Differences in SARS-CoV-2 infections during the first and second wave of SARS-CoV-2 between six ethnic groups in Amsterdam, the Netherlands: A population-based longitudinal serological study.
Surveillance data in high-income countries have reported more frequent SARS-CoV-2 diagnoses in ethnic minority groups. We examined the cumulative incidence of SARS-CoV-2 and its determinants in six ethnic groups in Amsterdam, the Netherlands. We analysed participants enrolled in the population-based HELIUS cohort, who were tested for SARS-CoV-2-specific antibodies and answered COVID-19-related questions between June 24-October 9, 2020 (after the first wave) and November 23, 2020-March 31, 2021 (during the second wave). We modelled SARS-CoV-2 incidence from January 1, 2020-March 31, 2021 using Markov models adjusted for age and sex. We compared incidence between ethnic groups over time and identified determinants of incident infection within ethnic groups. 2,497 participants were tested after the first wave; 2,083 (83·4%) were tested during the second wave. Median age at first visit was 54 years (interquartile range=44-61); 56·6% were female. Compared to Dutch-origin participants (15·9%), cumulative SARS-CoV-2 incidence was higher in participants of South-Asian Surinamese (25·0%; adjusted hazard ratio [aHR]=1·66; 95%CI=1·16-2·40), African Surinamese (28·9%, aHR=1·97; 95%CI=1·37-2·83), Turkish (37·0%; aHR=2·67; 95%CI=1·89-3·78), Moroccan (41·9%; aHR=3·13; 95%CI=2·22-4·42), and Ghanaian (64·6%; aHR=6·00; 95%CI=4·33-8·30) origin. Compared to those of Dutch origin, differences in incidence became wider during the second versus first wave for all ethnic minority groups (all p-values for interaction<0·05), except Ghanaians. Having household members with suspected SARS-CoV-2 infection, larger household size, and low health literacy were common determinants of SARS-CoV-2 incidence across groups. SARS-CoV-2 incidence was higher in the largest ethnic minority groups of Amsterdam, particularly during the second wave. Prevention measures, including vaccination, should be encouraged in these groups. ZonMw, Public Health Service of Amsterdam, Dutch Heart Foundation, European Union, European Fund for the Integration of non-EU immigrants.


Cholecystitis and cholelithiasis.
Cholelithiasis and cholecystitis, with their complications, remain major health problems in the United States. At this time, cholecystectomy is the treatment of choice for all patients with symptomatic gallstones and those with acute cholecystitis, except those who are too ill to undergo surgery. Present therapeutic options may be summarized as follows: Asymptomatic patients and those with flatulence and dyspepsia who have gallstones should be observed. Those who have symptoms of biliary pain, gallstone-induced pancreatitis, or common duct stones should have corrective surgery. Those who refuse surgery or who aren't surgical candidates might be treated with dissolution therapy. Dissolution of gallstones with chemical agents and extracorporeal shock-wave lithotripsy show some promise. We need a better understanding of the etiology and formation of gallstones to address the disease from a preventive standpoint and reduce the incidence of cholelithiasis and cholecystitis, and their complications.


The K index: a proxy measure of health care quality.
An index of health care quality is described that requires data on "sentinel health events"--unnecessary death and disability caused by specific ICDA-coded conditions on which medical agreement can be reached about avoidability of negative outcomes. The proposed index combines measures of incidence, severity, and concentration of sentinel health events in communities and compares the measures with mean values for a group of normative communities, to arrive at index values that are distributed as X2 for a group of communities with regard to the mean health conditions experienced by the normative communities. Calculation of the index is illustrated with hypothetical data, and problems of selecting normative communities are discussed.


Statins reduce the risk of pancreatic cancer in humans: a case-control study of half a million veterans.
Statins are commonly used cholesterol-lowering agents that are noted to suppress tumor cell growth in several in vitro and animal models. We studied the association between pancreatic cancer and statins in veterans. A retrospective, nested case-control study was conducted using prospectively collected data from the Veterans Integrated Service Networks 16 Veteran Affairs database from 1998 to 2004. We analyzed data on 483,733 patients from 8 states located in south central United States. The primary variables of interest were pancreatic cancer and the use of statins before the diagnosis of pancreatic cancer. Multiple logistic regression analysis was done to adjust for covariates including age, sex, body mass index, smoking, diabetes, and race. The SAS software was used for statistical computing. Of the 483,733 patients in the study, 163,467 (33.79%) were on statins, and 475 (0.098%) patients had a primary diagnosis of pancreatic cancer. Statin use of more than 6 months was associated with a risk reduction of pancreatic cancer of 67% (adjusted odds ratio, 0.33; 95% confidence interval, 0.26-0.41; P < 0.01).A dose-response relationship was noted between statin use and pancreatic cancer with an 80% risk reduction (adjusted odds ratio, 0.2; 95% confidence interval, 0.13-0.29; P < 0.01) with use of statin for more than 4 years. Furthermore, the protective effect of statin was seen across different age and racial groups, and was irrespective of the presence of diabetes, smoking, or alcohol use. Statins seem to be protective against the development of pancreatic cancer, and the magnitude of the effect correlates with the duration of statin use.


Effectiveness of neuronavigation in resecting solitary intracerebral contrast-enhancing tumors: a randomized controlled trial.
The goal of this study was to assess the impact of neuronavigation on the cytoreductive treatment of solitary contrast-enhancing intracerebral tumors and outcomes of this treatment in cases in which neuronavigation was preoperatively judged to be redundant. The authors conducted a prospective randomized study in which 45 patients, each harboring a solitary contrast-enhancing intracerebral tumor, were randomized for surgery with or without neuronavigation. Peri- and postoperative parameters under investigation included the following: duration of the procedure; surgeon's estimate of the usefulness of neuronavigation; quantification of the extent of resection, determined using magnetic resonance imaging; and the postoperative course, as evaluated by neurological examinations, the patient's quality-of-life self-assessment, application of the Barthel index and the Karnofsky Performance Scale score, and the patient's time of death. The mean amount of residual tumor tissue was 28.9% for standard surgery (SS) and 13.8% for surgery involving neuronavigation (SN). The corresponding mean amounts of residual contrast-enhancing tumor tissue were 29.2 and 24.4%, respectively. These differences were not significant. Gross-total removal (GTR) was achieved in five patients who underwent SS and in three who underwent SN. Median survival was significantly shorter in the SN group (5.6 months compared with 9 months, unadjusted hazard ratio = 1.6); however, this difference may be attributable to the coincidental early death of three patients in the SN group. No discernible important effect on the patients' 3-month postoperative course was identified. There is no rationale for the routine use of neuronavigation to improve the extent of tumor resection and prognosis in patients harboring a solitary enhancing intracerebral lesion when neuronavigation is not already deemed advantageous because of the size or location of the lesion.


Adventitial endothelial implants reduce matrix metalloproteinase-2 expression and increase luminal diameter in porcine arteriovenous grafts.
Vascular access dysfunction is a major problem in hemodialysis patients. Only 50% of arteriovenous grafts (AVGs) will remain patent 1 year after surgery. AVGs frequently develop stenoses and occlusions at the venous anastomoses in the venous outflow tract. Lumen diameter is not only determined by intimal thickening but is also influenced by remodeling of the vessel wall. Vascular remodeling requires degradation and reorganization of the extracellular matrix by the degradation enzymes, matrix metalloproteinases (MMPs). In this study, we aimed to provide further insight into the mechanism of endothelial regulation of vascular remodeling and luminal narrowing in AVGs. End-to-side carotid artery-jugular vein polytetrafluoroethylene grafts were created in 20 domestic swine. The anastomoses and outflow vein were treated with Gelfoam matrices (Pfizer, New York, NY) containing allogeneic porcine aortic endothelial (PAE, n = 10) cells or control matrices without cells (n = 10), and the biologic responses to PAE implants were investigated 3 and 28 days postoperatively. Angiograms before euthanasia were compared with baseline angiograms. Tissue sections were stained with hematoxylin and eosin, Verhoeff elastin, and antibodies specific to MMP-9 and MMP-2 and underwent histopathologic, morphometric and immunohistochemical analysis. Veins treated with PAE cell implants had a 2.8-fold increase in venous lumen diameter compared with baseline (P < .05), a 2.3-fold increase in lumen diameter compared with control, and an 81% decrease in stenosis (P < .05) compared with control at 28 days. The increase in lumen diameter by angiographic analysis correlated with morphometric analysis of tissue sections. PAE implants increased the venous lumen area 2.3-fold (P < .05), decreased venous luminal occlusion 66%, and increased positive venous remodeling 1.9-fold (P < .05) compared with control at 28 days. PAE cell implants reduced MMP-2 expression and neovascularization at 3 and 28 days and adventitial fibrosis at 28 days, suggesting a role of the implants in controlling the affects of medial and adventitial cells in the response to vascular injury. These results demonstrate that the adventitial application of endothelial implants significantly reduced MMP-2 expression within the venous wall, and increased venous lumen diameter and positive remodeling in a porcine arteriovenous graft model. Adventitial endothelial implants may be useful in decreasing luminal narrowing in a clinical setting.


Phase space reconstruction of an experimental model of cardiac field potential in normal and arrhythmic conditions.
Cardiac arrhythmias are one of the most important death causes in the world. Compared to the numerical models, the experimental ones provide a more realistic tool to study the mechanisms of cardiac arrhythmias. The in vitro culture of cardiac cells developed on the Multi-Electrodes Array (MEA) constitutes a suitable model in this context. The extracellular field potential (EFP) acquired from the MEA can be used to measure the electrophysiological parameters of action potential. In this article, the stability of this experimental model is investigated using the phase space reconstruction in normal and in arrhythmia conditions. The results show that the embedding dimension of signal EFP changed slightly in both cases (normal conditions and arrhythmia). The parameter time lag τ in the normal conditions is lower than in the arrhythmia. The shape of attractors remains similar but disturbed in case of arrhythmia compared to the normal conditions.


Socioeconomic inequalities in vaccine uptake: A global umbrella review.
This global umbrella review aimed to synthesise evidence of socioeconomic inequalities in the uptake of routine vaccinations and identify the mechanisms that may contribute to the association. To our knowledge, no attempt has been made to synthesise the global body of systematic reviews across a variety of vaccines, geographical locations, and measures of SES. The inclusion criteria were as follows: studies assessing vaccination uptake according to education, income, occupation/employment, and/or area-level deprivation; any country or universally recommended routine vaccination (according to the WHO); qualitative or quantitative reviews, published 2011-present. The searches were performed in eight databases. The screening process followed PRISMA-E guidelines, each stage was performed by one reviewer, and a 10% sample checked by a second for consistency. Included reviews underwent data extraction, quality appraisal (AMSTAR-2), and narrative synthesis according to country-context. After deduplication, 9,163 reports underwent title and abstract screening, leaving 119 full texts to be assessed for eligibility. Overall, 26 studies were included in the umbrella review. Evidence for lower uptake amongst disadvantaged SES individuals was found in all 26 reviews. However, 17 reviews showed mixed results, as inverse associations were also identified (lower uptake for advantaged SES, and/or higher uptake for disadvantaged SES). Those that explored high-income countries had a greater prevalence of mixed findings than those focusing on low/middle-income countries. The two most frequently cited mechanisms were vaccination knowledge, and confidence in vaccination or vaccination providers. These mechanisms were often understood by review authors as varying by level of education. We find socioeconomic differences in routine vaccination uptake, but the association did not always follow a gradient. Whilst education may be associated with uptake globally, our study indicates that its role varies by country-context. A limitation is the overlap of some primary studies across the included systematic reviews.


Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis.
Mechanotransduction, the pathway by which mechanical forces are translated to biological signals, plays important but poorly characterized roles in physiology. PIEZOs are recently identified, widely expressed, mechanically activated ion channels that are hypothesized to play a role in mechanotransduction in mammals. Here, we describe two distinct PIEZO2 mutations in patients with a subtype of Distal Arthrogryposis Type 5 characterized by generalized autosomal dominant contractures with limited eye movements, restrictive lung disease, and variable absence of cruciate knee ligaments. Electrophysiological studies reveal that the two PIEZO2 mutations affect biophysical properties related to channel inactivation: both E2727del and I802F mutations cause the PIEZO2-dependent, mechanically activated currents to recover faster from inactivation, while E2727del also causes a slowing of inactivation. Both types of changes in kinetics result in increased channel activity in response to a given mechanical stimulus, suggesting that Distal Arthrogryposis Type 5 can be caused by gain-of-function mutations in PIEZO2. We further show that overexpression of mutated PIEZO2 cDNAs does not cause constitutive activity or toxicity to cells, indicating that the observed phenotype is likely due to a mechanotransduction defect. Our studies identify a type of channelopathy and link the dysfunction of mechanically activated ion channels to developmental malformations and joint contractures.


Flight-muscle adenylate pool responses to flight demands and thermal constraints in individual Colias eurytheme (Lepidoptera, pieridae).
We study here the connections among body temperature variation, flight performance and flight 'fuel' metabolism in Colias eurytheme butterflies, to begin re-examining the metabolic reasons for animal thermoregulation. Methods are presented for (a) stable extraction of adenylates (and other metabolites) from the flight muscles of individual Colias eurytheme, (b) automated separation and quantitative analysis of individual adenylate samples by high-pressure liquid chromatography and (c) reliable, low-variance assay of inorganic phosphate levels in the same extracts. Correlations among metabolite concentrations and two indices of muscle cytosol ATP maintenance occur as expected on general metabolic principles. [ATP] and [ATP]/[ADP] decline from resting levels to reach a plateau in the first minute of free, interrupted flight, while [AMP] increases at the same time; these concentrations do not vary further for up to 6 min total flight time. In an initial test of the alternative metabolic bases of the thermoregulation of Colias eurytheme, we find that [ATP]/[ADP] rises between a body temperature, T(b), of 31 and 35 degrees C, at the base of the behavioral thermal optimum for flight, but then decreases again at T(b)=39 degrees C, at the top of the behavioral thermal optimum and well short of damaging temperatures. This is not consistent with the view that metabolic effectiveness increases monotonically up to the lower limits of thermal damage to enzymes, but supports an alternative hypothesis that the narrowness of thermoregulation results from a system-based constraint on the breadth of temperature over which maximal energy processing is possible.


Temporising and respect for patient self-determination.
The principle of self-determination plays a crucial role in contemporary clinical ethics. Somewhat simplified, it states that it is ultimately the patient who should decide whether or not to accept suggested treatment or care. Although the principle is much discussed in the academic literature, one important aspect has been neglected, namely the fact that real-world decision making is temporally extended, in the sense that it generally takes some time from the point at which the physician (or other health care professional) determines that there is a decision to be made and that the patient is capable of making it, to the point at which the patient is actually asked for his or her view. This article asks under what circumstances, if any, temporising-waiting to pose a certain treatment question to a patient judged to have decision-making capacity-is compatible with the principle of self-determination.


Interspecific and intraspecific comparisons reveal the importance of evolutionary context in sunfish brain form divergence.
Habitats can select for specialized phenotypic characteristics in animals. However, the consistency of evolutionary responses to particular environmental conditions remains difficult to predict. One trait of great ecological importance is brain form, which is expected to vary between habitats that differ in their cognitive requirements. Here, we compared divergence in brain form and oral jaw size across a common littoral-pelagic ecological axis in two sunfishes at both the intraspecific and interspecific levels. Brain form differed between habitats at every level of comparison; however, divergence was inconsistent, despite consistent differences in oral jaw size. Pumpkinseed and bluegill species differed in cerebellum, optic tectum and olfactory bulb size. These differences are consistent with a historical ecological divergence because they did not manifest between littoral and pelagic ecotypes within either species, suggesting constraints on changes to these regions over short evolutionary time scales. There were also differences in brain form between conspecific ecotypes, but they were inconsistent between species. Littoral pumpkinseed had larger brains than their pelagic counterpart, and littoral bluegill had smaller telencephalons than their pelagic counterpart. Inconsistent brain form divergence between conspecific ecotypes of pumpkinseed and bluegill sharing a common littoral-pelagic habitat axis suggests that contemporary ecological conditions and historic evolutionary context interact to influence evolutionary changes in brain form in fishes.


Hyphomonas adhaerens sp. nov., Hyphomonas johnsonii sp. nov. and Hyphomonas rosenbergii sp. nov., marine budding and prosthecate bacteria.
Three strains of prosthecate, budding bacteria, MHS-2T, MHS-3T and VP6T, were isolated from marine habitats including the open ocean (the pelagic zone), the offshore region (the neritic zone) and the hydrothermal vent region. A polyphasic approach including 16S rDNA sequencing, phenotypic analyses, serology, fatty acid analyses, membrane protein profiles and DNA-DNA hybridizations was used to place these strains in the genus Hyphomonas, a taxon of the alpha-Proteobacteria. The results of these analyses also showed that strains MHS-3T, MHS-2T and VP6T each represent a new species of Hyphomonas. The names Hyphomonas adhaerens (type strain MHS-3T, ATCC 43965T), Hyphomonas johnsonii (type strain MHS-2T, ATCC 43964T) and Hyphomonas rosenbergii (type strain VP6T, ATCC 43869T) are proposed for the new species. With these additions, Hyphomonas now contains eight species.


Characteristics of patients with community-acquired pneumococcal pneumonia.
To describe the level of activity, independence and demographics of elderly people hospitalised with community-acquired pneumococcal pneumonia. Prospective descriptive study. Seven university-affiliated hospitals and three community hospitals. People aged over 55 years admitted to hospital with a clinical history consistent with pneumococcal pneumonia, a Streptococcus pneumoniae isolate in blood or sputum, and a chest x-ray consistent with pneumonia. Significant immunosuppression or certain comorbidities (parenchymal lung disease and end-stage renal failure) were exclusion criteria. Level of independence, assessed by participation in a range of standardised activities before the patient's illness. 82 patients met our case definition. Five refused to participate, leaving 77 evaluable patients. The patients had high levels of independence: 64 (83%; 95% confidence interval [CI], 73%-91%) lived in their own home and 69 (90%; 95% CI, 81%-95%) participated in regular hobbies. Exercise tolerance was good, with 43 (56%; 95% CI, 45%-68%) able to climb a flight of stairs and 59 (76%; 95% CI, 65%-85%) able to walk more than 50 m without stopping; 41 (53%; 95% CI, 41%-64%) could continue further than a kilometre. Mortality was low (9 patients; 12%) despite a high rate of bacteraemia (43 patients; 56%). Within the past five years, 59 (77%) had been hospitalised and 53 (69%) vaccinated with influenza vaccine. Only 7% had ever received pneumococcal vaccination. Pneumococcal pneumonia is not the "old man's friend". It represents a major cause of morbidity and mortality in otherwise well, active and independent older Australians. Hospitalisation and attendance for influenza vaccination may represent opportunities for pneumococcal vaccination.


Matrix metalloproteinases in renal development.
Matrix metalloproteinases (MMPs) are enzymes with metal ion-dependent activity that degrade extracellular matrix (ECM) glycoproteins. MMPs play a vital role in various biological processes, such as embryogenesis, tissue remodeling, angiogenesis, and wound healing, and in certain disease processes, for example, metastasis of cancer cells. Following their activation, MMPs are believed to modulate both cell-cell and cell-matrix interactions, which in turn regulate cellular differentiation, migration, proliferation, and cell survival. Being involved in pericellular proteolysis, they maintain a gradient of ECM proteins by balancing ECM synthesis and degradation. Such a balance is critical for various mammalian developmental processes during embryonic life and also for the homeostasis of various organs and reparative processes in later life. During the past two decades the role of MMPs in the morphogenesis of various organs, including that of the metanephros, has been investigated extensively. Mammalian nephrogenesis comprises a series of intricate events characterized by a sustained remodeling and turnover of ECM, suggesting a potential role of MMPs in renal development. Conceivably, reciprocal inductive epithelial-mesenchymal interactions that take place at the very commencement of nephrogenesis are modulated by a number of ECM proteins. Their expression, especially at the epithelial-mesenchymal interface, are critical for metanephric development, and such a strategic expression is likely to be modified by a number of different macromolecules that exhibit spatiotemporal and stage-specific expression. Among them the most suitable candidate that could exert such a control would be MMPs. This review addresses the current status of our understanding of the functions and the role of MMPs in renal development.


Comparison of Biodosimetry Biomarkers for Radiation Dose and Injury Assessment After Mixed-Field (Neutron and Gamma) and Pure Gamma Radiation in the Mouse Total-Body Irradiation Model.
The detonation of a nuclear weapon and the occurrence of a nuclear accident represent possible mass-casualty events with significant exposure to mixed neutron and gamma radiation fields in the first few minutes after the event with the ensuing fallout, extending for miles from the epicenter, that would result primarily in photon (gamma- and/or x-ray) exposure. Circulating biomarkers represent a crucial source of information in a mass-casualty radiation exposure triage scenario. We evaluated multiple blood biodosimetry and organ-specific biomarkers for early-response assessment of radiation exposure using a mouse (B6D2F1, males and females) total-body irradiation model exposed to Co gamma rays over a broad dose range (3-12 Gy) and dose rates of either 0.6 or 1.9 Gy min and compared the results with those obtained after exposure of mice to a mixed field (neutrons and gamma rays) using the Armed Forces Radiobiology Research Institute Co gamma-ray source and TRIGA Mark F nuclear research reactor. The mixed-field studies were performed previously over a broad dose range (1.5-6 Gy), with dose rates of either 0.6 or 1.9 Gy min, and using different proportions of neutrons and gammas: either (67% neutrons + 33% gammas) or (30% neutrons + 70% gammas). Blood was collected 1, 2, 4, and 7 d after total-body irradiation. Results from Co gamma-ray studies demonstrate: (1) significant dose- and time-dependent reductions in circulating mature hematopoietic cells; (2) dose- and time-dependent changes in fms-related tyrosine kinase 3 ligand, interleukins IL-5, IL-10, IL-12, and IL-18, granulocyte colony-stimulating factors, thrombopoietin, erythropoietin, acute-phase proteins (serum amyloid A and lipopolysaccharide binding protein), surface plasma neutrophil (CD45) and lymphocyte (CD27) markers, ratio of CD45 to CD27, procalcitonin but not in intestinal fatty acid binding protein; (3) no significant differences were observed between dose-rate groups in hematological and protein profiles (fms-related tyrosine kinase 3 ligand, IL-5, IL-12, IL-18, erythropoietin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, CD27, CD45, and ratio of CD45 to CD27) for any radiation dose at any time after exposure (p > 0.148); (4) no significant differences were observed between sex groups in hematological and protein profiles (fms-related tyrosine kinase 3 ligand, IL-18, erythropoietin, granulocyte colony-stimulating factor, granulocyte-macrophage colony-stimulating factor, serum amyloid A, CD45) for any radiation dose at any time after exposure (p > 0.114); and (5) PCT level significantly increased (p < 0.008) in mice irradiated with 12 Gy on day 7 post-total-body irradiation without significant differences between groups irradiated at dose rates of either 0.6 or 1.9 Gy min (p > 0.287). Radiation-quality comparison results demonstrate that: (1) equivalent doses of pure gamma rays and mixed-field radiation do not produce equivalent biological effects, and hematopoietic syndrome occurs at lower doses of mixed-field radiation; (2) ratios of hematological and protein biomarker means in the Co study compared to mixed-field studies using 2× Co doses vs. 1× TRIGA radiation doses (i.e., 3 Gy Co vs. 1.5 Gy TRIGA) ranged from roughly 0.2 to as high as 26.5 but 57% of all ratios fell within 0.7 and 1.3; and (3) in general, biomarker results are in agreement with the relative biological effectiveness = 1.95 (Dn/Dt = 0.67) reported earlier by Armed Forces Radiobiology Research Institute scientists in mouse survival countermeasure studies.


In-Silico Algorithms for the Screening of Possible microRNA Binding Sites and Their Interactions.
MicroRNAs (miRNAs) comprise a recently discovered class of small, non-coding RNA molecules of 21-25 nucleotides in length that regulate the gene expression by base-pairing with the transcripts of their targets i.e. protein-coding genes, leading to down-regulation or repression of the target genes. However, target gene activation has also been described. miRNAs are involved in diverse regulatory pathways, including control of developmental timing, apoptosis, cell proliferation, cell differentiation, modulation of immune response to macrophages, and organ development and are associated with many diseases, such as cancer. Computational prediction of miRNA targets is much more challenging in animals than in plants, because animal miRNAs often perform imperfect base-pairing with their target sites, unlike plant miRNAs which almost always bind their targets with near perfect complementarity. In the past years, a large number of target prediction programs and databases on experimentally validated information have been developed for animal miRNAs to fulfil the need of experimental scientists conducting miRNA research. In this review we first succinctly describe the prediction criteria (rules or principles) adapted by prediction algorithms to generate possible miRNA binding site interactions and introduce most relevant algorithms, and databases. We then summarize their applications with the help of some previously published studies. We further provide experimentally validated functional binding sites outside 3'-UTR region of target mRNAs and the resources which offer such predictions. Finally, the issue of experimental validation of miRNA binding sites will be briefly discussed.


Huffman and linear scanning methods with statistical language models.
Current scanning access methods for text generation in AAC devices are limited to relatively few options, most notably row/column variations within a matrix. We present Huffman scanning, a new method for applying statistical language models to binary-switch, static-grid typing AAC interfaces, and compare it to other scanning options under a variety of conditions. We present results for 16 adults without disabilities and one 36-year-old man with locked-in syndrome who presents with complex communication needs and uses AAC scanning devices for writing. Huffman scanning with a statistical language model yielded significant typing speedups for the 16 participants without disabilities versus any of the other methods tested, including two row/column scanning methods. A similar pattern of results was found with the individual with locked-in syndrome. Interestingly, faster typing speeds were obtained with Huffman scanning using a more leisurely scan rate than relatively fast individually calibrated scan rates. Overall, the results reported here demonstrate great promise for the usability of Huffman scanning as a faster alternative to row/column scanning.


Test of "crab-waist" collisions at the DAPhiNE Phi factory.
The electron-positron collider DAPhiNE, the Italian Phi factory, has been recently upgraded in order to implement an innovative collision scheme based on large crossing angle, small beam sizes at the crossing point, and compensation of beam-beam interaction by means of sextupole pairs creating a "crab-waist" configuration in the interaction region. Experimental tests of the novel scheme exhibited an increase by a factor of 3 in the peak luminosity of the collider with respect to the performances reached before the upgrade. In this Letter we present the new collision scheme, discuss its advantages, describe the hardware modifications realized for the upgrade, and report the results of the experimental tests carried out during commissioning of the machine in the new configuration and standard operation for the users.


Online elicitation of Mamdani-type fuzzy rules via TSK-based generalized predictive control.
Many synergies have been proposed between soft-computing techniques, such as neural networks (NNs), fuzzy logic (FL), and genetic algorithms (GAs), which have shown that such hybrid structures can work well and also add more robustness to the control system design. In this paper, a new control architecture is proposed whereby the on-line generated fuzzy rules relating to the self-organizing fuzzy logic controller (SOFLC) are obtained via integration with the popular generalized predictive control (GPC) algorithm using a Takagi-Sugeno-Kang (TSK)-based controlled autoregressive integrated moving average (CARIMA) model structure. In this approach, GPC replaces the performance index (PI) table which, as an incremental model, is traditionally used to discover, amend, and delete the rules. Because the GPC sequence is computed using predicted future outputs, the new hybrid approach rewards the time-delay very well. The new generic approach, named generalized predictive self-organizing fuzzy logic control (GPSOFLC), is simulated on a well-known nonlinear chemical process, the distillation column, and is shown to produce an effective fuzzy rule-base in both qualitative (minimum number of generated rules) and quantitative (good rules) terms.


[The Health Care Quality Improvement Act of 1986].
The most important aspects of the federal law entitled "Health Care Quality Improvement Act of 1986" are discussed in general terms by the author from the point of view of hospital entities in Puerto Rico. In addition, aspects of suspension of privileges, obtention of immunity protection and the obligation to solicit and report information to the National Data Bank under the federal law are also discussed.


Decreased Expression of Sphingosine-1-Phosphate Receptor 1 in the Blood Leukocyte of Rheumatoid Arthritis Patients.
Sphingosine-1-phosphate (S1P) plays an important role in trafficking leukocytes and developing immune disorders including autoimmunity. In the synovium of rheumatoid arthritis (RA) patients, increased expression of S1P was reported, and the interaction between S1P and S1P receptor 1 (S1P1) has been suggested to regulate the expression of inflammatory genes and the proliferation of synovial cells. In this study, we investigated the level of S1P1 mRNA expression in the blood leukocytes of RA patients. In contrast to the previous reports, the expression level of this gene was not correlated to their clinical scores, disease durations and ages. However, S1P1 was transcribed at a significantly lower level in the circulating leukocytes of RA patients when compared to age-, and sex-matched healthy controls. Since these data may suggest the participation of S1P1, further studies are needed to determine the role of this receptor in the pathogenesis of RA.


Analysis of the antagonist effect of IFN-alpha on IFN-gamma-induced interferon consensus sequence binding protein messenger RNA in murine macrophages.
Interferon consensus sequence binding protein (ICSBP), a member of the interferon regulatory factor family of DNA binding proteins, was recently demonstrated in ICSBP knockout mice to play a critical role in hematopoiesis and virus susceptibility. In macrophages, ICSBP mRNA and protein are strongly induced by IFN-gamma, but only marginally by IFN-alpha/beta. When present concurrently, IFN-alpha/beta antagonizes IFN-gamma-induced ICSBP mRNA and protein synthesis. The unknown mechanism(s) underlying this antagonism may involve competitive interactions between these two IFN species or between molecules of their respective signaling cascades. The data presented demonstrate that IFN-alpha does not interfere with initiation of transmembrane signaling by IFN-gamma and that inhibition of ICSBP mRNA expression by IFN-alpha is independent of new protein synthesis. Nuclear proteins from IFN-gamma-treated or from IFN-alpha plus IFN-gamma-treated cells showed identical binding patterns in EMSAs using a palindromic interferon response element (pIRE) from the ICSBP promoter. These proteins were primarily reactive with antibodies directed against STAT1 alpha and, to a lesser extent, against STAT2 and ISGF3 gamma. However, when a second, upstream IRE-like sequence was evaluated by EMSA, a DNA binding pattern distinct from that seen following exposure to IFN-gamma alone was observed after prolonged stimulation with both IFN-alpha and IFN-gamma. These data suggest a possible novel mechanism for IFN-alpha-induced inhibition of IFN-gamma-induced gene expression.


Comprehending semantic and grammatical violations in Italian. N400 and P600 comparison with visual and auditory stimuli.
Arguments about the existence of language-specific neural systems and specifically about the independence of syntactic and semantic processing have focused on the event-related brain measures (ERPs) as tool to monitoring moment-by-moment the cognitive processes underlaid. In the present experiments, the available evidence indicates that the ERP response to semantic anomalies is at least partially distinct from the ERP response to syntactic anomalies and that two distinct processes are activated in sentences comprehension. ERPs were recorded from 10 electrodes while subjects read (Experiment 1) or listened (Experiment 2) to sentences containing semantic or syntactic violations. Final-words that were inconsistent with the sentence context elicited a negative-going wave at about 400 ms poststimulus, whereas penultimate-word incongruous with the grammatical structure (subject-verb non-agreement) elicited a positive-going wave about 600ms poststimulus. No differences based on the perceptual modality of the stimulus (visual or auditory) nor different ERP correlates as a function of task-relevance (explicit/implicit task induction) were found The implications of our results for Italian language are explained.


Low genome-wide homozygosity in 11 Spanish ovine breeds.
The population of Spanish sheep has decreased from 24 to 15 million heads in the last 75 years due to multiple social and economic factors. Such a demographic reduction might have caused an increase in homozygosity and inbreeding, thus limiting the viability of local breeds with excellent adaptations to harsh ecosystems. The main goal of our study was to investigate the homozygosity patterns of 11 Spanish ovine breeds and to elucidate the relationship of these Spanish breeds with reference populations from Europe, Africa and the Near East. By using Ovine SNP50 BeadChip data retrieved from previous publications, we have found that the majority of studied Spanish ovine breeds have close genetic relatedness with other European populations; the one exception is the Canaria de Pelo breed, which is similar to North African breeds. Our analysis has also demonstrated that, with few exceptions, the genomes of Spanish sheep harbor fewer than 50 runs of homozygosity (ROH) with a total length of less than 350 Mb. Moreover, the frequencies of very long ROH (>30 Mb) are very low, and the inbreeding coefficients (FROH ) are generally small (FROH < 0.10), ranging from 0.008 (Rasa Aragonesa) to 0.086 (Canaria de Pelo). The low levels of homozygosity observed in the 11 Spanish sheep under analysis might be due to their extensive management and the high number of small to medium farms.


Development of a Platform to Assess the Risk of Musculoskeletal Disorders in Manual Load Handling Activities - Preliminary Results.
Risk identification on workstations is a crucial step to prevent the occurrence of musculoskeletal disorders (MSD) in workers. The available methods and tools used by ergonomists to assess and estimate the risk related to manual handling of loads under repetitive work cycles are usually biased by the inter-evaluator error that can lead to a subjective determination of work-related risks due to the application of, mainly, observational methods. This paper shows the preliminary results of a platform to assess the risk of musculoskeletal disorders during manual load-handling tasks using an instrumented system and using the National Institute for Occupational Safety & Health (NIOSH) method. Eight healthy subjects were measured during lifting activities using an optical-based and inertial-based motion capture systems. The developed software implements a semi-automated instrumented version of the NIOSH method, helping the evaluator with automated calculations of body segment locations, displacements and joint angles making it possible to obtain a objective risk classification. Also, we achieved a reduction of 85% in the time for the estimation of the necessary factors for the digital evaluation methodology, making the proposed platform a promising and attractive alternative for its application in real environments for risk assessments.Occupational health relevance- This work proposes an assistance tool for the detection of musculoskeletal disorders in activities related to manual handling of loads, essential to initiate modification strategies in the workplace, reduce the occurrence of occupational diseases and reduce the time of risk classification.


Magnetoencephalography in neurosurgery.
To present applications of magnetoencephalography (MEG) in studies of neurosurgical patients. MEG maps magnetic fields generated by electric currents in the brain, and allows the localization of brain areas producing evoked sensory responses and spontaneous electromagnetic activity. The identified sources can be integrated with other imaging modalities, e.g., with magnetic resonance imaging scans of individual patients with brain tumors or intractable epilepsy, or with other types of brain imaging data. MEG measurements using modern whole-scalp instruments assist in tailoring individual therapies for neurosurgical patients by producing maps of functionally irretrievable cortical areas and by identifying cortical sources of interictal and ictal epileptiform activity. The excellent time resolution of MEG enables tracking of complex spaciotemporal source patterns, helping, for example, with the separation of the epileptic pacemaker from propagated activity. The combination of noninvasive mapping of subcortical pathways by magnetic resonance imaging diffusion tensor imaging with MEG source localization will, in the near future, provide even more accurate navigational tools for preoperative planning. Other possible future applications of MEG include the noninvasive estimation of language lateralization and the follow-up of brain plasticity elicited by central or peripheral neural lesions or during the treatment of chronic pain. MEG is a mature technique suitable for producing preoperative "road maps" of eloquent cortical areas and for localizing epileptiform activity.


Intake of key chronic disease-related nutrients among baby boomers.
The dietary habits of baby boomers (people born between 1946 and 1964) undoubtedly will have a substantial impact on their future health; however, dietary information regarding the intake of key chronic disease-related nutrients is lacking for this generation. The objective of this study was to compare the dietary intake of key chronic disease-related nutrients of the baby boomer generation with the previous generation of middle-aged adults. National cross-sectional study comparison analyzing data from the National Health and Nutrition Examination Survey (NHANES) including NHANES III (1988-1994) and the NHANES for 2007-2010, focused on adult respondents ages 46 to 64 years who were not institutionalized at the time of each survey. The two cohorts were compared with regard to dietary intake of key nutritional components. The main outcome measures were intake of total calories, sodium, cholesterol, fat, fruits, vegetables, vitamin C, water, and fiber. The baby boomers' average daily intake of nutrients exceeded that of the previous generation of middle-aged adults for total calories (2118/1999), total fat (82/76 g), sodium (3513/3291 mg), and cholesterol (294/262 g; all P < 0.001). The intake of vitamin C (105/89 g), water (1208/1001 g), and vegetables (199/229 g) was less than that of the previous generation (P < 0.001), and the dietary intake of fruit and fiber was unchanged. In regression analyses, dietary changes remained significant after controlling for age, race, sex, and socioeconomic status (all P < 0.01). The study findings document higher dietary intake of key chronic disease-related nutrients along with reduced vegetable intake among baby boomers compared with the previous generation of middle-aged adults. These findings are indicative of a diet that may contribute to increased rates of chronic disease among individuals in this age group.


Changes of autoantibodies against oxidatively modified low density lipoproteins during long-term LDL-apheresis.
The oxidation of low-density lipoproteins (LDL) is considered a key event in the initiation of atherosclerosis. The aim of this study was to follow-up the biological marker of in vivo LDL oxidation (oxidatively modified LDL autoantibody titres) during long-term LDL-apheresis treatment. A patient suffering from severe combined hyperlipidaemia underwent LDL-apheresis biweekly and was followed for two years. The significant reduction of baseline total cholesterol (58%), total triglycerides (80%), LDL-cholesterol (48%), apoprotein B (50%) and apolipoprotein (a) (61%) may be considered as a good response to the treatment. The titre of autoantibodies (IgG) against oxidatively modified LDL (malondialdehyde-derived LDL) was followed throughout the study and showed dynamic changes. The measured values were multiple compared as mean+/-SD over each semester of apheresis application: I semester 70.0+/-8.3 U/ml, n = 12; II semester 58.0+/-13.8 U/ml, n = 12; III semester 37.6+/-6.0 U/ml, n=12; IV semester 34.3+/-7.0 U/ml, n = 12; ANOVA: I vs. II semester p<0.083, II vs. III semester p<0.00053, III vs. IV semester p<0.248. In parallel to the changes in this biochemical parameter, regression of numerous xanthomas was clinically observed. In spite of this, the presence of oxidised-LDL (oxLDL) antibodies was enhanced in comparison to antibody titre detected in a group of age-matched normolipaemic healthy controls (n = 15; 19.4+/-8.6; p<0.01). Classical lipoprotein parameters were correlated with the titre of autoantibodies against oxLDL and showed low correlation coefficients: total cholesterol vs. oxLDLab, r = 0.36; triglycerides vs. oxLDLab, r = 0.43; LDL cholesterol vs. oxLDLab, r = 0.14; HDL cholesterol vs. oxLDLab, r = -0.33; apo B vs. oxLDLab, r = 0.25; apo (a) vs. oxLDLab, r = -0.05. Our study showed an additional benefit of LDL-apheresis therapy. The production of autoantibodies against oxLDL was reduced during the treatment, indicating a lower level of the atherogenic antigen.


Thoracic Endovascular Aortic Repair With Single/Double Chimney Technique for Aortic Arch Pathologies.
To summarize a single-center experience using the single/double chimney technique in association with thoracic endovascular aortic repairs (TEVAR) for aortic arch pathologies. From November 2007 to March 2016, 122 patients (mean age 50.4±12.7 years, range 29-80; 92 men) with aortic arch pathologies underwent TEVAR combined with single (n=101) or double (n=21) chimney grafts to reconstruct the supra-aortic branches: 21 innominate arteries, 114 left common carotid arteries, and 8 left subclavian arteries (LSA). Pathologies included type B aortic dissection (n=47), aortic arch dissection (n=49), retrograde type A aortic dissection (n=8), thoracic aortic aneurysm (n=7), penetrating aortic arch ulcer (n=9), and post-TEVAR type I endoleak (n=2). Follow-up examinations included computed tomography at 0.5, 3, 6, and 12 months and yearly thereafter. The aortic stent-grafts were deployed in zone 0 (n=21), zone 1 (n=93), and zone 2 (n=8). One (0.8%) of the 122 patients died at 4 days due to a perforated peptic ulcer. Type Ia endoleaks were found intraoperatively in 13 (10.7%) patients, including 3 with the double chimney technique. Type II endoleaks occurred in 6 (4.9%) patients; 3 were treated with duct occluders in the LSA. Postoperative chimney graft migration occurred in 1 (0.8%) patient with double chimneys; additional stent-grafts were deployed in both chimneys. Median follow-up was 32.3 months, during which 1 (0.8%) patient died after a stroke at 3 months. Chimney stent-graft patency was observed in the remaining 120 patients. Two (1.7%) secondary TEVARs were performed for distal aortic dissection. Nine asymptomatic type Ia endoleaks and 1 type II endoleak persisted in follow-up; a type II endoleak in 1 patient with Marfan syndrome sealed in 52 months. TEVAR with the chimney technique provides a safe, minimally invasive alternative with good chimney graft patency and low postoperative mortality during midterm follow-up. The double chimney technique should be used judiciously owing to its potential complications.


Comparison of induction-to-expulsion interval during second-trimester medication abortion in pregnancies with anencephaly and other congenital anomalies compared to those without anomalies: A retrospective cohort study.
To investigate whether the induction-to-expulsion interval during second-trimester medication abortion in pregnancies complicated by anencephaly or other fetal anomalies is prolonged compared to pregnancies without fetal anomalies STUDY DESIGN: This was a retrospective cohort study of women who had second-trimester medication abortion at St. Paul's Hospital Millennium Medical College (Addis Ababa, Ethiopia). We assigned subjects to one of three groups based on fetal diagnosis: 1) anencephaly group, 2) other congenital anomaly group, and 3) no anomaly group. Data were collected by reviewing patients' charts. We used SPSS version 23 to analyze the data. Simple descriptive analysis and χ2 test were performed as appropriate. A total of 303 women had second-trimester medication at 14-28 weeks, of which 58 had anencephaly, 19 had congenital anomalies other than anencephaly, and the remaining 226 had no fetal anomalies. The mean induction-to-expulsion interval was 18.4 hours in the anencephaly group versus 19.4 hours in the other congenital anomaly group versus 19.2 hours in those without anomaly (p-value = 0.924). The 24-hour nonexpulsion rate was also comparable among the groups, with 5.25% rate of nonexpulsion in the anencephaly group versus 15.8% in the other congenital anomaly group versus 11.15% in the no anomaly group (p-value = 0.594). In multivariable regression analysis after controlling for parity, the 24-hour nonexpulsion rate was not significantly different. In this study, pregnancies undergoing second-trimester medication abortion for fetal anomalies had comparable induction-to-expulsion interval and 24-hour expulsion rates compared to those who had the same procedure for other or no anomalies. Second-trimester medication abortion procedure length in pregnancies complicated by anencephaly is similar to those pregnancies without anomalies.


Home-based oral health program for adults with intellectual disabilities: An intervention study.
Poor oral health is common in adults with intellectual disabilities leading to risk of mouth and lung infections. Yet, little is known about the benefits of preventative oral health programs. This prospective longitudinal experimental mixed methods study evaluated the efficacy of an oral health program aimed at improving knowledge and behaviours in adults with intellectual disabilities living in supported housing. A 90-min training session was provided to residents and their staff at 12 houses (56 residents; 67 staff). Follow-up training sessions (at 1 week, 1,2,3 months) were tailored to the learning abilities, behavioural/physical challenges, and independence of residents. Outcome measures were collected pre, 1, 2 and 3 months (n = 36): dental exam, plaque index, gingival signs, tongue coating index and behavioural rating scale. At 3 months, support workers (n = 10) and residents (n = 19) were interviewed. Residents' interviews were supported by Talking Mats®. Most residents (94%) required support for oral cares; with 63% fully dependant on their support workers. 24 (63%) residents had significantly improved plaque scores at 3 months (p < .001). Resident interviews were restricted by communication competency but supported interviews indicated positive responses to 3-sided toothbrush 91%, interdental brush/flosser 60%, and mouthwash 100%. Support worker interviews revealed perceived health and social benefits including fresher breath and benefits of routines. Oral health programs for adults with intellectual disabilities living in supported housing are well received by staff and residents, leading to changes in oral care routines and measurable changes in oral health.


Intellectual disability, exercise and aging: the IDEA study: study protocol for a randomized controlled trial.
People with intellectual disabilities (ID) have low levels of physical activity (PA) together with accelerated aging profiles. Adherence to PA interventions for persons with ID is low based on barriers such as motivation. The IDEA study aims to determine the effect of two types of exercise programs, continuous aerobic (CAEP) vs sprint interval training (SIT), designed for seniors with ID on health-related physical fitness, cardiovascular parameters, quality of life (QoL), and emotional and cognitive function. In this trial, ninety seniors with ID between the ages of 40 and 75 yrs. from occupational health centers from the Autonomous Region of Catalonia (Spain) will be recruited. Participants will be randomly allocated to the CAEP, SIT, and control group. Both intervention groups will train 3 days/week, 1.5 h/day over 6 months. Outcome variables will be assessed at baseline, 6 months and 12 months. The outcome variables include weight, height, body composition, cardiorespiratory fitness, muscle strength, balance, flexibility, cardiovascular parameters (blood pressure, pulse-wave velocity, pulse-wave analysis), QoL and cognitive function. The intervention effect will be determined with mixed models with repeated measures to assess changes in the outcome variables over time (baseline to month 12) and between study arms. Relationship between variables will be analyzed with appropriate regression analyses. Various studies reported on CAEP and SIT as exercise interventions for persons with ID with beneficial outcomes on body composition, fitness and blood pressure. To our knowledge, this is the first trial designed to analyse the positive changes on fitness, PA levels, cardiovascular, QoL and cognitive function promoted by CAEP training and SIT in seniors with ID. The findings of this study will assist in the development of more effective exercise interventions to ensure better compliance and adherence to exercise in seniors with ID. The trial is registered at the ISRCTN registry. Registration number: ISRCTN43594228 . Registered 11 February 2019 - Retrospectively registered.


Natural course in tennis elbow--lateral epicondylitis after all?
Tennis elbow is a common and difficult-to-treat condition largely because of lack of evidence. The natural history is unknown, but the condition is described as self-limiting. The objective of this case report is to describe the natural course of two control participants (pain free), who later developed tennis elbow, patient history, clinical findings, and ultrasound and colour Doppler examination before, during and after a period of tennis elbow.


Quantifying the subjective cost of self-control in humans.
Since Odysseus committed to resisting the Sirens, mechanisms to limit self-control failure have been a central feature of human behavior. Psychologists have long argued that the use of self-control is an effortful process and, more recently, that its failure arises when the cognitive costs of self-control outweigh its perceived benefits. In a similar way, economists have argued that sophisticated choosers can adopt "precommitment strategies" that tie the hands of their future selves in order to reduce these costs. Yet, we still lack an empirical tool to quantify and demonstrate the cost of self-control. Here, we develop and validate an economic decision-making task to quantify the subjective cost of self-control by determining the monetary cost a person is willing to incur in order to eliminate the need for self-control. We find that humans will pay to avoid having to exert self-control in a way that scales with increasing levels of temptation and that these costs appear to be modulated both by motivational incentives and stress exposure. Our psychophysical approach allows us to index moment-to-moment self-control costs at the within-subject level, validating important theoretical work across multiple disciplines and opening avenues of self-control research in healthy and clinical populations.


Neuronal stability and drift across periods of sleep: premotor activity patterns in a vocal control nucleus of adult zebra finches.
How stable are neural activity patterns compared across periods of sleep? We evaluated this question in adult zebra finches, whose premotor neurons in the nucleus robustus arcopallialis (RA) exhibit sequences of bursts during daytime singing that are characterized by precise timing relative to song syllables. Each burst has a highly regulated pattern of spikes. We assessed these spike patterns in singing that occurred before and after periods of sleep. For about half of the neurons, one or more premotor bursts had changed after sleep, an average of 20% of all bursts across all RA neurons. After sleep, modified bursts were characterized by a discrete, albeit modest, loss of spikes with compensatory increases in spike intervals, but not changes in timing relative to the syllable. Changes in burst structure followed both interrupted bouts of sleep (1.5-3 h) and full nights of sleep, implicating sleep and not circadian cycle as mediating these effects. Changes in burst structure were also observed during the day, but far less frequently. In cases where multiple bursts in the sequence changed in a single cell, the sequence position of those bursts tended to cluster together. Bursts that did not show discrete changes in structure also showed changes in spike counts, but not biased toward losses. We hypothesize that changes in burst patterns during sleep represent active sculpting of the RA network, supporting auditory feedback-mediated song maintenance.


Quantitation of chondrocyte performance in growth-plate cartilage during longitudinal bone growth.
The longitudinal growth of bone depends on the activities of individual chondrocytes of the growth plate. Each chondrocyte remains in a fixed location throughout its life, and there accomplishes all of its functions. Although a cell may perform several or all of its activities simultaneously, one of these will usually predominate during a particular phase of its life. The two most prominent stages are those of cellular proliferation and hypertrophy (including the mineralization of matrix) before the resorption of tissue during vascular invasion. By applying recently developed stereological procedures and improved methods for the fixation of cartilage, we compared cellular shape modulation, various ultrastructural parameters (surface areas or volumes of endoplasmic reticulum, Golgi membranes, and mitochondria), the production of matrix, and cellular turnover for proliferating and hypertrophic chondrocytes within the proximal tibial growth plate of the rat. By the late hypertrophic stage, fourfold and tenfold increases in the mean cellular height and volume, respectively, and a threefold increase in the mean volume of the matrix per cell were achieved. The high metabolic activity of hypertrophic cells was reflected by a twofold to fivefold increase in the mean cellular surface area of rough endoplasmic reticulum, the Golgi membranes, and the mean cellular mitochondrial volume. Rates of longitudinal growth were determined by fluorochrome labeling and incident-light fluorescence microscopy. Using these values and the stereological estimators describing cellular height, the rates of cellular turnover were calculated. The rapid progression of the vascular invasion front was found to eliminate, for each column of cells, one chondrocyte every three hours; that is, eight cells a day. The maintenance of a steady-state structure for growth-plate cartilage in rats in a steady state of growth thus necessitates efficient compensation for these losses, which is achieved by a high rate of cellular proliferation and rapid hypertrophy.


Implementation of mass media community health education: the Forsyth County Cervical Cancer Prevention Project.
The Forsyth County Cervical Cancer Prevention Project (FCP) is a community-based health education project funded by the National Cancer Institute. The target population includes around 25 000 black women age 18 and older who reside in Forsyth County, North Carolina. The overall goal of the program is to prevent mortality from cervical cancer by promoting Pap smears and return for follow-up care when needed. Based on the principles of social marketing, a plan to reach the target population with mass media educational messages through electronic and print channels was developed. Guided by marketing objectives, the target population was divided into relatively discrete segments. The segments included church attenders, patients in waiting rooms of public and selected health providers, female students at local colleges, shoppers, viewers of radio and television, newspaper readers, and business owners and managers. Introduction of the program was based on strategies developed for reaching the target population in each segment with television, radio and print mass media messages. Qualitative assessment of the mass media developed by the program indicated that all forms of communication helped to increase awareness of the program.


Hearing ability in Danish symphony orchestra musicians.
The audiograms of fifty-seven musicians from four Danish symphony orchestras were determined in connection with an interview about their working experience. Measurements of sound levels and noise dose were performed during rehearsal and during concerts in the four orchestras with the measurement equipment placed in various instrument groups. The average audiogram showed a decrease at higher frequencies similar to an age-related hearing loss. Each audiogram was corrected for the age of the person by means of the median from ISO 7029 and the average audiogram from these age-corrected individual audiograms showed no signs of hearing loss. The audiograms were also compared to the expected audiograms from ISO 1999, which takes account of the number of years at work, the number of playing hours per week, and the average sound level in the orchestra for the instrument group. In almost all cases the measured audiograms looked better than the predictions from ISO 1999. It may be concluded from this investigation that musicians cannot be expected to get pronounced audiometric hearing losses from playing in a symphony orchestra. It should be noted, though, that the data material is limited, and that the subjects have not been selected in a systematically or representative way.


Bioavailability and biotransformation of sulforaphane and erucin metabolites in different biological matrices determined by LC-MS-MS.
The food-related isothiocyanate sulforaphane (SFN), a hydrolysis product of the secondary plant metabolite glucoraphanin, has been revealed to have cancer-preventive activity in experimental animals. However, these studies have often provided inconsistent results with regard to bioavailability, bioaccessibility, and outcome. This might be because the endogenous biotransformation of SFN metabolites to the structurally related erucin (ERN) metabolites has often not been taken into account. In this work, a fully validated liquid chromatography tandem mass spectrometry (LC-MS-MS) method was developed for the simultaneous determination of SFN and ERN metabolites in a variety of biological matrices. To reveal the importance of the biotransformation pathway, matrices including plasma, urine, liver, and kidney samples from mice and cell lysates derived from colon-cancer cell lines were included in this study. The LC-MS-MS method provides limits of detection from 1 nmol L(-1) to 25 nmol L(-1) and a mean recovery of 99 %. The intra and interday imprecision values are in the range 1-10 % and 2-13 %, respectively. Using LC-MS-MS, SFN and ERN metabolites were quantified in different matrices. The assay was successfully used to determine the biotransformation in all biological samples mentioned above. For a comprehensive analysis and evaluation of the potential health effects of SFN, it is necessary to consider all metabolites, including those formed by biotransformation of SFN to ERN and vice versa. Therefore, a sensitive and robust LC-MS-MS method was validated for the simultaneous quantification of mercapturic-acid-pathway metabolites of SFN and ERN.


Impulse control disorders in Parkinson's disease: decreased striatal dopamine transporter levels.
Impulse control disorders are commonly associated with dopaminergic therapy in Parkinson's disease (PD). PD patients with impulse control disorders demonstrate enhanced dopamine release to conditioned cues and a gambling task on [(11)C]raclopride positron emission tomography (PET) imaging and enhanced ventral striatal activity to reward on functional MRI. We compared PD patients with impulse control disorders and age-matched and gender-matched controls without impulse control disorders using [(123)I]FP-CIT (2β-carbomethoxy-3β-(4-iodophenyl)tropane) single photon emission computed tomography (SPECT), to assess striatal dopamine transporter (DAT) density. The [(123)I]FP-CIT binding data in the striatum were compared between 15 PD patients with and 15 without impulse control disorders using independent t tests. Those with impulse control disorders showed significantly lower DAT binding in the right striatum with a trend in the left (right: F(1,24)=5.93, p=0.02; left: F(1,24)=3.75, p=0.07) compared to controls. Our findings suggest that greater dopaminergic striatal activity in PD patients with impulse control disorders may be partly related to decreased uptake and clearance of dopamine from the synaptic cleft. Whether these findings are related to state or trait effects is not known. These findings dovetail with reports of lower DAT levels secondary to the effects of methamphetamine and alcohol. Although any regulation of DAT by antiparkinsonian medication appears to be modest, PD patients with impulse control disorders may be differentially sensitive to regulatory mechanisms of DAT expression by dopaminergic medications.


Detection of Pediatric Upper Extremity Motor Activity and Deficits With Accelerometry.
Affordable, quantitative methods to screen children for developmental delays are needed. Motor milestones can be an indicator of developmental delay and may be used to track developmental progress. Accelerometry offers a way to gather real-world information about pediatric motor behavior. To develop a referent cohort of pediatric accelerometry from bilateral upper extremities (UEs) and determine whether movement can accurately distinguish those with and without motor deficits. Children aged 0 to 17 years participated in a prospective cohort from December 8, 2014, to December 29, 2017. Children were recruited from Ranken Jordan Pediatric Bridge Hospital, Maryland Heights, Missouri, and Washington University School of Medicine in St Louis, St Louis, Missouri. Typically developing children were included as a referent cohort if they had no history of motor or neurological deficit; consecutive sampling and matching ensured equal representation of sex and age. Children with diagnosed asymmetric motor deficits were included in the motor impaired cohort. Bilateral UE motor activity was measured using wrist-worn accelerometers for a total of 100 hours in 25-hour increments. To characterize bilateral UE motor activity in a referent cohort for the purpose of detecting irregularities in the future, total activity and the use ratio between UEs were used to describe typically developing children. Asymmetric impairment was classified using the mono-arm use index (MAUI) and bilateral-arm use index (BAUI) to quantify the acceleration of unilateral movements. A total of 216 children enrolled, and 185 children were included in analysis. Of these, 156 were typically developing, with mean (SD) age 9.1 (5.1) years and 81 boys (52.0%). There were 29 children in the motor impaired cohort, with mean (SD) age 7.4 (4.4) years and 16 boys (55.2%). The combined MAUI and BAUI (mean [SD], 0.86 [0.005] and use ratio (mean [SD], 0.90 [0.008]) had similar F1 values. The area under the curve was also similar between the combined MAUI and BAUI (mean [SD], 0.98 [0.004]) and the use ratio (mean [SD], 0.98 [0.004]). Bilateral UE movement as measured with accelerometry may provide a meaningful metric of real-world motor behavior across childhood. Screening in early childhood remains a challenge; MAUI may provide an effective method for clinicians to measure and visualize real-world motor behavior in children at risk for asymmetrical deficits.


Advancing Well-Being Through Total Worker Health®.
Total Worker Health® (TWH) is a paradigm-shifting approach to safety, health, and well-being in the workplace. It is defined as policies, programs, and practices that integrate protection from work-related safety and health hazards with promotion of injury and illness prevention efforts to advance worker well-being. The most current TWH concepts are presented, including a description of issues relevant to TWH and introduction of a hierarchy of controls applied to TWH. Total Worker Health advocates for a foundation of safety and health through which work can contribute to higher levels of well-being.


TMPRSS9 and GRIN2B are associated with neuroticism: a genome-wide association study in a European sample.
Major depression disorder (MDD) is a complex and chronic disease that ranks fourth as cause of disability worldwide. About 14 million adults in the USA are believed to have MDD, and an estimated 75 % attempt suicide making MDD a major public health problem. Neuroticism has been recognized as an endophenotype of MDD; however, few genome-wide association (GWA) analyses of neuroticism as a quantitative trait have been reported to date. The aim of this study is to identify genome-wide genetic variants affecting neuroticism using a European sample. A linear regression model was used to analyze the association with neuroticism as a continuous trait in the Netherlands Study of Depression and Anxiety and Netherlands Twin Registry population-based sample of 2,748 individuals with Perlegen 600K single nucleotide polymorphisms (SNPs). In addition, the neuroticism-associated genes/loci of the top 20 SNPs (p < 10⁻⁴) were examined with anti-social personality disorder (ASPD) in an Australian twin family study. Through GWA analysis, 32 neuroticism-associated SNPs (p < 10⁻⁴) were identified. The most significant association was observed with SNP rs4806846 within the TMPRSS9 gene (p = 7.79 × 10⁻⁶) at 19p13.3. The next best signal was in GRIN2B gene (rs220549, p = 1.05 × 10⁻⁵) at 12p12. In addition, several SNPs within GRIN2B showed borderline associations with ASPD in the Australian sample. In conclusion, these results provide a possible genetic basis for the association with neuroticism. Our findings provide a basis for replication in other populations to elucidate the potential role of these genetic variants in neuroticism and MDD along with a possible relationship between ASPD and neuroticism.


Parents' Reports of Preschoolers' Diets: Relative Validity of a Food Frequency Questionnaire and Dietary Patterns.
The accurate assessment of food consumption is crucial in nutritional studies. Since modern nutrition science has become more interested in diet as a whole, studies validating food frequency questionnaires (FFQs) and exploratory dietary patterns are needed. We aimed at examining the relative validity of a 47-item FFQ against three-day food records among three- to six-year-old Finnish children, as well as investigating the consistency of the dietary patterns derived using the principal component analysis (PCA), with food record and FFQ data as inputs. We conducted the PCA without forcing the food record data to match the FFQ items. Altogether, 75% or more of the participants were classified into the same or adjacent quarter of vegetables and fruits as well as sugary food consumption. Furthermore, the intake of folate and vitamin C increased linearly in the quarters of vegetable and fruit consumption, as did the intake of sucrose in quarters of sugary food consumption. Three fairly similar dietary patterns were identified from food records and FFQ data. Concerning the patterns, more than 70% of the participants were classified into the same or adjacent quarter. However, the Spearman correlation coefficients between the respective pattern scores were low (0.25⁻0.33). The FFQ showed acceptable validity when ranking food group consumption compared to food records. Additionally, the FFQ-derived dietary patterns were consistent with those derived using food record data.


Essential genes in the hDf6 region of chromosome I in Caenorhabditis elegans.
In this paper we describe the analysis of essential genes in the hDf6 region of chromosome I of Caenorhabditis elegans. Nineteen complementation groups have been identified which are required for the growth, survival or fertility of the organism (essential genes). Since ten of these genes were represented by more than one allele, a Poisson calculation predicts a minimum estimate of 25 essential genes in hDf6. The most mutable gene in this region was let-354 with seventeen alleles. An average mutation rate of 5 x 10(-5) mutations/gene/chromosome screened was calculated for an ethyl methanesulfonate dose of 15 mM. Mutations were recovered by screening for lethal mutations using the duplication sDp2 for recovery. Our analysis shows that duplications are very effective for maintenance and mapping of large numbers of lethal mutations. Approximately 600 lethal mutations were mapped in order to identify the 54 that are in the deficiency hDf6. The hDf6 region appears to have a lower proportion of early arresting mutations than other comparably sized regions of the genome.


Seasonal effects on depression risk and suicidal symptoms in postpartum women.
Postpartum depression (PPD) is the most common complication of childbirth. Suicide is a leading cause of maternal death in the first postpartum year. Depressed mothers often have suicidal ideation (SI). Depression and suicidality may vary across the seasons. Previous studies of seasonality and PPD were relatively small or encumbered by study design constraints. We examined the possible relationship between seasonality, depression, and SI in 9,339 new mothers. From 2006 to 2010, the investigators screened women within 4-6 weeks postpartum with the Edinburgh Postnatal Depression Scale (EPDS). We used spectral analysis to explore seasonal variation in risk for depression and suicidality. The study team screened 9,339 new mothers, of whom 1,316 (14%) women had positive depression scores (EPDS≥10) which suggest PPD risk; 294 (3%) women had SI (item 10≥1). A positive EPDS was associated significantly with SI. PPD risk varied significantly across 12-months-risk was highest in December. We detected no seasonal variation in SI. Effects of seasonal light variation may contribute to increased risk for depressive symptoms. Suicidality could be related to maternal depression but not seasonal variation.


Evaluation of Rheumatology Workforce Supply Changes in Ontario, Canada, from 2000 to 2030.
Rheumatology workforces are increasingly challenged by too few physicians in face of the growing burden of rheumatic and musculoskeletal diseases (RMDs). Rheumatology is one of the most frequent non-surgical specialty referrals and has the longest wait times for subspecialists. We used a population-based approach to describe changes in the rheumatology workforce, patient volumes and geographic variation in the supply of and access to rheumatologists, in Ontario, Canada, between 2000 and 2019, and projected changes in supply by 2030. Over time, we observed greater feminization of the workforce and increasing age of workforce members. We identified a large regional variation in rheumatology supply. Fewer new patients are seen annually, which likely contributes to increasing wait times and reduced access to care. Strategies and policies to raise the critical mass and improve regional distribution of supply to effectively provide rheumatology care and support the healthcare delivery of patients with RMDs are needed.


Effect of executive functioning on perceived needs in chronic schizophrenia.
Recent approaches to needs assessment involve patients in this process; however, little is known of the effects of mental illness on patients' ability to assess their own needs. The needs of 26 subjects with schizophrenia were assessed over 22 domains by patients and staff, using the Camberwell Assessment of Need Short Appraisal Schedule (CANSAS). Patients' executive functioning was assessed using the Wisconsin Card Sorting Test (WCST). Mean discrepancies between ratings by staff and by patients were compared across executive functioning; results showed no effect of executive functioning on the discrepancy between staff and patient ratings. Higher executive functioning was associated with more met needs. Multivariate analysis showed higher executive functioning associated with more needs in some but not all areas. Results suggest that patients with schizophrenia and impaired executive functioning can validly estimate their needs. Better executive functioning may be associated with the ability to get one's needs met, increased awareness of needs, better ability to communicate needs, or more needs in certain areas. Need is shown to be a complex variable, and not simply an index of functioning. Hospitals and clinics must ensure that patients' views find full expression in ratings. Needs ratings and rehabilitation status should be viewed in the light of neuropsychological functioning.


Visual evoked potentials in macular disease.
Although a delayed visual evoked potential is considered to be the hallmark of optic nerve disease, relatively little has been published about VEP delays in macular disease. In this study, 20 patients with either acquired unilateral maculopathy or bilateral maculopathy in which one eye was more affected than the other were evaluated. VEP amplitudes and peak latencies were compared between eyes when recordable. Nine patients (45%) exhibited significant interocular delays in the affected or more affected eye while only four patients (20%) exhibited significant interocular attenuations in amplitude. In the nine patients exhibiting delays, three patients had a visual acuity of 20/30 or better in the affected eye or more affected eye. In the patients exhibiting amplitude attenuations, no patient had a visual acuity better than 20/50 in the affected or more affected eye. Although the mechanism of VEP delays in maculopathy is not clear, a VEP delay, in isolation of other tests, should not be used in the differential diagnosis of macular vs optic nerve disease. The clinician should specifically rule out macular disease in any patient with a delayed VEP before presuming the presence of a visual pathway dysfunction.


A Novel Apremilast Nail Lacquer Formulation for the Treatment of Nail Psoriasis.
The objective was to prepare a novel nail lacquer formulation to improve the ungual and trans-ungual delivery of apremilast for the potential treatment of nail psoriasis. Nail lacquer formulation was prepared using Eudragit® S 100 as a film-forming polymer and the mixture of ethanol, ethyl acetate, and water as a solvent system. As a result of high-throughput screening studies, dexpanthenol and salicylic acid were found to be the potential penetration enhancers. After 7 days of in vitro studies, the cumulative amount of apremilast delivered by the nail lacquer formulation across the nail plate was found to be ~3-fold (0.52 ± 0.07 μg/cm2) more compared to control (nail lacquer formulation without enhancers) (0.19 ± 0.02 μg/cm2). The cumulative amount of apremilast retained in the nail plate in the case of nail lacquer formulation was 1.26 ± 0.18 μg/mg which was found to be ~2-fold more compared to control (0.57 ± 0.07 μg/mg). Human subject studies were performed on the nails of thumb and index finger of six volunteers for 15 days. As a result, the cumulative amount of apremilast retained in the free distal edge of the nail plate in the case of nail lacquer was found to be ~2-fold (0.93 ± 0.14 μg/mg) more related to control (0.41 ± 0.04 μg/mg). As a conclusion, nail lacquer formulation was found to be capable of delivering a substantial amount of apremilast into the nail apparatus; thus, it can be a potential option for the treatment of nail psoriasis.


Optical Magnetoelectric Resonance in a Polar Magnet (Fe,Zn)_{2}Mo_{3}O_{8} with Axion-Type Coupling.
We report the polarization rotation of terahertz light resonant with the magnetoelectric (ME) spin excitation in the multiferroic (Fe,Zn)_{2}Mo_{3}O_{8}. This resonance reflects the frequency dispersion of the diagonal ME susceptibility (axion term), with which we quantitatively reproduce the thermal and magnetic-field evolution of the observed polarization rotation spectra. The application of the sum rule on the extrapolated dc value of the spectral weight of the ME oscillator provides insight into the dc linear ME effect. The present finding highlights a novel optical functionality of spin excitations in multiferroics that originates from diagonal ME coupling.


Adoptive T-cell transfer therapy and oncogene-targeted therapy for melanoma: the search for synergy.
The clinical strengths of immunotherapy and small-molecule inhibitors targeting the mitogen-activated protein kinase (MAPK) pathway appear to be largely complementary for the treatment of advanced melanoma. In current practice, most patients with BRAF V600 mutant melanomas will see both modalities. Several in vitro and in vivo studies suggest that combining immunotherapy with MAPK inhibition may have synergistic effects. First, mouse models show that adoptive cell therapy (ACT) can be enhanced by vaccination. Rapid tumor destruction by vemurafenib could provide a vaccine-like stimulus to adoptively transferred T cells. Second, both in mice and in early clinical trials, melanoma metastases treated with MAPK inhibitors seem to display increased T-cell infiltrates. Third, MAPK inhibition upregulates the expression of some melanoma antigens and, therefore, may enhance T-cell recognition of vemurafenib-treated melanomas. Fourth, vemurafenib may sensitize tumor cells to immune destruction. Finally, some investigators have found that an optimal antitumor effect from MAPK inhibition is dependent on an intact host immune response. Currently, the Surgery Branch of the National Cancer Institute has initiated a phase II trial combining the BRAF inhibitor vemurafenib with ACT using tumor-infiltrating lymphocytes in patients with BRAF-mutant tumors to investigate the safety and efficacy of this combination. The proposed mechanisms for synergy between these two modalities can be complex, and their optimal combination may require testing a variety of sequences and schedules.


Adjustments of embryonic photosynthetic activity modulate seed fitness in Arabidopsis thaliana.
In this work, we dissect the physiological role of the transient photosynthetic stage observed in developing seeds of Arabidopsis thaliana. By combining biochemical and biophysical approaches, we demonstrate that despite similar features of the photosynthetic apparatus, light absorption, chloroplast morphology and electron transport are modified in green developing seeds, as a possible response to the peculiar light environment experienced by them as a result of sunlight filtration by the pericarp. In particular, enhanced exposure to far-red light, which mainly excites photosystem I, largely enhances cyclic electron flow around this complex at the expenses of oxygen evolution. Using pharmacological, genetic and metabolic analyses, we show that both linear and cyclic electron flows are important during seed formation for proper germination timing. Linear flow provides specific metabolites related to oxygen and water stress responses. Cyclic electron flow possibly adjusts the ATP to NADPH ratio to cope with the specific energy demand of developing seeds. By providing a comprehensive scenario of the characteristics, function and consequences of embryonic photosynthesis on seed vigour, our data provide a rationale for the transient building up of a photosynthetic machinery in seeds.


Effect of absorbent pads containing oregano essential oil on the shelf life extension of overwrap packed chicken drumsticks stored at four degrees Celsius.
The addition of sachets or pads containing volatile antimicrobial agents into packages has been the most successful commercial application of antimicrobials to packaging. In this study, the effect of oregano (Origanum onites) essential oil on the extension of shelf life of overwrap packed fresh chicken drumsticks was investigated. Meat exudate absorbent pads were sprayed with 5 mL of oregano essential oil at a concentration of 1.5% in distillate water. Sampling was carried out at 0, 3, 5, and 7 d of the refrigerated storage. Total viable count, psychrotrophs, pseudomonads, members of the family Enterobacteriaceae, yeasts, and lactic acid bacteria were enumerated. Physicochemical analysis and sensorial evaluation were also conducted. The shelf life of fresh chicken drumsticks was approximately 3 d. Oregano essential oil extended product shelf life by approximately 2 d. Thus, incorporation of essential oils to absorbent pads may have supplementary applications in food packaging.


Medium-term results of percutaneous, arthroscopically-assisted osteosynthesis of fractures of the tibial plateau.
We carried out percutaneous, arthroscopically- and fluoroscopically-assisted osteosynthesis of fractures of the tibial plateau in 52 patients, of whom 38 were assessed using the HSS knee score and standing radiographs. We reviewed 31 AO type-B fractures and seven type-C fractures after a mean follow-up of five years (1 to 14). Fixation was achieved using percutaneous screws and/or an external frame; 33 associated intra-articular injuries, diagnosed in 21 out of the 38 patients, were treated arthroscopically. Subjectively, 94.7% of the patients reviewed were satisfied. According to the HSS knee score 78.9% of the results were excellent, 13.2% good, 7.9% fair and none was poor. Narrowing of the joint space was found in 28.9% of the injured and 5.3% of the unaffected knees and axial deviation of 5 degrees to 10 degrees in 15.8% of the injured and 10.5% of the unaffected knees. Of the 52 fractures, reduction was incomplete in one, and in two secondary displacement occurred, of which one required corrective osteotomy. Deep-venous thrombosis occurred in four cases. The technique has proved to be safe but demanding. It facilitates diagnosis and appropriate treatment of associated intra-articular lesions.


Activation of the central histaminergic system mediates arachidonic-acid-induced cardiovascular effects.
The aim of this study was to explain the involvement of the central histaminergic system in arachidonic acid (AA)-induced cardiovascular effects in normotensive rats using hemodynamic, immunohistochemistry, and microdialysis studies. Intracerebroventricularly (i.c.v.) administered AA (0.25, 0.5, and 1.0 μmol) induced dose- and time-dependent increases in mean arterial pressure and decreased heart rate in conscious normotensive Sprague-Dawley rats. Central injection of AA (0.5 μmol) also increased posterior hypothalamic extracellular histamine levels and produced strong COX-1 but not COX-2 immunoreactivity in the posterior hypothalamus of rats. Moreover, the cardiovascular effects and COX-1 immunoreactivity in the posterior hypothalamus induced by AA (0.5 μmol; i.c.v.) were almost completely blocked by the H2 receptor antagonist ranitidine (50 and 100 nmol; i.c.v.) and partially blocked by the H1 receptor blocker chlorpheniramine (100 nmol; i.c.v.) and the H3-H4 receptor antagonist thioperamide (50 and 100 nmol; i.c.v.). In conclusion, these results indicate that centrally administered AA induces pressor and bradycardic responses in conscious rats. Moreover, we suggest that AA may activate histaminergic neurons and increase extracellular histamine levels, particularly in the posterior hypothalamus. Acting as a neurotransmitter, histamine is potentially involved in AA-induced cardiovascular effects under normotensive conditions.


Telestroke: variations in intravenous thrombolysis by spoke hospitals.
Telestroke extends stroke expertise to underserved hospitals and facilitates treatment with tissue plasminogen activator (tPA). We investigated the variability in tPA treatment rates across 2 large telestroke networks-consisting of hubs at Georgia Regents Medical Center (GRMC) and Medical University of South Carolina (MUSC) and their affiliated spoke hospitals-to identify spoke-related factors predictive of greater tPA use. Observational study of tPA treatment rate at 32 spoke hospitals within the GRMC and MUSC telestroke networks. Spokes were characterized by primary stroke center status, local stroke nurse coordinator, local neurology support, hospital size, post-tPA management strategy, whether the spoke hospitals paid to participate in the network, and whether the hub or the spoke hospital initially proposed the telemedicine linkage for consultations with a remote stroke specialist. Primary outcome was tPA treatment rate adjusted for emergency department (ED) volume. There was substantial variation in the adjusted tPA rate across spokes (range, .85-8.74 administrations/10(4) ED visits/year). Only spokes with a stroke nurse coordinator (4.75/10(4) ED visits/year versus 2.84/10(4) ED visits/year, P = .03) were associated with higher tPA use. The application of telestroke has variable results on tPA delivery in spoke hospitals. However, the presence of a stroke nurse coordinator at the spoke facilitated treatment of ischemic stroke cases with tPA.


Sport involvement, sport violence and health behaviours of Greek adolescents.
Within the context of problem-behaviour theory, this study investigated the intra-relationship between attitudes and behaviours towards exercise, sport involvement, violence in sport-related events, eating fruits, smoking and hashish or ecstasy use in a sample of Greek adolescents. Age and gender patterns are considered. Participants were 5991 Greek school pupils who responded to questionnaires assessing behaviour and attitudes towards health-related behaviours. Positive associations were found between pupils' reports of violence in sport-related events, smoking and hashish or ecstasy use on the one hand, and eating fruits and participation in sport and exercise on the other. In contrast, small positive association was observed between sport involvement and violence in sport-related events. Attitudes towards health risk behaviours were inversely related to attitudes towards health-promoting behaviours, and attitudes were positively related to corresponding behaviours. Sport involvement and regular exercise decreased but smoking and use of hashish or ecstasy increased with age. More males than females participated in organized sport and violent acts in sport-related events. Males' involvement in sport violence increased with age. Sport is a suitable context for the promotion of several health-related behaviours apart from exercise. Nevertheless, the present sport structure excludes most young people and is positively linked with sport violence. A less demanding sport context should be provided for the majority of young people, particularly for females. Sport programmes designed to promote health behaviours should be encouraged. More concentrated actions to combat sport violence are required.


Role of Temozolomide in the Treatment of Cancers Involving the Central Nervous System.
Temozolomide has been available to oncologists for over 30 years. During this time, it has become an integral part of standard therapy in patients with high-grade gliomas. Given its ability to traverse the blood-brain barrier, temozolomide has also been evaluated in other cancers that involve the central nervous system (CNS). We review its role in the management of patients with primary brain tumors, brain metastases, leptomeningeal carcinomatosis, and other selected CNS cancers. There is strong evidence that temozolomide is effective in patients with high-grade astrocytomas and oligodendrogliomas. Modest evidence supports its activity in primary CNS lymphomas and aggressive pituitary adenomas. Temozolomide, however, has minimal efficacy in a wide variety of systemic cancers. Given that concentrations of temozolomide in the CNS are only 20% of those in the blood, it is not surprising that it is generally inactive in patients with CNS metastases from solid tumors.


Assessing trends in population size of three unmarked species: A comparison of a multi-species N-mixture model and random encounter models.
Estimation of changes in abundances and densities is essential for the research, management, and conservation of animal populations. Recently, technological advances have facilitated the surveillance of animal populations through the adoption of passive sensors, such as camera traps (CT). Several methods, including the random encounter model (REM), have been developed for estimating densities of unmarked populations but require additional information. Hierarchical abundance models, such as the N-mixture model (NMM), can estimate abundances without performing additional fieldwork but do not explicitly estimate the area effectively sampled. This obscures the interpretation of its densities and requires its users to focus on relative measures of abundance instead. Hence, the main objective of our study is to evaluate if REM and NMM yield consistent results qualitatively. Therefore, we compare relative trends: (i) between species, (ii) between years and (iii) across years obtained from annual density/abundance estimates of three species (fox, wild boar and red deer) in central Spain monitored by a camera trapping network for five consecutive winter periods. We reveal that NMM and REM provided density estimates in the same order of magnitude for wild boar, but not for foxes and red deer. Assuming a Poisson detection process in the NMM was important to control for inflation of abundance estimates for frequently detected species. Both methods consistently ranked density/abundance across species (between species trend), but did not always agree on relative ranks of yearly estimates within a single population (between years trend), nor on its linear population trends across years (across years trend). Our results suggest that relative trends are generally consistent when the range of variability is large, but can become inconsistent when the range of variability is smaller.


Work with video display terminals among office employees. II. Physical exposure factors.
This is the second report in a major epidemiologic health investigation on work with a video display terminal (VDT). The first study showed that VDT operators reported more eye discomfort than a reference group not employed in VDT work and that women reported more eye discomfort, musculoskeletal complaints, headache, and skin disorders than men, regardless of whether they worked with a VDT or not. The present report contains the results of the occupational hygiene measurements (indoor climate, lighting and electrostatic conditions). Considerable differences were found between VDT operators and referents and also between sexes. Indications were obtained of a possible relationship between eye discomfort and luminance ratios in the working field of vision. Otherwise, no association could be established between occupational exposure factors and subjective eye discomfort, musculoskeletal complaints, headache, or skin disorders.


Hyperinflation is associated with lower sleep efficiency in COPD with co-existent obstructive sleep apnea.
Prior research has shown that individuals with obstructive lung disease are at risk for sleep fragmentation and poor sleep quality. We postulated that patients with chronic obstructive pulmonary disease (COPD) and obstructive sleep apnea (known as overlap syndrome) who have more severe lung disease, as measured by lung hyperinflation (inspiratory capacity/total lung capacity), would have greater sleep disturbances independent of traditional measures of sleep apnea. We performed a retrospective chart review of consecutive patients evaluated and treated in an academic pulmonary clinic for overlap syndrome. Pulmonary function tests and polysomnogram data were collected. Thirty patients with overlap syndrome were included in the analysis. We found significant univariable associations between sleep efficiency and apnea/hypopnea index (beta = -0.285, p = 0.01) and between sleep efficiency and lung hyperinflation (beta = 0.654, p = 0.03). Using multivariable linear regression, the relationship between sleep efficiency and lung hyperinflation remained significant (beta = 1.13, p = 0.02) after adjusting for age, sex, body mass index, apnea/hypopnea index, FEV(1)% predicted, oxygen saturation nadir, medications, and cardiac disease. We conclude that increased severity of hyperinflation is associated with worse sleep efficiency, independent of apnea and nocturnal hypoxemia. The mechanisms underlying this observation are uncertain. We speculate that therapies aimed at reducing lung hyperinflation may improve sleep quality in patients with overlap syndrome.