Second hand smoke and risk assessment: what was in it for the tobacco industry?
To describe how the tobacco industry attempted to trivialise the health risks of second hand smoke (SHS) by both questioning the science of risk assessment of low dose exposure to other environmental toxins, and by comparing SHS to such substances about which debate might still exist. Analysis of tobacco industry documents made public as part of the settlement of litigation in the USA (Minnesota trial and the Master Settlement Agreement) and available on the internet. Search terms included: risk assessment, low dose exposure, and the names of key players and organisations. The tobacco industry developed a well coordinated, multi-pronged strategy to create doubt about research on exposure to SHS by trying to link it to the broader discussion of risk assessment of low doses of a number of toxins whose disease burden may still be a matter of scientific debate, thus trying to make SHS their equivalent; and by attempting, through third party organisations and persons, to impugn the agencies using risk assessment to establish SHS as a hazard.


The relative importance of disturbance and exotic-plant abundance in California coastal sage scrub.
Many ecosystems of conservation concern require some level of disturbance to sustain their species composition and ecological function. However, inappropriate disturbance regimes could favor invasion or expansion of exotic species. In southern California coastal sage scrub (CSS) fire is a natural disturbance, but because of human influence, frequencies may now be unnaturally high. Other anthropogenic disturbances such as grazing also occur in reserve areas. Managers charged with imposing or tolerating fire or other disturbance within their reserves are concerned that habitat quality may be degraded by an increasing abundance of exotic plants. We used vegetation monitoring data from Camp Pendleton, California, USA, to assess the correlation between past disturbances (frequent fire, agriculture, or grazing and mechanical disturbances) and current exotic species abundance in CSS. We found that disturbance history was only modestly related to exotic abundance overall, but fire frequency showed the strongest association. We also examined whether cover and richness of various native plant life forms (woody species, perennial herbs, and annual herbs) were more strongly influenced by disturbance history or by exotic-plant abundance. Native plant responses varied among life forms, but woody species and annual herbs were generally more strongly and negatively associated with exotic abundance than with disturbance. Effective CSS conservation will require developing means to curb the negative impacts of exotic plants, which may abound with or without severe or recent disturbance. Additionally, more focus should be given to understory herbs showing sensitivity to invasion. Though understudied, native herbs comprise the greatest portion of plant diversity in CSS and are critical to preservation of the community as a whole.


Assembly of polyethyleneimine in the hexagonal mesophase of nonionic surfactant: effect of pH and temperature.
We investigate the dispersion of a pH responsive polymer, polyethyleneimine, PEI, in a hexagonal (H(1)) mesophase of a nonionic surfactant, C(12)E(9), and water, at pH ranging from basic (pH = 12.8) to acidic (pH = 1). While the C(12)E(9)/H(2)O phase behavior is independent of pH, we demonstrate that, in the PEI/C(12)E(9)/H(2)O system, changing the pH influences PEI-C(12)E(9) interactions, and thus, influences the isotropic-H(1) phase transition. With decrease in pH, there is increasing protonation of the PEI chain, and consequently, the chain extends. We show, using a combination of SAXs, optical microscopy and visual experiments, that the inclusion of PEI in a 1:1 surfactant-water mixture, lowers the hexagonal-isotropic transition temperature, T(HI). At higher pH = 12.8, T(HI) shows a pronounced decrease from 50 to 13 °C on addition of PEI, and the PEI/C(12)E(9)/H(2)O system forms a transparent gel. At pH = 1, we observe qualitatively different behavior and an opaque gel forms below T(HI) = 25 °C. The isotropic-H(1) transition, in turn, influences the phase separation of PEI chains from the C(12)E(9)/H(2)O system. 2D NMR ROESY data provides evidence that there are strong surfactant-PEI interactions at high pH that significantly reduce at lower pH. The NMR data is in accord with molecular dynamics simulations that show that surfactants strongly aggregate with unprotonated PEI chains, but not with fully protonated chains; thus, in this system, the pH controls a cascade of microstructural organization: increasing pH decreases chain protonation and increases polymer-surfactant interactions, resulting in suppression of the isotropic-H(1) transition to lower temperatures, thus, influencing the phase separation of PEI from the surfactant/water system.


Catalyst and electrolyte synergy in Li-O2 batteries.
Understanding the interactions between catalyst and electrolyte in Li-O2 systems is crucial to improving capacities, efficiencies, and cycle life. In this study, supported noble metal catalysts Pt/C, Pd/C, and Au/C were paired with popular Li-O2 electrolyte solvents dimethoxyethane (DME), tetraglyme (TEGDME), and dimethyl sulfoxide (DMSO). The effects of these combinations on stability, kinetics, and activity were assessed. We show evidence of a synergistic effect between Pt and Pd catalysts and a DMSO-based electrolyte which enhances the kinetics of oxygen reduction and evolution reactions. DME and TEGDME are more prone to decomposition and less kinetically favorable for oxygen reduction and evolution than DMSO. While the order of oxygen reduction onset potentials with each catalyst was found to be consistent across electrolyte (Pd > Pt > Au), larger overpotentials with DME and TEGDME, and negative shifts in onset after only five cycles favor the stability of a DMSO electrolyte. Full cell cycling experiments confirm that catalyst-DMSO combinations produce up to 9 times higher discharge capacities than the same with TEGDME after 20 cycles (∼707.4 vs. 78.8 mA h g(-1) with Pd/C). Ex situ EDS and in situ EIS analyses of resistive species in the cathode suggest that improvements in capacity with DMSO are due to a combination of greater electrolyte conductivity and catalyst synergies. Our findings demonstrate that co-selection of catalyst and electrolyte is necessary to exploit chemical synergies and improve the performance of Li-O2 cells.


LightGBM: An Effective and Scalable Algorithm for Prediction of Chemical Toxicity-Application to the Tox21 and Mutagenicity Data Sets.
Machine learning algorithms have attained widespread use in assessing the potential toxicities of pharmaceuticals and industrial chemicals because of their faster speed and lower cost compared to experimental bioassays. Gradient boosting is an effective algorithm that often achieves high predictivity, but historically the relative long computational time limited its applications in predicting large compound libraries or developing in silico predictive models that require frequent retraining. LightGBM, a recent improvement of the gradient boosting algorithm, inherited its high predictivity but resolved its scalability and long computational time by adopting a leaf-wise tree growth strategy and introducing novel techniques. In this study, we compared the predictive performance and the computational time of LightGBM to deep neural networks, random forests, support vector machines, and XGBoost. All algorithms were rigorously evaluated on publicly available Tox21 and mutagenicity data sets using a Bayesian optimization integrated nested 10-fold cross-validation scheme that performs hyperparameter optimization while examining model generalizability and transferability to new data. The evaluation results demonstrated that LightGBM is an effective and highly scalable algorithm offering the best predictive performance while consuming significantly shorter computational time than the other investigated algorithms across all Tox21 and mutagenicity data sets. We recommend LightGBM for applications of in silico safety assessment and also other areas of cheminformatics to fulfill the ever-growing demand for accurate and rapid prediction of various toxicity or activity related end points of large compound libraries present in the pharmaceutical and chemical industry.


Genetic variability of bioactive compounds and selection for nutraceutical quality in kola [Cola nitida (Vent) Schott. and Endl.].
Cola nitida known as Kola serves as flavouring ingredient in the food industry and is also of great importance during traditional rites in Africa. Despite the well-known pharmaceutical values of the species, efforts to develop improved varieties with enhanced nutraceutical quality is limited due to unavailability of information on variation of genotypes in bioactive compounds in the nuts. The objectives of this research were to evaluate 25 genotypes of kola for bioactive contents, determine relationship between nutritional and phenolic traits and to identify kola genotypes with good nutraceutical quality for use in developing improved varieties. The kola genotypes were established in the field using a randomized complete block design with three replicates. Nuts harvested from the blocks, were bulked and used to quantify soluble and insoluble sugars, total protein, moisture, ash, fats, pH, polyphenols, tannins and flavonoids using completely randomized design with three replicates in the laboratory. Data were analysed by combining Analysis of Variance, Kruskal-Wallis test, correlation test and multivariate analysis. Significant variations (P < 0.05) were observed among the kola genotypes for the bioactive traits evaluated. Phenolic traits were more heritable than nutritional traits. Although not significant (P > 0.05), correlation between nutritional and phenolic traits was negative, whereas correlations among nutritional traits were weak. On the contrary, significant and positive correlations (P < 0.05) were observed among phenolic traits. The hierarchical clustering analysis based on the traits evaluated grouped the 25 genotypes of kola evaluated into four clusters. Genotypes A12, JB4, JB19, JB36, P2-1b, and P2-1c were identified as potential parental lines for phenolic traits selection in kola whereas genotypes A10, Club, Atta1 and JB10 can be considered for soluble and insoluble sugar-rich variety development. These findings represent an important step towards improving nutritional and nutraceutical quality of kola nuts.


Free space optical communications through clouds: analysis of signal characteristics.
Free space optical communications (FSOC) is a method by which one transmits a modulated beam of light through the atmosphere for broadband applications. Fundamental limitations of FSOC arise from the environment through which light propagates. This work addresses transmitted light beam dispersion (spatial, angular, and temporal dispersion) in FSOC operating as a ground-to-air link when clouds exist along the communications channel. Light signals (photons) transmitted through clouds will interact with the cloud particles. Photon-particle interaction causes dispersion of light signals, which has significant effects on signal attenuation and pulse spread. The correlation between spatial and angular dispersion is investigated as well, which plays an important role on the receiver design. Moreover, the paper indicates that temporal dispersion (pulse spread) and energy loss strongly depend on the aperture size of the receiver, the field-of-view (FOV), and the position of the receiver relative to the optical axis of the transmitter.


Homeopathic treatment of patients with migraine: a prospective observational study with a 2-year follow-up period.
The objective of this study was to evaluate treatment details and possible effects of an individualized homeopathic treatment in patients with migraine in usual care. This was a prospective multicenter observational study. Consecutive patients beginning homeopathic treatment in primary care practices were evaluated over 2 years using standardized questionnaires. The data recorded included diagnoses (International Classification of Diseases, Ninth Revision) and current complaints, including their severity (numeric rating scale = 0-10), health-related quality of life (QoL, 36-item Short-Form Health Survey), medical history, consultations, homeopathic and conventional treatments, as well as other health service use. Two hundred and twelve (212) adults (89.2% women), mean age 39.4 +/- 10.7 years were treated by 67 physicians. Patients had suffered from migraine for a period of 15.2 +/- 10.9 years. Most patients (90.0%) were conventionally pretreated. The physician workload included taking the initial patient history (120 +/- 45 minutes), case analysis (40 +/- 47 minutes), and follow-ups (7.3 +/- 7.0, totaling 165.6 +/- 118.8 minutes). Patients received 6.2 +/- 4.6 homeopathic prescriptions. Migraine severity showed marked improvement with a large effect size (Cohen's d = 1.48 after 3 months and 2.28 after 24 months. QoL improved accordingly (Mental Component Score and Physical Component Score after 24 months: 0.42 and 0.45). The use of conventional treatment and health services decreased markedly. In this observational study, patients seeking homeopathic treatment for migraine showed relevant improvements that persisted for the observed 24 month period. Due to the design of this study, however, it does not answer the question as to whether the effects are treatment specific or not.


Learning amid controversy: prostate cancer knowledge and screening practices among US medical students.
No studies have examined medical students' recommendation and use of prostate-specific antigen (PSA) testing and digital rectal exam (DRE) to screen for prostate cancer. We hypothesized that students' race and extent of training on these techniques would be associated with their administration of them. We analyzed multiinstitutional longitudinal data from a cohort of 2181 medical students in the class of 2003. We queried students' health behavior, their knowledge of prostate cancer racial disparities, their frequency of performing a PSA test or a DRE on a man 50 years of age or older (senior year only), the perceived relevance of such services to their future practice, and their training on PSA and DRE. We examined predictors of students' administering PSA and DRE tests to patients during the senior year and changes in the predictors over time. Respectively, 27% and 34% of students reported using the PSA and DRE "usually/always" during their senior year. Black students reported administering the PSA test more often than did students of other races, but race was not a significant predictor of PSA screening after controlling for personal healthy behavior. High perceived relevance to future practice and extensive training on PSA were most strongly associated with administration of PSA. The association between healthy personal behavior and PSA administration confounded the association between race and PSA screening. These results may help explain differences in prostate cancer screening among physicians and help medical educators tailor their curricula on prostate cancer screening.


The Perioperative Use of Dexmedetomidine in Pediatric Patients with Congenital Heart Disease: An Analysis from the Congenital Cardiac Anesthesia Society-Society of Thoracic Surgeons Congenital Heart Disease Database.
Dexmedetomidine is a selective α-2 receptor agonist with a sedative and cardiopulmonary profile that makes it an attractive anesthetic for pediatric patients with congenital heart disease (CHD). Although several smaller, single-center studies suggest that dexmedetomidine use is gaining traction in the perioperative setting in children with CHD, there are limited multicenter data, with little understanding of the variation in use across age ranges, procedural complexity, and centers. The aim of this study was to use the Congenital Cardiac Anesthesia Society-Society of Thoracic Surgeons (CCAS-STS) registry to describe patient- and center-level variability in the use of dexmedetomidine in the perioperative setting in children with heart disease. To describe the use of dexmedetomidine in patients for CHD surgery, we analyzed all index cardiopulmonary bypass operations entered in the CCAS-STS database from 2010 to 2013. Patient and operative characteristics were compared between those who received intraoperative dexmedetomidine and those who did not. Selective outcomes associated with dexmedetomidine use were also described. Of the 12,142 operations studied, 3600 (29.6%) received perioperative dexmedetomidine (DEX) and 8542 did not receive the drug (NoDEX). Patient characteristics were different between the 2 groups with the DEX group generally exhibiting both lower patient and procedural risk factors. Patients who received dexmedetomidine were more likely to have a lower level of Society of Thoracic Surgeons mortality complexity than patient who did not receive it. Consistent with their overall lower risk profile, children in the DEX group also demonstrated improved outcomes compared with patients who did not receive dexmedetomidine. We described the growing use of dexmedetomidine in children anesthetized for surgical repair of CHD. Dexmedetomidine appears to be preferentially given to older and larger children who are undergoing less complex CHD surgery. We believe that the data provided in this study are the largest investigating the use of an anesthetic drug in CHD patients. It is also the first analysis of the anesthesia data in the CCAS-STS Congenital Heart Disease database.


Liposomal 2-Methoxyestradiol Nanoparticles for Treatment of Uterine Leiomyoma in a Patient-Derived Xenograft Mouse Model.
Uterine leiomyomas represent a challenging problem with limited medical treatment options. The anti-tumor agent 2-methoxyestradiol (2-ME) shows promising results but its efficacy is limited by inadequate pharmacokinetics. We previously demonstrated that 2-ME nanoparticles can be successfully formulated and that they show improved in vitro anti-leiomyoma cell activity. Here, we examined the effects of the in vivo delivery of 2-ME nanoparticles in a patient-derived xenograft (PDX) leiomyoma mouse model. Patient-derived leiomyoma tumor tissues were xenografted subcutaneously in estrogen/progesterone pretreated immunodeficient NOG mice. Animals (n = 12) were treated with liposomal 2-ME nanoparticles by intra-peritoneal (IP) injection (50 mg/kg/dose, three times weekly) or control for 28 days. Tumor volume was measured weekly by calipers and prior to sacrifice by ultrasound. In addition, the expression of the cell proliferation marker Ki67 and the apoptosis marker cleaved caspase-3 in tumor tissues after treatment were measured by immunohistochemistry. Liposomal 2-ME treatment was associated with a significant tumor growth inhibition (30.5% less than controls as early as 2 weeks, p = 0.025). In addition, injections of liposomal 2-ME inhibited the expression of the proliferation marker Ki67 (55.8% reduction, p < 0.001). Furthermore, liposomal 2-ME treatment was associated with a 67.5% increase of cleaved caspase-3 expression of increase (p = 0.048). Our findings suggest that liposomal nanoparticle formulation can successfully deliver 2-ME and can be a promising therapeutic strategy for uterine leiomyoma. Further characterization of the liposomal-2ME, including pharmacokinetics, maximal tolerated dose, and safety, is needed in preclinical models prior to clinical trials.


Identification of cinnabarinic acid as a novel endogenous aryl hydrocarbon receptor ligand that drives IL-22 production.
The aryl hydrocarbon receptor (AHR) binds to environmental toxicants including synthetic halogenated aromatic hydrocarbons and is involved in a diverse array of biological processes. Recently, the AHR was shown to control host immunity by affecting the balance between inflammatory T cells that produce IL-17 (Th17) and IL-22 versus regulatory T cells (Treg) involved in tolerance. While environmental AHR ligands can mediate this effect, endogenous ligands are likely to be more relevant in host immune responses. We investigated downstream metabolites of tryptophan as potential AHR ligands because (1) tryptophan metabolites have been implicated in regulating the balance between Th17 and Treg cells and (2) many of the AHR ligands identified thus far are derivatives of tryptophan. We characterized the ability of tryptophan metabolites to bind and activate the AHR and to increase IL-22 production in human T cells. We report that the tryptophan metabolite, cinnabarinic acid (CA), is an AHR ligand that stimulates the differentiation of human and mouse T cells producing IL-22. We compare the IL-22-stimulating activity of CA to that of other tryptophan metabolites and define stimulation conditions that lead to CA production from immune cells. Our findings link tryptophan metabolism to AHR activation and define a novel endogenous AHR agonist with potentially broad biological functions.


Spectral simplicity of apparent complexity. II. Exact complexities and complexity spectra.
The meromorphic functional calculus developed in Part I overcomes the nondiagonalizability of linear operators that arises often in the temporal evolution of complex systems and is generic to the metadynamics of predicting their behavior. Using the resulting spectral decomposition, we derive closed-form expressions for correlation functions, finite-length Shannon entropy-rate approximates, asymptotic entropy rate, excess entropy, transient information, transient and asymptotic state uncertainties, and synchronization information of stochastic processes generated by finite-state hidden Markov models. This introduces analytical tractability to investigating information processing in discrete-event stochastic processes, symbolic dynamics, and chaotic dynamical systems. Comparisons reveal mathematical similarities between complexity measures originally thought to capture distinct informational and computational properties. We also introduce a new kind of spectral analysis via coronal spectrograms and the frequency-dependent spectra of past-future mutual information. We analyze a number of examples to illustrate the methods, emphasizing processes with multivariate dependencies beyond pairwise correlation. This includes spectral decomposition calculations for one representative example in full detail.


The BMP1 gene is essential for pathogenicity in the gray mold fungus Botrytis cinerea.
In Magnaporthe grisea, a well-conserved mitogen-activated protein (MAP) kinase gene, PMK1, is essential for fungal pathogenesis. In this study, we tested whether the same MAP kinase is essential for plant infection in the gray mold fungus Botrytis cinerea, a necrotrophic pathogen that employs infection mechanisms different from those of M. grisea. We used a polymerase chain reaction-based approach to isolate MAP kinase homologues from B. cinerea. The Botrytis MAP kinase required for pathogenesis (BMP) MAP kinase gene is highly homologous to the M. grisea PMK1. BMP1 is a single-copy gene. bmp1 gene replacement mutants produced normal conidia and mycelia but were reduced in growth rate on nutrient-rich medium. bmp1 mutants were nonpathogenic on carnation flowers and tomato leaves. Re-introduction of the wild-type BMP1 allele into the bmp1 mutant restored both normal growth rate and pathogenicity. Further studies indicated that conidia from bmp1 mutants germinated on plant surfaces but failed to penetrate and macerate plant tissues. bmp1 mutants also appeared to be defective in infecting through wounds. These results indicated that BMP1 is essential for plant infection in B. cinerea, and this MAP kinase pathway may be widely conserved in pathogenic fungi for regulating infection processes.


Anatomical optical coherence tomography for long-term, portable, quantitative endoscopy.
In this paper, we report on anatomical optical coherence tomography, a catheter-based optical modality designed to provide quantitative sectional images of internal hollow organ anatomy over extended observational periods. We consider the design and performance of an instrument and its initial intended application in the human upper airway for the characterization of obstructive sleep apnea (OSA). Compared with current modalities, the technique uniquely combines quantitative imaging, bedside operation, and safety for use over extended periods of time with no cumulative dose limit. Our experiments show that the instrument is capable of imaging subjects during sleep, and that it can record dynamic changes in airway size and shape.


Phosphorylation of the MET receptor on juxtamembrane tyrosine residue 1001 inhibits its caspase-dependent cleavage.
The MET tyrosine kinase is the hepatocyte growth factor/scatter factor (HGF/SF) receptor, which elicits multiple biological responses in epithelial cells, including cell survival. We previously demonstrated that in stress conditions, the MET receptor is cleaved by caspases within its juxtamembrane region, generating a pro-apoptotic intracellular fragment of 40 kDa. The caspase cleavage site at aspartic acid D1000 is adjacent to tyrosine Y1001, which when phosphorylated upon MET activation, is involved in CBL recruitment, allowing receptor ubiquitination and down regulation. Scanning mutagenesis of the MET juxtamembrane region led us to demonstrate that V999 and D1000 are essential for the caspase cleavage, while D1000 and Y1001 are essential for CBL recruitment. By examining whether overlapping of these sites leads to a functional interference, an inverse relationship was found between generation of p40 MET and phosphorylation of MET, with a direct involvement of phosphorylated Y1001 in protecting MET against its caspase cleavage. A molecular modeling analysis of caspase 3 interaction with the juxtamembrane region of MET confirmed that phosphorylation of this tyrosine is not compatible with its recognition by active caspase 3. These data demonstrate a direct protection mechanism of an activated phosphorylated MET receptor, against its caspase-dependent cleavage.


Travel to school and physical activity levels in 9-10 year-old UK children of different ethnic origin; Child Heart and Health Study in England (CHASE).
Travel to school may offer a convenient way to increase physical activity levels in childhood. We examined the association between method of travel to school and physical activity levels in urban multi-ethnic children. 2035 children (aged 9-10 years in 2006-7) provided data on their usual method of travel to school and wore an Actigraph-GT1M activity monitor during waking hours. Associations between method of travel and mean level of physical activity (counts per minute [CPM], steps, time spent in light, moderate or vigorous activity per day) were examined in models adjusted for confounding variables. 1393 children (69%) walked or cycled to school; 161 (8%) used public transport and 481 (24%) travelled by car. White European children were more likely to walk/cycle, black African Caribbeans to travel by public transport and South Asian children to travel by car. Children travelling by car spent less time in moderate to vigorous physical activity (-7 mins, 95%CI-9,-5), and had lower CPM (-32 CPM, 95%CI-44,-19) and steps per day (-813 steps, 95%CI,-1043,-582) than walkers/cyclists. Pupils travelling by public transport had similar activity levels to walkers/cyclists. Lower physical activity levels amongst car travellers' were especially marked at travelling times (school days between 8-9 am, 3-5 pm), but were also evident on weekdays at other times and at weekends; they did not differ by gender or ethnic group. Active travel to school is associated with higher levels of objectively measured physical activity, particularly during periods of travel but also at other times. If children travelling by car were to achieve physical activity levels (steps) similar to children using active travel, they would increase their physical activity levels by 9%. However, the population increase would be a modest 2%, because of the low proportion of car travellers in this urban population.


Role of perceptual organization in chromatic induction.
Color matches between two small patches were made in a display containing ten larger regions of different chromaticities. The spatial organization of the ten regions was varied while keeping constant the immediate surround of each patch as well as the space-average chromaticity of the entire stimulus. Different spatial arrangements were designed to alter the perceptual organization inferred by the observer without changing the ensemble of chromaticities actually in view. For example, one arrangement of the ten regions was consistent with five surfaces under two distinct illuminations, with one edge within the display (an "apparent illumination edge") dividing the stimulus into two areas, one under illuminant A and the other under illuminant C. Another spatial arrangement had the ten regions configured to induce an observer to infer ten surfaces under a single illumination. When the ten regions were arranged with an apparent illumination edge, the patch within the area of illuminant C was perceived as bluer than when the same patch and immediate surround were presented without an apparent illumination edge. The results are accounted for by positing that observers group together regions sharing the same inferred illumination, with a consequent effect on color perception: A fixed patch-within-surround shifts in hue and saturation toward the perceived illumination. We suggest that the change in color perception in a complex scene that results from a difference in real illumination may be caused by the inferred illumination at the perceptual level, not directly by the physical change in the light absorbed by photoreceptors.


How the COVID-19 infection tsunami revolutionized the work of respiratory physiotherapists: an experience from Northern Italy.
Due to COVID-19 outbreak, to lighten the burden of acute and critical care hospitals, some respiratory rehabilitation departments have been used to host patients with COVID-19 in the post-acute phase. This new and unexpected situation required a change of roles and scheduling of the rehabilitation teams. In this manuscript we describe the unexpected and urgent organizational change of the Cardio-Pulmonary Rehabilitation (CPR) service during the COVID-19 emergency in a Northern Italian rehabilitation hospital, focusing on the Respiratory Physiotherapists' (RPTs) role. A quick three-days complete reorganization of the entire hospital was needed. A COVID-19 care team including a multidisciplinary panel of physicians, nurses, and RPTs was quickly performed to manage 90 beds for post acute patients with COVID-19. Within the team, the RPTs changed their shifts, so as to be available 16h per day, 7 days out of 7. Remodelled tasks in charge of RPTs were: oxygen therapy daily monitoring, non invasive ventilation (NIV) and continuous positive airways pressure (CPAP) delivery, pronation and postural changes to improve oxygenation, reconditioning with leg/arm cranking and exercises, initial and final patients' functional assessment by short-physical performance battery (SPPB) and 1-minute sit-to-stand test (1-STS) to evaluate motor conditions and exercise-induced oxygen desaturation. Three "what-to-do" algorithms were developed to guide: i) oxygen de-escalation by reducing inhaled fraction of oxygen (FiO2); ii) oxygenation improvement through the use of Venturi mask; iii) reconditioning and physical activity. One-hundred seventy patients were treated in one month. As main topics, RPTs have been involved in oxygen therapy management in almost a third of the admitted patients, reconditioning exercises in 60% of the cases, and initial and final functional motor capacity assessment in all patients. Details of activities performed by the RPT in one typical working day are also shown. Our reorganization has exploited the professional skills and clinical expertise of the RPTs. This re-organization can provide practical insights to other facilities that are facing this crisis, and may be a starting point for implementing post-COVID-19 rehabilitation. Future studies will have to improve and review this organization.


[Comparative study of Vitek-2™ AIX versus Vitek-2™ PC: phenotypic resistance of enterobacteriaceae to β-lactams].
Vitek-2™ AIX versus Vitek-2™ PC have different rules for phenotypic interpretation. The aim of this study is to ensure that the raw results determined by these two versions of Vitek-2™ allow biologists to conclude to the same resistance phenotype, but also to evaluate their own phenotypic interpretation system (advanced expert system). A total of 251 strains of Enterobacteriaceae of different groups and phenotypes was tested. Each strain was studied simultaneously on both types of Vitek-2™ from the same calibrated inoculum. We then compared their resistance phenotype to beta-lactams. For strains not producing ESBL or CHN, the biologist concluded in 99.3% of cases to the same resistance phenotype by interpreting the raw results of Vitek-2™ AIX versus PC. The phenotypic interpretation of biologist is different from the Vitek-2™ in respectively 40% versus 43% of cases for AIX and PC versions. For multi-resistant strains, the biologist concluded in 100% of cases to the same resistance phenotype by interpreting the raw results of Vitek-2™ AIX versus PC. In 51.5% of cases the biologist use the disk diffusion method (DD). The results of this technique put forward 29% discrepancy with the two types of Vitek-2™. Finally, when Vitek-2™ claims the presence of an ESBL alone, this result is routinely confirmed by DD. The switch from Vitek-2™ AIX to Vitek-2™ PC does not alter the results of the phenotypic interpretation of biologist.


Coffee, Cake & Culture: Evaluation of an art for health programme for older people in the community.
Arts for health initiatives and networks are being developed in a number of countries and an international literature is emerging on the evidence of their benefits to people's health, wellbeing and quality of life. Engagement in cultural and creative arts by older people can increase their morale and self-confidence and provides opportunities for social connection. Museums and galleries are increasingly required to justify their expenditure, reach and impact and some are working in partnership with local councils, hospitals, schools and communities to improve access to their collections. There is a body of literature emerging that describes such initiatives but empirical evidence of their benefits is less developed. This article reports an evaluation of an art for health initiative - Coffee, Cake & Culture organised and delivered by Whitworth Art Gallery and Manchester Museum in 2012 for older people living in a care home and a supported living facility. The study has identified the benefits and impacts of the arts for health programme and its feasibility for older people, with or without diagnosed memory loss - dementia, living in a care home or supported living facility and their care staff. The findings demonstrate there were benefits to the older people and their care staff in terms of wellbeing, social engagement, learning, social inclusion and creativity. These benefits were immediate and continued in the short term on their return home. The majority of older people and care staff had not previously been to the art gallery or museum and the programme encouraged creative arts and cultural appreciation which promoted social inclusion, wellbeing and quality of life. The programme is feasible and important lessons were identified for future planning. Further research involving partnerships of researchers, arts for health curators, artists, care staff, older people and their families is warranted.


Enzymatic prenylation and oxime ligation for the synthesis of stable and homogeneous protein-drug conjugates for targeted therapy.
Targeted therapy based on protein-drug conjugates has attracted significant attention owing to its high efficacy and low side effects. However, efficient and stable drug conjugation to a protein binder remains a challenge. Herein, a chemoenzymatic method to generate highly stable and homogenous drug conjugates with high efficiency is presented. The approach comprises the insertion of the CaaX sequence at the C-terminal end of the protein binder, prenylation using farnesyltransferase, and drug conjugation through an oxime ligation reaction. MMAF and an EGFR-specific repebody are used as the antitumor agent and protein binder, respectively. The method enables the precisely controlled synthesis of repebody-drug conjugates with high yield and homogeneity. The utility of this approach is illustrated by the notable stability of the repebody-drug conjugates in human plasma, negligible off-target effects, and a remarkable antitumor activity in vivo. The present method can be widely used for generating highly homogeneous and stable PDCs for targeted therapy.


SABA Reliance Questionnaire (SRQ): Identifying Patient Beliefs Underpinning Reliever Overreliance in Asthma.
Patient overreliance on short-acting beta2 agonists (SABA), with concomitant underuse of inhaled corticosteroids (ICS), is associated with poor asthma control and increased risk of asthma attacks. To develop and validate a brief questionnaire to elicit patients' perceptions of SABA (eg, belief that asthma is best managed by SABA alone) that could lead them to be overly reliant on SABA. The 5-item SABA Reliance Questionnaire (SRQ) was adapted from the well-validated Beliefs about Medicines Questionnaire assessing patient perceptions of the importance of, and necessity for, SABA in managing their asthma. The psychometric properties of the questionnaire were studied using Amazon Mechanical Turk, an online survey platform, in 446 people with self-reported asthma. Internal reliability and criterion-related validity were assessed on the basis of relationships between SRQ scores and other variables, including self-reported adherence to ICSs and perceived importance of reliever inhalers. Internal reliability was good with Cronbach α = 0.74. Criterion-related validity was demonstrated by an inverse correlation between SRQ scores and self-reported adherence to ICSs (r = -0.291; P < .0001), and significant correlation between SRQ scores and perceived reliever importance (r = 0.216; P < .0001), as well as by significant differences in SRQ scores between those with high and those with low self-reported ICS adherence (adherence to ICS t = 4.825; P < .0001). The SRQ demonstrated acceptable internal reliability, and criterion validity, supporting its potential use as a pragmatic tool for identifying patients whose beliefs are indicative of overreliance on SABA for asthma.


Superconducting series nanowire detector counting up to twelve photons.
We demonstrate a superconducting photon-number-resolving detector capable of resolving up to twelve photons at telecommunication wavelengths. It is based on a series array of twelve superconducting NbN nanowire elements, each connected in parallel with an integrated resistor. The photon-induced voltage signals from the twelve elements are summed up into a single readout pulse with a height proportional to the detected photon number. Thirteen distinct output levels corresponding to the detection of n = 0-12 photons are observed experimentally. A detailed analysis of the linearity and of the excess noise shows the potential of scaling to an even larger dynamic range.


Risk assessment of human exposure to bioaccessible phthalate esters via indoor dust around the Pearl River Delta.
There is limited information on the bioaccessible fractions of phthalate esters in indoor dust in order to estimate human exposure. In the present study, workplace dust and settled house dust samples from Hong Kong, Shenzhen, and Guangzhou, the three major cities scattered around the Pearl River Delta (PRD) were collected. Chemical analyses showed that the phthalates in workplace dust ranged from 144 to 1810 μg/g, with dust from shopping malls containing the highest level, and in home dust ranged from 181 to 9240 μg/g. The most abundant phthalate ester found was bis(2-ethylhexyl) phthalate (DEHP) in both workplace dust and home dust, followed by di-n-butyl phthalate (DBP) and di-iso-butyl phthalate (DIBP). Principal Components Analysis (PCA) indicated that indoor dust around PRD showed similar phthalate esters patterns of composition. A significant correlation was observed between total phthalate esters concentrations in home dust and the number of year of house construction (p < 0.05). The oral bioaccessibility of phthalate esters in indoor dust ranged from 10.2% (DEHP) to 32% (DMP). Risk assessment indicated that the dominant exposure routes varied in different phthalate esters exposure profiles and the dermal contact exposure pathway was identified as an important route for indoor DEHP exposure.


Widening inequalities in self-rated health by material deprivation? A trend analysis between 2001 and 2011 in Germany.
Research on inequalities in health has shown a strong association between the lack of standard of living (defined as material deprivation) and self-rated health (SRH). In this study, we sought to further examine this association in a trend analysis of relative and absolute inequalities in SRH as defined by material deprivation in Germany. Data were obtained from the German Socio-Economic Panel (GSOEP) between 2001 and 2011. Material deprivation was measured on the basis of 11 living standard items missing due to financial reasons. We used the relative index of inequality (RII) and slope index of inequality (SII) to measure inequalities in SRH by material deprivation, calculating pooled interval logistic regression with robust SEs. Stepwise models were estimated, including demographic and socioeconomic variables, to assess their inter-relation with inequalities in SRH by material deprivation. The results showed a steady increase in poor SRH over the 10-year duration of the study. A quadratic (inverted U-shaped) trend was observed in material deprivation in the standards of living, which rose from 2001 to 2005, and then declined in 2011. A similar but non-significant trend was found in relative and absolute inequalities in SRH by material deprivation, which increased from 2001 to 2005 and then declined. Inequality in SRH by material deprivation was relatively stable; however, an observed quadratic trend coincided with active and passive labour market reforms in Germany in early 2005.


Long-term exercise maintenance in COPD via telerehabilitation: a two-year pilot study.
Introduction Pulmonary rehabilitation (PR) is an integral part of the management of chronic obstructive pulmonary disease (COPD). However, many patients do not access or complete PR, and long-term exercise maintenance has been difficult to achieve after PR. This study aimed to investigate feasibility, long-term exercise maintenance, clinical effects, quality of life and use of hospital resources of a telerehabilitation intervention. Methods Ten patients with COPD were offered a two-year follow-up via telerehabilitation after attending PR. The intervention consisted of home exercise, telemonitoring and self-management via a webpage combined with weekly videoconferencing sessions. Equipment included a treadmill, a pulse oximeter and a tablet. Data collected at baseline, one year and two years were six-minute walking distance (6MWD), COPD assessment test (CAT), EuroQol 5 dimensions (EQ-5D), hospitalisations and outpatient visits. Results No dropout occurred. Physical performance, lung capacity, health status and quality of life were all maintained at two years. At one year, 6MWD improved by a mean of 40 metres from baseline, CAT decreased by four points and EQ visual analogue scale (EQ VAS) improved by 15.6 points. Discussion Long-term exercise maintenance in COPD via telerehabilitation is feasible. Results are encouraging and suggest that telerehabilitation can prevent deterioration and improve physical performance, health status and quality of life.


Evolution of impulsive-compulsive behaviors and cognition in Parkinson's disease.
The longitudinal course of ICBs in patients with Parkinson's disease (PwP) relative to controls has not been explored as of yet. The aim of this study is to determine the frequency, evolution and associated cognitive and clinical features of impulsive and compulsive behaviors (ICBs) over 4 years of prospective follow-up in a population-based cohort with early Parkinson's disease (PD). We recruited 124 cognitively intact participants with early PD and 156 matched controls from the Norwegian ParkWest study. ICBs were assessed using the self-report short form version of the Questionnaire for Impulsive-Compulsive Disorders in PD. Cognitive changes were examined in PwP with and without ICBs who completed the 4-year follow-up. Generalized linear mixed modelling and mixed linear regression were used to analyze clinical factors and cognitive changes associated with ICBs in PwP over time. ICBs were more common in PwP than controls at all visits, with an age-adjusted odds ratio (OR) varying between 2.5 (95% CI 1.1-5.6; p = 0.022) and 5.1 (95% CI 2.4-11.0; p < 0.001). The 4-year cumulative frequency of ICBs in PwP was 46.8% and 23.3% developed incident ICBs during the study period, but the presence of ICBs was non-persistent in nearly 30%. ICBs were independently associated with younger age (OR 0.95, 95% CI 0.91-0.99: p = 0.008) and use of dopamine agonist (OR 4.1, 95% CI 1.56-10.69). Cognitive changes over time did not differ between patients with and without ICBs. In conclusion, ICBs are common in PwP, but are often non-persistent and not associated with greater cognitive impairment over time.


Motion of the rib cage and the abdomen in tetraplegic patients.
1. We have studied the motion of the abdomen and the rib cage in patients with a transection of the lower cervical spinal cord during normal breathing both in the supine and sitting posture, and compared it with that of normal subjects. 2. In the supine posture the rib cage of a patient moves paradoxically inward, therefore his chest wall is deformed, which explains the high work of breathing. 3. During expiration, beside the recoil of the respiratory system, there is also the recoil of the deformed chest wall, toward its passive configuration, with an expansion of the rib cage above its resting position during the first part of expiration and an alteration of the expiratory flow profile. 4. In a sitting 'relaxed' posture the paradoxical inward motion disappears in the lower rib cage, and it is reduced but still present in the higher rib cage. 5. We conclude that contraction of the diaphragm constricts the 'passive rib cage', either directly through its insertions or indirectly through the reduction of intrathoracic pressure. In seated subjects the diaphragm causes some expansion of the rib cage at its lower level. Therefore the motion of the rib cage is not only related to the balance between the forces developed by the diaphragm and the intercostal muscles, but also to the diaphragm dome configuration, the geometry of the rib cage and the lung volume.


A time-series method for automated measurement of changes in mitotic and interphase duration from time-lapse movies.
Automated time-lapse microscopy can visualize proliferation of large numbers of individual cells, enabling accurate measurement of the frequency of cell division and the duration of interphase and mitosis. However, extraction of quantitative information by manual inspection of time-lapse movies is too time-consuming to be useful for analysis of large experiments. Here we present an automated time-series approach that can measure changes in the duration of mitosis and interphase in individual cells expressing fluorescent histone 2B. The approach requires analysis of only 2 features, nuclear area and average intensity. Compared to supervised learning approaches, this method reduces processing time and does not require generation of training data sets. We demonstrate that this method is as sensitive as manual analysis in identifying small changes in interphase or mitotic duration induced by drug or siRNA treatment. This approach should facilitate automated analysis of high-throughput time-lapse data sets to identify small molecules or gene products that influence timing of cell division.


Clinical characteristics associated with postoperative intestinal epithelial barrier dysfunction in children with congenital heart disease.
Children with congenital heart disease have loss of intestinal epithelial barrier function, which increases their risk for postoperative sepsis and organ dysfunction. We do not understand how postoperative cardiopulmonary support or the inflammatory response to cardiopulmonary bypass might alter intestinal epithelial barrier function. We examined variation in a panel of plasma biomarkers to reflect intestinal epithelial barrier function (cellular and paracellular) after cardiopulmonary bypass and in response to routine ICU care. Prospective cohort. University medical center cardiac ICU. Twenty children aged between newborn and 18 years undergoing repair or palliation of congenital heart disease with cardiopulmonary bypass. We measured baseline and repeated plasma intestinal fatty acid-binding protein, citrulline, claudin 3, and dual sugar permeability testing to reflect intestinal epithelial integrity, epithelial function, paracellular integrity, and paracellular function, respectively. We measured baseline and repeated plasma proinflammatory (interleukin-6, tumor necrosis factor-α, and interferon-γ) and anti-inflammatory (interleukin-4 and interleukin-10) cytokines, known to modulate intestinal epithelial barrier function in murine models of cardiopulmonary bypass. All patients had abnormal baseline intestinal fatty acid-binding protein concentrations (mean, 3,815.5 pg/mL; normal, 41-336 pg/mL). Cytokine response to cardiopulmonary bypass was associated with early, but not late, changes in plasma concentrations of intestinal fatty acid-binding protein 2 and citrulline. Variation in biomarker concentrations over time was associated with aspects of ICU care indicating greater severity of illness: claudin 3, intestinal fatty acid-binding protein 2, and dual sugar permeability test ratio were associated with symptoms of feeding intolerance (p < 0.05), whereas intestinal fatty acid-binding protein was positively associated with vasoactive-inotrope score (p = 0.04). Citrulline was associated with larger arteriovenous oxygen saturation difference (p = 0.04) and had a complex relationship with vasoactive-inotrope score. Children undergoing cardiopulmonary bypass for repair or palliation of congenital heart disease are at risk for intestinal injury and often present with evidence for loss of intestinal epithelial integrity preoperatively. Greater severity of illness requiring increased cardiopulmonary support rather than the inflammatory response to cardiopulmonary bypass seems to mediate late postoperative intestinal epithelial barrier function.


The new approaches to preservation of graft cell integrity in preservation for transplantation.
Restoration of cell plasma membrane integrity after injury is essential for the survival of animal cells. In case of graft preservation or during chemotherapy in cancer, cell membrane integrity and the process of its repair are disrupted. Cytoprotective substances are important in such cases, as well as in other diseases, for example in myocardial infarction, acute insults and in chronic neurodegenerative diseases. Hyperosmolarity is a condition in which cell membrane stability may be damaged in vivo but preserved in the in vitro conditions. Hypertonicity causes water leaving from cells by osmosis, decreasing cell volume and increasing of intracellular ionic strength. High intracellular ionic strength perturbs cellular function by decreasing the rates of biochemical reaction. We review the new experimentally studied cytoprotective substances and their application in cell membrane protection. Moreover, we present our data on the effects of hyperosmolarity and its protective effect on cell internal structure.


The Edgecombe County High Blood Pressure Control Program: III. Social support, social stressors, and treatment dropout.
In a hypertension prevalence survey of a stratified random sample of 1,000 households, 2,030 adults (aged 18 years and over) were interviewed and information on psychosocial variables collected. Among 359 hypertensives, there was a consistent relationship between indicators of difficulty in the social environment and dropout from treatment in women. Compared to those who remained in treatment, women who dropped out can be characterized as having less social support on the job, having less perceived spouse approval (if married), having a lower level of perceived access to supportive resources, and being more likely to report feeling pushed most or all of the time if they are homemakers. Relationships between indicators of social support and dropout from treatment in men were found only with support on the job, and for White men, with perceived friend approval.


Self-assembled nanoparticle-stabilized photocatalytic reactors.
The efficiency of nanostructured photocatalysts continues to improve at an impressive pace and is closing in on those needed for commercial applications; however, present-day reactor strategies used to deploy these nanostructures fail to achieve the sufficient areas (>1 m(2)) needed for solar application. Here we report the Self-assembled Nanoparticle-stabilized Photocatalytic Reactor (SNPR), a fully-scalable reactor strategy comprised only of nanoparticles adsorbed at the fluid-fluid interfaces of oil-in-water emulsions, water-in-oil emulsions, and CO2-in-water foams. We show that SNPRs naturally disperse over open water and need no physical substrate, requiring only photocatalysts and fluid. In environmental applications the SNPR provides more than double the reaction rate of a comparable single-phase reactor. In continuous mode, the SNPR achieves 100% photocatalyst retention and processes 96% of the stream over 20 hours; in contrast, the performance of a comparable aqueous suspension declines to zero over this interval, losing all photocatalyst to the outlet stream. We further characterize the photoactivity of individual photocatalytic droplets, with reactants in both the continuous and dispersed phases. These results demonstrate SNPRs as a robust and flexible reactor strategy and a route-to-scale for nanomaterials.


Ossification of the posterior longitudinal ligament. Results of anterior cervical decompression and arthrodesis in sixty-one North American patients.
Ossification of the posterior longitudinal ligament is commonly associated with cervical myelopathy. Surgical treatment is a matter of controversy. We report on a series of patients who were managed with anterior cervical decompression and arthrodesis for the treatment of cervical myelopathy associated with ossification of the posterior longitudinal ligament. We retrospectively reviewed the records for all sixty-five patients who had been managed with anterior decompression and arthrodesis for the treatment of cervical ossification of the posterior longitudinal ligament and associated neurologic compression from 1982 to 2001. Sixty-one patients (thirty-nine men and twenty-two women) were followed for at least two years (or until the time of death). The average number of vertebrae resected was 2.2. The average duration of follow-up for the sixty surviving patients was four years (range, two years to fifteen years and four months). The preoperative, six-week postoperative, and final follow-up clinical status (including neurological function as assessed with the Nurick grading system) was recorded for each patient. Fifty-six of the sixty-one patients had neurological improvement, with an average improvement of 1.5 Nurick grades at the time of the final follow-up. Eight patients had absent dura at the time of surgery and, of these, five had development of a cerebrospinal fluid fistula. Eight patients had development of new neurological signs and/or symptoms in the upper extremity postoperatively. Eight patients required reoperation because of a painful pseudarthrosis (one patient), strut-graft dislodgment (three), cerebrospinal fluid leakage (three), or compression of a nerve root caudad to the area of the original procedure (one). One patient died as the result of cardiac arrest on the third postoperative day. Fifty-eight patients had an osseous fusion, one had an asymptomatic nonunion, and one had a symptomatic pseudarthrosis that was treated with revision surgery. Anterior decompression and arthrodesis is an effective way to achieve pain relief and neurological improvement in North American patients of non-Asian descent who have cervical myelopathy associated with ossification of the posterior longitudinal ligament. The risk of durocutaneous fistula, graft dislodgment, and postoperative neurological symptoms appears to be high in patients with cervical myelopathy associated with this condition.


Volume of the Human Hippocampus and Clinical Response Following Electroconvulsive Therapy.
Hippocampal enlargements are commonly reported after electroconvulsive therapy (ECT). To clarify mechanisms, we examined if ECT-induced hippocampal volume change relates to dose (number of ECT sessions and electrode placement) and acts as a biomarker of clinical outcome. Longitudinal neuroimaging and clinical data from 10 independent sites participating in the Global ECT-Magnetic Resonance Imaging Research Collaboration (GEMRIC) were obtained for mega-analysis. Hippocampal volumes were extracted from structural magnetic resonance images, acquired before and after patients (n = 281) experiencing a major depressive episode completed an ECT treatment series using right unilateral and bilateral stimulation. Untreated nondepressed control subjects (n = 95) were scanned twice. The linear component of hippocampal volume change was 0.28% (SE 0.08) per ECT session (p < .001). Volume change varied by electrode placement in the left hippocampus (bilateral, 3.3 ± 2.2%, d = 1.5; right unilateral, 1.6 ± 2.1%, d = 0.8; p < .0001) but not the right hippocampus (bilateral, 3.0 ± 1.7%, d = 1.8; right unilateral, 2.7 ± 2.0%, d = 1.4; p = .36). Volume change for electrode placement per ECT session varied similarly by hemisphere. Individuals with greater treatment-related volume increases had poorer outcomes (Montgomery-Åsberg Depression Rating Scale change -1.0 [SE 0.35], per 1% volume increase, p = .005), although the effects were not significant after controlling for ECT number (slope -0.69 [SE 0.38], p = .069). The number of ECT sessions and electrode placement impacts the extent and laterality of hippocampal enlargement, but volume change is not positively associated with clinical outcome. The results suggest that the high efficacy of ECT is not explained by hippocampal enlargement, which alone might not serve as a viable biomarker for treatment outcome.


Evaluating probabilistic dengue risk forecasts from a prototype early warning system for Brazil.
Recently, a prototype dengue early warning system was developed to produce probabilistic forecasts of dengue risk three months ahead of the 2014 World Cup in Brazil. Here, we evaluate the categorical dengue forecasts across all microregions in Brazil, using dengue cases reported in June 2014 to validate the model. We also compare the forecast model framework to a null model, based on seasonal averages of previously observed dengue incidence. When considering the ability of the two models to predict high dengue risk across Brazil, the forecast model produced more hits and fewer missed events than the null model, with a hit rate of 57% for the forecast model compared to 33% for the null model. This early warning model framework may be useful to public health services, not only ahead of mass gatherings, but also before the peak dengue season each year, to control potentially explosive dengue epidemics.


Development of a new generation of ammonia sensors on printed polymeric hotplates.
Conducting polyaniline-based chemiresistors on printed polymeric micro-hotplates were developed, showing sensitive and selective detection of ammonia vapor in air. The devices consist of a fully inkjet-printed silver heater and interdigitated electrodes on a polyethylene naphthalate substrate, separated by a thin dielectric film. The integrated heater allowed operation at elevated temperatures, enhancing the ammonia sensing performance. The printed sensor designs were optimized over two different generations, to improve the thermal performance through careful design of the shape and dimension of the heater element. A vapor-phase deposition polymerization technique was adapted to produce polyaniline sensing layers doped with poly(4-styrenesulfonic acid). The resulting sensor had better thermal stability and sensing performance when compared with conventional polyaniline-based sensors, and this was attributed to the polymeric dopant used in this study. Improved long-term stability of the sensors was achieved by electrodeposition of gold on the silver electrodes. Response to sub-parts-per-million concentrations of ammonia even under humid conditions was observed.


Eosinophilia in a patient from South America.
Asymptomatic eosinophilia is a common finding in returning travelers and immigrants from parasite-endemic areas. We present a 49-year-old man from Guyana who immigrated to the United States 4 years prior to examination. He had persistent asymptomatic eosinophilia, and multiple stool examinations were negative for ova and parasites. Although the list of parasitic diseases associated with eosinophilia is extensive, the differential diagnosis of asymptomatic eosinophilia with negative stool evaluations is rather limited. We discuss herein elements of the clinical history and examination essential for evaluating eosinophilia in patients at risk of parasitic diseases and present a simple algorithm to guide diagnostic testing. Despite the importance of repeated stool examinations for the presence of ova and parasites, in practice this test is not sensitive. Serologic testing for chronic parasitic infections is often necessary. Most cases without a definitive diagnosis can be conservatively managed with serial monitoring or empirically treated with antihelminthic therapy, but patients with an absolute eosinophil count of more than 3000/microL or more than 1500/microL for more than 6 months are at risk of end organ damage and should be referred for specialized parasitic and/or hematology consultation.


Method for finding metabolic properties based on the general growth law. Liver examples. A general framework for biological modeling.
We propose a method for finding metabolic parameters of cells, organs and whole organisms, which is based on the earlier discovered general growth law. Based on the obtained results and analysis of available biological models, we propose a general framework for modeling biological phenomena and discuss how it can be used in Virtual Liver Network project. The foundational idea of the study is that growth of cells, organs, systems and whole organisms, besides biomolecular machinery, is influenced by biophysical mechanisms acting at different scale levels. In particular, the general growth law uniquely defines distribution of nutritional resources between maintenance needs and biomass synthesis at each phase of growth and at each scale level. We exemplify the approach considering metabolic properties of growing human and dog livers and liver transplants. A procedure for verification of obtained results has been introduced too. We found that two examined dogs have high metabolic rates consuming about 0.62 and 1 gram of nutrients per cubic centimeter of liver per day, and verified this using the proposed verification procedure. We also evaluated consumption rate of nutrients in human livers, determining it to be about 0.088 gram of nutrients per cubic centimeter of liver per day for males, and about 0.098 for females. This noticeable difference can be explained by evolutionary development, which required females to have greater liver processing capacity to support pregnancy. We also found how much nutrients go to biomass synthesis and maintenance at each phase of liver and liver transplant growth. Obtained results demonstrate that the proposed approach can be used for finding metabolic characteristics of cells, organs, and whole organisms, which can further serve as important inputs and constraints for many applications in biology (such as protein expression), biotechnology (synthesis of substances), and medicine.


Role of Debt and Loan Forgiveness/Repayment Programs in Osteopathic Medical Graduates' Plans to Enter Primary Care.
Osteopathic medicine emphasizes partnering with patients to help them attain or maintain health. This philosophy encourages physicians to practice primary care and a mission of improving community health. However, there is currently a shortage of primary care physicians in many areas of the United States. To determine whether intended practice patterns of recent graduates of colleges of osteopathic medicine favor primary care and whether practice patterns correlate with medical education debt. Responses were analyzed from the American Association of Colleges of Osteopathic Medicine survey of pending medical school graduates from 2007 through 2016 regarding indebtedness and specialty selection. The percentage of graduating osteopathic medical students who chose a primary care specialty increased from 28.1% (676 students) in 2007 to 33.2% (1377 students) in 2016. Among graduates, those above the 75th percentile of debt had a general move toward more non-primary care positions, with a value of 74.4% in 2007 and 79.9% in 2016. Graduates below the 25th percentile had a gradual increase in primary care representation, moving from 24.6% in 2007 to 29.4% in 2016. In 2007, graduates with a loan forgiveness/repayment program were more likely to choose primary care over graduates without such a program (OR, 0.681 [95% CI, 0.505-0.920]; P=.02). Analysis of subsequent years showed a declining OR with increasing significance. Results of this analysis indicated that increased educational debt loan directly influenced physician practice choice. Graduates with high debt burden were more likely to enter primary care fields and use loan forgiveness/repayment programs. Graduates with high debt burden who did not use loan forgiveness/repayment programs were more likely to enter non-primary care specialty fields, with this trend increasing as mean medical school debt increased. This association has implications for policies that could affect choice of primary care. However, further research is needed to fully understand the primary care choice by graduates of colleges of osteopathic medicine.


Is health insurance affordable for the uninsured?
In this paper, we investigate the meaning of "affordability" in the context of health insurance. Assessing the relationship between the affordability of coverage and the large number of uninsured in the U.S. is important for understanding the barriers to purchasing coverage and evaluating the role of policy in reducing the number of uninsured. We propose several definitions of affordability and examine the implications of alternative definitions for estimates of the proportion of uninsured who are unable to afford coverage. We find that, depending on the definition, health insurance was affordable to between one-quarter and three-quarters of the uninsured in the United States in 2000.


Selective simulation of allelic expression: effectf antibodies to allotypic markers on lymphoid cells.
Peripheral blood leukocytes from rabbits which were heterozygous (b(5)/b(9)) for markers on their immunoglobulin light chains were maintained in vitro for up to 24 hours in the presence or absence of antibody to b9. After culture they were transferred into lethally irradiated b(4)/b(4)hosts. Recipients of cells exposed to antibodies to allotype markers showed a striking increase in concentration of circulating b9 molecules and number of b9 plasma cells in their spleens compared pared to control animals receiving untreated cells from the same donor. There was no appreciable difyerence between the two groups of recipients with respect to their content of b5 molecules and immunocytes.


In utero exposure to cigarette smoking influences lung function at birth.
To avoid the possible confounding effects of postnatal exposure to tobacco smoke, we investigated possible effects of uterine tobacco smoke (UTS) exposure upon infant lung function shortly after birth. Infants with no major disease, in one maternity ward in Oslo, Norway, participating in a cohort study established in 1992/1993, were included in the present study (n=803). Exposure information, assessed as maternal active and passive smoking during pregnancy and other personal and environmental factors, was obtained by questionnaire. Tidal flow-volume (TFV) loops (n=802) and compliance (Crs) and resistance (Rrs) of the respiratory system (n=663) were measured at a mean age of 2.7 days. In girls, the TFV ratio (time to reach peak expiratory flow to total expiratory time (tPEF/tE)), and Crs were significantly lower with active as well as passive maternal smoking compared to nonexposure to UTS. Respiratory rate and Rrs were not significantly influenced by UTS exposure. However, in linear regression analysis adjusted for confounding factors (including respiratory rate), tPEF/tE and Crs, but not Rrs, were related to maternal active but not passive daily smoking. One daily cigarette corresponded to a change in tPEF/tE of -0.0021 (95% confidence interval (95% CI) -0.0040 to -0.0002) and a change in Crs of -0.026 mL x cmH2O (95% CI -0.045 to -0.007 mL x cmH2O). The decrease was 0.023 and 0.29, respectively, in infants of an average smoker. Maternal smoking during pregnancy adversely affected tidal flow-volume ratios in healthy newborn babies, as well as the compliance of the respiratory system in girls, independently of the reduced body size also resulting from maternal smoking.


Increased levels of soluble tumor necrosis factor receptors in the sera and synovial fluid of patients with rheumatic diseases.
Recently, 2 classes of cytokine inhibitors have been defined at the molecular level. The largest group comprises the extracellular domains of cell surface cytokine receptors, and includes both tumor necrosis factor receptors (TNF-R). The present study was conducted to investigate the role of TNF inhibitors in arthritis. We measured p55 and p75 soluble TNF-R (sTNF-R) in serum and synovial fluid (SF) samples from patients with rheumatic diseases and compared their levels with levels of soluble interleukin-2 receptors (sIL-2R). Sensitive enzyme-linked immunosorbent assays (ELISA), specific for p55 and p75 sTNF-R and for sIL-2R, were used. Serum levels of p75 sTNF-R were 3-4-fold higher than levels of p55 sTNF-R, and both were significantly elevated in patients with osteoarthritis (OA) and rheumatoid arthritis (RA) compared with healthy controls. RA SF levels of sTNF-R were 4-5-fold higher than levels in serum, suggesting local production in the joint, and were significantly higher than levels in the SF of patients with seronegative arthropathy or OA. Furthermore, levels of p55 and p75 sTNF-R, but not sIL-2R or TNF alpha measured by ELISA, were increased in the SF of patients with clinically active RA. The soluble TNF-R in RA and OA SF were functional since they inhibited TNF activity in a cytotoxicity assay in proportion to the levels of inhibitor present. Evaluation of serially obtained serum samples suggested that sTNF-R may be a useful parameter for monitoring RA disease activity. Biologically active soluble TNF-R are up-regulated in patients with rheumatic disease and are produced locally in the joints. Measurement of serum levels of TNF-R may be useful for monitoring of disease, and determination of SF levels could be of diagnostic value.


Phylogenomic evidence for ancient recombination between plastid genomes of the Cupressus-Juniperus-Xanthocyparis complex (Cupressaceae).
Phylogenetic relationships among Eastern Hemisphere cypresses, Western Hemisphere cypresses, junipers, and their closest relatives are controversial, and generic delimitations have been in flux for the past decade. To address relationships and attempt to produce a more robust classification, we sequenced 11 new plastid genomes (plastomes) from the five variously described genera in this complex (Callitropsis, Cupressus, Hesperocyparis, Juniperus, and Xanthocyparis) and compared them with additional plastomes from diverse members of Cupressaceae. Phylogenetic analysis of protein-coding genes recovered a topology in which Juniperus is sister to Cupressus, whereas a tree based on whole plastomes indicated that the Callitropsis-Hesperocyparis-Xanthocyparis (CaHX) clade is sister to Cupressus. A sliding window analysis of site-specific phylogenetic support identified a ~ 15 kb region, spanning the genes ycf1 and ycf2, which harbored an anomalous signal relative to the rest of the genome. After excluding these genes, trees based on the remainder of the genes and genome consistently recovered a topology grouping the CaHX clade and Cupressus with strong bootstrap support. In contrast, trees based on the ycf1 and ycf2 region strongly supported a sister relationship between Cupressus and Juniperus. These results demonstrate that standard phylogenomic analyses can result in strongly supported but conflicting trees. We suggest that the conflicting plastomic signals result from an ancient introgression event involving ycf1 and ycf2 that occurred in an ancestor of this species complex. The introgression event was facilitated by plastomic recombination in an ancestral heteroplasmic individual carrying distinct plastid haplotypes, offering further evidence that recombination occurs between plastomes. Finally, we provide strong support for previous proposals to recognize five genera in this species complex: Callitropsis, Cupressus, Hesperocyparis, Juniperus, and Xanthocyparis.


Understanding Asian/american gay, lesbian, and bisexual experiences from a poststructural perspective.
This study explores the college experiences of nine Asian/American gay, lesbian, and bisexual students and, specifically, the impact of concealing or revealing their sexual orientation on their emerging sense of self. By utilizing a Foucauldian, poststructural theoretical perspective, the researcher found that the students navigated multiple discourses, and their decisions about revealing their sexual orientation were based on relationships formed within those discourses. These decisions, in turn, helped many of the students grasp their emerging agency within the dominant discourse. To conclude, the researcher discusses the implications of these findings for higher education as a whole.


Persistence of past stimulations: storing sounds within the inner ear.
Tones cause vibrations within the hearing organ. Conventionally, these vibrations are thought to reflect the input and therefore end with the stimulus. However, previous recordings of otoacoustic emissions and cochlear microphonic potentials suggest that the organ of Corti does continue to move after the end of a tone. These after-vibrations are characterized here through recordings of basilar membrane motion and hair cell extracellular receptor potentials in living anesthetized guinea pigs. We show that after-vibrations depend on the level and frequency of the stimulus, as well as on the sensitivity of the ear. Even a minor loss of hearing sensitivity caused a sharp reduction in after-vibration amplitude and duration. Mathematical models suggest that after-vibrations are driven by energy added into organ of Corti motion after the end of an acoustic stimulus. The possible importance of after-vibrations for psychophysical phenomena such as forward masking and gap detection are discussed.


Satellite image deconvolution based on nonlocal means.
The deconvolution of blurred and noisy satellite images is an ill-posed inverse problem, which can be regularized under the Bayesian framework by introducing an appropriate image prior. In this paper, we derive a new image prior based on the state-of-the-art nonlocal means (NLM) denoising approach under Markov random field theory. Inheriting from the NLM, the prior exploits the intrinsic high redundancy of satellite images and is able to encode the image's nonsmooth information. Using this prior, we propose an inhomogeneous deconvolution technique for satellite images, termed nonlocal means-based deconvolution (NLM-D). Moreover, in order to make our NLM-D unsupervised, we apply the L-curve approach to estimate the optimal regularization parameter. Experimentally, NLM-D demonstrates its capacity to preserve the image's nonsmooth structures (such as edges and textures) and outperforms the existing total variation-based and wavelet-based deconvolution methods in terms of both visual quality and signal-to-noise ratio performance.


Germ line variants predispose to both JAK2 V617F clonal hematopoiesis and myeloproliferative neoplasms.
We conducted a genome-wide association study (GWAS) to identify novel predisposition alleles associated with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs) and JAK2 V617F clonal hematopoiesis in the general population. We recruited a web-based cohort of 726 individuals with polycythemia vera, essential thrombocythemia, and myelofibrosis and 252 637 population controls unselected for hematologic phenotypes. Using a single-nucleotide polymorphism (SNP) array platform with custom probes for the JAK2 V617F mutation (V617F), we identified 497 individuals (0.2%) among the population controls who were V617F carriers. We performed a combined GWAS of the MPN cases plus V617F carriers in the control population (n = 1223) vs the remaining controls who were noncarriers for V617F (n = 252 140). For these MPN cases plus V617F carriers, we replicated the germ line JAK2 46/1 haplotype (rs59384377: odds ratio [OR] = 2.4, P = 6.6 × 10(-89)), previously associated with V617F-positive MPN. We also identified genome-wide significant associations in the TERT gene (rs7705526: OR = 1.8, P = 1.1 × 10(-32)), in SH2B3 (rs7310615: OR = 1.4, P = 3.1 × 10(-14)), and upstream of TET2 (rs1548483: OR = 2.0, P = 2.0 × 10(-9)). These associations were confirmed in a separate replication cohort of 446 V617F carriers vs 169 021 noncarriers. In a joint analysis of the combined GWAS and replication results, we identified additional genome-wide significant predisposition alleles associated with CHEK2, ATM, PINT, and GFI1B All SNP ORs were similar for MPN patients and controls who were V617F carriers. These data indicate that the same germ line variants endow individuals with a predisposition not only to MPN, but also to JAK2 V617F clonal hematopoiesis, a more common phenomenon that may foreshadow the development of an overt neoplasm.


Haemodynamic changes after surgical reversal of chronic two-kidney, one-clip hypertension in the rat.
1. Within 24 h of surgical reversal of chronic Goldblatt two-kidney, one-clip hypertension in the rat, of greater than 4 months duration, blood pressure had fallen to normal levels. At this time there was no difference between the effects of removal of the clip or the ischaemic kidney but, at 60 days after reversal, the blood pressure of rats which had been nephrectomized was significantly higher than that of normal controls. 2. The fall in blood pressure was associated with a fall in total peripheral resistance to normal by 24 h despite the previous established fact that structural vascular changes take much longer to reverse. There was a corresponding rise in cardiac output, mainly due to an increase in stroke volume. Nephrectomized rats had a significantly higher stroke volume compared with those unclipped 24 h after operation. 3. As blood pressure can become normal in the presence of structural cardiovascular change by a fall in total peripheral resistance it would seem unlikely that resistance vessel hypertrophy is responsible for the maintenance of blood pressure in this model. Another peripherally acting mechanism therefore has to be postulated.


Cytosolic Phospholipase A2 Alpha Regulates TLR Signaling and Migration in Metastatic 4T1 Cells.
Metastatic disease is the leading cause of death in breast cancer patients. Disrupting the cancer cell's ability to migrate may be a strategy for hindering metastasis. Cytosolic phospholipase A2 α (cPLA2α), along with downstream proinflammatory and promigratory metabolites, has been implicated in several aspects of tumorigenesis, as well as metastasis, in various types of cancer. In this study, we aim to characterize the response to reduced cPLA2α activity in metastatic versus non-metastatic cells. We employ an isogenic murine cell line pair displaying metastatic (4T1) and non-metastatic (67NR) phenotype to investigate the role of cPLA2α on migration. Furthermore, we elucidate the effect of reduced cPLA2α activity on global gene expression in the metastatic cell line. Enzyme inhibition is achieved by using a competitive pharmacological inhibitor, cPLA2α inhibitor X (CIX). Our data show that 4T1 expresses significantly higher cPLA2α levels as compared to 67NR, and the two cell lines show different sensitivity to the CIX treatment with regards to metabolism and proliferation. Inhibition of cPLA2α at nontoxic concentrations attenuates migration of highly metastatic 4T1 cells, but not non-metastatic 67NR cells. Gene expression analysis indicates that processes such as interferon type I (IFN-I) signaling and cell cycle regulation are key processes regulated by cPLA2a in metastatic 4T1 cells, supporting the findings from the biological assays. This study demonstrates that two isogenic cancer cell lines with different metastatic potential respond differently to reduced cPLA2α activity. In conclusion, we argue that cPLA2α is a potential therapeutic target in cancer and that enzyme inhibition may inhibit metastasis through an anti-migratory mechanism, possibly involving Toll-like receptor signaling and type I interferons.


Dual-mode surface-plasmon sensor based on bimetallic film.
We propose a plasmonic structure, based on a silver-gold two-layered metallic film, where two surface plasmons (SPs) with equal propagation constants are excited simultaneously at different wavelengths. We show theoretically that the bimetallic film provides unique opportunities for manipulation of plasmons and optimization of the accuracy and cross-sensitivity. The structure can be used as an effective self-reference SP sensor in wavelength-interrogated design.


Anatomic alterations in aging and age-related diseases of the eye.
We described anatomic age-related changes in the human eye to determine potential areas of investigation that may lead to identifying eyes at risk for age-related disease. A descriptive review of anatomic changes in the eye related to aging was performed in the context of current areas of investigation. The review was performed specifically for differing anatomic ocular structures, including cornea, trabecular meshwork, lens, uveal tract, Bruch's membrane, retina, RPE, vitreous, sclera, and optic nerve. Age-related changes occur in all ocular tissues. The cornea flattens and there is an attrition of endothelial cells. The shape of the trabecular meshwork changes and there is a loss of trabecular endothelium. The lens grows and becomes cataractous. The ciliary body becomes collagenized, there are choroidal vascular changes, and Bruch's membrane thickens. Retinal vessels become hyalinized and there is a loss of rods before cones in the macula. RPE morphometric changes occur with aging. The vitreous becomes liquefied and there is a loss of vitreous compartmentalization. The sclera becomes rigid and may become calcified. The optic nerve exhibits structural changes with age. There are numerous anatomic age-related changes in the human eye. Current areas of investigation related to these changes include adaptive optics scanning laser ophthalmoscopy imaging of the RPE mosaic in the context of aging, and drug delivery devices that overcome age-related alterations to retinal and macular perfusion.