Distributed Signal Processing for Wireless EEG Sensor Networks.
Inspired by ongoing evolutions in the field of wireless body area networks (WBANs), this tutorial paper presents a conceptual and exploratory study of wireless electroencephalography (EEG) sensor networks (WESNs), with an emphasis on distributed signal processing aspects. A WESN is conceived as a modular neuromonitoring platform for high-density EEG recordings, in which each node is equipped with an electrode array, a signal processing unit, and facilities for wireless communication. We first address the advantages of such a modular approach, and we explain how distributed signal processing algorithms make WESNs more power-efficient, in particular by avoiding data centralization. We provide an overview of distributed signal processing algorithms that are potentially applicable in WESNs, and for illustration purposes, we also provide a more detailed case study of a distributed eye blink artifact removal algorithm. Finally, we study the power efficiency of these distributed algorithms in comparison to their centralized counterparts in which all the raw sensor signals are centralized in a near-end or far-end fusion center.


Shining light at working interfaces and chiral nanoparticles.
In this article we present an overview of our recent research in the fields of in situ spectroscopy, nanomaterials and chirality. Our research focuses around the spectroscopic investigation of chemical reactions taking place at solid-liquid interfaces. This research goes hand in hand with the development of experimental techniques that enable us to study interface phenomena in situ. Using such techniques we try to shed light on photocatalytic reactions like the decomposition of organic pollutants in water or the reduction of carbon dioxide. We are moreover interested in chiral surfaces and their ability to discriminate between enantiomers. Again this relies on special techniques that highlight the enantiodiscriminating surface-adsorbate interactions. We furthermore seek to transfer chirality from adsorbates to metal nanoparticles. The latter are probed by chiroptical techniques, particularly also vibrational circular dichroism (VCD). Finally, we aim at preparing metamaterials with tailored optical properties by organizing plasmonic particles in two and three dimensions.


Characteristics of disorders associated with genetic mutations of surfactant protein C.
To present diagnosis and treatment modalities of children with interstitial lung disease associated with frequent or rare surfactant protein C gene (SFTPC) mutation. Twenty-two children with chronic lung disease associated with SFTPC mutation in a heterozygous form. Mutations located in the BRICHOS domain ('BRICHOS domain' group) were identified in six children, whereas 16 children carried mutations located outside the BRICHOS domain ('non-BRICHOS domain' group). The median age of onset was 3 (0-24) months. Four patients had neonatal respiratory distress, and symptom onset was associated with acute bronchiolitis in nine patients. Cough, tachypnoea and failure to thrive were initially noticed in all the children. Physical examination at presentation revealed tachypnoea (n=22), clubbing (n=1) and crackles (n=5). Low oxygen saturation (<95%) was observed in 18 patients. The predominant findings on initial high-resolution CT (HRCT) scans were basal-predominant ground-glass opacity (n=21) and cystic spaces (n=3). Bronchoalveolar lavage fluid (BALF) cell counts showed 379+/-56x10(3) cells/ml with increased neutrophil percentage (18+/-4%) independent of the mutation status. The median follow-up was 3.2 (1-18.3) years. Eighteen patients were treated by monthly methylprednisolone pulses associated with oral prednisolone (n=16), hydroxychloroquine (n=11) and/or azithromycin (n=4). Fifteen patients benefited from enteral nutrition. Initial diagnosis is based on clinical presentation, radiological features and BALF analysis, but the definitive diagnosis requires genetic analysis. Although progressive improvement was seen in most patients, the development of new therapeutic strategies with minimal side effects is needed.


Bioplastics for a circular economy.
Bioplastics - typically plastics manufactured from bio-based polymers - stand to contribute to more sustainable commercial plastic life cycles as part of a circular economy, in which virgin polymers are made from renewable or recycled raw materials. Carbon-neutral energy is used for production and products are reused or recycled at their end of life (EOL). In this Review, we assess the advantages and challenges of bioplastics in transitioning towards a circular economy. Compared with fossil-based plastics, bio-based plastics can have a lower carbon footprint and exhibit advantageous materials properties; moreover, they can be compatible with existing recycling streams and some offer biodegradation as an EOL scenario if performed in controlled or predictable environments. However, these benefits can have trade-offs, including negative agricultural impacts, competition with food production, unclear EOL management and higher costs. Emerging chemical and biological methods can enable the 'upcycling' of increasing volumes of heterogeneous plastic and bioplastic waste into higher-quality materials. To guide converters and consumers in their purchasing choices, existing (bio)plastic identification standards and life cycle assessment guidelines need revision and homogenization. Furthermore, clear regulation and financial incentives remain essential to scale from niche polymers to large-scale bioplastic market applications with truly sustainable impact.


A novel mechanism of complement-independent clearance of red cells deficient in glycosyl phosphatidylinositol-linked proteins.
Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired hemolytic anemia characterized by the increased sensitivity of red blood cells (RBCs) to complement, leading to intravascular hemolysis and hemoglobinuria. PNH is due to the expansion of a cell clone that has acquired a mutation in the PIGA gene. Mice with targeted Piga gene inactivation genetically mimic the human disease and have phosphatidylinositol glycan class A-negative (PIGA-) RBCs with a reduced half-life in circulation. Although PIGA-RBCs are hypersensitive to complement in vitro, their complement sensitivity in vivo is barely detectable. Here we show that the shortened survival of PIGA- RBCs is independent of complement either by using inhibitory C5 antibodies or by transfusion into C5-, C4-, C3-, or factor B-deficient mice. Splenectomy or high-dose cortisone treatment had no effect on the shorter survival of PIGA- RBCs. However, treatment with liposome-encapsulated clodronate, an agent that depletes macrophages in vivo, normalized the half-life of PIGA- RBCs. This indicates that the shortened survival of PIGA- RBCs is due to a novel pathway of PIGA- RBC clearance that is mediated by macrophages, but occurs independently of complement. Future investigations will show whether this novel pathway of PIGA- RBC destruction identified in mice may also operate in patients with PNH.


The stories they tell: How third year medical students portray patients, family members, physicians, and themselves in difficult encounters.
Physicians have long had patients whom they have labeled "difficult", but little is known about how medical students perceive difficult encounters with patients. In this study, we analyzed 134 third year medical students' reflective essays written over an 18-month period about difficult student-patient encounters. We used a qualitative computerized software program, Atlas.ti to analyze students' observations and reflections. Main findings include that students described patients who were angry and upset; noncompliant with treatment plans; discussed "nonmedical" problems; fearful, worried, withdrawn, or "disinterested" in their health. Students often described themselves as anxious, uncertain, confused, and frustrated. Nevertheless, they saw themselves behaving in empathic and patient-centered ways while also taking refuge in "standard" behaviors not necessarily appropriate to the circumstances. Students rarely mentioned receiving guidance from attendings regarding how to manage these challenging interactions. These third-year medical students recognized the importance of behaving empathically in difficult situations and often did so. However, they often felt overwhelmed and frustrated, resorting to more reductive behaviors that did not match the needs of the patient. Students need more guidance from attending physicians in order to approach difficult interactions with specific problem-solving skills while maintaining an empathic, patient-centered context.


Identification of Potential Virulence Factors in the Model Strain Acinetobacter baumannii A118.
Acinetobacter baumannii A118, a strain isolated from the blood of an infected patient, is naturally competent and unlike most clinical strains, is susceptible to a variety of different antibiotics including those usually used for selection in genetic manipulations. These characteristics make strain A118 a convenient model for genetic studies of A. baumannii. To identify potential virulence factors, its complete genome was analyzed and compared to other A. baumannii genomes. A. baumannii A118 includes gene clusters coding for the acinetobactin and baumannoferrin iron acquisition systems. Iron-regulated expression of the BauA outer membrane receptor for ferric-acinetobactin complexes was confirmed as well as the utilization of acinetobactin. A. baumannii A118 also possesses the feoABC genes, which code for the main bacterial ferrous uptake system. The functionality of baumannoferrin was suggested by the ability of A. baumannii A118 culture supernatants to cross feed an indicator BauA-deficient strain plated on iron-limiting media. A. baumannii A118 behaved as non-motile but included the csuA/BABCDE chaperone-usher pilus assembly operon and produced biofilms on polystyrene and glass surfaces. While a known capsular polysaccharide (K) locus was identified, the outer core polysaccharide (OC) locus, which belongs to group B, showed differences with available sequences. Our results show that despite being susceptible to most antibiotics, strain A118 conserves known virulence-related traits enhancing its value as model to study A. baumannii pathogenicity.


Preferential codons enhancing the expression level of human beta-defensin-2 in recombinant Escherichia coli.
Human beta-defensin-2 (hBD2) is a small antimicrobial peptide with potential as a therapeutic agent. The effect of codon usage on the expression of hBD2 in Escherichia coli was studied. Two coding sequences encoding the same hBD2 precursor were both expressed as fusion protein with thioredoxin in E. coli BL21 (DE3). One is the wild-type human cDNA and the other is a gene synthesized by a PCR-based method in which rare codons were altered to those frequently used in E. coli. The expression level of recombinant hBD2 was over 50% of the total cellular protein when the synthetic gene with preferential codons was employed which was a 9-fold enhancement over the wild-type cDNA. The result shows the codon bias of the host was a major barrier in high-level expression of recombinant hBD2 and suggests a similar approach may be used in the expression of other defensins in E. coli.


Diagnosing gastro-oesophageal reflux disease or lactose intolerance in babies who cry a lot in the first few months overlooks feeding problems.
This paper explores two areas in which the translation of research into practice may be improved in the management of cry-fuss behaviours in the first few months of life. Firstly, babies who cry excessively are often prescribed proton pump inhibitors, despite evidence that gastro-oesophageal reflux disease is very rarely a cause. The inaccuracy of commonly used explanatory mechanisms, the side-effects of acid-suppressive medications, and the failure to identify treatable problems, including feeding difficulty when the diagnosis of 'reflux' is applied, are discussed. Secondly, crying breastfed babies are still prescribed lactase or lactose-free formula, despite evidence that the problem of functional lactose overload is one of breastfeeding management. The mechanisms and management of functional lactose overload are discussed. These two problems of research translation need to be addressed because failure to identify and manage other causes of cry-fuss problems, including feeding difficulty, may have adverse outcomes for a small but significant minority of families.


Protein engineering for development of new hydrolytic biocatalysts.
Hydrolytic enzymes play important roles as biocatalysts in chemical synthesis. The chemical versatility and structurally sturdy features of Candida antarctica lipase B has placed this enzyme as a common utensil in the synthetic tool-box. In addition to catalyzing acyl transfer reactions, a number of promiscuous activities have been described recently. Some of these new enzyme activities have been amplified by mutagenesis. Epoxide hydrolases are of interest due to their potential as catalysts in asymmetric synthesis. This current update discusses recent development in the engineering of lipases and epoxide hydrolases aiming to generate new biocatalysts with refined features as compared to the wild-type enzymes. Reported progress in improvements in reaction atom economy from dynamic kinetic resolution or enantioconvergence is also included.


Electronmicroscopic autoradiographic study of the distribution of 3H-diltiazem in myocardial cells.
The distribution of 3H-diltiazem in myocardial cell organelles was studied using an electronmicroscopic autoradiographic technique. At 3, 5 and 10 min after 3H-diltiazem injection, silver grains, which indicate the existence of diltiazem, were detected in plasma membranes and intracellular organelles. Silver grains in T systems were observed more frequently at 3 min than at 5 and 10 min. In contrast, silver grains in sarcoplasmic reticula and mitochondria apparently increased with the passage of time. These findings suggest that diltiazem is transported through the T system and may accumulate within the sarcoplasmic reticula and mitochondria. Furthermore, our study revealed morphologically for the first time that the intracellular sites of action where diltiazem was directed were possibly the mitochondria.


MRI of neuronal ceroid lipofuscinosis. II. Postmortem MRI and histopathological study of the brain in 16 cases of neuronal ceroid lipofuscinosis of juvenile or late infantile type.
Postmortem MRI was carried out on the formalin-fixed brains of 14 patients with juvenile (JNCL) and two with late infantile neuronal ceroid lipofuscinosis, one of variant and the other of classical type. Two patients with JNCL had also undergone MRI during life. After MRI, specimens for histopathological analysis were taken from standard areas of the cerebral cortex, deep nuclei and white matter. The signal intensity of the periventricular white matter was usually higher than that of the peripheral white matter, a finding which correlated with the severe periventricular loss of myelin and gliosis observed histologically. The signal intensity was usually lower in the thalamus than in the putamen; in some patients the signal intensity of the thalamus was equal to or even lower than that of the white matter. However, myelin loss, gliosis, the storage process or neuronal loss in the thalamus did not correlate with the MRI findings. Since in one patient with JNCL the ante- and postmortem MRI did not differ basically, it appears probable that the periventricular changes detected in vivo on MRI are due to the severe loss of myelin and gliosis observed in this study. However, changes resulting from the fixation process must be considered, when postmortem and in vivo MRI are correlated.


Graphene fluorescence resonance energy transfer aptasensor for the thrombin detection.
Combining nanomaterials and biomolecule recognition units is promising in developing novel clinic diagnostic and protein analysis techniques. In this work, a highly sensitive and specific fluorescence resonance energy transfer (FRET) aptasensor for thrombin detection is developed based on the dye labeled aptamer assembled graphene. Due to the noncovalent assembly between aptamer and graphene, fluorescence quenching of the dye takes place because of FRET. The addition of thrombin leads to the fluorescence recovery due to the formation of quadruplex-thrombin complexes which have weak affinity to graphene and keep the dyes away from graphene surface. Because of the high fluorescence quenching efficiency, unique structure, and electronic properties of graphene, the graphene aptasensor exhibits extraordinarily high sensitivity and excellent specificity in both buffer and blood serum. A detection limit as low as 31.3 pM is obtained based on the graphene FRET aptasensor, which is two orders magnitude lower than those of fluorescent sensors based on carbon nanotubes. The excellent performance of FRET aptasensor based on graphene will also be ascribed to the unique structure and electronic properties of graphene.


Evaluation of Esophageal Functions by Manometry in Iron Deficiency Anemia Patients.
The aim of this study was to investigate whether any esophageal motor dysfunction exists in patients with iron deficiency anemia (IDA). The study included 39 patients (34 women, mean age: 44.17 ± 14.21 years) who met WHO diagnostic criteria for IDA. An additional 30 functional dyspepsia patients were also included as a control group. Esophageal motility testing was performed; esophagus contraction amplitude, peak velocity, contraction time, lower esophageal sphincter (LES) resting pressure, LES relaxation, and LES relaxation duration were assessed. A majority (76.4%) of patients had at least one IDA symptom, such as reflux, chest pain, or dysphagia. Manometric findings in IDA patients vs. controls were as follows: mean LES resting pressure (mm Hg): 25.41 ± 11.67 vs. 19.96 ± 6.58 (P = 0.025); mean esophageal contraction amplitude (mm Hg): 61.61 ± 24.21 vs. 63.23 ± 18.86 (P = 0.764); mean LES relaxation duration (s, x ± SD): 5.33 ± 1.61 vs. 8.75 ± 1.86 (P = 0.000); mean LES relaxation (%): 93.30 ± 9.88 vs. 95.53 ± 5.81 (P = 0.278); mean peak velocity (cm/s): 12.67 ± 37.95 vs. 3.50 ± 1.63 (P = 0.191). Esophageal dysmotility was found in 11 (28.2%) IDA patients. Non-specific esophageal motor disorder was found in three patients, hypomotility of the esophagus was found in three patients, achalasia was found in two patients, hypertensive LES was found in two patients, and hypotensive LES was found in one patient. LES resting pressure was higher and LES relaxation duration was shorter in patients with IDA. Esophageal dysmotility was present in 28.2% of the patients with IDA A little more than half of patients had dysphagia symptoms. IDA may contribute to esophageal motility dysfunction and esophageal symptoms.


Controllable fabrication of alginate/poly-L-ornithine polyelectrolyte complex hydrogel networks as therapeutic drug and cell carriers.
Polyelectrolyte complex (PEC) hydrogels are advantageous as therapeutic agent and cell carriers. However, due to the weak nature of physical crosslinking, PEC swelling and cargo burst release are easily initiated. Also, most current cell-laden PEC hydrogels are limited to fibers and microcapsules with unfavorable dimensions and structures for practical implantations. To overcome these drawbacks, alginate (Alg)/poly-L-ornithine (PLO) PEC hydrogels are fabricated into microcapsules, fibers, and bulk scaffolds to explore their feasibility as drug and cell carriers. Stable Alg/PLO microcapsules with controllable shapes are obtained through aqueous electrospraying technique, which avoids osmotic shock and prolongs the release time. Model enzyme and nanosized cargos are successfully encapsulated and continuously released for more than 21 days. Alg/PLO PEC fibers are then prepared to encapsulate brown adipose progenitors (BAPs) and Jurkat T cells. The electrostatic interactions between Alg and PLO are found to facilitate the printability and self-support ability of Alg/PLO bioinks. Alg/PLO PEC fibers and scaffolds support cell proliferation, differentiation, and functionalization. These results demonstrate new options for biocompatible PEC hydrogel preparation and improve the understanding of PEC hydrogels as drug and cell carriers. STATEMENT OF SIGNIFICANCE: In this study, the concept of polyelectrolyte complex hydrogel networks as drug and cell carriers has been demonstrated. Their feasibility to achieve sustained drug release and cell functionality was explored, from microcapsules to fibers to three-dimension printed scaffolds. PEC microcapsules with controllable shapes were obtained. Therapeutic drugs can be encapsulated and continuously release for more than 21 days. Benefiting from the dynamic interactions of physically crosslinked PEC, self-healing fibers were achieved. Besides, the electrostatic interactions between polyelectrolytes were found to facilitate the printability and self-support ability of PEC bioinks. The PEC fibers and scaffolds with controllable structure supported cell proliferation, differentiation, and function. The outcome of current research promotes design of new biocompatible PEC hydrogels and potential drug and cell carriers.


Genomics of coloration in natural animal populations.
Animal coloration has traditionally been the target of genetic and evolutionary studies. However, until very recently, the study of the genetic basis of animal coloration has been mainly restricted to model species, whereas research on non-model species has been either neglected or mainly based on candidate approaches, and thereby limited by the knowledge obtained in model species. Recent high-throughput sequencing technologies allow us to overcome previous limitations, and open new avenues to study the genetic basis of animal coloration in a broader number of species and colour traits, and to address the general relevance of different genetic structures and their implications for the evolution of colour. In this review, we highlight aspects where genome-wide studies could be of major utility to fill in the gaps in our understanding of the biology and evolution of animal coloration. The new genomic approaches have been promptly adopted to study animal coloration although substantial work is still needed to consider a larger range of species and colour traits, such as those exhibiting continuous variation or based on reflective structures. We argue that a robust advancement in the study of animal coloration will also require large efforts to validate the functional role of the genes and variants discovered using genome-wide tools.This article is part of the themed issue 'Animal coloration: production, perception, function and application'.


Photoreversible pigment: occurrence in a blue-green alga.
A new photoreversible pigment has been isolated from the blue-green alga Tolypothrix tenuis. This pigment bears certain resemblances to phytochrome, except that absorption maxima for the two forms are in the green and red portions of the spectrum instead of the red and far-red. The pigment may control diverse differentiative processes in blue-green algae.


Long term effect of low frequency chronic electrical stimulation on the fast hind limb muscles of dystrophic mice.
Low frequency chronic electrical stimulation can have a beneficial effect on dystrophic muscles. The present study was undertaken to assess the long term effect of such stimulation on the fast hind limb muscles of dystrophic mice. The relationship between the changes induced by stimulation and the initial condition of the dystrophic muscles, as well as other factors which might contribute to this relationship, were examined. The stimulation induced an increase in the force output of weak dystrophic muscles and a speeding of their time course of contraction and relaxation, as well as an increase in their fatigue resistance. In relatively strong dystrophic muscles, the stimulation induced similar changes in contractile speed and fatigue characteristics, but it led to a slight decrease in force output. Our results suggest that the stimulation promotes the growth and differentiation of the small regenerating fibres known to be present in the diseased muscles and, in addition, induces an increase in the mitochondrial content of the muscle fibres. Our results indicate that these effects are not permanent.


Polyphyenolics increase t-PA and u-PA gene transcription in cultured human endothelial cells.
Moderate red wine consumption has been associated with a reduced risk for coronary heart disease, and this cardioprotection may be mediated, in part, by promoting fibrinolysis. This protection may be attributed to the combined or perhaps synergistic effects of alcohol and other red wine components (i.e., polyphenolics). These studies were carried out to determine whether individual phenolics (i.e., catechin, epicatechin, quercetin, and resveratrol) affect fibrinolytic protein (tissue-type plasminogen activator [t-PA] and urokinase-type PA [u-PA]) expression and surface-localized fibrinolytic activity in cultured human umbilical vein endothelial cells (HUVECs). Cultured HUVECs were preincubated (1 hr, 37 degrees C) in the absence or presence of varying concentrations of catechin, epicatechin, quercetin, and resveratrol (0.001-10 microM) and then were washed and incubated for various times in the absence of phenolics. Secreted t-PA/u-PA antigen (24 hr, enzyme-linked immunoadsorbent assay) and mRNA [0-16 hr, reverse transcription-polymerase chain reaction(RT-PCR)] levels and fibrinolytic activity (direct activation of HUVEC-bound 125I-labeled glutamylplasminogen, quantitation of 125I-labeled Mr 20 kDa plasmin light-chain) were measured. Transient transfections of cultured HUVECs were carried out with the pt-PA222/luc and pu-PA236/luc promoter constructs, by using lipofectamine. Each of the phenolics similarly increased t-PA and u-PA antigen (2- to 3-fold) and mRNA (3- to 4-fold) levels, concomitant with an increase (2- to 3-fold) in sustained (24 hr), surface-localized fibrinolytic activity. Transcription inhibitor actinomycin D abolished the induction of t-PA and u-PA mRNA expression by these phenolics. Transfections with the pt-PA222/luc and pu-PA236/luc promoter constructs showed 2- to 3-fold and 2- to 4-fold increases in luciferase activity for t-PA and u-PA, respectively. These results demonstrate that each of these phenolics up-regulates both t-PA and u-PA gene transcription, which results in the sustained increased expression of surface-localized fibrinolytic activity in cultured HUVECs. Wine phenolics increase fibrinolytic activity, independent of ethanol, and it is likely that the overall cardioprotective benefits associated with moderate red wine consumption are attributable to the combined, additive, or perhaps synergistic effects of alcohol and other wine components.


[Pica, a strange symptom unveiled even in "Don Quixote"].
Pica, the compulsive eating of non edible substances, is known by the medical profession for centuries. In the novel by Miguel de Cervantes "Adventures of the famous knight Don Quixote de la Mancha'', there is a history in which "women that by caprice eat soil, plaster coal and other disgusting substances'' are mentioned. This description configures the clinical diagnosis of pica. This fact has not attracted the attention of the critics of Cervantes' novel, up to now. This unequivocal reference of pica suggests that iron deficiency anemia, caused by chronic hemorrhages in adults, was frequent in 1605, when the book was first published.


Role of protein kinase C and the Sp1-p53 complex in activation of p21(WAF-1) expression by 12-O-tetradecanoylphorbol-13-acetate in human T cells.
Previous reports have shown that, in certain cell types, p21(WAF-1), which plays a central role in cell proliferation, can be activated by HTLV-I Tax protein and by TPA. Tax and TPA are also known to stimulate HTLV-I gene expression. Since cell proliferation has a major impact on HTLV-I replication, it was of interest to investigate their effect on p21(WAF-1) in human T cells, which are the main target of HTLV-I in human infection. This study demonstrates that p21(WAF-1) is activated in such cells by both factors, each acting through a different mechanism that does not influence the other. The effect of TPA is shown to require PKC activity. Notably, however, examination of different PKC isoforms revealed that PKC-alpha and PKC-epsilon stimulated p21(WAF-1) expression, whereas PKC-eta was rather inhibitory and PKC-beta1 and beta2 were ineffective. All these isoforms were found to be activated by TPA in the employed T cells, but this apparent paradox was resolved by the observation that when coexpressed together in these cells, the stimulatory PKCs override the inhibitory isoform. Further experiments demonstrated that the PKC-induced p21(WAF-1) activation was mediated by binding of Sp1-p53 complex to the second most upstream of the six Sp1 recognition sites present in its promoter and that this effect did not require the cooperation of an p53-binding site.


The impact of a national clinician-led audit initiative on care and mortality after hip fracture in England: an external evaluation using time trends in non-audit data.
Hip fracture is the most common serious injury of older people. The UK National Hip Fracture Database (NHFD) was launched in 2007 as a national collaborative, clinician-led audit initiative to improve the quality of hip fracture care, but has not yet been externally evaluated. We used routinely collected data on 471,590 older people (aged 60 years and older) admitted with a hip fracture to National Health Service (NHS) hospitals in England between 2003 and 2011. The main variables of interest were the use of early surgery (on day of admission, or day after) and mortality at 30 days from admission. We compared time trends in the periods 2003-2007 and 2007-2011 (before and after the launch of the NHFD), using Poisson regression models to adjust for demographic changes. The number of hospitals participating in the NHFD increased from 11 in 2007 to 175 in 2011. From 2007 to 2011, the rate of early surgery increased from 54.5% to 71.3%, whereas the rate had remained stable over the period 2003-2007. Thirty-day mortality fell from 10.9% to 8.5%, compared with a small reduction from 11.5% to 10.9% previously. The annual relative reduction in adjusted 30-day mortality was 1.8% per year in the period 2003-2007, compared with 7.6% per year over 2007-2011 (P<0.001 for the difference). The launch of a national clinician-led audit initiative was associated with substantial improvements in care and survival of older people with hip fracture in England.


Kinetics and dosimetry of iodine-131-labelled antibody fragments after local administration in patients with rectal cancer.
In 11 patients with rectal cancer, a mixture of F(ab')2 fragments of anti-carcinoembryonic antigen and anti-CA 19.9 labelled with a diagnostic dose of iodine-131 (3-10 MBq) was administered submucosally around the tumour. In this study, the local kinetics in and the dose to the rectal wall, the whole body kinetics and the effective dose equivalent are presented. The early disappearance of the activity from the injection spot was characterized by a T1/2 of 21 h. Initially, about 50% of the plasma activity was due to free 131I. After 4 h, the plasma activity was almost completely protein bound (86%). Maximum plasma activity was observed after the 2nd day. From 72 h p.i., the plasma activity decreased with a T1/2 of 53 h. In the first 24 h, 14% of the injected dose was excreted in the urine and within 4 days about half of the administered activity. The absorbed radiation dose to the rectal wall was estimated to be 0.2 Gy/MBq, presuming a 20 cm3 distribution volume. The dose to the bone marrow was 0.2 mGy/MBq or 0.4 mGy/MBq, assuming a homogeneous tracer distribution or equal blood and bone marrow activity concentrations, respectively. The effective dose equivalent is 1.9 mSv/MBq, mainly determined by the dose to the rectal wall and to a lesser extent by the dose to the remaining body. Postulating comparable kinetics, 123I- or 111In- or 99mTc-labelled fragments would result in 4-25-fold lower effective dose equivalents.(ABSTRACT TRUNCATED AT 250 WORDS)


COVID-19 controlled human infection studies: worries about local community impact and demands for local engagement.
In spring, summer and autumn 2020, one abiding argument against controlled human infection (CHI) studies of SARS-CoV-2 vaccines has been their impact on local communities. Leading scientists and bioethicists expressed concern about undue usage of local residents' direly needed scarce resources at a time of great need and even about their unintended infection. They recommended either avoiding CHI trials or engaging local communities before conducting any CHIs. Similar recommendations were not made for the alternative-standard phase III field trials of these same vaccines. We argue that the health effects of CHI studies on local residents not participating in the study tend to be smaller and more positive than those of field trials. That is all the more so now that tested vaccines are being rolled out. Whether or not local community engagement is necessary for urgent vaccine studies in the pandemic, the case for its engagement is stronger prior to field trials than prior to CHI studies.


Tobacco Product Use Among High School Students - Youth Risk Behavior Survey, United States, 2019.
Tobacco product use is the leading cause of preventable disease, disability, and death in the United States. This report used data from the 2019 Youth Risk Behavior Survey to assess the following among U.S. high school students: ever use of cigarettes and electronic vapor products, current use (≥1 day during the 30 days before the survey) of tobacco products, frequent use (≥20 days during the 30 days before the survey) among current users of tobacco products, trends in use over time, and usual source of electronic vapor products among current electronic vapor product users. In 2019, a total of 50.1% of U.S. high school students had ever used electronic vapor products, and 24.1% had ever tried cigarette smoking. Current electronic vapor product use was 32.7%, current cigarette smoking was 6.0%, current cigar smoking was 5.7%, and current smokeless tobacco use was 3.8%. Approximately 36.5% of students were current users of any tobacco product, and 8.2% were current users of two or more tobacco products. Frequent use among users of individual products was 32.6% for electronic vapor products, 28.5% for smokeless tobacco, 22.2% for cigarettes, and 18.4% for cigars. Among current electronic vapor product users who were aged ≤17 years, the most commonly reported source was borrowing them from someone else (42.8%). Significant decreases occurred in current cigarette smoking (1991: 27.5%; 2019: 6.0%), cigar smoking (1997: 22.0%; 2019: 5.7%), and smokeless tobacco use (2017: 5.5%; 2019: 3.8%). However, significant increases occurred in current electronic vapor product use (2015: 24.1%; 2019: 32.7%) and any tobacco product use (2017: 19.5%; 2019: 36.5%). Although current cigarette smoking, cigar smoking, and smokeless tobacco use has decreased among high school students, the increased prevalence of electronic vapor product use among youths is concerning. Continued surveillance for all tobacco product use is warranted for guiding and evaluating public health policy at the local, state, tribal, and national levels.


A "twisting and bending" model-based nonrigid image registration technique for 3-D ultrasound carotid images.
Atherosclerosis at the carotid bifurcation resulting in cerebral emboli is a major cause of ischemic stroke. Most strokes associated with carotid atherosclerosis can be prevented by lifestyle/dietary changes and pharmacological treatments if identified early by monitoring carotid plaque changes. Registration of 3-D ultrasound (US) images of carotid plaque obtained at different time points is essential for sensitive monitoring of plaque changes in volume and surface morphology. This registration technique should be nonrigid, since different head positions during image acquisition sessions cause relative bending and torsion in the neck, producing nonlinear deformations between the images. We modeled the movement of the neck using a "twisting and bending" model with only six parameters for nonrigid registration. We evaluated the algorithm using 3-D US carotid images acquired at two different head positions to simulate images acquired at different times. We calculated the mean registration error (MRE) between the segmented vessel surfaces in the target image and the registered image using a distance-based error metric after applying our "twisting and bending" model-based nonrigid registration algorithm. We achieved an average registration error of 0.80 +/-0.26 mm using our nonrigid registration technique, which was a significant improvement in registration accuracy over rigid registration, even with reduced degrees-of-freedom compared to the other nonrigid registration algorithms.


Phylogenetic trends in phenolic metabolism of milkweeds (Asclepias): evidence for escalation.
Although plant-defense theory has long predicted patterns of chemical defense across taxa, we know remarkably little about the evolution of defense, especially in the context of directional phylogenetic trends. Here we contrast the production of phenolics and cardenolides in 35 species of milkweeds (Asclepias and Gomphocarpus). Maximum-likelihood analyses of character evolution revealed three major patterns. First, consistent with the defense-escalation hypothesis, the diversification of the milkweeds was associated with a trend for increasing phenolic production; this pattern was reversed (a declining evolutionary trend) for cardenolides, toxins sequestered by specialist herbivores. Second, phylogenetically independent correlations existed among phenolic classes across species. For example, coumaric acid derivatives showed negatively correlated evolution with caffeic acid derivatives, and this was likely driven by the fact that the former are used as precursors for the latter. In contrast, coumaric acid derivatives were positively correlated with flavonoids, consistent with competition for the precursor p-coumaric acid. Finally, of the phenolic classes, only flavonoids showed correlated evolution (positive) with cardenolides, consistent with a physiological and evolutionary link between the two via malonate. Thus, this study presents a rigorous test of the defense-escalation hypothesis and a novel phylogenetic approach to understanding the long-term persistence of physiological constraints on secondary metabolism.


Patterns of care and outcomes with the addition of chemotherapy to radiation therapy for stage I nasopharyngeal cancer.
The standard of care for stage I (T1N0) nasopharyngeal cancer (NPC) is definitive radiotherapy (RT). Given the phase III evidence supporting combined chemoradiotherapy (CRT) for stage II NPC, we investigated practice patterns and outcomes associated with administration of chemotherapy to RT alone for stage I NPC. The National Cancer Data Base (NCDB) was queried for clinical T1N0 primary NPC cases (2004-2013) receiving curative-intent RT. Patients with unknown RT/chemotherapy status were excluded, as were benign/sarcomatous histologies and receipt of pharyngectomy. Patient, tumor, and treatment parameters were extracted. Logistic regression analysis ascertained factors associated with receipt of additional chemotherapy. Kaplan-Meier analysis was used to evaluate overall survival (OS) between patients receiving RT versus CRT. Cox proportional hazards modeling determined variables associated with receipt of OS. In total, 396 patients were analyzed. Chemotherapy was delivered in 147 patients (37%). On multivariate analysis, patients treated at academic/integrated centers were less likely to receive chemotherapy (p = .008); a racial predilection was noted, as non-black/non-white patients were also less likely to receive chemotherapy (p = .006). Respective 5-year OS in patients receiving RT alone versus CRT were 77% and 75% (p = .428). Receipt of chemotherapy did not independently predict for greater OS (p = .447). These data do not support the routine addition of chemotherapy to definitive RT for T1N0 NPC.


Hemorrhagic fever with renal syndrome caused by the Seoul virus.
The Seoul virus is an important etiologic agent in hemorrhagic fever with renal syndrome (HFRS), and infections with the Seoul virus are less severe than those with the Hantaan virus. However, the information on HFRS caused by the Seoul virus is limited in Korea. Retrospective clinical analysis was done on 30 patients with Seoul virus infection who had been diagnosed as having HFRS by clinical features and serologic testing by the plaque reduction neutralization test from 1986 to 1991 at the Seoul National University Hospital. They were compared with 69 patients with Hantaan virus infection. The Seoul virus was the etiologic agent in 25% of Korean HFRS and the major cause of HFRS during the summer season although infections occurred throughout the year. The Seoul virus infection had a milder degree of bleeding and renal derangement but had severer liver dysfunction than the Hantaan virus infection. Renal histopathologic findings revealed a milder degree of hemorrhage and vascular changes than cases involving Hantaan virus infection. The precise mechanisms of vascular dysfunction and organ involvement in Seoul virus infection, however, still remain to be explored.


Gastric functions in gastrin gene knock-out mice.
The gastric hormone gastrin was the 2nd hormone to be identified and was initially recognized for its ability to induce acid secretion. Following the purification and subsequent development of specific radioimmunoassays for gastrin, it was also shown to be a regulator of oxyntic mucosal growth. To explore the importance of gastrin or its receptors for gastric development and gastric physiology both have been knocked out. The knock-out mice are viable, develop with any gross abnormalities, and are fertile. Even though gastrin acts as a growth factor during hypergastrinaemia there was no general atrophy of the gastrin mucosa in the knock-out mice. But the maturation of both parietal and ECL cells were disturbed and the number of parietal cells reduced. Furthermore, lack of gastrin impaired basal acid secretion and rendered the parietal cells unresponsive to histamine and acetylcholine, the other two major stimulators of gastric acid secretion. Despite the major changes in gastric physiology, the number of genes down-regulated in the gastrin knock-out mice is modest. The achlorhydria due to lack of gastrin also leads to bacterial overgrowth of the stomachs of the gastrin knockout mice, which could facilitate the development of gastric ulcer disease and cancer.


Prevalence of hip dislocation among children with cerebral palsy in regions with and without a surveillance programme: a cross sectional study in Sweden and Norway.
Hip dislocation is a serious complication among children with cerebral palsy (CP). The aim of this study was to compare the prevalence of hip dislocation among children with CP in an area providing regular care with an area providing hip surveillance services. This is a cross-sectional study in seven Norwegian counties providing regular care and one Swedish healthcare region where a hip surveillance programme was introduced in 1994. Data were provided by the Norwegian Cerebral Palsy Register and the CP Register in Southern Sweden. Children born 1996 - 2003 with moderate to severe CP, defined as Gross Motor Classification System (GMFCS) levels III - V, were included. In all, 119 Norwegian and 136 Swedish children fulfilled the criteria. In Norway, data on hip operations and radiographs of the hips were collected from medical records, while these data are collected routinely in the Swedish register. The hip migration percentage was measured on the recent radiographs. Hip dislocation was defined as a migration percent of 100%. The proportion of children at GMFCS levels III - V was 34% in the Norwegian and 38% in the Swedish population. In the Norwegian population, hip dislocation was diagnosed in 18 children (15.1%; CI: 9.8 - 22.6) compared with only one child (0.7%; 95% CI: 0.01 - 4.0) in Southern Sweden (p = < 0.001). Hip surgery was performed in 53 (44.5%) of the Norwegian children and in 43 (32%) of the Swedish children (p = 0.03). The total number of hip operations was 65 in Norway and 63 in Sweden. Norwegian children were first operated at a mean age of 7.6 years (SD: 2.9) compared with 5.7 years (SD: 2.3) in Sweden (p = 0.001). The surveillance programme reduced the number of hip dislocations and the proportion of children undergoing hip surgery was lower. However, with the surveillance programme the first operation was performed at a younger age. Our results strongly support the effectiveness of a specifically designed follow-up programme for the prevention of hip dislocation in children with CP.


Risk of vision loss in patients with cytomegalovirus retinitis and the acquired immunodeficiency syndrome.
To characterize the effect of cytomegalovirus (CMV) retinitis and its treatment on visual acuity in patients with the acquired immunodeficiency syndrome. We evaluated 648 consecutive patients with the acquired immunodeficiency syndrome at 1 center for the prevalence of visual impairment at the time of CMV retinitis diagnosis and for the incidence of visual impairment across time. Among affected eyes, the prevalence of a visual acuity measurement of 20/50 or worse or 20/200 or worse at the time of CMV retinitis diagnosis was 33% and 17%, respectively. White race and injection drug use were associated with a lower and a higher prevalence of visual impairment, respectively. At 1 year, the cumulative incidence of loss of 3, 6, and 10 lines of visual acuity was 42%, 30%, and 23%, respectively, and the incidence of visual impairment to the level of 20/50 or worse and 20/200 or worse was 34% and 24%, respectively. Patients who received highly active antiretroviral therapy had an approximately 75% lower risk of visual impairment, with the greatest benefit among those observed to have immune recovery. The incidence of loss of visual acuity did not significantly differ between eyes treated with systemic anti-CMV therapy only, initial ganciclovir implant therapy, or systemic followed by implant therapy. The prevalence of visual impairment at the time of CMV retinitis diagnosis is high and varies according to demographic characteristics. The incidence of visual impairment during follow-up is also high but is substantially lower among patients who receive highly active antiretroviral therapy, especially those observed to have immune recovery.


A Real-World Evaluation of a Smokeless Tobacco Cessation Text Message Program for Veterans: Outcomes and Comparison to Cigarette Smokers.
Smokeless tobacco (ST) use and cessation rates have remained unchanged while cigarette smoking has declined, and cessation rates have increased. Text message programs have proved effective for cigarette smokers but have not been evaluated for ST users. The Veterans Health Administration (VHA) created a ST-specific arm of its SmokefreeVET automated text message program to help veteran ST users quit. A retrospective evaluation was conducted on a real-world sample of veteran ST users (n = 1139) who subscribed to SmokefreeVET between 2017 and 2020. Time in program, abstinence, and nicotine replacement therapy (NRT) use were evaluated and compared to 9764 cigarette smokers who subscribed to SmokefreeVET. Younger subscribers were more likely to opt out early; 54% of ST users and 60% of cigarette smokers completed the 6-week program. ST users were more likely to report abstinence than cigarette smokers at all time points: the primary outcome, 30-day abstinence at 6 months, was 3.9% in ST users and 2.6% in cigarette smokers (p = .05) and the secondary outcome, abstinence at 3 months, was 5.3% in ST users and 3.4% in cigarette smokers (p = .03). NRT was used by 17% of ST users and was associated with a trend toward higher abstinence compared to ST users who did not use NRT. A real-world sample of ST users were more likely to report abstinence after using the SmokefreeVET text program than cigarette smokers. Automated text message programs may be effective for increasing cessation among ST users and warrant further investigation. Smokeless tobacco (ST) cessation is an important public health priority and of importance for veteran and military populations that have higher rates of ST use. There have been relatively few studies conducted investigating the effectiveness of text message interventions for ST cessation, despite the proven efficacy for cigarette smokers. This study provides evidence from a large, real-world sample that text message programs may be effective for ST users and suggests that further research into this treatment modality for ST users is needed.


Gravitational Lensing in Astronomy.
Deflection of light by gravity was predicted by General Relativity and observationally confirmed in 1919. In the following decades, various aspects of the gravitational lens effect were explored theoretically. Among them were: the possibility of multiple or ring-like images of background sources, the use of lensing as a gravitational telescope on very faint and distant objects, and the possibility of determining Hubble's constant with lensing. It is only relatively recently, (after the discovery of the first doubly imaged quasar in 1979), that gravitational lensing has became an observational science. Today lensing is a booming part of astrophysics. In addition to multiply-imaged quasars, a number of other aspects of lensing have been discovered: For example, giant luminous arcs, quasar microlensing, Einstein rings, galactic microlensing events, arclets, and weak gravitational lensing. At present, literally hundreds of individual gravitational lens phenomena are known. Although still in its childhood, lensing has established itself as a very useful astrophysical tool with some remarkable successes. It has contributed significant new results in areas as different as the cosmological distance scale, the large scale matter distribution in the universe, mass and mass distribution of galaxy clusters, the physics of quasars, dark matter in galaxy halos, and galaxy structure. Looking at these successes in the recent past we predict an even more luminous future for gravitational lensing. Supplementary material is available for this article at 10.12942/lrr-1998-12.


Occurrence of Marek's disease in vaccinated Algerian broiler breeder flocks: A histopathological survey.
Marek's disease (MD) is a lymphoproliferative disease that occurs in chickens. In the absence of control measures, MD causes devastating losses to commercial poultry flocks. Vaccination has enabled dramatic success in the prevention and control of MD. However, the MD vaccination program has failed frequently, and occasional clinical outbreaks have been reported in the vaccinated flocks as well. The present study aimed to describe the clinical and histopathological characteristics of the field cases of MD in broiler breeder flocks. A survey on the update of MD occurrence in Algerian broiler breeder flocks was conducted from June 2020 to September 2020. Ten vaccinated broiler breeder flocks located in Central Algeria and having progressive tumors in different visceral organs were evaluated for MD virus infection by conducting a histopathological examination of the birds. The age of the birds affected with MD ranged from 13 to 22 weeks. The mortality rate varied sensitively from 4% to 10%. The clinical symptoms reported in the affected flocks included locomotor, nervous, digestive, and respiratory symptoms. Necropsy of the dead or euthanized birds revealed visceral lymphomatosis in several organs and macroscopic changes in the peripheral nerves (including loss of longitudinal striation, color change [grayish], and volume increase). The histopathological findings included the infiltration and proliferation of lymphocytes and blast cells (lymphoblasts) in various organs of the birds, which are the typical characteristics of MD and, therefore, confirmed the field infection of MD in these birds. The present study provided evidence for the high prevalence of MD in the broiler breeder flocks vaccinated with a bivalent vaccine (turkey herpesvirus+Rispens) at the hatchery. The findings of the present study may indicate high-level failure of vaccination in these birds.


Rheumatoid arthritis-related interstitial lung disease: associations, prognostic factors and physiological and radiological characteristics--a large multicentre UK study.
The prevalence of interstitial lung disease (ILD) in RA is ∼5%. Previous work identified increasing age, active articular disease and articular damage as risk factors for RA-associated ILD (RA-ILD). The roles of high-resolution CT (HRCT) and lung function testing in defining the nature and extent of pulmonary involvement have recently been explored. This study is the first to examine predictive and prognostic factors for the development of RA-ILD and to report on the physiological and radiological characteristics of the condition from a large multicentre UK network. We collected data from centres across the UK on patients with both RA and ILD (proved on HRCT) diagnosed over a 25-year period from 1987 to 2012 using a standard pro forma. Potential predictors of RA-ILD were analysed. Baseline lung function data were recorded and related to HRCT findings. We analysed HRCT for subtype and extent of lung involved and examined the relationship between these and both all-cause and pulmonary mortality. We compared our results with case controls matched for age and gender using computer-generated selection from the RA population from one contributing centre. A total of 230 patients were identified from across the UK with proven RA-ILD diagnosed over 25 years. Median age at diagnosis was 64 years and the male:female ratio was 1:1.09. Univariate analysis showed anti-CCP antibody titres to be the single most strongly associated predictor of RA-ILD. Male gender, age at onset, smoking and RF were all independently associated with RA-ILD on multivariate analysis. Vital capacity (VC) was preserved in limited disease but reduced in extensive disease, while gas transfer was reduced in both. Usual interstitial pneumonia (UIP) was the most common subtype on HRCT and both this and extensive disease were associated with increased all-cause mortality. This is the largest study of RA-ILD in the UK. Anti-CCP antibodies were strongly associated with RA-ILD in both sexes. Smoking was strongly associated with ILD in males, which may explain the higher frequency of RA-ILD in men. The predominant HRCT pattern was UIP and most patients had limited disease at presentation. The presence of UIP and extensive disease are associated with increased mortality. Baseline gas transfer is a useful screening tool for ILD, while the preservation of VC at baseline might predict limited disease on HRCT.


Future directions in cardiac resynchronization therapy.
Cardiac resynchronization therapy (CRT) reduces symptoms and improves mortality in patients with moderate to severe chronic heart failure (New York Heart Association class III-IV) in sinus rhythm with reduced left ventricular ejection fraction and with wide QRS on the surface electrocardiogram as evidence of ventricular dyssynchrony. CRT's benefit in patients with atrial fibrillation, mild heart failure, or a conventional indication for antibradycardia pacing is being assessed. Moreover, the PROSPECT trial assessed whether the response rate to CRT might increase if, in addition to wide QRS, mechanical dyssynchrony criteria were required. The RethinQ study examined whether patients with narrow QRS but with mechanical dyssynchrony benefit from CRT. Finally, whether patients with heart failure with preserved left ventricular function also may benefit from CRT remains to be studied.


2D Projection Maps of WSS and OSI Reveal Distinct Spatiotemporal Changes in Hemodynamics in the Murine Aorta during Ageing and Atherosclerosis.
Growth, ageing and atherosclerotic plaque development alter the biomechanical forces acting on the vessel wall. However, monitoring the detailed local changes in wall shear stress (WSS) at distinct sites of the murine aortic arch over time has been challenging. Here, we studied the temporal and spatial changes in flow, WSS, oscillatory shear index (OSI) and elastic properties of healthy wildtype (WT, n = 5) and atherosclerotic apolipoprotein E-deficient (Apoe-/-, n = 6) mice during ageing and atherosclerosis using high-resolution 4D flow magnetic resonance imaging (MRI). Spatially resolved 2D projection maps of WSS and OSI of the complete aortic arch were generated, allowing the pixel-wise statistical analysis of inter- and intragroup hemodynamic changes over time and local correlations between WSS, pulse wave velocity (PWV), plaque and vessel wall characteristics. The study revealed converse differences of local hemodynamic profiles in healthy WT and atherosclerotic Apoe-/- mice, and we identified the circumferential WSS as potential marker of plaque size and composition in advanced atherosclerosis and the radial strain as a potential marker for vascular elasticity. Two-dimensional (2D) projection maps of WSS and OSI, including statistical analysis provide a powerful tool to monitor local aortic hemodynamics during ageing and atherosclerosis. The correlation of spatially resolved hemodynamics and plaque characteristics could significantly improve our understanding of the impact of hemodynamics on atherosclerosis, which may be key to understand plaque progression towards vulnerability.


Landscape patterns in rainforest phylogenetic signal: isolated islands of refugia or structured continental distributions?
Identify patterns of change in species distributions, diversity, concentrations of evolutionary history, and assembly of Australian rainforests. We used the distribution records of all known rainforest woody species in Australia across their full continental extent. These were analysed using measures of species richness, phylogenetic diversity (PD), phylogenetic endemism (PE) and phylogenetic structure (net relatedness index; NRI). Phylogenetic structure was assessed using both continental and regional species pools. To test the influence of growth-form, freestanding and climbing plants were analysed independently, and in combination. Species richness decreased along two generally orthogonal continental axes, corresponding with wet to seasonally dry and tropical to temperate habitats. The PE analyses identified four main areas of substantially restricted phylogenetic diversity, including parts of Cape York, Wet Tropics, Border Ranges, and Tasmania. The continental pool NRI results showed evenness (species less related than expected by chance) in groups of grid cells in coastally aligned areas of species rich tropical and sub-tropical rainforest, and in low diversity moist forest areas in the south-east of the Great Dividing Range and in Tasmania. Monsoon and drier vine forests, and moist forests inland from upland refugia showed phylogenetic clustering, reflecting lower diversity and more relatedness. Signals for evenness in Tasmania and clustering in northern monsoon forests weakened in analyses using regional species pools. For climbing plants, values for NRI by grid cell showed strong spatial structuring, with high diversity and PE concentrated in moist tropical and subtropical regions. Concentrations of rainforest evolutionary history (phylo-diversity) were patchily distributed within a continuum of species distributions. Contrasting with previous concepts of rainforest community distribution, our findings of continuous distributions and continental connectivity have significant implications for interpreting rainforest evolutionary history and current day ecological processes, and for managing rainforest diversity in changing circumstances.


In vitro models of the human heart.
Cardiac congenital disabilities are the most common organ malformations, but we still do not understand how they arise in the human embryo. Moreover, although cardiovascular disease is the most common cause of death globally, the development of new therapies is lagging compared with other fields. One major bottleneck hindering progress is the lack of self-organizing human cardiac models that recapitulate key aspects of human heart development, physiology and disease. Current in vitro cardiac three-dimensional systems are either engineered constructs or spherical aggregates of cardiomyocytes and other cell types. Although tissue engineering enables the modeling of some electro-mechanical properties, it falls short of mimicking heart development, morphogenetic defects and many clinically relevant aspects of cardiomyopathies. Here, we review different approaches and recent efforts to overcome these challenges in the field using a new generation of self-organizing embryonic and cardiac organoids.


Oral squamous cell carcinoma invasion is associated with a laminin-5 matrix re-organization but independent of basement membrane and hemidesmosome formation. clues from an in vitro invasion model.
The basement membrane (BM) molecule laminin-5 represents the major component of the anchoring filaments, the BM counterpart of the hemidesmosomes. Because laminin-5 is abundantly deposited adjacent to budding invasive carcinoma cells in vivo, a special invasion-promoting role is suspected. We present a 3D collagen type I gel invasion model for oral squamous cell carcinoma (OSCC) using the newly established OSCC cell lines PE/CA-PJ15, PE/CA-PJ34, and PE/CA-PJ41. The carcinoma cells on the surface of the collagen type I gel show an invasive growth exclusively in the presence of gel-inoculated (myo)fibroblasts yielded from nodular palmar fibromatosis or tumour stroma. The model is characterized by an immunohistochemical and ultrastrcutural failure of structural BM and hemidesmosome formation. In the model an invasion-associated modulation of the laminin-5 deposition (alpha3, clone BM165; gamma2, clone GB3) was demonstrated: in invasive areas a strong ribbon-like immunostaining in the tumor-gel interface. The results obtained from the invasion model suggest that the assumed invasion-promoting ability of the BM molecule laminin-5 is realized independent of a structural BM and hemidesmosome formation.


Clinically resolved psoriatic lesions contain psoriasis-specific IL-17-producing αβ T cell clones.
In psoriasis, an IL-17-mediated inflammatory skin disease, skin lesions resolve with therapy, but often recur in the same locations when therapy is discontinued. We propose that residual T cell populations in resolved psoriatic lesions represent the pathogenic T cells of origin in this disease. Utilizing high-throughput screening (HTS) of the T cell receptor (TCR) and immunostaining, we found that clinically resolved psoriatic lesions contained oligoclonal populations of T cells that produced IL-17A in both resolved and active psoriatic lesions. Putative pathogenic clones preferentially utilized particular Vβ and Vα subfamilies. We identified 15 TCRβ and 4 TCRα antigen receptor sequences shared between psoriasis patients and not observed in healthy controls or other inflammatory skin conditions. To address the relative roles of αβ versus γδ T cells in psoriasis, we carried out TCR/δ HTS. These studies demonstrated that the majority of T cells in psoriasis and healthy skin are αβ T cells. γδ T cells made up 1% of T cells in active psoriasis, less than 1% in resolved psoriatic lesions, and less than 2% in healthy skin. All of the 70 most frequent putative pathogenic T cell clones were αβ T cells. In summary, IL-17-producing αβ T cell clones with psoriasis-specific antigen receptors exist in clinically resolved psoriatic skin lesions. These cells likely represent the disease-initiating pathogenic T cells in psoriasis, suggesting that lasting control of this disease will require suppression of these resident T cell populations.


Body composition, strength static and isokinetic, and bone health: comparative study between active adults and amateur soccer players.
To compare tissue composition, total and regional bone mineral content and bone mineral density, static hand grip and knee joint isokinetic strength between amateur soccer players and Control Group. Cross-sectional study. Air displacement plethysmography was used to estimate body volume and, in turn, density. Body composition, bone mineral content and bone mineral density were assessed for the whole body and at standardized regions using dual energy X-ray absorptiometry. Static grip strength was assessed with an adjustable dynamometer, and peak torque derived from isokinetic strength dynamometer (concentric muscular knee actions at 60°/s). Magnitude of the differences between groups was examined using d-Cohen. Compared to healthy active adults, soccer players showed larger values of whole body bone mineral content (+651g; d=1.60; p<0.01). In addition, differences between groups were large for whole body bone mineral density (d=1.20 to 1.90; p<0.01): lumbar spine, i.e. L1-L4 (+19.4%), upper limbs (+8.6%) and lower limbs (+16.8%). Soccer players attained larger mean values in strength test given by static hand grip protocol (+5.6kg, d=0.99; p<0.01). Soccer adequately regulates body composition and is associated better bone health parameters (bone mineral content and density at whole-body and at particular sites exposed to mechanical loadings).


Massive symmetry breaking in LaAlO3/SrTiO3(111) quantum wells: a three-orbital strongly correlated generalization of graphene.
Density functional theory calculations with an on-site Coulomb repulsion term reveal competing ground states in (111)-oriented (LaAlO(3))(M)/(SrTiO(3))(N) superlattices with n-type interfaces, ranging from spin, orbitally polarized (with selective e(g)('), a(1g), or d(xy) occupation), Dirac point Fermi surface, to charge-ordered flat band phases. These phases are steered by the interplay of (i) Hubbard U, (ii) SrTiO(3) quantum well thickness, and (iii) crystal field splitting tied to in-plane strain. In the honeycomb lattice bilayer N = 2 under tensile strain, inversion symmetry breaking drives the system from a ferromagnetic Dirac point (massless Weyl semimetal) to a charge-ordered multiferroic (ferromagnetic and ferroelectric) flat band massive (insulating) phase. With increasing SrTiO(3) quantum well thickness an insulator-to-metal transition occurs.


Effect of the calcium antagonist felodipine as supplementary vasodilator therapy in patients with chronic heart failure treated with enalapril: V-HeFT III. Vasodilator-Heart Failure Trial (V-HeFT) Study Group.
Despite therapy with diuretics, ACE inhibitors and digoxin morbidity and mortality in heart failure remain high and might respond favorably to an additional vasodilator. Male patients (n=450) with chronic heart failure (cardiac dysfunction and impaired exercise performance) on optimal current therapy (97% enalapril, 89% diuretics) were randomly assigned to double-blind treatment with felodipine extended release (5 mg BID) or placebo for 3 to 39 months (average, 18 months). Felodipine significantly reduced blood pressure and, at 3 months, increased ejection fraction (2.1% versus -0.1% units in the placebo group, P=.001) and reduced plasma atrial natriuretic peptide levels (-2.9 versus 26.9 pg/mL in the placebo group, P=.01) but did not improve exercise tolerance, quality of life, or the need for hospitalization. During long-term follow-up, the favorable effects on ejection fraction and atrial peptide did not persist, but felodipine prevented worsening exercise tolerance and quality of life. In the felodipine and placebo groups, mortality (13.8% versus 12.8%, respectively) and hospitalization (43% versus 42%) rates were similar, and a higher incidence of peripheral edema was the only apparent side effect of felodipine therapy. Felodipine exerts a well-tolerated additional sustained vasodilator effect in patients with heart failure treated with enalapril, but the only possible long-term benefit was a trend for better exercise tolerance and less depression of quality of life in the second year of treatment. The drug appears to be safe but not clearly efficacious in patients with heart failure.


A new approach to the resection of pulmonary osteosarcoma metastases. Results of aggressive metastasectomy.
Pulmonary metastases are the primary cause of death from bone and soft-tissue sarcoma. Recognition that even multiple resections of metastases can improve survival has led to a more aggressive surgical approach to these patients. The authors instituted an aggressive approach and a new technique and retrospectively analyzed the results of multiple, pulmonary metastasectomies for pulmonary metastases in 34 patients, 21 of whom had osteogenic sarcoma (OGS). A number of cases were referred from other institutions, where they had been considered inoperable because of extensive or recurrent disease. Using lateral thoracotomies, laser technique with minimal parenchymal excision, and thin gloves for palpation, aggressive metastectomy was carried out. A mean of 3.1 thoracotomies were performed, with an average of 10.6 nodules resected per thoracotomy. Operative morbidity and mortality were minimal. Evaluation of potential prognostic factors revealed no statistically significant survival difference on the basis of disease-free interval (DFI), number of nodules resected, number of thoracotomies, or size of largest nodule resected. There was a clear trend toward decreased survival of patients with larger nodules (greater than 2 cm), but because of the small number of patients in this group, no firm conclusions can be drawn. Five-year survival was 49% for the study group as a whole, and 39% for the OGS patients. Aggressive surgical resection of pulmonary metastases from bone and soft-tissue sarcoma should be considered when there is control of local disease, no evidence of extrapulmonary metastasis, and adequate postresection pulmonary reserve. The presence of bilateral, extensive, or recurrent disease is not a contraindication to thoracotomy.(ABSTRACT TRUNCATED AT 250 WORDS)


Determination of DPYD enzyme activity in Korean population.
Dihydropyrimidine dehydrogenase (DPYD) is an enzyme that regulates the rate-limiting step in pyrimidine metabolism, especially catabolism of fluorouracil. This study was performed to analyze the association between DPYD genetic variants and DPYD enzyme activity in the Korean population. We screened the genetic variants and analyzed the enzyme activity in 73 healthy Korean subjects (69 men and 4 women; mean age, 22.6 years). Direct sequencing was conducted using the ABI 3730XL system, and enzyme activity was determined using high-performance liquid chromatography. A total of 83 genetic variants were observed. Among the identified genetic variants, 32 were polymorphic including 3 core and 11 novel genetic variants. Association analysis between each genetic variant and enzyme activity in Korean subjects showed that 2 novel genetic variants, -832 G>A and -131 C>A, induced a significant difference in enzyme activity (P < 0.05). To our knowledge, this is the first study that has examined the association between enzyme activity and DPYD genetic variants in the Korean population. In this study, we identified novel genetic variants that are associated with the enzyme activity. These findings will be valuable for further pharmacogenetic studies and especially useful for personalized medicine.


Effect of physical therapy interventions on spatiotemporal gait parameters in children with cerebral palsy: a systematic review.
To investigate the effect of physical therapy interventions on spatiotemporal gait parameters in children with cerebral palsy. Six databases were searched: PubMed, Embase, Web of Science, Science Direct, Lilacs, and Scopus. Two independent reviewers worked on primary study selection based on titles, abstracts, and full text reading. We included randomized controlled trials investigating the role of therapeutic interventions on gait kinematics in children with cerebral palsy. The independent reviewers extracted information about study population, intervention type, main outcomes, and methodological quality according to PEDro Scale. The body of evidence was synthesized through GRADE. Twenty-six studies were found addressing the following treatment categories: functional electrical stimulation, transcranial stimulation, gait training, muscular strengthening, vibratory platform training, and serial casting. A moderate level of evidence was identified for vibratory platform training, gait training, transcranial stimulation (positive effect), and isolated muscle strengthening (negative effect) in relation to gait velocity. Electrical stimulation showed a moderate level of evidence regarding stride length. The evidence for other outcomes was of low or very low quality. Vibratory platform, gait training, electrical stimulation, and transcranial stimulation were effective to improve spatiotemporal gait parameters, especially velocity in children with cerebral palsy.Implication for rehabilitationImprovement and maintenance of gait of children with cerebral palsy is a great challenge to rehabilitation professionalsVibratory platform, gait training, electrical stimulation, and transcranial stimulation improve gait parameters.Isolated strength training was not effective to improve gait parameters in Cerebral Palsy.Long-term effect of most techniques on gait parameters until unclear.


Hyperventilation impairs oxygenation after bidirectional superior cavopulmonary connection.
Bidirectional superior cavopulmonary connection (BSCC) may be complicated by systemic hypoxemia. Hyperventilation, which is standard therapy for postoperative hypoxemia, has opposing effects on the pulmonary and cerebral vascular beds, which are connected after BSCC. It is unknown which of these effects predominates and, therefore, whether hyperventilation improves or impairs systemic oxygenation after BSCC. Twelve consecutive patients (median age, 6.4 months; age range, 6.0 to 32.0, months) undergoing BSCC were studied prospectively. Patients were studied in the intensive care unit within 6 hours of surgery and while sedated, paralyzed, and mechanically ventilated. Inotropes were not altered, and no transfusions were given. FIO2 was set at 100%, and peak end-expiratory pressure was set at 0. Each patient was studied first during normal ventilation, then during hyperventilation, and finally again during normal ventilation. Hyperventilation resulted in significant decreases in arterial PO2, systemic oxygen saturation, and transpulmonary gradient. Cerebral blood flow velocity was measured in 6 patients through transcranial Doppler sonography of the middle cerebral artery. Mean cerebral flow velocity decreased significantly during hyperventilation. Hyperventilation significantly impairs systemic oxygenation after BSCC. This fall in oxygenation occurs despite a decrease in transpulmonary gradient. A possible mechanism for this effect is that hyperventilation lowers arterial PCO2, raising cerebral vascular resistance, and lowering cerebral, superior vena caval, and pulmonary blood flows. Supportive evidence for this mechanism is the decrease in cerebral flow velocity that occurs during hyperventilation. After BSCC, normal ventilation rather than hyperventilation should be used to improve systemic oxygen levels.


A Generic Method for Assessing the Quality of De-Identified Health Data.
Data sharing plays an important role in modern biomedical research. Due to the inherent sensitivity of health data, patient privacy must be protected. De-identification means to transform a dataset in such a way that it becomes extremely difficult for an attacker to link its records to identified individuals. This can be achieved with different types of data transformations. As transformation impacts the information content of a dataset, it is important to balance an increase in privacy with a decrease in data quality. To this end, models for measuring both aspects are needed. Non-Uniform Entropy is a model for data quality which is frequently recommended for de-identifying health data. In this work we show that it cannot be used in a meaningful way for measuring the quality of data which has been transformed with several important types of data transformation. We introduce a generic variant, which overcomes this limitation. We performed experiments with real-world datasets, which show that our method provides a unified framework in which the quality of differently transformed data can be compared to find a good or even optimal solution to a given data de-identification problem. We have implemented our method into ARX, an open source anonymization tool for biomedical data.


Risk factors for postherpetic neuralgia.
The risk factors for postherpetic neuralgia (PHN), the most common complication of herpes zoster, have not been well established. To elucidate the risk factors for PHN. Automated medical, claims, and pharmacy records of a health maintenance organization were used to identify cases of PHN and obtain data on risk factors. A case-base design was used to assess the impact of various patient, disease, and treatment factors on the prevalence of PHN 1 and 2 months after developing zoster. There were 821 cases of herpes zoster that met all eligibility criteria. The prevalence of PHN more than 30 days after onset of zoster was 8.0% (95% confidence interval [CI], 6.3%-10.1%) and 4.5% (95% CI, 3.2%-6.2%) after 60 days. Compared with patients younger than 50 years, individuals aged 50 years or older had a 14.7-fold higher prevalence (95% CI, 6.8-32.0) 30 days and a 27.4-fold higher prevalence (95% CI, 8.8-85.4) 60 days after developing zoster. Prodromal sensory symptoms and certain conditions associated with compromised immunity were also associated with PHN. Systemic corticosteroids before zoster and treatment of zoster with acyclovir or corticosteroids did not significantly affect the prevalence of PHN. Increased age and prodromal symptoms are associated with higher prevalence of PHN 1 and 2 months after onset of zoster. Overall, systemic acyclovir appears not to confer any protection against PHN, although benefit among elderly patients cannot be excluded.


Being "SMART" About Adolescent Conduct Problems Prevention: Executing a SMART Pilot Study in a Juvenile Diversion Agency.
The development of adaptive treatment strategies (ATS) represents the next step in innovating conduct problems prevention programs within a juvenile diversion context. Toward this goal, we present the theoretical rationale, associated methods, and anticipated challenges for a feasibility pilot study in preparation for implementing a full-scale SMART (i.e., sequential, multiple assignment, randomized trial) for conduct problems prevention. The role of a SMART design in constructing ATS is presented. The SMART feasibility pilot study includes a sample of 100 youth (13-17 years of age) identified by law enforcement as early stage offenders and referred for precourt juvenile diversion programming. Prior data on the sample population detail a high level of ethnic diversity and approximately equal representations of both genders. Within the SMART, youth and their families are first randomly assigned to one of two different brief-type evidence-based prevention programs, featuring parent-focused behavioral management or youth-focused strengths-building components. Youth who do not respond sufficiently to brief first-stage programming will be randomly assigned a second time to either an extended parent- or youth-focused second-stage programming. Measures of proximal intervention response and measures of potential candidate tailoring variables for developing ATS within this sample are detailed. Results of the described pilot study will include information regarding feasibility and acceptability of the SMART design. This information will be used to refine a subsequent full-scale SMART. The use of a SMART to develop ATS for prevention will increase the efficiency and effectiveness of prevention programing for youth with developing conduct problems.


Pharmacokinetics and safety of oseltamivir in patients with end-stage renal disease treated with automated peritoneal dialysis.
Patients with end-stage renal disease (ESRD) are at increased risk of developing complications associated with influenza infection. Oseltamivir is indicated for influenza treatment in ESRD patients, but the disposition is poorly understood in this patient population. This study aimed to characterize the pharmacokinetics and tolerability of oseltamivir in automated peritoneal dialysis (APD) and construct a pharmacokinetic model to assist with optimized dosing. Ten adults with ESRD were prescribed an aggressive APD regimen consisting of three continuous cycler-assisted peritoneal dialysis (CCPD) sessions during the day and two continuous ambulatory (CAPD) sessions overnight. Oseltamivir was administered as a single 75 mg dose, immediately before APD treatment. Oseltamivir was rapidly eliminated via first-pass metabolism, with most of the dose (Fraction metabolized = 0.964) reaching the circulation as the active metabolite, oseltamivir carboxylate. This metabolite was cleared slowly and was quantifiable throughout the sampling interval. The disposition of oseltamivir and oseltamivir carboxylate was described by a two- and a one-compartment model, respectively. Metabolite clearance by CCPD [0.32 l h(-1) (70 kg)(-1) ] was 1.9-fold faster than via CAPD [0.17 l h(-1) (70 kg)(-1) ], with renal elimination being dominant in patients with residual urine production. Model simulations showed that a single 75 mg dose attained target exposures in patients with negligible or low urine clearance. However, higher doses are recommended for further investigation in patients with high residual renal function. In all patients, oseltamivir was well tolerated. In APD patients with anuria or low residual renal elimination, a single 75 mg dose of oseltamivir produced exposures at the upper end of the safety margin.


Bioactive organic-inorganic poly(CLMA-co-HEA)/silica nanocomposites.
A series of novel poly(CLMA-co-HEA)/silica nanocomposites is synthesized from caprolactone 2-(methacryloyloxy)ethyl ester (CLMA) and 2-hydroxyethyl acrylate (HEA) as organic comonomers and the simultaneous sol-gel polymerization of tetraethyloxysilane (TEOS) as silica precursor, in different mass ratios up to a 30 wt% of silica. The nanocomposites are characterized as to their mechanical and thermal properties, water sorption, bioactivity and biocompatibility, reflecting the effect on the organic matrix provided by the silica network formation. The nanocomposites nucleate the growth of hydroxyapatite (HAp) on their surfaces when immersed in the simulated body fluid of the composition used in this work. Proliferation of the MC3T3 osteoblast-like cells on the materials was assessed with the MTS assay showing their biocompatibility. Immunocytochemistry reveals osteocalcin and type I collagen production, indicating that osteoblast differentiation was promoted by the materials, and calcium deposition was confirmed by von Kossa staining. The results indicate that these poly(CLMA-co-HEA)/silica nanocomposites could be a promising biomaterial for bone tissue engineering.


Vascular relaxation, antihypertensive effect, and cardioprotection of a novel peptide agonist of the MAS receptor.
Mas stimulation with angiotensin (Ang)-(1-7) produces cardioprotective effects and vasorelaxation. Using a computational discovery platform for predicting novel naturally occurring peptides that may activate G protein-coupled receptors, we discovered a novel Mas agonist peptide, CGEN-856S. An endothelium- and NO-dependent vasodilating effect was observed for CGEN-856S in thoracic aorta rings of rats (maximal value for the relaxant effect: 39.99+/-5.034%), which was similar to that produced by Ang-(1-7) (10(-10) to 10(-6) mol/L). In addition, the vasodilator activity of this peptide depended on a functional Mas receptor, because it was abolished in aorta rings of Mas-knockout mice. CGEN-856S appears to bind the Mas receptor at the same binding domain as Ang-(1-7), as suggested by the blocking of its vasorelaxant effect with the Ang-(1-7) analogue d-Ala(7)-Ang-(1-7), and by its competitive inhibition of Ang-(1-7) binding to Mas-transfected cells. The effect of CGEN-856S on reperfusion arrhythmias and cardiac function was studied on ischemia reperfusion of isolated rat hearts. We found that picomolar concentration of CGEN-856S (0.04 nmol/L) had an antiarrhythmogenic effect, as demonstrated by a reduction in the incidence and duration of reperfusion arrhythmias. Furthermore, acute infusion of CGEN-856S produced a shallow dose-dependent decrease in mean arterial pressure of conscious spontaneously hypertensive rats. The maximum change during infusion was observed at the highest dose. Strikingly, blood pressure continued to drop in the postinfusion period. The results presented here indicate that the novel Mas agonist, CGEN-856S, might have a therapeutic value, because it induces vasorelaxing, antihypertensive, and cardioprotective effects.


Radiomics to better characterize small renal masses.
Radiomics is a specific field of medical research that uses programmable recognition tools to extract objective information from standard images to combine with clinical data, with the aim of improving diagnostic, prognostic, and predictive accuracy beyond standard visual interpretation. We performed a narrative review of radiomic applications that may support improved characterization of small renal masses (SRM). The main focus of the review was to identify and discuss methods which may accurately differentiate benign from malignant renal masses, specifically between renal cell carcinoma (RCC) subtypes and from angiomyolipoma without visible fat (fat-poor AML) and oncocytoma. Furthermore, prediction of grade, sarcomatoid features, and gene mutations would be of importance in terms of potential clinical utility in prognostic stratification and selecting personalised patient management strategies. A detailed search of original articles was performed using the PubMed-MEDLINE database until 20 September 2020 to identify the English literature relevant to radiomics applications in renal tumour assessment. In total, 42 articles were included in the analysis in 3 main categories related to SRM: prediction of benign versus malignant SRM, subtypes, and nuclear grade, and other features of aggressiveness. Overall, studies reported the superiority of radiomics over expert radiological assessment, but were mainly of retrospective design and therefore of low-quality evidence. However, it is clear that radiomics is an attractive modality that has the potential to improve the non-invasive diagnostic accuracy of SRM imaging and prediction of its natural behaviour. Further prospective validation studies of radiomics are needed to augment management algorithms of SRM.


Long-Term Stability and Optoelectronic Performance Enhancement of InAsP Nanowires with an Ultrathin InP Passivation Layer.
The influence of nanowire (NW) surface states increases rapidly with the reduction of diameter and hence severely degrades the optoelectronic performance of narrow-diameter NWs. Surface passivation is therefore critical, but it is challenging to achieve long-term effective passivation without significantly affecting other qualities. Here, we demonstrate that an ultrathin InP passivation layer of 2-3 nm can effectively solve these challenges. For InAsP nanowires with small diameters of 30-40 nm, the ultrathin passivation layer reduces the surface recombination velocity by at least 70% and increases the charge carrier lifetime by a factor of 3. These improvements are maintained even after storing the samples in ambient atmosphere for over 3 years. This passivation also greatly improves the performance thermal tolerance of these thin NWs and extends their operating temperature from <150 K to room temperature. This study provides a new route toward high-performance room-temperature narrow-diameter NW devices with long-term stability.


Linkage disequilibrium among commonly genotyped SNP variants detected from bull sequence.
Genomic prediction utilizing causal variants could increase selection accuracy above that achieved with SNPs genotyped by currently available arrays used for genomic selection. A number of variants detected from sequencing influential sires are likely to be causal, but noticeable improvements in prediction accuracy using imputed sequence variant genotypes have not been reported. Improvement in accuracy of predicted breeding values may be limited by the accuracy of imputed sequence variants. Using genotypes of SNPs on a high-density array and non-synonymous SNPs detected in sequence from influential sires of a multibreed population, results of this examination suggest that linkage disequilibrium between non-synonymous and array SNPs may be insufficient for accurate imputation from the array to sequence. In contrast to 75% of array SNPs being strongly correlated to another SNP on the array, less than 25% of the non-synonymous SNPs were strongly correlated to an array SNP. When correlations between non-synonymous and array SNPs were strong, distances between the SNPs were greater than separation that might be expected based on linkage disequilibrium decay. Consistently near-perfect whole-genome linkage disequilibrium between the full array and each non-synonymous SNP within the sequenced bulls suggests that whole-genome approaches to infer sequence variants might be more accurate than imputation based on local haplotypes. Opportunity for strong linkage disequilibrium between sequence and array SNPs may be limited by discrepancies in allele frequency distributions, so investigating alternate genotyping approaches and panels providing greater chances of frequency-matched SNPs strongly correlated to sequence variants is also warranted. Genotypes used for this study are available from https://www.animalgenome.org/repository/pub/;USDA2017.0519/.


Assessment of MLA assertiveness training for librarians: students' behavior changes after taking C.E. 669, Assertiveness and Human Relations Skills.
C.E. 669, offered for three years, was MLA's first personal development continuing education course. Participants were asked to respond to a follow-up survey about their current assertive philosophy, awareness, and behavioral repertoire. They were also assessed by the Librarian's Assertiveness Inventory, a tool that indicates patterns of behavioral responses, for which some normative data were available from librarians who had not taken the class. Class participants were found to be more likely to behave assertively and less likely to behave aggressively than librarians who had not taken the class. In nine out of ten situational categories, librarians who had taken the class demonstrated assertive response patterns. They also reported remembering and using more than one third of the behavioral techniques covered in class, with particular use of the nonverbal techniques. A majority saw themselves as more assertive since taking the class, although most believed that others viewed them much the same as they had prior to the class. Positive progress toward reaching specific behavioral goals was also reported.


Pyrrolopyrrole aza-BODIPY near-infrared photosensitizer for dual-mode imaging-guided photothermal cancer therapy.
A NIR photosensitizer pyrrolopyrrole aza-BODIPY (PPAB) was synthesized in a straightforward manner. Through the use of PPAB NPs as a photothermal agent, photoacoustic imaging (PAI) and NIR fluorescence imaging (NIR-FI) can be achieved in vivo. In addition, the photothermal ablation of tumor cells can be realized both in vitro and in vivo, even at a low concentration (0.5 mg kg-1).


Ambient intelligence in health care.
Ambient Intelligence (AmI) is a new paradigm in information technology, in which people are empowered through a digital environment that is aware of their presence and context, and is sensitive, adaptive, and responsive to their needs, habits, gestures and emotions. The most ambitious expression of AmI is Intelligent Mixed Reality (IMR), an evolution of traditional virtual reality environments. Using IMR, it is possible to integrate computer interfaces into the real environment, so that the user can interact with other individuals and with the environment itself in the most natural and intuitive way. How does the emergence of the AmI paradigm influence the future of health care? Using a scenario-based approach, this paper outlines the possible role of AmI in health care by focusing on both its technological and relational nature. In this sense, clinicians and health care providers that want to exploit AmI potential need a significant attention to technology, ergonomics, project management, human factors and organizational changes in the structure of the relevant health service.


Aeromonas-related diarrhea in adults.
We have reviewed the incidence of Aeromonas in patients with enteric disease at our hospital and found it to be the highest of any potential enteric pathogen. Eighty adult patients with diarrhea had Aeromonas isolated from feces, and in 73 Aeromonas was the only potential bacterial or parasitic pathogen detected. The spectrum of illness in patients with Aeromonas-related diarrhea ranged from acute, self-limited diarrhea to a chronic, indolent diarrheal illness. Sixteen percent (13/80) of the patients had evidence of colitis noted during sigmoidoscopy or colonoscopy. Our data (and those from other studies) indicate that Aeromonas is relatively common in the feces of adults with diarrhea; they also indicate the need for prospective, controlled clinical and bacteriological studies to determine whether or not Aeromonas is an important enteric pathogen in adults.


HAS-BLED and CHA₂DS₂-VASc scores as predictors of bleeding and thrombotic risk after continuous-flow ventricular assist device implantation.
HAS-BLED and CHA₂DS₂-VASc scores predict bleeding in patients on anticoagulation and thromboembolic (TE) risk in patients with atrial fibrillation, respectively. We hypothesized that these scores would be predictive of bleeding and TE complications following continuous-flow ventricular assist device (CF-VAD) implantation. Baseline HAS-BLED and CHA2DS2-VASc scores were retrospectively determined for 173 consecutive patients who underwent HeartMate II CF-VAD implantation at a single center from 2005 to 2011. Forty-three patients had bleeding (24.9%) and 22 had TE (12.7%) events over a 290 patient-year follow-up period. The mean ± SD HAS-BLED scores were 2.7 ± 1.0 and 1.9 ± 1.1 (P < .0001) in patients with and without bleeding, respectively. The CHA₂DS₂-VASc scores were 3.6 ± 1.4 and 2.9 ± 1.5 (P = .03) in patients with and without TE events, respectively. A HAS-BLED score of ≥ 3 was associated with a significantly higher risk of bleeding events compared with a score of <3 (42% vs 15%, respectively; hazard ratio [HR] 3.40, 95% confidence interval [CI] 1.82-6.32; P < .001). A CHA₂DS₂-VASc score of ≥ 3 was associated with a higher risk of TE events compared with a score of <3 (18% vs 4%, respectively; HR 4.02, 95% CI 1.19-13.6; P = .025). Baseline HAS-BLED and CHA₂DS₂-VASc scores of ≥ 3 conferred significantly higher risks of bleeding and TE, respectively, following HeartMate II implantation.


Automated method for generating the arterial input function on perfusion-weighted MR imaging: validation in patients with stroke.
The choice of arterial input function (AIF) can have a profound effect on the blood flow maps generated on perfusion-weighted MR imaging (PWI). Automation of this process could substantially reduce operator dependency, increase consistency, and accelerate PWI analysis. We created an automated AIF identification program (auto-AIF) and validated its performance against conventional manual methods. We compared the auto-AIF against manually derived AIFs from multisection PWIs of 22 patients with stroke. Time to peak, curve width, curve height, and voxel location determined with both techniques were compared. The time to maximum of the tissue residue function (Tmax) and cerebral blood flow (CBF) were computed on a per-pixel basis for each AIF. Spatial patterns of 528 map pairs were compared by computing Pearson correlation coefficients between maps generated with each method. All auto-AIF-derived PWI map parameters, including bolus peak, width, and height, were consistently superior to manually derived ones. Reproducibility of the auto-AIF-based Tmax maps was excellent (r = 1.0). Paired Tmax maps and CBF maps from both techniques were well correlated (r = 0.82). Time to identify the AIF was significantly shorter with the auto-AIF method than with the manual technique (mean difference, 72 seconds; 95% confidence interval: 54, 89 seconds). An automated program that identifies the AIF is feasible and can create reliably reproducible and accurate Tmax and CBF maps. Automation of this process could reduce PWI analysis time and increase consistency and may allow for more effective use of PWI in the evaluation of acute stroke.


[Induction of alphavirus ts-mutations by N-methyl-N-nitro-N-nitrosoguanidine added to the replicating virus].
The possibility of producing ts mutants of Sindbis and eastern equine encephalomyelitis (EEE) virus by treatment of replicating virus with N-methyl-N-nitro-N-nitrosoguanidine was studied. N-methyl-N-nitro-N-nitrosoguanidine added in a concentration of 20 micrograms/ml to chick fibroblast cultures infected with Sindbis virus for 4 hours was shown to induce ts mutations in the virus. Under similar conditions no ts mutants of EEE virus could be obtained. The content of ts mutants in the mutagenized populations of Sindbis virus was 7.9%. Eight ts mutants were isolated. Their temperature-sensitive defect was expressed to various degrees. The plaque-forming efficiency at 40 degrees C/35 degrees C ranged from 6.3 X 10(-2) to 1.7 X 10(-8), and the yield from 5.6 X 10(-2) to 2.8 X 10(-4).