Women from racial or ethnic minority and low socioeconomic backgrounds receive more prenatal education: Results from the 2012 to 2014 Pregnancy Risk Assessment Monitoring System.
Racial or ethnic and socioeconomic disparities in adverse birth outcomes are well known, but few studies have examined disparities in the receipt of prenatal health education. The objectives of this study were to examine racial or ethnic and socioeconomic variations in receiving (1) comprehensive prenatal health education and (2) education about human immunodeficiency virus (HIV) testing, breastfeeding, alcohol, and smoking cessation from health care practitioners. Data were drawn from the 2012 to 2014 Pregnancy Risk Assessment Monitoring System (PRAMS). Twenty-seven states were included with an analysis sample size of 68 025 participants. Receiving counseling on all listed health topics during prenatal care visits was denoted as comprehensive prenatal health education. Logistic regression was used to examine the association of racial or ethnic and socioeconomic variables with receiving comprehensive prenatal health education, and HIV testing, breastfeeding, alcohol, and smoking cessation advice separately. Multivariable results showed that racial or ethnic minorities and women with a high school degree or less; receiving Women, Infant, and Children (WIC) assistance; and on Medicaid during pregnancy have higher odds of receiving comprehensive prenatal health education (all P ≤0 .001). Results were similar for receiving HIV testing, breastfeeding, alcohol, and smoking counseling. Low household income was associated with receiving counseling on HIV testing, alcohol, and smoking (all P ≤ 0.001). Despite reporting higher levels of prenatal health education on a variety of health-related topics, disadvantaged women continue to experience disparities in adverse birth outcomes suggesting that education is insufficient in promoting positive behaviors and birth outcomes.


Rotationally adiabatic pair interactions of para- and ortho-hydrogen with the halogen molecules F2, Cl2, and Br2.
The present work is concerned with the weak interactions between hydrogen and halogen molecules, i.e., the interactions of pairs H2-X2 with X = F, Cl, Br, which are dominated by dispersion and quadrupole-quadrupole forces. The global minimum of the four-dimensional (4D) coupled cluster with singles and doubles and perturbative triples (CCSD(T)) pair potentials is always a T shaped structure where H2 acts as the hat of the T, with well depths (De) of 1.3, 2.4, and 3.1 kJ/mol for F2, Cl2, and Br2, respectively. MP2/AVQZ results, in reasonable agreement with CCSD(T) results extrapolated to the basis set limit, are used for detailed scans of the potentials. Due to the large difference in the rotational constants of the monomers, in the adiabatic approximation, one can solve the rotational Schrödinger equation for H2 in the potential of the X2 molecule. This yields effective two-dimensional rotationally adiabatic potential energy surfaces where pH2 and oH2 are point-like particles. These potentials for the H2-X2 complexes have global and local minima for effective linear and T-shaped complexes, respectively, which are separated by 0.4-1.0 kJ/mol, where oH2 binds stronger than pH2 to X2, due to higher alignment to minima structures of the 4D-pair potential. Further, we provide fits of an analytical function to the rotationally adiabatic potentials.


Self-efficacy, planning and action control in an oral self-care intervention.
To evaluate a theory-guided intervention on oral self-care and examine the possible mechanisms among self-regulatory factors, two brief intervention arms were compared, an information-based education treatment and a self-regulation treatment focusing on planning and action control. Young adults (N = 284; aged 18-29 years) were assessed at baseline and 1 month later. The self-regulation intervention improved levels of oral self-care, dental planning and action control. Moreover, a moderated mediation model with planning as the mediator between experimental conditions and dental outcome, and self-efficacy as well as action control as moderators elucidated the mechanism of change. More self-efficacious participants in the self-regulation condition benefitted in terms of more planning, and those who monitored their actions yielded higher levels of oral hygiene. Dental self-efficacy, dental planning and action control are involved in the improvement of oral self-care. Their joint consideration may contribute to a better understanding of health behavior change.


Attention to inpatients' religious and spiritual concerns: predictors and association with patient satisfaction.
Little is known about how often patients desire and experience discussions with hospital personnel regarding R/S (religion and spirituality) or what effects such discussions have on patient satisfaction. OBJECTIVE, DESIGN AND PARTICIPANTS: We examined data from the University of Chicago Hospitalist Study, which gathers sociodemographic and clinical information from all consenting general internal medicine patients at the University of Chicago Medical Center. Primary outcomes were whether or not patients desired to have their religious or spiritual concerns addressed while hospitalized, whether or not anyone talked to them about religious and spiritual issues, and which member of the health care team spoke with them about these issues. Primary predictors were patients' ratings of their religious attendance, their efforts to carry their religious beliefs over into other dealings in life, and their spirituality. Forty-one percent of inpatients desired a discussion of R/S concerns while hospitalized, but only half of those reported having such a discussion. Overall, 32% of inpatients reported having a discussion of their R/S concerns. Religious patients and those experiencing more severe pain were more likely both to desire and to have discussions of spiritual concerns. Patients who had discussions of R/S concerns were more likely to rate their care at the highest level on four different measures of patient satisfaction, regardless of whether or not they said they had desired such a discussion (odds ratios 1.4-2.2, 95% confidence intervals 1.1-3.0). These data suggest that many more inpatients desire conversations about R/S than have them. Health care professionals might improve patients' overall experience with being hospitalized and patient satisfaction by addressing this unmet patient need.


Carboxyl-functionalized nanochannels based on block copolymer hierarchical structures.
When building artificial nanochannels, having a scalable robust platform with controlled morphology is important, as well as having the option for final functionalization of the channels for the selective transport of water and proteins. We have previously developed asymmetric membranes that have a surface layer of very sharp pore size distribution, surface charge and pore functionalization. Here, a more complex bioinspired platform is reported. Hierarchical isotropic porous structures with spherical micrometer-sized cavities, interconnected by hexagonally ordered nanochannels, were prepared based on the phase separation of polystyrene-b-poly(t-butyl acrylate) block copolymers, following a nucleation and growth mechanism. The structure was imaged by scanning electron microscopy, which demonstrated a high density of ordered nanochannels. The hexagonal order formed by the self-assembly in solution was confirmed by small-angle X-ray scattering. The structure evolution was investigated by time-resolved grazing-incidence small-angle X-ray scattering. The assembled hydrophobic hierarchical structure was then converted to a hydrophilic structure by acid hydrolysis, leading to nanochannels covered by carboxylic groups and therefore convenient for water transport.


Q fever epidemic in Hungary, April to July 2013.
We investigated a Q fever outbreak with human patients showing high fever, respiratory tract symptoms, headache and retrosternal pain in southern Hungary in the spring and summer of 2013. Seventy human cases were confirmed by analysing their serum and blood samples with micro-immunofluorescence test and real-time PCR. The source of infection was a merino sheep flock of 450 ewes, in which 44.6% (25/56) seropositivity was detected by enzyme-linked immunosorbent assay. Coxiella burnetii DNA was detected by real-time PCR in the milk of four of 20 individuals and in two thirds (41/65) of the manure samples. The multispacer sequence typing examination of C. burnetii DNA revealed sequence type 18 in one human sample and two manure samples from the sheep flock. The multilocus variable-number tandem repeat analysis pattern of the sheep and human strains were also almost identical, 4/5-9-3-3-0-5 (Ms23-Ms24-Ms27-Ms28-Ms33-Ms34). It is hypothesised that dried manure and maternal fluid contaminated with C. burnetii was dispersed by the wind from the sheep farm towards the local inhabitants. The manure was eliminated in June and the farm was disinfected in July. The outbreak ended at the end of July 2013.


Comparison of mitochondrial and nucleolar RNase MRP reveals identical RNA components with distinct enzymatic activities and protein components.
RNase MRP is a ribonucleoprotein endoribonuclease found in three cellular locations where distinct substrates are processed: the mitochondria, the nucleolus, and the cytoplasm. Cytoplasmic RNase MRP is the nucleolar enzyme that is transiently relocalized during mitosis. Nucleolar RNase MRP (NuMRP) was purified to homogeneity, and we extensively purified the mitochondrial RNase MRP (MtMRP) to a single RNA component identical to the NuMRP RNA. Although the protein components of the NuMRP were identified by mass spectrometry successfully, none of the known NuMRP proteins were found in the MtMRP preparation. Only trace amounts of the core NuMRP protein, Pop4, were detected in MtMRP by Western blot. In vitro activity of the two enzymes was compared. MtMRP cleaved only mitochondrial ORI5 substrate, while NuMRP cleaved all three substrates. However, the NuMRP enzyme cleaved the ORI5 substrate at sites different than the MtMRP enzyme. In addition, enzymatic differences in preferred ionic strength confirm these enzymes as distinct entities. Magnesium was found to be essential to both enzymes. We tested a number of reported inhibitors including puromycin, pentamidine, lithium, and pAp. Puromycin inhibition suggested that it binds directly to the MRP RNA, reaffirming the role of the RNA component in catalysis. In conclusion, our study confirms that the NuMRP and MtMRP enzymes are distinct entities with differing activities and protein components but a common RNA subunit, suggesting that the RNA must be playing a crucial role in catalytic activity.


Representations and evolutionary operators for the scheduling of pump operations in water distribution networks.
Reducing the energy consumption of water distribution networks has never had more significance. The greatest energy savings can be obtained by carefully scheduling the operations of pumps. Schedules can be defined either implicitly, in terms of other elements of the network such as tank levels; or explicitly, by specifying the time during which each pump is on/off. The traditional representation of explicit schedules is a string of binary values with each bit representing pump on/off status during a particular time interval. In this paper, we formally define and analyze two new explicit representations based on time-controlled triggers, where the maximum number of pump switches is established beforehand and the schedule may contain fewer than the maximum number of switches. In these representations, a pump schedule is divided into a series of integers with each integer representing the number of hours for which a pump is active/inactive. This reduces the number of potential schedules compared to the binary representation, and allows the algorithm to operate on the feasible region of the search space. We propose evolutionary operators for these two new representations. The new representations and their corresponding operations are compared with the two most-used representations in pump scheduling, namely, binary representation and level-controlled triggers. A detailed statistical analysis of the results indicates which parameters have the greatest effect on the performance of evolutionary algorithms. The empirical results show that an evolutionary algorithm using the proposed representations is an improvement over the results obtained by a recent state of the art hybrid genetic algorithm for pump scheduling using level-controlled triggers.


Ocular injury induced by methyl ethyl ketone peroxide.
Methyl ethyl ketone peroxide is a commonly used catalyst in various industries. We studied 19 eyes with a single exposure to methyl ethyl ketone peroxide that developed clinical patterns of mild injury, moderate injury, severe injury, or delayed keratitis. Delayed methyl ethyl ketone peroxide keratitis may cause exacerbations and remissions of corneal and limbal disease lasting more than 20 years with palpebral and bulbar hyperemia equal to the initial chemical exposure. With repeat exacerbation, further pannus may occur, which can be associated with a poorer outcome. Based on the capability of methyl ethyl ketone peroxide to change DNA to a new weak antigen, we suggest possible methods of therapy to prevent or limit delayed methyl ethyl ketone peroxide keratitis. This proposed type of injury has important implications in studying various limbal and corneal diseases. A major factor in the severity of ocular injury was the length of time from exposure to methyl ethyl ketone peroxide to obtaining a topical ocular local anesthetic to perform adequate lavage.


Essential Role of the Linker Region in the Higher Catalytic Efficiency of a Bifunctional MsrA-MsrB Fusion Protein.
Many bacteria, particularly pathogens, possess methionine sulfoxide reductase A (MsrA) and B (MsrB) as a fusion form (MsrAB). However, it is not clear why they possess a fusion MsrAB form rather than the separate enzymes that exist in most organisms. In this study, we performed biochemical and kinetic analyses of MsrAB from Treponema denticola (TdMsrAB), single-domain forms (TdMsrA and TdMsrB), and catalytic Cys mutants (TdMsrAB(C11S) and TdMsrAB(C285S)). We found that the catalytic efficiency of both MsrA and MsrB increased after fusion of the domains and that the linker region (iloop) that connects TdMsrA and TdMsrB is required for the higher catalytic efficiency of TdMsrAB. We also determined the crystal structure of TdMsrAB at 2.3 Å, showing that the iloop mainly interacts with TdMsrB via hydrogen bonds. Further kinetic analysis using the iloop mutants revealed that the iloop-TdMsrB interactions are critical to MsrB and MsrA activities. We also report the structure in which an oxidized form of dithiothreitol, an in vitro reductant for MsrA and MsrB, is present in the active site of TdMsrA. Collectively, the results of this study reveal an essential role of the iloop in maintaining the higher catalytic efficiency of the MsrAB fusion enzyme and provide a better understanding of why the MsrAB enzyme exists as a fused form.


Functional and biochemical subtypes of the haplotype HLA-DR3 in patients with celiac disease or idiopathic membranous nephropathy.
HLA class II beta-chain polymorphism was investigated in the haplotype HLA-DR3 to determine if patients with HLA-DR3-associated diseases express normal or variant class II polymorphisms. Analysis was carried out by two-dimensional gel electrophoresis of immunoprecipitated HLA class II molecules, DNA hybridization with DR beta and DQ beta gene probes on Taq 1, Bam H1, or Rsa 1 digests, and mixed lymphocyte culture. Two subtypes of HLA-DR3 were identified in normal homozygous DR3 individuals on the basis of polymorphism in one of two DR beta chains detected, corresponding to differences in DR beta restriction fragment patterns. These polymorphisms exhibited significant linkage disequilibrium with the A1,B8,DR3 and B18,DR3 haplotypes, respectively. In proliferative experiments, cells with the B18,DR3-associated polymorphism strongly stimulated cells from donors with the B8,DR3-related polymorphism, suggesting that a T-cell epitope recognized by B8,DR3 cells lies on the B18,DR3-associated DR beta chain. In seven HLA-DR3 homozygous patients with celiac disease and three HLA-DR3-homozygous patients with idiopathic membranous nephropathy, only the normal patterns of HLA class II molecules were displayed, the B8,DR3 type occurring in all patients and the B18,DR3 type in one patient. These data suggest that celiac disease and idiopathic membranous nephropathy are not related to disease-specific HLA-DR beta or -DQ beta gene variants within the DR3 population that are revealed by these methods.


Learning and performance of tracheal intubation by novice personnel: a comparison of the Airtraq and Macintosh laryngoscope.
Direct laryngoscopic tracheal intubation is taught to many healthcare professionals as it is a potentially lifesaving procedure. However, it is a difficult skill to acquire and maintain, and, of concern, the consequences of poorly performed intubation attempts are potentially serious. The Airtraq Laryngoscope is a novel intubation device which may possess advantages over conventional direct laryngoscopes for use by novice personnel. We conducted a prospective trial with 40 medical students who had no prior airway management experience. Following brief didactic instruction, each participant took turns in performing laryngoscopy and intubation using the Macintosh and Airtraq devices under direct supervision. Each student was allowed up to three attempts to intubate in three laryngoscopy scenarios using a Laerdal Intubation Trainer and one scenario in a Laerdal SimMan Manikin. They then performed tracheal intubation of the normal airway a second time to characterise the learning curve for each device. The Airtraq provided superior intubating conditions, resulting in greater success of intubation, particularly in the difficult laryngoscopy scenarios. In both easy and simulated difficult laryngoscopy scenarios, the Airtraq decreased the duration of intubation attempts, reduced the number of optimisation manoeuvres required, and reduced the potential for dental trauma. The Airtraq device showed a rapid learning curve and the students found it significantly easier to use. The Airtraq appears to be a superior device for novice personnel to acquire the skills of tracheal intubation.


The physical association of multiple molecular chaperone proteins with mutant p53 is altered by geldanamycin, an hsp90-binding agent.
Wild-type p53 is a short-lived protein which turns over very rapidly via selective proteolysis in the ubiquitin-proteasome pathway. Most p53 mutations, however, encode for protein products which display markedly increased intracellular levels and are associated with positive tumor-promoting activity. The mechanism by which mutation leads to impairment of ubiquitination and proteasome-mediated degradation is unknown, but it has been noted that many transforming p53 mutants are found in stable physical association with molecular chaperones of the hsp70 class. To explore a possible role for aberrant chaperone interactions in mediating the altered function of mutant p53 and its intracellular accumulation, we examined the chaperone proteins which physically associate with a temperature-sensitive murine p53 mutant. In lysate prepared from A1-5 cells grown under mutant temperature conditions, hsp70 coprecipitated with p53Val135 as previously reported by others, but in addition, other well-recognized elements of the cellular chaperone machinery, including hsp90, cyclophilin 40, and p23, were detected. Under temperature conditions favoring wild-type p53 conformation, the coprecipitation of chaperone proteins with p53 was lost in conjunction with the restoration of its transcriptional activating activity. Chaperone interactions similar to those demonstrated in A1-5 cells under mutant conditions were also detected in human breast cancer cells expressing two different hot-spot mutations. To examine the effect of directly disrupting chaperone interactions with mutant p53, we made use of geldanamycin (GA), a selective hsp90-binding agent which has been shown to alter the chaperone associations regulating the function of unliganded steroid receptors. GA treatment of cells altered heteroprotein complex formation with several different mutant p53 species. It increased p53 turnover and resulted in nuclear translocation of the protein in A1-5 cells. GA did not, however, appear to restore wild-type transcriptional activating activity to mutant p53 proteins in either A1-5 cells or human breast cancer cell lines.


BioCARS: a synchrotron resource for time-resolved X-ray science.
BioCARS, a NIH-supported national user facility for macromolecular time-resolved X-ray crystallography at the Advanced Photon Source (APS), has recently completed commissioning of an upgraded undulator-based beamline optimized for single-shot laser-pump X-ray-probe measurements with time resolution as short as 100 ps. The source consists of two in-line undulators with periods of 23 and 27 mm that together provide high-flux pink-beam capability at 12 keV as well as first-harmonic coverage from 6.8 to 19 keV. A high-heat-load chopper reduces the average power load on downstream components, thereby preserving the surface figure of a Kirkpatrick-Baez mirror system capable of focusing the X-ray beam to a spot size of 90 µm horizontal by 20 µm vertical. A high-speed chopper isolates single X-ray pulses at 1 kHz in both hybrid and 24-bunch modes of the APS storage ring. In hybrid mode each isolated X-ray pulse delivers up to ~4 × 10(10) photons to the sample, thereby achieving a time-averaged flux approaching that of fourth-generation X-FEL sources. A new high-power picosecond laser system delivers pulses tunable over the wavelength range 450-2000 nm. These pulses are synchronized to the storage-ring RF clock with long-term stability better than 10 ps RMS. Monochromatic experimental capability with Biosafety Level 3 certification has been retained.


Rapid recombinant protein production from piggyBac transposon-mediated stable CHO cell pools.
Heterogeneous populations of stably transfected cells (cell pools) can serve for the rapid production of moderate amounts of recombinant proteins. Here, we propose the use of the piggyBac (PB) transposon system to improve the productivity and long-term stability of cell pools derived from Chinese hamster ovary (CHO) cells. PB is a naturally occurring genetic element that has been engineered to facilitate the integration of a transgene into the genome of the host cell. In this report PB-derived cell pools were generated after 10 days of selection with puromycin. The resulting cell pools had volumetric productivities that were 3-4 times higher than those achieved with cell pools generated by conventional plasmid transfection even though the number of integrated transgene copies per cell was similar in the two populations. In 14-day batch cultures, protein levels up to 600 and 800 mg/L were obtained for an Fc-fusion protein and a monoclonal antibody, respectively, at volumetric scales up to 1L. In general, the volumetric protein yield from cell pools remained constant for up to 3 months in the absence of selection. In conclusion, transfection of CHO cells with the PB transposon system is a simple, efficient, and reproducible approach to the generation of cell pools for the rapid production of recombinant proteins.


Antihyperlipidemic effects of ginger extracts in alloxan-induced diabetes and propylthiouracil-induced hypothyroidism in (rats).
Diabetic mellitus and hypothyroidism lead to serum lipoproteins disorders. This study aims to investigate the potential effect of fresh ginger extracts Zingiber officinale roscoe (Family: Zingebiraceae) on serum lipid profile and on blood glucose in alloxan-induced diabetes and propylthiouracil-induced hypothyroidism in rats. Rats were divided into 11 groups: The normal G1, diabetic control rats G2, ginger 500 mg/kg treated diabetic rats G3, 10 mg/day atorvastatine-treated diabetic rats G4, [5 mg/day atorvastatine combined with 500 mg/kg ginger] treated diabetic rats G5, glibenclamid-treated diabetic rats G6, hypothyoidism control rats G7, 300 mg/kg ginger-treated hypothyroidism rats G8, 500 mg/kg ginger-treated hypothyroidism rats G9, 10 mg/day atorvastatine-treated hypothyroidism rats G10, [atorvastatine combined with 500 mg/kg ginger]treated hypothyroidism rats G11. Thirty days after treatment, samples were collected, to compare treated groups with normal and control groups, using Mann-Whitney U test P < 0.01. It revealed a decrease in the levels of total cholesterol (TC), and low density lipoprotein (LDL) in the serum of rats that were treated by ginger extracts, compared with the control groups. Previous extracts were also able to cause reduction in LDL to similar levels compared to normal group and that was the same effect of atorvastatin 10 mg/day. Combined effect was clear between the act of ginger at a dose of 500 mg/kg and atorvastatin; that levels of both TC and LDL in animals which received [atorvastatin 5 mg/day combined with ginger extract] was almost equal to levels in animals that received atorvastatin 10mg/day. Clear reduce in triglyceride, and clear increase in high density liopprotein were also recorded in the ginger-treated groups. Ginger was more active in hypothyroidism rats than in diabetic rats in reducing LDL and TC. Glucose levels were substantially reduced in ginger- treated diabetic groups.


Rapid granular flows on a rough incline: phase diagram, gas transition, and effects of air drag.
We report experiments on the overall phase diagram of granular flows on an incline with emphasis on high inclination angles where the mean layer velocity approaches the terminal velocity of a single particle free falling in air. The granular flow was characterized by measurements of the surface velocity, the average layer height, and the mean density of the layer as functions of the hopper opening, the plane inclination angle, and the downstream distance x of the flow. At high inclination angles the flow does not reach an x -invariant steady state over the length of the inclined plane. For low volume flow rates, a transition was detected between dense and very dilute (gas) flow regimes. We show using a vacuum flow channel that air did not qualitatively change the phase diagram and did not quantitatively modify mean flow velocities of the granular layer except for small changes in the very dilute gaslike phase.


Visual Acuity Outcome over Time in Non-Infectious Uveitis.
Introduction: We evaluated visual acuity (VA) over 5 years in a subspecialty noninfectious uveitis population.Methods: Retrospective data from 5,530 noninfectious uveitis patients with anterior, intermediate, posterior or panuveitis were abstracted by expert reviewers. Mean VA was calculated using inverse probability of censoring weighting to account for losses to follow-up.Results: Patients were a median of 41 years old, 65% female, and 73% white. Initial mean VA was worse among panuveitis (20/84) than posterior (20/64), intermediate (20/47), and anterior (20/37) uveitides. On average, mean VA improved by 0.62, 0.51, 0.37, and 0.26 logMAR-equivalent lines over 2 years, respectively (each P < .001), then remained stable, except posterior uveitis mean VA worsened to initial levels.Conclusion: Mean VA of uveitic eyes improved and, typically, improvement was sustained under uveitis subspecialty care. Because VA tends to improve under tertiary care, mean VA change appears a better outcome for clinical studies than time-to-loss of VA.


A 4-hour Profile of 17-hydroxyprogesterone in Salt-wasting Congenital Adrenal Hyperplasia: Is the Serial Monitoring Strategy Worth the Effort?
Since there is no gold standard laboratory variable for adjustment of treatment in congenital adrenal hyperplasia (CAH), the aim was to assess the use of a 4-hour profile of serum 17-hydroxyprogesterone (17-OHP) to determine the most appropriate sample time and level of 17-OHP in predicting the metabolic control and evaluate the role of sex hormone-binding globulin (SHBG) in hyperandrogenemia. This study included children with salt-wasting CAH. Measurements for 17-OHP and cortisol were made from samples obtained before and 1, 2, and 4 hours after the morning dose of hydrocortisone. Patients were designated to have poor metabolic control when androstenedione levels according to age and sex-specific reference intervals were high and annual height standard deviation score (SDS) changes were ≥0.5. The study cohort was 16 children (9 girls) with a median age of 7-years old. Premedication 17-OHP levels were strongly correlated with 17-OHP levels 1, 2, and 4 hours after the morning dose (rs=0.929, p<0.01; rs=0.943, p<0.01; rs=0.835, p<0.01, respectively). 17-OHP profiles (0, 1, 2, 4 hours) of poor (n=6) and good (n=10) metabolically controlled cases were similar. Among the patients with poor metabolic control, two cases had 17-OHP levels <2 ng/mL at all times. The remaining patients with poor metabolic control had median 17-OHP levels above 104 ng/mL, 82 ng/mL, 14 ng/mL, and 4 ng/mL, for baseline and 1, 2, and 4 hours, respectively. Differences between the poor and well-controlled group were androstenedione levels with respect to upper limit of normal [1.8 (1.5) and 0.5 (1.5) ng/mL, respectively p=0.03], annual change in height SDS [0.7 (0.2) and -0.03 (0.8) SDS, respectively, p=0.001], and daily hydrocortisone doses [7 (6) and 16 (8) mg/m2/day, respectively, p=0.02]. Androstenedione and SHBG levels were negatively correlated in the pubertal children (rs=-0.7, p=0.04). We conclude that: (i) a 4-hour 17-OHP profile is not useful in predicting hyperandrogenemia; (ii) suppressed levels of 17-OHP do not always indicate overtreatment; (iii) reference intervals of 17-OHP for different time periods might be of importance; (iv) low hydrocortisone doses should be avoided; and (v) SHBG could be used in pubertal children as an indicator of hyperandrogenemia.


Viroplasm matrix protein Pns9 from rice gall dwarf virus forms an octameric cylindrical structure.
The non-structural Pns9 protein of rice gall dwarf virus (RGDV) accumulates in viroplasm inclusions, which are structures that appear to play an important role in viral morphogenesis and are commonly found in host cells infected by viruses in the family Reoviridae. Immunofluorescence and immunoelectron microscopy of RGDV-infected vector cells in monolayers, using antibodies against Pns9 of RGDV and expression of Pns9 in Spodoptera frugiperda cells, demonstrated that Pns9 is the minimal viral factor necessary for formation of viroplasm inclusion during infection by RGDV. When Pns9 in solution was observed under a conventional electron microscope, it appeared as ring-like aggregates of approximately 100 Å in diameter. Cryo-electron microscopic analysis of these aggregates revealed cylinders of octameric Pns9, whose dimensions were similar to those observed under the conventional electron microscope. Octamerization of Pns9 in solution was confirmed by the results of size-exclusion chromatography. Among proteins of viruses that belong to the family Reoviridae whose three-dimensional structures are available, a matrix protein of the viroplasm of rotavirus, NSP2, forms similar octamers, an observation that suggests similar roles for Pns9 and NSP2 in morphogenesis in animal-infecting and in plant-infecting reoviruses.


Childhood obesity - what we can learn from existing data on societal trends, part 1.
The number of overweight and obese youth has increased in recent decades, and numerous theories on causes have been proposed. Yet almost no data are available to assess how the lives of children have changed during the "obesity epidemic." What are children and adolescents now doing with their time that they did not do before? Are they participating less in sports? Watching more television? Doing more homework? Without tracking these broader societal changes, it is difficult to identify the most (and least) promising areas for interventions. This two-part report compiles trend data for several areas. Part 1 discusses trends in time use, homework, and media use; part 2 discusses trends in transportation, physical education, and diet. The main findings of this article are the following: One, the free time of children has substantially declined because of increased time away from home, primarily in school, day care, and after-school programs. Two, participation in organized activities (including sports) has also increased. Three, unstructured playtime has decreased to make room for organized activities. Four, time spent in some sedentary activities like watching television, participating in conversations, or taking part in other passive leisure activities also declined just when obesity became a major concern. Five, increases in homework have not caused decreases in free time, contradicting a common belief in education circles.


Effect of pulsed electric fields on the flavour profile of red-fleshed sweet cherries (Prunus avium var. Stella).
The aim of this research was to study the effect of pulsed electric fields (PEF) on the flavour profile of red-fleshed sweet cherries (Prunus avium variety Stella). The cherry samples were treated at a constant pulse frequency of 100 Hz, a constant pulse width of 20 μs, different electric field strengths between 0.3 and 2.5 kV/cm and specific energy ranging from 31 to 55 kJ/kg. Volatile compounds of samples were analysed using an automated headspace solid phase microextraction (HS-SPME) method coupled with gas chromatography-mass spectrometry (GC-MS). A total of 33 volatile compounds were identified with benzaldehyde, hexanal, (E)-2-hexenal, (Z)-2-hexen-1-ol, and benzyl alcohol being the predominant volatiles in different PEF-treated samples. Aldehydes namely butanal, octanal, 2-octenal, and nonanal, and (Z)-2-hexen-1-ol increased significantly 24 h after PEF treatment at electric field strengths of more than 1.0 kV/cm. Samples incubated for 24 h after PEF treatment (S3) generated higher concentrations of volatiles than samples immediately after PEF treatments (S2). Quantitative results revealed that more flavour volatiles were released and associated with S3 samples after 24 h storage and S2 samples immediately after PEF both with the highest electric field intensities. Interestingly, this study found that the PEF treatments at the applied electric field strength and energy did not result in releasing/producing undesirable flavour compounds.


The multi-annual carbon budget of a peat-covered catchment.
This study estimates the complete carbon budget of an 11.4 km(2) peat-covered catchment in Northern England. The budget considers both fluvial and gaseous carbon fluxes and includes estimates of particulate organic carbon (POC); dissolved organic carbon (DOC); excess dissolved CO(2); release of methane (CH(4)); net ecosystem respiration of CO(2); and uptake of CO(2) by primary productivity. All components except CH(4) were measured directly in the catchment and annual carbon budgets were calculated for the catchment between 1993 and 2005 using both extrapolation and interpolation methods. The study shows that: Over the 13 year study period the total carbon balance varied between a net sink of -20 to -91 Mg C/km(2)/yr. The biggest component of this budget is the uptake of carbon by primary productivity (-178 Mg C/km(2)/yr) and in most years the second largest component is the loss of DOC from the peat profile (+39 Mg C/km(2)/yr). Direct exchanges of C with the atmosphere average -89 Mg C/km(2)/yr in the catchment. Extrapolating the general findings of the carbon budget across all UK peatlands results in an approximate carbon balance of -1.2 Tg C/yr (+/-0.4 Pg C/yr) which is larger than previously reported values. Carbon budgets should always be reported with a clear statement of the techniques used and errors involved as this is significant when comparing results across studies.


Genomic variation at the tips of the adaptive radiation of Darwin's finches.
Adaptive radiation unfolds as selection acts on the genetic variation underlying functional traits. The nature of this variation can be revealed by studying the tips of an ongoing adaptive radiation. We studied genomic variation at the tips of the Darwin's finch radiation; specifically focusing on polymorphism within, and variation among, three sympatric species of the genus Geospiza. Using restriction site-associated DNA (RAD-seq), we characterized 32 569 single-nucleotide polymorphisms (SNPs), from which 11 outlier SNPs for beak and body size were uncovered by a genomewide association study (GWAS). Principal component analysis revealed that these 11 SNPs formed four statistically linked groups. Stepwise regression then revealed that the first PC score, which included 6 of the 11 top SNPs, explained over 80% of the variation in beak size, suggesting that selection on these traits influences multiple correlated loci. The two SNPs most strongly associated with beak size were near genes associated with beak morphology across deeper branches of the radiation: delta-like 1 homologue (DLK1) and high-mobility group AT-hook 2 (HMGA2). Our results suggest that (i) key adaptive traits are associated with a small fraction of the genome (11 of 32 569 SNPs), (ii) SNPs linked to the candidate genes are dispersed throughout the genome (on several chromosomes), and (iii) micro- and macro-evolutionary variation (roots and tips of the radiation) involve some shared and some unique genomic regions.


Real-time monitoring of plasmonic evolution in thick Ag:SiO(2) films: nanocomposite optical tuning.
An in situ optical microspectroscopy study of the surface plasmon resonance (SPR) evolution of Ag nanoparticles (NPs) embedded in thick SiO(2) films deposited on soda-lime glass has been conducted during thermal processing in air. The temperature and time dependences of the SPR were analyzed in the context of Mie extinction and crystal growth theories and were discussed along with consideration of oxidation processes and film/substrate physicochemical interactions. At relatively high temperatures, Ag NPs were indicated to grow first through a diffusion-based process and subsequently via Ostwald ripening. At lower temperatures, an initial decrease in Ag particle size was indicated due to oxidation, followed by NP diffusion-based growth. The growth and oxidation stages appeared temperature and time dependent, allowing for the tuning of material properties. The product of Ag NP oxidation was revealed by photoluminescence spectroscopy performed ex situ as single Ag(+) ions. The oxidative effect of the air atmosphere on Ag NPs was shown to be ultimately circumvented by the thick nanocomposite film. The phenomenon was explained on the basis of the displacement of the Ag/Ag(+) redox equilibrium toward Ag NP stability after ion migration toward the substrate being self-constrained. In addition, the current spectroscopic approach has been proposed for estimating the activation energy for silver diffusion in the SiO(2) matrix.


Molecular evolution of the keratin associated protein gene family in mammals, role in the evolution of mammalian hair.
Hair is unique to mammals. Keratin associated proteins (KRTAPs), which contain two major groups: high/ultrahigh cysteine and high glycine-tyrosine, are one of the major components of hair and play essential roles in the formation of rigid and resistant hair shafts. The KRTAP family was identified as being unique to mammals, and near-complete KRTAP gene repertoires for eight mammalian genomes were characterized in this study. An expanded KRTAP gene repertoire was found in rodents. Surprisingly, humans have a similar number of genes as other primates despite the relative hairlessness of humans. We identified several new subfamilies not previously reported in the high/ultrahigh cysteine KRTAP genes. Genes in many subfamilies of the high/ultrahigh cysteine KRTAP genes have evolved by concerted evolution with frequent gene conversion events, yielding a higher GC base content for these gene sequences. In contrast, the high glycine-tyrosine KRTAP genes have evolved more dynamically, with fewer gene conversion events and thus have a lower GC base content, possibly due to positive selection. Most of the subfamilies emerged early in the evolution of mammals, thus we propose that the mammalian ancestor should have a diverse KRTAP gene repertoire. We propose that hair content characteristics have evolved and diverged rapidly among mammals because of rapid divergent evolution of KRTAPs between species. In contrast, subfamilies of KRTAP genes have been homogenized within each species due to concerted evolution.


Challenges in using geographic information systems (GIS) to understand and control malaria in Indonesia.
Malaria is a mosquito-borne disease of global concern with 1.5 to 2.7 million people dying each year and many more suffering from it. In Indonesia, malaria is a major public health issue with around six million clinical cases and 700 deaths each year. Malaria is most prevalent in the developing countries of the world. Aid agencies have provided financial and technical assistance to malaria-prone countries in an effort to battle the disease. Over the past decade, the focus of some of this assistance has been in the provision of geographic information systems (GIS) hardware, software and training. In theory, GIS can be a very effective tool in combating malaria, however, in practice there have been a host of challenges to its successful use.This review is based, in part, on the literature but also on our experience working with the Indonesian Ministry of Health. The review identifies three broad problem areas. The first of these relates to data concerns. Without adequate data, GIS is not very useful. Specific problem areas include: accurate data on the disease and how it is reported; basic environmental data on vegetation, land uses, topography, rainfall, etc.; and demographic data on the movement of people. The second problem area involves technology - specifically computer hardware, GIS software and training. The third problem area concerns methods - assuming the previous data and technological problems have been resolved - how can GIS be used to improve our understanding of malaria? One of the main methodological tools is spatial statistical analysis, however, this is a newly developing field, is not easy to understand and suffers from the fact that there is no agreement on standard methods of analysis.The paper concludes with a discussion of strategies that can be used to overcome some of these problems. One of these strategies involves using ArcView GIS software in combination with ArcExplorer (a public domain program that can read ArcView files) to deal with the problem of needing multiple copies of GIS software. Another strategy involves the development of a self-paced training package that can be used to train individuals


Vps4A functions as a tumor suppressor by regulating the secretion and uptake of exosomal microRNAs in human hepatoma cells.
The deregulation of microRNAs (miRNAs) plays an important role in human hepatocarcinogenesis. In this study, we highlight exosomes as mediators involved in modulating miRNA profiles in hepatocellular carcinoma (HCC) cells. First, we examined the different miRNA expression profiles in HCC cells and HCC cell-derived exosomes. Next, coculture experiments indicated that HCC cell-derived exosomes promoted the cell growth, migration, and invasion of HCC cells and had the ability to shuttle miRNAs to recipient cells. Further, our data showed that Vps4A, a key regulator of exosome biogenesis, was frequently down-regulated in HCC tissues. The reduction of Vps4A in HCC tissues was associated with tumor progression and metastasis. In vitro studies revealed that Vps4A repressed the growth, colony formation, migration, and invasion of HCC cells. We further investigated the role and involvement of Vps4A in suppressing the bioactivity of exosomes and characterized its ability to weaken the cell response to exosomes. By small RNA sequencing, we demonstrated that Vps4A facilitated the secretion of oncogenic miRNAs in exosomes as well as accumulation and uptake of tumor suppressor miRNAs in cells. A subset of Vps4A-associated miRNAs was identified. Kyoto Encyclopedia of Genes and Genomes pathway analysis indicated that the phosphatidylinositol-3-kinase/Akt signaling pathway was the most likely candidate pathway for modulation by these miRNAs. Indeed, we proved that the phosphatidylinositol-3-kinase/Akt pathway was inactivated by Vps4A overexpression. Exosome-mediated miRNA transfer is an important mechanism of self-modulation of the miRNA expression profiles in HCC cells, and Vps4A may function as a tumor suppressor, which utilizes exosomes as mediators to regulate the secretion and uptake of miRNAs in hepatoma cells; these observations provide new insights into the development of HCC.


Corticosteroid and Biologic Use Not Associated With Adverse Outcomes for Inflammatory Bowel Disease Patients Hospitalized With COVID-19.
To date, studies investigating the inflammatory bowel disease (IBD) patient experience with coronavirus disease 2019 (COVID-19) have consistently reported that the observed rate of COVID-19 within this population is similar to the general population. Limited research has suggested that corticosteroid use in the IBD population may be associated with worse COVID-19 outcomes, but it is still yet to be determined if specific IBD-related clinical factors are associated with worse outcomes. Our goal was to describe clinical COVID-19 outcomes for IBD patients and to identify the clinical factors that may be associated with worse outcomes. In this retrospective study, we utilized the inpatient database within the largest hospital network in the New York City Metropolitan area to identify all IBD patients with confirmed COVID-19. Of 83 IBD/COVID-19 patients presenting to a hospital network emergency room, 56 were hospitalized. Overall, 19.6% of hospitalized IBD patients died, compared with 22.2% of all hospital system COVID-19 patients during the time period. There was no association between pre-admission corticosteroid use or biologic treatment with a severe course of COVID-19. In contrast to some prior reports, we did not observe an association of pre-admission corticosteroid use and adverse outcomes. While the mortality rate was high for IBD/COVID-19 patients, it was not greater than that for hospitalized COVID-19 patients generally. Though our results are encouraging, we continue to support the recommendations of the leading gastrointestinal and IBD societies to regard our patients as "at risk", and to observe caution in their care.


The Tobacco Industry's Abuse of Scientific Evidence and Activities to Recruit Scientists During Tobacco Litigation.
South Korea's state health insurer, the National Health Insurance Service (NHIS), is in the process of a compensation suit against tobacco industry. The tobacco companies have habitually endeavored to ensure favorable outcomes in litigation by misusing scientific evidence or recruiting scientists to support its interests. This study analyzed strategies that tobacco companies have used during the NHIS litigation, which has been receiving world-wide attention. To understand the litigation strategies of tobacco companies, the present study reviewed the existing literature and carried out content analysis of petitions, preparatory documents, and supporting evidence submitted to the court by the NHIS and the tobacco companies during the suit. Tobacco companies misrepresented the World Health Organization (WHO) report's argument and misused scientific evidence, and removed the word "deadly" from the title of the citation. Tobacco companies submitted the research results of scientists who had worked as a consultant for the tobacco industry as evidence. Such litigation strategies employed by the tobacco companies internationally were applied similarly in Korean lawsuits. Results of tobacco litigation have a huge influence on tobacco control policies. For desirable outcomes of the suits, healthcare professionals need to pay a great deal of attention to the enormous volume of written opinions and supporting evidence that tobacco companies submit. They also need to face the fact that the companies engage in recruitment of scientists. Healthcare professionals should refuse to partner with tobacco industry, as recommended by Article 5.3 of the WHO Framework Convention on Tobacco Control.


Inhibition of autophagy by 3-MA potentiates purvalanol-induced apoptosis in Bax deficient HCT 116 colon cancer cells.
The purine-derived analogs, roscovitine and purvalanol are selective synthetic inhibitors of cyclin-dependent kinases (CDKs) induced cell cycle arrest and lead to apoptotic cell death in various cancer cells. Although a number of studies investigated the molecular mechanism of each CDK inhibitor on apoptotic cell death mechanism with their therapeutic potential, their regulatory role on autophagy is not clarified yet. In this paper, our aim was to investigate molecular mechanism of CDK inhibitors on autophagy and apoptosis in wild type (wt) and Bax deficient HCT 116 cells. Exposure of HCT 116 wt and Bax(-/-) cells to roscovitine or purvalanol for 24h decreased cell viability in dose-dependent manner. However, Bax deficient HCT 116 cells were found more resistant against purvalanol treatment compared to wt cells. We also established that both CDK inhibitors induced apoptosis through activating mitochondria-mediated pathway in caspase-dependent manner regardless of Bax expression in HCT 116 colon cancer cells. Concomitantly, we determined that purvalanol was also effective on autophagy in HCT 116 colon cancer cells. Inhibition of autophagy by 3-MA treatment enhanced the purvalanol induced apoptotic cell death in HCT 116 Bax(-/-) cells. Our results revealed that mechanistic action of each CDK inhibitor on cell death mechanism differs. While purvalanol treatment activated apoptosis and autophagy in HCT 116 cells, roscovitine was only effective on caspase-dependent apoptotic pathway. Another important difference between two CDK inhibitors, although roscovitine treatment overcame Bax-mediated drug resistance in HCT 116 cells, purvalanol did not exert same effect.


The photodissociation of NO(2) by visible and ultraviolet light.
We present velocity map images of the NO, O((3)P(J)) and O((1)S(0)) photofragments from NO(2) excited in the range 7.6 to 9.0 eV. The molecule was initially pumped with a visible photon between 2.82-2.95 eV (440-420 nm), below the first dissociation threshold. A second ultraviolet laser with photon energies between 4.77 and 6.05 eV (260-205 nm) was used to pump high-lying excited states of neutral NO(2) and/or probe neutral photoproducts. Analysis of the kinetic energy release spectra revealed that the NO photofragments were predominantly formed in their ground electronic state with little kinetic energy. The O((3)P(J)) and O((1)S(0)) kinetic energy distributions were also dominated by kinetically 'cold' fragments. We discuss the possible excitation schemes and conclude that the unstable photoexcited states probed in the experiment were Rydberg states coupled to dissociative valence states. We compare our results with recent time-resolved studies using similar excitation and probe photon energies.


l-Ornithine stimulates growth hormone release in a manner dependent on the ghrelin system.
We found that intraduodenal administration of l-ornithine (l-Orn) stimulates growth hormone (GH) secretion in Wistar rats, and then investigated its mechanism. GH-releasing activity after intraduodenal administration of l-Orn was blocked by [d-Lys3]-GHRP-6, an antagonist of the ghrelin receptor; however, l-Orn (100 μM) has no affinity for the ghrelin receptor, suggesting that the GH-releasing activity of l-Orn is mediated via ghrelin release and activation of the ghrelin receptor. Intraduodenally administered l-Orn increased ghrelin mRNA expression in the duodenum but not in the stomach or hypothalamus. In addition, l-Orn-induced GH-releasing activity was inhibited by propranolol, an antagonist of β-adrenergic receptor, which is known to be coupled to ghrelin release. In conclusion, intraduodenally administered l-Orn stimulates GH secretion through the sympathetic nervous and ghrelin systems.


Perceptions of hatha yoga amongst persistently depressed individuals enrolled in a trial of yoga for depression.
To understand depressed individuals' experiences in a 10-week hatha yoga program. In a randomized controlled trial, participants were assigned to either 10 weeks of hatha yoga classes or a health education control group. This report includes responses from participants in yoga classes. At the start of classes, average depression symptom severity level was moderate. After 10 weeks of yoga classes, we asked participants (n=50) to provide written responses to open-ended questions about what they liked about classes, what they did not like or did not find helpful, and what they learned. We analyzed qualitative data using thematic analysis. Elements of yoga classes that may increase acceptability for depressed individuals include having instructors who promote a non-competitive and non-judgmental atmosphere, who are knowledgeable and able to provide individualized attention, and who are kind and warm. Including depression-related themes in classes, teaching mindfulness, teaching breathing exercises, and providing guidance for translating class into home practice may help to make yoga effective for targeting depression. Participants' comments reinforced the importance of aspects of mindfulness, such as attention to the present moment and acceptance of one's self and one's experience, as potential mechanisms of action. Other potential mechanisms include use of breathing practices in everyday life and the biological mechanisms that underlie the positive impact of yogic breathing. The most serious concern highlighted by a few participants was the concern that the yoga classes were too difficult given their physical abilities.


Dissociations in semantic cognition: Oscillatory evidence for opposing effects of semantic control and type of semantic relation in anterior and posterior temporal cortex.
How does the brain represent and process different types of knowledge? The Dual Hub account postulates that anterior temporal lobes (ATL) support taxonomic relationships based on shared physical features (mole - cat), while temporoparietal regions, including posterior middle temporal gyrus (pMTG), support thematic associations (mole - earth). Conversely, the Controlled Semantic Cognition account proposes that ATL supports both aspects of knowledge, while left pMTG contributes to controlled retrieval. This study used magnetoencephalography to test these contrasting predictions of functional dissociations within the temporal lobe. ATL and pMTG responded more strongly to taxonomic and thematic trials respectively, matched for behavioural performance, in line with predictions of the Dual Hub account. In addition, ATL showed a greater response to strong than weak thematic associations, while pMTG showed the opposite pattern, supporting a key prediction of the Controlled Semantic Cognition account. ATL showed a stronger response for word pairs that were more semantically coherent, either because they shared physical features (in taxonomic trials) or a strong thematic association. These effects largely coincided in time and frequency (although an early oscillatory response in ATL was specific to taxonomic trials). In contrast, pMTG showed non-overlapping effects of semantic control demands and thematic judgements: this site showed a larger oscillatory response to weak associations, when ongoing retrieval needed to be shaped to suit the task demands, and also a larger response to thematic judgements contrasted with taxonomic trials (which was reduced but not eliminated when the thematic trials were easier). Consequently, time-sensitive neuroimaging supports a complex pattern of functional dissociations within the left temporal lobe, which reflects both coherence versus control and distinctive oscillatory responses for taxonomic overlap (in ATL) and thematic relations (in pMTG).


WebCT: integrating computer-mediated communication and resource delivery into a new problem-based curriculum.
WebCT, front-end software for Internet-delivered material, became an integral part of a problem-based learning, student-centred curriculum introduced in January 2001 at the Nelson R. Mandela School of Medicine (South Africa). A template for six curriculum and two supplementary modules was developed. Organiser and Tool pages were added and files uploaded as each module progressed. This study provides feedback from students with regard to the value of WebCT in their curriculum, as well as discussing the value of WebCT for the delivery of digitized material (e.g., images, videos, PowerPoint presentations). In an anonymous survey following the completion of the first module, students, apparently irrespective of their level of computer literacy, responded positively to the communication facility between staff and students and amongst students, the resources and the URLs. Based on these preliminary responses, WebCT courses for all six modules were developed during 2001. With Faculty support, WebCT will probably be integrated into the rest of the MBChB programme. It will be particularly useful when students are off campus, undertaking electives and community service in the later years.


Effect of bioglass on growth and biomineralization of SaOS-2 cells in hydrogel after 3D cell bioprinting.
We investigated the effect of bioglass (bioactive glass) on growth and mineralization of bone-related SaOS-2 cells, encapsulated into a printable and biodegradable alginate/gelatine hydrogel. The hydrogel was supplemented either with polyphosphate (polyP), administered as polyP • Ca2+-complex, or silica, or as biosilica that had been enzymatically prepared from ortho-silicate by silicatein. These hydrogels, together with SaOS-2 cells, were bioprinted to computer-designed scaffolds. The results revealed that bioglass (nano)particles, with a size of 55 nm and a molar ratio of SiO2 : CaO : P2O5 of 55 : 40 : 5, did not affect the growth of the encapsulated cells. If silica, biosilica, or polyP • Ca2+-complex is co-added to the cell-containing alginate/gelatin hydrogel the growth behavior of the cells is not changed. Addition of 5 mg/ml of bioglass particles to this hydrogel significantly enhanced the potency of the entrapped SaOS-2 cells to mineralize. If compared with the extent of the cells to form mineral deposits in the absence of bioglass, the cells exposed to bioglass together with 100 µmoles/L polyP • Ca2+-complex increased their mineralization activity from 2.1- to 3.9-fold, or with 50 µmoles/L silica from 1.8- to 2.9-fold, or with 50 µmoles/L biosilica from 2.7- to 4.8-fold or with the two components together (100 µmoles/L polyP • Ca2+-complex and 50 µmoles/L biosilica) from 4.1- to 6.8-fold. Element analysis by EDX spectrometry of the mineral nodules formed by SaOS-2 revealed an accumulation of O, P, Ca and C, indicating that the mineral deposits contain, besides Ca-phosphate also Ca-carbonate. The results show that bioglass added to alginate/gelatin hydrogel increases the proliferation and mineralization of bioprinted SaOS-2 cells. We conclude that the development of cell-containing scaffolds consisting of a bioprintable, solid and cell-compatible inner matrix surrounded by a printable hard and flexible outer matrix containing bioglass, provide a suitable strategy for the fabrication of morphogenetically active and biodegradable implants.


Effects of dehydration on body-water distribution in desert kangaroos.
The effect of dehydration on the distribution of water in the bodies of two species of desert kangaroos, the red kangaroo Megaleia rufa and the euro Macropus robustus, has been examined. The volumes of various body-fluid compartments were determined in normally hydrated animals and then after the kangaroos had been dehydrated until body weight declined to 80% of the initial weight. The fluid compartments examined were total body water, plasma volume, intracellular volume (cellular and gut water), and extracellular volume. Both species were camel-like in their response to dehydration in that plasma volume was maintained in both species, falling by only 8.3% in red kangaroos and 7.4% in euros. The pattern of water loss from other compartments differed between species, particularly gut water loss. This compartment, which includes the large rumenlike fore stomach, contributed 56% of the total water loss of red kangaroos but only 22% of the loss from euros. The ecological implications of the preferential maintenance of gut water by the sedentary, cave-dwelling euros have been discussed.


A novel tool for evaluating non-cognitive traits of doctor of physical therapy learners in the United States.
The primary aim of this study was to develop a survey addressing an individual's non-cognitive traits, such as emotional intelligence, interpersonal skills, social intelligence, psychological flexibility, and grit. Such a tool would provide beneficial information for the continued development of admissions standards and would help better capture the full breadth of experience and capabilities of applicants applying to doctor of physical therapy (DPT) programs. This was a cross-sectional survey study involving learners in DPT programs at 3 academic institutions in the United States. A survey was developed based on established non-proprietary, non-cognitive measures affiliated with success and resilience. The survey was assessed for face validity, and exploratory factor analysis (EFA) was used to identify subgroups of factors based on responses to the items. A total of 298 participants (90.3%) completed all elements of the survey. EFA yielded 39 items for dimensional assessment with regression coefficients < 0.4. Within the 39 items, 3 latent constructs were identified: adaptability (16 items), intuitiveness (12 items), and engagement (11 items). This preliminary non-cognitive assessment survey will be able to play a valuable role in DPT admissions decisions following further examination and refinement.


Comparison of HGF (hepatocyte growth factor) levels of epithelial ovarian cancer cyst fluids with benign ovarian cysts.
Hepatocyte growth factor (HGF) is known to take a role in oncogenesis and tumoral behavior of the tumors of the organs that contain both mesenchymal and epithelial cells. This study compares HGF levels in cyst fluids of epithelial ovarian cancer and benign ovarian cysts to look for the role of HGF in ovarian carcinogenesis. Twenty-four consecutive patients with ovarian cancer and 34 with benign ovarian cysts were recruited prospectively at the Gynecologic Oncology Departments of SSK Ankara Maternity Hospital and Hacettepe University School of Medicine between 2001 and 2002. Cyst fluids were collected during primary staging in cancer patients and during laparatomy for benign patients. HGF levels were measured by ELISA method. Median HGF levels of the benign ovarian cysts and epithelial ovarian tumoral fluids were found to be 3822 pg/ml (85-15253 pg/ml) and 12962 pg/ml (4136-16025 pg/ml), respectively. Malignant cyst fluids have higher HGF levels when compared with benign ovarian cysts (P < 0.01). This finding suggests that HGF may take a paracrine role in oncogenic differentiation and tumoral development of epithelial ovarian cancers. Mechanisms that take a role in HGF secretion and the responses of neighboring epithelial cells to HGF during tumoral development need to be investigated.


VHL-gene deletion in single renal tubular epithelial cells and renal tubular cysts: further evidence for a cyst-dependent progression pathway of clear cell renal carcinoma in von Hippel-Lindau disease.
Inheritance of a mutant allele of the von Hippel-Lindau tumor suppressor gene predisposes affected individuals to develop renal cysts and clear cell renal cell carcinoma. Von Hippel-Lindau gene inactivation in single renal tubular cells has indirectly been showed by immunohistochemical staining for the hypoxia-inducible factor alpha target gene product carbonic anhydrase IX. In this study we were able to show von Hippel-Lindau gene deletion in carbonic anhydrase IX positive nonneoplastic renal tubular cells, in epithelial cells lining renal cysts and in a clear cell renal cell carcinoma of a von Hippel-Lindau patient. This was carried out by means of laser confocal microscopy and immunohistochemistry in combination with fluorescence in situ hybridization. Carbonic anhydrase IX negative normal renal tubular cells carried no von Hippel-Lindau gene deletion. Furthermore, recent studies have indicated that the von Hippel-Lindau gene product is necessary for the maintenance of primary cilia stability in renal epithelial cells and that disruption of the cilia structure by von Hippel-Lindau gene inactivation induces renal cyst formation. In our study, we show a significant shortening of primary cilia in epithelial cells lining renal cysts, whereas, single tubular cells with a von Hippel-Lindau gene deletion display to a far lesser extent signs of cilia shortening. Our in vivo results support a model in which renal cysts represent precursor lesions for clear cell renal cell carcinoma and arise from single renal tubular epithelial cells owing to von Hippel-Lindau gene deletion.


Risk assessment of aflatoxins in food.
EFSA was asked to deliver a scientific opinion on the risks to public health related to the presence of aflatoxins in food. The risk assessment was confined to aflatoxin B1 (AFB1), AFB2, AFG1, AFG2 and AFM1. More than 200,000 analytical results on the occurrence of aflatoxins were used in the evaluation. Grains and grain-based products made the largest contribution to the mean chronic dietary exposure to AFB1 in all age classes, while 'liquid milk' and 'fermented milk products' were the main contributors to the AFM1 mean exposure. Aflatoxins are genotoxic and AFB1 can cause hepatocellular carcinomas (HCCs) in humans. The CONTAM Panel selected a benchmark dose lower confidence limit (BMDL) for a benchmark response of 10% of 0.4 μg/kg body weight (bw) per day for the incidence of HCC in male rats following AFB1 exposure to be used in a margin of exposure (MOE) approach. The calculation of a BMDL from the human data was not appropriate; instead, the cancer potencies estimated by the Joint FAO/WHO Expert Committee on Food Additives in 2016 were used. For AFM1, a potency factor of 0.1 relative to AFB1 was used. For AFG1, AFB2 and AFG2, the in vivo data are not sufficient to derive potency factors and equal potency to AFB1 was assumed as in previous assessments. MOE values for AFB1 exposure ranged from 5,000 to 29 and for AFM1 from 100,000 to 508. The calculated MOEs are below 10,000 for AFB1 and also for AFM1 where some surveys, particularly for the younger age groups, have an MOE below 10,000. This raises a health concern. The estimated cancer risks in humans following exposure to AFB1 and AFM1 are in-line with the conclusion drawn from the MOEs. The conclusions also apply to the combined exposure to all five aflatoxins.


Strain-rate dependence of viscous properties of the plantar soft tissue identified by a spherical indentation test.
The mechanical properties of the plantar soft tissue are known to vary in diabetic patients, indicating that parameter identification of the mechanical properties of the foot tissue using an indentation test is clinically important for possible early diagnosis and interventions of diabetic foot. However, accurate mechanical characterization of the viscous properties of the plantar soft tissue has been difficult, as measured force-relaxation curves of the same soft tissue differ depending on how the material is loaded. In the present study, we attempted to clarify how the indentation rate of the plantar soft tissue affects the measured force-relaxation curves, which is necessary in order to identify the viscoelastic properties. The force-relaxation curves of the heel pads were obtained from the indentation experiment in vivo at indentation rates of 15, 25, 50, 75, and 100 mm/s. The curves were fit to an analytical contact model of spherical indentation incorporating a five-element Maxwell model. The results of the present study demonstrated that, although experimentally obtained force-relaxation curves were actually variable depending on the indentation rate, similar viscous parameters could be identified for the same heel if the effects of (1) the underestimation of the peak force due to the energy dissipation occurring during indentation and (2) the deceleration of the indenter at the target position were incorporated in the parameter identification process. The indentation-rate-independent viscous properties could therefore be estimated using the proposed method.


Racial and ethnic variation in the provision of dental procedures.
Most of the available information on racial/ethnic disparities in oral health is based on differences in sociodemographic variables related to dental disease burden, dental visits, and access to care. However, very little is known regarding racial/ethnic variation in the provision of dental procedures. This study examined trends in the provision of dental procedures and sought to determine whether there are racial/ethnic differences in the provision of dental procedures. This is a retrospective observational study of patients treated at a dental training institution. Data for all patients 18 to 60 years of age in axiUm (electronic database) for 2001 to 2003 were analyzed. Data include demographic information, poverty status, insurance coverage, dental procedure, and race/ethnicity. Separate logistic regression models (by dental procedure category and year) were fitted while considering race/ethnicity, insurance coverage, poverty status, marital status, and age as possible covariates. The total number of dental procedures completed by providers increased by 14,000 between 2001 and 2003. African-Americans were significantly less likely to have restorative procedures [odds ratio (OR): 0.60, 95 percent confidence interval (CI): 0.42 to 0.86], (OR: 0.52, 95 percent CI: 0.38 to 0.73), (OR: 0.46, 95 percent CI: 0.36 to 0.58) in 2001, 2002, and 2003, respectively, than the White population. Significant differences in the use of other dental procedures (prosthodontics--removable) and oral surgery procedures by race/ethnicity were observed. Substantial racial/ethnic variation in the provision of dental procedures exists. This study presents findings beyond anecdotal information on racial/ethnic variation in the provision of dental procedures and requires further research to compile more detailed data.


Performance characteristics of recombinant enzyme immunoassay to detect antibodies to human immunodeficiency virus type 1 (HIV-1) and HIV-2 and to measure early antibody responses in seroconverting patients.
We investigated the performance of a double-antigen sandwich recombinant enzyme immunoassay (EIA; Abbott Laboratories, North Chicago, Ill.) and compared it with that of a synthetic-peptide-based EIA (Biochem Immunosystems, Montreal, Quebec, Canada) for the detection of human immunodeficiency type 1 (HIV-1) and HIV-2 antibodies in 2,321 clinical serum samples. The results of both EIA methods and Western blot (immunoblot) were in agreement for 1,046 HIV-1 and 10 HIV-2 specimens from a panel of known positives. From a prospective panel of 1,085 specimens, 38 proved to be positive by both EIAs and Western blot, 3 were positive by the recombinant EIA only, and 9 were positive by the peptide EIA only, for calculated specificities of 99.71 and 99.04%, respectively. Of 180 specimens from a seroconversion panel collected from 77 patients, the results for 170 were in agreement by all antibody testing methods and 10 were found to be repeat reactive for HIV antibodies by the recombinant EIA only. All 10 were initial specimens of seroconverting patients; 7 were also reactive for HIV p24 antigen. An examination of four of these sera by radioimmunoprecipitation assay showed gp120 and gp160 bands in each. Analysis of the anti-Env antibody class in three of these samples showed that one consisted of immunoglobulin M (IgM) only and two contained both IgG and IgM antibodies. Although both EIA procedures were sensitive and specific in the detection of antibodies to HIV-1 and HIV-2 and both were capable of detecting early antibodies, the recombinant assay was more sensitive for antibody detection during early seroconversion.


Tunable one-dimensional photonic crystal slabs based on preferential etching of silicon-on-insulator.
We design and assess a one-dimensional photonic crystal slab fabricated by preferential etching of a silicon-on-insulator substrate. The etched grooves are considered to be infiltrated by a highly-birefringent nematic liquid crystalline material. A detailed analysis of the nematic director response within the grooves is presented. We investigate different configurations and demonstrate large band gap shifting when switching the liquid crystal with an applied voltage. Furthermore, we assess this type of device as an efficient alternative for compact refractometric optical sensing applications.


Reformulation of a new vancomycin analog: an example of the importance of buffer species and strength.
The purpose of this research was to use our previously validated dynamic injection apparatus as a rapid method for screening pH-adjusted formulations of a new vancomycin analog, Van-An, for their potential to precipitate upon dilution. In 1 vial, Van-An was reconstituted according to the manufacturer's instructions. In a separate vial, the Van-An formulation's existing phosphate buffer species was supplemented with acetate buffer, which has a pKa in the desired range: between the pH values of the formulation (pH 3.9) and blood (pH 7.4). The formulations were injected using the dynamic injection apparatus into a flowing stream of isotonic Sorensen's phosphate buffer at rates of 0.25, 0.5, 1, and 2 mL/min. The peaks obtained with the spectrophotometer were reproducible for each injection rate/formulation combination. For the phosphate-buffered formulation, the least amount of precipitation was obtained at the 0.25 mL/min injection rate. Acetate buffer was able to substantially reduce such precipitation, even at the highest injection rate. The opacity peaks for the formulation with the acetate addition were significantly smaller (P < .05) than those obtained for the unaltered formulation at all 4 injection rates. The results suggest that acetate is a better buffer species than phosphate for the pH range defined. Furthermore, we present evidence to support a generally applicable approach to screening new formulations of drug products that may be clinically useful for reducing the incidence of phlebitis in humans.


The relationship between cognitive change and physical health and behavioural outcomes in a Ugandan cohort of adults living with HIV - a longitudinal study.
We investigated changes in cognitive function and physical health and behavioural outcomes (HIV disease progression, health-seeking behaviour, adherence to HIV medications and risky sexual behaviour) at baseline and 12 months later among 1126 Ugandan adults living with HIV. Overall, cognitive function improved from baseline to follow-up, except for gait speed, which was slower at follow-up compared to baseline. There were improvements in physical health and behavioural outcomes by follow-up, with greater improvements among individuals on ART compared to those not on ART. Change in gait speed over time significantly predicted risky sexual behaviours at follow-up. This is the first study to investigate the longitudinal relationships between cognitive function and health outcomes among Ugandan adults living with HIV and provide insights into the possible links between cognitive function and negative clinical and behavioural health outcomes in people living with HIV.


Neutrophil Subsets in Periodontal Health and Disease: A Mini Review.
Neutrophils are amongst the most abundant immune cells within the periodontal tissues and oral cavity. As innate immune cells, they are first line defenders at the tooth-mucosa interface, and can perform an array of different functions. With regard to these, it has been observed over many years that neutrophils are highly heterogeneous in their behavior. Therefore, it has been speculated that neutrophils, similarly to other leukocytes, exist in distinct subsets. Several studies have investigated different markers of neutrophils in oral health and disease in recent years in order to define potential cell subsets and their specific tasks. This research was inspired by recent advancements in other fields of medicine in this field. The aim of this review is to give an overview of the current evidence regarding the existence and presence of neutrophil subsets and their possible functions, specifically in the context of periodontitis, gingivitis, and periodontal health.


The Role of Ontogeny in the Evolution of Human Cooperation.
To explain the evolutionary emergence of uniquely human skills and motivations for cooperation, Tomasello et al. (2012, in Current Anthropology 53(6):673-92) proposed the interdependence hypothesis. The key adaptive context in this account was the obligate collaborative foraging of early human adults. Hawkes (2014, in Human Nature 25(1):28-48), following Hrdy (Mothers and Others, Harvard University Press, 2009), provided an alternative account for the emergence of uniquely human cooperative skills in which the key was early human infants' attempts to solicit care and attention from adults in a cooperative breeding context. Here we attempt to reconcile these two accounts. Our composite account accepts Hrdy's and Hawkes's contention that the extremely early emergence of human infants' cooperative skills suggests an important role for cooperative breeding as adaptive context, perhaps in early Homo. But our account also insists that human cooperation goes well beyond these nascent skills to include such things as the communicative and cultural conventions, norms, and institutions created by later Homo and early modern humans to deal with adult problems of social coordination. As part of this account we hypothesize how each of the main stages of human ontogeny (infancy, childhood, adolescence) was transformed during evolution both by infants' cooperative skills "migrating up" in age and by adults' cooperative skills "migrating down" in age.


Labeled EF-Tus for rapid kinetic studies of pretranslocation complex formation.
The universally conserved translation elongation factor EF-Tu delivers aminoacyl(aa)-tRNA in the form of an aa-tRNA·EF-Tu·GTP ternary complex (TC) to the ribosome where it binds to the cognate mRNA codon within the ribosomal A-site, leading to formation of a pretranslocation (PRE) complex. Here we describe preparation of QSY9 and Cy5 derivatives of the variant E348C-EF-Tu that are functional in translation elongation. Together with fluorophore derivatives of aa-tRNA and of ribosomal protein L11, located within the GTPase associated center (GAC), these labeled EF-Tus allow development of two new FRET assays that permit the dynamics of distance changes between EF-Tu and both L11 (Tu-L11 assay) and aa-tRNA (Tu-tRNA assay) to be determined during the decoding process. We use these assays to examine: (i) the relative rates of EF-Tu movement away from the GAC and from aa-tRNA during decoding, (ii) the effects of the misreading-inducing antibiotics streptomycin and paromomycin on tRNA selection at the A-site, and (iii) how strengthening the binding of aa-tRNA to EF-Tu affects the rate of EF-Tu movement away from L11 on the ribosome. These FRET assays have the potential to be adapted for high throughput screening of ribosomal antibiotics.


A prospective multicenter study of paroxysmal nocturnal hemoglobinuria cells in patients with bone marrow failure.
Paroxysmal nocturnal hemoglobinuria (PNH), a rare clonal hematopoietic stem cell disorder, is characterized by chronic, uncontrolled complement activation leading to intravascular hemolysis and an inflammatory prothrombotic state. The EXPLORE study aimed to determine the prevalence of undiagnosed PNH in patients with aplastic anemia (AA), myelodysplastic syndrome (MDS), and/or other bone marrow failure (BMF) syndromes and the effect of PNH clone size on hemolysis. Patients, selected from medical office chart reviews, had blood samples collected for hematologic panel testing and for flow cytometry detection of PNH clones. Granulocyte PNH clones ≥ 1% were detected in 199 of all 5,398 patients (3.7%), 93 of 503 AA patients (18.5%), 50 of 4,401 MDS patients (1.1%), and 3 of 130 other BMF patients (2.3%). Higher-sensitivity analyses detected PNH clones ≥ 0.01% in 167 of 1,746 patients from all groups (9.6%) and in 22 of 1,225 MDS patients (1.8%), 116 of 294 AA patients (39.5%), and four of 54 other BMF patients (7.8%). Among patients with PNH clones ≥ 1%, median clone size was smaller in patients with AA (5.1%) than in those with MDS (17.6%) or other BMF (24.4%), and the percentage of patients with lactate dehydrogenase levels (a marker for intravascular hemolysis) ≥ 1.5 × upper limit of normal was smaller in patients with AA (18.3%) than in those with MDS (42.0%). These results confirm the presence of PNH clones in high-risk patient groups and suggest that screening of such patients may facilitate patient management and care.


A strategy for increasing use of autogenous hemodialysis access procedures: impact of preoperative noninvasive evaluation.
We studied the efficacy of preoperative noninvasive assessment of the upper extremity to identify arteries and veins suitable for hemodialysis access to increase our use of autogenous fistulas (AF). From Sep. 1, 1994, to Apr. 1, 1997, 172 patients who required chronic hemodialysis underwent segmental upper extremity Doppler pressures and duplex ultrasound with mapping of arteries and veins. The following criteria were necessary for satisfactory arterial inflow: absence of a pressure gradient between arms, patent palmar arch, and arterial lumen diameter 2.0 mm or more. The criteria necessary for satisfactory venous outflow were venous luminal diameter greater than or equal to 2.5 mm for AF and greater than or equal to 4.0 mm for synthetic bridging grafts (BG) and continuity with distal superficial veins in the arm. Intraoperative and duplex ultrasound measurements were compared. Contemporary experience was compared with the 2-year period (1992 to 1994) before implementation of the protocol. During the period from Sep. 1, 1994, to Apr. 1, 1997, 108 patients (63%) had AF, 52 (30%) had prosthetic BG, and 12 (7%) had permanent catheters (PC) placed. Early failure was seen in 8.3% of AFs. Primary cumulative patency rates were 83% for AF and 74% for BG at 1 year (p < 0.05), with a mean clinical follow-up of 15.2 months. No postoperative infections were observed with AF, whereas six infections (12%) were observed with BG and two (17%) with PC insertion. During the period from June 1, 1992, to Aug. 31, 1994, 183 procedures were performed with a distribution of 14% AF, 62% BG, and 24% PC. In this earlier period the AF early failure rate was 36%, and the patency rates were 48%, 63%, and 48% for AF, BG, and PC, respectively (mean follow-up, 13.8 months). A protocol of noninvasive assessment increased use of AFs. The cumulative patency rate of AFs was improved, and early failure rates were reduced when compared with the preceding institutional experience. Routine noninvasive assessment is recommended to document adequacy of arterial inflow and delineate venous outflow to maximize opportunities for AF.


Notch signaling alters sensory or neuronal cell fate specification of inner ear stem cells.
Multipotent progenitor cells in the otic placode give rise to the specialized cell types of the inner ear, including neurons, supporting cells, and hair cells. The mechanisms governing acquisition of specific fates by the cells that form the cochleovestibular organs remain poorly characterized. Here we show that whereas blocking Notch signaling with a γ-secretase inhibitor increased the conversion of inner ear stem cells to hair cells by a mechanism that involved the upregulation of bHLH transcription factor, Math1 (mouse Atoh1), differentiation to a neuronal lineage was increased by expression of the Notch intracellular domain. The shift to a neuronal lineage could be attributed in part to continued cell proliferation in cells that did not undergo sensory cell differentiation due to the high Notch signaling, but also involved upregulation of Ngn1. The Notch intracellular domain influenced Ngn1 indirectly by upregulation of Sox2, a transcription factor expressed in many neural progenitor cells, and directly by an interaction with an RBP-J binding site in the Ngn1 promoter/enhancer. The induction of Ngn1 was blocked partially by mutation of the RBP-J site and nearly completely when the mutation was combined with inhibition of Sox2 expression. Thus, Notch signaling had a significant role in the fate specification of neurons and hair cells from inner ear stem cells, and decisions about cell fate were mediated in part by a differential effect of combinatorial signaling by Notch and Sox2 on the expression of bHLH transcription factors.


Evaluation of renormalised entropy for risk stratification using heart rate variability data.
Standard time and frequency parameters of heart rate variability (HRV) describe only linear and periodic behaviour, whereas more complex relationships cannot be recognised. A method that may be capable of assessing more complex properties is the non-linear measure of 'renormalised entropy.' A new concept of the method, RE(AR), has been developed, based on a non-linear renormalisation of autoregressive spectral distributions. To test the hypothesis that renormalised entropy may improve the result of high-risk stratification after myocardial infarction, it is applied to a clinical pilot study (41 subjects) and to prospective data of the St George's Hospital post-infarction database (572 patients). The study shows that the new RE(AR) method is more reproducible and more stable in time than a previously introduced method (p<0.001). Moreover, the results of the study confirm the hypothesis that on average, the survivors have negative values of RE(AR) (-0.11+/-0.18), whereas the non-survivors have positive values (0.03+/-0.22, p<0.01). Further, the study shows that the combination of an HRV triangular index and RE(AR) leads to a better prediction of sudden arrhythmic death than standard measurements of HRV. In summary, the new RE(AR) method is an independent measure in HRV analysis that may be suitable for risk stratification in patients after myocardial infarction.


Interim Analysis of a Two-Institution, Prospective Clinical Trial of 4DCT-Ventilation-based Functional Avoidance Radiation Therapy.
Functional imaging has been proposed that uses 4DCT images to calculate 4DCT-based lung ventilation (4DCT-ventilation). We have started a 2-institution, phase 2 prospective trial evaluating the feasibility, safety, and preliminary efficacy of 4DCT-ventilation functional avoidance. The trial hypothesis is that the rate of grade ≥2 radiation pneumonitis could be reduced to 12% with functional avoidance, compared with a 25% rate of pneumonitis with a historical control. The trial employed a Simon 2-stage design with a planned futility analysis after 17 evaluable patients. The purpose of this work is to present the trial design and implementation, dosimetric data, and clinical results for the planned futility analysis. Eligible patients were patients with lung cancer who were prescribed doses of 45 to 75 Gy. For each patient, the 4DCT data were used to generate a 4DCT-ventilation image using the Hounsfield unit technique along with a compressible flow-based image registration algorithm. Two intensity modulated radiation therapy treatment plans were generated: (1) a standard lung plan and (2) a functional avoidance treatment plan that aimed to reduce dose to functional lung while meeting target and normal tissue constraints. Patients were treated with the functional avoidance plan and evaluated for thoracic toxicity (presented as rate and 95% confidence intervals [CI]) with a 1-year follow-up. The V20 to functional lung was 21.6% ± 9.5% (mean ± standard deviation) with functional avoidance, representing a decrease of 3.2% (P < .01) relative to standard, nonfunctional treatment plans. The rates of grade ≥2 and grade ≥3 radiation pneumonitis were 17.6% (95% CI, 3.8%-43.4%) and 5.9% (95% CI, 0.1%-28.7%), respectively. Dosimetrically, functional avoidance achieved reduction in doses to functional lung while meeting target and organ at risk constraints. On the basis of Simon's 2-stage design and the 17.6% grade ≥2 pneumonitis rate, the trial met its futility criteria and has continued accrual.


Automated classification of normal and Stargardt disease optical coherence tomography images using deep learning.
Recent advances in deep learning have seen an increase in its application to automated image analysis in ophthalmology for conditions with a high prevalence. We wanted to identify whether deep learning could be used for the automated classification of optical coherence tomography (OCT) images from patients with Stargardt disease (STGD) using a smaller dataset than traditionally used. Sixty participants with STGD and 33 participants with a normal retinal OCT were selected, and a single OCT scan containing the centre of the fovea was selected as the input data. Two approaches were used: Model 1 - a pretrained convolutional neural network (CNN); Model 2 - a new CNN architecture. Both models were evaluated on their accuracy, sensitivity, specificity and Jaccard similarity score (JSS). About 102 OCT scans from participants with a normal retinal OCT and 647 OCT scans from participants with STGD were selected. The highest results were achieved when both models were implemented as a binary classifier: Model 1 - accuracy 99.6%, sensitivity 99.8%, specificity 98.0% and JSS 0.990; Model 2 - accuracy 97.9%, sensitivity 97.9%, specificity 98.0% and JSS 0.976. The deep learning classification models used in this study were able to achieve high accuracy despite using a smaller dataset than traditionally used and are effective in differentiating between normal OCT scans and those from patients with STGD. This preliminary study provides promising results for the application of deep learning to classify OCT images from patients with inherited retinal diseases.


Multi-modal label-free imaging based on a femtosecond fiber laser.
We demonstrate multi-mode microscopy based on a single femtosecond fiber laser. Coherent anti-Stokes Raman scattering (CARS), stimulated Raman scattering (SRS) and photothermal images can be obtained simultaneously with this simplified setup. Distributions of lipid and hemoglobin in sliced mouse brain samples and blood cells are imaged. The dependency of signal amplitude on the pump power and pump modulation frequency is characterized, which allows to isolate the impact from different contributions.


New effects of Roundup on amphibians: predators reduce herbicide mortality; herbicides induce antipredator morphology.
The use of pesticides is important for growing crops and protecting human health by reducing the prevalence of targeted pest species. However, less attention is given to the potential unintended effects on nontarget species, including taxonomic groups that are of current conservation concern. One issue raised in recent years is the potential for pesticides to become more lethal in the presence of predatory cues, a phenomenon observed thus far only in the laboratory. A second issue is whether pesticides can induce unintended trait changes in nontarget species, particularly trait changes that might mimic adaptive responses to natural environmental stressors. Using outdoor mesocosms, I created simple wetland communities containing leaf litter, algae, zooplankton, and three species of tadpoles (wood frogs [Rana sylvatica or Lithobates sylvaticus], leopard frogs [R. pipiens or L. pipiens], and American toads [Bufo americanus or Anaxyrus americanus]). I exposed the communities to a factorial combination of environmentally relevant herbicide concentrations (0, 1, 2, or 3 mg acid equivalents [a.e.]/L of Roundup Original MAX) crossed with three predator-cue treatments (no predators, adult newts [Notophthalmus viridescens], or larval dragonflies [Anax junius]). Without predator cues, mortality rates from Roundup were consistent with past studies. Combined with cues from the most risky predator (i.e., dragonflies), Roundup became less lethal (in direct contrast to past laboratory studies). This reduction in mortality was likely caused by the herbicide stratifying in the water column and predator cues scaring the tadpoles down to the benthos where herbicide concentrations were lower. Even more striking was the discovery that Roundup induced morphological changes in the tadpoles. In wood frog and leopard frog tadpoles, Roundup induced relatively deeper tails in the same direction and of the same magnitude as the adaptive changes induced by dragonfly cues. To my knowledge, this is the first study to show that a pesticide can induce morphological changes in a vertebrate. Moreover, the data suggest that the herbicide might be activating the tadpoles' developmental pathways used for antipredator responses. Collectively, these discoveries suggest that the world's most widely applied herbicide may have much further-reaching effects on nontarget species than previous considered.


Frequency of bacterial isolates and pattern of antimicrobial resistance in patients with hematological malignancies: A snapshot from tertiary cancer center.
Infections are the most important cause of mortality in patients with high-risk febrile neutropenia. Emergence of multi-drug resistant organisms (MDROs) has become a major challenge for hemato-oncologists. Knowledge of the prevalent organisms and their antimicrobial sensitivity can help deciding the empirical therapy at individual centers and allows timely measures to reduce the risk of antimicrobial resistance. To evaluate the frequency of bacterial isolates from all the samples and the pattern of bacterial bloodstream infections and incidence of MDROs. This is a retrospective analysis from a tertiary care cancer center. From January to June 2014 information on all the samples received in Department of Microbiology was collected retrospectively. The data from samples collected from patients with hematological cancers were analyzed for types of bacterial isolates and antimicrobial sensitivity. A total of 739 isolates were identified with 67.9% of isolates being Gram-negative. The predominant Gram-negative organisms were Escherichia coli, Psuedomonas spp. and Klebsiella spp. Among the bacterial bloodstream infections, 66% were Gram-negative isolates. MDROs constituted 22% of all isolates in blood cultures. Incidence of resistant Gram-positive organisms was low in the present dataset (methicillin resistant Staphylococcus aureus and vancomycin-resistant enterococci-1.3%). The analysis reconfirms the Gram-negative organisms as the predominant pathogens in bacteremia seen in patients with hematological cancers. The high frequency of multi-drug resistance in the dataset calls for the need of emergency measures to curtail further development and propagation of resistant organisms.


Presence of granulocytic ehrlichia in ticks and serological evidence of human infection in La Rioja, Spain.
In order to estimate the risks of human granulocytic ehrlichiosis (HGE) in an endemic area for Lyme disease in the North of Spain (La Rioja), we collected and investigated by PCR specific to the E. phagocytophila group DNA, a total of 6870 Ixodes ricinus ticks. We also used an indirect immunofluorescence (IFI) test to study the presence of antibodies to the HGE agent in 147 human serum samples including patients with Lyme disease (LD), forestry workers, and persons with history of previous tick bite. Fifty serum samples from healthy people resident in urban areas and with no history of tick-bite disorder and without tick exposure were used as controls. Four of 76 adults and 49 of 203 nymphs pools carried E. phagocytophila DNA. This result, and the finding of 1.4% of sera reacting in the IFI test confirms that this tick-borne agent is present in La Rioja, and that humans show evidence of contact with it. HGE should be considered in the differential diagnosis of flu-like syndromes in the study area in the north of Spain.


Polydispersity of a mammalian chaperone: mass spectrometry reveals the population of oligomers in alphaB-crystallin.
The quaternary structure of the polydisperse mammalian chaperone alphaB-crystallin, a member of the small heat-shock protein family, has been investigated by using electrospray mass spectrometry. The intact assemblies give rise to mass spectra that are complicated by the overlapping of charge states from the different constituent oligomers. Therefore, to determine which oligomers are formed by this protein, tandem mass spectrometry experiments were performed. The spectra reveal a distribution, primarily of oligomers containing 24-33 subunits, the relative populations of which were quantified, to reveal a dominant species being composed of 28 subunits. Additionally, low levels of oligomers as small as 10-mers and as large as 40-mers were observed. Interpretation of the tandem mass spectral data was confirmed by simulating and summing spectra arising from the major individual oligomers. The ability of mass spectrometry to quantify the relative populations of particular oligomeric states also revealed that, contrary to the dimeric associations observed in other small heat-shock proteins, there is no evidence for any stable substructures of bovine alphaB-crystallin isolated from the lens.