Spacing between GT-1 binding sites within a light-responsive element is critical for transcriptional activity.
Dissection of the light-responsive element (LRE) located between -166 and -50 of rbcS-3A from pea has revealed critical spacing requirements between the two GT-1 binding sites for light-responsive transcription. An increase in spacing between the two sites by as little as 2 bp reduces dramatically the rbcS-3A transcript levels in vivo. Mutation of the 10 bp between the binding sites leads to slightly lower transcript levels, as do deletions of either 3 bp or 8 bp. Deletions of 5 bp or 7 bp from between the GT-1 binding sites do not affect rbcS-3A transcript levels; however, a deletion of 10 bp virtually abolishes the activity of this element. These spacing changes within the light-responsive element similarly affect transcription of a divergently oriented and truncated nopaline synthase promoter. Most spacing changes between the two GT-1 binding sites, however, do not impair the binding of GT-1 to this element in vitro. Together with previous observations, these results suggest that the nuclear factor GT-1 may interact with the binding sites in either a productive or nonproductive manner and that GT-1 binding is necessary but not sufficient for light-responsive transcription. We also discuss our results in relation to the observed spacing of similar sequence elements present within other light-responsive promoters.


The cachexia assessment scale: development and psychometric properties.
To develop a tool to identify patients with cancer who suffer from cachexia throughout all stages of the disease. Tool development study. Oncology day care, follow-up clinics, radiotherapy, and hospice home care. 90 patients with cancer (25 men and 65 women). The Cachexia Assessment Scale (CAS) was created based on a thorough review of the literature and was tested for its psychometric properties. Presence of cachexia. Measures of reliability were determined by inter-rater, test-retest, and internal consistency reliability. Measures of validity were content validity, criterion validity, sensitivity, and specificity. The CAS possesses adequate levels of reliability and validity and can be used to evaluate cachexia at all stages of cancer. The CAS can be used as an assessment tool for cachexia in various treatment settings.


Effect of metals, with special attention of Cd, content of the Svitava and Svratka rivers on levels of thiol compounds in fish liver and their use as biochemical markers.
The aim of this study was to assess the effect of metals, with special attention of cadmium (Cd), content of the Svitava and Svratka rivers (Czech Republic) on levels of thiol compounds such as metallothioneins (MT), glutathione (GSH/GSSG), and cysteine (Cys) concentrations in chub (Leuciscus cephalus L.) liver and their use as biomarkers. Levels of thiol compounds in fish liver were determined by the differential pulse voltammetry Brdicka reaction. Cadmium content in L. cephalus liver was measured by atomic absorption spectometry (AAS) with electrothermal atomization. The contents of thiols and Cd were correlated with the Cd and metals content of river bottom sediments. Results were inconsistent with those of experimental studies. Correlations between liver Cd content and MT, Cys, GSSG were not significant in any locality (p > 0.05). Cd liver content was negatively (p< 0.05) correlated with GSH at one (Zidlochovice) of the seven tested sites. GSH and GSSG correlated negatively in five localities (p > 0.05). Correlations between Cd in sediment and Cys and GSSG (p > 0.05), and MT was negative (p< 0.05). The relationship between sum of metals value and MT was negative (p< 0.05), similarly with GSSG (p > 0.05). Many factors influence content of MT, GSH, and GSSG, and data for Cd were equivocal. Monitoring the aquatic ecosystem to identify metal content using thiol compounds in fish liver as biomarkers is complex. More relevant data including laboratory experiments will be required to assess most of the factors influencing thiols and their relevance to Cd contamination.


Differential Mortality Risks Associated With PM2.5 Components: A Multi-Country, Multi-City Study.
The association between fine particulate matter (PM2.5) and mortality widely differs between as well as within countries. Differences in PM2.5 composition can play a role in modifying the effect estimates, but there is little evidence about which components have higher impacts on mortality. We applied a 2-stage analysis on data collected from 210 locations in 16 countries. In the first stage, we estimated location-specific relative risks (RR) for mortality associated with daily total PM2.5 through time series regression analysis. We then pooled these estimates in a meta-regression model that included city-specific logratio-transformed proportions of seven PM2.5 components as well as meta-predictors derived from city-specific socio-economic and environmental indicators. We found associations between RR and several PM2.5 components. Increasing the ammonium (NH4+) proportion from 1% to 22%, while keeping a relative average proportion of other components, increased the RR from 1.0063 (95% confidence interval [95% CI] = 1.0030, 1.0097) to 1.0102 (95% CI = 1.0070, 1.0135). Conversely, an increase in nitrate (NO3-) from 1% to 71% resulted in a reduced RR, from 1.0100 (95% CI = 1.0067, 1.0133) to 1.0037 (95% CI = 0.9998, 1.0077). Differences in composition explained a substantial part of the heterogeneity in PM2.5 risk. These findings contribute to the identification of more hazardous emission sources. Further work is needed to understand the health impacts of PM2.5 components and sources given the overlapping sources and correlations among many components.


'Living cantilever arrays' for characterization of mass of single live cells in fluids.
The size of a cell is a fundamental physiological property and is closely regulated by various environmental and genetic factors. Optical or confocal microscopy can be used to measure the dimensions of adherent cells, and Coulter counter or flow cytometry (forward scattering light intensity) can be used to estimate the volume of single cells in a flow. Although these methods could be used to obtain the mass of single live cells, no method suitable for directly measuring the mass of single adherent cells without detaching them from the surface is currently available. We report the design, fabrication, and testing of 'living cantilever arrays', an approach to measure the mass of single adherent live cells in fluid using silicon cantilever mass sensor. HeLa cells were injected into microfluidic channels with a linear array of functionalized silicon cantilevers and the cells were subsequently captured on the cantilevers with positive dielectrophoresis. The captured cells were then cultured on the cantilevers in a microfluidic environment and the resonant frequencies of the cantilevers were measured. The mass of a single HeLa cell was extracted from the resonance frequency shift of the cantilever and was found to be close to the mass value calculated from the cell density from the literature and the cell volume obtained from confocal microscopy. This approach can provide a new method for mass measurement of a single adherent cell in its physiological condition in a non-invasive manner, as well as optical observations of the same cell. We believe this technology would be very valuable for single cell time-course studies of adherent live cells.


[Pathogenetic bases of oncologic risk].
Modern concepts on the etiology and pathogenesis of malignant tumors are reported, two basic links being distinguished-genetic factors and environmental factors--modifying ones. The specific weight of both factors in the etiology and pathogenesis of different oncological affections is varied. Based on the analysis of the modern concepts of the origin and development of a tumor the authors have elaborated a working scheme of selection of oncological risk groups among the population. The modifying factors being of primary importance for tumor growth are grouped by the authors into exogenous and endogenous ones. It is suggested to judge the degree of their manifestation in different individuals by the duration of their effect. The working scheme concerned may provide a logical basis for assessment of risk groups in various oncological lesions, but it needs some further verification in clinical practice.


A systematic review on changed biomechanics of lower extremities in obese individuals: a possible role in development of osteoarthritis.
Obesity has been identified as a risk factor for osteoarthritis. For the weight-bearing joints, the combination of increased load and changed joint biomechanics could be regarded as underlying principle for this relation. This systematic review of the literature focused on the differences between obese and normal-weight subjects in biomechanics of the hip, knee and ankle joint during every day movements to summarize differences in joint load due to both higher body weight and differences in movement patterns. A systematic search, up to November 2010, was performed in the Pubmed and Embase databases. This review showed that obese individuals adjust their movement strategy of every day movements. At self-selected speed, obese individuals walked slower, with shorter and wider steps, had longer stance duration and had a greater toe-out angle compared with normal-weight individuals. Obese sit-to-stand movement was characterized by less hip flexion and greater foot displacement. Obese individuals showed altered biomechanics during every day movements. These altered biomechanics could be related to the initiation of osteoarthritis by a change in the load-bearing regions of the articular cartilage in the weight-bearing joints.


Lack of EULAR/ERA-EDTA response at 1 year predicts poor long-term renal outcome in patients with lupus nephritis.
Short-term predictive endpoints of chronic kidney disease (CKD) are needed in lupus nephritis (LN). We tested response to therapy at 1 year. We considered patients with LN who underwent renal biopsy followed by induction therapy between January 1970 and December 2016. LN was assessed using the International Society of Nephrology/Renal Pathology Society (2003) criteria and the National Institute of Health (NIH) activity and chronicity index. The renal outcome was CKD. Response was defined according to EULAR/European League Against Rheumatism/European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations: complete: proteinuria <0.5 g/24 hours, (near) normal estimated glomerular filtration rate (eGFR); partial: ≥50% proteinuria reduction to subnephrotic levels, (near) normal eGFR; and no response: all the other cases. Logistic regression analysis was employed for 12-month response and Cox regression for CKD prediction. We studied 381 patients (90.5% Caucasians). After 12-month therapy, 58%, 26% and 16% of patients achieved complete, partial and no response, respectively, according to EULAR/ERA-EDTA. During a median follow-up of 10.7 (IQR: 4.97-18.80) years, 53 patients developed CKD. At 15 years, CKD-free survival rate was 95.2%, 87.6% and 55.4% in patients with complete, partial and no response at 12 months, respectively (p<0.0001). CKD-free survival rates did not differ between complete and partial responders (p=0.067). Serum creatinine (HR: 1.485, 95% CI 1.276 to 1.625), eGFR (HR 0.967, 95% CI 0.957 to 0.977) and proteinuria at 12 months (HR 1.234, 95% CI 1.111 to 1.379) were associated with CKD, yet no reliable cut-offs were identified on the receiver operating characteristic curve. In multivariable analysis, no EULAR/ERA-EDTA response at 12 months (HR 5.165, 95% CI 2.770 to 7.628), low C4 (HR 1.053, 95% CI 1.019 to 1.089) and persistent arterial hypertension (HR 3.154, 95% CI 1.500 to 4.547) independently predicted CKD. Lack of EULAR/ERA-EDTA response at 12 months predicts CKD.


Acylated Ghrelin as a Multi-Targeted Therapy for Alzheimer's and Parkinson's Disease.
Much thought has been given to the impact of Amyloid Beta, Tau and Alpha-Synuclein in the development of Alzheimer's disease (AD) and Parkinson's disease (PD), yet the clinical failures of the recent decades indicate that there are further pathological mechanisms at work. Indeed, besides amyloids, AD and PD are characterized by the culminative interplay of oxidative stress, mitochondrial dysfunction and hyperfission, defective autophagy and mitophagy, systemic inflammation, BBB and vascular damage, demyelination, cerebral insulin resistance, the loss of dopamine production in PD, impaired neurogenesis and, of course, widespread axonal, synaptic and neuronal degeneration that leads to cognitive and motor impediments. Interestingly, the acylated form of the hormone ghrelin has shown the potential to ameliorate the latter pathologic changes, although some studies indicate a few complications that need to be considered in the long-term administration of the hormone. As such, this review will illustrate the wide-ranging neuroprotective properties of acylated ghrelin and critically evaluate the hormone's therapeutic benefits for the treatment of AD and PD.


Manifestations of factor VIII inhibitor in the head and neck.
Hemophilia A is the most severe of the inherited bleeding disorders. Otolaryngologists are frequently asked to assist in the care of a patient with this disorder who has intractable bleeding from sites in the head and neck. This disorder is transmitted in an X-linked recessive manner and results from factor VIII deficiency. Factor replacement therapy has contributed much to the management of acute bleeding episodes and the prevention of long-term sequelae in patients with hemophilia. A consequence of factor replacement therapy that occurs in as much as 16% of patients is the development of antibodies to the exogenous factor. These antibodies inactivate any supplemental factor VIII, resulting in continued bleeding despite attempts at replacement therapy. This poses an extremely challenging clinical problem because other standard therapies have had limited usefulness. Activated prothrombin complex has been shown to be efficacious in the treatment of patients with inhibitors. This has led to the production of factor VIII inhibitor bypassing activity (FEIBA), which contains activated forms of factors II, VII, IX, and X. The mechanism of action of this preparation remains unknown, but it seems to bypass the need for factor VIII in the clotting cascade. Factor VIII inhibitor bypassing activity is not as effective as factor VIII concentrates in patients with normally responsive hemophilia, and patients with low inhibitor levels may be given larger doses of factor VIII. Disseminated intravascular coagulation is most often mentioned as a potential complication of the administration of factor VIII inhibitor bypassing activity, although it has been rarely reported. Otolaryngologists should be familiar with this clinical phenomenon and understand its implications. Two patients with bleeding diatheses were recently treated at our institution.


Cloning of mouse telomerase reverse transcriptase gene promoter and identification of proximal core promoter sequences essential for the expression of transgenes in cancer cells.
Telomerase is a ribonucleoprotein complex, whose function is to add motif-specific nucleotides to the end of chromosomes. Telomerase consists of three major subunits, the telomerase RNA template (hTR), the telomerase-associated protein (TEP1) and telomerase reverse transcriptase (TERT). TERT is the most important component responsible for the catalytic activity of telomerase and a rate-limiting determinant of the activity. Telomerase activities were at high levels in approximately 90% of mouse cancers or tumor-derived cell lines through TERT transcriptional up-regulation. Unlike human telomerase, telomerase activity exists in colon, liver, ovary and testis but not in brain, heart, stomach and muscle in normal mouse tissues. In this study, we prepared 5' truncations of 1086 bp fragments upstream of the initiating ATG codon of the mTERT gene to construct luciferase reporter gene plasmids, and transfected these plasmids into a normal mouse cell line and several cancer lines to identify the core promoter region essential for transcriptional activation in cancer cells by a luciferase assay. We constructed a eukaryotic expression vector of membrane-expressing staphylococcal endotoxin A (SEA) gene driven by the core promoter region of the mTERT gene and observed if the core promoter region could express the SEA gene in these cancer cells, but not in normal cells following transfection with the construct. The results showed that the transcriptional activities of each fragment of the mTERT gene promoter in the cancer cell lines Hepa1-6, B16 and CT26 were higher than those in NIH3T3 cells, and the proximal 333-bp fragment was the core promoter of the mTERT gene in the cancer cells. The proximal 333-bp fragment was able to make the SEA express on the surface of the cancer cells, but not in NIH3T3 cells. It provides a foundation for cancer targeting gene therapy by using the mTERT gene promoter.


Glucagon-like peptide-1 in the rat brain: distribution of expression and functional implication.
Glucagon-like-peptide 1 (GLP-1) is expressed not only in gut endocrine cells, but also in cells in the caudal brainstem and taste buds. To better understand the functions of central GLP-1, GLP-1 expression was immunohistochemically profiled in normal rat brain and its distribution correlated with FOS induction following systemic administration of a GLP-1 receptor agonist, exendin-4. In the present study, only a small number of GLP-1-immunoreactive cell bodies were observed in the nucleus of the solitary tract (NTS). However, these neurons send abundant projections to other regions of the brain, in particular the forebrain, including the paraventricular and dorsomedial nuclei of the hypothalamus, the central nucleus of the amygdala, the oval nucleus of the bed nuclei of the stria terminalis, and the paraventricular nucleus of the thalamus. Intraperitoneal administration of exendin-4 resulted in extensive FOS expression in areas of the forebrain and the hindbrain. In the forebrain, FOS expression was largely confined to regions where a high density of GLP-1-immunoreactive terminals was also localized. The majority of GLP-1-immunoreactive cells in the NTS were not FOS-positive. FOS-positive cells appeared to represent a different population from those expressing GLP-1. Thus, GLP-1-containing neurons in the brainstem may not be involved in receiving and relaying to other regions of the brain the physiological signals of prandial GLP-1 secreted by intestinal L-cells. Projections of GLP-1-containing neurons to the distinctive structures in the forebrain imply that central GLP-1 may play an important role in the behavioral and metabolic integration of autonomic control and arousal in the rat.


Creativity and ALife.
Three forms of creativity are exemplified in biology and studied in ALife. Combinational creativity exists as the first step in genetic algorithms. Exploratory creativity is seen in models using cellular automata or evolutionary programs. Transformational creativity can result from evolutionary programming. Even radically novel forms can do so, given input from outside the program itself. Transformational creativity appears also in reaction-diffusion models of morphogenesis. That there are limits to biological creativity is suggested by ALife work bearing on instances of biological impossibility.


Spinal Myxopapillary Ependymomas Demonstrate a Warburg Phenotype.
Myxopapillary ependymoma (MPE) is a distinct histologic variant of ependymoma arising commonly in the spinal cord. Despite an overall favorable prognosis, distant metastases, subarachnoid dissemination, and late recurrences have been reported. Currently, the only effective treatment for MPE is gross-total resection. We characterized the genomic and transcriptional landscape of spinal ependymomas in an effort to delineate the genetic basis of this disease and identify new leads for therapy. Gene expression profiling was performed on 35 spinal ependymomas, and copy number profiling was done on an overlapping cohort of 46 spinal ependymomas. Functional validation experiments were performed on tumor lysates consisting of assays measuring pyruvate kinase M activity (PKM), hexokinase activity (HK), and lactate production. At a gene expression level, we demonstrate that spinal grade II and MPE are molecularly and biologically distinct. These are supported by specific copy number alterations occurring in each histologic variant. Pathway analysis revealed that MPE are characterized by increased cellular metabolism, associated with upregulation of HIF1α. These findings were validated by Western blot analysis demonstrating increased protein expression of HIF1α, HK2, PDK1, and phosphorylation of PDHE1A. Functional assays were performed on MPE lysates, which demonstrated decreased PKM activity, increased HK activity, and elevated lactate production. Our findings suggest that MPE may be driven by a Warburg metabolic phenotype. The key enzymes promoting the Warburg phenotype: HK2, PKM2, and PDK are targetable by small-molecule inhibitors/activators, and should be considered for evaluation in future clinical trials for MPE.


"The System Had Choked Me Too": Abused Mothers' Perceptions of the Custody Determination Process That Resulted in Negative Custody Outcomes.
Intimate partner violence (IPV) is a public health problem that continues to affect abused mothers after separation from an abusive partner. In addition to the risk of ongoing control and violence by abusers, the custody determination process may present challenges for mothers who end up with negative custody outcomes (e.g., share custody with abusers or lose custody). Using constructivist grounded theory techniques, we conducted a qualitative analysis of interviews with 24 abused mothers with negative custody outcomes to understand how they perceive and make sense of the process as a whole, and how they cope with these outcomes. The custody determination process was reportedly complex and stressful, and most mothers did not anticipate a negative custody outcome. Mothers' perceptions and experiences followed three phases: "trusting "the system" to protect them and their children, adapting to "the system" in search of positive outcomes, and, once custody decisions were determined, coping with the aftermath of the judicial system process, either by accepting or resisting the outcome. This study echoes previous calls for further training and policies that make the custody determination process less burdensome and harmful for survivors and their children.


Comparison of Alternative Meat Inspection Regimes for Pigs From Non-Controlled Housing - Considering the Cost of Error.
Denmark has not had cases of bovine tuberculosis (bovTB) for more than 30 years but is obliged by trade agreements to undertake traditional meat inspection (TMI) of finisher pigs from non-controlled housing to detect bovTB. TMI is associated with higher probability of detecting bovTB but is also more costly than visual-only inspection (VOI). To identify whether VOI should replace TMI of finisher pigs from non-controlled housing, the cost of error - defined here as probability of overlooking infection and associated economic costs - should be assessed and compared with surveillance costs. First, a scenario tree model was set up to assess the ability of detecting bovTB in an infected herd (HSe) calculated for three within-herd prevalences, WHP (1, 5 and 10%), for four different surveillance scenarios (TMI and VOI with or without serological test, respectively). HSe was calculated for six consecutive 4-week surveillance periods until predicted bovTB detection (considered high-risk periods HRP). 1-HSe was probability of missing all positives by each HRP. Next, probability of spread of infection, Pspread, and number of infected animals moved were calculated for each HRP. Costs caused by overlooking bovTB were calculated taking into account Pspread , 1-HSe, eradication costs, and trade impact. Finally, the average annual costs were calculated by adding surveillance costs and assuming one incursion of bovTB in either 1, 10 or 30 years. Input parameters were based on slaughterhouse statistics, literature and expert opinion. Herd sensitivity increased by high-risk period and within-herd prevalence. Assuming WHP=5%, HSe reached median 90% by 2nd HRP for TMI, whereas for VOI this would happen after 6th HRP. Serology had limited impact on HSe. The higher the probability of infection, the higher the probability of detection and spread. TMI resulted in lowest average annual costs, if one incursion of bovTB was expected every year. However, when assuming one introduction in 10 or 30 years, VOI resulted in lowest average costs. It may be more cost-effective to focus on imported high-risk animals coming into contact with Danish livestock, instead of using TMI as surveillance on all pigs from non-controlled housing.


Human resources for health: overcoming the crisis.
In this analysis of the global workforce, the Joint Learning Initiative-a consortium of more than 100 health leaders-proposes that mobilisation and strengthening of human resources for health, neglected yet critical, is central to combating health crises in some of the world's poorest countries and for building sustainable health systems in all countries. Nearly all countries are challenged by worker shortage, skill mix imbalance, maldistribution, negative work environment, and weak knowledge base. Especially in the poorest countries, the workforce is under assault by HIV/AIDS, out-migration, and inadequate investment. Effective country strategies should be backed by international reinforcement. Ultimately, the crisis in human resources is a shared problem requiring shared responsibility for cooperative action. Alliances for action are recommended to strengthen the performance of all existing actors while expanding space and energy for fresh actors.


Explaining semantic short-term memory deficits: evidence for the critical role of semantic control.
Patients with apparently selective short-term memory (STM) deficits for semantic information have played an important role in developing multi-store theories of STM and challenge the idea that verbal STM is supported by maintaining activation in the language system. We propose that semantic STM deficits are not as selective as previously thought and can occur as a result of mild disruption to semantic control processes, i.e., mechanisms that bias semantic processing towards task-relevant aspects of knowledge and away from irrelevant information. We tested three semantic STM patients with tasks that tapped four aspects of semantic control: (i) resolving ambiguity between word meanings, (ii) sensitivity to cues, (iii) ignoring irrelevant information and (iv) detecting weak semantic associations. All were impaired in conditions requiring more semantic control, irrespective of the STM demands of the task, suggesting a mild, but task-general, deficit in regulating semantic knowledge. This mild deficit has a disproportionate effect on STM tasks because they have high intrinsic control demands: in STM tasks, control is required to keep information active when it is no longer available in the environment and to manage competition between items held in memory simultaneously. By re-interpreting the core deficit in semantic STM patients in this way, we are able to explain their apparently selective impairment without the need for a specialised STM store. Instead, we argue that semantic STM patients occupy the mildest end of spectrum of semantic control disorders.


Non-planar nanofluidic devices for single molecule analysis fabricated using nanoglassblowing.
A method termed 'nanoglassblowing' is presented for fabricating integrated microfluidic and nanofluidic devices with gradual depth changes and wide, shallow nanochannels. This method was used to construct fused silica channels with out-of-plane curvature of channel covers from over ten micrometers to a few nanometers, nanochannel aspect ratios smaller than 2 × 10(-5):1 (depth:width), and nanochannel depths as shallow as 7 nm. These low aspect ratios and shallow channel depths would be difficult to form otherwise without collapse of the channel cover, and the gradual changes in channel depth eliminate abrupt free energy barriers at the transition from microfluidic to nanofluidic regions. Devices were characterized with atomic force microscopy (AFM), white light interferometry, scanned height measurements, fluorescence intensity traces, and single molecule analysis of double-stranded deoxyribonucleic acid (DNA) velocity and conformation. Nanochannel depths and aspect ratios formed by nanoglassblowing allowed measurements of the radius of gyration, R(g), of single λ DNA molecules confined to slit-like nanochannels with depths, d, ranging from 11 nm to 507 nm. Measurements of R(g) as a function of d agreed qualitatively with the scaling law R(g)∝d(-0.25) predicted by Brochard for nanochannel depths from 36 nm to 156 nm, while measurements of R(g) in 11 nm and 507 nm deep nanochannels deviated from this prediction.


Pooled association genome scanning for alcohol dependence using 104,268 SNPs: validation and use to identify alcoholism vulnerability loci in unrelated individuals from the collaborative study on the genetics of alcoholism.
Association genome scanning can identify markers for the allelic variants that contribute to vulnerability to complex disorders, including alcohol dependence. To improve the power and feasibility of this approach, we report validation of "100k" microarray-based allelic frequency assessments in pooled DNA samples. We then use this approach with unrelated alcohol-dependent versus control individuals sampled from pedigrees collected by the Collaborative Study on the Genetics of Alcoholism (COGA). Allele frequency differences between alcohol-dependent and control individuals are assessed in quadruplicate at 104,268 autosomal SNPs in pooled samples. One hundred eighty-eight SNPs provide (1) the largest allele frequency differences between dependent versus control individuals; (2) t values >or= 3 for these differences; and (3) clustering, so that 51 relatively small chromosomal regions contain at least three SNPs that satisfy criteria 1 and 2 above (Monte Carlo P = 0.00034). These positive SNP clusters nominate interesting genes whose products are implicated in cellular signaling, gene regulation, development, "cell adhesion," and Mendelian disorders. The results converge with linkage and association results for alcohol and other addictive phenotypes. The data support polygenic contributions to vulnerability to alcohol dependence. These SNPs provide new tools to aid the understanding, prevention, and treatment of alcohol abuse and dependence.


210Po and 210Pb activity in Chinese cigarettes.
The radon decay products lead-210 ((210)Pb) and polonium-210 ((210)Po) are known components of tobacco. China is the world's largest producer and consumer of cigarettes, yet no comprehensive published reports of the (210)Pb and (210)Po activity concentrations in Chinese cigarettes are available. Twelve brands of cigarettes that were commonly smoked within a group of 184 Chinese smokers were selected for (210)Pb and (210)Po activity analysis. For each brand, the tobacco from two cigarettes was isolated, dried, weighed, spiked with a (209)Po tracer for yield, and digested with concentrated HNO3, followed by HCl. The polonium in each digested solution was spontaneously deposited onto a nickel disc. The polonium activity was then counted using alpha spectroscopy. The mean (range) (210)Po activity for all brands was 23 (18-29) mBq cig(-1). The state of radioactive equilibrium between (210)Po and (210)Pb in each cigarette was verified in three brands of cigarettes. Cigarettes from two brands were smoked on a machine in order to estimate the fraction of (210)Pb and (210)Po inhaled. An average of 8% of the (210)Pb and 13% of the (210)Po in the tobacco of the cigarettes was transferred to the mainstream smoke. It is thus estimated that a person smoking 20 of these cigarettes per day in China would inhale a mean (range) of 37 (29-46) mBq d(-1) of (210)Pb and 60 (47-75) mBq d(-1) of (210)Po. Cigarette smoking in China may therefore be a large source of a person's daily intake of (210)Pb and (210)Po.


Extracorporeal high intensity focused ultrasound for renal tumours: a 3-year follow-up.
To determine whether primary extracorporeal high-intensity focused ultrasound (HIFU) is safe, feasible and effective for managing small renal tumours. Although surgery currently remains the standard treatment for localized renal cell carcinoma (RCC), the increasing incidence of small renal cancers has led to a shift towards nephron-sparing surgery, with associated morbidity in 20-25% of cases, and minimally invasive ablative therapies present an alternative management. HIFU results in 'trackless' homogenous tissue ablation and when administered via an extracorporeal device, is entirely noninvasive. The study comprised 17 patients (mean tumour size 2.5 cm) with radiologically suspicious renal tumours who underwent extracorporeal HIFU using the Model-JC System (Chongqing HAIFU™, China), under general anaesthesia with one overnight hospital stay. Real-time diagnostic ultrasonography was used for targeting and monitoring. Patients were followed with a clinical review and gadolinium-enhanced magnetic resonance imaging at 12 days and every 6 months for a mean of 36 months. The outcomes measures were patient morbidity and oncological efficacy of HIFU treatment. Of the 17 patients, 15 were treated according to protocol; two procedures were abandoned due to intervening bowel. There were no major complications related to HIFU. Radiological evidence of ablation was apparent at 12 days in seven of the 15 patients. Before the 6-month follow-up one patient had surgery due to persisting central enhancement. Fourteen patients were evaluated at the 6-month follow-up; eight tumours had involuted (mean 12% decrease in tumour area). Four patients had irregular enhancement on imaging and had alternative therapies. Ten patients remain on follow-up at a mean (range) of 36 (14-55) months after HIFU (mean 30% decrease in tumour area). There was central loss of enhancement in all. Renal HIFU achieves stable lesions in two-thirds of patients, with minimal morbidity, and might be appropriate in selected cases. Further trials with accurate histological follow-up are essential to fully evaluate this novel technique.


Impaired circadian rhythmicity of beta-lipotrophin, beta-endorphin and ACTH in heroin addicts.
The circadian rhythm of plasma proopiocortin-related peptides was studied in 15 heroin addicts and in 6 sex- and age-matched controls. ACTH, beta-lipotrophin, (beta-LPH), beta-endorphin (beta-EP) and cortisol were measured by RIA either directly (cortisol), or after plasma extraction (ACTH) and Sephadex G-75 gel chromatography (beta-LPH and beta-EP) every 4 h from 8 a.m. to 8 p.m. and again at 8 a.m. the next morning. The means of the two 8 a.m. measurements of beta-LPH (2.67 +/- 0.34 fmol/ml, mean +/- SE), ACTH (2.74 +/- 0.71) and cortisol (218 +/- 31 pmol/ml) levels in heroin addicts were significantly lower than those in controls (6.28 +/- 0.61, 10.1 +/- 0.74 and 364 +/- 27, respectively, P less than 0.01) while beta-EP concentrations in heroin addicts (5.1 +/- 0.6) were similar to those of healthy volunteers (6.44 +/- 0.56). In controls, all three peptides and cortisol show a circadian rhythm of secretion, the lowest values being in the evening and the highest ones in the morning. Heroin addicts partially lack this phenomenon showing constant levels of the three proopiocortin-related peptides throughout the day, with a slight but significant decrease of plasma cortisol. In the 7 subjects who took heroin throughout the study, no systematic changes were observed in the three proopiocortin-related peptides, while it seems that this group of addicts shows a cortisol decrease in the evening to a lesser extent than subjects receiving methadone maintenance only.(ABSTRACT TRUNCATED AT 250 WORDS)


Isolation and characterization of microsatellite loci for mountain mullet (Agonostomus monticola).
We report on the isolation of 15 polymorphic microsatellite loci from mountain mullet (Agonostomus monticola). In the two populations sampled, loci exhibited two to 21 alleles and observed heterozygosity values ranged from 0.222 to 1.000. All loci conformed to Hardy-Weinberg equilibrium expectations, and none exhibited linkage disequilibrium. Although A. monticola is an important subsistence fishery in parts of its range, little is known about its ecology and many populations appear to be experiencing declines. These microsatellite loci should prove useful in the study of population structure of A. monticola and aid in other potential conservation efforts such as the management of hatchery broodstock.


Association of traumatic police event exposure with sleep quality and quantity in the BCOPS Study cohort.
Police officers are exposed to traumatic and life-threatening events, which may lead to sleep problems. Prior studies of police officers have found them to have poor sleep quality and reduced sleep time. This study examined associations between traumatic events and sleep quality. Participants were 372 police officers from the Buffalo Cardio-metabolic Occupational Police Stress (BCOPS) Study. Police incidents were measured by the Police Incident Survey; sleep quality and quantity were derived from the Pittsburgh Sleep Quality Index (PSQI). Analysis of covariance (ANCOVA) was used to examine mean PSQI scores across categories of traumatic event frequency. Models were adjusted for age, education and ethnicity and stratified by sex and workload. In men, significant associations were found for the 'shooting of another officer' and sleep quality (p-value = 0.024) and sleep disturbances (p-value = 0.022). In women, seeing more 'abused children' was associated with poorer sleep quality (p-value = 0.050); increasing frequency of 'seeing victims of a serious traffic accident' was associated with shorter sleep duration (p-value = 0.032). Increased frequency of 'seeing dead bodies' was associated with poorer sleep quality (p-value = 0.040) and shorter sleep duration (p-value = 0.048). Among women with a high workload, a significant inverse association was found between 'seeing serious traffic accident victims' and global sleep quality (p-value = 0.031). In conclusion, a significant inverse association between frequency of select traumatic events and sleep quality was found in male and female police officers. The significant events differed by sex. Future research could examine longitudinal associations between career-long traumatic event exposures and sleep quality and how these associations differ by sex.


Analysis of mutations in the tudor domain of the survival motor neuron protein SMN.
Autosomal recessive childhood onset spinal muscular atrophy (SMA) is a leading cause of infant mortality caused by mutations in the survival motor neuron (SMN) gene. The SMN protein is involved in RNA processing and is localised in structures called GEMs in the nucleus. Nothing is yet understood about why mutations in SMN gene result in the selective motor neuron loss observed in patients. The SMN protein domains conserved across several species may indicate functionally significant regions. Exon 3 of SMN contains homology to a tudor domain, where a Type I SMA patient has been reported to harbour a missense mutation. We have generated missense mutants in this region of SMN and have tested their ability to form GEMs when transfected into HeLa cells. Our results show such mutant SMN proteins still localise to GEMs. Furthermore, exon 7 deleted SMN protein appears to exert a dominant negative effect on localisation of endogenous SMN protein. However, exon 3 mutant protein and exon 5 deleted protein exert no such effect.


Structure Characterization and Properties of Metal-Surfactant Complexes Dispersed in Organic Solvents.
This work describes the synthesis and characterization of metal-surfactant complexes. Dioctyl sulfosuccinate and dodecylbenzenesulfonate are associated with multivalent aluminum, iron, and vanadium ions using an ion exchange reaction. The metal complexes are dispersible in various organic solvents. In solvents with low polarity, the complexes form "inverse" macromolecular structures with multiple metal ions. In contrast, in alcohols, the complex size is reduced, showing a more disperse conformation. The metal and surfactant ions are still strongly bonded to each other in all the solvents probed. Small-angle X-ray and neutron scattering (SAXS and SANS) are used to characterize the structures. Simultaneous fitting of neutron and X-ray scattering spectra is performed in order to obtain an accurate description of the system. Scattering results are also validated by performing molecular dynamics (MD) simulations. The conductive and electrochemical properties of the complexes in solution are also evaluated. The dispersion of metal-organic complexes significantly increases electric conductivity, and some metal ions in the core of the complexes are shown to be electrochemically active in apolar solvents.


Aging Modulates the Hemispheric Specialization during Word Production.
Although older adults exhibit normal accuracy in performing word retrieval and generation (lexical production; e.g., object naming), they are generally slower in responding than younger adults. To maintain accuracy, older adults recruit compensatory mechanisms and strategies. We focused on two such possible compensatory mechanisms, one semantic and one executive. These mechanisms are reflected at inter- and intra-hemispheric levels by various patterns of reorganization of lexical production cerebral networks. Hemispheric reorganization (HR) changes were also evaluated in relation to increase naming latencies. Using functional magnetic resonance imaging (fMRI), we examined 27 healthy participants (from 30 years to 85 years) during an object naming task, exploring and identifying task-related patterns of cerebral reorganization. We report two main results. First, we observed a left intra-hemispheric pattern of reorganization, the left anterior-posterior aging (LAPA) effect, consisting of supplementary activation of left posterior (temporo-parietal) regions in older adults and asymmetric activation along the left fronto-temporal axis. This pattern suggests that older adults recruit posterior semantic regions to perform object naming. The second finding consisted of bilateral recruitment of frontal regions to maintain appropriate response times, especially in older adults who were faster performers. This pattern is discussed in terms of compensatory mechanism. We suggest that aging is associated with multiple, co-existing compensation and reorganization mechanisms and patterns associated with lexical production.


Five-meter rope-climbing: a commando-specific power test of the upper limbs.
To examine the concurrent validity and absolute and relative reliabilities of a commando-specific power test. 21 antiterrorism commandos. All participants were assessed on a 5-m rope-climbing test (RCT) and the following tests: pull-ups, push-ups, estimated-1-repetition-maximum (est-1RM), medicine-ball put, and handgrip-strength test. The stopwatch method related to the execution time (ET) was validated by comparison with video motion analysis. The best individual attempt of 3 trials was kept for analysis, and the performance was expressed in absolute power output (APO) and body-mass relative power output (RPO). Stopwatch assessment had an excellent criterion validity (r=.99, P<.001), intraclass correlation coefficient (ICC3,1) of .98, standard errors of measurement (SEM%) of 1.19%, bias±the 95% limits of agreement of 0.03±0.26 s, and minimal detectable change (MDC95) of 0.51 s. The ET, APO, and RPO were significantly correlated (P<.05) with all cited tests (absolute-value r range .55-.98), while est-1RM was not significantly correlated with the other tests. Test-retest reliability coefficients were excellent for ET, APO, and RPO (ICC3,1>.90). The SEM% values for the ET, APO, and RPO were all under 5% (range 3.73-4.52%), all being smaller than the corresponding smallest worthwhile change. The coefficients of variation for the ET, APO, and RPO were all under 10%. %MDC95 ranged from 10.37% to 12.53%. Considering the strong concurrent validity and excellent test-retest reliability, the RCT is simple to administer, has ecological validity, and is a valid specific field test of upper-body power for commandos and, in addition, can be accurately assessed with a stopwatch.


INFRAFRONTIER--providing mutant mouse resources as research tools for the international scientific community.
The laboratory mouse is a key model organism to investigate mechanism and therapeutics of human disease. The number of targeted genetic mouse models of disease is growing rapidly due to high-throughput production strategies employed by the International Mouse Phenotyping Consortium (IMPC) and the development of new, more efficient genome engineering techniques such as CRISPR based systems. We have previously described the European Mouse Mutant Archive (EMMA) resource and how this international infrastructure provides archiving and distribution worldwide for mutant mouse strains. EMMA has since evolved into INFRAFRONTIER (http://www.infrafrontier.eu), the pan-European research infrastructure for the systemic phenotyping, archiving and distribution of mouse disease models. Here we describe new features including improved search for mouse strains, support for new embryonic stem cell resources, access to training materials via a comprehensive knowledgebase and the promotion of innovative analytical and diagnostic techniques.


Tweeting celebrity suicides: Users' reaction to prominent suicide deaths on Twitter and subsequent increases in actual suicides.
A substantial amount of evidence indicates that news coverage of suicide deaths by celebrities is followed by an increase in suicide rates, suggesting a copycat behavior. However, the underlying process by which celebrity status and media coverage leads to increases in subsequent suicides is still unclear. This study collected over 1 million individual messages ("tweets") posted on Twitter that were related to 26 prominent figures in Japan who died by suicide between 2010 and 2014 and investigated whether media reports on suicide deaths that generated a greater level of reactions by the public are likely to be followed by a larger increase in actual suicides. We also compared the number of Twitter posts and the number of media reports in newspaper and on television to understand whether the number of messages on Twitter in response to the deaths corresponds to the amount of coverage in the traditional media. Using daily data from Japan's national death registry between 2010 and 2014, our analysis found an increase in actual suicides only when suicide deaths generated a large reaction from Twitter users. In contrast, no discernible increase in suicide counts was observed when the analysis included suicide deaths to which Twitter users did not show much interest, even when these deaths were covered considerably by the traditional media. This study also found suicides by relatively young entertainers generated a large number of posts on Twitter. This sharply contrasts with the relatively smaller volume of reaction to them generated by traditional forms of media, which focuses more on the deaths of non-entertainers. The results of this study strongly suggest that it is not sufficient to examine only traditional news media when investigating the impact of media reports on actual suicides.


Raman spectroscopy of GaSe and InSe post-transition metal chalcogenides layers.
III-VI post-transition metal chalcogenides (InSe and GaSe) are a new class of layered semiconductors, which feature a strong variation of size and type of their band gaps as a function of number of layers (N). Here, we investigate exfoliated layers of InSe and GaSe ranging from bulk crystals down to monolayer, encapsulated in hexagonal boron nitride, using Raman spectroscopy. We present the N-dependence of both intralayer vibrations within each atomic layer, as well as of the interlayer shear and layer breathing modes. A linear chain model can be used to describe the evolution of the peak positions as a function of N, consistent with first principles calculations.


[Pallidotomy in the treatment of complicated Parkinson's disease: clinical results at two years and analysis of prognostic factors].
There is a renewed interest in pallidotomy as a treatment for complicated Parkinson's disease (PD). To present the clinical results as well as the analysis of prognostic factors obtained in 28 patients with PD and motor complications submitted to pallidotomy and followed by one year (n = 28) and 2 years (n = 12). The total motor score (Unified Parkinson's Disease Rating Scale [UPDRS]) in the off state improved by 33 and 23% at one and two years, respectively (p < 0.01). All the cardinal signs of the disease were significantly improved (p < 0.01): tremor (92%), rigidity (67%), bradykinesia (46%) and axial symptoms (21%). A slight tendency to worsening in axial symptoms was observed. Dyskinesias disappeared in all but one patient. The Schawb & England Scale in off was improved by 21%. No improvement in the non-operated side was observed. The subgroup of patients with an improvement of less than 30% in the UPDRS was older than the one with larger clinical benefit. The observed tendency to worsening in the total motor score was related mainly to the progression of the symptoms in the non-operated side. Complications were mild and transient. Pallidotomy is a relatively safe and effective therapeutic option for complicated PD patients. An adequate selection of patients is necessary, since efficacy is partial and limited to one hemibody.


Animal research nexus: a new approach to the connections between science, health and animal welfare.
Animals used in biological research and testing have become integrated into the trajectories of modern biomedicine, generating increased expectations for and connections between human and animal health. Animal research also remains controversial and its acceptability is contingent on a complex network of relations and assurances across science and society, which are both formally constituted through law and informal or assumed. In this paper, we propose these entanglements can be studied through an approach that understands animal research as a nexus spanning the domains of science, health and animal welfare. We introduce this argument through, first, outlining some key challenges in UK debates around animal research, and second, reviewing the way nexus concepts have been used to connect issues in environmental research. Third, we explore how existing social sciences and humanities scholarship on animal research tends to focus on different aspects of the connections between scientific research, human health and animal welfare, which we suggest can be combined in a nexus approach. In the fourth section, we introduce our collaborative research on the animal research nexus, indicating how this approach can be used to study the history, governance and changing sensibilities around UK laboratory animal research. We suggest the attention to complex connections in nexus approaches can be enriched through conversations with the social sciences and medical humanities in ways that deepen appreciation of the importance of path-dependency and contingency, inclusion and exclusion in governance and the affective dimension to research. In conclusion, we reflect on the value of nexus thinking for developing research that is interdisciplinary, interactive and reflexive in understanding how accounts of the histories and current relations of animal research have significant implications for how scientific practices, policy debates and broad social contracts around animal research are being remade today.


A Comparison of Mainstream Genotyping Platforms for the Evaluation and Use of Barley Genetic Resources.
We compared the performance of two commonly used genotyping platforms, genotyping-by-sequencing (GBS) and single nucleotide polymorphism-arrays (SNP), to investigate the extent and pattern of genetic variation within a collection of 1,000 diverse barley genotypes selected from the German Federal ex situ GenBank hosted at IPK Gatersleben. Each platform revealed equivalent numbers of robust bi-allelic SNPs (39,733 and 37,930 SNPs for the 50K SNP-array and GBS datasets respectively). A small overlap of 464 SNPs was common to both platforms, indicating that the methodologies we used selectively access informative polymorphism in different portions of the barley genome. Approximately half of the GBS dataset was comprised of SNPs with minor allele frequencies (MAFs) below 1%, illustrating the power of GBS to detect rare alleles in diverse germplasm collections. While desired for certain applications, the highly robust calling of alleles at the same SNPs across multiple populations is an advantage of the SNP-array, allowing direct comparisons of data from related or unrelated studies. Overall MAFs and diversity statistics (π) were higher for the SNP-array data, potentially reflecting the conscious removal of markers with a low MAF in the ascertainment population. A comparison of similarity matrices revealed a positive correlation between both approaches, supporting the validity of using either for entire GenBank characterization. To explore the potential of each dataset for focused genetic analyses we explored the outcomes of their use in genome-wide association scans for row type, growth habit and non-adhering hull, and discriminant analysis of principal components for the drivers of sub-population differentiation. Interpretation of the results from both types of analysis yielded broadly similar conclusions indicating that choice of platform used for such analyses should be determined by the research question being asked, group preferences and their capabilities to extract and interpret the different types of output data easily and quickly. Access to the requisite infrastructure for running, processing, analyzing, querying, storing, and displaying either datatype is an additional consideration. Our investigations reveal that for barley the cost per genotyping assay is less for SNP-arrays than GBS, which translates to a cost per informative datapoint being significantly lower for the SNP-array.


Effects of continuous and pulsed 2450-MHz radiation on spontaneous lymphoblastoid transformation of human lymphocytes in vitro.
Normal human lymphocytes were isolated from the peripheral blood of healthy donors. One-ml samples containing (10(6)) cells in chromosome medium 1A were exposed for 5 days to conventional heating or to continuous wave (CW) or pulsed wave (PW) 2450-MHz radiation at non-heating (37 degrees C) and various heating levels (temperature increases of 0.5, 1.0, 1.5, and 2 degrees C). The pulsed exposures involved 1-microsecond pulses at pulse repetition frequencies from 100 to 1,000 pulses per second at the same average SAR levels as the CW exposures. Actual average SARs ranged to 12.3 W/kg. Following termination of the incubation period, spontaneous lymphoblastoid transformation was determined with an image analysis system. The results were compared among each of the experimental conditions and with sham-exposed cultures. At non-heating levels, CW exposure did not affect transformation. At heating levels both conventional and CW heating enhanced transformation to the same extent and correlate with the increases in incubation temperature. PW exposure enhanced transformation at non-heating levels. This finding is significant (P less than .002). At heating levels PW exposure enhanced transformation to a greater extent than did conventional or CW heating. This finding is significant at the .02 level. We conclude that PW 2450-MHz radiation acts differently on the process of lymphoblastoid transformation in vitro compared with CW 2450-MHz radiation at the same average SARs.


Care management practices for chronic pain in veterans prescribed high doses of opioid medications.
There is growing interest in the primary care management of patients with chronic non-cancer pain (CNCP) who are prescribed long-term opioid therapy. The aim of this study was to examine the care management practices and medical utilization of patients prescribed high doses of opioids relative to patients prescribed traditional doses of opioids. We conducted a retrospective cohort study of veterans who had CNCP in 2008 and reviewed medical care for the prior 2 years. Patients with CNCP who were prescribed high-dose opioid therapy (≥180mg morphine equivalent per day for 90+ consecutive days; n = 60) were compared with patients prescribed traditional dose opioid therapy (5-179mg morphine equivalent per day for 90+ consecutive days; n = 60). Patients in the high-dose group had several aspects of documented care that differed from patients in the traditional dose group, including more medical visits, attempting an opioid taper, receiving a urine drug screen and developing a pain goal. The majority of variables that were assessed did not differ between groups, including documented assessments of functional status or co-morbid psychopathology, opioid rotation, discussion of treatment side effects, non-pharmacological treatments or collaboration with mental health or pain specialists. Further work is needed to identify mechanisms for optimizing care management for patients with CNCP who are prescribed high doses of opioid medications.


Crystal structure analysis reveals Pseudomonas PilY1 as an essential calcium-dependent regulator of bacterial surface motility.
Several bacterial pathogens require the "twitching" motility produced by filamentous type IV pili (T4P) to establish and maintain human infections. Two cytoplasmic ATPases function as an oscillatory motor that powers twitching motility via cycles of pilus extension and retraction. The regulation of this motor, however, has remained a mystery. We present the 2.1 A resolution crystal structure of the Pseudomonas aeruginosa pilus-biogenesis factor PilY1, and identify a single site on this protein required for bacterial translocation. The structure reveals a modified beta-propeller fold and a distinct EF-hand-like calcium-binding site conserved in pathogens with retractile T4P. We show that preventing calcium binding by PilY1 using either an exogenous calcium chelator or mutation of a single residue disrupts Pseudomonas twitching motility by eliminating surface pili. In contrast, placing a lysine in this site to mimic the charge of a bound calcium interferes with motility in the opposite manner--by producing an abundance of nonfunctional surface pili. Our data indicate that calcium binding and release by the unique loop identified in the PilY1 crystal structure controls the opposing forces of pilus extension and retraction. Thus, PilY1 is an essential, calcium-dependent regulator of bacterial twitching motility.


Mortality among displaced former UNITA members and their families in Angola: a retrospective cluster survey.
To measure retrospectively mortality among a previously inaccessible population of former UNITA members and their families displaced within Angola, before and after their arrival in resettlement camps after ceasefire of 4 April 2002. Three stage cluster sampling for interviews. Recall period for mortality assessment was from 21 June 2001 to 15-31 August 2002. Eleven resettlement camps over four provinces of Angola (Bié, Cuando Cubango, Huila, and Malange) housing 149 000 former UNITA members and their families. 900 consenting family heads of households, or most senior household members, corresponding to an intended sample size of 4500 individuals. Crude mortality and proportional mortality, overall and by period (monthly, and before and after arrival in camps). Final sample included 6599 people. The 390 deaths reported during the recall period corresponded to an average crude mortality of 1.5/10 000/day (95% confidence interval 1.3 to 1.8), and, among children under 5 years old, to 4.1/10 000/day (3.3 to 5.2). Monthly crude mortality rose gradually to a peak in March 2002 and remained above emergency thresholds thereafter. Malnutrition was the leading cause of death (34%), followed by fever or malaria (24%) and war or violence (18%). Most war victims and people who had disappeared were women and children. This population of displaced Angolans experienced global and child mortality greatly in excess of normal levels, both before and after the 2002 ceasefire. Malnutrition deaths reflect the extent of the food crisis affecting this population. Timely humanitarian assistance must be made available to all populations in such conflicts.


Dietary fiber effects in chronic kidney disease: a systematic review and meta-analysis of controlled feeding trials.
Chronic kidney disease (CKD) is a major health concern associated with increased risk of cardiovascular disease, morbidity and mortality. Current CKD practice guidelines overlook dietary fiber, which is chronically low in the renal diet. However, increasing dietary fiber has been proposed to ameliorate the progress of CKD. We therefore conducted a systematic review and meta-analysis on the effect of dietary fiber intake on serum urea and creatinine as classical markers of renal health in individuals with CKD. We searched MEDLINE, EMBASE, CINHAL and the Cochrane Library for relevant clinical trials with a follow-up ⩾7 days. Data were pooled by the generic inverse variance method using random-effects models and expressed as mean difference (MD) with 95% confidence intervals (95% CIs). Heterogeneity was assessed by the Cochran Q statistic and quantified by I(2). A total of 14 trials involving 143 participants met the eligibility criteria. Dietary fiber supplementation significantly reduced serum urea and creatinine levels in the primary pooled analyses (MD, -1.76 mmol/l (95% CI, -3.00, -0.51), P<0.01 and MD, -22.83 mmol/l (95% CI, -42.63, -3.02), P=0.02, respectively) with significant evidence of interstudy heterogeneity only in the analysis of serum urea. This is the first study to summarize the potential beneficial effects of dietary fiber in the CKD population demonstrating a reduction in serum urea and creatinine, as well as highlighting the lack of clinical trials on harder end points. Larger, longer, higher-quality clinical trials measuring a greater variety of uremic toxins in CKD are required (NCT01844882).


Characteristics and immune-enhancing activity of pectic polysaccharides from sweet cherry (Prunus avium).
Two water soluble polysaccharides components PAPS-1 and PAPS-2 with homogeneously distributed molecular weight were obtained from Prunus avium. PAPS-1 and PAPS-2 contained GalA: Ara: Gal: Rha: GluA: Glu in 49.38: 32.39: 10.68: 4.66: 1.94: 0.48 and 77.18: 14.91: 3.39: 3.46: 0.93: 0.19 M ratios respectively, as well as trace amount of mannose and fucose. Infrared spectroscopy (IR), nuclear magnetic resonance (NMR) and methylation analysis indicated that both fractions were type I rhamnogalacturonan (RG-I) pectic polysaccharides with glycan side chains constituted mainly of arabinose with minor amount of galactose. Galacturonic acid methylation and sugar acetylation was found in both PAPS-1 and PAPS-2. Both PAPS-1 and PAPS-2 significantly induced the NO release from RAW264.7 cells and the expression of several immune-related molecular (TNFα, IL6, IL10, GCSF, iNOS, COX-2) was induced in RAW264.7 cells.


A National Profile of Family and Unpaid Caregivers Who Assist Older Adults With Health Care Activities.
Family and unpaid caregivers commonly help older adults who are at high risk for poorly coordinated care. To examine how caregivers' involvement in older adults' health care activities relates to caregiving responsibilities, supportive services use, and caregiving-related effects. A total of 1739 family and unpaid caregivers of 1171 community-dwelling older adults with disabilities who participated in the 2011 National Health and Aging Trends Study (NHATS) and National Study of Caregiving (NSOC). Caregiving-related effects, including emotional, physical, and financial difficulty; participation restrictions in valued activities; and work productivity loss. Caregivers assisting older adults who provide substantial, some, or no help with health care, defined by coordinating care and managing medications (help with both, either, or neither activity, respectively). Based on NHATS and NSOC responses from 1739 family and unpaid caregivers of 1171 older adults with disabilities, weighted estimates were produced that accounted for the sampling designs of each survey. From these weighted estimates, 14.7 million caregivers assisting 7.7 million older adults, 6.5 million (44.1%) provided substantial help, 4.4 million (29.8%) provided some help, and 3.8 million (26.1%) provided no help with health care. Almost half (45.5%) of the caregivers providing substantial help with health care assisted an older adult with dementia. Caregivers providing substantial help with health care provided more hours of assistance per week than caregivers providing some or no help (28.1 vs 15.1 and 8.3 hours, P < .001 for both). The use of supportive services was low but was greater among caregivers providing substantial vs some or no help (26.7% vs 15.5% and 7.6%, P < .001 for both). In multivariable regression models adjusting for older adults' function and caregivers' sociodemographic and health characteristics, caregivers providing substantial help with health care were significantly more likely to experience emotional difficulty (adjusted odds ratio [aOR], 1.79; 95% CI, 1.20-2.66), physical difficulty (aOR, 2.03; 95% CI, 1.39-2.97), and financial difficulty (aOR, 2.21; 95% CI, 1.52-3.22) than caregivers providing no help. Compared with caregivers providing no help with health care activities, caregivers providing substantial help with health care activities were more than 5 times as likely to experience participation restrictions in valued activities (aOR, 5.32; 95% CI, 3.31-8.59) and more than 3 times as likely to experience work productivity loss (aOR, 3.14; 95% CI, 1.40-7.02). Family caregivers providing substantial assistance with health care experience significant emotional difficulty and role-related effects, yet only one-quarter use supportive services.


Inferring Individual Inbreeding and Demographic History from Segments of Identity by Descent in Ficedula Flycatcher Genome Sequences.
Individual inbreeding and historical demography can be estimated by analyzing runs of homozygosity (ROH), which are indicative of chromosomal segments of identity by descent (IBD). Such analyses have so far been rare in natural populations due to limited genomic resources. We analyzed ROH in whole genome sequences from 287 Ficedula flycatchers representing four species, with the objectives of evaluating the causes of genome-wide variation in the abundance of ROH and inferring historical demography. ROH were clearly more abundant in genomic regions with low recombination rate. However, this pattern was substantially weaker when ROH were mapped using genetic rather than physical single nucleotide polymorphism (SNP) coordinates in the genome. Empirical results and simulations suggest that high ROH abundance in regions of low recombination was partly caused by increased power to detect the very long IBD segments typical of regions with a low recombination rate. Simulations also showed that hard selective sweeps (but not soft sweeps or background selection) likely contributed to variation in the abundance of ROH across the genome. Comparisons of the abundance of ROH among several study populations indicated that the Spanish pied flycatcher population had the smallest historical effective population size (Ne) for this species, and that a putatively recently founded island (Baltic) population had the smallest historical Ne among the collared flycatchers. Analysis of pairwise IBD in Baltic collared flycatchers indicated that this population was founded <60 generations ago. This study provides a rare genomic glimpse into demographic history and the mechanisms underlying the genome-wide distribution of ROH.


Suicide prevention via the Internet: a descriptive review.
While concerns abound regarding the impact of the Internet on suicidal behaviors, its role as a medium for suicide prevention remains underexplored. The study examines what is currently known about the operation and effectiveness of Internet programs for suicide and self-harm prevention that are run by professionals. Systematic searches of scholarly databases and suicide-related academic journals yielded 15 studies that presented online prevention strategies. No professional programs with a sole focus on nonsuicidal self-harm were identified, thus all studies reviewed focused on suicide prevention. Studies were predominantly descriptive and summarized the nature of the strategy and the target audience. There was no formal evaluation of program effectiveness in preventing suicide. Studies either presented strategies that supported individuals at risk of suicide (n = 8), supported professionals working with those at risk (n = 6), or attempted to improve website quality (n = 1). Although the Internet increasingly serves as an important medium for suicidal individuals, and there is concern about websites that both promote and encourage suicidal activity, there is lack of published evidence about online prevention strategies. More attention is needed in the development and evaluation of such preventative approaches.


Effects of single-dose antipurinergic therapy on behavioral and molecular alterations in the valproic acid-induced animal model of autism.
Autism spectrum disorder (ASD) is characterized by deficits in communication and social interaction, restricted interests, and stereotyped behavior. Environmental factors, such as prenatal exposure to valproic acid (VPA), may contribute to the increased risk of ASD. Since disturbed functioning of the purinergic signaling system has been associated with the onset of ASD and used as a potential therapeutic target for ASD in both clinical and preclinical studies, we analyzed the effects of suramin, a non-selective purinergic antagonist, on behavioral, molecular and immunological in an animal model of autism induced by prenatal exposure to VPA. Treatment with suramin (20 mg/kg, intraperitoneal) restored sociability in the three-chamber apparatus and decreased anxiety measured by elevated plus maze apparatus, but had no impact on decreased reciprocal social interactions or higher nociceptive threshold in VPA rats. Suramin treatment did not affect VPA-induced upregulation of P2X4 and P2Y2 receptor expression in the hippocampus, and P2X4 receptor expression in the medial prefrontal cortex, but normalized an increased level of interleukin 6 (IL-6). Our results suggest an important role of purinergic signaling modulation in behavioral, molecular, and immunological aberrations described in VPA model, and indicate that the purinergic signaling system might be a potential target for pharmacotherapy in preclinical studies of ASD.


Physical activity for people with dementia: a scoping study.
This scoping study aimed to identify how physical activity may benefit people with dementia; how and/or if current service provide these benefits; and what support they need to do so. Methods included an evidence review using literature; mapping current service provision through a survey; and in-depth interviews with a sample of service providers. The 26 studies included in the review indicated the potential effectiveness of physical activity for people with dementia, including improvements in cognition and mood, behaviour and physical condition. Mechanisms of action and the link with outcomes were poorly defined and implemented.The mapping survey and related interviews showed that service providers were delivering a range of services broadly consistent with the scientific evidence. They tended to take a holistic view of possible benefits, and focused on enjoyment and well-being, more than specific cognitive, physical and behavioural outcomes highlighted in literature. Service providers needed more evidence based information and resources to develop services and realise their potential. Despite potential benefits demonstrated in literature and practice, there is a need for further research to optimise interventions and to consider some neglected issues including delivery at home and in communities; impacts for carers; physical activities through ADLs; and individual needs. Studies are needed which take a more holistic approach to the effects of physical activity, and outcomes should be broader and include mental health and wellbeing.


p300 regulates p53-dependent apoptosis after DNA damage in colorectal cancer cells by modulation of PUMA/p21 levels.
Activation of the tumor suppressor p53 by DNA damage induces either cell cycle arrest or apoptosis, but what determines the choice between cytostasis and death is not clear. In this report, we show that the E1A-binding p300 nucleoprotein is a key determinant of p53-dependent cell fate in colorectal cancer cells: absence of p300 increases apoptosis in response to DNA damage. In addition, p300-deficient (p300(-)) cells fail to undergo G(1)/S arrest after UV irradiation. These abnormalities are associated with prolongation of p53 stability, reduced p53-acetylation, blunting of MDM2 activation, failure to transactivate p21, and a disproportionate increase in PUMA levels. When xenografted, p300(-) cells are more sensitive to chemotherapy with doxorubicin. These results show that p300 is a key regulator of the p53 response and suggest that p300 inhibition could be used to modulate chemotherapy.


Factors determining the spontaneous activation of splenic dendritic cells in culture.
Dendritic cells (DCs) serve as a link between the innate and adaptive immune systems. The activation state of DCs is crucial in this role. However, when DCs are isolated from lymphoid tissues, purified and placed in culture they undergo 'spontaneous' activation. The basis of this was explored, using up-regulation of DC surface MHC II, CD40, CD80 and CD86 as indicators of DC activation. No evidence was found for DC damage during isolation or for microbial products causing the activation. The culture activation of spleen DCs differed from that of Langerhans cells when released from E-cadherin-mediated adhesions, since E-cadherin was not detected and activation still occurred with β-catenin null DCs. Much of the activation could be attributed to DC-DC interactions. Although increases in surface MHC II levels occurred under all culture conditions tested, the increase in expression of CD40, CD80 and CD86 was much less under culture conditions where such interactions were minimised. DC-to-DC contact under the artificial conditions of high DC concentration in culture induced the production of soluble factors and these, in turn, induced the up-regulation of co-stimulatory molecules on the DC surface.


[Environmental and workers' health, within the framework of primary health care in the Brazilian National Health System (SUS): opportunities and challenges].
This paper has the purpose of contributing to the discussion of the crossing areas between Environmental Health and Workers Health, in the Brazilian context of Labor, Production, Environment and Health. This paper emerges in the context of the current organizational changes of the Brazilian National Health System (SUS), with a major focus on Primary Health Care, having in mind, also, the preparation of the 1st National Environmental Health Conference (1 feminine CNSA) to be held in December of 2009. So, historical and conceptual aspects of those fields are described in a summarized manner, as well as some shared features and expected actions of the Health System, with emphasis to the role of Primary Health Care and to the importance of the dialogue with the social movement. Finally, some topics for a common agenda were identified by the authors.


The prevalence of glaucoma in the Melbourne Visual Impairment Project.
The purpose of the study was to determine the prevalence of glaucoma in Melbourne, Australia. All subjects were participants in the Melbourne Visual Impairment Project (Melbourne VIP), a population-based prevalence study of eye disease that included residential and nursing home populations. Each participant underwent a standardized eye examination, which included a Humphrey Visual Field test, applanation tonometry, fundus examination including fundal photographs, and a medical history interview. Glaucoma status was determined by a masked assessment and consensus adjudication of visual fields, optic disc photographs, intraocular pressure, and glaucoma history. A total of 3271 persons (83% response rate) participated in the residential Melbourne VIP. The overall prevalence rate of definite primary open-angle glaucoma in the residential population was 1.7% (95% confidence limits = 1.21, 2.21). Of these, 50% had not been diagnosed previously. Only two persons (0.1%) had primary angle-closure glaucoma and six persons (0.2%) had secondary glaucoma. The prevalence of glaucoma increased steadily with age from 0.1% at ages 40 to 49 years to 9.7% in persons aged 80 to 89 years. There was no relationship with gender. The authors examined 403 (90.2% response rate) nursing home residents. The age standardized rate for this component was 2.36% (95% confidence limits = 0, 4.88). The rate of glaucoma in Melbourne rises significantly with age. With only half of patients being diagnosed, glaucoma is a major eye health problem and will become increasingly important as the population ages.


Energy drinks and youth self-reported hyperactivity/inattention symptoms.
To describe patterns in sweetened beverage consumption by race/ethnicity and sex, documenting both the amount and types of sweetened beverages consumed; and to examine the association of sweetened beverage consumption with hyperactivity/inattention symptoms among middle school students in a single urban school district. Middle school students (n = 1649; 47% Hispanic and 38% black, non-Hispanic) from 12 schools, randomly selected out of 27 district schools, completed health behavior surveys in fall 2011. Students reported quantity and types of sweetened beverages consumed in the past 24 hours and completed the 5-item Hyperactivity/Inattention subscale of the Strengths and Difficulties Questionnaire to measure symptoms. Amount and variety of reported sweetened beverage consumption (including energy drinks) were greater among boys versus girls and among black and Hispanic versus white students. Risk of hyperactivity/inattention increased by 14% for each additional sweetened beverage consumed, adjusting for age, race/ethnicity, sex, school lunch eligibility, family structure, and sugary food consumption. Students reporting consumption of energy drinks were 66% more likely to be at risk for hyperactivity/inattention after adjusting for number of drinks, other types of drinks consumed, and other potential confounders. Results support recommendations to limit consumption of sweetened beverages and to avoid consumption of energy drinks among children. Interventions to reduce sweetened beverage consumption should explicitly focus on energy drinks and other emerging sweetened beverages such as sports and sweetened coffee drinks. More research is needed to understand the direction of effects and the mechanisms behind the association between sweetened beverages and hyperactivity/inattention symptoms.


Anti-plasmodial and Chloroquine Resistance Suppressive Effects of Embelin.
Emergence of chloroquine (CQ) resistance among different strains of Plasmodium falciparum is the worst catastrophe that has ever perplexed the dedicated efforts to eradicate malaria. This urged the scientists to search for new alternatives or sensitizers to augment its antiplasmodium effect. In this experiment, the potential of embelin, isolated from Embelia ribes, to inhibit the growth and sensitize CQ action was screened using SYBRE-green-I based drug sensitivity and isobologram assays, respectively. Its effect on red blood cells stability was screened to assess its safety. To explore its molecular mechanism, its effect on plasmodial Hemozoin and the in vitro β-hematin formation was screened as well. Furthermore, its anti-oxidant activity was measured using the conventional in vitro tests and its molecular characters were obtained using Molispiration program. The results showed that its anti-plasmodial effect was weaker than CQ but synergism was obtained when they were combined at ratios lower than 5:5 CQ/embelin. Furthermore, β-hematin formation was inhibited by embelin without showing any synergism after mixing with CQ. Overall, embelin is not ideal to be suggested as a conventional antiplasmodium but it has a potential to ameliorate CQ resistance. Furthermore, its action is not related to its impact on hemozoin formation. Further, investigations are recommended to illustrate its detailed mechanism of action. Abbreviation used: CQ-DV-PBS-HEPES: Chloroquine-Digestive vacuole-Phosphate-buffer-saline-4-(2-hydroxyethyl-1-piperazin-ethan-sulphoni-acid), EDTA: Ethylen-diamin-tetra-acetic-acid, g.m.wt: Gram molecular weight, cMCM: Complete-malaria-culture-medium, Hct: Hematocrite, PRBCs: Parasitized-redblood-cells, nRBCs: Normal-red-blood-cells, RT: Room temperature, IC: Inhibitory concentration, FIC: Fractional inhibitory concentration, iCM: Incomplete-culturemedium, BSA: Bovin serum albumin, MTT: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, DPPH: 2,2-diphenyl-1- picrylhydrazy, BHT: Butylatedhydroxyl-toleuen, PSA: Polar surface area, ClogP: Log partition coefficient (octanol/water), GPCR: G-protein-coupled-receptors, DMSO: Dimethylsulphoxide, NaOH: Sodium hydroxide.


Effect of psychosocial interventions on social functioning in depression and schizophrenia: meta-analysis.
Psychosocial interventions may contribute to reducing the burden of mental disorders in low- and middle-income (LAMI) countries by improving social functioning, but the evidence has not been systematically reviewed. Systematic review and meta-analysis of the effect of psychosocial interventions on social functioning in people with depression and schizophrenia in LAMI countries. Studies were identified through database searching up to March 2011. Randomised controlled trials were included if they compared the intervention group with a control group receiving placebo or treatment as usual. Random effects meta-analyses were performed separately for depressive disorders and schizophrenia and for each intervention type. Of the studies that met the inclusion criteria (n = 24), 21 had sufficient data to include in the meta-analysis. Eleven depression trials showed good evidence for a moderate positive effect of psychosocial interventions on social functioning (standardised mean difference (SMD) = 0.46, 95% CI 0.24-0.69, n = 4009) and ten schizophrenia trials showed a large positive effect on social functioning (SMD = 0.84, 95% CI 0.49-1.19, n = 1671), although seven of these trials were of low quality. Excluding these did not substantially affect the size or direction of effect, although the precision of the estimate was substantially reduced (SMD = 0.89, 95% CI 0.05-1.72, n = 863). Psychosocial interventions delivered in out-patient and primary care settings are effective at improving social functioning in people with depression and should be incorporated into efforts to scale up services. For schizophrenia there is an absence of evidence from high-quality trials and the generalisabilty of the findings is limited by the over-representation of trials conducted in populations of hospital patients in China. More high-quality trials of psychosocial interventions for schizophrenia delivered in out-patient settings are needed.


Mutation of Aspartate 238 in FAD Synthase Isoform 6 Increases the Specific Activity by Weakening the FAD Binding.
FAD synthase (FADS, or FMN:ATP adenylyl transferase) coded by the FLAD1 gene is the last enzyme in the pathway of FAD synthesis. The mitochondrial isoform 1 and the cytosolic isoform 2 are characterized by the following two domains: the C-terminal PAPS domain (FADSy) performing FAD synthesis and pyrophosphorolysis; the N-terminal molybdopterin-binding domain (FADHy) performing a Co++/K+-dependent FAD hydrolysis. Mutations in FLAD1 gene are responsible for riboflavin responsive and non-responsive multiple acyl-CoA dehydrogenases and combined respiratory chain deficiency. In patients harboring frameshift mutations, a shorter isoform (hFADS6) containing the sole FADSy domain is produced representing an emergency protein. With the aim to ameliorate its function we planned to obtain an engineered more efficient hFADS6. Thus, the D238A mutant, resembling the D181A FMNAT "supermutant" of C. glabrata, was overproduced and purified. Kinetic analysis of this enzyme highlighted a general increase of Km, while the kcat was two-fold higher than that of WT. The data suggest that the FAD synthesis rate can be increased. Additional modifications could be performed to further improve the synthesis of FAD. These results correlate with previous data produced in our laboratory, and point towards the following proposals (i) FAD release is the rate limiting step of the catalytic cycle and (ii) ATP and FMN binding sites are synergistically connected.


Incidence of incompatible crossmatch results in dogs admitted to a veterinary teaching hospital with no history of prior red blood cell transfusion.
OBJECTIVE To determine the incidence of incompatible crossmatch results in dogs without a history of prior RBC transfusion and to evaluate changes in Hct following RBC administration for transfusion-naïve dogs that did and did not have crossmatching performed. DESIGN Retrospective study. ANIMALS 169 client-owned dogs. PROCEDURES Information obtained from the medical records included signalment, pretransfusion Hct or PCV, and crossmatching results where applicable. Dogs that underwent major crossmatching (n = 149) as part of pretransfusion screening were each crossmatched with 3 potential donors. Donor blood was obtained from a commercial source and tested negative for dog erythrocyte antigens (DEAs) 1.1, 1.2, and 7 but positive for DEA 4. Mean change in Hct after transfusion was compared between crossmatch-tested dogs (57/91 that subsequently underwent RBC transfusion) and 20 other dogs that underwent RBC transfusion without prior crossmatching by statistical methods. RESULTS 25 of 149 (17%) dogs evaluated by crossmatching were incompatible with 1 or 2 of the 3 potential donors. All 149 dogs were compatible with ≥ 1 potential donor. Mean ± SD change in Hct after transfusion was significantly higher in dogs that had crossmatching performed (12.5 ± 8.6%) than in dogs that did not undergo crossmatching (9.0 ± 4.3%). CONCLUSIONS AND CLINICAL RELEVANCE Results indicated immunologic incompatibility can exist between first-time transfusion recipients and potential blood donor dogs. The clinical importance of these findings could not be evaluated, but considering the potential for immediate or delayed hemolytic transfusion reactions or shortened RBC life span, the authors suggest veterinarians consider crossmatching all dogs prior to transfusion when possible.


Comparison of antral tap with endoscopically directed nasal culture.
The diagnosis of acute bacterial rhinosinusitis continues to generate controversy in critically ill patients. The efficacy of endoscopically directed cultures in these patients is unknown. We compared antral tap (AT) with endoscopic tissue culture (ETC) of the osteomeatal complex in an intensive care unit (ICU) setting. Twenty patients admitted to a surgical/trauma ICU were evaluated by AT and ENB for the presence of rhinosinusitis. All patients had 1) a fever of unknown origin without resolution on empiric antibiotic therapy for > or =48 hrs; 2) other sources of fever ruled out; 3) computed tomography scan evidence of mucoperiosteal thickening +/- sinus air/fluid levels; and 4) attempt at conservative treatment with topical decongestants and removal of all nasal intubation. Microbiologic data were collected and analyzed for any statistical difference between groups. A total of 29 sides underwent simultaneous tap and endoscopically directed tissue culture. The mean age was 40 years (range, 23-77 y) with 85% being males. Fifteen of 20 (75%) patients in the AT group were culture-positive. Of the 49 isolates from the AT, 55% yielded Gram-negative bacilli (Acinetobacter sp. 37%) and 45% yielded Gram-positive cocci. The ETC group was culture-positive in 18 of 20 (90%) patients. Of the 52 isolates from the ETC, Gram-negative bacilli were found in 58% (Acinetobacter sp. 33%) and 42% yielded Gram-positive cocci. The ETCs were culture-positive in all but 1 patient with positive taps. There appeared to be a concordance between AT and ETC in 60% of the patients. In five instances (25%), results of the AT or ETC changed ICU management. Two patients ultimately required sinus surgery. Sinus taps and/or endoscopically directed tissue cultures led to a change in ICU care in 25% of ICU patients studied. In patients with fever of unknown origin and computed tomography evidence of sinusitis, an antral tap continues to provide important information concerning maxillary sinusitis. However, ETC may give as good a representation of the microbiology and secondary inflammatory changes responsible for bacterial ICU rhinosinusitis causing fever of unknown origin. Further study on a larger group of patients is needed.


Summarizing disease features over time: II. Variability measures of SLEDAI-2K.
o determine if the variability of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), along with the Adjusted Mean SLEDAI-2K (AMS), can better predict major outcomes in SLE than the AMS alone. Patients were followed in the Lupus Clinic at 2-6 month intervals. Clinical and laboratory information necessary to compute the SLEDAI-2K and Systemic Lupus International Collaborating Clinics/American College of Rheumatology damage index was collected prospectively and entered onto a computerized database. Patients followed for a minimum of 3 visits, and without absence for a period > 18 consecutive months, were included in the study. Six different approaches to measure variability of SLEDAI-2K were evaluated for each visit, along with AMS. Approaches were the standard deviation, the slope, average rate of change by visit, the range, the coefficient of variation, and the Percentage of the visits with a change in SLEDAI-2K > or = 3. The SLE outcomes under study were death, presence of damage, coronary artery disease (CAD), and osteonecrosis (ON). The predictability of each outcome was evaluated through time-dependent covariate survival analyses. Regression models included other known major risk factors such as sex, age at diagnosis, SLEDAI-2K at presentation, and disease duration. Five hundred seventy-five patients seen from 1970 to 2002 were included. The average time between visits was 4.0 +/- 2.2 months. Eighty-five patients died, 325 developed damage, 55 had CAD, and 68 had ON. None of the 6 variability measures added more statistical significance in the prediction of any of the 4 outcomes. For the prediction of survival, AMS [hazard ratio (HR) = 1.16, p < 0.0001] and age at diagnosis (HR 1.05, p < 0.0001) were the only significant risk factors. For presence of damage, AMS (HR 1.06, p < 0.0001), age at diagnosis (HR 1.02, p = 0.0004), and disease duration (HR 1.05, p < 0.0001) were predictors. CAD was predicted by AMS (HR 1.12, p = 0.0003), male sex (HR 2.31, p = 0.02), age at diagnosis (HR 1.06, p < 0.0001), and disease duration (HR 1.10, p < 0.0001). For ON, SLEDAI-2K at presentation (HR 1.04, p = 0.003) and disease duration (HR 0.92, p = 0.05) were significant risk factors. Multivariate analysis revealed that AMS, independent of variability of the SLEDAI-2K, is an important predictor of major outcomes in SLE.


Interspecific variation in leaf functional and defensive traits in oak species and its underlying climatic drivers.
Plants exhibit a diverse set of functional traits and ecological strategies which reflect an adaptation process to the biotic and abiotic components of the environment. The Plant Economic Spectrum organizes these traits along a continuum from conservative to acquisitive resource use strategies and shows how the abiotic environment governs a species' position along the continuum. However, this framework does not typically account for leaf traits associated with herbivore resistance, despite fundamental metabolic links (and therefore co-variance) between resource use traits and defensive traits. Here we analyzed a suite of leaf traits associated with either resource use (specific leaf area [SLA], nutrients and water content) or defenses (phenolic compounds) for saplings of 11 species of oaks (Quercus spp.), and further investigated whether climatic variables underlie patterns of trait interspecific variation. An ordination of leaf traits revealed the primary axis of trait variation to be leaf economic spectrum traits associated with resource use (SLA, nitrogen, water content) in conjunction with a defensive trait (condensed tannins). Secondary and tertiary axes of trait variation were mainly associated with other defensive traits (lignins, flavonoids, and hydrolysable tannins). Within the primary axis we found a trade-off between resource use traits and both water content and condensed tannins; species with high SLA and leaf N values invested less in condensed tannins and viceversa. Moreover, temperature and precipitation mediated the trait space occupied by species, such that species distributed in warmer and drier climates had less leaf N, lower SLA, and more defenses (condensed tannins, lignins and flavonoids), whereas opposite values were observed for species distributed in colder and wetter climates. These results emphasize the role of abiotic controls over all-inclusive axes of trait variation and contribute to a more complete understanding of interspecific variation in plant functional strategies.


Relationships between infarct growth, clinical outcome, and early recanalization in diffusion and perfusion imaging for understanding stroke evolution (DEFUSE).
The purpose of this study was to determine the relationships between ischemic lesion growth, recanalization, and clinical response in stroke patients with and without a perfusion/diffusion mismatch. DEFUSE is an open label multicenter study in which 74 consecutive acute stroke patients were treated with intravenous tPA 3 to 6 hours after stroke onset. Magnetic resonance imaging (MRI) scans were obtained before, 3 to 6 hours after, and 30 days after treatment. Lesion growth was defined as the difference between the final infarct volume (30 day FLAIR) and the baseline diffusion lesion. Baseline MRI profiles were used to categorize 44 patients into Mismatch versus Absence of Mismatch subgroups. Early recanalization was assessed in 28 patients with an initial vessel lesion on magnetic resonance angiography. Infarct growth was compared based on whether a favorable clinical response (FCR) occurred and whether early recanalization was achieved. In the Mismatch subgroup, FCR was associated with less infarct growth P=0.03 and early recanalization was predictive of both FCR (odds ratio: 22, P=0.047) and reduced infarct growth P=0.024. There was no significant relationship between recanalization, infarct growth, and clinical outcome in the Absence of Mismatch subgroup. A threshold of <7 cc of growth had the highest sensitivity and specificity for predicting a FCR in Mismatch patients (odds ratio: 65, P=0.015, sensitivity 82%, specificity 75%). In contrast to Absence of Mismatch patients, significant associations between recanalization, reduced infarct growth, and favorable clinical response were documented in patients with a perfusion/diffusion mismatch who were treated with tPA within 3 to 6 hours after stroke onset. These findings support the Mismatch hypothesis but require validation in a larger study.


Light scattering from unclad fibers: ray theory.
Information contained in the position of the peaks of backscattered light intensity from an unclad fiber, with laser light incident at right angles to the fiber axis, is utilized to determine the parameter b/lambda (b = fiber radius, lambda free space wavelength). For known laser wavelength the fiber diameter can thus be determined. The theory is based on an approximate ray analysis and is compared with the results of the exact wave theory. Good agreement is obtained. The accuracy of this procedure may vary between 1% and 10%.


Doctors' perspectives of informed consent for non-emergency surgical procedures: a qualitative interview study.
The need to involve patients more in decisions about their care, the ethical imperative and concerns about ligation and complaints has highlighted the issue of informed consent and how it is obtained. In order for a patient to make an informed decision about their treatment, they need appropriate discussion of the risks and benefits of the treatment. To explore doctors' perspectives of gaining informed consent for routine surgical procedures. Qualitative study using semi-structured interviews selected by purposive sampling. Data were analysed thematically. Twenty doctors in two teaching hospitals in the UK. Doctors described that while consent could be taken over a series of consultations, it was common for consent to be taken immediately prior to surgery. Juniors were often taking consent when they were unfamiliar with the procedure. Doctors used a range of communication techniques to inform patients about the procedure and its risks including quantifying risks, personalizing risk, simplification of language and use of drawings. Barriers to effective consent taking were reported to be shortage of time, clinician inexperience and patients' reluctance to be involved. Current consent processes do not appear to be ideal for many doctors. In particular, junior doctors are often not confident taking consent for surgical procedures and require more support to undertake this task. This might include written information for junior staff, observation by senior colleagues when undertaking the task and ward-based communication skills teaching on consent taking.