Bioterrorism and Emergency Preparedness in Aging (BTEPA): HRSA-funded GEC collaboration for curricula and training.
Frail elders living alone or in long-term care settings are particularly vulnerable to bioterrorism and other emergencies due to their complex physical, social and psychological needs. This paper provides an overview of the recent literature on bioterrorism and emergency preparedness in aging (BTEPA); discusses federal initiatives by the health resources and services administration (HRSA) to address BTEPA; describes the collaborative efforts of six HRSA-funded geriatric education centers (GECS) to develop BTEPA geriatric curricula and training; and offers recommendations for BTEPA education and training, clinical practices, policy, and research. The GEC/BTEPA collaboration has produced model curricula, including emergency planning for diverse groups of older persons; enhanced networking among stakeholders in a fast paced environment of information sharing and changing policies; and developed interdisciplinary educational resources and approaches to address emergency preparedness for various settings in the elder care continuum.


Clinical Evaluation of Humira® Biosimilar ONS-3010 in Healthy Volunteers: Focus on Pharmacokinetics and Pharmacodynamics.
ONS-3010 is being developed by Oncobiologics Inc. (Cranbury, NJ, USA) as a biosimilar of Humira®. This randomized, double blind, single-center phase I study (EudraCT registration # 2013-003551-38) was performed to demonstrate pharmacokinetic (PK) biosimilarity between two reference products (Humira® EU and US) and ONS-3010 in healthy volunteers, and to compare the safety and immunogenicity profiles. In addition, the intended pharmacological activity was assessed and compared by application of a whole blood challenge. Hundred ninety-eight healthy volunteers received a single 40 mg subcutaneous dose of ONS-3010, Humira® EU, or US. The pharmacodynamic effects were assessed by lipopolysaccharide (LPS)/aluminum hydroxide whole blood challenges (n = 36; n = 12 per treatment arm; male:female, 1:1). Equivalence was demonstrated on the PK endpoints (AUC0-inf, Cmax, and AUC0-last) based on bounds of 80-125% for the ratio of the geometric means (ONS-3010/Humira®). The immunogenicity profiles were comparable between treatment groups, and there were no indications for differences in routine safety parameters. Administration of adalimumab resulted in the observation of dramatically reduced tumor necrosis factor-α (TNFα) levels upon stimulation with LPS/aluminum hydroxide (>99%), with no differences between the three treatment groups in terms of magnitude or duration. Adalimumab also resulted in a reduction of LPS/aluminum hydroxide-induced interleukin (IL)-8 release (maximally 30%), suggested to have a causal relationship with the anti-TNFα treatment. LPS/aluminum hydroxide-induced release of IL-1β and IL-6 was not inhibited by anti-TNFα treatment. Taken together, these data are promising for the further clinical development of ONS-3010, demonstrate the relevance of the LPS/aluminum challenge to monitor Humira® effects, and emphasize the value of whole blood challenges for monitoring of proximal drug effects in healthy volunteers, and potentially in the target population.


No association of coffee consumption with gastric ulcer, duodenal ulcer, reflux esophagitis, and non-erosive reflux disease: a cross-sectional study of 8,013 healthy subjects in Japan.
Probably due to caffeine-induced gastric acid secretion, negative effects of coffee upon various upper-gastrointestinal diseases have been precariously accepted, despite the inadequate epidemiological evidence. Our aim is to evaluate the effect of coffee consumption on four major acid-related diseases: gastric ulcer (GU), duodenal ulcer (DU), reflux esophagitis (RE), and non-erosive reflux disease (NERD) based on the large-scale multivariate analysis. Of the 9,517 healthy adults, GU, DU, and RE were diagnosed by endoscopy, and NERD was diagnosed by the symptoms of heartburn and regurgitation without esophageal erosion. Associations between coffee consumption and the four disorders were evaluated, together with age, gender, body mass index (BMI), Helicobacter pylori (HP) infection status, pepsinogen I/II ratio, smoking, and alcohol. We further performed meta-analysis using the random effects model to redefine the relationship between coffee intake and peptic ulcer disease. The eligible 8,013 study subjects comprised of 5,451 coffee drinkers and 2,562 non-coffee drinkers. By univariate analysis, age, BMI, pepsinogen I/II ratio, smoking, and alcohol showed significant associations with coffee consumption. By multiple logistic regression analysis, positively correlated factors with significance were HP infection, current smoking, BMI, and pepsinogen I/II ratio for GU; HP infection, pepsinogen I/II ratio, and current smoking for DU; HP non-infection, male, BMI, pepsinogen I/II ratio, smoking, age, and alcohol for RE; younger age, smoking, and female for NERD. The meta-analyses could detect any association of coffee consumption with neither GU nor DU. In conclusion, there are no significant relationship between coffee consumption and the four major acid-related upper gastrointestinal disorders.


Therapeutic touch in the treatment of carpal tunnel syndrome.
Alternative medical therapies are widely utilized, but there are few objective data to evaluate the effectiveness of these techniques. The purpose of this study was to determine whether one alternative therapy, Therapeutic Touch (TT), can improve objective indices of median nerve function in patients with carpal tunnel syndrome. Participants with electrodiagnostically confirmed carpal tunnel syndrome were randomly assigned in single-blind fashion to receive either TT or sham therapeutic touch once weekly for 6 consecutive weeks. The distal latency of the median motor nerve along with visual analog assessments of pain and relaxation were measured before and after each treatment session. Twenty-one participants completed the study. Changes in median motor nerve distal latencies, pain scores, and relaxation scores did not differ between participants in the TT group and participants in the sham treatment group, either immediately after each treatment session or cumulatively. Immediately after each treatment session, however, there were improvements from baseline among all the outcome variables in both groups. In this small study, TT was no better than placebo in influencing median motor nerve distal latencies, pain scores, and relaxation scores. The changes in the outcome variables from baseline in both groups suggest a possible physiologic basis for the placebo effect.


Health Care's Other "Big Deal": Direct Primary Care Regulation in Contemporary American Health Law.
Direct primary care is a promising, market-based alternative to the fee-for-service payment structure that shapes doctor–patient relationships in America. Instead of billing patients and insurers service by service, direct primary care doctors charge their patients a periodic, prenegotiated fee in exchange for providing a wide range of healthcare services and increased availability compared to traditional practices. This "subscription" model is intended to eliminate the administrative burdens associated with insurer interaction, which, in theory, allows doctors to spend more time with their patients and less time doing paperwork. Direct practices have become increasingly popular since Congress passed the Affordable Care Act (ACA). This growth has been driven by legislation in several states that resolves a number of legal questions that slowed the model's growth and by the ACA's recognition of the model as a permissible way to cover primary care in "approved" health plans. Yet legal scholars have hardly focused on direct primary care. Given the model's growth, however, the time is ripe for a more focused legal inquiry. This Note begins that inquiry. After tracing the model's evolution and its core components, this Note substantively examines the laws in states that regulate direct practices and analyzes how those laws address a number of potential policy concerns. It then analyzes direct primary care's broader role in the contemporary American healthcare marketplace. Based upon that analysis, this Note concludes that direct primary care is a beneficial innovation that harmonizes well with a cooperative-federalism-based healthcare policy model.


Subcortical brain volume differences in participants with attention deficit hyperactivity disorder in children and adults: a cross-sectional mega-analysis.
Neuroimaging studies have shown structural alterations in several brain regions in children and adults with attention deficit hyperactivity disorder (ADHD). Through the formation of the international ENIGMA ADHD Working Group, we aimed to address weaknesses of previous imaging studies and meta-analyses, namely inadequate sample size and methodological heterogeneity. We aimed to investigate whether there are structural differences in children and adults with ADHD compared with those without this diagnosis. In this cross-sectional mega-analysis, we used the data from the international ENIGMA Working Group collaboration, which in the present analysis was frozen at Feb 8, 2015. Individual sites analysed structural T1-weighted MRI brain scans with harmonised protocols of individuals with ADHD compared with those who do not have this diagnosis. Our primary outcome was to assess case-control differences in subcortical structures and intracranial volume through pooling of all individual data from all cohorts in this collaboration. For this analysis, p values were significant at the false discovery rate corrected threshold of p=0·0156. Our sample comprised 1713 participants with ADHD and 1529 controls from 23 sites with a median age of 14 years (range 4-63 years). The volumes of the accumbens (Cohen's d=-0·15), amygdala (d=-0·19), caudate (d=-0·11), hippocampus (d=-0·11), putamen (d=-0·14), and intracranial volume (d=-0·10) were smaller in individuals with ADHD compared with controls in the mega-analysis. There was no difference in volume size in the pallidum (p=0·95) and thalamus (p=0·39) between people with ADHD and controls. Exploratory lifespan modelling suggested a delay of maturation and a delay of degeneration, as effect sizes were highest in most subgroups of children (<15 years) versus adults (>21 years): in the accumbens (Cohen's d=-0·19 vs -0·10), amygdala (d=-0·18 vs -0·14), caudate (d=-0·13 vs -0·07), hippocampus (d=-0·12 vs -0·06), putamen (d=-0·18 vs -0·08), and intracranial volume (d=-0·14 vs 0·01). There was no difference between children and adults for the pallidum (p=0·79) or thalamus (p=0·89). Case-control differences in adults were non-significant (all p>0·03). Psychostimulant medication use (all p>0·15) or symptom scores (all p>0·02) did not influence results, nor did the presence of comorbid psychiatric disorders (all p>0·5). With the largest dataset to date, we add new knowledge about bilateral amygdala, accumbens, and hippocampus reductions in ADHD. We extend the brain maturation delay theory for ADHD to include subcortical structures and refute medication effects on brain volume suggested by earlier meta-analyses. Lifespan analyses suggest that, in the absence of well powered longitudinal studies, the ENIGMA cross-sectional sample across six decades of ages provides a means to generate hypotheses about lifespan trajectories in brain phenotypes. National Institutes of Health.


Alternative Oxidase Capacity of Mitochondria in Microsporophylls May Function in Cycad Thermogenesis.
Cone thermogenesis is a widespread phenomenon in cycads and may function to promote volatile emissions that affect pollinator behavior. Given their large population size and intense and durable heat-producing effects, cycads are important organisms for comprehensive studies of plant thermogenesis. However, knowledge of mitochondrial morphology and function in cone thermogenesis is limited. Therefore, we investigated these mitochondrial properties in the thermogenic cycad species Cycas revoluta Male cones generated heat even in cool weather conditions. Female cones produced heat, but to a lesser extent than male cones. Ultrastructural analyses of the two major tissues of male cones, microsporophylls and microsporangia, revealed the existence of a population of mitochondria with a distinct morphology in the microsporophylls. In these cells, we observed large mitochondria (cross-sectional area of 2 μm2 or more) with a uniform matrix density that occupied >10% of the total mitochondrial volume. Despite the size difference, many nonlarge mitochondria (cross-sectional area <2 μm2) also exhibited a shape and a matrix density similar to those of large mitochondria. Alternative oxidase (AOX) capacity and expression levels in microsporophylls were much higher than those in microsporangia. The AOX genes expressed in male cones revealed two different AOX complementary DNA sequences: CrAOX1 and CrAOX2 The expression level of CrAOX1 mRNA in the microsporophylls was 100 times greater than that of CrAOX2 mRNA. Collectively, these results suggest that distinctive mitochondrial morphology and CrAOX1-mediated respiration in microsporophylls might play a role in cycad cone thermogenesis.


Metal concentrations in coastal sharks from The Bahamas with a focus on the Caribbean Reef shark.
Over the last century anthropogenic activities have rapidly increased the influx of metals and metalloids entering the marine environment, which can bioaccumulate and biomagnify in marine top consumers. This may elicit sublethal effects on target organisms, having broad implications for human seafood consumers. We provide the first assessment of metal (Cd, Pb, Cr, Mn, Co, Cu, Zn, As, Ag, and THg) and metalloid (As) concentrations in the muscle tissue of coastal sharks from The Bahamas. A total of 36 individual sharks from six species were evaluated, spanning two regions/study areas, with a focus on the Caribbean reef shark (Carcharhinus perezi), and to a lesser extent the tiger shark (Galeocerdo cuvier). This is due their high relative abundance and ecological significance throughout coastal Bahamian and regional ecosystems. Caribbean reef sharks exhibited some of the highest metal concentrations compared to five other species, and peaks in the concentrations of Pb, Cr, Cu were observed as individuals reached sexual maturity. Observations were attributed to foraging on larger, more piscivorous prey, high longevity, as well a potential slowing rate of growth. We observed correlations between some metals, which are challenging to interpret but may be attributed to trophic level and ambient metal conditions. Our results provide the first account of metal concentrations in Bahamian sharks, suggesting individuals exhibit high concentrations which may potentially cause sublethal effects. Finally, these findings underscore the potential toxicity of shark meat and have significant implications for human consumers.


Mahayograj guggulu: Heavy metal estimation and safety studies.
This study was conducted to estimate the heavy metal profile and determine the safety of Mahayograj guggulu, an Ayurvedic herbo-mineral preparation. Mahayograj guggulu, manufactured by Shree Baidynath Ayurved Bhawan Pvt. Ltd., Gwalior Road, Jhansi - 284 003 (of batch number-07 and manufacturing date October 2004) was procured from the local market. Heavy metal concentrations were measured using an atomic absorption spectrophotometer. A total of 40 Charles Foster strain albino rats of either sex with an average body weight of 160-250 g were divided into four groups (Groups I, II, III and IV), with 10 animals in each group. Group I served as the control, while Group II, III and IV rats received Mahayograj guggulu at a dose of 54 (dose equivalent to human therapeutic dose), 270 (five-times the dose equivalent to the human therapeutic dose) and 540 (10-times the dose equivalent to human therapeutic dose) mg/kg, p.o. for 120 days. The effect of drug administration was noted on the ponderal, biochemical, hematological and histopathological parameters. In addition, urine examination was also carried out. At the end of the study, only six rats per group were sacrificed as per the IAEC advice. Mahayograj guggulu was found to be safe at all dose levels tested. No significant behavioral changes were noted in any of the groups studied. The effect on food and water consumption and fecal and urine output remained unaffected in all groups during the study period. No major alterations were observed in hematology, serum biochemistry, necropsy and histopathology at the therapeutically advocated dose level. Heavy metal content measurement indicated levels of 25.8 µg/g for lead, 0.07 µg/g for mercury and 5.19 µg/g for arsenic. The test drug is well tolerated as no changes of a serious nature could be observed in any of the parameters assessed.


Controversies in the management of paratesticular rhabdomyosarcoma: is staging retroperitoneal lymph node dissection necessary for adolescents with resected paratesticular rhabdomyosarcoma?
Use of retroperitoneal lymph node dissection (RPLND) in paratesticular rhabdomyosarcoma (PTRMS) is controversial and has changed over the past 2 decades. The Intergroup Rhabdomyosarcoma Study Group (IRSG) required ipsilateral RPLND (IRPLND) for all patients with PTRMS treated on IRS-III (1984-91), but changed to clinical evaluation of RPLNs using computerized tomography (CT) in IRS-IV (1991 through 1997). In IRS-IV, only those patients with identified lymph node involvement on CT required surgical evaluation of the RPLNs. Nodal radiation therapy was administered only to patients with RPLNs recognized as positive; such patients received more intensive chemotherapy as well. Thus, they compared the incidence of recognized RPLN involvement using these 2 different approaches. They then analyzed patient outcome to determine whether this change in management affected outcome. Eligible patients with group I or II PTRMS who were treated on IRS III (n = 100) or IRS IV (n = 134) were analyzed. Failure-free survival (FFS) and survival (S) rates were estimated using the Kaplan-Meier method and compared using the log-rank test. There was a significant change in the distribution of patients with group I versus II tumors from IRS-III to IRS-IV (group I, 68% in IRS-III versus 82% in IRS-IV). This was the result of decreased node recognition when CT was used to stage RPLNs in IRS-IV and was most notable for adolescents (>10 years of age). Overall, 3-year FFS was 92% for patients treated on IRS-III and 86% for those treated on IRS-IV (P =.10), whereas survival estimates were 96% and 92%, respectively (P =.30). Adolescents were at higher risk of RPLN relapse than were children (<10 years of age) and their FFS and survival were worse, regardless of IRS protocol. Furthermore, adolescents with recognized group II tumors experienced better 3-year FFS than those with group I tumors on IRS-IV (100% versus 68%, P =.06), most likely as a result of receiving radiotherapy and intensified chemotherapy. Use of only CT scan evaluation of RPLN in IRS-IV led to a decrease in identification of RPLN involvement in boys who present with localized PTRMS, and a higher rate of regional relapse as compared with IRS-III. Adolescents had much higher likelihood of RPLN disease, and they fared significantly worse than did younger children on both studies. Furthermore, adolescent boys with group I tumors experienced worse FFS than those with Group II tumors on IRS-IV, probably because some patients with group II tumors were not identified by CT imaging and thus received less effective therapy. These data suggest that adolescents should have ipsilateral RPLN dissection as part of their routine staging, and those with positive lymph nodes require intensified chemotherapy as well as nodal irradiation.


Optical tolerances and electric fields in resonant reflectors.
The importance of flatness, parallelism, and equality in thickness of the elements and spacers of a resonant reflector is discussed. Using the matrix method, the reflectivity vs wavelength is computed for several types of resonators, the thicknesses of whose elements were subject to variations. For a two-element device, the exact mechanical thickness of the spacer is not important, but the equality of thickness of the dielectric elements is critical. For a three- or four-element device, the exact thickness of the center element is least important to reflectivity, but the reflectivity decreases if the total error in orders on either side of the center approaches (1/2). The results indicate that it is extremely difficult to produce a practical device of this complexity. Pressure and temperature scanning is discussed. Experimental results were obtained for two-element devices showing the importance in equality of thickness and the sensitivity to nonparallelism of the spacer. The relative electric field strengths within the reflector were mapped to investigate susceptibility to radiation damage. The amplitude of the field and the position in the resonator where damage would first occur depends upon the reflectivity at the wavelength used.


Concussion Clinical Profiles Screening (CP Screen) Tool: Preliminary Evidence to Inform a Multidisciplinary Approach.
Current concussion symptom inventories emphasize total number or symptoms and severity and overlap with other conditions, such as mental health disorders, which may limit their specificity and clinical utility. To develop and test the reliability and validity of a new Concussion Clinical Profiles Screening tool (CP Screen) in both healthy controls and concussed. CP Screen is a 29-item self-report, clinical profile-based symptom inventory that measures the following 5 concussion clinical profiles: 1) anxiety/mood, 2) cognitive/fatigue, 3) migraine, 4) ocular, and 5) vestibular; and the following 2 modifying factors: 1) sleep and 2) neck. Post-Concussion Symptom Scale (PCSS), vestibular/ocular motor screening (VOMS) tool, and Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT) were conducted. CP Screen was administered in community a concussion surveillance program and 2 sports medicine concussion clinics. Responses include 248 athletes, 121 concussed, and 127 controls, enrolled between 2018 and 2019. Internal consistency of the CP Screen in the control (Cronbach's alpha = .87) and concussed (Cronbach's alpha = .93) samples was high. Moderate to high correlations among the CP Screen factors and PCSS factors and VOMS items, supporting concurrent validity. ROC curve analysis for identifying concussed from controls was significant (P < .001) for all CP Screen factor and modifier scores with excellent AUCs for migraine (.93), ocular (.88), vestibular (.85), and cognitive (.81) factors, demonstrating predictive validity. The CP Screen demonstrated strong reliability, concurrent validity with commonly used concussion assessment (ie, PCSS, VOMS, and ImPACT), and predictive validity for identifying concussion. The CP Screen extends current symptom inventories by evaluating more specific symptoms that may reflect clinical profiles and inform better clinical care.


New radiographic programs for transverse conventional tomograms in the dentomaxillofacial region.
Using only 7 programs, Orthophos Plus permits transverse conventional tomograms of all maxillomandibular regions. The precision of the magnification factors of these programs is very high. Factors influencing the image quality of the 7 programs were assessed. Image quality depends on technical precision and on correct patient positioning, i.e., jaw axis alignment to the direction of projection. This procedure with 7 programs is more demanding than the procedure for x-ray units that use many programs for the different projections. Especially for implantology, it is important that the patient's jaw be positioned in accordance with the projection to avoid oblique cuts and incorrect information about the jaw dimensions. The correct region is best selected by positioning a cast in the positioning aids prior to exposure and using the same setting for the patient's exposures. For correct implant planning, it is helpful to digitize the tomograms with Friacom so that, despite different magnification factors of the programs, the correct implant dimensions are determined. If these suggestions are followed, use of these programs in dental practice can be recommended.


New molecular tools for the identification of 2 endangered smooth-hound sharks, Mustelus mustelus and Mustelus punctulatus.
The smooth-hounds represent a significant proportion of the elasmobranch catch in the Adriatic basin of the Mediterranean Sea, where the common (Mustelus mustelus) and blackspotted (Mustelus punctulatus) smooth-hounds co-occur. The 2 species share several morphological and morphometric characters that lead to frequent misidentification. In order to provide information useful for their species identification, we performed a morphological identification of several Mustelus specimens to select individuals unambiguously attributed to 1 of the 2 species, and assayed these with 3 new molecular tests. First, we developed and validated a mitochondrial DNA assay based on species-specific amplification of the cytochrome c oxidase subunit 1 (COI). Second, a fragment analysis of 15 microsatellites cross-amplified from several triakid species was performed to identify diagnostic loci. Finally, a length difference was identified in the internal transcribed spacer 2 (ITS2) region and a diagnostic test based on its amplification was established. All the samples classified morphologically as M. mustelus and M. punctulatus showed a species-specific profile using all the 3 molecular tests. In addition, cross-amplification of microsatellites allowed identification of 9 highly polymorphic loci that will be useful for the study of the mating system and population differentiation of the 2 species.


The induction, desensitization and de-induction of tyrosine aminotransferase by 8-bromo-cyclic AMP in rat hepatoma cells.
Addition of 1-3 mM-8-bromo-cyclic AMP to monolayer cultures of H-4 rat hepatoma cells resulted in a rapid but short-lived increase in tyrosine aminotransferase (EC 126.96.36.199) activity. The transient nature of this induction is due to desensitization to 8-bromo-cyclic AMP. Throughout this time course of induction and desensitization, removal of 8-bromo-cyclic AMP resulted in a rapid and significant decrease in tyrosine aminotransferase activity, a process referred to as 'de-induction' in this study. We showed that the changes in tyrosine aminotransferase activity in its induction, desensitization and de-induction by 8-bromo-cyclic AMP were directly attributable to changes in the synthesis rate of the protein, and the amount of translatable and hybridizable mRNA encoding for tyrosine aminotransferase (mRNATAT). We further showed that this desensitization was specific to cyclic AMP. First, only active analogues of cyclic AMP and agents which increased cellular concentrations of cyclic AMP elicited this desensitization. Second, the desensitized cells were refractory only to the effects of 8-bromo-cyclic AMP; dexamethasone and insulin induced the tyrosine aminotransferase activity in the 8-bromo-cyclic AMP-desensitized cells in a manner similar to that of the controls. Studies on the metabolism of 8-bromo-cyclic AMP suggest that neither its degradation nor the accumulation of its primary metabolite, 8-bromoadenosine, played a significant role in modulating the expression of tyrosine aminotransferase during the time course of action of 8-bromo-cyclic AMP. These results provide evidence for a specific pretranslational mode of action of cyclic AMP in the control of tyrosine aminotransferase expression in its desensitization and de-induction, in addition to the early phase of induction.


[Quantitative imaging in nephrology: limits and potentials of elastosonography].
Chronic kidney disease is characterized by increasingly amplified fibrotic processes regardless of etiology. The severity of renal fibrosis seems to correlate with an increased risk of end-stage renal disease; therefore, monitoring of renal fibrosis over time may play an important role in the follow-up of both focal and diffuse renal diseases and in evaluating the response to treatments. Renal biopsy is the only method capable of providing objective and comparable information on the extent of fibrosis, but it is not suitable for outpatient monitoring of chronic kidney disease due to its invasiveness. Elastosonography is an innovative and non-invasive ultrasound method that allows the measurement of tissue elasticity through the transmission of mechanical waves and the measurement of their propagation speed. Although some authors have demonstrated the usefulness of elastosonographic techniques for the quantification of liver fibrosis, few studies have investigated the applications of elastosonography in renal pathology. Furthermore, the depth of native kidneys, the high anisotropy of the renal tissue, and the possibility of examining only a small region of interest currently limit its spread in clinical practice. The aim of this review is to examine the physical principles of elastosonography and to review the latest evidence about the possible applications of the ARFI (acoustic radiation force impulse) technique in the study of kidney diseases.


Activity, climate, and postcranial robusticity: implications for modern human origins and scenarios of adaptive change.
Postcranial robusticity--the massiveness of the skeleton--figures prominently in the debate over the origin of modern humans. Anthropologists use postcranial robusticity to infer the activity levels of prehistoric populations, and changes in robusticity are often used to support scenarios of adaptive change. These scenarios explain differences in morphology as the result of a change in lifestyle (habitual activity). One common scenario posits that early modern humans were more gracile than Neandertals because the modern humans' complex culture required less physical exertion. However, lifestyle is only one of many influences on morphology. Climate has clear correlations with physique and skeletal proportions. Analysis of recent humans that differ in terms of lifestyle and climatic adaptations reveals that limb bone robusticity varies with climate as much as or more than with lifestyle. Many of the differences in robusticity between Neandertals and early modern humans appear to be related to climatic adaptations. The results support the single-recent origin model of modern human origins. The differences in robusticity between Neandertals and early modern humans suggest that population replacement rather than local evolution best explains the emergence of modern humans in Europe. Both climatic adaptations (primarily body proportions) and lifestyle should be considered in analyses of robusticity.


Changes in male reproductive health and effects of endocrine disruptors in Scandinavian countries.
Male reproductive health has deteriorated in many ways during the last decades. The incidence of testicular cancer has rapidly increased in Europe and European-derived populations. Sperm concentrations have declined and sperm motility and morphology have worsened in many areas. Both adverse trends have been shown to be associated with year of birth. Older birth cohorts have better reproductive health than the younger generations. Incidences of cryptorchidism and hypospadias have also increased according to several studies. The reasons for secular trends are unknown, but the rapid pace of the change points to environmental causes. Endocrine disrupting chemicals have been hypothesized to influence male reproductive health.


Accelerated evolutionary rate of housekeeping genes in tunicates.
Phylogenomics has recently revealed that tunicates represent the sister-group of vertebrates in the newly defined clade Olfactores. However, phylogenomic and comparative genomic studies have also suggested that tunicates are characterized by an elevated rate of molecular evolution and a high degree of genomic divergence. Despite the recurrent interest in the group, the picture of tunicate peculiar evolutionary dynamics is still fragmentary, as it mainly lies in studies focusing on only a few model species. In order to expand the available genomic data for the group, we used the high-throughput 454 technology to sequence the partial transcriptome of a previously unsampled tunicate, Microcosmus squamiger. This allowed us to get further insights into tunicate-accelerated evolution through a comparative analysis based on pertinent phylogenetic markers, i.e., a core of 35 housekeeping genes conserved across bilaterians. Our results showed that tunicates evolved on average about two times faster than the other chordates, yet the degree of this acceleration varied extensively upon genes and upon lineages. Appendicularia and Aplousobranchia were detected as the most divergent groups which were also characterized by highly heterogeneous substitution rates across genes. Finally, an estimation of the d (N)/d (S) ratio in three pairs of closely related taxa within Olfactores did not reveal strong differences between the tunicate and vertebrate lineages suggesting that for this set of housekeeping genes, the accelerated evolution of tunicates is plausibly due to an elevated mutation rate rather than to particular selective effects.


Quadruplex DNA-guided ligand selection from dynamic combinatorial libraries of acylhydrazones.
Dynamic combinatorial libraries of acylhydrazones were prepared from diacylhydrazides and several cationic or neutral aldehydes in the presence of 5-methoxyanthranilic acid catalyst. Pull-down experiments with magnetic beads functionalized with a G-quadruplex (G4)-forming oligonucleotide led to the identification of putative ligands, which were resynthesized or emulated by close structural analogues. G4-binding properties of novel derivatives were assessed by fluorimetric titrations, mass spectrometry and thermal denaturation experiments, giving evidence of strong binding (Kd < 10 nM) for two compounds.


Development and Validation of a Diabetic Retinopathy Risk Stratification Algorithm.
Although diabetic retinopathy is a leading cause of blindness worldwide, diabetes-related blindness can be prevented through effective screening, detection, and treatment of disease. The study goal was to develop risk stratification algorithms for the onset of retinal complications of diabetes, including proliferative diabetic retinopathy, referable retinopathy, and macular edema. Retrospective cohort analysis of patients from the Kaiser Permanente Northern California Diabetes Registry who had no evidence of diabetic retinopathy at a baseline diabetic retinopathy screening during 2008-2020 was performed. Machine learning and logistic regression prediction models for onset of proliferative diabetic retinopathy, diabetic macular edema, and referable retinopathy detected through routine screening were trained and internally validated. Model performance was assessed using area under the curve (AUC) metrics. The study cohort (N = 276,794) was 51.9% male and 42.1% White. Mean (±SD) age at baseline was 60.0 (±13.1) years. A machine learning XGBoost algorithm was effective in identifying patients who developed proliferative diabetic retinopathy (AUC 0.86; 95% CI, 0.86-0.87), diabetic macular edema (AUC 0.76; 95% CI, 0.75-0.77), and referable retinopathy (AUC 0.78; 95% CI, 0.78-0.79). Similar results were found using a simpler nine-covariate logistic regression model: proliferative diabetic retinopathy (AUC 0.82; 95% CI, 0.80-0.83), diabetic macular edema (AUC 0.73; 95% CI, 0.72-0.74), and referable retinopathy (AUC 0.75; 95% CI, 0.75-0.76). Relatively simple logistic regression models using nine readily available clinical variables can be used to rank order patients for onset of diabetic eye disease and thereby more efficiently prioritize and target screening for at risk patients.


The dilemma of aspirin resistance in obese patients.
Aspirin resistance (AR) commonly refers to the concept of reduced aspirin efficacy in preventing cardiovascular disease and platelet inhibition. Obesity increases the risk of heart disease three- to four-fold and has been associated with AR. Aspirin is used as a tool for both primary and secondary prevention, but recent studies suggest that its lack of efficacy for primary prevention is partly attributable to obesity. Several mechanisms have been described that contribute to AR in obese patients using pharmacokinetics and pharmacodynamics. AR may be attenuated through weight loss, alternative dosing regimens, and different drug formulations. With the global rise of obesity, it is imperative to find preventive therapies that adequately address atherosclerotic cardiovascular disease (ASCVD) risk in this population.


Allele coding in genomic evaluation.
Genomic data are used in animal breeding to assist genetic evaluation. Several models to estimate genomic breeding values have been studied. In general, two approaches have been used. One approach estimates the marker effects first and then, genomic breeding values are obtained by summing marker effects. In the second approach, genomic breeding values are estimated directly using an equivalent model with a genomic relationship matrix. Allele coding is the method chosen to assign values to the regression coefficients in the statistical model. A common allele coding is zero for the homozygous genotype of the first allele, one for the heterozygote, and two for the homozygous genotype for the other allele. Another common allele coding changes these regression coefficients by subtracting a value from each marker such that the mean of regression coefficients is zero within each marker. We call this centered allele coding. This study considered effects of different allele coding methods on inference. Both marker-based and equivalent models were considered, and restricted maximum likelihood and Bayesian methods were used in inference. Theoretical derivations showed that parameter estimates and estimated marker effects in marker-based models are the same irrespective of the allele coding, provided that the model has a fixed general mean. For the equivalent models, the same results hold, even though different allele coding methods lead to different genomic relationship matrices. Calculated genomic breeding values are independent of allele coding when the estimate of the general mean is included into the values. Reliabilities of estimated genomic breeding values calculated using elements of the inverse of the coefficient matrix depend on the allele coding because different allele coding methods imply different models. Finally, allele coding affects the mixing of Markov chain Monte Carlo algorithms, with the centered coding being the best. Different allele coding methods lead to the same inference in the marker-based and equivalent models when a fixed general mean is included in the model. However, reliabilities of genomic breeding values are affected by the allele coding method used. The centered coding has some numerical advantages when Markov chain Monte Carlo methods are used.


Mean systolic and diastolic blood pressure in adults aged 18 and over in the United States, 2001-2008.
This report presents estimates for the period 2001-2008 of means and selected percentiles of systolic and diastolic blood pressure by sex, race or ethnicity, age, and hypertension status in adults aged 18 and over. Demographic characteristics were collected during a personal interview, and blood pressures were measured during a physician examination. All estimates were calculated using the mean of up to three measurements. The final analytic sample consisted of 19,921 adults aged 18 and over with complete data. Examined sample weights and sample design variables were used to calculate nationally representative estimates and standard error estimates that account for the complex design, using SAS and SUDAAN statistical software. Mean systolic blood pressure was 122 mm Hg for all adults aged 18 and over; it was 116 mm Hg for normotensive adults, 130 mm Hg for treated hypertensive adults, and 146 mm Hg for untreated hypertensive adults. Mean diastolic blood pressure was 71 mm Hg for all adults 18 and over; it was 69 mm Hg for normotensive adults, 75 mm Hg for treated hypertensive adults, and 85 mm Hg for untreated hypertensive adults. There was a trend of increasing systolic blood pressure with increasing age. A more curvilinear trend was seen in diastolic blood pressure, with increasing then decreasing means with age in both men and women. Men had higher mean systolic and diastolic pressures than women. There were some differences in mean blood pressure by race or ethnicity, with non-Hispanic black adults having higher mean systolic and diastolic blood pressures than non-Hispanic white and Mexican-American adults, but these differences were not consistent after stratification by hypertension status and sex. These estimates of the distribution of blood pressure may be useful for policy makers who are considering ways to achieve a downward shift in the population distribution of blood pressure with the goal of reducing morbidity and mortality related to hypertension.


Nfib Regulates Transcriptional Networks That Control the Development of Prostatic Hyperplasia.
A functional complex consisting of androgen receptor (AR) and forkhead box A1 (FOXA1) proteins supports prostatic development, differentiation, and disease. In addition, the interaction of FOXA1 with cofactors such as nuclear factor I (NFI) family members modulates AR target gene expression. However, the global role of specific NFI family members has yet to be described in the prostate. In these studies, chromatin immunoprecipitation followed by DNA sequencing in androgen-dependent LNCaP prostate cancer cells demonstrated that 64.3% of NFIB binding sites are associated with AR and FOXA1 binding sites. Interrogation of published data revealed that genes associated with NFIB binding sites are predominantly induced after dihydrotestosterone treatment of LNCaP cells, whereas NFIB knockdown studies demonstrated that loss of NFIB drives increased AR expression and superinduction of a subset of AR target genes. Notably, genes bound by NFIB only are associated with cell division and cell cycle. To define the role of NFIB in vivo, mouse Nfib knockout prostatic tissue was rescued via renal capsule engraftment. Loss of Nfib expression resulted in prostatic hyperplasia, which did not resolve in response to castration, and an expansion of an intermediate cell population in a small subset of grafts. In human benign prostatic hyperplasia, luminal NFIB loss correlated with more severe disease. Finally, some areas of intermediate cell expansion were also associated with NFIB loss. Taken together, these results show a fundamental role for NFIB as a coregulator of AR action in the prostate and in controlling prostatic hyperplasia.


Bayesian approach to determining penetrance of pathogenic SDH variants.
Until recently, determining penetrance required large observational cohort studies. Data from the Exome Aggregate Consortium (ExAC) allows a Bayesian approach to calculate penetrance, in that population frequencies of pathogenic germline variants should be inversely proportional to their penetrance for disease. We tested this hypothesis using data from two cohorts for succinate dehydrogenase subunits A, B and C (SDHA-C) genetic variants associated with hereditary pheochromocytoma/paraganglioma (PC/PGL). Two cohorts were 575 unrelated Australian subjects and 1240 unrelated UK subjects, respectively, with PC/PGL in whom genetic testing had been performed. Penetrance of pathogenic SDHA-C variants was calculated by comparing allelic frequencies in cases versus controls from ExAC (removing those variants contributed by The Cancer Genome Atlas). Pathogenic SDHA-C variants were identified in 106 subjects (18.4%) in cohort 1 and 317 subjects (25.6%) in cohort 2. Of 94 different pathogenic variants from both cohorts (seven in SDHA, 75 in SDHB and 12 in SDHC), 13 are reported in ExAC (two in SDHA, nine in SDHB and two in SDHC) accounting for 21% of subjects with SDHA-C variants. Combining data from both cohorts, estimated lifetime disease penetrance was 22.0% (95% CI 15.2% to 30.9%) for SDHB variants, 8.3% (95% CI 3.5% to 18.5%) for SDHC variants and 1.7% (95% CI 0.8% to 3.8%) for SDHA variants. Pathogenic variants in SDHB are more penetrant than those in SDHC and SDHA. Our findings have important implications for counselling and surveillance of subjects carrying these pathogenic variants.


Interaction between Streptococcus suis serotype 2 and porcine reproductive and respiratory syndrome virus in specific pathogen-free piglets.
Secondary specific pathogen-free (sSPF) piglets were inoculated intranasally with Streptococcus suis serotype 2 alone, porcine reproductive and respiratory syndrome virus (PRRSV) alone, or with PRRSV followed by S suis. Uninfected piglets were used as controls. Pigs inoculated with PRRSV (ATCC VR-2332) followed by challenge with a virulent strain (87555) of S suis serotype 2 developed clinical signs, suppurative meningitis and large numbers of S suis in their tissues, including the brain and meninges. Pigs inoculated with PRRSV alone, S suis (87555) alone, or with PRRSV and the DH5 strain of S suis serotype 2 (lacking a protein associated with virulence) and the uninfected piglets did not develop clinical signs or lesions or have large numbers of bacteria in their tissues. The results suggest that PRRSV predisposes sSPF pigs to infection and disease caused by virulent S suis serotype 2. Co-infection of piglets with PRRSV and a virulent strain of S suis may provide a useful model for the study of S suis septicaemia and meningitis.


Evaluating follow-up and complexity in cancer clinical trials (EFACCT): an eDelphi study of research professionals' perspectives.
To evaluate patient follow-up and complexity in cancer clinical trial delivery, using consensus methods to: (1) identify research professionals' priorities, (2) understand localised challenges, (3) define study complexity and workloads supporting the development of a trial rating and complexity assessment tool (TRACAT). A classic eDelphi completed in three rounds, conducted as the launch study to a multiphase national project (evaluating follow-up and complexity in cancer clinical trials). Multicentre online survey involving professionals at National Health Service secondary care hospital sites in Scotland and England varied in scale, geographical location and patient populations. Principal investigators at 13 hospitals across nine clinical research networks recruited 33 participants using pre-defined eligibility criteria to form a multidisciplinary panel. Statements achieving a consensus level of 70% on a 7-point Likert-type scale and ranked trial rating indicators (TRIs) developed by research professionals. The panel developed 75 consensus statements illustrating factors contributing to complexity, follow-up intensity and operational performance in trial delivery, and specified 14 ranked TRIs. Seven open questions in the first qualitative round generated 531 individual statements. Iterative survey rounds returned rates of 82%, 82% and 93%. Clinical trials operate within a dynamic, complex healthcare and innovation system where rapid scientific advances present opportunities and challenges for delivery organisations and professionals. Panellists highlighted cultural and organisational factors limiting the profession's potential to support growing trial complexity and patient follow-up. Enhanced communication, interoperability, funding and capacity have emerged as key priorities. Future operational models should test dialectic Singerian-based approaches respecting open dialogue and shared values. Research capacity building should prioritise innovative, collaborative approaches embedding validated review and evaluation models to understand changing operational needs and challenges. TRACAT provides a mechanism for continual knowledge assimilation to improve decision-making.


A novel supermatrix approach improves resolution of phylogenetic relationships in a comprehensive sample of danthonioid grasses.
Phylogeny reconstruction is challenging when branch lengths vary and when different genetic loci show conflicting signals. The number of DNA sequence characters required to obtain robust support for all the nodes in a phylogeny becomes greater with denser taxon sampling. We test the usefulness of an approach mixing densely sampled, variable non-coding sequences (trnL-F; rpl16; atpB-rbcL; ITS) with sparsely sampled, more conservative protein coding and ribosomal sequences (matK; ndhF; rbcL; 26S), for the grass subfamily Danthonioideae. Previous phylogenetic studies of Danthonioideae revealed extensive generic paraphyly, but were often impeded by insufficient character and taxon sampling and apparent inter-gene conflict. Our variably-sampled supermatrix approach allowed us to represent 79% of the species with up to c. 9900 base pairs for taxa representing the major clades. A 'taxon duplication' approach for taxa with conflicting phylogenetic signals allowed us to combine the data whilst representing the differences between chloroplast and nuclear encoded gene trees. This approach efficiently improves resolution and support whilst maximising representation of taxa and their sometimes composite evolutionary histories, resulting in a phylogeny of the Danthonioideae that will be useful both for a wide range of evolutionary studies and to inform forthcoming realignment of generic delimitations in the subfamily.


Scientific Utopia: II. Restructuring Incentives and Practices to Promote Truth Over Publishability.
An academic scientist's professional success depends on publishing. Publishing norms emphasize novel, positive results. As such, disciplinary incentives encourage design, analysis, and reporting decisions that elicit positive results and ignore negative results. Prior reports demonstrate how these incentives inflate the rate of false effects in published science. When incentives favor novelty over replication, false results persist in the literature unchallenged, reducing efficiency in knowledge accumulation. Previous suggestions to address this problem are unlikely to be effective. For example, a journal of negative results publishes otherwise unpublishable reports. This enshrines the low status of the journal and its content. The persistence of false findings can be meliorated with strategies that make the fundamental but abstract accuracy motive-getting it right-competitive with the more tangible and concrete incentive-getting it published. This article develops strategies for improving scientific practices and knowledge accumulation that account for ordinary human motivations and biases.


An essential developmental function for murine phosphoglycolate phosphatase in safeguarding cell proliferation.
Mammalian phosphoglycolate phosphatase (PGP) is thought to target phosphoglycolate, a 2-deoxyribose fragment derived from the repair of oxidative DNA lesions. However, the physiological role of this activity and the biological function of the DNA damage product phosphoglycolate is unknown. We now show that knockin replacement of murine Pgp with its phosphatase-inactive PgpD34N mutant is embryonically lethal due to intrauterine growth arrest and developmental delay in midgestation. PGP inactivation attenuated triosephosphate isomerase activity, increased triglyceride levels at the expense of the cellular phosphatidylcholine content, and inhibited cell proliferation. These effects were prevented under hypoxic conditions or by blocking phosphoglycolate release from damaged DNA. Thus, PGP is essential to sustain cell proliferation in the presence of oxygen. Collectively, our findings reveal a previously unknown mechanism coupling a DNA damage repair product to the control of intermediary metabolism and cell proliferation.


Profiling of the three circulating monocyte subpopulations in human obesity.
Three subpopulations of circulating monocytes have been described: CD14(2+)CD16(-) (classical monocytes [CM]), CD14(2+)CD16(+) (intermediate monocytes [IM]), and CD14(+)CD16(2+) (nonclassical monocytes [NCM]). We previously showed that obesity is associated with an increased proportion of IM and NCM. Our objective is to decipher the migratory and inflammatory functions of each monocyte subset in obesity-related low-grade inflammation. Twenty-six healthy, normal-weight and nondiabetic volunteers (C) and 40 obese nondiabetic (Ob) individuals were included in this study. We explored the gene expression profile of 18 inflammatory genes in each subset of C and Ob subjects and measured protein expression of the upregulated genes. We then tested their functional response to TLR signaling in both groups. We showed an increased expression of CX3CR1 in all monocyte subpopulations and of CCR2 and CCR5 in CM and IM in the Ob group. We found negative correlation between CCR2 and CX3CR1 expressions and high-density lipoprotein-cholesterol, whereas CCR5 expression was positively linked to obesity-related metabolic traits. Production of inflammatory proteins upon bacterial LPS and viral ssRNA stimulation was higher in CM and NCM of the Ob group compared with the C group. Our work highlights an enhanced inflammatory phenotype of monocytes with a higher response to TLR4 and TLR8 stimulations in obesity. Moreover, it suggests an increased migration capacity of CM and IM subpopulations.


Resistance rates to commonly used antimicrobials among pathogens of both bacteremic and non-bacteremic community-acquired urinary tract infection.
This study examined the distribution of organisms and their antimicrobial resistance in patients admitted due to acute bacteremic and non-bacteremic community-acquired urinary tract infection (UTI). During a period of 1 year and 1 month, a total of 201 patients and 253 bacterial isolates were studied. Fever higher than 38.5 degrees C was significantly more common in the bacteremic group than the non-bacteremic group (68% vs 48%; p<0.05). Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Proteus mirabilis were the most common organisms isolated. E. coli was the leading pathogen and it was significantly more predominant in bacteremic UTI than non-bacteremic UTI (73% vs 49%; p<0.01). Bacteria other than E. coli (i.e., K. pneumoniae, P. aeruginosa, Proteus spp., Morganella morganii, Enterobacter cloacae, Citrobacter spp., Acinetobacter baumannii, Serratia marcescens, and Providencia spp.) were more common in non-bacteremic UTI than bacteremic UTI (44% vs 22%; p<0.01). E. coli isolated from both bacteremic and non-bacteremic patients had a high rate of resistance to ampicillin (80%), cephalothin (59%), gentamicin (29%), piperacillin (61%), trimethoprim-sulfamethoxazole (56%), amoxicillin-clavulanic acid (34%), and ticarcillin-clavulanic acid (36%). Isolates of P. aeruginosa, K. pneumoniae, and Proteus spp. from the non-bacteremic group showed a higher proportion of resistance to extended-spectrum cephalosporins, aminoglycosides (netilmicin and amikacin) and ciprofloxacin. The emergence of a high rate of resistance to commonly used antimicrobials (ampicillin, cephalothin, gentamicin, trimethoprim-sulfamethoxazole, piperacillin, amoxicillin-clavulanic acid and ticarcillin-clavulanic acid) may have an impact on the antibiotic treatment of patients admitted due to acute community-acquired bacteremic or non-bacteremic UTI in Taiwan. Further studies are needed to clarify the impact of antimicrobial resistance on the outcome in these conditions.


Multiple Two-Photon Targeted Whole-Cell Patch-Clamp Recordings From Monosynaptically Connected Neurons in vivo.
Although we know a great deal about monosynaptic connectivity, transmission and integration in the mammalian nervous system from in vitro studies, very little is known in vivo. This is partly because it is technically difficult to evoke action potentials and simultaneously record small amplitude subthreshold responses in closely (<150 μm) located pairs of neurons. To address this, we have developed in vivo two-photon targeted multiple (2-4) whole-cell patch clamp recordings of nearby neurons in superficial cortical layers 1-3. Here, we describe a step-by-step guide to this approach in the anesthetized mouse primary somatosensory cortex, including: the design of the setup, surgery, preparation of pipettes, targeting and acquisition of multiple whole-cell recordings, as well as in vivo and post hoc histology. The procedure takes ~4 h from start of surgery to end of recording and allows examinations both into the electrophysiological features of unitary excitatory and inhibitory monosynaptic inputs during different brain states as well as the synaptic mechanisms of correlated neuronal activity.


Shear-mediated dilation of the internal carotid artery occurs independent of hypercapnia.
Evidence for shear stress as a regulator of carotid artery dilation in response to increased arterial CO2 was recently demonstrated in humans during sustained elevations in CO2 (hypercapnia); however, the relative contributions of CO2 and shear stress to this response remains unclear. We examined the hypothesis that, after a 30-s transient increase in arterial CO2 tension and consequent increase in internal carotid artery shear stress, internal carotid artery diameter would increase, indicating shear-mediated dilation, in the absence of concurrent hypercapnia. In 27 healthy participants, partial pressures of end-tidal O2 and CO2, ventilation (pneumotachography), blood pressure (finger photoplethysmography), heart rate (electrocardiogram), internal carotid artery flow, diameter, and shear stress (high-resolution duplex ultrasound), and middle cerebral artery blood velocity (transcranial Doppler) were measured during 4-min steady-state and transient 30-s hypercapnic tests (both +9 mmHg CO2). Internal carotid artery dilation was lower in the transient compared with steady-state hypercapnia (3.3 ± 1.9 vs. 5.3 ± 2.9%, respectively, P < 0.03). Increases in internal carotid artery shear stress preceded increases in diameter in both transient (time: 16.8 ± 13.2 vs. 59.4 ± 60.3 s, P < 0.01) and steady-state (time: 18.2 ± 14.2 vs. 110.3 ± 79.6 s, P < 0.01) tests. Internal carotid artery dilation was positively correlated with shear rate area under the curve in the transient (r2 = 0.44, P < 0.01) but not steady-state (r2 = 0.02, P = 0.53) trial. Collectively, these results suggest that hypercapnia induces shear-mediated dilation of the internal carotid artery in humans. This study further promotes the application and development of hypercapnia as a clinical strategy for the assessment of cerebrovascular vasodilatory function and health in humans.NEW & NOTEWORTHY Shear stress dilates the internal carotid artery in humans. This vasodilatory response occurs independent of other physiological factors, as demonstrated by our transient CO2 test, and is strongly correlated to shear area under the curve. Assessing carotid shear-mediated dilation may provide a future avenue for assessing cerebrovascular health and the risk of cerebrovascular events.


Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease.
High blood pressure and stroke are associated with increased risks of dementia and cognitive impairment. This study aimed to determine whether blood pressure lowering would reduce the risks of dementia and cognitive decline among individuals with cerebrovascular disease. The Perindopril Protection Against Recurrent Stroke Study (PROGRESS) was a randomized, double-blind, placebo-controlled trial conducted among 6105 people with prior stroke or transient ischemic attack. Participants were assigned to either active treatment (perindopril for all participants and indapamide for those with neither an indication for nor a contraindication to a diuretic) or matching placebo(s). The primary outcomes for these analyses were dementia (using DSM-IV criteria) and cognitive decline (a decline of 3 or more points in the Mini-Mental State Examination score). During a mean follow-up of 3.9 years, dementia was documented in 193 (6.3%) of the 3051 randomized participants in the actively treated group and 217 (7.1%) of the 3054 randomized participants in the placebo group (relative risk reduction, 12% [95% confidence interval, -8% to 28%]; P =.2). Cognitive decline occurred in 9.1% of the actively treated group and 11.0% of the placebo group (risk reduction, 19% [95% confidence interval, 4% to 32%]; P =.01). The risks of the composite outcomes of dementia with recurrent stroke and of cognitive decline with recurrent stroke were reduced by 34% (95% confidence interval, 3% to 55%) (P =.03) and 45% (95% confidence interval, 21% to 61%) (P<.001), respectively, with no clear effect on either dementia or cognitive decline in the absence of recurrent stroke. Active treatment was associated with reduced risks of dementia and cognitive decline associated with recurrent stroke. These findings further support the recommendation that blood pressure lowering with perindopril and indapamide therapy be considered for all patients with cerebrovascular disease.


Effect of Aging in the Perception of Health-Related Quality of Life in End-Stage Renal Disease Patients under Online-Hemodiafiltration.
This work aimed to evaluate how aging could influence patients' perception of health quality of life (HRQOL), as well as, the effect of aging on dialysis adequacy and in hematological, iron status, inflammatory and nutritional markers. In this transversal study were enrolled 305 ESRD patients under online-hemodiafiltration (OL-HDF) (59.67% males; 64.9 ± 14.3 years old). Data about comorbidities, hematological data, iron status, dialysis adequacy, nutritional and inflammatory markers were collected from patient's records. Moreover, HRQOL score, by using the Kidney Disease Quality of Life-Short Form (KDQOL-SF), was assessed. Analyzing the results according to quartiles of age, significant differences were found for some parameters evaluated by the KDQOL-SF instrument, namely for work status, physical functioning and role-physical, which decreased with increasing age. We also found a higher proportion of diabetic patients, a decrease in creatinine, iron, albumin serum levels, transferrin saturation and nPCR, with increasing age. Moreover, significant negative correlations were found between age and mean cell hemoglobin concentration, iron, transferrin saturation, albumin, nPCR, work status, physical functioning and role-physical. In conclusion, our results showed that aging is associated with a decreased work status, physical functioning and role-physical, with a decreased dialysis adequacy, iron availability and nutritional status, and with an increased proportion of diabetic patients and of patients using central venous catheter, as the vascular access. The knowledge of these changes associated with aging, which have impact in the quality of life of the patients, could be useful in their management.


Investigation of Stroke Needs (INVISION) Study: Stroke Awareness and Education.
The objective of this study was to assess the overall understanding and effectiveness of current inpatient stroke education practice by using the data from the Investigation of Stroke Needs (INVISION) Study, a qualitative study assessing various challenges and barriers of the hemorrhagic stroke survivors and their caregivers. Semi-structured interviews were conducted on patients who were recently hospitalized with intracerebral hemorrhage (ICH) and their caregivers during the follow-up visits. The electronic medical record for each patient was reviewed to assess whether they received standard stroke education material during their hospitalization. A phenomenological approach was utilized to identify gaps of education and knowledge in the targeted sample. A total of 21 participants were interviewed. Despite receiving formal stroke education material during their hospitalization, there were three major gaps in stroke knowledge that participants noted, including (1) lack of stroke knowledge/awareness, (2) need for stroke education, and (3) fear of recurrent stroke and comorbid diseases. The majority of ICH survivors had no memory of their hospitalization. This study suggests a need for increased continuity and communication with health-care providers to address the evolving educational and practical needs of stroke patients and their caregivers after hospital discharge.


Digital Technologies for Forest Supply Chain Optimization: Existing Solutions and Future Trends.
The role of digital technologies for fostering sustainability and efficiency in forest-based supply chains is well acknowledged and motivated several studies in the scope of precision forestry. Sensor technologies can collect relevant data in forest-based supply chains, comprising all activities from within forests and the production of the woody raw material to its transformation into marketable forest-based products. Advanced planning systems can help to support decisions of the various entities in the supply chain, e.g., forest owners, harvest companies, haulage companies, and forest product processing industry. Such tools can help to deal with the complex interdependencies between different entities, often with opposing objectives and actions-which may increase efficiency of forest-based supply chains. This paper analyzes contemporary literature dealing with digital technologies in forest-based supply chains and summarizes the state-of-the-art digital technologies for real-time data collection on forests, product flows, and forest operations, as well as planning systems and other decision support systems in use by supply chain actors. Higher sustainability and efficiency of forest-based supply chains require a seamless information flow to foster integrated planning of the activities over the supply chain-thereby facilitating seamless data exchange between the supply chain entities and foster new forms of collaboration. Therefore, this paper deals with data exchange and multi-entity collaboration aspects in combination with interoperability challenges related with the integration among multiple process data collection tools and advanced planning systems. Finally, this interdisciplinary review leads to the discussion of relevant guidelines that can guide future research and integration projects in this domain.


MTHFR Gene variants C677T, A1298C and association with Down syndrome: A Case-control study from South India.
The 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and low folate levels are associated with inhibition of DNA methyltransferase and consequently DNA hypomethylation. The expanding spectrum of common conditions linked with MTHFR polymorphisms includes certain adverse birth outcome, pregnancy complications, cancers, adult cardiovascular diseases and psychiatric disorders, with several of these associations remaining still controversial. Trisomy 21 or Down syndrome (DS) is the most common genetic cause of mental retardation. It stems predominantly from the failure of chromosome 21 to segregate normally during meiosis. Despite substantial research, the molecular mechanisms underlying non-disjunction leading to trisomy 21 are poorly understood. Two common variants C677T and A1298C of the MTHFR gene were screened in 36 parents with DS children and 60 healthy couples from Tamil Nadu and Karnataka. The MTHFR genotypes were studied by RFLP analysis of PCR-amplified products and confirmed by sequencing. The CT genotype was seen in three each (8.3%) of case mothers and fathers. One case father showed TT genotype. All the control individuals exhibited the wild type CC genotype. A similar frequency for the uncommon allele C of the second polymorphism was recorded in case mothers (0.35) and fathers (0.37) in comparison with the control mothers (0.39) and fathers (0.37). This first report on MTHFR C677T and A1298C polymorphisms in trisomy 21 parents from south Indian population revealed that MTHFR 677CT polymorphism was associated with a risk for Down syndrome.


Automatically Appraising the Credibility of Vaccine-Related Web Pages Shared on Social Media: A Twitter Surveillance Study.
Tools used to appraise the credibility of health information are time-consuming to apply and require context-specific expertise, limiting their use for quickly identifying and mitigating the spread of misinformation as it emerges. The aim of this study was to estimate the proportion of vaccine-related Twitter posts linked to Web pages of low credibility and measure the potential reach of those posts. Sampling from 143,003 unique vaccine-related Web pages shared on Twitter between January 2017 and March 2018, we used a 7-point checklist adapted from validated tools and guidelines to manually appraise the credibility of 474 Web pages. These were used to train several classifiers (random forests, support vector machines, and recurrent neural networks) using the text from a Web page to predict whether the information satisfies each of the 7 criteria. Estimating the credibility of all other Web pages, we used the follower network to estimate potential exposures relative to a credibility score defined by the 7-point checklist. The best-performing classifiers were able to distinguish between low, medium, and high credibility with an accuracy of 78% and labeled low-credibility Web pages with a precision of over 96%. Across the set of unique Web pages, 11.86% (16,961 of 143,003) were estimated as low credibility and they generated 9.34% (1.64 billion of 17.6 billion) of potential exposures. The 100 most popular links to low credibility Web pages were each potentially seen by an estimated 2 million to 80 million Twitter users globally. The results indicate that although a small minority of low-credibility Web pages reach a large audience, low-credibility Web pages tend to reach fewer users than other Web pages overall and are more commonly shared within certain subpopulations. An automatic credibility appraisal tool may be useful for finding communities of users at higher risk of exposure to low-credibility vaccine communications.


Climate change. Climate in Medieval time.
Many papers have referred to a "Medieval Warm Period." But how well defined is climate in this period, and was it as warm as or warmer than it is today? In their Perspective, Bradley et al. review the evidence and conclude that although the High Medieval (1100 to 1200 A.D.) was warmer than subsequent centuries, it was not warmer than the late 20th century. Moreover, the warmest Medieval temperatures were not synchronous around the globe. Large changes in precipitation patterns are a particular characteristic of "High Medieval" time. The underlying mechanisms for such changes must be elucidated further to inform the ongoing debate on natural climate variability and anthropogenic climate change.


Explicit description of polarization coupling in lidar applications.
Depolarization lidar requires discrimination of received power in polarized and unpolarized components of backscattered light. This can be accomplished with only two polarization measurements. However, parallel- and cross-polarization channels in depolarization lidar cannot always be regarded as independent, because system optical components can cause coupling between these channels and transmitter and receiver polarization planes are rarely perfectly aligned. Calibration constants, while in some instances reasonable approximations, do not fully describe the physics of the receiver and potential for coupling between orthogonal polarization modes. We present an analysis of a general receiver design and introduce an algorithm for decoupling the received data, which only requires the parallel- and cross-polarization data typically recorded in depolarization lidar measurements.


Intake of selected nutrients from foods, from fortification and from supplements in various European countries.
Recent European Union regulation requires setting of maximum amount of micronutrients in dietary supplements or foods taking into account the tolerable upper intake level (ULs) established by scientific risk assessment and population reference intakes. To collect and evaluate recently available data on intakes of selected vitamins and minerals from conventional foods, food supplements and fortified foods in adults and children. Intake of calcium, copper, iodine, iron, magnesium, phosphorus, selenium, zinc, folic acid, niacin and total vitamin A/retinol, B(6), D and E was derived from nationally representative surveys in Denmark, Germany, Finland, Ireland, Italy, the Netherlands, Poland, Spain and the United Kingdom. Intake of high consumers, defined as the 95th percentile of each nutrient, was compared to the UL. For most nutrients, adults and children generally consume considerably less than the UL with exceptions being retinol, zinc, iodine, copper and magnesium. The major contributor to intakes for all nutrients and in all countries is from foods in the base diet. The patterns of food supplements and voluntary fortification vary widely among countries with food supplements being responsible for the largest differences in total intakes. In the present study, for those countries with data on fortified foods, fortified foods do not significantly contribute to higher intakes for any nutrient. Total nutrient intake expressed as percentage of the UL is generally higher in children than in adults. The risk of excessive intakes is relatively low for the majority of nutrients with a few exceptions. Children are the most vulnerable group as they are more likely to exhibit high intakes relative to the UL. There is a need to develop improved methods for estimating intakes of micronutrients from fortified foods and food supplements in future dietary surveys.


Computer-assisted chromosome mapping by protoplast fusion in Staphylococcus aureus.
Protoplasts of genetically marked derivatives of Staphylococcus aureus NCTC 8325 were fused with polyethylene glycol and regenerated without selection. Recombinants possessing one specific resistance marker from each parent were selected from the regenerated population and scored for seven or eight unselected markers. The results of these 9- and 10-factor crosses were entered directly into a programmed microcomputer from prescored replica plates. The data then were condensed into an array of phenotypes, together with the frequency with which each occurred. Further analyses by computer included the calculation of coinheritance frequencies for all possible pairs of markers; after entering a proposed order for the markers being analyzed, the minimum number of crossover events required to generate each phenotypic class was calculated. The linkage relationships of markers, based on the protoplast fusion data, were entirely consistent with the linkage relationships of markers already known to exist within each of the three linkage groups previously defined by transformation. The fusion data defined an arrangement of the three linkage groups into a circular chromosome map and predicted the approximate location of four previously unmapped markers (tet-3490, fus-149, purC193::Tn551, and omega [Chr::Tn551]42) on this map.


Monocyte heterogeneity underlying phenotypic changes in monocytes according to SIV disease stage.
Infection by HIV is associated with the expansion of monocytes expressing CD16 antigens, but the significance of this in HIV pathogenesis is largely unknown. In rhesus macaques, at least three subpopulations of blood monocytes were identified based on their expression of CD14 and CD16: CD14(high)CD16(-), CD14(high)CD16(low), and CD14(low)CD16(high). The phenotypes and functions of these subpopulations, including CD16(+) monocytes, were investigated in normal, uninfected rhesus macaques and macaques that were infected with SIV or chimeric SHIV. To assess whether these different monocyte subpopulations expand or contract in AIDS pathogenesis, we conducted a cross-sectional study of 54 SIV- or SHIV-infected macaques and 48 uninfected controls. The absolute numbers of monocyte populations were examined in acutely infected animals, chronically infected animals with no detectable plasma virus RNA, chronically infected animals with detectable plasma virus RNA, and animals that died with AIDS. The absolute numbers of CD14(high)CD16(low) and CD14(low)CD16(high) monocytes were elevated significantly in acutely infected animals and chronically infected animals with detectable plasma virus RNA compared with uninfected controls. Moreover, a significant, positive correlation was evident between the number of CD14(high)CD16(low) or CD14(low)CD16(high) monocytes and plasma viral load in the infected cohort. These data show the dynamic changes of blood monocytes, most notably, CD14(high)CD16(low) monocytes during lentiviral infection, which are specific to disease stage.


Predicting mental health outcomes in female working carers: a longitudinal analysis.
This study investigated the factors contributing to psychological distress and positive affect over time in female working carers of older people. Questionnaires (including measures of work-related, care-related, interpersonal and psychological aspects of working and caring) were distributed to 275 female working carers in the UK, the majority of whom were working as nurses in the National Health Service. In cross-sectional analyses, higher work stress and work demands predicted higher psychological distress among respondents. Better carer health, lower external pressures to care and higher work satisfaction predicted greater positive affect. The combined effects of greater work stress and work demands also predicted higher levels of psychological distress at follow-up (after one year), whereas younger age and lower work stress predicted greater positive affect over time. We conclude that more stressful and demanding work roles appear detrimental to carers' mental health, while lower stress occupational roles may be beneficial, providing satisfaction and fulfilment outside of the caring role. Older female carers may be especially at risk of psychological distress, possibly due in part to increasing health problems of their own.


Seasonal variations of oxygen radical scavenging ability in rosemary leaf extract.
This investigation demonstrates that the oxygen radical scavenging ability of rosemary leaf extract has significant seasonal variations. The scavenging ability of rosemary leaf extract was quantitatively evaluated for five active oxygen species by using the ESR spin-trapping method. It was found that leaves that were picked in the cold season showed higher scavenging ability than those picked in the warm season. Measurement of the scavenging rate in pure rosmarinic acid and caffeic acid indicated that the scavenging ability in the warm season was mainly derived from rosmarinic acid. In the boiled extract, rosmarinic acid decomposed into caffeic acid. Therefore, a marked increase in the scavenging ability against superoxide and singlet oxygen in the boiled extract is in line with the high activity of caffeic acid. This study demonstrates that the multiple free radical scavenging method can be a useful method in comparative antioxidant capacity studies of plant extracts.


Hybrid Quantum Device with Nitrogen-Vacancy Centers in Diamond Coupled to Carbon Nanotubes.
We show that nitrogen-vacancy (NV) centers in diamond interfaced with a suspended carbon nanotube carrying a dc current can facilitate a spin-nanomechanical hybrid device. We demonstrate that strong magnetomechanical interactions between a single NV spin and the vibrational mode of the suspended nanotube can be engineered and dynamically tuned by external control over the system parameters. This spin-nanomechanical setup with strong, intrinsic, and tunable magnetomechanical couplings allows for the construction of hybrid quantum devices with NV centers and carbon-based nanostructures, as well as phonon-mediated quantum information processing with spin qubits.


Mural endocarditis caused by Corynebacterium mustelae in a dog with a VSD.
A 6 yr old female spayed large Munsterlander was evaluated following a 3 wk history of lethargy, inappetence, intermittent fever, and a recent change to the timing of her previously diagnosed heart murmur. Physical examination revealed marked dehydration, lethargy, and a grade 5/6 to-and-fro heart murmur that was auscultated best at the right sternal border. The dog was febrile, and echocardiography revealed a large, mobile, vegetative lesion in the right ventricular outflow tract associated with a ventricular septal defect (VSD). Mild aortic insufficiency was present. Corynebacterium mustelae (C. mustelae) was isolated from a pooled blood culture. Treatment of infective endocarditis (IE) was initiated along with supportive care, and the patient was discharged 9 days later. The dog remained without clinical signs 132 days after discharge. VSD is rarely mentioned as a predisposing factor for development of IE in veterinary literature; however, this report highlights that dogs with a VSD may be at risk for IE. To the authors' knowledge, this is the first documented case of a canine infection with C. mustelae. Infection with C. mustelae in this case represents a novel agent for IE in the dog.


Genetic parameters for agronomic characteristics. I. Early and intermediate breeding populations of true potato seed.
The original variation in the source population as well as the selection method may influence the genetic variation in further cycles of genetic improvement. Therefore, the objectives of this research were to determine genetic parameters (variance components and heritability) in source and intermediate stages of a true potato seed (TPS) breeding population and to calculate the genetic and phenotypic correlations in this breeding material developed by the Centro Internacional de la Papa (CIP). The intermediate stage was derived from a source population adapted to the warm lowland tropics plus introduction of exotic germplasm from North America and Europe. Non-additive genetic variation was almost nil for plant survival, tuber yield and tuber shape uniformity in both stages of the breeding population and no quantitative genetic variation for uniformity of tuber color was observed in both source and intermediate breeding materials. Heritability was higher in the intermediate stage than in the source population for plant survival (0.86 vs 0.66), tuber yield (0.30 vs 0.14) and tuber shape (0.77 vs 0.51), but it was the reverse for tuber uniformity (0.11 vs 0.72). These results suggest that potato breeders at CIP were able to keep enough genetic variation for most important characteristics for potato production from true seed in their intermediate breeding materials by adding new sources of variation to the original breeding population. Additive genetic and phenotypic correlations were significant and positive between plant vigor after transplanting and tuber yield, and tuber shape and tuber uniformity, which suggest that high yielding offspring result from early vigorous growth, and that tuber uniformity could depend on tuber shape uniformity in this breeding material.


Microfluidic, label-free enrichment of prostate cancer cells in blood based on acoustophoresis.
Circulating tumor cells (CTC) are shed in peripheral blood at advanced metastatic stages of solid cancers. Surface-marker-based detection of CTC predicts recurrence and survival in colorectal, breast, and prostate cancer. However, scarcity and variation in size, morphology, expression profile, and antigen exposure impairs reliable detection and characterization of CTC. We have developed a noncontact, label-free microfluidic acoustophoresis method to separate prostate cancer cells from white blood cells (WBC) through forces generated by ultrasonic resonances in microfluidic channels. Implementation of cell prealignment in a temperature-stabilized (±0.5 °C) acoustophoresis microchannel dramatically enhanced the discriminatory capacity and enabled the separation of 5 μm microspheres from 7 μm microspheres with 99% purity. Next, we determined the feasibility of employing label-free microfluidic acoustophoresis to discriminate and divert tumor cells from WBCs using erythrocyte-lysed blood from healthy volunteers spiked with tumor cells from three prostate cancer cell-lines (DU145, PC3, LNCaP). For cells fixed with paraformaldehyde, cancer cell recovery ranged from 93.6% to 97.9% with purity ranging from 97.4% to 98.4%. There was no detectable loss of cell viability or cell proliferation subsequent to the exposure of viable tumor cells to acoustophoresis. For nonfixed, viable cells, tumor cell recovery ranged from 72.5% to 93.9% with purity ranging from 79.6% to 99.7%. These data contribute proof-in-principle that label-free microfluidic acoustophoresis can be used to enrich both viable and fixed cancer cells from WBCs with very high recovery and purity.


How to Sync to the Beat of a Persistent Fractal Metronome without Falling Off the Treadmill?
In rehabilitation, rhythmic acoustic cues are often used to improve gait. However, stride-time fluctuations become anti-persistent with such pacing, thereby deviating from the characteristic persistent long-range correlations in stride times of self-paced walking healthy adults. Recent studies therefore experimented with metronomes with persistence in interbeat intervals and successfully evoked persistent stride-time fluctuations. The objective of this study was to examine how participants couple their gait to a persistent metronome, evoking persistently longer or shorter stride times over multiple consecutive strides, without wandering off the treadmill. Twelve healthy participants walked on a treadmill in self-paced, isochronously paced and non-isochronously paced conditions, the latter with anti-persistent, uncorrelated and persistent correlations in interbeat intervals. Stride-to-stride fluctuations of stride times, stride lengths and stride speeds were assessed with detrended fluctuation analysis, in conjunction with an examination of the coupling between stride times and stride lengths. Stride-speed fluctuations were anti-persistent for all conditions. Stride-time and stride-length fluctuations were persistent for self-paced walking and anti-persistent for isochronous pacing. Both stride times and stride lengths changed from anti-persistence to persistence over the four non-isochronous metronome conditions, accompanied by an increasingly stronger coupling between these gait parameters, with peak values for the persistent metronomes. These results revealed that participants were able to follow the beat of a persistent metronome without falling off the treadmill by strongly coupling stride-length fluctuations to the stride-time fluctuations elicited by persistent metronomes, so as to prevent large positional displacements along the treadmill. For self-paced walking, in contrast, this coupling was very weak. In combination, these results challenge the premise that persistent metronomes in gait rehabilitation would evoke stride-to-stride dynamics reminiscent of self-paced walking healthy adults. Future studies are recommended to include an analysis of the interrelation between stride times and stride lengths in addition to the correlational structure of either one in isolation.


Education and health of children with hearing loss: the necessity of signed languages.
Medical and educational interventions for children with hearing loss often adopt a single approach of spoken language acquisition through the use of technology, such as cochlear implants. These approaches generally ignore signed languages, despite no guarantees that the child will acquire fluency in a spoken language. Research with children who have a cochlear implant and do not use a signed language indicates that language outcomes are very variable and generally worse than their non-deaf peers. In contrast, signing children with cochlear implants have timely language development similar to their non-deaf peers that also exceeds their non-signing peers with cochlear implants. Natural signed languages have been shown to have the same neurocognitive benefits as natural spoken language while being fully accessible to deaf children. However, it is estimated less than 2% of the 34 million deaf children worldwide receive early childhood exposure to a signed language. Most deaf children are, therefore, at risk for language deprivation during the critical period of language acquisition in the first five years of life. Language deprivation has negative consequences for developmental domains, which rely on timely language acquisition. Beyond the adverse effects on a child's education, language deprivation also affects deaf people's mental and physical health and access to health care, among others. Therefore, policies in accordance with the United Nations Convention on the rights of persons with disabilities are needed. Such policies would ensure early intervention and education services include signed languages and bilingual programmes where the signed language is the language of instruction.


Impaired differentiation of Schwann cells in transgenic mice with increased PMP22 gene dosage.
An intrachromosomal duplication containing the PMP22 gene is associated with the human hereditary peripheral neuropathy Charcot-Marie-Tooth disease type 1A, and PMP22 overexpression as a consequence of increased PMP22 gene dosage has been suggested as causative event in this frequent disorder of peripheral nerves. We have generated transgenic mice that carry additional copies of the pmp22 gene to prove that increased PMP22 gene dosage is sufficient to cause PNS myelin deficiencies. Mice carrying approximately 16 and 30 copies of the pmp22 gene display a severe congenital hypomyelinating neuropathy as characterized by an almost complete lack of myelin and marked slowing of nerve conductions. Affected nerves contain an increased number of nonmyelinating Schwann cells, which do not form onion bulbs but align in association with axons. The mutant Schwann cells are characterized by a premyelination-like state as indicated by the expression of embryonic Schwann cell markers. Furthermore, continued Schwann cell proliferation is observed into adulthood. We hypothesize that Schwann cells are impaired in their differentiation into the myelinating phenotype, leading to a disorder comparable to severe cases of hereditary motor and sensory neuropathies. Our findings, combined with the analysis of heterozygous and homozygous PMP22-deficient mice, indicate that aberrant pmp22 gene copy numbers cause various forms of myelination defects.


Evaluations of pleasurable experiences: the peak-end rule.
Prior research suggests that the addition of mild pain to an aversive event may lead people to prefer and directly choose more pain over less pain (Kahneman, Fredrickson, Schreiber, & Redelmeier, 1993). Kahneman et al. suggest that pain ratings are based on a combination of peak pain and final pain. Similarly, people rate a happy life that ends suddenly as being better than one with additional years of mild happiness (Diener, Wirtz, & Oishi, 2001), even though the former objectively consists of less pleasure than the latter. Applying these concepts to material goods, we investigated the impact of positivity and timing on the retrospective evaluations of material goods. We found strong evidence that the peak-end rule applies to both material goods and pain.


Individual differences in Sternberg's memory scanning task.
This study provides a new perspective on both the cognitive processes actually implemented and the effect of a simple experimental control - the recall constraint - in Sternberg's memory scanning task. These findings were highlighted by adopting a new approach based on the comparison of qualitative and quantitative results. The analysis of individual processing, on 72 adults, each participating in one of two experimental conditions (with or without sequence recall), highlighted a large variability in quantitative results as well as qualitative procedures. Based on the participants' retrospective verbalisations, two categories of strategies were identified: (1) the procedures used to memorize the sequence of digits, and (2) the procedures used to compare this sequence with the test digit, which includes strategies for coding the items and processes for searching them in memory. The analysis of the strategies shows that their frequencies of use depend not only on the experimental condition, but also on the participants, the level of task difficulty and the interaction between participants and level of difficulty. This variability questions the accuracy of Sternberg's mean model. Furthermore, this approach suggests some answers to the old debate concerning the exhaustive search pattern for the yes response. Indeed, our results show three types of strategies that can be identified according to the different models of search suggested in the literature. The "exhaustive" search, that would only be involved in the recall condition and only for some of the participants, the "self-terminating" search and the "immediate" strategy, which can be identified with a model of parallel search with limited resources. Thus our study suggests that the different search models are appropriate but depend on both the specific experimental conditions and participant's strategy. Our results should help to improve the interpretation of data collected with this paradigm in cognitive and neuroscientific studies of memory.


Effect of urbanization on the structure and functional traits of remnant subtropical evergreen broad-leaved forests in South China.
We investigated the effects of major environmental drivers associated with urbanization on species diversity and plant functional traits (PFTs) in the remnant subtropical evergreen broad-leaved forests in Metropolitan Guangzhou (Guangdong, China). Twenty environmental factors including topography, light, and soil properties were used to quantify the effects of urbanization. Vegetation data and soil properties were collected from 30 400-m(2) plots at 6 study sites in urban and rural areas. The difference of plant species diversity and PFTs of remnant forests between urban and rural areas were analyzed. To discern the complex relationships, multivariate statistical analyses (e.g., canonical correspondence analysis and regression analysis) were employed. Pioneer species and stress-tolerant species can survive and vigorously establish their population dominance in the urban environment. The native herb diversity was lower in urban forests than in rural forests. Urban forests tend to prefer the species with Mesophanerophyte life form. In contrast, species in rural forests possessed Chamaephyte and Nanophanerophyte life forms and gravity/clonal growth dispersal mode. Soil pH and soil nutrients (K, Na, and TN) were positively related to herb diversity, while soil heavy metal concentrations (Cu) were negatively correlated with herb diversity. The herb plant species diversity declines and the species in the remnant forests usually have stress-tolerant functional traits in response to urbanization. The factors related to urbanization such as soil acidification, nutrient leaching, and heavy metal pollution were important in controlling the plant diversity in the forests along the urban-rural gradients. Urbanization affects the structure and functional traits of remnant subtropical evergreen broad-leaved forests.


Forum on osmosis. II. A criticism of "solvent tension" in osmosis.
Concepts about the liquid state that are inconsistent with the facts are noted, and solvent under tension is one of them. Osmosis is not present in a solution: it is a process in the presence of a semipermeable membrane that can be quantified by the operation of applying a hydrostatic pressure. The classical derivation of the van't Hoff equation from Raoult's law is reviewed. The soundness of the early views of G. H. Lewis has not changed.


Lidar system model for use with path obscurants and experimental validation.
When lidar pulses travel through a short path that includes a relatively high concentration of aerosols, scattering phenomena can alter the power and temporal properties of the pulses significantly, causing undesirable effects in the received pulse. In many applications the design of the lidar transmitter and receiver must consider adverse environmental aerosol conditions to ensure the desired performance. We present an analytical model of lidar system operation when the optical path includes aerosols for use in support of instrument design, simulations, and system evaluation. The model considers an optical path terminated with a solid object, although it can also be applied, with minor modifications, to cases where the expected backscatter occurs from nonsolid objects. The optical path aerosols are characterized by their attenuation and backscatter coefficients derived by the Mie theory from the concentration and particle size distribution of the aerosol. Other inputs include the lidar system parameters and instrument response function, and the model output is the time-resolved received pulse. The model is demonstrated and experimentally validated with military fog oil smoke for short ranges (several meters). The results are obtained with a lidar system operating at a wavelength of 0.905 microm within and outside the aerosol. The model goodness of fit is evaluated using the statistical coefficient of determination whose value ranged from 0.88 to 0.99 in this study.