufficient follow-up, and an additional group of 101 patients was added. All 225 patients in the present study were followed for a minimum of six years. Methods: Patients were randomly assigned to reconstruction with a double-stranded semitendinosus-gracilis graft with use of a two‐incision technique (group I), reconstruction with a patellar ligament graft with use of a two‐incision technique (group II), or reconstruction with a patellar ligament graft with use of a single‐incision endoscopic technique (group III). The groups were compared with regard to the rate of graft failure, the amount of instability, knee strength, radiographic signs of degenerative changes, and functional outcome. Results: There was no significant difference among the three groups with regard to the rate of graft failure, the amount of knee instability, or the functional outcome. A normal or nearly normal functional outcome was recorded for 208 (92%) of the 225 patients. There were significant differences among the groups with regard to quadriceps muscle-strength deficits: group I had fewer patients with deficits than group III, and groups I and III both had fewer patients with deficits than group II (p = 0.04). There also were significant differences among the groups with regard to hamstring muscle-strength deficits: group III had fewer patients with deficits than group II, and group II had fewer patients with deficits than group I (p < 0.01). Twelve knees (16%) in group I, six knees (8%) in group II, and eight knees (11%) in group III showed radiographic evidence of progressive degenerative changes, but the differences among the three groups were not significant. Conclusion: Although 11.6% of the 225 knees had radiographic evidence of degenerative arthritis at a minimum of six years after arthroscopically assisted reconstruction of the anterior cruciate ligament, the choice of graft and the technique of reconstruction did not seem to affect the rate of development of these changes.

Acute pancreatitis is an uncommon cause of abdominal pain during pregnancy, and rarely progresses to the necrotizing from of the disease in this clinical setting. Hyperlipidemia is an infrequent cause of acute pancreatitis. Whereas only 100 cases of hyperlipidemia-induced necrotizing pancreatitis have been reported in the literature to date, all of the cases were mild in severity and responsive to conservative medical management. Herein we present a case of life-threatening necrotizing pancreatitis, which developed in a hyperlipidemic pregnant woman and required multiple peripartum pancreatic necrosectomies. Additionally, we review the evaluation of pregnant patients with abdominal pain, the pathophysiology of hyperlipidemia-induced necrotizing pancreatitis, and the operative care of this challenging group of patients, revisiting an innovative technique for management of the retroperitoneum.

A growing interest in the development of high aspect ratio photoresists for micromachining microsystems (MST) products has resulted in the availability of a number of commercially available photoresist products. This paper describes in detail the applications of three such resists, namely EPON SU-8, Clariant AZ 4562 and the Shipley electroplated photoresist ED2100. Applications such as etch hard masks, micromoulds, severe topography coatings for metal interconnects and photoplastic mouldings are discussed, and novel examples are presented of where these resists are currently used in both telecomm and microfluidic markets. In particular, the versatility of the photoplastic negative resist EPON SU-8, which is used in a number of MST prototypes, is demonstrated. Future trends in resist technologies for MST are discussed.

Examining the impact of test type in Principles of Macroeconomics via two-stage estimation of an education production function, I find that students do better on a post–course TUCE when they take multiple choice exams throughout the semester instead of taking essay exams. The type of test, however, does not impact the student's attitude toward economics or the decision to complete the course.

Summary Early diagnosis of malaria followed by appropriate treatment can help reduce related morbidity and mortality as well as interrupt transmission. Previous studies of household responses to malaria have tended to focus on endemic areas where the burden of this disease is greatest. With the apparent increasing frequency of epidemics in African highlands, a better understanding of treatment behaviours in areas of unstable transmission may be important to future public health interventions. This study was undertaken following a serious epidemic of malaria in the highlands of south-western Uganda. Our objectives were to characterize actions taken by both adults and caretakers of children ≤5 years old during their most recent episode of self-diagnosed malaria, and to identify factors that were associated with prompt treatment at a health facility. A survey of 300 households selected in a 2-stage cluster sampling procedure produced 453 adult respondents and 133 caretakers of children ≤5 years old. We found that almost 65% of adults and 62% of children who had experienced an episode of malaria in the last year (most during the epidemic) had sought treatment from a health facility first as opposed to self-treatment. Most of these people had visited the health facility within 1 day of symptom onset. By the end of their malaria episode, over 87% of adults and 80% of children had visited a health facility at least once. Factors associated with prompt presentation at a health facility included severity of illness, household proximity to a health facility, and knowledge of malaria prevention methods. Our results indicate that there is an important role for the formal health care system in mitigating morbidity and mortality and reducing transmission during malaria epidemics in Uganda.

Given the genetically heterogeneous nature of many dominantly inherited disorders, it will be imperative to design mutation-independent therapeutic strategies to circumvent such heterogeneity. Intragenic polymorphism represents a genomic resource that may be harnessed in the development of allele-specific mutation-independent therapeutics. A hammerhead ribozyme, Rzpol1a1, selectively cleaves a common single-nucleotide polymorphism (SNP) of the human COL1A1 transcript (heterozygosity frequency of 2 pq = 0.4032, from Hardy-Weinberg equilibrium). One SNP variant contains a hammerhead ribozyme cleavage site, and the other does not. Kinetic evaluation shows Rzpol1a1 to be both specific and extremely efficient in vitro. Thus, a single efficient ribozyme has been characterized that should be valuable in the development of a gene therapy suitable for up to 1 in 5 dominant-negative osteogenesis imperfecta (OI) patients, where over 150 different mutations have been identified to date. Given the increasing characterization of intragenic SNP, it is predicted that such a mutation-independent strategy, based on selective silencing of mutant alleles at SNP, may become increasingly important in future genomics-driven drug development for many heterogeneous dominant disorders and complex traits.

Background: The purpose of this study was to evaluate the results of an arthroscopic transglenoid suture-stabilization procedure in athletically active patients who had recurrent, unilateral, unidirectional anterior dislocations of the shoulder and an isolated anterior detachment of the glenoid labrum. Methods: Forty-one patients who had unilateral, unidirectional anterior dislocations of the shoulder and an isolated anterior detachment of the glenoid labrum were managed with arthroscopic repair. All patients were athletic, and seventeen of the male patients were football players. No patient had inferior or posterior laxity or a posterior detachment. The sutures were anchored to the posterior aspect of the scapula, and the knots were tied anteriorly to secure the detached region of the labrum and the inferior glenohumeral ligament to the anterior aspect of the scapula. The mean duration of follow-up was fifty-two months (range, twenty-five months to seven years). The patients were evaluated annually with a physical examination, radiographs, isokinetic strength-testing, the modified shoulder-rating scale of Rowe and Zarins, and the scoring system of the American Shoulder and Elbow Surgeons. Results: Forty (98 percent) of the forty-one athletes returned to their preoperative sport postoperatively. Thirty-nine patients (95 percent) had no additional dislocations or subluxations, and two (5 percent), both of whom were football players, had a single episode of subluxation. Thirty-seven patients (90 percent) had a score of at least 80 points on the scale of Rowe and Zarins, and thirty-four (83 percent) had a score of at least 90 points. Thirty-nine patients (95 percent) had a score of at least 80 points on the scale of the American Shoulder and Elbow Surgeons, and twenty-five (61 percent) had a score of at least 90 points. Lower scores were associated with loose bodies seen on arthroscopy (p = 0.001), osseous lesions seen on postoperative radiographs (p = 0.036), and subluxation (p = 0.000). Twenty-two shoulders (54 percent) had a full range of motion in all planes, and eighteen (44 percent) had no strength deficit in any position on isokinetic testing. With the numbers available for study, no significant association was found between the presence of a Hill-Sachs or an osseous Bankart lesion on preoperative radiographs and the overall score on the scale of Rowe and Zarins or the scale of the American Shoulder and Elbow Surgeons; however, there was a significant association between the range of motion and an osseous Bankart lesion on preoperative radiographs (p = 0.002) and between decreased strength on isokinetic testing and a Hill-Sachs lesion on preoperative radiographs and an osseous lesion on postoperative radiographs (p = 0.022). There also was a significant association between a decreased range of motion (p < 0.002) and decreased strength (p = 0.014) and the arthroscopic finding of loose bodies. Muscle strength also was affected by arm dominance and the number of preoperative dislocations. Conclusions: Arthroscopic transglenoid repair of isolated anterior labral detachments restored stability of the shoulder and led to a favorable outcome in thirty-nine (95 percent) of the forty-one athletes. Only the two football players who had postoperative subluxation had a score of less than 80 points according to the scale of the American Shoulder and Elbow Surgeons.

CONTEXT AND QUESTION ASKED: In patients with metastatic cancer, chemotherapy may provide symptom control, prevent complications, prolong life, or improve quality of life. Except in rare cases, however, patients with metastatic disease will not be cured. In older patients with metastatic cancer, hospitalization for treatment toxicity may reduce the quality of an already limited life expectancy. We evaluated the association between chemotherapy for metastatic cancer and risk of hospitalization. MAIN CONCLUSION: Hospitalizations are common in patients with incurable advanced malignancies and are more likely among those who receive chemotherapy. APPROACH: In the linked SEER-Medicare dataset, we identified Medicare beneficiaries aged 66 years or older with a primary diagnosis of metastatic breast, colorectal, ovarian, bladder, lung, pancreas, esophageal, stomach, or prostate cancer between 2001 and 2009 who died by the end of 2010. Chemotherapy recipients and nonrecipients were pair-matched by age, sex, race, comorbidity, geographic region and survival duration. The primary endpoint was hospital admission, identified in inpatient claims between cancer diagnosis and the first of hospice admission or death. We also identified the subset of admissions associated with a primary or secondary diagnosis code suggestive of an adverse effect of chemotherapy. The association between chemotherapy and hospitalization was estimated in separate multivariable Cox proportional-hazards regression models for each cancer site, accounting for the matched-pairs design and controlling for unmatched demographic and disease characteristics. RESULTS: Of 18,486 patients who received chemotherapy for metastatic cancer, 92% were hospitalized at least once for any reason, including 51% hospitalized for a likely toxicity. The corresponding rates among matched non-recipients were 83% and 34% (Figure). In nearly all cancers, chemotherapy recipients had a greater risk of hospitalization for a likely toxicity or for any cause. Chemotherapy recipients had substantially higher hospitalization for infection or fever (21% v 15%), hematologic complications (11% v 3%), dehydration (13% v 6%), and PE or DVT (9% v 4%) compared with nonrecepients. Chemotherapy was associated with a significantly increased risk of likely toxicity-related hospitalization in nearly all cancers, controlling for sociodemographic characteristics and other treatment. The association was greatest in patients with metastatic esophageal cancer (adjusted hazard ratio, 2.00; 95% CI, 1.11 to 3.60) and smallest in patients with metastatic prostate cancer (adjusted hazard ratio, 1.22; 95% CI, 1.01 to 1.47). INTERPRETATION: Older patients receiving chemotherapy for incurable advanced cancers are at high risk of hospitalization, of which a non-negligible proportion is likely attributable to adverse effects of treatment. Infection, fever, dehydration, and hematologic complications constitute a large proportion of these events, some of which may be preventable through evidence-based patient management, prophylactic interventions, and effective outpatient care. Our findings might be limited to older patients with advanced cancer who have a generally poor prognosis or limited expected survival. SIGNIFICANCE OF FINDINGS: Understanding the common reasons for hospital admissions and developing toxicity management programs and educational resources may help patients and their families make informed treatment decisions, minimize adverse effects and reduce hospitalizations in this population with limited life expectancy. [Figure: see text]

The color, density and porosity of apple cubes dried in air and modified atmospheres were measured to identify the potential of modified atmosphere drying for foods. The modified atmospheres were achieved by flushing nitrogen gas through a specially designed laboratory dryer. The drying temperature was varied from 17 to 75°C. The results indicated that dried apple cubes with no browning could be produced under low oxygen atmospheres. Thus, chemical additives, such as sulfur dioxide can be completely eliminated from the process. The temperature and oxygen levels in the drying atmosphere were important factors in achieving the best quality in terms of color. Apple cubes dried in low oxygen atmospheres gave more porous products than those dried in air. Moreover, apple cubes dried in a nitrogen atmosphere had the greater number of open pore structures connected to the the exterior surface of the cubes.

Injections of quinolinic acid (60, 180, and 600 nmol) in the dorsal hippocampus induced significant neurotoxicity that was evident 1 day after the injection. By day 3, pyramidal as well as granular cells were affected even at the lowest dose of quinolinic acid, an effect that persisted up to 20 days. Consistent with the histological findings, animals with bilateral injections in the dorsal hippocampus were cognitively impaired during acquisition and retention of spatial information in the water maze. A subacute treatment with (-)-nicotine (62 micromol/kg/day) delivered by subcutaneous minipumps prevented the histological and cognitive deficits induced by the bilateral quinolinic acid (60 nmol) injections. These data indicate that quinolinic acid can induce degeneration of both pyramidal as well as granule cells in the hippocampus, leading to cognitive impairments in the rat, and that activation of neuronal nicotinic acetylcholine receptors can prevent the neurodegenerative process induced by quinolinic acid.

Background.Histoplasma capsulatumis the most common endemic mycosis in the United States and is a frequent cause of opportunistic infection in immunodeficient hosts. Histoplasmosis is most often self-limiting and goes unrecognized in the immunocompetent population but can progress to disseminated histoplasmosis in patients with an impaired immune system. Liver involvement as a part of disseminated histoplasmosis which usually originates in the lung is well known. However, extrapulmonary hepatic histoplasmosis as a primary manifestation is extremely rare.Case Presentation. We report a rare case of histoplasmosis that presented as persistent fever and abnormal liver function tests in a 66-year-old female with rheumatoid arthritis, receiving infliximab.Conclusion. Emphasizing histoplasmosis as a major cause of acute granulomatous hepatitis and fever of unknown origin in cell mediated immunodeficient population, this case highlights the need for high index of suspicion and the importance of prompt diagnosis since any delay of treatment can be life threatening in this population.

A prospective, randomized study was performed to compare the results of arthroscopic lateral retinacular release (Group I) with those of open lateral retinacular lengthening (Group II). The study included eighty-six patients (eighty-six knees) who had had pain in the anterior peripatellar aspect of the knee and lateral patellar tilting (rotational malalignment), as seen on Merchant tangential patellofemoral radiographs, that had not improved after participation in a structured rehabilitation program for the quadriceps and the hamstrings for a minimum of six months. The mean duration of follow-up after the operative procedures was forty-six months (range, two to six years). At the time of the latest follow-up evaluation, forty (93 per cent) of the forty-three patients in Group I and all forty-three (100 per cent) of the patients in Group II had resumed the level of athletic activity that they had engaged in before the onset of symptoms (p = 0.08, analysis of variance). With the numbers available for study, no significant difference could be detected between the groups with regard to deficits in the range of motion, atrophy (the circumference) of the thigh, operative or postoperative complications, or the need for subsequent operative procedures. Additionally, no significant difference could be detected between the groups with regard to the results of open or closed-chain testing with an isokinetic dynamometer. According to the knee-rating system of Lysholm and Gillquist as modified by Tegner and Lysholm, thirty-three knees (77 per cent) in Group I had a score of 80 points or more compared with thirty-eight knees (88 per cent) in Group II. Six knees (14 per cent) in Group I had a score of less than 70 points compared with no knees in Group II. The difference in the knee ratings between the two groups was significant (p = 0.028, analysis of variance). Although there seemed to be a definite trend toward improved function of the knee in association with a longer duration of follow-up, no significant association could be detected between the duration of follow-up and improvement in the outcome measures in either group.

ABT-089 [2-methyl-3-(2-(S)-pyrrolidinylmethoxy) pyridine dihydrochloride] is a novel cholinergic channel modulator (ChCM) with cognitive-enhancing and neuroprotective activities. Experiments were conducted to determine the discriminative stimulus properties of ABT-089 in comparison with (–)-nicotine. While rats were able to discriminate (–)-nicotine (1.9 μmol/kg s.c.) from saline in 43 ± 1.9 days, they were not able to discriminate ABT-089 (19 or 62 μmol/kg s.c.) from a saline solution after 64 days of training. In rats trained to discriminate 1.9 μmol/kg (–)-nicotine from saline, ABT-089 induced a reduced maximal generalization (up to 52% with 6.2–190 μmol/kg, s.c.) and was 100 times less potent than (–)-nicotine to induce the cue. A-94224.3, the R-enantiomer of ABT-089, induced a saline response at 62 μmol/kg in nicotine-trained rats. The effects of (–)-nicotine and ABT-089 were completely blocked by the cholinergic channel blocker, mecamylamine (15 μmol/kg). Consistent with its oral bioavailability, ABT-089 exhibited comparable effects in (–)-nicotine-trained rats after oral administration. Electrophysiological studies in dopamine-containing neurons in the ventral tegmental area indicate that ABT-089 is a weak partial agonist that can also block the excitatory actions of (–)-nicotine. The low intrinsic efficacy of ABT-089 to cross-generalize with (–)-nicotine is consistent with the minimal activity of the compound at the ganglia-like α3 subtype. Drug Dev. Res. 40:259–266, 1997. © 1997 Wiley-Liss, Inc.

Objective: To compare the acceptability, compliance, and effectiveness of two forms of cholestyramine resin in the treatment of hypercholesterolemia in children. Study design: Patients aged 10 to 18 years with familial hypercholesterolemia were enrolled in a randomized, crossover trial of two 8-week periods of either a pill or powder form of cholestyramine at a dose of 8 gm/day. Results: Of 40 children enrolled, 38 completed both medication periods, with a median age of 13 years (range, 10 to 18). At the end of the study, 82% preferred the pill form, 16% the powder form and 2% neither form. Mean (±SD) compliance as assessed by the amount of medication taken was significantly greater for pills (61% ± 31%) than powder (50% ± 30%, p = 0.01). The form of the medication increased compliance by at least 25% for 16 patients (42%), 13 in favor of pills and 3 in favor of powder. Compliance was not associated with patient attitudes and perceptions of hypercholesterolemia, demographics, family history, previous experience with lipid-lowering medication, or lipid profile parameters. Significant mean reductions in low-density lipoprotein cholesterol concentrations were noted for both pills (−10% ± 20%, p = 0.006) and powder (−15% ± 17%, p = 0.0001), with no significant difference between forms ( p = 0.16). Conclusions: A change in bile acid–binding resin formulation from powder to pills significantly increases acceptability and compliance in some children with hypercholesterolemia. (J Pediatr 1997;130:266-73)

William Gill (1854-1943) was a respected and prolific scene-painter based in Halifax and Boston. Of his many works, only one known example remains--an Italianate Garden Scene sitting in a small theatre in Musquodoboit, Nova Scotia. This feature briefly outlines the career of a neglected Canadian artist, and provides for the journal's readers the images of his damaged, deteriorating, but still evocative legacy of scene design in Canada. William Gill (1854-1943) etait un peintre de decors respecte et prolifique dont la vie se partageait entre Halifax et Boston. De ces nombreuses oeuvres, une seule reste – une scene de jardin italienne qui demeure dans un petit theâtre a Musquodoboit, Nouvelle-Ecosse. Cette chronique passe brievement en revue la carriere d’un artiste canadien neglige, et fournit aux lecteurs de cette revue des images d’un heritage endommage, mais toujours evocateur, de la peinture de scene au Canada.