A sex-influenced modifier in Drosophila that affects a broad spectrum of target loci including the histone repeats.
A second chromosomal trans-acting modifier, Lightener of white (Low), modulates the phenotypic expression of various alleles of the white eye color gene. This modifier has an unusually broad spectrum of affected genes including white, brown, scarlet and the eye developmental genes, Bar and Lobe. In addition, Low weakly suppresses position effect variegation. Northern blot hybridization with different X and autosomal probes reveals that Low modulates genes of independent expression patterns. Interestingly, many of the modulations of gene expression are developmentally restricted and differ in intensity between the sexes. Low also elevates the expression of the histone tandem repeats in three distinct developmental stages. A deficiency encompassing the histone cluster reduces their transcript levels and significantly alters the expression of some of the tested genes. Thus, Low is a modifier that plays a role in modulating the expression of genes governing various processes including pigment deposition, eye development, chromosomal proteins and position effect variegation.


Uneven adaptive capacity among fishers in a sea of change.
Fishers worldwide operate in an environment of uncertainty and constant change. Their ability to manage risk associated with such uncertainty and subsequently adapt to change is largely a function of individual circumstances, including their access to different fisheries. However, explicit attention to the heterogeneity of fishers' connections to fisheries at the level of the individual has been largely ignored. We illustrate the ubiquitous nature of these connections by constructing a typology of commercial fishers in the state of Maine based on the different fisheries that fishers rely on to sustain their livelihoods and find that there are over 600 combinations. We evaluate the adaptive potential of each strategy, using a set of attributes identified by fisheries experts in the state, and find that only 12% of fishers can be classified as being well positioned to adapt in the face of changing socioeconomic and ecological conditions. Sensitivity to the uneven and heterogeneous capacity of fishers to manage risk and adapt to change is critical to devising effective management strategies that broadly support fishers. This will require greater attention to the social-ecological connectivity of fishers across different jurisdictions.


Fate of Cry1Ab protein in agricultural systems under slurry management of cows fed genetically modified maize (Zea mays L.) MON810: a quantitative assessment.
The objective of the study was to track the fate of recombinant Cry1Ab protein in a liquid manure field trial when feeding GM maize MON810 to dairy cows. A validated ELISA was applied for quantification of Cry1Ab in the agricultural chain from GM maize plants, feed, liquid manure and soil to crops grown on manured fields. Starting with 23.7 μg of Cry1Ab g(-1) dry weight GM maize material, a rapid decline of Cry1Ab levels was observed as 2.6% and 0.9% of Cry1Ab from the GM plant were detected in feed and liquid manure, respectively. Half of this residual Cry1Ab persisted during slurry storage for 25 weeks. After application to experimental fields, final degradation of Cry1Ab to below detectable levels in soil was reported. Cry1Ab exhibited a higher rate of degradation compared to total protein in the agricultural processes. Immunoblotting revealed a degradation of the 65 kDa Cry1Ab into immunoreactive fragments of lower size in all analyzed materials.


Efficient nuclear localization of the Ad5 E1A 12S protein is necessary for immortalization but not cotransformation of primary epithelial cells.
The Ad5 E1A 12S gene encodes a nuclear protein that can immortalize and cooperate with other oncoproteins to transform primary epithelial cells. Expression of the first exon is necessary for the activation of cellular proliferation, immortalization, and transformation. The second exon is necessary for the maintenance of cellular proliferation, immortalization, and the induction of an epithelial cell growth factor but is dispensable for cotransformation with T24 ras. Expression of the second exon is also necessary for efficient nuclear localization of the 12S polypeptide. A five-amino acid nuclear localization signal (NLS), Lys-Arg-Pro-Arg-Pro is encoded by the last 15 nucleotides of the second exon. To determine the role of subcellular localization in immortalization and transformation, a mutational analysis of the second exon and the 12S NLS was undertaken. The results from our analysis indicate that regions of the second exon outside the NLS affect nuclear localization. These regions necessary for efficient nuclear localization of the 12S protein are coincident with regions necessary for immortalization. In contrast, these regions are dispensable for cotransformation with T24 ras. The importance of the positively charged amino acids of the NLS in signal function and immortalization is varied. Lys 239 is the most critical residue, followed by Arg 240 and Arg 242, respectively. These data indicate that efficient nuclear localization of 12S is necessary for immortalization but not cotransformation with T24 ras.


Heterogeneity of smooth muscle myosin heavy chain expression at the single cell level.
Expression of the smooth muscle myosin heavy chain (SM-MHC) isoforms was examined in individual rabbit arterial smooth muscle cells with the use of reverse transcription-polymerase chain reactions (RT-PCR). The RT-PCR amplification protocol used oligonucleotide primers complementary to regions that flank the alternative exon that encodes the nine unique amino acids found in the carboxy terminal domain of SM2. RT-PCR products of SM1 and SM2 mRNA differ in length and electrophoretic mobility. Partial DNA sequencing of the PCR products confirmed SM1 and SM2 identity. Densitometric analyses of adjacent samples extracted from the same tissues and processed for SM2-to-SM1 protein and PCR-amplified SM2-to-SM1 RNA ratios exhibited a high correlation (R = 0.92). RT-PCR-amplified SM2-to-SM1 mRNA ratios of individual adult rabbit arterial cells ranged from 0.0 to 1.8 (n = 59), whereas multicellular vascular samples varied much less (0.4-0.6, n = 5). These results indicate that individual cells within a blood vessel differ significantly in SM-MHC expression. This difference may be important for the regulation of contraction in these vessels.


Norway maple displays greater seasonal growth and phenotypic plasticity to light than native sugar maple.
Norway maple (Acer platanoides L), which is among the most invasive tree species in forests of eastern North America, is associated with reduced regeneration of the related native species, sugar maple (Acer saccharum Marsh) and other native flora. To identify traits conferring an advantage to Norway maple, we grew both species through an entire growing season under simulated light regimes mimicking a closed forest understorey vs. a canopy disturbance (gap). Dynamic shade-houses providing a succession of high-intensity direct-light events between longer periods of low, diffuse light were used to simulate the light regimes. We assessed seedling height growth three times in the season, as well as stem diameter, maximum photosynthetic capacity, biomass allocation above- and below-ground, seasonal phenology and phenotypic plasticity. Given the north European provenance of Norway maple, we also investigated the possibility that its growth in North America might be increased by delayed fall senescence. We found that Norway maple had significantly greater photosynthetic capacity in both light regimes and grew larger in stem diameter than sugar maple. The differences in below- and above-ground biomass, stem diameter, height and maximum photosynthesis were especially important in the simulated gap where Norway maple continued extension growth during the late fall. In the gap regime sugar maple had a significantly higher root : shoot ratio that could confer an advantage in the deepest shade of closed understorey and under water stress or browsing pressure. Norway maple is especially invasive following canopy disturbance where the opposite (low root : shoot ratio) could confer a competitive advantage. Considering the effects of global change in extending the potential growing season, we anticipate that the invasiveness of Norway maple will increase in the future.


Lidar measurements taken with a large-aperture liquid mirror. 2. Sodium resonance-fluorescence system.
Sodium resonance-fluorescence lidar is an established technique for measuring atmospheric composition and dynamics in the mesopause region. A large-power-aperture product (6.6-W m(2)) sodium resonance-fluorescence lidar has been built as a part of the Purple Crow Lidar (PCL) at The University of Western Ontario. This sodium resonance-fluorescence lidar measures, with high optical efficiency, both sodium density and temperature profiles in the 83-100-km region. The sodium lidar operates simultaneously with a powerful Rayleigh- and Raman-scatter lidar (66 W m(2)). The PCL is thus capable of simultaneous measurement of temperature from the tropopause to the lower thermosphere. The sodium resonance-fluorescence lidar is shown to be able to measure temperature to an absolute precision of 1.5 K and a statistical accuracy of 1 K with a spatial-temporal resolution of 72 (km s) at an altitude of 92 km. We present results from three nights of measurements taken with the sodium lidar and compare these with coincident Rayleigh-scatter lidar measurements. These measurements show significant differences between the temperature profiles derived by the two techniques, which we attribute to variations in the ratio of molecular nitrogen to molecular oxygen that are not accounted for in the standard Rayleigh-scatter temperature analysis.


Oral receptivity of Aedes aegypti from Cape Verde for yellow fever, dengue, and chikungunya viruses.
At the end of 2009, 21,313 cases of dengue-3 virus (DENV-3) were reported in the islands of Cape Verde, an archipelago located in the Atlantic Ocean 570 km from the coast of western Africa. It was the first dengue outbreak ever reported in Cape Verde. Mosquitoes collected in July 2010 in the city of Praia, on the island of Santiago, were identified morphologically as Aedes aegypti formosus. Using experimental oral infections, we found that this vector showed a moderate ability to transmit the epidemic dengue-3 virus, but was highly susceptible to chikungunya and yellow fever viruses.


The kinase domain of CK1δ can be phosphorylated by Chk1.
Members of the casein kinase 1 (CK1) family are key regulators in numerous cellular signal transduction pathways and in order to prevent the development of certain diseases, CK1 kinase activity needs to be tightly regulated. Modulation of kinase activity by site-specific phosphorylation within the C-terminal regulatory domain of CK1δ has already been shown for several cellular kinases. By using biochemical methods, we now identified residues T161, T174, T176, and S181 within the kinase domain of CK1δ as target sites for checkpoint kinase 1 (Chk1). At least residues T176 and S181 show full conservation among CK1δ orthologues from different eukaryotic species. Enzyme kinetic analysis furthermore led to the hypothesis that site-specific phosphorylation within the kinase domain finally contributes to fine-tuning of CK1δ kinase activity. These data provide a basis for the extension of our knowledge about the role of site-specific phosphorylation for regulation of CK1δ and associated signal transduction pathways.


Triple A syndrome mimicking cystic fibrosis.
We report a 2-8/12 year-old male who presented with symptoms resembling cystic fibrosis (failure to thrive, developmental delay and recurrent diarrhea) and had elevated sweat chloride concentration. Mucosal hyperpigmentation led to the diagnosis of adrenal insufficiency which was ultimately shown to be a component of triple A syndrome (achalasia, alacrima, adrenal insufficiency). Elevated sweat chloride concentration normalized after initiation of adrenal replacement therapy. We suggest that non-CF conditions causing elevated sweat chloride concentration should be considered in patients with atypical findings or who do not have objective evidence of pulmonary or exocrine pancreatic disease.


Pressure distension in leg vessels as influenced by prolonged bed rest and a pressure habituation regimen.
Bed rest increases pressure distension in arteries, arterioles, and veins of the leg. We hypothesized that bed-rest-induced deconditioning of leg vessels is governed by the removal of the local increments in transmural pressure induced by assuming erect posture and, therefore, can be counteracted by intermittently increasing local transmural pressure during the bed rest. Ten men underwent 5 wk of horizontal bed rest. A subatmospheric pressure (-90 mmHg) was intermittently applied to one lower leg [pressure habituation (PH) leg]. Vascular pressure distension was investigated before and after the bed rest, both in the PH and control (CN) leg by increasing local distending pressure, stepwise up to +200 mmHg. Vessel diameter and blood flow were measured in the posterior tibial artery and vessel diameter in the posterior tibial vein. In the CN leg, bed rest led to 5-fold and 2.7-fold increments (P < 0.01) in tibial artery pressure-distension and flow responses, respectively, and to a 2-fold increase in tibial vein pressure distension. In the PH leg, arterial pressure-distension and flow responses were unaffected by bed rest, whereas bed rest led to a 1.5-fold increase in venous pressure distension. It thus appears that bed-rest-induced deconditioning of leg arteries, arterioles, and veins is caused by removal of gravity-dependent local pressure loads and may be abolished or alleviated by a local pressure-habituation regimen.


Method for Angiographically Guided Fine-Needle Diathermy in the Treatment of Corneal Neovascularization.
To describe a method to assess corneal neovascular (CoNV) complexes and identify feeder vessels for selective arterial fine-needle diathermy (FND). In patients with CoNV, color photography and corneal indocyanine green angiography (ICGA) and fluorescein angiography are performed. After injection of indocyanine green and sodium fluorescein dye, videography and single-frame images of the region of interest are recorded. Videography is used to measure the time to leakage to assess vessel maturity to guide medical treatment and to discern afferent from efferent vessels. Single-frame images are then selected to locate the number of afferent vessels for surgery, which are selectively cut with a 25-gauge marked needle for the application of FND. Angiography using fluorescein and indocyanine green allows the characterization of CoNV based on assessment of both morphologic (ICGA) and functional (fluorescein angiography) parameters. The time to leakage of fluorescein dye provides important functional information on vessel maturity and helps discern whether medical treatment should be followed before surgical. ICGA allows the identification and delineation of afferent feeder vessels even in the presence of corneal opacities affecting biomicroscopic visibility. Colocalizing the afferent vessel to a visible venous landmark or branch is helpful for placement of the incision and application of FND. Using the described approach, angiographically identified feeder vessels can be selectively treated by FND with minimal thermal energy applied to the corneoscleral limbus. The described method for angiographically guided assessment of CoNV is a useful approach for guiding the medical and surgical treatment of CoNV.


The effect of footrot on body weight and wool growth of sheep.
Body weight and traits associated with production of wool were measured over a 2-year period between 1985 and 1987 in south-western New South Wales in a flock of Merino wethers experimentally infected with footrot. The disease was allowed to spread freely amongst 150 of the flock but kept at very low prevalence in the remaining 50 by preventive footbathing during transmission periods. Severe, underrunning footrot had a significant adverse effect on body weight, for each year of the trial. Body weight was most severely reduced at times of the year when footrot was spreading among animals and lesions were severe. The mean body weight of the infected group at the end of the 2 years of observation was 7.3 kg (11.6%) below that of the control group. Footrot also depressed wool growth, with the mean clean fleece weight of the infected group being 0.4 kg (8%) lighter than that of the controls at each of the 2 annual shearings. There were no consistent differences between the groups for the other wool characteristics measured.


Quantifying Heterogeneity of Individual Organelles in Mixed Populations via Mass Cytometry.
Macroautophagy is a complex degradative intracellular process by which long-lived proteins and damaged organelles are cleared. Common methods for the analysis of autophagy are bulk measurements which mask organelle heterogeneity and complicate the analysis of interorganelle association and trafficking. Thus, methods for individual organelle quantification are needed to address these deficiencies. Current techniques for quantifying individual autophagy organelles are either low through-put or are dimensionally limited. We make use of the multiparametric capability of mass cytometry to investigate phenotypic heterogeneity in autophagy-related organelle types that have been isolated from murine brain, liver, and skeletal muscle. Detection and phenotypic classification of individual organelles were accomplished through the use of a lanthanide-chelating membrane stain and organelle-specific antibodies. Posthoc sample matrix background correction and nonspecific antibody binding corrections provide measures of interorganelle associations and heterogeneity. This is the first demonstration of multiparametric individual organelle analysis via mass cytometry. The method described here illustrates the potential for further investigation of the inherently complex interorganelle associations, trafficking, and heterogeneity present in most eukaryotic biological systems.


De Novo Mutation in Genes Regulating Neural Stem Cell Fate in Human Congenital Hydrocephalus.
Congenital hydrocephalus (CH), featuring markedly enlarged brain ventricles, is thought to arise from failed cerebrospinal fluid (CSF) homeostasis and is treated with lifelong surgical CSF shunting with substantial morbidity. CH pathogenesis is poorly understood. Exome sequencing of 125 CH trios and 52 additional probands identified three genes with significant burden of rare damaging de novo or transmitted mutations: TRIM71 (p = 2.15 × 10-7), SMARCC1 (p = 8.15 × 10-10), and PTCH1 (p = 1.06 × 10-6). Additionally, two de novo duplications were identified at the SHH locus, encoding the PTCH1 ligand (p = 1.2 × 10-4). Together, these probands account for ∼10% of studied cases. Strikingly, all four genes are required for neural tube development and regulate ventricular zone neural stem cell fate. These results implicate impaired neurogenesis (rather than active CSF accumulation) in the pathogenesis of a subset of CH patients, with potential diagnostic, prognostic, and therapeutic ramifications.


Identification and appraisal of outcome measures used to evaluate hypodontia care: A systematic review.
Identification and appraisal of the outcome measures that have been used to evaluate hypodontia treatment and deliver services are essential for improving care. A lack of alignment between outcomes and patient values can limit the scope for patient-centered care. Our objectives were to identify and appraise the outcomes selected to evaluate hypodontia care. Data sources included 10 electronic databases and grey literature, searched using terms for hypodontia and its treatment methods. Study eligibility included mixed study designs to ensure comprehensive identification of outcomes, excluding case reports and case series with fewer than 10 participants and nonsystematic reviews. Participants and interventions involved people with hypodontia receiving any dental treatment to manage their hypodontia. Simulated treatment, purely laboratory-based interventions, and future treatments still in development were excluded. Research outcomes were identified and synthesised into 4 categories: clinical indicators, and patient-reported, clinician-reported, and lay-reported outcomes. No synthesis of efficacy data was planned, and consequently no methodologic quality appraisal of the studies was undertaken. The search identified 497 abstracts, from which 106 eligible articles were retrieved in full. Fifty-six studies and 8 quality-improvement reports were included. Clinical indicators were reported in 49 studies (88%) including appearance, function, dental health, treatment longevity, treatment success and service delivery. Patient-reported outcomes were given in 22 studies (39%) including oral health-related quality of life, appearance, function, symptoms of temporomandibular dysfunction, and patient experience. Clinician-reported outcomes were limited to appearance. Variability was seen in the tools used for measuring outcomes. There is a lack of rationale and consistency in the selection of outcome measures used to evaluate hypodontia care. Outcomes are largely clinician and researcher-driven with little evidence of their relevance to patients. There was a paucity of outcomes measuring access to care, quality of care, and cost. Evidence from hypodontia research is clinician-focused and likely to have limited value to support patients during decision making. Attempts to synthesise the evidence base for translation into practice will be challenging. There is a need for a core outcomes set with a patient-centric approach to drive improvements in health services.


High rates of reinfection and incidence of bacterial sexually transmitted infections in a cohort of female sex workers from two Indian cities: need for different STI control strategies?
Female sex workers (FSWs) in India are provided a standardised package of clinical interventions for management of sexually transmitted infections (STIs). A study was conducted among FSWs at known high STI prevalence sites to determine the effectiveness of the service package. A cohort of FSW clinic attendees in two cities, Hyderabad and Mumbai, were enrolled and followed up from October 2008 to November 2009. At each visit, behavioural and clinical data were obtained and vaginal swabs collected for laboratory testing of cervical infections (gonorrhoea and chlamydia). 417 participants were enrolled, of whom 360 attended at least a follow-up visit. Prevalence of cervical infections did not change between the baseline and final visits (27.7% and 21.3% respectively, p=0.08) in spite of presumptive treatment at baseline and syndromic management at all visits. The proportion of asymptomatic cervical infections increased from 36% at baseline to 77% at the final visit. Incidence rate of cervical infections was high (85.6/100 person years) and associated with a prevalent cervical infection at baseline (HR=2.7, p<0.001) and inconsistent condom use with non-commercial partners (HR=2.5, p=0.014). High rates of STIs persisted despite the interventions due to poor condom use, minimal partner treatment, and high prevalence and incidence of STIs with a large proportion of asymptomatic infections. High-prevalence FSW sites in India need to design more effective partner treatment strategies and consider increasing the frequency of presumptive treatment as a temporary measure for quickly reducing STI prevalence, with renewed emphasis on consistent condom use with all partners.


Distribution of Virulence Factors According to Antibiotic Susceptibility among Escherichia coli Isolated from Urinary Tract Infection.
Escherichia coli is the major causative pathogen of urinary tract infection (UTI) in humans. Virulence and drug resistance play important roles in the pathogenesis of E. coli infections. The aims were to investigate the presence of uropathogenic virulence genes and to evaluate a relationship between antibiotic resistance and virulence in E. coli from UTI. A total of 132 E. coli were collected between April and June 2015 in two hospitals of Sanandaj, Iran. Isolates were examined for susceptibility to 16 antibiotic disks using the disk diffusion method and for possession of virulence genes by polymerase chain reaction. Associations between antimicrobial resistance and virulence genes were investigated. A P < 0.05 was considered significant. Of the 132 isolates, the most prevalent virulence gene was pap (31.1%), followed by cnf (28.8%), hly (16.7%), and afa (10.6%). Different patterns of virulence genes were identified. A significant association was detected between the simultaneous presence of hly and pap. The most effective antibiotics were nitrofurantoin, cefoxitin, and imipenem and the least effective were ampicillin, trimethoprim-sulfamethoxazole, and cefotaxime. An association was seen between the presence of cnf and susceptibility to the certain antibiotics, whereas strains with a reduced susceptibility to the certain antibiotics were associated with a significantly increased prevalence of afa and hly (P < 0.05). These findings suggest a correlation between the presence of virulence gene and resistance in E. coli strains from UTI. The results indicate that there is a need for surveillance programs to monitor drug resistance in pathogenic E. coli.


Methylthioinosine phosphorylase from Pseudomonas aeruginosa. Structure and annotation of a novel enzyme in quorum sensing.
The PA3004 gene of Pseudomonas aeruginosa PAO1 was originally annotated as a 5'-methylthioadenosine phosphorylase (MTAP). However, the PA3004 encoded protein uses 5'-methylthioinosine (MTI) as a preferred substrate and represents the only known example of a specific MTI phosphorylase (MTIP). MTIP does not utilize 5'-methylthioadenosine (MTA). Inosine is a weak substrate with a k(cat)/K(m) value 290-fold less than MTI and is the second best substrate identified. The crystal structure of P. aeruginosa MTIP (PaMTIP) in complex with hypoxanthine was determined to 2.8 Å resolution and revealed a 3-fold symmetric homotrimer. The methylthioribose and phosphate binding regions of PaMTIP are similar to MTAPs, and the purine binding region is similar to that of purine nucleoside phosphorylases (PNPs). The catabolism of MTA in P. aeruginosa involves deamination to MTI and phosphorolysis to hypoxanthine (MTA → MTI → hypoxanthine). This pathway also exists in Plasmodium falciparum, where the purine nucleoside phosphorylase (PfPNP) acts on both inosine and MTI. Three tight-binding transition state analogue inhibitors of PaMTIP are identified with dissociation constants in the picomolar range. Inhibitor specificity suggests an early dissociative transition state for PaMTIP. Quorum sensing molecules are associated with MTA metabolism in bacterial pathogens suggesting PaMTIP as a potential therapeutic target.


An Advanced Model to Precisely Estimate the Cell-Free Fetal DNA Concentration in Maternal Plasma.
With the speedy development of sequencing technologies, noninvasive prenatal testing (NIPT) has been widely applied in clinical practice for testing for fetal aneuploidy. The cell-free fetal DNA (cffDNA) concentration in maternal plasma is the most critical parameter for this technology because it affects the accuracy of NIPT-based sequencing for fetal trisomies 21, 18 and 13. Several approaches have been developed to calculate the cffDNA fraction of the total cell-free DNA in the maternal plasma. However, most approaches depend on specific single nucleotide polymorphism (SNP) allele information or are restricted to male fetuses. In this study, we present an innovative method to accurately deduce the concentration of the cffDNA fraction using only maternal plasma DNA. SNPs were classified into four maternal-fetal genotype combinations and three boundaries were added to capture effective SNP loci in which the mother was homozygous and the fetus was heterozygous. The median value of the concentration of the fetal DNA fraction was estimated using the effective SNPs. A depth-bias correction was performed using simulated data and corresponding regression equations for adjustments when the depth of the sequencing data was below 100-fold or the cffDNA fraction is less than 10%. Using our approach, the median of the relative bias was 0.4% in 18 maternal plasma samples with a median sequencing depth of 125-fold. There was a significant association (r = 0.935) between our estimations and the estimations inferred from the Y chromosome. Furthermore, this approach could precisely estimate a cffDNA fraction as low as 3%, using only maternal plasma DNA at the targeted region with a sequencing depth of 65-fold. We also used PCR instead of parallel sequencing to calculate the cffDNA fraction. There was a significant association (r = 98.2%) between our estimations and those inferred from the Y chromosome.


Renal cell carcinoma: Atypical metastasis to inguinal lymph nodes.
Renal cell carcinoma (RCC) is a common tumor of the urinary tract. It is known to have variable presentations due to the extremely vascular nature of the organ. RCC are known to metastasize to lungs, bone, and brain commonly but atypical metastasis to various sites are reported in literature but as very rare pathology. We report a case of a 60-year-old female who presented with multiple inguinal and axillary lymph node enlargements which on excision biopsy showed metastatic RCC. RCC can present with synchronous metastatic deposits in the various organs. RCC can metastasize to some atypical sites as well such as thyroid, orbit, and neck as mentioned earlier in literature. The patient presenting with extra-regional lymph nodes like inguinal and axillary is extremely rare, and so far only one clinical case could be found from India in 2008. A 61-year-old female presented in the emergency department with left flank pain and hematuria. Imaging showed left swollen kidney but multiple lymph nodes in retroperitoneum, left inguinal and axillary region. Excisional biopsy confirmed metastatic renal clear cell carcinoma. The case was referred to an oncologist after left radical nephrectomy for further treatment. Renal cancer is quite common aggressive disease. Due to its vascular nature, it may present quite atypically as evident from literature. Although treatment of metastatic carcinoma is still controversial surgery is the mainstay of treatment and guidelines consider metastasectomy and cytoreductive nephrectomy as valid option followed by targeted systemic therapies. RCC has quite a high potential to metastasize in the versatile pattern, in our case, it is evident that valid management is still surgery but needs support from the multidisciplinary team.


Membrane resealing in cultured rat septal neurons after neurite transection: evidence for enhancement by Ca(2+)-triggered protease activity and cytoskeletal disassembly.
Neurites of cultured septal neurons were transected with a laser under sterile conditions, and the subsequent membrane resealing was assayed using a dye exclusion method. In agreement with findings in other preparations, Ca2+ enhanced resealing: in normal culture medium the percentage of lesioned neurons that resealed within 20-30 min after transection increased with increasing bath [Ca2+] over the range 10(-7) to 2 x 10(-3) M; about 75% of cells resealed in 2 mM Ca2+. Mn2+ and Sr2+ also enhanced resealing, but Mg2+ inhibited it. The percentage of resealing neurons was sensitive to agents known to alter the stability of cytoskeletal components. Agents that tend to disassemble microtubules and/or neurofilaments (e.g., colchicine, low-ionic-strength media) strongly promoted resealing, whereas treatments that tend to stabilize microtubules (taxol, Mg2+) inhibited resealing. Addition of exogenous proteases (papain, trypsin, or dispase) enhanced resealing, whereas inhibitors of cysteine proteases (including a specific inhibitor of calpain, a Ca-activated neutral protease) strongly inhibited resealing. Calmodulin inhibitors inhibited resealing, consistent with reports that calmodulin facilitates calpain-mediated proteolysis of fodrin, a component of the cortical cytoskeleton. Based on these results, we hypothesize that one of the major mechanisms involved in resealing is activation of endogenous proteases by Ca2+ entry into the injured neurite. The resulting changes in the cellular cytoskeleton might promote fusion and resealing of the cut ends of the plasma membrane by enhancing membrane mobility and/or by removing structures that normally prevent membrane-membrane contact.


Four RNA families with functional transient structures.
Protein-coding and non-coding RNA transcripts perform a wide variety of cellular functions in diverse organisms. Several of their functional roles are expressed and modulated via RNA structure. A given transcript, however, can have more than a single functional RNA structure throughout its life, a fact which has been previously overlooked. Transient RNA structures, for example, are only present during specific time intervals and cellular conditions. We here introduce four RNA families with transient RNA structures that play distinct and diverse functional roles. Moreover, we show that these transient RNA structures are structurally well-defined and evolutionarily conserved. Since Rfam annotates one structure for each family, there is either no annotation for these transient structures or no such family. Thus, our alignments either significantly update and extend the existing Rfam families or introduce a new RNA family to Rfam. For each of the four RNA families, we compile a multiple-sequence alignment based on experimentally verified transient and dominant (dominant in terms of either the thermodynamic stability and/or attention received so far) RNA secondary structures using a combination of automated search via covariance model and manual curation. The first alignment is the Trp operon leader which regulates the operon transcription in response to tryptophan abundance through alternative structures. The second alignment is the HDV ribozyme which we extend to the 5' flanking sequence. This flanking sequence is involved in the regulation of the transcript's self-cleavage activity. The third alignment is the 5' UTR of the maturation protein from Levivirus which contains a transient structure that temporarily postpones the formation of the final inhibitory structure to allow translation of maturation protein. The fourth and last alignment is the SAM riboswitch which regulates the downstream gene expression by assuming alternative structures upon binding of SAM. All transient and dominant structures are mapped to our new alignments introduced here.


Whispering-gallery-mode biosensing: label-free detection down to single molecules.
Optical label-free detectors, such as the venerable surface plasmon resonance (SPR) sensor, are generally favored for their ability to obtain quantitative data on intermolecular binding. However, before the recent introduction of resonant microcavities that use whispering gallery mode (WGM) recirculation, sensitivity to single binding events had not materialized. Here we describe the enhancement mechanisms responsible for the extreme sensitivity of the WGM biosensor, review its current implementations and applications, and discuss its future possibilities.


Hot-wire polysilicon waveguides with low deposition temperature.
We fabricated and measured the optical loss of polysilicon waveguides deposited using hot-wire chemical vapor deposition at a temperature of 240°C. A polysilicon film 220 nm thick was deposited on top of a 2000 nm thick plasma-enhanced chemical vapor deposition silicon dioxide layer. The crystalline volume fraction of the polysilicon film was measured by Raman spectroscopy to be 91%. The optical propagation losses of 400, 500, and 600 nm waveguides were measured to be 16.9, 15.9, and 13.5 dB/cm, respectively, for transverse electric mode at the wavelength of 1550 nm. Scattering loss is expected to be the major contributor to the propagation loss.


Lipoleiomyoma of uterus in a postmenopausal woman.
Lipoleiomyomas are uncommon benign neoplasms of uterus and are considered to be a variant of uterine myomas. Their reported incidence varies from 0.03 to 0.2%. Lipoleiomyoma consists of variable proportion of mature lipocytes and smooth muscle cells. These tumors generally occur in asymptomatic obese perimenopausal or menopausal women. We report this case of uterine lipoleiomyoma because of its rarity.


Innovation in mental health care: Bertram Mandelbrote, the Phoenix Unit and the therapeutic community approach.
Bertram Mandelbrote was Physician Superintendent and Consultant Psychiatrist at Littlemore Hospital in Oxford from 1959 to 1988. A humane pragmatist rather than theoretician, Mandelbrote was known for his facilitating style of leadership and working across organisational boundaries. He created the Phoenix Unit, an innovative admission unit run on therapeutic community lines which became a hub for community outreach. Material drawn from oral histories and witness seminars reflects the remarkably unstructured style of working on the Phoenix Unit and the enduring influence of Mandelbrote and fellow consultant Benn Pomryn's styles of leadership. Practices initiated at Littlemore led to a number of innovative services in Oxfordshire. These innovations place Mandelbrote as a pioneer in social psychiatry and the therapeutic community approach.


Bactericidal antibiotics induce mitochondrial dysfunction and oxidative damage in Mammalian cells.
Prolonged antibiotic treatment can lead to detrimental side effects in patients, including ototoxicity, nephrotoxicity, and tendinopathy, yet the mechanisms underlying the effects of antibiotics in mammalian systems remain unclear. It has been suggested that bactericidal antibiotics induce the formation of toxic reactive oxygen species (ROS) in bacteria. We show that clinically relevant doses of bactericidal antibiotics-quinolones, aminoglycosides, and β-lactams-cause mitochondrial dysfunction and ROS overproduction in mammalian cells. We demonstrate that these bactericidal antibiotic-induced effects lead to oxidative damage to DNA, proteins, and membrane lipids. Mice treated with bactericidal antibiotics exhibited elevated oxidative stress markers in the blood, oxidative tissue damage, and up-regulated expression of key genes involved in antioxidant defense mechanisms, which points to the potential physiological relevance of these antibiotic effects. The deleterious effects of bactericidal antibiotics were alleviated in cell culture and in mice by the administration of the antioxidant N-acetyl-l-cysteine or prevented by preferential use of bacteriostatic antibiotics. This work highlights the role of antibiotics in the production of oxidative tissue damage in mammalian cells and presents strategies to mitigate or prevent the resulting damage, with the goal of improving the safety of antibiotic treatment in people.


Description of depolarization effects in double-quantum solid state nuclear magnetic resonance experiments using multipole-multimode Floquet theory.
Using an analytical model based on multipole-multimode Floquet theory (MMFT), we describe the polarization loss (or depolarization) observed in double-quantum (DQ) dipolar recoupling magic angle spinning (MAS) experiments. Specifically, the factors responsible for depolarization are analyzed in terms of higher order corrections to the spin Hamiltonian in addition to the usual phenomenological decay rate constant. From the MMFT model and the effective Hamiltonians, we elucidate the rationale behind the inclusion of a phenomenological damping term in DQ recoupling experiments. As a test of this theoretical approach, the recoupling efficiency of one class of (13)C-(13)C and (13)C-(15)N resonance width dipolar recoupling experiments are investigated at different magnetic field strengths and compared with the more exact numerical simulations. In contrast to existing analytical treatments, the role of higher order corrections is clearly explained in the context of the MMFT approach leading to a better understanding of the underlying spin physics. Furthermore, the analytical model presented herein provides a general framework for describing coherent and incoherent effects in homonuclear and heteronuclear DQ MAS recoupling experiments.


Confronting intimate partner violence: a global health priority.
Intimate partner violence--physical, psychological, or sexual abuse of women perpetrated by intimate partners--is one of the most common forms of violence against women, and is associated with adverse women's reproductive and maternal health outcomes. We review the opportunities for addressing intimate partner violence by the health system, examine promising approaches, and outline future challenges for developing effective health-systems responses to violence. Evidence shows that women seldom approach support services in response to violence, but do seek health care at some point in their lives. In fact, women's utilization of reproductive-health services in particular has been increasing globally. These services have a broad reach and represent an important opportunity to engage in violence prevention. Although health systems-based responses to intimate partner violence have emerged, rigorous evaluations to guide program planning and policy efforts to reduce violence are limited. Programs in the United States have expanded from improving individual provider prevention practices to instituting system-wide changes to ensure sustainability of these practices. Developing-country program responses, though limited, have been system-wide and multisectoral right from the start. Our review highlights 3 challenges for developing and expanding health-systems responses to violence. First, interventions should focus on creating a supportive environment within the health system and strengthening linkages across health care and allied sectors. Second, rigorous evaluations of health sector-based interventions are needed for a sound evidence base to guide programmatic and policy decisions. Finally, research is needed to identify the entry points for engaging men on violence prevention, and to examine the feasibility and effectiveness of such interventions.


Bayesian trio models for association in the presence of genotyping errors.
Errors in genotyping can greatly affect family-based association studies. If a mendelian inconsistency is detected, the family is usually removed from the analysis. This reduces power, and may introduce bias. In addition, a large proportion of genotyping errors remain undetected, and these also reduce power. We present a Bayesian framework for performing association studies with SNP data on samples of trios consisting of parents with an affected offspring, while allowing for the presence of both detectable and undetectable genotyping errors. This framework also allows for the inclusion of missing genotypes. Associations between the SNP and disease were modelled in terms of the genotypic relative risks. The performances of the analysis methods were investigated under a variety of models for disease association and genotype error, looking at both power to detect association and precision of genotypic relative risk estimates. As expected, power to detect association decreased as genotyping error probability increased. Importantly, however, analyses allowing for genotyping error had similar power to standard analyses when applied to data without genotyping error. Furthermore, allowing for genotyping error yielded relative risk estimates that were approximately unbiased, together with 95% credible intervals giving approximately correct coverage. The methods were also applied to a real dataset: a sample of schizophrenia cases and their parents genotyped at SNPs in the dysbindin gene. The analysis methods presented here require no prior information on the genotyping error probabilities, and may be fitted in WinBUGS.


Noncoeliac gluten sensitivity: a diagnostic dilemma.
Noncoeliac gluten sensitivity (NCGS) has gained attention as an emerging clinical entity. Data regarding the epidemiology, pathogenesis, and management of NCGS are scattered in view of the diagnostic uncertainty surrounding the disorder. We aim to provide a current perspective of NCGS and its associated controversies. NCGS consists of a spectrum of intestinal and extraintestinal symptoms related to the ingestion of gluten-containing food, yet in the absence of coeliac disease or wheat allergy. To date, no specific biomarker exists for NCGS, thereby leaving the diagnosis to be confirmed by dietary elimination followed by double-blind placebo-controlled gluten-based rechallenges. Unfortunately, this technique is cumbersome, not readily-available in routine clinical practise, and can still leave the diagnosis of NCGS open to debate as to whether the effects demonstrated can be specifically attributed to the gluten-protein per se or rather coexisting nongluten components, such as fermentable carbohydrates and amylase-trypsin inhibitors. Physicians are increasingly being posed with the dilemma of patients presenting with self-reported NCGS. However, this appears to be the tip of the iceberg and future studies are in need of delineating which gluten-based component is responsible for each individual patient's complaint.


Surgical management of early-stage hepatocellular carcinoma: resection or transplantation?
The surgical management of hepatocellular carcinoma in patients with well-compensated cirrhosis is controversial. The purpose of the current study was to compare the outcome of patients with well-compensated cirrhosis and early stage hepatocellular carcinoma treated with initial hepatic resection versus transplantation. Between 1985 and 2008, 245 patients underwent hepatic resection, and 134 patients underwent liver transplantation for early stage hepatocellular carcinoma. All patients had well-compensated cirrhosis. Prognostic factors were evaluated using univariate and multivariate analyses; survival was calculated using the Kaplan-Meier method. Compared with transplantation, patients undergoing resection had larger tumors and a higher incidence of microscopic vascular invasion. Transplantation was associated with better 5-year disease-free and overall survival compared with resection. Hepatitis status, presence of microscopic vascular invasion, and tumor size were predictors for recurrence, while the presence of microscopic vascular invasion and tumor size conferred an increased risk of death. The disease-free survival advantage with transplantation was more pronounced in hepatitis C patients compared with non-hepatitis and hepatitis B patients. The overall survival advantage with transplantation persisted in cases of solitary lesions < or = 3 cm, but was attenuated in patients with a MELD score < or = 8. In well-compensated cirrhotic patients with early stage hepatocellular carcinoma, transplantation was associated with longer disease-free and overall survival. Patients undergoing resection did, however, have tumors with more advanced pathologic features. Patients best suited for initial resection as the treatment of hepatocellular carcinoma were those with a MELD score </= 8 without evidence of hepatitis.


Characterisation of the aerobic bacterial flora of boid snakes: application of MALDI-TOF mass spectrometry.
The aim of this study was to identify aerobic bacterial isolates from the respiratory tract of boids with matrix-assisted laser desorption ionisation-time-of-flight mass spectrometry (MALDI-TOF MS). From 47 boid snakes, swabs from the oral cavity, tracheal wash samples and, in cases in which postmortem examination was performed, pulmonary tissue samples were taken. Each snake was classified as having inflammation of the respiratory tract and/or oral cavity, or without evidence of inflammation based on combination of clinical, cytological and histopathological findings. Samples collected from the respiratory tract and oral cavity were inoculated onto routine media and bacteria were cultured aerobically. All morphologically distinct individual colonies obtained were analysed using MALDI-TOF MS. Unidentified isolates detected in more than three snakes were selected for further 16S rDNA PCR and sequencing. Among all examined isolates (n=243), 49 per cent (n=119) could be sufficiently speciated using MALDI-TOF MS. Molecular biology revealed several bacterial species that have not been previously described in reptiles. With an average of 6.3 different isolates from the respiratory tract and/or oral cavity, boids with inflammatory disease harboured significantly more bacterial species than boids without inflammatory disease (average 2.8 isolates).


Cerebral ischemia in gerbils: polyribosomal function during progression and recovery.
Cerebral ischemia was produced by clipping the right common carotid artery in Mongolian gerbils. Polyribosomal function in cerebral ischemia during progression and recovery was studied by investigation of morphology (electronmicroscopy), physical property (size distribution profiles) and biochemical property (polypeptide synthesis). Polyribosomes and their function were relatively well preserved during progression of ischemia. The most striking finding was an extensive disaggregation of polyribosomes and suppression of polypeptide synthesis immediately after re-establishment of cerebral circulation. These phenomena occurred not only with irreversible ischemia at 3 h but also with reversible ischemia at 30 min. In the latter, disaggregation of polyribosomes gradually recovered, but no tendency for recovery was observed after an ischemic period of 3 h. The disaggregation and delay in reaggregation of ribosomes after re-establishment of cerebral circulation may be a significant factor in the irreversibility of cerebral ischemia. The observed deterioration of cellular function during the recovery process may have an important implication not only for medical management of stroke but also for surgical recirculation during acute stroke.


Impact of telemedicine on neonatal resuscitation in the emergency department: a simulation-based randomised trial.
The delivery and initial resuscitation of a newborn infant are required but rarely practised skills in emergency medicine. Deliveries in the emergency department are high-risk events and deviations from best practices are associated with poor outcomes. Telemedicine can provide emergency medicine providers real-time access to a Neonatal Resuscitation Program (NRP)-trained paediatric specialist. We hypothesised that adherence to NRP guidelines would be higher for participants with access to a remotely located NRP-trained paediatric specialist via telemedicine compared with participants without access. Prospective single-centre randomised trial. Emergency Medicine residents were randomised into a telemedicine or standard care group. The participants resuscitated a simulated, apnoeic and bradycardic neonate. In the telemedicine group a remote paediatric specialist participated in the resuscitation. Simulations were video recorded and assessed for adherence to guidelines using four critical actions. The secondary outcome of task load was measured through participants' completion of the NASA Task Load Index (NASA-TLX) and reviewers completed a detailed NRP checklist. Twelve participants were included. The use of telemedicine was associated with significantly improved adherence to three of the four critical actions reflecting NRP guidelines as well as a significant improvement in the overall score (p<0.001). On the NASA-TLX, no significant difference was seen in overall subjective workload assessment, but of the subscore components, frustration was statistically significantly greater in the control group (p<0.001). In this study, telemedicine improved adherence to NRP guidelines. Future work is needed to replicate these findings in the clinical environment.


Sequence context- and temperature-dependent nucleotide excision repair of a benzo[a]pyrene diol epoxide-guanine DNA adduct catalyzed by thermophilic UvrABC proteins.
The influence of DNA base sequence context on the removal of a bulky benzo[a]pyrene diol epoxide-guanine adduct, (+)-trans-B[a]P-N2-dG (G*), by UvrABC nuclease from the thermophilic organism Bacillus caldotenax was investigated. The lesion was flanked by either T or C in otherwise identical complementary 43-mer duplexes (TG*T or CG*C, respectively). It was reported earlier that in the CG*C context, a dominant minor groove adduct structure was observed by NMR methods with all Watson-Crick base pairs intact, and the duplex exhibited a rigid bend. In contrast, in the TG*T context, a highly flexible bend was observed, base pairing at G*, and two 5'-base pairs flanking the adduct were impaired, and multiple solvent-accessible adduct conformations were observed. The TG*T-43-mer duplexes are incised with consistently greater efficiency by UvrABC proteins from B. caldotenax by a factor of 2.3 +/- 0.3. The rates of incisions increase with increasing temperature and are characterized by linear Arrhenius plots with activation energies of 27.0 +/- 1.5 and 23.4 +/- 1.0 kcal/mol for CG*C and TG*T duplexes, respectively. These values reflect the thermophilic characteristics of the UVrABC nuclease complex and the contributions of the different DNA substrates to the overall activation energies. These effects are consistent with base sequence context-dependent differences in structural disorder engendered by a loss of local base stacking interactions and Watson-Crick base pairing in the immediate vicinity of the lesions in the TG*T duplexes. The local weakening of base pairing interactions constitutes a recognition element of the UvrABC nucleotide excision repair apparatus.


Neural Processes of Psychological Stress and Relaxation Predict the Future Evolution of Quality of Life in Multiple Sclerosis.
Health-related quality of life (HRQoL) is an essential complementary parameter in the assessment of disease burden and treatment outcome in multiple sclerosis (MS) and can be affected by neuropsychiatric symptoms, which in turn are sensitive to psychological stress. However, until now, the impact of neurobiological stress and relaxation on HRQoL in MS has not been investigated. We thus evaluated whether the activity of neural networks triggered by mild psychological stress (elicited in an fMRI task comprising mental arithmetic with feedback) or by stress termination (i.e., relaxation) at baseline (T0) predicts HRQoL variations occurring between T0 and a follow-up visit (T1) in 28 patients using a robust regression and permutation testing. The median delay between T0 and T1 was 902 (range: 363-1,169) days. We assessed HRQoL based on the Hamburg Quality of Life Questionnaire in MS (HAQUAMS) and accounted for the impact of established HRQoL predictors and the cognitive performance of the participants. Relaxation-triggered activity of a widespread neural network predicted future variations in overall HRQoL (t = 3.68, p family-wise error [FWE]-corrected = 0.008). Complementary analyses showed that relaxation-triggered activity of the same network at baseline was associated with variations in the HAQUAMS mood subscale on an αFWE = 0.1 level (t = 3.37, p FWE = 0.087). Finally, stress-induced activity of a prefronto-limbic network predicted future variations in the HAQUAMS lower limb mobility subscale (t = -3.62, p FWE = 0.020). Functional neural network measures of psychological stress and relaxation contain prognostic information for future HRQoL evolution in MS independent of clinical predictors.


Long-term oncologic outcomes of robotic low anterior resection for rectal cancer: a comparative study with laparoscopic surgery.
The aim of this study is to evaluate long-term oncologic outcomes of robotic surgery for rectal cancer compared with laparoscopic surgery at a single institution. Robotic surgery is regarded as a new modality to surpass the technical limitations of conventional surgery. Short-term outcomes of robotic surgery for rectal cancer were acceptable in previous reports. However, evidence of long-term feasibility and oncologic safety is required. Between April 2006 and August 2011, 217 patients who underwent minimally invasive surgery for rectal cancer with stage I-III disease were enrolled prospectively (robot, n = 133; laparoscopy, n = 84). Median follow-up period was 58 months (range, 4-80 months). Perioperative clinicopathologic outcomes, morbidities, 5-year survival rates, prognostic factors, and cost were evaluated. Perioperative clinicopathologic outcomes demonstrated no significant differences except for the conversion rate and length of hospital stay. The 5-year overall survival rate was 92.8% in robotic, and 93.5% in laparoscopic surgical procedures (P = 0.829). The 5-year disease-free survival rate was 81.9% and 78.7%, respectively (P = 0.547). Local recurrence was similar: 2.3% and 1.2% (P = 0.649). According to the univariate analysis, this type of surgical approach was not a prognostic factor for long-term survival. The patient's mean payment for robotic surgery was approximately 2.34 times higher than laparoscopic surgery. No significant differences were found in the 5-year overall, disease-free survival and local recurrence rates between robotic and laparoscopic surgical procedures. We concluded that robotic surgery for rectal cancer failed to offer any oncologic or clinical benefits as compared with laparoscopy despite an increased cost.


Mental health problems and medically unexplained physical symptoms in adult survivors of childhood sexual abuse: an integrative literature review.
People sexually abused in childhood are at higher risk than non-abused people of medically unexplained symptoms such as irritable bowel syndrome or chronic pain, with mental ill health and high healthcare use. Friction and frustration, with high, unproductive healthcare costs, can often develop between these patients and health-care professionals such as general practitioners and nursing staff. The aim of this integrative literature review was to seek a sound evidence base from which to develop helpful interventions, improve relationships and identify gaps in knowledge. It found some theories about interconnections among childhood sexual abuse mental health and medically unexplained symptoms, such as 'somatization' or 'secondary gain', were used prejudicially, stigmatizing survivors. Conflicting theories make more difficult the search for effective interventions. Researchers rarely collaborated with sexual abuse specialists. Emphasis on identifying key risk factors, rather than providing support or alleviating distress, and lack of studies where survivors voiced their own experiences, meant very few targeted interventions for this group were proposed. Recommendations to enable effective interventions include making abuse survivors the prime study focus; qualitative research with survivors, to assist doctors and nursing staff with sensitive care; case histories using medical records; prospective studies with sexually abused children; support for the growing field of neurobiological research.


Cdc2-like kinase 2 (Clk2) promotes early neural development in Xenopus embryos.
Neural induction and patterning in vertebrates are regulated during early development by several morphogens, such as bone morphogenetic proteins (BMPs) and fibroblast growth factors (FGFs). Ventral ectoderm differentiates into epidermis in response to BMPs, whereas BMP signaling is tightly inhibited in the dorsal ectoderm which develops into neural tissues. Here, we show that Cdc2-like kinase 2 (Clk2) promotes early neural development and inhibits epidermis differentiation in Xenopus embryos. clk2 is specifically expressed in neural tissues along the anterior-posterior axis during early Xenopus embryogenesis. When overexpressed in ectodermal explants, Clk2 induces the expression of both anterior and posterior neural marker genes. In agreement with this observation, overexpression of Clk2 in whole embryos expands the neural plate at the expense of epidermal ectoderm. Interestingly, the neural-inducing activity of Clk2 is increased following BMP inhibition and activation of the FGF signaling pathway in ectodermal explants. Clk2 also downregulates the level of p-Smad1/5/8 in cooperation with BMP inhibition, in addition to increasing the level of activated MAPK together with FGF. These results suggest that Clk2 plays a role in early neural development of Xenopus possibly via modulation of morphogen signals such as the BMP and FGF pathways.


Cardiovascular effects of growth hormone treatment in growth-hormone-deficient adults: stimulation of the renin-aldosterone system.
1. In adult humans with growth hormone deficiency, treatment with growth hormone has recently been shown to have major anabolic effects and to improve exercise performance. The cardiovascular effects of growth hormone in adults with growth hormone deficiency were examined in 24 patients treated with recombinant human growth hormone (0.07 units/kg at night) in a double-blind, placebo-controlled trial lasting 6 months. 2. Compared with placebo, resting M-mode echocardiography showed increases in left ventricular end-diastolic dimension and stroke volume in the group treated with recombinant human growth hormone. No differences were noted between the groups with respect to left ventricular end-systolic dimension, fractional shortening, wall thicknesses or mean arterial blood pressure. Left ventricular myocardial mass increased in the group given recombinant human growth hormone. 3. The supine plasma renin activity was increased and remained elevated over the 6 months, whereas the plasma aldosterone concentration was unchanged, after treatment with recombinant human growth hormone. Clinical signs of sodium retention were evident during the first 3 months of treatment with recombinant human growth hormone. 4. We conclude that treatment with recombinant human growth hormone in adults with growth hormone deficiency resulted in small increases in left ventricular pre-load, due to the sodium-retaining action of growth hormone. Activation of the renin-aldosterone system was involved in such changes. Myocardial hypertrophy was observed without changes in mean arterial pressure, reflecting the anabolic action of growth hormone.


The influence of the molecular weight of the water-soluble polymer on phase-separated films for controlled release.
Hydroxypropyl cellulose (HPC) and ethyl cellulose (EC) can be used for extended release coatings, where the water-soluble HPC may act as a pore former. The aim was to investigate the effect of the molecular weight of HPC on the microstructure and mass transport in phase-separated freestanding EC/HPC films with 30% w/w HPC. Four different HPC grades were used, with weight averaged molecular weights (Mw) of 30.0 (SSL), 55.0 (SL), 83.5 (L) and 365 (M) kg/mol. Results showed that the phase-separated structure changed from HPC-discontinuous to bicontinuous with increasing Mw of HPC. The film with the lowest Mw HPC (SSL) had unconnected oval-shaped HPC-rich domains, leaked almost no HPC and had the lowest water permeability. The remaining higher Mw films had connected complex-shaped pores, which resulted in higher permeabilities. The highest Mw film (M) had the smallest pores and very slow HPC leakage, which led to a slow increase in permeability. Films with grade L and SL released most of their HPC, yet the permeability of the L film was three times higher due to greater pore connectivity. It was concluded that the phase-separated microstructure, the level of pore percolation and the leakage rate of HPC will be affected by the choice of HPC Mw grade used in the film and this will in turn have strong impact on the film permeability.


Assessment of the effects of exogenous long-acting insulin on glucose tolerance in alpacas.
To evaluate the effects of long-acting insulin on glucose clearance in alpacas. 8 adult castrated alpacas. On 2 days, food was withheld from alpacas for 8 hours. Alpacas were randomly allocated to receive an SC injection of long-acting insulin (0.4 U/kg) or saline (0.9% NaCI) solution 1 hour before the first of 3 administrations of glucose (at 60, 480, and 1,200 minutes after treatment) on day 1 and the alternate treatment and procedure on day 2. Plasma glucose concentration was determined before and 15, 45, 120, and 240 minutes after each glucose administration, and fractional turnover rates were calculated. The data were compared between alpacas with and without insulin administration and among the 3 glucose administrations for each day. Compared with sham-treated alpacas, insulin-treated alpacas had significantly lower blood glucose concentrations from 180 to 600 minutes after treatment; they also had glucose concentrations significantly below baseline values from 120 to 480 minutes, at which time the mean glucose concentration was in the hypoglycemic range. Also, mean fractional turnover of glucose was significantly higher in insulin-treated alpacas from 105 through 300 minutes. Compared with known effects of regular insulin in alpacas, the action of long-acting insulin was of slower onset but longer lasting; its administration may induce hypoglycemia, even in alpacas that receive glucose. To maintain the hypoglycemic effect, long-acting insulin may have to be administered more than once daily and blood glucose concentration should be monitored to avoid hypoglycemic complications in alpacas.


Hopelessness, depression and suicidal intent in parasuicide.
Previous work on the inter-relationships among depression, hopelessness and suicidal intent in parasuicide is reviewed. Our own study of 120 hospital-referred parasuicides confirms previous findings that, while both depression and hopelessness correlate with the degree of suicidal intent as measured on a Suicide Intent Scale, the relationship between depression and suicidal intent is dependent on that between hopelessness and suicidal intent. Some practical and theoretical implications are discussed.


Serum neurofilament levels and patient-reported outcomes in multiple sclerosis.
Serum neurofilament light (sNfL) is a promising new biomarker in multiple sclerosis (MS). We explored the relationship between sNfL and health outcomes and resource use in MS patients. MS patients with serum samples and health-outcome measurements collected longitudinally between 2011 and 2016 were analyzed. sNfL values were evaluated across age and gender. Data were analyzed using correlation with log-transformed sNfL values. A total of 304 MS patients with a mean age of 32.9 years, average EDSS of 1.6 (SD = 1.5) and baseline sNfL of 8.8 (range 1.23-78.3) pg/mL were studied. Baseline sNFL values increased with age and were higher in females. Baseline sNfL correlated with baseline Multiple Sclerosis Quality of Life physical composite (mean = 49.4 (9.1), P = 0.035) and baseline EDSS (P = 0.002). Other PRO measures at baseline did not show a significant relationship with baseline sNfL. Average of baseline and follow-up sNfL correlated with MSQoL physical-role limitations (mean = 48.9 (10.8), P = 0.043) and social-functioning (mean = 52.3 (7), P = 0.034) at 24-month follow-up. We found a trend for numerically higher sNfL levels in nonpersistent patients compared to those who were persistent to treatment (11.13 vs. 8.53 pg/mL, P = 0.093) measured as average of baseline and 24-month values. Baseline NfL was associated with number of intravenous steroid infusions (mean = 0.2; SD = 3.0, P = 0.013), whereas the average of baseline and 12 months NfL values related to inpatient stays at 12 months (mean = 0.2; SD = 3.0 P = 0.053). Serum NfL is a patient-centric biomarker that correlated with MS patient health-outcomes and healthcare utilization measures in a real-world cohort.


Commentary: Health care reform and primary care: training physicians for tomorrow's challenges.
Although Congress recently passed health insurance reform legislation, the real catalyst for change in the health care delivery system, the author's argue, will be changes to the reimbursement model. To rein in increasing costs, the Centers for Medicare and Medicaid aims to move Medicare from the current fee-for-service model to a reimbursement approach that shifts the risk to providers and encourages greater accountability both for the cost and the quality of care. This level of increased accountability can only be achieved by clinical integration among health care providers. Central to this reorganized delivery model are primary care providers who coordinate and organize the care of their patients, using best practices and evidence-based medicine while respecting the patient's values, wishes, and dictates. Thus, the authors ask whether primary care physicians will be available in sufficient numbers and if they will be adequately and appropriately trained to take on this role. Most workforce researchers report inadequate numbers of primary care doctors today, a shortage that will only be exacerbated in the future. Even more ominously, the authors argue that primary care physicians being trained today will not have the requisite skills to fulfill their contemplated responsibilities because of a variety of factors that encourage fragmentation of care. If this training issue is not debated vigorously to determine new and appropriate training approaches, the future workforce may eventually have the appropriate number of physicians but inadequately trained individuals, a situation that would doom any effort at system reform.


Glutathione transferase mu deficiency is not a marker for predisposition to sulphonamide toxicity.
Glutathione transferase mu activity, a marker for susceptibility to lung cancer and chemically induced cytogenetic damage, is not a predictive index for the predisposition to sulphonamide hypersensitivity reactions. However, considering the functional diversity and broad, overlapping substrate specificity of GSH-dependent enzymes, it is conceivable that an as yet unidentified deficiency in another GST isozyme or GSH-related enzyme may be a marker for sulphonamide toxicity. In addition, heterogeneity in cellular repair mechanisms and the diversity of the human immune response [22] may also contribute to the manifestation of the toxic effects of sulphonamides. Experiments are currently in progress to determine which of this myriad of variables is predominantly responsible for inter-individual susceptibility to the idiosyncratic reactions produced by these antibacterial agents.


Suicidal ideation and attempts among psychiatric patients with major depressive disorder.
Few studies have investigated risk factors for suicidal ideation and attempts, or possible variations in them, among representative samples of psychiatric patients with major depressive disorder. As part of the Vantaa Depression Study in Vantaa, Finland, 269 patients with DSM-IV major depressive disorder (MDD), diagnosed by interview using semistructured World Health Organization Schedules for Clinical Assessment in Neuropsychiatry, version 2.0, and Structured Clinical Interview for DSM-III-R Personality Disorders, were thoroughly investigated. Information was gathered on patients' levels of depression, anxiety, hopelessness, perceived social support, social and occupational functioning, and alcohol use. Suicidal behavior was assessed by interviews, including the Scale for Suicidal Ideation, and by information from psychiatric records. Data were gathered from Feb. 1, 1997, to May 31, 1998. During the current MDD episode, 58% of all patients had experienced suicidal ideation; among the 15% of the total who had attempted suicide, almost all (95%) had also had suicidal ideation. In nominal regression models predicting suicidal ideation, hopelessness, alcohol dependence or abuse, low level of social and occupational functioning, and poor perceived social support were found to be significant (p < .05) independent risk factors. High severity of depression and current alcohol dependence or abuse in particular, but also younger age and low level of social and occupational functioning, predicted suicide attempt. Suicidal ideation is prevalent and appears to be a precondition for suicide attempts among psychiatric patients with MDD. The risk factors for suicidal ideation and attempts locate in several clinical and psychosocial domains. While these risk factors largely overlap, the overall level of psychopathology of suicide attempters is higher compared with that in patients with ideation, and substance use disorders and severity of depression may be of particular importance in predicting suicide attempts.


Intensity-modulated radiation treatment for head-and-neck squamous cell carcinoma--the University of Iowa experience.
To review the University of Iowa experience with intensity-modulated radiotherapy (IMRT) in the treatment of head-and-neck squamous cell carcinoma. From October 1999 to April 2004, 151 patients with head-and-neck squamous cell carcinoma were treated with IMRT for curative intent. One patient was lost to follow-up 2 months after treatment and therefore excluded from analysis. Of the remaining 150 patients, 99 were treated with definitive IMRT, and 51 received postoperative IMRT. Sites included were nasopharynx, 5; oropharynx, 56; larynx, 33; oral cavity, 29; hypopharynx, 8; nasal cavity/paranasal sinus, 8; and unknown primary, 11. None of the patients treated with postoperative IMRT received chemotherapy. Of 99 patients who had definitive IMRT, 68 patients received concurrent cisplatin-based chemotherapy. One patient received induction cisplatin-based chemotherapy, but no concurrent chemotherapy was given. Three clinical target volumes (CTV1, CTV2, and CTV3) were defined. The prescribed doses to CTV1, CTV2, and CTV3 in the definitive cohort were 70-74 Gy, 60 Gy, and 54 Gy, respectively. For high-risk postoperative IMRT, the prescribed doses to CTV1, CTV2, and CTV3 were 64-66 Gy, 60 Gy, and 54 Gy, respectively. For intermediate-risk postoperative IMRT, the prescribed doses to CTV1, CTV2, and CTV3 were 60 Gy, 60 Gy, and 54 Gy. The median follow-up was 18 months (range, 2-60 months). All living patients were followed for at least 6 months. There were 11 local-regional failures: 7 local failures, 3 regional failures, and 1 failure both in the primary tumor and regional lymph node. There were 16 patients who failed distantly, either with distant metastasis or new lung primaries. The 2-year overall survival, local progression-free survival, locoregional progression-free survival, and distant disease-free survival rates were 85%, 94%, 92%, and 87%, respectively. The median time from treatment completion to local-regional recurrence was 4.7 months (range, 1.8 to 15.6 months). Only one marginal failure was noted in a patient who had extensive tonsil cancer with tumor extension into the orbit and cavernous sinus. Patients with oropharyngeal cancer did significantly better than patients with oral cavity and laryngeal cancer, with a 2-year local-regional control rate of 98%, compared with 78% for oral cavity cancer and 85% for laryngeal cancer (p = 0.005). There was no significant difference in local-regional control for patients who received postoperative radiation or definitive radiation (p = 0.339) and for patients who had chemotherapy or not (p = 0.402). Neither T stage nor N stage had a significant effect on local-regional control (p = 0.722 and 0.712, respectively). Our results have confirmed the effectiveness of IMRT in head-and-neck cancer. It offers excellent outcomes in local-regional control and overall survival. More studies are necessary to further improve the outcomes of laryngeal cancer as well as oral cavity cancer.


Evictions and short-term all-cause mortality: a 3-year follow-up study of a middle-aged Swedish population.
This study sets out to explore whether being forcibly removed from one's home is related to all-cause mortality. With the help of unique register data covering all middle-aged persons registered at the Swedish Enforcement Authority with a case closed by an eviction during the period 2009-2011 (n = 2092), evictees' deaths from any cause that occurred within 3 years of the date of the eviction are compared with the all-cause mortality of a random sample of the Swedish population (n = 426,117). The analysis is based on penalized maximum likelihood logistic regressions. Those who had been evicted from their homes were found to be approximately one and a half times more likely to die from any cause than those who had not been exposed to this experience (OR = 1.59), controlling for several demographic, socio-economic and health conditions prior to the date of the eviction. The results provide support for the notion that the experience of losing one's dwelling place should be treated as a major life event in its own right, just like other well-established social stressors.


Transcriptional and posttranslational regulation of the general amino acid permease of Saccharomyces cerevisiae.
The cellular level and activity of the general amino acid permease, the product of the GAP1 gene of Saccharomyces cerevisiae, are regulated at the level of transcription by two systems, the products of URE2/GLN3 and NIL1 in response to the nitrogen sources of the growth medium and inactivation in response to the presence of glutamine or glutamate. Active permease is phosphorylated. The addition of glutamine causes rapid dephosphorylation and inactivation of the permease with the same kinetics, which is followed by slower disappearance of the protein. These results suggest that inactivation of the permease results from its dephosphorylation.


Safe handling and administration of antineoplastic chemotherapy.
Antineoplastic chemotherapy describes a group of hazardous drugs commonly used in the treatment of cancer. Since the discovery of their presence in nurses and pharmacists more than 2 decades ago, numerous studies have reported on the short- and long-term consequences of exposure. Guidelines describing proper equipment and procedures have been established in an effort to eliminate or minimize environmental and biologic exposure. Nursing compliance, however, has been variable. This article describes the dangers of exposure, how it occurs, and steps to keep nurses safe while working with these hazardous drugs.


A Common Glaucoma-risk Variant of SIX6 Alters Retinal Nerve Fiber Layer and Optic Disc Measures in a European Population: The EPIC-Norfolk Eye Study.
A common missense variant in the SIX6 gene (rs33912345) is strongly associated with primary open-angle glaucoma (POAG). We aimed to examine the association of rs33912345 with optic disc and retinal nerve fiber layer (RNFL) measures in a European population. We examined participants of the population-based EPIC-Norfolk Eye Study. Participants underwent confocal laser scanning tomography (Heidelberg Retina Tomograph II, HRT) to estimate optic disc rim area and vertical cup-disc ratio (VCDR). Scanning laser polarimetry (GDxVCC) was used to estimate average RNFL thickness. The mean of right and left eye values was considered for each participant. Genotyping was performed using the Affymetrix UK Biobank Axiom Array. Multivariable linear regression with the optic nerve head parameter as outcome variable and dosage of rs33912345 genotype as primary explanatory variable was used, adjusted for age, sex, disc area, axial length, and intraocular pressure. We further repeated analyses stratified into age tertiles. In total, 5433 participants with HRT data and 3699 participants with GDxVCC data were included. Each "C" allele of rs33912345 was associated with a smaller rim area (-0.030 mm [95% CI -0.040, -0.020]; P=5.4×10), a larger VCDR (0.025 [95% CI 0.017, 0.033]; P=3.3×10) and a thinner RNFL (-0.39 μm [95% CI -0.62, -0.15]; P=0.001). The RNFL association was strongest in the oldest age tertile, whereas rim area and VCDR associations were strongest in the youngest and oldest age tertiles. The protein-coding SIX6 variant rs33912345, previously associated with POAG, has a functional effect on glaucoma-associated optic nerve head traits in Europeans.


Airway covering during bed-sharing.
Parent-infant bed-sharing is a common practice in Western post-industrial nations with up to 50% of infants sleeping with their parents at some point during early infancy. However, researchers have claimed that infants may be at risk of suffocation or sudden infant death syndrome related to airway covering or compression in the bed-sharing environment. To further understand the role of airway covering and compression in creating risks for bed-sharing infants, we report here on a sleep-lab trial of two infant sleep conditions. In a sleep-lab environment 20 infants aged 2-3 months old slept in their parents' bed, and in a cot by the bed, on adjacent nights. Infants' oxygen saturation and heart rate were monitored physiologically while infant and parental behaviours were recorded via ceiling-mounted infra-red cameras. Infants served as their own controls. Continuous 8-h recordings were obtained for covering of infant external airways, levels of infant oxygen saturation, infant heart rate, evidence of parental compression/overlying of infant, circumstances leading up to potential infant airway obstruction, and parental awareness of and responses to infant airway covering. The majority of infants (14/20) spent some part of the bed night with their airways (both mouth and nose) covered, compared with 2/20 on the cot night; however, no consistent effect on either oxygen saturation levels or heart rate was revealed, even during prolonged bouts of airway covering. All cases of airway covering were initiated by parents; 70% were terminated by parents, the remainder by infants. Seven bouts of potential compression were observed with parental limbs resting across infant bodies for lengthy periods, however, in only two cases was the full weight of a parental limb resting on an infant, both events lasting less than 15 s, both being terminated by infant movement. Although numerous authors have suggested that bed-sharing infants face risks because of airway covering by bed-clothes or parental bodies, the present trial does not lend support to this hypothesis.


Multimodal graph-based reranking for web image search.
This paper introduces a web image search reranking approach that explores multiple modalities in a graph-based learning scheme. Different from the conventional methods that usually adopt a single modality or integrate multiple modalities into a long feature vector, our approach can effectively integrate the learning of relevance scores, weights of modalities, and the distance metric and its scaling for each modality into a unified scheme. In this way, the effects of different modalities can be adaptively modulated and better reranking performance can be achieved. We conduct experiments on a large dataset that contains more than 1000 queries and 1 million images to evaluate our approach. Experimental results demonstrate that the proposed reranking approach is more robust than using each individual modality, and it also performs better than many existing methods.


Dominant expression of a distinctive V14+ T-cell antigen receptor alpha chain in mice.
A distinctive variable region 14-positive (V14+) alpha chain (V alpha 14+) of the T-cell antigen receptor is predominantly expressed in multiple mouse subspecies. The V alpha 14 family has two members, V alpha 14.1 and V alpha 14.2, which differ by only three amino acids at positions 50-52. Based on the EcoRI restriction fragment length polymorphism of the gene encoding V alpha 14, mice can be divided into three groups: type I with an 11.2-kilobase (kb) fragment, type II with a 2.0-kb fragment, and type III with the 2.0-kb and 11.2-kb fragments. Usage of V alpha 14-J alpha 281, where J alpha 281 is an alpha-chain joining segment, with a one-base N region dominates at the level of 0.02-1.5% of alpha chains in all laboratory strains, Mus musculus castaneus, and Mus musculus domesticus but not in Mus musculus molossinus, Mus musculus musculus, and Mus spicilegus samples. The preferential V alpha 14-J alpha 281 expression seems to be due to positive selection because the V-J junctional region is always glycine, despite the ability of the V alpha 14 gene to associate with J alpha other than J alpha 281. As V alpha 14-J alpha 281 expression is independent of known major histocompatibility complex antigens, including H-2, TLA, Qa, and HMT, the selecting ligand must be a monomorphic molecule of the mouse, expressed in a subspecies-specific manner. Additional observations, such as the expression of homogeneous V alpha 14-J alpha 281 in athymic mice, suggest that the positive selection of V alpha 14+ T cells occurs extrathymically.


The cancer care experiences of gay, lesbian and bisexual patients: A secondary analysis of data from the UK Cancer Patient Experience Survey.
Understanding the effects of population diversity on cancer-related experiences is a priority in oncology care. Previous research demonstrates inequalities arising from variation in age, gender and ethnicity. Inequalities and sexual orientation remain underexplored. Here, we report, for the first time in the UK, a quantitative secondary analysis of the 2013 UK National Cancer Patient Experience Survey which contains 70 questions on specific aspects of care, and six on overall care experiences. 68,737 individuals responded, of whom 0.8% identified as lesbian, gay or bisexual. Controlling for age, gender and concurrent mental health comorbidity, logistic regression models applying post-estimate probability Wald tests explored response differences between heterosexual, bisexual and lesbian/gay respondents. Significant differences were found for 16 questions relating to: (1) a lack of patient-centred care and involvement in decision-making, (2) a need for health professional training and revision of information resources to negate the effects of heteronormativity and (3) evidence of substantial social isolation through cancer. These findings suggest a pattern of inequality, with less positive cancer experiences reported by lesbian, gay and (especially) bisexual respondents. Poor patient-professional communication and heteronormativity in the healthcare setting potentially explain many of the differences found. Social isolation is problematic for this group and warrants further exploration.


Changes in Diet, Sleep, and Physical Activity Are Associated With Differences in Negative Mood During COVID-19 Lockdown.
The United Kingdom and Scottish governments instigated a societal lockdown in response to the COVID-19 pandemic. Subsequently, many experienced substantial lifestyle changes alongside the stresses of potentially catching the virus or experiencing bereavement. Stressful situations and poorer health behaviors (e.g., higher alcohol consumption, unhealthy diet, poorer sleep quality, physical inactivity) are frequently linked to poor mental health. Our objective was to examine changes in health behaviors and their relationship with negative mood during COVID-19 lockdown. We also considered associations between health behaviors and socio-demographic differences and COVID-19-induced changes. 399 participants completed a questionnaire asking about their personal situation and health behaviors during lockdown as well as a negative mood scale. The significance threshold for all analyses was α = 0.05. Poorer diet was linked to more-negative mood, and to changes to working status. Poorer sleep quality was linked with more-negative mood, and with 'shielding' from the virus. Being less physically active was related to more-negative mood and student status, whereas being more physically active was linked to having or suspecting COVID-19 infection within the household. Increased alcohol consumption was linked to living with children, but not to negative mood. Changes to diet, sleep quality, and physical activity related to differences in negative mood during COVID-19 lockdown. This study adds to reports on poor mental health during lockdown and identifies lifestyle restrictions and changes to health behaviors which may, to some extent, be responsible for higher negative mood. Our data suggests that it is advisable to maintain or improve health behaviors during pandemic-associated restrictions.


Immunohistochemical quantitation of polycyclic aromatic hydrocarbon-DNA adducts in human lymphocytes.
The formation of polycyclic aromatic hydrocarbon-DNA adducts was studied in peripheral blood lymphocytes obtained from men with occupational and environmental exposure. Subjects included coke factory workers, residents from the vicinity of the cokery, and rural region inhabitants (16 individuals in each exposure group). Adducts were determined by immunohistochemical analysis using a polyclonal antiserum recognizing benzo(a)pyrene and related polycyclic aromatic hydrocarbon diol epoxide-DNA adducts, a biotinylated secondary antiserum, and streptavidin-conjugated FITC. Propidium iodide was used to quantitate nuclear DNA. Dual fluorescence intensities were simultaneously measured with a Zeiss Axiovert microscope and a Bio-Rad MRC-600 argon laser scanning confocal attachment. Adducts were significantly elevated (P < 0.001) in both occupational and environmental groups, as compared to the rural control group by Mann-Whitney U test. The distribution of the data indicated the existence of cells with relatively higher adduct levels. The percentages of these so called "higher adduct-level cells" were 13.6, 11.5, and 3.7 in cokery workers, environmentally exposed individuals, and rural controls, respectively. The immunohistochemical method allows visualization and relative quantitation of polycyclic aromatic hydrocarbon-DNA adducts in individual lymphocytes. It requires a much smaller amount of blood than the previously used 32P-postlabeling and ELISA methods, which used isolated bulk DNA. It can also be used for adduct quantitation in biopsy material. The results of this pilot study indicate that this technique is a promising addition to biomonitoring studies.


Intraperitoneal alpha-interferon alternating with cisplatin in residual ovarian carcinoma: a phase II Gynecologic Oncology Group study.
The aim of this study was to study the combination of intraperitoneal alpha-interferon and cisplatin administered second-line in an alternating sequence in small volume residual epithelial ovarian cancer after second-look surgery and the activity of this combination based on prior response to first-line platinum compounds. Sixty-two patients with minimal residual (<0.5 cm) epithelial ovarian cancer at reassessment laparotomy were entered into a multicenter trial of intraperitoneal alpha-interferon alternating with cisplatin given for eight cycles unless disease progression or unacceptable toxicity occurred. The patients were considered favorable if they were platinum-sensitive and/or relapsed 6 months or longer after completing treatment. Another reassessment laparotomy was performed within 12 weeks of completion of treatment in patients who were in clinical remission. Fifty-four patients were clinically evaluable and 18 were surgically reassessed, 5 of whom had a negative reassessment operation (20% complete response and 8% partial response). Of the 54 patients evaluable for toxicity, the most common adverse effects of more than grade 2 were gastrointestinal in 13 (47%), neutropenia in 9 (17%), and leukopenia in 6 (12%). Grade 4 toxicity was seen in 10 instances: 4 gastrointestinal, 2 neutropenia, 2 thrombocytopenia, 1 wound infection, and 1 allergic reaction. alpha-Interferon and cisplatin are active agents in favorable patients with minimal residual epithelial ovarian cancer at second-look. The combination of the two drugs administered in an alternating sequence appears to be associated with more side effects than when either drug is administered alone. The combination produced response rates similar to those seen when either drug is given alone.


Describing inorganic nanoparticles in the context of surface reactivity and catalysis.
Fabrication of inorganic nanoparticles is now a mature field. However, further advances, in particular in the field of catalysis, require a more accurate description of their surface and of the transformations occurring beneath the surface in the environment of use. Through a selection of case studies, this feature article proposes a journey from surface science to nanoparticle design, while illustrating state-of-the-art spectroscopies that help provide a relevant description of inorganic nanoparticles in the context of surface reactivity.


Phase shift formulas in uniaxial media: an application to waveplates.
The calculation of phase shift and optical path difference in birefringent media is related to a wide range of applications and devices. We obtain an explicit formula for the phase shift introduced by an anisotropic uniaxial plane-parallel plate with arbitrary orientation of the optical axis when the incident wave has an arbitrary direction. This allows us to calculate the phase shift introduced by waveplates when considering oblique incidence as well as optical axis misalignments. The expressions were obtained by using Maxwell's equations and boundary conditions without any approximation. They can be applied both to single plane wave and space-limited beams.


Targeted social mobilization in a global manhunt.
Social mobilization, the ability to mobilize large numbers of people via social networks to achieve highly distributed tasks, has received significant attention in recent times. This growing capability, facilitated by modern communication technology, is highly relevant to endeavors which require the search for individuals that possess rare information or skills, such as finding medical doctors during disasters, or searching for missing people. An open question remains, as to whether in time-critical situations, people are able to recruit in a targeted manner, or whether they resort to so-called blind search, recruiting as many acquaintances as possible via broadcast communication. To explore this question, we examine data from our recent success in the U.S. State Department's Tag Challenge, which required locating and photographing 5 target persons in 5 different cities in the United States and Europe - in under 12 hours - based only on a single mug-shot. We find that people are able to consistently route information in a targeted fashion even under increasing time pressure. We derive an analytical model for social-media fueled global mobilization and use it to quantify the extent to which people were targeting their peers during recruitment. Our model estimates that approximately 1 in 3 messages were of targeted fashion during the most time-sensitive period of the challenge. This is a novel observation at such short temporal scales, and calls for opportunities for devising viral incentive schemes that provide distance or time-sensitive rewards to approach the target geography more rapidly. This observation of '12 hours of separation' between individuals has applications in multiple areas from emergency preparedness, to political mobilization.


Dedifferentiated liposarcoma of the pleura mimicking a malignant solitary fibrous tumor and associated with dedifferentiated liposarcoma of the mediastinum: usefulness of cytogenetic and molecular genetic analyses.
Dedifferentiated liposarcoma of the pleura is an extremely rare malignancy mimicking a variety of tumors, such as other sarcomas, mesothelioma, and malignant solitary fibrous tumor of the pleura. Liposarcoma of the pleura can be combined with mediastinal involvement, and in most cases it may be impossible to be certain where the primary tumor originated. In this report, we describe a very rare occurence of a dedifferentiated liposarcoma of the pleura in a 76-year-old woman associated with a distinct second dedifferentiated liposarcoma of the mediastinum. Histologically, the pleural tumor demonstrated spindle cells arranged in a fascicular pattern, whereas the mediastinal tumor was mostly adipocytic with small areas of spindle cells. Vimentin and protein S100 were focally expressed by the tumor cells. The differential diagnosis of the pleural mass included malignant solitary fibrous tumor. Cytogenetic analysis showed supernumerary ring chromosomes in the pleural tumor, as well as strong amplification of MDM2 and CDK4 genes in both tumors. Array comparative genomic hybridization showed amplifications of chromosome arms 6q, 12q, and 15q, shared by both tumors and strongly pointing to a common origin.


Optokinetic nystagmus elicited by filling-in in adults with central scotoma.
Filling-in is the perceptual completion of physiological, pathologic, or artificial scotomas. Three patients are described, in whom optokinetic nystagmus (OKN) was present during filling-in. Three patients with age-related macular degeneration with large central scotomas were included in the study. OKN was elicited with black and white stripes moving nasally to temporally or temporally to nasally at four velocities. OKN gain was measured using infrared oculography. While looking at the OKN stimuli, the patients either did not see the stimulus (without perceiving a positive scotoma) or filled in the scotoma and perceived the stripes. Simultaneously with filling in the scotoma, OKN eye movements were elicited in all three patients. The filling-in phenomenon was present for all stimulus directions and velocities, appeared within seconds, and was followed immediately by eye movements corresponding to OKN. OKN gains during filling-in were similar to those of age-matched control subjects without scotomas. No asymmetry was noted between temporal to nasal or nasal to temporal stimulation. Motion-sensitive areas of the visual cortex may be activated and trigger the generation of OKN, supporting an active process. Alternatively, OKN is suppressed when subjects are not filling-in, while the subjects are fixating the central scotoma or edges of the scotoma. That the subjects did not perceive positive scotomas suggests that an active process is more likely.