Daily job demands and employee work engagement: The role of daily transformational leadership behavior.
Using job demands-resources (JD-R) theory, the present study integrates the challenge stressor-hindrance stressor framework and leadership theory to investigate the relationship between daily transformational leadership behavior and employee work engagement. We hypothesized that daily transformational leadership behavior (a) sustains employee work engagement on days characterized by high challenge job demands, and (b) protects work engagement on days characterized by high hindrance job demands. Teachers filled out a short online questionnaire at the end of each workday during a 2-week period (N = 271 × 5.68 days = 1539). Results of latent moderated structural equation modeling showed that teachers' daily challenge demands (workload and cognitive demands) had a positive relationship with work engagement on the days transformational leadership was high (vs. low). In addition, teachers' daily hindrance demands (role-conflict, but not family to work conflict) had a negative relationship with work engagement on the days transformational leadership was low (vs. high). These findings show that the function of transformational leadership behavior changes from day to day, and depends on the type of job demand. We discuss the practical and theoretical implications of these findings. (PsycINFO Database Record


Descriptive epidemiology of clubfoot in Romania: a clinic-based study.
Congenital clubfoot affects 1 per 1000 live births per year in Romania. To date, no epidemiological studies have been conducted in this country to assess risk factors associated with the deformity. The aim of this study was to evaluate specific environmental and socio-demographic factors that may increase the risk of an infant to be born with clubfoot. A descriptive clinic-based study over a twelve-week period was conducted using structured questionnaires given to biological parents of clinically confirmed clubfoot and control subjects. 62 parents of probands and 66 parents of control patients were enrolled for risk factor questionnaires. Phenotypic data from clubfoot children was also collected. We found that males were twice as likely to have clubfoot and half of clubfoot subjects were affected bilaterally. There was no significant difference in the rate of left versus right clubfoot. Infant and maternal characteristics showing a strong association with clubfoot included breech presentation and old maternal age at conception. Our results support reported literature data that males are two times as likely to have clubfoot which indicates a genetic influence. Previous reports suggest clubfoot babies are born to young mothers but in Romania advanced maternal age (≥ 35 years) was an indicator which may suggest genetic influence. This clinic-based study does not support previously recorded data of a positive association for maternal or household smoking. Data from this Romanian population also does not support previous data suggesting strong associations with maternal diabetes.


Quality assurance of an image guided intracranial stereotactic positioning system for radiosurgery treatment with helical tomotherapy.
The aim of this work was to determine the accuracy and precision of stereotactic localization and treatment delivery using a helical tomotherapy based stereotactic radiosurgery (SRS) system. A tomotherapy specific radiosurgery workflow was designed that exploits the system's on board megavotage CT (MVCT) imaging system so that it not only provides a pre-treatment volumetric verification image that can be used for stereotactic localization, eliminating the need for a patient-frame based coordinate system, but also supplies the treatment planning image. Using an imaging guidance based intracranial stereotactic positioning system, a head ring and tabletop docking device are used only for fixation, while image guidance is used for localization. Due to the unconventional workflow, a methodology for determining the localization accuracy was developed and results were compared to other linear accelerator based radiosurgery systems. In this work, the localization error using volumetric localization was found to be 0.45 mm +/- 0.17 mm, indicating a localization precision of 0.3 mm within a 95% confidence interval. In addition, procedures for testing the delivery accuracy of the Tomotherapy system are described. Results show that the accuracy of the delivery can be verified to within +/-1 voxel dimension. These results are well within conventional SRS tolerances and compare favorably to other linear accelerator based techniques.


Modified HeartMate II driveline externalization technique significantly decreases incidence of infection and improves long-term survival.
Driveline (DL) infection has been a major source of morbidity and mortality following HeartMate II left ventricular assist device (LVAD) implant, despite a significantly lower incidence compared with pulsatile flow devices. The purpose of this study was to compare the incidence of DL infection using two different externalization techniques. Between July 1, 2008, and October 15, 2011, 125 consecutive patients underwent HeartMate II LVAD implant at a single institution. Patients that underwent implant in 2008-2009 (n = 45) had the velour portion of the DL externalized (Velour group) and those that were implanted in 2010-2011 (n = 80) had only the silicone portion externalized (Silicone group). Kaplan-Meier analysis with log-rank test was used to compare actuarial DL infection-free survival and a composite of death and DL infection-free survival. There were 20/45 (44.4%) DL infections in the Velour group compared with 7/80 (8.8%) in the Silicone group. Driveline infection-free survival was significantly better for the Silicone versus Velour group as was the composite end-point of death and infection-free survival (p < 0.001). Externalization of only the silicone portion of the DL led to a dramatic reduction in infections and significantly improved survival after implant. This represents an opportunity to decrease the incidence of this important cause of morbidity and mortality after LVAD implant.


Limits to robustness and reproducibility in the demarcation of operational taxonomic units.
The demarcation of operational taxonomic units (OTUs) from complex sequence data sets is a key step in contemporary studies of microbial ecology. However, as biologically motivated 'optimal' OTU-binning algorithms remain elusive, many conceptually distinct approaches continue to be used. Using a global data set of 887 870 bacterial 16S rRNA gene sequences, we objectively quantified biases introduced by several widely employed sequence clustering algorithms. We found that OTU-binning methods often provided surprisingly non-equivalent partitions of identical data sets, notably when clustering to the same nominal similarity thresholds; and we quantified the resulting impact on ecological data description for a well-defined human skin microbiome data set. We observed that some methods were very robust to varying clustering thresholds, while others were found to be highly susceptible even to slight threshold variations. Moreover, we comprehensively quantified the impact of the choice of 16S rRNA gene subregion, as well as of data set scope and context on algorithm performance. Our findings may contribute to an enhanced comparability of results across sequence-processing pipelines, and we arrive at recommendations towards higher levels of standardization in established workflows.


Antagonizing the Hedgehog Pathway with Vismodegib Impairs Malignant Pleural Mesothelioma Growth In Vivo by Affecting Stroma.
An autocrine-driven upregulation of the Hedgehog (Hh) signaling pathway has been described in malignant pleural mesothelioma (MPM), in which the ligand, desert Hh (DHH), was produced from tumor cells. However, our investigation revealed that the Hh pathway is activated in both tumor and stroma of MPM tumor specimens and an orthotopic immunocompetent rat MPM model. This was demonstrated by positive immunohistochemical staining of Glioma-associated oncogene 1 (GLI1) and Patched1 (PTCH1) in both tumor and stromal fractions. DHH was predominantly expressed in the tumor fractions. To further investigate the role of the Hh pathway in MPM stroma, we antagonized Hh signaling in the rat model of MPM using a Hh antagonist, vismodegib, (100 mg/kg orally). Daily treatment with vismodegib efficiently downregulated Hh target genes Gli1, Hedgehog Interacting Protein (Hhip), and Ptch1, and caused a significant reduction of tumor volume and tumor growth delay. Immunohistochemical analyses revealed that vismodegib treatment primarily downregulated GLI1 and HHIP in the stromal compartment along with a reduced expression of previously described fibroblast Hh-responsive genes such as Fibronectin (Fn1) and Vegfa Primary cells isolated from the rat model cultured in 3% O2 continued to express Dhh but did not respond to vismodegib in vitro However, culture supernatant from these cells stimulated Gli1, Ptch1, and Fn1 expression in mouse embryonic fibroblasts, which was suppressed by vismodegib. Our study provides new evidence regarding the role of Hh signaling in MPM stroma in the maintenance of tumor growth, emphasizing Hh signaling as a treatment target for MPM. Mol Cancer Ther; 15(5); 1095-105. ©2016 AACR.


Expression of bone sialoprotein in human lung cancer.
Lung cancer belongs to the group of malignant lesions that specifically select bone as secondary implantation site. The molecular bases for this property, defined as osteotropism, is still largely unknown. The recent demonstration that human breast cancer cells express and attach to bone sialoprotein (BSP), a sulfated phosphoprotein rich in bone and other mineralized tissues, could provide a clue to elucidating bone metastases formation. BSP contains the integrin binding peptide Arg-Gly-Asp (RGD), as well as non-RGD cell attachment domain. Using an immunoperoxidase technique and a specific polyclonal antibody directed against a BSP synthetic peptide, we examined the expression of BSP in 48 lung lesions including 25 squamous carcinoma, 21 adenocarcinoma, and 2 bronchioloalveolar cancers, as well as 38 human ovarian carcinoma that constitute a group of generally nonosteotropic cancers. BSP was not specifically detected in normal lung tissue with the exception of cartilage associated with bronchi. Most of the adenocarcinoma (74%) and all squamous carcinoma of the lung examined exhibited detectable levels of BSP. Staining was mainly cytoplasmic and membrane associated. The two bronchioloalveolar lung cancers examined did not show detectable amounts of BSP. When microcalcifications were observed in pulmonary malignant lesions, they were usually associated with cancer cells expressing BSP. Only 21% of the ovarian cancers examined contained malignant cells with 2+ or 3+ positivity for BSP. We further demonstrated that in 8 of 10 additional lung cancers, BSP was detected at the mRNA level. Our observation is the first demonstration that BSP is expressed in non-small cell lung carcinoma. Lung cancer cells are now the second type of osteotropic malignant cells described to express BSP. Added to the observation that BSP expression is not frequent in ovarian carcinoma, a low osteotropic cancer, our study supports our hypothesis that BSP could play a role in determining the affinity of cancer cells to bone.


Validity of ICD-9 and ICD-10 codes used to identify acute liver injury: A study in three European data sources.
Validating cases of acute liver injury (ALI) in health care data sources is challenging. Previous validation studies reported low positive predictive values (PPVs). Case validation was undertaken in a study conducted from 2009 to 2014 assessing the risk of ALI in antidepressants users in databases in Spain (EpiChron and SIDIAP) and the Danish National Health Registers. Three ALI definitions were evaluated: primary (specific hospital discharge codes), secondary (specific and nonspecific hospital discharge codes), and tertiary (specific and nonspecific hospital and outpatient codes). The validation included review of patient profiles (EpiChron and SIDIAP) and of clinical data from medical records (EpiChron and Denmark). ALI cases were confirmed when liver enzyme values met a definition by an international working group. Overall PPVs (95% CIs) for the study ALI definitions were, for the primary ALI definition, 84% (60%-97%) (EpiChron), 60% (26%-88%) (SIDIAP), and 74% (60%-85%) (Denmark); for the secondary ALI definition, 65% (45%-81%) (EpiChron), 40% (19%-64%) (SIDIAP), and 70% (64%-77%) (Denmark); and for the tertiary ALI definition, 25% (18%-34%) (EpiChron), 8% (7%-9%) (SIDIAP), and 47% (42%-52%) (Denmark). The overall PPVs were higher for specific than for nonspecific codes and for hospital discharge than for outpatient codes. The nonspecific code "unspecified jaundice" had high PPVs in Denmark. PPVs obtained apply to patients using antidepressants without preexisting liver disease or ALI risk factors. To maximize validity, studies on ALI should prioritize hospital specific discharge codes and should include hospital codes for unspecified jaundice. Case validation is required when ALI outpatient cases are considered.


Engaging rural preceptors in new longitudinal community clerkships during workforce shortage: a qualitative study.
In keeping with its mission to produce doctors for rural and regional Australia, the University of Wollongong, Graduate School of Medicine has established an innovative model of clinical education. This includes a 12-month integrated community-based clerkship in a regional or rural setting, offering senior students longitudinal participation in a 'community of practice' with access to continuity of patient care experiences, continuity of supervision and curriculum, and individualised personal and professional development. This required developing new teaching sites, based on attracting preceptors and providing them with educational and physical infrastructure. A major challenge was severe health workforce shortages. Before the new clerkship started, we interviewed 28 general practitioners to determine why they engaged as clerkship preceptors. Independent researchers conducted semi-structured interviews. Responses were transcribed for inductive qualitative content analysis. The new model motivated preceptors to engage because it enhanced their opportunities to contribute to authentic learning when compared with the perceived limitations of short-term attachments. Preceptors appreciated the significant recognition of the value of general practice teaching and the honour of major involvement in the university. They predicted that the initiative would have positive effects on general practitioner morale and improve the quality of their practice. Other themes included the doctors' commitment to their profession, 'handing on' to the next generation and helping their community to attract doctors in the future. Supervisors perceive that new models of clinical education offer alternative solutions to health care education, delivery and workforce. The longitudinal relationship between preceptor, student and community was seen as offering reciprocal benefits. General practitioners are committed to refining practice and ensuring generation of new members in their profession. They are motivated to engage in novel regional and rural longitudinal clinical clerkships as they perceive that they offer students an authentic learning experience and are a potential strategy to help address workforce shortages and maldistribution.


Towards Web 3.0: taxonomies and ontologies for medical education -- a systematic review.
Both for curricular development and mapping, as well as for orientation within the mounting supply of learning resources in medical education, the Semantic Web ("Web 3.0") poses a low-threshold, effective tool that enables identification of content related items across system boundaries. Replacement of the currently required manual with an automatically generated link, which is based on content and semantics, requires the use of a suitably structured vocabulary for a machine-readable description of object content. Aim of this study is to compile the existing taxonomies and ontologies used for the annotation of medical content and learning resources, to compare those using selected criteria, and to verify their suitability in the context described above. Based on a systematic literature search, existing taxonomies and ontologies for the description of medical learning resources were identified. Through web searches and/or direct contact with the respective editors, each of the structured vocabularies thus identified were examined in regards to topic, structure, language, scope, maintenance, and technology of the taxonomy/ontology. In addition, suitability for use in the Semantic Web was verified. Among 20 identified publications, 14 structured vocabularies were identified, which differed rather strongly in regards to language, scope, currency, and maintenance. None of the identified vocabularies fulfilled the necessary criteria for content description of medical curricula and learning resources in the German-speaking world. While moving towards Web 3.0, a significant problem lies in the selection and use of an appropriate German vocabulary for the machine-readable description of object content. Possible solutions include development, translation and/or combination of existing vocabularies, possibly including partial translations of English vocabularies.


Changes in the genetic requirements for microbial interactions with increasing community complexity.
Microbial community structure and function rely on complex interactions whose underlying molecular mechanisms are poorly understood. To investigate these interactions in a simple microbiome, we introduced E. coli into an experimental community based on a cheese rind and identified the differences in E. coli's genetic requirements for growth in interactive and non-interactive contexts using Random Barcode Transposon Sequencing (RB-TnSeq) and RNASeq. Genetic requirements varied among pairwise growth conditions and between pairwise and community conditions. Our analysis points to mechanisms by which growth conditions change as a result of increasing community complexity and suggests that growth within a community relies on a combination of pairwise and higher-order interactions. Our work provides a framework for using the model organism E. coli as a readout to investigate microbial interactions regardless of the genetic tractability of members of the studied ecosystem.


Use of community resources before inflammatory bowel disease surgery is associated with postsurgical quality of life.
Research in chronic illness shows that community resources can have a lasting influence on the course of the illness; however, little research has been done to evaluate the community agencies that specifically address the needs of inflammatory bowel disease (IBD) patients. To survey awareness of community agency resources among patients who have surgery for IBD, and to analyze the association between using these resources and qualitative postsurgical outcomes. Ninety-two subjects who had surgery over a 12-month period completed, in full, the Inflammatory Bowel Disease Questionnaire (IBDQ), and a self-report instrument used to probe awareness and use of local community resources. Community resources were divided into two groups: those involving primarily social and educational participation ('social/ educational') and those involving some individualized attention, usually from a professional or trained lay facilitator ('professional/individual'). The contribution of presurgical participation in each type of resource to postsurgical quality of life was tested using ANOVA, with IBDQ score as the dependent variable. The ANOVA was repeated with postsurgical disease activity as a covariable. IBDQ subscale scores were compared between groups that were found to differ in the ANOVA. Almost all subjects were aware of at least one available resource. Participation in resources before surgery was variable, but 50% of the sample participated in at least one social/educational resource, and 46.9% participated in at least one professional/individual support. For the 92 subjects who completed both the IBDQ and the survey of resources, ANOVA revealed a main effect of professional/individual resource use on postsurgical quality of life but no main effect of social/educational resources and no interaction. The association between presurgical participation in professional or individualized community resources and better subjective outcome of IBD surgery may be explained by a positive contribution of participation to coping with surgery for IBD. The data do not support the alternative explanation that subjects with less severe disease (and thus better outcome) have greater ability to participate, although further research is required.


Inflammation selectively enhances amygdala activity to socially threatening images.
Although social withdrawal is a prominent symptom of sickness, the mechanisms associated with this behavioral change remain unclear. In animals, the amygdala is a key neural region involved in sickness-induced social withdrawal. Consistent with this, in humans, heightened amygdala activity to negative social cues is associated with social avoidance tendencies. Based on these findings, we investigated whether an experimental inflammatory challenge selectively increased amygdala activity to socially threatening images as well as whether this activity related to feelings of social disconnection. Thirty-nine participants were randomly assigned to receive either placebo or low-dose endotoxin, which increases inflammatory activity. Pro-inflammatory cytokines were assessed at 7 hourly time points via blood draws; self-reported feelings of social disconnection and physical sickness symptoms were assessed hourly as well. Two hours post-injection, participants underwent an fMRI procedure to assess amygdala reactivity during the presentation of socially threatening images (fear faces) as well as non-socially threatening images (guns), socially non-threatening images (happy faces), and non-social, non-threatening images (household objects). Endotoxin led to greater amygdala activity in response to socially threatening vs. all other types of images. No such differences were found for placebo participants. Additionally, increased amygdala activity in endotoxin participants during the viewing of socially vs. non-socially threatening images was associated with increased feelings of social disconnection. These findings highlight the amygdala as a neural region that may be important for sickness-induced social withdrawal. The implications of amygdalar involvement in sickness-induced social withdrawal are discussed.


Neuroscience and occupational therapy: vital connections. 1989 Eleanor Clarke Slagle lecture.
This paper presents the hypothesis that in-depth knowledge of the neurosciences serves as a common denominator that enhances our ability to interpret all aspects of human behavior. Neurobiological information can be used to design research to evaluate our existing treatment philosophy and methodology and to develop new theories and technology. Because occupational therapy addresses widely divergent diagnostic populations, three separate areas along the practice continuum were selected to demonstrate the application of neurobiological concepts: (a) neuroimmunomodulation, (b) organic bases of psychopathology, and (c) traumatic brain injury. Philosophical statements regarding effective methods of teaching neurobiology to occupational therapists are included.


Cyprinid herpesvirus 3 Evolves In Vitro through an Assemblage of Haplotypes that Alternatively Become Dominant or Under-Represented.
Viruses are able to evolve in vitro by mutations after serial passages in cell cultures, which can lead to either a loss, or an increase, of virulence. Cyprinid herpesvirus 3 (CyHV-3), a 295-kb double-stranded DNA virus, is the etiological agent of the koi herpesvirus disease (KHVD). To assess the influence of serial passages, an isolate of CyHV-3 (KHV-T) was passaged 99 times onto common carp brain (CCB) cells, and virus virulence was evaluated during passages through the experimental infections of common carp. After 78 CCB passages, the isolate was much less virulent than the original form. A comparative genomic analysis of these three forms of KHV-T (P0, P78 and P99) revealed a limited number of variations. The largest one was a deletion of 1363 bp in the predicted ORF150, which was detected in P78, but not in P99. This unexpected finding was confirmed by conventional PCR and digital PCR. The results presented here primarily suggest that, CyHV-3 evolves, at least in vitro, through an assemblage of haplotypes that alternatively become dominant or under-represented.


Human chorionic gonadotropin administration is associated with high pregnancy rates during ovarian stimulation and timed intercourse or intrauterine insemination.
There are different factors that influence treatment outcome after ovarian stimulation and timed-intercourse or intrauterine insemination (IUI). After patient age, it has been suggested that timing of insemination in relation to ovulation is probably the most important variable affecting the success of treatment. The objective of this study is to study the value of human chorionic gonadotropin (hCG) administration and occurrence of luteinizing hormone (LH) surge in timing insemination on the treatment outcome after follicular monitoring with timed-intercourse or intrauterine insemination, with or without ovarian stimulation. Retrospective analysis of 2000 consecutive completed treatment cycles (637 timed-intercourse and 1363 intrauterine insemination cycles). Stimulation protocols included clomiphene alone or with FSH injection, letrozole (an aromatase inhibitor) alone or with FSH, and FSH alone. LH-surge was defined as an increase in LH level > or =200% over mean of preceding two days. When given, hCG was administered at a dose of 10,000 IU. The main outcome was clinical pregnancy rate per cycle. Higher pregnancy rates occurred in cycles in which hCG was given. Occurrence of an LH-surge was associated with a higher pregnancy rate with clomiphene treatment, but a lower pregnancy rate with FSH treatment. hCG administration is associated with a favorable outcome during ovarian stimulation. Awaiting occurrence of LH-surge is associated with a better outcome with CC but not with FSH treatment.


The MOTIV-HEART Study: A Prospective, Randomized, Single-Blind Pilot Study of Brief Strategic Therapy and Motivational Interviewing among Cardiac Rehabilitation Patients.
Background: Psychological distress, biomedical parameters, and unhealthy lifestyles contribute to a poorer prognosis for cardiac disease. Public health's challenge is to motivate patients to utilize self-care. Objective: This prospective, randomized, single-blind pilot study aimed at testing the incremental efficacy of Brief Strategic Therapy (BST) combined with Motivational Interviewing (MI) in improving selected biomedical and psychological outcomes over and beyond those of the stand-alone BST in a residential Cardiac Rehabilitation (CR) program. Method: Fourty-two inpatients (17 females), enrolled in a 1-month CR program, were randomly allocated into two conditions: (a) Three sessions of BST and (b) Three sessions of BST plus MI. Data were collected at baseline, discharge, and after 3 months through phone interviews. Results: At discharge, no significant between-group difference was found in any outcome variable. Changes from pre- to post-treatment within each condition showed significant improvements only in the BST group, where the level of external regulation diminished, and both the participants' self-regulation (Relative Autonomous Motivation Index, RAI) and willingness to change improved. At the 3-month follow-up, within-group analyses on responders (BST = 9; BST + MI = 11) showed a statistically significant improvement in the level of systolic blood pressure in both groups. Discussion: Findings showed no evidence of the incremental efficacy of combining BST and MI over and beyond BST alone on either selected biomedical or psychological outcomes among CR patients. Conclusions: Ends and limitations from the present pilot study should be considered and addressed in future investigations.


A 2- to 7-year follow-up study of 54 obsessive-compulsive children and adolescents.
Due to the generally poor prognosis previously reported for patients with obsessive-compulsive disorder (OCD), this report systematically assessed the outcome of patients who had had access to new psychopharmacologic treatments to determine whether there had been any long-term gains and if there were any predictors of outcome. Prospective follow-up study of a cohort of consecutive pediatric patients with OCD who had participated in controlled treatment (clomipramine hydrochloride) trials and then received a variety of interim treatments. Fifty-four children and adolescents were reevaluated 2 to 7 years (mean, 3.4 +/- 1.0 years) after initial clomipramine treatment. Information for 48 (89%) of the patients was from direct interview and for the remaining six (11%) from at least two sources. On follow-up, 23 of the subjects (43%) still met diagnostic criteria for OCD, and only three (6%) could be considered in true remission. Thirty-eight subjects (70%) were taking psychoactive medication at the time of follow-up. Although OCD symptoms continued, the group as a whole was significantly improved at follow-up, with only 10 subjects (19%) rated as unchanged or worse. A worse OCD outcome score at follow-up was predicted in a stepwise multiple regression by (1) more severe OCD symptoms score after 5 weeks of clomipramine therapy, (2) lifetime history of a tic disorder, and (3) presence of parental Axis I psychiatric diagnosis (R2 = .31, P < .01). With new treatments available, most patients with pediatric OCD can expect significant longterm improvements but not complete remission. This study supports previous reports of the chronicity and intractability of the disorder, as there still remained a significant subgroup of subjects who exhibited continued morbidity despite multiple interventions.


Transdermal microgels of gentamicin.
Phospholipid-modified solid lipid microparticles (SLMs) of Phospholipon® 90G and 90H encapsulating the hydrophilic drug, gentamicin were produced and loaded into three polymeric hydrogels of Poloxamer 407 and polyacrylic acids (Carbopols® 971P and 974P). The SLMs were characterized by morphology and particle size, drug encapsulation efficiency, thermal properties, pH, and storage stability, whereas the microgels were evaluated for viscosity, spreadability, pH, drug content, and in vitro antimicrobial drug release against five microorganisms (Klebsiella spp., Escherichia coli, Bacillus subtilis, Staphylococcus aureus, and Pseudomonas aeruginosa). Our results generally showed Poloxamer 407 microgels of P90H and P90G as having the most desirable properties in terms of fast antibacterial activity on all tested microorganisms, in vitro diffusion-dependent permeation through rat abdominal skin, spreadability, pH, and viscosity, superior to polyacrylic acids microgels.


Ebola virus in West Africa: new conquered territories and new risks-or how I learned to stop worrying and (not) love Ebola virus.
After being restricted to Central Africa for 35 years, the Ebola virus has suddenly emerged in Guinea in early 2014. The virus rapidly spread to Liberia and Sierra Leone and was imported to Nigeria, Senegal, Mali and even USA. The main features of this outbreak are a relentless dissemination among several countries, a dramatic number of cases including health-care workers and an inability to control the outbreak which grows exponentially. This conquest of new territories by Ebola virus implies that new risks have now to be taken into account. Filoviruses have been promoted from the status of neglected diseases to that of international public health and security concerns and we now have to live with that threat. A vaccine is probably the only efficient approach to avoid future re-emergence.


Statistically significant papers in psychiatry were cited more often than others.
Citations by other researchers are important in the dissemination of research findings. We aimed to investigate whether preferential citation of statistically significant articles exists in the psychiatric literature. We analyzed all original research papers published in 1996 in four psychiatric journals. Using a standardized questionnaire, from each paper, we extracted the primary outcome and its statistical significance. The number of citations, excluding authors' "self-citations," received by April 2005 was obtained. Regression analysis was used to relate citation frequency to statistical significance, adjusting for confounders. Of 448 extracted papers, 368 used statistical significance testing and 287 (77.8%) reported P<0.05. The median number of citations for papers reporting "significant" and "nonsignificant" results was 33 vs. 16. After adjustment for journal, study design, reporting quality, whether outcome confirmed previous findings and study size, the ratio of the number of citations per article for articles reporting "P<0.05" on the primary outcome to those reporting "P>0.05" was 1.63 (95% confidence interval [CI]: 1.32, 2.02, P<0.001). Authors cite studies based on their P-value rather than intrinsic scientific merit. This practice skews the research evidence. Systematic study registration and inclusion in meta-analysis should be encouraged.


Considerations in the surgical management of ovarian cancer in the elderly.
Elderly patients with advanced epithelial ovarian cancer present a complex treatment dilemma. On the one hand, patients can be treated with primary debulking surgery to achieve the ideal oncologic outcomes but at the expense of risk of surgical morbidity and mortality. On the other hand, they can be treated with alternative, less morbid approaches, reducing toxicity, but sacrificing the survival benefits of low residual disease by surgical cytoreduction. Retrospective studies have attempted to identify risk factors for poor surgical outcome. Although there is no consensus to define "elderly" or "frail," current evidence identifies age, performance status, nutritional status, and surgical complexity as major risk factors for surgical morbidity. Accepting the shortcomings of these retrospective data, candidates for primary debulking surgery can be assessed for risk of surgical morbidity. Age is likely a contributor to morbidity, particularly in the face of comorbid conditions. Clinicians should strive to treat elderly patients with a standard approach of primary debulking surgery and adjuvant chemotherapy when healthy and in the absence of other risk factors. Elderly patients with the following are poor surgical candidates and an alternative treatment approach should be considered: poor nutritional status (characterized by serum albumin <3.0 g/dL), or poor performance status (ASA ≥3), and stage IV disease. Several of these factors are modifiable by treating the underlying cancer. These patients should be treated with two to three cycles of neoadjuvant chemotherapy and reassessed for surgical debulking. Patients with improvement in their nutritional or performance status can undergo interval debulking with the goal to resect all visible disease.


A case of video-assisted thoracoscopic resection of malignant transformation of pulmonary recurrent respiratory papillomatosis.
Recurrent respiratory papillomatosis (RRP) is a disease of the respiratory tract caused by infection with the human papillomavirus (HPV) and is characterized by multiple recurring papillomas throughout the respiratory tract. Although rare, extra laryngeal involvement carries the risk of malignant transformation in 3-7% of adults. We report the case of a patient with unmonitored juvenile onset RRP with pulmonary involvement found to have malignant transformation to squamous cell carcinoma (SCC). Incidentally found on chest radiography for mild chest wall trauma, she was found to have a large left lower lobe mass with pathology consistent with SCC. The patient underwent surgical management with thoracoscopic left lower lobectomy and mediastinal lymph node dissection followed by adjuvant chemoradiation for pathologic stage IIIA SCC. Surveillance imaging at 6 months shows no evidence of disease progression.


Targeting Bcl-2 family proteins modulates the sensitivity of B-cell lymphoma to rituximab-induced apoptosis.
The chimeric monoclonal antibody rituximab is the standard of care for patients with B-cell non-Hodgkin lymphoma (B-NHL). Rituximab mediates complement-dependent cytotoxicity and antibody-dependent cellular cytotoxicity of CD20-positive human B cells. In addition, rituximab sensitizes B-NHL cells to cytotoxic chemotherapy and has direct apoptotic and antiproliferative effects. Whereas expression of the CD20 antigen is a natural prerequisite for rituximab sensitivity, cell-autonomous factors determining the response of B-NHL to rituximab are less defined. To this end, we have studied rituximab-induced apoptosis in human B-NHL models. We find that rituximab directly triggers apoptosis via the mitochondrial pathway of caspase activation. Expression of antiapoptotic Bcl-xL confers resistance against rituximab-induced apoptosis in vitro and rituximab treatment of xenografted B-NHL in vivo. B-NHL cells insensitive to rituximab-induced apoptosis exhibit increased endogenous expression of multiple antiapoptotic Bcl-2 family proteins, or activation of phosphatidylinositol-3-kinase signaling resulting in up-regulation of Mcl-1. The former resistance pattern is overcome by treatment with the BH3-mimetic ABT-737, the latter by combining rituximab with pharmacologic phosphatidylinositol-3-kinase inhibitors. In conclusion, sensitivity of B-NHL cells to rituximab-induced apoptosis is determined at the level of mitochondria. Pharmacologic modulation of Bcl-2 family proteins or their upstream regulators is a promising strategy to overcome rituximab resistance.


The evolutionary history of plant T2/S-type ribonucleases.
A growing number of T2/S-RNases are being discovered in plant genomes. Members of this protein family have a variety of known functions, but the vast majority are still uncharacterized. We present data and analyses of phylogenetic relationships among T2/S-RNases, and pay special attention to the group that contains the female component of the most widespread system of self-incompatibility in flowering plants. The returned emphasis on the initially identified component of this mechanism yields important conjectures about its evolutionary context. First, we find that the clade involved in self-rejection (class III) is found exclusively in core eudicots, while the remaining clades contain members from other vascular plants. Second, certain features, such as intron patterns, isoelectric point, and conserved amino acid regions, help differentiate S-RNases, which are necessary for expression of self-incompatibility, from other T2/S-RNase family members. Third, we devise and present a set of approaches to clarify new S-RNase candidates from existing genome assemblies. We use genomic features to identify putative functional and relictual S-loci in genomes of plants with unknown mechanisms of self-incompatibility. The widespread occurrence of possible relicts suggests that the loss of functional self-incompatibility may leave traces long after the fact, and that this manner of molecular fossil-like data could be an important source of information about the history and distribution of both RNase-based and other mechanisms of self-incompatibility. Finally, we release a public resource intended to aid the search for S-locus RNases, and help provide increasingly detailed information about their taxonomic distribution.


Genetic effects of non-ionizing electromagnetic fields.
This is a review of the research on the genetic effects of non-ionizing electromagnetic field (EMF), mainly on radiofrequency radiation (RFR) and static and extremely low frequency EMF (ELF-EMF). The majority of the studies are on genotoxicity (e.g., DNA damage, chromatin conformation changes, etc.) and gene expression. Genetic effects of EMF depend on various factors, including field parameters and characteristics (frequency, intensity, wave-shape), cell type, and exposure duration. The types of gene expression affected (e.g., genes involved in cell cycle arrest, apoptosis and stress responses, heat-shock proteins) are consistent with the findings that EMF causes genetic damages. Many studies reported effects in cells and animals after exposure to EMF at intensities similar to those in the public and occupational environments. The mechanisms by which effects are induced by EMF are basically unknown. Involvement of free radicals is a likely possibility. EMF also interacts synergistically with different entities on genetic functions. Interactions, particularly with chemotherapeutic compounds, raise the possibility of using EMF as an adjuvant for cancer treatment to increase the efficacy and decrease side effects of traditional chemotherapeutic drugs. Other data, such as adaptive effects and mitotic spindle aberrations after EMF exposure, further support the notion that EMF causes genetic effects in living organisms.


A Slit/miR-218/Robo regulatory loop is required during heart tube formation in zebrafish.
Members of the Slit family of secreted ligands interact with Roundabout (Robo) receptors to provide guidance cues for many cell types. For example, Slit/Robo signaling elicits repulsion of axons during neural development, whereas in endothelial cells this pathway inhibits or promotes angiogenesis depending on the cellular context. Here, we show that miR-218 is intronically encoded in slit2 and slit3 and that it suppresses Robo1 and Robo2 expression. Our data indicate that miR-218 and multiple Slit/Robo signaling components are required for heart tube formation in zebrafish and that this network modulates the previously unappreciated function of Vegf signaling in this process. These findings suggest a new paradigm for microRNA-based control of ligand-receptor interactions and provide evidence for a novel signaling pathway regulating vertebrate heart tube assembly.


Imaging of neuroinflammation in migraine with aura: A [11C]PBR28 PET/MRI study.
To determine if migraine with aura is associated with neuroinflammation, which has been suggested by preclinical models of cortical spreading depression (CSD) as well as imaging of human pain conditions. Thirteen migraineurs with aura and 16 healthy controls received integrated PET/MRI brain scans with [11C]PBR28, a radioligand that binds to the 18 kDa translocator protein, a marker of glial activation. Standardized uptake value ratio (SUVR) was compared between groups, and regressed against clinical variables, using region of interest and whole-brain voxelwise analyses. Compared to healthy controls, migraineurs demonstrated SUVR elevations in nociceptive processing areas (e.g., thalamus and primary/secondary somatosensory and insular cortices) as well as in areas previously shown to be involved in CSD generation (visual cortex). SUVR levels in frontoinsular cortex, primary/secondary somatosensory cortices, and basal ganglia were correlated with frequency of migraine attacks. These findings demonstrate that migraine with aura is associated with neuroimmune activation/neuroinflammation, and support a possible link between CSD and glial activation, previously observed in animals.


Surveying multiple health professional team members within institutional settings: an example from the nursing home industry.
Quality improvement and cost containment initiatives in health care increasingly involve interdisciplinary teams of providers. To understand organizational functioning, information is often needed from multiple members of a leadership team since no one person may have sufficient knowledge of all aspects of the organization. To minimize survey burden, it is ideal to ask unique questions of each member of the leadership team in areas of their expertise. However, this risks substantial missing data if all eligible members of the organization do not respond to the survey. Nursing home administrators (NHA) and directors of nursing (DoN) play important roles in the leadership of long-term care facilities. Surveys were administered to NHAs and DoNs from a random, nationally representative sample of U.S. nursing homes about the impact of state policies, market forces, and organizational factors that impact provider performance and residents' outcomes. Responses were obtained from a total of 2,686 facilities (response rate [RR] = 66.6%) in which at least one individual completed the questionnaire and 1,693 facilities (RR = 42.0%) in which both providers participated. No evidence of nonresponse bias was detected. A high-quality representative sample of two providers in a long-term care facility can be obtained. It is possible to optimize data collection by obtaining unique information about the organization from each provider while minimizing the number of items asked of each individual. However, sufficient resources must be available for follow-up to nonresponders with particular attention paid to lower resourced, lower quality facilities caring for higher acuity residents in highly competitive nursing home markets.


Effects of a multifaceted medication reconciliation quality improvement intervention on patient safety: final results of the MARQUIS study.
Unintentional discrepancies across care settings are a common form of medication error and can contribute to patient harm. Medication reconciliation can reduce discrepancies; however, effective implementation in real-world settings is challenging. We conducted a pragmatic quality improvement (QI) study at five US hospitals, two of which included concurrent controls. The intervention consisted of local implementation of medication reconciliation best practices, utilising an evidence-based toolkit with 11 intervention components. Trained QI mentors conducted monthly site phone calls and two site visits during the intervention, which lasted from December 2011 through June 2014. The primary outcome was number of potentially harmful unintentional medication discrepancies per patient; secondary outcome was total discrepancies regardless of potential for harm. Time series analysis used multivariable Poisson regression. Across five sites, 1648 patients were sampled: 613 during baseline and 1035 during the implementation period. Overall, potentially harmful discrepancies did not decrease over time beyond baseline temporal trends, adjusted incidence rate ratio (IRR) 0.97 per month (95% CI 0.86 to 1.08), p=0.53. The intervention was associated with a reduction in total medication discrepancies, IRR 0.92 per month (95% CI 0.87 to 0.97), p=0.002. Of the four sites that implemented interventions, three had reductions in potentially harmful discrepancies. The fourth site, which implemented interventions and installed a new electronic health record (EHR), saw an increase in discrepancies, as did the fifth site, which did not implement any interventions but also installed a new EHR. Mentored implementation of a multifaceted medication reconciliation QI initiative was associated with a reduction in total, but not potentially harmful, medication discrepancies. The effect of EHR implementation on medication discrepancies warrants further study. NCT01337063.


New perspectives in the management of severe cranio-facial deformity.
It is postulated that craniosynostosis is due to a growth abnormality in all or part of the cranial capsule. Release of the stenosed part in the first months of life will re-establish the balance between the rapidly growing brain and eye, and the cranial capsule. Three periods for operative treatment are described: early, intermediate and late. Only in the early period can operative treatment restore normal growth dynamics; in the late period the aim is correction of an established deformity. The relationship between cranial clefts and frontonasal encephaloceles is explored. If the space-occupying encephalocele is removed early, the distorted facial bones adopt a more normal position, whereas cranial clefts do not respond to early operation by remoulding. The treatment of the acquired deformities of acute cranio-facial trauma have taken on new perspectives with the application of the multi-disciplinary approach and surgical techniques developed in the treatment of congenital deformities resulting in considerable reduction in the period of hospitalisation.


Rearrangement of a unique Kv1.3 selectivity filter conformation upon binding of a drug.
We report two structures of the human voltage-gated potassium channel (Kv) Kv1.3 in immune cells alone (apo-Kv1.3) and bound to an immunomodulatory drug called dalazatide (dalazatide-Kv1.3). Both the apo-Kv1.3 and dalazatide-Kv1.3 structures are in an activated state based on their depolarized voltage sensor and open inner gate. In apo-Kv1.3, the aromatic residue in the signature sequence (Y447) adopts a position that diverges 11 Å from other K+ channels. The outer pore is significantly rearranged, causing widening of the selectivity filter and perturbation of ion binding within the filter. This conformation is stabilized by a network of intrasubunit hydrogen bonds. In dalazatide-Kv1.3, binding of dalazatide to the channel's outer vestibule narrows the selectivity filter, Y447 occupies a position seen in other K+ channels, and this conformation is stabilized by a network of intersubunit hydrogen bonds. These remarkable rearrangements in the selectivity filter underlie Kv1.3's transition into the drug-blocked state.


ACE2, the kidney and the emergence of COVID-19 two decades after ACE2 discovery.
Angiotensin-converting enzyme II (ACE2) is a homologue of angiotensin-converting enzyme discovered in 2000. From the initial discovery, it was recognized that the kidneys were organs very rich on ACE2. Subsequent studies demonstrated the precise localization of ACE2 within the kidney and the importance of this enzyme in the metabolism of Angiotensin II and the formation of Angiotensin 1-7. With the recognition early in 2020 of ACE2 being the main receptor of severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2), the interest in this protein has dramatically increased. In this review, we will focus on kidney ACE2; its localization, its alterations in hypertension, diabetes, the effect of ACE inhibitors and angiotensin type 1 receptor blockers (ARBs) on ACE2 and the potential use of ACE2 recombinant proteins therapeutically for kidney disease. We also describe the emerging kidney manifestations of COVID-19, namely the frequent development of acute kidney injury. The possibility that binding of SARS-CoV-2 to kidney ACE2 plays a role in the kidney manifestations is also briefly discussed.


Task shifting and integration of HIV care into primary care in South Africa: the development and content of the streamlining tasks and roles to expand treatment and care for HIV (STRETCH) intervention.
Task shifting and the integration of human immunodeficiency virus (HIV) care into primary care services have been identified as possible strategies for improving access to antiretroviral treatment (ART). This paper describes the development and content of an intervention involving these two strategies, as part of the Streamlining Tasks and Roles to Expand Treatment and Care for HIV (STRETCH) pragmatic randomised controlled trial. DEVELOPING THE INTERVENTION: The intervention was developed following discussions with senior management, clinicians, and clinic staff. These discussions revealed that the establishment of separate antiretroviral treatment services for HIV had resulted in problems in accessing care due to the large number of patients at ART clinics. The intervention developed therefore combined the shifting from doctors to nurses of prescriptions of antiretrovirals (ARVs) for uncomplicated patients and the stepwise integration of HIV care into primary care services. COMPONENTS OF THE INTERVENTION: The intervention consisted of regulatory changes, training, and guidelines to support nurse ART prescription, local management teams, an implementation toolkit, and a flexible, phased introduction. Nurse supervisors were equipped to train intervention clinic nurses in ART prescription using outreach education and an integrated primary care guideline. Management teams were set up and a STRETCH coordinator was appointed to oversee the implementation process. Three important processes were used in developing and implementing this intervention: active participation of clinic staff and local and provincial management, educational outreach to train nurses in intervention sites, and an external facilitator to support all stages of the intervention rollout.The STRETCH trial is registered with Current Control Trials ISRCTN46836853.


Association of Urban Green Space With Mental Health and General Health Among Adults in Australia.
Recent studies indicate that living near more green space may support mental and general health and may also prevent depression. However, most studies are cross-sectional, and few have considered whether some types of green space matter more for mental health. To assess whether total green space or specific types of green space are associated with better mental health. This cohort study included a residentially stable, city-dwelling sample of 46 786 participants from Sydney, Wollongong, and Newcastle, Australia, in the baseline of the Sax Institute's 45 and Up Study (data collected from January 1, 2006, to December 31, 2009). Follow-up was conducted from January 1, 2012, to December 31, 2015. Analyses were conducted in January 2019. Percentage of total green space, tree canopy, grass, and other low-lying vegetation measured within 1.6-km (1-mile) road network distance buffers around residential addresses at baseline. Three outcome variables were examined at baseline (prevalence) and follow-up (incidence without baseline affirmatives): (1) risk of psychological distress (10-item Kessler Psychological Distress Scale), (2) self-reported physician-diagnosed depression or anxiety, and (3) fair to poor self-rated general health. This study included 46 786 participants (mean [SD] age, 61.0 [10.2] years; 25 171 [53.8%] female). At baseline, 5.1% of 37 775 reported a high risk of psychological distress, 16.0% of 46 786 reported depression or anxiety, and 9.0% of 45 577 reported fair to poor self-rated health. An additional 3.3% of 32 991 experienced psychological distress incidence, 7.5% of 39 277 experienced depression or anxiety incidence, and 7.3% of 40 741 experienced fair to poor self-rated health incidence by follow-up (mean [SD] of 6.2 [1.62] years later). Odds ratios (ORs) adjusted for age, sex, income, economic status, couple status, and educational level indicated that exposures of 30% or more total green space (OR, 0.46; 95% CI, 0.29-0.69) and tree canopy specifically (OR, 0.69; 95% CI, 0.54-0.88) were associated with lower incidence of psychological distress. Exposure to tree canopy of 30% or more, compared with 0% to 9%, was also associated with lower incidence of fair to poor general health (OR, 0.67; 95% CI, 0.57-0.80). Exposure to grass of 30% or more, compared with 0% to 4%, was associated with higher odds of incident fair to poor general health (OR, 1.47; 95% CI, 1.12-1.91) and prevalent psychological distress (OR, 1.71; 95% CI, 1.25-2.28). Exposure to low-lying vegetation was not consistently associated with any outcome. No green space indicator was associated with prevalent or incident depression or anxiety. Protection and restoration of urban tree canopy specifically, rather than any urban greening, may be a good option for promotion of community mental health.


Approaches to influencing food choice across the age groups: from children to the elderly.
Nutrition across the lifespan encompasses both preventative and treatment options to maintain health and vitality. This review will focus on the challenge of overconsumption of energy relative to energy expenditure and the consequent development of overweight and obesity, since they are responsible for much of the burden of chronic disease in the developed world. Understanding the mechanisms of hunger and satiety and how particular foodstuffs and nutrients affect appetite and motivation to eat is important for evidence-based interventions to achieve weight control and design of community-wide dietary strategies that reach across the lifespan. Food reformulation for appetite control and weight management requires a knowledge of the mechanisms of hunger and satiety, how food interacts with peripheral and central regulatory systems, and how these interactions change across the lifecourse, allied to the technical capability to generate, evaluate and develop new ingredients and foods with enhanced biological potency based on these mechanisms. Two European Union-funded research projects, Full4Health and SATIN, are adopting these complementary approaches. These research projects straddle the sometimes conflicted ground between justifiable public health concerns on the one hand and the food and drink industry on the other. These multi-disciplinary projects pull together expertise in nutrition, neuroimaging, psychology and food technology that combines with food industry partners to maximise expected impact of the research. Better knowledge of mechanisms regulating hunger/satiety will lead to evidence base for preventive strategies for the European population, to reduction of chronic disease burden and to increased competitiveness of European food industry through the development of new food products.


First Report of Bacterial Wilt in Mandevilla (= Dipladenia) splendens 'Red Riding Hood' in the United States Caused by Ralstonia solanacearum Biovar 3.
In November of 2007, 6-inch rooted cuttings of Mandevilla (= Dipladenia) splendens 'Red Riding Hood' were submitted from a greenhouse in Indiana to the Purdue Plant and Pest Diagnostic Lab. Plants exhibited leaf dieback, wilting, and reduced top growth. Microscopic observation revealed no fungal structures within the roots, stems, and leaves; however bacterial streaming was observed from the cut edge of stem and root tissue using ×100 magnification with phase contrast. A Ralstonia solanacearum ImmunoStrip test (Agdia Inc., Elkhart, IN) was used to determine that the samples (roots and stem) were positive for R. solanacearum, the causal agent of southern wilt. A bacterial suspension was prepared from infected tissue and streaked onto King's Medium B (KB). Gram-negative, nonfluorescent, oxidase-positive bacteria were consistently isolated from the diseased tissues and determined as R. solanacearum by BIOLOG (Hayward, CA) carbohydrate utilization. A culture of R. solanacearum and infected plant material were submitted to USDA APHIS PPQ as per select agent protocol. (3) CPHST NPGBL generated pure cultures and together with submitted plant materials they tested positive for R. solanacearum using Agdia ImmunoStrips. Culture and plant material tested positive for R. solanacearum and negative for biovar 2 using the Fegan conventional PCR (1) and the Central Science Lab (CSL, York, UK) real-time PCR (4). Pure cultures were determined to be negative for biovar 2 but positive for biovar 3 using the biovar carbohydrate utilization plate assay (2). On the basis of these results, the bacteria were identified as R. solanacearum biovar 3 and not as the select agent R. solanacearum race 3 biovar 2. Koch's postulates confirmed pathogenicity of the isolated bacteria on tomato, a susceptible host. Three 6-week-old plants were mechanically inoculated with a bacterial suspension of approximately 1 × 108 CFU/ml prepared from cultures grown on KB for 2 days at 28°C. Inoculum (0.1ml of bacterial suspension) was injected into stem axils with a 22-gauge hypodermic needle. Three 6-week-old control plants were inoculated with sterile water. Plants were kept at 24°C with supplemental 400W high-pressure sodium light. Within 5 days, all three inoculated plants exhibited wilt symptoms. No symptoms were observed in control plants. Bacteria were reisolated from symptomatic plants on KB medium as described above, and gram negative, nonfluorescent, oxidase-positive bacteria were obtained. Reisolated strains were identical to R. solanacearum using BIOLOG carbohydrate utilization testing, confirming the causal agent of the disease. Personal correspondence with other diagnosticians also confirms the presence of R. solanacearum biovar 3 in Mandevilla in Ohio, Michigan, and Minnesota. To our knowledge, this is the first documented report in the world of R. solanacearum biovar 3 on Mandevilla. References: (1) M. Fegan et al. Page 34 in: Bacterial Wilt Disease Molecular and Ecological Aspects. P. Prior et al., eds. INRA Editions-Springer. Verlag, Germany, 1998. (2) E. R. French et al. Fitopatologia 30:126, 1995. (3) USDA/APHIS/PPQ New Pest Response Guidelines. Ralstonia Solanacearum race3 biovar 2, from http://www.aphis.usda.gov/import_export/plants/manuals/emergency/ downloads/nprg-ralstonia.pdf , retrieved May 2008. (4) S. A. Weller et al. Appl Environ. Microbiol. 7:2853, 2000.


Inequalities in Children's Experiences of Home Learning during the COVID-19 Lockdown in England.
This paper combines novel data on the time use, home-learning practices and economic circumstances of families with children during the COVID-19 lockdown with pre-lockdown data from the UK Time Use Survey to characterise the time use of children and how it changed during lockdown, and to gauge the extent to which changes in time use and learning practices during this period are likely to reinforce the already large gaps in educational attainment between children from poorer and better-off families. We find considerable heterogeneity in children's learning experiences - amount of time spent learning, activities undertaken during this time and availability of resources to support learning. Concerningly, but perhaps unsurprisingly, this heterogeneity is strongly associated with family income and in some instances more so than before lockdown. Furthermore, our analysis suggests that any impacts of inequalities in time spent learning between poorer and richer children are likely to be compounded by inequalities not only in learning resources available at home, but also in those provided by schools.


Economic instruments for population diet and physical activity behaviour change: a systematic scoping review.
Unhealthy diet and low levels of physical activity are common behavioural factors in the aetiology of many non-communicable diseases. Recent years have witnessed an upsurge of policy and research interest in the use of taxes and other economic instruments to improve population health. To assemble, configure and analyse empirical research studies available to inform the public health case for using economic instruments to promote dietary and physical activity behaviour change. We conducted a systematic scoping review of evidence for the effects of specific interventions to change, or general exposure to variations in, prices or income on dietary and physical activity behaviours and corollary outcomes. Systematic electronic searches and parallel snowball searches retrieved >1 million study records. Text mining technologies were used to prioritise title-abstract records for screening. Eligible studies were selected, classified and analysed in terms of key characteristics and principal findings, using a narrative, configuring synthesis focused on implications for policy and further research. We identified 880 eligible studies, including 192 intervention studies and 768 studies that incorporated evidence for prices or income as correlates or determinants of target outcomes. Current evidence for the effects of economic instruments and exposures on diet and physical activity is limited in quality and equivocal in terms of its policy implications. Direct evidence for the effects of economic instruments is heavily skewed towards impacts on diet, with a relative lack of evidence for impacts on physical activity. The evidence-based case for using economic instruments to promote dietary and physical activity behaviour change may be less compelling than some proponents have claimed. Future research should include measurement of people's actual behavioural responses using study designs capable of generating reliable causal inferences regarding intervention effects. Policy implementation needs to be carefully aligned with evaluation planning and design.


In vivo imaging of chikungunya virus in mice and Aedes mosquitoes using a Renilla luciferase clone.
Chikungunya virus (CHIKV) is a mosquito-borne alphavirus that in humans causes an acute febrile illness characterized by fever, arthralgia, and rash. It is currently associated with large outbreaks in Asia, Africa, and islands of the Indian Ocean and has been introduced from these tropical regions into Europe, where local transmission has been recorded on two occasions. The underlying basis of the pathogenesis of CHIKV and related alphaviruses that produce similar symptoms remains unclear. By applying new techniques, for example, in vivo imaging in live animals and arthropods, we may improve our understanding of viral pathogenesis in vertebrates and viral replication in mosquitoes. This technical report describes the evaluation of a CHIKV?luciferase clone to visualize infection and dissemination in both Aedes aegypti and Aedes albopictus mosquitoes and mice. In mosquitoes, luciferase activity was seen at 3 and 7 days post-infection in both head and abdomens. In vivo imaging of CHIKV-luciferase was detected in mice for up to 5 days post-infection at the site of inoculation with limited dissemination to the skeletal muscle.


Limited polymorphism in Plasmodium falciparum sexual-stage antigens.
In areas highly endemic for malaria, individuals are frequently found to be infected simultaneously with multiple Plasmodium falciparum clones. This raises the question of whether all parasite clones produce gametocytes equally or whether gametocytogenesis is suppressed in some clones. In order to assess this in epidemiological studies, polymorphic genes specifically expressed in gametocytes could be analyzed by both amplification of genomic DNA from blood samples and by reverse transcribed polymerase chain reaction amplifying expressed gametocyte-specific genes only. Here we report the analysis of diversity in the three gametocyte-specific genes Pfs16, Pfs48/45, and Pfs230. In addition to the previously published data, limited polymorphism was found in the coding sequences of Pfs16 and Pfs48/45. Larger polymorphism was identified in Pfs230, which might allow the development of a discriminating PCR-based genotyping scheme for transmission studies. However, the limited polymorphism in Pfs16 and Pfs48/45 renders these molecules poorly useful for such studies.


Evidence-based pharmacological treatment of anxiety disorders, post-traumatic stress disorder and obsessive-compulsive disorder: a revision of the 2005 guidelines from the British Association for Psychopharmacology.
This revision of the 2005 British Association for Psychopharmacology guidelines for the evidence-based pharmacological treatment of anxiety disorders provides an update on key steps in diagnosis and clinical management, including recognition, acute treatment, longer-term treatment, combination treatment, and further approaches for patients who have not responded to first-line interventions. A consensus meeting involving international experts in anxiety disorders reviewed the main subject areas and considered the strength of supporting evidence and its clinical implications. The guidelines are based on available evidence, were constructed after extensive feedback from participants, and are presented as recommendations to aid clinical decision-making in primary, secondary and tertiary medical care. They may also serve as a source of information for patients, their carers, and medicines management and formulary committees.


Isochromosome 9q as a sole anomaly in an Omani boy with acute lymphoblastic leukaemia.
This report describes a case of acute lymphoblastic leukaemia in which isochromosome 9q (i(9q)) was the sole acquired cytogenetic abnormality. The Immunophenotype showed positivity for CD3, CD4, CD5, CD7, CD8, CD10, CD71, CD117 and TdT, consistent with T cell acute lymphoblastic leukaemia (ALL). The chromosomal analysis of bone marrow showed 46,XY,i(9)(q10) in all the metaphases analysed. The bone marrow morphology was ALL-L2 as per the French-American-British criteria. Isochromosomes are rare chromosomal abnormalities in childhood ALL and the effect of i(9q) is not well established. The patient's good response to therapy with normal cytogenetics within a month of induction, and disease-free survival after bone marrow transplant are indicative of a good prognosis in such cases.


Retention forestry influences understory diversity and functional identity.
In recent decades, a paradigm shift in forest management and associated policies has led to greater emphasis on harvest practices that retain mature, overstory trees in forest stands that would otherwise be clear-cut. While it is often assumed that the maintenance of compositional and structural complexity, such as that achieved through retention forestry approaches, will also mitigate negative impacts to functional diversity, empirical evidence of this relationship is sparse. We examined the effects of an aggregated retention system on taxonomic and functional diversity in a regenerating aspen-dominated forest. Sampling was conducted along transects arranged to capture the transition from harvested (regenerating) forest to mature, unharvested forest (both intact forest stands and 0.1 ha retention aggregates). We then assessed the magnitude and distance of edge effects on multiple indices of taxonomic and functional diversity as well as functional identity. Twelve years after harvest, the distance and magnitude of edge effects on functional and taxonomic diversity did not differ between the two unharvested patch sizes (intact vs. aggregate); however, intact forest exhibited greater resistance to edge effects and greater depth of edge influence into harvested areas for some traits compared to aggregates. Analyses relying on functional traits were generally applicable across sites within a highly variable forest type, and our results demonstrate the promise of using functional traits to assess management impacts on plant diversity across a landscape. Aggregates maintained some functional attributes associated with interior forest and influenced adjacent regeneration. However, trends in some traits (i.e., shade tolerance and seed mass), particularly in the seedling layer, suggest aggregates of this size provide primarily edge habitat.


A cautionary approach in transitioning to 'green' energy technologies and practices is required.
Renewable energy technologies (wind turbines, solar cells, biofuels, etc.) are often referred to as 'clean' or 'green' energy sources, while jobs linked to the field of environmental protection and energy efficiency are referred to as 'green' jobs. The energy efficiency of clean technologies, which is likely to reduce and/or eliminate reliance on fossil fuels, is acknowledged. However, the potential contribution of green technologies and associated practices to ill health and environmental pollution resulting from consumption of energy and raw materials, generation of waste, and the negative impacts related to some life cycle phases of these technologies are discussed. Similarly, a point is made that the green jobs theme is mistakenly oversold because the employment opportunities generated by transitioning to green technologies are not necessarily safe and healthy jobs. Emphasis is put on identifying the hazards associated with these green designs, assessing the risks to the environment and worker health and safety, and either eliminating the hazards or minimizing the risks as essential elements to the design, construction, operation, and maintenance of green technologies. The perception that it is not always economically possible to consider all risk factors associated with renewable energy technologies at the beginning without hampering their implementation, especially in the poor developing countries, is dismissed. Instead, poor countries are encouraged to start implementing environmentally sound practices while transitioning to green technologies in line with their technological development and overall economic growth.


Functional neuromuscular stimulation controlled by surface electromyographic signals produced by volitional activation of the same muscle: adaptive removal of the muscle response from the recorded EMG-signal.
In order to use the volitional electromyography (EMG) as a control signal for the stimulation of the same muscle, it is necessary to eliminate the stimulation artifacts and the muscle responses caused by the stimulation. The stimulation artifacts, caused by the electric field in skin and tissue generated by the stimulation current, are relatively easy to eliminate by shutting down the EMG-amplifier at the onset of the stimulation pulses. The muscle response is a nonstationary signal, therefore, an adaptive linear prediction filter is proposed. The filter is implemented and for three filter lengths tested on both simulated and real data. The filter performance is compared with a conventional fixed comb filter. The simulations indicate that the adaptive filter is relatively insensitive to variations in amplitude of the muscle responses, and for all filter lengths produces a good filtering. For variations in shape of the muscle responses and for real data, an increased filter performance can be achieved by increasing the filter length. Using a filter length of up to seven stimulation periods, it is possible to reduce real muscle responses to a level comparable with the background noise. Using the shut-down circuit and the adaptive filter both the stimulation artifacts and the muscle responses can be effectively eliminated from the EMG signal from a stimulated muscle. It is therefore possible to extract the volitional EMG from a partly paralyzed muscle and use it for controlling the stimulation of the same muscle.


Attitudes of postmenopausal women toward interactive video dance for exercise.
Although physical activity (PA) is universally recommended, most adults are not regular exercisers. Interactive video dance is a novel form of PA in widespread use among young adults, but interest among adults is not known. Postmenopausal women are an appropriate target for interventions to promote PA because they have an increased risk of health problems related to sedentary behavior. We explored perceived advantages and disadvantages of video dance as a personal exercise option in postmenopausal women. Forty sedentary postmenopausal women (mean age +/- SD 57 +/- 5 years), were oriented in eight small groups to interactive video dance, which uses a force-sensing pad with directional panels: the player steps on the panels in response to arrows scrolling on a screen, synchronized to music. Perceived advantages and disadvantages were elicited through a nominal group technique (NGT) process. Participants generated 113 advantages and 71 disadvantages. The most frequently cited advantages were "it's fun" and "improves coordination" (seven of eight groups), the fact that challenge encourages progress (five of eight groups), the potential for weight loss (four of eight groups), and the flexibility of exercise conditions (three of eight groups). Concerns were the potentially long and frustrating learning process, cost (six of eight groups), and possible technical issues (two of eight groups). The recreational nature of interactive dance exercise was widely appealing to postmenopausal women and might help promote adherence to PA. Initial support to learn basic technical and movement skills may be needed.


Organic nanofibers integrated by transfer technique in field-effect transistor devices.
The electrical properties of self-assembled organic crystalline nanofibers are studied by integrating these on field-effect transistor platforms using both top and bottom contact configurations. In the staggered geometries, where the nanofibers are sandwiched between the gate and the source-drain electrodes, a better electrical conduction is observed when compared to the coplanar geometry where the nanofibers are placed over the gate and the source-drain electrodes. Qualitatively different output characteristics were observed for top and bottom contact devices reflecting the significantly different contact resistances. Bottom contact devices are dominated by contact effects, while the top contact device characteristics are determined by the nanofiber bulk properties. It is found that the contact resistance is lower for crystalline nanofibers when compared to amorphous thin films. These results shed light on the charge injection and transport properties for such organic nanostructures and thus constitute a significant step forward toward a nanofiber-based light-emitting device.


Trunk, pelvis, hip, and knee kinematics, hip strength, and gluteal muscle activation during a single-leg squat in males and females with and without patellofemoral pain syndrome.
Controlled laboratory study using a cross-sectional design. To determine whether there are any differences between the sexes in trunk, pelvis, hip, and knee kinematics, hip strength, and gluteal muscle activation during the performance of a single-leg squat in individuals with patellofemoral pain syndrome (PFPS) and control participants. Though there is a greater incidence of PFPS in females, PFPS is also quite common in males. Trunk kinematics may affect hip and knee function; however, there is a lack of studies of the influence of the trunk in individuals with PFPS. Eighty subjects were distributed into 4 groups: females with PFPS, female controls, males with PFPS, and male controls. Trunk, pelvis, hip, and knee kinematics and gluteal muscle activation were evaluated during a single-leg squat. Hip abduction and external rotation eccentric strength was measured on an isokinetic dynamometer. Group differences were assessed using a 2-way multivariate analysis of variance (sex by PFPS status). Compared to controls, subjects with PFPS had greater ipsilateral trunk lean (mean ± SD, 9.3° ± 5.3° versus 6.7° ± 3.0°; P = .012), contralateral pelvic drop (10.3° ± 4.7° versus 7.4° ± 3.8°; P = .003), hip adduction (14.8° ± 7.8° versus 10.8° ± 5.6°; P<.0001), and knee abduction (9.2° ± 5.0° versus 5.8° ± 3.4°; P<.0001) when performing a single-leg squat. Subjects with PFPS also had 18% less hip abduction and 17% less hip external rotation strength. Compared to female controls, females with PFPS had more hip internal rotation (P<.05) and less muscle activation of the gluteus medius (P = .017) during the single-leg squat. Despite many similarities in findings for males and females with PFPS, there may be specific sex differences that warrant consideration in future studies and when clinically evaluating and treating females with PFPS.


Residential self-selection bias in the estimation of built environment effects on physical activity between adolescence and young adulthood.
Built environment research is dominated by cross-sectional designs, which are particularly vulnerable to residential self-selection bias resulting from health-related attitudes, neighborhood preferences, or other unmeasured characteristics related to both neighborhood choice and health-related outcomes. We used cohort data from the National Longitudinal Study of Adolescent Health (United States; Wave I, 1994-95; Wave III, 2001-02; n = 12,701) and a time-varying geographic information system. Longitudinal relationships between moderate to vigorous physical activity (MVPA) bouts and built and socioeconomic environment measures (landcover diversity, pay and public physical activity facilities per 10,000 population, street connectivity, median household income, and crime rate) from adolescence to young adulthood were estimated using random effects models (biased by unmeasured confounders) and fixed effects models (within-person estimator, which adjusts for unmeasured confounders that are stable over time). Random effects models yielded null associations except for negative crime-MVPA associations [coefficient (95% CI): -0.056 (-0.083, -0.029) in males, -0.061 (-0.090, -0.033) in females]. After controlling for measured and time invariant unmeasured characteristics using within-person estimators, MVPA was higher with greater physical activity pay facilities in males [coefficient (95% CI): 0.024 (0.006, 0.042)], and lower with higher crime rates in males [coefficient (95% CI): -0.107 (-0.140, -0.075)] and females [coefficient (95% CI): -0.046 (-0.083, -0.009)]. Other associations were null or in the counter-intuitive direction. Comparison of within-person estimates to estimates unadjusted for unmeasured characteristics suggest that residential self-selection can bias associations toward the null, as opposed to its typical characterization as a positive confounder. Differential environment-MVPA associations by residential relocation suggest that studies examining changes following residential relocation may be vulnerable to selection bias. The authors discuss complexities of adjusting for residential self-selection and residential relocation, particularly during the adolescent to young adult transition.


First Record of A Species of Mermithidae Braun, 1883 Infecting a Decapod, Palaemon paludosus (Palaemonidae).
The hemocoel of 26 of 30 (86%) eastern grass shrimps, Palaemon paludosus (Gibbes, 1850) (Decapoda: Palaemonidae), captured during June 2017 from several freshwater lakes near Leesburg and Lake Kissimmee, Florida, was infected by juveniles of a nematode species (Mermithidae sp.). Some infected eastern grass shrimps were preserved whole for histopathology, whereas others were dissected to excise parasitic juvenile nematodes, and still others were kept alive in glass aquaria such that post-parasitic (emerged) juvenile nematodes could be opportunistically observed alive and ultimately preserved. Parasitic and post-parasitic juvenile nematodes had cuticle cross-fibers, cephalic papillae, cup-shaped amphids, a horn-shaped vagina, a trophosome, and a caudal appendage, which collectively diagnosed them as Mermithidae sp. They differed from those of nematomorphs (Nematomorpha) by lacking 4 giant cells anteriorly, tegumental bristles, scale or plate-like areoles, a bifurcate or trifurcate posterior end, and an anus. A phylogenetic analysis of the small subunit rDNA (18S) that included all of the available mermithid sequences corresponding to morphologically diagnosed specimens recovered Mermithidae sp. within the clade of mermithids and sister to Ovomermis sinensis Chen, Jian, and Ren, 1991 . This is the first record of a mermithid infection in a decapod and first report of a mermithid infection in an aquatic crustacean from North America (another mermithid infects a terrestrial isopod there). The high prevalence of infection and the multiple geographic localities harboring infected eastern grass shrimps indicated that these infections were not spurious. Because no other decapod is confirmed as a mermithid host, we suspect that these specimens likely represent a new species with a life cycle worth studying, since none for a mermithid involving a decapod nor a crustacean has been elucidated to date. We also provide a table of all mermithid and nematomorph infections in crustaceans.


Increased serotonin transporter immunoreactivity intensity in the ileum of patients with irritable bowel disease.
Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disorder, which represents an economic burden to society and considerably reduces the quality of life of patients. In a previous study, the density of serotonin cells in the ileum of IBS patients was lower compared with control subjects. The present study aimed to further investigate the immunoreactivity intensity of serotonin and serotonin‑selective reuptake transporter (SERT) in the ileum of IBS patients. A total of 98 patients (77 females and 21 males; mean age, 35 years; range, 18‑66 years), which fulfilled Rome III Criteria for IBS, were included in the study. This cohort included 35 patients with diarrhoea‑predominant (IBS‑D), 31 patients with mixed diarrhoea and constipation (M‑IBS) and 32 patients with constipation‑predominant (IBS‑C) symptoms. A total of 27 subjects were included as controls (16 females and 11 males; mean age, 52 years; range, 20‑69 years). Ileal biopsy specimens were immunostained using the avidin‑biotin (ABC) complex method for serotonin and SERT. The immunoreactivity intensity was quantified by computerised image analysis using Olympus cellSens imaging software. No statistical difference of serotonin immunoreactivity intensity was identified in multiple comparisons between controls, IBS‑total, IBS‑D, IBS‑M and IBS‑C. The SERT immunoreactivity intensity was significantly increased in IBS patients as compared with controls, regardless of the subtype. It was concluded that the increase in ileal epithelial content of SERT increases the intracellular uptake of serotonin and its degradation in the gut epithelial cells and consequently decreases the availability of serotonin within the gut mucosa. The low availability of serotonin at its receptors occurred in all IBS subtypes. This may indicate that this abnormality is associated with a common symptom in all IBS subtypes, namely abdominal pain/discomfort. Serotonin acts upon sensory neurons in the submucosal and myenteric ganglia, as well as in the spinal cord, which is in agreement with this hypothesis.


One percent tenofovir applied topically to humanized BLT mice and used according to the CAPRISA 004 experimental design demonstrates partial protection from vaginal HIV infection, validating the BLT model for evaluation of new microbicide candidates.
Recent iPrEx clinical trial results provided evidence that systemic preexposure prophylaxis (PrEP) with emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) can partially prevent rectal HIV transmission in humans. Similarly, we have previously demonstrated that systemic administration of the same FTC-TDF combination efficiently prevented rectal transmission in humanized bone marrow/liver/thymus (BLT) mice. The CAPRISA 004 trial recently demonstrated that topical application of the tenofovir could partially prevent vaginal HIV-1 transmission in humans. To further validate the usefulness of the BLT mouse model for testing HIV prevention strategies, we evaluated the topical administration of tenofovir as used in CAPRISA 004 to prevent vaginal HIV transmission in BLT mice. Our results demonstrate that vaginally administered 1% tenofovir significantly reduced HIV transmission in BLT mice (P = 0.002). Together with the results obtained after systemic antiretroviral PrEP, these topical inhibitor data serve to validate the use of humanized BLT mice to evaluate both systemic and topical inhibitors of HIV transmission. Based on these observations, we tested six additional microbicide candidates for their ability to prevent vaginal HIV transmission: a C-peptide fusion inhibitor (C52L), a membrane-disrupting amphipathic peptide inhibitor (C5A), a trimeric d-peptide fusion inhibitor (PIE12-Trimer), a combination of reverse transcriptase inhibitors (FTC-TDF), a thioester zinc finger inhibitor (TC247), and a small-molecule Rac inhibitor (NSC23766). No protection was seen with the Rac inhibitor NSC23766. The thioester compound TC247 offered partial protection. Significant protection was afforded by FTC-TDF, and complete protection was offered by three different peptide inhibitors tested. Our results demonstrate that these effective topical inhibitors have excellent potential to prevent vaginal HIV transmission in humans.


Impact of historical land-use changes on greenhouse gas exchange in the U.S. Great Plains, 1883-2003.
European settlement of North America has involved monumental environmental change. From the late 19th century to the present, agricultural practices in the Great Plains of the United States have dramatically reduced soil organic carbon (C) levels and increased greenhouse gas (GHG) fluxes in this region. This paper details the development of an innovative method to assess these processes. Detailed land-use data sets that specify complete agricultural histories for 21 representative Great Plains counties reflect historical changes in agricultural practices and drive the biogeochemical model, DAYCENT, to simulate 120 years of cropping and related ecosystem consequences. Model outputs include yields of all major crops, soil and system C levels, soil trace-gas fluxes (N2O emissions and CH4 consumption), and soil nitrogen mineralization rates. Comparisons between simulated and observed yields allowed us to adjust and refine model inputs, and then to verify and validate the results. These verification and validation exercises produced measures of model fit that indicated the appropriateness of this approach for estimating historical changes in crop yield. Initial cultivation of native grass and continued farming produced a significant loss of soil C over decades, and declining soil fertility led to reduced crop yields. This process was accompanied by a large GHG release, which subsided as soil fertility decreased. Later, irrigation, nitrogen-fertilizer application, and reduced cultivation intensity restored soil fertility and increased crop yields, but led to increased N2O emissions that reversed the decline in net GHG release. By drawing on both historical evidence of land-use change and scientific models that estimate the environmental consequences of those changes, this paper offers an improved way to understand the short- and long-term ecosystem effects of 120 years of cropping in the Great Plains.