Psychometric assessment of scales for a Model of Goal Directed Vegetable Parenting Practices (MGDVPP).
Vegetable intake has been related to lower risk of chronic illnesses in the adult years. The habit of vegetable intake should be established early in life, but many parents of preschoolers report not being able to get their child to eat vegetables. The Model of Goal Directed Behavior (MGDB) has been employed to understand vegetable parenting practices (VPP) to encourage a preschool child's vegetable intake. The Model of Goal Directed Vegetable Parenting Practices (MGDVPP) provides possible determinants and may help explain why parents use effective or ineffective VPP. Scales to measure effective and ineffective vegetable parenting practices have previously been validated. This manuscript presents the psychometric characteristics and factor structures of new scales to measure the constructs in MGDVPP. Participants were 307 parents of preschool (i.e. 3 to 5 year old) children, used for both exploratory (EFA) and confirmatory factor analyses (CFA). Data were collected via an internet survey. First, EFA were conducted using the scree plot criterion for factor extraction. Next, CFA assessed the fit of the exploratory derived factors. Then, classical test theory procedures were employed with all scales. Finally, Pearson correlations were calculated between each scale and composite effective and ineffective VPP as a test of scale predictive validity. Twenty-nine subscales (164 items) within 11 scales were extracted. The number of items per subscale ranged from 2 to 13, with three subscales having 10 or more items and 12 subscales having 4 items or less. Cronbach's alphas varied from 0.13 to 0.92, with 17 being 0.70 or higher. Most alphas <0.70 had only three or four items. Twenty-five of the 29 subscales significantly bivariately correlated with the composite effective or ineffective VPP scales. This was the initial examination of the factor structure and psychometric assessment of MGDVPP scales. Most of the scales displayed acceptable to desirable psychometric characteristics. Research is warranted to add items to those subscales with small numbers of items, test their validity and reliability, and characterize the model's influence on child vegetable consumption.


Exploring the relationship between depressive and anxiety symptoms and neuronal response to alcohol cues.
Depressive and anxiety symptoms tend to co-occur with heavy drinking. Specifically, their presence may exacerbate the severity and intractability of heavy drinking. Similarly, heavy drinking may increase the risk for and experience of depressive and anxiety symptoms. Although depressive and anxiety symptoms have been significantly correlated with alcohol craving in cue-exposure paradigms, physiological responses have not always mapped onto emotional responses. Therefore, this study sought to examine the role of depressive and anxiety symptoms using a more basic science approach, through examining functional brain changes. Seventy nontreatment seeking, heavy drinking adults were recruited through a college campus (n = 45 men; mean age = 22.8). They completed measures of drinking, smoking, depressive symptoms, anxiety symptoms, and a functional magnetic resonance imaging (fMRI) cue-exposure paradigm. As hypothesized, depressive symptoms were positively correlated with activation during the alcohol (vs. appetitive control) cue in the insula, cingulate, ventral tegmentum, striatum, and thalamus (cluster-corrected p < 0.05, z = 2.3). Similarly, anxiety symptoms were positively correlated with activation during the alcohol (vs. appetitive control) cue in the striatum, thalamus, insula, and inferior frontal, mid-frontal, and cingulate gyri (cluster-corrected p < 0.05, z = 2.3). Significant correlations were found between depressive symptoms, anxiety symptoms, and differential brain activation in response to an alcohol versus an appetitive control cue in an fMRI paradigm. Moreover, the pattern of activation mapped onto expected regions. This study strongly supports the posited relationships between depressive symptoms, anxiety symptoms, and differential brain activation in an alcohol cue-exposure paradigm with a sample of heavy drinking adults.


Mechano-active scaffold design based on microporous poly(L-lactide-co-epsilon-caprolactone) for articular cartilage tissue engineering: dependence of porosity on compression force-applied mechanical behaviors.
An essential component of functional articular cartilage tissue engineering is a mechano-active scaffold, which responds to applied compression stress and causes little permanent deformation. As the first paper of a series on mechano-active scaffold-based cartilage tissue engineering, this study focused on mechanical responses to various modes of loading of compression forces and subsequent selection of mechano-active scaffolds from the biomechanical viewpoint. Scaffolds made of elastomeric microporous poly(L-lactide-co-epsilon-caprolactone) (PLCL) with open-cell structured pores (300 approximately 500 microm) and with different porosities ranging from 71 to 86% were used. The PLCL sponges and rabbit articular cartilage tissue were subjected to compression/unloading tests (0.1 and 0.005 Hz) at 5 kPa, and stress relaxation tests at 10, 30, and 50% strain. The measurements of the maximum strain under loading and residual strain under unloading for compression tests and the maximum stress and equilibrium stress in the stress relaxation test showed that the lower the porosity, the closer the mechanical properties are to those of native cartilage tissue. Among the PLCL sponges, the sponge with 71% porosity appears to be a suitable cartilage scaffold.


Does routine fenestration improve early and late postoperative outcomes in patients undergoing Fontan palliation?
A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: 'In [patients undergoing Fontan palliation] does [fenestration] affect [early and late postoperative outcomes]?' Altogether 509 papers were found using the reported search, of which 11 papers represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Current data suggest that the use of fenestration has advantages in the immediate postoperative course, with fewer complications such as pleural effusions, shorter hospitalization and decreased early Fontan failure, but comparable long-term outcomes to a non-fenestrated approach. Fenestration should be used in high-risk patients or based on the haemodynamic parameters measured before weaning from cardiopulmonary bypass. Routine use may potentially lead to additional late fenestration closure procedures in some patients, without improving long-term outcomes.


GDGT distribution in a stratified lake and implications for the application of TEX86 in paleoenvironmental reconstructions.
We investigated the relationship between distributions of GDGTs, GDGT-based proxies and environmental factors in a stratified lake in northwestern Norway. More than 90% of isoGDGTs were produced at the bottom of the oxycline, indicating a predominance of ammonia-oxidizing Group I.1a of Thaumarchaeota, supported by high crenarchaeol/caldarchaeol ratios. Dissolved oxygen content, rather than temperature, exercised a primary control on TEX86 values. In spite of low BIT value in surface sediment, the reconstructed lake surface temperature was "cold" biased. MBT values in streams and lake surface water were significantly smaller than those in the catchment soil, suggesting in situ production of brGDGTs in streams. A rapid transition of MBT vs. temperature/pH relationships occurring at the bottom of oxycline indicated the differential production of various brGDGTs with D.O. and depths. Only within the oxycline were CBT-based pH values close to in situ pH. Our results confirm earlier studies calling for caution in applying TEX86 as a surface temperature proxy, or MBT and/or CBT for reconstructing pH, in anoxic or euxinic lakes, estuaries and ocean basins. We propose that caldarchaeol/crenarchaeol ratio, an indicator of contributions from methanogenic archaea, together with the BIT and TEX86 proxies, can help reconstruct past levels of stratification.


Substrate specificity of microbial transglutaminase as revealed by three-dimensional docking simulation and mutagenesis.
Transglutaminases (TGases) are used in fields such as food and pharmaceuticals. Unlike other TGases, microbial transglutaminase (MTG) activity is Ca(2+)-independent, broadening its application. Here, a three-dimensional docking model of MTG binding to a peptide substrate, CBZ-Gln-Gly, was simulated. The data reveal CBZ-Gln-Gly to be stretched along the MTG active site cleft with hydrophobic and/or aromatic residues interacting directly with the substrate. Moreover, an oxyanion binding site for TGase activity may be constructed from the amide groups of Cys64 and/or Val65. Alanine mutagenesis verified the simulated binding region and indicated that large molecules can be widely recognized on the MTG cleft.


Skin conductance habituation and cerebrospinal fluid 5-hydroxyindoleacetic acid in suicidal patients.
The concentration of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid (CSF) and psychophysiologic variables, such as habituation of the skin conductance response, were measured in 35 drug-free, suicidal inpatients. Twenty-four patients were hospitalized after a suicide attempt, and another 11 had suicidal ideation. The suicide attempters were classified into nonviolent (drug overdoses taken orally, or a single wrist cut) and violent (all other methods). As in previous studies, the suicide attempters had significantly lower CSF concentrations of 5-HIAA compared with healthy, matched controls. The distribution of habituation rate was bimodal (slow and fast habituators). All violent attempters were fast habituators, as were all four patients who in a one-year follow-up were found to have completed a suicide (all by violent methods). The lowest frequency of fast habituators was found in the group of patients with suicidal ideation. There was no correlation between CSF 5-HIAA and habituation rate. A combination of these two variables yielded a highly significant correlation with type of suicide behavior, both retrospectively and prospectively.


Successful implementation of a perioperative glycemic control protocol in cardiac surgery: barrier analysis and intervention using lean six sigma.
Although the evidence strongly supports perioperative glycemic control among cardiac surgical patients, there is scant literature to describe the practical application of such a protocol in the complex ICU environment. This paper describes the use of the Lean Six Sigma methodology to implement a perioperative insulin protocol in a cardiac surgical intensive care unit (CSICU) in a large academic hospital. A preintervention chart audit revealed that fewer than 10% of patients were admitted to the CSICU with glucose <200 mg/dL, prompting the initiation of the quality improvement project. Following protocol implementation, more than 90% of patients were admitted with a glucose <200 mg/dL. Key elements to success include barrier analysis and intervention, provider education, and broadening the project scope to address the intraoperative period.


Estimation in generalized linear models under censored covariates with an application to MIREC data.
In many biological experiments, certain values of a biomarker are often nondetectable due to low concentrations of an analyte or the limitations of a chemical analysis device, resulting in left-censored values. There is an increasing demand for the analysis of data subject to detection limits in clinical and environmental studies. In this paper, we develop a novel statistical method for the maximum likelihood estimation in generalized linear models with covariates subject to detection limits. Simulations are carried out to study the relative performance of the proposed estimators, as compared to other existing estimators. The proposed method is also applied to a real dataset from the Maternal-Infant Research on Environmental Chemicals cohort study, where we investigate how different chemical mixtures affect the health outcomes of infants and pregnant women.


Regional brain activity associated with visual backward masking.
In visual backward masking, the visibility of a briefly presented visual target is disrupted by a mask that is presented shortly thereafter. The goal of the current study was to identify regions in the human cortex that may provide the neural basis of visual masking. We searched for areas whose activity correlated with perception as we systematically varied the strength of masking. A total of 13 subjects performed a backward masking task during functional magnetic resonance imaging. Target and mask were presented at three delay intervals (34, 68, and 102 msec) and behavioral measures confirmed that the targets were more visible at longer masking intervals. Two sets of regions of interest were identified: Distinct regions in the visual cortex (V1/V2, LO, hMT+) were segregated using scans to localize visual processing drawn from the existing literature. Additional cortical regions were selected in a data-driven approach based on their activity during the backward masking task. For each set, we determined the regions whose magnitude of activation increased at longer masking intervals. Nine of the subjects provided valid behavioral performance data on the visual masking task and imaging data from these subjects were used for subsequent analysis. The scans of visual processing areas identified four regions, including: early visual areas (V1 and V2), the motion-sensitive regions in the lateral occipital (LO) lobe (hMT+), and two components (dorsal and ventral) of the object-sensitive region, LO. Of these, the ventral and dorsal LO regions were sensitive to the strength of the mask. For the data-driven approach, six regions were identified on the basis of a difference map in which all masking intervals were contrasted with rest. These included the inferior parietal, anterior cingulate, precentral, insula, thalamic, and occipital areas. The predicted effects of more activity with weaker masking were seen in the thalamus, inferior parietal, and anterior cingulate. This study isolated three types of visual processing areas. The first included regions that subserve key stages of vision (including object and motion processing). The second type responded to the presentation of brief ly presented visual stimuli, regardless of masking interval. The third type (selected from the first two) included regions sensitive to the interval between the target and mask. These latter regions (including ventral LO, inferior parietal, anterior cingulate, and thalamus) may form the neural substrate of backward masking.


A quantitative real-time PCR assay for the identification and enumeration of Alexandrium cysts in marine sediments.
Harmful algal blooms (HABs) are a global problem that affects both human and ecosystem health. One of the most serious and widespread HAB poisoning syndromes is paralytic shellfish poisoning, commonly caused by Alexandrium spp. dinoflagellates. Like many toxic dinoflagellates, Alexandrium produces resistant resting cysts as part of its life cycle. These cysts play a key role in bloom initiation and decline, as well as dispersal and colonization of new areas. Information on cyst numbers and identity is essential for understanding and predicting blooms, yet comprehensive cyst surveys are extremely time- and labor-intensive. Here we describe the development and validation of a quantitative real-time PCR (qPCR) technique for the enumeration of cysts of A. tamarense of the toxic North American/Group I ribotype. The method uses a cloned fragment of the large subunit ribosomal RNA gene as a standard for cyst quantification, with an experimentally determined conversion factor of 28,402±6152 LSU ribosomal gene copies per cyst. Tests of DNA extraction and PCR efficiency show that mechanical breakage is required for adequate cyst lysis, and that it was necessary to dilute our DNA extracts 50-fold in order to abolish PCR inhibition from compounds co-extracted from the sediment. The resulting assay shows a linear response over 6 orders of magnitude and can reliably quantify ≥10cysts/cc sediment.For method validation, 129 natural sediment samples were split and analyzed in parallel, using both the qPCR and primulin-staining techniques. Overall, there is a significant correlation (p<0.001) between the cyst abundances determined by the two methods, although the qPCR counts tend to be lower than the primulin values. This underestimation is less pronounced in those samples collected from the top 1 cm of sediment, and more pronounced in those derived from the next 1-3 cm of the core. These differences may be due to the condition of the cysts in the different layers, as the top 1cm contains more recent cysts while those in the next 1-3cm may have been in the sediments for many years. Comparison of the cyst densities obtained by both methods shows that a majority (56.6%) of the values are within a two-fold range of each other and almost all of the samples (96.9%) are within an order of magnitude. Thus, the qPCR method described here represents a promising alternative to primulin-staining for the identification and enumeration of cysts. The qPCR method has a higher throughput, enabling the extraction and assay of 24 samples in the time required to process and count 8-10 samples by primulin staining. Both methods require prior expertise, either in taxonomy or molecular biology. Fewer person-hours per sample are required for qPCR, but primulin staining has lower reagent costs. The qPCR method might be more desirable for large-scale cyst mapping, where large numbers of samples are generated and a higher sample analysis rate is necessary. While the qPCR and primulin-staining methods generate similar data, the choice of counting method may be most influenced by the practical issue of the different relative costs of labor and materials between the two methods.


The complementary medicine (CAM) for the treatment of chronic pain: scientific evidence regarding the effects of healing touch massage.
Evidence-based medicine offers effective pathways of pharmacological treatment for chronic pain that may compromise the quality of life of patients; this is one of the main reasons why more and more people resort to traditional and complementary approaches, to try to maintain or regain their health. The effectiveness of the various forms of complementary treatments often cannot be proven objectively, which is why, given the need to find more concrete evidence of the effectiveness of complementary therapies with particular reference to the method of healing touch massage, a review of the literature was conducted in order to gather evidence of the efficacy of the specific method regarding pain and other health outcomes of patients with malignant disease to support a proposal for improvement, based on the practice of healing touch massage conducted by nurses. Systematic review. There are several examples (in some cases specifically regarding patients with tumors) of the positive effects of healing touch massage on pain, anxiety and fatigue, and also on biochemical parameters. The way to full recognition by both the institutional and the scientific community seems to promise fairly well, although it should be noted that the achievement of this goal will require further research avoiding the limitations of previous studies.


Recurrence rates of cardiac manifestations associated with neonatal lupus and maternal/fetal risk factors.
Identifying the frequency of recurrent cardiac manifestations of neonatal lupus (NL) in a second child is critical to understanding the pathogenesis of anti-SSA/Ro-mediated injury and would improve counseling strategies regarding future pregnancies and power the design of clinical prevention trials. Accordingly, this study was undertaken to address the recurrence rates of cardiac NL and associated risk factors in a large US-based cohort. Families enrolled in the Research Registry for Neonatal Lupus were evaluated for rates of recurrence of cardiac NL and potential risk factors, with a focus on pregnancies immediately following the birth of an affected child. The overall rate of recurrence of cardiac NL in 161 pregnancies of 129 mothers with anti-SSA/Ro antibodies was 17.4% (95% confidence interval 11.1-23.6%). Analysis of the potential risk factors among 129 mothers with a pregnancy immediately following the birth of a child with cardiac NL showed that the maternal diagnosis was not associated with the outcome in a subsequent pregnancy. In this group, 23% of mothers who were either asymptomatic or had an undifferentiated autoimmune syndrome, compared with 14% of mothers with systemic lupus erythematosus or Sjögren's syndrome, had a second child with cardiac NL (P = 0.25). The recurrence rate was not statistically significantly different in mothers who had taken steroids compared with those who had not taken steroids (16% versus 21%; P = 0.78). The antibody status of the mother was not predictive of outcome in subsequent pregnancies. Moreover, death of the first child with cardiac NL was not predictive of recurrence of cardiac NL in a subsequent pregnancy (P = 0.31). The risk of cardiac NL was similar between male and female children (17.2% versus 18.3%; P = 1.0). In this cohort, the overall recurrence rate for cardiac NL was 17%. The recurrence rate appeared to be unaffected by maternal health, use of steroids, antibody status, severity of cardiac disease in the first affected child, or sex of the subsequent child.


Accuracy of Diagnostic Tests.
Following the outbreak of the coronavirus disease 2019 (COVID-19) pandemic, design, development, validation, verification and implementation of diagnostic tests were actively addressed by a large number of diagnostic test manufacturers. This paper deals with the biases and sources of variation which influence the accuracy of diagnostic tests, including calculating and interpreting test characteristics, defining what is meant by test accuracy, understanding the basic study design for evaluating test accuracy, understanding the meaning of Sensitivity, Specificity, Positive Predictive Value and Negative Predictive Value, and evaluating them numerically, and the ROC curve (or Receiver Operating Characteristic ) and the Area under the Curve (AUC).


Gender Dysphoria, Mental Health, and Poor Sleep Health Among Transgender and Gender Nonbinary Individuals: A Qualitative Study in New York City.
Background: A vast amount of research has demonstrated the numerous adverse health risks of short sleep duration and poor sleep health among the general population, and increasing studies have been conducted among lesbian, gay, and bisexual individuals. However, although poor sleep health is disproportionately experienced by sexual and gender minority populations, little research has examined sleep quality and associated factors among transgender and gender nonbinary (TGNB) individuals. This study qualitatively explored the relationship that factors such as gender identity, mental health, and substance use have with sleep health among a sample of TGNB individuals in New York City. Methods: Forty in-depth interviews were conducted among an ethnically diverse sample who identified as transgender male, transgender female, and gender nonbinary from July to August 2017. All interviews were transcribed, coded, and thematically analyzed for domains affecting overall sleep, including mental health, gender identity, and various coping mechanisms to improve overall sleep. Results: TGNB interview participants frequently described one or more problems with sleeping. Some (15%) participants suggested that mental health issues caused them to have difficulty falling asleep, but that psychiatric medication was effective in reducing mental health issues and allowing them to sleep. An even larger number (35%) told us that their gender identity negatively impacted their sleep. Specifically, participants described that the presence of breasts, breast binding, stress and anxiety about their identity, and concerns about hormonal therapy and gender-affirming surgery were all reported as contributing to sleep problems. Given these sleep challenges, it is not surprising that most (60%) participants used various strategies to cope with and manage their sleep problems, including prescription and over-the-counter sleep medications (33%) and marijuana (18%). Conclusions: Our findings document that sleep health is frequently an issue for TGNB individuals, and they also offer insight into the various ways that TGNB individuals attempt to cope with these sleep problems. Sleep health promotion interventions should be developed for TGNB people, which would promote positive mental health, reduce the risk of pharmaceutical adverse events, and help alleviate psychosocial stress in this target population.


Wafer-scale broadband antireflective silicon fabricated by metal-assisted chemical etching using spin-coating Ag ink.
We report broadband antireflective disordered subwavelength structures (d-SWSs), which were fabricated on 4-inch silicon wafers by spin-coating Ag ink and metal-assisted chemical etching. The antireflection properties of the d-SWSs depend on its dimensions and heights, which were changed by the sintering temperature of the spin-coated Ag ink and etching time. The fabricated d-SWSs drastically reduced surface reflection over a wide range of wavelengths and incident angles, providing good surface uniformity. The d-SWSs with the most appropriate geometry for practical solar cell applications exhibit only 1.23% solar-weighted reflectance in the wavelength range of 300-1100 nm and average reflectance <5% up to an incident angle of 55° in the wavelength range of 300-2500 nm. This simple and low-cost nanofabrication method for antireflection could be of great importance in optical device applications because it allows mass production without any lithography processes or sophisticated equipment.


Nonprescription, padded, lightweight support socks in treatment of mild to moderate lower extremity venous insufficiency.
Currently, strength greater than 20 mm Hg of compression is considered necessary for support hose used to treat symptomatic venous insufficiency in lower extremities. This strength is frequently uncomfortable, which reduces compliance and therefore clinical effectiveness. Whether more comfortable, nonprescription, light-compression support hose is effective in the treatment of mild to moderate venous insufficiency was investigated in 36 men with subjective complaints and objective signs (per Doppler ultrasound) of lower extremity venous insufficiency. All participants wore padded, light-compression (6 mm Hg), crew-height socks for 1 month. Then, participants were assigned to one of two groups on the basis of initial Doppler results. The half with the worst results wore stronger-compression (12 mm Hg) over-the-calf support socks, on the assumption that patients with worse venous insufficiency would require more support; those with the better Doppler results continued to wear the light-compression socks. Participants were retested at monthly intervals for 3 months. In each group, data indicated that the venous insufficiency for all patients improved objectively and subjectively. Many of the objective venous values improved with either statistical or highly statistical significance--specifically deep venous valve function, superficial venous valve functions, and venous capacity--without statistically altering arterial function. Improvement occurred in the first month of the trial and continued throughout the study. The use of light-compression support socks is effective and should be considered as a first line of therapy in treatment of mild to moderate venous insufficiency.


Identification of in vitro autophosphorylation sites and effects of phosphorylation on the Arabidopsis CRINKLY4 (ACR4) receptor-like kinase intracellular domain: insights into conformation, oligomerization, and activity.
Arabidopsis CRINKLY4 (ACR4) is a receptor-like kinase (RLK) that consists of an extracellular domain and an intracellular domain (ICD) with serine/threonine kinase activity. While genetic and cell biology experiments have demonstrated that ACR4 is important in cell fate specification and overall development of the plant, little is known about the biochemical properties of the kinase domain and the mechanisms that underlie the overall function of the receptor. To complement in planta studies of the function of ACR4, we have expressed the ICD in Escherichia coli as a soluble C-terminal fusion to the N-utilization substance A (NusA) protein, purified the recombinant protein, and characterized the enzymatic and conformational properties. The protein autophosphorylates via an intramolecular mechanism, prefers Mn(2+) over Mg(2+) as the divalent cation, and displays typical Michaelis-Menten kinetics with respect to ATP with an apparent K(m) of 6.67 ± 2.07 μM and a V(max) of 1.83 ± 0.18 nmol min(-1) mg(-1). Autophosphorylation is accompanied by a conformational change as demonstrated by circular dichroism, fluorescence spectroscopy, and limited proteolysis with trypsin. Analysis by nanoliquid chromatography and mass spectrometry revealed 16 confirmed sites of phosphorylation at Ser and Thr residues. Sedimentation velocity and gel filtration experiments indicate that the ICD has a propensity to oligomerize and that this property is lost upon autophosphorylation.


A Breathing-Based Meditation Intervention for Patients With Major Depressive Disorder Following Inadequate Response to Antidepressants: A Randomized Pilot Study.
To evaluate feasibility, efficacy, and tolerability of Sudarshan Kriya yoga (SKY) as an adjunctive intervention in patients with major depressive disorder (MDD) with inadequate response to antidepressant treatment. Patients with MDD (defined by DSM-IV-TR) who were depressed despite ≥ 8 weeks of antidepressant treatment were randomized to SKY or a waitlist control (delayed yoga) arm for 8 weeks. The primary efficacy end point was change in 17-item Hamilton Depression Rating Scale (HDRS-17) total score from baseline to 2 months. The key secondary efficacy end points were change in Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI) total scores. Analyses of the intent-to-treat (ITT) and completer sample were performed. The study was conducted at the University of Pennsylvania between October 2014 and December 2015. In the ITT sample (n = 25), the SKY arm (n = 13) showed a greater improvement in HDRS-17 total score compared to waitlist control (n = 12) (-9.77 vs 0.50, P = .0032). SKY also showed greater reduction in BDI total score versus waitlist control (-17.23 vs -1.75, P = .0101). Mean changes in BAI total score from baseline were significantly greater for SKY than waitlist (ITT mean difference: -5.19; 95% CI, -0.93 to -9.34; P = .0097; completer mean difference: -6.23; 95% CI, -1.39 to -11.07; P = .0005). No adverse events were reported. Results of this randomized, waitlist-controlled pilot study suggest the feasibility and promise of an adjunctive SKY-based intervention for patients with MDD who have not responded to antidepressants. ClinicalTrials.gov identifier: NCT02616549.


Use of the xCELLigence system for real-time analysis of changes in cellular motility and adhesion in physiological conditions.
Investigation of the mechanisms behind the regulation of cellular motility and adhesion is key to understanding metastasis and the biology of tumor spreading. There are many technologies available for these studies, but the majority of them are either dependent on the use of labels or limited to endpoint analysis. The xCELLigence RTCA (real-time cell analysis) provides a platform for label free and operator independent investigation of the migration, invasion and adhesion proprieties of cells in physiologically relevant conditions. The real-time kinetic data acquisition also allows for a more accurate characterization of short-lived cellular events. In this chapter we describe the use of the xCELLigence Real-Time Cell Analyzer to investigate changes in cellular adhesion and motility in real time.


Free formula milk in the prevention of mother-to-child transmission programme: voices of a peri-urban community in South Africa on policy change.
In 2001, South Africa began implementing the Prevention of Mother-to-Child Transmission of HIV (PMTCT) programme. This programme included distribution of free formula milk for infants up to 6 months of age at all public health facilities. Effective from 1 January 2011, KwaZulu-Natal became the first province to phase out free formula milk from its PMTCT programme. On 23 August 2011, the South African National Department of Health adopted promotion of exclusive breastfeeding as the national infant feeding strategy and made a decision to withdraw free formula milk from the PMTCT programme. To explore the perceptions and understanding of households at community level on the policy decision to phase out free formula milk from the PMTCT programme in South Africa. An exploratory qualitative study was conducted amongst women enrolled in a community randomized trial known as Good Start III. Focus group discussions were held with grandmothers, fathers and teenage mothers; and in-depth interviews were performed with HIV-positive and HIV-negative mothers. Data were analysed using thematic analysis. Identified themes included: (1) variations in awareness and lack of understanding of the basis for the policy change, (2) abuse of and dysfunctional policy as perceived reasons for policy change and (3) proposed strategies for communicating the policy change. There is an urgent need to develop a multifaceted communication strategy clearly articulating the reasons for the infant feeding policy change and promoting the new breastfeeding strategy. The communication strategy should take into account inputs from the community. With a supportive environment and one national infant feeding strategy, South Africa has an opportunity to reverse years of poor infant feeding practices and to improve the health of all children in the country.


An analysis of battlefield cricothyrotomy in Iraq and Afghanistan.
Historical review of modern military conflicts suggests that airway compromise accounts for 1?2% of total combat fatalities. This study examines the specific intervention of pre-hospital cricothyrotomy (PC) in the military setting using the largest studies of civilian medics performing PC as historical controls. The goal of this paper is to help define optimal airway management strategies, tools and techniques for use in the military pre-hospital setting. This retrospective chart review examined all patients presenting to combat support hospitals following prehospital cricothyrotomy during combat operations in Iraq and Afghanistan during a 22-month period. A PC was determined ?successful? if it was documented as functional on arrival to the hospital. All PC complications that were documented in the patients? record were also noted in the review. Two thirds of the patients died. The most common injuries were caused by explosions, followed by gunshot wounds (GSW) and blunt trauma. Eighty-two percent of the casualties had injures to face, neck or head. Those injured by gunshot wounds to the head or thorax all died. The largest group of survivors had gunshot wounds to the face and/or neck (38%) followed by explosion related injury to the face, neck and head (33%). Pre-hospital cricothyrotomy was documented as successful in 68% of the cases while 26% of the PC?s failed to cannulate the trachea. In 6% of cases the patient was pronounced dead on arrival without documentation of PC function. The majority of PC?s (62%) were performed by combat medics at the point of injury. Physicians and physician assistants (PA) were more successful performing PC than medics with a 15% versus a 33% failure rate. Complications were not significantly different than those found in civilian PC studies, including incorrect anatomic placement, excessive bleeding, air leak and right main stem placement. The majority of patients who underwent PC died (66%). The largest group of survivors had gunshot wounds to the face and/or neck (38%) followed by explosion related injury to the face, neck and head (33%). Military medics have a 33% failure rate when performing this procedure compared to 15% for physicians and physician assistants. Minor complications occurred in 21% of cases. The survival rate and complication rates are similar to previous civilian studies of medics performing PC. However the failure rate for military medics is three to five times higher than comparable civilian studies. Further study is required to define the optimal equipment, technique, and training required for combat medics to master this infrequently performed but lifesaving procedure.


Biomechanical and lifestyle risk factors for medial tibia stress syndrome in army recruits: a prospective study.
Medial tibial stress syndrome (MTSS) is a common injury in active populations and has been suggested to be a result of both biomechanical and lifestyle factors. The main aim of this study was to determine prospectively whether gait biomechanics and lifestyle factors can be used as a predictor of MTSS development. British infantry male recruits (n=468) were selected for the study. Plantar pressure variables, lifestyle factors comprising smoking habit and aerobic fitness as measured by a 1.5 mile timed-run were collected on the first day of training. Injury data were collected during the 26 week training period and incidence rate was 7.9% (n=37). A logistic regression model for membership of the MTSS and non-MTSS groups was developed. An imbalance in foot pressure with greater pressure on the medial side than on the lateral side was the primary risk factor. Low aerobic fitness, as deduced from a 1.5 mile timed-run and smoking habit were also important, but were additive risk factors for MTSS. In conclusion, "poor" biomechanics were the strongest predictors of MTSS development but lifestyle factors were also important. The logistic regression model combining all three risk factors was capable of predicting 96.9% of the non-injured group and 67.5% of the MTSS group with an overall accuracy of 87.7%. While the model has yet to be validated against an external sample and limitations exist with regards to the quality of the data collected, it is nonetheless suggested that the combined analysis of biomechanical and lifestyle factors has the potential to improve the prediction of MTSS.


Toward the complete yeast mitochondrial proteome: multidimensional separation techniques for mitochondrial proteomics.
Proteomic analyses of different subcellular compartments, so-called organellar proteomics, facilitate the understanding of cellular functions on a molecular level. In this work, various orthogonal multidimensional separation techniques both on the protein and on the peptide level are compared with regard to the number of identified proteins as well as the classes of proteins accessible by the respective methodology. The most complete overview was achieved by a combination of such orthogonal techniques as shown by the analysis of the yeast mitochondrial proteome. A total of 851 different proteins (PROMITO dataset) were identified by use of multidimensional LC-MS/MS, 1D-SDS-PAGE combined with nano-LC-MS/MS and 2D-PAGE with subsequent MALDI-mass fingerprinting. Our PROMITO approach identified the 749 proteins, which were found in the largest previous study on the yeast mitochondrial proteome, and additionally 102 proteins including 42 open reading frames with unknown function, providing the basis for a more detailed elucidation of mitochondrial processes. Comparison of the different approaches emphasizes a bias of 2D-PAGE against proteins with very high isoelectric points as well as large and hydrophobic proteins, which can be accessed more appropriately by the other methods. While 2D-PAGE has advantages in the possible separation of protein isoforms and quantitative differential profiling, 1D-SDS-PAGE with nano-LC-MS/MS and multidimensional LC-MS/MS are better suited for efficient protein identification as they are less biased against distinct classes of proteins. Thus, comprehensive proteome analyses can only be realized by a combination of such orthogonal approaches, leading to the largest dataset available for the mitochondrial proteome of yeast.


Scapulothoracic and Glenohumeral Kinematics During Daily Tasks in Users of Manual Wheelchairs.
Rates of shoulder pain in individuals who use manual wheelchairs (MWCs) as their primary means of mobility have been reported to be as high as 70% during activities of daily living. Current prevailing thought is that mechanical impingement of the soft tissues that reside within the subacromial space between the humeral head and coracoacromial arch is a major contributor to the shoulder pain in users of MWCs. The subacromial space size is directly related to the kinematics at the shoulder joint. Yet to be answered are questions about which common daily tasks are characterized by the most potentially detrimental kinematics. The purpose of this analysis was to quantify and compare potentially detrimental kinematics in three common tasks performed by individuals with spinal cord injury and shoulder pain. These data will add to the body of knowledge and test common assumptions about relative risk of tasks. A cross-sectional study of 15 MWC users with shoulder pain. Electromagnetic surface sensor measures of mean and peak scapulothoracic (ST) internal and downward rotation, anterior tilt, and glenohumeral (GH) internal rotation were compared across propulsion, weight relief, and scapular plane abduction tasks using one-way repeated-measure ANOVA. Statistical differences were observed between the tasks for all rotations. Mean ST anterior tilt was greater in weight relief and propulsion than during scapular plane abduction (24°, 23°, and 13° of anterior tilt, respectively). Mean GH axial rotation during weight relief was more internally rotated than during propulsion and scapular plane abduction (9°, 26°, and 51° of external rotation, respectively). Surface-based measures of kinematics are subject to skin motion artifact, especially in translation which was not addressed in this study. Each task presented with specific variables that might contribute to risk of developing shoulder "impingement" and pain. These data may assist therapists in their assessment of movement contributions to shoulder pain in this population, as well as in subsequent treatment planning.


Dynamic nuclear polarization by frequency modulation of a tunable gyrotron of 260GHz.
An increase in Dynamic Nuclear Polarization (DNP) signal intensity is obtained with a tunable gyrotron producing frequency modulation around 260GHz at power levels less than 1W. The sweep rate of frequency modulation can reach 14kHz, and its amplitude is fixed at 50MHz. In water/glycerol glassy ice doped with 40mM TEMPOL, the relative increase in the DNP enhancement was obtained as a function of frequency-sweep rate for several temperatures. A 68 % increase was obtained at 15K, thus giving a DNP enhancement of about 80. By employing λ/4 and λ/8 polarizer mirrors, we transformed the polarization of the microwave beam from linear to circular, and achieved an increase in the enhancement by a factor of about 66% for a given power.


Calculations of wave propagation through statistical random media, with and without a waveguide.
Simulations of laser-beam propagation through atmospheric turbulence and acoustic pulse propagation though ocean internal waves in the presence of a transverse waveguide are described. Both these problems are amenable to the parabolic wave equation for propagation in the forward direction. In the optical case, the question treated is the irradiance variance and spatial spectrum. In the ocean case, pulse propagation over long ranges is investigated. Determining the travel time of a pulse requires expanding the numerical simulation in a broadband, multifrequency calculation that takes even more time. Much effort has been expended in approximating the propagation by rays, so that the trajectory of the energy propagating from a given source to a given receiver can be tracked, and coherence calculations can be ray-based, using semi-classical formulas. This paper reviews the comparisons of several analytic ray-based approximations with numerical parabolic-equation simulations to determine their accuracies.


Rhythmic entrainment of slow brain activity preceding leg movements.
The time course of the contingent negative variation (CNV) as well as beta-power are known to entrain to regular task rhythms, revealing implicit anticipatory timing. Thus far, these effects have been established for manual responses only. Here we investigate entrainment preceding leg movements. High-density EEG was recorded while participants were standing and responded to series of rhythmically presented arrow stimuli by making brisk leg movements. The standard interval between reaction stimuli differed between series and was either 1500 or 2000 ms. Each series' final interval was 1750 ms, representing a timing perturbation. Entrainment was manifested in the CNV time course, where the maximum amplitude was reached just before the next stimulus was presented. The pattern of beta-(de)synchronization similarly entrained to the task rhythm. CNV scalp topographies suggested effector dependency of the entrainment-induced CNV. We demonstrate that lower limb motor control, like upper limb control, readily entrains to a regular task rhythm. These findings are relevant to Parkinson's disease (PD), where problems are found in rhythm processing and temporal preparation. Investigation of the neural correlates of leg movement entrainment is important in view of presumed relations between entrainment and cueing of gait in PD.


Time to angiographic reperfusion in acute ischemic stroke: decision analysis.
Our objective was to use decision analytic modeling to compare 2 treatment strategies of intravenous recombinant tissue-type plasminogen activator (r-tPA) alone versus combined intravenous r-tPA/endovascular therapy in a subgroup of patients with large vessel (internal carotid artery terminus, M1, and M2) occlusion based on varying times to angiographic reperfusion and varying rates of reperfusion. We developed a decision model using Interventional Management of Stroke (IMS) III trial data and comprehensive literature review. We performed 1-way sensitivity analyses for time to reperfusion and 2-way sensitivity for time to reperfusion and rate of reperfusion success. We also performed probabilistic sensitivity analyses to address uncertainty in total time to reperfusion for the endovascular approach. In the base case, endovascular approach yielded a higher expected utility (6.38 quality-adjusted life years) than the intravenous-only arm (5.42 quality-adjusted life years). One-way sensitivity analyses demonstrated superiority of endovascular treatment to intravenous-only arm unless time to reperfusion exceeded 347 minutes. Two-way sensitivity analysis demonstrated that endovascular treatment was preferred when probability of reperfusion is high and time to reperfusion is small. Probabilistic sensitivity results demonstrated an average gain for endovascular therapy of 0.76 quality-adjusted life years (SD 0.82) compared with the intravenous-only approach. In our post hoc model with its underlying limitations, endovascular therapy after intravenous r-tPA is the preferred treatment as compared with intravenous r-tPA alone. However, if time to reperfusion exceeds 347 minutes, intravenous r-tPA alone is the recommended strategy. This warrants validation in a randomized, prospective trial among patients with large vessel occlusions.


Enhanced intimal thickening of expanded polytetrafluoroethylene grafts coated with fibrin or fibrin-releasing vascular endothelial growth factor in the pig carotid artery interposition model.
Intimal hyperplasia and surface thrombogenicity are major factors in the high failure rate of synthetic small-diameter bypass grafts. Vascular endothelial growth factor is a potent stimulus for endothelial growth, and its provision in a fibrin matrix coating at the luminal graft surface may hold a key to spontaneous graft endothelialization and improved graft patency. Pigs underwent bilateral carotid artery interposition of expanded polytetrafluoroethylene grafts either impregnated with fibrin (n = 11)--engineered to locally release vascular endothelial growth factor121 (vascular endothelial growth factor-fibrin; n = 11)--or left uncoated (n = 12). Graft patency was assessed by quantitative carotid angiography followed by graft histomorphometry at the 1-month experimental end point. Patency rates were not significantly different between study groups. Grafts coated with fibrin or vascular endothelial growth factor-fibrin exhibited significantly increased angiographic narrowing at the proximal anastomosis (for both P < .05 vs uncoated) and no difference at the distal anastomosis and the grafts' middle. Histological analysis showed 80% to 90% endothelial coverage and buildup of intima throughout the lengths of all grafts. Examination of the grafts' midportion revealed significantly enlarged neointimal layers of smooth muscle actin-positive cells in grafts coated with vascular endothelial growth factor-fibrin (242 +/- 47 microm2/micron) and fibrin (177 +/- 41 microm2/micron), compared with uncoated grafts (131 +/- 39 microm2/micron) (for both P < .05 vs uncoated). This thickening could not be explained by enhanced inflammation or vessel wall angiogenesis, which were minimal at the experimental end point. Fibrin and vascular endothelial growth factor produced effects deleterious to graft healing, by increasing the narrowing at proximal anastomosis and neointimal growth beyond that seen in uncoated grafts. It may reflect direct activation by exogenous vascular endothelial growth factor of vascular smooth muscle cells.


Human neuronal acetylcholine receptor A5-A3-B4 haplotypes are associated with multiple nicotine dependence phenotypes.
Previous research revealed significant associations between haplotypes in the CHRNA5-A3-B4 subunit cluster and scores on the Fagerström Test for Nicotine Dependence among individuals reporting daily smoking by age 17. The present study used subsamples of participants from that study to investigate associations between the CHRNA5-A3-B4 haplotypes and an array of phenotypes not analyzed previously (i.e., withdrawal severity, ability to stop smoking, and specific scales on the Wisconsin Inventory of Smoking Dependence Motives (WISDM-68) that reflect loss of control, strong craving, and heavy smoking. Two cohorts of current or former smokers (N = 886) provided both self-report data and DNA samples. One sample (Wisconsin) comprised smokers making a quit smoking attempt, which permitted the assessment of withdrawal and relapse during the attempt. The other sample (Utah) comprised participants studied for risk factors for nicotine dependence and chronic obstructive pulmonary disease and included individuals originally recruited in the Lung Health Study. The CHRNA5-A3-B4 haplotypes were significantly associated with the targeted WISDM-68 scales (Tolerance, Craving, Loss of Control) in both samples of participants but only among individuals who began smoking early in life. The haplotypes were significantly associated with relapse likelihood and withdrawal severity, but these associations showed no evidence of an interaction with age at daily smoking. The CHRNA5-A3-B4 haplotypes are associated with a broad range of nicotine dependence phenotypes, but these associations are not consistently moderated by age at initial smoking.


Classification: purposes, principles, progress, prospects.
There is an intimate interrelation between principles and procedures in classification, and modern work in this field has been profoundly affected by the development of electronic computers. Besides the delineation of natural systems and the achievement of economy of memory and ease of manipulation, the primary purpose of classification is the description of the structure and relationship of groups of similar objects. Successful classifications generate scientific hypotheses, although much classificatory work has applied, practical goals. The acceptance of polythetic taxa is a major conceptual advance and has directly led to classifications based on many, equally weighted characteristics. The specification of data for classification by computer will enhance objectivity but not eliminate cultural and subjective biases. Techniques of classification include cluster analysis and ordination, and numerous ways of representing classifications have been elaborated recently. By the application of graph theory to some classificatory problems it has been possible to reconstruct evolutionary branching sequences. Computer classification has been successfully applied across a broad range of disciplines.


Adhesion of Pseudomonas aeruginosa strains to untreated and oxygen-plasma treated poly(vinyl chloride) (PVC) from endotracheal intubation devices.
Pseudomonas aeruginosa pneumonia is a life threatening complication in mechanically ventilated patients that requires the ability of the bacteria to adhere to, and colonize the endotracheal intubation device. New strategies to prevent or reduce these nosocomial infections are greatly needed. We report here the study of a set of P. aeruginosa clinical isolates, together with specific mutants, regarding their adhesion on native and chemically modified poly(vinyl chloride) (PVC) surfaces from endotracheal intubation devices. The adhesion of the different strains to untreated PVC varied widely, correlating with several physico-chemical characteristics known to influence the attachment of bacteria to inert surfaces. The adhesion patterns were compared to the calculations obtained with the DLVO theory of colloidal stability. These results illustrate the importance of testing different clinical isolates when investigating bacterial adhesion. Oxygen plasma treatment of the PVC pieces yielded a hydrophilic surface and reduced the number of adhering bacteria by as much as 70%. This reduction is however unlikely to be sufficient to prevent P. aeruginosa colonization of endotracheal intubation devices.


Female-released sex pheromones mediating courtship behavior in Lysiphlebus testaceipes males.
Ethological aspects and chemical communication at close-range between the sexes of Lysiphlebus testaceipes Cresson (Hymenoptera: Braconidae) have been investigated through behavioral bioassays and chemical analysis. The attractiveness toward males of whole-body extracts of females and males in hexane and acetone was evaluated, adopting male fanning behavior as a key behavioral component. Also, the activity of polar and nonpolar fraction of female-body extract in hexane obtained using solid-phase extraction technique was investigated. In order to identify cuticular compounds, male and female whole-body extracts with hexane and acetone were analyzed by gas chromatography-mass spectrometry. The results showed that males exhibit a behavior including 4 phases when exposed to virgin females: premount, mount, copulation, and post-copulation. A preliminary courtship of the male included wing fanning, an extension and vibration of the wings for 1 to 2 seconds. Also, some original aspects not described for other species were carried out. The average duration of the entire sequence of events was 138.80 ± 19.51 sec. Also, males displayed significantly more wing fanning behavior in response to female whole-body hexane extracts (70.83%) than female whole-body acetone extracts (33.3%). Furthermore, males did not respond to male-body extracts or to the control (pure hexane and acetone), suggesting that the sex pheromone is composed of cuticular hydrocarbons that are also involved in the male courtship behavior. When hexane extracts of whole females were fractionated on silica gel and exposed to males, more activity was recorded for the nonpolar fraction (50.0%) than the polar fraction (27.7%), but no significant statistical difference was found. Significant differences were detected comparing the control (not fractionated extract) with the polar fraction, but not with the nonpolar fraction. A homologous series of n-alkanes with chain lengths from C19 to C30 carbon atoms was identified and quantified in the solvent extracts of wasp males and females. Between male and female extracts, there was a statistically significant difference in the average quantity of some of these hydrocarbons, such as C₂₇, C₂₈, and C₂₉.


In vivo modulation of LPS induced leukotrienes generation and oxidative stress by sesame lignans.
The role of inflammation and oxidative stress is critical during onset of metabolic disorders and this has been sufficiently established in literature. In the present study, we evaluated the effects of sesamol and sesamin, two important bioactive molecules present in sesame oil, on the generation of inflammatory and oxidative stress factors in LPS injected rats. Sesamol and sesamin lowered LPS induced expression of cPLA2 (61 and 56%), 5-LOX (44 and 51%), BLT-1(32 and 35%) and LTC4 synthase (49 and 50%), respectively, in liver homogenate. The diminished serum LTB4 (53 and 64%) and LTC4 (67 and 44%) levels in sesamol and sesamin administered groups, respectively, were found to be concurrent with the observed decrease in the expression of cPLA2 and 5-LOX. The serum levels of TNF-α (29 and 19%), MCP-1 (44 and 57%) and IL-1β (43 and 42%) were found to be reduced in sesamol and sesamin group, respectively, as given in parentheses, compared to LPS group. Sesamol and sesamin offered protection against LPS induced lipid peroxidation in both serum and liver. Sesamol, but not sesamin, significantly restored the loss of catalase and glutathione reductase activity due to LPS (P<.05). However, both sesamol and sesamin reverted SOD activities by 92 and 98%, respectively. Thus, oral supplementation of sesamol and sesamin beneficially modulated the inflammatory and oxidative stress markers, as observed in the present study, in LPS injected rats. Our report further advocates the potential use of sesamol and sesamin as an adjunct therapy wherein, inflammatory and oxidative stress is of major concern.


The effect of contrast on perceived speed and flicker.
Slowly moving low contrast patterns appear to drift more slowly than higher contrast patterns. It has been reported that this effect of contrast is reversed for flickering patterns such that they appear to flicker faster than high contrast patterns. This apparent difference in the effect of contrast on perceived speed and flicker may place important constraints upon models of speed encoding in the human visual system. We have measured perceived speed and flicker over a range of spatial and temporal frequencies. The results indicate that contrast has qualitatively (but not quantitatively) similar effects upon perceived speed and flicker. The results also indicate that the effect of contrast upon perceived speed is likely to be inherited from the effect of contrast upon perceived flicker. These findings allow a relaxation of previous constraints upon models of speed encoding.


QTL analysis of internode elongation in response to gibberellin in deepwater rice.
Gibberellin (GA) is a plant hormone that has important roles in numerous plant developmental phases. Rice plants known as deepwater rice respond to flooding by elongating their internodes to avoid anoxia. Previous studies reported that GA is essential for internode elongation in deepwater rice. Quantitative trait locus (QTL) analyses identified QTLs regulating internode elongation in response to deepwater conditions. However, the interaction between internode elongation and regulators of GA sensitivity in deepwater rice is unknown. In this study, we applied GA to recombinant inbred lines of T65 (non-deepwater rice) and Bhadua (deepwater rice), and performed a QTL analysis of internode elongation in response to GA. GA-induced internode elongation was detected only in deepwater rice. Our QTL analysis revealed two major QTLs on chromosomes 3 and 9 regulating total internode length, lowest elongated internode and number of elongated internodes. Furthermore, the QTL on chromosome 3 acted as an enhancer of other QTLs (e.g. the QTL on chromosome 12). Nearly isogenic lines of deepwater rice carrying the QTL regions from chromosomes 3 and 12 of the deepwater rice C9285 showed internode elongation in response to GA. Thus, these QTLs may regulate GA responsiveness in deepwater rice. This study furthers our understanding of the mechanism of internode elongation in rice.


The Effect of Resistant Soybean on Male and Female Development and Adult Sex Ratios of Heterodera glycines.
To determine whether currently used sources of resistance (soybean Plant Introductions [PI] 548402, 88788, 90763, 437654, 209332, 89772, and 548316) influence sex ratios in H. glycines, four inbred lines of the nematode characterized by zero or high numbers of females on resistant soybean were used to observe the number of adult males produced. Nematodes were allowed to infect soybean roots for 5 days in pasteurized sand. Infected plants were washed and transferred to hydroponic culture tubes. Males were collected every 2 to 3 days up to 30 days after infestation (DAI), and females were collected at 30 DAI. Resistance that suppressed adult females also altered adult male numbers. On PI 548402, 90763, and 437654, male numbers were low and close to zero, whereas on PI 88788, male numbers were higher (alpha = 0.05). In a separate experiment, the same PIs were infected by an inbred line that tested as an HG Type 0 (i.e., the numbers of females that developed on each PI were less than 10% of the number that developed on the standard susceptible soybean cultivar Lee). In this experiment, male numbers were similar to female numbers on PI 548402, 90763, 437654, and 89772, whereas male numbers on PI 88788, 209332, and 548316 were higher than those of females (alpha = 0.05). In all experiments, the total number of adults that developed to maturity relative to the number of second-stage juveniles that initially penetrated the root was less on resistant than on susceptible soybean (P </= 0.05), indicating that resistance influenced H. glycines survival and not sexual development.


Functional characterization of Drosophila sialyltransferase.
Sialylation is an important carbohydrate modification of glycoconjugates in the deuterostome lineage of animals. By contrast, the evidence for sialylation in protostomes has been scarce and somewhat controversial. In the present study, we characterize a Drosophila sialyltransferase gene, thus providing experimental evidence for the presence of sialylation in protostomes. This gene encodes a functional alpha2-6-sialyltransferase (SiaT) that is closely related to the vertebrate ST6Gal sialyltransferase family, indicating an ancient evolutionary origin for this family. Characterization of recombinant, purified Drosophila SiaT revealed a novel acceptor specificity as it exhibits highest activity toward GalNAcbeta1-4GlcNAc carbohydrate structures at the non-reducing termini of oligosaccharides and glycoprotein glycans. Oligosaccharides are preferred over glycoproteins as acceptors, and no activity toward glycolipid acceptors was detected. Recombinant Drosophila SiaT expressed in cultured insect cells possesses in vivo and in vitro autosialylation activity toward beta-linked GalNAc termini of its own N-linked glycans, thus representing the first example of a sialylated insect glycoconjugate. In situ hybridization revealed that Drosophila SiaT is expressed during embryonic development in a tissue- and stage-specific fashion, with elevated expression in a subset of cells within the central nervous system. The identification of a SiaT in Drosophila provides a new evolutionary perspective for considering the diverse functions of sialylation and, through the powerful genetic tools available in this system, a means of elucidating functions for sialylation in protostomes.


Immunophenotypic analysis of hematologic malignancy by laser scanning cytometry.
The authors tested a newly-developed computerized laser scanning cytometer (LSC) as a means of performing immunophenotypic analysis of hematologic specimens within their community hospital. Results were compared on a case-by-case basis with parallel flow cytometric and immunohistochemical data. A total of 71 specimens analyzed include 22 excised lymph nodes or other tissue biopsies, 18 peripheral bloods, 17 bone marrow aspirates, 7 body fluids, and 7 fine-needle aspiration biopsies of lymphoid tissue. The LSC proved to be a useful instrument capable of generating simultaneous two-color immunofluorescent data directly analogous to that obtained via conventional flow cytometry. However, laser scanning cytometric analysis provides advantages over flow cytometric analysis, because the LSC measures cells on a slide rather than in a fluid stream. Specifically, cells can be microscopically examined at any time--before, during, or after automated immunofluorescent analysis. In addition, specimen preparation techniques are less restricted and more cost efficient. Lastly, even extremely small and/or hypocellular specimens (such as body fluids and fine-needle aspiration biopsies) can be successfully analyzed.


Trimeric HIV-1 glycoprotein gp140 immunogens and native HIV-1 envelope glycoproteins display the same closed and open quaternary molecular architectures.
The initial step in HIV-1 infection occurs with the binding of cell surface CD4 to trimeric HIV-1 envelope glycoproteins (Env), a heterodimer of a transmembrane glycoprotein (gp41) and a surface glycoprotein (gp120). The design of soluble versions of trimeric Env that display structural and functional properties similar to those observed on intact viruses is highly desirable from the viewpoint of designing immunogens that could be effective as vaccines against HIV/AIDS. Using cryoelectron tomography combined with subvolume averaging, we have analyzed the structure of SOSIP gp140 trimers, which are cleaved, solubilized versions of the ectodomain of trimeric HIV-1 Env. We show that unliganded gp140 trimers adopt a quaternary arrangement similar to that displayed by native unliganded trimers on the surface of intact HIV-1 virions. When complexed with soluble CD4, Fab 17b, which binds to gp120 at its chemokine coreceptor binding site, or both soluble CD4 and 17b Fab, gp140 trimers display an open conformation in which there is an outward rotation and displacement of each gp120 protomer. We demonstrate that the molecular arrangements of gp120 trimers in the closed and open conformations of the soluble trimer are the same as those observed for the closed and open states, respectively, of trimeric gp120 on intact HIV-1 BaL virions, establishing that soluble gp140 trimers can be designed to mimic the quaternary structural transitions displayed by native trimeric Env.


What is eHealth (5): a research agenda for eHealth through stakeholder consultation and policy context review.
In 2003, the National Health Service in England and Wales, despite its large investment in information and communication technology, had not set a national research agenda. The National Health Service has three main research and development programs: one is the Service Delivery and Organisation program, commissioned in 2003, and the others are two parallel "scoping exercises" to help set a research agenda. This paper reports on one of those projects. A parallel literature review was carried out by others and has been reported elsewhere. The objective was to explore the concerns of stakeholders and to review relevant policy in order to produce recommendations and a conceptual map of eHealth research. There were two parallel strands. For the stakeholder consultation, 37 professionals representing 12 "stakeholder" groups participated in focus groups or interviews. Discussion was prompted by eHealth "scenarios" and analyzed using thematic content analysis. Subsequently, 17 lay participants, in three focus groups, discussed and prioritized these themes. For the policy review, 26 policy makers were interviewed, and 95 policy documents were reviewed. Recommendations were subsequently reviewed in a conference workshop. Recommendations for research from both strands were combined into a conceptual map. Themes from stakeholder consultation and policy review were combined as 43 recommendations under six headings. Four of these headings (using, processing, sharing, and controlling information) describe the scope of eHealth research. The other two relate to how research should be carried out (ensuring best practice is first identified and disseminated) and to the values considered important by stakeholders (in particular, measuring improvement in health). The scope of eHealth research (using, processing, sharing, controlling information) derived empirically from this study corresponds with "textbook" descriptions of informatics. Stakeholders would like eHealth research to include outcomes such as improved health or quality of life, but such research may be long term while changes in information technology are rapid. Longer-term research questions need to be concerned with human behavior and our use of information, rather than particular technologies. In some cases, "modelling" longer-term costs and benefits (in terms of health) may be desirable.


In vivo and in vitro inhibition of CYP1A-dependent activity in Fundulus heteroclitus by the polynuclear aromatic hydrocarbon fluoranthene.
Certainpolynuclear aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (BaP) induce CYP1A-dependent enzyme activities. Because PAHs are ubiquitous environmental contaminants, and some are aryl hydrocarbon agonists, CYP1A has been used as a biomarker for PAH exposure. However, PAHs exist in the environment in complex mixtures that may confound biomarker results. In in vitro studies, the PAH fluoranthene (FL) failed to increase or enhance CYP1A1-dependent ethoxyresorufin-O-deethylase (EROD) activity in cells, but rather inhibited activities induced by AhR agonists such as 2,3,7,8-tetrachlorodibenzo-p-dioxin and benzo(k)fluoranthene. In order to determine the in vivo effects of FL on CYP1A and DNA adduct levels, Fundulus heteroclitus were given single ip injections of either BaP (5 mg/kg), BaP + FL (5 mg/kg each), BaP + FL (5 and 50 mg/kg, respectively), FL (5 mg/kg), FL (50 mg/kg), or corn oil control. BaP-treated fish had liver microsome EROD activities significantly higher than controls, whereas FL-treated fish were not different from controls. EROD activities in BaP + FL cotreatments were significantly lower compared to fish treated with BaP alone. When FL was incubated with BaP-induced microsomes, the IC50 for inhibition of EROD activity was 1.4 x 10(-5) M FL. Kinetic studies indicated a significant noncompetitive component to the FL inhibition. When fish were treated with [(14)C]FL, the concentration of radiolabel associated with microsomal preparations was four orders of magnitude lower than the IC50. Therefore, the presence of FL or a FL metabolite was insufficient to account for the inhibition by a kinetic mechanism. In contrast to cell studies, CYP1A immunoreactive protein was significantly decreased in vivo by FL cotreatment, indicating that FL may inhibit EROD activity by down-regulating the CYP1A protein. A covalent interaction of [(14)C]FL with CYP1A was not detected. Total (32)P-postlabeled DNA adducts were not significantly changed by cotreatment of FL and BaP; however, cotreatment with 50 mg/kg FL decreased one adduct and increased another significantly. Because FL and perhaps other inhibitory PAHs, co-occur in the environment with CYP1A inducers, CYP1A-dependent bioassays may cause an underestimation of PAH exposures.


Response of the neurovascular unit to brain metastatic breast cancer cells.
Therapeutic resistance of cerebral secondary tumours largely depends on unique aspects linked to the neurovascular unit, especially cerebral endothelial cells and astrocytes. By using advanced microscopy techniques, here we explored novel mechanisms related to the neurovascular unit during extravasation and proliferation of triple negative breast cancer cells in the brain. Metastatic mammary carcinoma cells arrested and elongated within one hour in cerebral microvessels, but their number decreased by almost 80% in the first two days. Interestingly, malignant cells induced vasoconstriction and development of intraluminal endothelial plugs, which isolated invading cells from the circulation. During diapedesis - which usually took place on day four and five after inoculation of the tumour cells - continuity of cerebral endothelial tight junctions remained intact, indicating migration of cancer cells through the transcellular pathway. In addition, metastatic cells induced formation of multiluminal vessels and claudin-5-positive endothelial blebs. However, even severe endothelial blebbing could be reversed and the vessel morphology was restored shortly after the tumour cells completed transendothelial migration. Similar to neuro-inflammatory leukocytes, tumour cells migrated not only through the endothelial layer, but through the glia limitans perivascularis as well. Nevertheless, along with the growth of metastatic lesions by co-option of pre-existing capillaries, astrocytes and astrocyte end-feet were gradually expelled from the vessels to the border of the tumour. Taken together, we identified previously unknown mechanisms involved in the reaction of brain resident cells to invading breast cancer cells. Our results contribute to a better understanding of the complex cross-talk between tumour cells and host cells in the brain, which is essential for the identification of new therapeutic targets in this devastating disease.


Content-based image retrieval of multiphase CT images for focal liver lesion characterization.
Characterization of focal liver lesions with various imaging modalities can be very challenging in the clinical practice and is experience-dependent. The authors' aim is to develop an automatic method to facilitate the characterization of focal liver lesions (FLLs) using multiphase computed tomography (CT) images by radiologists. A multiphase-image retrieval system is proposed to retrieve a preconstructed database of FLLs with confirmed diagnoses, which can assist radiologists' decision-making in FLL characterization. It first localizes the FLL on multiphase CT scans using a hybrid generative-discriminative FLL detection method and a nonrigid B-spline registration method. Then, it extracts the multiphase density and texture features to numerically represent the FLL. Next, it compares the query FLL with the model FLLs in the database in terms of the feature and measures their similarities using the L1-norm based similarity scores. The model FLLs are ranked by similarities and the top results are finally provided to the users for their evidence studies. The system was tested on a database of 69 four-phase contrast-enhanced CT scans, consisting of six classes of liver lesions, and evaluated in terms of the precision-recall curve and the Bull's Eye Percentage Score (BEP). It obtained a BEP score of 78%. Compared with any single-phase based representation, the multiphase-based representation increased the BEP scores of the system, from 63%-65% to 78%. In a pilot study, two radiologists performed characterization of FLLs without and with the knowledge of the top five retrieved results. The results were evaluated in terms of the diagnostic accuracy, the receiver operating characteristic (ROC) curve and the mean diagnostic confidence. One radiologist's accuracy improved from 75% to 92%, the area under ROC curves (AUC) from 0.85 to 0.95 (p = 0.081), and the mean diagnostic confidence from 4.6 to 7.3 (p = 0.039). The second radiologist's accuracy did not change, at 75%, with AUC increasing from 0.72 to 0.75 (p = 0.709), and the mean confidence from 4.5 to 4.9 (p = 0.607). Multiphase CT images can be used in content-based image retrieval for FLL's categorization and result in good performance in comparison with single-phase CT images. The proposed method has the potential to improve the radiologists' diagnostic accuracy and confidence by providing visually similar lesions with confirmed diagnoses for their interpretation of clinical studies.


"Ziziphus jujuba": A red fruit with promising anticancer activities.
Ziziphus jujuba Mill. (Z. jujuba) is a traditional herb with a long history of use for nutrition and the treatment of a broad spectrum of diseases. It grows mostly in South and East Asia, as well as in Australia and Europe. Mounting evidence shows the health benefits of Z. jujuba, including anticancer, anti-inflammation, antiobesity, antioxidant, and hepato- and gastrointestinal protective properties, which are due to its bioactive compounds. Chemotherapy, such as with cis-diamminedichloroplatinium (CDDP, cisplatin) and its derivatives, is widely used in cancer treatment. It is an effective treatment for human cancers, including ovarian cancer; however, drug resistance is a major obstacle to successful treatment. A better understanding of the mechanisms and strategies for overcoming chemoresistance can greatly improve therapeutic outcomes for patients. In this review article, the bioactive compounds present in Z. jujuba are explained. The high prevalence of many different cancers worldwide has recently attracted the attention of many researchers. This is why our research group focused on studying the anticancer activity of Z. jujuba as well as its impact on chemoresistance both in vivo and in vitro. We hope that these studies can lead to a promising future for cancer patients.


Absence of pressure overload induced myocardial hypertrophy after conditional inactivation of Galphaq/Galpha11 in cardiomyocytes.
Myocardial hypertrophy is an adaptational response of the heart to increased work load, but it is also associated with a high risk of cardiac mortality due to its established role in the development of cardiac failure, one of the leading causes of death in developed countries. Multiple growth factors and various downstream signaling pathways involving, for example, ras, gp-130 (ref. 4), JNK/p38 (refs. 5,6) and calcineurin/NFAT/CaM-kinase have been implicated in the hypertrophic response. However, there is evidence that the initial phase in the development of myocardial hypertrophy involves the formation of cardiac para- and/or autocrine factors like endothelin-1, norepinephrine or angiotensin II (refs. 7,8), the receptors of which are coupled to G-proteins of the Gq/11-, G12/13- and Gi/o-families. Cardiomyocyte-specific transgenic overexpression of alpha1-adrenergic or angiotensin (AT1)-receptors as well as of the Gq alpha-subunit, Galphaq, results in myocardial hypertrophy. These data demonstrate that chronic activation of the Gq/G11-family is sufficient to induce myocardial hypertrophy. In order to test whether Gq/G11 mediate the physiological hypertrophy response to pressure overload, we generated a mouse line lacking both Galphaq and Galpha11 in cardiomyocytes. These mice showed no detectable ventricular hypertrophy in response to pressure-overload induced by aortic constriction. The complete lack of a hypertrophic response proves that the Gq/G11-mediated pathway is essential for cardiac hypertrophy induced by pressure overload and makes this signaling process an interesting target for interventions to prevent myocardial hypertrophy.


The role of B cell receptor stimulation in CLL pathogenesis.
Chronic lymphocytic leukemia (CLL) is the most frequent leukemia in adults in the Western world and is characterized by the accumulation of monoclonal CD5(+) mature B cells in the blood. The disease has a highly variable clinical course. CLL is subdivided into two disease subtypes, whereby leukemias with hypermutated immunoglobulin heavy chain variable (IGHV) genes have a more favorable prognosis than those with unmutated IGHV genes, which tend to show advanced, progressive disease, adverse cytogenetic features and resistance to therapy. The current view is that both CLL types derive from antigen-experienced cells. Based on the finding that the IGHV repertoire is highly restricted and biased, as compared to the normal adult B-cell repertoire, it has been hypothesized that CLL cells are selected by some sort of antigenic pressure. Hereby, either autoantigens or antigens derived from apoptotic cells or pathogens are essential to trigger CLL pathogenesis. Although different cytogenetic aberrations were shown to contribute to CLL leukemogenesis, it remains unclear which abnormalities are primary events. Very recently, whole-genome sequencing identified genes that are recurrently mutated and provided novel insights into the mechanisms of oncogenic transformation. Because of the impact on prognosis, it is important to unravel the role of antigenic selection in CLL. Interestingly, B cell receptor (BCR) signaling is aberrantly increased in CLL and expression of tyrosine kinase ZAP70, which is able to signal downstream of the BCR, is a prognostic indicator. In this context we discuss the functional significance of antigenic selection in CLL and describe emerging agents to target BCR signaling that are currently being tested as a novel therapeutic strategy for CLL.


The 2019-2020 Novel Coronavirus (Severe Acute Respiratory Syndrome Coronavirus 2) Pandemic: A Joint American College of Academic International Medicine-World Academic Council of Emergency Medicine Multidisciplinary COVID-19 Working Group Consensus Paper.
What started as a cluster of patients with a mysterious respiratory illness in Wuhan, China, in December 2019, was later determined to be coronavirus disease 2019 (COVID-19). The pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel Betacoronavirus, was subsequently isolated as the causative agent. SARS-CoV-2 is transmitted by respiratory droplets and fomites and presents clinically with fever, fatigue, myalgias, conjunctivitis, anosmia, dysgeusia, sore throat, nasal congestion, cough, dyspnea, nausea, vomiting, and/or diarrhea. In most critical cases, symptoms can escalate into acute respiratory distress syndrome accompanied by a runaway inflammatory cytokine response and multiorgan failure. As of this article's publication date, COVID-19 has spread to approximately 200 countries and territories, with over 4.3 million infections and more than 290,000 deaths as it has escalated into a global pandemic. Public health concerns mount as the situation evolves with an increasing number of infection hotspots around the globe. New information about the virus is emerging just as rapidly. This has led to the prompt development of clinical patient risk stratification tools to aid in determining the need for testing, isolation, monitoring, ventilator support, and disposition. COVID-19 spread is rapid, including imported cases in travelers, cases among close contacts of known infected individuals, and community-acquired cases without a readily identifiable source of infection. Critical shortages of personal protective equipment and ventilators are compounding the stress on overburdened healthcare systems. The continued challenges of social distancing, containment, isolation, and surge capacity in already stressed hospitals, clinics, and emergency departments have led to a swell in technologically-assisted care delivery strategies, such as telemedicine and web-based triage. As the race to develop an effective vaccine intensifies, several clinical trials of antivirals and immune modulators are underway, though no reliable COVID-19-specific therapeutics (inclusive of some potentially effective single and multi-drug regimens) have been identified as of yet. With many nations and regions declaring a state of emergency, unprecedented quarantine, social distancing, and border closing efforts are underway. Implementation of social and physical isolation measures has caused sudden and profound economic hardship, with marked decreases in global trade and local small business activity alike, and full ramifications likely yet to be felt. Current state-of-science, mitigation strategies, possible therapies, ethical considerations for healthcare workers and policymakers, as well as lessons learned for this evolving global threat and the eventual return to a "new normal" are discussed in this article.


Are children of moderately low birth weight at increased risk for poor health? A new look at an old question.
The goal was to examine whether moderately low birth weight children were at greater risk for health problems than normal birth weight children in a nationally representative sample of US children. Data were analyzed for 7817 children, 0 to 12 years of age, from the sample child file of the 2002 National Health Interview Survey. Logistic regressions were estimated to examine whether morbidity rates were higher among moderately low birth weight children than among normal birth weight children and to control for covariates. Health was measured as having a special health care need, having a chronic condition, being hospitalized in the past year, having a learning disability, attention-deficit disorder/attention-deficit/hyperactivity disorder, or other behavioral disorders, having minor health conditions, and having acute illnesses. With control for other confounders, moderately low birth weight children were significantly more likely than normal birth weight children to be identified as having a special health care need, having a chronic condition, having a learning disability, and having attention-deficit disorder or attention-deficit/hyperactivity disorder. They were not more likely to have a hospitalization in the past year, other behavioral disorders, or minor health conditions or acute illnesses. This population-based study of rates of current morbidity shows that moderately low birth weight children born since 1990 are vulnerable to a wide range of health, learning, and behavioral problems, compared with normal birth weight children. This suggests the need for continued focus on ways to reduce morbidity rates for moderately low birth weight children.


Myeloid and T-Cell Microenvironment Immune Features Identify Two Prognostic Sub-Groups in High-Grade Gastroenteropancreatic Neuroendocrine Neoplasms.
High-grade Gastroenteropancreatic Neuroendocrine neoplasms (H-NENs) comprehend well-differentiated tumors (NET G3) and poorly differentiated carcinomas (NEC) with proliferative activity indexes as mitotic count (MC) >20 mitoses/10 HPF and Ki-67 >20%. At present, no specific therapy for H-NENs exists and the several evidences of microenvironment involvement in their pathogenesis pave the way for tailored therapies. Forty-five consecutive cases, with available information about T-cell, immune, and non-immune markers, from surgical pathology and clinical databases of 2 Italian institutions were immunostained for Arginase, CD33, CD163 and CD66 myeloid markers. The association between features was assessed by Spearman's correlation coefficient. A unsupervised K-means algorithm was used to identify clusters of patients according to inputs of microenvironment features and the relationship between clusters and clinicopathological features, including cancer-specific survival (CSS), was analyzed. The H-NEN population was composed of 6 (13.3%) NET G3 and 39 (86.7%) NEC. Overall, significant positive associations were found between myeloid (CD33, CD163 and Arginase) and T/immune markers (CD3, CD4, CD8, PD-1 and HLA-I). Myeloid and T-cell markers CD3 and CD8 identified two clusters of patients from unsupervised K-means analysis. Cases grouped in cluster 1 with more myeloid infiltrates, T cell, HLA and expression of inhibitory receptors and ligands in the stroma (PD-1, PD-L1) had significantly better CSS than patients in cluster 2. Multivariable analysis showed that Ki-67 (>55 vs. <55, HR 8.60, CI 95% 2.61-28.33, p < 0.0001) and cluster (1 vs. 2, HR 0.43, CI 95% 0.20-0.93, p = 0.03) were significantly associated with survival. High grade gastroenteropancreatic neuroendocrine neoplasms can be further classified into two prognostic sub-populations of tumors driven by different tumor microenvironments and immune features able to generate the framework for evaluating new therapeutic strategies.


Mitochondrial mechanosensor in cardiovascular diseases.
The role of mitochondria in cardiac tissue is of utmost importance due to the dynamic nature of the heart and its energetic demands, necessary to assure its proper beating function. Recently, other important mitochondrial roles have been discovered, namely its contribution to intracellular calcium handling in normal and pathological myocardium. Novel investigations support the fact that during the progression toward heart failure, mitochondrial calcium machinery is compromised due to its morphological, structural and biochemical modifications resulting in facilitated arrhythmogenesis and heart failure development. The interaction between mitochondria and sarcomere directly affect cardiomyocyte excitation-contraction and is also involved in mechano-transduction through the cytoskeletal proteins that tether together the mitochondria and the sarcoplasmic reticulum. The focus of this review is to briefly elucidate the role of mitochondria as (mechano) sensors in the heart.


Mitochondrial clearance by autophagy in developing erythrocytes: clearly important, but just how much so?
Erythrocytes are anucleated cells devoid of organelles. Expulsion of the nucleus from erythroblasts leads to the formation of reticulocytes, which still contain organelles. The mechanisms responsible for the final removal of organelles from developing erythroid cells are still being elucidated. Mitochondria are the most abundant organelles to be cleared for the completion of erythropoiesis. Macroautophagy, referred to as autophagy, is a regulated catabolic pathway consisting of the engulfment of cytoplasmic cargo by a double membraned-vesicle, the autophagosome, which typically then fuses to lysosomal compartments for the degradation of the sequestered material. Early electron microscopic observations of reticulocytes suggested the autophagic engulfment of mitochondria (mitophagy) as a possible mechanism for mitochondrial clearance in these. Recently, a number of studies have backed this hypothesis with molecular evidence. Indeed, the absence of Nix, which targets mitochondria to autophagosomes, or the deficiency of proteins in the autophagic pathway lead to impaired mitochondrial clearance from developing erythroid cells. Importantly, however, the extent to which the absence of mitophagy affects erythroid development differs depending on the model and gene investigated. This review will therefore focus on comparing the different studies of mitophagy in erythroid development and highlight some of the remaining controversial points.


Elliptical-hole photonic crystal fibers.
We study the dispersive properties of photonic crystal fibers (PCF's) with elliptical air holes. The unusual guidance of PCF leads to novel behavior of the birefringence, group-velocity walk-off, and dispersion parameters, including the possibility of zero walk-off with high birefringence in the single-mode regime. A number of these effects are closely tied to the underlying radiation states of the air-hole lattice.


Physical interventions to interrupt or reduce the spread of respiratory viruses: systematic review.
To review systematically the evidence of effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. Cochrane Library, Medline, OldMedline, Embase, and CINAHL, without restrictions on language or publication. Data selection Studies of any intervention to prevent the transmission of respiratory viruses (isolation, quarantine, social distancing, barriers, personal protection, and hygiene). A search of study designs included randomised trials, cohort, case-control, crossover, before and after, and time series studies. After scanning of the titles, abstracts and full text articles as a first filter, a standardised form was used to assess the eligibility of the remainder. Risk of bias of randomised studies was assessed for generation of the allocation sequence, allocation concealment, blinding, and follow-up. Non-randomised studies were assessed for the presence of potential confounders and classified as being at low, medium, or high risk of bias. 58 papers of 59 studies were included. The quality of the studies was poor for all four randomised controlled trials and most cluster randomised controlled trials; the observational studies were of mixed quality. Meta-analysis of six case-control studies suggested that physical measures are highly effective in preventing the spread of severe acute respiratory syndrome: handwashing more than 10 times daily (odds ratio 0.45, 95% confidence interval 0.36 to 0.57; number needed to treat=4, 95% confidence interval 3.65 to 5.52), wearing masks (0.32, 0.25 to 0.40; NNT=6, 4.54 to 8.03), wearing N95 masks (0.09, 0.03 to 0.30; NNT=3, 2.37 to 4.06), wearing gloves (0.43, 0.29 to 0.65; NNT=5, 4.15 to 15.41), wearing gowns (0.23, 0.14 to 0.37; NNT=5, 3.37 to 7.12), and handwashing, masks, gloves, and gowns combined (0.09, 0.02 to 0.35; NNT=3, 2.66 to 4.97). The combination was also effective in interrupting the spread of influenza within households. The highest quality cluster randomised trials suggested that spread of respiratory viruses can be prevented by hygienic measures in younger children and within households. Evidence that the more uncomfortable and expensive N95 masks were superior to simple surgical masks was limited, but they caused skin irritation. The incremental effect of adding virucidals or antiseptics to normal handwashing to reduce respiratory disease remains uncertain. Global measures, such as screening at entry ports, were not properly evaluated. Evidence was limited for social distancing being effective, especially if related to risk of exposure-that is, the higher the risk the longer the distancing period. Routine long term implementation of some of the measures to interrupt or reduce the spread of respiratory viruses might be difficult. However, many simple and low cost interventions reduce the transmission of epidemic respiratory viruses. More resources should be invested into studying which physical interventions are the most effective, flexible, and cost effective means of minimising the impact of acute respiratory tract infections.


Participation in EHR based simulation improves recognition of patient safety issues.
Electronic health records (EHR) are becoming increasingly integrated into the clinical environment. With the rapid proliferation of EHRs, a number of studies document an increase in adverse patient safety issues due to the EHR-user interface. Because of these issues, greater attention has been placed on novel educational activities which incorporate use of the EHR. The ICU environment presents many challenges to integrating an EHR given the vast amounts of data recorded each day, which must be interpreted to deliver safe and effective care. We have used a novel EHR based simulation exercise to demonstrate that everyday users fail to recognize a majority of patient safety issues in the ICU. We now sought to determine whether participation in the simulation improves recognition of said issues. Two ICU cases were created in our EHR simulation environment. Each case contained 14 safety issues, which differed in content but shared common themes. Residents were given 10 minutes to review a case followed by a presentation of management changes. Participants were given an immediate debriefing regarding missed issues and strategies for data gathering in the EHR. Repeated testing was performed in a cohort of subjects with the other case at least 1 week later. 116 subjects have been enrolled with 25 subjects undergoing repeat testing. There was no difference between cases in recognition of patient safety issues (39.5% vs. 39.4%). Baseline performance for subjects who participated in repeat testing was no different than the cohort as a whole. For both cases, recognition of safety issues was significantly higher among repeat participants compared to first time participants. Further, individual performance improved from 39.9% to 63.6% (p = 0.0002), a result independent of the order in which the cases were employed. The degree of improvement was inversely related to baseline performance. Further, repeat participants demonstrated a higher rate of recognition of changes in vitals, misdosing of antibiotics and oversedation compared to first time participants. Participation in EHR simulation improves EHR use and identification of patient safety issues.


Gene dosage effects of the imprinted delta-like homologue 1 (dlk1/pref1) in development: implications for the evolution of imprinting.
Genomic imprinting is a normal process that causes genes to be expressed according to parental origin. The selective advantage conferred by imprinting is not understood but is hypothesised to act on dosage-critical genes. Here, we report a unique model in which the consequences of a single, double, and triple dosage of the imprinted Dlk1/Pref1, normally repressed on the maternally inherited chromosome, can be assessed in the growing embryo. BAC-transgenic mice were generated that over-express Dlk1 from endogenous regulators at all sites of embryonic activity. Triple dosage causes lethality associated with major organ abnormalities. Embryos expressing a double dose of Dlk1, recapitulating loss of imprinting, are growth enhanced but fail to thrive in early life, despite the early growth advantage. Thus, any benefit conferred by increased embryonic size is offset by postnatal lethality. We propose a negative correlation between gene dosage and survival that fixes an upper limit on growth promotion by Dlk1, and we hypothesize that trade-off between growth and lethality might have driven imprinting at this locus.