Education resources of the National Center for Biotechnology Information.
The National Center for Biotechnology Information (NCBI) hosts 39 literature and molecular biology databases containing almost half a billion records. As the complexity of these data and associated resources and tools continues to expand, so does the need for educational resources to help investigators, clinicians, information specialists and the general public make use of the wealth of public data available at the NCBI. This review describes the educational resources available at NCBI via the NCBI Education page (www.ncbi.nlm.nih.gov/Education/). These resources include materials designed for new users, such as About NCBI and the NCBI Guide, as well as documentation, Frequently Asked Questions (FAQs) and writings on the NCBI Bookshelf such as the NCBI Help Manual and the NCBI Handbook. NCBI also provides teaching materials such as tutorials, problem sets and educational tools such as the Amino Acid Explorer, PSSM Viewer and Ebot. NCBI also offers training programs including the Discovery Workshops, webinars and tutorials at conferences. To help users keep up-to-date, NCBI produces the online NCBI News and offers RSS feeds and mailing lists, along with a presence on Facebook, Twitter and YouTube.


Ocean warming and sea level rise along the southwest u.s. Coast.
Hydrographic time-series data recorded during the past 42 years in the upper 500 meters off the coast of southern California indicate that temperatures have increased by 0.8 degrees C uniformly in the upper 100 meters and that temperatures have risen significantly to depths of about 300 meters. The effect of warming the surface layer of the ocean and there by expanding the water column has been to raise sea level by 0.9 +/- 0.2 millimeter per year. Tide gauge records along the coast are coherent with steric height and show upward trends in sea level that vary from about 1 to 3 millimeters per year.


Mammalian HCA66 protein is required for both ribosome synthesis and centriole duplication.
Ribosome production, one of the most energy-consuming biosynthetic activities in living cells, is adjusted to growth conditions and coordinated with the cell cycle. Connections between ribosome synthesis and cell cycle progression have been described, but the underlying mechanisms remain only partially understood. The human HCA66 protein was recently characterized as a component of the centrosome, the major microtubule-organizing center (MTOC) in mammalian cells, and was shown to be required for centriole duplication and assembly of the mitotic spindle. We show here that HCA66 is also required for nucleolar steps of the maturation of the 40S ribosomal subunit and therefore displays a dual function. Overexpression of a dominant negative version of HCA66, accumulating at the centrosome but absent from the nucleoli, alters centrosome function but has no effect on pre-rRNA processing, suggesting that HCA66 acts independently in each process. In yeast and HeLa cells, depletion of MTOC components does not impair ribosome synthesis. Hence our results suggest that both in yeast and human cells, assembly of a functional MTOC and ribosome synthesis are not closely connected processes.


Age-dependent association of white matter abnormality with cognition after TIA or minor stroke.
To investigate if the association between MRI-detectable white matter hyperintensity (WMH) and cognitive status reported in previous studies persists at older ages (>80 years), when some white matter abnormality is almost universally reported in clinical practice. Consecutive eligible patients from a population-based cohort of all TIA/nondisabling stroke (Oxford Vascular Study) underwent multimodal MRI, including fluid-attenuated inversion recovery and diffusion-weighted imaging, allowing automated measurement of WMH volume, mean diffusivity (MD), and fractional anisotropy (FA) in normal-appearing white matter using FSL tools. These measures were related to cognitive status (Montreal Cognitive Assessment) at age ≤80 vs >80 years. Of 566 patients (mean [range] age 66.7 [20-102] years), 107 were aged >80 years. WMH volumes and MD/FA were strongly associated with cognitive status in patients aged ≤80 years (all p < 0.001 for WMH, MD, and FA) but not in patients aged >80 years (not significant for WMH, MD, and FA), with age interactions for WMH volume (p interaction = 0.016) and MD (p interaction = 0.037). Voxel-wise analyses also showed that lower Montreal Cognitive Assessment scores were associated with frontal WMH in patients ≤80 years, but not >80 years. MRI markers of white matter damage are strongly related to cognition in patients with TIA/minor stroke at younger ages, but not at age >80 years. Clinicians and patients should not overinterpret the significance of these abnormalities at older ages.


The biggest bang for the buck: cost-effective vegetation treatment outcomes across drylands of the western United States.
Restoration and rehabilitation are globally implemented to improve ecosystem condition but often without tracking treatment expenditures relative to ecological outcomes. We evaluated the cost-effectiveness of widely conducted woody plant and herbaceous invasive plant removals and seeding treatments in drylands of the western United States from 2004 to 2018 to determine how land managers can optimize efforts. Woody plant cover decreased at a similar rate per dollar spent regardless of vegetation removal type, and the dominant invasive species was reduced by herbicide application. Relatively inexpensive herbicide application also had a large positive effect on seeded perennial grass cover that was enhanced by additional cost; while expensive woody mastication treatments had little effect regardless of additional cost. High seed cost was driven by including a large proportion of native species in seed mixes, and combined with high seeding cost, promoted a short-term (2-3 yr) gain in perennial forb cover and species richness. In contrast, seeding and seed mix cost had no bearing on seeded perennial grass cover, in part, because relatively cheap nonnative seeded species rapidly increased in cover. Our results suggest the differential benefits of commonly implemented treatments aimed at reducing wildfire risk, improving wildlife habitat and forage, and reducing erosion. Given the growing need and cost of restoration and rehabilitation, we raise the importance of specifying treatment budgets and objectives, coupled with effectiveness monitoring, to improve future outcomes.


Prognostic value of echocardiographic parameters in congenital diaphragmatic hernia: a systematic review and meta-analysis.
Prognostication of mortality and decision to offer extracorporeal membrane oxygenation (ECMO) treatment in infants with congenital diaphragmatic hernia (CDH) can inform clinical management. To summarise the prognostic value of echocardiography in infants with CDH. Electronic databases Ovid MEDLINE, Embase, Scopus, CINAHL, the Cochrane Library and conference proceedings up to July 2022 were searched. Studies evaluating the prognostic performance of echocardiographic parameters in newborn infants were included. Risk of bias and applicability were assessed using the Quality Assessment of Prognostic Studies tool. We used a random-effect model for meta-analysis to compute mean differences (MDs) for continuous outcomes and relative risk (RR) for binary outcomes with 95% CIs. Our primary outcome was mortality; secondary outcomes were need for ECMO, duration of ventilation, length of stay, and need for oxygen and/or inhaled nitric oxide. Twenty-six studies were included that were of acceptable methodological quality. Increased diameters of the right and left pulmonary arteries at birth (mm), MD 0.95 (95% CI 0.45 and 1.46) and MD 0.79 (95% CI 0.58 to 0.99), respectively) were associated with survival. Left ventricular (LV) dysfunction, RR 2.40, (95% CI 1.98 to 2.91), right ventricular (RV) dysfunction, RR 1.83 (95% CI 1.29 to 2.60) and severe pulmonary hypertension (PH), RR 1.69, (95% CI 1.53 to 1.86) were associated with mortality. Left and RV dysfunctions, RR 3.30 (95% CI 2.19 to 4.98) and RR 2.16 (95% CI 1.85 to 2.52), respectively, significantly predicted decision to offer ECMO treatment. Limitations are lack of consensus on what parameter is optimal and standardisation of echo assessments. LV and RV dysfunctions, PH and pulmonary artery diameter are useful prognostic factors among patients with CDH.


Molecular methods for the detection of Mycoplasma and ureaplasma infections in humans: a paper from the 2011 William Beaumont Hospital Symposium on molecular pathology.
Mycoplasma and Ureaplasma species are well-known human pathogens responsible for a broad array of inflammatory conditions involving the respiratory and urogenital tracts of neonates, children, and adults. Greater attention is being given to these organisms in diagnostic microbiology, largely as a result of improved methods for their laboratory detection, made possible by powerful molecular-based techniques that can be used for primary detection in clinical specimens. For slow-growing species, such as Mycoplasma pneumoniae and Mycoplasma genitalium, molecular-based detection is the only practical means for rapid microbiological diagnosis. Most molecular-based methods used for detection and characterization of conventional bacteria have been applied to these organisms. A complete genome sequence is available for one or more strains of all of the important human pathogens in the Mycoplasma and Ureaplasma genera. Information gained from genome analyses and improvements in efficiency of DNA sequencing are expected to significantly advance the field of molecular detection and genotyping during the next few years. This review provides a summary and critical review of methods suitable for detection and characterization of mycoplasmas and ureaplasmas of humans, with emphasis on molecular genotypic techniques.


The degradation of gelatin/alginate/fibrin hydrogels is cell type dependent and can be modulated by targeting fibrinolysis.
In tissue engineering, cell origin is important to ensure outcome quality. However, the impact of the cell type chosen for seeding in a biocompatible matrix has been less investigated. Here, we investigated the capacity of primary and immortalized fibroblasts of distinct origins to degrade a gelatin/alginate/fibrin (GAF)-based biomaterial. We further established that fibrin was targeted by degradative fibroblasts through the secretion of fibrinolytic matrix-metalloproteinases (MMPs) and urokinase, two types of serine protease. Finally, we demonstrated that besides aprotinin, specific targeting of fibrinolytic MMPs and urokinase led to cell-laden GAF stability for at least forty-eight hours. These results support the use of specific strategies to tune fibrin-based biomaterials degradation over time. It emphasizes the need to choose the right cell type and further bring targeted solutions to avoid the degradation of fibrin-containing hydrogels or bioinks.


Phytochrome Kinase Substrate 4 is phosphorylated by the phototropin 1 photoreceptor.
Phototropism allows plants to redirect their growth towards the light to optimize photosynthesis under reduced light conditions. Phototropin 1 (phot1) is the primary low blue light-sensing receptor triggering phototropism in Arabidopsis. Light-induced autophosphorylation of phot1, an AGC-class protein kinase, constitutes an essential step for phototropism. However, apart from the receptor itself, substrates of phot1 kinase activity are less clearly established. Phototropism is also influenced by the cryptochromes and phytochromes photoreceptors that do not provide directional information but influence the process through incompletely characterized mechanisms. Here, we show that Phytochrome Kinase Substrate 4 (PKS4), a known element of phot1 signalling, is a substrate of phot1 kinase activity in vitro that is phosphorylated in a phot1-dependent manner in vivo. PKS4 phosphorylation is transient and regulated by a type 2-protein phosphatase. Moreover, phytochromes repress the accumulation of the light-induced phosphorylated form of PKS4 showing a convergence of photoreceptor activity on this signalling element. Our physiological analyses suggest that PKS4 phosphorylation is not essential for phototropism but is part of a negative feedback mechanism.


Immunohistochemical and tracer studies of macrophages/microglia in the pineal gland of postnatal rats.
The pineal gland of rats of various ages (1-21 days old) was examined by immunohistochemistry and electron microscopy. Numerous widely distributed cells identified as macrophages/microglia were immunoreactive with the monoclonal antibodies OX-42, OX-18, OX-6, and ED1, indicating that they expressed complement type 3 (CR3) receptors, major histocompatibility complex class I and II antigens, and antigens of monocyte/macrophage lineage as detected by the antibodies, respectively. Following an intraperitoneal injection of rhodamine isothiocyanate (RhIC) in all age groups, the cells emitted a bright fluorescence. They were also labeled by horseradish peroxidase (HRP), as demonstrated in both light and electron microscopy. An HRP reaction was observed in vesicles and lysosomes at the ultrastructural level. A remarkable feature was the uptake of these tracers by pinealocytes. In light microscopy, the pinealocytes showed a punctate reaction product 3-24 hours after HRP injection. By electron microscopy, the reaction product was observed in vesicles, lysosomes, and some rod-like structures in the cytoplasm. On the basis of their immunophenotypic features, it is suggested that the macrophages/microglia in the pineal gland are active phagocytes which are also probably involved in the immunoregulatory function in the gland. The avid uptake of RhIC and HRP from the circulation by these cells suggests that serum-derived substances that may gain access to the parenchyma of the gland are being constantly monitored. The labeling of pinealocytes with HRP suggests that the functional activities of these cells are being modulated by serum-derived substances.


A new laser scanning system for measuring action potential propagation in the heart.
A rapid laser scanning system was developed to map the spread of excitation in amphibian and mammalian hearts stained with fluorescent dye. Isochronic maps of conduction were constructed by timing the upstroke of the optical action potential; 128 sites could be scanned in 4 milliseconds. The accuracy of this technique was verified by recording simultaneously from 16 unipolar electrodes placed in different areas of the heart. Conducted action potentials in normal frog heart propagated at 0.1 meter per second. Propagation of action potentials was also monitored in ischemic cat heart, in which both driven and arrhythmic action potential upstrokes could be tracked. The results suggest that this system is capable of scanning the normal and abnormal spread of electrical activity in the heart.


A single-centre experience of 40 laparoscopic liver resections.
To review results of laparoscopic liver resections, particularly in those patients with hepatic malignancy and recurrent pyogenic cholangitis. Retrospective analysis. Minimal access surgery training centre, Hong Kong. Patients with pathologies located at anterio-inferio-lateral segments (Couinaud segments 2, 3, 4b, 5, 6) for laparoscopic resection were recruited during the period 1998 to 2005. Patients were excluded from review if they had: pathologies at central locations and the superior and posterior segments (4a, 7, 8), large tumours (>5 cm in diameter), and those close to major vasculature or the liver hilum. During the study period, we attempted 40 such laparoscopic liver resections, excluding marsupialisations and resections for simple liver cysts. There were 20 female and 20 male patients, with a mean age of 57 (standard deviation, 13; range, 29-81) years. All but one underwent a successful laparoscopic operation. Pathology included hepatocellular carcinoma (n=17), recurrent pyogenic cholangitis (n=14), colorectal liver metastasis (n=4), benign liver tumour (n=4), and intrahepatic cholangiocarcinoma (n=1). All except four were hand-assisted laparoscopic liver resections. The mean operating time was 169 (range, 60-290) minutes and mean blood loss amounted to 270 mL (range, 0-1000 mL). Complications occurred in eight (20%) patients, which included six wound infections, one postoperative bile leak, and two incisional hernias. There was no operative or hospital mortality. For hepatocellular carcinoma, clear resection (>10 mm) was achieved in all except five patients, and the 1-year and 2-year survival rates were 86% and 59% respectively. Favourable results were also obtained for resections in patients with recurrent pyogenic cholangitis; after a mean (standard deviation) follow-up of 29 (23) months, only one was readmitted (for cholangitis). In appropriately selected patients, laparoscopic liver resection is feasible and safe, and achieves acceptable survival among individuals with hepatic malignancy and very favourable long-term outcomes in those with recurrent pyogenic cholangitis undergoing hand-assisted laparoscopic segmentectomy.


A systematic review of the cost and cost effectiveness of using standard oral nutritional supplements in community and care home settings.
Despite the clinical benefits of using standard (non-disease specific) oral nutritional supplements (ONS) in the community and care homes, there is uncertainty about their economic consequences. A systematic review was undertaken according to recommended procedures to assess whether ONS can produce cost savings and cost-effective outcomes. 19 publications with and without a hospital component were identified: 9 full text papers, 9 abstracts, and 1 report with retrospective analyses of 6 randomised controlled trials. From these publications a total of 31 cost and 4 cost-effectiveness analyses were identified. Most were retrospective analyses based on clinical data from randomised controlled trials (RCTs). In 9 studies/economic models involving ONS use for <3 months, there were consistent cost savings compared to the control group (median cost saving 9.2%; P < 0.01). When used for ≥3 months, the median cost saving was 5% (P > 0.05; 5 studies). In RCTs, ONS accounted for less than 5% of the total costs and the investment in the community produced a cost saving in hospital. Meta-analysis indicated that ONS reduced hospitalisation significantly (16.5%; P < 0.001; 9 comparisons) and mortality non-significantly (Relative risk 0.86 (95% CI, 0.61, 1.22); 8 comparisons). Many clinically relevant outcomes favouring ONS were reported: improved quality of life, reduced infections, reduced minor post-operative complications, reduced falls, and functional limitations. Of the cost-effectiveness analyses involving quality adjusted life years or functional limitations, most favoured the ONS group. The care home studies (4 cost analyses; 2 cost-effectiveness analyses) had differing aims, designs and conclusions. Overall, the reviewed studies, mostly based on retrospective cost analyses, indicate that ONS use in the community produce an overall cost advantage or near neutral balance, often in association with clinically relevant outcomes, suggesting cost effectiveness. There is a need for prospective studies designed to examine primary economic outcomes.


Recognition Memory in Marmoset and Macaque Monkeys: A Comparison of Active Vision.
The core functional organization of the primate brain is remarkably conserved across the order, but behavioral differences evident between species likely reflect derived modifications in the underlying neural processes. Here, we performed the first study to directly compare visual recognition memory in two primate species-rhesus macaques and marmoset monkeys-on the same visual preferential looking task as a first step toward identifying similarities and differences in this cognitive process across the primate phylogeny. Preferences in looking behavior on the task were broadly similar between the species, with greater looking times for novel images compared with repeated images as well as a similarly strong preference for faces compared with other categories. Unexpectedly, we found large behavioral differences among the two species in looking behavior independent of image familiarity. Marmosets exhibited longer looking times, with greater variability compared with macaques, regardless of image content or familiarity. Perhaps most strikingly, marmosets shifted their gaze across the images more quickly, suggesting a different behavioral strategy when viewing images. Although such differences limit the comparison of recognition memory across these closely related species, they point to interesting differences in the mechanisms underlying active vision that have significant implications for future neurobiological investigations with these two nonhuman primate species. Elucidating whether these patterns are reflective of species or broader phylogenetic differences (e.g., between New World and Old World monkeys) necessitates a broader sample of primate taxa from across the Order.


The ABCs of pesticide toxicology: amounts, biology, and chemistry.
Everyone is affected directly or indirectly by pesticide use and safety. The magnitude and perception of this effect depend on one's individual involvement or vantage point. The researcher seeks discovery and the entrepreneur goes after financial rewards. The general public wants food, health and safety. Pesticide toxicology is a core issue in these relationships. The three goals of toxicology research on pesticides are first to create new knowledge and chemicals, second to evaluate their effectiveness and safety and third to regulate their use. What amounts of pesticides are applied and do we really understand their biology and chemistry? This review addresses the ABCs of pesticide toxicology, i.e. their amounts, biology and chemistry.


Using Diffusion Tractography to Predict Cortical Connection Strength and Distance: A Quantitative Comparison with Tracers in the Monkey.
Tractography based on diffusion MRI offers the promise of characterizing many aspects of long-distance connectivity in the brain, but requires quantitative validation to assess its strengths and limitations. Here, we evaluate tractography's ability to estimate the presence and strength of connections between areas of macaque neocortex by comparing its results with published data from retrograde tracer injections. Probabilistic tractography was performed on high-quality postmortem diffusion imaging scans from two Old World monkey brains. Tractography connection weights were estimated using a fractional scaling method based on normalized streamline density. We found a correlation between log-transformed tractography and tracer connection weights of r = 0.59, twice that reported in a recent study on the macaque. Using a novel method to estimate interareal connection lengths from tractography streamlines, we regressed out the distance dependence of connection strength and found that the correlation between tractography and tracers remains positive, albeit substantially reduced. Altogether, these observations provide a valuable, data-driven perspective on both the strengths and limitations of tractography for analyzing interareal corticocortical connectivity in nonhuman primates and a framework for assessing future tractography methodological refinements objectively. Tractography based on diffusion MRI has great potential for a variety of applications, including estimation of comprehensive maps of neural connections in the brain ("connectomes"). Here, we describe methods to assess quantitatively tractography's performance in detecting interareal cortical connections and estimating connection strength by comparing it against published results using neuroanatomical tracers. We found the correlation of tractography's estimated connection strengths versus tracer to be twice that of a previous study. Using a novel method for calculating interareal cortical distances, we show that tractography-based estimates of connection strength have useful predictive power beyond just interareal separation. By freely sharing these methods and datasets, we provide a valuable resource for future studies in cortical connectomics.


Rewiring the specificity of two-component signal transduction systems.
Two-component signal transduction systems are the predominant means by which bacteria sense and respond to environmental stimuli. Bacteria often employ tens or hundreds of these paralogous signaling systems, comprised of histidine kinases (HKs) and their cognate response regulators (RRs). Faithful transmission of information through these signaling pathways and avoidance of detrimental crosstalk demand exquisite specificity of HK-RR interactions. To identify the determinants of two-component signaling specificity, we examined patterns of amino acid coevolution in large, multiple sequence alignments of cognate kinase-regulator pairs. Guided by these results, we demonstrate that a subset of the coevolving residues is sufficient, when mutated, to completely switch the substrate specificity of the kinase EnvZ. Our results shed light on the basis of molecular discrimination in two-component signaling pathways, provide a general approach for the rational rewiring of these pathways, and suggest that analyses of coevolution may facilitate the reprogramming of other signaling systems and protein-protein interactions.


Important role of mechanical circulatory support in acute myocardial infarction complicated by cardiogenic shock.
Acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) remains associated with significant mortality despite the widespread application of early revascularization strategies. Recent evidence suggests that the use of intra-aortic balloon pump (IABP) counterpulsation does not improve mortality in this cohort of patients. We summarize our experience with mechanical circulatory support (MCS) therapy for AMI/CS. This is a retrospective review of 61 patients who received MCS therapy for AMI/CS at our institution between March 2007 and March 2013. Mean age was 60.2 ± 10.3 years; mean ejection fraction was 24 ± 15% and 29% of patients were receiving active cardiopulmonary resuscitation at the time of support initiation. Prior to the initiation of MCS, 70.5% of patients had an IABP. Mean arterial pressure improved significantly with MCS (63 mmHg prior to MCS, 82 mmHg after MCS, P ≤ 0.01). Mean length of support was 9.5 ± 11.0 days, and overall survival to 30 days was 59.0%. Among 30-day survivors, 44.4% required device exchange to a durable MCS device. Ultimately, only 31% (52.8% of patients who survived to 30 days) achieved myocardial recovery. Short-term MCS therapy with subsequent aggressive use of durable MCS device may improve the unacceptably high mortality rate in AMI/CS. Rigorous prospective studies of MCS therapy in AMI/CS are warranted.


Light Olefin Diffusion during the MTO Process on H-SAPO-34: A Complex Interplay of Molecular Factors.
The methanol-to-olefins process over H-SAPO-34 is characterized by its high shape selectivity toward light olefins. The catalyst is a supramolecular system consisting of nanometer-sized inorganic cages, decorated by Brønsted acid sites, in which organic compounds, mostly methylated benzene species, are trapped. These hydrocarbon pool species are essential to catalyze the methanol conversion but may also clog the pores. As such, diffusion of ethene and propene plays an essential role in determining the ultimate product selectivity. Enhanced sampling molecular dynamics simulations based on either force fields or density functional theory are used to determine how molecular factors influence the diffusion of light olefins through the 8-ring windows of H-SAPO-34. Our simulations show that diffusion through the 8-ring in general is a hindered process, corresponding to a hopping event of the diffusing molecule between neighboring cages. The loading of different methanol, alkene, and aromatic species in the cages may substantially slow down or facilitate the diffusion process. The presence of Brønsted acid sites in the 8-ring enhances the diffusion process due to the formation of a favorable π-complex host-guest interaction. Aromatic hydrocarbon pool species severely hinder the diffusion and their spatial distribution in the zeolite crystal may have a significant effect on the product selectivity. Herein, we unveil how molecular factors influence the diffusion of light olefins in a complex environment with confined hydrocarbon pool species, high olefin loadings, and the presence of acid sites by means of enhanced molecular dynamics simulations under operating conditions.


Relationship between daily fluoride intake from diet and the use of dentifrice and human plasma fluoride concentrations.
The literature contains reports of the relationship between the fluoride concentrations in drinking water and human plasma. None of these studies, however, documented individual levels of daily fluoride intake, which can vary considerably among individuals served by the same water supply. Furthermore, while water can be an important source of fluoride, other sources, especially fluoridated dentifrices, also contribute substantially. This 2-day study with five 25-35-year-old subjects in each of three communities (Bauru, 0.6-0.8 ppm F; Domelia, 0.7 ppm F; Floresta, 0.3 ppm F) determined plasma fluoride concentrations and fluoride intake from diet and the use of dentifrice which, together, approximate total daily fluoride intake. The purposes were to determine: (1) the extent to which plasma fluoride concentrations approached levels known to affect the quality and quantity of bone; (2) the relationship between fluoride intake and plasma concentrations. Plasma was collected at 4-h intervals starting at 0800 h and ending at 2000 h each day. Average fluoride intakes from diet and the use of dentifrice in the three communities ranged from 0.16 to 0.82 mg/day and from 0.29 to 3.16 mg/day, respectively. The overall average plasma concentrations in the three communities were 0.44, 0.45 and 0.54 micromol/l (P<0.005). They were directly related to intake from the use of dentifrice (P=0.030) and to total intake (P=0.033), but were not related to dietary intake (P=0.176). In conclusion, despite fluoride intake from various sources, the plasma fluoride concentrations of the study subjects remained at levels far below those associated with effects on bone production.


Thermal stratification in the arctic ocean.
Fine scale measurements of the vertical temperature profile in an Arctic water column show the presence of several cascaded isothermal layers. Layers between the depths of 300 anid 350 meters range from 2 to 10 meters in thickness, while the temperature change between adjacent layers is approximately 0.026 degrees C. The individual layers are isothermal to within +/- 0.001 degrees C.


The efficacy of a thrombin-based hemostatic agent in unilateral total knee arthroplasty: a randomized controlled trial.
Blood loss following total knee arthroplasty can lead to substantial morbidity and the need for blood transfusions. Hemostatic agents have been used to minimize blood loss and to decrease transfusion rates. Floseal is a thrombin-based hemostatic agent with unknown efficacy for achieving these goals in patients undergoing total knee arthroplasty. We performed a prospective randomized controlled trial on the use of Floseal in patients undergoing total knee arthroplasty, with the primary end point being blood loss as measured through drain output. Demographic characteristics, operative side, diagnosis, intraoperative details, implant choice, hospital course, laboratory values, visual analog scale pain scores, knee range of motion, adverse events, transfusion rates, and deviations from protocol were recorded. A total of 196 patients were enrolled, with ninety-seven patients being randomized to the Floseal group and ninety-nine patients being randomized to the control group. There were no significant differences between the Floseal and control groups in terms of drain output at twenty-four hours (711 compared with 702 mL; p = 0.823). No differences were noted between the groups in terms of operative side, diagnosis, intraoperative details, implant choice, hospital course, laboratory values, visual analog scale pain scores, knee range of motion, or transfusion rates. Complications occurred infrequently. In the acute postoperative period, there were two cases of cellulitis (one in each group), two deep venous thromboses (one in each group), and one paralytic ileus (in the control group), all of which resolved with nonoperative measures. At the six-week follow-up, one patient in the Floseal group had died from a cause unrelated to surgery, two patients (one in each group) had suture abscesses with cellulitis that resolved with postoperative antibiotics, and four patients (two in each group) underwent knee manipulation under anesthesia to achieve improved knee motion. With the numbers available, there was no significant association between Floseal use and the occurrence of these adverse events. The present study showed that Floseal had no demonstrable effect on blood loss as measured through drain output following total knee arthroplasty. There were also no notable adverse events associated with its use. The usefulness of Floseal as a hemostatic agent in total knee arthroplasty remains unclear.


AIDS-Related Kaposi Sarcoma, Version 2.2019, NCCN Clinical Practice Guidelines in Oncology.
As treatment of HIV has improved, people living with HIV (PLWH) have experienced a decreased risk of AIDS and AIDS-defining cancers (non-Hodgkin's lymphoma, Kaposi sarcoma, and cervical cancer), but the risk of Kaposi sarcoma in PLWH is still elevated about 500-fold compared with the general population in the United States. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for AIDS-Related Kaposi Sarcoma provide diagnosis, treatment, and surveillance recommendations for PLWH who develop limited cutaneous Kaposi sarcoma and for those with advanced cutaneous, oral, visceral, or nodal disease.


Nucleo-cytoplasmic shuttling of the hdm2 oncoprotein regulates the levels of the p53 protein via a pathway used by the human immunodeficiency virus rev protein.
The hdm2 gene is overexpressed in a variety of human tumors. Its gene product localizes predominantly to the nucleus, where it acts as an inhibitor of the p53 tumor suppressor gene product. It is shown here that the hdm2 oncoprotein constantly shuttles between the nucleus and the cytoplasm. Shuttling of hdm2 does not depend on its interaction with p53. Nuclear export of hdm2 is mediated by a signal sequence similar to the nuclear export signal of the rev protein from human immunodeficiency virus and other lentiviruses. Mutation of this signal sequence abolishes detectable nucleo-cytoplasmic shuttling. When fused to a carrier protein, the hdm2 signal sequence can mediate nuclear export after intranuclear microinjection into HeLa cells. The export of hdm2 can be blocked by a competitive inhibitor of rev export, arguing that the export pathways for hdm2 and rev are either overlapping or identical. Inhibition of its export modifies the ability of hdm2 to block p53-mediated transcriptional activation, and hdm2's export function is required to accelerate the degradation of p53. Thus the rev nuclear export pathway may be used to regulate an oncogene product's activity and modulate cellular growth.


Development of BK channels in neocortical pyramidal neurons.
1. Postnatal development of a large conductance Ca(2+)-activated K+ channel (BK channel) was investigated in neocortical infragranular pyramidal neurons with inside-out and outside-out patchclamp configurations. Neurons were acutely isolated from slices of 1- to 28-day-old rats (P1-P28) by using a vibrating glass probe after preincubation with low concentrations of enzymes. Patch membrane area was estimated by measuring membrane capacitance. The density, distribution, voltage dependence, Ca2+ sensitivity, kinetics, and pharmacological properties of BK channels were examined in neurons from animals of different ages. 2. In somata, the density of BK channels was 0.056 +/- 0.011/ micron 2 in P1 neurons and 0.312 +/- 0.008/micron 2 in P28 neurons. There was an abrupt increase between P5 and P7 at a rate of approximately 0.042/ micron 2/day. Before P5 and after P7, the density of BK channels also increased but at slower rates. 3. The density of BK channels in proximal apical dendrites underwent a similar developmental sequence. There was a relatively large increase between P5 and P7 with a rate of approximately 0.021/ micron 2/day, and after P7, channel density increased more slowly (approximately 0.002/microns 2/day). In P1 neurons, channel density in apical dendrites was 0.039 +/- 0.008/micron 2, which was close to that in somata, whereas in P28 neurons, channel density (0.134 +/- 0.008/micron 2) was less than one-half of that in somata. 4. The distribution of BK channels was different in immature and mature neurons. In somata of P1 neurons, BK channels were distributed singly without evidence of clustering, whereas in P28 neurons BK channels were clustered in groups of approximately 4. 5. BK channels in both P1 and P14 neurons showed a steep increase in the probability of opening (Po) as intracellular Ca2+ concentration was raised from 50 to 100 nM, especially at positive membrane potentials. The Ca2+ dependence, as measured by the [Ca2+]i that provided half-maximal Po at a variety of membrane potentials, was not different in patches from P1 and P14 neurons. On the other hand, the voltage dependence of BK channels shifted during ontogeny such that Po was larger at negative potentials in P14 than in P1 neurons. 6. The voltage dependence of P1 BK channels was bimodally distributed with 57% of channels exhibiting an "immature" pattern consisting of a more positive V1/2 and a smaller change in voltage required to produce an e-fold increase in Po. Immature type P1 BK channels showed a longer mean closed time at negative membrane potentials than either P14 or "mature" P1 BK channels. 7. No postnatal developmental changes in pharmacological properties of BK channels were observed. In both mature and immature neurons, BK channels were partially inhibited by 30 or 100 nM charybdotoxin (ChTX) and fully blocked by 1 microM ChTX. The IC50 for ChTX was 100 nM, indicating that BK channels in neocortical pyramidal neurons are much less sensitive to ChTX than those in muscle cells and sympathetic ganglion neurons. BK channels were also inhibited by 0.5 mM tetraethylammonium chloride (TEA) and 50 microM trifluoperazine. 8. These data indicate that functional somatic and dendritic BK channels are inserted into neuronal membranes during neocortical development, with an especially rapid increment in density occurring around P5-P7. These changes, which occur at a time when other voltage-gated ion channels are known to be increasing in density, contribute to the development of neocortical excitability.


Assessment of time-related deficits in older adults: a scoping review protocol.
People with cognitive impairments often have difficulties in managing their time for daily activities. In older adults with cognitive impairments such as dementia and stroke, these may present as disorientation, poor time awareness, time perception, daily time management and so on. Time-related deficits and associated behaviours impede independent living and add considerably to caregiver strain. Several interventions are being investigated to help people with cognitive impairments orient and navigate time and do their daily activities. The provision of interventions requires the use of sound assessment tools. However, it is not clear how time-related concepts are specifically evaluated in practice, what are the available assessments and how these assessments should be selected. This protocol follows the Joanna Briggs Institute Reviewer's Manual (2020) for scoping reviews and is registered with the Open Science Framework (https://osf.io/4ptgy/). We will include the following databases: PubMed, CINAHL, Scopus, Web of Science and PsycINFO. Two reviewers will independently screen eligible studies for inclusion against the selection criteria and then review the full-text of the selected studies. We will extract the bibliographic data, study design and setting, and details of assessments used in the studies to evaluate time-related concepts including format, mode and duration of administration, psychometric properties and so on. The identified assessments will be mapped with regard to time-related concepts being evaluated and described using narrative synthesis. As secondary data analysis, ethics approval is not required for this scoping review. We plan to disseminate the results through peer-reviewed journals and conferences targeting health professionals working with older adults.


Measuring the Effects of Self-Awareness: Construction of the Self-Awareness Outcomes Questionnaire.
Dispositional self-awareness is conceptualized in several different ways, including insight, reflection, rumination and mindfulness, with the latter in particular attracting extensive attention in recent research. While self-awareness is generally associated with positive psychological well-being, these different conceptualizations are also each associated with a range of unique outcomes. This two part, mixed methods study aimed to advance understanding of dispositional self-awareness by developing a questionnaire to measure its outcomes. In Study 1, expert focus groups categorized and extended an initial pool of potential items from previous research. In Study 2, these items were reduced to a 38 item self-report questionnaire with four factors representing three beneficial outcomes (reflective self-development, acceptance and proactivity) and one negative outcome (costs). Regression of these outcomes against self-awareness measures revealed that self-reflection and insight predicted beneficial outcomes, rumination predicted reduced benefits and increased costs, and mindfulness predicted both increased proactivity and costs. These studies help to refine the self-awareness concept by identifying the unique outcomes associated with the concepts of self-reflection, insight, reflection, rumination and mindfulness. It can be used in future studies to evaluate and develop awareness-raising techniques to maximize self-awareness benefits while minimizing related costs.


Distinct roles for retinoic acid receptors alpha and beta in early lung morphogenesis.
Retinoic acid (RA) signaling is required for normal development of multiple organs. However, little is known about how RA influences the initial stages of lung development. Here, we used a combination of genetic, pharmacological and explant culture approaches to address this issue, and to investigate how signaling by different RA receptors (RAR) mediates the RA effects. We analyzed initiation of lung development in retinaldehyde dehydrogenase-2 (Raldh2) null mice, a model in which RA signaling is absent from the foregut from its earliest developmental stages. We provide evidence that RA is dispensable for specification of lung cell fate in the endoderm. By using synthetic retinoids to selectively activate RAR alpha or beta signaling in this model, we demonstrate novel and unique functions of these receptors in the early lung. We show that activation of RAR beta, but not alpha, induces expression of the fibroblast growth factor Fgf10 and bud morphogenesis in the lung field. Similar analysis of wild type foregut shows that endogenous RAR alpha activity is required to maintain overall RA signaling, and to refine the RAR beta effects in the lung field. Our data support the idea that balanced activation of RAR alpha and beta is critical for proper lung bud initiation and endodermal differentiation.


Peritonitis due to Rhizobium radiobacter.
Rhizobium radiobacter (Agrobacterium radiobacter) is an aerobic Gram-negative rod belonging to Agrobacterium genus, a group of phytopathogenic bacteria present in the soil that has been implicated in human opportunistic infections. We report a clinical case of bacterial peritonitis in a 5-year-old child with chronic renal disease in peritoneal dialysis, who had a history of direct soil contact identified. The infection was treated with ceftazidime and piperaciline+tazobactam without relapses or the need to remove the peritoneal dialysis catheter.


Prospective surveillance of sympathetic ophthalmia in the UK and Republic of Ireland.
To establish current epidemiological data, risks, and interventional outcomes of newly diagnosed sympathetic ophthalmia (SO). Prospective surveillance took place of all permanently employed ophthalmologists in the UK and Republic of Ireland by a monthly reporting card through the British Ophthalmological Surveillance Unit. Case ascertainment was made of newly diagnosed SO from July 1997 and questionnaire data were returned at baseline, 6 months, and 1 year after diagnosis. 23 patients with newly diagnosed SO were recruited over 15 months, corresponding to a minimum estimated incidence of 0.03/100 000. Baseline data were available on 18 patients, in whom SO occurred after surgery in 11 patients, after retinal surgery alone in six patients, and after accidental trauma in seven patients. 12 of the 16 patients with 1 year follow up had a visual acuity of 6/12 or better. Good visual outcome was related to prompt and adequate systemic immunosuppressive therapy. The incidence of sympathetic ophthalmia is very low. The main current risk is surgery, particularly retinal surgery, but visual prognosis is good if early diagnosis is made and rapid, adequate immunotherapy is commenced.


Febrile Seizures After 2010-2011 Trivalent Inactivated Influenza Vaccine.
In the Post-Licensure Rapid Immunization Safety Monitoring Program, we examined risk of febrile seizures (FS) after trivalent inactivated influenza vaccine (TIV) and 13-valent pneumococcal conjugate vaccine (PCV13) during the 2010-2011 influenza season, adjusted for concomitant diphtheria tetanus acellular pertussis-containing vaccines (DTaP). Assuming children would receive both vaccines, we examined whether same-day TIV and PCV13 vaccination was associated with greater FS risk when compared with separate-day vaccination. We used a self-controlled risk interval design, comparing the FS rate in a risk interval (0-1 days) versus control interval (14-20 days). Vaccinations were identified in claims and immunization registry data. FS were confirmed with medical records. No statistically significant TIV-FS associations were found in unadjusted or adjusted models (incidence rate ratio [IRR] adjusted for age, seasonality, and concomitant PCV13 and DTaP: 1.36, 95% confidence interval [CI] 0.78 to 2.39). Adjusted for age and seasonality, PCV13 was significantly associated with FS (IRR 1.74, 95% CI 1.06 to 2.86), but not when further adjusting for concomitant TIV and DTaP (IRR 1.61, 95% CI 0.91 to 2.82). Same-day TIV and PCV13 vaccination was not associated with excess risk of FS when compared with separate-day vaccination (1.08 fewer FS per 100 000 with same day administration, 95% CI -5.68 to 6.09). No statistically significant increased risk of FS was found for 2010-2011 TIV or PCV13, when adjusting for concomitant vaccines. Same-day TIV and PCV13 vaccination was not associated with more FS compared with separate-day vaccination.


Informational content of cosine and other similarities calculated from high-dimensional Conceptual Property Norm data.
To study concepts that are coded in language, researchers often collect lists of conceptual properties produced by human subjects. From these data, different measures can be computed. In particular, inter-concept similarity is an important variable used in experimental studies. Among possible similarity measures, the cosine of conceptual property frequency vectors seems to be a de facto standard. However, there is a lack of comparative studies that test the merit of different similarity measures when computed from property frequency data. The current work compares four different similarity measures (cosine, correlation, Euclidean and Chebyshev) and five different types of data structures. To that end, we compared the informational content (i.e., entropy) delivered by each of those 4 × 5 = 20 combinations, and used a clustering procedure as a concrete example of how informational content affects statistical analyses. Our results lead us to conclude that similarity measures computed from lower-dimensional data fare better than those calculated from higher-dimensional data, and suggest that researchers should be more aware of data sparseness and dimensionality, and their consequences for statistical analyses.


Knowledge retrieval from PubMed abstracts and electronic medical records with the Multiple Sclerosis Ontology.
In order to retrieve useful information from scientific literature and electronic medical records (EMR) we developed an ontology specific for Multiple Sclerosis (MS). The MS Ontology was created using scientific literature and expert review under the Protégé OWL environment. We developed a dictionary with semantic synonyms and translations to different languages for mining EMR. The MS Ontology was integrated with other ontologies and dictionaries (diseases/comorbidities, gene/protein, pathways, drug) into the text-mining tool SCAIView. We analyzed the EMRs from 624 patients with MS using the MS ontology dictionary in order to identify drug usage and comorbidities in MS. Testing competency questions and functional evaluation using F statistics further validated the usefulness of MS ontology. Validation of the lexicalized ontology by means of named entity recognition-based methods showed an adequate performance (F score = 0.73). The MS Ontology retrieved 80% of the genes associated with MS from scientific abstracts and identified additional pathways targeted by approved disease-modifying drugs (e.g. apoptosis pathways associated with mitoxantrone, rituximab and fingolimod). The analysis of the EMR from patients with MS identified current usage of disease modifying drugs and symptomatic therapy as well as comorbidities, which are in agreement with recent reports. The MS Ontology provides a semantic framework that is able to automatically extract information from both scientific literature and EMR from patients with MS, revealing new pathogenesis insights as well as new clinical information.


Depletion of Bhmt elevates sonic hedgehog transcript level and increases β-cell number in zebrafish.
Betaine homocysteine S-methyltransferase (BHMT, EC 22.214.171.124) is a key enzyme in the methionine cycle and is highly expressed in the liver. Despite its important biochemical function, it is not known whether BHMT plays a role during organ development. In this report, we showed that early in development of zebrafish before endoderm organogenesis, bhmt is first expressed in the yolk syncytial layer and then after liver formation becomes a liver-enriched gene. By using the anti-bhmt morpholinos that deplete the Bhmt, we found that in morphant embryos, several endoderm-derived organs, including liver, exocrine pancreas, and intestine are hypoplastic. Strikingly, the number of β-cells in the pancreatic islet was increased rather than reduced in the morphant. Additional studies showed that Bhmt depletion elevates the sonic hedgehog (shh) transcript level in the morphant, whereas Bhmt-depletion in the Shh-deficient mutant syu failed to rescue the isletless phenotype. These molecular and genetic data strongly suggest that Shh functions downstream of Bhmt to promote β-cell development. Therefore, although there are still many intriguing questions to be answered, our finding may identify a novel function for Bhmt involving modulation of Shh signaling to control β-cell development.


A laplace transform-based technique for solving multiscale and multidomain problems: Application to a countercurrent hemodialyzer model.
An integral-based method was employed to evaluate the behavior of a countercurrent hemodialyzer model. Solute transfer from the blood into the dialysate was described by writing mass balance equations over a section of the device. The approach provided Laplace transform concentration profiles on both sides of the membrane. Applications of the final value theorem led to the development of the effective time constants and steady-state concentrations in the exit streams. Transient responses were derived by a numerical inversion algorithm. Simulations show that the period elapsed, before reaching equilibrium in the effluents, decreased when the blood flow rate increased from 0.25 to 0.30 ml/s. The performance index decreased from 0.80 to 0.71 when the blood-to-dialysate flow ratio increased by 20% and increased from 0.80 to 0.85 when this fraction was reduced by 17%. The analytical solution predicted methadone removal in patients undergoing dialysis. Clinicians can use these findings to predict the time required to achieve a target extraction ratio.


A comparison of calcium gluconate and methocarbamol (Robaxin) in the treatment of Latrodectism (black widow spider envenomation).
Calcium gluconate and methocarbamol were compared by using an algorithmic treatment protocol on all cases of Latrodectus (black widow) envenomation seen over a period of 3 years. Six of 13 patients were effectively cured of their symptoms by calcium gluconate, while only one of 10 patients was relieved by methocarbamol. Calcium gluconate remains the drug of first choice for this syndrome. It was also noted that calcium gluconate was more effective in patients who presented 3 hours of more after they were bitten. Antivenom may be necessary in those who present with symptoms in less than 3 hours.


Metabolic Syndrome and Nephrolithiasis Risk: Should the Medical Management of Nephrolithiasis Include the Treatment of Metabolic Syndrome?
This article reviews the relationship between metabolic syndrome (MetS) and nephrolithiasis, as well as the clinical implications for patients with this dual diagnosis. MetS, estimated to affect 25% of adults in the United States, is associated with a fivefold increase in the risk of developing diabetes, a doubling of the risk of acquiring cardiovascular disease, and an increase in overall mortality. Defined as a syndrome, MetS is recognized clinically by numerous constitutive traits, including abdominal obesity, hypertension, dyslipidemia (elevated triglycerides, low high-density lipoprotein cholesterol), and hyperglycemia. Urologic complications of MetS include a 30% higher risk of nephrolithiasis, with an increased percentage of uric acid nephrolithiasis in the setting of hyperuricemia, hyperuricosuria, low urine pH, and low urinary volume. Current American Urological Association and European Association of Urology guidelines suggest investigating the etiology of nephrolithiasis in affected individuals; however, there is no specific goal of treating MetS as part of the medical management. Weight loss and exercise, the main lifestyle treatments of MetS, counter abdominal obesity and insulin resistance and reduce the incidence of cardiovascular events and the development of diabetes. These recommendations may offer a beneficial adjunctive treatment option for nephrolithiasis complicated by MetS. Although definitive therapeutic recommendations must await further studies, it seems both reasonable and justifiable for the urologist, as part of a multidisciplinary team, to recommend these important lifestyle changes to patients with both conditions. These recommendations should accompany the currently accepted management of nephrolithiasis.


Error-prone polymerization by HIV-1 reverse transcriptase. Contribution of template-primer misalignment, miscoding, and termination probability to mutational hot spots.
We have observed previously that DNA template-directed polymerization by the type 1 human immunodeficiency virus reverse transcriptase is error-prone for single-nucleotide substitution, addition and deletion errors at homopolymeric sequences. We have also noted strong termination of processive synthesis at these positions (Bebenek, K., Abbotts, J., Roberts, J. D., Wilson, S. H., and Kunkel, T. A. (1989) J. Biol. Chem. 264, 16948-16956). Here we have tested three models to explain errors at these hot spots: template-primer misalignment for deletion errors, and dislocation and direct miscoding for substitution errors. The approach involves introducing single-nucleotide changes within or flanking the homopolymeric hot spots and examining the effects that these changes have on human immunodeficiency virus type 1 (HIV-1) reverse transcriptase error rate, error specificity, and termination probability. The results obtained suggest that single-nucleotide deletion errors in homopolymeric runs result from template-primer misalignment and that both direct miscoding and template-primer dislocation contribute to the base substitution hot spots. The data also suggest that base substitution errors at one position can be templated by the preceding nucleotide or either of the next two nucleotides. Frameshift error rates at homopolymeric sites were affected by changes in the sequences flanking the runs, including single-nucleotide differences in the single-stranded template strand and in the double-stranded primer region as many as six nucleotides distant from the hot spot. Both increases and decreases in frameshift fidelity were observed, and most of these correlated with concomitant increases or decreases in the probability that HIV-1 reverse transcriptase terminated processive synthesis within the run. These data provide further support for a relationship between the frameshift fidelity and the processivity of DNA-dependent DNA synthesis by HIV-1 reverse transcriptase.


Combined effects of atrazine and chlorpyrifos on susceptibility of the tiger salamander to Ambystoma tigrinum virus.
Several hypotheses have been examined as potential causes of global amphibian declines, including emerging infectious diseases and environmental contaminants. Although these factors are typically studied separately, animals are generally exposed to both stressors simultaneously. We examined the effects of the herbicide atrazine and the insecticide chlorpyrifos on the susceptibility of tiger salamander larvae, Ambystoma tigrinum, to a viral pathogen, Ambystoma tigrinum virus (ATV). Environmentally relevant concentrations of atrazine (0, 20, 200 microg/L) and chlorpyrifos (0, 2, 20, 200 microg/L) were used along with ATV in a fully factorial experimental design whereby individually housed, 4-week-old larvae were exposed for 2 weeks. Atrazine alone was not lethal to larvae, and chlorpyrifos alone was lethal only at the highest concentration. When combined with ATV, chlorpyrifos increased susceptibility to viral infection and resulted in increased larval mortality. A significant interactive effect between atrazine and ATV was detected. Atrazine treatments slightly decreased survival in virus-exposed treatments, yet slightly increased survival in the virus-free treatments. These findings corroborate earlier research on the impacts of atrazine, in particular, on disease susceptibility, but exhibit greater effects (i.e., reduced survival) when younger larvae were examined. This study is the first of its kind to demonstrate decreases in amphibian survival with the combination of pesticide and a viral disease. Further examination of these multiple stressors can provide key insights into potential significance of environmental cofactors, such as pesticides, in disease dynamics.


The effect of aging on the brain network for exception word reading.
Cognitive and computational models of reading aloud agree on the existence of two procedures for reading. Pseudowords (e.g., atendier) are correctly read through subword processes only while exception words (e.g., pint) are only correctly read via whole-words processes. Regular words can be correctly read by means of either way. Previous behavioral studies showed that older adults relied more on whole-word processing for reading. The aim of the present fMRI study was to verify whether this larger whole-word reliance for reading in older adults was reflected by changes in the pattern of brain activation. Both young and elderly participants read aloud pseudowords, exception and regular words in the scanner. Behavioral results reproduced those of previous studies showing that older adults made significantly less errors when reading exception words. Neuroimaging results showed significant activation of the left anterior temporal lobe (ATL), a key region implicated in whole-word reading for exception word reading in both young and elderly participants. Critically, ATL activation was also found for regular word reading in the elderly. No differences were observed in the pattern of activation between regular and pseudowords in the young. In conclusion, these results extend evidence on the critical role of the left ATL for exception word reading to elderly participants. Additionally, our study shows for the first time from a developmental point of view that the behavioral changes found in reading during normal aging also have a brain counterpart in the reading network changes that sustain exception and regular word reading in the elderly.


Decadal changes in zooplankton of the Northeast U.S. continental shelf.
The abundance of the subarctic copepod, Calanus finmarchicus, and temperate, shelf copepod, Centropages typicus, was estimated from samples collected bi-monthly over the Northeast U.S. continental shelf (NEUS) from 1977-2010. Latitudinal variation in long term trends and seasonal patterns for the two copepod species were examined for four sub-regions: the Gulf of Maine (GOM), Georges Bank (GB), Southern New England (SNE), and Mid-Atlantic Bight (MAB). Results suggested that there was significant difference in long term variation between northern region (GOM and GB), and the MAB for both species. C. finmarchicus generally peaked in May - June throughout the entire study region and Cen. typicus had a more complex seasonal pattern. Time series analysis revealed that the peak time for Cen. typicus switched from November - December to January - March after 1985 in the MAB. The long term abundance of C. finmarchicus showed more fluctuation in the MAB than the GOM and GB, whereas the long term abundance of Cen. typicus was more variable in the GB than other sub-regions. Alongshore transport was significantly correlated with the abundance of C. finmarchicus, i.e., more water from north, higher abundance for C. finmarchicus. The abundance of Cen. typicus showed positive relationship with the Gulf Stream north wall index (GSNWI) in the GOM and GB, but the GSNWI only explained 12-15% of variation in Cen. typicus abundance. In general, the alongshore current was negatively correlated with the GSNWI, suggesting that Cen. typicus is more abundant when advection from the north is less. However, the relationship between Cen. typicus and alongshore transport was not significant. The present study highlights the importance of spatial scales in the study of marine populations: observed long term changes in the northern region were different from the south for both species.


Family understanding and communication about an adult relative's mental health problem: A systematic narrative review.
WHAT IS KNOWN ON THE SUBJECT?: Adults who support an adult family member with a severe and enduring mental health problem often experience carer burden. Over time, this often negatively affects their mental and physical health and social well-being. Understanding and communicating about mental health problems in families can help to improve resilience and coping among both adults and children. WHAT DOES THIS PAPER ADD TO EXISTING KNOWLEDGE?: We conducted a review of studies looking at how adult relatives understand and communicate about an adult family member's mental health problem. The findings highlight that how relatives make sense of MHP is related to historical family relationships, their mental health literacy and whether they see themselves as a "carer" or not. The findings also show that little research to date has explored how adult relatives talk with children about their parent's difficulties, and how the adults' understanding might affect what children learn about the MHP. WHAT ARE THE IMPLICATIONS FOR PRACTICE?: There is a research gap to be addressed regarding family communication with children about parental mental health problems. This knowledge gap likely impacts family-focused mental health nursing and therapy provision. Mental health nursing, therapeutic and support workers and advocates are ideally positioned to assist relatives with improving their mental health literacy and confidence communicating about mental health, and to promote inclusion of relatives and children in interventions. ABSTRACT: Introduction Relatives are profoundly affected by an adult family member's severe and enduring mental health problem (MHP). The burdens of caring impact on adult relatives' emotional, physical and social well-being. How relatives make meaning and communicate about the MHP is thought to affect family talk about mental health, and this can impact family coping and well-being. Aim No review has yet drawn together research about how adult relatives of people with severe and enduring MHP make meaning and communicate about their relatives' difficulties. We aimed to address this gap. Method We conducted a systematic review of peer-reviewed primary research. SCOPUS, PubMed, Psychnet, SCIE, Cochrane and CINAHL+ databases were searched. Results Nineteen papers qualified for inclusion. Findings are organized under four themes: making meaning about the MHP and affected individual; conceptualizing the self in the presence of the MHP; meaning-making processes underlying relatives' well-being outcomes; and relatives' perspectives on family talk about the MHP. Discussion Historical relationships, caregiver identity and mental health literacy moderate relatives' understanding and talk about the MHP. Implications for practice Psychoeducation and communication support for relatives should be provided by mental health practitioners. Future research should address familial communication about MHP, including with children.


The influence of anti-platelet resistance on the development of cerebral ischemic lesion after carotid artery stenting.
Cerebral ischemic lesions are frequently observed after carotid artery stenting (CAS), and anti-platelet agents are used to prevent stent thrombosis and peri-procedural complications. However, despite the premedication, cerebral ischemic lesions are observed, suggesting that they may rather be related to anti-platelet resistance. We, therefore, investigated the effects of anti-platelet resistance on the development of cerebral ischemic lesions after CAS. We retrospectively reviewed patients who received CAS and selected patients for whom brain MRI was performed within 24 hours after CAS and for whom anti-platelet resistance was checked. Anti-platelet resistance was examined by the VerifyNow system. We analyzed the correlation between anti-platelet resistance and cerebral ischemic lesions detected on follow-up MRI. Among 76 patients, 45 (59.2%) developed new ischemic lesions after CAS. Twelve (15.8%) patients showed aspirin resistance and 50 (65.8%) patients showed clopidogrel resistance. Patients with a new ischemic lesion demonstrated a significantly greater frequency of clopidogrel resistance than those who had no new ischemic lesion (82.2% versus 41.9%, p=0.001). The frequency of aspirin resistance was not significantly different between the groups of patients with and without new ischemic lesions (20.0% versus 9.7%, p=0.340). In multivariate analysis, clopidogrel resistance was a significant risk factor for post-procedural cerebral ischemia. Anti-platelet resistance can be used to predict new ischemic lesions after CAS. Anti-platelet resistance should be evaluated in all patients prior to CAS to prevent ischemic complications related to CAS.


Prognostic value of Y deletion analysis: what is the clinical prognostic value of Y chromosome microdeletion analysis?
In many centres, Y chromosome deletion analysis is still not performed routinely and if so, the results are used for genetic counselling but are not considered as having a useful prognostic value. The type of deletion (AZFa, b or c) has been proposed as a potential prognostic factor for sperm retrieval in men undergoing TESE. AZFc deletions and partial AZFb deletions are associated with sperm retrieval in approximately 50% of cases while in the case of a patient with complete AZFb deletion the probability of finding mature spermatozoa is virtually nil. Therefore the extent and position of a Y microdeletion is important (complete or partial). The prognostic value of Y chromosome deletion analysis in cases of oligozoospermia is important when one considers the progressive decrease of sperm number over time in men with AZFc deletions. Cryo-conservation of spermatozoa in these cases could avoid invasive techniques, such as TESE/ICSI, in the future. Male offspring that are conceived by ICSI or IVF techniques from father with oligozoospermia or azoospermia would also benefit from knowledge of their Y status, since the identification of the genetic defect will render future medical or surgical therapies unnecessary. Y microdeletion screening is therefore important, not only to define the aetiology of spermatogenic failure, but also because it gives precious information for a more appropriate clinical management of both the infertile male and his future male child.


miR-224/miR-141 ratio as a novel diagnostic biomarker in renal cell carcinoma.
Biomarkers to guide the clinical treatment of patients with renal cell carcinoma (RCC) are not yet routinely available. MicroRNAs (miRNAs) have been demonstrated to serve as biomarkers for a number of types of cancer. Based on a previous study by this group, we hypothesize that several highly differentially expressed miRNAs may serve as tissue and plasma biomarkers in patients with RCC. The expression levels of miR-210, miR-224 and miR-141 were analyzed in tissue samples from the same cohort of 78 patients with RCC, in paired pre- and post-operative plasma samples from 66 patients with clear cell RCC (ccRCC) and in 67 healthy controls by reverse transcription-quantitative polymerase chain reaction. Receiver operating characteristic (ROC) was used to evaluate the diagnostic accuracy associated with the expression of miR-210, miR-224 and miR-141. ROC curves revealed that the diagnostic accuracy (area under the curve) of tissue miR-210, miR-224, the ratio of miR-210/miR-141 (miR210/141), miR-224/miR-141 (miR224/141) and miR-210× miR-224/miR-141 (miR210×224/141) in ccRCC was 0.8329, 0.8511, 0.9412, 0.9898 and 0.9771, respectively. Notably, miR224/141 demonstrated the highest accuracy among these miRNAs for discriminating ccRCC tissues from normal tissues, with a sensitivity of 97.06% and a specificity of 98.53%. The expression levels of plasma miR-210 and miR-224 were significantly increased in patients compared with healthy control patients, and were reduced postoperatively (P<0.05). The diagnostic accuracy of plasma miR-210 and miR-224 were 0.6775 (89.55% sensitivity and 48.48% specificity) and 0.6056 (88.06% sensitivity and 40.91% specificity), respectively. The present study indicated that the tissue miR-224/miR-141 ratio is a potentially powerful tool for detecting ccRCC. However, plasma miR-210 and miR-224 may not be associated with diagnosis of ccRCC.


MR Imaging of Joint Infection and Inflammation with Emphasis on Dynamic Contrast-Enhanced MR Imaging.
Contrast-enhanced MR imaging (CE-MR imaging) is recommended for diagnosis and monitoring of infectious and most inflammatory joint diseases. CE-MR imaging clearly differentiates soft and bony tissue from fluid collections and infectious debris. To improve imaging information, a dynamic CE-MR imaging sequence (DCE-MR imaging) sequence can be applied using fast T1-weighted sequential image acquisition during contrast injection. Use of DCE-MR imaging allows robust extraction of quantitative information regarding blood flow and capillary permeability, especially when dedicated analysis methods and software are used to analyze contrast kinetics. This article describes principles of DCE-MR imaging for the assessment of infectious and inflammatory joint diseases.


Usability of the Turkish Translation of the Dutch Talking Touch Screen Questionnaire for Physical Therapy Patients With a Turkish Background: Qualitative Study.
The Turkish translation of the Dutch Talking Touch Screen Questionnaire (TTSQ) has been developed to help physical therapy patients with a Turkish background in the Netherlands to autonomously elucidate their health problems and impairments and set treatment goals, regardless of their level of health literacy. The aim of this study was to evaluate the usability of the Turkish TTSQ for physical therapy patients with a Turkish background with diverse levels of health literacy and experience in using mobile technology. The qualitative Three-Step Test-Interview method was carried out to gain insight into the usability of the Turkish TTSQ. A total of 10 physical therapy patients participated. The interview data were analyzed using a thematic content analysis approach aimed at determining the accuracy and completeness with which participants completed the questionnaire (effectiveness), the time it took participants to complete the questionnaire (efficiency), and the extent to which the participants were satisfied with the ease of use of the questionnaire (satisfaction). The problems encountered by the participants in this study were given a severity rating, which was used to provide a rough estimate of the need for additional usability improvements. No participant in this study was able to complete the questionnaire without encountering at least one usability problem. A total of 17 different kinds of problems were found. On the basis of their severity score, 3 problems that should be addressed during future development of the tool were "Not using the navigation function of the photo gallery in Question 4 causing the participant to not see all presented response items;" "Touching the text underneath a photo in Question 4 to select an activity instead of touching the photo itself, causing the activity not to be selected;" and "Pushing too hard or tapping too softly on the touch screen causing the touch screen to not respond." The data on efficiency within this study were not valid and are, therefore, not reported in this study. No participant was completely satisfied or dissatisfied with the overall ease of use of the Turkish TTSQ. Two participants with no prior experience of using tablet computers felt that, regardless of what kinds of improvement might be made, it would just be too difficult for them to learn to work with the device. As with the Dutch TTSQ, the Turkish TTSQ needs improvement before it can be released. The results of this study confirm the conclusion of the Dutch TTSQ study that participants with low levels of education and little experience in using mobile technology are less able to operate the TTSQ effectively. Using a Dutch speaking interviewer and Turkish interpreter has had a negative effect on data collection in this study.


Fabrication of multifunctional monometallic nanohybrids for reactive oxygen species-mediated cell apoptosis and enhanced fluorescence cell imaging.
Novel fluorescent monometallic Ag nanohybrids (Ag NHs) have been synthesized via polycytosine-mediated biomineralization on Ag nanoparticles (Ag NPs). Thiolated polycytosine dC12 was anchored on the Ag NPs, followed by dC12-templated synthesis of the Ag nanoclusters (Ag NCs). The Ag NHs exhibited strong fluorescence emission and improved resistance to dissolved oxygen in solution as compared to the Ag NCs. As an efficient therapeutic agent, the delivery of aptamer-functionalized Ag NHs into target cells induced reactive oxygen species (ROS) generation and cell apoptosis. The ROS-mediated apoptotic effect of the Ag NHs was stronger than that of the Ag NCs. For cell imaging, the target cells treated with aptamer-functionalized Ag NHs exhibited a higher fluorescence brightness than those treated with Ag NCs. Due to the fluorescence quenching of Ag NHs by the intracellularly generated ROS, the Ag NHs served as a fluorescent indicator for real-time monitoring of ROS-mediated cell apoptosis. The In vivo antitumor efficacy of the Ag NHs was also evaluated.


Conducting quantitative synthesis when comparing medical interventions: AHRQ and the Effective Health Care Program.
This article is to establish recommendations for conducting quantitative synthesis, or meta-analysis, using study-level data in comparative effectiveness reviews (CERs) for the Evidence-based Practice Center (EPC) program of the Agency for Healthcare Research and Quality. We focused on recurrent issues in the EPC program and the recommendations were developed using group discussion and consensus based on current knowledge in the literature. We first discussed considerations for deciding whether to combine studies, followed by discussions on indirect comparison and incorporation of indirect evidence. Then, we described our recommendations on choosing effect measures and statistical models, giving special attention to combining studies with rare events; and on testing and exploring heterogeneity. Finally, we briefly presented recommendations on combining studies of mixed design and on sensitivity analysis. Quantitative synthesis should be conducted in a transparent and consistent way. Inclusion of multiple alternative interventions in CERs increases the complexity of quantitative synthesis, whereas the basic issues in quantitative synthesis remain crucial considerations in quantitative synthesis for a CER. We will cover more issues in future versions and update and improve recommendations with the accumulation of new research to advance the goal for transparency and consistency.


Genetics of kidney disease and related cardiometabolic phenotypes in Zuni Indians: the Zuni Kidney Project.
The objective of this study is to identify genetic factors associated with chronic kidney disease (CKD) and related cardiometabolic phenotypes among participants of the Genetics of Kidney Disease in Zuni Indians study. The study was conducted as a community-based participatory research project in the Zuni Indians, a small endogamous tribe in rural New Mexico. We recruited 998 members from 28 extended multigenerational families, ascertained through probands with CKD who had at least one sibling with CKD. We used the Illumina Infinium Human1M-Duo version 3.0 BeadChips to type 1.1 million single nucleotide polymorphisms (SNPs). Prevalence estimates for CKD, hyperuricemia, diabetes, and hypertension were 24%, 30%, 17% and 34%, respectively. We found a significant (p < 1.58 × 10(-7)) association for a SNP in a novel gene for serum creatinine (PTPLAD2). We replicated significant associations for genes with serum uric acid (SLC2A9), triglyceride levels (APOA1, BUD13, ZNF259), and total cholesterol (PVRL2). We found novel suggestive associations (p < 1.58 × 10(-6)) for SNPs in genes with systolic (OLFML2B), and diastolic blood pressure (NFIA). We identified a series of genes associated with CKD and related cardiometabolic phenotypes among Zuni Indians, a population with a high prevalence of kidney disease. Illuminating genetic variations that modulate the risk for these disorders may ultimately provide a basis for novel preventive strategies and therapeutic interventions.


Intravenous fluid resuscitation for the trauma patient.
Although longstanding practice in trauma care has been to provide immediate, aggressive intravenous fluid resuscitation to injured patients with presumed internal hemorrhage, recent experimental and clinical data suggest a more discriminating approach that first considers concurrent head injury, hemodynamic stability, and the presence of potentially uncontrollable hemorrhage (e.g., deep truncal injury) versus a controllable source (e.g., distal extremity wound). The data suggest that rapid intravenous fluid infusions could be used for patients with isolated extremity, thermal or head injury. However, intravenous fluids should be limited in conditions with potentially uncontrollable internal hemorrhage, and particularly in patients with penetrating truncal injury being transported immediately to a trauma center. Likewise, positive pressure ventilatory support should be limited with severe hemorrhage due to the secondary reductions in venous return off-setting the effects of the fluids. For trauma patients with severe bleeding, there is growing evidence for the increased use of plasma and factor VIIa, as well as tourniquets, intra-osseus devices, and evolving monitoring techniques. Future research efforts in trauma should focus on the timing and rate of infusions as well as the concept of infusing alternative intravenous resuscitative fluids such as hemoglobin-based oxygen carriers (HBOCs) and the use of hemostatic agents and special blood products.


Effects of histatin 5 modifications on antifungal activity and kinetics of proteolysis.
Histatin 5 (Hst-5) is an antimicrobial peptide with strong antifungal activity against Candida albicans, an opportunistic pathogen that is a common cause of oral thrush. The peptide is natively secreted by human salivary glands and shows promise as an alternative therapeutic against infections caused by C. albicans. However, Hst-5 can be cleaved and inactivated by a family of secreted aspartic proteases (Saps) produced by C. albicans. Single-residue substitutions can significantly affect the proteolytic resistance of Hst-5 to Saps and its antifungal activity; the K17R substitution increases resistance to proteolysis, while the K11R substitution enhances antifungal activity. In this work, we showed that the positive effects of these two single-residue modifications can be combined in a single peptide, K11R-K17R, with improved proteolytic resistance and antifungal activity. We also investigated the effect of additional single-residue substitutions, with a focus on the effect of addition or removal of negatively charged residues, and found Sap-dependent effects on degradation. Both single- and double-substitutions affected the kinetics of proteolytic degradation of the intact peptide and of the fragments formed during degradation. Our results demonstrate the importance of considering proteolytic stability and not just antimicrobial activity when designing peptides for potential therapeutic applications.


Forests of the past: a window to future changes.
The study of past forest change provides a necessary historical context for evaluating the outcome of human-induced climate change and biological invasions. Retrospective analyses based on fossil and genetic data greatly advance our understanding of tree colonization, adaptation, and extinction in response to past climatic change. For instance, these analyses reveal cryptic refugia near or north of continental ice sheets, leading to reevaluation of postglacial tree migration rates. Species extinctions appear to have occurred primarily during periods of high climatic variability. Transoceanic dispersal and colonization in the tropics were widespread at geological time scales, inconsistent with the idea that tropical forests are particularly resistant to biological invasions.


Cognitive impairment and preferences for current health.
We assessed preferences for current health using the visual analogue scale (VAS), standard gamble (SG), time trade-off (TTO), and willingness to pay (WTP) in patients with cerebral aneurysms, a population vulnerable to cognitive deficits related to aneurysm bleeding or treatment. We measured VAS, SG, TTO, and WTP values for current health in 165 outpatients with cerebral aneurysms. We assessed cognitive impairment with the Mini Mental State Examination (MMSE; scores < 24 = cognitive impairment). We examined the distributions of preference responses stratified by cognitive status, and the relationship between preferences and cognitive impairment, patient characteristics, and aneurysm history. Eleven patients (7%) had MMSE scores < 24. The distribution of preferences responses from patients with cognitive impairment had greater variance (SG, 0.39 vs. 0.21, P = 0.001; TTO, 0.36 vs. 0.24, P = 0.017) and altered morphology (VAS, P = 0.012; SG, P = 0.023) compared to the responses of unimpaired patients. There was good correlation between most preference measures for unimpaired patients (VAS:TTO, rho = 0.19, P = 0.018; SG:TTO, rho = 0.36, P < 0.001; SG:WTP, rho = -0.33, P < 0.001) and a trend towards significance with another pairing (VAS:WTP, rho = 0.16, P = 0.054). In subjects with cognitive impairment, there was a significant correlation only between VAS and TTO scores (rho = 0.76, P = 0.023). Separate regression models showed that cognitive impairment was associated with lower preferences on the VAS (beta = -0.12, P = 0.048), SG (beta = -0.23, P = 0.002), and TTO (beta = -0.17, P = 0.035). Cognitive impairment is associated with lower preferences for current health in patients with cerebral aneurysms. Cognitively impaired patients have poor inter-preference test correlations and different response distributions compared to unimpaired patients.


Host species barriers to influenza virus infections.
Most emerging infectious diseases in humans originate from animal reservoirs; to contain and eradicate these diseases we need to understand how and why some pathogens become capable of crossing host species barriers. Influenza virus illustrates the interaction of factors that limit the transmission and subsequent establishment of an infection in a novel host species. Influenza species barriers can be categorized into virus-host interactions occurring within individuals and host-host interactions, either within or between species, that affect transmission between individuals. Viral evolution can help surmount species barriers, principally by affecting virus-host interactions; however, evolving the capability for sustained transmission in a new host species represents a major adaptive challenge because the number of mutations required is often large.


Early fetal hydropic changes are associated with moderate dilatation of the brain ventricular system: A clue to a possible link between cervical lymphatic engorgement and ventricular dilatation?
The aim of this study is to assess whether early cervical lymphatic obstruction is associated with a sonographically detectable dilatation of the ventricular system in the 1st trimester of pregnancy. In particular, the objective is to assess whether fetuses with non-immune hydrops fetalis (NIHF), cystic hygroma, or enlarged nuchal translucency (NT) have a greater atrial width/biparietal diameter (AW/BPD) ratio than normal at time of the combined first trimester screening scan. This retrospective study included 96 first trimester fetuses (33 normal and 63 with various degree of cervical lymphatic engorgement). Inclusion criteria were CRL in the 45-84 mm range and availability of one or more three-dimensional volume datasets of the fetal head, acquired from the BPD plane. Each three-dimensional volume dataset was opened and multiplanar correlation employed to align the three orthogonal planes. The ratio between the atrial width and the BPD (AW/BPD ratio) was used to evaluate the possible presence of increased amount of cerebrospinal fluid. Abnormal cases were placed into 4 categories: 1) enlarged non-septated NT 2.5-3.9 mm, no hydrops; 2) grossly enlarged non-septated NT / edema >3.9 mm; 3) cystic hygroma and/ or NIHF; 4) major anomalies with NT <2.5 mm. Presence of dilatation of the laterocervical jugular lymphatic sacs, karyotype and presence of congenital anomalies were also recorded. The One-way ANOVA test was used to compare means. Intra- and inter-observer variability were also assessed. The AW/BPD ratio was found to be significantly higher in fetuses with grossly enlarged NT/nuchal edema and NIHF/septated cystic hygroma than in normal (p <0.05 and p <0.01, respectively). Also, the AW/BPD ratio was significantly higher in NIHF/septated cystic hygroma than in enlarged NT 2.5-3.9 mm (p <0.05). In case of enlarged NT (2.5-3.9 mm), the AW/BPD ratio is significantly higher in presence of JLS (p <0.01). At the end of the first trimester, presence of cervical lymphatic engorgement, in terms of grossly enlarged NT, nuchal edema, septated cystic hygroma, and NIHF, is statistically associated with a moderate dilatation of the ventricular system. Of note, among fetuses with moderately enlarged NT, those with evidence of dilatation of the JLS show a statistically significant increase in the AW/BPD ratio.


Surgery for cervical radiculomyelopathy.
Cervical spondylosis causes pain and disability by compressing the spinal cord or roots. Surgery to relieve the compression may reduce the pain and disability, but is associated with a small but definite risk. We sought to assess the balance of risk and benefit from surgery. To determine whether: 1) surgical treatment of cervical radiculopathy or myelopathy is associated with improved outcome, compared with conservative management and 2) timing of surgery (immediate or delayed upon persistence/progression of relevant symptoms and signs) has an impact on outcome. We searched Medline (between 1966 and 1998), Embase (between 1980 and 1998) and the Cochrane Controlled Trials Register. Authors of the identified randomised controlled trials were contacted to detect any additional published or unpublished data. All unconfounded truly or quasi-randomised controlled trials allocating patients with cervical radiculopathy or myelopathy to 1) "best medical management" or "decompressive surgery (with or without some form of fusion) plus best medical management" 2) "early decompressive surgery" or "delayed decompressive surgery". Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. Two trials involving a total of 130 patients were included. One trial with 81 patients compared surgical decompression with either physiotherapy or cervical collar immobilization in patients with cervical radiculopathy. The short-term effects of surgery, in terms of pain, weakness or sensory loss were superior, however, at one year no significant differences between groups were present. One trial with 49 patients compared the effects of surgery with those of conservative treatment in patients with mild functional deficit associated with cervical myelopathy. No significant differences were observed between groups, up to two years following treatment.


Use of galeal or pericranial flaps for reconstruction or orbital and eyelid defects.
The use of galeal or pericranial flaps for craniofacial reconstruction is well recognized. The excellent blood supply of the flap permits vascularized support for skin, bone, or cartilage grafts in otherwise unsatisfactory recipient sites. The pericranial flap was used in 1 patient with a large orbital bony defect and the galeopericranial flap was used in 3 patients with various periocular defects produced by trauma or following tumor extirpation. In the case of an orbital defect induced by chronic cocaine abuse, the pericranial flap successfully sequestered the orbit from the nasal cavity while providing support for the globe. In 3 of the 4 cases involving eyelid reconstruction, the galeopericranial flap served a dual function in providing vascular supply to the underlying free tarsal graft and to the overlying free skin graft. This tissue flap is analogous to a median forehead flap, except skin is not transposed and a second-stage inset revision is not required.


A Systematic Review of Risk Factors Associated With Cognitive Impairment After Pediatric Critical Illness.
To identify risk factors associated with cognitive impairment as assessed by neuropsychologic tests in neurotypical children after critical illness. For this systematic review, we searched the Cochrane Library, Scopus, PubMed, Ovid, Embase, and CINAHL databases from January 1960 to March 2017. Included were studies with subjects 3-18 years old at the time of post PICU follow-up evaluation and use of an objective standardized neuropsychologic test with at least one cognitive functioning dimension. Excluded were studies featuring patients with a history of cardiac arrest, traumatic brain injury, or genetic anomalies associated with neurocognitive impairment. Twelve studies met the sampling criteria and were rated using the Newcastle-Ottawa Quality Assessment Scale. Ten studies reported significantly lower scores in at least one cognitive domain as compared to healthy controls or normed population data; seven of these-four case-control and three prospective cohort studies-reported significant lower scores in more than one cognitive domain. Risk factors associated with post critical illness cognitive impairment included younger age at critical illness and/or older age at follow-up, low socioeconomic status, high oxygen requirements, and use of mechanical ventilation, sedation, and pain medications. Identifying risk factors for poor cognitive outcomes post critical illness may help healthcare teams modify patient risk and/or provide follow-up services to improve long-term cognitive outcomes in high-risk children.


Fluidic timers for time-dependent, point-of-care assays on paper.
This article describes an integrated approach to tracking the end point of a time-based assay that is conducted on an analytical device made out of paper. The timing mechanism is built directly into a paper-based analytical device and does not require starting, stopping, reset buttons, batteries, or maintenance; the timer simply starts once the sample is added to the device. These "fluidic timers" are composed of paraffin wax and a signaling feature (e.g., a dye). The timing function is made possible by the specific time required for a liquid sample to wick through predefined regions in the device. This time period can be anywhere between 1 min and 2 h and is controlled by the quantity of wax present in the timer. Because both the fluidic timers and paper-based assays depend on the wicking rate of the sample, the fluidic timers automatically calibrate themselves (relative to the assay) to account for differences in wicking rates that are caused by variations in humidity. Fluidic timers are 97% accurate (with respect to the time required for the assay) and provide slightly better accuracy than an external timer when used to track an assay that measured the level of glucose in a sample.


Experimental comparison of terahertz and infrared data signal attenuation in dust clouds.
In order to study and compare propagation features of terahertz (THz) links with infrared (IR) links under different weather conditions such as turbulence, fog, and dust particles, THz and IR free space communication links at 625 GHz carrier frequency and 1.5 μm wavelength, respectively, with a maximum data rate of 2.5 Gb/s have been developed. After propagating through the same channel perturbation caused by dust, attenuation of the carrier frequencies by dust as well as scintillation effects on both channels are analyzed by measuring the power attenuation and bit error rates. Attenuation by the presence of dust degrades the IR channel but exhibits almost no measurable impact on the THz signal. Numerical simulations of THz attenuation with different dust concentrations are presented and agree with the measured results.


Characterization of the ToxB gene from Pyrenophora tritici-repentis.
The ToxB gene was cloned and characterized from a race 5 isolate of Pyrenophora tritici-repentis from North Dakota. ToxB contains a 261-bp open reading frame that encodes a 23 amino acid putative signal peptide and a 64 amino acid host-selective toxin, Ptr ToxB. Analysis of Ptr ToxB from heterologous expression in Pichia pastoris confirms that ToxB encodes a host-selective toxin.


Transient division of labor and behavioral specialization in the ant Formica schaufussi.
Cooperative prey retrieval in the monomorphic ant Formica schaufussi is carried out by workers that perform functionally distinct roles which persist only for the duration of a single retrieval event. A forager (scout) that locates prey too large to retrieve individually organizes cooperative prey transport by recruiting nestmates (recruits) to assist in retrieval. The scout and recruit roles appear to be determined by whether a worker activates recruitment or is recruited from the nest. Scouts organize recruitment and play a key role in maintaining the cohesion of the retrieval group. If a scout that has initiated group transport is experimentally removed, the recruited workers composing the retrieval group typically abandon the prey and cooperative foraging is terminated. In this context, recruits are unable to function as scouts and reorganize group transport. Individuals marked as recruits in one prey retrieval, however, can switch and act as scouts in subsequent retrievals. Because the roles of individuals persist within but not between retrieval events, the specialization involved in cooperative prey retrieval cannot easily be explained as a response associated with age-related or genetic predispositions. This transient division-of-labor, in which individual roles may persist only for the duration of a single group action, represents a novel type of short-term individual specialization.