Prevalence and cost of musculoskeletal disorders: a population-based, public hospital system healthcare consumption approach.
To use a population-level, public-hospital approach to compare the prevalence and cost of musculoskeletal diseases (MSD) with other clinical specialties. A healthcare utilization survey of 4 million individual records over 4 years, from all major public hospitals in the state of Victoria (estimated population 4.8 million residents in 2000/01) from 1997/98 to 2000/01. Main outcome measures were inpatient episodes of care, bed-days, and outpatient clinic encounters. MSD was defined as the combination of orthopedics and rheumatology. After obstetrics, MSD was the most frequent outpatient service, with orthopedics accounting for 9.9% of all visits in 2000/01. The proportion of MSD outpatient encounters (on average 11.6% of the total) was constant over the study period. Among 26 medical specialties, MSD had the sixth highest number of inpatient episodes (6.2% in 2000/01), following renal dialysis (14.6%), general surgery (8.2%), obstetrics (7.6%), gastroenterology (7.1%), and general medicine (6.7%). MSD was the fifth highest consumer of bed-days, occupying on average 7.7% of all beds per annum in the period 1997/98 to 2000/01, behind psychiatry (10.1%), respiratory medicine (8.5%), rehabilitation (8.3%), and general medicine (7.8%). MSD was the third most-costly discipline in 2000/01, with total costs of over A dollars 169 million (9.7% of total inpatient costs that year), behind respiratory medicine (11.6%) and general surgery (11.5%). Compared to other diseases, MSD consumes a substantial proportion of healthcare resources in Victorian public hospitals. These data have important implications for allocation of healthcare resources, clinical care pathways, and prevention strategies.


LIN28B overexpression defines a novel fetal-like subgroup of juvenile myelomonocytic leukemia.
Juvenile myelomonocytic leukemia (JMML) is a rare and aggressive stem cell disease of early childhood. RAS activation constitutes the core component of oncogenic signaling. In addition, leukemic blasts in one-fourth of JMML patients present with monosomy 7, and more than half of patients show elevated age-adjusted fetal hemoglobin (HbF) levels. Hematopoietic stem cell transplantation is the current standard of care and results in an event-free survival rate of 50% to 60%, indicating that novel molecular-driven therapeutic options are urgently needed. Using gene expression profiling in a series of 82 patient samples, we aimed at understanding the molecular biology behind JMML and identified a previously unrecognized molecular subgroup characterized by high LIN28B expression. LIN28B overexpression was significantly correlated with higher HbF levels, whereas patients with monosomy 7 seldom showed enhanced LIN28B expression. This finding gives a biological explanation of why patients with monosomy 7 are rarely diagnosed with high age-adjusted HbF levels. In addition, this new fetal-like JMML subgroup presented with reduced levels of most members of the let-7 microRNA family and showed characteristic overexpression of genes involved in fetal hematopoiesis and stem cell self-renewal. Lastly, high LIN28B expression was associated with poor clinical outcome in our JMML patient series but was not independent from other prognostic factors such as age and age-adjusted HbF levels. In conclusion, we identified elevated LIN28B expression as a hallmark of a novel fetal-like subgroup in JMML.


Monitoring the effect of first line treatment in RAS/RAF mutated metastatic colorectal cancer by serial analysis of tumor specific DNA in plasma.
Precision medicine calls for an early indicator of treatment efficiency. Circulating tumor DNA (ctDNA) is a promising marker in this setting. Our prospective study explored the association between disease development and change of ctDNA during first line chemotherapy in patients with RAS/RAF mutated metastatic colorectal cancer (mCRC). The study included 138 patients with mCRC receiving standard first line treatment. In patients with RAS/RAF mutated tumor DNA the same mutation was quantified in the plasma using droplet digital PCR. The fractional abundance of ctDNA was assessed in plasma before treatment start and at every treatment cycle until radiologically defined progressive disease. RAS/RAF mutations were detected in the plasma from 77 patients. Twenty patients progressed on treatment and 57 stopped treatment without progression. The presence of mutated DNA in plasma was correlated with poor overall survival. A low level of ctDNA after the first cycle of chemotherapy was associated with a low risk of progression. On the other hand, a significant increase of ctDNA at any time during the treatment course was associated with a high risk of progression on continuous treatment. The first increase in ctDNA level occurred at a median of 51 days before radiologically confirmed progression. The results indicate that the ctDNA level holds potential as a clinically valuable marker in first line treatment of mCRC. A rapid decrease was associated with a prolonged progression free interval, whereas a significant increase gave notice of early progression with a relevant lead time.


Pretransplantation risk factors for death after heart transplantation: a multiinstitutional study. The Transplant Cardiologists Research Database Group.
Risk factors for death after heart transplantation were identified by analyzing the total primary heart transplantation experience (n = 911) among 25 institutions from January 1, 1990, through June 30, 1991. Overall actuarial survival was 93% at 1 month and 84% at 12 months. The hazard function for death was highest early after heart transplantation and fell rapidly over the first 6 months, with a gradually declining hazard thereafter. The two most common causes of death were infection (n = 29) and early graft failure (n = 28), accounting for 45% of the overall deaths. By multivariable analysis, risk factors for death during the study period included very young recipient age (p = 0.004), advanced age (p = 0.009), ventilator support at time of transplantation (p = 0.09), abnormal renal function (p = 0.1), lower pretransplantation cardiac output (p = 0.009), higher pulmonary vascular resistance in children (p = 0.006), longer donor ischemic time (p = 0.001), older donor age (p = 0.001), and donor and recipient not both blood type O (p = 0.009). The recipient age effect was greatest in patients under 5 years of age (1-year survival rate 68% versus 85% for all others, p = 0.002). Patients aged 60 years and older had a 1-year survival rate of 81%. Patients who were ventilator dependent at transplantation fared especially poorly, with a 3-month survival rate of 65%. Transplantation of a blood group O heart into a non-O recipient had a somewhat lower 1-year survival rate than did blood group O into an O recipient (82% versus 88%, p = 0.06). The adverse effect of a longer ischemic time was most notable after 4 hours (1-month survival rate 71% for more than 4 hours versus 85% for less than 4 hours, p = 0.0003). Inference: These multiinstitutional-derived risk factors for early-term death after heart transplantation may help improve patient and donor selection and focus further scientific investigations to increase the safety of heart transplantation.


Evaluation of a QAA-based algorithm using MODIS land bands data for retrieval of IOPs in the Eastern China Seas.
A quasi-analytical algorithm (QAA)-based algorithm which is applied to moderate imaging spectroradiometer (MODIS) land band data (469, 555, and 645 nm) is proposed and named QAA-RGR (Red-Green-bands-Ratio). The performance has been evaluated using in situ measurements data and MODIS data from the Eastern China Seas (ECS). The QAA-RGR algorithm uses the ratio of the remote sensing reflectance at 645nm (Rrs645) to the Rrs555 to estimate the absorption coefficient at 555nm. In addition, the spectral slope of the backscattering coefficient (bb) is estimated using a statistical relationship based on bb555. The other steps of the retrieval algorithm are the same as those of the extensively used QAA version 5 (QAAv5). First, the QAA-RGR algorithm was applied to an in situ measurement data set for the ECS to retrieve inherent optical properties (IOPs), and the results were compared with the QAAv5. The results demonstrate that, the two algorithms exhibit similar performance for in situ measurements. Second, the algorithm was applied to the land bands data and ocean bands data of MODIS over the ECS to obtain the distribution of IOPs at 500m and 1000m resolutions. The results of the retrieval algorithm were evaluated against the corresponding in situ measurements and compared to those from QAAv5. The results demonstrate that, the QAA-RGR algorithm is characterized by a better performance than QAAv5 for MODIS data. For QAAv5, the averaged mean absolute percentage error (MAPE) values of retrieval results of absorption coefficients and backscattering coefficients compared with in situ match-up measurements are 25.2% and 22.2%, respectively. For QAA-RGR, the averaged MAPE values are 15.9% and 18.3%, respectively. The QAAv5 retrieval results are often significantly underestimated especially for turbid coastal waters because of the easy saturation at 667nm band in addition to a large uncertainty in the estimation of Rrs of the blue bands. The QAA-RGR algorithm may be used to retrieve IOPs from MODIS measurements over the ECS for the measurement periods used in the study.


What has Royal Society Open Science achieved in its first few years?
It has been a pleasure and a privilege to serve as the first Editor-in-Chief of Royal Society Open Science for the past 6 years. I step down at the end of December 2021, having completed two 3-year terms, and am taking the opportunity here to reflect on some of the successes and challenges that the journal has experienced and the innovations that we have introduced. When I was first approached back in 2015, the breadth of the journal, covering the whole of science, resonated with my own interests: my research career has ranged across the entire landscape of chemistry, while my leadership roles have embraced all of science, technology and medicine. The open access ethos, the objective refereeing policy that rejects the idea of only publishing what is in fashion, and the opportunities offered by a new venture that could transcend traditional disciplinary boundaries also all appealed to me. Among our successful innovations are Registered Reports, Replication Studies and the new 'Science, Society and Policy' section. The challenges have included the transition to paid article processing charges (APCs), whether to resist pressure to retract a controversial paper, and bullying of young female authors by established senior males in the same field. I explore all of these below, provide some statistics on the journal's performance, also cover some of the notable papers we have published, and provide some concluding thoughts.


Type of hospital setting and treatment outcome with heroin addicts. Results from a randomised trial.
General psychiatrists have recently been encouraged to provide treatment to heroin addicts, including in-patient detoxification. No comparison has previously been made of specialist versus general psychiatric in-patient care. During a randomised study of cue exposure, 186 opiate addicts were also randomised to either specialist in-patient (DDU; n = 115) or general psychiatric (GEN; n = 71) wards in the same hospital. From pre-treatment (post-randomisation) onwards, patient outcomes differed across the two in-patient settings. Of the original randomised sample, significantly more DDU than GEN subjects accepted their randomisation (100 v. 77%), were subsequently admitted (60 v. 42%), and completed in-patient detoxification (45 v. 18%). Of patients admitted, more DDU than GEN patients completed detoxification (75 v. 43%). During seven-month follow-up, of those 43 patients who reached the end of treatment, significantly more ex-DDU than ex-GEN subjects were opiate-free. From pre-treatment onwards, significant differences in process and outcome were found after allocation to treatment on either DDU or GEN. Further randomised studies are required to replicate and explain these findings.


Nuclear localization and interaction of RolB with plant 14-3-3 proteins correlates with induction of adventitious roots by the oncogene rolB.
The rooting-locus gene B (rolB) on the T-DNA of the root-inducing (Ri) plasmid in Agrobacterium rhizogenes is responsible for the induction of transformed adventitious roots, although the root induction mechanism is unknown. We report here that the RolB protein of pRi1724 (1724RolB) is associated with Nicotianatabacum14-3-3-like protein omegaII (Nt14-3-3 omegaII) in tobacco bright yellow (BY)-2 cells. Nt14-3-3 omegaII directly interacts with 1724RolB protein. Green fluorescent protein (GFP)-fused 1724RolB is localized to the nucleus. GFP-fused mutant 1724RolB proteins having a deletion or amino acid substitution are unable to interact with Nt14-3-3 omegaII and also show impaired nuclear localization. Moreover, these 1724RolB mutants show decreased capacity for adventitious root induction. These results suggest that adventitious root induction by 1724RolB protein correlates with its interaction with Nt14-3-3 omegaII and the nuclear localization of 1724RolB protein.


Higher order aberrations in holographic lenses.
Third-, fifth-, and seventh-order aberrations have been analyzed for in-line and off-axis holographic lenses of different f/No. The seventh-order wave aberrations and the corresponding aberration coefficients are reported here for the first time. It has been concluded that when the holograms are to be used as optical elements, fifth- and seventh-order aberrations should also be considered along with the third order to achieve ideal imagery as both the chromatic and nonchromatic aberrations are quite large even when only small deviations from the recording geometry are present in the reconstruction step.


Polymorphic organic anion transporting polypeptide 1B1 is a major determinant of repaglinide pharmacokinetics.
A large interindividual variability exists in the plasma concentrations of repaglinide. Our aim was to investigate possible associations between the pharmacokinetics of repaglinide and single nucleotide polymorphisms (SNPs) in the genes encoding for the drug transporters organic anion transporting polypeptide 1B1 (OATP1B1) (SLCO1B1 ) and P-glycoprotein ( MDR1 , ABCB1 ) and the drug-metabolizing enzymes cytochrome P450 (CYP) 2C8 and CYP3A5. A total of 56 healthy volunteers ingested a single 0.25-mg dose of repaglinide. Plasma repaglinide and blood glucose concentrations were measured for up to 7 hours. All subjects were genotyped for the -11187G>A and 521T>C SNPs in SLCO1B1 and the 3435C>T and 2677G>T/A SNPs in ABCB1 , as well as for the CYP2C8*3 (416G>A, 1196A>G), CYP2C8*4 (792C>G), and CYP3A5*3 (6986A>G) alleles. The area under the plasma concentration-time curve from time 0 to infinity [AUC(0-infinity)] and peak concentration in plasma (Cmax) of repaglinide varied 16.9-fold and 10.7-fold, respectively, between individual subjects. Multiple regression analyses indicated that the SLCO1B1 521T>C SNP and the CYP2C8*3 allele were independent predictors of the AUC(0-infinity) and Cmax of repaglinide (adjusted multiple R2 = 45% and 36%, respectively). In subjects with the SLCO1B1 521CC genotype, the AUC(0-infinity) of repaglinide was 107% and 188% higher, respectively, than in subjects with the SLCO1B1 521TC or 521TT (reference) genotype (P < .0001). In subjects with the CYP2C8*1/*3 genotype, the AUC(0-infinity) and Cmax of repaglinide were 48% and 44% lower, respectively, than in those with the CYP2C8*1/*1 genotype (P < .05). The pharmacokinetics of repaglinide was not associated with the studied ABCB1 SNPs or the CYP3A5*3 allele. The elimination half-life of repaglinide was not associated with any SNP. Only the SLCO1B1 -11187GA genotype was significantly associated with an enhanced effect of repaglinide on blood glucose. Genetic polymorphism in SLCO1B1 is a major determinant of interindividual variability in the pharmacokinetics of repaglinide. The effect of SLCO1B1 polymorphism on the pharmacokinetics of repaglinide may be clinically important.


Adolescents' Use of Nicotine-Free and Nicotine E-Cigarettes: A Longitudinal Study of Vaping Transitions and Vaper Characteristics.
Although adolescents' nicotine addiction from e-cigarettes is a concern, few studies differentiate between vaping with and without nicotine. This study examines the prevalence of nicotine and nicotine-free vaping, maps transitions between vaping behaviors, and assesses differences in the personal characteristics of vapers in a sample of Norwegian adolescents. Data came from a nationwide longitudinal study of adolescents (n = 2018) conducted in 2017 (T1), 2018 (T2), and 2019 (T3) (mean age: 14.2, 15.0, and 16.2). Using an online questionnaire, we measured vaping with and without nicotine, snus use, smoking, sensation-seeking, conduct problems, and levels of depression. Past 12-month vaping prevalence was stable (12%, 13%, and 15%). Among adolescents reporting vaping at T1, 66% had used e-cigarettes without nicotine, 22% with nicotine, and 12% were unsure of nicotine content. Individual vaping trajectories were unstable: of nicotine-free vapers, 54% became non-users, while 14% became nicotine vapers from T1 to T2. From T2 to T3, 50% became non-users, while 17% became nicotine vapers. Of nicotine vapers, 39% became non-users from T1 to T2, while 46% became non-users from T2 to T3. Compared to nicotine-free vapers, nicotine vapers had more conduct problems (mean = 3.67 vs 2.17), had more symptoms of depression (mean = 11.38 vs 6.95), and comprised more past 30-day snus users (33% vs 14%) and cigarette users (33% vs 9%). Adolescent vapers most commonly used e-cigarettes without nicotine, few of these transitioned into nicotine vaping, and a majority became non-users. Nicotine vapers were more likely to use other tobacco products and have more conduct problems and symptoms of depression compared to nicotine-free vapers. Reporting the prevalence of nicotine-free vaping is critical for assessing nicotine exposure and subsequent risks of nicotine addiction. This multi-cohort longitudinal study showed that use of nicotine-free e-cigarettes is common among young vapers in Norway. Adolescents' vaping patterns-both with and without nicotine-are generally temporal and experimental. Despite the majority of nicotine vapers becoming non-users, they are characterized by having more conduct problems and poorer mental health, and they more often used other tobacco products.


Evaluation of a First PET Tracer Suitable for Imaging the Sigma-2 Receptor in the Brain of Nonhuman Primates.
The sigma-2 receptor (σ2R), recently identified as transmembrane protein 97, is expressed in many cell types and mediates important functions in both the peripheral and central nervous systems. Over the years, σ2R has emerged as a potential therapeutic target for cancer and neurological disorders such as Alzheimer's disease (AD). The currently available σ2R radiotracers have been developed primarily for cancer imaging with limited brain uptake. Here, we report the evaluation of the first brain penetrant 18F-labeled radiotracer suitable for positron emission tomography (PET) imaging of σ2R in nonhuman primate brain.


Colorimetric discriminatory array for detection and discrimination of antioxidants based on HAuCl4/3,3',5,5'-tetramethylbenzidine.
Here, we report a simple but effective nose/tongue-mimic sensor array based on HAuCl4/3,3',5,5'-tetramethylbenzidine (TMB) for colorimetric discrimination and determination of antioxidants. Two concentrations of HAuCl4 were employed as receptor units to construct the colorimetric sensor array. The sensing strategy is based on the fact that HAuCl4 with different concentrations (0.08 and 0.03 mM) could oxidize TMB to oxidized TMB (oxTMB), resulting in a blue and green color solution, respectively, corresponding to an absorption peak centered at 440 nm and 657 nm. However, the presence of different antioxidants could cause the reduction in HAuCl4, leading to the fading of the blue and green color and the decrease in the absorbance at 440 nm and 657 nm to varying degrees. Based on the above phenomena, by taking advantage of linear discriminant analysis (LDA), five antioxidants (i.e. ascorbic acid (AA), melatonin (MT), uric acid (UA), tannic acid (TCA), and glycine (Gly)) at five concentrations (200, 120, 60, 20, and 1 nM) were successfully discriminated both in buffer and serum. More importantly, this approach is simple, fast, and without the use of any nanomaterials.


Some acridine-resistant mutations of bacteriophage T4D.
Three new 9-aminoacridine (9AA) resistant mutations of bacteriophage T4D have been isolated and characterized. Two of the mutations, rs and rc, have identical patterns of acridine resistance, but they map on opposite sides of the rII region. In addition, rs has an effect on the plaque morphology of r mutations, whereas rc does not. The third mutation, ama, maps very close to rs but exhibits a different pattern of resistance to 9AA. None of the three is resistant to acridines by virtue of reduced permeability. Taken together with other mutations that have been previously characterized, these new mutations permit us to set the minimum number of acridine-sensitive processes in T4 development at four.


Vibrational and electronic absorption spectroscopy of dibenzo[b,def]chrysene and its ions.
The vibrational and electronic absorption spectra of dibenzo[b,def]chrysene (DBC) and its ions in argon matrixes have been recorded. Assignment of the observed infrared (IR) bands has been made by comparison with the density functional theory (DFT) computations of harmonic vibrational frequencies (with 6-31G(d,p) or 6-311+G(d,p) basis sets). Extensive time-dependent (TD) DFT calculations of vertical excitation energies have aided in the assignment of the experimental electronic absorption transitions. In general, the theoretical predictions are in good agreement with the observed ultraviolet and visible bands. By correlating IR and UV-visible band intensities (after UV photolysis), it has been shown that both DBC cations and anions are formed. The IR band intensity distributions of the DBC ions differ markedly from neutral DBC. A synthetic spectrum composed of neutral, cationic, and anionic DBC contributions compares reasonably well with the interstellar features of the "unidentified infrared" (UIR) bands from the reflection nebula NGC 7023. Finally, it is shown that the electronic absorption bands of the DBC ions lie in close proximity to several of the diffuse interstellar visible absorption bands (DIBs).


Can polygenic risk scores help identify pediatric bipolar spectrum and related disorders?: A systematic review.
The genetic basis of mood disorders can, theoretically, provide diagnostic information in scenarios of clinical uncertainty. Therefore, we examined the available body of knowledge on the association between polygenic risk scores for bipolar disorder (BP-PRSs) and pediatric bipolar spectrum and related disorders. We performed a literature search through PubMed in March of 2020. The following variables were extracted from relevant studies: population age, study sample size, source of polygenic risk scores, source of data, the primary goal of the study, the assessments used during the course of the study, and the main findings/outcomes of each study. BP-PRSs were associated with deficits in executive functioning and the diagnosis of attention deficit/hyperactivity disorder (ADHD). Three studies included in our analysis directly compared major depressive disorder (MDD)-PRSs to BP-PRSs in youth. Results showed that MDD-PRSs, and not BP-PRSs, were associated with ADHD symptoms, internalizing problems, and social problems. ADHD-PRSs were associated with conduct problems, depressive symptomatology, and externalizing disorders symptoms. Findings revealed that ADHD-PRSs were more clearly associated with emotional reactivity, emotional dysregulation, and irritability-frequent correlates of pediatric BP disorder. These findings suggest that ADHD-PRSs may have an important contribution to the development of mood related problems in youth.


Source attribution of Campylobacter jejuni shows variable importance of chicken and ruminants reservoirs in non-invasive and invasive French clinical isolates.
Campylobacter jejuni is the most common cause of bacterial gastroenteritis worldwide. Mainly isolated from stool samples, C. jejuni can also become invasive. C. jejuni belongs to the commensal microbiota of a number of hosts, and infection by this bacterium can sometimes be traced back to exposure to a specific source. Here we genome sequenced 200 clinical isolates (2010-2016) and analyzed them with 701 isolate genomes from human infection, chicken, ruminants and the environment to examine the relative contribution of different reservoirs to non-invasive and invasive infection in France. Host-segregating genetic markers that can discriminate C. jejuni source were used with STRUCTURE software to probabilistically attribute the source of clinical strains. A self-attribution correction step, based upon the accuracy of source apportionment within each potential reservoir, improved attribution accuracy of clinical strains and suggested an important role for ruminant reservoirs in non-invasive infection and a potentially increased contribution of chicken as a source of invasive isolates. Structured sampling of Campylobacter in the clinic and from potential reservoirs provided evidence for variation in the contribution of different infection sources over time and an important role for non-poultry reservoirs in France. This provides a basis for ongoing genomic epidemiology surveillance and targeted interventions.


Haplotypic QTL mapping in an outbred pedigree.
An offspring genome can be viewed as a mosaic of chromosomal segments or haplotypes contributed by multiple founders in any quantitative trait locus (QTL) detection study but tracing these is especially complex to achieve for outbred pedigrees. QTL haplotypes can be traced from offspring back to individual founders in outbred pedigrees by combining founder-origin probabilities with fully informative flanking markers. This haplotypic method was illustrated for QTL detection using a three-generation pedigree for a woody perennial plant, Pinus taeda L. Growth rate was estimated using height measurements from ages 2 to 10 years. Using simulated and actual datasets, power of the experimental design was shown to be efficient for detecting QTLs of large effect. Using interval mapping and fully informative markers, a large QTL accounting for 11.3% of the phenotypic variance in the growth rate was detected. This same QTL was expressed at all ages for height, accounting for 7.9-12.2% of the phenotypic variance. A mixed-model inheritance was more appropriate for describing genetic architecture of growth curves in P. taeda than a strictly polygenic model. The positive QTL haplotype was traced from the offspring to its contributing founder, GP3, then the haplotypic phase for GP3 was determined by assaying haploid megagametophytes. The positive QTL haplotype was a recombinant haplotype contributed by GP3. This study illustrates the combined power of fully informative flanking markers and founder origin probabilities for (1) estimating QTL haplotype magnitude, (2) tracing founder origin and (3) determining haplotypic transmission frequency.


Clinical Features and Short-Term Outcomes in COVID-19-Infected Patients with Cancer.
Coronavirus disease 2019 (COVID-19) is an infectious disease that has been spreading very fast worldwide. Up to now, there is scarce information regarding the clinical features and short-term outcomes of infected patients with cancer. We performed a retrospective study in Wuhan Union Hospital from Feb 14, 2020, to Mar 15, 2020, China. Data were retrieved including demographic and clinical features, laboratory findings, and outcome data. Patients were classified into the discharged group and undischarged group by the 4-week outcomes from admission. Difference analysis and correlation analysis were performed between the two groups. A total of 37 patients were enrolled in the study, including 27 cancer survivors in routine follow-up. Breast cancer (18.9%) was the most frequent cancer type, and common symptoms included cough (54.1%), fever (48.6%), and fatigue (27%). Lymphocytopenia and hypoproteinemia were much frequent in patients who had received chemotherapy, radiotherapy, or surgery within the past month. However, the concentration of D-dimer (median: 3.75 vs 0.43, P =0.010) and fibrin degradation products (median: 23.60 vs 1.80, P =0.002) were evidently increased in this population compared with cancer survivors. At the end of follow-up, 83.8% of the enrolled patients were discharged. Among the discharged, women (48.6%) and cancer survivors (67.6%) showed better short-term outcomes. The elevated level of FDP was significantly higher in the undischarged group (median: 21.85 vs 2.00, P =0.049). The proportion of CD3-positive lymphocyte cells and CD4-positive lymphocytes was correlated with short-term outcomes. Peripheral lymphocyte subset (CD3-positive and CD4-positive) on admission as a novel biomarker had a potential association with early efficacy. Cancer survivors in routine follow-up would achieve better short-term outcomes. COVID-19 patients with cancer should gain more attention and close monitoring.


MCD4 encodes a conserved endoplasmic reticulum membrane protein essential for glycosylphosphatidylinositol anchor synthesis in yeast.
Glycosylphosphatidylinositol (GPI)-anchored proteins are cell surface-localized proteins that serve many important cellular functions. The pathway mediating synthesis and attachment of the GPI anchor to these proteins in eukaryotic cells is complex, highly conserved, and plays a critical role in the proper targeting, transport, and function of all GPI-anchored protein family members. In this article, we demonstrate that MCD4, an essential gene that was initially identified in a genetic screen to isolate Saccharomyces cerevisiae mutants defective for bud emergence, encodes a previously unidentified component of the GPI anchor synthesis pathway. Mcd4p is a multimembrane-spanning protein that localizes to the endoplasmic reticulum (ER) and contains a large NH2-terminal ER lumenal domain. We have also cloned the human MCD4 gene and found that Mcd4p is both highly conserved throughout eukaryotes and has two yeast homologues. Mcd4p's lumenal domain contains three conserved motifs found in mammalian phosphodiesterases and nucleotide pyrophosphases; notably, the temperature-conditional MCD4 allele used for our studies (mcd4-174) harbors a single amino acid change in motif 2. The mcd4-174 mutant (1) is defective in ER-to-Golgi transport of GPI-anchored proteins (i.e., Gas1p) while other proteins (i.e., CPY) are unaffected; (2) secretes and releases (potentially up-regulated cell wall) proteins into the medium, suggesting a defect in cell wall integrity; and (3) exhibits marked morphological defects, most notably the accumulation of distorted, ER- and vesicle-like membranes. mcd4-174 cells synthesize all classes of inositolphosphoceramides, indicating that the GPI protein transport block is not due to deficient ceramide synthesis. However, mcd4-174 cells have a severe defect in incorporation of [3H]inositol into proteins and accumulate several previously uncharacterized [3H]inositol-labeled lipids whose properties are consistent with their being GPI precursors. Together, these studies demonstrate that MCD4 encodes a new, conserved component of the GPI anchor synthesis pathway and highlight the intimate connections between GPI anchoring, bud emergence, cell wall function, and feedback mechanisms likely to be involved in regulating each of these essential processes. A putative role for Mcd4p as participating in the modification of GPI anchors with side chain phosphoethanolamine is also discussed.


Racial Representation Disparity of Population-Level Genomic Sequencing Efforts.
To develop personalized treatments for diseases, it is essential that they reflect the population of individuals that may be affected by a given disease. Amidst claims that there may be racial disparities in research populations, there have been no direct studies to explore this disparity in disease incidence and research projects that involve genomic sequencing. The precise relationship between underrepresentation of certain races in genomic sequencing studies and health outcomes relative to these races is unknown. Here, we examine the disparities in racial representation of national datasets pertaining to clinical data, mortality rates, and a major initiative involving genomic sequence analysis (The Cancer Genome Atlas [TCGA]). The results suggest that black Americans are underrepresented for most cancers in TCGA compared to clinical and mortality datasets, whereas Asian Americans are overrepresented. These findings accentuate the importance of targeted efforts to recruit representative patient populations into studies involving genomic sequencing.


Reversible Control of Gelatin Hydrogel Stiffness by Using DNA Crosslinkers*.
Biomaterials with dynamically tunable properties are critical for a range of applications in regenerative medicine and basic biology. In this work, we show the reversible control of gelatin methacrylate (GelMA) hydrogel stiffness through the use of DNA crosslinkers. We replaced some of the inter-GelMA crosslinks with double-stranded DNA, allowing for their removal through toehold-mediated strand displacement. The crosslinks could be restored by adding fresh dsDNA with complementary handles to those on the hydrogel. The elastic modulus (G') of the hydrogels could be tuned between 500 and 1000 Pa, reversibly, over two cycles without degradation of performance. By functionalizing the gels with a second DNA strand, it was possible to control the crosslink density and a model ligand in an orthogonal fashion with two different displacement strands. Our results demonstrate the potential for DNA to reversibly control both stiffness and ligand presentation in a protein-based hydrogel, and will be useful for teasing apart the spatiotemporal behavior of encapsulated cells.


Evidence of frontotemporal structural hypoconnectivity in social anxiety disorder: A quantitative fiber tractography study.
Investigation of the brain's white matter fiber tracts in social anxiety disorder (SAD) may provide insight into the underlying pathophysiology. Because models of pathological anxiety posit altered frontolimbic interactions, the uncinate fasciculus (UF) connecting (orbito-) frontal and temporal areas including the amygdala is of particular interest. Microstructural alterations in parts of the UF have been reported previously, whereas examination of the UF as discrete fiber tract with regard to more large-scale properties is still lacking. Diffusion tensor imaging was applied in 25 patients with generalized SAD and 25 healthy control subjects matched by age and gender. By means of fiber tractography, the UF was reconstructed for each participant. The inferior fronto-occipital fasciculus (IFOF), originating from the frontal cortex similarly to the UF, was additionally included as control tract. Volume and fractional anisotropy (FA) were compared between the groups for both tracts. Volume of left and right UF was reduced in patients with SAD, reaching statistical significance for the left UF. Bilateral IFOF volume was not different between groups. A similar pattern was observed for FA. Reduced volume of the left UF in SAD fits well into pathophysiological models of anxiety, as it suggests deficient structural connectivity between higher-level control areas in the orbitofrontal cortex and more basal limbic areas like the amygdala. The results point to a specific role of the left UF with regard to altered white matter volume in SAD. However, results should be replicated and functional correlates of altered UF volume be determined in future studies.


Role of quantitative endotracheal aspirate and cultures as a surveillance and diagnostic tool for ventilator associated pneumonia: a pilot study.
Accurate diagnosis and appropriate treatment of ventilator associated pneumonia (VAP) is crucial for good outcomes. Endotracheal suctioning is performed in ventilated patients as part of routine care and for tracheal toileting. We evaluated if quantitative endotracheal aspirate (ETA) was a suitable alternative to bronchoalveolar lavage (BAL) for suspected VAP. In addition we assessed if surveillance ETA guided antibiotic selection for subsequent VAP. Prospective study in the surgical intensive care unit (ICU) of a tertiary hospital in India. Two hundred consecutive patients with mean (standard deviation) APACHE II score of 12.3+/-5 and requiring mechanical ventilation beyond 48 hours underwent surveillance ETA cultures. A second ETA and BAL were performed if the patient developed features of VAP. The threshold for microbiological diagnosis of VAP was taken as 10 5 colony forming units/ml (cfu/ml) for ETA and 10 4 cfu/ml for BAL. The sensitivity and specificity of surveillance and concurrent ETA aspirate cultures were compared with BAL cultures. VAP was suspected clinically and corroborated radiologically in 27/177 patients (15.3%). Although microbiological support for VAP was obtained by ETA in 19 patients, bronchoscopy was possible only in 13 patients, 8 of whom had isolates at significant threshold. Of the 16 organisms isolated from BAL, 11 were of significant threshold with 9/11 (82%) BAL isolates having a similar antibiogram to a concurrent ETA. Only one BAL isolate (9%), at significant threshold, was not isolated on a concurrent ETA. On the other hand just 6/11 BAL isolates (55%) had an identical antibiogram to surveillance ETA. BAL had 3 additional isolates (27%) at significant threshold not isolated on surveillance ETA. Concurrent quantitative ETA could substitute BAL cultures for VAP. Surveillance ETA at 48 hours of ventilation does not appear to assist with antibiotic selection for a subsequent VAP.


Pancreatic acinar cells: the role of calcium in stimulus-secretion coupling.
1. Segments of mouse or rat pancreas were placed in a flow cell through which physiological salt solutions of varying composition were pumped at a constant rate. Intracellular recordings of membrane potential, resistance and electrical time constant were made from the acini using fine glass micro-electrodes. In some experiments two micro-electrodes were inserted into two acinar cells within the same acinus to assess directly cell to cell coupling. The concentration of amylase in the effluent was measured continuously. 2. Electrical coupling between two acinar cells was observed when the tips of the two micro-electrodes were less than 50 mum from each other. The coupling ratio was close to 1. Acetylcholine (ACh) always evoked depolarization of exactly the same amplitude in two coupled cells and reduced the amplitude of current-pulse induced membrane potential changes in both cell simultaneously. 3. Stimulation with ACh caused an immediate increase in amylase output. Replacement of superfusion fluid Na by Tris or Cl by sulphate abolished ACh-evoked increase in amylase release, but the subsequent reintroduction of Na or Cl caused an increase in amylase release of a magnitude similar to what was normally observed following stimulation. 4. Omitting Ca from the superfusion fluid and adding EGTA rapidly depolarized the acinar cell membrane, reduced the input resistance and caused a marked reduction in amylase secretion. During exposure to a Ca-free, EGTA containing solution a marked increase in amylase release occurred following maximal ACh stimulation. 5. Addition of small amounts of Mg, Ca or Mn to a Ca-, Mg-free solution caused an increase in membrane potential, input resistance and electrical time constant and markedly increased amylase release. The effect on the electrical parameters was reversed in the absence of extracellular Na while extracellular Na was of no importance for the effect on amylase release. 6. The effect of ACh on amylase was enhanced during superfusion with a fluid containing 20 mM-Ca. The presence of Mn (5 mM) in an otherwise normal control had no effect on ACh-evoked release. 7. These results show that ACh acts on the acinus by reducing the surface cell membrane resistance. It is suggested that the ACh-receptor interaction causes a release of Ca from the surface cell membrane and that the concentration of Ca in the surface cell membrane determines the specific membrane resistance particularly for Na. The release of Ca to the cytosol activates exocytosis while the Na influx is of importance for acinar fluid secretion. The effect of ACh on amylase secretion can be mimicked by agents displacing membrane-bound Ca (Mg, Ca, Mn).


The development of dentotropic micelles with biodegradable tooth-binding moieties.
Development of dentotropic (tooth-binding) micelle formulations to improved efficacy and safety of antimicrobial therapy for dental plaque prevention and treatment. Because of their excellent biocompatibility and biodegradability, diphosphoserine peptide and pyrophosphate were selected as the tooth-binding moieties to replace alendronate, which was used previously. Diphosphoserine peptide was conjugated to Pluronic P123 using "click" chemistry, whereas pyrophosphate was attached to P123 through an ester bond. The tooth-binding micelles (TBMs) were prepared by self-assembly of the modified P123 with the antimicrobial agent triclosan. The influence of human saliva and/or its components on TBMs' drug-releasing profile, tooth-binding potential and binding stability was evaluated in vitro. S. mutans UA159 biofilm formed on hydroxyapatite (HA) discs was used to evaluate the TBMs' therapeutic potential. Saliva does not affect triclosan release from TBMs. More than 60% of TBMs' HA binding capacity was maintained in the presence of saliva. Less than 5% of TBMs bound to HA was released over 24 h in human saliva, protease or phosphatase, suggesting the retention properties of the TBMs will not be compromised due to the biodegradable nature of the binding moieties. In both in vitro biofilm prevention and treatment studies, the TBM treated group showed significantly lower CFU per HA disc compared to the controls (2-log reduction, p < 0.05). The data from these studies suggest that the novel dentotropic micelle formulations bearing biodegradable tooth-binding moieties can be used as an effective and safe delivery tool for antimicrobials to improve dental plaque prevention and treatment.


Toward oriented surface architectures with three coaxial charge-transporting pathways.
We report a synthetic method to build oriented architectures with three coaxial π-stacks directly on solid surfaces. The approach operates with orthogonal dynamic bonds, disulfides and hydrazones, self-organizing surface-initiated polymerization (SOSIP), and templated stack-exchange (TSE). Compatibility with naphthalenediimides, perylenediimides, squaraines, fullerenes, oligothiophenes, and triphenylamine is confirmed. Compared to photosystems composed of two coaxial channels, the installation of a third channel increases photocurrent generation up to 10 times. Limitations concern giant stack exchangers that fail to enter SOSIP architectures (e.g., phthalocyanines surrounded by three fullerenes), and planar triads that can give folded or interdigitated charge-transfer architectures rather than three coaxial channels. The reported triple-channel surface architectures are as sophisticated as it gets today, the directionality of their construction promises general access to multichannel architectures with multicomponent gradients in each individual channel. The reported approach will allow us to systematically unravel the ultrafast photophysics of molecular dyads and triads in surface architectures, and might become useful to develop conceptually innovative optoelectronic devices.


Radial or ulnar artery laceration. Repair or ligate?
To determine the relationship between patency of radial or ulnar artery repair and later hand symptoms. Call-back survey. Urban trauma center. Thirty-two subjects with wrist artery lacerations undergoing 26 arterial repairs and six artery ligations during an 8-year period. Directed history and hand examination (palpation of wrist pulses, Doppler Allen test, and Doppler interrogation of palmar arch and digital vessels). History of hand claudication, weakness, or cold sensitivity or paresthesias and patency of wrist arteries. Twelve (46%) of 26 wrist artery repairs were patent. There was no evident benefit of optical magnification or specialization in hand or vascular surgery. No subjects had hand claudication; there was a 50% incidence of hand weakness and a 12% incidence of cold sensitivity independent of patency of the damaged wrist artery and present only in subjects with associated nerve injury. Professional charges for wrist artery repair were threefold to fourfold higher than those for wrist artery ligation. Consonant with prior reports, patency following repair of radial or ulnar artery laceration does not exceed 50%. Later hand symptoms relate to nerve or tendon damage, not to arterial patency. In the absence of acute hand ischemia, simple ligation of a lacerated radial or ulnar artery is safe and cost-effective.


Oxidative stress markers at birth: Analyses of a neonatal population.
In order to further understand neonatal stress and, thus, control it efficaciously, there is a need for more information on the manifestations of stress at the molecular level in the newborn, with particular regard to oxidants, and anti-oxidant and anti-stress mechanisms, including mitochondrial heat shock protein-chaperones such as Hsp60. We investigated patterns of anti-oxidants, biomarkers of oxidative stress, and Hsp60 levels in sera from newborns and found significant associations between glutathione (GSH) levels and gestational age, delivery modality, and lipid hydroperoxydes (LOOH) level. LOOH levels and spontaneous (vaginal) delivery were independently associated with increased GSH levels when these were above the median. Hsp60 and LOOH levels were positively correlated whereas Hsp60 and GSH levels were inversely correlated in spontaneously delivered newborns; in contrast, Hsp60 and GSH levels were positively correlated in newborns delivered by cesarea. Our results point to new directions in the search for definite patterns of GSH, LOOH, and Hsp60 in the newborn's serum that might have functional and diagnostic significance and that could help in the monitoring of newborn health during and after delivery. In addition, the data provide a starting basis for investigating the precise roles and interplay of GSH and Hsp60 in the maintenance of an optimal redox balance at birth to cope with the stress inherent to delivery, and also for investigating the predictive value of any given pattern of GSH, LOOH, and Hsp60 at birth with regard to health status and risk of disease in adult life.


Resveratrol protects against oxidized low‑density lipoprotein‑induced human umbilical vein endothelial cell apoptosis via inhibition of mitochondrial‑derived oxidative stress.
Resveratrol, a natural phytochemical found in grapes and red wine, has been found to possess protective effects against endothelial cell apoptosis and oxidative damage. Oxidized‑low density lipoprotein (ox‑LDL) can induce apoptosis of endothelial cells, which is an important initial event in several cardiovascular diseases. However, the effect of resveratrol on ox‑LDL‑induced apoptosis and oxidative damage, and the possible associated mechanisms remain to be elucidated. In the present study, following exposure to ox‑LDL, human umbilical vein endothelial cells (HUVECs) were treated with or without resveratrol. Cell viability was examined using Cell Counting Kit‑8 and 5‑bromo‑2'‑deoxyuridine uptake assays, respectively. Cell apoptosis was determined by flow cytometry. Apoptosis‑associated markers were detected using western blot analysis. Oxidative stress was analyzed using molecular and biochemical approaches. Resveratrol restored ox‑LDL‑induced HUVEC injury and apoptosis in a dose‑dependent manner. In addition, compared with the control group, ox‑LDL treatment decreased the B cell lymphoma‑2 (Bcl‑2)/Bcl‑2‑associated X protein ratio, mitochondrial membrane potential and activation of superoxide dismutase, and enhanced the release of mitochondrial cytochrome c into the cytoplasm, the activation of caspase and lipid peroxidation. All these alterations were significantly inhibited following treatment with resveratrol. The results demonstrated that resveratrol prevented HUVEC apoptosis through inhibiting mitochondria‑derived oxidative damage. These findings may provide a novel mechanism by which resveratrol prevents against endothelial cell apoptosis.


Applications of virtual environments in medicine.
This paper intends to investigate the role of virtual reality (VR) in medicine. In particular it outlines the current state of research and technology that is relevant to the development of effective virtual environments in medicine. After describing the two different visions of VR we can find in medicine--the presentation of virtual objects to all of the human senses in a way identical to their natural counterpart, and a new human-computer interaction paradigm in which users are active participants within a computer-generated three-dimensional virtual world--the paper presents some of the most interesting applications actually developed in the area. Finally, it discusses the clinical principles, technological devices and safety issues associated with the use of VR in medicine. With more than 1,000 VR papers already indexed in Medline, VR is a reality health care. Even if the number of controlled studies is still limited, its merging with emerging technologies like Ambient Intelligence and wireless communication will further improve its diffusion. The possible impact of VR on health care could be even higher than the one offered by the new communication technologies like Internet. In fact, VR is at the same time technology, a communication interface and an experience: a communication interface based on interactive 3D visualization, able to collect and integrate in single real-like experience different inputs and data sets. However, significant efforts are still required to move VR into commercial success and therefore routine clinical use.


Deubiquitinating Enzymes Related to Autophagy: New Therapeutic Opportunities?
Autophagy is an evolutionary conserved catabolic process that allows for the degradation of intracellular components by lysosomes. This process can be triggered by nutrient deprivation, microbial infections or other challenges to promote cell survival under these stressed conditions. However, basal levels of autophagy are also crucial for the maintenance of proper cellular homeostasis by ensuring the selective removal of protein aggregates and dysfunctional organelles. A tight regulation of this process is essential for cellular survival and organismal health. Indeed, deregulation of autophagy is associated with a broad range of pathologies such as neuronal degeneration, inflammatory diseases, and cancer progression. Ubiquitination and deubiquitination of autophagy substrates, as well as components of the autophagic machinery, are critical regulatory mechanisms of autophagy. Here, we review the main evidence implicating deubiquitinating enzymes (DUBs) in the regulation of autophagy. We also discuss how they may constitute new therapeutic opportunities in the treatment of pathologies such as cancers, neurodegenerative diseases or infections.


56Fe Particle Exposure Results in a Long-Lasting Increase in a Cellular Index of Genomic Instability and Transiently Suppresses Adult Hippocampal Neurogenesis in Vivo.
The high-LET HZE particles from galactic cosmic radiation pose tremendous health risks to astronauts, as they may incur sub-threshold brain injury or maladaptations that may lead to cognitive impairment. The health effects of HZE particles are difficult to predict and unfeasible to prevent. This underscores the importance of estimating radiation risks to the central nervous system as a whole as well as to specific brain regions like the hippocampus, which is central to learning and memory. Given that neurogenesis in the hippocampus has been linked to learning and memory, we investigated the response and recovery of neurogenesis and neural stem cells in the adult mouse hippocampal dentate gyrus after HZE particle exposure using two nestin transgenic reporter mouse lines to label and track radial glia stem cells (Nestin-GFP and Nestin-CreERT2/R26R:YFP mice, respectively). Mice were subjected to 56Fe particle exposure (0 or 1 Gy, at either 300 or 1000 MeV/n) and brains were harvested at early (24h), intermediate (7d), and/or long time points (2-3mo) post-irradiation. 56Fe particle exposure resulted in a robust increase in 53BP1+ foci at both the intermediate and long time points post-irradiation, suggesting long-term genomic instability in the brain. However, 56Fe particle exposure only produced a transient decrease in immature neuron number at the intermediate time point, with no significant decrease at the long time point post-irradiation. 56Fe particle exposure similarly produced a transient decrease in dividing progenitors, with fewer progenitors labeled at the early time point but equal number labeled at the intermediate time point, suggesting a recovery of neurogenesis. Notably, 56Fe particle exposure did not change the total number of nestin-expressing neural stem cells. These results highlight that despite the persistence of an index of genomic instability, 56Fe particle-induced deficits in adult hippocampal neurogenesis may be transient. These data support the regenerative capacity of the adult SGZ after HZE particle exposure and encourage additional inquiry into the relationship between radial glia stem cells and cognitive function after HZE particle exposure.


Near-infrared optical properties of ex vivo human uterus determined by the Monte Carlo inversion technique.
The optical properties, absorption (mua) and reduced scattering coefficient (mu's), of ex vivo human myometrium and leiomyoma (fibroid) have been determined by the Monte Carlo inversion technique over the wavelength range 600-1000 nm. This region is currently of interest for new, minimal-access, surgical laser procedures such as photodynamic therapy (PDT) for abnormalities of the uterus, and interstitial laser photocoagulation (ILP) for the thermal ablation of fibroids. In the region 630-675 nm (corresponding to PDT), the optical coefficients of myometrium are mua = 0.041+/-0.012 mm(-1) and mu's = 1.37+/-0.19 mm(-1). For the wavelength range 800-1000 nm (associated with infrared lasers for ILP), the optical coefficients of fibroid were found to be mua = 0.020+/-0.003 mm(-1) and mu's = 0.56+/-0.03 mm(-1). Overall, the optical properties of fibroid were found to be lower than myometrium, and this was attributed to the differences in both anatomy and vascularity. The results show that PDT for ablation of the uterine endometrium is most unlikely to affect any tissues beyond the myometrium, and that the region around 800 nm is the most effective for ablation of fibroids using ILP as the penetration depth of light is greatest at this wavelength.


Mediating Triple Ions Migration Behavior via a Fluorinated Separator Interface toward Highly Reversible Aqueous Zn Batteries.
Rampant dendrite growth, electrode passivation and severe corrosion originate from the uncontrolled ions migration behavior of Zn2+ , SO4 2- , and H+ , which are largely compromising the aqueous zinc ion batteries (AZIBs) performance. Exploring the ultimate strategy to eliminate all the Zn anode issues is challenging but urgent at present. Herein, a fluorinated separator interface (PVDF@GF) is constructed simply by grafting the polyvinylidene difluoride (PVDF) on the GF surface to realize high-performance AZIBs. Experimental and theoretical studies reveal that the strong interaction between C─F bonds in the PVDF and Zn2+ ions enables evenly redistributed Zn2+ ions concentration at the electrode interface and accelerates the Zn transportation kinetics, leading to homogeneous and fast Zn deposition. Furthermore, the electronegative separator interface can spontaneously repel the SO4 2- and anchor H+ ions to alleviate the passivation and corrosion. Accordingly, the Zn|Zn symmetric cell with PVDF@GF harvests a superior cycling stability of 500 h at 10 mAh cm-2 , and the Zn|VOX full cell delivers 76.8% capacity retention after 1000 cycles at 2 A g-1 . This work offers an all-round solution and provides new insights for the design of advanced separators with ionic sieve function toward stable and reversible Zn metal anode chemistry.


Do Bedside Visual Tools Improve Patient and Caregiver Satisfaction? A Systematic Review of the Literature.
Although common, the impact of low-cost bedside visual tools, such as whiteboards, on patient care is unclear. To systematically review the literature and assess the influence of bedside visual tools on patient satisfaction. Medline, Embase, SCOPUS, Web of Science, CINAHL, and CENTRAL. Studies of adult or pediatric hospitalized patients reporting physician identification, understanding of provider roles, patient-provider communication, and satisfaction with care from the use of visual tools were included. Outcomes were categorized as positive, negative, or neutral based on survey responses for identification, communication, and satisfaction. Two reviewers screened studies, extracted data, and assessed the risk of study bias. Sixteen studies met the inclusion criteria. Visual tools included whiteboards (n = 4), physician pictures (n = 7), whiteboard and picture (n = 1), electronic medical record-based patient portals (n = 3), and formatted notepads (n = 1). Tools improved patients' identification of providers (13/13 studies). The impact on understanding the providers' roles was largely positive (8/10 studies). Visual tools improved patient-provider communication (4/5 studies) and satisfaction (6/8 studies). In adults, satisfaction varied between positive with the use of whiteboards (2/5 studies) and neutral with pictures (1/5 studies). Satisfaction related to pictures in pediatric patients was either positive (1/3 studies) or neutral (1/3 studies). Differences in tool format (individual pictures vs handouts with pictures of all providers) and study design (randomized vs cohort) may explain variable outcomes. The use of bedside visual tools appears to improve patient recognition of providers and patient-provider communication. Future studies that include better design and outcome assessment are necessary before widespread use can be recommended.


[The neuronal reactions of the posterior ventral thalamic nucleus in the rat during vibrissal movements].
The unit activity responses to induced and spontaneous rat whiskers movements were studied. Spontaneous movements were induced by the Author's method of partial curarization. The unit responses were obtained both to induced and spontaneous movements of the whiskers but from same cells. These findings suggest that the analysis of tactile information is being carried out through the information on the movements of whiskers.


Coaxial holographic data storage without recording the dc components.
A technique of recovering the data pages from Fourier holograms recorded without the dc components is demonstrated theoretically and experimentally by use of a coaxial holographic storage system. A reconstructed image is obtained by adding a phase-modulated dc component of the signal beam on reading. The bit error rate of the reconstructed image is comparable with that for the hologram recorded with the dc component as well. Since high intensities of the dc components are not recorded in this technique, the dynamic range of the recording media can be saved, which potentially contributes to increasing the number of multiplexed holograms.


[The pathomorphological changes in the epiphysis in chronic alcoholism].
Routine, histochemical and morphometric methods were used in examination of epiphyses in 45 autopsy cases of persons that suffered of alcoholism. Characteristic morphofunctional features of the epiphysis were found in those suffering from alcoholism with a stable and hard drinking character, alcohol epilepsy showing involvement of the epiphysis in the complex pathogenesis of the disease.


Thermochemical functionalisation of graphenes with minimal framework damage.
Graphene and graphene nanoplatelets can be functionalised via a gas-phase thermochemical method; the approach is versatile, readily scalable, and avoids the introduction of additional defects by exploiting existing sites. Direct TEM imaging confirmed covalent modification of single layer graphene, without damaging the connectivity of the lattice, as supported by Raman spectrometry and AFM nano-indentation measurements of mechanical stiffness. The grafting methodology can also be applied to commercially-available bulk graphene nanoplatelets, as illustrated by the preparation of anionic, cationic, and non-ionic derivatives. Successful bulk functionalisation is evidenced by TGA, Raman, and XPS, as well as in dramatic changes in aqueous dispersability. Thermochemical functionalisation thus provides a facile approach to modify both graphene monolayers, and a wide range of graphene-related nanocarbons, using variants of simple CVD equipment.


Oral and dental late effects in survivors of childhood cancer: a Children's Oncology Group report.
Multi-modality therapy has resulted in improved survival for childhood malignancies. The Children's Oncology Group Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers provide practitioners with exposure- and risk-based recommendations for the surveillance and management of asymptomatic survivors who are at least 2 years from completion of therapy. This review outlines the pathophysiology and risks for oral and dental late effects in pediatric cancer survivors and the rationale for oral and dental screening recommended by the Children's Oncology Group. An English literature search for oral and dental complications of childhood cancer treatment was undertaken via MEDLINE and encompassed January 1975 to January 2013. Proposed guideline content based on the literature review was approved by a multi-disciplinary panel of survivorship experts and scored according to a modified version of the National Comprehensive Cancer Network "Categories of Consensus" system. The Children's Oncology Group oral-dental panel selected 85 relevant citations. Childhood cancer therapy may impact tooth development, salivary function, craniofacial development, and temporomandibular joint function placing some childhood cancer survivors at an increased risk for poor oral and dental health. Additionally, head and neck radiation and hematopoietic stem cell transplantation increase the risk of subsequent malignant neoplasms in the oral cavity. Survivors require routine dental care to evaluate for potential side effects and initiate early treatment. Certain childhood cancer survivors are at an increased risk for poor oral and dental health. Early identification of oral and dental morbidity and early interventions can optimize health and quality of life.


Acute respiratory distress syndrome, mechanical ventilation, and right ventricular function.
To reiterate the effects of positive pressure ventilation on right ventricular (RV) function in acute respiratory distress syndrome (ARDS), to explain in which conditions acute cor pulmonale (ACP) may worsen prognosis, and to define an approach to protection of the right ventricle. In unselected populations of ARDS patients, large studies have reported a 25% incidence of ACP. ACP has deleterious consequences, such as patent foramen ovale shunting and fewer ventilator-free days within the first 28 days. ACP may also worsen prognosis if not taken into account to adapt respiratory settings to RV function. ACP reflects the balance between lung recruitment and lung overdistension. To prevent ACP or to correct it, plateau pressure must be below 27-28 cmH2O, hypercapnia controlled, intrinsic positive end-expiratory pressure (PEEP) avoided, and a 'low' PEEP applied. Recent findings have suggested a negative correlation between the deleterious effect of PEEP on RV function and its ability to recruit the lung. Routine RV function assessment leads to an approach to mechanical ventilation in ARDS patients designed for protection of the right ventricle. This approach called 'RV protective approach' must be associated with prone positioning, a method of ventilation that improves RV function.


Neighborhood-level LGBT hate crimes and current illicit drug use among sexual minority youth.
To investigate whether past-30 day illicit drug use among sexual minority youth was more common in neighborhoods with a greater prevalence of hate crimes targeting lesbian, gay, bisexual, and transgender (LGBT, or sexual minority) individuals. We used a population-based survey of public school youth in Boston, Massachusetts, consisting of 1292 9th-12th grade students from the 2008 Boston Youth Survey Geospatial Dataset (sexual minority n=108). Data on LGBT hate crimes involving assaults or assaults and battery between 2005 and 2008 were obtained from the Boston Police Department and linked to youths' residential address. Youth reported past-30 day use of marijuana and other illicit drugs. Wilcoxon-Mann-Whitney tests and corresponding p-values were computed to assess differences in substance use by neighborhood-level LGBT assault hate crime rate among sexual minority youth (n=103). The LGBT assault hate crime rate in the neighborhoods of sexual minority youth who reported current marijuana use was 23.7 per 100,000, compared to 12.9 per 100,000 for sexual minority youth who reported no marijuana use (p=0.04). No associations between LGBT assault hate crimes and marijuana use among heterosexual youth (p>0.05) or between sexual minority marijuana use and overall neighborhood-level violent and property crimes (p>0.05) were detected, providing evidence for result specificity. We found a significantly greater prevalence of marijuana use among sexual minority youth in neighborhoods with a higher prevalence of LGBT assault hate crimes. These results suggest that neighborhood context (i.e., LGBT hate crimes) may contribute to sexual orientation disparities in marijuana use.


Extended in-field and out-of-field validation of a compact Monte Carlo model of an IBA PROTEUS®ONE proton beam in TOPAS/GEANT4.
Objective:This study evaluates a compact Monte Carlo (MC) model of a pencil beam scanning clinical proton beam using TOPAS to estimate the dose out-of-field (OOF). Compact modelling means that the model starts from a pristine proton beam at the nozzle exit, customised based on acceptance and commissioning data, instead of modelling the full treatment head and room.Approach: First, in-field validation tests were performed. Then, the OOF dose was validated in an RW3 phantom with bubble detectors for personal neutron dosimetry (measuring the neutron dose equivalent) and thermoluminiescent detectors (measuring the absorbed dose by protons and gammas). Measurements were performed at 15 and 35 cm from the distal edge of the field for five different irradiation plans, covering different beam orientations, proton energies and a 40 mm range shifter. TOPAS simulations were performed with QGSP Binary Cascade HP (BIC) and QGSP Bertini HP (Bertini) hadron physics lists.Main results: In-field validation shows that MC simulations agree with point dose measurements within -2.5 % and +1.5 % at locations on- and off-axis and before, in and after the Bragg peak or plateau. The gamma passing rate 2%/3mm of four simulated treatment plans compared to the dose distribution calculated by the TPS exceeds 97 % agreement score. OOF dose simulations showed an average overestimation of 27 % of the neutron dose equivalent for the BIC hadron physics list and an average underestimation of 20 % for the Bertini hadron physics list. The simulated absorbed dose of protons and gammas showed a systematic underestimation which was on average 21 % and 51 % for BIC and Bertini respectively.Significance: Our study demonstrates that a compact MC model can reliably produce in-field data, while out-of-field dose data are within the uncertainties of the detector systems and MC simulations nuclear models, and do so with shorter modelling and faster calculation time.


Acoustic Characterization Study of Beef Loins Using Ultrasonic Transducers.
The objective of this study was to non-destructively characterize samples of fresh beef loin by low-intensity ultrasound inspection at various frequencies and to correlate the acoustic parameters of these inspections with quality parameters. In this regard, ultrasonic parameters such as ultrasound pulse velocity (UPV) and variables related to attenuation and frequency components obtained from fast Fourier transform (FFT) were considered. For this, pulsed ultrasonic signal transducers with a frequency of 0.5 and 1.0 MHz were used. Acoustic parameters and those obtained through traditional instrumental analyses (physicochemical and texture) underwent a Pearson correlation analysis. The acoustic determinations revealed numerous significant correlations with the rest of the studied parameters. The results demonstrate that ultrasonic inspection has the ability to characterize samples with a non-destructive nature, and likewise, this methodology can be postulated as a promising predictive tool for determining quality parameters in beef loin samples.


Effect of serum from partially hepatectomized cirrhotic and noncirrhotic rats on liver regeneration with primary hepatocyte cultures.
The effects of serum from cirrhotic and noncirrhotic rats after 33% and 70% partial hepatectomy on the hepatocyte culture were studied. Liver cirrhosis was produced by weekly intragastric feeding with carbon tetrachloride (CCl4) for 12-16 weeks. The serum was prepared with blood withdrawn from the rats 2 and 48 h after partial hepatectomy or sham operation. The incorporation of [3H]thymidine in the hepatocyte culture after addition of rat serum (1.0 +/- 10(5) cells/ml) was assessed. We found that the mitogenic effect of the serum at 2 and 48 h after partial hepatectomy was not significant. In the 70% hepatectomy group, the serum from cirrhotic rats had a stronger stimulatory effect to induce hepatocytes in primary culture entering DNA synthesis than that from noncirrhotic rats; but the difference was not statistically significant. The mitogenic effect of the serum from noncirrhotic rats after 33% hepatectomy was significantly lower than that from cirrhotic rats after 33% hepatectomy (p < 0.05). In this series, the serum from the cirrhotic rats after 33% hepatectomy had the strongest mitogenic effect; the serum from the partially hepatectomized rats with cirrhotic and non-cirrhotic livers increased [3H]thymidine uptake into hepatocyte DNA significantly more than control serum or plasma.


A Low-Operating-Power and Flexible Active-Matrix Organic-Transistor Temperature-Sensor Array.
An organic flexible temperature-sensor array exhibits great potential in health monitoring and other biomedical applications. The actively addressed 16 × 16 temperature sensor array reaches 100% yield rate and provides 2D temperature information of the objects placed in contact, even if the object has an irregular shape. The current device allows defect predictions of electronic devices, remote sensing of harsh environments, and e-skin applications.


Differential radio-sensitivities of human chromosomes 1 and 2 in one donor in interphase- and metaphase-spreads after 60Co gamma-irradiation.
Radiation-induced chromosome aberrations lead to a plethora of detrimental effects at cellular level. Chromosome aberrations provide broad spectrum of information ranging from probability of malignant transformation to assessment of absorbed dose. Studies mapping differences in radiation sensitivities between human chromosomes are seldom undertaken. Consequently, health risk assessment based on radio-sensitivities of individual chromosomes may be erroneous. Our efforts in this article, attempt to demonstrate differences in radio-sensitivities of human chromosome-1 and/or -2, both in interphase and metaphase spreads. Upon blood collection, dosimetry and irradiation were performed. Lymphocytes were isolated after whole-blood irradiation with 60Co gamma-rays in the dose range of 0-5 Gy for both interphase, and metaphase aberration studies. Induction of premature chromosome condensation in interphase cells was accomplished using a phosphatase inhibitor, calyculin-A. Metaphase spreads were harvested from short-term peripheral blood lymphocyte cultures following colcemid arrest and using an automated metaphase harvester and spreader. Aberration analysis in both interphase and metaphase spreads were done using FISH. In interphase, aberrant cell and aberration frequency involving chromosome 1 and/or 2 increased linearly with radiation dose. In metaphase, aberrations increased in a linear-quadratic manner with dose. Our studies ascertain that chromosome-2 is more radio-sensitive than chromosome-1 in both interphase and metaphase stages, albeit the DNA content of chromosome-2 is lesser than chromosome-1 by almost 10 million base pairs. Differences in radio-sensitivities of chromosomes have implications in genetic damage, chromosome organization, and chromosome function. Designing research experiments based on our vital findings may bring benefit to radiation-induced risk assessment, therapeutics and development of chromosome specific biomarkers.


Oxygen Regulates Nitrous Oxide Production Directly in Agricultural Soils.
Oxygen (O2) plays a critical and yet poorly understood role in regulating nitrous oxide (N2O) production in well-structured agricultural soils. We investigated the effects of in situ O2 dynamics on N2O production in a typical intensively managed Chinese cropping system under a range of environmental conditions (temperature, moisture, ammonium, nitrate, dissolved organic carbon, and so forth). Climate and management (fertilization, irrigation, precipitation, and temperature), and their interactions significantly affected soil O2 and N2O concentrations (P < 0.05). Soil O2 concentration was the most significant factor correlating with soil N2O concentration (r = -0.71) when compared with temperature, water-filled pore space, and ammonium concentration (r = 0.30, 0.25, and 0.26, respectively). Soil N2O concentration increased exponentially with decreasing soil O2 concentrations. The exponential model of N treatments and fertilization with irrigation/precipitation events predicted 74-90% and 58% of the variance in soil N2O concentrations, respectively. Our results highlight that the soil O2 status is the proximal, direct, and the most decisive environmental trigger for N2O production, outweighing the effects of other factors and could be a key variable integrating the aggregated effects of various complex interacting variables. This study offers new opportunities for developing more sensitive approaches to predicting and through appropriate management interventions mitigating N2O emissions from agricultural soils.


Improvements in the shelf life of commercial corn dry masa flour (CMF) by reducing lipid oxidation.
To improve the shelf life of commercial nixtamalized corn dry masa flour (CMF), the modified atmosphere packaging (MAP) was used. Pouches (20 × 20 cm) of ethyl vinyl alcohol (EVOH) with 180 g of CMF were stored at 55 °C, and a(w) of 0.45; under Light and Dark conditions, antioxidants (0.02% TBHQ), Vacuum, and N(2) and CO(2), and used as treatments. Thereafter, changes in their linoleic acid (LA) concentration by GC, peroxide (PV), and anisidine values (p-A), which were monitored for 180 d. EVOH showed a significantly lower consumption of LA by autoxidation (11.7% ± 0.2% in 117 d) than polyethylene film (70.5% ± 0.3% in 113 d) under the same storage temperature. The elimination of oxygen by vacuum in each pouch allowed a low consumption (16.4% ± 0.1%) of LA. PV (14.5 ± 0.09 mEq/kg of fat), and p-A (63 ± 0.16 mmol/kg) were low, and generated over 121 d of storage. CMF stored under MAP had 100% protection against oxidation of LA. A combination of Vacuum and EVOH packaging extended the shelf life of CMF to 108 d with only 10% of LA loss. For retail stores, the EVOH packaging will reduce lipid oxidation of CMF and safety related to off odors and flavors from the oxidation of tortillas will increase dramatically.


Vaginal malignant peripheral nerve sheath tumor treated with complete surgical resection and postoperative radiation therapy.
Malignant peripheral nerve sheath tumors (MPNSTs) are neoplasms originating from or differentiating into nerve sheaths of peripheral nerves. Vaginal origin is rare, with only six vaginal primary cases reported to date. A 55-year-old woman presented to our hospital with a 7 cm vulvar mass. Tumor biopsy results were suspicious of sarcoma, and pelvic magnetic resonance imaging and hysterofiberscopy showed that the tumor originated from the lower vagina. The mass was transvaginally excised, and histological examination confirmed the diagnosis of a vaginal MPNST with negative surgical margins. The patient underwent radiotherapy because the risk of recurrence was high, owing to the large tumor size and high mitotic index. The patient remained recurrence-free for 1 year after the primary treatment. This is the first case of a high-risk vaginal MPNST that avoided early disease recurrence with additional radiotherapy after complete tumor resection.


Does central fatigue exist under low-frequency stimulation of a low fatigue-resistant muscle?
The aim of the present study was to determine whether central fatigue occurs when fatigue is electrically induced in the abductor pollicis brevis muscle. Three series of 17 trains (30 Hz, 450 μs, 4 s on/6 s off, at the maximal tolerated intensity) were used to fatigue the muscle. Neuromuscular tests consisting of electrically evoked and voluntary contractions were performed before and after every 17-train series. Both the force induced by the stimulation trains and maximal voluntary force generation capacity significantly decreased throughout the protocol (-27 and -20%, respectively, at the end of the protocol, P < 0.001). These decreases were accompanied by failure in muscle excitability (P < 0.01), as assessed by the muscle compound action potential (M-wave or Mmax), leading to significant impairment in the muscle contractile properties (P < 0.05), as assessed by the muscle mechanical response (Pt). Central fatigue indices (level of activation, RMS/Mmax and H reflex) were not significantly changed at any point in the protocol. This gives evidence of preserved motor command reaching the motor neurons and preserved spinal excitability. The results indicate that this low-frequency stimulation protocol entails purely peripheral fatigue development when applied to a low fatigue-resistant muscle.


The tfdR gene product can successfully take over the role of the insertion element-inactivated TfdT protein as a transcriptional activator of the tfdCDEF gene cluster, which encodes chlorocatechol degradation in Ralstonia eutropha JMP134(pJP4)
The tfdT gene is located upstream of and transcribed divergently from the tfdCDEF chlorocatechol-degradative operon on plasmid pJP4 of Ralstonia eutropha (formerly Alcaligenes eutrophus) JMP134. It is 684 bp long and encodes a 25-kDa protein. On the basis of its predicted amino acid sequence, the TfdT protein could be classified as a LysR-type transcriptional regulator. It has the highest degree of similarity with the proteins TcbR, ClcR, and TfdR, which are involved in the regulation of chloroaromatic breakdown. Despite this homology, the TfdT protein failed to activate the expression of its presumed target operon, tfdCDEF. This failure could be attributed to the inability of TfdT to bind the tfdC promoter region, an absolute requirement for transcriptional activation. Sequence analysis downstream of the tfdT gene revealed the presence of an insertion element-like element. We postulate that this element disrupted the tfdT open reading frame, leading to a premature termination and the production of a truncated, disfunctional TfdT protein. As an alternative to the inactivated TfdT protein, we propose that the product of the tfdR gene (or its identical twin, tfdS), located elsewhere on plasmid pJP4, can successfully take over the regulation of tfdCDEF expression. The TfdR protein was capable of binding to the tfdC promoter region and activated tfdCDEF gene expression by a factor of 80 to 100 when provided in cis as a tfdR-tfdCDEF hybrid regulon. Although to a lesser extent, induction of tfdCDEF expression was also observed when no functional TfdR protein was provided, implying cross-activation by chromosomally encoded regulatory elements in R. eutropha JMP134(pJP4).


BCR-ABL1 transcript decline ratio combined BCR-ABL1IS as a precise predictor for imatinib response and outcome in the patients with chronic myeloid leukemia.
Purpose: The early BCR-ABL1 reduction had the prognostic impact of the chronic-phase chronic myeloid leukemia (CML-CP) patients. This study was to find a more precise early prognosis index at 3 months in the patients with newly diagnosed CML-CP, especially for the patients with BCR-ABL1IS >10%. Methods: We retrospectively analyzed the data of 79 newly diagnosed CML-CP patients from October 2013 to April 2017. All patients took imatinib regularly and continuously and monitored BCR-ABL1 transcript level at baseline and 3, 6, 9, 12, 18 months after starting imatinib treatment. Results: Among the 44(55.7%) patients with BCR/ABL1IS ≤10% at 3 months after imatinib treatment, 12(27.3%) cases did not achieve major molecular response (MMR) at 12 months, and 7(14.9%) patients with the halving time BCR-ABL1 transcript ≤40 days failed to achieve MMR at 12 months. However, approximately twenty-six percent of the patients with BCR-ABL1IS >10% still obtained MMR. Moreover, the patients with BCR-ABL1IS ≤10% and halving time ≤40 days had a significantly better MMR than that of the patients with the BCR-ABL1IS ≤10% and halving time >40 days (88.6% versus 11.1%, P <0.001). However, the patients with the BCR-ABL1IS >10% and halving time >40 days rarely achieved MMR at 12 months. Conclusion: These data indicated that the halving time of BCR-ABL1 transcript was also an important prognostic factor as that of the BCR-ABL1IS. Combined observations of these two prognosis indexes are more accurate predictor for the long-term molecular response, especially for the CML-CP patients with BCR-ABL1IS >10%, and which is helpful for TKI switching as early as possible to improve patients' survival and reduce drug costs.


Lysyl oxidase and endothelial dysfunction: mechanisms of lysyl oxidase down-regulation by pro-inflammatory cytokines.
Lysyl oxidase (LOX) plays a pivotal role in extracellular matrix (ECM) maturation. Furthermore, novel biological functions has been ascribed to LOX, among them cell differentiation, migration, transformation and regulation of gene expression. In this context, it has been suggested that abnormalities of LOX expression could underlie the development of multiple pathological processes including cardiovascular diseases. LOX seems to be crucial in the preservation of endothelial barrier function. In fact, accumulating evidences suggest a role of this enzyme in atherogenesis and endothelial dysfunction triggered by atherosclerotic risk factors and pro-inflammatory cytokines. Indeed, cytokines such as tumour necrosis factor-alpha (TNF-alpha) modulate vascular LOX expression. This cytokine decreases LOX expression and activity in endothelial cells through a transcriptional mechanism that involves TNF receptor-2 and protein kinase C activation. Interestingly, in vivo studies reveal that TNF-alpha causes a down-regulation of vascular LOX expression. Thus, LOX down-regulation seems to be associated to the endothelial dysfunction elicited by multiple pathological factors. LOX rises as a promising target gene for the development of therapeutic strategies in the treatment of cardiovascular diseases.


Independent effects of Apo E phenotype and plasma triglyceride on lipoprotein particle sizes in the fasting and postprandial states.
LDL particle sizes and Apo E phenotypes were determined in 212 subjects of whom 51 had angina. LDL diameter was significantly less in subjects with an epsilon2 allele (24.76+/-0.08 vs 24.94+/-0.02 nm, P=0.02), and this was evident for both E2/E3 (24.77+/-0.09 nm) and E2/E4 (24.69+/-0.08 nm) phenotypes. Although there was a negative relation between LDL diameter and plasma triglyceride, the effect of apo E2 was still evident with adjustment for triglyceride. In multiple regression analysis, the significant determinants of LDL diameter were gender (with females having larger particles than males), body mass index, and the presence (or absence) of E2. HDL particle sizes and compositions were determined on fasting samples and, additionally, 5 and 8 hours after a fat-rich meal for 48 coronary heart disease cases and 49 control subjects. Fasting HDL particle sizes were not related to the presence of E2 but were significantly smaller for subjects possessing an epsilon4 allele (8. 09+/-0.08 vs 8.39+/-0.05 nm, P=0.003) and were negatively related to plasma triglyceride. However, the effect of E4 persisted after adjustment for triglyceride. In a multiple regression analysis, the only significant determinant of fasting HDL diameter was the presence (or absence) of E4 with fasting plasma triglyceride just failing to reach significance (P=0.06). There was a postprandial increase in HDL diameter that was less marked in subjects with coronary heart disease. The postprandial increase in HDL diameter was of sufficient magnitude to result in size reclassification of HDL particles. The influence of E4 was also evident at both postprandial time points. Compositional analysis demonstrated that the increase in HDL diameters postprandially could be attributed to triglyceride enrichment, with an accompanying fall in cholesterol ester content. Phospholipid changes postprandially were biphasic with an initial fall followed by a rise in concentration. The increase in triglyceride content was significantly less in those subjects with angina despite an equivalent rise in plasma triglyceride. The present study demonstrates significant, but different, effects of variation in apo E phenotype on the particle sizes of both HDL and LDL. Such effects were still evident with adjustment for differences in plasma triglyceride and suggests that variation in apo E phenotype exerts effects on lipoprotein particle sizes by mechanisms additional to those dependent on change in plasma triglyceride.


Intermetallic compounds for high-temperature structural use.
The next generation of efficient turbines and engines will require materials that can withstand operating temperatures approaching 2000 degrees C. Intermetallic compounds with high melting temperatures are candidates for this application, but the obstacle of their limited ductility must first be overcome. Because the available data on these materials is limited, a survey of the effects of chemistry and crystal structure must be performed. With the use of melting temperature and density as figures of merit, the most likely candidates have been identified for preliminary screening.


Combination of corticosteroids and 5-aminosalicylates or corticosteroids alone for patients with moderate-severe active ulcerative colitis: A global survey of physicians' practice.
To examine treatment decisions of gastroenterologists regarding the choice of prescribing 5-aminosalycilates (5ASA) with corticosteroids (CS) versus corticosteroids alone for patients with active ulcerative colitis (UC). A cross-sectional questionnaire exploring physicians' attitude toward 5ASA + CS combination therapy vs CS alone was developed and validated. The questionnaire was distributed to gastroenterology experts in twelve countries in five continents. Respondents' agreement with stated treatment choices were assessed by standardized Likert scale. Background professional characteristics of respondents were analyzed for correlation with responses. Six hundred and sixty-four questionnaires were distributed and 349 received (52.6% response rate). Of 340 eligible respondents, 221 (65%) would continue 5ASA in a patient hospitalized for intravenous CS treatment due to a moderate-severe UC flare, while 108 (32%) would stop the 5ASA (P < 0.001), and 11 (3%) are undecided. Similarly, 62% would continue 5ASA in an out-patient starting oral CS. However, only 140/340 (41%) would proactively start 5ASA in a hospitalized patient not receiving 5ASA before admission. Most (94%) physicians consider the safety profile of 5ASA as very good. Only 52% consider them inexpensive, 35% perceive them to be expensive and 12% are undecided. On multi-variable analysis, less years of practice and perception of a plausible additive mechanistic effect of 5ASA + CS were positively associated with the decision to continue 5ASA with CS. Despite the absence of data supporting its benefit, most gastroenterologists endorse combination of 5ASA + CS for patients with active moderate-to-severe UC. Randomized controlled trials are needed to assess if 5ASA confer any benefit for these patients.


New hybrid layered molybdates based on (2/∞)[Mo(n)O(3n+1)]2- units (n = 7, 9) with systematic organic-inorganic interfaces.
Two new hybrid organic-inorganic molybdates based on layered (2/∞)[Mo(n)O(3n+1)](2-) blocks and organoammonium cations (+)(Me(x)H(3-x)N)(CH(2))(6)(NH(3-x)Me(x))(+) (x = 0-1), namely, (H(3)N(CH(2))(6)NH(3))[Mo(7)O(22)]·H(2)O (1) and (MeH(2)N(CH(2))(6)NH(2)Me)[Mo(9)O(28)] (2), have been synthesized under hydrothermal conditions. The (2/∞)[Mo(9)O(28)](2-) unit in 2 is an unprecedented member of the (2/∞)[Mo(n)O(3n+1)](2-) family with the n value extended to 9. The structural filiation between the (2/∞)[Mo(n)O(3n+1)](2-) (n = 5, 7, 9) blocks is well established, and their structural similarity with the (2/∞)[MoO(3)] slabs in α-MoO(3) is also discussed. Single-crystal X-ray analyses show that the (2/∞)[Mo(n)O(3n+1)](2-) layers in 1 and 2 are pillared in the three-dimensional networks by the organic cations with a similar connection at the organic-inorganic interface. In addition, a correlation between the topology of the (2/∞)[Mo(n)O(3n+1)](2-) blocks in 1 and 2 and the overall sizes of the associated organic cations is pointed out. Finally, the efficiency of Fourier transform Raman spectroscopy to easily discriminate the different (2/∞)[Mo(n)O(3n+1)](2-) blocks (n = 5, 7, 9) in hybrid organic-inorganic layered molybdate materials is clearly evidenced.


Speech recognition for school-age children and adults tested in multi-tone vs multi-noise-band maskers.
The present study set out to test whether greater susceptibility to modulation masking could be responsible for immature recognition of speech in noise for school-age children. Listeners were normal-hearing four- to ten-year-olds and adults. Target sentences were filtered into 28 adjacent narrow bands (100-7800 Hz), and the masker was either spectrally matched noise bands or tones centered on each of the speech bands. In experiment 1, odd- and even-numbered bands of target-plus-masker were presented to opposite ears. Performance improved with child age in all conditions, but this improvement was larger for the multi-tone than the multi-noise-band masker. This outcome is contrary to the expectation that children are more susceptible than adults to masking produced by inherent modulation of the noise masker. In experiment 2, odd-numbered bands were presented to both ears, with the masker diotic and the target either diotic or binaurally out of phase. The binaural difference cue was particularly beneficial for young children tested in the multi-tone masker, suggesting that development of auditory stream segregation may play a role in the child-adult difference for this condition. Overall, results provide no evidence of greater susceptibility to modulation masking in children than adults.


Parallel stochastic systems biology in the cloud.
The stochastic modelling of biological systems, coupled with Monte Carlo simulation of models, is an increasingly popular technique in bioinformatics. The simulation-analysis workflow may result computationally expensive reducing the interactivity required in the model tuning. In this work, we advocate the high-level software design as a vehicle for building efficient and portable parallel simulators for the cloud. In particular, the Calculus of Wrapped Components (CWC) simulator for systems biology, which is designed according to the FastFlow pattern-based approach, is presented and discussed. Thanks to the FastFlow framework, the CWC simulator is designed as a high-level workflow that can simulate CWC models, merge simulation results and statistically analyse them in a single parallel workflow in the cloud. To improve interactivity, successive phases are pipelined in such a way that the workflow begins to output a stream of analysis results immediately after simulation is started. Performance and effectiveness of the CWC simulator are validated on the Amazon Elastic Compute Cloud.


Evaluation of 10 AMD Associated Polymorphisms as a Cause of Choroidal Neovascularization in Highly Myopic Eyes.
Choroidal neovascularization (CNV) commonly occurs in age related macular degeneration and pathological myopia patients. In this study we conducted a case-control prospective study including 431 participants. The aim of this study was to determine the potential association between 10 single nucleotide polymorphisms (SNPs) located in 4 different genetic regions (CFI, COL8A1, LIPC, and APOE), and choroidal neovascularization in age-related macular degeneration and the development of choroidal neovascularization in highly myopic eyes of a Caucasian population. Univariate and multivariate logistic regression analysis adjusted for age, sex and hypertension was performed for each allele, genotype and haplotype frequency analysis. We found that in the univariate analysis that both single-nucleotide polymorphisms in COL8A1 gene (rs13095226 and rs669676) together with age, sex and hypertension were significantly associated with myopic CNV development in Spanish patients (p<0.05). After correcting for multiple testing none of the polymorphisms studied remained significantly associated with myopic CNV (p>0.05); however, analysis of the axial length between genotypes of rs13095226 revealed an important influence of COL8A1 in the development of CNV in high myopia. Furthermore we conducted a meta-analysis of COL8A1, CFI and LIPC genes SNPs (rs669676, rs10033900 and rs10468017) and found that only rs669676 of these SNPs were associated with high myopia neovascularization.


Requirement for sphingosine 1-phosphate receptor-1 in tumor angiogenesis demonstrated by in vivo RNA interference.
Angiogenesis, or new blood vessel formation, is critical for the growth and spread of tumors. Multiple phases of this process, namely, migration, proliferation, morphogenesis, and vascular stabilization, are needed for optimal tumor growth beyond a diffusion-limited size. The sphingosine 1-phosphate (S1P) receptor-1 (S1P(1)) is required for stabilization of nascent blood vessels during embryonic development. Here we show that S1P(1) expression is strongly induced in tumor vessels. We developed a multiplex RNA interference technique to downregulate S1P(1) in mice. The small interfering RNA (siRNA) for S1P(1) specifically silenced the cognate transcript in endothelial cells and inhibited endothelial cell migration in vitro and the growth of neovessels into subcutaneous implants of Matrigel in vivo. Local injection of S1P(1) siRNA, but not a negative control siRNA, into established tumors inhibited the expression of S1P(1) polypeptide on neovessels while concomitantly suppressing vascular stabilization and angiogenesis, which resulted in dramatic suppression of tumor growth in vivo. These data suggest that S1P(1) is a critical component of the tumor angiogenic response and argue for the utility of siRNA technology in antiangiogenic therapeutics.


Classification and natural history of clinically identifiable subtypes of cerebral infarction.
We describe the incidence and natural history of four clinically identifiable subgroups of cerebral infarction in a community-based study of 675 patients with first-ever stroke. Of 543 patients with a cerebral infarct, 92 (17%) had large anterior circulation infarcts with both cortical and subcortical involvement (total anterior circulation infarcts, TACI); 185 (34%) had more restricted and predominantly cortical infarcts (partial anterior circulation infarcts, PACI); 129 (24%) had infarcts clearly associated with the vertebrobasilar arterial territory (posterior circulation infarcts, POCI); and 137 (25%) had infarcts confined to the territory of the deep perforating arteries (lacunar infarcts, LACI). There were striking differences in natural history between the groups. The TACI group had a negligible chance of good functional outcome and mortality was high. More than twice as many deaths were due to the complications of immobility than to direct neurological sequelae of the infarct. Patients in the PACI group were much more likely to have an early recurrent stroke than were patients in other groups. Those in the POCI group were at greater risk of a recurrent stroke later in the first year after the index event but had the best chance of a good functional outcome. Despite the small anatomical size of the infarcts in the LACI group, many patients remained substantially handicapped. The findings have important implications for the planning of stroke treatment trials and suggest that various therapies could be directed specifically at the subgroups.