New insights into the evolution of human Y chromosome palindromes through mutation and gene conversion.
About one-quarter of the euchromatic portion of the male-specific region of the human Y chromosome consists of large duplicated sequences that are organized in eight palindromes (termed P1-P8), which undergo arm-to arm gene conversion, a proposed mechanism for maintaining their sequence integrity. Although the relevance of gene conversion in the evolution of palindromic sequences has been profoundly recognized, the dynamic of this mechanism is still nuanced. To shed light into the evolution of these genomic elements, we performed a high-depth (50×) targeted next-generation sequencing of the palindrome P6 in 157 subjects belonging to the most divergent evolutionary lineages of the Y chromosome. We found 118 new paralogous sequence variants, which were placed into the context of a robust Y chromosome phylogeny based on 7240 SNPs of the X-degenerate region. We mapped along the phylogeny 80 gene conversion events that shaped the diversity of P6 arms during recent human history. In contrast to previous studies, we demonstrated that arm-to-arm gene conversion, which occurs at a rate of 6.01 × 10 -6 conversions/base/year, is not biased toward the retention of the ancestral state of sequences. We also found a significantly lower mutation rate of the arms (6.18 × 10-10 mutations/base/year) compared with the spacer (9.16 × 10-10 mutations/base/year), a finding that may explain the observed higher inter-species conservation of arms, without invoking any bias of conversion. Finally, by formally testing the mutation/conversion balance in P6, we found that the arms of this palindrome reached a steady-state equilibrium between mutation and gene conversion.


C-reactive protein (CRP) and autoimmune disease: facts and conjectures.
C-reactive protein (CRP) is a blood component comprised of five identical subunits with a combined molecular mass of 110 kDa; in the presence of Ca++ it binds phosphocholine (PC) with high affinity. Ligand-bound CRP activates complement and the protein reportedly binds various Fc receptors. Coincident with a now decade-long resurgence in clinical interest in associations of CRP with disease, our laboratory has been investigating the biology of CRP in vivo using human CRP transgenic mice (CRPtg). At that time we confirmed that CRP affects a host defense function mediated at least in part through the elimination of pathogens. Less appreciated and not as well understood as CRP's ability to bind antigen and aid in the elimination of microbes, is its known ability to bind autoantigens and presumed capacity to promote clearance of apoptotic cells. These latter properties of CRP have long been suspected to contribute to homeostasis and to autoimmune disease. In this article we review and update the evidence generated in CRPtg by our group and in vitro by others' that indicates CRP is more than just an antimicrobial molecule and convenient marker of inflammation-rather, it protects against autoimmunity. A mechanistic hypothesis is presented to account for this cause-and-effect relationship.


A prospective randomized trial comparing 2 diuresis renography techniques for evaluation of suspected upper urinary tract obstruction in children.
We compare the diagnostic impact of 2 diuresis renography techniques for evaluation of suspected upper urinary tract obstruction in children. A total of 72 children were randomly assigned to 1 of 2 standardized diuresis renography protocols. The protocols were identical, except for the time of furosemide (F) injection. In the F+20 scans furosemide was given 20 minutes after the 99mtechnetium pentetic acid radiopharmaceutical. With the modified F-15 scans furosemide was injected 15 minutes before renography. Hydration, bladder catheterization, urine output determination, radiopharmaceutical injection and scan acquisition were identical. Renography outcomes (obstructed, nonobstructed or equivocal) were analyzed for the investigated side(s) and for the contralateral side, which was used as a control in children with suspected unilateral obstruction. Chi-square test was used to compare the percentage of obstructed and nonobstructed scans of both protocols. Fisher's exact test was used to compare the nonobstructed scans and equivocal results of both protocols. Of the 96 scans performed 8 were excluded because of technical problems. The remaining scans included 44 F+20 and 44 F-15. Of the 88 scans 10 were used to evaluate possible bilateral obstruction. A total of 48 boys and 24 girls were evaluated. Because 2 children had a solitary kidney each, the total number of renal units studied for outcome was 174. The F-15 scan showed 7 times more obstruction than the F+20 scan on the investigated side, and this difference was statistically significant. No obstruction was diagnosed on the contralateral side with either technique when used to investigate cases of suspected unilateral obstruction. The timing of the furosemide injection (F-15 scan versus F+20) has a significant impact on the obstructive versus nonobstructive renography results when evaluating children with suspected upper urinary tract obstruction.


Ludwig angina, empyema, pulmonary infiltration, and pericarditis secondary to extraction of a tooth.
A case of Ludwig angina after extraction of a mandibular third molar, progressing to pleural effusion and empyema, pericarditis, pulmonary infiltration, and pericardial effusion has been presented. The importance of early diagnosis and treatment as well as appropriate antibiotic and surgical therapy have been discussed. The practice of empirically prescribed antimicrobial agents has also been discussed, and the relevance of the organism E corrodans in oral infections has been emphasized.


Targeting the B7 family of co-stimulatory molecules: successes and challenges.
As more patient data is cross-referenced with animal models of disease, the primary focus on T(h)1 autoreactive effector cell function in autoimmune diseases, such as rheumatoid arthritis and multiple sclerosis, has shifted towards the role of T(h)17 autoreactive effector cells and the ability of regulatory T cells (T(reg)) to modulate the pro-inflammatory autoimmune response. Therefore, the currently favored hypothesis is that a delicate balance between T(h)1/17 effector cells and T(reg) cell function is critical in the regulation of inflammatory autoimmune disease. An intensive area of research with regard to the T(h)1/17:T(reg) cell balance is the utilization of blockade and/or ligation of various co-stimulatory or co-inhibitory molecules, respectively, during ongoing disease to skew the immune response toward a more tolerogenic/regulatory state. Currently, FDA-approved therapies for multiple sclerosis patients are all aimed at the suppression of immune cell function. The other favored method of treatment is a modulation or deletion of autoreactive immune cells via short-term blockade of activating co-stimulatory receptors via treatment with fusion proteins such as CTLA4-Ig and CTLA4-FasL. Based on the initial success of CTLA4-Ig, there are additional fusion proteins that are currently under development. Examples of the more recently identified B7/CD28 family members are PD-L1, PD-L2, inducible co-stimulatory molecule-ligand (ICOS-L), B7-H3, and B7-H4, all of which may emerge as potential fusion protein therapeutics, each with unique, yet often overlapping functions. The expression of both stimulatory and inhibitory B7 molecules seems to play an essential role in modulating immune cell function through a variety of mechanisms, which is supported by findings that suggest each B7 molecule has developed its own indispensable niche in the immune system. As more data are generated, the diagnostic and therapeutic potential of the above B7 family-member-derived fusion proteins becomes ever more apparent. Besides defining the biology of these B7/CD28 family members in vivo, additional difficulty in the development of these therapies lies in maintaining the normal immune functions of recognition and reaction to non-self-antigens following viral or bacterial infection in the patient. Further complicating the clinical translation of these therapies, the mechanism of action identified for a particular reagent may depend upon the method of immune-cell activation and the subset of immune cells targeted in the study.


State Public Insurance Coverage Policies and Postpartum Care Among Immigrants.
Professional medical organizations recommend that adults receive routine postpartum care. Yet, some states restrict public insurance coverage for undocumented immigrants and recently documented immigrants (those who received legal documentation status within the past 5 years). To examine the association between public insurance coverage and postpartum care among low-income immigrants and the difference in receipt of postpartum care among immigrants relative to nonimmigrants. A pooled, cross-sectional analysis was conducted using data from the Pregnancy Risk Assessment Monitoring System for 19 states and New York City including low-income adults with a live birth between 2012 and 2019. Giving birth in a state that offered public insurance coverage for postpartum care to recently documented or undocumented immigrants. Self-reported receipt of postpartum care by the category of coverage offered (full coverage: states that offered publicly funded postpartum care regardless of immigration status; moderate coverage: states that offered publicly funded postpartum care to lawfully residing immigrants without a 5-year waiting period, but did not offer postpartum care to undocumented immigrants; no coverage: states that did not offer publicly funded postpartum care to lawfully present immigrants before 5 years of legal residence or to undocumented immigrants). The study included 72 981 low-income adults (20 971 immigrants [29%] and 52 010 nonimmigrants [71%]). Of the 19 included states and New York City, 6 offered full coverage, 9 offered moderate coverage, and 4 offered no coverage; 1 state (Oregon) switched from offering moderate coverage to offering full coverage. Compared with the states that offered full coverage, receipt of postpartum care among immigrants was 7.0-percentage-points lower (95% CI, -10.6 to -3.4 percentage points) in the states that offered moderate coverage and 11.3-percentage-points lower (95% CI, -13.9 to -8.8 percentage points) in the states that offered no coverage. The differences in the receipt of postpartum care among immigrants relative to nonimmigrants were also associated with the coverage categories. Compared with the states that offered full coverage, there was a 3.3-percentage-point larger difference (95% CI, -5.3 to -1.4 percentage points) in the states that offered moderate coverage and a 7.7-percentage-point larger difference (95% CI, -10.3 to -5.0 percentage points) in the states that offered no coverage. Compared with states without insurance restrictions, immigrants living in states with public insurance restrictions were less likely to receive postpartum care. Restricting public insurance coverage may be an important policy-driven barrier to receipt of recommended pregnancy care and improved maternal health among immigrants.


Hand-Assisted Laparoscopic vs Hand-Assisted Retroperitoneoscopic Living-Donor Nephrectomy: A Retrospective, Single-Center, Propensity-Score Analysis of 840 Transplants Using 2 Techniques.
Living-donor kidney transplantation (LDKT) is the most realistic option for patients with end-stage kidney disease because of a severe shortage of deceased donors. Hand-assisted laparoscopic donor nephrectomy (HALDN) and hand-assisted retroperitoneoscopic donor nephrectomy (HARDN) have been undertaken at our institute. We compared these 2 surgical procedures with respect to donor outcome and the graft function of recipients. We reviewed data from 840 consecutive live-donor kidney transplants from October 2003 to April 2019. Propensity scores were calculated for each patient using bivariate logistic regression. After propensity-score matching, the 2 groups each contained 205 patients. Donors in the HALDN group had a longer procedure time (217 minutes, P < .0001), less estimated blood loss (51 mL, P < .0001), lower serum levels of C-reactive protein at postoperative day (POD) 1 (7.9 mg/dL, P < .0001) than those in the HARDN group. There were 22 modified Clavien-classifiable complications among the study groups. A significantly higher conversion to open surgery was noted in the HARDN group (P = .0181) than in the HALDN group, but there was no significant difference in the prevalence of complications in either group. There was no significant difference in the estimated glomerular filtration rate of recipients at POD14 between the 2 groups. Safety and early graft function of HALDN in LDKT are comparable to or even better than that of HARDN.


Management of renal extraskeletal mesenchymal chondrosarcoma.
Primary mesenchymal chondrosarcoma of the kidney is an extremely rare malignant tumor. To our best knowledge, only 9 such cases have been reported so far. In the current paper, we present the case of a 67 year-old patient with recurrent left lumbar pain, increased fatigability and intermittent macroscopic hematuria. He underwent a surgical resection of the left kidney and left hemicolon.The pathological diagnosis was primary extraskeletal renal mesenchymal chondrosarcoma. Overall survival was 9 months, with pulmonary metastasis and local recurrence at 6 months. The management of the patient is described, from the initial differential diagnosis, after the first clinical examination to the surgical resection, with a special emphasis on the surgical procedures that were carried out. Extraskeletal chondrosarcoma of primary origin in the kidney are extremely rare tumors with a highly malignant potential and very poor prognosis. Because the role of chemotherapy or radiation therapy has not been evaluated properly yet, we underline the importance of surgery in the management of such cases as the main and best approach to achieve clinical remission and long-term survival, provided the patient is referred to a surgical consult in time.


The arginine methyltransferase PRMT5 promotes mucosal defense in the intestine.
PRMT5 is a type II arginine methyltransferase abundantly expressed in the colonic epithelium. It is up-regulated in inflammatory bowel disease and colorectal cancer. However, its role in mucosal defense against enteric infection has not been studied. Here, we report that Prmt5 in the murine colon is up-regulated in response to Citrobacter rodentium infection. Pathogen clearance in mice with haploinsufficient expression of Prmt5 is significantly delayed compared with wildtype littermate controls. Transcriptomic analyses further reveal that PRMT5 regulates the expression of canonical crypt goblet cell genes involved in mucus production, assembly, and anti-microbial responses via methyltransferase activity-dependent and -independent mechanisms. Together, these findings uncover PRMT5 as a novel regulator of mucosal defense and a potential therapeutic target for treating intestinal diseases.


Predictive value of infant lung function testing for airway malacia.
Airway malacia is present in a small proportion of wheezing infants. The usefulness of infant lung-function testing (ILFT) in ruling out malacia in wheezy infants is unknown. We assessed the predictive value of ILFT parameters for airway malacia diagnosed by flexible bronchoscopy. Thirty-two term infants (mean (SD) age, 11.0 (4.6) months) with chronic wheeze unresponsive to asthma treatment underwent ILFT prior to bronchoscopy. Functional residual capacity measured by plethysmograph (FRCp), maximal flow at FRC (V'max(FRC)), and tidal breathing parameters were obtained. Expiratory flow-volume curves were visually examined for tidal flow limitation. Malacia was observed during bronchoscopy in 20 infants. V'max(FRC) (Z-score) was significantly lower in the group with malacia as compared with the group without malacia. Lung-function measurements had a low negative predictive value and sensitivity. While flow limitation during tidal breathing was highly predictive and 100% specific for airway malacia, only half of the infants with malacia had tidal flow limitation. In this selected group of infants, routine lung function testing could not discriminate between infants with and without airway malacia. However, the presence of tidal flow limitation was 100% predictive and specific for airway malacia.


Highly-sensitive amplification-free analysis of multiple miRNAs by capillary electrophoresis.
Sets of deregulated microRNAs (miRNAs), termed miRNA signatures, are promising biomarkers for cancer. Validation of miRNA signatures requires a technique that is accurate, sensitive, capable of detecting multiple miRNAs, fast, robust, and not cost-prohibitive. Direct quantitative analysis of multiple miRNAs (DQAMmiR) is a capillary electrophoresis (CE)-based hybridization assay that was suggested as a methodological platform for validation and clinical use of miRNA signatures. While satisfying the other requirements, DQAMmiR is not sufficiently sensitive to detect low-abundance miRNAs. Here, we solve this problem by combining DQAMmiR with the preconcentration technique, isotachophoresis (ITP). The sensitivity improved 100 times (to 1 pM) allowing us to detect low-abundance miRNAs in an RNA extract. Importantly, ITP-DQAMmiR can be performed in a fully automated mode using a commercial CE instrument making it suitable for practical applications.


Skin cancer: national awareness campaigns.
Skin cancer is the most common form of cancer in the United States and it is imperative that health care providers promote national awareness campaigns and prevention efforts to children and adults. This article outlines facts about skin cancer, who is at risk, and current Centers for Disease Control (CDC) national awareness programs and prevention tips.


Cyclooxygenase-2 inhibitor-induced acute interstitial nephritis.
A 64-year-old female patient presented to the emergency department with a 3-week history of persistent nausea and vomiting. Her serum creatine prior to admission was 118 µmol/L and on presentation was elevated to 420 µmol/L. On clinical history, she indicated that 3 weeks prior, she had been initiated on a cyclooygenase-2 (COX-2) inhibitor, celecoxib, for her osteoarthritis of her knees. Renal biopsy confirmed the diagnosis of acute interstitial nephritis (AIN). Celecoxib was discontinued and the patient's renal function improved to a discharge creatine of 205-220 µmol/L. Nine months later, her creatine had decreased to 195 µmol/L and she was initiated on tapering doses of prednisone therapy for 4 months, after which time her creatine had improved further to 143 µmol/L. She was later transitioned to mycophenolatemofetil for 9 months and her creatine improved to 110 µmol/L. This report provides further evidence that COX-2 inhibitors are associated with AIN.


Liver Stiffness Measurements with MR Elastography: Agreement and Repeatability across Imaging Systems, Field Strengths, and Pulse Sequences.
Purpose To prospectively assess agreement and repeatability of magnetic resonance (MR) elastography liver stiffness measurements across imager manufacturers, field strengths, and pulse sequences. Materials and Methods This prospective cross-sectional study was approved by the institutional review board; informed consent was obtained from all subjects. On the basis of an a priori power calculation, 24 volunteer adult subjects underwent MR elastography with four MR imaging systems (two vendors) and multiple pulse sequences (two-dimensional [2D] gradient-echo [GRE] imaging, 2D spin-echo [SE] echo-planar imaging, and three-dimensional [3D] SE echo-planar imaging). Each sequence was performed twice in each patient with each imaging system. Intraclass correlation coefficients (ICCs) were used to assess agreement and repeatability. P < .05 was considered indicative of a statistically significant difference. Results Pairwise ICCs were 0.67-0.82 and 0.62-0.83 for agreement between pulse sequences across manufacturers (n = 4) and field strengths (n = 5), respectively. ICCs were 0.45-0.90 for pairwise agreement between sequences while fixing manufacturer and field strength (n = 8). Test-retest repeatability across the various manufacturer, field strength, and pulse sequence combinations (n = 10) was excellent (ICCs, 0.77-0.94). The overall ICC for all manufacturer, field strength, and sequence combinations (n = 10) was 0.68 (95% confidence interval [CI]: 0.55, 0.82). ICC according to field strength was 0.78 (95% CI: 0.67, 0.88) at 1.5 T (n = 5) and 0.64 (95% CI: 0.49, 0.78) at 3.0 T (n = 5). ICCs according to vendor were 0.83 (95% CI: 0.73, 0.91) (n = 4) and 0.65 (95% CI: 0.51, 0.79) (n = 6). Average patient level variance was 0.042 kPa, with a coefficient of variation of 10.7%. Conclusion MR elastography is a reliable method for assessing liver stiffness, with small amounts of variability between imager manufacturers, field strengths, and pulse sequences. © RSNA, 2016.


The role of seminal reactive oxygen species assessment in the setting of infertility and early pregnancy loss.
The male contribution to a couple suffering with adverse early pregnancy outcomes is being increasingly investigated. Seminal oxidative stress is considered to cause sperm DNA damage, thus affecting the functional capacity of the sperm. Multiple lines of evidence support an association between elevated seminal reactive oxygen species (ROS) and infertility. In the setting of assisted reproduction various factors in the in vitro environment, differing from the in vivo environment, may exacerbate oxidative stress. Furthermore, seminal ROS levels have been found to be higher in the male partners of couple's affected by both spontaneous and recurrent pregnancy loss. There are several methods by which to assess ROS levels however they are costly, inconsistent and their incorporation into clinical practice is unclear. The value of ROS assessment lies in the ability to plan targeted therapies to improve pregnancy and live birth rates. As such, further robust study is required before firm conclusions can be made to inform clinical practice. We aim to review the available evidence regarding the role of seminal ROS in infertility and pregnancy loss.


Identification of a novel orally bioavailable phosphodiesterase 10A (PDE10A) inhibitor with efficacy in animal models of schizophrenia.
We report the continuation of a focused medicinal chemistry program aimed to further optimize a series of imidazo[1,2-a]pyrazines as a novel class of potent and selective phosphodiesterase 10A (PDE10A) inhibitors. In vitro and in vivo pharmacokinetic and pharmacodynamic evaluation allowed the selection of compound 25a for its assessment in preclinical models of psychosis. The evolution of our medicinal chemistry program, structure-activity relationship (SAR) analysis, as well as a detailed pharmacological profile for optimized lead 25a are described.


Planar-chiral imidazole-based phosphine ligands derived from [2.2]paracyclophane.
Two planar chiral heteroaryl monophosphines have been synthesised and studied. The phosphines are readily prepared from 4-imidazole[2.2]paracyclophane by selective deprotonation and reaction with the appropriate dialkylchlorophosphines. The planar chiral imidazole was constructed in four steps from readily available [2.2]paracyclophane. The 2-phosphino-N-[2.2]paracyclophanes were active in the Suzuki-Miyaura coupling of aryl bromides and chlorides. Coordination studies indicate P,N-chelation in the solid-state. These studies lay the foundations for asymmetric couplings.


Suicidal behaviors in homosexual and bisexual males.
A stratified random sample of 750 males in Calgary, Canada, aged 18-27 years, were given questions on sexual activity and orientation. Mental health questions included a measure of suicidality and of acts of deliberate self-harm. A computerized response format, which has been established as a good method for eliciting sensitive personal data, ensured anonymity. Almost 13% of the males were classified as homosexual or bisexual on the basis of being currently homosexually active or by self-identification. Significantly higher rates of previous suicidal ideas and actions were reported by homosexually oriented males than by heterosexual males. Homosexually oriented males accounted for 62.5% of suicide attempters. These findings, which indicate that homosexual and bisexual males are 13.9 times more at risk for a serious suicide attempt, are consonant with previous findings. The predominant reason for the suicidality of these young males may be linked to the process of "coming out," especially for those who currently have high levels of depression. These results underscore the need for qualified services rarely available to homosexually oriented youth.


Visualization and correction of automated segmentation, tracking and lineaging from 5-D stem cell image sequences.
Neural stem cells are motile and proliferative cells that undergo mitosis, dividing to produce daughter cells and ultimately generating differentiated neurons and glia. Understanding the mechanisms controlling neural stem cell proliferation and differentiation will play a key role in the emerging fields of regenerative medicine and cancer therapeutics. Stem cell studies in vitro from 2-D image data are well established. Visualizing and analyzing large three dimensional images of intact tissue is a challenging task. It becomes more difficult as the dimensionality of the image data increases to include time and additional fluorescence channels. There is a pressing need for 5-D image analysis and visualization tools to study cellular dynamics in the intact niche and to quantify the role that environmental factors play in determining cell fate. We present an application that integrates visualization and quantitative analysis of 5-D (x,y,z,t,channel) and large montage confocal fluorescence microscopy images. The image sequences show stem cells together with blood vessels, enabling quantification of the dynamic behaviors of stem cells in relation to their vascular niche, with applications in developmental and cancer biology. Our application automatically segments, tracks, and lineages the image sequence data and then allows the user to view and edit the results of automated algorithms in a stereoscopic 3-D window while simultaneously viewing the stem cell lineage tree in a 2-D window. Using the GPU to store and render the image sequence data enables a hybrid computational approach. An inference-based approach utilizing user-provided edits to automatically correct related mistakes executes interactively on the system CPU while the GPU handles 3-D visualization tasks. By exploiting commodity computer gaming hardware, we have developed an application that can be run in the laboratory to facilitate rapid iteration through biological experiments. We combine unsupervised image analysis algorithms with an interactive visualization of the results. Our validation interface allows for each data set to be corrected to 100% accuracy, ensuring that downstream data analysis is accurate and verifiable. Our tool is the first to combine all of these aspects, leveraging the synergies obtained by utilizing validation information from stereo visualization to improve the low level image processing tasks.


Noncoding RNAs prevent spreading of a repressive histone mark.
Transcription of eukaryotic genomes is more widespread than was previously anticipated and results in the production of many non-protein-coding RNAs (ncRNAs) whose functional relevance is poorly understood. Here we demonstrate that ncRNAs can counteract the encroachment of heterochromatin into neighboring euchromatin. We have identified a long ncRNA (termed BORDERLINE) that prevents spreading of the HP1 protein Swi6 and histone H3 Lys9 methylation beyond the pericentromeric repeat region of Schizosaccharomyces pombe chromosome 1. BORDERLINE RNAs act in a sequence-independent but locus-dependent manner and are processed by Dicer into short RNAs referred to as brdrRNAs. In contrast to canonical centromeric short interfering RNAs, brdrRNAs are rarely loaded onto Argonaute. Our analyses reveal an unexpected regulatory activity of ncRNAs in demarcating an epigenetically distinct chromosomal domain that could also be operational in other eukaryotes.


Enhanced electronic and magnetic properties by functionalization of monolayer GaS via substitutional doping and adsorption.
The structural, electronic, and magnetic properties of two-dimensional (2D) GaS are investigated using density functional theory (DFT). After confirming that the pristine 2D GaS is a non-magnetic, indirect band gap semiconductor, we consider N and F as substitutional dopants or adsorbed atoms. Except for N substituting for Ga (NGa), all considered cases are found to possess a magnetic moment. Fluorine, both in its atomic and molecular form, undergoes a highly exothermic reaction with GaS. Its site preference (FS or FGa) as substitutional dopant depends on Ga-rich or S-rich conditions. Both for FGa and F adsorption at the Ga site, a strong F-Ga bond is formed, resulting in broken bonds within the GaS monolayer. As a result, FGa induces p-type conductivity in GaS, whereas FS induces a dispersive, partly occupied impurity band about 0.5 e below the conduction band edge of GaS. Substitutional doping with N at both the S and the Ga site is exothermic when using N atoms, whereas only the more favourable site under the prevailing conditions can be accessed by the less reactive N2 molecules. While NGa induces a deep level occupied by one electron at 0.5 eV above the valence band, non-magnetic NS impurities in sufficiently high concentrations modify the band structure such that a direct transition between N-induced states becomes possible. This effect can be exploited to render monolayer GaS a direct-band gap semiconductor for optoelectronic applications. Moreover, functionalization by N or F adsorption on GaS leads to in-gap states with characteristic transition energies that can be used to tune light absorption and emission. These results suggest that GaS is a good candidate for design and construction of 2D optoelectronic and spintronics devices.


X-ray absorption spectral analyses by theoretical calculations for TiO2 and Ni-doped TiO2 thin films on glass plates.
Ni L- and Ti L-edge as well as Ti K-edge X-ray absorption experiments for TiO2 thin films and Ni-doped TiO2 thin films coated on glass plates were performed using synchrotron radiation to investigate the structures around Ni and Ti ions in the films. The obtained spectra were compared with the results of theoretical calculations. It has consequently been found that the spectral features were affected by a change in the oxidizing form of Ni ions due to hydrogen reduction, by the charge variation and/or slight orbital splitting of Ti ions, and by the magnitude of the interaction between the center Ti ion and neighboring Ti ions.


Scale invariance in the dynamics of spontaneous behavior.
Typically one expects that the intervals between consecutive occurrences of a particular behavior will have a characteristic time scale around which most observations are centered. Surprisingly, the timing of many diverse behaviors from human communication to animal foraging form complex self-similar temporal patterns reproduced on multiple time scales. We present a general framework for understanding how such scale invariance may arise in nonequilibrium systems, including those that regulate mammalian behaviors. We then demonstrate that the predictions of this framework are in agreement with detailed analysis of spontaneous mouse behavior observed in a simple unchanging environment. Neural systems operate on a broad range of time scales, from milliseconds to hours. We analytically show that such a separation between time scales could lead to scale-invariant dynamics without any fine tuning of parameters or other model-specific constraints. Our analyses reveal that the specifics of the distribution of resources or competition among several tasks are not essential for the expression of scale-free dynamics. Rather, we show that scale invariance observed in the dynamics of behavior can arise from the dynamics intrinsic to the brain.


High-precision measurement and analysis of colloidal monolayers.
This technical note describes an imaging algorithm for analyzing colloidal monolayers, including the measurement of particle-to-particle distances with nanometer-scale resolution and the automated detection of defects and edges, as well as determining the uniformity of the colloid size distribution. The algorithm also allows for the automatic detection and measurement of scaling introduced by nonsquare detector pixels, a common problem in imaging. As an application, we demonstrate the use of this method for spatially calibrating digital video microscopy systems that can be applied in situations where conventional methods may be inappropriate. Here, we provide an overview of the workings of the algorithm, which we have made freely available.


A radiation hybrid map of bovine X chromosome (BTAX).
We present a comprehensive radiation hybrid map of the bovine X chromosome (Chr) containing 20 new markers, including both microsatellites and expressed genes. This study was conducted with a 5000-rad whole genome RH cell panel consisting of 90 hybrid cell lines. Retention frequencies of individual markers range from 7.8% for XIST to 31.1% for TGLA325. Statistical analysis with RHMAPPER placed all the loci into five linkage groups under a LOD score criterion of 6.0. These groups could be oriented relative to each other because they included multiple microsatellite loci from the consensus linkage map of the X Chr. Markers included in both this RH map and the bovine cytogenetic map were in a consistent order. The comparative bovine-human map thus generated consists of five blocks of genes, the order of which is conserved, although in the opposite direction when presented as ideograms with p and q arms. Inversions of three blocks account for the difference in gene order across the entirety of the two X Chrs.


Differences between rodent and human cell lines in the amount of integrated DNA after transfection.
The suitability of Chinese hamster and human cell lines for DNA-mediated gene transformation was investigated with respect to two parameters: the average quantity of and the integrity of integrated exogenous DNA fragments. No large differences were observed between most cell lines concerning the extent of fragmentation of the transferred DNA molecules. By contrast, the average number of sequences stably incorporated by the human cells (four lines tested) was 20- to 100-fold lower than the average amount inserted in the five Chinese hamster lines investigated. The very low uptake exhibited by the human cells, ranging from less than 100 up to 500 kb, renders these cells less suitable for transfection with genomic DNA to isolate specific genes.


CCAAT/enhancer-binding protein-α suppresses lung tumor development in mice through the p38α MAP kinase pathway.
The transcription factor CCAAT/enhancer-binding protein α (C/EBPα) is a basic leucine zipper transcription factor and is expressed in alveolar type II cells, alveolar macrophages and Clara cells in the lung. Although decrease or absence of C/EBPα expression in human non-small cell lung cancer suggests a possible role of C/EBPα as a lung tumor suppressor, there is no direct proof for this hypothesis. In this study, we investigated, for the first time, the role of C/EBPα in lung tumors in vivo using transgenic mice with lung epithelial specific conditional deletion of Cebpa (Cebpα(Δ/Δ) mice) and a urethane-induced lung tumor model. C/EBPα expression in the lung was dispensable, and its deletion was not oncogenic under unstressed conditions. However, at 28 wk after urethane injection, the number and size of tumors and the tumor burden were significantly higher in Cebpα(Δ/Δ) mice than in littermate control mice. Urethane-injected Cebpα(Δ/Δ) mice showed highly proliferative adenomas and adenocarcinomas in the lung, and survival time after urethane-injection was significantly shorter than that in control mice. In control mice, C/EBPα was strongly induced in the tumor tissues at 28 weeks after urethane-injection, but became weakened or absent as tumors progressed after long-term observation for over 1 year. Using intraperitoneal injection of p38 inhibitor (SB203580), we demonstrated that the induction of C/EBPα is strongly regulated by the p38 MAP kinase in murine alveolar epithelial cells. A high correlation was demonstrated between the expression of C/EBPα and p38α MAP kinase in tumor cells, suggesting that C/EBPα silencing in tumor cells is caused by down-regulation of p38α MAP kinase. In conclusion, the role of C/EBPα as a lung tumor suppressor was demonstrated for the first time in the present study, and the extinguished C/EBPα expression through p38α inactivation leads tumor promotion and progression.


Future burden of myocardial infarction in Australia: impact on health outcomes between 2019 and 2038.
Myocardial infarction (MI) remains a major health burden in Australia. Yet the future burden of MI has not been extensively studied for the Australian population. A multistate lifetable model was constructed to estimate the lifetime risk of MI and project the health burden of MI for the Australian population aged between 40 and 100 years over a 20-year period (2019-2028). Data for the model was primarily sourced from the Victorian linked dataset and supplemented with other national data. The lifetime risk of MI from age 40 years was estimated as 24.4% for males and 13.2% for females in 2018. From 2019-2038, 891 142 Australians were projected to develop incident MI. By 2038, the model estimated there would be 702 226 people with prevalent MI, 51 262 incident non-fatal MI and 3 717 incident fatal MI; these numbers represent a significant increase compared to the 2019 estimates, with a 27.0% (148 827), 62.0% (19 629), and 104.7% (1 901) rise, respectively. Projected years of life lived (YLL) (5% discount) accrued by the Australian population were 174 795 232 (84, 356 304 in males and 90 438 928 in females), with 7 657 423 YLL among people with MI (4 997 009 in males and 2 660 414 in females). The burden of MI was projected to increase between 2019 to 2038 in Australia. The outcomes of the model provide important information for decision-makers to prioritise population-wide prevention strategies to reduce the burden of MI.


Biomechanical consequences of branching in flexible wave-swept macroalgae.
Wave-swept macroalgae present an excellent system for studying the effects of chronic physical stress on the morphological evolution of plants. Wave-induced water velocities impose great drag forces, leading to a morphological tradeoff between light interception and drag reduction/tolerance. What are the hydrodynamic consequences of morphological diversification, such as increased branching? Drag was measured on artificial macroalgae of constant 'photosynthetic' area, but differing branching patterns, in a high-speed flume at water velocities up to 3.5 m s(-1). A meta-analysis was used to compare dislodgement forces of branched and unbranched species of comparable sizes in the field to determine if drag-prone morphologies had greater attachment strengths. Branched fronds experienced greater drag than unbranched fronds of the same size. Greater drag in branched forms was not the result of increased projected area but probably resulted from greater pressure or friction drag. In the field, branched species resisted greater dislodgement forces than unbranched species of comparable size, suggesting that branched species compensate for increased drag with stronger attachment to the substratum. Branching has clear biomechanical consequences, increasing drag and the need for increased attachment. This raises questions about physiological and ecological advantages that may have driven the repeated evolution of biomechanically costly, branched morphologies.


Assessment of an embedded primary care-derived electronic health record (EHR) frailty index (eFI) in older adults with acute myeloid leukemia.
Assessing frailty is integral to treatment decision-making for older adults with acute myeloid leukemia (AML). Prior electronic frailty indices (eFI) derive from an accumulated-deficit model and are associated with mortality in older primary care populations. We evaluated use of an embedded eFI in AML by describing baseline eFI categories by treatment type and exploring associations between eFI categories, survival, and treatment received. This was a retrospective study of subjects ≥60 years old with new AML treated at an academic medical center from 1/2018-10/2020. The eFI requires ≥2 ambulatory visits over two years and uses demographics, vitals, ICD-10 codes, outpatient labs, and available functional information from Medicare Annual Wellness Visits. Frailty was defined as fit (eFI ≤ 0.10), pre-frail (0.10 < eFI ≤ 0.21), and frail (eFI > 0.21). Chemotherapy was intensive (anthracycline-based) or less-intensive (hypomethylating agent, low dose cytarabine +/- venetoclax). Therapy type, pre-treatment characteristics, and chemotherapy cycles were compared by eFI category using chi-square and Fisher's exact tests and ANOVA. Median survival was compared by eFI category using log-rank tests stratified by therapy type. Among 166 older adults treated for AML (mean age 74 years, 61% male, 85% Caucasian), only 79 (48%) had a calculable eFI score before treatment. Of these, baseline eFI category was associated with treatment received (fit (n = 31): 68% intensive, 32% less intensive; pre-frail (n = 38): 37% intensive, 63% less intensive; frail (n = 10): 0% intensive, 100% less intensive; not calculable (n = 87): 48% intensive, 52% less-intensive; p < 0.01). The prevalence of congestive heart failure and secondary AML differed by frailty status (p < 0.01). Median survival did not differ between eFI categories for intensively (p = 0.48) or less-intensively (p = 0.09) treated patients. For those with less-intensive therapy who lived ≥6 months, eFI category was not associated with the number of chemotherapy cycles received (p = 0.97). The main reason for an incalculable eFI was a lack of outpatient visits in our health system prior to AML diagnosis. A primary care-derived eFI was incalculable for half of older adults with AML at an academic medical center. Frailty was associated with chemotherapy intensity but not survival or treatment duration. Next steps include testing adaptations of the eFI to the AML setting.


In Situ Tissue Regeneration of Renal Tissue Induced by Collagen Hydrogel Injection.
Host stem/progenitor cells can be mobilized and recruited to a target location using biomaterials, and these cells may be used for in situ tissue regeneration. The objective of this study was to investigate whether host biologic resources could be used to regenerate renal tissue in situ. Collagen hydrogel was injected into the kidneys of normal mice, and rat kidneys that had sustained ischemia/reperfusion injury. After injection, the kidneys of both animal models were examined up to 4 weeks for host tissue response. The infiltrating host cells present within the injection regions expressed renal stem/progenitor cell markers, PAX-2, CD24, and CD133, as well as mesenchymal stem cell marker, CD44. The regenerated renal structures were identified by immunohistochemistry for renal cell specific markers, including synaptopodin and CD31 for glomeruli and cytokeratin and neprilysin for tubules. Quantitatively, the number of glomeruli found in the injected regions was significantly higher when compared to normal regions of renal cortex. This phenomenon occurred in normal and ischemic injured kidneys. Furthermore, the renal function after ischemia/reperfusion injury was recovered after collagen hydrogel injection. These results demonstrate that introduction of biomaterials into the kidney is able to facilitate the regeneration of glomerular and tubular structures in normal and injured kidneys. Such an approach has the potential to become a simple and effective treatment for patients with renal failure. Stem Cells Translational Medicine 2018;7:241-250.


Implementation and evaluation of a central coordination office for clinical trials in a tertiary care hospital.
Controlled clinical trials are essential tools for establishing new standards in patient care. Nevertheless, the majority of cancer patients are not treated within clinical trials. We report about a project now running for 7 years that was started in order to enhance the recruitment of patients into clinical trials, to improve trial-related quality, and to comply with the regulatory issues related to these studies. We established a Central Coordination Office (CCO) for clinical trials, an associated internal clinical trials review board, a register of active clinical trials, and a computer-based medical information system at our department. Inpatient recruitment into clinical trials at our department improved over the last 7 years from 40% in 1997 to 70% in 2003. The internal review board approved 276 trial projects since its establishment. A clinical trials register is now in its 9th edition. Currently, 50 to 60 clinical trials in oncology/hematology are active while 10 to 20 new trials are being implemented per year. All clinical trials comply with the regulatory requirements, and trial documentation is provided in a timely manner. The establishment of a CCO for clinical trials substantially improves and maintains patient recruitment into clinical trials and improves the quality of clinical research.


CO2 insufflation versus air insufflation for endoscopic submucosal dissection: A meta-analysis of randomized controlled trials.
Carbon dioxide (CO2) insufflation is increasingly used for endoscopic submucosal dissection (ESD) owing to the faster absorption of CO2 as compared to that of air. Studies comparing CO2 insufflation and air insufflation have reported conflicting results. This meta-analysis is aimed to assess the efficacy and safety of use of CO2 insufflation for ESD. Clinical trials of CO2 insufflation versus air insufflation for ESD were searched in PubMed, Embase, the Cochrane Library and Chinese Biomedical Literature Database. We performed a meta-analysis of all randomized controlled trials (RCTs). Eleven studies which compared the use of CO2 insufflation and air insufflation, with a combined study population of 1026 patients, were included in the meta-analysis (n = 506 for CO2 insufflation; n = 522 for air insufflation). Abdominal pain and VAS scores at 6h and 24h post-procedure in the CO2 insufflation group were significantly lower than those in the air insufflation group, but not at 1h and 3h after ESD. The percentage of patients who experienced pain 1h and 24h post-procedure was obviously decreased. Use of CO2 insufflation was associated with lower VAS scores for abdominal distention at 1h after ESD, but not at 24h after ESD. However, no significant differences were observed with respect to postoperative transcutaneous partial pressure carbon dioxide (PtcCO2), arterial blood carbon dioxide partial pressure (PaCO2), oxygen saturation (SpO2%), abdominal circumference, hospital stay, white blood cell (WBC) counts, C-Reactive protein (CRP) level, dosage of sedatives used, incidence of dysphagia and other complications. Use of CO2 insufflation for ESD was safe and effective with regard to abdominal discomfort, procedure time, and the residual gas volume. However, there appeared no significant differences with respect to other parameters namely, PtcCO2, PaCO2, SpO2%, abdominal circumference, hospital stay, sedation dosage, complications, WBC, CRP, and dysphagia.


Use of Leishmania major derived leishmanin for skin test surveys of visceral leishmaniasis in Ethiopia.
The potential use of Leishmania major derived leishmanin in surveys of visceral leishmaniasis (VL) was examined. The study was conducted in Konso sub-district, southwest Ethiopia involving 51 VL patients, 18 VL contacts, four localised cutaneous leishmaniasis (LCL) cases and 15 healthy controls. Sixty three percent of treated VL patients, 44.4% of VL contacts, all of LCL cases and none of untreated VL patients were positive to the test. Leishmanin skin test (LST) induration sizes of 41 treated VL patients were in the ranges of 0 to 10 mm, with a mean of 4.9 mm. The mean induration size and the positive LST rates in female patients were found to be significantly lower than in males. The major drawback of the antigen in the survey was the relatively smaller and flatter indurations. The relationship of LST to gender and leishmanial disease variant is discussed.


[A case of small cell carcinoma of the stomach].
We report a rare case of small cell carcinoma of the stomach with metastasis to the liver and invasion of the pancreas, which was associated with acute peritonitis due to perforation of the stomach. CPT-11/CDDP chemotherapy achieved a partial response. A 60-year-old man suddenly developed abdominal pain and visited the emergency room. We diagnosed acute peritonitis due to perforation of the digestive tract because CT scan showed free air in the abdominal cavity. An emergency operation was performed with an omental patch for closing the perforated hole in the stomach. Excisional biopsy was performed to the small liver nodule. Histological findings showed that the liver nodule was metastasis from small cell carcinoma. There was no finding from the thoracic CT scan, but gastroscopy revealed a giant tumor, which was diagnosed as small cell carcinoma in histology. Therefore, we diagnosed small cell carcinoma of the stomach with liver metastasis and invasion of the pancreas. After operation, one course of FP chemotherapy was performed, but the liver metastasis increased in size. Then we changed to CPT-11/CDDP chemotherapy as second-line therapy, and achieved partial remission (PR) of both the liver metastasis and gastric tumor.


The H+-linked monocarboxylate transporter (MCT1/SLC16A1): a potential therapeutic target for high-risk neuroblastoma.
Neuroblastomas produce high amounts of lactic acid and upregulate the H(+)-linked monocarboxylate transporter isoform 1 (MCT1/SLC16A1). We found elevated MCT1 mRNA levels in fresh neuroblastoma biopsy samples that correlated positively with risk of fatal disease and amplification of the "proto-oncogenic" transcription factor MYCN. We further investigated MCT as a potential therapeutic target in vitro. The neuroblastoma cell lines evaluated were Sk-N-SH, CHP134, IMR32, and NGP. All lines exhibited decreased intracellular pH at low tumor-like extracellular pH. Lonidamine or exogenous lactate further lowered intracellular pH. Immediate early lowering of intracellular pH with lonidamine or lactate at extracellular pH 6.5 correlated positively with diminished cell viability within 48 h. These findings indicate that MCT1 is a potential therapeutic target and that neuroblastoma therapy may be enhanced by therapeutic strategies to inhibit or overwhelm MCT. Additional experiments indicated that the mechanism of cell death by lonidamine or exogenous lactate is similar to that obtained using alpha-cyano-4-OH-cinnamate, a well established MCT inhibitor. Because lactate production is also high in melanoma and many other tumor types, MCT inhibitors may have broad application in cancer treatment. Such treatment would have selectivity by virtue of the acidic milieu surrounding tumors, because MCT is increasingly active as extracellular pH decreases below 7.0 and lactic acid production increases.


A neural circuit mechanism for regulating vocal variability during song learning in zebra finches.
Motor skill learning is characterized by improved performance and reduced motor variability. The neural mechanisms that couple skill level and variability, however, are not known. The zebra finch, a songbird, presents a unique opportunity to address this question because production of learned song and induction of vocal variability are instantiated in distinct circuits that converge on a motor cortex analogue controlling vocal output. To probe the interplay between learning and variability, we made intracellular recordings from neurons in this area, characterizing how their inputs from the functionally distinct pathways change throughout song development. We found that inputs that drive stereotyped song-patterns are strengthened and pruned, while inputs that induce variability remain unchanged. A simple network model showed that strengthening and pruning of action-specific connections reduces the sensitivity of motor control circuits to variable input and neural 'noise'. This identifies a simple and general mechanism for learning-related regulation of motor variability.


Metabarcoding of the phytotelmata of Pseudalcantarea grandis (Bromeliaceae) from an arid zone.
Pseudalcantarea grandis (Schltdl.) Pinzón & Barfuss is a tank bromeliad that grows on cliffs in the southernmost portion of the Chihuahuan desert. Phytotelmata are water bodies formed by plants that function as micro-ecosystems where bacteria, algae, protists, insects, fungi, and some vertebrates can develop. We hypothesized that the bacterial diversity contained in the phytotelma formed in a bromeliad from an arid zone would differ in sites with and without surrounding vegetation. Our study aimed to characterize the bacterial composition and putative metabolic functions in P. grandis phytotelmata collected in vegetated and non-vegetated sites. Water from 10 individuals was sampled. Five individuals had abundant surrounding vegetation, and five had little or no vegetation. We extracted DNA and amplified seven hypervariable regions of the 16S gene (V2, V4, V8, V3-6, 7-9). Metabarcoding sequencing was performed on the Ion Torrent PGM platform. Taxonomic identity was assigned by the binning reads and coverage between hit and query from the reference database of at least 90%. Putative metabolic functions of the bacterial families were assigned mainly using the FAPROTAX database. The dominance patterns in each site were visualized with rank/abundance curves using the number of Operational Taxonomic Units (OTUs) per family. A percentage similarity analysis (SIMPER) was used to estimate dissimilarity between the sites. Relationships among bacterial families (identified by the dominance analysis and SIMPER), sites, and their respective putative functions were analyzed with shade plots. A total of 1.5 million useful bacterial sequences were obtained. Sequences were clustered into OTUs, and taxonomic assignment was conducted using BLAST in the Greengenes databases. Bacterial diversity was 23 phyla, 52 classes, 98 orders, 218 families, and 297 genera. Proteobacteria (37%), Actinobacteria (19%), and Firmicutes (15%) comprised the highest percentage (71%). There was a 68.3% similarity between the two sites at family level, with 149 families shared. Aerobic chemoheterotrophy and fermentation were the main metabolic functions in both sites, followed by ureolysis, nitrate reduction, aromatic compound degradation, and nitrogen fixation. The dominant bacteria shared most of the metabolic functions between sites. Some functions were recorded for one site only and were related to families with the lowest OTUs richness. Bacterial diversity in the P. grandis tanks included dominant phyla and families present at low percentage that could be considered part of a rare biosphere. A rare biosphere can form genetic reservoirs, the local abundance of which depends on external abiotic and biotic factors, while their interactions could favor micro-ecosystem resilience and resistance.


Thymidine phosphorylase participates in platelet signaling and promotes thrombosis.
Platelets contain abundant thymidine phosphorylase (TYMP), which is highly expressed in diseases with high risk of thrombosis, such as atherosclerosis and type II diabetes mellitus. To test the hypothesis that TYMP participates in platelet signaling and promotes thrombosis. By using a ferric chloride (FeCl3)-induced carotid artery injury thrombosis model, we found time to blood flow cessation was significantly prolonged in Tymp(-/-) and Tymp(+/-) mice compared with wild-type mice. Bone marrow transplantation and platelet transfusion studies demonstrated that platelet TYMP was responsible for the antithrombotic phenomenon in the TYMP-deficient mice. Collagen-, collagen-related peptide-, adenosine diphosphate-, or thrombin-induced platelet aggregation were significantly attenuated in Tymp(+/-) and Tymp(-/-) platelets, and in wild type or human platelets pretreated with TYMP inhibitor KIN59. Tymp deficiency also significantly decreased agonist-induced P-selectin expression. TYMP contains an N-terminal SH3 domain-binding proline-rich motif and forms a complex with the tyrosine kinases Lyn, Fyn, and Yes in platelets. TYMP-associated Lyn was inactive in resting platelets, and TYMP trapped and diminished active Lyn after collagen stimulation. Tymp/Lyn double haploinsufficiency diminished the antithrombotic phenotype of Tymp(+/-) mice. TYMP deletion or inhibition of TYMP with KIN59 dramatically increased platelet-endothelial cell adhesion molecule 1 tyrosine phosphorylation and diminished collagen-related peptide- or collagen-induced AKT phosphorylation. In vivo administration of KIN59 significantly inhibited FeCl3-induced carotid artery thrombosis without affecting hemostasis. TYMP participates in multiple platelet signaling pathways and regulates platelet activation and thrombosis. Targeting TYMP might be a novel antiplatelet and antithrombosis therapy.


Neuromuscular but Not Technical Performance is Affected by Time-of-Day in Semiprofessional, Female Basketball Players.
Purpose: The aim of this study was to determine whether variations in technical and neuromuscular performance occur across different times of the day in basketball players. Methods: Twenty semiprofessional, female basketball players (23 ± 4 years) competing in a second-division national basketball competition completed separate testing batteries in the morning (08:30) and in the afternoon (17:30) in a randomized counterbalanced order. Testing sessions consisted of a free-throw accuracy test to assess technical performance, as well as flexibility (ankle dorsiflexion range-of-motion test), dynamic balance (modified star excursion balance test), vertical jump height (squat jump, countermovement jump with and without arm swing), strength (isometric handgrip), change-of-direction speed (V-cut test), and linear speed (20-m sprint) tests to assess neuromuscular performance. Mechanism variables were also obtained including tympanic temperature, urinary specific gravity, and rating of perceived exertion at each session. Results: Squat jump height (6.7%; p = .001; effect size (ES) = 0.33), countermovement jump height with (4.1%; p = .018; ES = 0.27) and without arm swing (5.9%; p = .007; ES = 0.30), and 20-m sprint time (-1.4%; p = .015; ES = -0.32) were significantly superior in the afternoon compared to morning. Tympanic temperature was significantly higher in the afternoon than morning (1.4%; p < .001; ES = 1.31). In contrast, no significant differences between timepoints were evident for all remaining variables (p > .05; ES = -0.33 to 0.16). Conclusions: Some neuromuscular variables exhibited a time-of-day effect with better jump and sprint performance in the afternoon compared to morning in semiprofessional, female basketball players.


Sustainable sunlight to biogas is via marginal organics.
Although biogas production from algae offers higher sunlight to biomass energy conversion efficiencies its production costs simply cannot compete with terrestrial plants. Unfortunately terrestrial plant cropping for biogas production is, in its own right, neither particularly sustainable nor profitable and its ongoing application is only driven by energy security concerns resulting in taxpayer subsidies. By comparison, scavenging the organic energy residual/wastes from food production offers a far more profitable and sustainable proposition and has an energy potential that dwarfs anything biogas production from dedicated energy crops can realistically offer. Thus researchers wanting to assist the development of sustainable biogas systems with viable process economics should forget about terrestrial and algal energy cropping and focus on the realm of scavengers.


Rapid and efficient removal of immature Aedes aegypti in metal drums by sweep net and modified sweeping method.
A modified sweeping method was developed using a cotton sweep net for control of Ae. aegypti immatures in 200 liter (44 gallon) metal drums which are major sources of breeding in Yangon. Laboratory experiments revealed that with only 4 sweeps (approximately 10 minutes duration), the mean % removal (+/- SD) of Ae. aegypti fourth stage larvae was 88.5% +/- 1.47. This was followed by a field study undertaken in Sanchaung township, Yangon. Twenty-eight drums with moderate (< 500 immatures) to high (> or = 500 immatures) Ae. aegypti density were tested in the field. It was found that with only 4 sweeps per drum, a total of 24,886 immatures were removed out of 29,155 immatures in these 28 drums, giving a mean % removal per drum of 85.36% +/- 10.74 (range = 55.54-98.62%). This sweeping method is simple, cost-effective, and readily accepted by the community. It could be an appropriate technology for control of the dengue hemorrhagic fever (DHF) vector Ae. aegypti.


EVOLUTIONARY STEPS AND TRANSPOSABLE ELEMENTS IN DROSOPHILA MELANOGASTER: THE MISSING RP TYPE OBTAINED BY GENETIC TRANSFORMATION.
The I-R and P-M hybrid dysgenesis systems in Drosophila melanogaster have been interpreted as due to recent invasions of the genome by the I and P mobile genetic elements. Temporal and geographical surveys have never shown individuals harboring P sequences but devoid of active I elements. We describe here the successful genetic transformation by autonomous P elements of embryos initially devoid of active I elements and any P sequences. The results demonstrate that P elements may invade the genome of Drosophila melanogaster in the absence of active I elements. Using gel blotting, in situ hybridization techniques, and genetic experiments, we have monitored the behavior of newly introduced P elements in several transformed lines over 30 generations. The switch of cytotype from M to P occurred very slowly and the number of P copies simultaneously increased to about 25. These RP lines possess the properties required to induce P-M hybrid dysgenesis but totally retain the R cellular state. Consequently, this new mobile element combination presents a strong reciprocal post-zygotic isolation with IM strains due to both P-M and I-R hybrid dysgenesis systems. This genomic incompatibility could be considered as a first step toward speciation in Drosophila populations.


Estimating the additional costs of living with a disability in the United Kingdom between 2013 and 2016.
In the United Kingdom, more than 20% of the population live with a disability. Past evidence shows that being disabled is associated with functional limitations that often cause social exclusion and poverty. Therefore, it is necessary to analyse the connection between disability and poverty. This paper examines whether households with disabled members face extra costs of living to attain the same standard of living as their peers without disabled members. The modelling framework is based on the standard of living approach which estimates the extra income required to close the gap between households with and without disabled members. We apply an ordered logit regression to data from the Family Resources Survey between 2013 and 2016 to analyse the relationship between standard of living, income, and disability, conditional on other explanatory variables. We find that households with disabled members face considerable extra costs that go beyond the transfer payment of the government. The average household with disabled members saw their weekly extra costs continually increase from £293 in 2013 to £326 in 2016 [2020 prices]. Therefore, the government needs to adjust welfare policies to address the problem of extra costs faced by households with disabled members.


A longterm endoscopic evaluation of patients with arthritis treated with nabumetone vs naproxen.
To compare the gastrointestinal safety, ulcerogenic potential, and clinical efficacy over 5 years of nabumetone and naproxen therapy, in patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Fifty-two patients entered a randomized, double blind study. Patients were randomized to 3 months treatment with either nabumetone, 1000 mg nightly, or naproxen, 250 mg twice daily, followed by an endoscopist-blind 5-year followup study. After the double blind phase, 15 patients in the nabumetone group and 12 in the naproxen group continued in the longterm endoscopist-blind phase. Endoscopic evaluations for gastroduodenal damage and global assessments of arthritis activity and degree of pain for efficacy were measured. Over the 5-year period, endoscopically visible gastroduodenal ulceration was found in 8 of the naproxen treated patients compared with one of the nabumetone treated patients (p = 0.02). There was a significant difference in the time to develop an ulcer, with a greater risk of developing an ulcer sooner while taking naproxen (p < 0.01). Patients in both groups reported significant improvements in arthritis symptoms (p < 0.01). Nabumetone appears to have a significantly lower ulcerogenic potential than naproxen over a 5-year period, and there is a trend toward better tolerability as measured by withdrawals for adverse experiences.


[The Brugada Syndrome as a Cause of Sudden Death. Diagnostics and Clinical Manifestations in Children].
The Brugada syndrome is a hereditary potentially arrhythmogenic disease related to the category of channelopathies. It is manifested as syncopal states and sudden death in young people in the absence of structural cardiac disease. The basis of the disease is genetically determined abnormality of function of ionic channels of cardiomyocytes (sodium, potassium, calcium) phenotypically manifesting as sustained or transitory segment-ST elevation and high risk of polymorphic ventricular tachycardia, fibrillation, and sudden death. The only proven method of prevention of fatal arrhythmia and sudden death is cardioverter defibrillator implantation.


Structural basis for topoisomerase I inhibition by nucleoside analogs.
Nucleoside analogs such as 1-beta-D-arabinofuranosyl cytidine (AraC) and 2',2'-difluoro deoxycytidine (dFdC) are important components of the anticancer chemotherapeutic arsenal and are among the most effective anticancer drugs currently available. Although both AraCTP and dFdCTP impede DNA replication through pausing of DNA polymerases, both nucleoside analogs are ultimately incorporated into replicated DNA and interfere in DNA-mediated processes. Our laboratories are investigating the structural basis for the poisoning of topoisomerase I (top1) due to antipyrimidine incorporation into duplex DNA. We recently reported that both AraC and dFdC induce formation of top1 cleavage complexes, and poisoning of top1 contributes to the anticancer activities of both these drugs. Recent NMR and thermodynamic studies from our laboratories provide insight into the mechanism by which AraC and dFdC poison top1. NMR studies from our laboratories have revealed that the arabinosyl sugar of AraC adopted a C2'-endo conformation. Although this is a B-type sugar pucker characteristic of duplex DNA, the conformation is rigid, and this lack of flexibility probably contributes to inhibition of the religation step of the top1 reaction. In contrast to AraC, NMR studies revealed dFdC adopted a C3' endo sugar pucker characteristic of RNA, rather than DNA duplexes. dFdC substitution enhanced formation of top1 cleavage complexes, but did not inhibit religation. The enhancement of top1 cleavage complexes most likely results from a combination of conformational and electrostatic effects. The structural effects of dFdC and AraC are being further investigated in duplex DNA with well-defined top1 cleavage sites to analyze more specifically how these structural perturbations lead to enzyme poisoning.


Introduction to hierarchical clustering.
Hierarchical clustering of spike events is a method of grouping events that are similar in topology, morphology, or both, and it provides a method of efficient, detailed analysis of interictal events. Information about the relative populations of spikes at multiple foci is presented, and artifact events are grouped and eliminated en masse. The process of hierarchical clustering is explained, and a set of simulated traces is used to illustrate the process of hierarchical clustering and the development of a cluster tree to display the relative populations of similar spike events. Using EEG data from long-term monitoring, the use of a "review wizard" is explored as a means of structuring the process of hierarchical clustering and traversing the cluster tree. This aid is also used to streamline the process of determining the similarity of events within each group and of verifying that events exhibiting clinically important differences are not hidden within the groups comprising the average traces.


Development of a Modular Research Platform to Create Medical Observational Studies for Mobile Devices.
Observational studies have proven to be a valuable resource in medical research, especially when performed on a large scale. Recently, mobile device-based observational studies have been discovered by an increasing number of researchers as a promising new source of information. However, the development and deployment of app-based studies is not trivial and requires profound programming skills. The aim of this project was to develop a modular online research platform that allows researchers to create medical studies for mobile devices without extensive programming skills. The platform approach for a modular research platform consists of three major components. A Web-based platform forms the researchers' main workplace. This platform communicates via a shared database with a platform independent mobile app. Furthermore, a separate Web-based login platform for physicians and other health care professionals is outlined and completes the concept. A prototype of the research platform has been developed and is currently in beta testing. Simple questionnaire studies can be created within minutes and published for testing purposes. Screenshots of an example study are provided, and the general working principle is displayed. In this project, we have created a basis for a novel research platform. The necessity and implications of a modular approach were displayed and an outline for future development given. International researchers are invited and encouraged to participate in this ongoing project.


Hydrogel device for analgesic drugs with in-situ loading and polymerization.
The high prevalence of opioid addiction and the shortcomings of systemic opioids has increased the pace of the search for alternative methods of pain management. The local delivery of pain medications has started to be used as a tool for pain management and to decrease the use of systemic opioids for these patients. Here, we explored an in-situ polymerizable hydrogel system for the local delivery of analgesics and nonsteroid anti-inflammatory drugs (NSAID) for orthopaedic applications. We synthesized a series of methacrylated oligomeric polyethylene glycol-co-lactic acid polymer using microwave radiation for the delivery of bupivacaine hydrochloride as an analgesic and ketorolac tromethamine as an NSAID. We determined drug elution and gel degradation profiles in vitro. Biocompatibility was assessed against osteoblasts in vitro and by histological analysis after subcutaneous implantation for 4 weeks in vivo. Intra-articular and systemic concentrations and pharmacokinetic parameters were estimated using a two-compartment pharmacodynamic model based on in-vitro elution profiles. This type of in-situ applicable hydrogels is promising for extending the local efficacy of pain medication and further reducing the need for opioids.


Presence of antiheart and antiskeletal muscle glycolipid autoantibodies in the sera of patients with chagasic cardiopathy.
To characterize biochemically and isolate the skeletal and heart muscle cell epitope recognized by the autoantibodies present in the serum of chronically infected Trypanosoma cruzi patients. Secondly, to use that epitope in an immunoenzymatic assay for determining differences in antibody titre among Chagas' and other protozoan and heart diseases and between asymptomatic and cardiopathic chagasic patients. Isolated human skeletal and heart muscle cells were treated with organic solvents, pronase, neuraminidase and sodium metaperiodate before immunofluorescence assay. Glycolipids were extracted from human skeletal muscle for ELISA. Sera were collected from 155 patients with positive serology for T cruzi infection; 44 healthy blood bank donors; and from patients after heart transplantation (16 patients), during the first month after cardiac infarction (eight) or cardiotomy (10), dilated myocardiopathy (21), leishmaniasis (12), acute toxoplasmosis (four) and hyperthyroid ophthalmopathy (five). Immunofluorescence assay revealed that the chagasic sera recognized epitopes that appeared to be glycolipid in nature. ELISA showed that the chagasic sera contained a higher titre of antiskeletal muscle glycolipid antibodies than the control sera and that, in the chagasic population, antibody titre was significantly higher in patients with heart failure than in asymptomatic subjects or in those presenting only electrocardiographic abnormalities. The skeletal and heart muscle epitope recognized by antibodies present in the sera of chagasic patients has the characteristics of a glycolipid. ELISA with glycolipids extracted from human skeletal muscle indicated that chagasic patients presented a higher antibody titre and that patients with heart failure showed a titre significantly higher than those who were asymptomatic or with electrocardiographic abnormalities, suggesting that those antibodies could be immunological markers and even predictors of heart failure in Chagas' disease.


Spatial accessibility to pediatric services.
The objective of this study was to assess spatial accessibility (SA) to pediatric healthcare services at hospitals in Chiba Prefecture, Japan in 2006. We considered the distribution of general pediatricians and neonatologists relative to the geographical distribution of children using the two-step floating catchment area method, which accounts for the pediatrician-to-children ratios within catchment areas with defined travel distance (TD) thresholds. All measurements were carried out within a geographic information system. We found varied growth rate trends of children within the 61 municipalities of Chiba Prefecture between 1995 and 2006. The eastern and southern areas of the prefecture were less populated and had a small number of children in contrast to the central and northwestern areas, which had higher density of child population, less negative growth rates and even positive growth rate trends in some municipalities. For neonatology services, we used the number of live births (LB) and low birth weight (LBW) infants as populations. Lower LBW rates were found within the northern area while higher LBW rates were found within the southern area (minimum, 3.1%; maximum, 18.4%). The average LBW rate was 9.0% in Chiba Prefecture, whereas it was 9.5% for all Japan in 2005. SA analysis showed that 98.8% of children distributed within a 10 km TD threshold from a hospital with general pediatric services, and that 82.3% of LB and LBW distributed within a 30 km TD threshold from a hospital with neonatology services. The distribution of pediatricians relative to the population they serve was not homogeneous at local level. Through the methodology applied, we visualized areas short of pediatric services. The assessment of SA at local level provided informative results to achieve social equity in hospital access. The practical implications of this study are the need for reliable data for research purposes and policy development for children.


Assays to Monitor Autophagy in Saccharomyces cerevisiae.
Autophagy is an intracellular process responsible for the degradation and recycling of cytoplasmic components. It selectively removes harmful cellular material and enables the cell to survive starvation by mobilizing nutrients via the bulk degradation of cytoplasmic components. While research over the last decades has led to the discovery of the key factors involved in autophagy, the pathway is not yet completely understood. The first studies of autophagy on a molecular level were conducted in the yeast Saccharomyces cerevisiae. Building up on these studies, many homologs have been found in higher eukaryotes. Yeast remains a highly relevant model organism for studying autophagy, with a wide range of established methods to elucidate the molecular details of the autophagy pathway. In this review, we provide an overview of methods to study both selective and bulk autophagy, including intermediate steps in the yeast Saccharomyces cerevisiae. We compare different assays, discuss their advantages and limitations and list potential applications.


A novel risk factor of contrast associated acute kidney injury in patients after enhanced computed tomography: a retrospective study.
Contrast associated acute kidney injury (CA-AKI) is a major cause of acute renal failure and the incidence of CA-AKI is still high in recent years. Risk stratification is traditionally based on glomerular filtration rate(GFR). Hence, the aim of this study was to explore the novel risk factors for CA-AKI after enhanced computed tomography (CT). A retrospective cohort study was conducted in 632 in-hospital patients undergoing enhanced CT. The patients were divided into CA-AKI and no-CA-AKI groups. For comparative analyses, we applied one-to-four cohorts of those two groups using propensity score-matching methods addressing the imbalances of age, gender, weight, and smoking. The baseline clinical and biochemical data were compared. Logistic regression analysis was employed to investigate the CA-AKI risk factors. The receiver operating characteristic (ROC) curve was adopted to test the value of RDW in predicting CA-AKI after enhanced CT. 25 (3.96%) patients suffered from CA-AKI. Those subjects who developed CA-AKI had advanced age, severer renal functional injury, lower albumin, higher baseline RDW, neutrophil to lymphocyte ratio (NLR) and platelet to lymphocyte ratio (PLR) than those without CA-AKI. It also exhibited more severe anemia including decreased hemoglobin and red blood cell count (all p < 0.05). The baseline RDW, albumin and PLR between the two groups were statistically significant different after PSM. Binary logistic regression analysis showed that baseline RDW, albumin and eGFR were correlated with CA-AKI after contrast-enhanced CT examination. The RDW exhibited moderated discrimination ability for predicting CA-AKI beyond eGFR, with an AUC of 0.803 (95% CI [0.702-0.90]) vs 0.765 (95% CI [0.70-0.83]). Increased baseline RDW and decreased eGFR are risk factors for CA-AKI after enhanced CT. RDW exhibited good predictive value and can be used as an early warning marker for patients suffering from CA-AKI after enhanced CT.


Down-regulation of protein kinase Ceta potentiates the cytotoxic effects of exogenous tumor necrosis factor-related apoptosis-inducing ligand in PC-3 prostate cancer cells.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a highly promising candidate for the treatment of cancer because it elicits cell death in the majority of tumor cells while sparing most normal cells. Some cancers, however, display resistance to TRAIL, suggesting that treatment with TRAIL alone may be insufficient for cancer therapy. In the present study, we explored whether the apoptotic responsiveness of PC-3 prostate cancer cells to TRAIL could be enhanced by targeting the novel protein kinase C (PKC) isoform eta. Transfection of PC-3 cells with second-generation chimeric antisense oligonucleotides against PKCeta caused a time- and dose-dependent knockdown of PKCeta, as revealed by real-time RT-PCR and Western blot analyses. Knockdown of PKCeta resulted in a marked amplification of TRAIL's cytotoxic activity. Cell killing could be substantially prevented by the pan-caspase inhibitor z-VAD-fmk. In addition, PKCeta knockdown and administration of TRAIL significantly synergized in activation of caspase-3 and internucleosomal DNA fragmentation. Knockdown of PKCeta augmented TRAIL-induced dissipation of the mitochondrial transmembrane potential and release of cytochrome c from mitochondria into the cytosol, indicating that PKCeta acts upstream of mitochondria. We conclude that PKCeta represents a considerable resistance factor with respect to TRAIL and a promising target to exploit the therapeutic potential of TRAIL.


Controllable synthesis and magnetism of iron oxides nanorings.
Hematite (alpha-Fe2O3) nanorings were prepared via a facile hydrothermal route without using any template. The products were characterized by X-ray powder diffraction (XRD), X-ray photoelectron spectroscopy (XPS), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). On the basis of these characterizations and condition experiments, an "oriented dissolution and recrystallization" mechanism under the effect of H2PO4- ions was proposed to explain the formation process of nanoring structure. Magnetite (Fe3O4) nanorings were obtained by reducing alpha-Fe2O3 nanorings, and then maghemite (gamma-Fe2O3) nanorings were obtained by reoxidizing Fe3O4 nanorings. The magnetic properties of these nanorings were investigated, and it was found that these nanorings have higher coercivity and lower saturation magnetization than many other nanostructures of iron oxides. The adsorbed phosphate on the surface and the nanoring morphology might be responsible for this phenomenon. Furthermore, it is interesting to find that the coercivity of the nanorings increased with the increase of d(in)/d(out) (d(in) and d(out) are the inner and outer diameters of the rings, respectively), and a rapid increase was observed at the value of d(in)/d(out) around 0.5.


Clinical significance of residual platelet reactivity in patients treated with platelet P2Y12 inhibitors.
Platelet P2Y12 inhibitors have become an essential component of the treatment strategy for patients with acute coronary syndromes and patients undergoing percutaneous coronary intervention. It is now well-established that approximately 30% of patients treated with the P2Y12 inhibitor clopidogrel display high residual platelet reactivity despite treatment. Patients with high on-treatment platelet reactivity have approximately 2-3-fold greater risk of adverse cardiovascular events and stent thrombosis than those without high platelet reactivity. Conversely, clopidogrel-treated patients with low platelet reactivity display approximately 1.7-fold increased risk of major bleeding. High platelet reactivity is uncommon during treatment with prasugrel and ticagrelor, which achieve a greater reduction in adverse cardiovascular events compared to clopidogrel in ACS patients treated with PCI. This is at the expense of an increase in spontaneous bleeding, however. Minor bleeding events, such as skin haematomas, are more common in prasugrel- and ticagrelor-treated patients that have particularly low platelet reactivity values. These minor bleeding events may occasionally prompt discontinuation of therapy, but their overall prognostic impact is uncertain. However, risk factors for bleeding tend to overlap with risk factors for adverse cardiovascular events. Therefore, patients with these minor bleeding events may also be at higher risk of adverse cardiovascular events, conferring a benefit from low platelet reactivity. Further work is needed to determine the optimal level of platelet reactivity in individuals by taking into account their risk of subsequent adverse cardiovascular events and bleeding.


A novel carbohydrate labeling method utilizing transfer hydrogenation-mediated reductive amination.
One of the most frequently used high-resolution glycan analysis methods in the biopharmaceutical and biomedical fields is capillary electrophoresis with laser-induced fluorescence (CE-LIF) detection. Glycans are usually labeled by reductive amination with a charged fluorophore containing a primary amine, which reacts with the aldehyde group at the reducing end of the glycan structures. In this reaction, first a Schiff base is formed that is reduced to form a stable conjugate by a hydrogenation reagent, such as sodium cyanoborohydride. In large scale biopharmaceutical applications, such as clone selection for glycoprotein therapeutics, hundreds of reactions are accomplished simultaneously, so the HCN generated in the process poses a safety concern. To alleviate this issue, here we propose catalytic hydrogen transfer from formic acid catalyzed by water-soluble iridium(III)- and ruthenium(II)-phosphine complexes as a novel alternative to hydrogenation. The easily synthesized water-soluble iridium(III) and the ruthenium(II) hydrido complexes showed high catalytic activity in carbohydrate labeling. This procedure is environmentally friendly and reduces the health risks for the industry. Using carbohydrate standards, oligosaccharides released from glycoproteins with highly sialylated (fetuin), high mannose (ribonuclease B) and mixed sialo and neutral (human plasma) N-glycans, we demonstrated similar labeling efficiencies for iridium(III) dihydride to that of the conventionally used sodium cyanoborohydride based reaction. The derivatization reaction time was less than 20min with no bias towards the above mentioned specific glycan structures.


High-speed optical sensor interrogator with a silicon-ring-resonator-based thermally tunable filter.
On-chip optical interrogators employing a silicon-ring-resonator-based thermally tunable filter (SRRTF) offer a promising solution for realizing portable, compact optical sensing systems. However, the slow interrogation speed of conventional SRRTF-based interrogators (less than a few Hz) hinders real-time sensing of dynamic parameters. In this Letter, we report a 100 kHz of high-speed optical interrogation system based on the SRRTF. The speed enhancement is achieved by using the nonlinear transient response of the SRRTF to a square-wave input voltage. The entire spectral range of the SRRTF is scanned twice during its thermal response cycle. The time-domain sensor output signal, which is obtained by scanning the SRRTF over the sensor spectrum, is converted into spectrum domain based on the experimentally characterized, time-dependent resonance wavelength shifts of the SRRTF. With this system, we demonstrate high-speed interrogation of a fiber Bragg grating sensor under dynamic temperature change (200 Hz).


Increased Incidence of Barotrauma in Patients with COVID-19 on Invasive Mechanical Ventilation.
Background A high number of patients with coronavirus disease 2019 (COVID-19) pneumonia who had barotrauma related to invasive mechanical ventilation at the authors' institution were observed. Purpose To determine if the rate of barotrauma in patients with COVID-19 infection was greater than in other patients requiring invasive mechanical ventilation at the authors' institution. Materials and Methods In this retrospective study, clinical and imaging data of patients seen between March 1, 2020, and April 6, 2020, who tested positive for COVID-19 and experienced barotrauma associated with invasive mechanical ventilation, were compared with patients without COVID-19 infection during the same period. Historical comparison was made to barotrauma rates of patients with acute respiratory distress syndrome from February 1, 2016, to February 1, 2020, at the authors' institution. Comparison of patient groups was performed using categoric or continuous statistical testing as appropriate, with multivariable regression analysis. Patient survival was assessed using Kaplan-Meier curves analysis. Results A total of 601 patients with COVID-19 infection underwent invasive mechanical ventilation (mean age, 63 years ± 15 [standard deviation]; 71% men). Of the total, there were 89 (15%) patients with one or more barotrauma events for a total of 145 barotrauma events (24% overall events) (95% confidence interval [CI]: 21%, 28%). During the same period, 196 patients without COVID-19 infection (mean age, 64 years ± 19; 52% men) with invasive mechanical ventilation had one barotrauma event (0.5%; 95% CI: 0%, 3%; P < .001 vs the group with COVID-19 infection). Of 285 patients with acute respiratory distress syndrome on invasive mechanical ventilation during the previous 4 years (mean age, 68 years ± 17; 60% men), 28 patients (10%) had 31 barotrauma events, with an overall barotrauma rate of 11% (95% CI: 8%, 15%; P < .001 vs the group with COVID-19 infection). Barotrauma is an independent risk factor for death in COVID-19 (odds ratio = 2.2; P = .03) and is associated with a longer hospital stay (odds ratio = 0.92; P < .001). Conclusion Patients with coronavirus disease 2019 (COVID-19) infection and invasive mechanical ventilation had a higher rate of barotrauma than patients with acute respiratory distress syndrome and patients without COVID-19 infection. © RSNA, 2020 Online supplemental material is available for this article.


Trunk rotation due to persistence of primitive reflexes in early school-age children.
The angle of trunk rotation (ATR) is a measurement that allows an objective assessment of a growing child's spine. Early detection of trunk rotation prevents the progression of scoliosis. One of the factors that predispose children to the formation of faulty posture may be primitive reflexes, which should be integrated in the central nervous system (CNS) by the age of one year. If retained, primitive reflexes affect children's physical development as well as their development at school. The aim of the study was to determine the prevalence of trunk asymmetry and the persistence of primitive reflexes and their inter-relationships in early school-age children. In this population-based survey, 61 children, average age 6.3 years (SD ±1.43), were examined. The ATR was examined using a scoliometer. The degree of integration of reflexes was assessed using tests developed by S. Goddard to assess the asymmetrical tonic neck reflex (ATNR), symmetrical tonic neck reflex (STNR), and spinal Galant reflex (SGR) on a 0-4 scale. Spearman's rank correlation coefficient and the χ2 test were used in the statistical analysis. In almost half of the children body rotation was observed, in most cases toward the right (p = 0.012). This asymmetry was positively correlated with non-integrated Galant reflex on the same side (r = 0.335, p = 0.050). The presence of trunk rotation is associated with sex: There was higher frequency of asymmetry among the girls than among the boys. In the evaluation of scoliosis, it could be useful to examine primitive reflexes as a possible reason for trunk rotation. In the treatment of scoliosis, primitive reflex integration methods should be used in some cases.


Study of guinea pig and human antibodies to toluene diisocyanate.
Antibodies to toluene diisocyanate (TDI) have previously been reported in both sensitized guinea pigs and industrial workers. Detection of antibodies to TDI is difficult because the ability of TDI to self-polymerize and cross-link carrier proteins causes problems in preparing satisfactory hapten-protein conjugate antigens. Use of monoisocyanate analogues of TDI for antigen preparation eliminates the problem. This study compared 3 tolyl monoisocyanate isomers with TDI for haptenic ability to detect antibodies to TDI in sensitized guinea pigs and humans. Using the gel-diffusion technique, antibodies from guinea pigs reacted with ortho-, meta- and para-tolyl monoisocyanate haptens and with a TDI hapten. In the guinea pigs, reactions appeared to be strongest with the TDI hapten and weakest with meta-tolyl isocyanate hapten. On the other hand, antibodies in TDI-sensitized workers, as determined by radioallergosorbent testing, reacted comparably with each of the haptens.


Chemical sintering of direct-written silver nanowire flexible electrodes under room temperature.
Transparent and flexible electrodes on cost effective plastic substrates for wearable electronics have attract great attention recently. Due to the conductivity and flexibility in network form, metal nanowire is regarded as one of the most promising candidates for flexible electrode fabrication. Prior to application, low temperature joining of nanowire processes are required to reduce the resistance of electrodes and simultaneously maintain the dimensionality and uniformity of those nanowires. In the present work, we presented an innovative, robust and cost effective method to minimize the heat effect to plastic substrate and silver nanowires which allows silver nanowire electrodes been directly written on polycarbonate substrate and sintered by different electrolyte solutions at room temperature or near. It has been rigorously demonstrated that the resistance of silver nanowire electrodes has been reduced by 90% after chemical sintering at room temperature due to the joining of silver nanowires at junction areas. After ∼1000 bending cycles, the measured resistance of silver nanowire electrode was stable during both up-bending and down-bending states. The changes of silver nanowires after sintering were characterized using x-ray photoelectron spectroscopy and transmission electron microscopy and a sintering mechanism was proposed and validated. This direct-written silver nanowire electrode with good performance has broad applications in flexible electronics fabrication and packaging.


Expanding the infection control team: development of the infection control liaison position for the neonatal intensive care unit.
Neonatal survival has risen progressively during the past 30 years. As the limits of viability continue to decline, the challenges of providing care to infants at the lowest extremes of gestational age and birth weight continually increase. Nosocomial infections in this very fragile population can be devastating. The complexity of care of these premature infants requires specialized knowledge of the neonate, infectious disease processes, and methods to reduce infection risks in the neonatal intensive care unit. The role of infection control liaison has been established in our institution as an adjunct to meeting this challenge by providing a line of communication between staff, neonatologists, and the infection control team. This article describes the role of the infection control liaison and its overall impact on the infection control program in an 87-bed level II, III, and IV neonatal intensive care unit from 1995 to 1999.


Destruction of human solid tumors by alkyl lysophospholipids.
Alkyl lysophospholipids (ALP) are synthetic analogs of the naturally occurring 2-lysophosphatidylcholine. The effect of ALP on the proliferation of 22 different gynecologic malignant tumors in humans was studied in vitro. ALP caused progressive death of tumor cells over 24-96 hours. In addition, tumor specimens from the tested human tumors were xenotransplanted into NMRI nude mice. ALP induced a highly significant retardation of the in vivo growing human tumors. Neither oral nor iv administration of these compounds caused any recognizable side effects.


A covariate-adjusted response-adaptive allocation in clinical trials for a general class of responses.
A class of covariate-adjusted adaptive allocation procedures is developed for a general class of responses with an aim to satisfy relevant clinical requirements. Some exact and asymptotic properties of the procedures, proposed and a reasonable competitor, are studied and compared under the presence of treatment-covariate interaction.


Nanothermite with Meringue-like Morphology: From Loose Powder to Ultra-porous Objects.
The goal of the protocol described in this article is to prepare aluminothermic compositions (nanothermites) in the form of porous, monolithic objects. Nanothermites are combustible materials made up of inorganic fuel and an oxidizer. In nanothermite foams, aluminum is the fuel and aluminum phosphate and tungsten trioxide are the oxidizing moieties. The highest flame propagation velocities (FPVs) in nanothermites are observed in loose powders and FPVs are strongly decreased by pelletizing nanothermite powders. From a physical standpoint, nanothermite loose powders are metastable systems. Their properties can be altered by unintentional compaction induced by shocks or vibrations or by the segregation of particles over time by settling phenomena, which originates from the density differences of their components. Moving from a powder to an object is the challenge that must be overcome to integrate nanothermites in pyrotechnic systems. Nanothermite objects must have both a high open porosity and good mechanical strength. Nanothermite foams meet both of these criteria, and they are prepared by dispersing a nano-sized aluminothermic mixture (Al/WO3) in orthophosphoric acid. The reaction of aluminum with the acid solution gives the AlPO4 "cement" in which Al and WO3 nanoparticles are embedded. In nanothermite foams, aluminum phosphate plays the dual role of binder and oxidizer. This method can be used with tungsten trioxide, which is not altered by the preparation process. It could probably be extended to some oxides, which are commonly used for the preparation of high performance nanothermites. The WO3-based nanothermite foams described in this article are particularly insensitive to impact and friction, which makes them far safer to handle than loose Al/WO3 powder. The fast combustion of these materials has interesting applications in pyrotechnic igniters. Their use in detonators as primers would require the incorporation of a secondary explosive in their composition.