Ballistic InSb Nanowires and Networks via Metal-Sown Selective Area Growth.
Selective area growth is a promising technique to realize semiconductor-superconductor hybrid nanowire networks, potentially hosting topologically protected Majorana-based qubits. In some cases, however, such as the molecular beam epitaxy of InSb on InP or GaAs substrates, nucleation and selective growth conditions do not necessarily overlap. To overcome this challenge, we propose a metal-sown selective area growth (MS SAG) technique, which allows decoupling selective deposition and nucleation growth conditions by temporarily isolating these stages. It consists of three steps: (i) selective deposition of In droplets only inside the mask openings at relatively high temperatures favoring selectivity, (ii) nucleation of InSb under Sb flux from In droplets, which act as a reservoir of group III adatoms, done at relatively low temperatures, favoring nucleation of InSb, and (iii) homoepitaxy of InSb on top of the formed nucleation layer under a simultaneous supply of In and Sb fluxes at conditions favoring selectivity and high crystal quality. We demonstrate that complex InSb nanowire networks of high crystal and electrical quality can be achieved this way. We extract mobility values of 10 000-25 000 cm2 V-1 s-1 consistently from field-effect and Hall mobility measurements across single nanowire segments as well as wires with junctions. Moreover, we demonstrate ballistic transport in a 440 nm long channel in a single nanowire under a magnetic field below 1 T. We also extract a phase-coherent length of ∼8 μm at 50 mK in mesoscopic rings.


Measuring oxygen saturation in retinal and choroidal circulations in rats using visible light optical coherence tomography angiography.
Visible light optical coherence tomography (vis-OCT) has demonstrated its capability of measuring vascular oxygen saturation (sO2) in vivo. Enhanced by OCT angiography, the signal from microvasculature can be further isolated and directly used for sO2 extraction. In this work, we extended the theoretical formulation for OCT angiography-based oximetry by incorporating the contribution from motion contrast enhancement. We presented a new method to eliminate the associated confounding variables due to blood flow. First, we performed in vitro experiments to verify our theory, showing a stable spectral derivative within the selected wavelength bands for sO2 extraction. Then, we tested our method in vivo to measure retinal sO2 in rats inhaling different gas mixtures: normal air, 5% CO2, pure O2, and 10% O2. Absolute sO2 values in major arterioles and venules in the retinal circulation can be accurately measured. In addition, we demonstrated the relative changes of sO2 can be measured non-invasively from choriocapillaris immediately underneath the retinal pigmented epithelium (RPE) in rodents.


Genetic diversity in Oryza glumaepatula wild rice populations in Costa Rica and possible gene flow from O. sativa.
Wild crop relatives are an important source of genetic diversity for crop improvement. Diversity estimates are generally lacking for many wild crop relatives. The objective of the present study was to analyze how genetic diversity is distributed within and among populations of the wild rice species Oryza glumaepatula in Costa Rica. We also evaluated the likelihood of gene flow between wild and commercial rice species because the latter is commonly sympatric with wild rice populations. Introgression may change wild species by incorporating alleles from domesticated species, increasing the risk of losing original variation. Specimens from all known O. glumaepatula populations in Costa Rica were analyzed with 444 AFLP markers to characterize genetic diversity and structure. We also compared genetic diversity estimates between O. glumaepatula specimens and O. sativa commercial rice. Our results showed that O. glumaepatula populations in Costa Rica have moderately high levels of genetic diversity, comparable to those found in South American populations. Despite the restricted distribution of this species in Costa Rica, populations are fairly large, reducing the effects of drift on genetic diversity. We found a dismissible but significant structure (θ = 0.02 ± 0.001) among populations. A Bayesian structure analysis suggested that some individuals share a significant proportion of their genomes with O. sativa. These results suggest that gene flow from cultivated O. sativa populations may have occurred in the recent past. These results expose an important biohazard: recurrent hybridization may reduce the genetic diversity of this wild rice species. Introgression may transfer commercial traits into O. glumaepatula, which in turn could alter genetic diversity and increase the likelihood of local extinction. These results have important implications for in situ conservation strategies of the only wild populations of O. glumaepatula in Costa Rica.


Mobile microrobots for bioengineering applications.
Untethered micron-scale mobile robots can navigate and non-invasively perform specific tasks inside unprecedented and hard-to-reach inner human body sites and inside enclosed organ-on-a-chip microfluidic devices with live cells. They are aimed to operate robustly and safely in complex physiological environments where they will have a transforming impact in bioengineering and healthcare. Research along this line has already demonstrated significant progress, increasing attention, and high promise over the past several years. The first-generation microrobots, which could deliver therapeutics and other cargo to targeted specific body sites, have just been started to be tested inside small animals toward clinical use. Here, we review frontline advances in design, fabrication, and testing of untethered mobile microrobots for bioengineering applications. We convey the most impactful and recent strategies in actuation, mobility, sensing, and other functional capabilities of mobile microrobots, and discuss their potential advantages and drawbacks to operate inside complex, enclosed and physiologically relevant environments. We lastly draw an outlook to provide directions in the veins of more sophisticated designs and applications, considering biodegradability, immunogenicity, mobility, sensing, and possible medical interventions in complex microenvironments.


Electrokinetically driven microfluidic chips with surface-modified chambers for heterogeneous immunoassays.
This article presents the first example of a microfluidic chip for heterogeneous bioassays using a locally immobilized biospecific layer and operated electrokinetically. The reaction chamber has picoliter dimensions and is integrated into a network of microchannels etched in glass. The high affinity of protein A (PA) for rabbit immunoglobulin G (rIgG) was exploited for chip testing, with PA being immobilized on microchannel walls and fluorescently labeled (Cy5) rIgG serving as sample. It was possible to operate the chip in an immunoaffinity chromatographic manner, using electrokinetically pumped solutions. Concentration of antibody from dilute solution onto the solid phase was demonstrated, with signal gains of approximately 30 possible. A dose-response curve for Cy5-rIgG was obtained for concentrations down to 50 nM, for an incubation time of 200 s. The flexibility of chip layout was demonstrated for competitive immunoassay of rIgG, using both a combined sample/tracer incubation and sequential addition of these solutions. With assay times generally below 5 min for this unoptimized device, the microfluidic approach described shows great potential for many high-throughput screening applications.


Intuition and evidence--uneasy bedfellows?
Intuition is a decision-making method that is used unconsciously by experienced practitioners but is inaccessible to the novice. It is rapid, subtle, contextual, and does not follow simple, cause-and-effect logic. Evidence-based medicine offers exciting opportunities_for improving patient outcomes, but the 'evidence-burdened' approach of the inexperienced, protocol-driven clinician is well documented Intuition is not unscientific. It is a highly creative process, fundamental to hypothesis generation in science. The experienced practitioner should generate and follow clinical hunches as well as (not instead of applying the deductive principles of evidence-based medicine. The educational research literature suggests that we can improve our intuitive powers through systematic critical reflection about intuitive judgements--for example, through creative writing and dialogue with professional colleagues. It is time to revive and celebrate clinical storytelling as a method for professional education and development. The stage is surely set for a new, improved--and, indeed, evidence-based--'Balint'group.


Ultrafast excited-state dynamics and fluorescence deactivation of near-infrared fluorescent proteins engineered from bacteriophytochromes.
Near-infrared fluorescent proteins, iRFPs, are recently developed genetically encoded fluorescent probes for deep-tissue in vivo imaging. Their functions depend on the corresponding fluorescence efficiencies and electronic excited state properties. Here we report the electronic excited state deactivation dynamics of the most red-shifted iRFPs: iRFP702, iRFP713 and iRFP720. Complementary measurements by ultrafast broadband fluorescence and absorption spectroscopy show that single exponential decays of the excited state with 600~700 ps dominate in all three iRFPs, while photoinduced isomerization was completely inhibited. Significant kinetic isotope effects (KIE) were observed with a factor of ~1.8 in D2O, and are interpreted in terms of an excited-state proton transfer (ESPT) process that deactivates the excited state in competition with fluorescence and chromophore mobility. On this basis, new approaches for rational molecular engineering may be applied to iRFPs to improve their fluorescence.


Bayesian population decoding of motor cortical activity using a Kalman filter.
Effective neural motor prostheses require a method for decoding neural activity representing desired movement. In particular, the accurate reconstruction of a continuous motion signal is necessary for the control of devices such as computer cursors, robots, or a patient's own paralyzed limbs. For such applications, we developed a real-time system that uses Bayesian inference techniques to estimate hand motion from the firing rates of multiple neurons. In this study, we used recordings that were previously made in the arm area of primary motor cortex in awake behaving monkeys using a chronically implanted multielectrode microarray. Bayesian inference involves computing the posterior probability of the hand motion conditioned on a sequence of observed firing rates; this is formulated in terms of the product of a likelihood and a prior. The likelihood term models the probability of firing rates given a particular hand motion. We found that a linear gaussian model could be used to approximate this likelihood and could be readily learned from a small amount of training data. The prior term defines a probabilistic model of hand kinematics and was also taken to be a linear gaussian model. Decoding was performed using a Kalman filter, which gives an efficient recursive method for Bayesian inference when the likelihood and prior are linear and gaussian. In off-line experiments, the Kalman filter reconstructions of hand trajectory were more accurate than previously reported results. The resulting decoding algorithm provides a principled probabilistic model of motor-cortical coding, decodes hand motion in real time, provides an estimate of uncertainty, and is straightforward to implement. Additionally the formulation unifies and extends previous models of neural coding while providing insights into the motor-cortical code.


Quantitative studies on T cell diversity. II. Determination of the frequencies and Lyt phenotypes of two types of precursor cells for alloreactive cytotoxic T cells in polyclonally and specifically activated splenic T cells.
Two different limiting dilution systems have been applied to compare precursor frequencies of alloreactive cytotoxic T cells (CTL-P) in the polyclonally and specifically activated lymphocyte populations and in selected Lyt T cell subsets. Both systems make use of T cell growth factor for T cell expansion but differ with respect to the activation step in that lymphocytes are either activated directly with allogenetic stimulator cells or are sensitized polyclonally with concanavalin A (Con A) in bulk culture before their expansion under limiting dilution conditions. In polyclonally activated C57BL/6 lymphocyte populations, two types of CTL-P specific for H-2d alloantigens could be identified: a frequent set with a frequency of 1/100-1/300, and a rare set with a frequency of 1/2,000-1/8,000. In contrast, only a single CTL-P set was found in specifically activated populations with a frequency similar to that of the frequent CTL-P found on Con A blasts. In Con A blasts, the frequent at higher cell concentrations by suppressor T cells, whereas rare CTL-P were insensitive to this suppressive mechanism. Whereas in specifically activated T cells, the predominant CTL-P phenotype was Lyt-123, the predominant Lyt phenotypes for the frequent and the rare CTL-P found in Con A blasts were Lyt-123 and Lyt-123, respectively, which suggests that they represent primary and secondary CTL-P, respectively. The results are discussed with respect to previous reports on the involvement of Lyt T cell subsets in the generation of cytotoxic responses and their regulation by T suppressor cells.


Burden of hospitalisation among older people in the Brazilian public health system: a big data analysis from 2009 to 2015.
The world's population is progressively ageing, and this trend imposes several challenges to society and governments. The aim of this study was to investigate the burden generated by the hospitalisation of older (>60 years) compared with non-older population, as well as the epidemiology of these hospital admissions. Using the Brazilian Unified Health System (known as 'Sistema Único de Saúde' (SUS)), an analysis of all hospital admissions of adult patients in the SUS from 2009 to 2015 was undertaken. The following indicators were used: hospital admission rate, intensive care unit (ICU) admission rate, average length of hospital and ICU stay, hospital mortality and average reimbursement per hospitalisation. A total of 61 958 959 admissions during the 7-year period, were analysed, encompassing 17 893 392 (28.9%) older patients. Elderly represent 15% (n=21 294 950) of the Brazilian adult population, but are responsible for 29% (n=17 893 392) of hospitalisations, 52% (n=1 731 299) of ICU admissions and 66% (n=1 885 291) of hospital mortality. Among the adults, elderly represents 39% of the total reimbursement made related to admission/hospitalisation. For 2009 to 2015, while the older population increased 27%, ICU admission rate increased 20%; the average length of ICU stay was 12% higher in 2015 (6.5 days) compared with 2009 (5.8 days); and the hospital mortality increased from 9.8% to 11.2%. These findings illustrate the current panorama of the burden due to hospitalisation of older people in the Brazilian public health system, and evidence the consolidation of the epidemiological transition toward the predominance of non-communicable diseases as the main cause of hospitalisation among the elderly in Brazil.


Prevalence and risk factors for hepatitis B virus infections among STD patients in northeast region of Iran.
In many parts of the world, sexual transmission of hepatitis B virus plays a major role in acquisition of infections. In Northeast region of Iran the prevalence rate and risk factors influencing this type of transmission was not investigated. Therefore, the concurrence of hepatitis B virus (HBV) and STDs was studied to determine the prevalence and risk factors of sexual transmission of hepatitis B virus. This study was carried out among 1500 attendances to the laboratories for STDs examination between 1998 and 2000. Those who were positive for STDs (syphilis & gonorrhea) were examined for HBV infection by determination of hepatitis B surface antigen (HBsAg). The data was analyzed and compared to the normal population. The prevalence of STD in this population was 4.66% for syphilis and 6% for gonorrhea. Among this population the seroprevalence of HBsAg was 10% in women and 14.2% in men (mean seroprevalence of HBsAg was 13.13%). The concurrence of hepatitis B virus and syphilis was 14.28% which was slightly higher than concurrence for gonorrhea (12.22%). The prevalence of HBV in our patient population was high, exceeding the national estimates. This population also represents a high-risk group in Northeast of Iran. Further, our data indicates that such high prevalence is significantly more evident in patients with low socioeconomic status.


Prenatal BoBsTM in the cytogenetic analysis of products of spontaneous miscarriage.
Fifty percent of spontaneous miscarriages (SMs) are attributed to chromosomal abnormalities. Cytogenetic analysis is an important tool for patient counselling and assessment of the risk of recurrence in future pregnancies. Conventional karyotyping has been the gold standard for chromosomal investigation of products of conception (POC), but it has limitations due to sample maceration, culture failure and maternal cell contamination. Molecular cytogenetic approaches have therefore been developed and found valuable in the cytogenetic investigation of these samples. The Prenatal BoBsTM and KaryoLite BoBsTM, based on the newly developed BACs-on-BeadsTM technology, have been described as reliable tests for rapid detection of aneuploidies in prenatal and POC samples, respectively. To describe our clinical experience of routine screening of POC samples with Prenatal BoBsTM, the test used by our laboratory in France. Seventeen samples collected at the University Hospital of Sidi Bel Abbès (Western Algeria) and a further 60 from the University Hospital of Clermont-Ferrand (France) were analysed (19 chorionic villi from products of curettage, 12 placentas, 9 amniotic cells and 37 biopsy specimens). All were screened for the frequent aneuploidies (chromosomes 13, 18, 21, X and Y) in addition to nine microdeletion/microduplication syndrome regions by Prenatal BoBsTM. Standard karyotyping was performed on 51 samples, but failed in 38 cases. Prenatal BoBsTM identified one trisomy 21 and one deletion of 17p13.3. Furthermore, it provided a conclusive result in cases of culture failure (n=38) and in samples with macerated tissue (n=19). The overall failure rate was 11.4%. Prenatal BoBsTM is a promising technology that represents a fast, sensitive and robust alternative to routine screening for chromosomal abnormality in products of SM. Furthermore, it overcomes the limitations of conventional karyotyping and current molecular cytogenetic techniques.


Regularized Multitask Learning for Multidimensional Log-Density Gradient Estimation.
Log-density gradient estimation is a fundamental statistical problem and possesses various practical applications such as clustering and measuring nongaussianity. A naive two-step approach of first estimating the density and then taking its log gradient is unreliable because an accurate density estimate does not necessarily lead to an accurate log-density gradient estimate. To cope with this problem, a method to directly estimate the log-density gradient without density estimation has been explored and demonstrated to work much better than the two-step method. The objective of this letter is to improve the performance of this direct method in multidimensional cases. Our idea is to regard the problem of log-density gradient estimation in each dimension as a task and apply regularized multitask learning to the direct log-density gradient estimator. We experimentally demonstrate the usefulness of the proposed multitask method in log-density gradient estimation and mode-seeking clustering.


Induction of glutamate dehydrogenase in the ovine fetal liver by dexamethasone infusion during late gestation.
Glucocorticoids near term are known to upregulate many important enzyme systems prior to birth. Glutamate dehydrogenase (GDH) is a mitochondrial enzyme that catalyzes both the reversible conversion of ammonium nitrogen into organic nitrogen (glutamate production) and the oxidative deamination of glutamate resulting in 2-oxoglutarate. The activity of this enzyme is considered to be of major importance in the development of catabolic conditions leading to gluconeogenesis prior to birth. Ovine hepatic GDH mRNA expression and activity were determined in near-term (130 days of gestation, term 147 +/- 4 days) control and acutely dexamethasone-treated (0.07 mg(-1) hr(-1) for 26 hr) fetuses. Dexamethasone infusion had no effect on placental or fetal liver weights. Dexamethasone infusion for 26 hr significantly increased hepatic GDH mRNA expression. This increased GDH mRNA expression was accompanied by an increase in hepatic mitochondrial GDH activity, from 30.0 +/- 7.4 to 58.2 +/- 8.1 U GDH/U CS (citrate synthase), and there was a significant correlation between GDH mRNA expression and GDH activity. The generated ovine GDH sequence displayed significant similarity with published human, rat, and murine GDH sequence. These data are consistent with the in vivo studies that have shown a redirection of glutamine carbon away from net hepatic glutamate release and into the citric acid cycle through the forward reaction catalyzed by GDH, i.e., glutamate to oxoglutarate.


The interaction of GSK3B and FXR1 genotypes may influence the mania and depression dimensions in mood disorders.
Previous evidence in healthy subjects suggested that functional polymorphisms GSK3B rs12630592 and FXR1 rs496250 interact in regulating mood and emotional processing. We attempted to replicate this interaction primarily on manic and depressive dimensions in mood disorder patients, and secondarily on schizophrenia patients, diagnosis itself and age of onset. Symptom dimensions were derived from the Comprehensive Assessment of Symptoms and History 82 items rated lifetime in acute episodes and stabilized interepisode intervals in 384 patients from the Schizophrenia and Bipolar Disorder Eastern Quebec Kindred Study. Linear mixed effect models of symptom dimensions included rs12630592-rs496250 main and interaction fixed effects (obtained from TaqMan genotypes), and a polygenic random effect. The distribution of lifetime best-estimate DSM-IV diagnosis of 855 kindred members was studied versus genotype under a polytomous logistic model. In mood disorder patients, the level of mania (in both acute and stabilized periods) and depression in stabilized periods was positively associated with GSK3B rs12630592 T only in FXR1 rs496250 A-allele carriers (Bonferroni-corrected interaction p=0.024, 0.052 and 0.017 respectively). The two polymorphisms explained 11% of mania variance and 5% of interepisode depression variance. The association was observed neither in schizophrenia patients nor with the psychotic dimension in mood disorder patients. Interaction with the diagnosis distribution (p=0.03) was driven by the decreasing prevalence of recurrent major depression with rs12630592 T also only in carriers of rs496250 A. Sample size was limited, but power was sufficient to detect the tested interaction effect in this replication sample. We replicate in affective patients an interaction between the FXR1 rs496250 and GSK3B rs12630592 polymorphisms in regulating mood dimensions.


Fatal brain damage associated with cardiomyopathy of pregnancy, with notes on Caesarean section in a hyperbaric chamber.
Three weeks after admission to a maternity hospital for observation following minor antepartum haemorrhage, a primiparous patient aged 22 suffered a sudden left hemiplegia and became comatose. Congestive cardiac failure ensued and because of the subsequent severe hypoxaemia she was transferred to the hyperbaric oxygen unit at the Western Infirmary, Glasgow, where it was found possible to improve her condition by means of oxygen at increased pressure. A caesarean section was w successfully performed in the hyperbaric chamber, and a normal live female infant was delivered. Though the patient's general condition improved she never regained consciousness and died almost three months later. Necropsy confirmed the clinical diagnosis of cardiomyopathy of pregnancy with severe ischaemic changes in the brain.


Mathematical modelling of tumour acidity.
Acid-mediated tumour invasion is receiving increasing experimental and clinical attention. Previous models proposed to describe this phenomenon failed to capture key properties of the system, such as the existence of the benign steady state, or predicted incorrectly the size of the inter-tissue gap. Here we show that taking proper account of quiescence ameliorates these drawbacks as well as revealing novel behaviour. The simplicity of the model allows us to fully identify the key parameters controlling different aspects of behaviour.


Evaluation of solid substrates for enzyme production by Coriolus versicolor, for use in bioremediation of chlorophenols in aqueous effluents.
In the development of a system for the removal of chlorophenols from aqueous effluents, a range of solid substrates for the growth of Coriolus versicolor were investigated. Substrates included wood chips, cereal grain, wheat husk and wheat bran. Suitability for transformation of chlorophenols depended on laccase production by the fungus. The greatest amount of laccase (<25 Units g(-1) substrate) was produced on wheat husk and wheat bran over 30 days colonisation. Aqueous extracts of laccase from wheat husk and wheat bran cultures removed 100% of 2,4-dichlorophenol (50 ppm) from solution within 5 h and 75-80% of pentachlorophenol (50 ppm) within 24 h. Wheat bran was formulated into pellets with biscuit flour to provide a compact substrate for fungal immobilisation. Addition of 8-12% yeast extract to the pellets increased laccase production five-fold. Colonised pellets were added to chlorophenol solutions in 200-4000-ml bioreactors, resulting in >90% removal of chlorophenols within 100 min.


The impact of smoking and quitting on household expenditure patterns and medical care costs in China.
Smoking remains very common in Chinese men, and the economic burden caused by cigarette consumption on smokers and their families may be substantial. Using a large nationally representative household survey, the third National Health Services Survey (NHSS, 2003), we estimated the economic impact of smoking on households. Smoking status of all household members (over 15 years) was collected by interview for the NHSS, and households classified into one of seven categories based on their smoking status. Information on household income and expenditure, and use of health services was also obtained. We assessed both the "direct" costs (reducing funds available for spending on other commodities such as food, education, medical care, etc, using a fractional logit model), and "indirect costs" (increasing medical expenditures, using a log-linear model). Every five packets of cigarettes consumed per capita per month reduces household spending on other commodities, most notably on education (by about 17 yuan per capita per annum) and medical care (11 yuan). The effects are greatest among low-income rural households. Households with quitters spend substantially more on medical care than never-smoking households (64 yuan for households with two or more quitters). If a household member smokes, there is less money available for commodities such as education and medical care. Medical care expenditure is substantially higher among households with quitters, as ill-health is the main reason for quitting smoking in China. Smoking impoverishes a substantial number of poorer rural households.


Gene expression in human embryonic stem cell lines: unique molecular signature.
Human embryonic stem (huES) cells have the ability to differentiate into a variety of cell lineages and potentially provide a source of differentiated cells for many therapeutic uses. However, little is known about the mechanism of differentiation of huES cells and factors regulating cell development. We have used high-quality microarrays containing 16 659 seventy-base pair oligonucleotides to examine gene expression in 6 of the 11 available huES cell lines. Expression was compared against pooled RNA from multiple tissues (universal RNA) and genes enriched in huES cells were identified. All 6 cell lines expressed multiple markers of the undifferentiated state and shared significant homology in gene expression (overall similarity coefficient > 0.85).A common subset of 92 genes was identified that included Nanog, GTCM-1, connexin 43 (GJA1), oct-4, and TDGF1 (cripto). Gene expression was confirmed by a variety of techniques including comparison with databases, reverse transcriptase-polymerase chain reaction, focused cDNA microarrays, and immunocytochemistry. Comparison with published "stemness" genes revealed a limited overlap, suggesting little similarity with other stem cell populations. Several novel ES cell-specific expressed sequence tags were identified and mapped to the human genome. These results represent the first detailed characterization of undifferentiated huES cells and provide a unique set of markers to profile and better understand the biology of huES cells.


Intracranial Pressure and Its Relationship to Glaucoma: Current Understanding and Future Directions.
Retrospective and prospective studies looking at the role of cerebrospinal fluid pressure (CSFP)/intracranial pressure (ICP) have stimulated new theories and hypotheses regarding the underlying causal events for glaucoma. Most recently, studies supporting a low CSFP/ICP as a risk factor for glaucoma have been published. This review summarizes the current understanding of CSFP/ICP and its potential role in the pathogenicity of the disease.


Cerebral artery thrombosis and intramural hemorrhage.
Thirty-nine thrombosed arterial segments of the branches of the circle of Willis were studied by a complete serial section technique. Twenty-two patients had been hypertensive and 8 had hypercholesterolemia before the onset of cerebral artery thrombosis. The histological characteristics of the thrombosed arterial segments were intramural hemorrhage in 28 segments, superficial edema of the fibrous cap of the atheroma of fibrous plaque in 4, rupture of the atheromatous plaque in 1, superficial accumulation of foam cells in the atheroma in 1 and an atheroma or fibrous plaque without any other changes in 5. They were many intramural small blood vessels in the atheroma or fibrous plaques of 22 segments with intramural hemorrhage. Fibrinoid degeneration of these small blood vessels was noted in 5. These findings suggested that intramural hemorrhage from the intramural small blood vessels was the major cause of cerebral artery thrombosis and that persistent hypertension not only promoted cerebral atherosclerosis but also induced hemorrhage from the intramural small blood vessels.


Estimation of Radiation Doses to U.S. Military Test Participants from Nuclear Testing: A Comparison of Historical Film-Badge Measurements, Dose Reconstruction and Retrospective Biodosimetry.
Retrospective radiation dose estimations, whether based on physical or biological measurements, or on theoretical dose reconstruction, are limited in their precision and reliability, particularly for exposures that occurred many decades ago. Here, we studied living U.S. military test participants, believed to have received high-dose radiation exposures during nuclear testing-related activities approximately six decades ago, with two primary goals in mind. The first was to compare three different approaches of assessing past radiation exposures: 1. Historical personnel monitoring data alone; 2. Dose reconstruction based on varying levels of completeness of individual information, which can include film badge data; and 3. Retrospective biodosimetry using chromosome aberrations in peripheral blood lymphocytes. The second goal was to use the collected data to make the best possible estimates of bone marrow dose received by a group with the highest military recorded radiation doses of any currently living military test participants. Six nuclear test participants studied had been on Rongerik Atoll during the 1954 CASTLE Bravo nuclear test. Another six were present at the Nevada Test Site (NTS) and/or Pacific Proving Ground (PPG) and were believed to have received relatively high-dose exposures at those locations. All were interviewed, and all provided a blood sample for cytogenetic analysis. Military dose records for each test participant, as recorded in the Defense Threat Reduction Agency's Nuclear Test Review and Information System, were used as the basis for historical film badge records and provided exposure scenario information to estimate dose via dose reconstruction. Dose to bone marrow was also estimated utilizing directional genomic hybridization (dGH) for high-resolution detection of radiation-induced chromosomal translocations and inversions, the latter being demonstrated for the first time for the purpose of retrospective biodosimetry. As the true dose for each test participant is not known these many decades after exposure, this study gauged the congruence of different methods by assessing the degree of correlation and degree of systematic differences. Overall, the best agreement between methods, defined by statistically significant correlations and small systematic differences, was between doses estimated by a dose reconstruction methodology that exploited all the available individual detail and the biodosimetry methodology derived from a weighted average dose determined from chromosomal translocation and inversion rates. Employing such a strategy, we found that the Rongerik veterans who participated in this study appear to have received, on average, bone marrow equivalent doses on the order of 300-400 mSv, while the NTS/ PPG participants appear to have received approximately 250-300 mSv. The results show that even for nuclear events that occurred six decades in the past, biological signatures of exposure are still present, and when taken together, chromosomal translocations and inversions can serve as reliable retrospective biodosimeters, particularly on a group-average basis, when doses received are greater than statistically-determined detection limits for the biological assays used.


Anxiety levels in dreams: relation to changes in plasma free fatty acids.
Blood samples for determination of plasma free fatty acids were obtained throughout the night by means of an indwelling catheter. The first sample was drawn at the onset of rapid eye movements and a second after 15 minutes of these movements. Subjects were then awakened and asked to relate their dreams; a third sample was drawn 15 to 25 minutes later. Anxiety scores derived from 20 dreams of nine subjects had significant positive correlations with changes in free fatty acids occurring during REM sleep. No statistically significant relation was found between anxiety and the changes in free fatty acids occurring from the time just before awakening to 15 to 25 minutes later. Presumably, anxiety in dreams triggers the release of catecholamines into the circulation, and these catecholamines mobilize proportional amounts of free fatty acids from body fat.


A National Effort to Prevent Type 2 Diabetes: Participant-Level Evaluation of CDC's National Diabetes Prevention Program.
To assess participant-level results from the first 4 years of implementation of the National Diabetes Prevention Program (National DPP), a national effort to prevent type 2 diabetes in those at risk through structured lifestyle change programs. Descriptive analysis was performed on data from 14,747 adults enrolled in year-long type 2 diabetes prevention programs during the period February 2012 through January 2016. Data on attendance, weight, and physical activity minutes were summarized and predictors of weight loss were examined using a mixed linear model. All analyses were performed using SAS 9.3. Participants attended a median of 14 sessions over an average of 172 days in the program (median 134 days). Overall, 35.5% achieved the 5% weight loss goal (average weight loss 4.2%, median 3.1%). Participants reported a weekly average of 152 min of physical activity (median 128 min), with 41.8% meeting the physical activity goal of 150 min per week. For every additional session attended and every 30 min of activity reported, participants lost 0.3% of body weight (P < 0.0001). During the first 4 years, the National DPP has achieved widespread implementation of the lifestyle change program to prevent type 2 diabetes, with promising early results. Greater duration and intensity of session attendance resulted in a higher percent of body weight loss overall and for subgroups. Focusing on retention may reduce disparities and improve overall program results. Further program expansion and investigation is needed to continue lowering the burden of type 2 diabetes nationally.


Robot-assisted aortic valve replacement using a novel sutureless bovine pericardial prosthesis: proof of concept as an alternative to percutaneous implantation.
: Percutaneous aortic valve implantation within native valve calcium has progressed to clinical use despite the absence of data proving equivalence to complete surgical excision and prosthetic valve replacement. A novel self-expanding sutureless bovine pericardial prosthesis (Sorin Perceval) derived from a proven stented valve has been successfully used in humans recently through an open transaortic approach. We sought to develop a minimally invasive technique for native aortic valve excision and sutureless prosthetic aortic valve replacement using robot assistance. : The da Vinci S-HD system was used to open and suspend the pericardium anterior to the phrenic nerve in cadavers. A transthoracic cross-clamp was placed across the midascending aorta, following which a transverse aortotomy was made. The native aortic valve cusps were excised, and annular calcium was removed with robotic instruments. After placement of three guide sutures, the Perceval self-expanding pericardial prosthesis mounted on a flexible delivery system was inserted through a working port and lowered into the aortic annulus. : Successful implantation of all valves was possible using a 3-cm right second intercostal space working port, along with two additional 1-cm instrument ports. A standard transverse aortotomy was sufficient for examination/debridement of the native aortic valve cusps, sizing of the annulus, and deployment of the nitinol-stented, bovine pericardial prosthesis. Delivery, seating, and stability of the device were easily confirmed above and below the aortic valve annulus using the robotic camera. : Complete excision of diseased native aortic valve cusps with robot assistance facilitates accurate and reproducible aortic valve replacement using a novel self-expanding sutureless version of a proven bovine pericardial prosthesis. This approach is comparable to the current surgical gold standard and is ready for clinical use as an alternative to percutaneous aortic valve implantation.


Dental usage under changing economic conditions.
The purpose of this article is to examine the relationship between changes in household finances (wealth and income) and changes in dental utilization at the onset of the recent recession in a population of older Americans. Data from the Health and Retirement Study (HRS) were analyzed for U.S. individuals aged 51 years and older during the 2006 and 2008 waves of the HRS. We estimated logistic models of (a) starting and (b) stopping dental use between 2006 and 2008 survey periods as a function of changes in household wealth and income, controlling for other potentially confounding covariates. We found that only when household wealth falls by 50 percent or more were older adults less likely to seek dental care. Changes in household income and other changes in household wealth were not associated with changes in dental utilization among this population. Older Americans' dental care utilization appeared to be fairly resilient to changes in household finances; only when wealth fell by 50 percent or more did individuals decrease dental use. This finding might extend to other health-care services that are preventive, routine, and relatively inexpensive.


Effect of pulsed radiofrequency for postherpetic neuralgia.
Postherpetic neuralgia (PHN) is one of the most intractable pain disorders, particularly among elderly patients. Lesioning of dorsal root ganglion (DRG) using pulsed radiofrequency (PRF) has shown pain reduction for PHN. We assessed the efficacy of PRF lesioning of DRG for PHN via an open, nonrandomized study. Forty-nine patients with PHN refractory to conservative therapy were involved. After impedance and sensory electrical nerve stimulation thresholds were assessed, PRF was performed three times adjacent to the DRG of corresponding levels at 42 degrees C for 120 s under the fluoroscopic guidance. Pain ratings were conducted on a visual analogue scale at 4-, 8- and 12-week follow-up. The data were analyzed using the one-way ANOVA test. P<0.05 was considered to be statistically significant. There was excellent pain relief (about 55%) at 4 weeks after PRF lesioning adjacent to the DRG and the effectiveness was maintained at the subsequent 12-week follow-up. The pain duration, age and stimulation level did not influence the outcome. There were no procedure-related complications. PRF lesioning of DRG showed significant pain relief compared with the conventional treatments in patients with intractable PHN. In order to elucidate the mode of action of PRF, further research is needed and the optimal electrical parameters of PRF have to be determined.


[Health promotion as a political decision in nursing education].
It is a descriptive-exploratory study with a qualitative approach that has the objective of analyzing the health promotion in training nurses. The setting of the research was two nursing undergraduate courses in the State of Minas Gerais, Brazil. The results show that both schools used settings favorable to a health promotion approach in this training. They anchor this approach in the need to provide students experiences of learning from an immersion in the reality of professional life. It is prevalent on formation a tension between good educational pratices for health promotion were revealed those become into the daily of the service and practices that arrest the subjects on their ways of thinking. It is concluded that health promotion is recognized as a political decision in nursing education, although this is yet incipient and has a mixed theoretical formulation, indicating the need to increase opportunities for conceptual and operational discussion.


Influences of the community and consumer nutrition environment on the food purchases and dietary behaviors of adolescents: A systematic review.
Adolescence is a period of increased autonomy over decision-making, including food choices, and increased exposure to influences outside the home, including the food environment. This review aims to synthesize the evidence for the influence of community nutrition environments, spatial access to food outlets, and consumer nutrition environments, environments inside food outlets, on adolescent food purchasing and dietary behaviors in high-income countries. Six databases were searched for articles published before January 2023. Results were synthesized using a vote-counting technique and effect direction plots that record the direction of the effect in relation to the anticipated relationship with health. Thirty-four observational and two intervention studies met the inclusion criteria. In the 13 studies assessing adolescent exposure to healthy community nutrition environments, results did not show clear associations with dietary and purchasing outcomes. Thirty studies assessed adolescents' exposure to unhealthy community nutrition environments with the majority (n = 17/30, 57%) reporting results showing that greater exposure to food outlets classified as unhealthy was associated with less healthy food purchases and dietary intakes. Inconsistent results were observed across the seven studies investigating associations with the consumer environment. Further research in these areas, including more high-quality intervention studies, may help to develop policy strategies to improve adolescents' dietary behaviors.


Dietary protein for athletes: from requirements to metabolic advantage.
The Dietary Reference Intakes (DRI) specify that the requirement for dietary protein for all individuals aged 19 y and older is 0.8 g protein.kg-1.d-1. This Recommended Dietary Allowance (RDA) is cited as adequate for all persons. This amount of protein would be considered by many athletes as the amount to be consumed in a single meal, particularly for strength-training athletes. There does exist, however, published data to suggest that individuals habitually performing resistance and (or) endurance exercise require more protein than their sedentary counterparts. The RDA values for protein are clearly set at "...the level of protein judged to be adequate... to meet the known nutrient needs for practically all healthy people...". The RDA covers protein losses with margins for inter-individual variability and protein quality; the notion of consumption of excess protein above these levels to cover increased needs owing to physical activity is not, however, given any credence. Notwithstanding, diet programs (i.e., energy restriction) espousing the virtue of high protein enjoy continued popularity. A number of well-controlled studies are now published in which "higher" protein diets have been shown to be effective in promoting weight reduction, particularly fat loss. The term "higher" refers to a diet that has people consuming more than the general populations' average intake of approximately 15% of energy from protein, e.g., as much as 30%-35%, which is within an Acceptable Macronutrient Distribution Range (AMDR) as laid out in the DRIs. Of relevance to athletes and those in clinical practice is the fact that higher protein diets have quite consistently been shown to result in greater weight loss, greater fat loss, and preservation of lean mass as compared with "lower" protein diets. A framework for understanding dietary protein intake within the context of weight loss and athletic performance is laid out.


Gene-gene interactions in folate and adenosine biosynthesis pathways affect methotrexate efficacy and tolerability in rheumatoid arthritis.
As no single nucleotide polymorphism has emerged as pivotal to predict the lack of efficacy and dose-limiting toxicities to methotrexate (MTX), we evaluated the contribution of gene-gene interactions to the effects of this prodrug in rheumatoid arthritis. A total of 255 patients treated with MTX for at least 3 months were evaluated with efficacy assessed using the European League Against Rheumatism response criteria or a physician's assessment of patient's response to MTX visual analog scale. Gastrointestinal and neurological idiosyncrasies were recorded in 158 patients. Fourteen single nucleotide polymorphisms in folate and adenosine biosynthesis pathways were measured and detection of gene-gene interactions was performed using multifactor-dimensionality reduction, a method that reduces high-dimensional genetic data into a single dimension of predisposing or risk-genotype combinations. Efficacy to MTX (53% responders) was associated with high-order epistasis among variants in inosine-triphosphate pyrophosphatase, aminoimidazole-carboxamide ribonucleotide transformylase, and reduced folate carrier genes. In the absence of predisposing genotype combinations, a 3.8-fold lower likelihood of efficacy was observed (vs. in their presence, 95% confidence interval: 2.2-6.4; P<0.001). Increasing MTX polyglutamate concentrations tended to partially overcome this selective disadvantage. Idiosyncrasies occurred in 29% of patients. In the presence of risk-genotype combinations among variants in methylene tetrahydrofolate reductase, γ-glutamyl-hydrolase, thymidylate synthase, serine hydroxymethyltransferase, and inosine-triphosphate pyrophosphatase genes, an 8.9-fold higher likelihood to exhibit toxicities was observed (vs. in their absence, 95% confidence interval: 3.6-21.9; P<0.001). False-positive report probabilities were below 0.2, thereby indicating that true signals were likely detected in this cohort. These data indicate that gene-gene interactions impact MTX efficacy and tolerability in rheumatoid arthritis.


Lived experiences of adolescents admitted for first-episode psychosis in South Africa.
First-episode psychosis is common in adolescents and can be distressful to the person experiencing it for the first time. However, there is limited research globally and specifically in Africa about the lived experiences of adolescents admitted into a psychiatric facility for first-episode psychosis. To understand the adolescents' experiences of psychosis and receiving treatment in a psychiatric facility. Adolescent Inpatient Psychiatric Unit, Tygerberg Hospital, Cape Town, South Africa. This was a qualitative study that used purposive sampling to recruit 15 adolescents with first-episode psychosis and admitted to the Adolescent Inpatient Psychiatric Unit, Tygerberg Hospital in Cape Town, South Africa. Individual interviews were audio recorded, transcribed and analysed using thematic analysis consisting of both inductive and deductive coding. The participants described negative experiences of their first episode psychosis, provided varying explanations for their first episode psychosis and had the insight that cannabis precipitated their episodes. They described both positive and negative interactions with both the other patients and staff. They did not wish to return to the hospital again following their discharge. Participants stated that they wanted to change their lives, return to school and try to prevent a second episode of psychosis. This study provides insights into the lived experiences of adolescents presenting with first-episode psychosis and calls for future research to delve deeper into factors that support or enable recovery among adolescents with psychosis. The findings of this study call for improving the quality of care in the management of first-episode psychosis in adolescents.


In search of a reliable technique for the determination of the biological stability of the organic matter in the mechanical-biological treated waste.
The biological stability determines the extent to which readily biodegradable organic matter has decomposed. In this work, a massive estimation of indices suitable for the measurement of biological stability of the organic matter content in solid waste samples has been carried out. Samples from different stages in a mechanical-biological treatment (MBT) plant treating municipal solid wastes (MSW) were selected as examples of different stages of organic matter stability in waste biological treatment. Aerobic indices based on respiration techniques properly reflected the process of organic matter biodegradation. Static and dynamic respirometry showed similar values in terms of aerobic biological activity (expressed as oxygen uptake rate, OUR), whereas cumulative oxygen consumption was a reliable method to express the biological stability of organic matter in solid samples. Methods based on OUR and cumulative oxygen consumption were positively correlated. Anaerobic methods based on biogas production (BP) tests also reflected well the degree of biological stability, although significant differences were found in solid and liquid BP assays. A significant correlation was found between cumulative oxygen consumption and ultimate biogas production. The results obtained in this study can be a basis for the quantitative measurement of the efficiency in the stabilization of organic matter in waste treatment plants, including MBT plants, anaerobic digestion of MSW and composting plants.


Upregulation of insulin receptor substrate-2 in pancreatic beta cells prevents diabetes.
The insulin receptor substrate-2 (Irs2) branch of the insulin/IGF signaling system coordinates peripheral insulin action and pancreatic beta cell function, so mice lacking Irs2 display similarities to humans with type 2 diabetes. Here we show that beta cell-specific expression of Irs2 at a low or a high level delivered a graded physiologic response that promoted beta cell growth, survival, and insulin secretion that prevented diabetes in Irs2-/- mice, obese mice, and streptozotocin-treated mice; and that upon transplantation, the transgenic islets cured diabetes more effectively than WT islets. Thus, pharmacological approaches that promote Irs2 expression in beta cells, especially specific cAMP agonists, could be rational treatments for beta cell failure and diabetes.


DNA G-segment bending is not the sole determinant of topology simplification by type II DNA topoisomerases.
DNA topoisomerases control the topology of DNA. Type II topoisomerases exhibit topology simplification, whereby products of their reactions are simplified beyond that expected based on thermodynamic equilibrium. The molecular basis for this process is unknown, although DNA bending has been implicated. To investigate the role of bending in topology simplification, the DNA bend angles of four enzymes of different types (IIA and IIB) were measured using atomic force microscopy (AFM). The enzymes tested were Escherichia coli topo IV and yeast topo II (type IIA enzymes that exhibit topology simplification), and Methanosarcina mazei topo VI and Sulfolobus shibatae topo VI (type IIB enzymes, which do not). Bend angles were measured using the manual tangent method from topographical AFM images taken with a novel amplitude-modulated imaging mode: small amplitude small set-point (SASS), which optimises resolution for a given AFM tip size and minimises tip convolution with the sample. This gave improved accuracy and reliability and revealed that all 4 topoisomerases bend DNA by a similar amount: ~120° between the DNA entering and exiting the enzyme complex. These data indicate that DNA bending alone is insufficient to explain topology simplification and that the 'exit gate' may be an important determinant of this process.


Trends of population-based breast cancer survival in Germany and the US: decreasing discrepancies, but persistent survival gap of elderly patients in Germany.
Studies have revealed both higher cancer survival in the US than in Germany and substantial improvement of cancer survival in the past in these countries. This population-based study aims at comparing most recent 5-year relative survival of breast cancer patients and preceding trends in both countries. Women with a first invasive breast cancer diagnosed and followed up between 1988 and 2008 from Germany and the US (utilizing data from the Saarland Cancer Registry and the Surveillance, Epidemiology, and End Results Program, respectively) were included. Period analysis was used to derive most up-to-date 5-year relative survival and preceding survival trends according to age and stage. Since 1993, age standardized relative survival has steadily improved in Germany and the US to 83% and 88%, respectively. In the period 2005-08, relative survival of localized cancer was above 97% in both countries, and 79% and 83% for locally/regionally spread breast cancer, respectively. Prognosis of metastasized disease has remained very poor overall, with improvement essentially being restricted to younger patients. The proportion of patients diagnosed with localized breast cancer was consistently higher in the US. If adjusted for stage, the differences in relative survival between both countries diminished over time and eventually disappeared. Similar survival is now observed in both countries for patients below the age of 70 years, but in Germany survival is still much lower for elderly patients. The observed trends point to treatment advances as a major cause for improved survival. However, substantial differences in mammography usage existed between both countries and might probably also account for the observed differences (to a lesser extent, also differences in health care systems, and delivery of cancer care). Encouraging, survival of breast cancer patients has improved in Germany to a much greater extent than in the US, albeit the persisting survival gap for elderly patients in Germany requires particular attention by researchers, public health authorities, and clinicians.


MHC class II gene products specific autoreactive T cell clones provide inducer as well as amplifier function for B cell Ig production.
Autoreactive T lymphocytes were generated by culturing human peripheral blood mononuclear cells with an antigen-specific/MHC restricted autologous inducer T cell, termed RW17C and subsequently cloned in soft agar. The majority of such clones expressed the T3+T4+T8-T11+Ia+ phenotype and were directed at autologous class II MHC gene products found on B cells, macrophages and B lymphoblastoid cells as judged by their proliferative response to the latter. For this recognition, the clones employed a T3-Ti molecular complex and a T4 structure analogous to those found on allospecific T cells. Perhaps more importantly, it was observed that the same AC (autoreactive clone) induced autologous B cells to produce high levels of immunoglobulin in the absence of exogenous antigen and could synergize with the RW17C clone to effect maximal B cell Ig production. In addition, supernatant from T3-Ti triggering of AC clone induced both polyclonal proliferation and differentiation of small B lymphocytes. These results support the notion that such autoreactive cells can function in a physiologic amplifier role by facilitating induction via an internal set of signals (i.e. autologous MHC).


Infection- or vaccine mediated immunity reduces SARS-CoV-2 transmission, but increases competitiveness of Omicron in hamsters.
Omicron has demonstrated a competitive advantage over Delta in vaccinated people. To understand this, we designed a transmission chain experiment using naïve, intranasally (IN) or intramuscularly (IM) vaccinated, and previously infected (PI) hamsters. Vaccination and previous infection protected animals from disease and virus replication after Delta and Omicron dual challenge. A gradient in transmission blockage was observed: IM vaccination displayed moderate transmission blockage potential over three airborne chains (approx. 70%), whereas, IN vaccination and PI blocked airborne transmission in >90%. In naïve hamsters, Delta completely outcompeted Omicron within and between hosts after dual infection in onward transmission. Although Delta also outcompeted Omicron in the vaccinated and PI transmission chains, an increase in Omicron competitiveness was observed in these groups. This correlated with the increase in the strength of the humoral response against Delta, with the strongest response seen in PI animals. These data highlight the continuous need to assess the emergence and spread of novel variants in populations with pre-existing immunity and address the additional evolutionary pressure this may exert on the virus.


Alignment of European Regulatory and Health Technology Assessments: A Review of Licensed Products for Alzheimer's Disease.
Aims: To facilitate regulatory learning, we evaluated similarities and differences in evidence requirements between regulatory and health technology assessment (HTA) bodies of Alzheimer's disease (AD) approved products. Methods: The European marketing authorisation application dossiers and European public assessment reports (EPARs) of the licensed AD drugs were screened to identify the phase III randomised controlled trials (RCTs) and outcomes used. We also screened the assessment reports of the National Institute of Health and Care Excellence (NICE, England) and the National Health Care Institute (ZiN, the Netherlands) to identify the studies and outcomes used in HTA assessments. Results: The application dossiers of donepezil, galantamine, rivastigmine, and memantine contained 16 phase III RCTs in total. These trials were also included in HTA assessments except that NICE excluded studies that were not published (n = 2) or trials that included patients with other types of dementia (n = 3). In the regulatory assessments the focus was on cognitive and global outcomes, and to some extent on function. In the HTA assessments of clinical effectiveness other domains were also covered including: function, behaviour and mood, and, occasionally, quality of life. In the economic analyses of NICE the domains cognition, function, and quality of life were included. Conclusion: There was a large overlap in inclusion of trials in regulatory and HTA assessments, although the focus on specific outcomes slightly differed. Understanding the methods and perceptions of both authorities can stimulate regulatory and HTA cross-talk and further alignment, and therefore more rapid patient access to new treatments.


Bacteriophage LM33_P1, a fast-acting weapon against the pandemic ST131-O25b:H4 Escherichia coli clonal complex.
Amongst the highly diverse Escherichia coli population, the ST131-O25b:H4 clonal complex is particularly worrisome as it is associated with a high level of antibiotic resistance. The lack of new antibiotics, the worldwide continuous increase of infections caused by MDR bacteria and the need for narrow-spectrum antimicrobial agents have revived interest in phage therapy. In this article, we describe a virulent bacteriophage, LM33_P1, which specifically infects O25b strains, and provide data related to its therapeutic potential. A large panel of E. coli strains (n = 283) was used to assess both the specificity and the activity of bacteriophage LM33_P1. Immunology, biochemistry and genetics-based methods confirmed this specificity. Virology methods and sequencing were used to characterize this bacteriophage in vitro, while three relevant mouse models were employed to show its in vivo efficacy. Bacteriophage LM33_P1 exclusively infects O25b E. coli strains with a 70% coverage on sequence types associated with high antibiotic resistance (ST131 and ST69). This specificity is due to an interaction with the LPS mediated by an original tail fibre. LM33_P1 also has exceptional intrinsic properties with a high adsorption constant and produces over 300 virions per cell in <10 min. Using animal pneumonia, septicaemia and urinary tract infection models, we showed the in vivo efficacy of LM33_P1 to reduce the bacterial load in several organs. Bacteriophage LM33_P1 represents the first weapon that specifically and quickly kills O25b E. coli strains. Therapeutic approaches derived from this bacteriophage could be developed to stop or slow down the spread of the ST131-O25b:H4 drug-resistant clonal complex in humans.


Nitric oxide decreases endothelin-1 secretion through the activation of soluble guanylate cyclase.
The use of exogenous nitric oxide (NO) has been shown to alter the regulation of other endothelially derived mediators of vascular tone, such as endothelin-1 (ET-1). However, the interaction between NO and ET-1 appears to be complex and remains incompletely understood. One of the major actions of NO is the activation of soluble guanylate cyclase (sGC) with the subsequent generation of cGMP. Therefore, we undertook this study to test the hypothesis that NO regulates ET-1 production via the activation of the sGC/cGMP pathway. The results obtained indicated that the exposure of primary cultures of 4-wk-old ovine pulmonary arterial endothelial cells (4-wk PAECs) to the long-acting NO donor DETA NONOate induced both a dose- and time-dependent decrease in secreted ET-1. This decrease in ET-1 secretion occurred in the absence of changes in endothelin-converting enzyme-1 or sGC expression but in conjunction with a decrease in prepro-ET-1 mRNA. The changes in ET-1 release were inversely proportional to the cellular cGMP content. Furthermore, the NO-independent activator of sGC, YC-1, or treatment with a cGMP analog also produced significant decreases in ET-1 secretion. Conversely, pretreatment with the sGC inhibitor ODQ blocked the NO-induced decrease in ET-1. Therefore, we conclude that exposure of 4-wk PAECs to exogenous NO decreases secreted ET-1 resulting from the activation of sGC and increased cGMP generation.


Radiosensitivity of colorectal cancer to 90Y and the radiobiological implications for radioembolisation therapy.
Approximately 50% of all colorectal cancer (CRC) patients will develop metastasis to the liver. 90Y selective internal radiation therapy (SIRT) is an established treatment for metastatic CRC. There is still a fundamental lack of understanding regarding the radiobiology underlying the dose response. This study was designed to determine the radiosensitivity of two CRC cell lines (DLD-1 and HT-29) to 90Y β - radiation exposure, and thus the relative effectiveness of 90Y SIRT in relation to external beam radiotherapy (EBRT). A 90Y-source dish was sandwiched between culture dishes to irradiate DLD-1 or HT-29 cells for a period of 6 d. Cell survival was determined by clonogenic assay. Dose absorbed per 90Y disintegration was calculated using the PENELOPE Monte Carlo code. PENELOPE simulations were benchmarked against relative dose measurements using EBT3 GAFchromic™ film. Statistical regression based on the linear-quadratic model was used to determine the radiosensitivity parameters [Formula: see text] and [Formula: see text] using R. These results were compared to radiosensitivity parameters determined for 6 MV clinical x-rays and 137Cs γ-ray exposure. Equivalent dose of EBRT in 2 Gy ([Formula: see text]) and 10 Gy ([Formula: see text]) fractions were derived for 90Y dose. HT-29 cells were more radioresistant than DLD-1 for all treatment modalities. Radiosensitivity parameters determined for 6 MV x-rays and 137Cs γ-ray were equivalent for both cell lines. The [Formula: see text] ratio for 90Y β --particle exposure was over an order of magnitude higher than the other two modalities due to protraction of dose delivery. Consequently, an 90Y SIRT absorbed dose of 60 Gy equates to an [Formula: see text] of 28.7 and 54.5 Gy and an [Formula: see text] of 17.6 and 19.3 Gy for DLD-1 and HT-29 cell lines, respectively. We derived radiosensitivity parameters for two CRC cell lines exposed to 90Y β --particles, 6 MV x-rays, and 137Cs γ-ray irradiation. These radiobiological parameters are critical to understanding the dose response of CRC lesions and ultimately informs the efficacy of 90Y SIRT relative to other radiation therapy modalities.


The economic burden of sunscreen usage.
Excessive sun exposure is known to be the leading cause of skin cancer. The direct cellular damage inflicted by the ultraviolet (UV) radiation from the sun results in premature aging, DNA damage, and mutations that ultimately lead to skin cancer. Sunscreens are highly recommended to protect against UV radiation. However, little research has been conducted on the economic burden of sunscreen use. In this study, we aimed to evaluate the annual cost of sunscreen under both ideal and actual use conditions while stratifying for the sun protection factor (SPF) and by the name brand or equivalent store brand sunscreen. Pricing data was collected for sunscreens of SPF 30, 50, 70, and 100. For each type of sunscreen, the size and price of the container were recorded. Our results demonstrated that sunscreen prices increased with SPF but purchasing a generic sunscreen resulted in savings of 40%-50%. Our estimates reveal that sunscreens are affordable with annual expenditures ranging from $30.21 to $61.94, depending on brand, for SPF 50 sunscreens used with minimal application density for the average person.


Consumer Preferences, Product Characteristics, and Potentially Allergenic Ingredients in Best-selling Moisturizers.
Because moisturizer use is critical for the prevention and treatment of numerous dermatological conditions, patients frequently request product recommendations from dermatologists. To determine the product performance characteristics and ingredients of best-selling moisturizers. This cohort study involved publicly available data of the top 100 best-selling whole-body moisturizing products at 3 major online retailers (Amazon, Target, and Walmart). Products marketed for use on a specific body part (eg, face, hands, eyelids) were excluded. Pairwise comparisons of median price per ounce on the basis of marketing claims (eg, dermatologist recommended, fragrance free, hypoallergenic) and presence of ingredients represented in the North American Contact Dermatitis Group (NACDG) series were conducted using Wilcoxon rank sum tests. The effect of vehicle type (eg, ointment, lotion, cream, butter) was assessed using the Kruskal-Wallis test. Cross-reactors and botanicals for fragrances were derived from the American Contact Dermatitis Society's Contact Allergen Management Program database. A total of 174 unique best-selling moisturizer products were identified, constituting 109 713 reviews as of August 2016. The median price per ounce was $0.59 (range, $0.10-$9.51 per ounce) with a wide range (9400%). The most popular vehicles were lotions (102 [59%]), followed by creams (22 [13%]), oils (21 [12%]), butters (14 [8%]), and ointments (3 [2%]). Only 12% (n = 21) of best-selling moisturizer products were free of NACDG allergens. The 3 most common allergens were fragrance mix (n = 87), paraben mix (n = 75), and tocopherol (n = 74). Products with the claim "dermatologist recommended" had higher median price per ounce ($0.79; interquartile range [IQR], $0.56-$1.27) than products without the claim ($0.59; IQR, $0.34-$0.92). Products with the claim "phthalate free" had higher median price per ounce ($1.38; IQR, $0.86-$1.63) than products without the claim ($0.59; IQR, $0.35-$0.91). Lotions (median, $0.49; IQR, $0.31-0.68) were statistically less expensive per ounce than butters (median, $1.20; IQR, $0.76-$1.63), creams (median, $0.80; IQR, $0.69-$1.25) and oils (median, $1.30; IQR, $0.64-$2.43). For products with a claim of "fragrance free," 18 (45%) had at least 1 fragrance cross-reactor or botanical ingredient. Products without any ingredients in the NACDG (median, $0.83; IQR, $0.47-$1.69) were not statistically more expensive per ounce than products with 1 or more allergens (median, $0.60; IQR, $0.35-$1.06). Best-selling moisturizers vary widely by price and product characteristics. Given the lack of readily available comparison data on moisturizer efficacy, dermatologists should balance consumer preference, price, and allergenicity in their recommendations.


The isometric torque at which knee-extensor muscle reoxygenation stops.
We investigated the knee-extensor torque at which reoxygenation (inflow of arterial blood) during an isometric contraction stopped, whether this torque depended on maximal torque capacity (MTC), and whether there were differences among the synergists. Isometric knee-extension torque was measured using a dynamometer with 90 degrees angles in the hip and knee. Maximal voluntary activation (established with superimposed nerve stimulation) was > 90% in the 15 healthy male subjects (20-30 yr). Near-infrared spectroscopy (NIRS) was used to measure changes in muscle oxygenation of the vastus medialis (VM), vastus lateralis (VL), and rectus femoris (RF) muscle during submaximal isometric contractions at intensities of 20-45% MTC with 5% increments, applied in randomized order and divided over 2 d. At each torque, a contraction with an inflated pressure cuff (450 mm Hg), inducing full arterial occlusion, was followed (10 min of rest) by a second contraction without the cuff. MTC ranged from 178 to 348 N.m. The torque at which maximal deoxygenation (all oxygen consumed) during contraction without the cuff became similar (P < 0.05) to the maximal deoxygenation reached with the cuff (indicative for complete occlusion of blood flow during the contraction without the cuff) was significantly higher for the RF (35% MTC) than for both vasti (25% MTC). There was no significant relation between MTC and relative (% MTC) torque at which muscle reoxygenation stopped. Knee-extensor reoxygenation stopped at lower torques than previously reported for blood flow in this muscle, and this occurred at the same % MTC in subjects of different strength but at different % MTC for the different synergists.


Sex-dependent dissociation between emotional appraisal and memory: a large-scale behavioral and fMRI study.
Extensive evidence indicates that women outperform men in episodic memory tasks. Furthermore, women are known to evaluate emotional stimuli as more arousing than men. Because emotional arousal typically increases episodic memory formation, the females' memory advantage might be more pronounced for emotionally arousing information than for neutral information. Here, we report behavioral data from 3398 subjects, who performed picture rating and memory tasks, and corresponding fMRI data from up to 696 subjects. We were interested in the interaction between sex and valence category on emotional appraisal, memory performances, and fMRI activity. The behavioral results showed that females evaluate in particular negative (p < 10(-16)) and positive (p = 2 × 10(-4)), but not neutral pictures, as emotionally more arousing (pinteraction < 10(-16)) than males. However, in the free recall females outperformed males not only in positive (p < 10(-16)) and negative (p < 5 × 10(-5)), but also in neutral picture recall (p < 3.4 × 10(-8)), with a particular advantage for positive pictures (pinteraction < 4.4 × 10(-10)). Importantly, females' memory advantage during free recall was absent in a recognition setting. We identified activation differences in fMRI, which corresponded to the females' stronger appraisal of especially negative pictures, but no activation differences that reflected the interaction effect in the free recall memory task. In conclusion, females' valence-category-specific memory advantage is only observed in a free recall, but not a recognition setting and does not depend on females' higher emotional appraisal.


Posterior segment toxicity after gemcitabine and docetaxel chemotherapy.
To report outer retinal disruption and uveal effusion after gemcitabine and docetaxel combination therapy. A 78-year-old woman presented with blurry vision after two cycles of gemcitabine and docetaxel combination chemotherapy for stage IV sarcoma. At presentation, visual acuity was finger counting and 20/25 in the right and left eyes, respectively. Slit-lamp examination and B-scan ultrasonography revealed severe uveal effusion in the right eye and choroidal folds in the left eye. Spectral domain optical coherence tomography showed disruption of photoreceptor inner segment ellipsoid band in the right eye. The patient was monitored weekly with ophthalmic examination and B-scan ultrasonography, while continuing with gemcitabine monotherapy. At 8 weeks follow-up, uveal effusion improved considerably and visual acuity was 20/40 and 20/20 in the right and left eyes, respectively. Uveal effusion and outer retinal disruption were reported after gemcitabine and docetaxel chemotherapy. Early detection and close ophthalmic monitoring may allow concurrent cancer treatment and prevention of possible chemotherapy-induced ocular side effects.


Social isolation and loneliness as risk factors for hospital admissions for respiratory disease among older adults.
Rising hospital admissions due to respiratory disease (RD) are a major challenge to hospitals. This study explored modifiable social risk factors among 4478 older adults from the English Longitudinal Study of Ageing. Data were linked with administrative hospital records and mortality registry data (follow-up 9.6 years) and analysed using survival analysis accounting for competing risks. Living alone and social disengagement but not social contact or loneliness were associated with an increased risk of RD admissions, independent of socio-demographic, health and behaviour factors. Providing support for disengaged adults living alone who are at risk of RD admissions should be explored.


Defining a Core Data Set for the Economic Evaluation of Precision Oncology.
Precision oncology is generating vast amounts of multiomic data to improve human health and accelerate research. Existing clinical study designs and attendant data are unable to provide comparative evidence for economic evaluations. This lack of evidence can cause inconsistent and inappropriate reimbursement. Our study defines a core data set to facilitate economic evaluations of precision oncology. We conducted a literature review of economic evaluations of next-generation sequencing technologies, a common application of precision oncology, published between 2005 and 2018 and indexed in PubMed (MEDLINE). Based on this review, we developed a preliminary core data set for informal expert feedback. We then used a modified-Delphi approach with individuals involved in implementation and evaluation of precision medicine, including 2 survey rounds followed by a final voting conference to refine the data set. Two authors determined that variation in published data elements was reached after abstraction of 20 economic evaluations. Expert consultation refined the data set to 83 unique data elements, and a multidisciplinary sample of 46 experts participated in the modified-Delphi process. A total of 68 elements (81%) were selected as required, spanning demographics and clinical characteristics, genomic data, cancer treatment, health and quality of life outcomes, and resource use. Cost-effectiveness analyses will fail to reflect the real-world impacts of precision oncology without data to accurately characterize patient care trajectories and outcomes. Data collection in accordance with the proposed core data set will promote standardization and enable the generation of decision-grade evidence to inform reimbursement.


Development of a Novel and Robust Pharmacological Model of Okadaic Acid-induced Alzheimer's Disease in Zebrafish.
Alzheimer's disease (AD) is the leading neurodegenerative disorder affecting the world's elderly population. Most experimental models of AD are transgenic or pharmacological in nature, and do not simulate the entire pathophysiology. In the present study, we developed a pharmacologically induced AD using the zebrafish, a species that can recapitulate most of the phenotypes of the disease. The pharmacological agent being used, okadaic acid (OKA) has also been utilized to study AD in other species. In this model, the immunohistochemistry of phosphorylated glycogen synthase-3α/β, Aβ, p-tau, tau protein, and senile plaque formation in zebrafish brain were all significantly increased with increasing exposure to OKA. These represent the majority of the histological hallmarks of AD pathophysiology. The observed changes were also accompanied by learning and memory deficits which are also important components in AD pathophysiology. Zebrafish disease models are gaining popularity mostly due to their economic cost and relevance to human disease pathophysiology. Current pharmacological methods of inducing AD in zebrafish are not adequately developed and do not represent all the features of the disease. OKA-induced AD in zebrafish can become a cost efficient model to study drug discovery for AD. It may also be used to unravel the molecular mechanisms underlying the complex pathophysiology that leads to AD using relatively economical species.


Mutant KB cells with decreased EGF receptor expression: biochemical characterization.
Mutants of the human KB carcinoma cell line resistant to a cytotoxic conjugate of epidermal growth factor and Pseudomonas exotoxin (EGF-PE) express a pleiotropic phenotype, which includes reduced levels of 125I-EGF binding, without altered affinity for EGF (Lyall et al., 1987). Here, the EGF-toxin (ET) resistant mutants were further characterized with respect to the amount and size of the EGF receptor and the level of EGF receptor RNA. These data indicate that decreased binding of 125I-EGF in the mutants is due to reduced amounts of EGF receptor, which is associated with decreased mRNA levels. Changes in other proteins in the ET mutants were also examined. Five of the six ET mutants had a decrease in a 78,000 Mr- membrane glycoprotein. In addition, an increase in a protein with a Mr- of 40,000 and a pl = 8.0 was found in all the mutants, and an increase in a series of proteins with a Mr- of 36,000 and a pl of 6.3-6.5 was found in some of the mutants. These results confirm the pleiotropic nature of the EGF-PE resistant mutants and show that reduced EGF binding is due to altered expression of the EGF receptor gene in the mutants.


Vitamin D and cancer mini-symposium: the risk of additional vitamin D.
Any benefit of vitamin D needs to be balanced against the risk of toxicity, which is characterized by hypercalcemia. Daily brief, suberythemal exposure of a substantial area of the skin to ultraviolet light, climate allowing, provides adults with a safe, physiologic amount of vitamin D, equivalent to an oral intake of about 10,000 IU vitamin D(3) per day, with the plasma 25-hydroxyvitamin D (25(OH)D) concentration potentially reaching 220 nmol/L (88 ng/mL). The incremental consumption of 40 IU/d of vitamin D(3) raises plasma 25(OH)D by about 1 nmol/L (0.4 ng/mL). High doses of vitamin D may cause hypercalcemia once the 25(OH)D concentration is well above the top of the physiologic range. The physiological buffer for vitamin D safety is the capacity of plasma vitamin D-binding protein to bind the total of circulating 25(OH)D, vitamin D, and 1,25-dihydroxyvitamin D [1,25(OH)2D]. Hypercalcemia occurs when the free concentration is inappropriately high because vitamin D and its other metabolites have displaced 1,25(OH)2D from vitamin D-binding protein. Evidence from clinical trials shows, with a wide margin of confidence, that a prolonged intake of 10,000 IU/d of vitamin D(3) poses no risk of adverse effects for adults, even if this is added to a rather high physiologic background level of vitamin D.


Virtual Point Removal for Large-Scale 3D Point Clouds with Multiple Glass Planes.
Large-scale 3D point clouds (LS3DPCs) captured by terrestrial LiDAR scanners often include virtual points which are generated by glass reflection. The virtual points may degrade the performance of various computer vision techniques when applied to LS3DPCs. In this paper, we propose a virtual point removal algorithm for LS3DPCs with multiple glass planes. We first estimate multiple glass regions by modeling the reliability with respect to each glass plane, respectively, such that the regions are assigned high reliability when they have multiple echo pulses for each emitted laser pulse. Then we detect each point whether it is a virtual point or not. For a given point, we recursively traverse all the possible trajectories of reflection, and select the optimal trajectory which provides a point with a similar geometric feature to a given point at the symmetric location. We evaluate the performance of the proposed algorithm on various LS3DPC models with diverse numbers of glass planes. Experimental results show that the proposed algorithm estimates multiple glass regions faithfully and detects the virtual points successfully. Moreover, we also show that the proposed algorithm yields a much better performance of reflection artifact removal compared with the existing method qualitatively and quantitatively.


Influence of thiamin supplementation on the health and general well-being of an elderly Irish population with marginal thiamin deficiency.
The effect of thiamin supplementation on the health and general well-being of 80 randomly selected healthy elderly Irish women, from a population with marginal thiamin deficiency, was studied. Key variables affecting thiamin status were controlled. Weekly dietary intakes, subjective feelings, and activity assessments were measured during a 4-week baseline and 6-week double blind treatment period. Clinical assessments were performed during the last week of each period. For treatment, subjects were randomly assigned to either thiamin (10 mg daily) or placebo groups. Compared to baseline and placebo supplemented values, thiamin-supplemented women experienced significantly increased appetite, energy intake, body weight and general well-being, and decreased fatigue. Thiamin supplementation also tended to reduce daytime sleep time, improve sleep patterns, and increase activity. These data suggest that evaluation of thiamin status is indicated when nonspecific conditions such as anorexia, weight loss, fatigue, depression, and sleep disorders are present in elderly persons.


Porous nanosheet wrapping for live imaging of suspension cells.
In the field of cell imaging, it is still a practical challenge to obtain the high quality live imaging of suspension cells, mainly due to undesirable cell movement in the imaging field during observation. This study describes a porous nanosheet wrapping method to noninvasively immobilize suspension cells for their live imaging. Perforated nanopores are fabricated on a nanosheet to enable the addition of external chemicals to cells, ranging from small molecules to macromolecules. Through several case studies, such as the live imaging of membrane staining of liposomes, transferrin endocytosis of B cells, and activation of platelets, it is verified that the confined space made by the nanosheet could provide a hydrodynamically stable environment for suspension cells, even if an aqueous stimulus is added through the nanopores in a static or a flowing condition. With this method, the live imaging of the whole activation process on a specific suspension cell in the imaging field is achieved, which is not feasible with the existing cell immobilization methods. This study suggests that the method of porous nanosheet wrapping will facilitate the visualization of the dynamic functions of suspension cells.


Molecular cloning and characterization of a novel glycoprotein, gp34, that is specifically induced by the human T-cell leukemia virus type I transactivator p40tax.
We have cloned and sequenced a cDNA encoding gp34, a novel glycoprotein expressed in cells bearing human T-cell leukemia virus type I (HTLV-I). HTLV-I has a trans-acting transcriptional activator, p40tax, that is thought to be implicated in leukemogenesis through the activation of cellular enhancers. With a subline (JPX-9) of the human T-cell line Jurkat, in which p40tax is inducible, gp34 was shown to be of cellular origin and to be transcriptionally activated by p40tax. It was also demonstrated that two species of mRNA are generated from one copy of the gp34 gene and that these mRNAs encode the identical gp34 product and differ in the 3' untranslated region. Analysis of the deduced amino acid sequence of gp34 showed that it lacks typical signal peptides; however, it has a hydrophobic stretch for membrane anchoring and four possible N-linked glycosylation sites at the carboxy-terminal portion, indicating that it belongs to the family of membrane proteins whose carboxy-terminal portion protrudes out of the cell. The gp34 gene displayed relatively delayed induction compared with other genes activated by p40tax. Taken together with the observation of the dependence of gp34 expression on HTLV-I p40tax, unlike other p40tax-dependent genes such as those for the interleukin-2 receptor alpha chain and c-fos, which are expressed or induced under physiological conditions, we predict that the mechanism involved in the induction of gp34 expression by p40tax is distinct from and more intricate than those for the previously characterized genes.


Acute administration of red yeast rice (Monascus purpureus) depletes tissue coenzyme Q(10) levels in ICR mice.
In this study, we attempted to evaluate the effect of administration of a high quantity of red yeast rice on coenzyme Q10 (CoQ10) synthesis in the tissues of ICR mice. Eighty-eight adult male ICR mice were housed and divided into control and experimental groups for red yeast rice treatment. Animals were gavaged with a low (1 g/kg body weight) or a high dose (5 g/kg body weight, approximately five times the typical recommended human dose) of red yeast rice dissolved in soyabean oil. After gavagement, animals of the control group were immediately killed; mice of the experimental groups (eight for each subgroup) were killed at different time intervals of 0.5, 1, 1.5, 4 and 24 h. The liver, heart and kidney were taken for analysis of monacolin K (liver only) and CoQ10 analysis. Liver and heart CoQ10 levels declined dramatically in both groups administered red yeast rice, especially in the high-dose group, within 30 min. After 24 h, the levels of hepatic and cardiac CoQ10 were still reduced. A similar trend was also observed in the heart, but the inhibitory effect began after 90 min. The higher dose of red yeast rice presented a greater suppressive effect than did the lower dose on tissue CoQ10 levels. In conclusion, acute red yeast rice gavage suppressed hepatic and cardiac CoQ10 levels in rodents; furthermore, the inhibitory effect was responsive to the doses administered.


Racial Disparities in the Utilization and Outcomes of TAVR: TVT Registry Report.
This study sought to evaluate racial disparities in the performance and outcomes of transcatheter aortic valve replacement (TAVR). Racial disparities in cardiovascular diseases are well described. Whether the racial disparities observed in surgical aortic valve replacement also exist with TAVR remains unknown. Patients undergoing TAVR between November 2011 and June 2016 were identified in the American College of Cardiology/Society of Thoracic Surgeons/Transcatheter Valve Therapy Registry. We described the racial distribution, and the risk-adjusted in-hospital morbidity, and mortality stratified by race. We evaluated 1-year outcomes in a subset of patients via linkage to Medicare (Centers for Medicare and Medicaid Services) claims. Among the 70,221 included patients, 91.3% were white, 3.8% were black, 3.4% were Hispanic, and 1.5% were of Asian/Native American/Pacific Islander race. This represented significant underrepresentation of nonwhite patients compared with their proportion of the population. After risk-adjustment, there was no difference in the rates of in-hospital mortality, myocardial infarction, stroke, major bleeding, vascular complications, or new pacemaker requirements among the 4 racial groups. Among 29,351 patients with Centers for Medicare and Medicaid Services linkage, 1-year adjusted mortality rates were similar in blacks and Hispanics compared with whites, but lower among patients of Asian/Native American/Pacific Islander race (adjusted hazard ratio: 0.71; 95% confidence interval: 0.55 to 0.92; p = 0.028). Black and Hispanic patients had more heart failure hospitalizations compared with whites (adjusted hazard ratio: 1.39; 95% confidence interval: 1.16 to 1.67; p < 0.001; and adjusted hazard ratio: 1.37; 95% confidence interval: 1.13 to 1.66; p = 0.004, respectively). These differences persisted after additional risk-adjustment for socioeconomic status. Racial minorities are underrepresented among patients undergoing TAVR in the United States, but their adjusted 30-day and 1-year clinical outcomes are comparable with those of white race.


A detailed appraisal of mesocolic lymphangiology--an immunohistochemical and stereological analysis.
Inadequate resection of the adjoining mesentery is associated with adverse outcome for colon cancer. Disruption of the integrity of the mesenteric lymphatic package has been implicated in this, though not proven. Recent studies have determined mesenteric anatomy and histology and now provide an opportunity to determine accurately the distribution of lymphatic vessels. The aim of this study was to characterise the distribution of the lymphatic vessels (LV) within the small intestinal and colonic mesentery, and in Toldt's fascia, which lies between the mesocolon and underlying retroperitoneum. Mesenteric samples were harvested from 12 human cadavers. Samples were taken from the small bowel mesentery, ascending, transverse, descending mesocolon and from both apposed and non-apposed portions of the mesosigmoid. Serial sections were stained immunohistochemically with monoclonal antibody D2-40 (podoplanin), and Masson's Trichrome. Lymphatic vessel (LV) density and radius of diffusion were determined using a stereological approach. A lymphatic network was embedded within the mesenteric connective tissue lattice throughout each mesenteric region. LV were identifiable within the submesothelial connective tissue where they measured 10.2 ± 4.1 μm in diameter and had an average radius of diffusion of 174.72 ± 97.68 μm. Unexpectedly, LV were identified in Toldt's fascia, where they measured 4.3 ± 3.1 μm in diameter and had a radius of diffusion of 165.12 ± 66.26 μm. This is the first study systematically to determine and quantify the distribution of lymphatic vessels within the mesenteric organ and to demonstrate the presence of such vessels within Toldt's fascia. A rich lymphatic network occupies all levels of the mesenteric connective tissue lattice. Within the latter, they are found within 0.1 mm of peritonealised mesenteric surfaces and are separated by an average distance of 0.17 mm and may be particularly vulnerable during surgery.


An Open MRI Dataset For Multiscale Neuroscience.
Multimodal neuroimaging grants a powerful window into the structure and function of the human brain at multiple scales. Recent methodological and conceptual advances have enabled investigations of the interplay between large-scale spatial trends (also referred to as gradients) in brain microstructure and connectivity, offering an integrative framework to study multiscale brain organization. Here, we share a multimodal MRI dataset for Microstructure-Informed Connectomics (MICA-MICs) acquired in 50 healthy adults (23 women; 29.54 ± 5.62 years) who underwent high-resolution T1-weighted MRI, myelin-sensitive quantitative T1 relaxometry, diffusion-weighted MRI, and resting-state functional MRI at 3 Tesla. In addition to raw anonymized MRI data, this release includes brain-wide connectomes derived from (i) resting-state functional imaging, (ii) diffusion tractography, (iii) microstructure covariance analysis, and (iv) geodesic cortical distance, gathered across multiple parcellation scales. Alongside, we share large-scale gradients estimated from each modality and parcellation scale. Our dataset will facilitate future research examining the coupling between brain microstructure, connectivity, and function. MICA-MICs is available on the Canadian Open Neuroscience Platform data portal ( https://portal.conp.ca ) and the Open Science Framework ( https://osf.io/j532r/ ).


Evaluation of the implementation of a whole-workplace walking programme using the RE-AIM framework.
Promoting walking for the journey to/from work and during the working day is one potential approach to increase physical activity in adults. Walking Works was a practice-led, whole-workplace walking programme delivered by employees (walking champions). This study aimed to evaluate the implementation of Walking Works using the RE-AIM framework and provide recommendations for future delivery of whole-workplace walking programmes. Two cross sectional surveys were conducted; 1544 (28%) employees completed the baseline survey and 918 employees (21%) completed the follow-up survey. Effectiveness was assessed using baseline and follow-up data; reach, implementation and maintenance were assessed using follow-up data only. For categorical data, Chi square tests were conducted to assess differences between surveys or groups. Continuous data were analysed to test for significant differences using a Mann-Whitney U test. Telephone interviews were conducted with the lead organisation co-ordinator, eight walking champions and three business representatives at follow-up. Interviews were transcribed verbatim and analysed to identify key themes related to adoption, implementation and maintenance. Adoption: Five workplaces participated in Walking Works. Reach: 480 (52.3%) employees were aware of activities and 221 (24.1%) participated. A variety of walking activities were delivered. Some programme components were not delivered as planned which was partly due to barriers in using walking champions to deliver activities. These included the walking champions' capacity, skills, support needs, ability to engage senior management, and the number and type of activities they could deliver. Other barriers included lack of management support, difficulties communicating information about activities and challenges embedding the programme into normal business activities. Effectiveness: No significant changes in walking to/from work or walking during the working day were observed. Maintenance: Plans to continue activities were mainly dependent on identifying continued funding. RE-AIM provided a useful framework for evaluating Walking Works. No changes in walking behaviour were observed. This may have been due to barriers in using walking champions to deliver activities, programme components not being delivered as intended, the types of activities delivered, or lack of awareness and participation by employees. Recommendations are provided for researchers and practitioners implementing future whole-workplace walking programmes.