Ultrasonicated Lespedeza cuneata extract prevents TNF-α-induced early atherosclerosis in vitro and in vivo.
This study evaluated the use of ultrasonication to extract Lespedeza cuneata as a potential nutraceutical for preventing vascular inflammation. Ultrasonicated L. cuneata extract (ULCE) was prepared using 20% ethanol and 2 h of ultrasonication at room temperature, and its effects were investigated using relevant in vitro and in vivo models. ULCE suppressed tumor necrosis factor-alpha (TNF-α)-induced adhesion capacity, vascular cell adhesion protein 1 (VCAM-1) expression, and nuclear factor kappa-B (NF-κB) activity in human umbilical vein endothelial cells (HUVECs). ULCE also suppressed TNF-α-induced NF-κB signaling pathways and p65 translocation from the cytosol to the nucleus, as well as the mRNA expression of IL-1β, IL-6, and TNF-α in HUVECs. Oral administration of ULCE suppressed TNF-α-induced monocyte infiltration into the intima and VCAM-1 expression, as well as the IL-1β, IL-6, TNF-α, and monocyte chemoattractant protein-1 (MCP-1) mRNA expression in the main artery in mice. Among the compounds identified in the hydrolyzed ULCE, quercetin exhibited the strongest inhibitory effect against TNF-α-induced cell adhesion capacity. These results demonstrate that ULCE contains potent preventive factors against early atherosclerosis, which act by suppressing the NF-κB and VCAM-1 signaling axis.


Prevalence, incidence, and factors associated with pre-stroke and post-stroke dementia: a systematic review and meta-analysis.
Reliable data on the prevalence and predictors of post-stroke dementia are needed to inform patients and carers, plan services and clinical trials, ascertain the overall burden of stroke, and understand its causes. However, published data on the prevalence and risk factors for pre-stroke and post-stroke dementia are conflicting. We undertook this systematic review to assess the heterogeneity in the reported rates and to identify risk factors for pre-stroke and post-stroke dementia. Studies published between 1950 and May 1, 2009, were identified from bibliographic databases, reference lists, and journal contents pages. Studies were included if they were on patients with symptomatic stroke, were published in English, reported on a series of consecutive eligible patients or volunteers in prospective cohort studies, included all stroke or all ischaemic stroke, measured dementia by standard criteria, and followed up patients for at least 3 months after stroke. Pooled rates of dementia were stratified by study setting, inclusion or exclusion of pre-stroke dementia, and by first, any, or recurrent stroke. Pooled odds ratios were calculated for factors associated with pre-stroke and post-stroke dementia. We identified 22 hospital-based and eight population-based eligible cohorts (7511 patients) described in 73 papers. The pooled prevalence of pre-stroke dementia was higher (14.4%, 95% CI 12.0-16.8) in hospital-based studies than in population-based studies (9.1%, 6.9-11.3). Although post-stroke (<or=1 year) dementia rates were heterogeneous overall, 93% of the variance was explained by study methods and case mix; the rates ranged from 7.4% (4.8-10.0) in population-based studies of first-ever stroke in which pre-stroke dementia was excluded to 41.3% (29.6-53.1) in hospital-based studies of recurrent stroke in which pre-stroke dementia was included. The cumulative incidence of dementia after the first year was little greater (3.0%, 1.3-4.7) per year in hospital-based studies than expected on the basis of recurrent stroke alone. Medial temporal lobe atrophy, female sex, and a family history of dementia were strongly associated with pre-stroke dementia, whereas the characteristics and complications of the stroke and the presence of multiple lesions in time and place were more strongly associated with post-stroke dementia. After study methods and case mix are taken into account, reported estimates of the prevalence of dementia are consistent: 10% of patients had dementia before first stroke, 10% developed new dementia soon after first stroke, and more than a third had dementia after recurrent stroke. The strong association of post-stroke dementia with multiple strokes and the prognostic value of other stroke characteristics highlight the central causal role of stroke itself as opposed to the underlying vascular risk factors and, thus, the likely effect of optimum acute stroke care and secondary prevention in reducing the burden of dementia. None.


Evaluation of Cervical Cancer Screening Programs in Côte d'Ivoire, Guyana, and Tanzania: Effect of HIV Status.
HIV infection increases a woman's risk for cervical cancer, and cervical cancer incidence and mortality rates are higher in countries with high HIV prevalence and limited resources for screening. Visual inspection with acetic acid (VIA) allows screening and treatment of cervical lesions in a single-visit approach (SVA), but data on its performance in HIV-infected women are limited. This study's objective was to examine cervical cancer screening using VIA/SVA in programs serving HIV-infected women. A VIA/SVA program with cryotherapy for VIA-positive lesions was implemented in Côte d'Ivoire, Guyana, and Tanzania from 2009 to 2012. The effect of HIV status on VIA positivity and on presence of cryotherapy-eligible lesions was examined using a cross-sectional study design, with Chi-square tests for comparisons and constructed multivariate logistic regression models. A P-value of < 0.05 was significant. VIA was performed on 34,921 women, 10% (3,580) were VIA positive; 2,508 (85%) eligible women received cryotherapy during the same visit; only 234 (52%) of those who postponed returned for treatment; 622 (17%) VIA-positive women had lesions too large to be treated with cryotherapy and were referred for excisional treatment. In multivariate analysis-controlling for HIV status, location of the screening clinic, facility location, facility type, and country-compared to HIV-uninfected/unknown women, HIV-infected women had higher odds of being VIA positive (OR 1.95, 95% CI 1.76, 2.16, P<0.0001) and of having large lesions requiring referral (OR 1.93, 95% CI 1.49, 2.51, P< 0.0001). Minor treatment complications occurred in 19 of 3,032 (0.63%) women; none required further intervention. This study found that compared to HIV-uninfected/unknown women, HIV-infected women had nearly twice the odds of being VIA-positive and to require referral for large lesions. SVA was safe and resulted in significant reductions in loss to follow-up. There is increased need for excisional treatment in countries with high HIV prevalence.


The Relationship Between Depression and Frailty in Community-Dwelling Older People: A Systematic Review and Meta-Analysis of 84,351 Older Adults.
In this study we investigated the correlation between depression and frailty in older adults. Additionally, correlations among study designs (prospective vs. cross-sectional), regions, depression indices, frailty indices, covariance corrections, and sexes were explored to support the analysis. A systematic literature review and meta-analysis were conducted. A total of 84,351 older adults, all 65 years of age or older, were analyzed. Both authors independently extracted and examined retrieved articles. Searched keywords included "depression" or "depressive"; "frailty" or "frail"; and "older people," "elderly," "geriatric," or "senior." Articles published between January 2000 and December 2016 were searched. A literature quality assessment was conducted in accordance with the guidelines of the Preferred Reporting Items for Systematic REVIEWS AND META-ANALYSES: Systematic literature searches were conducted on the Embase, PubMed, MEDLINE, Cumulative Index to Nursing and Allied Health Literature, and Cochrane Library databases, and collected studies were analyzed using a random effects model. Fourteen studies on people 65 years of age or older were collected, and a correlation analysis was conducted for depression and frailty. According to the meta-analysis, the risk for frailty due to depression was nonsignificant among the subgroups for study design (p for heterogeneity = .149), region (p = .429), depression criteria (p = .934), covariate adjustment (p = .702), and frailty criteria (p = .661). Notably, the risk for frailty due to depression was significantly higher in men than in women (pooled odds ratios for men and women: 4.76 and 2.25, respectively; Qbetween χ2 = 9.93, p = .002). Older adults with depression are more prone to frailty than are those without depression. Regardless of study design, region, depression index, frailty index, and covariance corrections, no significant differences were observed in the results of studies on depression and frailty in older adults. The only factor that had a significant influence was sex; older men with depression were at a higher risk for frailty than were older women with depression. Depression and frailty are pertinent health concerns related to geriatric syndromes. Because older adults with depression have a high risk for frailty, nursing personnel should use a depression index as early as possible to screen for depression and further reduce the occurrence of frailty in older adults. Furthermore, based on the aforementioned differences between the sexes, special attention should be paid to older men with depression to reduce their risk for frailty.


Extreme Inverted Trophic Pyramid of Reef Sharks Supported by Spawning Groupers.
The extent of the global human footprint [1] limits our understanding of what is natural in the marine environment. Remote, near-pristine areas provide some baseline expectations for biomass [2, 3] and suggest that predators dominate, producing an inverted biomass pyramid. The southern pass of Fakarava atoll-a biosphere reserve in French Polynesia-hosts an average of 600 reef sharks, two to three times the biomass per hectare documented for any other reef shark aggregations [4]. This huge biomass of predators makes the trophic pyramid inverted. Bioenergetics models indicate that the sharks require ∼90 tons of fish per year, whereas the total fish production in the pass is ∼17 tons per year. Energetic theory shows that such trophic structure is maintained through subsidies [5-9], and empirical evidence suggests that sharks must engage in wide-ranging foraging excursions to meet energy needs [9, 10]. We used underwater surveys and acoustic telemetry to assess shark residency in the pass and feeding behavior and used bioenergetics models to understand energy flow. Contrary to previous findings, our results highlight that sharks may overcome low local energy availability by feeding on fish spawning aggregations, which concentrate energy from other local trophic pyramids. Fish spawning aggregations are known to be targeted by sharks, but they were previously believed to play a minor role representing occasional opportunistic supplements. This research demonstrates that fish spawning aggregations can play a significant role in the maintenance of local inverted pyramids in pristine marine areas. Conservation of fish spawning aggregations can help conserve shark populations, especially if combined with shark fishing bans.


Adrenaline stimulates glucagon secretion in pancreatic A-cells by increasing the Ca2+ current and the number of granules close to the L-type Ca2+ channels.
We have monitored electrical activity, voltage-gated Ca2+ currents, and exocytosis in single rat glucagon-secreting pancreatic A-cells. The A-cells were electrically excitable and generated spontaneous Na+- and Ca2+-dependent action potentials. Under basal conditions, exocytosis was tightly linked to Ca2+ influx through omega-conotoxin-GVIA-sensitive (N-type) Ca2+ channels. Stimulation of the A-cells with adrenaline (via beta-adrenergic receptors) or forskolin produced a greater than fourfold PKA-dependent potentiation of depolarization-evoked exocytosis. This enhancement of exocytosis was due to a 50% enhancement of Ca2+ influx through L-type Ca2+ channels, an effect that accounted for <30% of the total stimulatory action. The remaining 70% of the stimulation was attributable to an acceleration of granule mobilization resulting in a fivefold increase in the number of readily releasable granules near the L-type Ca2+ channels.


Cell shape in proliferating epithelia: a multifaceted problem.
A specific and unexpected distribution pattern of polygonal cell shapes in proliferating epithelia is revealed in a recent study that combines mathematical modeling with experimental data (Gibson et. al., 2006). This pattern is conserved in epithelia from diverse species, suggesting that this distribution is a fundamental property of proliferating epithelial sheets.


Developing cancer-related educational content and goals tailored to the Comanche Nation.
Cancer-related educational content and goals should be modified to the needs of Native Americans to ensure adherence to healthy lifestyles. The current article describes the development of cancer-related educational modules that include creating behavioral goals specific to the people of the Comanche Nation. A community-based participatory research approach was used to conduct focus groups in the Comanche Nation and obtain feedback related to cancer-related educational modules and behavioral goals. Content analysis, verbatim transcriptions, field notes, and observations were used to analyze data and create five major themes. Comanche people need cancer educational modules and goals tailored to their culture to become engaged and maintain interest, thereby improving the likelihood of increasing cancer-related knowledge. Oncology nurses should respect guidance provided by Comanche community members to adapt cancer-related education materials and processes, as well as goal development, to address cultural concepts. When Comanche community members become knowledgeable and work toward healthy behavioral change, cancer health disparities may decrease.


Galaxy workflows for fragment-based virtual screening: a case study on the SARS-CoV-2 main protease.
We present several workflows for protein-ligand docking and free energy calculation for use in the workflow management system Galaxy. The workflows are composed of several widely used open-source tools, including rDock and GROMACS, and can be executed on public infrastructure using either Galaxy's graphical interface or the command line. We demonstrate the utility of the workflows by running a high-throughput virtual screening of around 50000 compounds against the SARS-CoV-2 main protease, a system which has been the subject of intense study in the last year.


Moody microbes or fecal phrenology: what do we know about the microbiota-gut-brain axis?
The microbiota-gut-brain axis is a term that is commonly used and covers a broad set of functions and interactions between the gut microbiome, endocrine, immune and nervous systems and the brain. The field is not much more than a decade old and so large holes exist in our knowledge. At first sight it appears gut microbes are largely responsible for the development, maturation and adult function of the enteric nervous system as well as the blood brain barrier, microglia and many aspects of the central nervous system structure and function. Given the state of the art in this exploding field and the hopes, as well as the skepticism, which have been engendered by its popular appeal, we explore recent examples of evidence in rodents and data derived from studies in humans, which offer insights as to pathways involved. Communication between gut and brain depends on both humoral and nervous connections. Since these are bi-directional and occur through complex communication pathways, it is perhaps not surprising that while striking observations have been reported, they have often either not yet been reproduced or their replication by others has not been successful. We offer critical and cautionary commentary on the available evidence, and identify gaps in our knowledge that need to be filled so as to achieve translation, where possible, into beneficial application in the clinical setting.


Tackling cancer burden in low-income and middle-income countries: Morocco as an exemplar.
Examples of successful implementations of national cancer control plans in low-income or middle-income countries remain rare. Morocco, a country where cancer is already the second leading cause of death after cardiovascular diseases, is one exception in this regard. Population ageing and lifestyle changes are the major drivers that are further increasing the cancer burden in the country. Facing this challenge, the Moroccan Ministry of Health has developed a we l planned and pragmatic National Plan for Cancer Prevention and Control (NPCPC) that, since 2010, has been implemented with government financial support to provide basic cancer care services across the entire range of cancer control. Several features of the development and implementation of the NPCPC and health-care financing in Morocco provide exemplars for other low-income and middle-income countries to follow. Additionally, from the first 5 years of NPCPC, several areas were shown to require further focus through implementation research, notably in strengthening cancer awareness, risk reduction, and the referral pathways for prevention, early detection, treatment, and follow-up care. Working together with a wide range of stakeholders, and engagement with stakeholders outside the health-care system on a more holistic approach can provide further opportunities for the national authorities to build on their successes and realise the full potential of present and future cancer control efforts in Morocco.


Stress fractures in athletes.
A stress fracture is a partial or complete bone fracture that results from repeated application of stress lower than the stress required to fracture the bone in a single loading. Otherwise healthy athletes, especially runners, sustain stress injuries or fractures. Prevention or early intervention is the preferable treatment. However, it is difficult to predict injury because runners vary with regard to biomechanical predisposition, training methods, and other factors such as diet, muscle strength, and flexibility. Stress fractures account for 0.7% to 20% of all sports medicine clinic injuries. Track-and-field athletes have the highest incidence of stress fractures compared with other athletes. Stress fractures of the tibia, metatarsals, and fibula are the most frequently reported sites. The sites of stress fractures vary from sport to sport (eg, among track athletes, stress fractures of the navicular, tibia, and metatarsal are common; in distance runners, it is the tibia and fibula; in dancers, the metatarsals). In the military, the calcaneus and metatarsals were the most commonly cited injuries, especially in new recruits, owing to the sudden increase in running and marching without adequate preparation. However, newer studies from the military show the incidence and distribution of stress fractures to be similar to those found in sports clinics. Fractures of the upper extremities are relatively rare, although most studies have focused only on lower-extremity injuries. The ulna is the upper-extremity bone injured most frequently. Imaging plays a key role in the diagnosis and management of stress injuries. Plain radiography is useful when positive, but generally has low sensitivity. Radionuclide bone scanning is highly sensitive, but lacks specificity and the ability to directly visualize fracture lines. In this article, we focus on magnetic resonance imaging, which provides highly sensitive and specific evaluation for bone marrow edema, periosteal reaction as well as detection of subtle fracture lines.


Global patterns of mortality in international migrants: a systematic review and meta-analysis.
258 million people reside outside their country of birth; however, to date no global systematic reviews or meta-analyses of mortality data for these international migrants have been done. We aimed to review and synthesise available mortality data on international migrants. In this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Library, and Google Scholar databases for observational studies, systematic reviews, and randomised controlled trials published between Jan 1, 2001, and March 31, 2017, without language restrictions. We included studies reporting mortality outcomes for international migrants of any age residing outside their country of birth. Studies that recruited participants exclusively from intensive care or high dependency hospital units, with an existing health condition or status, or a particular health exposure were excluded. We also excluded studies limited to maternal or perinatal outcomes. We screened studies using systematic review software and extracted data from published reports. The main outcomes were all-cause and International Classification of Diseases, tenth revision (ICD-10) cause-specific standardised mortality ratios (SMRs) and absolute mortality rates. We calculated summary estimates using random-effects models. This study is registered with PROSPERO, number CRD42017073608. Of the 12 480 articles identified by our search, 96 studies were eligible for inclusion. The studies were geographically diverse and included data from all global regions and for 92 countries. 5464 mortality estimates for more than 15·2 million migrants were included, of which 5327 (97%) were from high-income countries, 115 (2%) were from middle-income countries, and 22 (<1%) were from low-income countries. Few studies included mortality estimates for refugees (110 estimates), asylum seekers (144 estimates), or labour migrants (six estimates). The summary estimate of all-cause SMR for international migrants was lower than one when compared with the general population in destination countries (0·70 [95% CI 0·65-0·76]; I2=99·8%). All-cause SMR was lower in both male migrants (0·72 [0·63-0·81]; I2=99·8%) and female migrants (0·75 [0·67-0·84]; I2=99·8%) compared with the general population. A mortality advantage was evident for refugees (SMR 0·50 [0·46-0·54]; I2=89·8%), but not for asylum seekers (1·05 [0·89-1·24]; I2=54·4%), although limited data was available on these groups. SMRs for all causes of death were lower in migrants compared with the general populations in the destination country across all 13 ICD-10 categories analysed, with the exception of infectious diseases and external causes. Heterogeneity was high across the majority of analyses. Point estimates of all-cause age-standardised mortality in migrants ranged from 420 to 874 per 100 000 population. Our study showed that international migrants have a mortality advantage compared with general populations, and that this advantage persisted across the majority of ICD-10 disease categories. The mortality advantage identified will be representative of international migrants in high-income countries who are studying, working, or have joined family members in these countries. However, our results might not reflect the health outcomes of more marginalised groups in low-income and middle-income countries because little data were available for these groups, highlighting an important gap in existing research. Our results present an opportunity to reframe the public discourse on international migration and health in high-income countries. Wellcome Trust, National Institute for Health Research, Medical Research Council, Alliance for Health Policy and Systems Research, Department for International Development, Fogarty International Center, Grand Challenges Canada, International Development Research Centre Canada, Inter-American Institute for Global Change Research, National Cancer Institute, National Heart, Lung and Blood Institute, National Institute of Mental Health, Swiss National Science Foundation, World Diabetes Foundation, UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, and European Society for Clinical Microbiology and Infectious Diseases (ESCMID) Study Group Research Funding for the ESCMID Study Group for Infections in Travellers and Migrants.


Cognitive predictors and age-based adverse impact among business executives.
Age differences on measures of general mental ability and specific cognitive abilities were examined in 2 samples of job applicants to executive positions as well as a mix of executive/nonexecutive positions to determine which predictors might lead to age-based adverse impact in making selection and advancement decisions. Generalizability of the pattern of findings was also investigated in 2 samples from the general adult population. Age was negatively related to general mental ability, with older executives scoring lower than younger executives. For specific ability components, the direction and magnitude of age differences depended on the specific ability in question. Older executives scored higher on verbal ability, a measure most often associated with crystallized intelligence. This finding generalized across samples examined in this study. Also, consistent with findings that fluid abilities decline with age, older executives scored somewhat lower on figural reasoning than younger executives, and much lower on a letter series test of inductive reasoning. Other measures of inductive reasoning, such as Raven's Advanced Progressive Matrices, also showed similar age group mean differences across settings. Implications for employee selection and adverse impact on older job candidates are discussed.


Inhibition of aryl sulfotransferase by carboxylic acids.
Aryl sulfotransferase (AST) IV catalyzes the 3'-phosphoadenosine-5'-phosphosulfate-dependent formation of sulfuric acid esters of a wide range of phenols, benzylic alcohols, hydroxamic acids, catecholamines, tyrosine carboxylesters, and peptides with N-terminal tyrosines. The objective of this investigation was to determine whether aryl carboxylic acids could act either as substrates or inhibitors for AST IV. These studies were conducted with AST IV that was purified to homogeneity from male Sprague-Dawley rats. Although none of the carboxylic acids tested were substrates for AST IV, they did competitively inhibit the enzyme with 1-naphthalenemethanol as substrate at pH 7.0. 1-Naphthoic acid, 2-naphthoic acid, and salicylic acid were particularly effective inhibitors of the sulfotransferase. The distance of the carboxyl group from the aromatic ring influenced the inhibitory capability of the carboxylic acids examined. The Kis for 1-naphthylacetic acid and 2-naphthylacetic acid as inhibitors of AST IV-catalyzed sulfation of 1-naphthalenemethanol were approximately 10-fold higher than those of the corresponding naphthoic acids. A substituted 2-naphthylacetic acid derivative, naproxen, also inhibited the aryl sulfotransferase. Preliminary studies indicate that aryl carboxylic acids also inhibit sulfation of phenols catalyzed by AST IV. 2-Naphthoic acid inhibited the sulfation of 2-naphthol catalyzed by AST IV at pH 5.5 with a Ki of 260 microM. In addition to these results with the homogeneous sulfotransferase, inhibition of aryl sulfotransferase activity by carboxylic acids was also observed in rat hepatic 100,000 g supernatant fractions. Thus, aryl carboxylic acids represent a new class of inhibitors for AST IV.


A comparative study of violence risk assessment tools: a systematic review and metaregression analysis of 68 studies involving 25,980 participants.
There are a large number of structured instruments that assist in the assessment of antisocial, violent and sexual risk, and their use appears to be increasing in mental health and criminal justice settings. However, little is known about which commonly used instruments produce the highest rates of predictive validity, and whether overall rates of predictive validity differ by gender, ethnicity, outcome, and other study characteristics. We undertook a systematic review and meta-analysis of nine commonly used risk assessment instruments following PRISMA guidelines. We collected data from 68 studies based on 25,980 participants in 88 independent samples. For 54 of the samples, new tabular data was provided directly by authors. We used four outcome statistics to assess rates of predictive validity, and analyzed sources of heterogeneity using subgroup analysis and metaregression. A tool designed to detect violence risk in juveniles, the Structured Assessment of Violence Risk in Youth (SAVRY), produced the highest rates of predictive validity, while an instrument used to identify adults at risk for general offending, the Level of Service Inventory-Revised (LSI-R), and a personality scale commonly used for the purposes of risk assessment, the Psychopathy Checklist-Revised (PCL-R), produced the lowest. Instruments produced higher rates of predictive validity in older and in predominantly White samples. Risk assessment procedures and guidelines by mental health services and criminal justice systems may need review in light of these findings.


A modified mobilization-with-movement to treat a lateral ankle sprain.
Lateral ankle sprains (LAS) are common in sports medicine and can result in a high rate of re-injury and chronic ankle instability (CAI). Recent evidence supports the use on mobilizations directed at the ankle in patients who have suffered a LAS. The Mulligan Concept of Mobilization-with-Movement (MWM) provides an intervention strategy for LASs, but requires pain-free mobilization application and little literature exists on modifications of these techniques. To present the use of a modified MWM to treat LASs when the traditional MWM technique could not be performed due to patient reported pain and to assess outcomes of the treatment. The subject of this case report is a 23 year-old female collegiate basketball player who had failed to respond to initial conservative treatments after being diagnosed with a lateral ankle sprain. The initial management and subsequent interventions are presented. After re-examination, the addition of a modification of a MWM technique produced immediate and clinically significant changes in patient symptoms. The use of the modified-MWM resulted in full resolution of symptoms and a rapid return to full athletic participation. After the initial application of the modified-MWM, the patient reported immediate pain-free ankle motion and ambulation. Following a total of 5 treatments, using only the modified MWM and taping technique, the patient was discharged with equal range of motion (ROM) bilaterally, a decreased Disablement in the Physically Active (DPA) Scale score, and an asymptomatic physical exam. Follow-up exam 6 weeks later indicated a full maintenance of these results. Recent evidence has been presented to support the use of mobilization techniques to treat patient limitations following ankle injury; however, the majority of evidence is associated with addressing the talar and dorsiflexion limitations. Currently, little evidence is available regarding the use of the MWM technique designed for LASs and the expected outcomes. This case adds to the emerging evidence supporting the use for MWMs to treat ankle pathology and introduces a modification that may be applied in cases where patient reported pain prevents traditional application. Level 5; Single case report.


Different traits determine introduction, naturalization and invasion success in woody plants: Proteaceae as a test case.
A major aim of invasion ecology is to identify characteristics of successful invaders. However, most plant groups studied in detail (e.g. pines and acacias) have a high percentage of invasive taxa. Here we examine the global introduction history and invasion ecology of Proteaceae--a large plant family with many taxa that have been widely disseminated by humans, but with few known invaders. To do this we compiled a global list of species and used boosted regression tree models to assess which factors are important in determining the status of a species (not introduced, introduced, naturalized or invasive). At least 402 of 1674 known species (24%) have been moved by humans out of their native ranges, 58 species (14%) have become naturalized but not invasive, and 8 species (2%) are invasive. The probability of naturalization was greatest for species with large native ranges, low susceptibility to Phytophthora root-rot fungus, large mammal-dispersed seeds, and with the capacity to resprout. The probability of naturalized species becoming invasive was greatest for species with large native ranges, those used as barrier plants, tall species, species with small seeds, and serotinous species. The traits driving invasiveness of Proteaceae were similar to those for acacias and pines. However, while some traits showed a consistent influence at introduction, naturalization and invasion, others appear to be influential at one stage only, and some have contrasting effects at different stages. Trait-based analyses therefore need to consider different invasion stages separately. On their own, these observations provide little predictive power for risk assessment, but when the causative mechanisms are understood (e.g. Phytophthora susceptibility) they provide valuable insights. As such there is considerable value in seeking the correlates and mechanisms underlying invasions for particular taxonomic or functional groups.


Effect of caregiving at end of life on grief, quality of life and general health: A prospective, longitudinal, comparative study.
Determining the effect of caregiving and bereavement remains a challenge. To date, no study has employed a comparison group to investigate caregivers' grief, quality of life and general health in relation to non-caregivers. We aimed to determine how caregivers' grief, quality of life and general health changed following death compared to non-caregivers and whether pre-death grief predicted these outcomes. A prospective, longitudinal study of family caregivers and a comparison group matched for age, gender and postcode was conducted. All participants completed questionnaires at four points - once pre-death and three times post-death (3-4 months, 6-7 months and 9-10 months). Participants (N = 70) were family caregivers of persons receiving palliative care, mostly for cancer, recruited from three palliative care providers in Western Australia and matched comparisons recruited from advertisements. There were significant differences between the caregivers' and comparisons' grief, general health and quality of life at pre-death, 3-4 months and 6-7 months post-death, but not at 9-10 months post-death. The rate of progression in these constructs following death was independent from the intensity of pre-death grief. However, caregiver prolonged grief score significantly predicted prolonged grief score at 6-7 and 9-10 months post-death. It took 9-10 months for the caregivers' grief, general health and quality of life to correspond to the comparison group. These findings present an opportunity for palliative care research and practice to consider how best to support the majority of caregivers without grief complications so that their pre- and post-death support needs are realised.


Double-Edge Sword of Sustained ROCK Activation in Prion Diseases through Neuritogenesis Defects and Prion Accumulation.
In prion diseases, synapse dysfunction, axon retraction and loss of neuronal polarity precede neuronal death. The mechanisms driving such polarization defects, however, remain unclear. Here, we examined the contribution of RhoA-associated coiled-coil containing kinases (ROCK), key players in neuritogenesis, to prion diseases. We found that overactivation of ROCK signaling occurred in neuronal stem cells infected by pathogenic prions (PrPSc) and impaired the sprouting of neurites. In reconstructed networks of mature neurons, PrPSc-induced ROCK overactivation provoked synapse disconnection and dendrite/axon degeneration. This overactivation of ROCK also disturbed overall neurotransmitter-associated functions. Importantly, we demonstrated that beyond its impact on neuronal polarity ROCK overactivity favored the production of PrPSc through a ROCK-dependent control of 3-phosphoinositide-dependent kinase 1 (PDK1) activity. In non-infectious conditions, ROCK and PDK1 associated within a complex and ROCK phosphorylated PDK1, conferring basal activity to PDK1. In prion-infected neurons, exacerbated ROCK activity increased the pool of PDK1 molecules physically interacting with and phosphorylated by ROCK. ROCK-induced PDK1 overstimulation then canceled the neuroprotective α-cleavage of normal cellular prion protein PrPC by TACE α-secretase, which physiologically precludes PrPSc production. In prion-infected cells, inhibition of ROCK rescued neurite sprouting, preserved neuronal architecture, restored neuronal functions and reduced the amount of PrPSc. In mice challenged with prions, inhibition of ROCK also lowered brain PrPSc accumulation, reduced motor impairment and extended survival. We conclude that ROCK overactivation exerts a double detrimental effect in prion diseases by altering neuronal polarity and triggering PrPSc accumulation. Eventually ROCK emerges as therapeutic target to combat prion diseases.


Body-Weight Fluctuation and Incident Diabetes Mellitus, Cardiovascular Disease, and Mortality: A 16-Year Prospective Cohort Study.
Body-weight fluctuation (weight cycling) has been found to be associated with higher mortality and cardiovascular events in patients with coronary artery disease. However, there are very limited data regarding the relationship between body-weight fluctuation and health-related outcomes in the general population. We examined whether body-weight fluctuation can associate incident diabetes mellitus and cardiovascular events, and mortality in a Korean population from the Korean Genome and Epidemiology Study. The intraindividual fluctuations of body weight were calculated by average successive variability (ASV); health-related outcomes were collected every 2 years for 16 years in 3,678 participants. Participants with a high ASV of body weight were more obese and had higher blood pressure and HbA1c levels at baseline than those with a low ASV of body weight. A 1-unit increase in ASV of body weight was associated with increase in mortality (HR, 1.46; 95% CI, 1.32 to 1.62; P < 0.001). However, the association between the ASV of body weight and incident diabetes mellitus seemed to be influenced by baseline body mass index (BMI): negative effect in subjects with BMI <25 kg/m2 (HR, 1.36; 95% CI, 1.11 to 1.65; P = 0.003) and protective effect in those with BMI ≥25 kg/m2 (HR, 0.76; 95% CI, 0.60 to 0.95; P = 0.014). There was no association between the ASV of body weight and cardiovascular event. Body-weight fluctuation was associated with mortality. In addition, the effect of body-weight fluctuation on incident diabetes mellitus depended on the presence of obesity at baseline.


Genetic differentiation between resistance phenotypes in the phytophagous flea beetle, Phyllotreta nemorum.
The flea beetle Phyllotreta nemorum L. (Coleoptera: Chrysomelidae) is genetically polymorphic for resistance against the defences of one of its host plants, Barbarea vulgaris R.Br. (Brassicales: Brassicaceae). Whereas resistant flea beetles are able to use B. vulgaris as well as other cruciferous plants as food, non-resistant beetles cannot survive on B. vulgaris. This limitation to host plant use of non-resistant beetles could potentially lead to asymmetric gene flow and some degree of genetic isolation between the different resistance-genotypes. Therefore, we studied the extent of genetic differentiation at neutral allozyme loci between samples of flea beetles that were collected at different locations and first tested for resistance phenotype. Since earlier work has shown a weak, but significant, effect of geographical distance between the samples on their genetic differentiation, in the present study variation at the neutral allozyme loci in P. nemorum was partitioned between geographical distance and resistance-phenotype. Both sources independently contributed statistically significantly to population differentiation. Thus, there appears to be a limitation to genetic exchange between the resistant and non-resistant flea beetles when corrections are made for their geographic differentiation. This is consistent with the presence of some degree of host race formation in this flea beetle.


Amorphous to crystal conversion as a mechanism governing the structure of luminescent YVO4:Eu nanoparticles.
The development of functional materials by taking advantage of the physical properties of nanoparticles needs an optimal control over their size and crystal quality. In this context, the synthesis of crystalline oxide nanoparticles in water at room temperature is a versatile and industrially appealing process but lacks control especially for "large" nanoparticles (>30 nm), which commonly consist of agglomerates of smaller crystalline primary grains. Improvement of these syntheses is hampered by the lack of knowledge on possible intermediate, noncrystalline stages, although their critical importance has already been outlined in crystallization processes. Here, we show that during the synthesis of luminescent Eu-doped YVO4 nanoparticles a transient amorphous network forms with a two-level structuration. These two prestructuration scales constrain topologically the nucleation of the nanometer-sized crystalline primary grains and their aggregation in nanoparticles, respectively. This template effect not only clarifies why the crystal size is found independent of the nucleation rate, in contradiction with the classical nucleation models, but also supports the possibility to control the final nanostructure with the amorphous phase.


Quantum state specific reactant preparation in a molecular beam by rapid adiabatic passage.
Highly efficient preparation of molecules in a specific rovibrationally excited state for gas/surface reactivity measurements is achieved in a molecular beam using tunable infrared (IR) radiation from a single mode continuous wave optical parametric oscillator (cw-OPO). We demonstrate that with appropriate focusing of the IR radiation, molecules in the molecular beam crossing the fixed frequency IR field experience a Doppler tuning that can be adjusted to achieve complete population inversion of a two-level system by rapid adiabatic passage (RAP). A room temperature pyroelectric detector is used to monitor the excited fraction in the molecular beam and the population inversion is detected and quantified using IR bleaching by a second IR-OPO. The second OPO is also used for complete population transfer to an overtone or combination vibration via double resonance excitation using two spatially separated RAP processes.


Calcium-Activated Chloride Channel A4 (CLCA4) Plays Inhibitory Roles in Invasion and Migration Through Suppressing Epithelial-Mesenchymal Transition via PI3K/AKT Signaling in Colorectal Cancer.
BACKGROUND Calcium-activated chloride channel A4 (CLCA4) is known as a tumor suppressor which contributes to the progression of a number of types of malignant tumors. However, little is known about the functional roles of CLCA4 in colorectal cancer (CRC). MATERIAL AND METHODS In this study, the expression patterns and dysregulation of mRNAs in CRC tissues were profiled by analyzing GSE21510 datasets from Gene Expression Omnibus database which contains 104 primary hepatocellular carcinoma tissues and 24 normal liver tissues, and by performing Kaplan-Meier analysis of TCGA data. Additionally, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) were performed using clinical tissues collected at our institute. In order to explore the functional role of CLCA4, gain-of-function cell models were constructed in SW620 and LoVo cells. Wound healing assay and Transwell assay were carried out to access the cell migration and invasion ability. RESULTS It was found that CLCA4 was an independent predictor for overall survival and lymph node metastasis. Additionally, immunohistochemistry and qRT-PCR results of the clinical tissues collected as part of our study further confirmed this correlation. In vitro experiments demonstrated that over-expression of CLCA4 could inhibit cell migration and invasion by suppressing epithelial-mesenchymal transition (EMT) via PI3K/ATK signaling and change the expression patterns of EMT markers in CLCA4-gain-of-function cell models. CONCLUSIONS CLCA4 inhibits migration and invasion by suppressing EMT via PI3K/ATK signaling and predicts favorable prognosis of CRC which may help to distinguish potential risk of lymph node metastasis in CRC.


Problematic Child Mealtime Behavior and Caregiver Mobile Phone Use.
To evaluate the associations of caregiver mobile phone problematic use and child problematic mealtime behaviors (PMBs) to improve understanding of the possible implications of caregiver mobile phone problematic use. Surveys were administered to caregivers of children aged 3 to 8 years. The survey included demographics, a validated measure for caregiver mobile phone problematic use (Mobile Phone Problematic Use Scale-10 [MPPUS-10]), and a validated measure for the perception of child PMB (Meals in our Household [MIOH]). The bivariate associations between child and caregiver characteristics, mobile phone problematic use, and PMBs of children were analyzed. Partial correlations examined these relations while controlling for significant (p ≤ 0.05) covariates. Eighty-four caregivers (mean age 32.6 years, 63% white, 21% ≤ high school completion) participated. The correlation of MIOH problematic behavior total with MPPUS-10 was significant (r = 0.33, p ≤ 0.01). Significantly correlated caregiver variables with MPPUS-10 included age (r = -0.25, p = 0.02) and female sex (p = 0.01). No significant caregiver variables were noted for PMB. Child's age was significantly correlated with PMB (r = -0.27, p = 0.01). MPPUS-10 and PMB correlation remained significant when controlling for significant covariates. A positive correlation existed between MPPUS-10 and PMB. Understanding the potential association between caregiver mobile phone problematic use and child PMB strengthens the pediatricians' ability to counsel about the implications of caregiver mobile phone problematic use when discussing child PMB.


Multigrid algorithm for least-squares wavefront reconstruction.
Multigrid (MG) methods are presented for fast, efficient, flexible, and robust least-squares wavefront reconstruction in extremely high-resolution conventional adaptive optics, or ExAO. We demonstrate that MG can robustly handle a variety of sensor-actuator geometries, and it can accommodate deformable mirror influence function models that are more realistic than the common piecewise bilinear model. With MG one can also easily incorporate additional penalty, or regularization, terms to damp out the waffle mode in Fried geometry and to damp out instabilities due to actuators near the pupil boundary with poorly sensed influence. We present closed-loop simulation results that suggest that only one or two MG iterations per time step are needed to control an ExAO system.


Decreasing pro-inflammatory cytokine and reversing the immunosenescence with extracts of Pu-erh tea in senescence accelerated mouse (SAM).
Immunosenescence, the progressive decline of adaptive immunity and chronic inflammation with ageing has been demonstrated to be the main factor responsible for infections, cancer and autoimmune conditions in the elderly. Senescence-accelerated mouse (SAM) was used to study the protective effects of Pu-erh tea in the elderly. The senile-prone sub-strain, SAM-P8 mice were administered individually with ripened or crude Pu-erh tea at 125, 250 or 500mg/kg. The results showed that Pu-erh tea significantly increased the fractions of naïve T lymphocytes, CD8(+)CD28(+) T lymphocytes and NK cells in the peripheral blood, but decreased the levels of IL-6 in aged mice. These data suggested that the Pu-erh tea reversed the immunosenescence by restoring the immune deficiency and decreasing pro-inflammatory cytokine. Thus, long term drinking of Pu-erh tea may be beneficial for the aged population in terms of increasing the body's resistance to infection and cancer.


Modulation of ion transport across rat distal colon by cysteine.
The aim of this study was to identify the actions of stimulation of endogenous production of H(2)S by cysteine, the substrate for the two H(2)S-producing enzymes, cystathionine-β-synthase and cystathionine-γ-lyase, on ion transport across rat distal colon. Changes in short-circuit current (Isc) induced by cysteine were measured in Ussing chambers. Free cysteine caused a concentration-dependent, transient fall in Isc, which was sensitive to amino-oxyacetate and β-cyano-L-alanine, i.e., inhibitors of H(2)S-producing enzymes. In contrast, Na cysteinate evoked a biphasic change in Isc, i.e., an initial fall followed by a secondary increase, which was also reduced by these enzyme inhibitors. All responses were dependent on the presence of Cl(-) and inhibited by bumetanide, suggesting that free cysteine induces an inhibition of transcellular Cl(-) secretion, whereas Na cysteinate - after a transient inhibitory phase - activates anion secretion. The assumed reason for this discrepancy is a fall in the cytosolic pH induced by free cysteine, but not by Na cysteinate, as observed in isolated colonic crypts loaded with the pH-sensitive dye, BCECF. Intracellular acidification is known to inhibit epithelial K(+) channels. Indeed, after preinhibition of basolateral K(+) channels with tetrapentylammonium or Ba(2+), the negative Isc induced by free cysteine was reduced significantly. In consequence, stimulation of endogenous H(2)S production by Na cysteinate causes, after a short inhibitory response, a delayed activation of anion secretion, which is missing in the case of free cysteine, probably due to the cytosolic acidification. In contrast, diallyl trisulfide, which is intracellularly converted to H(2)S, only evoked a monophasic increase in Isc without the initial fall observed with Na cysteinate. Consequently, time course and amount of produced H(2)S seem to strongly influence the functional response of the colonic epithelium evoked by this gasotransmitter.


Spinning out a star.
Spinouts rarely take off; most, in fact, fall into one or more of four traps that doom them from the start. Some companies spin out ventures that are too close to the core of their businesses, in effect selling off their crown jewels. Sometimes, a parent company uses the spinout primarily to pawn off debt or expenses or to quickly raise external capital for itself. Other times, a company may try to spin out an area of its business that lacks one or more of the critical legs of a successful company--a coherent business model, say, or a solid financial base. And in many cases, parent companies can't bring themselves to sever their ownership ties and give up control of their spinouts. R.J. Reynolds, the tobacco giant, managed to avoid these traps when it successfully spun out a most unlikely venture, the pharmaceutical company Targacept. As the story illustrates, the problem with spinouts is similar to the problem of rich children. Their parents have the wherewithal to spoil them or shelter them or cling to them, but what they need is tough love and discipline--much the same discipline that characterizes successful start-ups. R.J. Reynolds recognized that it didn't know that much about the pharmaceutical business and couldn't merely try to spin out a small clone of itself. It had to treat the venture as if it were essentially starting from scratch, with a passionate entrepreneurial leader, a solid business plan, help from outside partners in the industry, and ultimately substantial venture backing. That these lessons are less obvious to executives contemplating spinning out ventures closer to their core businesses may be why so many spinouts fail.


Rotating Night-Shift Work and the Risk of Breast Cancer in the Nurses' Health Studies.
In 2007, the International Agency for Research on Cancer declared shift work that involved circadian disruption to be a "probable" carcinogen (group 2A), noting that human evidence was limited. Using data from 2 prospective cohort studies, the Nurses' Health Study (1988-2012; n = 78,516) and Nurses' Health Study II (1989-2013; n = 114,559), we examined associations between rotating night-shift work and breast cancer risk. In the 2 cohorts, there were a total of 9,541 incident invasive breast malignancies and 24 years of follow-up. In the Nurses' Health Study, women with 30 years or more of shift work did not have a higher risk of breast cancer (hazard ratio (HR) = 0.95, 95% confidence interval (95% CI): 0.77, 1.17; P for trend = 0.63) compared with those who never did shift work, although follow-up occurred primarily after retirement from shift work. Among participants in the Nurses' Health Study II, who were younger than participants in the other cohort, the risk of breast cancer was significantly higher in women with 20 years or more of shift work at baseline, reflecting young-adult exposure (HR = 2.15, 95% CI: 1.23, 3.73; P for trend = 0.23), and was marginally significantly higher for women with 20 years or more of cumulative shift work when we used updated exposure information (HR = 1.40, 95% CI: 1.00, 1.97; P for trend = 0.74). In conclusion, long-term rotating night-shift work was associated with a higher risk of breast cancer, particularly among women who performed shift work during young adulthood. Further studies should explore the role of shift work timing on breast cancer risk.


Management of alcohol misuse in Scotland: the role of A&E nurses.
Despite national targets to reduce excessive drinking in Scotland, rates have increased dramatically since the mid-eighties. The role of Accident and Emergency (A&E) departments in the management of alcohol misuse is much debated. This postal survey was conducted with senior medical and nursing staff in A&E departments and minor injury units throughout Scotland to examine the prevalence of alcohol-related attendances and staff's attitudes towards identifying and responding to alcohol-related attendances. A 57% response rate was achieved, representing 87% of all A&E institutions in Scotland (n = 84). The results reveal an estimated 1 in 7 attendances in A&E in Scotland are alcohol-related, and 1 in 5 of these result in admission. However, over two-fifths of departments do not routinely screen for, or keep records of, patients who attend with alcohol problems. Intervention is normally limited to a brief dialogue and referral to the patient's GP. Despite considerable barriers, A&E nursing staff express a willingness to assume a preventive role, but acknowledge lack of appropriate training and sources of support. It is concluded that there is scope for developing identification and brief intervention services within A&E. However, such developments are dependent upon alcohol issues assuming a higher priority among senior A&E staff.


Measurement of the radioactivity in the excreta of cats treated with iodine-131 for hyperthyroidism.
When hyperthyroidism is treated with radioiodine, up to 75 per cent of the injected dose is excreted in the faeces and urine, which poses hazards to handlers. Three groups of hyperthyroid cats were treated with 120, 150 and 200 megabecquerel (MBq) of radioiodine, and samples of faeces and urine-soaked litter (USL) were collected over a 24-hour period, once a week, for four weeks. The amount of radioactivity in each homogenised sample was then measured using a sodium iodide detector. Radioactivity significantly decreased in both the faecal and USL samples over the first three weeks. Regardless of dose, there was no significant difference in faecal and USL samples between weeks 3 and 4. Faecal radioactivity was generally higher than the USL, but both were variable between cats at each time point. There were some significant differences in radioactivity between doses at various time points, but these were very small compared with the differences between time points. From the results, the maximum likely exposure to a worker or owner handling the waste was calculated. For cats treated with up to 200 MBq, radioactivity levels after two weeks were such that the waste could be designated as 'very low level waste' (a UK statutory definition) for disposal purposes.


Polyamine quinoline rhodium complexes: synthesis and pharmacological evaluation as antiparasitic agents against Plasmodium falciparum and Trichomonas vaginalis.
A series of mono- and bis-salicylaldimine ligands and their corresponding Rh(i) complexes were prepared. The compounds were characterised using standard spectroscopic techniques including NMR, IR spectroscopy and mass spectrometry. The salicylaldimine ligands and complexes were screened for antiparasitic activity against two strains of Plasmodium falciparum i.e. the NF54 CQ-sensitive and K1 CQ-resistant strain as well as against the G3 isolate of Trichomonas vaginalis. The monomeric salicylaldimine quinolines exhibited good activity against the NF54 strain and the dimeric salicylaldimine quinolines exhibited no cross resistance across the two strains. The binuclear 5-chloro Rh(i) complex displayed the best activity against the Trichomonas vaginalis parasite, possibly a consequence of its enhanced lipophilicity. The compounds were also screened for cytotoxicity in vitro against WHCO1 oesophageal cancer cells. The monomeric salicylaldimine quinolines exhibited high selectivity towards malaria parasites compared to cancer cells, while the dimeric compounds were less selective.


Extending resuscitative endovascular balloon occlusion of the aorta: Endovascular variable aortic control in a lethal model of hemorrhagic shock.
The duration of use and efficacy of resuscitative endovascular balloon occlusion of the aorta (REBOA) is limited by distal ischemia. We developed a hybrid endovascular-extracorporeal circuit variable aortic control (VAC) device to extend REBOA duration in a lethal model of hemorrhagic shock to serve as an experimental surrogate to further the development of endovascular VAC (EVAC) technologies. Nine Yorkshire-cross swine were anesthetized, instrumented, splenectomized, and subjected to 30% liver amputation. Following a short period of uncontrolled hemorrhage, REBOA was instituted for 20 minutes. Automated variable occlusion in response to changes in proximal mean arterial pressure was applied for the remaining 70 minutes of the intervention phase using the automated extracorporeal circuit. Damage-control surgery and whole blood resuscitation then occurred, and the animals were monitored for a total of 6 hours. Seven animals survived the initial surgical preparation. After 20 minutes of complete REBOA, regulated flow was initiated through the extracorporeal circuit to simulate VAC and provide perfusion to distal tissue beds during the 90-minute intervention phase. Two animals required circuit occlusion for salvage, while five animals tolerated sustained, escalating restoration of distal blood flow before surgical hemorrhage control. Animals tolerating distal flow had preserved renal function, maintained proximal blood pressure, and rapidly weaned from complete REBOA. We combined a novel automated, extracorporeal circuit with complete REBOA to achieve EVAC in a swine model of uncontrolled hemorrhage. Our approach regulated proximal aortic pressure, alleviated supranormal values above the balloon, and provided controlled distal aortic perfusion that reduced ischemia without inducing intolerable bleeding. This experimental model serves as a temporary surrogate to guide future EVAC catheter designs that may provide transformational approaches to hemorrhagic shock.


Nathusius' bats optimize long-distance migration by flying at maximum range speed.
Aerial migration is the fastest, yet most energetically demanding way of seasonal movement between habitats. However, for many taxa, and bats in particular, we lack a clear understanding of the energy requirements for migration. Here, we examined the energetic cost and flight speed of the long-distance migratory Nathusius' bat (Pipistrellus nathusii). We measured flight metabolism in relation to airspeed in a wind tunnel, inferred the optimal traveling speed over long distances, i.e. maximum range speed, and compared this value with flight speed measured in wild conspecifics. Body mass and wing morphologies were similar in captive and wild bats, indicating that the body condition of captive bats was similar to that of migratory bats. Nine out of the 12 captive bats exhibited a U-shaped relationship between flight metabolic power and airspeed when flying in the wind tunnel. The flight metabolic rate across all airspeeds averaged 0.98±0.28 W, which corresponds well to established allometric relationships between flight metabolic rate and body mass for bats. During summer migration, P. nathusii traveled at an average speed of 6.9±0.7 m s-1, which was significantly higher than the minimum power speed (5.8±1.0 m s-1), yet within the range of expected maximum range speed inferred from wind tunnel experiments. This suggests that P. nathusii may migrate at an energetically optimal speed and that aerial refueling does not substantially lower migratory speed in P. nathusii.


Stakeholders' perspectives on the future of artificial intelligence in radiology: a scoping review.
Artificial intelligence (AI) has the potential to impact clinical practice and healthcare delivery. AI is of particular significance in radiology due to its use in automatic analysis of image characteristics. This scoping review examines stakeholder perspectives on AI use in radiology, the benefits, risks, and challenges to its integration. A search was conducted from 1960 to November 2019 in EMBASE, PubMed/MEDLINE, Web of Science, Cochrane Library, CINAHL, and grey literature. Publications reflecting stakeholder attitudes toward AI were included with no restrictions. Commentaries (n = 32), surveys (n = 13), presentation abstracts (n = 8), narrative reviews (n = 8), and a social media study (n = 1) were included from 62 eligible publications. These represent the views of radiologists, surgeons, medical students, patients, computer scientists, and the general public. Seven themes were identified (predicted impact, potential replacement, trust in AI, knowledge of AI, education, economic considerations, and medicolegal implications). Stakeholders anticipate a significant impact on radiology, though replacement of radiologists is unlikely in the near future. Knowledge of AI is limited for non-computer scientists and further education is desired. Many expressed the need for collaboration between radiologists and AI specialists to successfully improve patient care. Stakeholder views generally suggest that AI can improve the practice of radiology and consider the replacement of radiologists unlikely. Most stakeholders identified the need for education and training on AI, as well as collaborative efforts to improve AI implementation. Further research is needed to gain perspectives from non-Western countries, non-radiologist stakeholders, on economic considerations, and medicolegal implications. Stakeholders generally expressed that AI alone cannot be used to replace radiologists. The scope of practice is expected to shift with AI use affecting areas from image interpretation to patient care. Patients and the general public do not know how to address potential errors made by AI systems while radiologists believe that they should be "in-the-loop" in terms of responsibility. Ethical accountability strategies must be developed across governance levels. Students, residents, and radiologists believe that there is a lack in AI education during medical school and residency. The radiology community should work with IT specialists to ensure that AI technology benefits their work and centres patients.


Mechanisms controlling phosphorus retention capacity in freshwater wetlands.
Freshwater wetland ecosystems do not effectively conserve phosphorus in the way that terrestrial ecosystems do. The phosphorus retention capacity varies greatly among bogs, fens, and swamps and is concomitant with the amorphous acid oxalate-extractable aluminum and iron content in the soil. However, the phosphorus adsorption potential in wetland ecosystems may be predicted solely from the extractable aluminum content of the soil. Wetlands tested as wastewater filtration systems became phosphorus-saturated in a few years, with the export of excessive quantities of phosphate.


Carrier-Assisted Single-Tube Processing Approach for Targeted Proteomics Analysis of Low Numbers of Mammalian Cells.
Heterogeneity in composition is inherent in all cell populations, even those containing a single cell type. Single-cell proteomics characterization of cell heterogeneity is currently achieved by antibody-based technologies, which are limited by the availability of high-quality antibodies. Herein we report a simple, easily implemented, mass spectrometry (MS)-based targeted proteomics approach, termed cLC-SRM (carrier-assisted liquid chromatography coupled to selected reaction monitoring), for reliable multiplexed quantification of proteins in low numbers of mammalian cells. We combine a new single-tube digestion protocol to process low numbers of cells with minimal loss together with sensitive LC-SRM for protein quantification. This single-tube protocol builds upon trifluoroethanol digestion and further minimizes sample losses by tube pretreatment and the addition of carrier proteins. We also optimized the denaturing temperature and trypsin concentration to significantly improve digestion efficiency. cLC-SRM was demonstrated to have sufficient sensitivity for reproducible detection of most epidermal growth factor receptor (EGFR) pathway proteins expressed at levels ≥30 000 and ≥3000 copies per cell for 10 and 100 mammalian cells, respectively. Thus, cLC-SRM enables reliable quantification of low to moderately abundant proteins in less than 100 cells and could be broadly useful for multiplexed quantification of important proteins in small subpopulations of cells or in size-limited clinical samples. Further improvements of this method could eventually enable targeted single-cell proteomics when combined with either SRM or other emerging ultrasensitive MS detection.


Optimizing the restoration and maintenance of fluid balance after exercise-induced dehydration.
Hypohydration, or a body water deficit, is a common occurrence in athletes and recreational exercisers following the completion of an exercise session. For those who will undertake a further exercise session that day, it is important to replace water losses to avoid beginning the next exercise session hypohydrated and the potential detrimental effects on performance that this may lead to. The aim of this review is to provide an overview of the research related to factors that may affect postexercise rehydration. Research in this area has focused on the volume of fluid to be ingested, the rate of fluid ingestion, and fluid composition. Volume replacement during recovery should exceed that lost during exercise to allow for ongoing water loss; however, ingestion of large volumes of plain water results in a prompt diuresis, effectively preventing longer-term maintenance of water balance. Addition of sodium to a rehydration solution is beneficial for maintenance of fluid balance due to its effect on extracellular fluid osmolality and volume. The addition of macronutrients such as carbohydrate and protein can promote maintenance of hydration by influencing absorption and distribution of ingested water, which in turn effects extracellular fluid osmolality and volume. Alcohol is commonly consumed in the postexercise period and may influence postexercise rehydration, as will the coingestion of food. Future research in this area should focus on providing information related to optimal rates of fluid ingestion, advisable solutions to ingest during different duration recovery periods, and confirmation of mechanistic explanations for the observations outlined.


Matrilysin-1 (MMP7) cleaves galectin-3 and inhibits wound healing in intestinal epithelial cells.
Galectin-3 is an animal lectin that has been implicated in wound healing and is decreased in inflammatory bowel disease (IBD). Matrix metalloproteinase-7 (MMP7), also known as matrilysin-1, a protease shown to cleave extracellular matrix proteins, is highly expressed in IBD tissues, especially at the leading edge of gastrointestinal ulcers. The ability of MMP7 to cleave galectin-3 and influence wound healing has not been reported previously. The aim was to determine whether MMP7 cleaves galectin-3 and modulates wound healing in intestinal epithelial cells. The cleaved fragments of galectin-3 were identified by N-terminal sequencing and mass spectrometry. Western blotting was used to detect the cleaved galectin-3 products in a colonic epithelial cell line (T84 cells). Cell migration was studied by the in vitro scratch method. We demonstrate for the first time that MMP7 cleaves galectin-3 in vitro, resulting in three cleaved fragments (20.2 kDa, 18.9 kDa, and 15.5 kDa). Exogenous treatment of T84 cells with recombinant MMP7 resulted in the appearance of secreted galectin-3 cleavage fragments in the supernatant. MMP7 inhibited cell migration and resulted in wound retraction and the addition of MMP7 to galectin-3 abrogated the wound healing and cell migration induced by galectin-3. We have demonstrated that galectin-3 is a substrate for MMP7. Cleavage of galectin-3 may be one mechanism by which MMP7 inhibits wound healing. This study has significance in understanding delayed wound healing in chronic intestinal diseases like intestinal ulcers and IBD, where MMP7 protein expression is elevated with a decreased galectin-3 protein expression.


Health-related quality of life in childhood epilepsy: moving beyond 'seizure control with minimal adverse effects'.
Childhood epilepsy is one of the most important and prevalent neurological conditions in the developing years. Persons with childhood onset epilepsy are at a high risk for poor psychosocial outcomes, even without experiencing co-morbidities. The goal of management of children with epilepsy should be to enable the child and the family to lead a life as free as possible from the medical and psychosocial complications of epilepsy. This comprehensive care needs to go beyond simply trying to control seizures with minimal adverse drug reactions. Seizure frequency and severity is only one important outcome variable. Other factors such as social, psychological, behavioural, educational, and cultural dimensions of their lives affect children with epilepsy, their families and their close social networks. A number of epilepsy-specific health-related quality of life (HRQL) scales for children have been developed with the aim to include and measure accurately the impact and burden of epilepsy. Their target populations, details of the origin of the items, and psychometric properties vary significantly. Their strengths and weaknesses will be identified more clearly through their continued use in the clinical setting and in research studies. Only a few studies to date have utilized these or generic HRQL measures to assess the HRQL of specific populations with epilepsy. Future research needs to develop theory driven models of HRQL and identify measurable factors that have important correlations with outcomes. Since biomedical variables like seizure frequency and severity have only moderate correlations with HRQL, other independent factors including the child's resilience, co-morbid conditions, parental well-being, family factors and societal/cultural variables may play a major role. We also need to learn what encompasses comprehensive patient care, define the goals of management and evaluate the impact of different interventions. Future studies need to include the children's own perspectives of their HRQL in addition to parental reports. Finally, clinicians need to familiarize themselves with outcome measures, be able to evaluate them, and use them routinely in their day-to-day practice.


Four-factor prothrombin complex concentrate versus plasma for rapid vitamin K antagonist reversal in patients needing urgent surgical or invasive interventions: a phase 3b, open-label, non-inferiority, randomised trial.
Rapid reversal of vitamin K antagonist (VKA)-induced anticoagulation is often necessary for patients needing urgent surgical or invasive procedures. The optimum means of VKA reversal has not been established in comparative clinical trials. We compared the efficacy and safety of four-factor prothrombin complex concentrate (4F-PCC) with that of plasma in VKA-treated patients needing urgent surgical or invasive procedures. In a multicentre, open-label, phase 3b randomised trial we enrolled patients aged 18 years or older needing rapid VKA reversal before an urgent surgical or invasive procedure. We randomly assigned patients in a 1:1 ratio to receive vitamin K concomitant with a single dose of either 4F-PCC (Beriplex/Kcentra/Confidex; CSL Behring, Marburg, Germany) or plasma, with dosing based on international normalised ratio (INR) and weight. The primary endpoint was effective haemostasis, and the co-primary endpoint was rapid INR reduction (≤1·3 at 0·5 h after infusion end). The analyses were intended to evaluate, in a hierarchical fashion, first non-inferiority (lower limit 95% CI greater than -10% for group difference) for both endpoints, then superiority (lower limit 95% CI >0%) if non-inferiority was achieved. Adverse events and serious adverse events were reported to days 10 and 45, respectively. This trial is registered at ClinicalTrials.gov, number NCT00803101. 181 patients were randomised (4F-PCC n=90; plasma n=91). The intention-to-treat efficacy population comprised 168 patients (4F-PCC, n=87; plasma, n=81). Effective haemostasis was achieved in 78 (90%) patients in the 4F-PCC group compared with 61 (75%) patients in the plasma group, demonstrating both non-inferiority and superiority of 4F-PCC over plasma (difference 14·3%, 95% CI 2·8-25·8). Rapid INR reduction was achieved in 48 (55%) patients in the 4F-PCC group compared with eight (10%) patients in the plasma group, demonstrating both non-inferiority and superiority of 4F-PCC over plasma (difference 45·3%, 95% CI 31·9-56·4). The safety profile of 4F-PCC was generally similar to that of plasma; 49 (56%) patients receiving 4F-PCC had adverse events compared with 53 (60%) patients receiving plasma. Adverse events of interest were thromboembolic adverse events (six [7%] patients receiving 4F-PCC vs seven [8%] patients receiving plasma), fluid overload or similar cardiac events (three [3%] patients vs 11 [13%] patients), and late bleeding events (three [3%] patients vs four [5%] patients). 4F-PCC is non-inferior and superior to plasma for rapid INR reversal and effective haemostasis in patients needing VKA reversal for urgent surgical or invasive procedures. CSL Behring.


The role of mobile phones as a possible pathway for pathogen movement, a cross-sectional microbial analysis.
Mobile phones are used the world over, including in healthcare settings. This study aimed to investigate the viable microbial colonisation of mobile phones used by healthcare personnel. Swabs collected on the same day from 30 mobile phones belonging to healthcare workers from three separate paediatric wards of an Australian hospital were cultured on five types of agar plate, then colonies from each phone were pooled, extracted and sequenced by shotgun metagenomics. Questionnaires completed by staff whose phones were sampled assisted in the analysis and interpretation of results. All phones sampled cultured viable bacteria. Overall, 399 bacterial operational taxonomic units were identified from 30 phones, with 1432 cumulative hits. Among these were 58 recognised human pathogenic and commensal bacteria (37 Gram-negative, 21 Gram-positive). The total number of virulence factor genes detected was 347, with 1258 cumulative hits. Antibiotic resistance genes (ARGs) were detected on all sampled phones and overall, 133 ARGs were detected with 520 cumulative hits. The most important classes of ARGs detected encoded resistance to beta-lactam, aminoglycoside and macrolide antibiotics and efflux pump mediated resistance mechanisms. Mobile phones carry viable bacterial pathogens and may act as fomites by contaminating the hands of their users and indirectly providing a transmission pathway for hospital-acquired infections and dissemination of antibiotic resistance. Further research is needed, but meanwhile adding touching mobile phones to the five moments of hand hygiene is a simple infection control strategy worth considering in hospital and community settings. Additionally, the implementation of practical and effective guidelines to decontaminate mobile phone devices would likely be beneficial to the hospital population and community at large.