Three-year patient-related and stent-related outcomes of second-generation everolimus-eluting Xience V stents versus zotarolimus-eluting resolute stents in real-world practice (from the Multicenter Prospective EXCELLENT and RESOLUTE-Korea Registries).
Long-term outcomes are imperative to confirm safety of drug-eluting stents. There have been 2 randomized controlled trials comparing everolimus-eluting stents (EESs) and Resolute zotarolimus-eluting stents (ZES-Rs). To date, long-term clinical outcomes of these stents were limited to only 1 report, which has recently reported 4-year comparisons of these stents. Therefore, more evidence is needed regarding long-term clinical outcomes of the second-generation stents. This study compared the long-term clinical outcomes of EES with ZES-R in "all-comer" cohorts up to 3-year follow-up. The EXCELLENT and RESOLUTE-Korea registries prospectively enrolled 3,056 patients treated with EES and 1,998 with ZES-R, respectively, without exclusions. Stent-related composite outcomes (target lesion failure) and patient-related composite events up to 3-year follow-up were compared in crude and propensity score-matched analyses. Of 5,054 patients, 3,830 patients (75.8%) had off-label indication (2,217 treated with EES and 1,613 treated with ZES-R). The stent-related outcome (189 [6.2%] vs 127 [6.4%], p = 0.812) and the patient-related outcome (420 [13.7%] vs 250 [12.5%], p = 0.581) did not differ between EES and ZES-R, respectively, at 3 years, which was corroborated by similar results from the propensity score-matched cohort (hazard ratio [HR] 0.92, 95% confidence interval [CI] 0.70 to 1.20, p = 0.523 and 0.85, 95% CI 0.70 to 1.02, p = 0.081, for stent- and patient-related outcomes, respectively). The rate of definite or probable stent thrombosis up to 3 years (22 [0.7%] vs 10 [0.5%], p = 0.370) was also similar. The rate of very late definite or probable stent thrombosis was very low and comparable between the 2 stents (3 [0.1%] vs 1 [0.1%], p = 0.657). In multivariate analysis, chronic renal failure (adjusted HR 3.615, 95% CI 2.440 to 5.354, p <0.001) and off-label indication (adjusted HR 1.782, 95% CI 1.169 to 2.718, p = 0.007) were the strongest predictors of target lesion failure at 3 years. In conclusion, both stents showed comparable safety and efficacy at 3-year follow-up in this robust real-world registry with unrestricted use of EES and ZES-R. Overall incidences of target lesion failure and definite stent thrombosis, including very late stent thrombosis, were low, even in the patients with off-label indications, suggesting excellent long-term safety and sustained efficacy of both types of second-generation drug-eluting stents.


Association of a cystatin C gene variant with cystatin C levels, CKD, and risk of incident cardiovascular disease and mortality.
Carriers of the T allele of the single-nucleotide polymorphism rs13038305 tend to have lower cystatin C levels and higher cystatin C-based estimated glomerular filtration rate (eGFRcys). Adjusting for this genetic effect on cystatin C concentrations may improve GFR estimation, reclassify cases of chronic kidney disease (CKD), and strengthen risk estimates for cardiovascular disease (CVD) and mortality. Observational. 4 population-based cohorts: Atherosclerosis Risk in Communities (ARIC), Cardiovascular Health (CHS), Framingham Heart (FHS), and Health, Aging, and Body Composition (Health ABC) studies. We estimated the association of rs13038305 with eGFRcys and serum creatinine-based eGFR (eGFRcr) and performed longitudinal analyses of the associations of eGFRcys with mortality and cardiovascular events following adjustment for rs13038305. We assessed reclassification by genotype-adjusted eGFRcys across CKD categories: <45, 45-59, 60-89, and ≥ 90 mL/min/1.73 m(2). We compared mortality and CVD outcomes in those reclassified to a worse eGFRcys category with those unaffected. Results were combined using fixed-effect inverse-variance meta-analysis. In 14,645 participants, each copy of the T allele of rs13038305 (frequency, 21%) was associated with a 6.4% lower cystatin C concentration, 5.5-mL/min/1.73 m(2) higher eGFRcys, and 36% [95% CI, 29%-41%] lower odds of CKD. Associations with CVD (HR, 1.17; 95% CI, 1.14-1.20) and mortality (HR, 1.22; 95% CI, 1.19-1.24) per 10-mL/min/1.73 m(2) lower eGFRcys were similar with or without rs13038305 adjustment. 1,134 (7.7%) participants were reclassified to a worse CKD category following rs13038305 adjustment, and rates of CVD and mortality were higher in individuals who were reclassified. However, the overall net reclassification index was not significant for either outcome, at 0.009 (95% CI, -0.003 to 0.022) for mortality and 0.014 (95% CI, 0.0 to 0.028) for CVD. rs13038305 explains only a small proportion of cystatin C variation. Statistical adjustment can correct a genetic bias in GFR estimates based on cystatin C in carriers of the T allele of rs13038305 and result in changes in disease classification. However, on a population level, the effects on overall reclassification of CKD status are modest.


Antiretrovirals and isoniazid preventive therapy in the prevention of HIV-associated tuberculosis in settings with limited health-care resources.
Antiretroviral therapy and isoniazid preventive therapy (IPT) are both effective interventions to prevent HIV-associated tuberculosis, but work via different mechanisms. We propose that these two interventions might best be used as complementary strategies at different stages of HIV progression. At relatively high CD4-cell counts, IPT reduces tuberculosis risk by 64% (95% CI 39-78%) in patients with positive tuberculin skin tests, and is the key tuberculosis preventive intervention before patients are eligible for antiretroviral therapy. However, at low CD4-cell counts, reliable exclusion of active tuberculosis is difficult, fewer patients are eligible for IPT, and waning immune function might limit the durability of its effect. In such patients, antiretroviral therapy is the primary intervention needed, reducing tuberculosis incidence by 67% (95% CI 61-73%). However, tuberculosis risk during long-term antiretroviral therapy remains several times higher than background, especially in those with poor immune recovery. Patients might therefore derive additional benefit from combined use of IPT and antiretroviral therapy to simultaneously treat mycobacterial infection and restore tuberculosis-specific immune function. For those first presenting with advanced immunodeficiency, we propose that concurrent IPT might best be delayed until completion of the first few months of antiretroviral therapy, when active tuberculosis can be more reliably excluded. Data from randomised controlled trials are needed to underpin further development of public-health policy.


Protease-activated receptor 2-mediated vasodilatation in humans in vivo: role of nitric oxide and prostanoids.
Systemic hypotension as a consequence of vascular dysfunction is a well-recognized and important feature of critical illness. Although serine protease activation has been implicated as a cause of vascular dysfunction in systemic inflammation, the mechanism is unknown. Recently, a class of receptors with an entirely novel mechanism of action, protease-activated receptors (PARs), has been identified that would explain the link between protease activation and systemic hypotension. Our aim was to test the hypothesis that in vivo activation of protease-activated receptor 2 (PAR-2) in humans would mediate vasodilatation. For these first-in-human studies, an activating peptide for the human PAR-2 receptor was synthesized and administered to healthy volunteers. Using both the dorsal hand vein technique and forearm plethysmography, we studied the effects of PAR-2 activation in human blood vessels and investigated the mechanism of vasodilation. Activation of PAR-2 receptors in vivo dilated human blood vessels in a dose-dependent manner, and the effects were reduced by inhibition of both nitric oxide and prostanoid synthesis These findings demonstrate that serine protease activity can cause human vasodilation and provide a possible explanation of why serine protease activation in critical illness is associated with vascular dysfunction.


A Rare Case of Tubulointerstitial Nephritis and Uveitis Syndrome Treated with a Multi-Specialty Approach.
BACKGROUND It is important for an ophthalmologist and nephrologist to look for hidden causes of uveitis and nephritis, respectively. Delay in diagnosis leads to increased morbidity and failure to systemically manage the patient results in future recurrence of disease. It is likely that TINU remains underdiagnosed and could potentially account for some of the cases of idiopathic uveitis, especially when greater than 50% of uveitis cases have no identifiable cause. Fewer than 300 cases of tubulointerstitial nephritis and uveitis (TINU) syndrome have been reported. In TINU syndrome, inflammation affects the renal tubules, interstitial tissue, and uveal tract. Its pathogenesis remains poorly understood. CASE REPORT We report a rare case of TINU syndrome in a 23-year-old female who was treated using a multispecialty approach. Her primary care physician diagnosed her with proteinuria and acute kidney injury and referred her to the nephrologist, who later referred her to the ophthalmologist. A left kidney biopsy confirmed acute interstitial nephritis. Following the discovery of a "pink eye", the patient was referred to ophthalmology and diagnosed with anterior uveitis, confirming TINU syndrome. Without the additional findings of uveitis, the diagnosis would have been missed. Resolution was obtained through steroid therapy. CONCLUSIONS Correctly diagnosing TINU syndrome requires a multispecialty approach and may not be obvious upon initial presentation. Therefore, the ophthalmologist needs to consider TINU in the differential diagnosis for a patient with bilateral uveitis and evaluate a urinalysis for proteinuria as part of the work up.


A three-dimensional electrochemical paper-based analytical device for low-cost diagnostics.
Paper-based microfluidic devices with screen-printed electrodes (SPEs) for electrochemical sensing are popular for low-cost point-of-care diagnostics. The electroactive sensing area in these devices is always the irregular, bottom-SPE surface which is in contact with the analyte flowing within the paper substrate. Unfortunately, this results in an electroactive area which varies widely from sensor to sensor. In this paper, we present a three-dimensional paper-based analytical device with a hollow 3D fluid reservoir which allows for use of a more uniform top-SPE surface as the electroactive sensing area. The use of this isolated reservoir eliminates the need for dielectric inks used in conventional SPEs on paper. Our sensors are fabricated using a combination of wax-printing, screen-printing and simple folding via a cleanroom free process without the need for expensive equipment. Additionally, for the first time, we demonstrate an electrochemical paper-based analytical device with a custom designed potentiostat integrated circuit (IC) as a miniaturized reader. The versatility of the sensor is demonstrated through voltammetric, amperometric and potentiometric measurements of important biochemical analytes such as dopamine, glucose and pH. The 3D ePAD together with a custom CMOS potentiostat demonstrates a low-cost, versatile, self-contained system suitable for point-of-care diagnostic devices.


Eugenic sterilization and a qualified Nazi analogy: the United States and Germany, 1930-1945.
In the United States and Germany before World War II, physicians participated in state-authorized eugenic sterilization programs in an attempt to prevent persons deemed to possess undesirable heritable characteristics from propagating. A comparison of U.S. and German histories reveals similarities that argue against easy dismissal of a Nazi analogy. On the basis of a review of editorials in New England Journal of Medicine and Journal of the American Medical Association from 1930 to 1945 it is difficult to accept the suggestion that the alliance between the medical profession and the eugenics movement in the United States was short-lived. Comparison of the histories of the eugenic sterilization campaigns in the United States and Nazi Germany reveals important similarities of motivation, intent, and strategy and differences that explain why support for eugenic sterilization in the United States gradually weakened. The eugenics movement in Germany was influenced by economic crisis, radical nationalism, Hitler's totalitarianism, and the medical profession's willing participation and attraction to Nazism for financial and ideological reasons. In the United States, a combination of public unease, Roman Catholic opposition, federal democracy, judicial review, and critical scrutiny by the medical profession reversed the momentum of the eugenics movement and led to the conclusion that eugenic sterilization should be voluntary.


An integrated testing strategy for in vitro skin corrosion and irritation assessment using SkinEthic™ Reconstructed Human Epidermis.
The SkinEthic™ Reconstructed Human Epidermis (RHE) method has been formally adopted for the regulatory assessment of skin irritation (OECD TG 439) and corrosion (OECD TG 431). Recently, the OECD adopted an Integrated Approach on Testing and Assessment (IATA) for skin corrosion and skin irritation (OECD GD 203), which provides guidance on the integration of existing and new information in a modular approach for classification and labelling. The present study aimed to evaluate the use of the SkinEthic™ RHE model within the proposed OECD IATA. Data on 86 substances were integrated in a bottom-up and top-down testing strategy to assess their capacity for EU CLP and UN GHS classifications. For EU CLP, strategies showed an accuracy of 84.8% to discriminate non-classified from classified substances, 94.4% to discriminate corrosive from non-corrosive substances, and 68.5% to discriminate the four (sub)-categories. For UN GHS, strategies showed an accuracy of 89.5% to discriminate non-classified from classified substances, 93.4% to discriminate corrosive from non-corrosive substances, and 74.2% to discriminate four GHS (sub)-categories (excluding Category 3). In conclusion, the integration of SkinEthic™ RHE irritation and corrosion data in a bottom-up and top-down testing strategy allows the classification of substances according to EU CLP and UN GHS.


Herd immunity, vaccination and moral obligation.
The public health benefits of herd immunity are often used as the justification for coercive vaccine policies. Yet, 'herd immunity' as a term has multiple referents, which can result in ambiguity, including regarding its role in ethical arguments. The term 'herd immunity' can refer to (1) the herd immunity threshold, at which models predict the decline of an epidemic; (2) the percentage of a population with immunity, whether it exceeds a given threshold or not; and/or (3) the indirect benefit afforded by collective immunity to those who are less immune. Moreover, the accumulation of immune individuals in a population can lead to two different outcomes: elimination (for measles, smallpox, etc) or endemic equilibrium (for COVID-19, influenza, etc). We argue that the strength of a moral obligation for individuals to contribute to herd immunity through vaccination, and by extension the acceptability of coercion, will depend on how 'herd immunity' is interpreted as well as facts about a given disease or vaccine. Among other things, not all uses of 'herd immunity' are equally valid for all pathogens. The optimal conditions for herd immunity threshold effects, as illustrated by measles, notably do not apply to the many pathogens for which reinfections are ubiquitous (due to waning immunity and/or antigenic variation). For such pathogens, including SARS-CoV-2, mass vaccination can only be expected to delay rather than prevent new infections, in which case the obligation to contribute to herd immunity is much weaker, and coercive policies less justifiable.


Providing grief resolution as an oncology nurse retention strategy: a literature review.
Oncology nurses play a pivotal role in optimizing care provided to patients at the end of life (EOL). Although oncology nurses commonly provide EOL care and witness deaths of patients that they have maintained long-standing relationships with, they are frequently excluded from grief resolution endeavors. With a worldwide shortage of oncology nurses, retention is paramount to ensuring that the care patients with cancer receive is not jeopardized. Various strategies were identified to resolve grief and increase nurse retention, including creating supportive work environments, debriefing with colleagues, providing EOL and grief education, and altering patient care assignments. Future research on emerging technologies and their effects on oncology nurse coping and retention strategies also was suggested.


Incidence and outcomes of unstable angina compared with non-ST-elevation myocardial infarction.
Assess the relative incidence and compare characteristics and outcome of unstable angina (UA) and non-ST-elevation myocardial infarction (NSTEMI). Two independent prospective multicentre diagnostic studies (Advantageous Predictors of Acute Coronary Syndromes Evaluation [APACE] and High-Sensitivity Troponin in the Evaluation of Patients With Acute Coronary Syndrome [High-STEACS]) enrolling patients with acute chest discomfort presenting to the emergency department. Central adjudication of the final diagnosis was done by two independent cardiologists using all clinical information including serial measurements of high-sensitivity cardiac troponin (hs-cTn). All-cause death and future non-fatal MI were assessed at 30 days and 1 year. 8992 patients were enrolled at 11 centres. UA was adjudicated in 8.9%(95% CI 8.0 to 9.7) and 2.8% (95% CI 2.3 to 3.3) patients in APACE and High-STEACS, respectively, and NSTEMI in 15.1% (95% CI 14.0 to 16.2) and 13.4% (95% CI 12.4 to 14.3). Coronary artery disease was pre-existing in 73% and 76% of patients with UA. At 30 days, all-cause mortality in UA was substantially lower as compared with NSTEMI (0.5% vs 3.7%, p=0.002 in APACE, 0.7% vs 7.4%, p=0.004 in High-STEACS). Similarly, at 1 year in UA all-cause mortality was 3.3% (95% CI 1.2 to 5.3) vs 10.4% (95% CI 7.9 to 12.9) in APACE, and 5.1% (95% CI 0.7 to 9.5) vs 22.9% (95% CI 19.3 to 26.4) in High-STEACS, and similar to non-cardiac chest pain (NCCP). In contrast, future non-fatal MI in APACE was comparable in UA and NSTEMI (11.2%, 95% CI 7.8 to 14.6 and 7.9%, 95% CI 5.7 to 10.2), and higher than in NCCP (0.6%, 95% CI 0.2 to 1.0). The relative incidence and mortality of UA is substantially lower than that of NSTEMI, while the rate of future non-fatal MI is similar.


Some aspects of the optical estimation of microstructure in fog and cloud.
Indirect measurement of parameters related to the drop size distribution in fog and cloud is discussed. Analysis of the kernel functions in the integral equation relating physical measurements (of transmission, forward scattering, and back scattering, respectively) to the drop size distribution reveals the number of useful independent inferences which can be made, with a specified error in measurement and from a given number of observations.


Wilson's disease: a great masquerader.
Wilson's disease (WD) is a treatable autosomal recessive metabolic disorder which could lead to protean hepatic or neurologic manifestations. WD could mimic many neurologic disorders and is often diagnosed with a long delay. This study describes central nervous system manifestations of a group of Iranian patients with neurologic WD. Data from case records of patients with neurologic WD presenting at a referral university hospital and a private clinic in Tehran from 1984 to 2004 were analyzed. Fifty patients from 44 unrelated families with WD were identified, whose mean duration of follow-up was 51.8 (+/-58.5) months. The median age of onset of neurologic symptoms in 37 patients with primary neurologic or simultaneous hepatic-neurologic presentation was 16 (10-38) years, whereas in 13 patients with prior hepatic damage, this was 18.5 (11-34) years. The 6 most common manifestations were dysarthria (80%), drooling (48%), tremor in limbs (44%), abnormal gait (44%), psychiatric and/or sleep symptoms (44%), and dystonia in limbs (42%). Neurologic WD has heterogeneous manifestations and should be considered in young patients presenting with dysarthria, drooling, any kind of movement disorders or psychiatric symptoms.


A targeted maximum likelihood estimator of a causal effect on a bounded continuous outcome.
Targeted maximum likelihood estimation of a parameter of a data generating distribution, known to be an element of a semi-parametric model, involves constructing a parametric model through an initial density estimator with parameter ɛ representing an amount of fluctuation of the initial density estimator, where the score of this fluctuation model at ɛ = 0 equals the efficient influence curve/canonical gradient. The latter constraint can be satisfied by many parametric fluctuation models since it represents only a local constraint of its behavior at zero fluctuation. However, it is very important that the fluctuations stay within the semi-parametric model for the observed data distribution, even if the parameter can be defined on fluctuations that fall outside the assumed observed data model. In particular, in the context of sparse data, by which we mean situations where the Fisher information is low, a violation of this property can heavily affect the performance of the estimator. This paper presents a fluctuation approach that guarantees the fluctuated density estimator remains inside the bounds of the data model. We demonstrate this in the context of estimation of a causal effect of a binary treatment on a continuous outcome that is bounded. It results in a targeted maximum likelihood estimator that inherently respects known bounds, and consequently is more robust in sparse data situations than the targeted MLE using a naive fluctuation model. When an estimation procedure incorporates weights, observations having large weights relative to the rest heavily influence the point estimate and inflate the variance. Truncating these weights is a common approach to reducing the variance, but it can also introduce bias into the estimate. We present an alternative targeted maximum likelihood estimation (TMLE) approach that dampens the effect of these heavily weighted observations. As a substitution estimator, TMLE respects the global constraints of the observed data model. For example, when outcomes are binary, a fluctuation of an initial density estimate on the logit scale constrains predicted probabilities to be between 0 and 1. This inherent enforcement of bounds has been extended to continuous outcomes. Simulation study results indicate that this approach is on a par with, and many times superior to, fluctuating on the linear scale, and in particular is more robust when there is sparsity in the data.


Adult physical dysfunction content in professional curricula.
This study examined the content of occupational therapy professional curricula as it pertains to adult physical dysfunction and the opinions and perceptions of faculty responsible for this content area. Survey results from 28 of 66 academic institutions offering professional-level education were received and analyzed. A great diversity in content and emphasis was reflected in the areas of medical conditions, general approaches to evaluation and treatment, specific evaluations, and specific treatment techniques and modalities. Most of the respondents were pleased with students' performances in physical dysfunction Level II fieldwork, believed that course work was applicable to local clinical settings, and agreed that courses were constantly changing to reflect evolving occupational therapy theory. Approximately 30% of the respondents believed that they had inadequate time to prepare students for entry-level practice, and about half agreed that their department had the necessary equipment to teach evaluation and treatment content.


Disseminated tuberculosis following liver transplant presenting with an axillary abscess.
Four years after an orthoptic liver transplant for hepatocellular carcinoma secondary to alcoholic liver disease, the patient presented in a crescendo manner with skin infections and finally a septic right arm wound. The abscess was drained and cultures grew Mycobacterium tuberculosis. The patient reported a previous episode of 'pneumonia' and subsequent hospitalisations for recurrent chest infections, and following further investigation, he was diagnosed with disseminated tuberculosis. The infection responded to triple therapy, but primary closure of the arm wound was unsuccessful and it was treated conservatively with negative pressure wound therapy. The patient remains an inpatient 3 months after his presentation, responding well to therapy and anticipating imminent discharge. The patient's case serves as a reminder that infections are common in solid organ transplant recipients and clinicians should be aware of unusual or recurrent presentations in these patients, to allow for early diagnosis and timely management.


Effects of thermocycling and occlusal force on adhesive composite crowns.
The aim of this in vitro study was to provide first quantitative data on the marginal adaptation and the required load to fracture of adhesive composite crowns with and without adhesive composite cores. Eighteen caries-free extracted human premolars were restored using fine hybrid composite crowns with margins located entirely in dentin. Six crowns were adhesively luted to dentin stubs, six to endodontically treated teeth with adhesive titanium posts and adhesive composite cores, and six to adhesive composite cores without posts. Another ten unprepared teeth served as a control. All restored teeth were subjected to long-term occlusal and thermal stresses. The marginal adaptation was evaluated in the SEM before and after loading. Load to fracture was recorded at the end of the stress. Before stressing, 72.2 to 85.0%, and after stressing, 51.9 to 66.2% of "continuous margin" were recorded at the dentin-luting composite interface. The best results after stressing were achieved with crowns luted to adhesive composite cores without titanium posts. At the luting composite-composite crown interface, 61.6 to 88.7% of "continuous margin" before and 57.7 to 75.5% after stressing were recorded. The required load to fracture the restored teeth ranged from 72.0 to 89.2% of the unrestored, unloaded control. Adhesive composite cores without titanium posts yielded the best results.


Temporal control of feeding behaviour and its association with gastrointestinal function.
This paper summarises knowledge about temporal control of ad libitum feeding in poultry, from minute to minute, hour to hour and day to day, and about how it relates to aspects of gastrointestinal function. Evidence is presented of only loose control over initiation and termination of spontaneous meals, and it is proposed that degrees of hunger and satiety determine probabilities of feeding starting and stopping. Voluntary regulation of food intake can be considered in terms of adjustments in mean meal size, meal frequency or both. Short-term variation is associated more with meal frequency and longer-term changes more with meal size. Short-term adjustments appear to depend more on alimentary control and longer-term adjustments more on metabolic control (not considered here). Long-term changes affecting meal size are associated with changes in capacity of parts of the alimentary tract. Food can accumulate in the crop and gizzard, and meal initiation and termination are associated with varying degrees of emptying and filling of these diverticula during most of the day. Later in the day there is usually a conditioned change to cumulative filling of the crop (and gizzard) with food that is digested overnight. Possible roles of osmo-/chemoreceptors and gut peptides are discussed.


Plasminogen Activator Inhibitor Type 1 (PAI-1) A15T Gene Polymorphism Is Associated with Prognosis in Patients with EGFR Mutation Positive Pulmonary Adenocarcinoma.
Plasminogen activator inhibitor type 1 (PAI-1), an important regulator of plasminogen activator system which controls degradation of extracellular membrane and progression of tumor cells, and PAI-1 gene polymorphic variants have been known as the prognostic biomarkers of non-small cell lung cancer patients. Recently, experimental in vitro study revealed that transforming growth factor-β1 initiated PAI-1 transcription through epithelial growth factor receptor (EGFR) signaling pathway. However, there is little clinical evidence on the association between PAI-1 A15T gene polymorphism and prognosis of Korean population with pulmonary adenocarcinoma and the influence of activating mutation of EGFR kinase domain. We retrospectively reviewed the medical records of 171 patients who were diagnosed with pulmonary adenocarcinoma and undergone EGFR mutation analysis from 1995 through 2009. In all patients with pulmonary adenocarcinoma, there was no significant association between PAI-1 A15T polymorphic variants and prognosis for overall survival. However, further subgroup analysis showed that the group with AG/AA genotype had a shorter 3-year survival time than the group with GG genotype in patients with EGFR mutant-type pulmonary adenocarcinoma (mean survival time, 24.9 months vs. 32.5 months, respectively; p=0.015). In multivariate analysis of 3-year survival for patients with pulmonary adenocarcinoma harboring mutant-type EGFR, the AG/AA genotype carriers had poorer prognosis than the GG genotype carriers (hazard ratio, 7.729; 95% confidence interval, 1.414-42.250; p=0.018). According to our study of Korean population with pulmonary adenocarcinoma, AG/AA genotype of PAI-1 A15T would be a significant predictor of poor short-term survival in patients with pulmonary adenocarcinoma harboring mutant-type EGFR.


Impact of asynchronous emergence of two lethal pathogens on amphibian assemblages.
Emerging diseases have been increasingly associated with population declines, with co-infections exhibiting many types of interactions. The chytrid fungus (Batrachochytrium dendrobatidis) and ranaviruses have extraordinarily broad host ranges, however co-infection dynamics have been largely overlooked. We investigated the pattern of co-occurrence of these two pathogens in an amphibian assemblage in Serra da Estrela (Portugal). The detection of chytridiomycosis in Portugal was linked to population declines of midwife-toads (Alytes obstetricans). The asynchronous and subsequent emergence of a second pathogen - ranavirus - caused episodes of lethal ranavirosis. Chytrid effects were limited to high altitudes and a single host, while ranavirus was highly pathogenic across multiple hosts, life-stages and altitudinal range. This new strain (Portuguese newt and toad ranavirus - member of the CMTV clade) caused annual mass die-offs, similar in host range and rapidity of declines to other locations in Iberia affected by CMTV-like ranaviruses. However, ranavirus was not always associated with disease, mortality and declines, contrasting with previous reports on Iberian CMTV-like ranavirosis. We found little evidence that pre-existing chytrid emergence was associated with ranavirus and the emergence of ranavirosis. Despite the lack of cumulative or amplified effects, ranavirus drove declines of host assemblages and changed host community composition and structure, posing a grave threat to all amphibian populations.


Examination of the antiglycemic properties of vinegar in healthy adults.
Vinegar reduces postprandial glycemia (PPG) in healthy adults. This study investigated the vinegar dosage (10 vs. 20 g), timing (during mealtime vs. 5 h before meal) and application (acetic acid as vinegar vs. neutralized salt) for reducing PPG. Four randomized crossover trials were conducted in adults (n = 9-10/trial) with type 2 diabetes (1 trial) or without diabetes (3 trials). All trials followed the same protocol: a standardized meal the evening prior to testing, an overnight fast ( 1 10 h) and 2-hour glucose testing following consumption of a bagel and juice test meal (3 trials) or dextrose solution (1 trial). For each trial, PPG was compared between treatments using area-under-the-curve calculations 120 min after the meal. Two teaspoons of vinegar ( 10 g) effectively reduced PPG, and this effect was most pronounced when vinegar was ingested during mealtime as compared to 5 h before the meal. Vinegar did not alter PPG when ingested with monosaccharides, suggesting that the antiglycemic action of vinegar is related to the digestion of carbohydrates. Finally, sodium acetate did not alter PPG, indicating that acetate salts lack antiglycemic properties. The antiglycemic properties of vinegar are evident when small amounts of vinegar are ingested with meals composed of complex carbohydrates. In these situations, vinegar attenuated PPG by 20% compared to placebo.


Thrombolytic Therapy for Acute Myocardial Infarction in Patients with Prior Coronary Bypass Surgery: Results from the Thrombolysis in Myocardial Infarction (TIMI) 4 Trial.
Little data exist on the value of intravenous thrombolysis for acute myocardial infarction in patients with previous coronary bypass surgery. The Thrombolysis In Myocardial Infarction (TIMI) 4 trial was a randomized study comparing tissue plasminogen activator, anistreplase, or a combination in patients with evolving myocardial infarction; patients with previous coronary bypass surgery were not excluded. Coronary angiography was performed 90 minutes and 18-36 hours after randomization, a myocardial perfusion scan was performed at 18-36 hours and predischarge, and a radionuclide ventriculogram was obtained predischarge. Angiographic and clinical outcome variables were determined in patients with and without a history of coronary bypass surgery. A total of 416 patients were randomized and 13 of them had previous bypass surgery; of these, 6 had an occluded vein graft as the infarct-related vessel. The incidence of TIMI grade 3 flow at 90 minutes was lower in patients with previous coronary surgery as compared with controls (42% vs. 49%), and overall patency was significantly lower (50% vs. 77%, p = 0.04). This trend persisted at 18-36 hours after randomization. Furthermore, patients with previous coronary surgery had more thrombus in their infarct-related arteries, especially with occlusion of a vein graft (83% vs. 32%, p = 0.04) and higher rates of recurrent ischemia (15% vs. 8%) and recurrent infarction (23% vs. 5%, p = 0.03) than controls. Thus, in patients with previous coronary bypass surgery intravenous thrombolysis yields results that are inferior to those achieved in patients without such a history and alternative methods of reperfusion should be considered.


Trends in tuberculosis notification and treatment outcomes in prisons: a country-wide assessment in El Salvador from 2009-2014.
Objective To describe trends in tuberculosis (TB) notification and treatment outcomes in 25 prisons in El Salvador from 2009-2014 and to determine if a set of interventions introduced in 2011 affected TB case finding and management. Methods This was operational research that utilized a retrospective cohort study of program data from 2009-2014. The package of interventions introduced in 2011 provides staff training, engages inmates in TB case finding, and offers diagnosis through mobile X-ray and Xpert® MTB/RIF. Results Case notification rates per 100 000 prisoners tripled, from 532 in 2009 to 1 688 in 2014-about 50 times that of the general population. Individual data were analyzed for 1 177 patients who started TB treatment, among whom 1 056 (89.7%) cases were bacteriologically-confirmed: 966 (92%) were diagnosed through smear microscopy; 42 (4%) with Xpert® MTB/RIF; and 48 (5%) through cultures. Cumulative treatment success and cure rates were over 95% and 90%, respectively. However, among 113 patients with previously-treated TB, drug sensitivity testing results were available for only 53 (47.%). One patient was diagnosed with mono-drug resistant TB. Conclusions These findings show that TB notification increased exponentially since introduction of the intervention package and that excellent treatment outcomes were sustained. Both are of vital relevance to countries striving for TB elimination. Notification might be improved further by providing systematic TB screening upon prison entry and periodically thereafter. Furthermore, previously-treated TB patients should receive prioritized screening for drug resistance.


Designing clinical trials with (restricted) mean survival time endpoint: Practical considerations.
The difference in mean survival time, which quantifies the treatment effect in terms most meaningful to patients and retains its interpretability regardless of the shape of the survival distribution or the proportionality of the treatment effect, is an alternative endpoint that could be used more often as the primary endpoint to design clinical trials. The underuse of this endpoint is due to investigators' lack of familiarity with the test comparing the mean survival times and the lack of tools to facilitate trial design with this endpoint. The aim of this article is to provide investigators with insights and software to design trials with restricted mean survival time as the primary endpoint. A closed-form formula for the asymptotic power of the test of restricted mean survival time difference is presented. The effects of design parameters on power were evaluated for the mean survival time test and log-rank test. An R package which calculates the power or the sample size for user-specified parameter values and provides power plots for each design parameter is provided. The R package also calculates the probability that the restricted mean survival time is estimable for user-defined trial designs. Under proportional hazards and late differences in survival, the power of the mean survival time test can approach that of the log-rank test if the restriction time is late. Under early differences, the power of the restricted mean survival time test is higher than that of the log-rank test. Duration of accrual and follow-up have little influence on the power of the restricted mean survival time test. The choice of restriction time, on the other hand, has a large impact on power. Because the power depends on the interplay among the design factors, plotting the relationship between each design parameter and power allows the users to select the designs most appropriate for their trial. When modification is necessary to ensure the difference in restricted mean survival time is estimable, the three available modifications all perform adequately in the scenarios studied. The restricted mean survival time is a survival endpoint that is meaningful to investigators and to patients and at the same time requires less restrictive assumptions. The biggest challenge with this endpoint is selection of the restriction time. We recommend selecting a restriction time that is clinically relevant to the disease and the clinical setting of the trial of interest. The practical considerations and the R package provided in this work are readily available tools that researchers can use to design trials with restricted mean survival time as the primary endpoint.


Ocean acidification-induced food quality deterioration constrains trophic transfer.
Our present understanding of ocean acidification (OA) impacts on marine organisms caused by rapidly rising atmospheric carbon dioxide (CO(2)) concentration is almost entirely limited to single species responses. OA consequences for food web interactions are, however, still unknown. Indirect OA effects can be expected for consumers by changing the nutritional quality of their prey. We used a laboratory experiment to test potential OA effects on algal fatty acid (FA) composition and resulting copepod growth. We show that elevated CO(2) significantly changed the FA concentration and composition of the diatom Thalassiosira pseudonana, which constrained growth and reproduction of the copepod Acartia tonsa. A significant decline in both total FAs (28.1 to 17.4 fg cell(-1)) and the ratio of long-chain polyunsaturated to saturated fatty acids (PUFA:SFA) of food algae cultured under elevated (750 µatm) compared to present day (380 µatm) pCO(2) was directly translated to copepods. The proportion of total essential FAs declined almost tenfold in copepods and the contribution of saturated fatty acids (SFAs) tripled at high CO(2). This rapid and reversible CO(2)-dependent shift in FA concentration and composition caused a decrease in both copepod somatic growth and egg production from 34 to 5 eggs female(-1) day(-1). Because the diatom-copepod link supports some of the most productive ecosystems in the world, our study demonstrates that OA can have far-reaching consequences for ocean food webs by changing the nutritional quality of essential macromolecules in primary producers that cascade up the food web.


Evaluation of the genotoxicity of chitosan nanoparticles for use in food packaging films.
The use of nanoparticles in food packaging has been proposed on the basis that it could improve protection of foods by, for example, reducing permeation of gases, minimizing odor loss, and increasing mechanical strength and thermal stability. Consequently, the impacts of such nanoparticles on organisms and on the environment need to be investigated to ensure their safe use. In an earlier study, Moura and others (2008a) described the effect of addition of chitosan (CS) and poly(methacrylic acid) (PMAA) nanoparticles on the mechanical properties, water vapor, and oxygen permeability of hydroxypropyl methylcellulose films used in food packaging. Here, the genotoxicity of different polymeric CS/PMAA nanoparticles (size 60, 82, and 111 nm) was evaluated at different concentration levels, using the Allium cepa chromosome damage test as well as cytogenetic tests employing human lymphocyte cultures. Test substrates were exposed to solutions containing nanoparticles at polymer mass concentrations of 1.8, 18, and 180 mg/L. Results showed no evidence of DNA damage caused by the nanoparticles (no significant numerical or structural changes were observed), however the 82 and 111 nm nanoparticles reduced mitotic index values at the highest concentration tested (180 mg/L), indicating that the nanoparticles were toxic to the cells used at this concentration. In the case of the 60 nm CS/PMAA nanoparticles, no significant changes in the mitotic index were observed at the concentration levels tested, indicating that these particles were not toxic. The techniques used show promising potential for application in tests of nanoparticle safety envisaging the future use of these materials in food packaging.


Unveiling the Hidden Bat Diversity of a Neotropical Montane Forest.
Mountain environments, characterized by high levels of endemism, are at risk of experiencing significant biodiversity loss due to current trends in global warming. While many acknowledge their importance and vulnerability, these ecosystems still remain poorly studied, particularly for taxa that are difficult to sample such as bats. Aiming to estimate the amount of cryptic diversity among bats of a Neotropical montane cloud forest in Talamanca Range-south-east Central America-, we performed a 15-night sampling campaign, which resulted in 90 captured bats belonging to 8 species. We sequenced their mitochondrial cytochrome c oxidase subunit I (COI) and screened their inter- and intraspecific genetic variation. Phylogenetic relations with conspecifics and closely related species from other geographic regions were established using Maximum Likelihood and Bayesian inference methods, as well as median-joining haplotype networks. Mitochondrial lineages highly divergent from hitherto characterized populations (> 9% COI dissimilarity) were found in Myotis oxyotus and Hylonycteris underwoodi. Sturnira burtonlimi and M. keaysi also showed distinct mitochondrial structure with sibling species and/or populations. These results suggest that mountains in the region hold a high degree of endemicity potential that has previously been ignored in bats. They also warn of the high extinction risk montane bats may be facing due to climatic change, particularly in isolated mountain systems like Talamanca Range.


Connecting μ-fluidics to electron microscopy.
A versatile methodology for electron microscopy (EM) grid preparation enabling total content sample analysis is presented. A microfluidic-dialysis conditioning module to desalt or mix samples with negative stain solution is used, combined with a robotic writing table to micro-pattern the EM grids. The method allows heterogeneous samples of minute volumes to be processed at physiological pH for structure and mass analysis, and allows the preparation characteristics to be finely tuned.


Unusual strain-dependent thermal conductivity modulation of silver nanoflower-polyurethane fibers.
Thermal management of stretchable and wearable electronic devices is an important issue in enhancing performance, reliability, and human thermal comfort. Here, we constructed a unique experimental setup which investigated the strain-dependent thermal conductivity. The thermal conductivity of flower-shaped silver nanoparticle (silver nanoflower)-polyurethane (Ag-PU) composite fibers was systematically investigated as a function of strain. The strain-dependent temperature distribution of the Joule-heated fiber was measured using an infrared camera, and the thermal conductivity was obtained from the 1-dimensional Fourier's conduction model. There was a monotonic decrease in both lattice and electronic thermal conductivity with stretching at 25 °C. However, there was an initial increase in lattice and total thermal conductivity in the low strain region (<10%), when the fiber was stretched at 45 °C, although the electronic thermal conductivity decreased monotonically. The softening of the polymer at increased temperatures enhanced Poisson's ratio. Resultantly, the fiber cross-sectional area and radial-direction inter-particle distance between silver nanoflowers decreased. This could increase the thermal transport in conductive fibers by modulating the interfaces between silver nanoflowers and polyurethane. A further stretching decreased the lattice thermal conductivity due to the significantly increased axial distance between silver nanoflowers and the decreased filler fraction. The weft-knitted fabric also demonstrated an increased thermal conductance in the low strain region (≤30%) at 45 °C.


Speech pathologists' perspectives on transitioning to telepractice: What factors promote acceptance?
Little is understood about factors that influence speech-language pathologists' (SLPs') acceptance of telepractice. The aim of this study was to investigate SLPs' perceptions and experiences of transitioning to a school-based telepractice service to identify factors that contributed to positive clinician attitudes. In-depth interviews were conducted with 15 SLPs who recently commenced providing school-based telepractice services. Interviews were recorded and transcribed verbatim and thematic analysis was used to interpret interviews, with themes compared and contrasted across the group. Results indicated that although SLPs reported initially having mixed feelings towards telepractice, they later evaluated telepractice positively and viewed it as a legitimate service delivery mode. The overarching theme was that positive beliefs about telepractice were associated with perceptions of its consistency with the underlying principles of face-to-face therapy. In evaluating telepractice, SLPs considered: (a) therapeutic relationships with children; (b) collaboration with parents and teachers; (c) adequacy of technology and resources; and (d) access to support for learning telepractice. Therapy assistants and specific clinician attributes emerged as key strategies used to manage threats to acceptability. Preparation of SLPs transitioning to telepractice should address factors that support positive experiences with, and attitudes towards, telepractice to ensure that training achieves the greatest, most sustained change.


Systematic review of the value of ultrasound and magnetic resonance musculoskeletal imaging in the evaluation of response to treatment of gout.
Imaging may be useful for monitoring response to therapy. Within the OMERACT proposal for the core set domains for outcome measures in chronic gout, serum urate levels, recurrence of gouty flares, tophus regression, and joint damage imaging have been included, among other proposed issues. To perform a systematic literature review of the usefulness of magnetic resonance imaging (MRI) and ultrasound (US) on assessment of treatment response in patients with gout. MEDLINE, EMBASE, Cochrane Library (up to February 2012), and abstracts presented at the 2010 and 2011 meetings of the American College of Rheumatology and European League Against Rheumatism, were searched for treatment studies of any duration and therapeutic options, examining the ability of MRI/US to assess treatment response in gouty patients. Meta-analyses, systematic reviews, randomized clinical trials, cohort and case-control studies and validation studies were included. Quality was appraised using validated scales. There were only 3 US published studies in the literature that analysed US utility on assessment of response to treatment in patients with gout. All of them were prospective case studies with a small number of patients and they were reviewed in detailed. A total of 36 patients with gout were examined with US. All of them had a baseline serum urate >6mg/dL. US features of gout (double contour sign, hyperechoic spots in synovial fluid, hyperechoic cloudy areas, tophus diameter and volume) achieved significant reduction in patients who reached the objective of uricemia ≤6mg/dL in all the studies; however, patients in whom levels did not drop below 6mg/dL had no change of US features of gout. Other parameters evaluated in one study included ESR, CRP, number of tender joints (TRN), number of swollen joints, and pain score (SP). All of them decreased with uricemia reduction, but only TRN and SP were statistically significant. No data was found on the value of MRI on treatment response assessment in patients with gout. The improvement in ultrasound features shows concurrent validity with uric acid reduction. According to the published evidence, US can be a useful tool for monitoring treatment of gouty patients, although more research is needed. The value of MRI on treatment response assessment in patients with gout remains to be determined.


Superficially located white matter structures commonly seen in the human and the macaque brain with diffusion tensor imaging.
The white matter of the brain consists of fiber tracts that connect different regions of the brain. Among these tracts, the intrahemispheric cortico-cortical connections are called association fibers. The U-fibers are short association fibers that connect adjacent gyri. These fibers were thought to work as part of the cortico-cortical networks to execute associative brain functions. However, their anatomy and functions have not been documented in detail for the human brain. In past studies, U-fibers have been characterized in the human brain with diffusion tensor imaging (DTI). However, the validity of such findings remains unclear. In this study, DTI of the macaque brain was performed, and the anatomy of U-fibers was compared with that of the human brain reported in a previous study. The macaque brain was chosen because it is the most commonly used animal model for exploring cognitive functions and the U-fibers of the macaque brain have been already identified by axonal tracing studies, which makes it an ideal system for confirming the DTI findings. Ten U-fibers found in the macaque brain were also identified in the human brain, with a similar organization and topology. The delineation of these species-conserved white matter structures may provide new options for understanding brain anatomy and function.


A critical evaluation of bioimpedance spectroscopy analysis in estimating body composition during GH treatment: comparison with bromide dilution and dual X-ray absorptiometry.
To compare estimates by bioimpedance spectroscopy analysis (BIS) of extracellular water (ECW), fat mass (FM), and fat-free mass (FFM) against standard techniques of bromide dilution and dual energy X-ray absorptiometry (DXA) during intervention that causes significant changes in water compartments and body composition. Body composition analysis using BIS, bromide dilution, and DXA was performed in 71 healthy recreational athletes (43 men, 28 women; aged 18-40 years; BMI 24 ± 0.4 kg/m(2)) who participated in a double-blinded, randomized, placebo-controlled study of GH and testosterone treatment. The comparison of BIS with bromide dilution and DXA was analyzed using linear regression and the Bland-Altman method. At baseline, there was a significant correlation between BIS and bromide dilution-derived estimates for ECW, and DXA for FM and FFM (P<0.001). ECW by BIS was 3.5 ± 8.1% lower compared with bromide dilution, while FM was 22.4 ± 26.8% lower and FFM 13.7 ± 7.5% higher compared with DXA (P<0.01). During treatment, the change in ECW was similar between BIS and bromide dilution, whereas BIS gave a significantly greater reduction in FM (19.4 ± 44.8%) and a greater increase in FFM (5.6 ± 3.0%) compared with DXA (P<0.01). Significant differences in body composition estimates between the BIS and DXA were observed only in men, particularly during the treatment that caused greatest change in water compartments and body composition. In healthy adults, bioimpedance spectroscopy is an acceptable tool for measuring ECW; however, BIS overestimates FFM and substantially underestimates FM compared with DXA.


Intraoperative optical imaging of intrinsic signals: a reliable method for visualizing stimulated functional brain areas during surgery.
Intraoperative optical imaging (IOI) is an experimental technique used for visualizing functional brain areas after surgical exposure of the cerebral cortex. This technique identifies areas of local changes in blood volume and oxygenation caused by stimulation of specific brain functions. The authors describe a new IOI method, including innovative data analysis, that can facilitate intraoperative functional imaging on a routine basis. To evaluate the reliability and validity of this approach, they used the new IOI method to demonstrate visualization of the median nerve area of the somatosensory cortex. In 41 patients with tumor lesions adjacent to the postcentral gyrus, lesions were surgically removed by using IOI during stimulation of the contralateral median nerve. Optical properties of the cortical tissue were measured with a sensitive camera system connected to a surgical microscope. Imaging was performed by using 9 cycles of alternating prolonged stimulation and rest periods of 30 seconds. Intraoperative optical imaging was based on blood volume changes detected by using a filter at an isosbestic wavelength (λ = 568 nm). A spectral analysis algorithm was used to improve computation of the activity maps. Movement artifacts were compensated for by an elastic registration algorithm. For validation, intraoperative conduction of the phase reversal over the central sulcus and postoperative evaluation of the craniotomy site were used. The new method and analysis enabled significant differentiation (p < 0.005) between functional and nonfunctional tissue. The identification and visualization of functionally intact somatosensory cortex was highly reliable; sensitivity was 94.4% and specificity was almost 100%. The surgeon was provided with a 2D high-resolution activity map within 12 minutes. No method-related side effects occurred in any of the 41 patients. The authors' new approach makes IOI a contact-free and label-free optical technique that can be used safely in a routine clinical setup. Intraoperative optical imaging can be used as an alternative to other methods for the identification of sensory cortex areas and offers the added benefit of a high-resolution map of functional activity. It has great potential for visualizing and monitoring additional specific functional brain areas such as the visual, motor, and speech cortex. A prospective national multicenter clinical trial is currently being planned.


Building political will for HIV response: an operational model and strategy options.
As global programs for HIV response look to transfer responsibility and financing increasingly to country governments, the political will to take on these responsibilities becomes increasingly prominent. However, defining and assessing political will are problematic; it involves intent and motivation, and thus is inherently difficult to observe. It is intimately connected to capacity and is contextually embedded. This article describes an operational model of political will comprised of seven components that are observable and measurable. Two case studies illustrate the application of the model and shed light on the interconnections among commitment, capacity and context: South Africa and China. Strategy options to build political will for HIV response identify possible actions for both government and civil society. Political will as a concept is most usefully viewed as integrated within larger political and bureaucratic processes, as a product of the complex array of incentives and disincentives that those processes create. However, this conclusion is not a recipe for discouragement or inaction. Agent-based conceptualizations of policy change offer a solid grounding for building political will that supports HIV policy and programs. Copyright © 2015 John Wiley & Sons, Ltd.


Current status of cardiovascular surgery in Japan, 2013 and 2014: a report based on the Japan Cardiovascular Surgery Database 5. Thoracic aortic surgery.
Although open aortic repair (OAR) is still considered to be a standard treatment for thoracic aortic diseases, the indications for thoracic endovascular treatment (TEVAR)/hybrid aortic repair (HAR) have expanded in recent years. The purpose of this study was to review the current status of treatment of thoracic aortic diseases in Japan. Data for 2013 and 2014 concerning surgery for diseases of the thoracic/thoracoabdominal aorta were extracted from the Japan Cardiovascular Surgery Database (JCVSD). The number of cases and operative mortality were evaluated in terms of pathologic diagnosis (acute dissection, chronic dissection, ruptured aneurysm, unruptured aneurysm), treatment modality (OAR, HAR, TEVAR), JapanSCORE (JS; <5%, 5-10%, 10-15%, ≥15%), and their correlations. There were 30,271 total cases in this study and the overall operative mortality was 5.9%. Among the three types of treatment, 73.2% of patients underwent OAR (root 98.3%; ascending 97.4%; root to arch 95.5%; arch 81.7%; descending 34.2%; thoracoabdominal 64.4%). While the rate of OAR was negatively correlated with JS for the treatment of the thoracoabdominal region (JS < 5, 80.4%; 5% ≤ JS < 10, 67.6%; 10% ≤ JS < 15, 58.8%; JS ≥ 15, 55.7%), a correlation was not observed in other anatomic regions. The operative mortality associated with OAR was well reflected by JS (JS < 5, 2.1%; 5% ≤ JS < 10, 5.5%; 10% ≤ JS < 15, 10.2%; JS ≥ 15, 20.3%); however, the operative mortality associated with TEVAR/HAR was less than that with JS. The distribution of treatment differs depending on the site of disease and is not markedly influenced by JS. It is clear that JS is a reliable tool for estimating operative mortality in OAR. However, the observed operative mortality was lower than the JS in TEVAR/HAR, and a new risk score for TEVAR/HAR should be established.


NADPH oxidase in the renal microvasculature is a primary target for blood pressure-lowering effects by inorganic nitrate and nitrite.
Renal oxidative stress and nitric oxide (NO) deficiency are key events in hypertension. Stimulation of a nitrate-nitrite-NO pathway with dietary nitrate reduces blood pressure, but the mechanisms or target organ are not clear. We investigated the hypothesis that inorganic nitrate and nitrite attenuate reactivity of renal microcirculation and blood pressure responses to angiotensin II (ANG II) by modulating nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and NO bioavailability. Nitrite in the physiological range (10(-7)-10(-5) mol/L) dilated isolated perfused renal afferent arterioles, which were associated with increased NO. Contractions to ANG II (34%) and simultaneous NO synthase inhibition (56%) were attenuated by nitrite (18% and 26%). In a model of oxidative stress (superoxide dismutase-1 knockouts), abnormal ANG II-mediated arteriolar contractions (90%) were normalized by nitrite (44%). Mechanistically, effects of nitrite were abolished by NO scavenger and xanthine oxidase inhibitor, but only partially attenuated by inhibiting soluble guanylyl cyclase. Inhibition of NADPH oxidase with apocynin attenuated ANG II-induced contractility (35%) similar to that of nitrite. In the presence of nitrite, no further effect of apocynin was observed, suggesting NADPH oxidase as a possible target. In preglomerular vascular smooth muscle cells and kidney cortex, nitrite reduced both basal and ANG II-induced NADPH oxidase activity. These effects of nitrite were also abolished by xanthine oxidase inhibition. Moreover, supplementation with dietary nitrate (10(-2) mol/L) reduced renal NADPH oxidase activity and attenuated ANG II-mediated arteriolar contractions and hypertension (99±2-146±2 mm Hg) compared with placebo (100±3-168±3 mm Hg). In conclusion, these novel findings position NADPH oxidase in the renal microvasculature as a prime target for blood pressure-lowering effects of inorganic nitrate and nitrite.


Evaluation of email alerts in practice: Part 1. Review of the literature on clinical emailing channels.
Methods to systematically assess electronic knowledge resources by health professionals may enhance evaluation of these resources, knowledge exchange between information users and providers, and continuing professional development. We developed the Information Assessment Method (IAM) to document health professional perspectives on the relevance, cognitive impact, potential use and expected health outcomes of information delivered by (push) or retrieved from (pull) electronic knowledge resources. However, little is known about push communication in health sciences, and what we propose to call clinical emailing channels (CECs). CECs can be understood as a communication infrastructure that channels clinically relevant research knowledge, email alerts, from information providers to the inboxes of individual practitioners. In two companion papers, our objectives are to (part 1) explore CEC evaluation in routine practice, and (part 2) examine the content validity of the cognitive component of IAM. The present paper (part 1) critically reviews the literature in health sciences and four disciplines: communication, information studies, education and knowledge translation. Our review addresses the following questions. What are CECs? How are they assessed? The review contributes to better define CECs, and proposes a 'push-pull-acquisition-cognition-application' evaluation framework, which is operationalized by IAM. Compared with existing evaluation tools, our review suggests IAM is comprehensive, generic and systematic.


Temporal partitioning and spatiotemporal avoidance among large carnivores in a human-impacted African landscape.
Africa is home to some of the world's most functionally diverse guilds of large carnivores. However, they are increasingly under threat from anthropogenic pressures that may exacerbate already intense intra-guild competition. Understanding the coexistence mechanisms employed by these species in human-impacted landscapes could help shed light on some of the more subtle ways in which humans may impact wildlife populations, and inform multi-species conservation planning. We used camera trap data from Tanzania's Ruaha-Rungwa landscape to explore temporal and spatiotemporal associations between members of an intact East African large carnivore guild, and determine how these varied across gradients of anthropogenic impact and protection. All large carnivores except African wild dog (Lycaon pictus) exhibited predominantly nocturnal road-travel behaviour. Leopard (Panthera pardus) appeared to employ minor temporal avoidance of lion (Panthera leo) in all sites except those where human impacts were highest, suggesting that leopard may have been freed up from avoidance of lion in areas where the dominant competitor was less abundant, or that the need for leopard to avoid humans outweighed the need to avoid sympatric competitors. Lion appeared to modify their activity patterns to avoid humans in the most impacted areas. We also found evidence of avoidance and attraction among large carnivores: lion and spotted hyaena (Crocuta crocuta) followed leopard; leopard avoided lion; spotted hyaena followed lion; and lion avoided spotted hyaena. Our findings suggest that large carnivores in Ruaha-Rungwa employ fine-scale partitioning mechanisms to facilitate coexistence with both sympatric species and humans, and that growing human pressures may interfere with these behaviours.


Lower Extremity Peripheral Artery Disease: Contemporary Epidemiology, Management Gaps, and Future Directions: A Scientific Statement From the American Heart Association.
Lower extremity peripheral artery disease (PAD) affects >230 million adults worldwide and is associated with increased risk of various adverse clinical outcomes (other cardiovascular diseases such as coronary heart disease and stroke and leg outcomes such as amputation). Despite its prevalence and clinical importance, PAD has been historically underappreciated by health care professionals and patients. This underappreciation seems multifactorial (eg, limited availability of the first-line diagnostic test, the ankle-brachial index, in clinics; incorrect perceptions that a leg vascular disease is not fatal and that the diagnosis of PAD would not necessarily change clinical practice). In the past several years, a body of evidence has indicated that these perceptions are incorrect. Several studies have consistently demonstrated that many patients with PAD are not receiving evidence-based therapies. Thus, this scientific statement provides an update for health care professionals regarding contemporary epidemiology (eg, prevalence, temporal trends, risk factors, and complications) of PAD, the present status of diagnosis (physiological tests and imaging modalities), and the major gaps in the management of PAD (eg, medications, exercise therapy, and revascularization). The statement also lists key gaps in research, clinical practice, and implementation related to PAD. Orchestrated efforts among different parties (eg, health care providers, researchers, expert organizations, and health care organizations) will be needed to increase the awareness and understanding of PAD and improve the diagnostic approaches, management, and prognosis of PAD.


Lack of effect of blood-volume expansion on short-circuit current across an isolated toad skin incorporated in the circulation of a rat.
1. Evidence for the existence of 'natriuretic hormone' resides, in part, in the demonstration that blood volume expansion in the dog is followed by a transient fall in short-circuit current (SCC) across a frog skin incorporated within its circulation. 2. We have attempted to confirm this effect in the rat, with a toad skin (Xenopus laevis) incorporated within the circulation. The skins, bathed in whole rat blood, displayed low SCC; skins bathed in 'mammalian' Ringer solution displayed equally low SCC, but responded normally to pitressin or amiloride. 3. When volume expansion was induced in ten rats by infusion of equilibrated whole blood (28 ml/kg body weight) there was a brisk rise in systemic blood pressure, diuresis, natriuresis and kaliuresis. 4. This blood-volume expansion was without detectable effect on the SCC across the skins incorporated within the rats' circulations.


Europa's magnetic signature: report from Galileo's pass on 19 December 1996.
On 19 December 1996 as Galileo passed close to Jupiter's moon, Europa, the magnetometer measured substantial departures from the slowly varying background field of Jupiter's magnetosphere. Currents coupling Europa to Jupiter's magnetospheric plasma could produce perturbations of the observed size. However, the trend of the field perturbations is here modeled as the signature of a Europa-centered dipole moment whose maximum surface magnitude is approximately 240 nanotesla, giving a rough upper limit to the internal field. The dipole orientation is oblique to Europa's spin axis. This orientation may not be probable for a field generated by a core dynamo, but higher order multipoles may be important as they are at Uranus and Neptune. Although the data can be modeled as contributions of an internal field of Europa, they do not confirm its existence. The dipole orientation is also oblique to the imposed field of Jupiter and thus not directly produced as a response to that field. Close to Europa, plasma currents appear to produce perturbations with scale sizes that are small compared with a Europa radius.


The effects of perceived mating opportunities on patterns of reproductive investment by male guppies.
Males pay considerable reproductive costs in acquiring mates (precopulatory sexual selection) and in producing ejaculates that are effective at fertilising eggs in the presence of competing ejaculates (postcopulatory sexual selection). Given these costs, males must balance their reproductive investment in a given mating to optimise their future reproductive potential. Males are therefore expected to invest in reproduction prudently according to the likelihood of obtaining future matings. In this study we tested this prediction by determining whether male reproductive investment varies with expected future mating opportunities, which were experimentally manipulated by visually exposing male guppies (Poecilia reticulata) to high or low numbers of females in the absence of competing males. Our experiment did not reveal consistent effects of perceived future mating opportunity on either precopulatory (male mate choice and mating behaviour) or postcopulatory (sperm quality and quantity) investment. However, we did find that male size and female availability interacted to influence mating behaviour; large males visually deprived of females during the treatment phase became more choosy and showed greater interest in their preferred female than those given continuous visual access to females. Overall, our results suggest males tailor pre- rather than postcopulatory traits according to local female availability, but critically, these effects depend on male size.


A cluster of pathogenic mutations in the 3'-5' exonuclease domain of DNA polymerase gamma defines a novel module coupling DNA synthesis and degradation.
Mutations in DNA polymerase gamma (pol g), the unique replicase inside mitochondria, cause a broad and complex spectrum of diseases in human. We have used Mip1, the yeast pol g, as a model enzyme to characterize six pathogenic pol g mutations. Four mutations clustered in a highly conserved 3'-5' exonuclease module are localized in the DNA-binding channel in close vicinity to the polymerase domain. They result in an increased frequency of point mutations and high instability of the mitochondrial DNA (mtDNA) in yeast cells, and unexpectedly for mutator mutations in the exonuclease domain, they favour exonucleolysis versus polymerization. This trait is associated with highly decreased DNA-binding affinity and poorly processive DNA synthesis. Our data show for the first time that a 3'-5' exonuclease module of pol g plays a crucial role in the coordination of the polymerase and exonuclease functions and they strongly suggest that in patients the disease is not caused by defective proofreading but results from poor mtDNA replication generated by a severe imbalance between DNA synthesis and degradation.


CSF somatostatin and abnormal response to dexamethasone administration in schizophrenic and depressed patients.
Low levels of cerebrospinal fluid (CSF) somatostatin and abnormal response to dexamethasone are two neuroendocrine disturbances reported to appear in depression and other neuropsychiatric disorders. We measured the levels of CSF somatostatin in patients with schizophrenia (n = 44) and depression (n = 19). In view of in vitro and animal evidence of the ability of somatostatin to inhibit stimulated corticotropin secretion, we also administered the dexamethasone suppression test to a subgroup of the patients with schizophrenia (n = 16) and the total depressed group. Lower levels of CSF somatostatin were found in dexamethasone nonsuppressors regardless of diagnosis and were negatively correlated with maximum postdexamethasone cortisol level in the total and depressed patient groups. These data suggest a functional relationship between hypothalamic-pituitary-adrenal axis hyperactivity and reduced CSF somatostatin level.


There are no caterpillars in a wicked forest.
Species trees represent the historical divergences of populations or species, while gene trees trace the ancestry of individual gene copies sampled within those populations. In cases involving rapid speciation, gene trees with topologies that differ from that of the species tree can be most probable under the standard multispecies coalescent model, making species tree inference more difficult. Such anomalous gene trees are not well understood except for some small cases. In this work, we establish one constraint that applies to trees of any size: gene trees with "caterpillar" topologies cannot be anomalous. The proof of this involves a new combinatorial object, called a population history, which keeps track of the number of coalescent events in each ancestral population.


Essential oils from Taiwan: Chemical composition and antibacterial activity against Escherichia coli.
The chemical compositions of seven essential oils from Taiwan were analyzed by gas chromatography-mass spectrometry. The eluates were identified by matching the mass fragment patents to the National Institute of Standards and Technology (NIST) 08 database. The quantitative analysis showed that the major components of lemon verbena are geranial (26.9%) and neral (23.1%); those of sweet marjoram are γ-terpinene (18.5%), thymol methyl ether (15.5%), and terpinen-4-ol (12.0%); those of clove basil are eugenol (73.6%), and β-(Z)-ocimene (15.4%); those of patchouli are carvacrol (47.5%) and p-cymene (15.2%); those of rosemary are α-pinene (54.8%) and 1,8-cineole (22.2%); those of tea tree are terpinen-4-ol (33.0%) and 1,8-cineole (27.7%); and those of rose geranium are citronellol (28.9%) and 6,9-guaiadiene (20.1%). These components are somewhat different from the same essential oils that were obtained from other origins. Lemon verbena has the same major components everywhere. Tea tree, rose geranium, and clove basil have at least one major component throughout different origins. The major components and their amounts in sweet marjoram, patchouli, and rosemary vary widely from one place to another. These results demonstrate that essential oils have a large diversity in their composition in line with their different origins. The antibacterial activity of essential oils against Escherichia coli was evaluated using the optical density method (turbidimetry). Patchouli is a very effective inhibitor, in that it completely inhibits the growth of E. coli at 0.05%. Clove basil and sweet marjoram are good inhibitors, and the upper limit of their minimum inhibitory concentration is 0.1%.


What do the bereaved by suicide communicate in online support groups? A content analysis.
Every year, more than six million people lose a loved one through suicide. These bereaved by suicide are at relatively high risk for mental illnesses including suicide. The social stigma attached to suicide often makes it difficult to talk about grief. Participating in online forums may be beneficial for the bereaved by suicide, but it is unknown what they communicate in these forums. What do the bereaved by suicide communicate in online forums? We examined which self-help mechanisms, grief reactions, and experiences with health-care services they shared online. We conducted a content analysis of 1,250 messages from 165 members of two Dutch language forums for the bereaved by suicide. We found that sharing personal experiences featured most prominently in the messages, often with emotional expressions of grief. Other frequently used self-help mechanisms were expressions of support or empathy, providing advice, and universality (recognition), while experiences with health-care services featured only occasionally. Compared with previous studies about online forums for somatic illnesses, the bereaved by suicide communicated more personal experiences and engaged much less in chitchat. Online forums appear to have relevant additional value as a platform for talking about grief and finding support.


High-resolution ISAR imaging of maneuvering targets by means of the range instantaneous Doppler technique: modeling and performance analysis.
Very high resolution inverse synthetic aperture radar (ISAR) imaging of maneuvering targets is a complicated task. In fact, the conventional range Doppler (RD) ISAR technique does not work properly when target motions generate terms higher than the first order in the phase of the received signal relative to each scatterer. This effect typically happens when at least one of these situations occur: (1) very high resolution images are required; (2) the target maneuvers; and (3) the target undergoes significant angular motions (roll, pitch, and yaw). A novel ISAR technique, named range instantaneous Doppler (RID), has been proposed for the reconstruction of very high resolution images of maneuvering targets. In this paper, we analytically show that the RID technique works properly when high-resolution ISAR images are required of maneuvering and/or rolling, pitching, and yawing targets; we also quantify the performance improvement of the RID technique with respect to the RD technique. The problem is tackled from an analytical point of view. First, we define a new model of the ISAR received signal that is valid for maneuvering targets, then we derive and compare the analytical expression of the point spread function (PSF) for the two techniques. Furthermore, we perform a statistical analysis to evaluate the improvement of the RID technique versus the RD technique in terms of spatial resolution. Finally, we prove the effectiveness of the RID technique by simulating the imaging process for two different targets: (1) a ship that undergoes roll, pitch and yaw motions and (2) a fast maneuvering airplane.


Platelet Adhesion and Fibrinogen Accretion on a Family of Elastin-Like Polypeptides.
Previous work in our laboratory showed the potential of using a human recombinant elastin-like polypeptide (ELP) as a thromboresistant coating. In this work we investigate the use of three particular ELPs (ELP1, ELP2 and ELP4), that differ by molecular weight and number of repeating hydrophobic and cross-linking domains, as coatings to improve blood-contacting properties. All three ELPs were passively adsorbed on Mylar surfaces. Differences in water contact angle and surface concentration were found among the three ELP coatings, with the shortest polypeptide, ELP1, being the most hydrophilic and abundant on the surface (55°, 0.76 μg/cm(2)), followed by ELP2 (55°, 0.35 μg/cm(2)) and ELP4, the longest of the three (66°, 0.25 μg/cm(2)), respectively. The blood interactions of the ELP coatings were investigated by measuring fibrinogen adsorption and platelet adhesion in whole blood under laminar flow in a cone and plate viscometer configuration. In general, platelet adhesion to the ELP-coated surfaces was found to correlate with fibrinogen adsorption. Decreases in fibrinogen accretion and platelet adhesion were observed for ELP-coated compared to uncoated surfaces. The magnitude of the decreases was found to depend on the ELP sequence length, with ELP4 exhibiting the lowest levels of fibrinogen adsorption and platelet adhesion at 43 ± 24 ng/cm(2) and 113 ± 77 platelets/mm(2), respectively.


The in vivo antifungal activity of the aqueous extract from Nigella sativa seeds.
The effect of an aqueous extract of Nigella sativa seeds was studied on candidiasis in mice. An intravenous inoculum of Candida albicans produced colonies of the organism in the liver, spleen and kidneys. Treatment of mice with the plant extract (6.6 mL/kg equivalent to 5 mg of estimated protein, once daily for 3 days) 24 h after the inoculation caused a considerable inhibitory effect on the growth of the organism in all organs studied. A 5-fold decrease in Candida in kidneys, 8-fold in liver and 11-fold in spleen was observed in the groups of animals post-treated with the plant extract. Histopathological examination of the respective organs confirmed these findings. These results indicate that the aqueous extract of Nigella sativa seeds exhibits inhibitory effect against candidiasis and this study validates the traditional use of the plant in fungal infections.


Shape-memory polymer nanocomposites with a 3D conductive network for bidirectional actuation and locomotion application.
Electrical stimulation of shape-memory polymers (SMPs) has many advantages over thermal methods; creating an efficient conductive path through the bulk polymers is essential for developing high performance electroactive systems. Here, we show that a three-dimensional (3D) porous carbon nanotube sponge can serve as a built-in integral conductive network to provide internal, homogeneous, in situ Joule heating for shape-memory polymers, thus significantly improving the mechanical and thermal behavior of SMPs. As a result, the 3D nanocomposites show a fast response and produce large exerting forces (with a maximum flexural stress of 14.6 MPa) during shape recovery. We further studied the construction of a double-layer composite structure for bidirectional actuation, in which the shape change is dominated by the temperature-dependent exerting force from the top and bottom layer, alternately. An inchworm-type robot is demonstrated whose locomotion is realized by such bidirectional shape memory. Our large stroke shape-memory nanocomposites have promising applications in many areas including artificial muscles and bionic robots.


Fast retrospectively triggered local pulse-wave velocity measurements in mice with CMR-microscopy using a radial trajectory.
The aortic pulse-wave velocity (PWV) is an important indicator of cardiovascular risk. In recent studies MRI methods have been developed to measure this parameter noninvasively in mice. Present techniques require additional hardware for cardiac and respiratory gating. In this work a robust self-gated measurement of the local PWV in mice without the need of triggering probes is proposed. The local PWV of 6-months-old wild-type C57BL/6J mice (n=6) was measured in the abdominal aorta with a retrospectively triggered radial Phase Contrast (PC) MR sequence using the flow-area (QA) method. A navigator signal was extracted from the CMR data of highly asymmetric radial projections with short repetition time (TR=3 ms) and post-processed with high-pass and low-pass filters for retrospective cardiac and respiratory gating. The self-gating signal was used for a reconstruction of high-resolution Cine frames of the aortic motion. To assess the local PWV the volume flow Q and the cross-sectional area A of the aorta were determined. The results were compared with the values measured with a triggered Cartesian and an undersampled triggered radial PC-Cine sequence. In all examined animals a self-gating signal could be extracted and used for retrospective breath-gating and PC-Cine reconstruction. With the non-triggered measurement PWV values of 2.3±0.2 m/s were determined. These values are in agreement with those measured with the triggered Cartesian (2.4±0.2 m/s) and the triggered radial (2.3±0.2 m/s) measurement. Due to the strong robustness of the radial trajectory against undersampling an acceleration of more than two relative to the prospectively triggered Cartesian sampling could be achieved with the retrospective method. With the radial flow-encoding sequence the extraction of a self-gating signal is feasible. The retrospective method enables a robust and fast measurement of the local PWV without the need of additional trigger hardware.


4-Amino-2,3-dihydro-1λ6-isothiazole-1,1-dioxides and their chemical properties evaluation.
The reactivity of the 4-amino-2,3-dihydro-1H-1λ6-isothiazole-1,1-dioxide (β-amino-γ-sultam) framework has not been studied sufficiently. Here we describe the chemical properties of this heterocyclic system toward electrophiles on spiranic and non-spiranic substrates. A variety of C-electrophiles (acetic anhydride, benzoyl chloride, DMFDMA, 4,4-dimethoxybutan-2-one) and heteroatom electrophiles (bromine, nitrosyl acetate) have been explored. Both the C-5 and 4-amino positions of the β-amino-γ-sultam system are able to undergo electrophilic reactions. Heteroatom electrophiles attack the C-5 position, whereas carbo-electrophiles affect the amino group. β-Amino-γ-sultams also were used as starting compounds for the synthesis of 6- or 7-substituted 1λ6-isothiazolo[4,5-b]pyridine-1,1-dioxides through condensation reaction and palladium-catalyzed oxidative coupling.


Aspirin monotherapy in the treatment of distal intracranial aneurysms with a surface modified flow diverter: a pilot study.
Flow diverters (FDs) result in high occlusion rates of aneurysms located distally to the carotid artery. However, the complications reported are not negligible. New modified surface FDs have low thrombogenic properties that may reduce ischemic complications related to the treatment. In addition, a modified surface FD may allow for the use of a single antiplatelet medication to reduce hemorrhagic risk during the procedure. The aim of this study was to assess the safety and efficacy of the p48 MW HPC (phenox, Bochum, Germany) to treat distal intracranial aneurysms under the use of aspirin monotherapy. The primary endpoint was the incidence of any neurologic deficit after treatment after 6 months of follow-up. The secondary endpoint was the rate of the complete occlusion of the aneurysms at the 6-month follow-up. Enrollment of 20 patients was planned, but after inclusion of seven patients the study was stopped due to safety issues. Seven patients with eight aneurysms were included. Among the seven patients, three (42.8%) had ischemic complications on the second day after FD deployment. Two patients experienced complete recovery at discharge (National Institutes of Health Stroke Scale (NIHSS) score=0), while one patient maintained mild dysarthria at discharge (NIHSS score=1) which improved after 6 months (NIHSS score=0). All three patients had no new symptoms during the 6-month follow-up. Complete aneurysm occlusion occurred in six (75%) of the eight aneurysms at the 6-month follow-up. Antiplatelet monotherapy with aspirin for the treatment of distal intracranial aneurysms with this modified surface FD resulted in a significant incidence of ischemic complications after treatment.


Evidence for non-communicable diseases: analysis of Cochrane reviews and randomised trials by World Bank classification.
Prevalence of non-communicable diseases (NCDs) is increasing globally, with the greatest projected increases in low-income and middle-income countries. We sought to quantify the proportion of Cochrane evidence relating to NCDs derived from such countries. We searched the Cochrane database of systematic reviews for reviews relating to NCDs highlighted in the WHO NCD action plan (cardiovascular, cancers, diabetes and chronic respiratory diseases). We excluded reviews at the protocol stage and those that were repeated or had been withdrawn. For each review, two independent researchers extracted data relating to the country of the corresponding author and the number of trials and participants from countries, using the World Bank classification of gross national income per capita. 797 reviews were analysed, with a reported total number of 12 340 trials and 10 937 306 participants. Of the corresponding authors 90% were from high-income countries (41% from the UK). Of the 746 reviews in which at least one trial had met the inclusion criteria, only 55% provided a summary of the country of included trials. Analysis of the 633 reviews in which country of trials could be established revealed that almost 90% of trials and over 80% of participants were from high-income countries. 438 (5%) trials including 1 145 013 (11.7%) participants were undertaken in low-middle income countries. We found that only 13 (0.15%) trials with 982 (0.01%) participants were undertaken in low-income countries. Other than the five Cochrane NCD corresponding authors from South Africa, only one other corresponding author was from Africa (Gambia). The overwhelming body of evidence for NCDs pertains to high-income countries, with only a small number of review authors based in low-income settings. As a consequence, there is an urgent need for research infrastructure and funding for the undertaking of high-quality trials in this area.


Multimodal connectivity mapping of the human left anterior and posterior lateral prefrontal cortex.
Working memory is essential for many of our distinctly human abilities, including reasoning, problem solving, and planning. Research spanning many decades has helped to refine our understanding of this high-level function as comprising several hierarchically organized components, some which maintain information in the conscious mind, and others which manipulate and reorganize this information in useful ways. In the neocortex, these processes are likely implemented by a distributed frontoparietal network, with more posterior regions serving to maintain volatile information, and more anterior regions subserving the manipulation of this information. Recent meta-analytic findings have identified the anterior lateral prefrontal cortex, in particular, as being generally engaged by working memory tasks, while the posterior lateral prefrontal cortex was more strongly associated with the cognitive load required by these tasks. These findings suggest specific roles for these regions in the cognitive control processes underlying working memory. To further characterize these regions, we applied three distinct seed-based methods for determining cortical connectivity. Specifically, we employed meta-analytic connectivity mapping across task-based fMRI experiments, resting-state BOLD correlations, and VBM-based structural covariance. We found a frontoparietal pattern of convergence which strongly resembled the working memory networks identified in previous research. A contrast between anterior and posterior parts of the lateral prefrontal cortex revealed distinct connectivity patterns consistent with the idea of a hierarchical organization of frontoparietal networks. Moreover, we found a distributed network that was anticorrelated with the anterior seed region, which included most of the default mode network and a subcomponent related to social and emotional processing. These findings fit well with the internal attention model of working memory, in which representation of information is processed according to an anteroposterior gradient of abstract-to-concrete representations.


Evaluation of the positional difference between two common geocoding methods.
Geocoding, the process of matching addresses to geographic coordinates, is a necessary first step when using geographical information systems (GIS) technology. However, different geocoding methodologies can result in different geographic coordinates. The objective of this study was to compare the positional (i.e. longitude/latitude) difference between two common geocoding methods, i.e. ArcGIS (Environmental System Research Institute, Redlands, CA, USA) and Batchgeo (freely available online at http://www.batchgeo.com). Address data came from the YMCA-Harvard After School Food and Fitness Project, an obesity prevention intervention involving children aged 5-11 years and their families participating in YMCA-administered, after-school programmes located in four geographically diverse metropolitan areas in the USA. Our analyses include baseline addresses (n = 748) collected from the parents of the children in the after school sites. Addresses were first geocoded to the street level and assigned longitude and latitude coordinates with ArcGIS, version 9.3, then the same addresses were geocoded with Batchgeo. For this analysis, the ArcGIS minimum match score was 80. The resulting geocodes were projected into state plane coordinates, and the difference in longitude and latitude coordinates were calculated in meters between the two methods for all data points in each of the four metropolitan areas. We also quantified the descriptions of the geocoding accuracy provided by Batchgeo with the match scores from ArcGIS. We found a 94% match rate (n = 705), 2% (n = 18) were tied and 3% (n = 25) were unmatched using ArcGIS. Forty-eight addresses (6.4%) were not matched in ArcGIS with a match score ≥80 (therefore only 700 addresses were included in our positional difference analysis). Six hundred thirteen (87.6%) of these addresses had a match score of 100. Batchgeo yielded a 100% match rate for the addresses that ArcGIS geocoded. The median for longitude and latitude coordinates for all the data was just over 25 m. Overall, the range for longitude was 0.04-12,911.8 m, and the range for latitude was 0.02-37,766.6 m. Comparisons show minimal differences in the median and minimum values, while there were slightly larger differences in the maximum values. The majority (>75%) of the geographic differences were within 50 m of each other; mostly <25 m from each other (about 49%). Only about 4% overall were ≥400 m apart. We also found geographic differences in the proportion of addresses that fell within certain meter ranges. The match-score range associated with the Batchgeo accuracy level "approximate" (least accurate) was 84-100 (mean = 92), while the "rooftop" Batchgeo accuracy level (most accurate) delivered a mean of 98.9 but the range was the same. Although future research should compare the positional difference of Batchgeo to criterion measures of longitude/latitude (e.g. with global positioning system measurement), this study suggests that Batchgeo is a good, free-of-charge option to geocode addresses.


Effects of Tai Chi on exercise capacity and health-related quality of life in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis.
Tai Chi is a traditional Chinese mind-body exercise that has been widely practiced in the People's Republic of China for many centuries. This exercise has also been applied as a training modality in pulmonary rehabilitation programs for stable chronic obstructive pulmonary disease (COPD). This systematic review and meta-analysis aimed to assess the effects of Tai Chi on exercise capacity and health-related quality of life (HRQoL) in COPD patients. Electronic databases (PubMed, Embase, Web of Science, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, ClinicalTrials.gov, China National Knowledge Infrastructure, and China Biology Medicine disc) were searched. Entries published from January 1980 to March 2014 were included in the search. Eligible studies included those that involved randomized controlled trials and those that lasted for at least 12 weeks. The primary outcome measures were six-minute walking distance (6 MWD), St George's Respiratory Questionnaire (SGRQ), and Chronic Respiratory Disease Questionnaire (CRQ). Effect estimates were pooled with random-effects meta-analysis. Eleven articles involving 824 patients met the inclusion criteria. All included articles compared COPD patients in a Tai Chi group versus COPD patients in nonexercise and/or physical exercise groups. The meta-analysis showed that compared with the nonexercise group, the COPD patients practicing Tai Chi demonstrated significantly enhanced 6 MWD (mean difference 35.99, 95% confidence interval [CI] 15.63-56.35, P=0.0005), decreased SGRQ total score (mean difference -10.02, 95% CI -17.59, -2.45, P=0.009), and increased CRQ total score (mean difference 0.95, 95% CI 0.22-1.67, P=0.01). Compared with the physical exercise group, the Tai Chi group showed significantly reduced SGRQ total score (mean difference -3.52, 95% CI -6.07, -0.97, P=0.007), but no statistical significance was found for 6 MWD between the two groups (mean difference 13.65, 95% CI -1.06, 28.37, P=0.07) in COPD patients. Preliminary evidence suggests that Tai Chi has beneficial effects on exercise capacity and HRQoL in COPD patients. This exercise can be recommended as an effective alternative training modality in pulmonary rehabilitation programs. Further studies are required to support the preliminary evidence and to observe the long-term effects of Tai Chi.