Social Justice Pedagogies in School Health and Physical Education-Building Relationships, Teaching for Social Cohesion and Addressing Social Inequities.
A focus on equity and social justice in school health and physical education (HPE) is pertinent in an era where there are growing concerns about the impact of neoliberal globalization and the precariousness of society. The aim of the present study was to identify school HPE teaching practices that promote social justice and more equitable health outcomes. Data were generated through 20 HPE lesson observations and post-lesson interviews with 13 HPE teachers across schools in Sweden, Norway, and New Zealand. The data were analysed following the principles of thematic analysis. In this paper, we present and discuss findings related to three overall themes: (i) relationships; (ii) teaching for social cohesion; (iii) and explicitly teaching about, and acting on, social inequities. Collectively, these themes represent examples of the enactment of social justice pedagogies in HPE practice. To conclude, we point out the difficulty of enacting social justice pedagogies and that social justice pedagogies may not always transform structures nor make a uniform difference to all students. However, on the basis of our findings, we are reaffirmed in our view that HPE teachers can make a difference when it comes to contributing to more socially just and equitable outcomes in HPE and beyond.


A parallel and distributed-processing model of joint attention, social cognition and autism.
The impaired development of joint attention is a cardinal feature of autism. Therefore, understanding the nature of joint attention is central to research on this disorder. Joint attention may be best defined in terms of an information-processing system that begins to develop by 4-6 months of age. This system integrates the parallel processing of internal information about one's own visual attention with external information about the visual attention of other people. This type of joint encoding of information about self and other attention requires the activation of a distributed anterior and posterior cortical attention network. Genetic regulation, in conjunction with self-organizing behavioral activity, guides the development of functional connectivity in this network. With practice in infancy the joint processing of self-other attention becomes automatically engaged as an executive function. It can be argued that this executive joint attention is fundamental to human learning as well as the development of symbolic thought, social cognition and social competence throughout the life span. One advantage of this parallel and distributed-processing model of joint attention is that it directly connects theory on social pathology to a range of phenomena in autism associated with neural connectivity, constructivist and connectionist models of cognitive development, early intervention, activity-dependent gene expression and atypical ocular motor control.


Implications of respiratory motion for small animal image-guided radiotherapy.
Image-guided small animal irradiators have the potential to make a significant impact on facilitating the translation of radiobiological research into the clinic. To fully exploit the improved precision in dose delivery to the target/tumour while minimizing dose to surrounding tissues, minimal positional error in the target is required. However, for many sites within the thorax and abdomen, respiratory motion may be a critical factor in limiting the accuracy of beam delivery and until now, very little attention has been paid to the impact and management of this motion. We report on the implications of respiratory motion with respect to the negative impact of delivered dose distributions and their assessment, ways being developed to effectively manage this motion, so that beam delivery only occurs during the stationary resting phase of the breathing cycle, and comment on the need to effectively integrate these developments into the software used to plan and control beam delivery. Altogether, the implementation of respiratory-gated imaging and beam delivery will lead to significant improvements in the precision in dose delivery and constitutes an important development for preclinical radiotherapy studies.


Vitamin D for cancer prevention: global perspective.
Higher serum levels of the main circulating form of vitamin D, 25-hydroxyvitamin D (25(OH)D), are associated with substantially lower incidence rates of colon, breast, ovarian, renal, pancreatic, aggressive prostate and other cancers. Epidemiological findings combined with newly discovered mechanisms suggest a new model of cancer etiology that accounts for these actions of 25(OH)D and calcium. Its seven phases are disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition (abbreviated DINOMIT). Vitamin D metabolites prevent disjunction of cells and are beneficial in other phases. It is projected that raising the minimum year-around serum 25(OH)D level to 40 to 60 ng/mL (100-150 nmol/L) would prevent approximately 58,000 new cases of breast cancer and 49,000 new cases of colorectal cancer each year, and three fourths of deaths from these diseases in the United States and Canada, based on observational studies combined with a randomized trial. Such intakes also are expected to reduce case-fatality rates of patients who have breast, colorectal, or prostate cancer by half. There are no unreasonable risks from intake of 2000 IU per day of vitamin D(3), or from a population serum 25(OH)D level of 40 to 60 ng/mL. The time has arrived for nationally coordinated action to substantially increase intake of vitamin D and calcium.


Treatment satisfaction and bothersome bladder, bowel, sexual symptoms in multiple sclerosis.
Bladder, bowel, and sexual symptoms are common among persons with multiple sclerosis (MS). We aimed to investigate the frequency and severity of bladder, bowel, and sexual symptoms, the relationships between these symptoms, satisfaction with treatment of these symptoms, and factors associated with symptom severity and treatment satisfaction. In the fall 2010, we surveyed participants in the North American Research Committee on Multiple Sclerosis (NARCOMS) Registry regarding the severity of being bothered by bladder, bowel, and sexual symptoms, their satisfaction of health providers' inquiry and treatment with these symptoms, and whether their quality of life (QOL) had changed with the treatment. Logistic regression was used to evaluate demographic and clinical factors associated with each outcome. Of 9341 respondents included in the study, 7720 (77.4%) were female and their mean (SD) age was 50.3 (10.5) years. Ninety-one percent of participants were mildly, moderately or severely bothered by bladder, bowel or sexual symptoms. Severity of disability (measured using the Patient Determined Disease Steps), having a relapse in the last 6 months, and catheter use were consistently associated with being bothered (versus not bothered) by each of the three symptoms. Among respondents, 5764 (62.1%) reported that their MS health providers asked about bladder problems, 4523 (51.1%) about bowel problems, and 1890 (20.6%) about sexual problems. At most one-third of participants were completely satisfied with treatment for any of the symptoms. For those who reported how their QOL changed with treatment, 23.0% reported their QOL being better. Bladder, bowel, and sexual problems remain common among persons with MS, and treatment satisfaction is low. Health care providers should consider systematically asking about these symptoms in clinical practice. Greater efforts could be devoted to developing novel, effective therapies to manage these symptoms and thereby improve QOL.


Self-administration and standardisation of the chronic respiratory questionnaire: a randomised trial in three German-speaking countries.
The chronic respiratory questionnaire (CRQ) has demonstrated excellent measurement properties in patients with chronic obstructive pulmonary disease (COPD), but in its original form it is limited by the requirement for interviewer-administration and the individualised dyspnoea questions. The objective of this randomised trial was to examine the evaluative properties of the interviewer and self-administered German CRQ as well as of a standardised CRQ dyspnoea domain. In a multinational trial we randomly allocated 71 patients with COPD to complete the interviewer administered CRQ (CRQ-IA) or the self-administered CRQ (CRQ-SA) and other validation measures at the beginning and end of a respiratory rehabilitation program. We assessed and compared responsiveness and longitudinal validity of the CRQ. The change scores of all CRQ domains were above the minimal clinically important difference of 0.5. Responsiveness of the fatigue domain was higher for the CRQ-SA compared to CRQ-IA (P = 0.02), but there was no difference in responsiveness on the other domains. Compared to the standardised dyspnoea domain the individualised dyspnoea questions tended to show greater responsiveness for both the CRQ-IA (P = 0.07) and CRQ-SA (P = 0.10). We found better longitudinal validity for the CRQ-SA represented by larger correlations between CRQ change scores and those of other validation instruments. Taken these results into consideration, researchers in COPD, in particular those in German-language countries can utilise any one of four CRQ formats that have proved both valid and responsive.


A Case Report of Rivaroxaban-Induced Urticaria and Angioedema With Possible Cross-Reaction to Dabigatran.
Anticoagulants are commonly associated with hemorrhagic complications. However, rare hypersensitivity drug reactions associated with direct oral anticoagulants (DOACs) in form of cutaneous reactions such as urticaria as well as angioedema can have significant burden owing to increase in morbidity and mortality. Angioedema can be allergic, hereditary or idiopathic and can occur in isolation, in combination with urticaria as contributing component of anaphylaxis. With increase in the use of DOACs over warfarin as choice of anticoagulant in the treatment of atrial fibrillation (AF) as well as venous thromboembolism (VTE), recent post marketing surveillance has identified several reports of adverse drug reactions. This case report describes the clinical course of patient being treated for VTE, who experienced rivaroxaban-induced urticaria and angioedema. We further provide evidence for cross-reactivity to dabigatran manifested as significant cutaneous reaction. Patient was transitioned to warfarin with enoxaparin bridge and tolerated it well without any complications.


Hepatic giant cells in hepatitis C virus (HCV) mono-infection and HCV/HIV co-infection.
The clinical and biological significance of syncytial giant cell change of hepatocytes in hepatitis C viral (HCV) infection is poorly understood. To investigate the clinical and histological correlates of giant cell transformation in the setting of HCV mono-infection and co-infection with HCV and HIV. The prevalence of hepatocyte giant cell transformation was determined and serological, biochemical and histological findings examined. Among 856 liver biopsy specimens, 22 cases (2.6%) showed giant cell transformation, representing 18 individuals. The median serum ALT was 37 IU/l, AST 49 IU/l, and alkaline phosphatase 97 IU/l. Eleven cases had HCV RNA loads available, with a median HCV RNA of 5.52 log IU/ml. Twelve of 17 individuals with available test results were also HIV positive (71%), compared to 46% of controls (p = 0.08). Giant cell transformation was found exclusively in zone 3 hepatocytes; the accompanying histological findings were otherwise typical of chronic HCV. The hepatic giant cells typically had a cytoplasmic appearance that resembled smooth endoplasmic reticulum proliferation. Most cases had only mild inflammation and fibrosis, with a median modified hepatic activity index (MHAI) grade of 3/18 and a median MHAI stage of 1/6. Three individuals had follow-up biopsies; all continued to have giant cell change. Giant cell transformation occurs most commonly in the setting of HCV/HIV co-infection, but can also be seen in chronic HCV infection alone. Histologically, giant cells were located in zone 3 hepatocytes, were persistent over time, and do not appear to be a marker of aggressive hepatitis.


The ups and downs of global motion perception: a paradoxical advantage for smaller stimuli in the aging visual system.
Recent evidence suggests that normal aging is typically accompanied by impairment in the ability to perceive the global (overall) motion of visual objects in the world. The purpose of this study was to examine the interplay between age-related changes in the ability to perceive translational global motion (up vs. down) and important factors such as the spatial extent (size) over which movement occurs and how cluttered the moving elements are (density). We used random dot kinematograms (RDKs) and measured motion coherence thresholds (% signal elements required to reliably discriminate global direction) for young and older adults. We did so as a function of the number and density of local signal elements, and the aperture area in which they were displayed. We found that older adults' performance was relatively unaffected by changes in aperture size, the number and density of local elements in the display. In young adults, performance was also insensitive to element number and density but was modulated markedly by display size, such that motion coherence thresholds decreased as aperture area increased (participants required fewer local elements to move coherently to determine the overall image direction). With the smallest apertures tested, young participants' motion coherence thresholds were considerably higher (~1.5 times worse) than those of their older counterparts. Therefore, when RDK size is relatively small, older participants were actually better than young participants at processing global motion. These findings suggest that the normal (disease-free) aging process does not lead to a general decline in perceptual ability and in some cases may be visually advantageous. The results have important implications for the understanding of the consequences of aging on visual function and a number of potential explanations are explored. These include age-related changes in spatial summation, reduced cortical inhibition, neural blur and attentional resource allocation.


Reducing marine pollution from single-use plastics (SUPs): A review.
Single-use plastics, or SUPs (plastic bags, microbeads, cutlery, straws and polystyrene) are substantial sources of plastic marine pollution, yet preventable via legislative and non-legislative interventions. Various international legislative strategies have been reported to address plastic marine pollution from plastic bags and microbeads, but these have since been accompanied by recent increasing public awareness triggered by international agencies and organizations. The Sixth International Marine Debris Conference highlighted increasing intervention strategies to mitigate SUP pollution. This study presents new multi-jurisdictional legislative interventions to reduce SUPs since 2017 and incorporates emergence of new non-legislative interventions to mitigate other types of SUPs at individual and private-sector levels that complement or influence legislative interventions. Further, effectiveness of SUP bag interventions (e.g., bans vs. levies) to help reduce SUP marine pollution are presented and range between 33 and 96% reduction in bag use.


Nitrogen relations of the sorghum-Striga hermonthica host-parasite association: germination, attachment and early growth.
The probability of the parasitic angiosperm Striga hermonthica achieving a successful union with its sorghum host is in part dependent on the concentration of ammonium nitrate in the growth medium. Germination rates were higher with 1 mM than with 3 mM ammonium nitrate. Ammonium nitrate did not influence either the stability of active components of host root exudate, or their perception by the parasite's seed. High concentrations of ammonium nitrate did not significantly reduce the leakage of potassium ions from sorghum roots (although patterns of exudation may differ between groups of compounds). Thus, it appears that ammonium nitrate reduced either the production of stimulatory compounds, or their specific leakage from host roots. Subsequent attachment of the parasite radicle and early growth of the plant were also lower at higher concentration of ammonium nitrate, and possible reasons for these observations are discussed.


Photochemistry on ultrathin metal films: strongly enhanced cross sections for NO2 on Ag/Si(100).
The surface photochemistry of NO(2) on ultrathin Ag(111) films (5-60 nm) on Si(100) substrates has been studied. NO(2), forming N(2)O(4) on the surface, dissociates to release NO and NO(2) into the gas phase with translational energies exceeding the equivalent of the sample temperature. An increase of the photodesorption cross section is observed for 266 nm light when the film thickness is decreased below 30 nm despite the fact that the optical absorptivity decreases. For 4.4 nm film thickness this increase is about threefold. The data are consistent with a similar effect for 355 nm light. The reduced film thickness has no significant influence on the average translation energy of the desorbing molecules or the branching into the different channels. The increased photodesorption cross section is interpreted to result from photon absorption in the Si substrate producing electrons with no or little momenta parallel to the surface at energies where this is not allowed in Ag. It is suggested that these electrons penetrate through the Ag film despite the gap in the surface projected band structure.


Process and Effects Evaluation of a Digital Mental Health Intervention Targeted at Improving Occupational Well-Being: Lessons From an Intervention Study With Failed Adoption.
Digital interventions have the potential to serve as cost-effective ways to manage occupational stress and well-being. However, little is known about the adoption of individual-level digital interventions at organizations. The aim of this paper is to study the effects of an unguided digital mental health intervention in occupational well-being and the factors that influence the adoption of the intervention. The intervention was based on acceptance and commitment therapy (ACT) and its aim was to teach skills for stress management and mental well-being. It was delivered via a mobile and a Web-based app that were offered to employees of two information and communication technology (ICT) companies. The primary outcome measures were perceived stress and work engagement, measured by a 1-item stress questionnaire (Stress) and the Utrecht Work Engagement Scale (UWES-9). The intervention process was evaluated regarding the change mechanisms and intervention stages using mixed methods. The initial interviews were conducted face-to-face with human resource managers (n=2) of both companies in August 2013. The participants were recruited via information sessions and email invitations. The intervention period took place between November 2013 and March 2014. The participants were asked to complete online questionnaires at baseline, two months, and four months after the baseline measurement. The final phone interviews for the volunteer participants (n=17) and the human resource managers (n=2) were conducted in April to May 2014, five months after the baseline. Of all the employees, only 27 (8.1%, 27/332) took the app into use, with a mean use of 4.8 (SD 4.7) different days. In the beginning, well-being was on good level in both companies and no significant changes in well-being were observed. The activities of the intervention process failed to integrate the intervention into everyday activities at the workplace. Those who took the app into use experienced many benefits such as relief in stressful situations. The app was perceived as a toolkit for personal well-being that gives concrete instructions on how mindfulness can be practiced. However, many barriers to participate in the intervention were identified at the individual level, such as lack of time, lack of perceived need, and lack of perceived benefits. The findings suggest that neither the setting nor the approach used in this study were successful in adopting new digital interventions at the target organizations. Barriers were faced at both the organizational as well as the individual level. At the organizational level, top management needs to be involved in the intervention planning for fitting into the organization policies, the existing technology infrastructure, and also targeting the organizational goals. At the individual level, concretizing the benefits of the preventive intervention and arranging time for app use at the workplace are likely to increase adoption.


Differences in ultrasonic vocalizations between wild and laboratory California mice (Peromyscus californicus).
Ultrasonic vocalizations (USVs) emitted by muroid rodents, including laboratory mice and rats, are used as phenotypic markers in behavioral assays and biomedical research. Interpretation of these USVs depends on understanding the significance of USV production by rodents in the wild. However, there has never been a study of muroid rodent ultrasound function in the wild and comparisons of USVs produced by wild and laboratory rodents are lacking to date. Here, we report the first comparison of wild and captive rodent USVs recorded from the same species, Peromyscus californicus. We used standard ultrasound recording techniques to measure USVs from California mice in the laboratory (Peromyscus Genetic Stock Center, SC, USA) and the wild (Hastings Natural History Reserve, CA, USA). To determine which California mouse in the wild was vocalizing, we used a remote sensing method that used a 12-microphone acoustic localization array coupled with automated radio telemetry of all resident Peromyscus californicus in the area of the acoustic localization array. California mice in the laboratory and the wild produced the same types of USV motifs. However, wild California mice produced USVs that were 2-8 kHz higher in median frequency and significantly more variable in frequency than laboratory California mice. The similarity in overall form of USVs from wild and laboratory California mice demonstrates that production of USVs by captive Peromyscus is not an artifact of captivity. Our study validates the widespread use of USVs in laboratory rodents as behavioral indicators but highlights that particular characteristics of laboratory USVs may not reflect natural conditions.


Parasite strain specificity of bovine cytotoxic T cell responses to Theileria parva is determined primarily by immunodominance.
The parasite strain specificity of CTL responses to Theileria parva varies among cattle immunized with the same parasite stock. We have investigated the influence of class I MHC on the strain specificity of CTL responses to T. parva in 19 cattle of defined class I phenotype immunized with either of two T. parva populations, in which protection to subsequent reciprocal challenge correlated with CTL strain specificity. In the majority of animals the response was restricted by the products of one MHC haplotype and there was a consistent bias to some haplotypes in preference to others. In 10 of 13 cattle expressing the molecularly defined MHC specificities A10 and KN104 on one haplotype, the CTL response was restricted entirely by this haplotype, thus allowing a precise analysis of the MHC restriction specificities. The MHC restriction specificity and the parasite population used for immunization both influenced the strain specificity of the response. By examining responses in identical twins immunized with different parasites or in animals before and after challenge with heterologous parasites, animals that mounted a strain-specific response to primary infection were shown to be capable of responding to Ags shared by the two parasite populations. These findings indicate that the strain specificity of CTL responses to T. parva is not determined primarily by immune response genes that define the inherent capacity to respond, but rather is a consequence of the response in individual animals being biased toward a limited number of immunodominant peptide-MHC determinants.


The effect of chronic exposure to 835.62 MHz FDMA or 847.74 MHz CDMA radiofrequency radiation on the incidence of spontaneous tumors in rats.
This study was designed to determine whether chronic exposure to radiofrequency (RF) radiation from cellular phones increased the incidence of spontaneous tumors in F344 rats. Eighty male and 80 female rats were randomly placed in each of three irradiation groups. The sham group received no irradiation; the Frequency Division Multiple Access (FDMA) group was exposed to 835.62 MHz FDMA RF radiation; and the Code Division Multiple Access (CDMA) group was exposed to 847.74 MHz CDMA RF radiation. Rats were irradiated 4 h per day, 5 days per week over 2 years. The nominal time-averaged specific absorption rate (SAR) in the brain for the irradiated animals was 0.85 +/- 0.34 W/kg (mean +/- SD) per time-averaged watt of antenna power. Antennas were driven with a time-averaged power of 1.50 +/- 0.25 W (range). That is, the nominal time-averaged brain SAR was 1.3 +/- 0.5 W/kg (mean +/- SD). This number was an average from several measurement locations inside the brain, and it takes into account changes in animal weight and head position during irradiation. All major organs were evaluated grossly and histologically. The number of tumors, tumor types and incidence of hyperplasia for each organ were recorded. There were no significant differences among final body weights or survival days for either males or females in any group. No significant differences were found between treated and sham-exposed animals for any tumor in any organ. We conclude that chronic exposure to 835.62 MHz FDMA or 847.74 MHz CDMA RF radiation had no significant effect on the incidence of spontaneous tumors in F344 rats.


Effectiveness and safety of misoprostol distributed to antenatal women to prevent postpartum haemorrhage after child-births: a stepped-wedge cluster-randomized trial.
Oral misoprostol, administered by trained health-workers is effective and safe for preventing postpartum haemorrhage (PPH). There is interest in expanding administration of misoprostol by non-health workers, including task-shifting to pregnant women themselves. However, the use of misoprostol for preventing PPH in home-births remains controversial, due to the limited evidence to support self-administration or leaving it in the hands of non-health workers. This study aimed to determine if antenatally distributing misoprostol to pregnant women to self-administer at home birth reduces PPH. Between February 2013 and March 2014, we conducted a stepped-wedge cluster-randomized trial in six health facilities in Central Uganda. Women at 28+ weeks of gestation attending antenatal care were eligible. Women in the control-arm received the standard-of-care; while the intervention-arm were offered 600 mcg of misoprostol to swallow immediately after birth of baby, when oxytocin was not available. The primary outcome (PPH) was a drop in postpartum maternal haemoglobin (Hb) by ≥ 2 g/dl, lower than the prenatal Hb. Analysis was by intention-to-treat at the cluster level and we used a paired t-tests to assess whether the mean difference between the control and intervention groups was statistically significant. 97% (2466/2545) of eligible women consented to participate; 1430 and 1036 in the control and intervention arms respectively. Two thousand fifty-seven of the participants were successfully followed up and 271 (13.2%) delivered outside a health facility. There was no significant difference between the study group in number of women who received a uterotonic at birth (control 80.4% vs intervention 91.4%, mean difference = -11.0%, 95% confidence interval [CI] -25.7% to 3.6%, p = 0.11). No woman took misoprostol before their baby's birth. Shivering and fever were 14.9% in the control arm compared to 22.2% in the intervention arm (mean difference = -7.2%, 95% CI -11.1% to -3.7%), p = 0.005). There was a slight, but non-significant, reduction in the percentage of women with Hb drop ≥ 2g/dl from 18.5% in the control arm to 11.4% in the intervention arm (mean difference = 7.1%, 95% CI -3.1% to 17.3%, p = 0.14). Similarly, there was no significant difference between the groups in the primary outcome in the women who delivered at home (control 9.6% vs intervention 14.5%, mean difference -4.9; 95% CI -12.7 to 2.9), p = 0.17). This study was unable to detect a significant reduction in PPH following the antenatal distribution of misoprostol. The study was registered with Pan-African Clinical Trials Network ( PACTR201303000459148, on 19/11/2012).


Impact of vitamin D supplementation on endothelial and inflammatory markers in adults: A systematic review.
This systematic review aims to evaluate randomised controlled trials (RCTs) investigating the effect of vitamin D supplementation on endothelial function and inflammation in adults. An electronic search of published randomised controlled trials, using Cochrane, Pubmed and Medline databases was conducted, with the search terms related to vitamin D and endothelial function. Inclusion criteria were RCTs in adult humans with a measure of vitamin D status using serum/plasma 25(OH)D and studies which administered the intervention through the oral route. Among the 1107 studies retrieved, 29 studies met the full inclusion criteria for this systematic review. Overall, 8 studies reported significant improvements in the endothelial/inflammatory biomarkers/parameters measured. However, in 2 out of the 8 studies, improvements were reported at interim time points, but improvements were absent post-intervention. The remaining 21 trial studies did not show significant improvements in the markers of interest measured. Evidence from the studies included in this systematic review did not demonstrate that vitamin D supplementation in adults, results in an improvement in circulating inflammatory and endothelial function biomarkers/parameters. This systematic review does not therefore support the use of vitamin D supplementation as a therapeutic or preventative measure for CVD in this respect.


Breeding together: kin selection and mutualism in cooperative vertebrates.
In cooperatively breeding vertebrates, nonbreeding helpers raise young produced by dominant breeders. Although the evolution of cooperative breeding has often been attributed primarily to kin selection (whereby individuals gain "indirect" benefits to their fitness by assisting collateral relatives), there is increasing evidence that helpers can be unrelated to the young they are raising. Recent studies also suggest that the indirect benefits of cooperative behavior may often have been overestimated while the direct benefits of helping to the helper's own fitness have probably been underestimated. It now seems likely that the evolutionary mechanisms maintaining cooperative breeding are diverse and that, in some species, the direct benefits of helping may be sufficient to maintain cooperative societies. The benefits of cooperation in vertebrate societies may consequently show parallels with those in human societies, where cooperation between unrelated individuals is frequent and social institutions are often maintained by generalized reciprocity.


Do adolescent anorexia nervosa patients have deficits in emotional functioning?
Adult eating disorder patients have been characterised by alexithymia. We investigated whether adolescent eating disorder patients also show deficits in emotional functioning. To measure emotional functioning a questionnaire (the TAS) and an emotion recognition test were administered to 30 eating disorder (ED) adolescent girls and 31 healthy controls (HC), matched for age, education, and social status. Non-emotional, cognitive parallel tasks were administered on the same occasion to find out whether a possible deficit was emotion-specific or of a more general cognitive nature. The ED patients scored higher on the TAS and performed worse on the emotion recognition test, but no differences between the groups were found on the non-emotional cognitive instruments. It was concluded that adolescent eating disorder patients, just like adult eating disorder patients, are characterised by alexithymia and show specific deficits in emotional functioning. The implications of these findings are discussed.


Efficient system-wide coordination in noisy environments.
Many natural and social systems display global organization and coordination without centralized control. The origin of this global coordination is a topic of great current interest. Here we investigate a density-classification task as a model system for coordination and information processing in decentralized systems. We show that sophisticated strategies, selected under idealized conditions, are not robust to environmental changes. We also demonstrate that a simple heuristic is able to successfully complete the classification task under a broad range of environmental conditions. Our findings hint at the possibility that complex networks and ecologically efficient rules coevolve over time.


Fast randomization of large genomic datasets while preserving alteration counts.
Studying combinatorial patterns in cancer genomic datasets has recently emerged as a tool for identifying novel cancer driver networks. Approaches have been devised to quantify, for example, the tendency of a set of genes to be mutated in a 'mutually exclusive' manner. The significance of the proposed metrics is usually evaluated by computing P-values under appropriate null models. To this end, a Monte Carlo method (the switching-algorithm) is used to sample simulated datasets under a null model that preserves patient- and gene-wise mutation rates. In this method, a genomic dataset is represented as a bipartite network, to which Markov chain updates (switching-steps) are applied. These steps modify the network topology, and a minimal number of them must be executed to draw simulated datasets independently under the null model. This number has previously been deducted empirically to be a linear function of the total number of variants, making this process computationally expensive. We present a novel approximate lower bound for the number of switching-steps, derived analytically. Additionally, we have developed the R package BiRewire, including new efficient implementations of the switching-algorithm. We illustrate the performances of BiRewire by applying it to large real cancer genomics datasets. We report vast reductions in time requirement, with respect to existing implementations/bounds and equivalent P-value computations. Thus, we propose BiRewire to study statistical properties in genomic datasets, and other data that can be modeled as bipartite networks. BiRewire is available on BioConductor at http://www.bioconductor.org/packages/2.13/bioc/html/BiRewire.html. Supplementary data are available at Bioinformatics online.


Markets, information asymmetry and health care: towards new social contracts.
This paper explores the implications of the increasing role of informal as well as formal markets in the health systems of many low and middle-income countries. It focuses on institutional arrangements for making the benefits of expert medical knowledge widely available in the face of the information asymmetries that characterise health care. It argues that social arrangements can be understood as a social contract between actors, underpinned by shared behavioural norms, and embedded in a broader political economy. This contract is expressed through a variety of actors and institutions, not just through the formal personnel and arrangements of a health sector. Such an understanding implies that new institutional arrangements, such as the spread of reputation-based trust mechanisms can emerge or be adapted from other parts of the society and economy. The paper examines three relational aspects of health systems: the encounter between patient and provider; mechanisms for generating trust in goods and services in the context of highly marketised systems; and the establishment of socially legitimated regulatory regimes. This analysis is used to review experiences of health system innovation and change from a number of low income and transition countries.


Risk factors associated with peripherally inserted central venous catheter-related large vein thrombosis in neurological intensive care patients.
Using Virchow's triad as a framework, we sought to identify risk factors independently associated with symptomatic peripherally inserted central venous catheter (PICC)-related large vein thrombosis (PRLVT) in neurological intensive care patients. A retrospective cohort study and detailed chart review were performed for 431 consecutive PICCs placed in patients admitted to our neurological intensive care unit between March 2008 and February 2010. Variables theorized to potentially increase the risk of PRLVT were abstracted from the medical record. Each variable was then tested for its independent association with PRLVT. During the study period, 431 PICCs were placed with an incidence rate for symptomatic thrombosis of 8.4%. In adjusted analysis, catheter placement in a paretic arm (OR, 9.85; 95% CI, 4.42-21.95), surgery longer than 1 h during dwell time of the catheter (OR, 3.26; 95% CI, 1.48-7.17), a history of venous thromboembolism (OR, 6.66; 95% CI, 2.38-18.62), and mannitol use (OR, 3.27; 95% CI 1.27-8.43) were independently associated with the development of thrombosis. Alterations in blood flow and consistency, but not vessel injury, appear associated with symptomatic thrombosis following placement of PICCs in neurological intensive care patients. Mannitol use and placement in a paretic arm are potentially modifiable risk factors. Given the high incidence rate of symptomatic thrombosis, future studies should focus on comparing cumulative complications of centrally inserted venous catheters and PICCs in intensive care patients.


Estimating sample sizes for continuous, binary, and ordinal outcomes in paired comparisons: practical hints.
Paired data occur in crossover trials and matched case-control studies, and it is rare to find studies reporting sample size calculations associated with these types of studies, despite recommendations from editors that sample size calculations should be justified. In this article we describe some simple formulas and strategies for calculating the number of patients that should be entered into a matched or paired study when the outcome measures are continuous, binary, or ordinal.


Erythropoietin and renal function in sickle-cell disease.
The relation between haemoglobin concentration, creatinine clearance, and the serum concentration of erythropoiesis-stimulating factor were assessed in 31 patients with homozygous sickle-cell disease. Haemoglobin concentrations fell significantly with decreasing creatinine clearance (r = 0.58, p less than 0.001) and were positively correlated with the concentration of erythropoiesis-stimulating factor (r = 0.65, p less than 0.001). These observations suggest that erythropoietin concentration is the factor limiting production of red cells in sickle-cell disease with renal insufficiency and have implications for treatment.


Helicobacter pylori infection: approach of primary care physicians in a developing country.
The aim of the study was to assess the knowledge and practices of primary care physicians in diagnosis and management of Helicobacter pylori (H. pylori) infection in developing country. This convenient sample based, cross sectional study was conducted in primary care physicians of Karachi, Pakistan from March 2008 to August 2008 through a pretested self-designed questionnaire, which contained 11 items pertaining to H. pylori route of transmission, diagnosis, indication for testing, treatment options, follow up and source of information. Out of 509 primary care physicians, 451 consented to participate with the response rate of 88.6%. Responses of 426 primary care physicians were analyzed after excluding 19 physicians. 78% of the physicians thought that contaminated water was the source of spread of infection, dyspepsia was the most frequent indication for investigating H. pylori infection (67% of the physicians), while 43% physicians were of the view that serology was the most appropriate test to diagnose active H. pylori infection. 77% of physicians thought that gastric ulcer was the most compelling indication for treatment, 61% physicians preferred Clarithromycin based triple therapy for 7-14 days. 57% of the physicians would confirm H. pylori eradication after treatment in selected patients and 47% physicians preferred serological testing for follow-up. In case of treatment failure, only 36% of the physicians were in favor of gastroenterologist referral. The primary care physicians in this study lacked in knowledge regarding management of H. pylori infection. Internationally published guidelines and World gastroenterology organization (WGO) practice guideline on H. pylori for developing countries have little impact on current practices of primary care physicians. We recommend more teaching programs, continuous medical education activities regarding H. pylori infection.


Organellar inheritance in the green lineage: insights from Ostreococcus tauri.
Along the green lineage (Chlorophyta and Streptophyta), mitochondria and chloroplast are mainly uniparentally transmitted and their evolution is thus clonal. The mode of organellar inheritance in their ancestor is less certain. The inability to make clear phylogenetic inference is partly due to a lack of information for deep branching organisms in this lineage. Here, we investigate organellar evolution in the early branching green alga Ostreococcus tauri using population genomics data from the complete mitochondrial and chloroplast genomes. The haplotype structure is consistent with clonal evolution in mitochondria, while we find evidence for recombination in the chloroplast genome. The number of recombination events in the genealogy of the chloroplast suggests that recombination, and thus biparental inheritance, is not rare. Consistent with the evidence of recombination, we find that the ratio of the number of nonsynonymous to the synonymous polymorphisms per site is lower in chloroplast than in the mitochondria genome. We also find evidence for the segregation of two selfish genetic elements in the chloroplast. These results shed light on the role of recombination and the evolutionary history of organellar inheritance in the green lineage.


Protective Effect of GM1 Attenuates Hippocampus and Cortex Apoptosis After Ketamine Exposure in Neonatal Rat via PI3K/AKT/GSK3β Pathway.
Ketamine is a widely used analgesic and anesthetic in obstetrics and pediatrics. Ketamine is known to promote neuronal death and cognitive dysfunction in the brains of humans and animals during development. Monosialotetrahexosyl ganglioside (GM1), a promoter of brain development, exerts neuroprotective effects in many neurological disease models. Here, we investigated the neuroprotective effect of GM1 and its potential underlying mechanism against ketamine-induced apoptosis of rats. Seven-day-old Sprague Dawley (SD) rats were randomly divided into the following four groups: (1) group C (control group: normal saline was injected intraperitoneally); (2) group K (ketamine); (3) group GM1 (GM1 was given before normal saline injection); and (4) GM1+K group (received GM1 30 min before continuous exposure to ketamine). Each group contained 15 rats, received six doses of ketamine (20 mg/kg), and was injected with saline every 90 min. The Morris water maze (MWM) test, the number of cortical and hippocampal cells, apoptosis, and AKT/GSK3β pathway were analyzed. To determine whether GM1 exerted its effect via the PI3K/AKT/GSK3β pathway, PC12 cells were incubated with LY294002, a PI3K inhibitor. We found that GM1 protected against ketamine-induced apoptosis in the hippocampus and cortex by reducing the expression of Bcl-2 and Caspase-3, and by increasing the expression of Bax. GM1 treatment increased the expression of p-AKT and p-GSK3β. However, the anti-apoptotic effect of GM1 was eliminated after inhibiting the phosphorylation of AKT. We showed that GM1 lessens ketamine-induced apoptosis in the hippocampus and cortex of young rats by regulating the PI3K/AKT/GSK3β pathway. Taken together, GM1 may be a potential preventive treatment for the neurotoxicity caused by continuous exposure to ketamine.


The Cost-Effectiveness of Continuous Versus Intermittent Renal Replacement Therapies in Acute Kidney Injury: Perspective of the Social Services for the Elderly in Argentina.
Acute kidney injury (AKI) is a public health problem that affects millions of hospitalized patients worldwide. In Argentina, evidence suggests that its incidence has risen in recent years. When severe, AKI may require a renal replacement therapy (RRT) where continuous RRT (CRRT) and intermittent RRT (IRRT) are plausible options for patients in the intensive care unit. To evaluate the cost utility of CRRT versus IRRT for the National Institute of Social Services for Retirees and Pensioners, the largest social security health insurance for elders in Argentina. This was a model-based cost-utility analysis. Long-term costs and health outcomes were estimated for a hypothetical cohort with a Markov model. Parameters used were obtained from published literature and validated with local experts. Local costs were estimated and expressed in $AR of 2016. Several sensitivity analyses were run to analyze the impact of uncertainty on results. Continuous RRT dominated IRRT by cumulating over the model more quality-adjusted life years and less costs. Total discounted quality-adjusted life years for both cohorts were 1049 and 1034, respectively, and total costs were $95 362 and $103 871. Cost-effectiveness (CE) results reflect these differences in favor of CRRT with a deterministic cost-saving incremental CE ratio and a probability of CRRT being CE of 65.4%, considering a CE threshold of 1 gross domestic product per capita. Continuous RRT for patients with AKI eligible for CRRT or IRRT would probably be a cost-effective intervention for the National Institute of Social Services for Retirees and Pensioners' view. Nevertheless, there is considerable uncertainty around results, mainly due to the lack of adequate controlled studies and local data on the prognosis of these patients in Argentina.


Insights from engineering the Affibody-Fc interaction with a computational-experimental method.
The interaction between the Staphylococcal Protein A (SpA) domain B (the basis of the Affibody) molecule and the Fc of IgG is key to the use of Affibodies in affinity chromatography and in potential therapies against certain inflammatory diseases. Despite its importance and four-decade history, to our knowledge this interaction has never been affinity matured. We elucidate reasons why single-substitutions in the SpA which improve affinity to Fc may be very rare, and also discover substitutions which potentially serve several engineering purposes. We used a variation of FoldX to predict changes in protein-protein-binding affinity, and produce a list of 41 single-amino acid substitutions on the SpA molecule, of which four are near wild type (wt) and five are at most a factor of four from wt affinity. The nine substitutions include one which removes lysine, and several others which change charge. Subtle modulations in affinity may be useful for modifying column elution conditions. The method is applicable to other protein-protein systems, providing molecular insights with lower workload than existing experimental techniques.


Recurrent skin and soft tissue infections in HIV-infected patients during a 5-year period: incidence and risk factors in a retrospective cohort study.
Skin and soft tissue infections (SSTIs) are common in the era of community-associated methicillin resistant Staphylococcus aureus among HIV-infected patients. Recurrent infections are frequent. Risk factors for recurrence after an initial SSTI have not been well-studied. Retrospective cohort study, single center, 2005-2009. Paper and electronic medical records were reviewed by one of several physicians. Subjects with initial SSTI were followed until the time of SSTI recurrence. Standard descriptive statistics were calculated to describe the characteristics of subjects who did and did not develop a recurrent SSTI. Kaplan-Meier methods were used to estimate the risk of recurrent SSTI. A Cox regression model was developed to identify predictors of SSTI recurrence. 133 SSTIs occurred in 87 individuals. 85 subjects were followed after their initial SSTI, of whom 30 (35.3 %) had a recurrent SSTI in 118.3 person-years of follow-up, for an incidence of second SSTI of 253.6 SSTIs/1000 person-years (95 % CI 166.8-385.7). The 1-year Kaplan-Meier estimated risk of a second SSTI was 29.2 % (95 % CI 20.3-41.0 %), while the 3-year risk was 47.0 % (95 % CI 34.4-61.6 %). Risk factors for recurrent SSTI in a multivariable Cox regression model were non-hepatitis liver disease (HR 3.44; 95 % CI 1.02-11.5; p = 0.05), the presence of an intravenous catheter (HR 6.50; 95 % CI 1.47-28.7; p = 0.01), and a history of intravenous drug use (IVDU) (HR 2.80; 95 % CI 1.02-7.65; p = 0.05); African-American race was associated with decreased risk of recurrent SSTI (HR 0.12; 95 % CI 0.04-0.41; p < 0.01). Some evidence was present for HIV viral load ≥ 1000 copies/mL as an independent risk factor for recurrent SSTI (HR 2.21; 95 % CI 0.99-4.94; p = 0.05). Hemodialysis, currently taking HAART, CD4+ count, trimethoprim-sulfamethoxazole or azithromycin use, initial SSTI type, diabetes mellitus, incision and drainage of the original SSTI, or self-report of being a man who has sex with men were not associated with recurrence. Of HIV-infected patients with an SSTI, nearly 1/3 had a recurrent SSTI within 1 year. Risk factors for recurrent SSTI were non-hepatitis liver disease, intravenous catheter presence, a history of IVDU, and non-African-American race. Low CD4+ count was not a significant risk factor for recurrence.


Electro-Acupuncture Alleviates Chronic Unpredictable Stress-Induced Depressive- and Anxiety-Like Behavior and Hippocampal Neuroinflammation in Rat Model of Depression.
Depression is the second leading cause of disability worldwide. The effects of clinical depression may be mediated by neuroinflammation such as activation of microglia and high levels of proinflammatory cytokines in certain brain areas. Traditional Chinese medicine techniques such as electro-acupuncture (EA) are used extensively in Asia to treat mental health disorders. However, EA has not been rigorously studied in treatment of depression. This study was designed to assess the effectiveness of EA on depressive-like behavior and explore the role of hippocampal neuroinflammation in the potential antidepressant effect of EA. In this study, we used six chronic unpredictable stressors daily in a random sequence for 10 weeks. EA were performed on "Bai-Hui" (Du-20) (+) and "Yang-Ling-Quan" (GB-34, the right side; -) acupoints by an EA apparatus (HANS Electronic Apparatus, LH202H, 2/100 Hz, 0.3 mA) for 30 min once every other day for last 4 weeks. The behavior tests including open field test and forced swimming test, which are widely used to assess depressive and anxiety-like behavior were performed on the Monday and Tuesday of the eleventh week. The results showed that 10 week of chronic unpredictable stress (CUS) caused behavioral deficits in rats and neuroinflammation in hippocampus, such as increased expression of NLRP3 inflammasome components, upregulated mRNA level of IL-1β and the protein level of IL-1β mature form (p17) and activation of microglia. Moreover, 4 weeks of EA treatment significantly attenuated behavioral deficits caused by CUS. EA's antidepressant effect was accompanied by markedly decreased expression of certain NLRP3 inflammasome components and matured IL-1β. Meanwhile, EA treatment can significantly reverse CUS-induced increases in P2X7 receptor, Iba-1, IL-18, TNFα and IL-6 expression and decreases in GFAP expression. In conclusion, EA exhibited the antidepressant effect and alleviated the hippocampal neuroinflammation. These findings may provide insight into the role of hippocampal neuroinflammation in the antidepressant effect of EA.


Comparison of uterine activity induced by nipple stimulation and oxytocin.
Intermittent nipple stimulation has been proposed as a substitute for exogenous oxytocin infusion in the performance of contraction stress tests. To compare the uterine activity produced by these two methods, we studied a group of 45 term pregnant women undergoing indicated inductions of labor. Twenty-five patients had nipple stimulation and 20 patients received oxytocin infusions according to a study protocol. The two groups were similar in all obstetric parameters. Pre- and posttest uterine activity was measured by internal tocodynamometry and quantified in Montevideo units. A significant increase in uterine activity occurred in both groups (P less than .01). Regular uterine activity (three contractions in ten minutes) was achieved more rapidly (P less than .005), but at a lower level (P less than .001) in the nipple stimulation group. Pre- and posttest tonus did not change significantly in either group. In the nipple stimulation group, five patients (20%) did not achieve adequate contraction patterns after 15 stimulation-rest cycles (a total of 110 minutes) and three subjects (12%) experienced uterine hyperstimulation. These observations suggest that exogenous oxytocin and intermittent nipple stimulation may not have equivalent effects on uterine contractility. Therefore, it may not be justified to substitute one technique for the other or to use the same criteria for interpretation of contraction stress tests produced by both techniques.


Adaptation is maintained by the parliament of genes.
Fields such as behavioural and evolutionary ecology are built on the assumption that natural selection leads to organisms that behave as if they are trying to maximise their fitness. However, there is considerable evidence for selfish genetic elements that change the behaviour of individuals to increase their own transmission. How can we reconcile this contradiction? Here we show that: (1) when selfish genetic elements have a greater impact at the individual level, they are more likely to be suppressed, and suppression spreads more quickly; (2) selection on selfish genetic elements leads them towards a greater impact at the individual level, making them more likely to be suppressed; (3) the majority interest within the genome generally prevails over 'cabals' of a few genes, irrespective of genome size, mutation rate and the sophistication of trait distorters. Overall, our results suggest that even when there is the potential for considerable genetic conflict, this will often have negligible impact at the individual level.


Focal adhesion kinase-Tyr407 and -Tyr397 exhibit antagonistic effects on blood-testis barrier dynamics in the rat.
Focal adhesion kinase (FAK), a nonreceptor protein tyrosine kinase, displays phosphorylation-dependent localization in the seminiferous epithelium of adult rat testes. FAK is an integrated component of the blood-testis barrier (BTB) involved in regulating Sertoli cell adhesion via its effects on the occludin-zonula occludens-1 complex. Herein, we report that p-FAK-Tyr(407) and p-FAK-Tyr(397) display restricted spatiotemporal and almost mutually exclusive localization in the epithelium, affecting BTB dynamics antagonistically, with the former promoting and the latter disrupting the Sertoli cell tight junction-permeability barrier function. Using primary cultured Sertoli cells as an in vitro model that mimics the BTB in vivo both functionally and ultrastructurally, effects of FAK phosphorylation on BTB function were studied by expressing nonphosphorylatable and phosphomimetic mutants, with tyrosine replaced by phenylalanine (F) and glutamate (E), respectively. Compared with WT FAK, Y407E and Y397F mutations each promoted barrier function, and the promoting effect of the Y407E mutant was abolished in the Y397E-Y407E double mutant, demonstrating antagonism between Tyr(407) and Tyr(397). Furthermore, Y407E mutation induced the recruitment of actin-related protein 3 to the Sertoli cell-cell interface, where it became more tightly associated with neuronal Wiskott-Aldrich syndrome protein, promoting actin-related protein 2/3 complex activity. Conversely, Y407F mutation reduced the rate of actin polymerization at the Sertoli cell BTB. In summary, FAK-Tyr(407) phosphorylation promotes BTB integrity by strengthening the actin filament-based cytoskeleton. FAK serves as a bifunctional molecular "switch" to direct the cyclical disassembly and reassembly of the BTB during the epithelial cycle of spermatogenesis, depending on its phosphorylation status, to facilitate the transit of preleptotene spermatocytes across the BTB.


Autonomy and authenticity of enhanced personality traits.
There is concern that the use of neuroenhancements to alter character traits undermines consumer's authenticity. But the meaning, scope and value of authenticity remain vague. However, the majority of contemporary autonomy accounts ground individual autonomy on a notion of authenticity. So if neuroenhancements diminish an agent's authenticity, they may undermine his autonomy. This paper clarifies the relation between autonomy, authenticity and possible threats by neuroenhancements. We present six neuroenhancement scenarios and analyse how autonomy accounts evaluate them. Some cases are considered differently by criminal courts; we demonstrate where academic autonomy theories and legal reasoning diverge and ascertain whether courts should reconsider their concept of autonomy. We argue that authenticity is not an appropriate condition for autonomy and that new enhancement technologies pose no unique threats to personal autonomy.


Effects of copper and cross-linking on the extracellular matrix of tissue-engineered arteries.
In many cases, the mechanical strengths of tissue-engineered arteries do not match the mechanical strengths of native arteries. Ultimate arterial strength is primarily dictated by collagen in the extracellular matrix, but collagen in engineered arteries is not as dense, as organized, or as mature as collagen in native arteries. One step in the maturation process of collagen is the formation of hydroxylysyl pyridinoline (HP) cross-links between and within collagen molecules. HP cross-link formation, which is triggered by the copper-activated enzyme lysyl oxidase, greatly increases collagen fibril stability and enhances tissue strength. Increased cross-link formation, in addition to increased collagen production, may yield a stronger engineered tissue. In this article, the effect of increasing culture medium copper ion concentration on engineered arterial tissue composition and mechanics was investigated. Engineered vessels grown in low copper ion concentrations for the first 4 weeks of culture, followed by higher copper ion concentrations for the last 3 weeks of culture, had significantly elevated levels of cross-link formation compared to those grown in low copper ion concentrations. In contrast, vessels grown in high copper ion concentrations throughout culture failed to develop higher collagen cross-link densities than those grown in low copper ion concentrations. Although the additional cross-linking of collagen in engineered vessels may provide collagen fibril stability and resistance to proteolysis, it failed to enhance global tissue strength.


Drug resistance patterns of Mycobacterium tuberculosis complex and associated factors among retreatment cases around Jimma, Southwest Ethiopia.
Information on the pattern of drug resistant tuberculosis (TB) among re-treatment cases is crucial to develop appropriate control strategies. Therefore, we conducted this study to assess the drug resistance pattern of M. tuberculosis complex (MTBC) isolates and associated factors among re-treatment cases in Jimma area, Southwest Ethiopia. Health facility-based cross-sectional study was conducted between March 2012 and April 2013 in Jimma area, Southwest Ethiopia. We included 79 re-treatment cases selected conveniently. Socio demographic and clinical data were collected using structured questionnaire. Sputum sample processing, mycobacterial culture, isolation and drug susceptibility testing (DST) were done at Mycobacteriology Research Centre (MRC) of Jimma University. All data were registered and entered in to SPSS version 20. Crude odds ratio (COR) and adjusted odds ratios (AOR) were calculated. P-values less than 0.05 were considered statistically significant. Seventy-nine re-treatment cases included in the study; 48 (60.8%) were males. Forty-seven (59.5%) study participants were from rural area with the mean age of 31.67 ± 10.02 SD. DST results were available for 70 MTBC isolates. Majority (58.6% (41/70)) isolates were resistant to at least one of the four first line drugs. The prevalence of multidrug-resistant TB (MDR-TB) was 31.4% (22/70). Place of residence (AOR = 3.44 (95 % CI: 1.12, 10.60), duration of illness (AOR = 3.00 (95 % CI: 1.17, 10.69) and frequency of prior TB therapy (AOR = 2.99, (95 % CI: 1.01, 8.86) were significant factors for any drug resistance. Moreover, history of treatment failure was found to be associated with MDR-TB (AOR = 3.43 (95 % CI: 1.14, 10.28). The overall prevalence of MDR-TB among re-treatment cases around Jimma was high. The rate of MDR-TB was higher in patients with the history of anti-TB treatment failure. Timely identification and referral of patients with the history of treatment failure for culture and DST need to be strengthened.


Metapopulation Vicariance, Age of Island Taxa and Dispersal: A Case Study Using the Pacific Plant Genus Planchonella (Sapotaceae).
Oceanic islands originate from volcanism or tectonic activity without connections to continental landmasses, are colonized by organisms, and eventually vanish due to erosion and subsidence. Colonization of oceanic islands occurs through long-distance dispersals (LDDs) or metapopulation vicariance, the latter resulting in lineages being older than the islands they inhabit. If metapopulation vicariance is valid, island ages cannot be reliably used to provide maximum age constraints for molecular dating. We explore the relationships between the ages of members of a widespread plant genus (Planchonella, Sapotaceae) and their host islands across the Pacific to test various assumptions of dispersal and metapopulation vicariance. We sampled three nuclear DNA markers from 156 accessions representing some 100 Sapotaceae taxa, and analyzed these in BEAST with a relaxed clock to estimate divergence times and with a phylogeographic diffusion model to estimate range expansions over time. The phylogeny was calibrated with a secondary point (the root) and fossils from New Zealand. The dated phylogeny reveals that the ages of Planchonella species are, in most cases, consistent with the ages of the islands they inhabit. Planchonella is inferred to have originated in the Sahul Shelf region, to which it back-dispersed multiple times. Fiji has been an important source for range expansion in the Pacific for the past 23 myr. Our analyses reject metapopulation vicariance in all cases tested, including between oceanic islands, evolution of an endemic Fiji-Vanuatu flora, and westward rollback vicariance between Vanuatu and the Loyalty Islands. Repeated dispersal is the only mechanism able to explain the empirical data. The longest (8900 km) identified dispersal is between Palau in the Pacific and the Seychelles in the Indian Ocean, estimated at 2.2 Ma (0.4-4.8 Ma). The first split in a Hawaiian lineage (P. sandwicensis) matches the age of Necker Island (11.0 Ma), when its ancestor diverged into two species that are distinguished by purple and yellow fruits. Subsequent establishment across the Hawaiian archipelago supports, in part, progression rule colonization. In summary, we found no explanatory power in metapopulation vicariance and conclude that Planchonella has expanded its range across the Pacific by LDD. We contend that this will be seen in many other groups when analyzed in detail.


Emotional words impact the mind but not the body: evidence from pupillary responses.
Pupillary responses have been shown to be sensitive to both task load and emotional content. We investigated the interplay of these factors in the processing of single words that varied in emotional valence and arousal. Two tasks of different cognitive load, uninstructed reading and a lexical decision task, were employed, followed by an unannounced recognition task. Reaction times were faster and incidental memory performance was better for high-arousing than for low-arousing words. In contrast to previous findings for pictures and sounds, high-arousing words elicited smaller pupillary responses than low-arousing words; these effects were independent of task load, which increased pupil diameter. Therefore, emotional arousal attributed to words does not mandatorily activate the autonomic nervous system, but rather works on a cognitive level, facilitating word processing.


Optimal choice of pH for toxicity and bioaccumulation studies of ionizing organic chemicals.
It is recognized that the pH of exposure solutions can influence the toxicity and bioaccumulation of ionizing compounds. The present study investigates whether it can be considered a general rule that an ionizable compound is more toxic and more bioaccumulative when in the neutral state. Three processes were identified to explain the behavior of ionizing compounds with changing pH: the change in lipophilicity when a neutral compound becomes ionized, electrical attraction, and the ion trap. The literature was screened for bioaccumulation and toxicity tests of ionizing organic compounds performed at multiple pH levels. Toxicity and bioconcentration factors (BCFs) were higher for acids at lower pH values, whereas the opposite was true for bases. The effect of pH was most pronounced when pH - pK(a) was in the range of -1 to 3 for acids, and -3 to 1 for bases. The factor by which toxicity and BCF changed with pH was correlated with the lipophilicity of the compound (log K(OW) of the neutral compound). For both acids and bases, the correlation was positive, but it was significant only for acids. Because experimental data in the literature were limited, results were supplemented with model simulations using a dynamic flux model based on the Fick-Nernst-Planck diffusion equation known as the cell model. The cell model predicts that bases with delocalized charges may in some cases show declining bioaccumulation with increasing pH. Little information is available for amphoteric and zwitterionic compounds; however, based on simulations with the cell model, it is expected that the highest toxicity and bioaccumulation of these compounds will be found where the compounds are most neutral, at the isoelectric point.


The relationship between surgical changes in dentofacial morphology and changes in maximum bite force.
This study determined whether patients with greater surgical changes, and presumably greater normalization of their skeletal morphology, showed greater increases in their maximum voluntary bite forces after orthognathic surgery. A total of 104 adult patients (32 males and 72 females) treated with 1 of 8 different orthognathic surgical procedures were examined. Patients' presurgical and postsurgical morphologic and biomechanical measurements were taken from lateral cephalograms. Measurements known to be related to maximum bite force were used in the analysis. Patients' presurgical and postsurgical maximum bite forces were measured at 8 tooth positions (ie, right and left incisors, canines, premolars and molars). Presurgical and postsurgical morphology and biomechanics variables were strongly correlated with each other, suggesting that orthognathic surgery produced relatively little change in patients' overall craniofacial form. Maximum voluntary bite forces were primarily correlated with variables relating to jaw size-both before and after surgery. No correlations were noted between the increases in maximum voluntary bite forces and surgically produced changes in skeletal morphology and the biomechanics variables. Factors other than surgically produced changes in skeletal morphology are responsible for increases in maximum voluntary bite force after orthognathic surgery.


The duffy antigen/receptor for chemokines exists in an oligomeric form in living cells and functionally antagonizes CCR5 signaling through hetero-oligomerization.
The Duffy antigen/receptor for chemokines (DARC) is an unusual chemokine receptor that binds a large number of inflammatory chemokines of both the CC and CXC families with nanomolar affinity, yet it lacks the ability to signal upon ligand binding. Using bioluminescent resonant energy transfer, we have demonstrated for the first time that DARC exists as a constitutive homo-oligomer in living cells and furthermore that DARC hetero-oligomerizes with the CC chemokine receptor CCR5. DARC-CCR5 interaction impairs chemotaxis and calcium flux through CCR5, whereas internalization of CCR5 in response to ligand binding remains unchanged. These results suggest a novel mechanism by which DARC could modulate inflammatory responses to chemokines in vivo.


Long-term physical activity is associated with reduced arterial stiffness in older adults: longitudinal results of the SAPALDIA cohort study.
longitudinal analyses of physical activity (PA) and arterial stiffness in populations of older adults are scarce. We examined associations between long-term change of PA and arterial stiffness in the Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA). we assessed PA in SAPALDIA 2 (2001-03) and SAPALDIA 3 (2010-11) using a short questionnaire with a cut-off of at least 150 min of moderate-to-vigorous PA per week for sufficient activity. Arterial stiffness was measured oscillometrically by means of the brachial-ankle pulse wave velocity (baPWV) in SAPALDIA 3. We used multivariable mixed linear regression models adjusted for several potential confounders in 2,605 persons aged 50-81. adjusted means of baPWV were significantly lower in persons with sufficient moderate-to-vigorous PA (i) in SAPALDIA 2 but not in SAPALDIA 3 (P = 0.048) and (ii) in both surveys (P = 0.001) compared with persons with insufficient activity in both surveys. There was a significant interaction between sex and the level of change in PA concerning baPWV (P = 0.03). The triples of parameter estimates describing the association between level of PA change and baPWV were not significantly different between the two sex-specific models (P = 0.07). keeping up or adopting a physically active lifestyle was associated with lower arterial stiffness in older adults after a follow-up of almost a decade. Increasing the proportion of older adults adhering to PA recommendations incorporating also vigorous PA may have a considerable impact on vascular health at older age and may contribute to healthy ageing in general.


Lifestyle practices and cardiovascular disease mortality in the elderly: the leisure world cohort study.
Modifiable behavioral risk factors are major contributing causes of death, but whether the effects are maintained in older adults is uncertain. We explored the association of smoking, alcohol consumption, caffeine intake, physical activity, and body mass index on cardiovascular disease (CVD) mortality in 13,296 older adults and calculated risk estimates using Cox regression analysis in four age groups (<70, 70-74, 75-79, and 80+ years). The most important factor was current smoking, which increased risk in all age-sex groups. In women, alcohol consumption (≤3 drinks/day) was related to decreased (15-30%) risk in those <80 years old; in men, 4+ drinks/day was associated with reduced (15-30%) risk. Active 70+ year olds had 20-40% lower risk. Both underweight and obese women were at increased risk. Lifestyle practices impact CVD death rates in older adults, even those aged 80+ years. Not smoking, moderate alcohol consumption, physical activity, and normal weight are important health promoters in our aging population.


Triton's Geyser-Like Plumes: Discovery and Basic Characterization.
At least four active geyser-like eruptions were discovered in Voyager 2 images of Triton, Neptune's large satellite. The two best documented eruptions occur as columns of dark material rising to an altitude of about 8 kilometers where dark clouds of material are left suspended to drift downwind over 100 kilometers. The radii of the rising columns appear to be in the range of several tens of meters to a kilometer. One model for the mechanism to drive the plumes involves heating of nitrogen ice in a subsurface greenhouse environment; nitrogen gas pressurized by the solar heating explosively vents to the surface carrying clouds of ice and dark partides into the atmosphere. A temperature increase of less than 4 kelvins above the ambient surface value of 38 +/- 3 kelvins is more than adequate to drive the plumes to an 8-kilometer altitude. The mass flux in the trailing clouds is estimated to consist of up to 10 kilograms of fine dark particles per second or twice as much nitrogen ice and perhaps several hundred or more kilograms of nitrogen gas per second. Each eruption may last a year or more, during which on the order of a tenth of a cubic kilometer of ice is sublimed.


Autism spectrum disorders and intestinal microbiota.
Through extensive microbial-mammalian co-metabolism, the intestinal microbiota have evolved to exert a marked influence on health and disease via gut-brain-microbiota interactions. In this addendum, we summarize the findings of our recent study on the fecal microbiota and metabolomes of children with pervasive developmental disorder-not otherwise specified (PDD-NOS) or autism (AD) compared with healthy children (HC). Children with PDD-NOS or AD have altered fecal microbiota and metabolomes (including neurotransmitter molecules). We hypothesize that the degree of microbial alteration correlates with the severity of the disease since fecal microbiota and metabolomes alterations were higher in children with PDD-NOS and, especially, AD compared to HC. Our study indicates that the levels of free amino acids (FAA) and volatile organic compounds (VOC) differ in AD subjects compared to children with PDD-NOS, who are more similar to HC. Finally, we propose a new perspective on the implications for the interaction between intestinal microbiota and AD.


A Spatial and Temporal Investigation of Medical Surge in Dallas-Fort Worth During Hurricane Harvey, Texas 2017.
When 2017 Hurricane Harvey struck the coastline of Texas on August 25, 2017, it resulted in 88 fatalities and more than US $125 billion in damage to infrastructure. The floods associated with the storm created a toxic mix of chemicals, sewage and other biohazards, and over 6 million cubic meters of garbage in Houston alone. The level of biohazard exposure and injuries from trauma among persons residing in affected areas was widespread and likely contributed to increases in emergency department (ED) visits in Houston and cities receiving hurricane evacuees. We investigated medical surge resulting from these evacuations in Dallas-Fort Worth (DFW) metroplex EDs. We used data sourced from the North Texas Syndromic Surveillance Region 2/3 in ESSENCE to investigate ED visit surge following the storm in DFW hospitals because this area received evacuees from the 60 counties with disaster declarations due to the storm. We used the interrupted time series (ITS) analysis to estimate the magnitude and duration of the ED surge. ITS was applied to all ED visits in DFW and visits made by patients residing in any of the 60 counties with disaster declarations due to the storm. The DFW metropolitan statistical area included 55 hospitals. Time series analyses examined data from March 1, 2017-January 6, 2018 with focus on the storm impact period, August 14-September 15, 2017. Data from before, during, and after the storm were visualized spatially and temporally to characterize magnitude, duration, and spatial variation of medical surge attributable to Hurricane Harvey. During the study period overall, ED visits in the DFW area rose immediately by about 11% (95% CI: 9%, 13%), amounting to ~16 500 excess total visits before returning to the baseline on September 21, 2017. Visits by patients identified as residing in disaster declaration counties to DFW hospitals rose immediately by 127% (95% CI: 125%, 129%), amounting to 654 excess visits by September 29, 2017, when visits returned to the baseline. A spatial analysis revealed that evacuated patients were strongly clustered (Moran's I = 0.35, P < 0.0001) among 5 of the counties with disaster declarations in the 11-day window during the storm surge. The observed increase in ED visits in DFW due to Hurricane Harvey and ensuing evacuation was significant. Anticipating medical surge following large-scale hurricanes is critical for community preparedness planning. Coordinated planning across stakeholders is necessary to safeguard the population and for a skillful response to medical surge needs. Plans that address hurricane response, in particular, should have contingencies for support beyond the expected disaster areas.


Renal potassium wasting in renal tubular acidosis (RTA): its occurrence in types 1 and 2 RTA despite sustained correction of systemic acidosis.
IN TWO PATIENTS WITH CLASSIC RENAL TUBULAR ACIDOSIS (RTA) AND IN TWO PATIENTS WITH RTA ASSOCIATED WITH THE FANCONI SYNDROME, RENAL POTASSIUM WASTING PERSISTED DESPITE SUSTAINED CORRECTION OF ACIDOSIS: (a) during moderate degrees of hypokalemia, daily urinary excretion of potassium exceeded 80 mEq in each patient; (b) during more severe degrees of hypokalemia, daily urinary excretion of potassium exceeded 40 mEq in two patients and 100 mEq in another. These urinary excretion rates of potassium are more than twice those observed in potassium-depleted normal subjects with even minimal degrees of hypokalemia. The persistence of renal potassium wasting may have resulted in part from hyperaldosteronism, since urinary aldosterone was frankly increased in two patients and was probably abnormally high in the others relative to the degree of their potassium depletion. The hyperaldosteronism persisted despite sustained correction of acidosis, a normal sodium intake, and no reduction in measured plasma volume, and was not associated with hypertension; its cause was not defined. In the two patients with classic RTA, neither renal potassium wasting nor hyperaldosteronism could be explained as a consequence of a gradient restriction on renal H(+) - Na(+) exchange because the urinary pH remained greater than, or approximately equal to, the normal arterial pH or considerably greater than the minimal urinary pH attained during acidosis. The findings provide no support for the traditional view that renal potassium wasting in either classic RTA or RTA associated with the Fanconi syndrome is predictably corrected solely by sustained correction of acidosis with alkali therapy.


Build the co-creative enterprise.
These days more companies are inviting customers to help them design products. Now a few are taking things further and including their other stakeholders--employees, suppliers, distributors, and even regulators--in "co-creation" efforts, too. By focusing on improving the experiences of everyone involved, such firms are achieving breakthrough insights, lower costs, new revenues, and new business models. Consider how this worked at France's La Poste, which wanted to expand package delivery and banking services in light of a decline in its mail business. La Poste had three obstacles: unmotivated union tellers, customers disgruntled by long waits, and frustrated local managers, who felt caught in between. The company set some high-level goals and invited all three groups to decide how to reach them together. To get tellers' buy-in, La Poste gave them a say in their schedules. In workshops, the groups figured out when each office should be open and how its space should be configured. a 50% decrease in waiting time, a jump in satisfaction for customers, soaring job satisfaction among tellers, and significant growth in package delivery and banking, despite the recession.


Species on the menu of a generalist predator, the eastern red bat (Lasiurus borealis): using a molecular approach to detect arthropod prey.
One of the most difficult interactions to observe in nature is the relationship between a predator and its prey. When direct observations are impossible, we rely on morphological classification of prey remains, although this is particularly challenging among generalist predators whose faeces contain mixed and degraded prey fragments. In this investigation, we used a polymerase chain reaction and sequence-based technique to identify prey fragments in the guano of the generalist insectivore, the eastern red bat (Lasiurus borealis), and evaluate several hypotheses about prey selection and prey defences. The interaction between bats and insects is of significant evolutionary interest because of the adaptive nature of insect hearing against echolocation. However, measuring the successes of predator tactics or particular prey defences is limited because we cannot normally identify these digested prey fragments beyond order or family. Using a molecular approach, we recovered sequences from 89% of the fragments tested, and through comparison to a reference database of sequences, we were able to identify 127 different species of prey. Our results indicate that despite the robust jaws of L. borealis, most prey taxa were softer-bodied Lepidoptera. Surprisingly, more than 60% of the prey species were tympanate, with ears thought to afford protection against these echolocating bats. Moths of the family Arctiidae, which employ multiple defensive strategies, were not detected as a significant dietary component. Our results provide an unprecedented level of detail for the study of predator-prey relationships in bats and demonstrate the advantages which molecular tools can provide in investigations of complex ecological systems and food-web relationships.


Australian aid projects: What works, where projects work and how Australia compares.
In this article, we conduct the first-ever systematic study of Australian aid project appraisals. Using a previously unstudied data set of appraisals, we study project and recipient country factors influencing Australian aid effectiveness. We find effectiveness varies more within recipient countries than between countries. We find larger projects are more likely to be successful. Humanitarian projects are more successful on average than development projects. We also find that Australian aid is less likely to succeed in the Pacific than elsewhere, a significant finding given Australia's increased focus on the region. Finally, we show that Australia does not appear to be an unusual donor: when we compare Australia with other donors in a global data set, we find similar variables are correlated with effectiveness for most donors, including Australia.


Child-evoked maternal negativity from 9 to 27 months: Evidence of gene-environment correlation and its moderation by marital distress.
Past research has documented pervasive genetic influences on emotional and behavioral disturbance across the life span and on liability to adult psychiatric disorder. Increasingly, interest is turning to mechanisms of gene-environment interplay in attempting to understand the earliest manifestations of genetic risk. We report findings from a prospective adoption study, which aimed to test the role of evocative gene-environment correlation in early development. Included in the study were 561 infants adopted at birth and studied between 9 and 27 months, along with their adoptive parents and birth mothers. Birth mother psychiatric diagnoses and symptoms scales were used as indicators of genetic influence, and multiple self-report measures were used to index adoptive mother parental negativity. We hypothesized that birth mother psychopathology would be associated with greater adoptive parent negativity and that such evocative effects would be amplified under conditions of high adoptive family adversity. The findings suggested that genetic factors associated with birth mother externalizing psychopathology may evoke negative reactions in adoptive mothers in the first year of life, but only when the adoptive family environment is characterized by marital problems. Maternal negativity mediated the effects of genetic risk on child adjustment at 27 months. The results underscore the importance of genetically influenced evocative processes in early development.


Characterization of the gene structures, precursor processing and pharmacology of the endokinin peptides.
The endokinins represent several species-divergent and peripherally located mammalian tachykinins (hemokinin-1 in mouse and rat, endokinin-1 in rabbit and endokinins A and B in humans) and also the tachykinin gene-related peptides. These peptides are all encoded on the preprotachykinin 4 (TAC4) gene. Their complementary DNA sequences, gene structures and expression profiles have been determined from a number of different mammalian species. They are all flanked by adjacent upstream and downstream dibasic cleavage sites in their respective precursor proteins, except for human EKA/B that instead possesses a N-terminal monobasic cleavage site. Evidence for differential processing in the periphery at the N-terminal cleavage site of the tachykinins could explain why in humans the evolutionary pressure to maintain the N-terminal dibasic cleavage site of EKA/B has been lost. Furthermore, the TAC4 encoded tachykinins all exhibit a remarkable selectivity and potency for the highly species conserved tachykinin NK(1) receptor, similar to that of substance P. Particular consideration is also given to the potential interactions of the endokinins with the short NK(1) receptor isoform and to speculation of whether there could be an "endokinin-sensitive" NK(1) binding site.


Nurse documentation: not done or worse, done the wrong way--Part II.
To focus on nursing documentation and how it can lead to a malpractice lawsuit. Nursing, non-nursing healthcare and legal journals, case law, and related Internet sources. To avoid liability for inadequate or inaccurate documentation, nurses must be aware of how their documentation can either lead to a malpractice claim or actually decrease their chances of ever being named in a malpractice lawsuit. Malpractice cases often are decided based on documentation. The only viable way to defend against allegations of professional negligence is accurate and complete patient charting or defensive documentation. By examining case law involving inadequate or inaccurate documentation, nurses will be able to effectively adopt documentation practices or policies to decrease potential litigation. Educating nurses about the principles of documentation and the importance of implementing risk-reduction practices will help guard against liability and ultimately improve patient care.


Tacrolimus and minidose methotrexate for prevention of acute graft-versus-host disease after matched unrelated donor marrow transplantation.
Thirty adults with leukemia or lymphoma undergoing marrow transplantation from HLA-compatible unrelated donors received tacrolimus (FK506), a new immunosuppressive macrolide lactone, and minidose methotrexate to prevent acute graft-versus-host disease (GVHD). The group had a median age of 36 years (range 21 to 49 years). Twenty-four patients had advanced disease, and 11 were resistant to conventional therapy. Tacrolimus was administered at 0.03 mg/kg/d intravenously (i.v.) by continuous infusion from day -2, converted to oral at four times the i.v. dose following engraftment, and continued through day 180 posttransplant. Methotrexate 5 mg/m2 was given i.v. on days 1, 3, 6, and 11. All patients engrafted. Grades 2-4 GVHD occurred in 34% (95% CI, 17% to 52%), and grades 3-4 GVHD in 17% (95% CI, 3% to 31%). Mild renal toxicity was common before day 100; 63% of patients had a doubling of creatinine, and 52% had a peak creatinine greater than 2 mg/dL, but only one patient was dialyzed. The median last i.v. dose of tacrolimus was 53% of the scheduled dose, and the median oral dose on day 100 was 41% of that scheduled. Overall survival at 1 year was 47% (95% CI, 27% to 66%). We conclude that tacrolimus can be combined safely with minidose methotrexate, and the combination has substantial activity in preventing acute GVHD after unrelated donor marrow transplantation.


The prevalence of lifetime abuse among older adults in seven European countries.
To investigate the lifetime prevalence rate of abuse among older persons and to scrutinize the associated factors (e.g. demographics). This cross-sectional population-based study had 4467 participants, aged 60-84, from seven European cities. Abuse (psychological, physical, sexual, financial and injuries) was measured based on The Revised Conflict Tactics Scale, and the UK survey of abuse/neglect of older people. Over 34 % of participants reported experiencing lifetime psychological, 11.5 % physical, 18.5 % financial and 5 % sexual abuse and 4.3 % reported injuries. Lifetime psychological abuse was associated with country, younger age, education and alcohol consumption; physical abuse with country, age, not living in partnership; injuries with country, female sex, age, education, not living in partnership; financial abuse with country, age, not living in partnership, education, benefiting social/partner income, drinking alcohol; and sexual abuse with country, female sex and financial strain. High lifetime prevalence rates confirm that elder abuse is a considerable public health problem warranting further longitudinal studies. Country of residence is an independent factor associated with all types of elder abuse which highlights the importance of national interventions alongside international collaborations.


Ureaplasma urealyticum intrauterine infection: role in prematurity and disease in newborns.
Ureaplasma urealyticum, a common commensal of the urogenital tract of sexually mature humans, is gaining recognition as an important opportunistic pathogen during pregnancy. While its etiologic significance in many aspects of adverse pregnancy remains controversial, recent evidence indicates that U. urealyticum in the absence of other organisms is a cause of chorioamnionitis. Furthermore, ureaplasmal infection of the chorioamnion is significantly associated with premature spontaneous labor and delivery. In at least some cases, it appears to be causal. Present evidence indicates that U. urealyticum is a cause of septicemia, meningitis, and pneumonia in newborn infants, particularly those born prematurely. There is strong but not definitive evidence that ureaplasmal infection of the lower respiratory tract can lead to development of chronic lung disease in very low-birth-weight infants. Although risk factors for colonization of the lower genitourinary tract have been identified, little information is available concerning risk factors for intrauterine infection and host immune responses to invasive infection. Recent establishment of animal models of respiratory and central nervous system diseases should provide an opportunity to evaluate risk factors, pathogenic mechanisms, and operative immune mechanisms. However, the most critical need is additional information concerning indications for diagnosis and treatment as well as efficacy of treatment.


Impact of single-agent daily prednisone on outcomes in men with metastatic castration-resistant prostate cancer.
Despite palliative benefits and PSA responses, the objective clinical impact of daily oral prednisone (P) for metastatic castration-resistant prostate cancer (mCRPC) is unknown. We performed a pooled analysis of control arms of randomized trials that either did or did not administer single-agent P to evaluate its impact on overall survival (OS) and toxicities. Individual patient data from control arms of randomized trials of men with mCRPC who received placebo or P+placebo post docetaxel were eligible for analysis. The impact of P on OS and severe toxicities was investigated in Cox regression models adjusted for known prognostic factors. Statistical significance was defined as P<0.05 and all tests were two sided. Data from the control arms of two randomized phase III trials were available totaling 794 men: the COU-AA-301 trial (n=394) administered P plus placebo and the CA184-043 trial (n=400) administered placebo alone. P plus placebo was not significantly associated with OS compared with placebo in a multivariable analysis (hazard ratio=0.89 (95% confidence interval 0.72-1.10), P=0.27). Other factors associated with poor OS were Eastern Cooperative Oncology Group (ECOG)-performance status (PS) ⩾1, Gleason score ⩾8, liver metastasis, high PSA, hypoalbuminemia and elevated lactate dehydrogenase (LDH). Grade ⩾3 therapy-related toxicities were significantly increased with P plus placebo compared with placebo (hazard ratio=1.48 (95% confidence interval 1.03-2.13), P=0.034). Other baseline factors significantly associated with a higher risk of grade ⩾3 toxicities were ECOG-PS ⩾1, hypoalbuminemia and elevated LDH. Fatigue, asthenia, anorexia and pain were not different based on P administration. P plus placebo was associated with higher grade ⩾3 toxicities but not extension of OS compared with placebo alone in men with mCRPC who received prior docetaxel. Except for the use of P with abiraterone to alleviate toxicities, the use of P should be questioned given its association with toxicities and resistance.


Management of traumatic meniscus tears: the 2019 ESSKA meniscus consensus.
The importance of meniscus integrity in the prevention of early osteoarthritis is well known, and preservation is accepted as the primary goal. The purpose of the ESSKA (European Society for Sports Traumatology, Knee Surgery and Arthroscopy) European consensus on traumatic meniscus tears was to provide recommendations for the treatment of meniscus tears based on both scientific evidence and the clinical experience of knee experts. Three groups of surgeons and scientists elaborated and ratified the so-called formal consensus process to define the recommendations for the management of traumatic meniscus tears. A traumatic meniscus tear was defined as a tear with an acute onset of symptoms caused by a sufficient trauma. The expert groups included a steering group of eight European surgeons and scientists, a rating group of another nineteen European surgeons, and a peer review group. The steering group prepared twenty-seven question and answer sets based on the scientific literature. The quality of the answers received grades of A (a high level of scientific support), B (scientific presumption), C (a low level of scientific support) or D (expert opinion). These question and answer sets were then submitted to and evaluated by the rating group. All answers were scored from 1 (= totally inappropriate) to 9 (= totally appropriate) points. Thereafter, the comments of the members of the rating group were incorporated by the steering group and the consensus was submitted to the rating group a second time. Once a general consensus was reached between the steering and rating groups, the finalized question and answer sets were submitted for final review by the peer review group composed of representatives of the ESSKA-affiliated national societies. Eighteen representatives replied. The review of the literature revealed a rather low scientific quality of studies examining the treatment of traumatic meniscus tears. Of the 27 questions, only one question received a grade of A (a high level of scientific support), and another received a grade of B (scientific presumption). The remaining questions received grades of C and D. The mean rating of all questions by the rating group was 8.2 (95% confidence interval 8.1-8.4). A general agreement that MRI should be performed on a systematic basis was not achieved. However, MRI was recommended when arthroscopy would be considered to identify concomitant pathologies. In this case, the indication for MRI should be determined by a musculoskeletal specialist. Based on our data, stable left in situ lateral meniscus tears appear to show a better prognosis than medial tears. When repair is required, surgery should be performed as early as possible. Evidence that biological enhancement such as needling or the application of platelet-rich plasma would improve healing was not identified. Preservation of the meniscus should be considered as the first line of treatment because of an inferior clinical and radiological long-term outcome after partial meniscectomy compared to meniscus repair. The consensus was generated to present the best possible recommendations for the treatment of traumatic meniscus tears and provides some groundwork for a clinical decision-making process regarding the treatment of meniscus tears. Preservation of the meniscus should be the first line of treatment when possible, because the clinical and radiological long-term outcomes are worse after partial meniscectomy than after meniscus preservation. The consensus clearly states that numerous meniscus tears that were considered irreparable should be repaired, e.g., older tears, tears in obese patients, long tears, etc. LEVEL OF EVIDENCE: II.