Person-Centredness and Fundamentals of Care - Dancing with Beauty Rather than Fighting Ugliness.
The fundamentals of care have re-emerged as an important consideration in nursing following a period when these role elements were predominantly "delegated tasks" delivered by other (usually unregistered/unregulated) members of the health and social care team. Contemporary critiques of nursing highlight the technical focus of nursing at the expense of its caring function. Person-centred nursing theory offers a way of reinstating the value of fundamental care as a core part of providing holistic nursing to persons as well as highlighting the importance of the nursing role in coordinating healthcare services in ways that are consistent with a person's beliefs and values. This paper argues that a focus on person-centredness enables the core function of nurses as providers and coordinators of holistic person-centred fundamental care to be revalued. It highlights the importance of nurses being clear about "what matters" in caring practices and suggests that nurses adopting a person-centred approach can achieve effective care coordination through the lens of the fundamentals of care. In reading this paper, a greater understanding of person-centredness in the context of the fundamentals of care can be achieved.


The effect of the cation alkyl chain length on density and diffusion in dialkylpyrrolidinium bis(mandelato)borate ionic liquids.
The physicochemical properties of ionic liquids are strongly affected by the selective combination of the cations and anions comprising the ionic liquid. In particular, the length of the alkyl chains of ions has a clear influence on the ionic liquid's performance. In this paper, we study the self-diffusion of ions in a series of halogen-free boron-based ionic liquids (hf-BILs) containing bis(mandelato)borate anions and dialkylpyrrolidinium cations with long alkyl chains CnH2n+1 with n from 4 to 14 within a temperature range of 293-373 K. It was found that the hf-BILs with n = 4-7 have very similar diffusion coefficients, while hf-BILs with n = 10-14 exhibit two liquid sub-phases in almost the entire temperature range studied (293-353 K). Both liquid sub-phases differ in their diffusion coefficients, while values of the slower diffusion coefficients are close to those of hf-BILs with shorter alkyl chains. To explain the particular dependence of diffusion on the alkyl chain length, we examined the densities of the hf-BILs studied here. It was shown that the dependence of the density on the number of CH2 groups in long alkyl chains of cations can be accurately described using a "mosaic type" model, where regions of long alkyl chains of cations (named 'aliphatic' regions) and the residual chemical moieties in both cations and anions (named 'ionic' regions) give additive contributions. Changes in density due to an increase in temperature and the number of CH2 groups in the long alkyl chains of cations are determined predominantly by changes in the free volume of the 'ionic' regions, while 'aliphatic' regions are already highly compressed by van der Waals forces, which results in only infinitesimal changes in their free volumes with temperature.


Prelimbic Stimulation Ameliorates Depressive-Like Behaviors and Increases Regional BDNF Expression in a Novel Drug-Resistant Animal Model of Depression.
Approximately one third of all major depression patients fail to respond to conventional pharmacological antidepressants, and brain stimulation methods pose a promising alternative for this population. Recently, based on repeated multifactorial selective inbreeding of rats for depressive-like behaviors, we introduced a novel animal model for MDD. Rats from this Depressive Rat Line (DRL) exhibit inherent depressive-like behaviors, which are correlated with lower levels of brain-derived neurotrophic factor (BDNF) in specific brain regions. In addition, DRL rats do not respond to antidepressant medication but respond to electroconvulsive treatment, and they can thus be utilized to test the effectiveness of brain stimulation on hereditary, medication-resistant depressive-like behaviors. To test the effect of sub-convulsive electrical stimulation (SCES) of the prelimbic cortex, using TMS-like temporal pattern of stimulation, on depressive-like behaviors and regional BDNF levels in DRL rats. SCES sessions were administered daily for 10 days through chronically implanted electrodes. Temporal stimulation parameters were similar to those used in TMS for major depression in human patients. Depressive-like behaviors were assayed after treatment, followed by brain extraction and regional BDNF measurements. SCES normalized both the depressive-like behaviors and the reduced BDNF levels observed in DRL rats. Correlation analyses suggest that changes in specific behaviors are mediated, at least in part, by BDNF expression in reward-related brain regions. Brain stimulation is effective in a drug-resistant, inherited animal model for depression. BDNF alterations in specific regions may mediate different antidepressant effects.


Effects of Reduced Effort on Mechanical Output Obtained From Maximum Vertical Jumps.
The aim of this study was to evaluate the effect of reduced effort on maximum countermovement jumps. Groups of unskilled and skilled jumpers performed countermovement jumps without an arm swing at 100% and 50% effort. The results revealed markedly reduced jump height and work performed at 50% effort, although the maximum force and power output remained virtually unchanged. The observed differences were consistent across individuals with different jumping skills. A possible cause of differences in changes across the tested variables was a reduced countermovement depth associated with the 50% effort jumps. It is known to cause an increase in maximum force and power outputs, but not in jump height. Therefore, the jump height and work performed may be more closely related to our sense of effort when jumping, rather than our maximum force and power output. From a practical perspective, the present findings reiterate the importance of maximizing effort for making valid assessments of muscle mechanical capacities, as tested by maximal vertical jumps and, possibly, other maximum performance tasks.


SU-E-T-622: A Rapid Hybrid VMAT-IMRT Planning Method Using an Abbreviated Beam Angle Optimization Search.
To generate hybrid VMAT-IMRT treatment plans by utilizing an IMRT beam-angle-optimality (BAO) search under a commercially available TPS without the aid of custom optimization software or high performance computing. The high dose modulation provided by IMRT beams can be exploited to improve the quality of VMAT treatments. To achieve this, a VMAT treatment was created where the gantry pauses at predetermined angles to deliver IMRT segments. To determine IMRT BAO, an IMRT plan ('poly-IMRT') was made with many beams (>30) equally spaced around the patient. For practical reasons and to reduce the total time to approximately 1 hour, BAO was approximated by removing one beam out of the set and noting the new objective score. Determining this'score penalty' for each of the beams serves as a proxy for true BAO. The hybrid plan was created by combining the VMAT arc with a user-determined number of top-ranked beams from the poly-IMRT set. The BAO from this approach was compared with a more rigorous method ('VMAT+1'), in which a VMAT plan was optimized with 1 IMRT beam at various angles, allowing a direct determination of objective score versus gantry angle. The overall hybrid planning process was demonstrated by creating separate plans for a SBRT lung patient, with dose normalized to the limiting maximum aorta dose. Large score penalties from poly-IMRT coincided with large score benefits from VMAT+1, indicating both methods identified the same optimal beams. The VMAT, IMRT, and hybrid plans delivered the prescription dose to 84.3%, 85.6% and 87.7% of the PTV and had homogeneity indices of 1.38, 1.41, and 1.32 respectively. Normal tissue doses were within 0.5%. The presented method can create hybrid VMAT-IMRT plans which combine delivery efficiency with improved target coverage. The planning process takes about an hour using a standard TPS.


Analysis of the antimicrobial activity of propolis and lysozyme in semisolid emulsion systems.
Propolis as an active natural substance is attractive due to its antimicrobial and antimycotic properties. Lysozyme was added to semisolid dermatological preparations as a complementary substance capable of potentiating their antimicrobial and antimycotic effect; this substance has been used for several decades as a preservative in food industry. The aim of this study was to model a semisolid emulsion system (o/w) for cutaneous use with moisturizing and antimicrobial properties, where the active substances would be propolis and/or lysozyme. The microbiological examination was performed under aseptic conditions. The microbiological examination was aimed at determining the antimicrobial efficacy of the studied preparation in the solid growth media using the wells technique. The results of the antimicrobial assay showed that the effectiveness of propolis against the growth of S. aureus was intensified by the lysozyme introduced into the emulsion systems. In addition to that, the results of examinations showed that the active substance propolis in emulsion systems more efficiently inhibited spore bacteria (Bacillus cereus) than lysozyme did, yet lysozyme had a more pronounced antimycotic (against Candida albicans) effect, compared to propolis. All studied cream samples inhibited the growth of Gram-negative microorganisms (Escherichia coli). The results of this study suggest that the application of propolis and lysozyme as the active substances may increase the antimycotic and antibacterial effect of the studied preparations.


Insulin resistance in essential hypertension.
High blood pressure is prevalent in obesity and in diabetes, both conditions with insulin resistance. To test whether hypertension is associated with insulin resistance independently of obesity and glucose intolerance, we measured insulin sensitivity (using the euglycemic insulin-clamp technique), glucose turnover (using [3H]glucose isotope dilution), and whole-body glucose oxidation (using indirect calorimetry) in 13 young subjects (38 +/- 2 years [+/- SEM]) with untreated essential hypertension (165 +/- 6/112 +/- 3 mm Hg), normal body weight, and normal glucose tolerance. In the postabsorptive state, all measures of glucose metabolism were normal. During steady-state euglycemic hyperinsulinemia (about 60 microU per milliliter), hepatic glucose production and lipolysis were effectively suppressed, and glucose oxidation and potassium disposal were normally stimulated. However, total insulin-induced glucose uptake was markedly impaired (3.80 +/- 0.32 vs. 6.31 +/- 0.42 mg per minute per kilogram of body weight in 11 age- and weight-matched controls, P less than 0.001). Thus, reduced nonoxidative glucose disposal (glycogen synthesis and glycolysis) accounted for virtually all the defect in overall glucose uptake (1.19 +/- 0.24 vs. 3.34 +/- 0.44 mg per minute per kilogram, P less than 0.001). Total glucose uptake was inversely related to systolic or mean blood pressure (r = 0.76 for both, P less than 0.001). These results provide preliminary evidence that essential hypertension is an insulin-resistant state. We conclude that this insulin resistance involves glucose but not lipid or potassium metabolism, is located in peripheral tissues but not the liver, is limited to nonoxidative pathways of intracellular glucose disposal, and is directly correlated with the severity of hypertension.


A Temporal Pattern Mining Approach for Classifying Electronic Health Record Data.
We study the problem of learning classification models from complex multivariate temporal data encountered in electronic health record systems. The challenge is to define a good set of features that are able to represent well the temporal aspect of the data. Our method relies on temporal abstractions and temporal pattern mining to extract the classification features. Temporal pattern mining usually returns a large number of temporal patterns, most of which may be irrelevant to the classification task. To address this problem, we present the Minimal Predictive Temporal Patterns framework to generate a small set of predictive and non-spurious patterns. We apply our approach to the real-world clinical task of predicting patients who are at risk of developing heparin induced thrombocytopenia. The results demonstrate the benefit of our approach in efficiently learning accurate classifiers, which is a key step for developing intelligent clinical monitoring systems.


Dynamic programming and graph algorithms in computer vision.
Optimization is a powerful paradigm for expressing and solving problems in a wide range of areas, and has been successfully applied to many vision problems. Discrete optimization techniques are especially interesting since, by carefully exploiting problem structure, they often provide nontrivial guarantees concerning solution quality. In this paper, we review dynamic programming and graph algorithms, and discuss representative examples of how these discrete optimization techniques have been applied to some classical vision problems. We focus on the low-level vision problem of stereo, the mid-level problem of interactive object segmentation, and the high-level problem of model-based recognition.


"Geography of suicide in Hong Kong: spatial patterning, and socioeconomic correlates and inequalities".
Past urban research on Western nations tends to show high suicide rates in inner city and socioeconomically deprived areas. However, little is known about geographic variations in suicide in non-Western cities. We used Bayesian hierarchical models to estimate smoothed standardised mortality ratios (2005-2010) for suicide in people aged 10 years or above in each geographic unit in Hong Kong at two levels, i.e. large street block (n = 1639; median population = 1860) and small tertiary planning unit group (n = 204; median population = 14,850). We further analysed their associations with a range of area socioeconomic characteristics and a deprivation index. The "city centre" of Hong Kong, a generally non-deprived area, showed mostly below average suicide rates. However, there were high rates concentrating in some socioeconomically deprived, densely populated areas, including some inner city areas, across the city. Males had greater geographic variations in rates than females, except the elderly group. The use of smaller geographic units revealed finer detailed suicide distribution than the use of larger units, and showed that suicide rates were associated with indicators of socioeconomic deprivation (population with non-professional jobs and low median household income), and social fragmentation (proportions of unmarried adults and divorced/separated adults), but not with Gini coefficient. Sex/age groups had different associations with suicide rates. Areas in the most deprived quintile had a suicide rate more than two times higher than the least deprived. The association between suicide and deprivation was stronger in males than females and more marked in the younger populations compared to the elderly. The spatial distribution of suicide in Hong Kong showed distinct patterning and a stronger association with income compared to findings from Western countries. Suicide prevention strategies should consider tackling the marked socioeconomic gradient in suicide and high risk in young and middle-aged males living in deprived areas.


Factor analysis of the clinical characteristics of primary Sjogren syndrome.
The purpose of this study was to use factor analysis to analyze 90 clinical characteristics of a cohort of 231 patients with primary Sjogren syndrome (pSS). The records of all patients seen at the University Health Network Sjogren Syndrome Clinic from October 1992 to July 2006 were reviewed and documented. Those diagnosed as pSS by the American European Consensus Criteria of 2002 were included. The 90 clinical variables, including health history, blood analysis, symptoms of dry eye and dry mouth, salivary flow and biopsy, tear flow and staining, were analyzed by factor analysis. Two hundred thirty-one patients with pSS charts were reviewed, and 90 variables were recorded. Factor analysis resulted in three factors: factor 1: ocular surface staining, factor 2: antimicrosomal antibodies and antithyroid antibodies, and factor 3: serum anti-Ro and anti-La. Ocular surface staining accounted for the greatest variance in this population of patients with pSS.


Interleukin 2 upregulates expression of its receptor on a T cell clone.
Stimulation of a class II-restricted, antigen-specific T cell clone with interleukin 2 (IL-2) resulted in substantial increases in both cell surface IL-2 receptor (IL-2-R) and cytoplasmic IL-2-R messenger RNA (mRNA), whereas no increase was observed for cell-surface expression of Thy-1 and L3T4 antigens, and only a modest increase in Thy-1 mRNA was observed. These experiments demonstrate that, after initial acquisition of the IL-2-R, IL-2 as well as antigen is able to directly upregulate both the level of IL-2-R mRNA and cell surface IL-2-R molecules.


Novel agents for the therapy of varicella-zoster virus infections.
Varicella-zoster virus (VZV), a member of the herpesvirus family, is responsible for both primary (varicella or chickenpox) as well as recurrent (zoster or shingles) infections. Acyclovir has been the mainstay for treating VZV infections in both immunocompetent and immunocompromised patients. Recently, newer anti-VZV drugs, i.e., valaciclovir (the oral prodrug form of acyclovir) and famciclovir (the oral prodrug form of penciclovir) have been developed and have enlarged the therapeutic options to treat VZV infections. Both acyclovir and penciclovir are dependent on the virus-encoded thymidine kinase (TK) for their intracellular activation. Although emergence of drug-resistant strains does not occur in immunocompetent patients, several reports have documented the isolation of drug-resistant VZV strains following long-term acyclovir therapy in immunocompromised patients. Mutations at the level of the TK are responsible for development of resistance to drugs that depend on the viral TK for their phosphorylation (i.e., acyclovir and penciclovir). Foscarnet, a direct inhibitor of the viral DNA polymerase, which does not require activation by the viral TK, is the drug of choice for the treatment of TK-deficient VZV mutants emerging under acyclovir therapy. Recently, emergence of foscarnet-resistant strains has also been reported. Both TK-deficient strains and foscarnet-resistant mutants are sensitive to the acyclic nucleoside phosphonate cidofovir, CDV, HPMPC, (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine. This agent does not depend on the virus-encoded TK, but on cellular enzymes for its conversion to the diphosphoryl derivative, which then inhibits the viral DNA polymerase.


A multimodal (FACILE) classification for optical diagnosis of inflammatory bowel disease associated neoplasia.
Characterization of colonic lesions in inflammatory bowel disease (IBD) remains challenging. We developed an endoscopic classification of visual characteristics to identify colitis-associated neoplasia using multimodal advanced endoscopic imaging (Frankfurt Advanced Chromoendoscopic IBD LEsions [FACILE] classification). The study was conducted in three phases: 1) development - an expert panel defined endoscopic signs and predictors of dysplasia in IBD and, using multivariable logistic regression created the FACILE classification; 2) validation - using 60 IBD lesions from an image library, two assessments of diagnostic accuracy for neoplasia were performed and interobserver agreement between experts using FACILE was determined; 3) reproducibility - the reproducibility of the FACILE classification was tested in gastroenterologists, trainees, and junior doctors after completion of a training module. The experts initially selected criteria such as morphology, color, surface, vessel architecture, signs of inflammation, and lesion border. Multivariable logistic regression confirmed that nonpolypoid lesion, irregular vessel architecture, irregular surface pattern, and signs of inflammation within the lesion were predictors of dysplasia. Area under the curve of this logistic model using a bootstrapped estimate was 0.76 (0.73 - 0.78). The training module resulted in improved accuracy and kappa agreement in all nonexperts, though in trainees and junior doctors the kappa agreement was still moderate and poor, respectively. We developed, validated, and demonstrated reproducibility of a new endoscopic classification (FACILE) for the diagnosis of dysplasia in IBD using all imaging modalities. Flat shape, irregular surface and vascular patterns, and signs of inflammation predicted dysplasia. The diagnostic performance of all nonexpert participants improved after a training module.


ARTs and the problematic conceptualisation of declining reproduction.
The routinisation of assisted reproduction in India has led to its proliferation and the easy identification of infertility. However, clinical and popular discourse tends to focus primarily on age-related deficiencies in reproduction. Here, both the "dangers" of declining reproduction as well as the facilitation of delayed reproduction are areas of focus and eulogisation. Bringing together the diverse elements of the medico-social conversation, the aim of this commentary is to examine the ways in which the ARTs are used to make sense of declining reproduction.


Non-invasive brain stimulation for speech in Parkinson's disease: A randomized controlled trial.
Hypokinetic dysarthria is a common but difficult-to-treat symptom of Parkinson's disease (PD). We evaluated the long-term effects of multiple-session repetitive transcranial magnetic stimulation on hypokinetic dysarthria in PD. Neural mechanisms of stimulation were assessed by functional MRI. A randomized parallel-group sham stimulation-controlled design was used. Patients were randomly assigned to ten sessions (2 weeks) of real (1 Hz) or sham stimulation over the right superior temporal gyrus. Stimulation effects were evaluated at weeks 2, 6, and 10 after the baseline assessment. Articulation, prosody, and speech intelligibility were quantified by speech therapist using a validated tool (Phonetics score of the Dysarthric Profile). Activations of the speech network regions and intrinsic connectivity were assessed using 3T MRI. Linear mixed models and post-hoc tests were utilized for data analyses. Altogether 33 PD patients completed the study (20 in the real stimulation group and 13 in the sham stimulation group). Linear mixed models revealed significant effects of time (F(3, 88.1) = 22.7, p < 0.001) and time-by-group interactions: F(3, 88.0) = 2.8, p = 0.040) for the Phonetics score. Real as compared to sham stimulation led to activation increases in the orofacial sensorimotor cortex and caudate nucleus and to increased intrinsic connectivity of these regions with the stimulated area. This is the first study to show the long-term treatment effects of non-invasive brain stimulation for hypokinetic dysarthria in PD. Neural mechanisms of the changes are discussed.


First Report of Leaf Spot Disease Caused by Glomerella magna on Lobelia chinensis in China.
Lobelia chinensis is a perennial herbaceous plant in the family Campanulaceae that is native to China, where it grows well in moist to wet soils. It is commonly used as a Chinese herbal medicine. In May 2012, symptoms of leaf spot were observed on leaves of L. chinensis in Nanning, Guangxi Zhuang Autonomous Region, China. The leaf lesions began as small, water-soaked, pale greenish to grayish spots, which enlarged to gray to pale yellowish spots, 4 to 6 mm in diameter. At later stages, numerous acervuli appeared on the lesions. Acervuli were mostly epiphyllous, and 40 to 196 μm in diameter. On potato dextrose agar (PDA), a fungus was consistently recovered from symptomatic leaf samples, with a 93% isolation rate from 60 leaf pieces that were surface sterilized in 75% ethanol for 30 s and then in 0.1% mercuric chloride for 45 s. Three single-spore isolates were used to evaluate cultural and morphological characteristics of the pathogen. Setae were two to three septate, dark brown at the base, acicular, and up to 90 μm long. Conidia were long oblong-elliptical, guttulate, hyaline, and 11 to 20 × 4.1 to 6.3 μm (mean 15.2 × 5.1 μm). These morphological characteristics of the fungus were consistent with the description of Colletotrichum magna (teleomorph Glomerella magna Jenkins & Winstead) (1). The rDNA internal transcribed spacer (ITS) region of one isolate, LC-1, was sequenced (GenBank Accession No. KC815123), and it showed 100% identity to G. magna, GenBank HM163187.1, an isolate from Brazil cultured from papaya (2). Although KC815123 was identified as G. magna, it shows 99% identity to GenBank sequences from isolates of C. magna, and more research is needed to elucidate the relationships between these taxa, especially with consideration to host specificity. Pathogenicity tests were performed with each of the three isolates by spraying conidial suspensions (1 × 106 conidia/ml) containing 0.1% Tween 20 onto the surfaces of leaves of 30-day-old and 6- to 8-cm-high plants. For each isolate, 30 leaves from five replicate plants were treated. Control plants were treated with sterilized water containing 0.1% Tween 20. All plants were incubated for 36 h at 25°C and 90% relative humidity in an artificial climate chamber, and then moved into a greenhouse. Seven days after inoculation, gray spots typical of field symptoms were observed on all inoculated leaves, but no symptoms were seen on water-treated control plants. Koch's postulates were fulfilled by reisolation of G. magna from diseased leaves. To our knowledge, this is the first report of G. magna infecting L. chinensis worldwide. References: (1) M. Z. Du et al. Mycologia 97:641, 2005. (2) R. J. Nascimento et al. Plant Dis. 94:1506, 2010.


Theory for controlling individual self-propelled micro-swimmers by photon nudging II: confinement.
Photon nudging allows the manipulation and confinement of individual self-propelled micro-swimmers in 2D and 3D environments using feedback controls. Presented in this second part of a two-part contribution are theoretical models that afford the characterization for the positioning distribution associated with active localization. A derivation for the optimal nudging speed and acceptance angle is given for minimal placement uncertainty. The analytical solutions allow for a discussion on the physical underpinning that underlies controllability and optimality.


Concentration-dependent rheological properties of ECM hydrogel for intracerebral delivery to a stroke cavity.
Biomaterials composed of mammalian extracellular matrix (ECM) promote constructive tissue remodeling with minimal scar tissue formation in many anatomical sites. However, the optimal shape and form of ECM scaffold for each clinical application can vary markedly. ECM hydrogels have been shown to promote chemotaxis and differentiation of neuronal stem cells, but minimally invasive delivery of such scaffold materials to the central nervous system (CNS) would require an injectable form. These ECM materials can be manufactured to exist in fluid phase at room temperature, while forming hydrogels at body temperature in a concentration-dependent fashion. Implantation into the lesion cavity after a stroke could hence provide a means to support endogenous repair mechanisms. Herein, we characterize the rheological properties of an ECM hydrogel composed of urinary bladder matrix (UBM) that influence its delivery and in vivo interaction with host tissue. There was a notable concentration-dependence in viscosity, stiffness, and elasticity; all characteristics important for minimally invasive intracerebral delivery. An efficient MRI-guided injection with drainage of fluid from the cavity is described to assess in situ hydrogel formation and ECM retention at different concentrations (0, 1, 2, 3, 4, and 8mg/mL). Only ECM concentrations >3mg/mL gelled within the stroke cavity. Lower concentrations were not retained within the cavity, but extensive permeation of the liquid phase ECM into the peri-infarct area was evident. The concentration of ECM hydrogel is hence an important factor affecting gelation, host-biomaterial interface, as well intra-lesion distribution. Extracellular matrix (ECM) hydrogel promotes constructive tissue remodeling in many tissues. Minimally invasive delivery of such scaffold materials to the central nervous system (CNS) would require an injectable form that exists in fluid phase at room temperature, while forming hydrogels at body temperature in a concentration-dependent fashion. We here report the rheological characterization of an injectable ECM hydrogel and its concentration-dependent delivery into a lesion cavity formed after a stroke based on MRI-guidance. The concentration of ECM determined its retention within the cavity or permeation into tissue and hence influenced its interaction with the host brain. This study demonstrates the importance of understanding the structure-function relationship of biomaterials to guide particular clinical applications.


The challenge of objective scar colour assessment in a clinical setting: using digital photography.
Scar assessment in the clinical setting is typically impeded by a lack of quantitative data and most systems rely on subjective rating scales which are user dependant and show considerable variability between raters. The growing use of digital photography in medicine suggests a more objective approach to scar evaluation. Our objective was to determine if cameras could be of practical use for measuring colour in a clinical setting. The measurement of colour and reflectance spectra in photographs faces two difficulties: firstly the effects of variable illumination spectra, and secondly to recover accurate colour and spectral information from the sparse red, green and blue (RGB) camera signals. As a result the colour rendition is often inaccurate, and spectral information is lost. To deal with variable illumination and other factors that systematically affect all reflectance spectra ColourWorker (a method for image-based colour measurement implemented in software) calibrates the spectral responses of the camera's RGB sensors using a colour standard in the image. To make best use of the calibrated signals, it takes advantage of the fact that although a given RGB signal can be caused by an infinite number of spectra, most natural reflectance spectra vary smoothly and have predictable forms. This means given a set of examples of spectra produced by the materials of interest, it is possible to estimate the specific spectrum that produced a given RGB signal once corrected for the illumination. We describe a method for recovering spectral and chromatic information relating to surface reflectance from ordinary digital images and apply this to analyse photographs of surgical scars, taken as part of a clinical trial, in an attempt to better quantify clinical scar assessment. It should be noted the pre-existing trial protocol did not allow for a comprehensive evaluation of the accuracy of the method which would require the spectrophotometric measurement of skin regions corresponding to those in the photographs. Scar colour was estimated reliably, and with simple image analysis we were able to record the change in colour across the skin. Furthermore, we describe a simple automated assessment procedure that enables scar severity to be quantified and defined using a single scalar value easily. Such image-based colour measurement and assessment offers considerable advantages over other current methods, including spectrometers, which measure only a single point, or printed charts.


GRADE guidelines: 21 part 2. Test accuracy: inconsistency, imprecision, publication bias, and other domains for rating the certainty of evidence and presenting it in evidence profiles and summary of findings tables.
This article provides updated GRADE guidance about how authors of systematic reviews and health technology assessments and guideline developers can rate the certainty of evidence (also known as quality of the evidence or confidence in the estimates) of a body of evidence addressing test accuracy (TA) on the domains imprecision, inconsistency, publication bias, and other domains. It also provides guidance for how to present synthesized information in evidence profiles and summary of findings tables. We present guidance for rating certainty in TA in clinical and public health and review the presentation of results of a body of evidence regarding tests. Supplemented by practical examples, we describe how raters of the evidence can apply the GRADE domains inconsistency, imprecision, and publication bias to a body of evidence of TA studies. Using GRADE in Cochrane and other reviews as well as World Health Organization and other guidelines helped refining the GRADE approach for rating the certainty of a body of evidence from TA studies. Although several of the GRADE domains (e.g., imprecision and magnitude of the association) require further methodological research to help operationalize them, judgments need to be made on the basis of what is known so far.


Necrosis Contributes to the Development of Hypertension in Male, but Not Female, Spontaneously Hypertensive Rats.
Necrosis is a pathological form of cell death that induces an inflammatory response, and immune cell activation contributes to the development and maintenance of hypertension. Necrosis was measured in kidney, spleen, and aorta of 12- to 13-week-old male and female SHRs (spontaneously hypertensive rats); male SHRs had greater renal necrotic cell death than female SHRs. Because male SHRs have a higher blood pressure (BP) and a more proinflammatory T-cell profile than female SHRs, the current studies tested the hypothesis that greater necrotic cell death in male SHRs exacerbates increases in BP and contributes to the proinflammatory T-cell profile. Male and female SHRs were randomized to receive vehicle or Necrox-5-a cell permeable inhibitor of necrosis-from 6 to 12 weeks of age or from 11 to 13 weeks of age. In both studies, Necrox-5 decreased renal necrosis and abolished the sex difference. Treatment with Necrox-5 beginning at 6 weeks of age attenuated maturation-induced increases in BP in male SHR; BP in female SHR was not altered by Necrox-5 treatment. Necrox-5 decreased proinflammatory renal T cells in both sexes, although sex differences were maintained. Administration of Necrox-5 for 2 weeks in SHR with established hypertension resulted in a small but significant decrease in BP in males with no effect in females. These results suggest that greater necrotic cell death in male SHR exacerbates maturation-induced increases in BP with age contributing to sex differences in BP. Moreover, although necrosis is proinflammatory, it is unlikely to explain sex differences in the renal T-cell profile.


The chlamydial OTU domain-containing protein ChlaOTU is an early type III secretion effector targeting ubiquitin and NDP52.
Chlamydia are obligate intracellular pathogens. Upon contact with the host, they use type III secretion to deliver proteins into the cell, thereby triggering actin-dependent entry and establishing the infection. We observed that Chlamydia caviae elicited a local and transient accumulation of ubiquitinated proteins at the entry sites, which disappeared within 20 min. We investigated the mechanism for the rapid clearance of ubiquitin. We showed that the OTU-like domain containing protein CCA00261, predicted to have deubiquitinase activity, was detected in infectious particles and was a type III secretion effector. This protein is present in several Chlamydia strains, including the human pathogen Chlamydia pneumoniae, and we further designate it as ChlaOTU. We demonstrated that ChlaOTU bound ubiquitin and NDP52, and we mapped these interactions to distinct domains. NDP52 was recruited to Chlamydia entry sites and was dispensable for infection and for bacterial growth. ChlaOTU functioned as a deubiquitinase in vitro. Heterologousexpression of ChlaOTU reduced ubiquitin accumulation at the entry sites, while a catalytic mutant of the deubiquitinase activity had the opposite effect. Altogether, we have identified a novel secreted protein of chlamydiae. ChlaOTU targets both ubiquitin and NDP52 and likely participates in the clearance of ubiquitin at the invasion sites.


Morphology of the trabecular meshwork and inner-wall endothelium after cationized ferritin perfusion in the monkey eye.
Nine eyes of five cynomolgus monkeys were perfused through the anterior chamber with cationized ferritin (CF) at normal and increased intraocular pressure. After perfusion with glutaraldehyde, the morphologic appearance of the endothelial lining of Schlemm's canal (SC) and of the adjacent regions was analyzed using tangential and sagittal serial sections. The CF, which binds to negatively charged surfaces, was observed to be adherent to the free surfaces of trabecular cell membranes and to accumulate in the cribriform layer underlining the endothelial lining of SC. Tangential sections of the inner-wall endothelium demonstrated that separations of the adjacent cell membranes occur between the tight junctions forming openings or lacunae and bent, tunnel-like channels that represent continuous paracellular pathways. Complete staining of these inner-wall paracellular pathways with CF were observed indicating that the adjoining membranes are negatively charged and that the perfused fluid had passed through these intercellular channels. These paracellular pathways appeared enlarged and were more easily identified at elevated perfusion pressure. In general, intracytoplasmic vacuoles demonstrated heavy staining with CF on their luminal surface but only faint staining on the adluminal (cribriform-facing) surface. Apparent giant vacuoles were observed to be often not real intracellular vacuoles but rather dilatations of the paracellular spaces. This study demonstrates that there are paracellular routes through the inner-wall endothelium by which high molecular-weight substances such as ferritin and macrophages can leave the anterior chamber. Probably there are both transcytoplasmic and paracellular mechanisms of aqueous outflow that may vary under different conditions of pressure or flow.


Decreased need for emergency services after changing management for suspected miscarriage.
We investigated the effect of a changed routine to identify women with a nonviable pregnancy, in order to utilize health care resources more efficiently during office hours rather than relying on emergency care services. From hospital register data about where and when women with miscarriages were treated, there was a significant trend during a nine-year period for miscarriages to be more rarely diagnosed (p-value<0.001) in the emergency ward after office hours. The proportion of miscarriages that were diagnosed and handled at the emergency ward decreased from 31% in 2001 to 17% in 2009. Furthermore, the number of women showing up with bleeding at the emergency ward, but who also had a normal viable pregnancy, declined during the same period (p-value<0.01). Women with suspected miscarriage benefit from structured information and standardized management and can effectively be scheduled for day-time assessment including ultrasound with a concomitant reduced need for emergency services.


In situ studies of the primary immune response to (4-hydroxy-3-nitrophenyl)acetyl. II. A common clonal origin for periarteriolar lymphoid sheath-associated foci and germinal centers.
In the genetically restricted response that follows immunization with (4-hydroxy-3-nitrophenyl)acetyl coupled to protein carriers, two distinct populations of B cells are observed in the spleens of C57BL/6 mice. By 48 h postimmunization, foci of antigen-binding B cells appear along the periphery of the periarteriolar lymphoid sheaths. These foci expand to contain large numbers of antibody-forming cells that neither bind the lectin, peanut agglutinin, nor mutate the rearranged immunoglobulin variable region loci. Germinal centers containing peanut agglutinin-positive B cells can be observed by 96-120 h after immunization. Although specific for the immunizing hapten, these B cells do not produce substantial amounts of antibody, but are the population that undergoes somatic hypermutation and affinity-driven selection. Both focus and germinal center populations are pauciclonal, founded, on average, by three or fewer B lymphocytes. Despite the highly specialized roles of the focus (early antibody production) and germinal center (higher affinity memory cells) B cell populations, analysis of VH to D to JH joins in neighboring foci and germinal centers demonstrate that these B cell populations have a common clonal origin.


Source-Related Effects of Wastewater on Transcription Factor (AhR, CAR and PXR)-Mediated Induction of Gene Expression in Cultured Rat Hepatocytes and Their Association with the Prevalence of Antimicrobial-Resistant Escherichia coli.
Extracts of wastewater collected from 4 sewage treatment plants (STPs) receiving effluents from different sources in South India were investigated for their levels of transcription factor-mediated gene induction in primary cultured rat hepatocytes. In addition, the relation between gene induction levels and the prevalence of antimicrobial-resistant Escherichia coli (E. coli) in wastewater was examined. STP-3, which treats only hospital wastewater, exhibited significantly greater induction potency of all 6 drug metabolizing cytochrome P450 (CYP) genes examined, CYP1A1, 1A2, 1B1, 2B15, 3A1, and 3A2, whereas the wastewater at STP-1, which exclusively receives domestic sewage, showed significantly diminished levels of induction of 3 CYP genes when compared to the levels of CYP induction at STP-2, which receives mixed wastewater. Samples collected during the monsoon season showed a significantly altered gene induction capacity compared to that of samples from the pre-monsoon period. The data suggest that the toxicity of wastewater in STPs was not significantly diminished during the treatment process. The chemical-gene interaction data predicted that a vast number of chemicals present in the wastewater would stimulate the genes studied in the rat hepatocytes. The multivariable logistic regression analysis demonstrated that the prevalence of isolates resistant to cefotaxime, imipenem and streptomycin was significantly correlated with the levels of induction of at least three CYP-isozymes in STP wastewater. In addition, the resistance of isolates in treatment plants was not altered by the treatment steps, whereas the sampling season did have an impact on the resistance to specific antimicrobials. The identification of receptor-mediated gene regulation capacities offers important data not limited to the (synergistic) physiological role of chemicals in biological systems but may provide new insight into the link between the effects of known/unknown drugs and prevalence of antimicrobial-resistant bacteria in wastewater.


The TLR signalling adaptor TRIF/TICAM-1 has an N-terminal helical domain with structural similarity to IFIT proteins.
TRIF/TICAM-1 (TIR domain-containing adaptor inducing interferon-β/TIR domain-containing adaptor molecule 1) is the adaptor protein in the Toll-like receptor (TLR) 3 and 4 signalling pathway that leads to the production of type 1 interferons and cytokines. The signalling involves TIR (Toll/interleukin-1 receptor) domain-dependent TRIF oligomerization. A protease-resistant N-terminal region is believed to be involved in self-regulation of TRIF by interacting with its TIR domain. Here, the structural and functional characterization of the N-terminal domain of TRIF (TRIF-NTD) comprising residues 1-153 is reported. The 2.22 Å resolution crystal structure was solved by single-wavelength anomalous diffraction (SAD) using selenomethionine-labelled crystals of TRIF-NTD containing two additional introduced Met residues (TRIF-NTDA66M/L113M). The structure consists of eight antiparallel helices that can be divided into two subdomains, and the overall fold shares similarity to the interferon-induced protein with tetratricopeptide repeats (IFIT) family of proteins, which are involved in both the recognition of viral RNA and modulation of innate immune signalling. Analysis of TRIF-NTD surface features and the mapping of sequence conservation onto the structure suggest several possible binding sites involved in either TRIF auto-regulation or interaction with other signalling molecules or ligands. TRIF-NTD suppresses TRIF-mediated activation of the interferon-β promoter, as well as NF-κB-dependent reporter-gene activity. These findings thus identify opportunities for the selective targeting of TLR3- and TLR4-mediated inflammation.


Coronary atherosclerotic burden in veteran male recreational athletes with low to intermediate cardiovascular risk.
Although there is evidence that a significant proportion of veteran athletes have coronary atherosclerotic disease (CAD), its prevalence in recreational athletes with low to intermediate cardiovascular (CV) risk is not established. This study aimed to characterize the coronary atherosclerotic burden in veteran male recreational athletes with low to intermediate CV risk. Asymptomatic male athletes aged ≥40 years with low to intermediate risk, who exercised >4 hours/week for >5 years, underwent cardiac computed tomography (CT) for coronary artery calcium (CAC) scoring and CT angiography. High coronary atherosclerotic burden was defined as at least one of the following: CAC score >100; CAC score ≥75th percentile; obstructive CAD; disease involving the left main, three vessels or two vessels including the proximal left anterior descending artery; segment involvement score >5; or CT Leaman score ≥5. Athletes were categorized by tertiles of exercise volume, calculated by metabolic equivalent of task (MET) scores. A total of 105 athletes were included, all with SCORE <4%, mainly engaged in high-dynamic sports. Median exercise volume was 66 (44-103) METs/hour/week, with 8±5 hours training/week and 17±10 years of exercise. A high coronary atherosclerotic burden was present in 27 (25.7%) athletes. Ten (9.5%) athletes had CAC score >100, 13 (12.4%) had CAC score ≥75th percentile and six (5.7%) had obstructive lesions. The extent and severity of coronary plaques did not differ according to exercise volume. The prevalence of subclinical CAD detected by cardiac CT in veteran male recreational athletes with low to intermediate CV risk was high. Up to a quarter of our cohort had a high coronary atherosclerotic burden.


Low-resolution real-space envelopes: an approach to the ab initio macromolecular phase problem.
An ab initio approach to the phase problem in macromolecular x-ray crystallography is described. A random gas of hard-sphere point scatterers is allowed to condense under the constraint of the solvent fraction and the restraint of the observed Fourier amplitude data. Two applications to real macromolecular examples are discussed. This method produces an approximate outline of the bulk solvent regions and thus yields a low-resolution picture of the unit cell that can be extended to higher resolutions in special cases, such as through the use of molecular replacement or of noncrystallographic symmetry-based phase extension.


As good as it gets? The problem of HIV persistence despite antiretroviral drugs.
Human immunodeficienty virus (HIV) infection is suppressed but not eliminated by antiretroviral drugs. Viral persistence in the face of therapy has been explained by viral latency, lowered effectiveness of drugs in some anatomical sites and cell types, and cell-to-cell spread. These mechanisms allow for drug-sensitive virus to persist despite treatment. Understanding the persistence mechanism at work at different times after infection, including the time of initial infection immediately following transmission when reservoirs are first formed, will reveal if we are at the limit of what can be achieved with the current therapy paradigm of suppressing ongoing virus replication with drugs. We discuss some of the possible reasons why HIV persists at different points on the infection timeline, focusing on the role ongoing replication may have in maintaining the infection despite drugs at early times postexposure.


Investigating the management of diabetes in nursing homes using a mixed methods approach.
As populations age there is an increased demand for nursing home (NH) care and a parallel increase in the prevalence of diabetes. Despite this, there is growing evidence that the management of diabetes in NHs is suboptimal. The reasons for this are complex and poorly understood. This study aimed to identify the current level of diabetes care in NHs using a mixed methods approach. The nursing managers at all 44 NHs in County Galway in the West of Ireland were invited to participate. A mixed methods approach involved a postal survey, focus group and telephone interviews. The survey response rate was 75% (33/44) and 27% (9/33) of nursing managers participated in the qualitative research. The reported prevalence of diagnosed diabetes was 14% with 80% of NHs treating residents with insulin. Hypoglycaemia was reported as 'frequent' in 19% of NHs. A total of 36% of NHs have staff who have received diabetes education or training and 56% have access to diabetes care guidelines. Staff education was the most cited opportunity for improving diabetes care. Focus group and interview findings highlight variations in the level of support provided by GPs and access to dietetic, podiatry and retinal screening services. There is a need for national clinical guidelines and standards of care for diabetes management in nursing homes, improved access to quality diabetes education for NH staff, and greater integration between healthcare services and NHs to ensure equity, continuity and quality in diabetes care delivery.


Who Spends Money to Play for Free? Identifying Who Makes Micro-transactions on Social Casino Games (and Why).
Social casino games are online gambling-like games found on social networking sites. They are initially free to play, however, players are encouraged to make micro-transactions (i.e., in-game purchases) for additional game credits or functionality. As a result, they generate billions of dollars in revenue. Yet, little is known as to who purchases virtual credits, let alone why. In the present research, we assessed whether there are individual differences (impulsivity, reward sensitivity, competitiveness, and problem gambling severity) between who is and who is not likely to make micro-transactions during social casino game play. Moreover, we examined possible motivations for making micro-transactions (e.g., extend play, win back lost credits) and whether the individual difference variables of interest predict reported motivation(s) for making micro-transactions. Results showed that social casino gamers who engaged in micro-transactions reported significantly higher levels of impulsivity, reward sensitivity and problem gambling severity, but not competitiveness. In terms of motivation to make micro-transactions, desire to extend play was endorsed most frequently, followed by a desire to access additional features, chasing lost credits, and to speed up play. Lastly, among participants who made micro-transactions, reward sensitivity predicted making micro-transactions to chase lost credits. These results suggest the personality make-up of social casino gamers is important to understand who is likely to make micro-transactions as well as their motivation to do so-information that could prove useful for regulation of the industry.


Myasthenia gravis seronegative for acetylcholine receptor antibodies.
Antibodies to muscle-specific kinase (MuSK) are found in a variable proportion of patients with myasthenia without typical acetylcholine receptor (AChR) antibodies, but their characteristics and pathogenic mechanisms are not fully understood. We discuss the incidence and pathogenicity of MuSK antibodies and how clinical studies, animal models, and cultured cell lines can be used to elucidate their pathogenic mechanisms. Patients without either AChR or MuSK antibodies (seronegative myasthenia) appear to present another disease subtype that is highly similar to that of typical myasthenia gravis. We demonstrate a new method that detects AChR antibodies in these patients and show that these low-affinity AChR antibodies are predominantly IgG1 and can activate complement C3b deposition. Similarly MuSK antibodies, although mainly IgG4, are partially IgG1 and can activate C3b deposition. Overall, these results suggest that complement-activation may be an important pathogenic mechanism even in patients without conventional AChR antibodies.


Integration of Cardiac Actin Mutants Causing Hypertrophic (p.A295S) and Dilated Cardiomyopathy (p.R312H and p.E361G) into Cellular Structures.
The human mutant cardiac α-actins p.A295S or p.R312H and p.E361G, correlated with hypertrophic or dilated cardiomyopathy, respectively, were expressed by the baculovirus/Sf21 insect cell system and purified to homogeneity. The purified cardiac actins maintained their native state but showed differences in Ca2+-sensitivity to stimulate the myosin-subfragment1 ATPase. Here we analyzed the interactions of these c-actins with actin-binding and -modifying proteins implicated in cardiomyocyte differentiation. We demonstrate that Arp2/3 complex and the formin mDia3 stimulated the polymerization rate and extent of the c-actins, albeit to different degrees. In addition, we tested the effect of the MICAL-1 monooxygenase, which modifies the supramolecular actin organization during development and adaptive processes. MICAL-1 oxidized these c-actin variants and induced their de-polymerization, albeit at different rates. Transfection experiments using MDCK cells demonstrated the preferable incorporation of wild type and p.A295S c-actins into their microfilament system but of p.R312H and p.E361G actins into the submembranous actin network. Transduction of neonatal rat cardiomyocytes with adenoviral constructs coding HA-tagged c-actin variants showed their incorporation into microfilaments after one day in culture and thereafter into thin filaments of nascent sarcomeric structures at their plus ends (Z-lines) except the p.E361G mutant, which preferentially incorporated at the minus ends.


Risk factors for wound complications after ankle fracture surgery.
The overall rate of complications after ankle fracture fixation varies between 5% and 40% depending on the population investigated, and wound complications have been reported to occur in 1.4% to 18.8% of patients. Large studies have focused on complications in terms of readmission, but few studies have examined risk factors for wound-related issues in the outpatient setting in a large number of patients. A review was performed to identify risk factors for wound complications tracked in the hospital and outpatient setting. Four hundred and seventy-eight patients underwent open reduction and internal fixation of an ankle fracture between 2003 and 2010 by a single surgeon at a single institution. Demographic characteristics, time to surgery, comorbidities, and postoperative care were tracked. Wound complications were defined as those requiring dressing care and oral antibiotics or requiring further surgical treatment. Of the 478 patients who were followed, six (1.25%) had wounds requiring surgical debridement. Fourteen patients (2.9%) required further dressing care or a course of oral antibiotics. There were significant associations between wound complications and a history of diabetes (p < 0.001), peripheral neuropathy (p = 0.003), wound-compromising medications (p = 0.011), open fractures (p = 0.05), and postoperative noncompliance (p = 0.027). There was a significant difference in age between patients with and without wound complications (p = 0.045). We did not identify a relationship between time to surgery and complications. These results highlight the difficulty of treating medically complex and noncompliant patient populations. With careful preoperative monitoring of swelling, time to surgery does not affect wound outcome. The failure of the patient to adhere to postoperative instructions should be a concern to the treating surgeon.


Total synthesis benzene and its derivatives as major gasoline extenders.
Synthesized benzene and simple alkylated derivatives are proposed as nonpetrochemical gasoline components. Feasible raw materials include coal, coke, charcoal, and carbonaceous wastes. The basic synthesis consists of the formation of lithium carbide by reaction of the metal with carbon, hydrolysis of the carbide to acetylene, cyclization of acetylene to benzene, and regeneration of lithium metal. Total synthesis benzene is substantially different from other synthetic hydrocarbon fuels in that its hydrogen content is obtained from water so that hydrogen gas is not needed as a major reactant.


Disease-modifying treatments for multiple sclerosis - a review of approved medications.
There is still no curative treatment for multiple sclerosis (MS), but during the last 20 years eight different disease-modifying compounds have been approved for relapsing-remitting MS (RRMS). A literature search was conducted on published randomized controlled phase III trials indexed in PubMed on the approved medications until 21 May 2015. In this review the mode of action, documented treatment effects and side effects of the approved MS therapies are briefly discussed. Based on current knowledge of risk-benefit of the approved MS medications, including factors influencing adherence, it is suggested that oral treatment with dimethyl fumarate or teriflunomide should be preferred as a starting therapy amongst the first-line preparations for de novo RRMS. In the case of breakthrough disease on first-line therapy, or rapidly evolving severe RRMS, second-line therapy with natalizumab, fingolimod or alemtuzumab should be chosen based on careful risk-benefit stratification.


Clinical applications of transient elastography.
Chronic liver disease represents a major public health problem, accounting for significant morbidity and mortality worldwide. As prognosis and management depend mainly on the amount and progression of liver fibrosis, accurate quantification of liver fibrosis is essential for therapeutic decision-making and follow-up of chronic liver diseases. Even though liver biopsy is the gold standard for evaluation of liver fibrosis, non-invasive methods that could substitute for invasive procedures have been investigated during past decades. Transient elastography (TE, FibroScan®) is a novel non-invasive method for assessment of liver fibrosis with chronic liver disease. TE can be performed in the outpatient clinic with immediate results and excellent reproducibility. Its diagnostic accuracy for assessment of liver fibrosis has been demonstrated in patients with chronic viral hepatitis; as a result, unnecessary liver biopsy could be avoided in some patients. Moreover, due to its excellent patient acceptance, TE could be used for monitoring disease progression or predicting development of liver-related complications. This review aims at discussing the usefulness of TE in clinical practice.


Antagonistic effects of Satureja hortensis essential oil against AFB1 on human lymphocytes in vitro.
Satureja hortensis L. (Lamiaceae) has been used as a folk remedy to treat various such as cramps, muscle pains, nausea, indigestion, diarrhea, and infectious diseases. In this study, the antagonistic effects of essential oil of S. hortensis (SHE) were studied against aflatoxin B1 (AFB1) in human lymphocytes in vitro. The analysis of the essential oil was performed by using Gas chromatography-mass spectrometry (GC-MS). Anti-genotoxic effects of the SHEs was evaluated using sister chromatid exchange (SCE), micronuclei (MN) tests against AFB1. Also level of malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities used to determine the anti-oxidative effects of the SHEs. This result showed AFB1 (5 microM) increased the frequencies of SCE, MN and the level of MDA. AFB1 at the same concentration decreased the activities of SOD and GPx. However, different concentrations of SHE with AFB1 decreased the frequency of SCE and MN and level of MDA and also increased the activities of SOD and GPx significantly. Especially, the 1.0, 1.5, 2.0 microL dose of SHE are more effective than other doses. The results of this experiment have clearly shown that SHE has strong antioxidative and antigenotoxic effects, these biological activities of SHEs can be due to its component.


Contrast-enhanced ultrasonography - An indispensable tool in the hands of any hepatologist.
Vascular complications after liver transplantation may lead to graft dysfunction and liver failure, which in turn results in need for retransplantation and death risk. Therefore, their early diagnosis is critical. Major vascular complications include hepatic artery thrombosis, stenosis and aneurysms; portal vein thrombosis and stenosis; and potential additional complications in hepatic veins and vena cava. Of all these vascular complications hepatic arterial thrombosis, which involves approximately 5% of transplant recipients, is most significant. Portal complications, which are second in significance, are less common (2%).


Direct and indirect costs of home healthcare in Japan: A cross-sectional study.
To tackle the rising healthcare expenditure in an ageing society in Japan, home healthcare has been promoted over the past several years. However, there is a dearth of literature on total costs incurring for home healthcare. In this study, we conducted a cross-sectional study among patients, who received home healthcare in the month of May, 2018. Direct healthcare costs and patients' clinical characteristics were collected from medical records and long-term care databases (n = 166). Indirect costs were estimated using a questionnaire survey which obtained information on job absenteeism and care time from the caregiver. A total of 112 patients responded to the survey. The median age was 82 years (interquartile range: 74-88). Total per-person per month home-care costs averaged USD 6,163 with direct costs (USD 2,547) and indirect costs (USD 3,596) accounted for 41.3% and 58.3% of the total costs, respectively. The largest components of direct costs were long-term care costs (48%) and medical costs (47%). Multivariable adjusted model showed that those with heavy healthcare were more likely to incur higher total as well as direct and indirect home healthcare cost (p<.05 for each). Patients aged >75 years (p = .041) were less likely and those who used oxygen at home were more likely to incur direct home healthcare cost (p = .001) than their counterpart. Our study findings show that indirect cost is a major contributor to total home healthcare costs in Japan. Also for patients who need heavy healthcare, both direct and indirect costs are large burden.


Intravenous Ketamine for Adolescents with Treatment-Resistant Depression: An Open-Label Study.
Novel interventions for treatment-resistant depression (TRD) in adolescents are urgently needed. Ketamine has been studied in adults with TRD, but little information is available for adolescents. This study investigated efficacy and tolerability of intravenous ketamine in adolescents with TRD, and explored clinical response predictors. Adolescents, 12-18 years of age, with TRD (failure to respond to two previous antidepressant trials) were administered six ketamine (0.5 mg/kg) infusions over 2 weeks. Clinical response was defined as a 50% decrease in Children's Depression Rating Scale-Revised (CDRS-R); remission was CDRS-R score ≤28. Tolerability assessment included monitoring vital signs and dissociative symptoms using the Clinician-Administered Dissociative States Scale (CADSS). Thirteen participants (mean age 16.9 years, range 14.5-18.8 years, eight biologically male) completed the protocol. Average decrease in CDRS-R was 42.5% (p = 0.0004). Five (38%) adolescents met criteria for clinical response. Three responders showed sustained remission at 6-week follow-up; relapse occurred within 2 weeks for the other two responders. Ketamine infusions were generally well tolerated; dissociative symptoms and hemodynamic symptoms were transient. Higher dose was a significant predictor of treatment response. These results demonstrate the potential role for ketamine in treating adolescents with TRD. Limitations include the open-label design and small sample; future research addressing these issues are needed to confirm these results. Additionally, evidence suggested a dose-response relationship; future studies are needed to optimize dose. Finally, questions remain regarding the long-term safety of ketamine as a depression treatment; more information is needed before broader clinical use.


Quantitative expression analysis of the cellular specificity of HECT-domain ubiquitin E3 ligases.
We evaluated the expression of 28 gene sequences with homology to the carboxy terminal of HECT E3 ubiquitin ligases in nine human cell lines using RT-PCR, to determine whether gene expression could be associated with cell-specific functions (HECT is "homologous to E6AP C-terminus"). In general, HECT-domain E3 ligases are constitutively expressed at low levels with a broad range between cell types. hecth3, 21, and 23 had higher levels in three leukocytic lines (Jurkat, MM6, THP1); hecth11 was more abundant in HepG2 and A495; and hecth15 and hecth12 were differentially expressed in lung fibroblasts derived from normal and severe emphysema patients (CCD16 and CCD29, respectively). Absolute quantitation showed that most HECT E3s have about 20-100 copies of mRNA per Jurkat cell. By comparison, UBCH7 (an ubiquitin-conjugating E2) is 10-fold more abundant in Jurkat cells and 30-fold more abundant than E2 UBCH5A. We interpret the broad range of transcript levels to be consistent with the hypothesis that the concentrations of E3 are important for ubiquitination selectivity, leading us to conclude that substrate activation is necessary but not sufficient for selectivity.


Postoperative Delirium in Older Patients: A Systematic Review of Assessment and Incidence of Postoperative Delirium.
Postoperative delirium is the most common complication of surgery particularly in older patients. The current study aimed to summarize the commonly used delirium assessment tools in assessing postoperative delirium (POD) and to estimate the incidence rates of POD. A systematic review that included empirical cohort studies reporting the use of delirium assessment tools in assessing POD between 2000 and 2019. Five core databases were searched for eligible studies. The methodological quality assessment of the included studies was undertaken using the Joanna Briggs Institute (JBI) critical appraisal checklist to examine the risk of bias. Pooled incidence estimates were calculated using a random effects model. Nineteen studies with a total of 3,533 postsurgery older patients were included in this review. The confusion assessment method (CAM) and CAM-ICU were the most commonly used tools to assess POD among older postoperative patients. The pooled incidence rate of POD was 24% (95% CI [0.20, 0.29]). The pooled incidence estimates for mixed (noncardiac) surgery, orthopedic surgery, and tumor surgery were 23% (95% CI [0.15, 0.31]), 27% (95% CI [0.20, 0.33]), and 19% (95% CI [0.15, 0.22]), respectively. More than 50% of included studies used CAM to assess POD in different types of postoperative patients. Using CAM to assess delirium is less time-consuming and it was suggested as the most efficient tool for POD detection. We identified that CAM could be implemented in different settings for assessing POD. The incidence and risk factors for POD introduced can be used for future research to target these potential indicators. The incidence rate, risk factors, and predictors of POD explored can provide robust evidence for clinical practitioners in their daily practice.


GGGGCC repeat expansion in C9orf72 compromises nucleocytoplasmic transport.
The GGGGCC (G4C2) repeat expansion in a noncoding region of C9orf72 is the most common cause of sporadic and familial forms of amyotrophic lateral sclerosis and frontotemporal dementia. The basis for pathogenesis is unknown. To elucidate the consequences of G4C2 repeat expansion in a tractable genetic system, we generated transgenic fly lines expressing 8, 28 or 58 G4C2-repeat-containing transcripts that do not have a translation start site (AUG) but contain an open-reading frame for green fluorescent protein to detect repeat-associated non-AUG (RAN) translation. We show that these transgenic animals display dosage-dependent, repeat-length-dependent degeneration in neuronal tissues and RAN translation of dipeptide repeat (DPR) proteins, as observed in patients with C9orf72-related disease. This model was used in a large-scale, unbiased genetic screen, ultimately leading to the identification of 18 genetic modifiers that encode components of the nuclear pore complex (NPC), as well as the machinery that coordinates the export of nuclear RNA and the import of nuclear proteins. Consistent with these results, we found morphological abnormalities in the architecture of the nuclear envelope in cells expressing expanded G4C2 repeats in vitro and in vivo. Moreover, we identified a substantial defect in RNA export resulting in retention of RNA in the nuclei of Drosophila cells expressing expanded G4C2 repeats and also in mammalian cells, including aged induced pluripotent stem-cell-derived neurons from patients with C9orf72-related disease. These studies show that a primary consequence of G4C2 repeat expansion is the compromise of nucleocytoplasmic transport through the nuclear pore, revealing a novel mechanism of neurodegeneration.


Sarcopenia, cardiopulmonary fitness, and physical disability in community-dwelling elderly people.
Sarcopenia refers to the loss of skeletal muscle mass with aging. It is believed to be associated with functional impairment and physical disability. The purposes of this study were: (1) to compare the physical activity, muscle strength (force-generating capacity), cardiopulmonary fitness, and physical disability in community-dwelling elderly people with sarcopenia, borderline sarcopenia, and normal skeletal muscle mass in Taiwan and (2) to test the hypothesis that sarcopenia is associated with physical disability and examine whether the association is mediated by decreased muscle strength or cardiopulmonary fitness. This was a cross-sectional investigation. Two hundred seventy-five community-dwelling elderly people (148 men, 127 women) aged > or =65 years participated in the study. The participants were recruited from communities in the district of Zhongzheng, Taipei. Predicted skeletal muscle mass was estimated using a bioelectrical impedance analysis equation. The skeletal muscle mass index (SMI) was calculated by dividing skeletal muscle mass by height squared. Physical disability was assessed using the Groningen Activity Restriction Scale. Physical activity was assessed using a 7-day recall physical activity questionnaire. Cardiopulmonary fitness was assessed using a 3-minute step test, and grip strength was measured to represent muscle strength. Cardiopulmonary fitness was significantly lower in elderly people with sarcopenia than in those with normal SMIs. Grip strength and daily energy expenditure (kcal/kg/day) were not significantly different between the participants with sarcopenia and those with normal SMIs. The odds ratio for physical disability between the participants with sarcopenia and those with normal SMIs was 3.03 (95% confidence interval=1.21-7.61). The odds ratio decreased and the significant difference diminished after controlling for cardiopulmonary fitness. A causal relationship between sarcopenia and physical activity, cardiopulmonary fitness, and physical disability cannot be established because of the cross-sectional nature of study design. Sarcopenia was associated with physical disability in elderly men. The association between sarcopenia and physical disability was mediated to a large extent by decreased cardiopulmonary fitness.


The detection of the methylated Wif-1 gene is more accurate than a fecal occult blood test for colorectal cancer screening.
The clinical benefit of guaiac fecal occult blood tests (FOBT) is now well established for colorectal cancer screening. Growing evidence has demonstrated that epigenetic modifications and fecal microbiota changes, also known as dysbiosis, are associated with CRC pathogenesis and might be used as surrogate markers of CRC. We performed a cross-sectional study that included all consecutive subjects that were referred (from 2003 to 2007) for screening colonoscopies. Prior to colonoscopy, effluents (fresh stools, sera-S and urine-U) were harvested and FOBTs performed. Methylation levels were measured in stools, S and U for 3 genes (Wif1, ALX-4, and Vimentin) selected from a panel of 63 genes; Kras mutations and seven dominant and subdominant bacterial populations in stools were quantified. Calibration was assessed with the Hosmer-Lemeshow chi-square, and discrimination was determined by calculating the C-statistic (Area Under Curve) and Net Reclassification Improvement index. There were 247 individuals (mean age 60.8±12.4 years, 52% of males) in the study group, and 90 (36%) of these individuals were patients with advanced polyps or invasive adenocarcinomas. A multivariate model adjusted for age and FOBT led to a C-statistic of 0.83 [0.77-0.88]. After supplementary sequential (one-by-one) adjustment, Wif-1 methylation (S or U) and fecal microbiota dysbiosis led to increases of the C-statistic to 0.90 [0.84-0.94] (p = 0.02) and 0.81 [0.74-0.86] (p = 0.49), respectively. When adjusted jointly for FOBT and Wif-1 methylation or fecal microbiota dysbiosis, the increase of the C-statistic was even more significant (0.91 and 0.85, p<0.001 and p = 0.10, respectively). The detection of methylated Wif-1 in either S or U has a higher performance accuracy compared to guaiac FOBT for advanced colorectal neoplasia screening. Conversely, fecal microbiota dysbiosis detection was not more accurate. Blood and urine testing could be used in those individuals reluctant to undergo stool testing.


Barriers and facilitators of thromboprophylaxis for medical-surgical intensive care unit patients: a multicenter survey.
The objective of this study was to identify the self-reported barriers to and facilitators of prescribing low-molecular-weight heparin (LMWH) thromboprophylaxis in the intensive care unit (ICU). We conducted an interviewer-administered survey of 4 individuals per ICU (the ICU director, a bedside pharmacist, a thromboprophylaxis research coordinator, and physician site investigator) regarding LMWH thromboprophylaxis for medical-surgical patients in 27 ICUs in Canada and the United States. Items were generated by the research team and adapted from previous surveys, audits, qualitative studies, and quality improvement research. Respondents rated the barriers to LMWH use, facilitators (effectiveness, affordability, and acceptability thereof), and perceptions regarding LMWH use. Respondents had 14.5 (SD, 7.7) years of ICU experience (response rate, 99%). The 5 most common barriers in descending order were as follows: drug acquisition cost, fear of bleeding, lack of resident education, concern about bioaccumulation in renal failure, and habit. The top 5 rated facilitators were preprinted orders, education, daily reminders, audit and feedback, and local quality improvement committee endorsement. Centers using preprinted orders (mean difference [P<.01]) and computerized physician order entry (P<.01) compared with those centers not using those tools reported higher affordability for these 2 facilitators. Compared with physicians and pharmacists, research coordinators considered ICU-specific audit and feedback of thromboprophylaxis rates to be a more effective, acceptable, and affordable facilitator (odds ratio, 6.67; 95% confidence interval, 1.97-22.53; P<.01). Facilitator acceptability ratings were similar within centers but differed across centers (P≤.01). This multicenter survey found several barriers to use of LMWH including cost, concern about bleeding, and lack of resident knowledge of effectiveness. The diversity of reported facilitators suggests that large scale programs may address generic barriers but also need site-specific interprofessional knowledge translation activities.


Oral Health-Related Knowledge, Attitudes and Behaviours of Arab Dental Students: Multi-National Cross-Sectional Study and Literature Analysis 2000-2020.
Dental students are the future leaders of oral health in their respective communities; therefore, their oral health-related attitudes and behaviours are of practical value for primary disease prevention. The present study aimed to evaluate oral health-related knowledge, attitudes, and behaviours of dental students in Arab countries and explore the potential sociodemographic predictors of their oral health outcomes. A multi-centre, cross-sectional study was conducted during the academic year 2019/2020 in three Arab countries: Lebanon, Syria, and Tunisia. The study used a validated Arabic version of the Hiroshima University Dental Behavioural Inventory (HU-DBI) composed of original twenty items that assess the level of oral health-related knowledge, attitudes, and behaviours, and four additional dichotomous items related to tobacco smoking, alcohol drinking, problematic internet use, and regular dental check-up The HU-DBI score ranges between 0 and 12. A total of 1430 students took part in this study, out of which 60.8% were females, 57.8% were enrolled in clinical years, 24.5% were tobacco smokers, 7.2% were alcohol drinkers, and 87% reported internet addiction. The mean HU-DBI score was 6.31 ± 1.84, with Lebanon having the highest score (6.67 ± 1.83), followed by Syria (6.38 ± 1.83) and Tunisia (6.05 ± 1.83). Clinical students (6.78 ± 1.70) had higher HU-DBI scores than their preclinical peers (5.97 ± 1.86). The year-over-year analysis revealed that dental public health and preventive dentistry courses had significantly and positively impacted the undergraduate students' knowledge, attitudes, and behaviours. The gender-based differences were not statistically significant, with a modest trend favouring males, especially oral health behaviours. Tobacco smoking, alcohol drinking, and problematic internet use were associated with lower HU-DBI scores. In the Arab world, the economic rank of the country where the dental students live/study was weakly correlated with the students' mean HU-DBI score.


Role of galactolipid biosynthesis in coordinated development of photosynthetic complexes and thylakoid membranes during chloroplast biogenesis in Arabidopsis.
The galactolipids monogalactosyldiacylglycerol (MGDG) and digalactosyldiacylglycerol (DGDG) are the predominant lipids in thylakoid membranes and indispensable for photosynthesis. Among the three isoforms that catalyze MGDG synthesis in Arabidopsis thaliana, MGD1 is responsible for most galactolipid synthesis in chloroplasts, whereas MGD2 and MGD3 are required for DGDG accumulation during phosphate (Pi) starvation. A null mutant of Arabidopsis MGD1 (mgd1-2), which lacks both galactolipids and shows a severe defect in chloroplast biogenesis under nutrient-sufficient conditions, accumulated large amounts of DGDG, with a strong induction of MGD2/3 expression, during Pi starvation. In plastids of Pi-starved mgd1-2 leaves, biogenesis of thylakoid-like internal membranes, occasionally associated with invagination of the inner envelope, was observed, together with chlorophyll accumulation. Moreover, the mutant accumulated photosynthetic membrane proteins upon Pi starvation, indicating a compensation for MGD1 deficiency by Pi stress-induced galactolipid biosynthesis. However, photosynthetic activity in the mutant was still abolished, and light-harvesting/photosystem core complexes were improperly formed, suggesting a requirement for MGDG for proper assembly of these complexes. During Pi starvation, distribution of plastid nucleoids changed concomitantly with internal membrane biogenesis in the mgd1-2 mutant. Moreover, the reduced expression of nuclear- and plastid-encoded photosynthetic genes observed in the mgd1-2 mutant under Pi-sufficient conditions was restored after Pi starvation. In contrast, Pi starvation had no such positive effects in mutants lacking chlorophyll biosynthesis. These observations demonstrate that galactolipid biosynthesis and subsequent membrane biogenesis inside the plastid strongly influence nucleoid distribution and the expression of both plastid- and nuclear-encoded photosynthetic genes, independently of photosynthesis.


Posttreatment Lyme disease syndrome.
The prognosis following appropriate antibiotic treatment of early or late Lyme disease is favorable but can be complicated by persistent symptoms of unknown cause termed posttreatment Lyme disease syndrome (PTLDS), characterized by fatigue, musculoskeletal pain, and cognitive complaints that persist for 6 months or longer after completion of antibiotic therapy. Risk factors include delayed diagnosis, increased severity of symptoms, and presence of neurologic symptoms at time of initial treatment. Two-tier serologic testing is neither sensitive nor specific for diagnosis of PTLDS because of variability in convalescent serologic responses after treatment of early Lyme disease. Optimal treatment of PTLDS awaits more precise understanding of the pathophysiologic mechanisms involved in this illness and future treatment trials.


REDD1 enhances protein phosphatase 2A-mediated dephosphorylation of Akt to repress mTORC1 signaling.
The protein kinase mTOR (mechanistic target of rapamycin) in complex 1 (mTORC1) promotes cell growth and proliferation in response to anabolic stimuli, including growth factors and nutrients. Growth factors activate mTORC1 by stimulating the kinase Akt, which phosphorylates and inhibits the tuberous sclerosis complex [TSC; which is composed of TSC1, TSC2, and TBC1D7 (Tre2-Bub2-Cdc16 domain family member 7)], thereby stimulating the mTORC1 activator Rheb (Ras homolog enriched in brain). We identified the mechanism through which REDD1 (regulated in DNA damage and development 1) represses the mTORC1 signaling pathway. We found that REDD1 promoted the protein phosphatase 2A (PP2A)-dependent dephosphorylation of Akt on Thr(308) but not on Ser(473). Consistent with previous studies showing that phosphorylation of Akt on Thr(308), but not on Ser(473), is necessary for phosphorylation of TSC2, we observed a REDD1-dependent reduction in the phosphorylation of TSC2 and subsequently in the activation state of Rheb. REDD1 and PP2A coimmunoprecipitated with Akt from wild-type but not REDD1 knockout mouse embryonic fibroblasts, suggesting that REDD1 may act as a targeting protein for the catalytic subunit of PP2A. Furthermore, binding to both Akt and PP2A was essential for REDD1 to repress signaling to mTORC1. Overall, the results demonstrate that REDD1 acts not only as a repressor of mTORC1 but also as a constant modulator of the phosphorylation of Akt in response to growth factors and nutrients.


Identifying gaps in the continuum of care for hypertension and diabetes in two Indian communities.
Non-communicable diseases (NCDs) represent the largest, and fastest growing, burden of disease in India. This study aimed to quantify levels of diagnosis, treatment, and control among hypertensive and diabetic patients, and to describe demand- and supply-side barriers to hypertension and diabetes diagnosis and care in two Indian districts, Shimla and Udaipur. We conducted household and health facility surveys, as well as qualitative focus group discussions and interviews. The household survey randomly sampled individuals aged 15 and above in rural and urban areas in both districts. The survey included questions on NCD knowledge, history, and risk factors. Blood pressure, weight, height, and blood glucose measurements were obtained. The health facility survey was administered in 48 health care facilities, focusing on NCD diagnosis and treatment capacity, including staffing, equipment, and pharmaceuticals. Qualitative data was collected through semi-structured key informant interviews with health professionals and public health officials, as well as focus groups with patients and community members. Among 7181 individuals, 32% either reported a history of hypertension or were found to have a systolic blood pressure ≥ 140 mmHg and/or diastolic ≥90 mmHg. Only 26% of those found to have elevated blood pressure reported a prior diagnosis, and just 42% of individuals with a prior diagnosis of hypertension were found to be normotensive. A history of diabetes or an elevated blood sugar (Random blood glucose (RBG) ≥200 mg/dl or fasting blood glucose (FBG) ≥126 mg/dl) was noted in 7% of the population. Among those with an elevated RBG/FBG, 59% had previously received a diagnosis of diabetes. Only 60% of diabetics on treatment were measured with a RBG <200 mg/dl. Lower-level health facilities were noted to have limited capacity to measure blood glucose as well as significant gaps in the availability of first-line pharmaceuticals for both hypertension and diabetes. We found high rates of uncontrolled diabetes and undiagnosed and uncontrolled hypertension. Lower level health facilities were constrained by capacity to test, monitor and treat diabetes and hypertension. Interventions aimed at improving patient outcomes will need to focus on the expanding access to quality care in order to accommodate the growing demand for NCD services.


Systematic review of perioperative and quality-of-life outcomes following surgical management of localised renal cancer.
For the treatment of localised renal cell carcinoma (RCC), uncertainties remain over the perioperative and quality-of-life (QoL) outcomes for the many different surgical techniques and approaches of nephrectomy. Controversy also remains on whether newer minimally invasive nephron-sparing interventions offer better QoL and perioperative outcomes, and whether adrenalectomy and lymphadenectomy should be performed simultaneously with nephrectomy. These non-oncological outcomes are important because they may have a considerable impact on localised RCC treatment decision making. To review systematically all the relevant published literature comparing perioperative and QoL outcomes of surgical management of localised RCC (T1-2N0M0). Relevant databases including Medline, Embase, and the Cochrane Library were searched up to January 2012. Randomised controlled trials (RCTs) or quasi-randomised controlled trials, prospective observational studies with controls, retrospective matched-pair studies, and comparative studies from well-defined registries/databases were included. The outcome measures were QoL, analgesic requirement, length of hospital stay, time to normal activity level, surgical morbidity and complications, ischaemia time, renal function, blood loss, length of operation, need for blood transfusion, and perioperative mortality. The Cochrane risk of bias tool was used to assess RCTs, and an extended version was used to assess nonrandomised studies (NRSs). The quality of evidence was assessed using Grading of Recommendations, Assessment, Development, and Evaluation. A total of 4580 abstracts and 380 full-text articles were assessed, and 29 studies met the inclusion criteria (7 RCTs and 22 NRSs). There were high risks of bias and low-quality evidence for studies meeting the inclusion criteria. There is good evidence indicating that partial nephrectomy results in better preservation of renal function and better QoL outcomes than radical nephrectomy regardless of technique or approach. Regarding radical nephrectomy, the laparoscopic approach has better perioperative outcomes than the open approach, and there is no evidence of a difference between the transperitoneal and retroperitoneal approaches. Alternatives to standard laparoscopic radical nephrectomy (LRN) such as hand-assisted, robot-assisted, or single-port techniques appear to have similar perioperative outcomes. There is no good evidence to suggest that minimally invasive procedures such as cryotherapy or radiofrequency ablation have superior perioperative or QoL outcomes to nephrectomy. Regarding concomitant lymphadenectomy during nephrectomy, there were low event rates for complications, and no definitive difference was observed. There was no evidence to base statements about concomitant ipsilateral adrenalectomy during nephrectomy. Partial nephrectomy results in significantly better preservation of renal function over radical nephrectomy. For tumours where partial nephrectomy is not technically feasible, there is no evidence that alternative procedures or techniques are better than LRN in terms of perioperative or QoL outcomes. In making treatment decisions, perioperative and QoL outcomes should be considered in conjunction with oncological outcomes. Overall, there was a paucity of data regarding QoL outcomes, and when reported, both QoL and perioperative outcomes were inconsistently defined, measured, or reported. The current evidence base has major limitations due to studies of low methodological quality marked by high risks of bias.


Psychosocial adjustment and mental health in former child soldiers--systematic review of the literature and recommendations for future research.
This article reviews the available quantitative research on psychosocial adjustment and mental health among children (age <18 years) associated with armed forces and armed groups (CAAFAG)--commonly referred to as child soldiers. PRISMA standards for systematic reviews were used to search PubMed, PsycInfo, JSTOR, and Sociological Abstracts in February 2012 for all articles on former child soldiers and CAAFAG. Twenty-one quantitative studies from 10 countries were analyzed for author, year of publication, journal, objectives, design, selection population, setting, instruments, prevalence estimates, and associations with war experiences. Opinion pieces, editorials, and qualitative studies were deemed beyond the scope of this study. Quality of evidence was rated according to the systematic assessment of quality in observational research (SAQOR). According to SAQOR criteria, among the available published studies, eight studies were of high quality, four were of moderate quality, and the remaining nine were of low quality. Common limitations were lack of validated mental health measures, unclear methodology including undefined sampling approaches, and failure to report missing data. Only five studies included a comparison group of youth not involved with armed forces/armed groups, and only five studies assessed mental health at more than one point in time. Across studies, a number of risk and protective factors were associated with postconflict psychosocial adjustment and social reintegration in CAAFAG. Abduction, age of conscription, exposure to violence, gender, and community stigma were associated with increased internalizing and externalizing mental health problems. Family acceptance, social support, and educational/economic opportunities were associated with improved psychosocial adjustment. Research on the social reintegration and psychosocial adjustment of former child soldiers is nascent. A number of gaps in the available literature warrant future study. Recommendations to bolster the evidence base on psychosocial adjustment in former child soldiers and other war-affected youth include more studies comprising longitudinal study designs, and validated cross-cultural instruments for assessing mental health, as well as more integrated community-based approaches to study design and research monitoring.


Remote sensing reveals Antarctic green snow algae as important terrestrial carbon sink.
We present the first estimate of green snow algae community biomass and distribution along the Antarctic Peninsula. Sentinel 2 imagery supported by two field campaigns revealed 1679 snow algae blooms, seasonally covering 1.95 × 106 m2 and equating to 1.3 × 103 tonnes total dry biomass. Ecosystem range is limited to areas with average positive summer temperatures, and distribution strongly influenced by marine nutrient inputs, with 60% of blooms less than 5 km from a penguin colony. A warming Antarctica may lose a majority of the 62% of blooms occupying small, low-lying islands with no high ground for range expansion. However, bloom area and elevation were observed to increase at lower latitudes, suggesting that parallel expansion of bloom area on larger landmasses, close to bird or seal colonies, is likely. This increase is predicted to outweigh biomass lost from small islands, resulting in a net increase in snow algae extent and biomass as the Peninsula warms.


Bone marrow transplantation may augment cardiac systolic function in patients with a reduced left ventricular ejection fraction.
Cardiac function is influenced by bone marrow transplantation (BMT). Studies have shown the various cardiotoxic effects of high-dose chemotherapy. In this study, we aimed to determine the effects of BMT on cardiac systolic function using echocardiographic indices. Patients with lymphoma (Hodgkin's and non-Hodgkin's), multiple myeloma, and solid tumors which were candidates for autologous BMT were selected. The tissue Doppler S wave velocity in left ventricular echocardiographic segments and the Swave velocity in right ventricle, the left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), and ejection fraction (EF) were measured before and after BMT. Nineteen patients studied. The mean systolic function variable measures were calculated before and after BMT. The tissue Doppler S mean decreased in the septal, lateral and anterior walls by 8%, 7.9%, and 4.9% (P = 0.017), respectively. The tissue Doppler S mean increased in the inferior, anteroseptal and posterior walls by 1%, 0.6%, and 6.1%, respectively (not significant). The right ventricle Doppler S mean decreased by 7.5% after BMT (P = 0.03). The LVEDD and LVESD decreased significantly by 4.8% (P = 0.003) and 3.3% (P = 0.015), respectively, following BMT. The ejection fraction increased by about 7% after BMT (P = 0.05). The tissue Doppler S increased in all LV walls in patients with an EF less than 47%; surprisingly, tissue Doppler S decreased in all patients with an EF greater than 47%; and the ejection fraction increased by 13.6% and 3.1% in patients with a pre-BMT EF less than 47% and above 47%, respectively.


Direct observations of submarine melt and subsurface geometry at a tidewater glacier.
Ice loss from the world's glaciers and ice sheets contributes to sea level rise, influences ocean circulation, and affects ecosystem productivity. Ongoing changes in glaciers and ice sheets are driven by submarine melting and iceberg calving from tidewater glacier margins. However, predictions of glacier change largely rest on unconstrained theory for submarine melting. Here, we use repeat multibeam sonar surveys to image a subsurface tidewater glacier face and document a time-variable, three-dimensional geometry linked to melting and calving patterns. Submarine melt rates are high across the entire ice face over both seasons surveyed and increase from spring to summer. The observed melt rates are up to two orders of magnitude greater than predicted by theory, challenging current simulations of ice loss from tidewater glaciers.


Eyewitness identifications after witnessing threatening and non-threatening scenes in 360-degree virtual reality (or 2D) from first and third person perspectives.
In eyewitness research the frequent use of video playback presented on a computer screen (i.e., 2D videos) in laboratory-based research is problematic due to the low realism of this method when presenting, for example, threatening (and non-threatening) first-person (and third-person) scenarios. However, in contrast to 2D videos, 360-degree videos presented in virtual reality (VR) presents the opportunity of achieving more realistic and immersive scenarios that might be better suited to mimic real-life incidents, as for example, in the case of a threatening first-person robbery. In the present study, we asked 37 participants to watch eight pre-recorded threatening or non-threatening 2D and VR videos, viewed from either a first- or third-person perspective. After each video, participants assessed the observed target's appearance and were then presented with either a target present (TP) or target absent (TA) six-person photograph line-up. We expected that VR would result in higher degrees of accuracy in both TP and TA line-ups compared with 2D and that the differences between manipulations would be more pronounced within VR compared with 2D. We found that TP (but not TA) accuracy was higher in 2D compared with VR videos (91 vs. 66%), that there was no main effect of perspective, and that threatening scenes increased TP (but not TA) accuracy compared to non-threatening scenes (86 vs. 70%). Furthermore, in VR (but not in 2D), threatening scenes increased TP (but not TA) accuracy compared with non-threatening scenes (85 vs. 40%). The results go against the expected increased accuracy in VR (vs. 2D) videos but support the notion that threatening (vs. non-threatening) scenes can increase identification accuracy in VR but not necessarily in 2D.