Sleep Disturbance Predicts Depression Symptoms in Early Adolescence: Initial Findings From the Adolescent Brain Cognitive Development Study.
The aim of the study was to investigate associations between sleep disturbances and mental health in adolescents. Data are from a national sample of 11,670 U.S. participants (5,594 females, aged 9-10 years, 63.5% white) in the Adolescent Brain Cognitive Development study. Initial longitudinal analyses were conducted for a subset of the sample (n = 4,951). Measures of youth sleep disturbance (disorders of initiating and maintaining sleep, sleep-wake transition disorders, and disorders of excessive somnolence) and "typical" total sleep time (number of hours slept on most nights in the past 6 months) were obtained from the parent-report Sleep Disturbance Scale (Data Release 2.0). Parent-report measures of youth mental health (depression, internalizing, and externalizing behaviors) from the Child Behavior Checklist and typical screen time were included. At baseline, greater sleep disturbance and shorter total sleep time were associated with greater internalizing, externalizing, and depression scores. After controlling for baseline mental health symptoms, baseline sleep disturbance significantly predicted depression and internalizing and externalizing scores at 1-year follow-up. A significant interaction with sex indicated that the association between disorders of excessive somnolence and depression 1 year later was steeper for girls, compared with boys (p < .001; 95% confidence interval 1.04-3.45). Sleep disturbances predicted future mental health, particularly depression in this young sample, highlighting the potential to harness sleep as a tool to mitigate the persistence of depression across early adolescence and potentially prevent an adolescent onset of major depressive disorder.


Leishmaniasis chemotherapy--challenges and opportunities.
Although there have been significant advances in the treatment of visceral leishmaniasis (VL), there remain challenges to ensure that treatments effective in India are also effective in other regions of the world and to identify treatment for post kala-azar dermal leishmaniasis as well as the opportunity to develop a safe oral short-course treatment. At the same time, there have been few advances for the treatment of simple or complex forms of cutaneous leishmaniasis (CL), other than topical paromomycin formulations. The main challenge for CL is to ensure that this disease is on the research and development agenda, so that new drugs are evaluated or compounds are screened in appropriate models, and that the standardization of quality of clinical trials is guaranteed. Problems also remain in the treatment of HIV/leishmaniasis co-infected patients. We are some way from having the ideal treatments for VL and CL and drug research and development for these diseases must remain focused.


Psychosis consequent to antimalarial drug use in a young child.
The empirical use of anti-malarial agents in patients of unexplained pyrexia is a common practice in developing countries especially where the prevalence of malaria is high. The use of artemisinin-based combined therapies has gained prominence since some time, but chloroquine is still commonly utilized as monotherapy or in combination. Neuropsychiatric adverse effects of artemisinin are rarely reported, while chloroquine is associated with a range of such events. Further, the reporting of such side effects was more so in the 1980s and 1990s, and with the turn of this century, very few cases of chloroquine-induced psychosis especially in child and adolescent population have been reported. Herein, we report the development of psychosis in a young child who was exposed to chloroquine.


Dynamical properties of two- and three-dimensional colloidal clusters of six particles.
Colloidal clusters are important systems for studying self-assembly. Clusters of six colloidal particles attracting each other via short-ranged interactions have been recently studied both theoretically and experimentally. Here we present a computer modelling study of the thermodynamics and dynamics of these clusters using a short-ranged Morse potential in two and three dimensions. We combine energy landscape methods with comprehensive sampling, both of configurations using Markov chain Monte Carlo and also of trajectories using Langevin molecular dynamics propagation. We show that the interaction energies between the particles are probably greater than previously assumed. The rates predicted by transition state theory using harmonic vibrational densities of states are off by four orders of magnitude, since the effects of viscosity are not accounted for. In contrast, sampling short trajectories using an appropriate friction constant and discrete relaxation path sampling produces reasonable agreement with the experimental rates.


Acute kidney injury, stroke and death after cardiopulmonary bypass surgery: the role of perfusion flow and pressure.
Acute kidney injury after cardiopulmonary bypass surgery is associated with morbidity and mortality. This study aims to evaluate the role of low perfusion flow and pressure in the development of cardiopulmonary bypass-associated acute kidney injury, stroke and death, using multicentre registry data. We identified patients from the Australian and New Zealand Collaborative Perfusion Registry who underwent coronary artery bypass grafting and/or valvular surgery between 2008 and 2018. Primary predictor variables were the length of time the perfusion flow was <1.6 L/min/m2 and the length of time perfusion pressure was < 50mmHg. The primary outcome was new postoperative acute kidney injury defined by the risk-injury-failure-loss-end stage criteria. Secondary outcomes were stroke and in-hospital death. The influence of perfusion flow and pressure during cardiopulmonary bypass on the primary and secondary outcomes was estimated using separate multivariate models. A total of 16,356 patients were included. The mean age was 66 years and 75% were male. Acute kidney injury was observed in 1,844 patients (11%), stroke in 204 (1.3%) and in-hospital death in 286 (1.8%). Neither the duration of the time spent for perfusion flow (<1.6 L/minute/m2) nor the duration of the time spent for perfusion pressure (<50 mmHg) was associated with postoperative acute kidney injury, stroke or death in adjusted models. Neither low perfusion pressure nor low perfusion flow during cardiopulmonary bypass were predictive of postoperative acute kidney injury, stroke or death.


Effect of triage nurse-led application of the Ottawa Ankle Rules on number of radiographic tests and length of stay in selected emergency departments in Oman.
Ankle injuries are commonly seen in the emergency department (ED) and contribute to overcrowding. In Oman, injuries are a leading cause of years of life lost, disability-adjusted life years, and pose a burden to the healthcare system. This study aimed to evaluate the effectiveness of ED triage nurse-led application of the Ottawa Ankle Rules (OARs) toward improving the healthcare outcomes of ankle injury patients. A quasi-experimental design was used to collect data (demographic characteristics, waiting time, length of stay, and number of radiographic tests) from 96 patients. The intervention group (n = 46) received ED triage nurse-led assessment and initiation of radiographic tests based on the OARs. The control group (n = 50) received usual care. The participants' mean age was 26.4 ± 7.90 years. The main causes of ankle injuries were football (36%), falls (31%) and twisting while walking (24%). There was a significant difference in number of ankle X-rays (t = 6.19; p < .001); length of stay (U = 549; p < .001); and waiting time (U = 167; p < .001) between the control and intervention group. The intervention reduced the mean waiting time and length of stay by 25.09 and 41.01 min, respectively. Application of the OARs by the ED triage nurse can decrease the number of unnecessary radiographic tests, waiting time and length of stay in the ED. Nurses' utilization of evidence-based clinical decision-making tools can improve ED care outcomes of common acute conditions such as ankle injuries.


Synovial pathology in an ovine model of osteoarthritis: effect of intraarticular hyaluronan (Hyalgan).
Published scoring methods for quantifying synovitis focus on acute inflammatory parameters, and are unsuitable as outcome measures in experimental surgical models of osteoarthritis (OA). The aim of the present study was to define a modified histopathological scoring system for ovine synovium more suited to the chronic pathology induced by ovine meniscectomy, and to apply it to detect any therapeutic effects following intraarticular injection of hyaluronan (HA) (Hyalgan). OA was induced in 12 sheep by bilateral lateral meniscectomy, before weekly intraarticular injections of HA or saline vehicle from 16-20 weeks post-operatively, prior to sacrifice at 26 weeks. Six matched sheep were used as controls. Synovial sections were qualitatively scored for hyperplasia, inflammatory infiltrate, fibrosis, and hypervascularity; cell number, depth of fibrosis, and vessel number were also quantified using a graticule. OA synovia had significantly elevated scores for inflammatory cell infiltration, subintimal fibrosis, vascularity, and aggregate score relative to controls. HA-treated sheep had significantly lower vascularity score (p=0.015), aggregate score (p=0.007), depth of fibrosis (p=0.003) and vessel number (p=0.048) compared to saline-injected sheep. This study confirms the presence of a chronic synovitis in this OA model, characterised by subintimal fibrosis and hypervascularity (but only modest infiltrate and minimal intimal hyperplasia), which is partially ameliorated by intraarticular hyaluronate therapy.


Strain rate dependent orthotropic properties of pristine and impulsively loaded porcine temporomandibular joint disk.
The purpose of this study was to characterize the tensile stress-strain behavior of the porcine temporomandibular joint (TMJ) disk with respect to collagen orientation and strain rate dependency. The apparent elastic modulus, ultimate tensile strength, and strain at maximum stress were measured at three elongation rates (0.5, 50, and 500 mm/min) for dumbbell-shaped samples oriented along either anteroposterior or mediolateral axes of the disks. In order to study the effects of impact-induced fissuring on the mechanical behavior, the same properties were measured along each orientation at an elongation rate of 500 mm/min for disks subjected to impulsive loads of 0.5 N. s. The results suggested a strongly orthotropic nature to the healthy pristine disk. The values for the apparent modulus and ultimate strength were 10-fold higher along the anteroposterior axis (p < or = 0.01), which represented the primary orientation of the collagen fibers. Strain rate dependency was evident for loading along the anteroposterior axis but not along the mediolateral axis. No significant differences in any property were noted between pristine and impulsively loaded disks for either orientation (p > 0.05). The results demonstrated the importance of choosing an orthotropic model for the TMJ disk to conduct finite element modeling, to develop failure criteria, and to construct tissue-engineered replacements. Impact-induced fissuring requires further study to determine if the TMJ disk is orthotropic with respect to fatigue.


Population pharmacokinetics of a single dose of meloxicam after oral and intramuscular administration to captive lesser flamingos (Phoeniconaias minor).
OBJECTIVE To determine the pharmacokinetics of a single dose of meloxicam after IM and oral administration to healthy lesser flamingos (Phoeniconaias minor) by use of a population approach. ANIMALS 16 healthy captive lesser flamingos between 1 and 4 years of age. PROCEDURES A single dose of meloxicam (0.5 mg/kg) was administered IM to each bird, and blood samples were collected from birds at 3 (n = 13 birds), 2 (2), or 1 (1) selected point between 0 and 13 hours after administration, with samples collected from birds at each point. After a 15-day washout period, the same dose of meloxicam was administered PO via a red rubber tube and blood samples were collected as described for IM administration. Pharmacokinetic values were determined from plasma concentrations measured by high-performance liquid chromatography. RESULTS Plasma drug concentrations after IM administration of meloxicam reached a mean ± SD maximum value of 6.01 ± 3.38 μg/mL. Mean area under the concentration-versus-time curve was 17.78 ± 2.79 μg•h/mL, and mean elimination half-life was 1.93 ± 0.32 hours. Plasma concentrations after oral administration reached a mean maximum value of 1.79 ± 0.33 μg/mL. Mean area under the curve was 22.16 ± 7.17 μg•h/mL, and mean elimination half-life was 6.05 ± 3.53 hours. CONCLUSIONS AND CLINICAL RELEVANCE In lesser flamingos, oral administration of meloxicam resulted in higher bioavailability and a longer elimination half-life than did IM administration, but the maximum plasma concentration was low and may be insufficient to provide analgesia in flamingos. Conversely, IM administration achieved the desired plasma concentration but would require more frequent administration.


Influence of the ten sessions of the whole body cryostimulation on aerobic and anaerobic capacity.
The aim of this study was to determine the influence of whole body cryostimulation on aerobic and anaerobic capacities. To test the hypothesis that whole body cryostimulation improves physical capacity, thirty subjects (fifteen males and fifteen females) undertook two ergocycle trials before and after the ten sessions of cryogenic chamber treatment. To assess baseline aerobic capacity, the progressive cycle ergometer test was applied. This allowed determination of maximal oxygen uptake and ventilatory thresholds. Twenty-second Wingate test was performed to assess baseline levels of anaerobic power. After finishing the treatments in the cryogenic chamber, the exercise protocol was repeated. Before the first, and after the last whole body cryostimulation, venous blood samples were drawn to determine basic blood values, including levels of erythrocytes, leukocytes and thrombocytes, hemoglobin concentration, and hematocrit. There were no changes in aerobic capacity, in both females and males, after ten sessions of 3-minute-long exposures to cryogenic temperature (-130 degrees C). Participation in the whole body cryostimulation caused an increase in maximal anaerobic power in males (from 11.1 to 11.9 W x kg(-1); P < 0.05), but not in females. It can be concluded that whole body cryostimulation can be beneficial, at least in males, for increasing anaerobic capacity in sport disciplines involving speed and strength.


Hot topic: Geographical distribution and strain diversity of Lactobacillus wasatchensis isolated from cheese with unwanted gas formation.
Lactobacillus wasatchensis, an obligate heterofermentative nonstarter lactic acid bacteria (NSLAB) implicated in causing gas defects in aged cheeses, was originally isolated from an aged Cheddar produced in Logan, Utah. To determine the geographical distribution of this organism, we isolated slow-growing NSLAB from cheeses collected in different regions of the United States, Australia, New Zealand, and Ireland. Seven of the cheeses showed significant gas defects and 12 did not. Nonstarter lactic acid bacteria were isolated from these cheeses on de Man, Rogosa, and Sharpe medium supplemented with ribose, a preferred substrate for Lb. wasatchensis. Identification was confirmed with 16S rRNA gene sequencing and the API50CH (bioMérieux, Marcy l'Etoile, France) carbohydrate panel. Isolates were also compared with one another by using repetitive element sequence-based PCR (rep-PCR). Lactobacillus wasatchensis was isolated only from cheeses demonstrating late-gas development and was found in samples from 6 of the 7 cheeses. This supports laboratory evidence that this organism is a causative agent of late gas production defects. The rep-PCR analysis produced distinct genetic fingerprints for isolates from each cheese, indicating that Lb. wasatchensis is found in several regions across the United States and is not a local phenomenon.


Refactoring and optimization of light-switchable Escherichia coli two-component systems.
Light-switchable proteins enable unparalleled control of molecular biological processes in live organisms. Previously, we have engineered red/far-red and green/red photoreversible two-component signal transduction systems (TCSs) with transcriptional outputs in E. coli and used them to characterize and control synthetic gene circuits with exceptional quantitative, temporal, and spatial precision. However, the broad utility of these light sensors is limited by bulky DNA encoding, incompatibility with commonly used ligand-responsive transcription factors, leaky output in deactivating light, and less than 10-fold dynamic range. Here, we compress the four genes required for each TCS onto two streamlined plasmids and replace all chemically inducible and evolved promoters with constitutive, engineered versions. Additionally, we systematically optimize the expression of each sensor histidine kinase and response regulator, and redesign both pathway output promoters, resulting in low leakiness and 72- and 117-fold dynamic range, respectively. These second-generation light sensors can be used to program the expression of more genes over a wider range and can be more easily combined with additional plasmids or moved to different host strains. This work demonstrates that bacterial TCSs can be optimized to function as high-performance sensors for scientific and engineering applications.


Does lowering the screening age for cervical cancer in The Netherlands make sense?
Recommendations for the age to initiate cervical cancer screening should be directed towards maximum detection of early cervical cancer. However, the screening programme should do more good than harm. The aim of this analysis was to determine whether the target age for cervical cancer screening should be lowered in view of apparent increases in new cases of invasive cancer below age 30 and in age group 30-44 years in The Netherlands. Therefore, all cervical cancer cases diagnosed between January 1, 1989 and December 31, 2003 were selected from the nationwide population-based Netherlands Cancer Registry. For age group 25-39 years, incidence data were also available for 2004 and 2005. To describe trends, the estimated annual percentage of change and joinpoint analysis were used. Between ages 25 and 28 years, the absolute number of new cases of cervical cancer annually has varied between 0 and 9 per age. Significantly decreasing trends in incidence were observed for age groups 35-39 and 45-49 (p < 0.0001 and p = 0.01, respectively). The annual number of deaths fluctuated with a decreasing trend for age groups 30-34 and 35-39 years (p = 0.01 and p = 0.03, respectively). Because the incidence and mortality rates for cervical cancer among women younger than 30 are low and not increasing, lowering the age for cervical cancer screening is not useful at this time. Although the number of years of life gained is high for every case of cervical cancer prevented, the disadvantages of lowering the screening age would be very large and even become disproportionate compared to the potential advantages.


APOL1 Genotype and Renal Function of Black Living Donors.
Black living kidney donors are at higher risk of developing kidney disease than white donors. We examined the effect of the APOL1 high-risk genotype on postdonation renal function in black living kidney donors and evaluated whether this genotype alters the association between donation and donor outcome. We grouped 136 black living kidney donors as APOL1 high-risk (two risk alleles; n=19; 14%) or low-risk (one or zero risk alleles; n=117; 86%) genotype. Predonation characteristics were similar between groups, except for lower mean±SD baseline eGFR (CKD-EPI equation) in donors with the APOL1 high-risk genotype (98±17 versus 108±20 ml/min per 1.73 m2; P=0.04). At a median of 12 years after donation, donors with the APOL1 high-risk genotype had lower eGFR (57±18 versus 67±15 ml/min per 1.73 m2; P=0.02) and faster decline in eGFR after adjusting for predonation eGFR (1.19; 95% confidence interval, 0 to 2.3 versus 0.4; 95% confidence interval, 0.1 to 0.7 ml/min per 1.73 m2 per year, P=0.02). Two donors developed ESRD; both carried the APOL1 high-risk genotype. In a subgroup of 115 donors matched to 115 nondonors by APOL1 genotype, we did not find a difference between groups in the rate of eGFR decline (P=0.39) or any statistical interaction by APOL1 status (P=0.92). In conclusion, APOL1 high-risk genotype in black living kidney donors associated with greater decline in postdonation kidney function. Trajectory of renal function was similar between donors and nondonors. The association between APOL1 high-risk genotype and poor renal outcomes in kidney donors requires validation in a larger study.


Herbal diuretics in medieval Persian and Arabic medicine.
In accord with the notions of humoralism that prevailed in medieval medicine, therapeutic interventions, including diuretics, were used to restore the disturbed balance among the four humors of the human body: blood, phlegm, yellow bile, and black bile. Most diuretics were derived from plants. The primary textual reference on herbal diuretics was Dioscorides's De Materia Medica, which was written during the first century CE. The authors reviewed the medieval medical texts written in Persian and Arabic and compiled a list of 135 herbal diuretics used by the medieval medical authorities for treating various ailments. Between the 8th and 11th centuries CE, Middle Eastern physicians systematically reviewed extant books on medicine and pharmacotherapy and compiled new and expanded lists of herbal medicines, diuretics in particular. Furthermore, they introduced new chemical methods of extraction, distillation, and compounding in the use of herbal medicines. Several herbal remedies now are considered as potentially safe and affordable alternatives to chemical pharmaceuticals. Thus, research on medieval herbal therapies may prove to be relevant to the practice of current cardiovascular and renal pharmacotherapy. The authors propose that modern research methods can be employed to determine which of these agents actually are effective as diuretics.


A population-based case-cohort study of the risk of myocardial infarction following radiation therapy for breast cancer.
To describe the risk of acute myocardial infarction (AMI) after radiation therapy (RT) for breast cancer (BrCa) in an exposed population. We identified and validated cases of AMI (vAMI), by electrocardiographic or enzyme criteria, among all 6680 women who received post-operative RT following lumpectomy or mastectomy, within 12 months following diagnosis of BrCa between 1982 and 1988 in Ontario, Canada. We identified women without vAMI whose death certification was ascribed to AMI (dAMI). We abstracted risk factors and treatment exposures for a random sample of women from the 6680, and for all with vAMI or dAMI. The hazards of vAMI and of dAMI were estimated using multivariate Cox proportional hazards models, corrected for study design. We validated 121 cases of vAMI and identified 92 cases of dAMI. The risk of vAMI associated with RT to the left breast HR=1.96 (1.09,3.54) among women at age >/= 60 at time of RT, adjusted for history of smoking and prior MI. The adjusted HR dAMI=1.90 (1.08,3.35) for exposure to anterior internal mammary node (IMC) RT. Among women who received anterior left breast boost RT, increasing area of the boost is associated with adjusted HR vAMI=1.02 (1.00,1.03)/cm(2), and adjusted HR dAMI=1.02 (1.01,1.03)/cm(2). The risks of vAMI and dAMI following RT for BrCa are related to anatomic sites of RT (left breast, area of anterior left breast boost field, and anterior IMC field).


Minimal Organizational Requirements for the Ascription of Animal Personality to Social Groups.
Recently, psychological phenomena have been expanded to new domains, crisscrossing boundaries of organizational levels, with the emergence of areas such as social personality and ecosystem learning. In this contribution, we analyze the ascription of an individual-based concept (personality) to the social level. Although justified boundary crossings can boost new approaches and applications, the indiscriminate misuse of concepts refrains the growth of scientific areas. The concept of social personality is based mainly on the detection of repeated group differences across a population, in a direct transposition of personality concepts from the individual to the social level. We show that this direct transposition is problematic for avowing the nonsensical ascription of personality even to simple electronic devices. To go beyond a metaphoric use of social personality, we apply the organizational approach to a review of social insect communication networks. Our conceptual analysis shows that socially self-organized systems, such as isolated ant trails and bee's recruitment groups, are too simple to have social personality. The situation is more nuanced when measuring the collective choice between nest sites or foraging patches: some species show positive and negative feedbacks between two or more self-organized social structures so that these co-dependent structures are inter-related by second-order, social information systems, complying with a formal requirement for having social personality: the social closure of constraints. Other requirements include the decoupling between individual and social dynamics, and the self-regulation of collective decision processes. Social personality results to be sometimes a metaphorical transposition of a psychological concept to a social phenomenon. The application of this organizational approach to cases of learning ecosystems, or evolutionary learning, could help to ground theoretically the ascription of psychological properties to levels of analysis beyond the individual, up to meta-populations or ecological communities.


The immediate sensorimotor effects of elbow orthoses in patients with lateral elbow tendinopathy: a prospective crossover study.
Counterforce orthoses are used to manage lateral elbow tendinopathy, and their effectiveness in improving motor function has been documented. Little is known about the impact of bracing on sensory function. The objective of this study was to investigate the immediate effectiveness of 2 counterforce orthoses in improving the sensorimotor abilities of the hand in patients with lateral elbow tendinopathy. In this crossover, randomized controlled trial, elbow proprioception, pain severity, pain-free grip strength, and finger dexterity were measured in 50 participants with a diagnosis of lateral elbow tendinopathy. Outcomes were measured in 3 randomized conditions (no brace, forearm band, or elbow sleeve). Data were analyzed using 1-way repeated-measures analysis of variance for each outcome measure. Better scores were observed with the forearm band, as compared with no orthosis, for multiple outcomes including joint position reproduction score at 70° of elbow flexion (P = .006), pain (P < .001), grip strength (P = .01), and dexterity (P < .001). The elbow sleeve yielded better scores than no orthosis for the following outcomes: joint position reproduction score at 110° (P < .001), pain (P < .001), and grip strength (P = .012). No statistically significant difference was found between the orthoses' effects on pain reduction and grip strength (P > .05). The forearm band showed better scores on joint position reproduction at 70° compared with the elbow sleeve (P = .006), whereas the elbow sleeve showed better scores at 110° (P < .001). Our results support the mechanisms occurring with the use of either of the described orthotic interventions. Future randomized trials with longer-term outcomes that include sensorimotor mechanisms might enhance our understanding of the comparative effectiveness.


Diversification and collapse of a telomere elongation mechanism.
In most eukaryotes, telomerase counteracts chromosome erosion by adding repetitive sequence to terminal ends. Drosophila melanogaster instead relies on specialized retrotransposons that insert exclusively at telomeres. This exchange of goods between host and mobile element-wherein the mobile element provides an essential genome service and the host provides a hospitable niche for mobile element propagation-has been called a "genomic symbiosis." However, these telomere-specialized, jockey family retrotransposons may actually evolve to "selfishly" overreplicate in the genomes that they ostensibly serve. Under this model, we expect rapid diversification of telomere-specialized retrotransposon lineages and, possibly, the breakdown of this ostensibly symbiotic relationship. Here we report data consistent with both predictions. Searching the raw reads of the 15-Myr-old melanogaster species group, we generated de novo jockey retrotransposon consensus sequences and used phylogenetic tree-building to delineate four distinct telomere-associated lineages. Recurrent gains, losses, and replacements account for this retrotransposon lineage diversity. In Drosophila biarmipes, telomere-specialized elements have disappeared completely. De novo assembly of long reads and cytogenetics confirmed this species-specific collapse of retrotransposon-dependent telomere elongation. Instead, telomere-restricted satellite DNA and DNA transposon fragments occupy its terminal ends. We infer that D. biarmipes relies instead on a recombination-based mechanism conserved from yeast to flies to humans. Telomeric retrotransposon diversification and disappearance suggest that persistently "selfish" machinery shapes telomere elongation across Drosophila rather than completely domesticated, symbiotic mobile elements.


Less Than One Millimeter Under the Great Toe is Enough to Change Balance Ability in Elite Women Handball Players.
Team handball is a complex intermittent sport game, which requires several motor abilities and effective postural control. Objective evaluation of stabilometric variables may be interesting to assess and improve functional parameters by postural control management. The purpose of the study was to evaluate the effects of a small additional thickness placed under the great toe (TUGT) on the Centre of Pressure (CoP) parameters in elite women handball players. Fourteen elite women handball players voluntarily participated in this study. Two conditions were compared: TUGT 0 (control) and TUGT 0.8 mm; four variables were computed from the CoP displacements. A paired T-test was performed for each variable. This study concludes that a low focal additional thickness placed under both great toes has an effect on the CoP measures used to assess postural control during an unperturbed stance. These results suggest that a low TUGT could contribute to a change in balance ability, and may be of clinical interest. This brings new perspectives in the management of athletes to prevent injury risk and optimize performance.


Does dissemination extend beyond publication: a survey of a cross section of public funded research in the UK.
In the UK, most funding bodies now expect a commitment or effort on the part of grant holders to disseminate the findings of their research. The emphasis is on ensuring that publicly funded research is made available, can be used to support decision making, and ultimately improve the quality and delivery of healthcare provided. In this study, we aimed to describe the dissemination practices and impacts of applied and public health researchers working across the UK. We conducted a survey of 485 UK-based principal investigators of publicly funded applied and public health research. Participants were contacted by email and invited to complete an online questionnaire via an embedded URL. Gift vouchers were given to all participants who completed the questionnaire. Four reminder emails were sent out to non-respondents at one, two, three, and four weeks; a fifth postal reminder was also undertaken. A total of 243/485 (50%) questionnaires were returned (232 completed, 11 declining to participate). Most researchers recognise the importance of and appear committed to research dissemination. However, most dissemination activity beyond the publishing of academic papers appears to be undertaken an ad hoc fashion. There is some evidence that access to dissemination advice and support may facilitate more policy interactions; though access to such resources is lacking at an institutional level, and advice from funders can be variable. Although a minority of respondents routinely record details about the impact of their research, when asked about impact in relation to specific research projects most were able to provide simple narrative descriptions. Researchers recognise the importance of and appear committed to disseminating the findings of their work. Although researchers are focussed on academic publication, a range of dissemination activities are being applied albeit in an ad hoc fashion. However, what constitutes effective dissemination (in terms of impact and return on investment) remains unclear. Researchers need greater and clearer guidance on how best to plan, resource, and facilitate their dissemination activities.


Where occupation and environment overlap: US Forest Service worker exposure to Libby Amphibole fibers.
The National Institute for Occupational Safety and Health (NIOSH) conducted an evaluation of exposures to asbestiform amphibole, known as Libby Amphibole (LA), to personnel from the US Department of Agriculture-Forest Service (USFS) working in the Kootenai National Forest near a former vermiculite mine close to Libby, Montana. LA is associated with vermiculite that was obtained from this mine; mining and processing over many years have resulted in the spread of LA into the surrounding Kootenai Forest where it has been found in tree bark, soil, and forest floor litter. As a result of this and other contamination, Libby and surrounding areas have been designated a "Superfund" site by the US Environmental Protection Agency (EPA). This article describes the application of EPA methods for assessing cancer risks to NIOSH sampling results. Phase-contrast microscopy for airborne asbestos fiber evaluation was found to be less useful than transmission electron microscopy in the presence of interfering organic (plant) fibers. NIOSH Method 7402 was extended by examination of larger areas of the filter, but fiber counts remained low. There are differences between counting rules in NIOSH 7402 and the ISO method used by EPA but these are minor in the context of the uncertainty in concentration estimates from the low counts. Estimates for cancer risk are generally compatible with those previously estimated by the EPA. However, there are limitations to extrapolating these findings of low risk throughout the entire area and to tasks that were not evaluated.


Endophytic bacterial diversity in grapevine (Vitis vinifera L.) leaves described by 16S rRNA gene sequence analysis and length heterogeneity-PCR.
Diversity of bacterial endophytes associated with grapevine leaf tissues was analyzed by cultivation and cultivation-independent methods. In order to identify bacterial endophytes directly from metagenome, a protocol for bacteria enrichment and DNA extraction was optimized. Sequence analysis of 16S rRNA gene libraries underscored five diverse Operational Taxonomic Units (OTUs), showing best sequence matches with gamma-Proteobacteria, family Enterobacteriaceae, with a dominance of the genus Pantoea. Bacteria isolation through cultivation revealed the presence of six OTUs, showing best sequence matches with Actinobacteria, genus Curtobacterium, and with Firmicutes genera Bacillus and Enterococcus. Length Heterogeneity-PCR (LH-PCR) electrophoretic peaks from single bacterial clones were used to setup a database representing the bacterial endophytes identified in association with grapevine tissues. Analysis of healthy and phytoplasma-infected grapevine plants showed that LH-PCR could be a useful complementary tool for examining the diversity of bacterial endophytes especially for diversity survey on a large number of samples.


Daclatasvir and Peginterferon/Ribavirin for Black/African-American and Latino Patients with HCV infection.
Background. Patient race and ethnicity have historically impacted HCV treatment response. This phase 3 study evaluated daclatasvir with peginterferon-alfa-2a/ribavirin (pegIFN alfa-2a/RBV) in treatment-naive black/African American (AA), Latino, and white non-Latino patients with chronic HCV genotype 1 infection. In this single-arm, open-label study, 246 patients received daclatasvir plus pegIFN alfa-2a and weight-based RBV. Patients with an extended rapid virologic response (eRVR; undetectable HCV-RNA at treatment weeks 4 and 12) received 24 weeks of treatment; those without eRVR received an additional 24 weeks of treatment with pegIFN alfa-2a/RBV. The primary endpoint was sustained virologic response at post-treatment week 12 (SVR12; HCV-RNA < 25 IU/mL) compared with the cohort historical rate. Most patients were IL28B non-CC (84.4% black/AA; 77.6% Latino) genotype 1a-infected (72.7%; 81.3%), with HCV-RNA ≥ 800,000 IU/mL (81.3%; 64.5%). SVR12 rates were 50.8% (65/128; 95% confidence interval [CI], 42.1-59.4) for black/AA and 58.9% (63/107; 95% CI, 49.6-68.2) for Latino patients. The majority (55.5%; 58.9%) received 24 weeks treatment; rapid reductions (> 4-log10) in HCV-RNA levels were observed. Only 60.9% (78/128) of black/AA and 63.6% (68/107) of Latino patients completed treatment. On-treatment serious adverse events (SAEs) occurred in 21 patients. Discontinuations due to adverse events (AEs) occurred in 9 black/AA and 6 Latino patients. SVR12 rates for black/AA (50.8%) and Latino (58.9%) cohorts treated with daclatasvir plus pegIFN alfa-2a/RBV and the lower bound of the 95% CIs were higher than the estimated historical control (black/AA, 26% SVR; Latino, 36% SVR) treated with pegIFN alfa-2a/RBV. These data support daclatasvir use in all-oral direct-acting antiviral combinations.


Diseases associated with chronic rhinosinusitis: what is the significance?
To discuss the systemic conditions that may impact the incidence, severity, prognosis, or treatment approach in patients with chronic rhinosinusitis. Patients with allergic rhinitis do not necessarily have more severe chronic rhinosinusitis as assessed by symptom scores, nasal endoscopy, or computed tomography staging. However, at least in pediatric patients with chronic rhinosinusitis who undergo surgery, consideration of allergy and allergy treatment appears to improve surgical results. Patients with aspirin sensitivity have a more severe disease, but benefit from surgical treatment to the same degree as non-aspirin-sensitive patients with chronic rhinosinusitis. Surgical treatment of polypoid rhinosinusitis in cystic fibrosis patients improves symptoms, and aggressive surgical opening of sinus cavities may provide long-lasting benefit, though polyps will regrow in most patients, and many will require repeat surgery. Rhinosinusitis is among the most common infectious complications of humoral immunodeficiency, and humoral immunodeficiency is not uncommon in patients with refractory chronic rhinosinusitis. Patients with granulomatous disease causing rhinosinusitis, such as Wegener's granulomatosis, appear to suffer from a symptom burden that is equivalent to the broader population of chronic rhinosinusitis patients. Systemic disease conditions influence the incidence, treatment, and severity of chronic rhinosinusitis. Specific diagnosis of these contributing conditions will facilitate appropriate treatment.


Ventilatory function and cardiovascular disease risk factors: a cross-sectional study in young adults.
The association between impaired lung function and cardiovascular disease (CVD) risk factors has been shown in adults. However, there is little evidence of such an association in young adults, particularly from South America, where the burden of CVD and chronic obstructive pulmonary disease (COPD) is as high as that observed in more developed countries. We therefore investigated the relation between CVD risk factors including metabolic syndrome (MS), and lung function status in young adults from Chile. 970 subjects from a sample of 998 adults born between 1974 and 1978 in Limache, Chile, were studied. A Spanish translation of the European Community Respiratory Health Survey (ECRHS) questionnaire was used. Forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were measured. Weight, height, waist circumference (WC), blood pressure, Homeostatic model assessment (HOMA-IR), triglycerides, high density lipoprotein (HDL), glycaemia, and metabolic syndrome (MS) were also assessed. The prevalence of MS was 11.8%. A lower FEV1 and lower FVC were associated with having MS (β-coefficient -0.13; 95% Confidence Interval [CI] -0.21 to -0.05, and β-coefficient -0.18; 95% CI -0.27 to -0.09, respectively). Both spirometric measures were also negatively associated with having an elevated HOMA-IR (β-coefficient for FEV1 -0.08; 95% CI -0.13 to -0.03, and β-coefficient for FVC -0.11; 95% CI -0.17 to -0.05). In males only, a lower FEV1 and FVC were associated with having elevated triglycerides (β-coefficient highest vs. lowest tertile -0.13, 95% CI -0.24 to -0.03, and β-coefficient -0.13, 95% CI -0.25 to -0.01, respectively). In women, a higher FEV1 and FVC were statistically significantly related to having higher levels of HDL. Ventilatory function was unrelated to hypertension or WC in this population. In this population-based study of young adults, a poorer ventilatory function was associated with many CVD risk factors. Endeavours to understand better causality issues of such associations are warranted.


The association of depression and mortality in elderly persons: a case for multiple, independent pathways.
The evidence for an association between depression and mortality among community-dwelling elderly persons remains inconclusive, although it is well established for younger individuals. Extant studies suggest that this association weakens when adjusted for potential confounding factors, especially functional impairment. A cohort of elderly subjects followed for 3 years was analyzed to determine the association of depression and 3-year mortality, controlling for the major known risk factors for mortality in the elderly population. Information on depression (CES-D scores), mortality, demographics, body mass index, chronic disease, smoking history, cognitive impairment, functional impairment, self-rated health, and social support was obtained from a stratified probability-based sample of community-dwelling elderly persons, with equal distribution between African Americans and whites in the Piedmont of North Carolina. Descriptive statistics were calculated, and logistic regression was used for a series of models with progressively more control variables. The unadjusted relative odds of mortality among depressed subjects at baseline was 1.98 over 3 years of follow-up. Inclusion of age, gender, and race into the model did not reduce the relative odds. When chronic disease and health habits, cognitive impairment, functional impairment, and social support were added to the model, the odds ratios for mortality with depression were 1.74, 1.69, 1.29, and 1.21, respectively. This decrease in odds ratios was not observed for other variables in the model when additional variables were added. The estimated odds of dying if depressed moved toward unity as other risk factors for mortality were controlled. Unlike other known risk factors for mortality in the elderly population, depression appears to be associated with mortality through a number of independent mechanisms, perhaps through complex feedback loops.


Multimodal fast optical interrogation of neural circuitry.
Our understanding of the cellular implementation of systems-level neural processes like action, thought and emotion has been limited by the availability of tools to interrogate specific classes of neural cells within intact, living brain tissue. Here we identify and develop an archaeal light-driven chloride pump (NpHR) from Natronomonas pharaonis for temporally precise optical inhibition of neural activity. NpHR allows either knockout of single action potentials, or sustained blockade of spiking. NpHR is compatible with ChR2, the previous optical excitation technology we have described, in that the two opposing probes operate at similar light powers but with well-separated action spectra. NpHR, like ChR2, functions in mammals without exogenous cofactors, and the two probes can be integrated with calcium imaging in mammalian brain tissue for bidirectional optical modulation and readout of neural activity. Likewise, NpHR and ChR2 can be targeted together to Caenorhabditis elegans muscle and cholinergic motor neurons to control locomotion bidirectionally. NpHR and ChR2 form a complete system for multimodal, high-speed, genetically targeted, all-optical interrogation of living neural circuits.


Challenges in Analyzing the Biological Effects of Resveratrol.
The suggested health effects (e.g., disease prevention) of dietary bioactive compounds such as resveratrol are challenging to prove in comparison to man-made drugs developed for therapeutic purposes. Dietary bioactive compounds have multiple cellular targets and therefore have a variety of biological effects. Extrapolating the biological effects of dietary compounds from in vitro and in vivo animal experiments to humans may lead to over- or under-estimation of the effect and role of these compounds. The present paper will discuss a few of these challenges and suggest directions for future research. Questions we address include: (1) Is the combinatorial effect of resveratrol and other compounds real? (2) What are the real and relevant doses of resveratrol after administration? and (3) Is it possible to estimate the preventive effect of resveratrol by clinical trials using standard experimental designs? The examples concerning resveratrol taken from the scientific literature are mainly from 2010 and later. The challenges pointed out in this review are similar to most naturally occurring bioactive compounds.


Proprotein convertase subtilisin/kexin type 9 (PCSK9) in Alzheimer's disease: A genetic and proteomic multi-cohort study.
Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a hepatic enzyme that regulates circulating low-density lipoprotein (LDL) cholesterol levels by binding to LDL receptors (LDLR) and promoting their degradation. Although PCSK9 inhibitors were shown to reduce the risk of cardiovascular disease, a warning was issued concerning their possible impact on cognitive functions. In Alzheimer's disease (AD), it is believed that cognitive impairment is associated with cholesterol metabolism alterations, which could involve PCSK9. The main objective of this study is to determine if PCSK9 plays a significant role in the pre-symptomatic phase of the disease when the pathophysiological markers of AD unfolds and, later, when cognitive symptoms emerge. To test if PCSK9 is associated with AD pathology, we measured its expression levels in 65 autopsy confirmed AD brains and 45 age and gender matched controls. Messenger ribonucleic acid (mRNA) were quantified using real-time polymerase chain reaction (RT-PCR) and protein levels were quantified using enzyme-linked immunosorbent assay (ELISA). PCSK9 was elevated in frontal cortices of AD subjects compared to controls, both at the mRNA and protein levels. LDLR protein levels were unchanged in AD frontal cortices, despite and upregulation at the mRNA level. To verify if PCSK9 dysregulation was observable before the onset of AD, we measured its expression in the cerebrospinal fluid (CSF) of 104 "at-risk" subjects and contrasted it with known apolipoproteins levels and specific AD biomarkers using ELISAs. Positive correlations were found between CSF PCSK9 and apolipoprotein E (APOE), apolipoprotein J (APOJ or CLU), apolipoprotein B (APOB), phospho Tau (pTau) and total Tau. To investigate if PCSK9 levels were driven by genetic variants, we conducted an expression quantitative trait loci (eQTL) study using bioinformatic tools and found two polymorphisms in strong association. Further investigation of these variants in two independent cohorts showed a female specific association with AD risk and with CSF Tau levels in cognitively impaired individuals. PCSK9 levels differ between control and AD brains and its protein levels correlate with those of other lipoproteins and AD biomarkers even before the onset of the disease. PCSK9 regulation seems to be under tight genetic control in females only, with specific variants that could predispose to increased AD risk.


Optical trapping, driving, and arrangement of particles using a tapered fibre probe.
The ability of manipulating mesoscopic objects with high precision and flexibility is extremely important for a wide variety of fields from physics, biochemistry, to biomedicine. Particularly, the ability of arranging particles/cells into desired patterns precisely is a challenge for numerous physical and biological applications. Here, we report a strategy of realizing highly flexible trapping, driving, and precise arrangement of particles using a tapered fibre probe. Using randomly distributed 3-µm-diameter silica particles as an example, we demonstrate that the strategy is able to stably trap the particles and drive them to targeted regions, subsequently arrange the particles into desired patterns. To further demonstrate the ability of this strategy, experiments were done using sub-micron sized particles and biological samples (bacteria and cells). This strategy provides a new approach to manipulate mesoscopic objects precisely and flexibly, and hopefully can be used in future fundamental and applied researches of interdiscipline.


Inter-annual variation in prevalence and intensity of mite parasitism relates to appearance and expression of damselfly resistance.
Insects can resist parasites using the costly process of melanotic encapsulation. This form of physiological resistance has been studied under laboratory conditions, but the abiotic and biotic factors affecting resistance in natural insect populations are not well understood. Mite parasitism of damselflies was studied in a temperate damselfly population over seven seasons to determine if melanotic encapsulation of mite feeding tubes was related to degree of parasitism, host sex, host size, emergence timing, duration of the emergence period, and average daily air temperature. Although parasite prevalence in newly emerged damselflies was > 77% each year, hosts did not resist mites in the early years of study. Resistance began the year that there was a dramatic increase in the number of mites on newly emerged damselflies. Resistance continued to be correlated with mite prevalence and intensity throughout the seven-year study. However, the percentage of hosts resisting only ranged from 0-13% among years and resistance was not sex-biased and was not correlated with host size. Resistance also was not correlated with air temperature or with timing or duration of damselfly emergence. Resistance in host damselflies was weakly and variably expressed over the study period. Factors such as temperature, which have been identified in laboratory studies as contributing to resistance by similar hosts, can be irrelevant in natural populations. This lack of temperature effect may be due to the narrow range in temperatures observed at host emergence among years. Degree of mite parasitism predicted both the appearance and continued expression of resistance among parasitized damselflies.


[The analysis of physicians' work: announcing the end of attempts at in vitro fertilization].
The purpose of this empirical study is to analyze modalities of announcing the end of attempts at in vitro ferti-lization to women who, for various reasons, were not able to have a child after several trials. What are the problems physicians face when, in the course of their work, they make these announcements? How do they give (or not give) support to these women who have placed so much hope in this technique? These are some of the questions that led the authors to conduct this empirical study within the framework of a clinical and qualitative approach to work psychology. Within this framework, work is conceptualised as a complex activity that involves the subject, both bodily and through his various modes of socialisation. The field of clinical and quali-tative approach to work psychology situations focuses on different ways of expressing distress related to contradictory work demands, as the activity is being performed; it also focuses on those creative processes used by the subject to cope with those internal and external conflicts that hinder task performance. A review of the literature and preliminary observations led us to postulate that the problems physicians are faced with when they announce the end of attempts at in vitro fertilisation (IVF) are linked to several conflicts between work values (that are specific to the medical world) and the recognition of work failure: termination of attempts at IVF. The popu-lation that participated in this research project belongs to a network of private practitioners who work with the in-house team of a Parisian clinic. But the group is not uniform and some physicians perform IVFs more frequently than others. Our qualitative study involved 10 semi-directive interviews of approximately 1 1/2 hours each, which were recorded and transcribed. Initial instructions focused on a concrete description of situations of abandonment of attempts at IVF, in terms of their preparation, development, and the way they are experienced . Interviews therefore centred on specific and limited practitioner activity. Each transcription was submitted to a Qualitative Analysis of Discourse, followed by a comparative analysis of the 10 transcriptions. We propose an original method of Qualitative Analysis of Discourse, to be applied to semi-structured clinical interviews. This method seeks to analyse the structure of the resulting egocentric monologue in research si-tuations of semi-directive interviewing. The method of Quali-tative Analysis of Discourse involves three steps, but only the first two were applied in this work: a) identification of sequences of discourse; b) analysis of relationships between statements; c) stylistic analysis of figures of speech. Our first set of analyses showed that seve-ral markers increase in physicians' discourse when they describe difficult and/or conflict-laden consultation situations: logical connectors, impersonal pronouns, reported discourse, anti-cipations regarding the interviewer's judgement. The logical balance of the discourse therefore appears threatened when pro-blems inherent in the work demands involved in ending IVF attempts are mentioned. As a whole, these markers underscore the importance of the implicit dimension of discourse (inferences, presuppositions, hints, allusions, etc.), thus reflecting complex speech that attempts to negotiate between subjective positions and shared cultural values. A comparative analysis of the markers identified in the 10 interviews revealed four areas, each involving nervous tension poles, that are suggestive of cognitive-emotional dissonance in the task to be performed. Some factors increase professional distress while others temper it. They act upon the work situation itself on the one hand, and on the working relationship between physician and patient on the other. 1. Areas of tension relating to the task to be performed. The first area contrasts individual with collective decision-making. The independent status which characterises private medical practice increases self-esteem in cases of success but weakens it when IVF attempts fail. In addition, it goes against collective involvement in the work situation, yet such involvement may act as a strong moderating factor for the experience of distress. The second area contrasts work that is well done with recognition by peers. Indeed, in the hierarchy of medical values, recognition by peers that work has been well performed is anchored in successful healing (in the broad sense of the term), whereas in situations of abandonment of IVF attempts, ending the attempt is considered by everyone to be a failure, even if it has been well conducted . The third area opposes objective medical practice to a necessarily subjective medical involvement. The scientific and ideal values which characterise medicine reflect its objective and scientific orientation, but IVF situations are a reminder that medicine is not an exact science and that it can make mistakes. There are numerous special individual cases which reduce certainty that a decision to terminate IVF is well-founded. The fourth area distinguishes between work that is considered to be well done and work considered to be well conducted . Personal estimation of work that is well done is based on the impression that the maximum feasible has been done . But in IVF situations, constant uncertainty leads to professional over-involvement (examinations, verifications, changes of protocols). Work that is poorly done is work that does not cure or that brings no relief. As a result, work that consists in ending IVF attempts, even if it is well conducted , remains a subjective failure for everyone since it does not bring a cure (pregnancy). 2. Areas of tension in the physician-patient relationship. The first area contrasts women's irrational desire with possible support from their husbands, when the time has come to announce the end of the attempts. But this voice/presence of husbands is consi-dered desirable and important only when attempts have failed, so that husbands are not encouraged to participate in the protocols except to help restrain their wives' over reactions . The second area opposes respect for the patient role with demands made by women. Lack of respect for the patient role, by making demands or by refusing to follow advice, particularly when IVF attempts are abandoned, crystallises all the resentment experienced by physicians in difficult work situations. Two cognitive-emotional worlds, more or less tuned to one another over the course of the IVF, start to clash and lose all mutual understanding: the medical world and the patient's subjective world. The third area results from the second one. It contrasts a listening physician with a powerful one. Physicians are very concerned that their relationship with their patients be one of partnership. But this (idealised) equilibrium is abruptly disrupted by the end of the attempts, inasmuch as it is the physician who has the power to stop these attempts and who decides to do so. The unveiling of this reality of a power relationship becomes a source of suffering and contradicts expressed surface values. The fourth area contrasts an attitude of ongoing patient support based on a belief in success with an attitude of patient support based on the prediction of a possible failure. Indeed, for a patient to be supported in a way physicians would consider right and adequate , the abandonment of IVF attempts should be anticipated in advance so that the physician can prepare both himself and the patients for the high risk of failure. But physicians insist on the fact that medical work can only succeed if they believe in it . As a result, the more energy the physician puts into launching the initial phase of IVF, the greater the feeling of self-accomplishment during the first phase of IVF; but conversely, the weaker the efficacy of the process of seeing the patient through the end of the attempts, the stronger the fee-ling of subjective distress at work will be. Overall, it is a para-doxical work situation for physicians to have to anticipate the interruption of IVF attempts and to have to prepare for seeing the patient through this abandonment. This situation creates conflicts of representations and values within their very practice and generates distress at work. It is worth noting that some moderating factors could alleviate their sense of suffering and contribute to improving their work experience: a) the deve-lopment of a protocol for seeing patients through the end of IVF attempts, which would make abandonment part of a job well done for physicians; b) regular participation by the spouse in these protocols; c) making all decisions to end IVF attempts a collective process, in order to avoid placing exclusive responsibility on the treating physician. The limitations of this study are inherent both in the qualitative nature of the data that involve a small number of physicians, and in the specificity of this population that works within a poorly structured network. On the other hand, our method of Qualitative Analysis of Discourse can be applied to all types of discourse obtained in research situations, provided the discourse is produced through semi-directive or non-directive interviews.


Social norms, misperceptions, and mosquito net use: a population-based, cross-sectional study in rural Uganda.
Mosquito net use is an essential part of malaria prevention. Although previous research has shown that many people sleep under a mosquito net in endemic areas, it is unknown whether people underestimate how common it is to sleep under a net every night. Furthermore, perceived social norms about whether most others sleep under a mosquito net every night may contribute to personally sleeping under a net, given decades of research showing that people often mimic others' behaviours. Population-based data were collected from 1669 adults across eight villages in one rural parish in southwestern Uganda. Individuals' perception about whether most adults in their community sleep under a mosquito net every night was compared with whether daily mosquito net use was the actual norm in their community to identify the extent of norm misperception. The association between whether an individual perceived daily mosquito net use to be the norm and personal mosquito net use was assessed while adjusting for the ratio of nets:people in the household and other factors. Although the majority (65%) of participants reported sleeping under a mosquito net every night (and 75% did so among the 86% of people with at least one net), one-quarter of participants thought that most adults in their community did not sleep under a mosquito net every night. Another 8% were unsure how many nights per week most adults in their community sleep under a mosquito net. Participants who perceived that daily mosquito net use was the norm were 2.94 times more likely to report personally sleeping under a mosquito net every night (95% CI 2.09-4.14, p < 0.001) compared to participants who thought doing so was not normative, adjusting for other factors. Results suggest an opportunity for anti-malarial interventions to reduce misperceptions about mosquito net use norms and emphasize the commonness of daily mosquito net use in malaria-endemic regions. If people correctly perceive most others to sleep under a net every night, then they may personally do so when possible and support others to do so too.


Combined regimen of cisplatin, doxorubicin, and alpha-2b interferon in the treatment of advanced malignant pleural mesothelioma: a Phase II multicenter trial of the Italian Group on Rare Tumors (GITR) and the Italian Lung Cancer Task Force (FONICAP).
The cisplatin-doxorubicin combination has shown moderate activity in malignant pleural mesothelioma (MPM; objective response, 25%), and preclinical studies suggest that interferons (IFNs) may have an antiproliferative effect on mesothelioma cell lines with a marked increase in cisplatin cytotoxicity. Therefore, the combined chemoimmunotherapy regimen is an worthwhile approach to evaluate in a Phase II trial. From December 1995 to June 1999, 37 previously untreated patients with MPM were treated with cisplatin 60 mg/m(2) intravenously on Day 1 plus doxorubicin 60 mg/m(2), recycled every 3-4 weeks and IFN-alpha-2b, 3 x 10((6)) international units subcutaneously 3 times a week for a total of 6 courses or until progression. Inclusion criteria were histologic diagnosis of MPM and measurable disease defined by computed tomography scan or magnetic resonance imaging. Thirty-four patients were assessable for toxicity and 35 for efficacy according to World Health Organization criteria. One hundred thirty-five courses were administered with a median of 4 cycles per patients. Seventy-six percent of patient presented at least 1 episode of severe myelosuppression (Grade 3 and 4). Severe anemia and thrombocytopenia occurred in 30% and 24% of patients, respectively. Sixty percent of patients presented constitutional symptoms. In the 35 patients assessable for response, the overall response rate was 29% (95% confidence interval, 15-47%). The median duration of response was 8.4 months. With a median follow-up of 19.6 months, the median survival was 9.3 months. One- and 2-year survival was 45% and 34%, respectively. This combined regimen has definite activity in MPM. However, toxicity, particularly myelosuppression and fatigue, is not negligible and may limit its application.


Parents' Perspectives on Radicalization: A Qualitative Study.
Radicalization of young people might be influenced by the way parents react towards the development of political or religious ideals. However, these reactions have hardly been explored. This study aimed to discover how parents reacted to the development of extreme ideals, and why they responded in the way that they did. To gain knowledge about the influence of parents on adolescents who developed extreme ideals, 82 in-depth interviews were held with adolescents and young adults who held extreme ideals. Interviews were also held with the parents or siblings of each adolescent and young adult. In line with parenting style theory, it was found that parents react in four possible ways: (1) by rejecting, (2) applauding, (3) ignoring, or (4) discussing the (extreme) ideals of their children. Few parents discuss ideals and values with their child, and this paper tries to show why (e.g., powerlessness, disassociation, occupation with other problems, believing it to be a phase that will pass, or that their reaction would not help). Most parents struggle to cope with radicalization and do not know how to react. Support and control are potentially important tools for parents to use to combat the development of extreme ideology.


Informed consent.
Under the law of informed consent, physicians must disclose to patients certain information about their medical condition and potential courses of treatment, and must obtain their consent to proceed. This article delineates the basic standards that govern such disclosure, with special reference to legal cases that have dealt with ophthalmic concerns. It concludes by discussing a number of special issues that have recently arisen in this area.


Hydrogel-coated coils for the treatment of cerebral aneurysms: preliminary results.
The authors present a retrospective analysis of their initial experience with the recently developed MicroVention HydroCoil to treat patients with cerebral aneurysms. Unlike the bare metal coils initially available for endovascular treatment of aneurysms, HydroCoils have a layer of hydrogel polymer surrounding a platinum metallic core. The hydrogel polymer expands soon after making contact with blood. The expanded hydrogel polymer provides increased volumetric filling compared with bare metal coils and offers a more biocompatible surface, as demonstrated in animal models. Over a 17-month period, the authors used HydroCoils to treat 30 patients with 33 aneurysms. All patients had been treated at least 6 months prior to data analysis. Initial treatment results as well as records of clinical and angiographic follow up were reviewed. Six-month posttreatment angiograms were available for 25 patients. The HydroCoils were implanted with few complications. On angiographic follow up, a clearly defined radiolucent separation of the coils from the parent artery was noted in many of the aneurysms treated. The authors have not previously observed angiographically demonstrated lucencies separating the coils from the parent artery. This frequent, but not consistent, appearance on follow-up angiograms obtained in this study indicates that HydroCoils support significant neointimal formation across the neck of treated aneurysms. The preliminary results indicate that HydroCoils can be used safely and effectively to treat aneurysms and that these devices may allow for improved aneurysm filling.


Stability of self-esteem across the life span.
Two studies examined the rank-order stability of self-esteem from age 6 to 83: Study 1 was a meta-analysis of 50 published articles (N = 29,839) and Study 2 analyzed data from 4 large national studies (N = 74,381). Self-esteem showed substantial continuity over time (disattenuated correlations ranged from the .50s to .70s), comparable to the stability found for personality traits. Both studies provided evidence for a robust developmental trend: Self-esteem stability was low during childhood, increased throughout adolescence and young adulthood, and declined during midlife and old age. This trend could not be explained by age differences in the reliability of self-esteem measures, and generally replicated across gender, ethnicity, self-esteem scale, nationality (U.S. vs. non-U.S.), and year of publication.


Hematological characterization of congenital osteopetrosis in op/op mouse. Possible mechanism for abnormal macrophage differentiation.
Compared with normal littermates, the op/op mice had very few macrophages in the peritoneal cavity and severely reduced numbers of monocytes in the peripheral blood. Moreover, osteopetrotic animals demonstrated an altered distribution of hemopoietic tissue with a 10-fold decrease in the number of marrow cells. Liver hemopoiesis persisted in 4-wk-old mice as evidenced by the presence of hemopoietic stem cells (HSC). Moreover, the concentration of HSC was decreased in marrow and increased in the spleen of op/op mice. In spite of the paucity of cells of monocyte-macrophage lineage in vivo, progenitor cells from hemopoietic tissues of op/op mice formed increased numbers of monocyte-macrophage colonies in vitro in the presence of exogenous colony-stimulating activity (CSA). The source of this critical CSA was a medium conditioned by stromal fibroblastoid colonies formed in vitro by normal marrow cells. Therefore, these data suggest that op/op mice possess normal monocyte-macrophage-osteoclast progenitor cells but these cells are unable to fully differentiate in the op/op mouse microenvironment. In support of this, in cultures of stromal fibroblastoid colonies from op/op marrow or spleen, the concomitant growth of macrophages, normally very dense, was drastically reduced. Moreover, transplantation of op/op spleen cells into lethally irradiated littermate recipients resulted in their hemopoietic reconstitution without signs of macrophage defect. Thus, the op/op splenic cells do not transfer the disease and are capable of normal differentiation in normal in vivo environment. These observations support the hypothesis that the defect in op/op mice is a result of the failure of hemopoietic stromal fibroblastoid cells to release sufficient amounts of CSA necessary for normal differentiation of cells of the monocyte-macrophage lineage.


"It's a maybe test": men's experiences of prostate specific antigen testing in primary care.
Prostate specific antigen (PSA) testing in primary care is an important and contentious issue. Due to concerns about the test and the value of early detection, countries such as the UK advocate 'informed choice' instead of population screening. It is not known whether this policy is actually adhered to in primary care. Furthermore, little is known of the experiences of men who face this decision. To explore the experiences, understanding, and views of men who considered or undertook PSA testing in UK primary care. Qualitative interview-based study. Primary care, Wales, UK. Semi-structured one-to-one interviews were conducted with 28 men, representing a range of clinical outcomes. Transcripts were coded and subjected to thematic analysis. Three themes were identified: the decision-making context, the locus of decision making, and uncertainty related to the PSA test. The decision to undertake PSA testing was affected by both social and media factors and it did not appear to be a patient-led decision. The decision created considerable uncertainty for men and this uncertainty persisted after the test, even if the result was normal. Raised PSA led to further investigations and this exacerbated the uncertainty. Anxiety and regret were consequences of this uncertainty.


Score for Neonatal Acute Physiology: a physiologic severity index for neonatal intensive care.
The substantial variation in birth weight-adjusted mortality among neonatal intensive care units (NICUs) may reflect differences in population illness severity. Development of an illness severity measure is essential for comparisons of outcomes. The Score for Neonatal Acute Physiology (SNAP) was developed and validated prospectively on 1643 admissions (114 deaths) in three NICUs. SNAP scores the worst physiologic derangements in each organ system in the first 24 hours. SNAP showed little correlation with birth weight and was highly predictive of neonatal mortality even within narrow birth weight strata. It was capable of separating patients into groups with 2 to 20 times higher mortality risk. It also correlated highly with other indicators of severity including nursing workload (r = .59), therapeutic intensity (r = .78), physician estimates of mortality risk (r = .65), and length of stay (R2 = .59). SNAP is an important new tool for NICU research.


The Teddy Bear Clinic Constitutional Court case: sexual conduct between adolescent consenting children aged under 16 years decriminalised and a moratorium on the reporting duties of doctors and others.
The Constitutional Court in the Teddy Bear Clinic appeal case held that the sections of the Sexual Offences Act that impose criminal liability for sexual offences on adolescent children under 16 years of age are invalid. The invalidity was suspended for 18 months to allow Parliament to correct the Act's defects. A moratorium was imposed on all investigations into, arrests in, prosecutions in, and criminal and ancillary proceedings regarding such section 15 and 16 offences. This includes the duty to report consensual sexual conduct between children under 16 years of age in terms of section 54 of the Act--pending Parliament's correction. However, it is submitted that the 'best interests of the child' principle in the Children's Act and the Constitution should guide all obligatory reporting situations involving sexual and other conduct of children, irrespective of whether they are adolescents under 16 years old or between 16 and 17 years old.


Sun-induced chlorophyll fluorescence from high-resolution imaging spectroscopy data to quantify spatio-temporal patterns of photosynthetic function in crop canopies.
Passive detection of sun-induced chlorophyll fluorescence (SIF) using spectroscopy has been proposed as a proxy to quantify changes in photochemical efficiency at canopy level under natural light conditions. In this study, we explored the use of imaging spectroscopy to quantify spatio-temporal dynamics of SIF within crop canopies and its sensitivity to track patterns of photosynthetic activity originating from the interaction between vegetation structure and incoming radiation as well as variations in plant function. SIF was retrieved using the Fraunhofer Line Depth (FLD) principle from imaging spectroscopy data acquired at different time scales a few metres above several crop canopies growing under natural illumination. We report the first maps of canopy SIF in high spatial resolution. Changes of SIF were monitored at different time scales ranging from quick variations under induced stress conditions to seasonal dynamics. Natural changes were primarily determined by varying levels and distribution of photosynthetic active radiation (PAR). However, this relationship changed throughout the day demonstrating an additional physiological component modulating spatio-temporal patterns of SIF emission. We successfully used detailed SIF maps to track changes in the canopy's photochemical activity under field conditions, providing a new tool to evaluate complex patterns of photosynthesis within the canopy.


CD30 ligand signal transduction involves activation of a tyrosine kinase and of mitogen-activated protein kinase in a Hodgkin's lymphoma cell line.
CD30 is a transmembrane receptor of the nerve growth factor/tumor necrosis factor receptor superfamily. Its expression associated with Hodgkin's lymphoma and a subset of non-Hodgkin's lymphoma. Recently, its ligand (CD30L) has been cloned. CD30L enhances the proliferation of peripheral T cells and the Hodgkin's cell line HDLM-2 but seems to exert antiproliferative effects on large cell anaplastic lymphoma cell lines. Since tyrosine kinases are critical regulators of cell growth, we investigated whether CD30L induced changes in cellular tyrosine phosphorylation in CD30-positive lymphoma cell lines. Stimulation with CD30L or with an agonistic mAb against CD30, M44, induced a rapid, transient, and concentration-dependent tyrosine phosphorylation of a cytosolic protein of M(r) 42,000 (p42) in the Hodgkin's lymphomas cell line HDLM-2 but not in other CD30-positive lymphomas. In HDLM-2 cells, the phrobol ester phorbol 12-myristate 13-acetate also stimulated tyrosine phosphorylation of p42, and this effect was enhanced by M44. In marked contrast, agents stimulating the protein kinase A pathway, like forskolin or dibutyryl cAMP, did not affect tyrosine phosphorylation of P42. By immunoprecipitation with mAbs against mitogen-activated protein kinase (MAPK; p42ERKII), a M(r) 42,000 protein was identified which comigrated with p42 on SDS gels and which was phosphorylated on tyrosine residues in response to stimulation of CD30. Immune complex kinase assays showed that M44 mAb induced the activation of MAPK (p42ERKII) and the phosphorylation of a MAPK substrate, myelin basic protein. Taken together, the results suggest that CD30L induces the tyrosine phosphorylation and activation of the MAPK p42ERKII isoform in HDLM-2 cells. These findings may have implications for the understanding of the pathogenesis of Hodgkin's disease.


The impact of eHealth group interventions on the mental, behavioral, and physical health of adults: a systematic review protocol.
COVID-19 has resulted in an increased demand for eHealth services globally. There is emerging evidence for the efficacy for group eHealth interventions that support population-based mental health and wellbeing, but a systematic review is lacking. The primary objective of this systematic review is to summarize the evidence for eHealth group counseling and coaching programs for adults. A second objective is to assess, within studies selected for our primary objective, the impact of programs that encourage PA on outcomes compared to those that do not. Randomized controlled trials that assess the impact of eHealth group counseling or coaching programs on mental health, health behavior, or physical health activity among community-dwelling adults will be included. We will search the following electronic databases (from January 2005 onwards): MEDLINE, PsycINFO, CINHAL, and the Central Register of Controlled Trials. The primary outcomes will be changes in mental health conditions (e.g., depression, anxiety, stress, quality of life), behavioral health conditions (e.g., substance use, smoking, sexual behavior, eating behavior, medication adherence), and physical health conditions (e.g., coping with cancer, menopausal symptoms, arthritis pain). Secondary outcomes will be changes in physical activity. Two reviewers will independently screen all citations, full-text articles, and abstract data. Potential conflicts will be resolved through discussion with a third reviewer. A narrative synthesis without meta-analysis will be conducted. The strength of the body of evidence will be assessed using GRADE. The risk of bias in individual studies will be appraised using the Cochrane Risk of Bias 2.0 tool. Potential sources of gender bias in included studies will be considered at all stages of the planned review. This review will contribute to the literature by providing evidence on the effectiveness of eHealth counseling and coaching programs delivered to adults in a group format. The protocol has been registered at the International Prospective Register of Systematic Reviews (PROSPERO: CRD42020187551 ).


The very 5' end and the constant region of Ig genes are spared from somatic mutation because AID does not access these regions.
Somatic hypermutation (SHM) is restricted to VDJ regions and their adjacent flanks in immunoglobulin (Ig) genes, whereas constant regions are spared. Mutations occur after about 100 nucleotides downstream of the promoter and extend to 1-2 kb. We have asked why the very 5' and most of the 3' region of Ig genes are unmutated. Does the activation-induced cytosine deaminase (AID) that initiates SHM not gain access to these regions, or does AID gain access, but the resulting uracils are repaired error-free because error-prone repair does not gain access? The distribution of mutations was compared between uracil DNA glycosylase (Ung)-deficient and wild-type mice in endogenous Ig genes and in an Ig transgene. If AID gains access to the 5' and 3' regions that are unmutated in wild-type mice, one would expect an "AID footprint," namely transition mutations from C and G in Ung-deficient mice in the regions normally devoid of SHM. We find that the distribution of total mutations and transitions from C and G is indistinguishable in wild-type and Ung-deficient mice. Thus, AID does not gain access to the 5' and constant regions of Ig genes. The implications for the role of transcription and Ung in SHM are discussed.


Double-blind, placebo-controlled study on the effect of the aldosterone receptor antagonist spironolactone in patients who have persistent proteinuria and are on long-term angiotensin-converting enzyme inhibitor therapy, with or without an angiotensin II receptor blocker.
Studies have shown that dual therapy with angiotensin-converting enzyme inhibitors (ACEI) and either angiotensin II receptor blockers or aldosterone receptor antagonists is more effective in reducing proteinuria than either agent used alone. The questions that remain are as follows: (1) Which of these agents should be used as dual therapy with the ACEI? (2) Does a higher level of blockade of the renin-angiotensin-aldosterone system with triple therapy offer an advantage over dual blockade? A 3-mo randomized, double-blind, placebo-controlled study was performed in 41 patients with proteinuria >1.5 g/d. Four treatment groups were compared: (1) Ramipril + spironolactone placebo + irbesartan placebo, (2) ramipril + irbesartan + spironolactone placebo, (3) ramipril + irbesartan placebo + spironolactone, and (4) ramipril + irbesartan + spironolactone. The percentage change in protein excretion differed according to treatment arm (ANOVA: F(3,35) = 8.6, P < 0.001). Pair-wise comparison showed that greater reduction in protein excretion occurred in treatment regimens that incorporated spironolactone. The reduction in proteinuria at 3 mo was as follows: Group 1, 1.4%; group 2, 15.7%; group 3, 42.0%; and group 4, 48.2%. The reduction in proteinuria among patients who were taking spironolactone-containing regimens was sustained at 6 and 12 mo. This study suggests that aldosterone receptor blockade offers a valuable adjuvant treatment when used with ACEI therapy for the reduction of proteinuria. Results suggest no advantage of triple blockade over dual blockade of the renin-angiotensin-aldosterone system to reduce proteinuria.


Morphology-based prediction of cancer cell migration using an artificial neural network and a random decision forest.
Metastasis is the cause of death in most patients of breast cancer and other solid malignancies. Identification of cancer cells with highly migratory capability to metastasize relies on markers for epithelial-to-mesenchymal transition (EMT), a process increasing cell migration and metastasis. Marker-based approaches are limited by inconsistences among patients, types of cancer, and partial EMT states. Alternatively, we analyzed cancer cell migration behavior using computer vision. Using a microfluidic single-cell migration chip and high-content imaging, we extracted morphological features and recorded migratory direction and speed of breast cancer cells. By applying a Random Decision Forest (RDF) and an Artificial Neural Network (ANN), we achieved over 99% accuracy for cell movement direction prediction and 91% for speed prediction. Unprecedentedly, we identified highly motile cells and non-motile cells based on microscope images and a machine learning model, and pinpointed and validated morphological features determining cell migration, including not only known features related to cell polarization but also novel ones that can drive future mechanistic studies. Predicting cell movement by computer vision and machine learning establishes a ground-breaking approach to analyze cell migration and metastasis.


Host-endoparasitoid-endosymbiont relationships: concealed Strepsiptera provide new twist to Wolbachia in Australian tephritid fruit flies.
Wolbachia are widespread endosymbionts that affect arthropod reproduction and fitness. Mostly maternally inherited, Wolbachia are occasionally transferred horizontally. Previously, two Wolbachia strains were reported at low prevalence and titres across seven Australian tephritid species, possibly indicative of frequent horizontal transfer. Here, we performed whole-genome sequencing of field-caught Wolbachia-positive flies. Unexpectedly, we found complete mitogenomes of an endoparasitic strepsipteran, Dipterophagus daci, suggesting that Wolbachia in the flies are linked to concealed parasitization. We performed the first genetic characterization of D. daci and detected D. daci in Wolbachia-positive flies not visibly parasitized, and most but not all Wolbachia-negative flies were D. daci-negative, presumably reflecting polymorphism for the Wolbachia infections in D. daci. We dissected D. daci from stylopized flies and confirmed that Wolbachia infects D. daci, but also found Wolbachia in stylopized fly tissues, likely somatic, horizontally transferred, non-heritable infections. Furthermore, no Wolbachia cif and wmk genes were detected and very low mitogenomic variation in D. daci across its distribution. Therefore, Wolbachia may influence host fitness without reproductive manipulation. Our study of 13 tephritid species highlights that concealed early stages of strepsipteran parasitization led to the previous incorrect assignment of Wolbachia co-infections to tephritid species, obscuring ecological studies of this common endosymbiont and its horizontal transmission by parasitoids.


A jaboticaba extract prevents prostatic damage associated with aging and high-fat diet intake.
Aging and overweight are involved in prostatic lesion development, due to their association with cell proliferation, hormonal imbalance and angiogenesis. The jaboticaba fruit is rich in bioactive compounds, showing potential chemopreventive action such as the capacity to modulate hormones and angiogenesis hallmarks. This study aimed to evaluate the jaboticaba extract (PJE) effect on the prostate morphology and on molecules related to hormone signaling and angiogenesis, during aging and/or high-fat diet (HFD) intake. Seventy FVB mice were distributed into experimental groups: YG group (young: 3 month old mice), AG group (aged: 11 month old mice), HfAG group (aged + HFD), JAGI group (aged + 2.9 g kg-1 PJE), JAGII group (aged + 5.8 g kg-1 PJE), HfJAGI group (aged + HFD + 2.9 g kg-1 PJE) and HfJAGII group (aged + HFD + 5.8 g kg-1 PJE). The ventral prostate was collected for morphological, immunohistochemistry and western-blotting analysis after 60 days of treatment. All PJE treatments promoted hormonal signaling balance and inhibited angiogenesis in the prostates of aged or HFD-fed aged mice, leading to the maintenance of healthy prostate morphology. A high dose of the PJE (JAGII and HfJAGII groups) led to the best capacity to reduce AR (58.40% and 74.42%; p = 0.0240 and p = 0.0023), ERα (30.29% and 45.12%; p = 0.0004 and p < 0.0001), aromatase (39.54% and 55.94%; p = 0.0038 and p = 0.0020), and VEGF (50.81% and 67.68%; p < 0.0001) and increase endostatin immunoexpression. Moreover, HFD intake intensified the hormonal and angiogenic alterations in the aged mouse prostates, contributing to the increase in premalignant lesion incidence. The PJE exerted a dose-dependent positive effect on aged or HFD-fed aged mouse prostates, contributing to the gland microenvironment recovery, mainly due to the hormonal and angiogenic balance. Therefore, we suggest that the PJE can be a potential candidate for prostatic lesion prevention.


Delivery of picosecond lasers in multimode fibers for coherent anti-Stokes Raman scattering imaging.
We investigated the possibility of using standard commercial multimode fibers (MMF), Corning SMF28 fibers, to deliver picosecond excitation lasers for coherent anti-Stokes Raman scattering (CARS) imaging. We theoretically and/or experimentally analyzed issues associated with the fiber delivery, such as dispersion length, walk-off length, nonlinear length, average threshold power for self-phase modulations, and four-wave mixing (FWM). These analyses can also be applied to other types of fibers. We found that FWM signals are generated in MMF, but they can be filtered out using a long-pass filter for CARS imaging. Finally, we demonstrated that MMF can be used for delivery of picosecond excitation lasers in the CARS imaging system without any degradation of image quality.


[Homicides in the Americas region: magnitude, distribution and trends, 1999-2009].
The scope of this study was to describe the magnitude and distribution of deaths by homicide in the Americas and to analyze the prevailing trends. Deaths by homicide (X85 to Y09 and Y35) were analyzed in 32 countries of the Americas Region from 1999 to 2009, recorded in the Mortality Information System/Pan American Health Organization. A negative binomial model was used to study the trends. There were around 121,297 homicides (89% men and 11% women) in the Americas, annually, predominantly in the 15 to 24 and 25 to 39 year age brackets. In 2009 the homicide age-adjusted mortality rate was 15.5/100,000 in the region. Countries with lower rates/100,000 were Canada (1.8), Argentina (4.4), Cuba (4.8), Chile (5.2), and the United States (5.8), whereas the highest rates/100,000 were in El Salvador (62.9), Guatemala (51.2), Colombia (42.5), Venezuela (33.2), and Puerto Rico (25.8). From 1999-2009, the homicide trend in the region was stable. They increased in nine countries: Venezuela (p<0.001), Panama (p<0.001), El Salvador (p<0.001), Puerto Rico (p<0.001); decreased in four countries, particularly in Colombia (p<0.001); and were stable in Brazil, the United States, Ecuador and Chile. The increase in Mexico occurred in recent years. Despite all efforts, various countries have high homicide rates and they are on the increase.


Using social media to monitor mental health discussions - evidence from Twitter.
Given the public health importance of communicating about mental illness and the growing use of social media to convey information, our goal was to develop an empirical model to identify periods of heightened interest in mental health topics on Twitter. We collected data on 176 million tweets from 2011 to 2014 with content related to depression or suicide. Using an autoregressive integrated moving average (ARIMA) data analysis, we identified deviations from predicted trends in communication about depression and suicide. Two types of heightened Twitter activity regarding depression or suicide were identified in 2014: expected increases in response to planned behavioral health events, and unexpected increases in response to unanticipated events. Tweet volume following expected increases went back to the predicted level more rapidly than the volume following unexpected events. Although ARIMA models have been used extensively in other fields, they have not been used widely in public health. Our findings indicate that our ARIMA model is valid for identifying periods of heightened activity on Twitter related to behavioral health. The model offers an objective and empirically based measure to identify periods of greater interest for timing the dissemination of credible information related to mental health. Spikes in tweet volume following a behavioral health event often last for less than 2 days. Individuals and organizations that want to disseminate behavioral health messages on Twitter in response to heightened periods of interest need to take this limited time frame into account.


[Postpartum pulmonary hypertension].
Pulmonary hypertension (PH) in pregnancy is a rare disorder that carries a high risk to mother and child, and as such, it is considered a contraindication to becoming pregnant. However, there are few published reports related to the diagnosis of this condition after delivery. We describe three PH cases diagnosed after their normal pregnancies and deliveries. Although the causes are unknown, several mechanisms such as hypercoagulation, placental hypoxia or amniotic fluid embolism have been considered as possible causes. It is difficult to define whether a PH diagnosed in the postpartum period, relates to an earlier asymptomatic PH period that was triggered by the physiological stress of labor or if it is a recently acquired condition. Despite the lack of data to support the absence of PH previous to pregnancy in our three patients, lack of events during this period, asymptomatic and normal deliveries, lead us to believe that they did not suffer this disease prior to pregnancy; considering that high hemodynamic demands impair a ventricle with little reserve, and its subsequent appearance at time of delivery.


Migration and Regional Differences in Access to Local Family Networks Among 60-year olds in Sweden.
Regional variations in access to local family networks has implications for future care burdens in different regions as well as the living conditions for both older and younger generations. The geographical distance between family members is a long-term consequence of accumulated migration and non-migration undertaken by the individual as well as other family members. This study contributes to this subject through offering a description of regional disparities in the access to local family networks among 60-year olds in Sweden. Additionally, this paper aims to analyse this pattern as an outcome of long-distance migration processes. The empirical study is based on Swedish register data, with a focus on 60-year olds in Sweden, linking them to their adult children, siblings and parents as well as in-laws. The dataset includes total population, where it is possible to identify family networks in their geographical context on various geographic scales, down to a neighbourhood level. As expected, results indicate that families in metropolitan areas are the most concentrated geographically while the left behind parent, embedded in a local network in their own and older generation, is a small category in urban areas but quite common in some rural municipalities. It is also shown that access to local family networks not only varies on a broad rural-urban scale but also locally, between neighbourhoods within metropolitan areas.


System building and improvement for the diagnosis and treatment of rare diseases in Shanghai, China.
Shanghai has always attached importance to the prevention and treatment of rare diseases and has been at the forefront in China. The Shanghai Rare Diseases Diagnosis and Treatment Center, Shanghai Children's Rare Diseases Diagnosis and Treatment Center, and Shanghai Rare Diseases Specialist Clinic were established in February 2018. Moreover, with the development of clinical pathways for rare diseases and the provision of related services such as diagnosis, treatment, screening, information and training, the service system for diagnosis and treatment of rare diseases in Shanghai has formed, which greatly improves the accessibility of medical services for patients with rare diseases in Shanghai and surrounding areas, and is of great significance in reducing the burden on patients with rare diseases. Meanwhile, it also gives an important reference for other regions of China for providing rare disease diagnosis and treatment services.


An overview of children's oral health-related quality of life assessment: from scale development to measuring outcomes.
The objectives of this paper are to present an overview of children's oral health-related quality of life and include specific applications for using quality of life assessment in dental research. The process of developing pediatric oral health- related quality of life measures, in particular the Child Oral Health Impact Profile, is outlined. Examples of children's oral health-related quality of life measurement in caries research are also provided. Quality of life outcomes are presented and discussed in the context of caries research. Lastly, the relevance of measuring clinically meaningful difference in the context of measuring outcomes research is highlighted with recommendations for future research.