Privacy-preserving record linkage in large databases using secure multiparty computation.
Practical applications for data analysis may require combining multiple databases belonging to different owners, such as health centers. The analysis should be performed without violating privacy of neither the centers themselves, nor the patients whose records these centers store. To avoid biased analysis results, it may be important to remove duplicate records among the centers, so that each patient's data would be taken into account only once. This task is very closely related to privacy-preserving record linkage. This paper presents a solution to privacy-preserving deduplication among records of several databases using secure multiparty computation. It is build upon one of the fastest practical secure multiparty computation platforms, called Sharemind. The tests on ca 10 million records of simulated databases with 1000 health centers of 10000 records each show that the computation is feasible in practice. The expected running time of the experiment is ca. 30 min for computing servers connected over 100 Mbit/s WAN, the expected error of the results is 2-40, and no errors have been detected for the particular test set that we used for our benchmarks. The solution is ready for practical use. It has well-defined security properties, implied by the properties of Sharemind platform. The solution assumes that exact matching of records is required, and a possible future research would be extending it to approximate matching.


Associations between a History of Traumatic Brain Injuries and Current Cigarette Smoking, Substance Use, and Elevated Psychological Distress in a Population Sample of Canadian Adults.
This study describes the prevalence of reported history of traumatic brain injury (TBI) and its association with reports of current substance use, cigarette smoking, and psychological distress among Canadian adults in a population sample. A cross-sectional sample of 1999 Ontario adults 18-93 years of age were surveyed by telephone in 2011 as part of the Center for Addiction and Mental Health's ongoing representative survey of adult mental health and substance use in Ontario, Canada. Loss of consciousness for at least 5 min or at least one overnight hospitalization resulting from symptoms associated with the TBI injury represented minimum criteria for TBI. An estimated 16.8% (95% confidence interval, 14.8, 19.0) of adults reported a TBI in their lifetime. Men had higher prevalence of TBI than women. Adults who reported a history of TBI had higher odds of reported past-year daily smoking (adjusted odds ratio [AOR] = 2.15), using cannabis (AOR = 2.80) and nonmedical opioids (AOR = 2.90), as well as screened significantly for recent elevated psychological distress (AOR = 1.97) in the past few weeks, compared to adults without a history of TBI. Co-occurrence of a history of TBI with current elevated psychological distress and substance use warrants vigilance among medical practitioners to assess the possibility of a history of TBI during reviews of the history leading to the occurrence of these conditions.


Clinical and Technical Aspects of Genomic Diagnostics for Precision Oncology.
The emergence of precision medicine has been predicated on significant recent advances in diagnostic technology, particularly the advent of next-generation sequencing (NGS). Although the chemical technology underlying NGS is complex, and the computational biology expertise required to build systems to facilely interpret the results is highly specialized, the variables involved in designing and deploying a genomic testing program for cancer can be readily understood and applied by understanding several basic considerations. In this review, we present key strategic decisions required to optimize a genomic testing program and summarize the technical aspects of different technologies that render those methods more or less suitable for different types of programs.


Effect of methoxyl group position on the regioselectivity of ammonia substitution reactions involving 3,3'-dichloro-2,2'-binaphthoquinones.
A series of methoxyl-substituted 3,3'-dichloro-2,2'-binaphthoquinones 2 were prepared and evaluated for regioselectivity in ammonia substitution reactions. Biquinone 2b underwent regiospecific amination at the unsubstituted chloronaphthoquinone unit whereas the isomeric biquinone, 2c, produced moderate regioselectivity (85:15). Biquinone 2d, however, showed no level of regioselectivity demonstrating that the position of the methoxyl group influences the regiochemistry. The intramolecular hydrogen bond in biquinone 5 altered the regioselectivity. Semiempirical calculations revealed comparatively larger LUMO coefficients at the chlorinated carbons that underwent preferential substitution.


Absence of proton channels in COS-7 cells expressing functional NADPH oxidase components.
Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an enzyme of phagocytes that produces bactericidal superoxide anion (O(2)(-)) via an electrogenic process. Proton efflux compensates for the charge movement across the cell membrane. The proton channel responsible for the H(+) efflux was thought to be contained within the gp91(phox) subunit of NADPH oxidase, but recent data do not support this idea (DeCoursey, T.E., V.V. Cherny, D. Morgan, B.Z. Katz, and M.C. Dinauer. 2001. J. Biol. Chem. 276:36063-36066). In this study, we investigated electrophysiological properties and superoxide production of COS-7 cells transfected with all NADPH oxidase components required for enzyme function (COS(phox)). The 7D5 antibody, which detects an extracellular epitope of the gp91(phox) protein, labeled 96-98% of COS(phox) cells. NADPH oxidase was functional because COS(phox) (but not COS(WT)) cells stimulated by phorbol myristate acetate (PMA) or arachidonic acid (AA) produced superoxide anion. No proton currents were detected in either wild-type COS-7 cells (COS(WT)) or COS(phox) cells studied at pH(o) 7.0 and pH(i) 5.5 or 7.0. Anion currents that decayed at voltages positive to 40 mV were the only currents observed. PMA or AA did not elicit detectable H(+) current in COS(WT) or COS(phox) cells. Therefore, gp91(phox) does not function as a proton channel in unstimulated cells or in activated cells with a demonstrably functional oxidase.


Arylpiperazinylalkylpyridazinones and analogues as potent and orally active antinociceptive agents: synthesis and studies on mechanism of action.
A number of arylpiperazinylalkylpyridazinones structurally related to the previously described lead A (5-{[4-(3-chlorophenyl)piperazin-1-yl]-propyl}-3-methyl-7-phenylisossazolo[4,5-d]pyridazin-4-(5H)-one) were synthesized and tested for their analgesic activity. Many of the tested molecules, at the dose of 20 mg kg-1 p.o., showed high antinociceptive activity, in particular, compounds 5a, 11c, 15a, 21 and 22, which were able to reduce the number of abdominal constrictions by more than 50% in writhing test. The pharmacological investigation of lead A led us to clarify the mechanism of action of this compound, showing that it carries out its analgesic action through the inhibition of reuptake of noradrenaline. The antinociception of some of the most interesting new molecules was completely prevented by pretreatment with alpha2-antagonist yohimbine, suggesting the involvement of alpha2-adrenoceptors, as with prototype A.


Nitrogen and Phosphorus Loss Potential from Biosolids-Amended Soils and Biotic Response in the Receiving Water.
Application of municipal biosolids to agricultural soil can improve soil quality and improve crop yields. However, runoff or tile leachate from biosolids-applied fields may contribute to localized eutrophication of surface water. A laboratory experiment was conducted to determine loss potential of nutrients from soils amended with two different biosolids (anaerobically digested and chemically stabilized) relative to loss from a reference soil and to determine response in freshwater microcosms to nutrients lost from soils. Total phosphorus (TP) and total nitrogen (TN) were measured in runoff, and equivalent amounts were added to reference microcosms to determine if aquatic systems would respond similarly to TN and TP loading in bioavailable forms (PO, NH, NO) simulating loading related to inorganic fertilizer application. Nutrient concentrations (TP, TN, PO, NH, NO, and organic P and N) were similar in the runoff from the two biosolids-amended soils and higher than those in the runoff from the reference soil. Runoff from biosolids-amended soils stimulated algal growth and production (chlorophyll a and dissolved oxygen) relative to runoff from reference soil, but the response was weaker than in microcosms receiving equivalent amounts of inorganic N and P. Nutrient runoff from land-applied biosolids does have potential to increase algal production in receiving waters; however, this experiment suggests receiving waters may absorb a single large nutrient loading event associated with runoff from biosolids-amended soil without substantial impact. Moreover, the response to N and P in biosolids versus inorganic nutrient additions suggests biosolids may contribute relatively less to eutrophication than inorganic fertilizers, assuming equivalent TN and TP loading to aquatic systems.


Girls' identity dilemmas: spaces defined by definitions of worth.
Many of the models and metaphors that underlie research on eating disorders reflect a modernist version of the self and, quite often, one that was developed in the early 1900s. Psychoanalytic theories persist despite new "postmodern" theories of the self that challenge these older theories by paying close attention to the processes of self-creation in relation to culture or discourse. I suggest using newer theories of the self in research and practice so that health care professionals may increase their understanding of how identities are formed in postmodern societies. In particular, I discuss how health professionals can work with adolescent girls to address the phenomenon of eating disorders and related health concerns. Whether one-to-one, in groups, in schools, or other settings, the strategies suggested can be used by nurses, educators, counselors, child and youth care workers, and psychologists.


Identification of feline calicivirus in cats with enteritis.
Feline calicivirus (FCV) is a major pathogen of cats associated with either respiratory disease or systemic disease, but its possible role as an enteric pathogen is neglected. Using RT-PCR, the RNA of FCV was identified in 25.9% (62/239) of stools of cats with enteritis and in 0/58 (0%) of cats without diarrhoea or other clinical signs. Isolates of enteric origin were obtained and a large 3.2-kb portion of the genome was sequenced, encompassing the 3' end of the RNA polymerase, the capsid protein precursor and the minor capsid protein. Also, the complete genome sequence of one such strain, the 160/2015/ITA, was determined. Upon sequence analysis, the enteric viruses were found to be genetically heterogeneous and to differ from each other and from isolates of respiratory origin. The enteric isolates were found to be more resistant to low pH conditions, to trypsin and to bile treatment than respiratory isolates. Overall, these findings are consistent with the hypothesis that some FCVs may acquire enteric tropism and eventually act as enteric pathogens. Whether this enteric tropism is maintained stably and whether it may affect, to some extent, the ability of the virus to trigger the classical and/or hypervirulent forms of disease should be assessed. Also, FCV should be included in the diagnostic algorithms of enteric diseases of cats to gain further information about FCV strains displaying enteric pathotype.


Dysphagia evaluation and care in the hospital setting: the need for protocolization.
Dysphagia accounts for a small portion of hospital admissions but is associated with severe complications. This has been shown to result in longer hospital length of stay and increased risk of mortality with certain other diagnoses. Although there has been much research on causes and interventions for dysphagia, there has been variable impact in actual hospital practice. Also, nonuniform approaches to evaluating patients, such as screening high-risk populations, makes it difficult to measure outcomes of care. This commentary advises a more systematic approach that includes standardized protocols, risk stratification, and screening high-risk patients; makes the case for broadening the classification of dysphagia; and suggests a growing role for adjunctive enteral nutrition in patients with some compromise to swallowing.


Declining drug use in relation to increased drug education: a trend study 1979-1991.
During the 1980s alcohol and drug education increased in Ontario schools, especially at the Grade 7 level. This article reports aggregate relationships between increased levels of exposure to classroom alcohol, tobacco, and cannabis education, and the use of alcohol, tobacco, and cannabis by students in Ontario schools. The data were derived from repeated cross-sectional probability surveys of alcohol and drug use conducted every two years since 1979. There were strong inverse associations between increases in exposure to alcohol and drug education and reported levels of use of these substances, especially for alcohol and for Grade 7 students.


Three methods of calculating force-time variables in the rebound jump squat.
The force-time qualities of the lower limb of athletes have been assessed using a variety of exercises and methodologies. The purpose of this study was to investigate the differences among 3 methods previously used to calculate various force-time measures during a rebound jump squat. Twenty-five professional rugby players performed 3 jump squats, each of which was analyzed using 3 different methods of calculation for a number of force-time variables. Method 1 analyzed the force-time curve from minimum force to maximum force; method 2 analyzed the concentric portion of the force-time curve only; and method 3 analyzed both the eccentric and concentric components of the force-time curve. Significant differences were found (p < 0.001) among all 3 methods of analysis (percent difference 1.1-364.3%) for all the force-time variables calculated. A number of variables had very high (r = 0.76-0.86) or practically perfect (r = 0.93-1.00) correlation coefficients among analysis methods, however, showing similar rank order of the population regardless of the analysis methods used. The results suggested that force-time variables that assess rate of force development relative to peak force produce significantly different values, but these values are highly correlated whether the concentric phase is included in the analysis or the eccentric and concentric phases are included in the analysis. When time-dependent variables are investigated, however, the starting point of calculation results in the measurement of functionally independent physical qualities.


Antimicrobial resistance and extended-spectrum β-lactamases of Salmonella enterica serotypes isolated from livestock and processed food in Portugal: an update.
As Salmonella is a common foodborne pathogen, the present study aimed to determine the distribution of Salmonella enterica serotypes isolated during 2011-2012 from poultry, swine, cattle, and processed food in Portugal, and to characterize the antimicrobial susceptibility and the extended-spectrum β-lactamases (ESBLs). Results were also compared with data obtained before the implementation of the National Control Program in Poultry and the ban of antimicrobial agents in animal feed in the European Union (EU). A total of 14 serotypes were identified, from 258 isolates recovered, with Salmonella Typhimurium (32.6%, n=84) and Salmonella Enteritidis (10.1%, n=26) being the most common. Salmonella Enteritidis in poultry was less frequent than in previous studies, which might be associated with the implementation of the National Control Program for Salmonella in poultry. Nevertheless, other serotypes seem to occupy this biological niche, and may be more common in human salmonellosis in the future. The majority of isolates (70.2%, n=181) were resistant to at least one class of antimicrobial agent and exhibited higher frequency of resistance to tetracycline (47.7%, n=123) and ampicillin (36.0%, n=93), with Salmonella Typhimurium being the more resistant serotype. Resistance to fluoroquinolones was shown in 8% (n=21) of isolates, a lower value compared to data obtained before 2004. ESBLs producers Salmonella Typhimurium bla(CTX-M-1) and Salmonella Enteritidis bla(SHV-12) were isolated from swine and poultry, respectively. The bla(CTX-M-1) and bla(SHV-12) genes were carried on conjugative plasmids of IncHI2replicon types and IncI1, respectively. This was the first report of a bla(CTX-M-1) in Salmonella Typhimurium in Portugal. Overall, the results revealed changes in animal origin Salmonella serotypes, mainly emerging serotypes, in frequency of resistance, and in occurrence of ESBLs-producing Salmonella. The control measures taken by the EU seem to have some impact on the resistance rate of some antibiotics such as quinolones. The emergence of ESBLs and its potential spread among animal reservoirs and the food chain highlight the continuous antimicrobial surveillance at the animal level.


Robust surface-correlation-function evaluation from experimental discrete digital images.
Correlation functions (CFs) are universal structural descriptors; surface-surface F_{ss} and surface-void F_{sv} CFs are a subset containing additional information about the interface between the phases. The description of the interface between pores and solids in porous media is of particular importance and recently Ma and Torquato [Phys. Rev. E 98, 013307 (2018)2470-004510.1103/PhysRevE.98.013307] proposed an elegant way to compute these functions for a wide variety of cases. However, their "continuous" approach is not always applicable to digital experimental 2D and 3D images of porous media as obtained using x-ray tomography or scanning electron microscopy due to nonsingularities in chemical composition or local solid material's density and partial volume effects. In this paper we propose to use edge-detecting filters to compute surface CFs in the "digital" fashion directly in the images. Computed this way, surface correlation functions are the same as analytically known for Poisson disks in case the resolution of the image is adequate. Based on the multiscale image analysis we developed a C_{0.5} criterion that can predict if the imaging resolution is enough to make an accurate evaluation of the surface CFs. We also showed that in cases when the input image contains all major features, but do not pass the C_{0.5} criterion, it is possible with the help of image magnification to sample CFs almost similar to those obtained for high-resolution image of the same structure with high C_{0.5}. The computational framework as developed here is open source and available within the CorrelationFunctions.jl package developed by our group. Our "digital" approach was applied to a wide variety of real porous media images of different quality. We discuss critical aspects of surface correlation functions computations as related to different applications. The developed methodology allows applying surface CFs to describe the structure of porous materials based on their experimental images and enhance stochastic reconstructions or super-resolution procedures, or serve as an efficient metrics in machine learning applications due to computationally effective GPU implementation.


Item ordering and computerized classification tests with cluster-based scoring: An investigation of the countdown method.
The countdown method is a well-known approach to reducing the average length of screening instruments that are presented by computer. In the countdown method, testing is terminated once the result of the screener ("positive" or "negative") has been unambiguously determined from prior answers. Previous research has examined whether presenting dichotomously scored items in order from "least to most frequently endorsed" or "most to least frequently endorsed" is more efficient when the countdown method is used. The current study describes the Mean Score procedure, an extension of the above item ordering procedures to polytomously scored items, and evaluates its efficiency relative to the distribution of other possible item orderings in 2 real-data simulations. Both simulations involve item responses to the Posttraumatic Stress Disorder (PTSD) Checklist for DSM-5 (PCL-5). In the first simulation, items were scored polytomously, and a single cutoff point was used to determine the screening result. In the second simulation, items were converted to dichotomous scores, as well as categorized into 4 clusters; a positive result for the entire assessment was obtained if and only if a positive result was obtained for each cluster. The latter simulation also investigated the effect of reordering the clusters themselves on the efficiency of the countdown method. Results indicated that the Mean Score procedure does not necessarily produce the optimal ordering, but tends to assemble an efficient item ordering relative to the distribution of possible orderings. In the second simulation, reordering the clusters themselves affected efficiency. Future research directions are suggested. (PsycINFO Database Record


[Radiotherapy of primary and secondary spinal tumors].
Radiotherapy in primary and metastatic spinal cord tumors following surgical treatment, or even without surgery, is very effective. The Authors analyse the different types of spinal tumors giving the survival time for every one. The results are related to the possible medullary damage before radiotherapy and to the sensibility of the tumor itself. The Authors emphasize the importance of two factors: 1) early diagnosis (myelography); 2) immediate therapy (high dose steroids, surgical decompression and/or radiotherapy).


Early bioavailability of paracetamol after oral or intravenous administration.
Paracetamol is a peripherally acting analgesic commonly used in multimodal post-operative pain management to reduce the need for more potent analgesics with their unwanted side-effects. The dose and optimal galenical form for achieving analgesic concentrations is not well defined. The primary aim of this pilot project was to study the early bioavailability for two fixed doses of orally administrated paracetamol and one dose of intravenous propacetamol, all of which were given after minor surgery. Thirty-five patients undergoing day surgery were divided into five groups, seven patients each. Groups received either 1 g of an ordinary paracetamol tablet, 2 g of an ordinary paracetamol tablet, 1 g of a bicarbonate paracetamol tablet, 2 g of a bicarbonate paracetamol tablet or 2 g intravenously of prodrug propacetamol. We studied the plasma concentration of paracetamol during the first 80 min after administration. Within 40 min, intravenous propacetamol gave a median plasma paracetamol concentration of 85 micromol/l (range 65-161) and decreased thereafter. After oral administration, median plasma paracetamol concentration increased with increasing dose and time, but there were huge inter-individual differences at all time points studied. At 80 min after oral paracetamol the median plasma concentrations were 36 and 129 micromol/l for the 1- and 2-g groups, respectively, with an overall range between 0 and 306 micromol/l. Oral administration of paracetamol as part of multimodal pain management immediately post-operatively resulted in a huge and unpredictable variation in plasma concentration compared with the intravenous administration.


Role of Bénard-Marangoni instabilities during solvent evaporation in polymer surface corrugations.
Film formation through the drying of polymer solutions is a widely used process in laboratories and in many industrial applications such as coatings. One of the main goals of these applications is to control the film surface morphology. In many cases, evaporation has been found to yield corrugated patterns on the free surface of films. This has been interpreted in terms of either mechanical or hydrodynamic instabilities. In this article, we present experimental results where mesoscale 2D well-ordered surface corrugation patterns are formed during solvent evaporation from polystyrene/toluene solutions. The transformation of Benard-Marangoni instabilities into surface corrugation is studied during the entire drying process using particle tracking, 3D morphology analyses, etc. We show that the corrugation wavelength is controlled by the Benard-Marangoni instability, whereas the corrugation amplitude is controlled by a mechanism that involves a high evaporation rate.


Early Application of ECMO after Sudden Cardiac Arrest to Prevent Further Deterioration: A Review and Case Report.
ECMO has become a therapeutic modality for in- and out-of-hospital scenarios and is also suitable as a bridging therapy until further decisions and interventions can be made. Case report: A 27-year-old male patient with mechanical aortic valve prothesis had a sudden cardiac arrest (SCA). ROSC had been achieved after more than 60 min of CPR and eight DC shocks due to ventricular fibrillation (VF). The National Ambulance Service unit transported the patient to our clinic for further treatment. Due to the trauma and therapeutic INR, a CT scan was performed and ruled out bleeding. Echocardiography described severely decreased left ventricular function. Coronary angiography was negative. Due to the therapeutic refractory circulatory and respiratory failure against intensive care, VA-ECMO implantation was indicated. After four days of ECMO treatment, the patient's circulation was stabilized without neurological deficit, and the functions of the end organs were normalized. Cardiac MRI showed no exact etiology behind SCA. ICD was implanted due to VF and SCA. The patient was discharged after 19 days of hospitalization. Conclusion: This case report points out that the early application of mechanical circulatory support could be an outcome-determinant therapeutic modality. Post-resuscitation care includes cardiorespiratory stabilization, treatment of reversible causes of malignant arrhythmia, and secondary prevention.


Expectations of millennial nurse graduates transitioning into practice.
Identified as Millennials, nurses born after 1980 are anticipated to redefine the employer-employee relationship as one based on the employee's wants and needs. The purpose of this study is to portray the expectations of Millennial student nurses immediately before graduation. Understanding these expectations may provide insight for leaders who are responsible for crafting a successful transition experience. Successful transition and decreased turnover are important elements of cost management for the nursing enterprise. A qualitative descriptive design was used to collect data from 14 students enrolled in a traditional BSN academic nursing program approximately 2 months prior to graduation. Upon completion of private, confidential semistructured interviews, data were transcribed, coded, and analyzed. Demographic data were compiled and interview data summarized according to identified themes. Three overarching themes emerged: the expectation that transition would be stressful, the expectation that there would be a safety net of support, and the expectation to be valued and respected as a professional. Revealing was the expectation of supportive relationships and a collaborative approach to patient care. Failure to meet those expectations may result in turnover as Millennials seek opportunities that meet their expectations.


Impact of ancestry categorisations on residential segregation measures using Swedish register data.
Country-of-birth data contained in registers are often aggregated to create broad ancestry group categories. We examine how measures of residential segregation vary according to levels of aggregation. We use Swedish register data to calculate pairwise dissimilarity indices from 1990 to 2012 for ancestry groups defined at four nested levels of aggregation: (1) micro-groups containing 50 categories, (2) meso-groups containing 16 categories, (3) macro-groups containing six categories and (4) a broad Western/non-Western binary. We find variation in segregation levels between ancestry groups that is obscured by data aggregation. This study demonstrates that the practice of aggregating country-of-birth statistics in register data can hinder the ability to identify highly segregated groups and therefore design effective policy to remedy both intergroup and intergenerational inequalities.


Dynamic view of the nuclear matrix.
The nuclear matrix is an operationally defined nuclear skeletal structure that is believed to be involved in many nuclear functions including DNA replication, transcription, repair, and prem RNA processing/transport. Until relatively recently, the nuclear matrix was thought to be a rigid and static structure, but it is now thought to be dynamic. This paradigm shift was based in part on the tracking of the intranuclear movement of proteins tagged with fluorochromes. In this review, we attempt to redefine the nuclear matrix in light of recent findings and describe some useful techniques for the dynamic analysis of nuclear function.


Effect of short-term outlet obstruction on rat bladder nerve density and contractility.
1 The present study was designed to investigate the relationship between innervation density and contractile responses to field stimulation and exogenous agonists at early time points after induction of bladder outlet obstruction (BOO) in rats. 2 When compared with sham-operated animals, 1, 3 and 7 days of BOO were associated with a 75%, 80% and 90% increase of bladder weight. Field stimulation caused a frequency-dependent increase in force of contraction. The force of contraction was reduced at each frequency in BOO rats with the greatest decrease after 1 day and a gradual but incomplete recovery thereafter. In contrast, contractile responses to ATP, carbachol and KCl were markedly reduced after 1 day of BOO and fully recovered after 7 days. The neurofilament staining was not altered by 1 day of BOO, but gradually decreased with increasing duration of BOO reaching the lowest levels after 7 days. 3 We conclude that impaired cellular contractility seems to underlie the early reductions of field stimulation-induced contraction, possibly reflecting surgical trauma of the tissue. However, at later time points a reduced nerve density, possibly reflecting a partial denervation, appears to be the main reason for impaired contractile response to field stimulation.


Iontophoretic R-apomorphine delivery in combination with surfactant pretreatment: in vitro validation studies.
To validate the efficacy and controllability of a newly developed transdermal delivery system for R-apomorphine in combination with the surfactant pretreatment, iontophoresis was performed in three-chamber continuous-flow-through diffusion cells in vitro. The transdermal iontophoretic transport of R-apomorphine was examined with both human SC and freshly dermatomed human skin, at room temperature and at 32 degrees C. Furthermore, the relationship between current density and iontophoretic flux was investigated. By increasing the temperature from 22 to 32 degrees C, the iontophoretic transport rate of R-apomorphine in human SC was increased 1.9-fold. Also the iontophoretic flux increased linearly with the increase in the current density from 100 to 500 microA/cm(2). When using dermatomed human skin instead of SC, the iontophoretic flux at a current density of 500 microA/cm(2) was decreased from 362+/-45 to 259+/-30 nmol/cm(2)h, and the corresponding lag time was prolonged from 0.8 to 2.8h. In conclusion, the combination of non-occlusive pretreatment with the surfactant formulation and iontophoresis has shown to substantially increase the transdermal transport rate of R-apomorphine. A linear relationship between current density and R-apomorphine flux indicates that the iontophoretic delivery combined with surfactant pretreatment allows a controlled and individualised administration of R-apomorphine.


Spiritual well-being as a dimension of quality of life for patients with advanced cancer and AIDS and their family caregivers: results of a longitudinal study.
Based on a longitudinal, quality-of-life study, this article presents pilot data regarding the spiritual well-being of patients with advanced cancer or AIDS and their family caregivers. Data include similarities and differences between the patient and caregiver populations and patient/family caregiver dyads as well as trends with regard to changes in spiritual well-being during the illness and dying process. The reliability of the Spiritual Well-Being Scale was examined for patient and caregiver groups, as was the relationship between selected demographic variables and spiritual well-being. Implications for practice are discussed.


Using Virtual Reality to Assess Ethical Decisions in Road Traffic Scenarios: Applicability of Value-of-Life-Based Models and Influences of Time Pressure.
Self-driving cars are posing a new challenge to our ethics. By using algorithms to make decisions in situations where harming humans is possible, probable, or even unavoidable, a self-driving car's ethical behavior comes pre-defined. Ad hoc decisions are made in milliseconds, but can be based on extensive research and debates. The same algorithms are also likely to be used in millions of cars at a time, increasing the impact of any inherent biases, and increasing the importance of getting it right. Previous research has shown that moral judgment and behavior are highly context-dependent, and comprehensive and nuanced models of the underlying cognitive processes are out of reach to date. Models of ethics for self-driving cars should thus aim to match human decisions made in the same context. We employed immersive virtual reality to assess ethical behavior in simulated road traffic scenarios, and used the collected data to train and evaluate a range of decision models. In the study, participants controlled a virtual car and had to choose which of two given obstacles they would sacrifice in order to spare the other. We randomly sampled obstacles from a variety of inanimate objects, animals and humans. Our model comparison shows that simple models based on one-dimensional value-of-life scales are suited to describe human ethical behavior in these situations. Furthermore, we examined the influence of severe time pressure on the decision-making process. We found that it decreases consistency in the decision patterns, thus providing an argument for algorithmic decision-making in road traffic. This study demonstrates the suitability of virtual reality for the assessment of ethical behavior in humans, delivering consistent results across subjects, while closely matching the experimental settings to the real world scenarios in question.


Delivering modern, high-quality, affordable pathology and laboratory medicine to low-income and middle-income countries: a call to action.
Modern, affordable pathology and laboratory medicine (PALM) systems are essential to achieve the 2030 Sustainable Development Goals for health in low-income and middle-income countries (LMICs). In this last in a Series of three papers about PALM in LMICs, we discuss the policy environment and emphasise three crucial high-level actions that are needed to deliver universal health coverage. First, nations need national strategic laboratory plans; second, these plans require adequate financing for implementation; and last, pathologists themselves need to take on leadership roles to advocate for the centrality of PALM to achieve the Sustainable Development Goals for health. The national strategic laboratory plan should deliver a tiered, networked laboratory system as a central element. Appropriate financing should be provided, at a level of at least 4% of health expenditure. Financing of new technologies such as molecular diagnostics is challenging for LMICs, even though many of these tests are cost-effective. Point-of-care testing can substantially reduce test-reporting time, but this benefit must be balanced with higher costs. Our research analysis highlights a considerable deficiency in advocacy for PALM; pathologists have been invisible in national and international health discourse and leadership. Embedding PALM in LMICs can only be achieved if pathologists advocate for these services, and undertake leadership roles, both nationally and internationally. We articulate eight key recommendations to address the current barriers identified in this Series and issue a call to action for all stakeholders to come together in a global alliance to ensure the effective provision of PALM services in resource-limited settings.


Ultrastructural localization of immunoreactivity in the developing piriform cortex.
The purpose of this study was to determine the ultrastructural basis for the immunoreactivity patterns in synaptic structures during development in layers I and II of the piriform cortex (PC) of rats. Antisera to cholecystokinin (CCK) and glutamic acid decarboxylase (GAD) were used at several different postnatal days (PN) and in adults to describe the distribution, characteristics, and relative frequency of labeled profiles--especially axons and terminals--with emphasis on details of the synaptic contacts. GAD-positive terminals occur from PN 2 to adulthood but only form contacts in deeper sublayers (Ib and II) initially. Contacts increase in layer I after PN 6 and are reduced in layer II after PN 21 when the GAD-labeled terminals and synapses take on adult features with flattened vesicles and symmetric contacts. CCK-labeled terminals are present in deeper sublayers at PN 2 but are few and rarely form contacts. Both terminals and contacts increase between PN 2 and 9, taking on distinctive shapes and vesicle morphology by PN 13. At PN 21 and older, CCK terminals have mainly flattened vesicles and mostly form symmetric contacts onto dendrites and somata in deeper layers (Ib and II). Superficial sublayer Ia has very few CCK-labeled synapses and axons. Thus immunoreactivity occurs in terminals prior to synapse formation; labeling of the presynaptic specializations precedes subsequent maturation; synaptic vesicle morphology and membrane specializations are similar for the vast majority of both CCK and GAD terminals; inhibitory (GABA) synapses are established sooner than the possibly excitatory CCK synapses; a deep to superficial gradient of synaptogenesis is associated with GAD-positive terminals in the PC; and the labeling patterns may be related to critical developmental or synaptogenic periods.


Using cluster and rest redistribution set structures as alternatives to resistance training prescription method based on velocity loss thresholds.
The purpose of this study was to compare the effects of cluster (CS), rest redistribution (RR) and traditional (TS) set configurations on acute neuromuscular performance, and to determine the viability of using CS and RR as alternatives to training prescription based on velocity loss (VL). Thirty-one resistance-trained men performed, in a randomised order, three experimental sessions consisting of the squat (SQ) and bench press (BP) exercises performed against the 10-repetition maximum load using CS (three sets of six repetitions; 30 s of intra-set rest every two repetitions; 3 min of inter-set rest), RR (9 sets of two repetitions; 45 s of inter-set rest), and TS (3 sets of 6 repetitions; 3 min of inter-set rest), set configurations. Linear mixed-effects model analysis revealed that participants had significantly lower VL (p = 0.0005) during CS and RR than TS. Generalised mixed-effects model analysis yielded significant main effects of set structure (p < 0.0001; RR > CS > TS), exercise (p < 0.0001; SQ > BP), and set number (p = 0.0006; Set 1 > Set 2 > Set 3) for maintaining repetition velocity above a 20% VL threshold. These findings suggest that CS and RR are effective at reducing the overall fatigue-included decrease in velocity compared to TS and allow the majority of repetitions to be completed with less than 20% VL. Therefore, both CS and RR can be used to manage fatigue during resistance training, and as alternatives to training prescription method based on 20% VL threshold.


Outcome of aneurysmal subarachnoid hemorrhage in a hospital population: a prospective study including early operation, intravenous nimodipine, and transcranial Doppler ultrasound.
A total of 153 consecutive patients with proven aneurysmal subarachnoid hemorrhages (SAHs) admitted immediately after diagnosis regardless of clinical condition were managed according to the same protocol. The initial evaluation included computed tomography (CT), transcranial Doppler ultrasound (TCD), angiography-CT, and/or angiography. Intravenous nimodipine (2 mg/hour) was started after confirmation of the diagnosis. The timing of operation was determined individually according to age, clinical course, and CT and TCD findings. Twenty-one Grade V patients treated with intensive care and ventriculostomy died or did not improve within 24 hours after SAH. Three patients with life-threatening intracerebral hematomas underwent emergency operation. Operation was early in 55 good risk patients and late in 57 patients because of poor initial grade, late admission, or logistic reasons. Seventeen patients had no operation because of old age, persistent poor clinical condition, medical complication, or lethal rebleeding before operation. In the total series, 90 patients (59%) made a full recovery, the overall morbidity rate was 14% (21 of 153 cases), and the mortality rate was 27% (42 of 153). Postoperative mortality including emergency evacuation of hematomas was 7.8% and mortality after elective operation was 6.2%. The causes of disability and death were the initial effect of the hemorrhage in 25 patients (16.3%), rebleeding in 15 (9.8%), delayed cerebral infarction in 8 (5.2%), surgical complications in 7 (4.5%), hydrocephalus in 4 (2.6%), and medical complications in 4 (2.6%).


[Regional cerebral blood flow and the collateral reserve of the blood supply to the brain in occlusion of the internal carotid artery].
Regional cerebral blood flow (rCBF) and CO2-reactivity were investigated by the clearance of inhalation 133Xe on a 32-detector system in 33 patients with occlusion of the internal carotid artery. The patients were divided into 2 groups: with few symptoms and residual effects of ischemic insult of various degrees of expression. rCBF asymmetry was more noticeable in the 2nd group than in the 1st group. Different types of reactions to hypercapnia were noted. Three types of cerebral hemodynamics (stable, unstable and decompensated) were singled out on the basis of a study of rCBF and CO2-reactivity results. It is more advisable that patients with an unstable type of hemodynamics should be operated on.


Effect of chitosan coating containing Nepeta pogonosperma extract on shelf life of chicken fillets during chilled storage.
Chicken meat is highly susceptible to microbial and chemical spoilage due to its high moisture and protein content. The use of edible coatings contains herbal extracts with antioxidant and antibacterial properties that help to extend the shelf life of meat products. In this study, the effect of chitosan coating (2%) and Nepeta pogonosperma extract (NPe) (0.2% and 0.6%) and their combination on chemical properties (pH, peroxide value (PV), thiobarbituric acid index (TBARS), total volatile basic nitrogen (TVB-N)) and microbial (aerobic mesophilic and psychrotrophic microorganisms, lactic acid bacteria, Enterobacteriaceae and Pseudomonas sp.) of chicken fillets were studied over a 12-day refrigerated storage period compared to the control sample. The results of NPe DPPH radical scavenging activity (DRSA) showed that IC50 and total phenolic contents values were 94.65 μg/ml and 113.53 mg GAE/g extract, respectively. Statistical results showed that the rate of increase in pH, PV, TBARS, and TVB-N of all coated treatments were lower than control. Microbial analysis results showed a decrease in the growth of different bacteria in chitosan-treated combined with NPe compared to the control sample during chilled storage. Chicken fillets coated with chitosan and 0.6% NPe displayed a longer shelf life compared to other samples.


Are the responses generated during a psychophysical task independent of previously presented stimuli or do they depend on earlier stimulus presentations?
Quinn and Watt (2006 Perception 35 267-280) showed that the optimal tempi for pieces of music (ie the appropriate speed for a melody) vary from melody to melody. The current study tested if such tempi responses depend on previous stimulus presentations. To do this, we ran a many-participants single-presentation version of the Quinn and Watt experiment. 616 visitors to the Glasgow Science Centre participated. We found that the results substantially matched those obtained earlier, and demonstrate that participants' responses are essentially independent of previously presented stimuli.


Young women's experiences of psychotic illness: a systematic review of qualitative research.
The relationship between young adulthood, women and psychosis was the focus for this systematic review. Age and gender are factors that can influence responses to illness. Research indicates that there are differences in how young men and women are affected biologically and psychosocially, including the presentation of a constellation of symptoms, response to anti-psychotic medications and how they assess their life circumstances. Yet in literature that examines experiences of young people with psychosis, the specific needs of young women are usually not presented separately. To better understand and address young adult women's healthcare and social service needs, a synthesis of evidence addressing the relationship between young adulthood, women and psychosis is needed. The aim of this systematic review was to synthesize the best available evidence on the experiences of young adult women (aged 18-35 years) living with a psychotic illness in the community. Specifically, the review question was:What are the experiences of young adult women living with a psychotic illness? Participants were young women between 18 and 35 years of age who were living with a psychotic illness in the community. The phenomenon of interest was the experiences of living with a psychotic illness of women aged 18-35 years in the community. Experiences were defined broadly as and inclusive of perceptions and experiences with health and social systems. The context for this review was the community setting. The current review included studies that focused on qualitative data including, but not limited to, designs such as phenomenology, grounded theory, ethnography, action research, feminist research and the qualitative component of mixed methods studies. A three-step search strategy was used to locate both published and unpublished studies. The search was limited to studies published from 1995 to the search date of May 13, 2015. Two reviewers independently appraised the nine included studies using the Joanna Briggs Institute Qualitative Assessment and Review Instrument (JBI-QARI) assessment tool. Data were extracted from included papers using the standardized data extraction tool from JBI-QARI. Two reviewers independently reviewed the extracted findings to identify potential categories to pool similar findings. A third member of the team met with the reviewers to collaboratively review these derived categories to create a meta-synthesis that reflected a comprehensive set of synthesized findings. Based on the thematic findings from nine qualitative studies, two synthesized findings were identified: (1) the complexity of living with psychosis and finding health, and (2) the presence of harming and healing relationships in young women's lives. The included studies explored a range of experiences relevant for women within the broader phenomenon of experiences of living with a psychotic illness, including experiences within healthcare and social systems. The systematic exploration of the literature resulted in identification of nine studies of moderate-to-high methodological quality that met the inclusion criteria. The ConQual evaluation of the level of evidence resulted in synthesized finding 1 (the complexity of living with psychosis and finding health) rated as moderate and synthesized finding 2 (the presence of harming and healing relationships in young women's lives) rated as low. Practitioners can use these findings to guide practice. Further research exploring other experiences relevant for this population is needed.


Determination of statin drugs in hospital effluent with dispersive liquid-liquid microextraction and quantification by liquid chromatography.
Statins are classified as being amongst the most prescribed agents for treating hypercholesterolaemia and preventing vascular diseases. In this study, a rapid and effective liquid chromatography method, assisted by diode array detection, was designed and validated for the simultaneous quantification of atorvastatin (ATO) and simvastatin (SIM) in hospital effluent samples. The solid phase extraction (SPE) of the analytes was optimized regarding sorbent material and pH, and the dispersive liquid-liquid microextraction (DLLME), in terms of pH, ionic strength, type and volume of extractor/dispersor solvents. The performance of both extraction procedures was evaluated in terms of linearity, quantification limits, accuracy (recovery %), precision and matrix effects for each analyte. The methods proved to be linear in the concentration range considered; the quantification limits were 0.45 µg L-1 for ATO and 0.75 µg L-1 for SIM; the matrix effect was almost absent in both methods and the average recoveries remained between 81.5-90.0%; and the RSD values were <20%. The validated methods were applied to the quantification of the statins in real samples of hospital effluent; the concentrations ranged from 18.8 µg L-1 to 35.3 µg L-1 for ATO, and from 30.3 µg L-1 to 38.5 µg L-1 for SIM. Since the calculated risk quotient was ≤192, the occurrence of ATO and SIM in hospital effluent poses a potential serious risk to human health and the aquatic ecosystem.


Store-operated Ca2+ entry is involved in transforming growth factor-β1 facilitated proliferation of rat airway smooth muscle cells.
To investigate the role and underlying mechanisms of store-operated Ca(2+) entry (SOCE) in mediating the promoting effect of transforming growth factor (TGF)-β1 on the proliferation of airway smooth muscle cells (ASMCs). Rat bronchial smooth muscle cells were cultured as we described previously. The intracellular Ca(2+) concentration ([Ca(2+)]i) of ASMCs was measured by laser confocal microscope Ca(2+) fluorescence imaging with Fluo-3/AM. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and p27 expression assay were used to determine the proliferation rate of ASMCs. We demonstrated that TGF-β1 (10 ng/ml) increased basal (Ca(2+)]i) level, [Ca(2+)]i rise induced by thapsigargin-induced Ca(2+) release and SOCE in rat ASMCs. This effect of TGF-β1 on SOCE was not inhibited by glucocorticoid dexamethasone (DXM, 100 nM), antioxidant α-tocopherol (100 μM), and intermediate-conductance Ca(2+)-activated K(+) channels (IKCa) inhibitor charybdotoxin (100 nM), suggesting that reactive oxygen species and IKCa channels might not mediate the effect of TGF-β1. TGF-β1 slightly increased the expression of Orai1 and STIM1, two important molecules involved in the molecule component and regulation of SOC channels, in the presence of 10% fetal bovine serum (FBS). The proliferation of ASMC stimulated with 2.5% FBS was promoted by TGF-β1, and partly inhibited by non-specific Ca(2+) channel blocker SKF-96365 (10 μM) and Ni(2+) (100 μM). DXM, α-tocopherol, and charybdotoxin had no effect on the proliferation promoted by TGF-β1. TGF-β1 promotes ASMC proliferation partly through increasing the expression and activity of SOC channels.


Improving the repeatability of Heidelberg retina tomograph and Heidelberg retina tomograph II rim area measurements.
To devise and test strategies for improving Heidelberg retina tomograph (HRT and HRT-II) rim area (RA) repeatability and assess the benefit of the strategies in time series of HRT images. The effect of the standard and 320 microm reference planes and image quality on RA repeatability was assessed in a test-retest HRT image dataset from 74 subjects. A longitudinal HRT image dataset from 30 ocular hypertensive subjects was analysed by linear regression of RA over time, with each of the reference planes and using a manual image alignment facility. RA variability was estimated by comparing the standard deviation of residuals (RSD) generated by each linear regression. RA repeatability was better with the 320 microm reference plane (repeatability coefficient 0.17 mm(2)), improving further with only good quality images (repeatability coefficient 0.08 mm(2)). For the longitudinal data, a significant (p<0.0001) reduction in the RSD from 0.10 to 0.05 mm(2) was obtained with the 320 microm reference plane. Manual alignment led to a further significant (p<0.0001) reduction in the RSD to 0.04 mm(2). The findings support the use of a 320 microm reference plane and manual image alignment to analyse RA over time. The estimates of RA repeatability may be used to define thresholds for glaucomatous change.


Manual ventilation and open suction procedures contribute to negative pressures in a mechanical lung model.
Removal of pulmonary secretions in mechanically ventilated patients usually requires suction with closed catheter systems or flexible bronchoscopes. Manual ventilation is occasionally performed during such procedures if clinicians suspect inadequate ventilation. Suctioning can also be performed with the ventilator entirely disconnected from the endotracheal tube (ETT). The aim of this study was to investigate if these two procedures generate negative airway pressures, which may contribute to atelectasis. The effects of device insertion and suctioning in ETTs were examined in a mechanical lung model with a pressure transducer inserted distal to ETTs of 9 mm, 8 mm and 7 mm internal diameter (ID). A 16 Fr bronchoscope and 12, 14 and 16 Fr suction catheters were used at two different vacuum levels during manual ventilation and with the ETTs disconnected. During manual ventilation with ETTs of 9 mm, 8 mm and 7 mm ID, and bronchoscopic suctioning at moderate suction level, peak pressure (PPEAK) dropped from 23, 22 and 24.5 cm H2O to 16, 16 and 15 cm H2O, respectively. Maximum suction reduced PPEAK to 20, 17 and 11 cm H2O, respectively, and the end-expiratory pressure fell from 5, 5.5 and 4.5 cm H2O to -2, -6 and -17 cm H2O. Suctioning through disconnected ETTs (open suction procedure) gave negative model airway pressures throughout the duration of the procedures. Manual ventilation and open suction procedures induce negative end-expiratory pressure during endotracheal suctioning, which may have clinical implications in patients who need high PEEP (positive end-expiratory pressure).


Rediscovery of the species of 'ancestral Volvox': morphology and phylogenetic position of Pleodorina sphaerica (Volvocales, Chlorophyceae) from Thailand.
Pleodorina sphaerica Iyengar was considered to be a phylogenetic link between Volvox and the type species Pleodorina californica Shaw because it has small somatic cells distributed from the anterior to posterior poles in 64- or 128-celled vegetative colonies. However, cultural studies and molecular and ultrastructural data are lacking in P. sphaerica, and this species has not been recorded since 1951. Here, we performed light and electron microscopy and molecular phylogeny of P. sphaerica based on newly established culture strains originating from Thailand. Morphological features of the present Thai species agreed well with those of the previous studies of the Indian material of P. sphaerica and with those of the current concept of the advanced members of the Volvocaceae. The present P. sphaerica strains exhibited homothallic sexuality; male and facultative female colonies developed within a single clonal culture. Chloroplast multigene phylogeny demonstrated that P. sphaerica was sister to two other species of Pleodorina (P. californica and Pleodorina japonica Nozaki) without posterior somatic cells, and these three species of Pleodorina formed a robust clade, which was positioned distally in the large monophyletic group including nine taxa of Volvox sect. Merrillosphaera and Volvox (sect. Janetosphaera) aureus Ehrenberg. Based on the present phylogenetic results, evolutionary losses of posterior somatic cells might have occurred in the ancestor of P. californica and P. japonica. Thus, P. sphaerica might represent an ancestral morphology of Pleodorina, rather than of Volvox.


Impact of rotavirus infections on outpatient clinic visits in chile.
Incorporation of new rotavirus vaccines into national programs of developing countries will rely on well-designed cost-effective analysis based on accurate assessment of disease burden. For Chile, rotavirus disease burden is determined mostly by outpatient clinic and emergency room visits and by hospitalizations. We previously estimated a yearly incidence of 8000 and 53,000 hospitalizations and emergency room visits respectively for children <or=3 years of age. The objective of this study was to quantify the impact of rotavirus as a cause of outpatient clinic visits. A prospective surveillance protocol between the Health Ministry and the University of Chile in 11 outpatient clinics from 6 regions included reporting of all acute diarrhea cases in children <5 years of age and collection of a stool sample for the first 5 children per week. A total of 5217 acute diarrhea episodes requiring an outpatient medical visit for a total assigned population of 41,927 children <5 years of age were reported from August 1, 2004, to October 30, 2005, in the 11 clinics. A total of 179 rotavirus positive samples were detected from 1313 stools collected for an overall positivity of 13.6% (95% confidence limit: 11.8-15.6%). Rotavirus outpatient visits occurred during all 15 months without a clear seasonal predominance and peaked between 6 months and 2 years of age. G4 types predominated during the 15-month period. For Chilean children </=3 years of age, a yearly estimate of 11,658 to 16,305 outpatient medical visits need to be added to previous disease burden estimates.


Design and characterization of an HIV-specific ribonuclease zymogen.
Ribonucleases are evoking medical interest because of their intrinsic cytotoxic activity. Most notably, ranpirnase, which is an amphibian ribonuclease, is in advanced clinical trials as a chemotherapeutic agent for the treatment of cancer. Here, we describe a strategy to create a novel antiviral agent based on bovine pancreatic ribonuclease (RNase A), a mammalian homologue of ranpirnase. Specifically, we have linked the N- and C-termini of RNase A with an amino acid sequence that is recognized and cleaved by human immunodeficiency virus (HIV) protease. This linkage obstructs the active site, forming an HIV-specific RNase A zymogen. Cleavage by HIV-1 protease increases ribonucleolytic activity by 50-fold. By relying on the proper function of HIV-1 protease, rather than its inhibition, our approach will not engender known mechanisms of resistance. Thus, we report an initial step toward a new class of agents for the treatment of HIV/AIDS.


Regulation of secretion from serous and mucous cells in the trachea.
The physical properties of mucus and the efficiency of tracheal mucociliary clearance depend on maintenance of a balanced interaction among several epithelial cell types. Some of these cell types are specialized to perform ion and water transport, others to perform synthesis and secretion of macromolecules. Our studies have been aimed specifically at identifying the neural mechanisms regulating macromolecule secretion from two of these cell types, i.e. serous and mucous gland cells. Because these cells occur as part of a complex epithelium, it is difficult to monitor the properties and functions of each cell type individually. We have therefore relied principally on morphological methods, which can potentially focus on a single cell type within a heterogeneous tissue. Such studies, however, depend on the availability of visible markers (enzyme-labelled antibodies, radioligands, etc.), and many important aspects of gland cell function cannot be assessed morphologically. Two alternative approaches are therefore being developed: the isolation and segregation of gland cells according to type, and the production of monoclonal antibodies that recognize secretory products of individual cell types. These methods allow serous and mucous cells to be studied by biochemical as well as morphological methods.


Pulmonary artery-bronchial fistula complicating chronic lymphocytic leukemia.
A 52-year-old man with chronic lymphocytic leukemia (CLL) entered the hospital because of repetitive bouts of massive hemoptysis requiring a right pneumonectomy. A bronchus intermedius-pulmonary artery fistula was found and felt to be due to necrosis of a peribronchial lymph node which was infiltrated by chronic lymphocytic leukemia cells. This represents another pulmonary complication in the clinical course of advanced CLL.


The methodology of the Australian Prehospital Outcomes Study of Longitudinal Epidemiology (APOStLE) Project.
This paper describes the methodology of a large emergency medical services (EMS) data linkage research project currently under way in the statewide EMS system of New South Wales, Australia. The paper is intended to provide the reader with an understanding of how linkage techniques can be used to facilitate EMS research. This project, the Australian Prehospital Outcomes Study of Longitudinal Epidemiology (APOStLE) Project, links data from six statewide sources (computer-assisted dispatch, EMS patient health care reports, emergency department data, inpatient data, and two death registries) to enable researchers to examine the patient's entire journey through the health care system, from the emergency 0-0-0 call to the emergency department and inpatient setting, through to discharge or death, for approximately 2.6 million patients transported by the Ambulance Service of New South Wales to emergency departments between June 2006 and July 2009. Manual, deterministic, and probabilistic data linkages are described, and potential applications of linked data in EMS research are outlined.


Treatment of uremic hyperphosphatemia--is there still a need for aluminum salts?
Aluminum-containing phosphate binders have been widely employed in the past in the management of uremic hyperphosphatemia. However, an increasing number of reports on aluminum toxicity has stimulated efforts to replace this therapy by safer methods. The aim of the present review is to critically evaluate other treatment strategies. It appears that aluminum-containing phosphate binders should no longer be considered the treatment of choice for controlling uremic hyperphosphatemia. Calcium carbonate, calcium citrate, magnesium carbonate and a mixture of ketoanalogues and amino acids present important therapeutical alternatives which could replace aluminum-containing phosphate binders in the majority of patients. However, it is mandatory, as these therapies also carry some risks, that side effects are detected early.


Analysis of Factors that Influence Hematopoietic Recovery in Autologous Transplanted Patients with Hematopoietic Stem Cells from Peripheral Blood.
Successful hematopoietic stem cell transplantation (HSCT) requires a rapid and durable hematopoietic recovery. The aim of our study was to analyse factors that influence hematopoietic recovery after autologous HSCT. Multiple regression analysis was used to analyse factors affecting neutrophil and platelet engraftment in 90 autologous transplanted patients - 30 with acute myeloid leukaemia (AML), 30 with lymphoma and 30 with multiple myeloma (MM) from 2008 till 2016. The neutrophil recovery in AML patients was significantly influenced by transfusion support with random-donor platelets, sex and number of transplanted mononuclear cells (MNC) and CD34+ cells; and in lymphoma patients, it was influenced by sex, age, mobilisation strategy and some transplanted MNC. The influence of investigated factors on neutrophil engraftment in MM patients was not statistically significant. The platelet recovery in AML patients was influenced by transfusion support with random-donor platelets; in lymphoma patients, it was influenced by sex, age, time from diagnosis to harvesting and time from diagnosis to HSCT; and in MM patients it was influenced by transfusion support with random-donor platelets. Additional studies are necessary to better understanding of engraftment kinetic to improve the safety of HSCT and to minimise potential complications and expenses related to HSCT.


Novel use of carbon dioxide arteriography in renal artery pseudoaneurysm in patients with poor renal function.
Renal artery pseudoaneurysm (RAP) is a rare complication of partial nephrectomy, but is usually effectively managed with renal vessel embolisation. We report a particularly challenging case of a patient with chronic kidney disease (CKD) who developed a RAP following a laparoscopic heminephrectomy and was treated using superselective renal vessel coil embolisation with carbon dioxide (CO2) as the primary contrast agent for arteriographic localisation of the RAP and feeder artery. To the best our knowledge we report the first utilisation of CO2 arteriography in the definitive diagnosis and treatment of RAP following heminephrectomy in a patient with severe CKD.


Multifunctional sensing ability of a new Pt/Zn-based luminescent coordination polymer.
We synthesized a new Pt/Zn-based coordination polymer, {Zn[Pt(CN)(2)(5,5'-dcbpy)].4H(2)O}(n), (5,5'-H(2)dcbpy = 5,5'-dicarboxy-2,2'-bipyridine), which exhibits reversible colour changes in response to temperature change or exposure to chemical vapours and liquids. Such chromic behaviour shows promise for sensing not only changes in temperature but also for detecting chemical solvents and vapours. The single crystal X-ray structure indicates that one-dimensional coordination polymeric chains formed by an alternating arrangement of [Zn(H(2)O)(3)](2+) and [Pt(CN)(2)(5,5'-dcbpy)](2-) stacked to produce moderate metallophilic interactions between the Pt(ii) ions. Thermogravimetric analysis and water vapour adsorption measurements show that both the crystal water and water coordinated to Zn(ii) ions can be removed and re-adsorbed reversibly by heating or under vacuum. Emission spectra at various temperatures and/or in the presence of vapours or liquids reveal that the complex exhibits thermochromic and solvatochromic-like behaviours, with the emission band shifting between 616 and 671 nm. IR spectroscopy and powder X-ray diffraction measurements suggest that this multichromic behaviour is a result of the cooperative phenomena of water adsorption/desorption around the Zn(ii) ions and the modification of the metallophilic interaction.


Double-blind placebo-controlled study with interleukin-18 and interleukin-12-encoding plasmid DNA shows antitumor effect in metastatic melanoma in gray horses.
Melanoma is a disease with high incidence in gray horses and has limited therapeutic options in metastatic disease. Gene therapy has shown some success in animal models and human patients. A randomized double-blind, placebo-controlled study was conducted to investigate 2 treatment options using cytokine-encoding plasmid DNA in horses with metastatic melanoma to induce immunologic antitumor effects. Adult gray horses with spontaneously occurring metastatic melanoma (n=26) were included in the study. Treatment of 26 gray horses with metastatic melanoma consisted of interleukin-18-encoding plasmid DNA, interleukin-12-encoding plasmid DNA, or empty plasmid DNA (control group), injected intratumorally, respectively. Tumor response was assessed using ultrasound and caliper measurements and histologic assessment of tumor biopsies. Significant tumor regression could be shown in both the treatment groups receiving IL-18 and IL-12-encoding plasmid DNA whereas placebo-treated control patients showed tumor growth over the course of the treatment. In addition, 7 of 10 tumors from horses treated with IL-18 or IL-12 showed peritumoral and/or intratumoral inflammatory infiltrates after treatment compared with 1 of the 6 in the control group. The treatment as assessed by serial blood draws and clinical investigation, was safe and well tolerated. These data suggest that the intratumoral treatment with IL-18 and IL-12-encoding plasmid DNA has antitumor effects, which is well tolerated and thus holds promise for the treatment of patients with metastatic melanoma.


[Long-term oral low-dose cyclophosphamide-induced hemorragic cystitis which was successfully treated by ureterostomy: a case report].
An 80-year-old man presented to our hospital with macroscopic hematuria. Before coming to our hospital, he was treated for multiple myeloma with cyclophosphamide. We detected diffuse dilation of capillary on urinary bladder mucosa on cystoscopy, and diagnosed the patient with cyclophosphamide-induced hemorrhagic cystitis. Macroscopic hematuria once resolved by indwelling urethral catheter, but recurred and bladder tamponade developed. We performed transurethral electric coagulation. Macroscopic hematuria temporarily disappeared, but again relapsed. Then we performed intravesical instillation of aluminum hydroxide gel, but without a clear effect and the patient developed hemorrhagic shock. Eventually, we performed bilateral ureterostomy because the disease was unresponsive to less invasive therapies. Vesical bleeding disappeared and the patient was discharged 32 days after surgery. The treatment for multiple myeloma has been continued without cyclophosphamide since surgery.


Statistics of single-molecule surface enhanced Raman scattering signals: fluctuation analysis with multiple analyte techniques.
The mathematical background, based on a variation of the principal component analysis (PCA) method, is developed for the understanding of fluctuating multiple analyte single-molecule (SM) surface enhanced Raman scattering (SERS) signals; with emphasis on the bianalyte SERS technique developed recently. The method and its significance are presented to provide a systematic framework with which several aspects of the statistics of SM-SERS signals can be analyzed in general. We also apply the method to a concrete example of bianalyte statistics in silver colloidal solutions and discuss related topics around experimental issues and the interpretation of single-molecule SERS data.


The role of nesfatin-1 expression in letrozole-induced polycystic ovaries in the rat.
Polycystic ovary syndrome (PCOS) is a complex and heterogeneous endocrine disorder, generally exhibiting the characteristic features of hyperandrogenemia, insulin resistance (IR) and obesity. Nesfatin-1 is derived from the precursor nucleobindin2 (NUCB2), and plays an active role in energy balance, glucose metabolism and most likely gonadal function. In order to explore the role of nesfatin-1, we employed a rat model that uses letrozole to induce PCOS. The PCOS rats exhibited increased body weight, irregular cycles, polycystic ovaries characterized by cysts formed from atretic follicles, and a diminished granulosa layer. The expression of both nesfatin-1 mRNA and protein in the ovarian tissues of PCOS group decreased significantly compared to the control group (p < 0.05). Nesfatin-1 expression in peripheral blood also decreased in the PCOS group, in contrast with the control group. Furthermore, we found that nesfatin-1 had a positive correlation with FSH, E2 and P, whereas it had a negative correlation with LH, and total T (p < 0.05). When taken together, these data indicated that the decrease in nesfatin-1 may contribute to the mechanism governing PCOS, and might provide a new potential target for therapies aimed at treating PCOS.


[Condition of the immune status at patients with the serous and purulent pyelonephritis according].
Studying of a condition of the immune status on for standard treatment at an acute serous and purulent pyelonephritis. The immune status of 62 patients with various forms of an acute pyelonephritis, randomized on age, sex, the minimum quantity of associated diseases in a remission stage is surveyed. and their discussion. Purulent form of acute pyelonephritis was accompanied by higher levels of pro-inflammatory cytokines with decreased levels of anti-inflammatory cytokines. In serous form, imbalance in the cytokine system was found. Both serous and purulent forms of pyelonephritis were characterized by the imbalance in the complement system, increased production of immunoglobulins with simultaneous reduction of circulating immune complexes, decreased activity and the intensity of phagocytosis with increased metabolic activity of neutrophils. At serous and purulent forms of a pyelonephritis there are differences in an orientation and expression of changes of the immune indicators demanding development of methods of the differentiated immunorehabilitation.


Recommendations for participation in leisure-time physical activity and competitive sports of patients with arrhythmias and potentially arrhythmogenic conditions. Part II: ventricular arrhythmias, channelopathies and implantable defibrillators.
This consensus paper on behalf of the Study Group on Sports Cardiology of the European Society of Cardiology follows a previous one on guidelines for sports participation in competitive and recreational athletes with supraventricular arrhythmias and pacemakers. The question of imminent life-threatening arrhythmias is especially relevant when some form of ventricular rhythm disorder is documented, or when the patient is diagnosed to have inherited a pro-arrhythmogenic disorder. Frequent ventricular premature beats or nonsustained ventricular tachycardia may be a hallmark of underlying pathology and increased risk. Their finding should prompt a thorough cardiac evaluation, including both imaging modalities and electrophysiological techniques. This should allow distinguishing idiopathic rhythm disorders from underlying disease that carries a more ominous prognosis. Recommendations on sports participation in inherited arrhythmogenic conditions and asymptomatic gene carriers are also discussed: congenital and acquired long QT syndrome, short QT syndrome, Brugada syndrome, catecholaminergic polymorphic ventricular tachycardia, arrhythmogenic right ventricular cardiomyopathy and other familial electrical disease of unknown origin. If an implantable cardioverter defibrillator is indicated, it is no substitute for the guidelines relating to the underlying pathology. Moreover, some particular recommendations for patients/athletes with an implantable cardioverter defibrillator are to be observed.


Heterogeneity of calcium clock functions in dormant, dysrhythmically and rhythmically firing single pacemaker cells isolated from SA node.
Current understanding of how cardiac pacemaker cells operate is based mainly on studies in isolated single sinoatrial node cells (SANC), specifically those that rhythmically fire action potentials similar to the in vivo behavior of the intact sinoatrial node. However, only a small fraction of SANC exhibit rhythmic firing after isolation. Other SANC behaviors have not been studied. Here, for the first time, we studied all single cells isolated from the sinoatrial node of the guinea pig, including traditionally studied rhythmically firing cells ('rhythmic SANC'), dysrhythmically firing cells ('dysrhythmic SANC') and cells without any apparent spontaneous firing activity ('dormant SANC'). Action potential-induced cytosolic Ca2+ transients and spontaneous local Ca2+ releases (LCRs) were measured with a 2D camera. LCRs were present not only in rhythmically firing SANC, but also in dormant and dysrhythmic SANC. While rhythmic SANC were characterized by large LCRs synchronized in space and time towards late diastole, dysrhythmic and dormant SANC exhibited smaller LCRs that appeared stochastically and were widely distributed in time. β-adrenergic receptor (βAR) stimulation increased LCR size and synchronized LCR occurrences in all dysrhythmic and a third of dormant cells (25 of 75 cells tested). In response to βAR stimulation, these dormant SANC developed automaticity, and LCRs became coupled to spontaneous action potential-induced cytosolic Ca2+ transients. Conversely, dormant SANC that did not develop automaticity showed no significant change in average LCR characteristics. The majority of dysrhythmic cells became rhythmic in response to βAR stimulation, with the rate of action potential-induced cytosolic Ca2+ transients substantially increasing. In summary, isolated SANC can be broadly categorized into three major populations: dormant, dysrhythmic, and rhythmic. We interpret our results based on simulations of a numerical model of SANC operating as a coupled-clock system. On this basis, the two previously unstudied dysrhythmic and dormant cell populations have intrinsically partially or completely uncoupled clocks. Such cells can be recruited to fire rhythmically in response to βAR stimulation via increased rhythmic LCR activity and ameliorated coupling between the Ca2+ and membrane clocks.


B cells play a cooperative role via CD40L-CD40 interaction in T cell-mediated experimental autoimmune neuritis in Lewis rats.
The expression of co-stimulatory molecules CD40 and CD40L was examined over the course of experimental autoimmune neuritis (EAN) induced in Lewis rats by immunization with bovine peripheral nerve myelin. In draining lymph nodes, highest level of CD40L expression was seen on day 7 post immunization (p.i.), i.e. before onset of clinical signs of EAN, while CD40 expression was increased on day 14 p.i., i.e. at peak of clinical disease. In contrast, both CD40 and CD40L expressing cells in sciatic nerves, a target organ of EAN, peaked on day 14 p.i., large numbers of both expressing cells were mainly detected on day 14-21 p.i. After co-culture with EAN rat B cells bearing CD40, P0 peptide 180-199-specific T cell line cells exhibited a rapid down-regulation of CD40L expression. Furthermore, EAN rats had enhanced P0 peptide 180-199-specific antibody responses on day 14 p.i., which might have contributed to their aggravated EAN and further demonstrated the role of antibodies in EAN. The results indicate that CD40L-CD40 interactions are involved in the initiation of the antigen-specific T cell responses associated with the generation and development of EAN, and may mediate autoantibody production in EAN. Evidently, B cells play a cooperative role via CD40L-CD40 interaction in T cell-mediated EAN of Lewis rats.


Schistosoma haematobium, S. intercalatum, S. japonicum, S. mansoni, and S. rodhaini in mice: relationship between patterns of lung migration by schistosomula and perfusion recovery of adult worms.
The development of five schistosome species was compared in mice by the recovery of schistosomula from chopped lung tissue and of adult worms by portal perfusion. Three developmental patterns appeared. (1) Schistosoma japonicum was unique in showing an early establishment of schistosomula in and a rapid departure from the lungs together with the highest worm recovery; (2) S. haematobium contrasted by establishing later and persisting in the lungs for at least 2 weeks while yielding the lowest adult worm recovery; and (3) S. intercalatum, S. mansoni, and S. rodhaini had an intermediate pattern--they resided in the lungs for several days, then disappeared and produced intermediate numbers of adults. Lung petechiae, known to accompany the migration of S. japonicum, were never detected after infection with the other species. We speculate that the three migration patterns of schistosomes are related to the size of the relative spectra of naturally infected definitive hosts.


Probucol decreases mevalonate pyrophosphate decarboxylase in the rat liver.
It is known that cholesterol biosynthesis in the liver is inhibited by probucol. This inhibition by probucol is caused at least in part by a decrease in 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity. In this study, we examined serum cholesterol and the change in the activity or protein level of mevalonate pyrophosphate decarboxylase (MPD), which is involved in cholesterol biosynthesis, in the livers of rats fed probucol. The results indicated that serum cholesterol, MPD activity and MPD protein were decreased by 70, 50 and 60% by probucol, respectively, as compared with those in rats fed normal chow. These data show for the first time that probucol decreases the level of an enzyme involved in cholesterol biosynthesis other than HMG-CoA reductase.


Characterization of a Whole-Cell Biotransformation Using a Constitutive Lysine Decarboxylase from Escherichia coli for the High-Level Production of Cadaverine from Industrial Grade L-Lysine.
Cadaverine is used for the synthesis of the novel bio-polyamides 54, 56, and 510. Here, we examine the feasibility of using a lysine decarboxylase (LdcC) from Escherichia coli for high-level production of cadaverine. After sequential optimization of whole-cell biotransformation conditions, recombinant E. coli-overexpressing LdcC (EcLdcC) could produce 1.0 M cadaverine from 1.2 M crude L-lysine solution after 9 h. EcLdcC retained a higher cadaverine yield after being reused 10 times at acidic and alkaline pH values than that of a recombinant E. coli strain overexpressing an inducible lysine decarboxylase (CadA), a conventional cadaverine producer (90 vs. 51% at pH 6 and 55 vs. 15% at pH 8). This study reveals that EcLdcC is a promising whole-cell biocatalyst for the bio-based production of cadaverine from industrial grade L-lysine in comparison to EcCadA.


Blocking endothelial protein C receptor (EPCR) accelerates thrombus development in vivo.
The endothelial protein C receptor (EPCR) plays an anticoagulant role by improving protein C activation. Although low levels of activated protein C (APC) constitute a thrombosis risk factor, the relationship between modulating EPCR function and thrombosis has not been addressed so far. Monoclonal antibodies (mAb) against murine EPCR were raised, and their ability to block protein C/APC binding was tested. The ferric chloride carotid artery injury model in mice was chosen to test the effect of anti-EPCR mAb on thrombus formation. The time to total occlusion of the vessel was analysed in three groups, given an isotype control mAb (IC), a blocking (RCR-16) or a non-blocking (RCR-20) anti-EPCR mAb. RCR-16 prevented the interaction between protein C/APC and EPCR as demonstrated by surface plasmon resonance and flow cytometry, and inhibited the activation of protein C on the endothelium. IC and RCR-20 were unable to induce such effects. In vivo , RCR-16 shortened the time to total vessel occlusion with respect to IC [13.4 +/- 1.0 (mean +/- SD) and 17.8 +/- 3.2 minutes, respectively, p<0.001]. Occlusive thrombi lasting for more than one hour were observed in all RCR-16-treated animals, but only in 43% of IC-treated ones. Results with RCR-20 were indistinguishable from those observed with IC. For the first time, a direct relationship between blocking EPCR and thrombosis is demonstrated. Blocking anti-EPCR autoantibodies can predispose to thrombosis episodes and may constitute a new therapeutic target.


Under-Reporting of Self-Reported Medical Conditions in Aviation: A Cross-Sectional Survey.
BACKGROUND: The applicants' self-declaration of medical history is crucial for safety. Some evidence indicates that under-reporting of medical conditions exists. However, the magnitude in a population of aviation personnel has not been reported earlier.METHODS: A total of 9941 applicants for medical certificate/attestation for aviation-related safety functions during the last 5 yr up to December 2019 were registered at the Civil Aviation Authority Norway. E-mail addresses were known for 9027 of these applicants, who were invited to participate in a web-based survey.RESULTS: Among the 1616 respondents, 726 (45%) were commercial pilots, 457 (28%) private pilots, 272 (17%) air traffic controllers, and the remaining were cabin crew or crew in aerodrome/helicopter flight information service (AFIS or HFIS, respectively). A total of 108 were initial applicants. The age group 50+ constituted the largest proportion of respondents (53%). Aeromedical certification in general was believed to improve flight safety "to a high" or "very high extent" by 64% of the respondents. A total of 188 individuals (12%) admitted having under-reported information related to one or more categories, including mental (3%) or physical health (4%), medications (2%), and drug use, including alcohol use (5%). Among these, 21 participants believed their own under-reporting "to some" or "to a high extent" affected flight safety. In total 50% of noninitial applicants reported that they knew colleagues who had under-reported information. Analyses revealed that being a commercial pilot showed a higher risk for under-reporting compared with other classes and the perception of aeromedical examiners in a supportive or authoritative role reduced the risk.CONCLUSIONS: Under-reporting of medical conditions could be significant in aviation. Further studies should be conducted to investigate the true extent of under-reporting and its impact on flight safety and what mitigating measures might be recommended.Strand T-E, Lystrup N, Martinussen M. Under-reporting of self-reported medical conditions in aviation: a cross-sectional survey. Aerosp Med Hum Perform. 2022; 93(4):376-383.


Influence of Biometric Variables on Refractive Outcomes after Cataract Surgery in Angle-closure Glaucoma Patients.
To evaluate the influence of biometric variables on refractive outcomes after cataract surgery in angle-closure glaucoma (ACG) patients. In this case-control study, 42 ACG patients, 40 open-angle glaucoma (OAG) patients, and 35 controls without glaucoma who had undergone conventional cataract surgery were enrolled consecutively. Electronic medical records, including preoperative biometric variables (keratometric diopter, axial length, anterior chamber depth, and lens thickness), the refractive change (RC), and the absolute value of refractive change (ARC) were reviewed. In the control and OAG patients, the anterior chamber depth was negatively correlated with the ARC (r = -0.344, p = 0.043 and r = -0.431, p = 0.006, respectively), whereas there was no correlation in the ACG patients. Lens thickness was positively correlated with the RC, but not with the ARC, in the control and OAG groups (r = 0.391, p = 0.020 and r = 0.501, p = 0.001, respectively). In contrast, lens thickness in the ACG group was not correlated with the RC but was positively correlated with the ARC (r = 0.331, p = 0.032). In contrast with the anterior chamber depth, preoperatively measured lens thickness may be a useful predictor of the direction of the RC after cataract surgery in control and OAG patients. However, in ACG patients, a thicker lens was correlated with a larger RC, regardless of the direction of the shift (hyperopic or myopic).


Phytodegradation of neonicotinoids in Cyperus papyrus from enzymatic and transcriptomic perspectives.
Neonicotinoids are widely used but environmentally hazardous insecticides. Constructed wetlands offer potential for neonicotinoid removal, but the corresponding metabolic pathways and mechanisms in wetland plants are incompletely understood. This study investigated the fate of six neonicotinoids and their metabolites in Cyperus papyrus, a common wetland plant, and the underlying metabolic mechanisms through enzymatic and transcriptomic analyses. Neonicotinoids were absorbed by roots and translocated upward, causing high levels in shoots. Concentrations of neonicotinoids and their metabolites declined to their minimum at day 28 of exposure. Nitro reduction, hydroxylation, and demethylation were the major metabolic reactions with which C. papyrus responded to neonicotinoids. These reactions may be mediated by cytochrome P450 enzyme, aldehyde oxidase, glutathione-disulfide reductase, and glucuronate reductase. The toxicity of neonicotinoids in C. papyrus was evaluated according to the peroxidase and catalase enzymatic activities. Transcriptomic analysis revealed that differentially expressed genes (DEGs) mainly encoded proteins related to immune processes and cell growth regulation. Co-expression correlation analysis of DEGs revealed that the genes encoding P450s, peroxidase and glutathione S-transferase were the key functional genes. This study elucidates the stress response and degradation mechanism of neonicotinoids in wetland plants, providing new insights into the phytoremediation of organic contaminants in constructed wetlands.


PUFA status at birth and allergy-related phenotypes in childhood: a pooled analysis of the Maastricht Essential Fatty Acid Birth (MEFAB) and RHEA birth cohorts.
Lower prenatal exposure to n-3 PUFA relative to n-6 PUFA has been hypothesised to influence allergy development, but evidence remains largely inconsistent. In the Dutch Maastricht Essential Fatty Acid Birth (MEFAB) (n 293) and Greek RHEA Mother-Child (n 213) cohorts, we investigated whether cord blood phospholipid PUFA concentrations are associated with symptoms of wheeze, asthma, rhinitis and eczema at the age of 6-7 years. Information on allergy-related phenotypes was collected using validated questionnaires. We estimated relative risks (RR) and 95 % CI for associations of PUFA with child outcomes using multivariable generalised linear regression models. In pooled analyses, higher concentration of the n-3 long-chain EPA and DHA and a higher total n-3:n-6 PUFA ratio were associated with lower risk of current wheeze (RR 0·61; 95 % CI 0·45, 0·82 per sd increase in EPA+DHA and 0·54; 95 % CI 0·39, 0·75 per unit increase in the n-3:n-6 ratio) and reduced asthma risk (RR 0·50; 95 % CI 0·31, 0·79 for EPA+DHA and 0·43; 95 % CI 0·26, 0·70 for the n-3:n-6 ratio). No associations were observed for other allergy-related phenotypes. The results were similar across cohorts. In conclusion, higher EPA and DHA concentrations and a higher n-3:n-6 fatty acid ratio at birth were associated with lower risk of child wheeze and asthma. Our findings suggest that dietary interventions resulting in a marked increase in the n-3:n-6 PUFA ratio, and mainly in n-3 long-chain PUFA intake in late gestation, may reduce the risk of asthma symptoms in mid-childhood.


Photoaffinity labeling of oxidosqualene cyclase and squalene cyclase by a benzophenone-containing inhibitor.
A new orally active oxidosqualene:lanosterol cyclase (OSLC) inhibitor (Ro48-8071; Morand, O. H. et al. (1997) J. Lipid Res. 38, 373-390) showed potent noncompetitive inhibition of bacterial squalene:hopene cyclase (SHC) from Alicyclobacillus acidocaldarius (IC50 = 9.0 nM, KI = 6.6 nM) and OSLC (IC50 = 40 nM, KI = 22 nM for homogeneous rat liver OSLC). A tritium-labeled isotopomer (18.8 Ci/mmol) of this nonterpenoid inhibitor, which possesses a benzophenone (BP) photophore, was chemically synthesized as a photoaffinity label. Specific, efficient covalent modification of both OSLC and SHC enzymes was observed after UV irradiation at 360 nm. Labeling of both OSLC and SHC by [3H]Ro48-8071 was competitively displaced by coincubation with a 1000-fold molar excess of 18-thia-2, 3-oxidosqualene or the nonterpenoid inhibitor BIBX79. Displacement of labeling of OSLC was also achieved with the suicide substrate (3S)-29-methylidene-2,3-oxidosqualene. Thus, the nonsubstrate Ro48-8071 and both terpenoid and nonterpenoid inhibitors of these enzymes appear to share a common binding site.


A machine learning approach for the factorization of psychometric data with application to the Delis Kaplan Executive Function System.
While a replicability crisis has shaken psychological sciences, the replicability of multivariate approaches for psychometric data factorization has received little attention. In particular, Exploratory Factor Analysis (EFA) is frequently promoted as the gold standard in psychological sciences. However, the application of EFA to executive functioning, a core concept in psychology and cognitive neuroscience, has led to divergent conceptual models. This heterogeneity severely limits the generalizability and replicability of findings. To tackle this issue, in this study, we propose to capitalize on a machine learning approach, OPNMF (Orthonormal Projective Non-Negative Factorization), and leverage internal cross-validation to promote generalizability to an independent dataset. We examined its application on the scores of 334 adults at the Delis-Kaplan Executive Function System (D-KEFS), while comparing to standard EFA and Principal Component Analysis (PCA). We further evaluated the replicability of the derived factorization across specific gender and age subsamples. Overall, OPNMF and PCA both converge towards a two-factor model as the best data-fit model. The derived factorization suggests a division between low-level and high-level executive functioning measures, a model further supported in subsamples. In contrast, EFA, highlighted a five-factor model which reflects the segregation of the D-KEFS battery into its main tasks while still clustering higher-level tasks together. However, this model was poorly supported in the subsamples. Thus, the parsimonious two-factors model revealed by OPNMF encompasses the more complex factorization yielded by EFA while enjoying higher generalizability. Hence, OPNMF provides a conceptually meaningful, technically robust, and generalizable factorization for psychometric tools.


Impact of IgG Monitoring and IVIG Supplementation on the Frequency of Febrile Illnesses in Pediatric Acute Lymphoblastic Leukemia Patients Undergoing Maintenance Chemotherapy.
Monitoring serum immunoglobulin G (IgG) levels in pediatric oncology patients and treating subtherapeutic levels with intravenous immunoglobulin (IVIG) may prevent infections; however, evidence is limited. This retrospective study assessed pediatric acute lymphoblastic leukemia patients diagnosed 2006 to 2011 to evaluate if monitoring/supplementing IgG would reduce febrile illnesses during maintenance chemotherapy. A subject was categorized as "ever IgG monitored" if they had ≥1 IgG levels checked and their risk days were stratified into not IgG monitored days and IgG monitored days. IgG monitored days were further stratified into IgG monitored with IVIG supplementation, monitored with no IVIG supplementation (IgG level >500 mg/dL) and monitored with no IVIG supplementation days (IgG level <500 mg/dL). Generalized linear mixed effects poisson models were used to compare events (febrile episode, positive blood culture, and febrile upper respiratory infection rates among these groups. In 136 patients, the febrile episode rate was higher in the ever IgG monitored cohort than the never monitored cohort (5.26 vs. 3.78 episodes/1000 d). Among monitored patients, IVIG monitoring and supplementation did not significantly impact the febrile episode, febrile upper respiratory infection, or the positive blood culture rates. These data suggest that monitoring/supplementing low IgG is not indicated for infection prophylaxis in acute lymphoblastic leukemia patients during maintenance chemotherapy.


eHealth Technologies, Multimorbidity, and the Office Visit: Qualitative Interview Study on the Perspectives of Physicians and Nurses.
eHealth is a broad term referring to the application of information and communication technologies in the health sector, ranging from health records to telemedicine and multiple forms of health education and digital tools. By providing increased and anytime access to information, opportunities to exchange experiences with others, and self-management support, eHealth has been heralded as transformational. It has created a group of informed, engaged, and empowered patients as partners, equipped to take part in shared decision making and effectively self-manage chronic illness. Less attention has been given to health care professionals' (HCPs) experiences of the role of eHealth in patient encounters. The objective of this study was to examine HCPs' perspectives on how eHealth affects their relationships with patients living with multiple chronic conditions, as well as its ethical and practical ramifications. We interviewed HCPs about their experiences with eHealth and its impact on the office visit. Eligible participants needed to report a caseload of ≥25% of patients with multimorbidity to address issues of managing complex chronic conditions and coordination of care. We used a semistructured discussion guide for in-depth interviews, and follow-up interviews served to clarify and expand upon initial discussions. Constant comparisons and a narrative approach guided the analyses, and a relational ethics conceptual lens was applied to the data to identify emergent themes. A total of 12 physicians and nurses (6 male, 6 female; median years of practice=13) participated. eHealth tools most frequently described were Web-based educational resources for patients and Web-based resources for HCPs such as curated scientific summaries on diagnostic criteria, clinical therapies, and dosage calculators. Analysis centered on a grand theme of the two-way conversation between HCPs and patients, which addresses a general recentering of the ethical relationship between HCPs and patients around engagement. Subthemes explain the evolution of the two-way conversation, and having, using, and supporting the two-way conversation with patients, primarily as this relates to achieving adherence and health outcomes. Emerging ethical concerns were related to the ambiguity of the ideal of empowered patients and the ways in which health professionals described enacting those ideals in practice, showing how the cultural shift toward truly mutually respectful and collaborative practice is in transition. HCPs aim to act in the best interests of their patients; the challenge is to benefit from emergent technologies that may enhance patient-HCP interactions and effective care, while abiding by regulations, dealing with the strictures of the technology itself, and managing changing demands on their time.