SATB2 Shows Different Profiles Between Appendiceal Adenocarcinomas Ex Goblet Cell Carcinoids and Appendiceal/Colorectal Conventional Adenocarcinomas: An Immunohistochemical Study With Comparison to CDX2.
Special AT-rich sequence-binding protein 2 (SATB2) is a novel marker for colorectal adenocarcinomas but little is known about its expression in appendiceal adenocarcinomas. We aim to investigate SATB2 in these tumors and colorectal adenocarcinomas with comparison to CDX2. Immunohistochemical stains for SATB2 and CDX2 were performed in 49 appendiceal adenocarcinomas (23 conventional, 26 adenocarcinoma ex goblet cell carcinoids (AdexGCCs)) and 57 colorectal adenocarcinomas. Their expression was correlated with tumor differentiation and growth patterns. SATB2 staining was positive in 26/26 (100%) appendiceal AdexGCCs and 15/23 (65%) appendiceal conventional adenocarcinomas (P = 0.001). Their mean percentage of SATB2-positive cells was 93% and 34%, respectively (P < 0.0001). CDX2 staining was seen in 26/26 (100%) AdexGCCs and 22/23 (96%) appendiceal conventional adenocarcinomas (P = 0.4694). SATB2 and CDX2 showed similar staining in AdexGCCs but CDX2 labeled more tumor cells than SATB2 in conventional adenocarcinomas (mean 84% vs. 34%, P < 0.0001). SATB2 and CDX2 staining was seen in 82% (47/57) and 96% (55/57) colorectal adenocarcinomas, respectively (P = 0.01). The mean percentage of cells positive for SATB2 and CDX2 was 48% and 91%, respectively (P < 0.00001). Decreased SATB2 immunoreactivity was associated with non-glandular differentiation particularly signet ring cells in colorectal (P = 0.001) and appendiceal conventional adenocarcinomas (P = 0.04) but not in appendiceal AdexGCCs. SATB2 is a highly sensitive marker for appendiceal AdexGCCs with similar sensitivity as CDX2. In colorectal and appendiceal conventional adenocarcinomas, SATB2 is not as sensitive as CDX2 and its immunoreactivity is dependent on tumor differentiation.


The European road safety decision support system on risks and measures.
The European Road Safety Decision Support System (roadsafety-dss.eu) is an innovative system providing the available evidence on a broad range of road risks and possible countermeasures. This paper describes the scientific basis of the DSS. The structure underlying the DSS consists of (1) a taxonomy identifying risk factors and measures and linking them to each other, (2) a repository of studies, and (3) synopses summarizing the effects estimated in the literature for each risk factor and measure, and (4) an economic efficiency evaluation instrument (E3-calculator). The DSS is implemented in a modern web-based tool with a highly ergonomic interface, allowing users to get a quick overview or go deeper into the results of single studies according to their own needs.


Pain imaging in health and disease--how far have we come?
Since modern brain imaging of pain began 20 years ago, networks in the brain related to pain processing and those related to different types of pain modulation, including placebo, have been identified. Functional and anatomical connectivity of these circuits has begun to be analyzed. Imaging in patients suggests that chronic pain is associated with altered function and structural abnormalities in pain modulatory circuits. Moreover, biochemical alterations associated with chronic pain are being identified that provide information on cellular correlates as well as potential mechanisms of structural changes. Data from these brain imaging studies reinforce the idea that chronic pain leads to brain changes that could have functional significance.


Quantifying the effect of adipose tissue in muscle oximetry by near infrared spectroscopy.
Change of muscle tissue oxygen saturation (StO2), due to exercise, measured by near infrared spectroscopy (NIRS) is known to be lower for subjects with higher adipose tissue thickness. This is most likely not physiological but caused by the superficial fat and adipose tissue. In this paper we assessed, in vitro, the influence of adipose tissue thickness on muscle StO2, measured by NIRS oximeters. We measured StO2 of a liquid phantom by 3 continuous wave (CW) oximeters (Sensmart Model X-100 Universal Oximetry System, INVOS 5100C, and OxyPrem v1.3), as well as a frequency-domain oximeter, OxiplexTS, through superficial layers with 4 different thicknesses. Later, we employed the results to calibrate OxyPrem v1.3 for adipose tissue thickness in-vivo.


Human Rif1 protein binds aberrant telomeres and aligns along anaphase midzone microtubules.
We identified and characterized a human orthologue of Rif1 protein, which in budding yeast interacts in vivo with the major duplex telomeric DNA binding protein Rap1p and negatively regulates telomere length. Depletion of hRif1 by RNA interference in human cancer cells impaired cell growth but had no detectable effect on telomere length, although hRif1 overexpression in S. cerevisiae interfered with telomere length control, in a manner specifically dependent on the presence of yeast Rif1p. No localization of hRif1 on normal human telomeres, or interaction with the human telomeric proteins TRF1, TRF2, or hRap1, was detectable. However, hRif1 efficiently translocated to telomerically located DNA damage foci in response to the synthesis of aberrant telomeres directed by mutant-template telomerase RNA. The hRif1 level rose during late S/G2 but hRif1 was not visible on chromosomes in metaphase and anaphase; however, notably, specifically during early anaphase, hRif1 aligned along a subset of the midzone microtubules between the separating chromosomes. In telophase, hRif1 localized to chromosomes, and in interphase, it was intranuclear. These results define a novel subcellular localization behavior for hRif1 during the cell cycle.


Quality of Cardiovascular Disease Care in Small Urban Practices.
We wanted to describe small, independent primary care practices' performance in meeting the Million Hearts ABCSs (aspirin use, blood pressure control, cholesterol management, and smoking screening and counseling), as well as on a composite measure that captured the extent to which multiple clinical targets are achieved for patients with a history of arteriosclerotic cardiovascular disease (ASCVD). We also explored relationships between practice characteristics and ABCS measures. We conducted a cross-sectional, bivariate analysis using baseline data from 134 practices in New York City. ABCS data were extracted from practices' electronic health records and aggregated to the site level. Practice characteristics were obtained from surveys of clinicians and staff at each practice. The proportion of at-risk patients meeting clinical goals for each of the ABCS measures was 73.0% for aspirin use, 69.6% for blood pressure, 66.7% for cholesterol management, and 74.2% screened for smoking and counseled. For patients with a history of ASCVD, only 49% were meeting all ABC (aspirin use, blood pressure control, cholesterol management) targets (ie, composite measure). Solo practices were more likely to meet clinical guidelines for aspirin (risk ratio [RR] =1.17, P =.007) and composite (RR=1.29, P = .011) than practices with multiple clinicians. Achieving targets for ABCS measures varied considerably across practices; however, small practices were meeting or exceeding Million Hearts goals (ie, 70% or greater). Practices were less likely to meet consistently clinical targets that apply to patients with a history of ASCVD risk factors. Greater emphasis is needed on providing support for small practices to address the complexity of managing patients with multiple risk factors for primary and secondary ASCVD.


Annotating Logical Forms for EHR Questions.
This paper discusses the creation of a semantically annotated corpus of questions about patient data in electronic health records (EHRs). The goal is to provide the training data necessary for semantic parsers to automatically convert EHR questions into a structured query. A layered annotation strategy is used which mirrors a typical natural language processing (NLP) pipeline. First, questions are syntactically analyzed to identify multi-part questions. Second, medical concepts are recognized and normalized to a clinical ontology. Finally, logical forms are created using a lambda calculus representation. We use a corpus of 446 questions asking for patient-specific information. From these, 468 specific questions are found containing 259 unique medical concepts and requiring 53 unique predicates to represent the logical forms. We further present detailed characteristics of the corpus, including inter-annotator agreement results, and describe the challenges automatic NLP systems will face on this task.


Amyloid beta peptide induces necrosis rather than apoptosis.
Amyloid beta peptide (A beta P), a major component of Alzheimer's disease plaques, is toxic to rat pheochromocytoma PC12 cells and to rat cortical neurons. A reduction in cell survival could be detected after 24 h incubation with 0.01 to 20 microM of the 25-35 peptide fragment (beta 25-35) of A beta P. To study the mechanism of cell death induced by A beta P, the morphological as well as the biochemical features of neuronal cell death were analyzed. To distinguish between necrosis and apoptosis, PC12 cell death caused by beta 25-35 was compared to that induced by serum deprivation, a process known to be apoptotic in these cells. The DNA-degradation pattern of A beta P treated cells appeared random rather than at distinct internucleosomal sites as with apoptosis. Electron microscopic studies of NGF-treated PC12 cells and cortical primary cultures exposed to 20 microM beta 25-35 revealed immediate cellular damage such as vacuolization of the cytoplasm, breakdown of Golgi-apparatus and other membrane systems, and neurite disintegration. This was followed by total collapse of the cytoplasm and cell lysis. These data show that A beta P toxicity occurs via a necrotic rather than an apoptotic pathway.


Calcineurin mediates human tumor necrosis factor alpha gene induction in stimulated T and B cells.
The tumor necrosis factor alpha (TNF-alpha) gene is rapidly transcribed in activated T cells via a calcium-dependent pathway that does not require de novo protein synthesis, but is completely blocked by the immunosuppressive drugs cyclosporin A (CsA) and FK506. Here we show that calcineurin phosphatase activity is both necessary and sufficient for TNF-alpha gene transcription in T cells, and identify the factor that binds to the kappa 3 element of the TNF-alpha gene promoter as the target for calcineurin action. The ability of analogues of CsA and FK506 to block calcineurin phosphatase activity correlates completely with their ability to inhibit induction of TNF-alpha mRNA, induction of a TNF-alpha promoter reporter plasmid in transiently transfected T cells, and induction of the kappa 3 binding factor in an electrophoretic mobility shift assay. Moreover, a cDNA encoding the constitutively active form of calcineurin is sufficient to activate the TNF-alpha promoter and the kappa 3 element. TNF-alpha gene transcription is also highly inducible, CsA-sensitive, and protein synthesis-independent in B cells stimulated through their surface immunoglobulin receptors. Using the panel of CsA and FK506 analogues, we show that calcineurin participates in the induction of TNF-alpha transcription in activated B cells. These results extend our previous demonstration that the kappa 3 binding factor is related to NFATp, the preexisting subunit of nuclear factor of activated T cells, and suggest that calcineurin-mediated modification of the kappa 3 binding factor in T cells is of key importance in the induction of TNF-alpha transcription.


The lack of chromosomal protein Hmg1 does not disrupt cell growth but causes lethal hypoglycaemia in newborn mice.
High mobility group 1 (HMG1) protein is an abundant component of all mammalian nuclei, and related proteins exist in all eukaryotes. HMG1 binds linear DNA with moderate affinity and no sequence specificity, but bends the double helix significantly on binding through the minor groove. It binds with high affinity to DNA that is already sharply bent, such as linker DNA at the entry and exit of nucleosomes; thus, it is considered a structural protein of chromatin. HMG1 is also recruited to DNA by interactions with proteins required for basal and regulated transcriptions and V(D)J recombination. Here we generate mice harbouring deleted Hmg1. Hmg1-/- pups are born alive, but die within 24 hours due to hypoglycaemia. Hmg1-deficient mice survive for several days if given glucose parenterally, then waste away with pleiotropic defects (but no alteration in the immune repertoire). Cell lines lacking Hmg1 grow normally, but the activation of gene expression by the glucocorticoid receptor (GR, encoded by the gene Grl1) is impaired. Thus, Hmg1 is not essential for the overall organization of chromatin in the cell nucleus, but is critical for proper transcriptional control by specific transcription factors.


Monoclonal antibodies to Escherichia coli F1-ATPase. Correlation of binding site location with interspecies cross-reactivity and effects on enzyme activity.
Twenty-one hybridoma cell lines which secret antibodies to the subunits of the Escherichia coli F1-ATPase were produced. Included within the set are four antibodies which are specific for alpha, six for beta, three for gamma, four for delta and four for epsilon. The antibodies were divided into binding competition subgroups. Two such competition subgroups are represented for the alpha, beta, and epsilon subunits, one for delta and three for gamma. The ability to bind intact F1-ATPase was demonstrated for some of the antibodies to alpha and beta, and for all of those to delta, while the antibodies to gamma and epsilon gave unclear results. All of the antibodies to alpha and beta which bound ATPase were found to have effects on the ATPase activity of purified E. coli F1-ATPase. One of those to alpha inhibited activity by about 30%. Another anti-alpha was mildly stimulatory. The four antibodies to beta which bound ATPase inhibited activity by 90%. In contrast, membrane-bound ATPase was hardly affected by the antibodies to alpha, but was inhibited by 40-60% by the antibodies to beta. The other antibodies to alpha and beta bound only free subunits, or partially dissociated ATPase, suggesting that their epitopes are buried between subunits in ATPase. These antibodies had no effects on activity. The ability of the antibodies to recognize ATPase subunits present in crude extracts from mitochondria, chloroplasts, and a variety of bacteria was tested using nitrocellulose blots of sodium dodecyl sulfate-polyacrylamide gels. One anti-beta specifically recognized proteins in the range of 50,000-60,000 daltons in each of the extracts, although the reaction with mitochondrial beta was weak. Some of the other antibodies had limited cross-reaction, but most were specific for the E. coli protein. In some species, those proteins which were recognized by the anti-beta ran with a higher apparent molecular weight than proteins which were recognized by an anti-alpha. All antibodies which exhibited cross-reactivity were found to recognize sites which were not exposed in intact ATPase, implying that the surfaces which lie between subunits are most highly conserved.


Comprehensive considerations in blepharoplasty in an Asian population: a 10-year experience.
This article discusses the effectiveness, patient selection criteria, complications, and the appropriate procedures for lower blepharoplasty in an Asian population. During the past 10 years (1998-2008), a total of 2400 patients underwent lower blepharoplasty in our department. Four different types of lower-blepharoplasty procedures were performed, including the traditional transcutaneous skin flap procedure (n = 862), the transcutaneous skin-muscle flap procedure (n = 738), the transconjunctival procedure (n = 433), and Hamra's procedure (septal reset and fat-replacing technique) (n = 367). Among these 2400 patients, 925 were available for follow-up. The length of follow-up ranged between 1 month and 10 years. Most of the patients were satisfied with the result, but 32 patients had some postoperative complications, including five patients with ectropion, five with hollow eyes, two with dry eyes, and 20 with retraction. Transconjunctival blepharoplasty is the first choice for primary eyelid bags. Transcutaneous lower blepharoplasty (skin flap or skin-muscle flap procedures) is indicated for the senile eyelid with excess skin and muscles. If supporting structures (skin, muscle, and septum) show laxity and other aging stigma are present, including tear trough deformity and obvious skeleton rim, Hamra's procedure (septal reset and fat-replacing technique) is performed.


Noninvasive detection of myocardial fibrosis in arrhythmogenic right ventricular cardiomyopathy using delayed-enhancement magnetic resonance imaging.
We evaluated the role of myocardial delayed-enhancement (MDE) magnetic resonance imaging (MRI) for noninvasive detection of fibrosis in Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C). Arrhythmogenic right ventricular dysplasia/cardiomyopathy is characterized by fibro-fatty replacement of the right ventricle (RV) leading to arrhythmias and RV failure. Endomyocardial biopsy can demonstrate fibro-fatty replacement of the RV myocardium; however, the test is invasive and carries a risk of perforation. Thirty consecutive patients were prospectively evaluated for ARVD/C. Magnetic resonance imaging was performed on a 1.5-T scanner. Ten minutes after intravenous administration of 0.2 mmol/kg of gadodiamide, MDE-MRI was obtained. Diagnosis of ARVD/C was based upon the Task Force criteria and did not include MRI findings. Twelve (40%) of 30 patients met the Task Force criteria for ARVD/C. Eight (67%) of the 12 ARVD/C patients demonstrated increased signal on MDE-MRI in the RV compared with none (0%) of the 18 patients without ARVD/C (p <0.001). Endomyocardial biopsy was performed in 9 of the 12 ARVD/C patients. Of the nine patients, four had fibro-fatty changes consistent with the diagnosis of ARVD/C. Each of these patients had increased RV signal on MDE-MRI. None of the patients without ARVD/C had any abnormalities either on histopathology or on MDE-MRI. Electrophysiologic testing revealed inducible sustained ventricular tachycardia (VT) in six of the eight ARVD/C patients with delayed enhancement, compared with none of the ARVD/C patients without delayed enhancement (p=0.01). Noninvasive detection of RV myocardial fibro-fatty changes in ARVD/C is possible by MDE-MRI. Magnetic resonance imaging findings had an excellent correlation with histopathology and predicted inducible VT on programmed electrical stimulation, suggesting a possible role in evaluation and diagnosis of patients with suspected ARVD/C.


Arsenic trioxide mediates intrinsic and extrinsic pathways of apoptosis and cell cycle arrest in acute megakaryocytic leukemia.
Arsenic trioxide (ATO) induces apoptosis in a range of solid tumors and leukemia cells, and has been clinically applied for the treatment of acute promyelocytic leukemia with confirmed efficacy. Acute megakaryocytic leukemia (AMKL) is an aggressive malignancy with poor prognosis, if bone marrow transplantation is not possible. In this study, we applied flow cytometry, Western blot analysis and microarray techniques to investigate the effects of ATO on apoptosis and the cell division cycle of AMKL cell lines CHRF-288-11 and MEG-01. Our data demonstrated that ATO is a potent agent against AMKL as indicated by apoptotic markers, Annexin V and caspase-3. ATO activated the intrinsic (mitochondrial) pathway of apoptosis, which involved disrupting mitochondrial membrane potential, increased Bax/Bcl-2 ratio and caspase-9 activation, as well as the extrinsic (death receptor) pathway mediated by Fas and caspase-8 activation. We provided the first evidence that ATO stimulated expressions of CD137 mRNA and protein, which might be relevant to the extrinsic mechanism. ATO induced delays of cell cycle progression at S phase and arrest at G2/M phase of AMKL cells, but caspase-3 expression appeared not to be phase-specific. The multiple-signaling mechanism of ATO warrants it a potential agent to incorporate in the treatment regimen of AMKL.


Continuous 12-lead electrocardiographic monitoring in an emergency department chest pain unit: an assessment of potential clinical effect.
Continuous 12-lead serial ECG monitoring has been proposed to assist in the evaluation of patients with acute coronary syndrome and nondiagnostic ECG in an emergency department chest pain unit. However, the ability of serial ECG to detect acute coronary syndrome and its benefit in addition to a standard protocol has not been established. We evaluate the ability of continuous 12-lead ECG to detect acute coronary syndrome, assess the incremental benefit of the serial ECG in association with a set protocol in an ED chest pain unit, and evaluate whether serial ECG changes could be considered as prognostic factors. Patients who met Agency for Health Care Policy and Research guidelines for intermediate risk for short-term cardiovascular event unstable angina were prospectively studied in the chest pain unit. Patients were monitored with the Mortara Instruments ELI 100 STM continuous 12-lead ECG system with ST-segment analysis. ST-segment changes of greater than 100 microV in 2 or more contiguous leads or greater than 200 microV in 1 lead were considered positive. Data were compared with serial serum cardiac markers, cardiac function study results, angiographic results, and 30-day outcome results. One hundred nineteen patients had serial ECG applied. The median duration of monitoring was 4.2 hours. Forty patients were given a diagnosis of acute coronary syndrome. Chest pain unit protocol detected 52 patients, and 23 were given a diagnosis of acute coronary syndrome (sensitivity 58%; specificity 63%). Sixteen patients had ST-segment changes of greater than 100 microV or greater than 200 microV, and 9 were given a diagnosis of acute coronary syndrome. The addition of the serial ECG to the chest pain unit protocol increased the sensitivity to 65% and decreased the specificity to 58%. Two patients with ST-segment changes but none without ST-segment changes had an adverse cardiac event, yielding a sensitivity of 100% and a specificity of 88%. Serial ECG is of limited value in the diagnostic evaluation of intermediate-risk patients managed in the chest pain unit with a standard protocol. However, when ST-segment changes are present, they indicate an increased likelihood for an adverse cardiac event.


Cumulative lead exposure and prospective change in cognition among elderly men: the VA Normative Aging Study.
Lead exposure has been found to affect cognitive function in several different populations. Whether chronic low-level environmental exposure to lead results in cognitive decline among adults has not been examined. The authors assessed the relation between biomarkers of lead exposure and change in Mini-Mental State Examination (MMSE) scores in the Normative Aging Study, a cohort of elderly US men. Bone lead was measured with K-shell x-ray fluorescence. A total of 466 men aged 67.4 (standard deviation, 6.6) years took the MMSE on two occasions that were an average of 3.5 (standard deviation, 1.1) years apart during the period 1993-2001 and had bone lead concentrations measured during the period 1991-2002. A one-interquartile range (20 microg/g of bone mineral) higher patella bone lead concentration was associated with a change in MMSE score of -0.24 (95% confidence interval: -0.44, -0.05) after adjustment for age, education, smoking, alcohol intake, and time between MMSE tests. This effect is approximately equivalent to that of aging 5 years in relation to the baseline MMSE score in study data. The association with tibia lead was weaker and that with blood lead was absent. The data suggest that higher patella bone lead levels, a marker of mobilizable accumulated lead burden, are associated with a steeper decline over time in performance on the MMSE test among nonoccupationally exposed elderly men.


Follicle-stimulating hormone as a predictor for sperm retrieval rate in patients with nonobstructive azoospermia: a systematic review and meta-analysis.
Noninvasive parameters for predicating sperm retrieval rate (SRR) are desirables. Follicle-stimulating hormone (FSH) has been an important predictor since the first years of testicular sperm extraction. Recent studies showed continuous interests in FSH, with both pros and cons. Thus, we conducted a meta-analysis to evaluate the diagnostic value of FSH as a predictor for patients with nonobstructive azoospermia (NOA) taking testicular sperm retrieval. Eligible diagnosis tests were identified from electronic databases (Cochrane Central Register of Controlled Trials, Medline, and EMBASE) without language restrictions. The database search, quality assessment, and data extraction were performed independently by two reviewers. The reference standard was the sperm retrieval result. Diagnostic value of FSH were explored by area under receiver operation characteristics (ROC) curve using Review Manager, version 5.1.0 (Cochrane Collaboration, Oxford, UK) and Meta-DiSc, version 1.4. Meta regression will be done if there is heterogeneity. Then, we find 11 tests including a total of 1350 patients met the inclusion criteria. Our pooled analysis showed that the area under ROC curve of FSH was 0.72 ± 0.04. Meta regression analyses showed that region and average age have an influence on the diagnostic value. FSH showed more diagnostic value with patients in East Asia and with younger patients. We concluded that FSH had moderate value in independently predicating SRR in men with NOA (area under curve >0.7). More detailed diagnosis tests should be anticipated in the future to confirm the diagnostic value of other noninvasive parameters.


Illicit cigarette trade in the cities of Pakistan: comparing findings between the consumer and waste recycle store surveys.
Concerns about the magnitude of illicit cigarette trade have prevented the Government of Pakistan from increasing tobacco taxes. We estimated the proportion of illicit cigarettes sold in Pakistani cities. Moreover, we compared two methods for collecting cigarette packs and investigated if the illicit cigarette trade equates to tax evasion. We analysed cigarette packs collected from 10 cities of Pakistan using two methods: consumer survey based on a two-stage random sampling strategy to recruit adult smokers and photograph their cigarette packs and waste recycle store survey to purchase used cigarette packs. Cigarettes were considered illicit if any one of the following was absent from their packs: text and pictorial health warning, underage sale prohibition warning, retail price and manufacturer's name. From the consumer survey, we also estimated the proportion of smokers who purchased loose cigarettes (illegal) and packs below the minimum retail price. Taxation officers (n=4) were consulted to assess their level of confidence in judging tax evasion using the above criteria. Out of 2416 cigarette packs in the consumer survey, 454 (17.8%; 95% CI 15.4% to 20.2%) were illicit. Similarly, out of 6213 packs from waste recycle shops, 1046 (16.8%; 95% CI 15.9% to 17.7%) were illicit; the difference was not statistically significant (p=0.473). Among consumers, 29.5% bought loose cigarettes and 13.8% paid less than the minimum retail price. The taxation officers considered the manufacturer's name and retail price on cigarette packs as the most relevant criteria to detect tax evasion. One in six cigarette packs consumed in Pakistan could be illicit. These figures are far less than those propagated by the tobacco industry. Collecting packs from waste recycle stores is an efficient and valid method to estimate illicit cigarette trade.


Molecularly imprinted polymer for the specific solid-phase extraction of kirenol from Siegesbeckia pubescens herbal extract.
Molecular imprinted polymers (MIPs) were prepared by thermal polymerization using a non-covalent molecularly imprinting strategy with kirenol as the template, acrylamide (AM) as the functional monomer and ethylene glycol dimethacrylamide (EGDMA) as the cross-linker in the porogen of tetrahydrofuran (THF). The synthesized MIPs were characterized by scanning electron microscopy (SEM) and Fourier transform infrared (FT-IR). Its molecular recognition property was investigated by UV spectrogram. High-pressure liquid chromatography (HPLC) was used for analysis of target analytes. The polymers were evaluated further by batch rebinding experiments, and from the derived isotherms their binding capacity and binding strength were determined. Then the selectivity of the MIPs was checked toward the selected structurally related compounds and the recognition coefficients for kirenol, darutigenol, and ent-2-oxo-15, 16, 19-trihydroxypimar-8(14)-ene (TD) were 2.47, 3.43 and 3.40, respectively. The properties of MIPs for SPE were also evaluated. The results obtained demonstrate that the good imprinting effect and the excellent selectivity of MIPs were obtained. The optimized molecular imprinted SPE procedure was applied to extract kirenol directly from the extracts of the aerial part of Siegesbeckia pubescens herb. A selective extraction of kirenol from traditional Chinese medicine (TCM) was achieved with extraction yield of 80.9%.


Broker genes in human disease.
Genes that underlie human disease are important subjects of systems biology research. In the present study, we demonstrate that Mendelian and complex disease genes have distinct and consistent protein-protein interaction (PPI) properties. We show that five different network properties can be reduced to two independent metrics when applied to the human PPI network. These two metrics largely coincide with the degree (number of connections) and the clustering coefficient (the number of connections among the neighbors of a particular protein). We demonstrate that disease genes have simultaneously unusually high degree and unusually low clustering coefficient. Such genes can be described as brokers in that they connect many proteins that would not be connected otherwise. We show that these results are robust to the effect of gene age and inspection bias variation. Notably, genes identified in genome-wide association study (GWAS) have network patterns that are almost indistinguishable from the network patterns of nondisease genes and significantly different from the network patterns of complex disease genes identified through non-GWAS means. This suggests either that GWAS focused on a distinct set of diseases associated with an unusual set of genes or that mapping of GWAS-identified single nucleotide polymorphisms onto the causally affected neighboring genes is error prone.


The poetics of babytalk.
Caretaker-infant attachment is a complex but well-recognized adaptation in humans. An early instance of (or precursor to) attachment behavior is the dyadic interaction between adults and infants of 6 to 24 weeks, commonly called "babytalk." Detailed analysis of 1 minute of spontaneous babytalk with an 8-week infant shows that the poetic texture of the mother's speech-specifically its use of metrics, phonetics, and foregrounding-helps to shape and direct the baby's attention, as it also coordinates the partners' emotional communication. We hypothesize that the ability to respond to poetic features of language is present as early as the first few weeks of life and that this ability attunes cognitive and affective capacities in ways that provide a foundation for the skills at work in later aesthetic production and response. By linking developmental social processes with formal cognitive aspects of art, we challenge predominant views in evolutionary psychology that literary art is a superfluous byproduct of adaptive evolutionary mechanisms or primarily an ornament created by sexual selection.


Can You Diagnose the Cause of This Patient's Diarrhea?
This article will review the case of a 53-year-old female with a diagnosis of metastatic esophageal cancer receiving treatment on a clinical trial protocol combining chemotherapy/immunotherapy with FOLFOX and nivolumab, who presents to the clinic with 2 weeks of progressively worsening diarrhea. She experienced up to 12 loosely formed to watery bowel movements that were brown in color, not malodorous, and did not float. She also experienced associated abdominal pain and cramping, but denied fever, malaise, nausea, or vomiting. Vital signs were stable. Labs and CT chest, abdomen, and pelvis did not reveal a definitive cause. Dietary modification with a bland diet and loperamide did not significantly improved her symptoms.


Geochemical influences and mercury methylation of a dental wastewater microbiome.
The microbiome of dental clinic wastewater and its impact on mercury methylation remains largely unknown. Waste generated during dental procedures enters the sewer system and contributes a significant fraction of the total mercury (tHg) and methyl mercury (MeHg) load to wastewater treatment facilities. Investigating the influence of geochemical factors and microbiome structure is a critical step linking the methylating microorganisms in dental wastewater (DWW) ecosystems. DWW samples from a dental clinic were collected over eight weeks and analyzed for geochemical parameters, tHg, MeHg and bacterio-toxic heavy metals. We employed bacterial fingerprinting and pyrosequencing for microbiome analysis. High concentrations of tHg, MeHg and heavy metals were detected in DWW. The microbiome was dominated by Proteobacteria, Actinobacteria, Bacteroidetes, Chloroflexi and many unclassified bacteria. Significant correlations were found between the bacterial community, Hg levels and geochemical factors including pH and the predicted total amount (not fraction) of neutral Hg-sulfide species. The most prevalent known methylators included Desulfobulbus propionicus, Desulfovibrio desulfuricans, Desulfovibrio magneticus and Geobacter sulfurreducens. This study is the first to investigate the impact of high loads of Hg, MeHg and other heavy metals on the dental clinic wastewater microbiome, and illuminates the role of many known and unknown sulfate-reducing bacteria in Hg methylation.


Respiratory infections in the military.
Military training facilities and operational theatres, and the stressful activities undertaken in such settings, are unique. Military personnel living and working in these environments are at considerable risk of the acquisition and onward transmission of a variety of respiratory infections. While these generally cause mild illness, severe disease may occur with significant associated morbidity and, occasionally, mortality. Epidemic outbreaks among military personnel may have a significant detrimental impact on training schedules and operational effectiveness. The recognition of the burden of such illness among British military personnel, and the development of strategies required to prevent or limit negative impacts, can only be achieved through the use of comprehensive laboratory-based surveillance programmes.


MiST 3.0: an updated microbial signal transduction database with an emphasis on chemosensory systems.
Bacteria and archaea employ dedicated signal transduction systems that modulate gene expression, second-messenger turnover, quorum sensing, biofilm formation, motility, host-pathogen and beneficial interactions. The updated MiST database provides a comprehensive classification of microbial signal transduction systems. This update is a result of a substantial scaling to accommodate constantly growing microbial genomic data. More than 125 000 genomes, 516 million genes and almost 100 million unique protein sequences are currently stored in the database. For each bacterial and archaeal genome, MiST 3.0 provides a complete signal transduction profile, thus facilitating theoretical and experimental studies on signal transduction and gene regulation. New software infrastructure and distributed pipeline implemented in MiST 3.0 enable regular genome updates based on the NCBI RefSeq database. A novel MiST feature is the integration of unique profile HMMs to link complex chemosensory systems with corresponding chemoreceptors in bacterial and archaeal genomes. The data can be explored online or via RESTful API (freely available at https://mistdb.com).


Competition assays and physiological experiments of soil and phyllosphere yeasts identify Candida subhashii as a novel antagonist of filamentous fungi.
While recent advances in next generation sequencing technologies have enabled researchers to readily identify countless microbial species in soil, rhizosphere, and phyllosphere microbiomes, the biological functions of the majority of these species are unknown. Functional studies are therefore urgently needed in order to characterize the plethora of microorganisms that are being identified and to point out species that may be used for biotechnology or plant protection. Here, we used a dual culture assay and growth analyses to characterise yeasts (40 different isolates) and their antagonistic effect on 16 filamentous fungi; comprising plant pathogens, antagonists, and saprophytes. Overall, this competition screen of 640 pairwise combinations revealed a broad range of outcomes, ranging from small stimulatory effects of some yeasts up to a growth inhibition of more than 80% by individual species. On average, yeasts isolated from soil suppressed filamentous fungi more strongly than phyllosphere yeasts and the antagonistic activity was a species-/isolate-specific property and not dependent on the filamentous fungus a yeast was interacting with. The isolates with the strongest antagonistic activity were Metschnikowia pulcherrima, Hanseniaspora sp., Cyberlindnera sargentensis, Aureobasidium pullulans, Candida subhashii, and Pichia kluyveri. Among these, the soil yeasts (C. sargentensis, A. pullulans, C. subhashii) assimilated and/or oxidized more di-, tri- and tetrasaccharides and organic acids than yeasts from the phyllosphere. Only the two yeasts C. subhashii and M. pulcherrima were able to grow with N-acetyl-glucosamine as carbon source. The competition assays and physiological experiments described here identified known antagonists that have been implicated in the biological control of plant pathogenic fungi in the past, but also little characterised species such as C. subhashii. Overall, soil yeasts were more antagonistic and metabolically versatile than yeasts from the phyllosphere. Noteworthy was the strong antagonistic activity of the soil yeast C. subhashii, which had so far only been described from a clinical sample and not been studied with respect to biocontrol. Based on binary competition assays and growth analyses (e.g., on different carbon sources, growth in root exudates), C. subhashii was identified as a competitive and antagonistic soil yeast with potential as a novel biocontrol agent against plant pathogenic fungi.


On the Application of a Diffusive Memristor Compact Model to Neuromorphic Circuits.
Memristive devices have found application in both random access memory and neuromorphic circuits. In particular, it is known that their behavior resembles that of neuronal synapses. However, it is not simple to come by samples of memristors and adjusting their parameters to change their response requires a laborious fabrication process. Moreover, sample to sample variability makes experimentation with memristor-based synapses even harder. The usual alternatives are to either simulate or emulate the memristive systems under study. Both methodologies require the use of accurate modeling equations. In this paper, we present a diffusive compact model of memristive behavior that has already been experimentally validated. Furthermore, we implement an emulation architecture that enables us to freely explore the synapse-like characteristics of memristors. The main advantage of emulation over simulation is that the former allows us to work with real-world circuits. Our results can give some insight into the desirable characteristics of the memristors for neuromorphic applications.


Neighbourhood effects on body constitution-A case study of Hong Kong.
Traditional Chinese Medicine (TCM) has long perceived environment as an integral part of the development of body constitution, which is a personal state of health closely related to disease presence. Despite of the ever-growing studies on the clinical effectiveness of TCM and the scientific linking between body constitution and diseases, the geographical influence on body constitution has yet remained an unexplored territory. This study sought to investigate whether the neighbourhood environment is relevant to the composition of body type of a population through statistical multilevel and Geographic Information Systems modelling. The analysis comprised 3277 participants who had completed their body type assessment between 2009 and 2012 inclusive. The multilevel analysis also took simultaneous accounts of both individual-level (gender, age, BMI, type of housing) and area-level (percent greenery, percent road surface, total road intersection, sky view factor, temperature, relative humidity, rainfall and social deprivation index) characteristics to explain geographical variation by body types. Significant random or place effects (p < 0.001) were identified in the multilevel models. The spatial variation of body constitution involved the dynamic interplay between individual and environmental factors. The findings amassed the first scientific indications to back the common belief that place does play a role in the development of body constitution and is worthy of further investigation. By considering spatial and personal attributes simultaneously, the study can yield valuable insights into the patterning of area variation in body constitution and disease presence.


Life after Harvest: Circadian Regulation in Photosynthetic Pigments of Rocket Leaves during Supermarket Storage Affects the Nutritional Quality.
Vegetables, once harvested and stored on supermarket shelves, continue to perform biochemical adjustments due to their modular nature and their ability to retain physiological autonomy. They can live after being harvested. In particular, the content of some essential nutraceuticals, such as carotenoids, can be altered in response to environmental or internal stimuli. Therefore, in the present study, we wondered whether endogenous rhythms continue to operate in commercial vegetables and if so, whether vegetable nutritional quality could be altered by such cycles. Our experimental model consisted of rocket leaves entrained under light/darkness cycles of 12/12 h over 3 days, and then we examined free-run oscillations for 2 days under continuous light or continuous darkness, which led to chlorophyll and carotenoid oscillations in both constant conditions. Given the importance of preserving food quality, the existence of such internal rhythms during continuous conditions may open new research perspective in nutrition science. However, while chromatographic techniques employed to determine pigment composition are accurate, they are also time-consuming and expensive. Here we propose for the first time an alternative method to estimate pigment content and the nutritional quality by the use of non-destructive and in situ optical techniques. These results are promising for nutritional quality assessments.


Case reports: the use of intermaxillary screws to achieve intermaxillary fixation in the treatment of mandibular fractures.
Treatment of mandibular fractures commonly involves the use of arch bars in temporary maxillo-mandibular fixation (also called intermaxillary fixation) to aid bone plating, for the postoperative application of light elastic traction to correct minor occlusal discrepancies and intermaxillary fixation for post reduction immobilisation. The purpose of this paper is to describe a quick and simple alternative for intermaxillary fixation. Three cases of mandibular fractures are presented to demonstrate the use of intermaxillary screws instead of conventional arch-bar wiring. Two cases were treated with closed reduction methods while the other case was treated with open reduction. Subsequent fracture healing was not compromised using this technique. With careful case selection, successful treatment outcome may be achieved using this time-saving and technically simple procedure. Some of the advantages and disadvantages of the intermaxillary screws are discussed.


Inhalant use among urban American Indian youth.
To assess the prevalence of inhalant use among urban American Indian youth and to examine differences between inhalant users and non-users. Baseline (T1) self-report questionnaires completed in 5th-6th grade and at seven annual follow-up assessments (T2-T8). Seattle metropolitan area. Two hundred and twenty-four Indian youth. Youth-completed measures of substance use, ethnic self-identity, involvement in traditional Indian activities, family conflict, family history of alcoholism, peer and sibling deviance, self-esteem, delinquency, aggression, anxiety, depression, sensation seeking, conduct disorder and alcohol dependence. Lifetime inhalant use was reported by 12.3% of adolescents. At T1, inhalant users had significantly lower perceived self-worth and average annual household incomes and significantly greater density of familial alcoholism and expression of aggressive and delinquent conduct than non-users. Aggressive behavior was the most important T1 predictor of inhalant use. Lifetime conduct and alcohol dependence disorders were 3.3 and 2.6 times more prevalent among inhalant users than non-users at T5. Inhalant users had more extensive deviant peer networks, were more sensation-seeking, and evidenced lower perceived self-worth than non-users at T8. Inhalant use was less prevalent in this particular sample of urban Indian adolescents than in most studies of reservation Indian youth. As with other studies of inhalant abuse, aggressive and delinquent males of low SES and low-perceived self-worth with family histories of alcohol dependence, were at highest risk for inhalant use.


EEG sharp waves and sparse ensemble unit activity in the macaque hippocampus.
Neural unit activity and EEGs were recorded from inferior temporal regions of three rhesus macaques chronically implanted with "hyperdrives" holding 12 individually movable tetrodes. Recordings were made from each monkey over a period of approximately 3 mo, while the electrodes were moved by small increments through the hippocampus and neighboring structures. After recording, the monkeys were necropsied, and the brains were sectioned and Nissl-stained, permitting identification of individual electrode tracks. The results establish that hippocampal pyramidal cells are "complex spike cells," firing at overall average rates of approximately 0.3 Hz, with spike trains consisting of long periods of silence interspersed with bursts of activity. The results also establish that the monkey hippocampal EEG shows "sharp wave" events consisting of a high-frequency "ripple" oscillation ( approximately 110 Hz) together with a large slow-wave EEG deflection lasting several hundred milliseconds. The evidence suggests that monkey sharp waves are probably generated mainly in the CA1 region and that sharp waves are associated with an inactive/drowsy-or-sleeping behavioral state, which is also associated with increased hippocampal pyramidal cell activity and increased hippocampal EEG amplitude. The results of this initial study of ensembles of primate hippocampal neurons are consistent with previous studies in rodents and consistent with the hypothesis that theories and models of hippocampal memory function developed on the basis of rat data may be applicable to a wide range of mammalian species.


The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): case reports of 23 new patients.
To further define the clinical spectrum of the disease for pediatric and metabolic specialists, and to suggest that the general pediatrician and pediatric neurologist consider succinic semialdehyde dehydrogenase (SSADH) deficiency in the differential diagnosis of patients with (idiopathic) mental retardation and emphasize the need for accurate, quantitative organic acid analysis in such patients. The clinical features of 23 patients (20 families) with SSADH deficiency (4-hydroxybutyric acid-uria) are presented. The age at diagnosis ranged from 3 months to 25 years in the 11 male and 12 female patients; consanguinity was noted in 39% of families. The following abnormalities were observed (frequency in 23 patients): motor delay, including fine-motor skills, 78%; language delay, 78%; hypotonia, 74%; mental delay, 74%; seizures, 48%; decreased or absent reflexes, 39%; ataxia, 30%; behavioral problems, 30%; hyperkinesis, 30%; neonatal problems, 26%; and electroencephalographic abnormalities, 26%. Associated findings included psychoses, cranial magnetic resonance or computed tomographic abnormalities, and ocular problems in 22% or less of patients. Therapy with vigabatrin proved beneficial to varying degrees in 35% of the patients. Normal early development was noted in 30% of patients. Our data imply that two groups of patients with SSADH deficiency exist, differentiated by the course of early development. Our recommendation would be that accurate, quantitative organic acid analysis in an appropriate specialist laboratory be requested for any patients presenting with two or more features of mental, motor, or language delay and hypotonia of unknown cause. Such analyses are the only definitive way to diagnose SSADH deficiency; the diagnosis can be confirmed by determination of enzyme activity in white cells from whole blood. We think that increased use of organic acid determination will lead to increased diagnosis of SSADH deficiency and a more accurate representation of disease frequency. As additional patients are identified, we should have a better understanding of both the metabolic and clinical profiles of SSADH deficiency.


A prospective, randomized, double-blind study assessing the clinical impact of integrated pharmacogenomic testing for major depressive disorder.
A prospective double-blind randomized control trial (RCT) to evaluate the benefit of a combinatorial, five gene pharmacogenomic test and interpretive report (GeneSight) for the management of psychotropic medications used in the treatment of major depression in an outpatient psychiatric practice. Depressed adult outpatients were randomized to a treatment as usual (TAU, n=25) arm or a pharmacogenomic-informed GeneSight (n=26) arm. Subjects were blinded to their treatment group and depression severity was assessed by blinded study raters. Within two days of enrollment, clinicians of subjects in the guided group received the GeneSight report that categorized each of 26 psychotropic medications within a green, yellow, or red "bin" based on the relationship of each medication to a subject's pharmacokinetic and pharmacodynamic combinatorial gene variant profile. Antidepressant medication changes began within 2 weeks after baseline assessments. Depression severity was assessed by blinded study raters using the HAMD-17, PHQ-9, QIDS-SR, and QIDS-CR administered 4, 6, and 10 weeks after baseline assessment. Between-group trends were observed with greater than double the likelihood of response and remission in the GeneSight group measured by HAMD-17 at week 10. Mean percent improvement in depressive symptoms on HAMD-17 was higher for the GeneSight group over TAU (30.8% vs 20.7%; p=0.28). TAU subjects who had been prescribed medications at baseline that were contraindicated based on the individual subject's genotype (i.e., red bin) had almost no improvement (0.8%) in depressive symptoms measured by HAMD-17 at week 10, which was far less than the 33.1% improvement (p=0.06) in the pharmacogenomic guided subjects who started on a red bin medication and the 26.4% improvement in GeneSight subjects overall (p=0.08). Pharmaco-genomic-guided treatment with GeneSight doubles the likelihood of response in all patients with treatment resistant depression and identifies 30% of patients with severe gene-drug interactions who have the greatest improvement in depressive symptoms when switched to genetically suitable medication regimens.


MathDAMP: a package for differential analysis of metabolite profiles.
With the advent of metabolomics as a powerful tool for both functional and biomarker discovery, the identification of specific differences between complex metabolite profiles is becoming a major challenge in the data analysis pipeline. The task remains difficult, given the datasets' size, complexity, and common shifts in migration (elution/retention) times between samples analyzed by hyphenated mass spectrometry methods. We present a Mathematica (Wolfram Research, Inc.) package MathDAMP (Mathematica package for Differential Analysis of Metabolite Profiles), which highlights differences between raw datasets acquired by hyphenated mass spectrometry methods by applying arithmetic operations to all corresponding signal intensities on a datapoint-by-datapoint basis. Peak identification and integration is thus bypassed and the results are displayed graphically. To facilitate direct comparisons, the raw datasets are automatically preprocessed and normalized in terms of both migration times and signal intensities. A combination of dynamic programming and global optimization is used for the alignment of the datasets along the migration time dimension. The processed datasets and the results of direct comparisons between them are visualized using density plots (axes represent migration time and m/z values while peaks appear as color-coded spots) providing an intuitive overall view. Various forms of comparisons and statistical tests can be applied to highlight subtle differences. Overlaid electropherograms (chromatograms) corresponding to the vicinities of the candidate differences from any result may be generated in a descending order of significance for visual confirmation. Additionally, a standard library table (a list of m/z values and migration times for known compounds) may be aligned and overlaid on the plots to allow easier identification of metabolites. Our tool facilitates the visualization and identification of differences between complex metabolite profiles according to various criteria in an automated fashion and is useful for data-driven discovery of biomarkers and functional genomics.


Association between non-subcutaneous adiposity and calcified coronary plaque: a substudy of the Multi-Ethnic Study of Atherosclerosis.
Excessive non-subcutaneous fat deposition may impair the functions of surrounding tissues and organs through the release of inflammatory cytokines and free fatty acids. We examined the cross-sectional association between non-subcutaneous adiposity and calcified coronary plaque, a noninvasive measure of coronary artery disease burden. Participants in the Multi-Ethnic Study of Atherosclerosis underwent computed tomography (CT) assessment of calcified coronary plaque. We measured multiple fat depots in 398 white and black participants (47% men, 43% black), aged 47-86 y, from Forsyth County, NC, during 2002-2005, with the use of cardiac and abdominal CT scans. In addition to examining each depot separately, we also created a non-subcutaneous fat index with the standard scores of non-subcutaneous fat depots. A total of 219 participants (55%) were found to have calcified coronary plaque. After adjusting for demographics, lifestyle factors, and height, calcified coronary plaque was associated with a 1 SD increment in the non-subcutaneous fat index [odds ratio (OR): 1.41; 95% CI: 1.08, 1.84], pericardial fat (OR: 1.38; 95% CI: 1.04, 1.84), abdominal visceral fat (OR: 1.35; 95% CI: 1.03, 1.76) but not with fat content in the liver, intermuscular fat, or abdominal subcutaneous fat. The relation between non-subcutaneous fat index and calcified coronary plaque remained after further adjustment for abdominal subcutaneous fat (OR: 1.40; 95% CI: 1.00, 1.94). The relation did not differ by sex and ethnicity. The overall burden of non-subcutaneous fat deposition, but not abdominal subcutaneous fat, may be a correlate of coronary atherosclerosis.


Intravenous immunoglobulin for preventing infection in preterm and/or low birth weight infants.
Nosocomial infections continue to be a significant cause of morbidity and mortality among preterm and/or low birth weight (LBW) infants. Preterm infants are deficient in immunoglobulin G (IgG); therefore, administration of intravenous immunoglobulin (IVIG) may have the potential of preventing or altering the course of nosocomial infections. To use systematic review/meta-analytical techniques to determine whether IVIG administration (compared with placebo or no intervention) to preterm (< 37 weeks' postmenstrual age (PMA) at birth) or LBW (< 2500 g birth weight) infants or both is effective/safe in preventing nosocomial infection. For this update, MEDLINE, EMBASE, CINAHL, The Cochrane Library, Controlled Trials, ClinicalTrials.gov and PAS Abstracts2view were searched in May 2013. We selected randomised controlled trials (RCTs) in which a group of participants to whom IVIG was given was compared with a control group that received a placebo or no intervention for preterm (< 37 weeks' gestational age) and/or LBW (< 2500 g) infants. Studies that were primarily designed to assess the effect of IVIG on humoral immune markers were excluded, as were studies in which the follow-up period was one week or less. Data collection and analysis was performed in accordance with the methods of the Cochrane Neonatal Review Group. Nineteen studies enrolling approximately 5000 preterm and/or LBW infants met inclusion criteria. No new trials were identified in May 2013. When all studies were combined, a significant reduction in sepsis was noted (typical risk ratio (RR) 0.85, 95% confidence interval (CI) 0.74 to 0.98; typical risk difference (RD) -0.03, 95% CI 0.00 to -0.05; number needed to treat for an additional beneficial outcome (NNTB) 33, 95% CI 20 to infinity), and moderate between-study heterogeneity was reported (I2 54% for RR, 55% for RD). A significant reduction of one or more episodes was found for any serious infection when all studies were combined (typical RR 0.82, 95% CI 0.74 to 0.92; typical RD -0.04, 95% CI -0.02 to -0.06; NNTB 25, 95% CI 17 to 50), and moderate between-study heterogeneity was observed (I2 50% for RR, 62% for RD). No statistically significant differences in mortality from all causes were noted (typical RR 0.89, 95% CI 0.75 to 1.05; typical RD -0.01, 95% CI -0.03 to 0.01), and no heterogeneity for RR (I2 = 21%) or low heterogeneity for RD was documented (I2 = 28%). No statistically significant difference was seen in mortality from infection; in incidence of necrotizing enterocolitis (NEC), bronchopulmonary dysplasia (BPD) or intraventricular haemorrhage (IVH) or in length of hospital stay. No major adverse effects of IVIG were reported in any of these studies. IVIG administration results in a 3% reduction in sepsis and a 4% reduction in one or more episodes of any serious infection but is not associated with reductions in other clinically important outcomes, including mortality. Prophylactic use of IVIG is not associated with any short-term serious side effects. The decision to use prophylactic IVIG will depend on the costs and the values assigned to the clinical outcomes. There is no justification for conducting additional RCTs to test the efficacy of previously studied IVIG preparations in reducing nosocomial infections in preterm and/or LBW infants.


Preoperative hepatic artery chemoembolization followed by orthotopic liver transplantation for hepatocellular carcinoma.
In our experience, the primary obstacle precluding the widespread use of orthotopic liver transplantation (OLT) for definitive therapy of hepatocellular carcinoma (HCC), even for early-stage disease, is preventing tumor recurrence. Chemoembolization is an attractive strategy to minimize tumor progression before OLT because of its shown antitumor effect, ability to be repeated, and minimal systemic toxicity. Thus, this pilot study was undertaken to determine the tolerability and treatment outcomes of pretransplantation chemoembolization of HCC followed by OLT. Between 1992 and 1997, 27 patients with HCC who had cirrhosis, no extrahepatic metastasis, less than three tumor nodules of less than 5 cm each, and no evidence of vascular invasion on preoperative imaging studies were enrolled onto the protocol. Chemoembolization was performed using Ivalon particles with mitomycin, doxorubicin, and cisplatin. Twenty-four patients completed the protocol with chemoembolization and a liver transplant. The mean United Network of Organ Sharing waiting time was 167 days. Chemoembolization was well tolerated. On examination of the explanted liver, the majority of patients had a single lesion, mean tumor size was 3.66 cm (range, 1.5 to 6 cm), and the majority of patients had stage II disease. None of the transplant recipients has developed recurrent HCC (mean follow-up, 29.2 months; range, 9 to 55 months). The 1- and 2-year disease-free survival rates are 91% and 84%, respectively. In conclusion, chemoembolization followed by OLT is well tolerated and associated with excellent outcomes in selected patients with HCC.


What makes health systems resilient against infectious disease outbreaks and natural hazards? Results from a scoping review.
The 2014-2016 Ebola outbreak was a wake-up call regarding the critical importance of resilient health systems. Fragile health systems can become overwhelmed during public health crises, further exacerbating the human, economic, and political toll. Important work has been done to describe the general attributes of a health system resilient to these crises, and the next step will be to identify the specific capacities that health systems need to develop and maintain to achieve resiliency. We conducted a scoping review of the literature to identify recurring themes and capacities needed for health system resiliency to infectious disease outbreaks and natural hazards and any existing implementation frameworks that highlight these capacities. We also sought to identify the overlap of the identified themes and capacities with those highlighted in the World Health Organization's Joint External Evaluation. Sources of evidence included PubMed, Web of Science, OAIster, and the websites of relevant major public health organizations. We identified 16 themes of health system resilience, including: the need to develop plans for altered standards of care during emergencies, the need to develop plans for post-event recovery, and a commitment to quality improvement. Most of the literature described the general attributes of a resilient health system; no implementation frameworks were identified that could translate these elements into specific capacities that health system actors can employ to improve resilience to outbreaks and natural hazards in a variety of settings. An implementation-oriented health system resilience framework could help translate the important components of a health system identified in this review into specific capacities that actors in the health system could work to develop to improve resilience to public health crises. However, there remains a need to further refine the concept of resilience so that health systems can simultaneously achieve sustainable transformations in healthcare practice and health service delivery as well as improve their preparedness for emergencies.


Tunable complex-valued multi-tap microwave photonic filter based on single silicon-on-insulator microring resonator.
A complex-valued multi-tap tunable microwave photonic filter based on single silicon-on-insulator microring resonator is presented. The degree of tunability of the approach involving two, three and four taps is theoretical and experimentally characterized, respectively. The constraints of exploiting the optical phase transfer function of a microring resonator aiming at implementing complex-valued multi-tap filtering schemes are also reported. The trade-off between the degree of tunability without changing the free spectral range and the number of taps is studied in-depth. Different window based scenarios are evaluated for improving the filter performance in terms of the side-lobe level.


Development of Dose-Response Calibration Curve for Dicentric Chromosome Induced by X-Rays.
Chromosome aberration is a biomarker that has been used as a standard tool in biological dosimetry (biodosimetry) of individuals after exposure to ionizing radiation. It is based mainly on the induction of dicentric chromosomes - one of the radiation-induced biological effects, in order to correlate them with radiation dose. In this study, a dose calibration curve for X-rays was generated by using the dicentric assay and by fitting the data to both Chromosomal Aberration Calculation Software and Dose Estimate programs to compare the output of each method. Peripheral blood samples from four nonsmoker healthy donors were irradiated with various doses ranging from 0 to 4 Gy with 250 kV or 122 keV X-rays at a dose rate of 0.17 Gy/min. The irradiated blood was cultured, harvested, and analyzed according to the standard procedure as described by the International Atomic Energy Agency with slight modifications. The dose-response calibration data for dicentrics were fitted with the linear-quadratic model (Ydic = 0.03987D2 + 0.00651D). The dose-response calibration curve obtained in this research was comparable to other estimations with similar radiation quality and dose rates. The results in this research convinced us in sustaining a biodosimetry using a dose-response calibration curve in our laboratory.


Manipulating the appearance of a badge of status causes changes in true badge expression.
Signals of dominance and fighting ability (i.e. status signals) are found in a wide range of taxa and are used to settle disputes between competitive rivals. Most previous research has considered status-signal phenotype as an attribute of the individual; however, it is more likely that signal expression is an emergent property that also incorporates aspects of the social environment. Furthermore, because an individual's signal phenotype is likely to influence its social interactions, the relationships between status signals, social environment and individual quality are probably much more complex than previously appreciated. Here, we explore the dynamic relationship between social interactions and signal expression in a previously undescribed status signal, the frontal shield of the pukeko (Porphyrio porphyrio melanotus: Aves). We demonstrate that frontal shield size is a strong predictor of dominance status within social groups, even after controlling for potentially confounding variables. Then, we evaluate the relationship between social interactions and signal expression by testing whether manipulating apparent shield size influences (i) dominance interactions and (ii) future signal expression. By showing that decreasing apparent shield size causes both an increase in the amount of aggression received and a decrease in an individual's true shield size, we provide the first evidence of dynamic feedback between signal expression and social interactions. Our study provides important insight into the role of receiver-dependent (i.e. social) costs in maintaining signal honesty and demonstrates a unique approach to studying status signalling applicable to future studies on dynamic morphological signals.


Craniosynostosis.
Craniosynostosis, defined as the premature fusion of the cranial sutures, presents many challenges in classification and treatment. At least 20% of cases are caused by specific single gene mutations or chromosome abnormalities. This article maps out approaches to clinical assessment of a child presenting with an unusual head shape, and illustrates how genetic analysis can contribute to diagnosis and management.


Robotic-assisted Sacrocolpopexy with versus without Concomitant Midurethral Sling: A 2-year Follow-up of Urinary Symptoms and Quality of Life.
The objective of this study was to assess long-term postoperative urinary incontinence (UI) symptoms and quality of life (QOL) in patients after robotic-assisted sacrocolpopexy (RASC) with or without concomitant midurethral sling (MUS). This is a cross-sectional survey of patients comparing long-term postoperative urinary symptoms and QOL measurements in women who underwent RASC with or without MUS. We included all patients from 2011 to 2014 who had RASC with or without MUS. All patients had preoperative urodynamic testing (UDS). Patients who demonstrated stress UI on UDS underwent MUS at the time of RASC. Urinary symptoms and QOL were assessed through the validated Urinary Distress Inventory-6 (UDI-6) and Incontinence Impact Questionnaire-7 (IIQ-7) patient questionnaires. Sixty-eight patients met inclusion criteria, 46 patients completed follow-up questionnaires, and were included in the final analysis. Average length of time to follow-up from surgery was 24 months (range: 6-36 months). A statistically significant difference in UDI-6 scores between the two groups (RASC vs. RASC + MUS) was observed. Median (25th and 75th percentiles) scores for UDI-6 were 22.92 (8.33 and 32.29, respectively) for the RASC group and 4.17 (0 and 13.54, respectively) for the RASC + MUS group (P = 0.0017). Median scores for IIQ-7 were 0 (0 and 29.73 for the 25th and 75th percentiles, respectively) for the RASC group and 0 (0 and 0, respectively) for the RASC + MUS group (P = 0.1691). Patients who underwent RASC + MUS scored significantly lower on the UDI-6, indicating fewer urinary distress symptoms. Although not statistically significant, patients in the RASC + MUS group had lower IIQ-7 scores, indicating less negative impact on QOL, compared to the RASC-only group.


Nanofabrication on monocrystalline silicon through friction-induced selective etching of Si3N4 mask.
A new fabrication method is proposed to produce nanostructures on monocrystalline silicon based on the friction-induced selective etching of its Si3N4 mask. With low-pressure chemical vapor deposition (LPCVD) Si3N4 film as etching mask on Si(100) surface, the fabrication can be realized by nanoscratching on the Si3N4 mask and post-etching in hydrofluoric acid (HF) and potassium hydroxide (KOH) solution in sequence. Scanning Auger nanoprobe analysis indicated that the HF solution could selectively etch the scratched Si3N4 mask and then provide the gap for post-etching of silicon substrate in KOH solution. Experimental results suggested that the fabrication depth increased with the increase of the scratching load or KOH etching period. Because of the excellent masking ability of the Si3N4 film, the maximum fabrication depth of nanostructure on silicon can reach several microns. Compared to the traditional friction-induced selective etching technique, the present method can fabricate structures with lesser damage and deeper depths. Since the proposed method has been demonstrated to be a less destructive and flexible way to fabricate a large-area texture structure, it will provide new opportunities for Si-based nanofabrication.


Novel strain properties distinguishing sporadic prion diseases sharing prion protein genotype and prion type.
In most human sporadic prion diseases the phenotype is consistently associated with specific pairings of the genotype at codon 129 of the prion protein gene and conformational properties of the scrapie PrP (PrPSc) grossly identified types 1 and 2. This association suggests that the 129 genotype favours the selection of a distinct strain that in turn determines the phenotype. However, this mechanism cannot play a role in the phenotype determination of sporadic fatal insomnia (sFI) and a subtype of sporadic Creutzfeldt-Jakob disease (sCJD) identified as sCJDMM2, which share 129 MM genotype and PrPSc type 2 but are associated with quite distinct phenotypes. Our detailed comparative study of the PrPSc conformers has revealed major differences between the two diseases, which preferentially involve the PrPSc component that is sensitive to digestion with proteases (senPrPSc) and to a lesser extent the resistant component (resPrPSc). We conclude that these variations are consistent with two distinct strains in sFI and sCJDMM2, and that the rarer sFI is the result of a variant strain selection pathway that might be favoured by a different brain site of initial PrPSc formation in the two diseases.


In vitro and in vivo antileishmanial effects of aloe-emodin on Leishmania major.
Cutaneous leishmaniasis is a common parasitic disease that is endemic in some parts of Iran. The drugs of choice used for leishmaniasis therapy are associated with a risk of recurrence and serious adverse effects. Therefore, finding a safe and effective treatment is of great importance. In the present study, the effect of aloe-emodin on the growth of Leishmania major amastigotes was evaluated under in vitro conditions. In addition, the efficacy of a topical of aloe-emodin ointment was investigated in BALB/c mice with cutaneous leishmanial ulcers. Different concentrations (40 μg/mL, 80 μg/mL, 120 μg/mL, and 160 μg/mL) of aloe-emodin were tested on Leishmania amastigotes twice: 24 hours and 48 hours. The induced apoptosis and necrotic effects of two concentrations (40 μg/mL and 120 μg/mL) of aloe-emodin on promastigotes were investigated by flow cytometry. Under the in vivo condition, aloe-emodin ointment efficacy was evaluated at two concentrations (i.e., 0.1% and 1%). Serum indicator factors of the test and control groups were tested to evaluate the toxic effects of this compound on the liver and kidney. Results showed that aloe-emodin inhibited the growth of Leishmania amastigotes and induced apoptosis in promastigotes. Topical application of aloe-emodin ointment likewise reduced the ulcer size. No significant differences in biochemical analysis were observed between the control and treated groups. In conclusion, aloe-emodin showed antileishmanial effects under in vitro and in vivo conditions and may be used in clinical trials.


All-electron quantum Monte Carlo calculations for the noble gas atoms He to Xe.
We report all-electron variational and diffusion quantum Monte Carlo (VMC and DMC) calculations for the noble gas atoms He, Ne, Ar, Kr, and Xe. The calculations were performed using Slater-Jastrow wave functions with Hartree-Fock single-particle orbitals. The quality of both the optimized Jastrow factors and the nodal surfaces of the wave functions declines with increasing atomic number Z, but the DMC calculations are tractable and well behaved in all cases. We discuss the scaling of the computational cost of DMC calculations with Z.


Renaming COPD exacerbations: the UK respiratory nursing perspective.
Patients with COPD experience acute worsenings, termed 'exacerbations'. While other terms to describe these events have been proposed there is no consensus on terminology which has led to multiple terms being used across the UK. Respiratory nurses are part of a multi-disciplinary team managing COPD patients, however, the nursing perspective on the term 'exacerbation' is unknown. An anonymised survey of 17 questions was sent to respiratory nurses through an email invitation link. The survey link was open for one month. The aim was to understand the nurse perspective on 'exacerbation'. Alternative terms used in the UK were compared versus the term 'exacerbation'. Responses were received from 113 nurses. The majority (88%) were female. There was no consensus on preference or meaning for the term 'exacerbation' between nurses. Less than 5% of nurses thought that patients with COPD would understand the term 'exacerbation'. In ranked order, the nurses preferred the following terms: 'flare-up', 'lung attack', 'crisis', 'exacerbation' and 'chest infection'. The term 'crisis', although new, was considered to be the term that most resonated with clinical practice. Respiratory nurses in the UK report that the term 'exacerbation' is not fit for purpose for patients, and alternatives should be sought.


VirSorter2: a multi-classifier, expert-guided approach to detect diverse DNA and RNA viruses.
Viruses are a significant player in many biosphere and human ecosystems, but most signals remain "hidden" in metagenomic/metatranscriptomic sequence datasets due to the lack of universal gene markers, database representatives, and insufficiently advanced identification tools. Here, we introduce VirSorter2, a DNA and RNA virus identification tool that leverages genome-informed database advances across a collection of customized automatic classifiers to improve the accuracy and range of virus sequence detection. When benchmarked against genomes from both isolated and uncultivated viruses, VirSorter2 uniquely performed consistently with high accuracy (F1-score > 0.8) across viral diversity, while all other tools under-detected viruses outside of the group most represented in reference databases (i.e., those in the order Caudovirales). Among the tools evaluated, VirSorter2 was also uniquely able to minimize errors associated with atypical cellular sequences including eukaryotic genomes and plasmids. Finally, as the virosphere exploration unravels novel viral sequences, VirSorter2's modular design makes it inherently able to expand to new types of viruses via the design of new classifiers to maintain maximal sensitivity and specificity. With multi-classifier and modular design, VirSorter2 demonstrates higher overall accuracy across major viral groups and will advance our knowledge of virus evolution, diversity, and virus-microbe interaction in various ecosystems. Source code of VirSorter2 is freely available ( https://bitbucket.org/MAVERICLab/virsorter2 ), and VirSorter2 is also available both on bioconda and as an iVirus app on CyVerse ( https://de.cyverse.org/de ). Video abstract.


High iron requirement for growth, photosynthesis, and low-light acclimation in the coastal cyanobacterium Synechococcus bacillaris.
Iron limits carbon fixation in much of the modern ocean due to the very low solubility of ferric iron in oxygenated ocean waters. We examined iron-limitation of growth rate under varying light intensities in the coastal cyanobacterium Synechococcus bacillaris, a descendent of the oxygenic phototrophs that evolved ca. 3 billion years ago when the ocean was reducing and iron was present at much higher concentrations as soluble Fe(II). Decreasing light intensity increased the cellular iron:carbon (Fe:C) ratio needed to support a given growth rate, indicating that iron and light may co-limit the growth of Synechococcus in the ocean, as shown previously for eukaryotic phytoplankton. The cellular Fe:C ratios needed to support a given growth rate were 5- to 8-fold higher than ratios for coastal eukaryotic algae growing under the same light conditions. The higher iron requirements for growth in the coastal cyanobacterium may be largely caused by the high demand for iron in photosynthesis, and to higher ratios of iron-rich photosystem I to iron-poor photosystem II in Synechococcus than in eukaryotic algae. This high iron requirement may also be vestigial and represent an adaptation to the much higher iron levels in the ancient reducing ocean. Due to the high cellular iron requirement for photosynthesis and growth, and for low light acclimation, Synechococcus may be excluded from many low-iron and low-light environments. Indeed, it decreases rapidly with depth within the ocean's deep chlorophyll maximum (DCM) where iron and light levels are low, and lower-iron requiring picoeukaryotes typically dominate the biomass of phytoplankton community within the mid to lower DCM.


Evaluating the contributions of task expectancy in the testing and guessing benefits on recognition memory.
Recently, we have shown that two types of initial testing (recall of a list or guessing of critical items repeated over 12 study/test cycles) improved final recognition of related and unrelated word lists relative to restudy. These benefits were eliminated, however, when test instructions were manipulated within subjects and presented after study of each list, procedures designed to minimise expectancy of a specific type of upcoming test [Huff, Balota, & Hutchison, 2016. The costs and benefits of testing and guessing on recognition memory. Journal of Experimental Psychology: Learning, Memory, and Cognition, 42, 1559-1572. doi: 10.1037/xlm0000269 ], suggesting that testing and guessing effects may be influenced by encoding strategies specific for the type of upcoming task. We follow-up these experiments by examining test-expectancy processes in guessing and testing. Testing and guessing benefits over restudy were not found when test instructions were presented either after (Experiment 1) or before (Experiment 2) a single study/task cycle was completed, nor were benefits found when instructions were presented before study/task cycles and the task was repeated three times (Experiment 3). Testing and guessing benefits emerged only when instructions were presented before a study/task cycle and the task was repeated six times (Experiments 4A and 4B). These experiments demonstrate that initial testing and guessing can produce memory benefits in recognition, but only following substantial task repetitions which likely promote task-expectancy processes.


Children with cerebral palsy: severity and trends over time.
Increasingly, more very-low-birthweight infants in the developed world are now expected to survive the neonatal period than was previously the case. There are concerns that there may be a related increase in the number of infants developing severe sensorimotor impairments. Pooled data from five registers contributing to the UK Network of Cerebral Palsy Registers, Surveys and Databases were used to identify patterns of motor impairment in relation to additional impairments and to birthweight, and to assess whether prevalence of cerebral palsy (CP) by birthweight and by severity of motor impairment had changed over time. Low-birthweight infants are at greater risk of developing CP than larger-birthweight babies. The CP rate amongst children with birthweights <2500 g was significantly higher at 16 per 1000 livebirths [95% confidence interval (CI) 14.9, 16.2] than 1.2 per 1000 livebirths [95% CI 11, 1.2] for normal-birthweight children. Despite being at greater risk of developing CP, smaller-birthweight babies are proportionately less likely to develop the most severe forms of motor impairment. Of those born weighing > or = 2500 g, 23% compared with 15% weighing <1000 g (P < 0.001) were in the most severely motor impaired group. Severe motor impairment is associated with higher levels of additional impairments. CP rates for each motor impairment group in the 1990s were similar to those in the late 1970s. Rates of CP among infants born below normal birthweight are high but have decreased over time. The CP rate for infants weighing 1000-1499 g at birth decreased from around 180 per 1000 livebirths in 1979 to around 50 per 1000 livebirths from the early 1990s onwards.


Magnetic CoPt nanoparticles as MRI contrast agent for transplanted neural stem cells detection.
Neural stem cells (NSCs) exhibit features that make them suitable candidates for stem cell replacement therapy and spinal cord reconstruction. Magnetic resonance imaging (MRI) offers the potential to track cells in vivo using innovative approaches to cell labeling and image acquisition. In this study, experiments were carried out to optimize the loading condition of magnetic CoPt hollow nanoparticles (CoPt NPs) into neural stem cells and to define appropriate MRI parameters. Both cell viability and multipotency analysis showed that CoPt NPs at a concentration of 16 µg ml(-1) reduced T2 relaxation times in labeled rat NSCs, producing greater contrast on spin echo acquisitions at 4.7 T, yet did not affect cell viability and in vitro differentiation potential compared to controls. After optimizing nanoparticle loading concentrations and labeled cell numbers for MRI detection, CoPt-loaded NSCs were transplanted into organotypic spinal cord slices. The results showed that MRI could efficiently detect low numbers of CoPt-labeled NSCs with the enhanced image contrast. Our study demonstrated that MRI of grafted NSCs labeled with CoPt NPs is a useful tool to evaluate organotypic spinal cord slice models and has potential applications in other biological systems.


Smoking, passive smoking and lung cancer cell types among women in Morocco: analysis of epidemiological profiling of 101 cases.
Recently women's lung cancer mortality rates have dramatically increased in developed countries, contrasting with a levelling off or decrease among men. Descriptive epidemiological data on primary lung cancer in women is scarce in Morocco. The aim of this study, conducted in the National Institute of Oncology in Rabat, was to describe the epidemiological profiling especially for the smoking status, to determine the most frequent type of lung cancer, and to analyse the survival of Moroccan women with lung cancer diagnosis. We found 101 women among 1680 (male and female) cases of lung cancer. The never-smokers were estimated to 75 %. The proportion of adenocarcinoma among never and passive smokers was higher than that of squamous cell carcinoma (SCC) (69.4 versus 30.6 %), while among women who were smokers, the most frequent histological type was SCC (63.6 %). The Cox regression analysis showed that smoking and passive smoking were not significantly associated with survival [HR: 0.62 (95 % CI 0.31, 1.30); p = 0.19] [HR: 0.56 (95 % CI 0.29, 1.08); p = 0.08] respectively. Adenocarcinoma was significantly associated with shorter survival [HR: 1.73 (95 % CI 1.05, 2.85); p = 0.03]. The majority Moroccan women affected by lung cancer have never smoked (75 %). Environmental exposures, genetic predisposition, hormonal factors, and viral infection may all play a role in lung cancer in this category. The relation between histological type and tobacco found in our series concurred with those reported in the literature--adenocarcinoma appears to be the most frequent cell type affecting never and passive smokers. Adenocarcinoma is significantly associated with poorer survival.


The importance of elastin to aortic development in mice.
Elastin is an essential component of vertebrate arteries that provides elasticity and stores energy during the cardiac cycle. Elastin production in the arterial wall begins midgestation but increases rapidly during the last third of human and mouse development, just as blood pressure and cardiac output increase sharply. The aim of this study is to characterize the structure, hemodynamics, and mechanics of developing arteries with reduced elastin levels and determine the critical time period where elastin is required in the vertebrate cardiovascular system. Mice that lack elastin (Eln(-/-)) or have approximately one-half the normal level (Eln(+/-)) show relatively normal cardiovascular development up to embryonic day (E) 18 as assessed by arterial morphology, left ventricular blood pressure, and cardiac function. Previous work showed that just a few days later, at birth, Eln(-/-) mice die with high blood pressure and tortuous, stenotic arteries. During this period from E18 to birth, Eln(+/-) mice add extra layers of smooth muscle cells to the vessel wall and have a mean blood pressure 25% higher than wild-type animals. These findings demonstrate that elastin is only necessary for normal cardiovascular structure and function in mice starting in the last few days of fetal development. The large increases in blood pressure during this period may push hemodynamic forces over a critical threshold where elastin becomes required for cardiovascular function. Understanding the interplay between elastin amounts and hemodynamic forces in developing vessels will help design treatments for human elastinopathies and optimize protocols for tissue engineering.


American College of Rheumatology/Spondylitis Association of America/Spondyloarthritis Research and Treatment Network 2015 Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial Spondyloarthritis.
To provide evidence-based recommendations for the treatment of patients with ankylosing spondylitis (AS) and nonradiographic axial spondyloarthritis (SpA). A core group led the development of the recommendations, starting with the treatment questions. A literature review group conducted systematic literature reviews of studies that addressed 57 specific treatment questions, based on searches conducted in OVID Medline (1946-2014), PubMed (1966-2014), and the Cochrane Library. We assessed the quality of evidence using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) method. A separate voting group reviewed the evidence and voted on recommendations for each question using the GRADE framework. In patients with active AS, the strong recommendations included use of nonsteroidal antiinflammatory drugs (NSAIDs), use of tumor necrosis factor inhibitors (TNFi) when activity persists despite NSAID treatment, not to use systemic glucocorticoids, use of physical therapy, and use of hip arthroplasty for patients with advanced hip arthritis. Among the conditional recommendations was that no particular TNFi was preferred except in patients with concomitant inflammatory bowel disease or recurrent iritis, in whom TNFi monoclonal antibodies should be used. In patients with active nonradiographic axial SpA despite treatment with NSAIDs, we conditionally recommend treatment with TNFi. Other recommendations for patients with nonradiographic axial SpA were based on indirect evidence and were the same as for patients with AS. These recommendations provide guidance for the management of common clinical questions in AS and nonradiographic axial SpA. Additional research on optimal medication management over time, disease monitoring, and preventive care is needed to help establish best practices in these areas.


Therapeutic alliance in videoconferencing psychotherapy: a review.
Psychotherapy services are limited in remote and rural areas in Australia and across the globe. Videoconferencing has become well established as a feasible and acceptable mode of psychological treatment delivery. Therapeutic alliance (TA) is an essential factor underlying successful therapy across therapeutic models. In order to determine the state of knowledge regarding TA in psychotherapy via videoconferencing, a literature review was conducted on research studies that formally measured TA as primary, secondary or tertiary outcome measures over the past 23 years. The databases searched were Medline, PsycArticles, PsycINFO, PsycEXTRA and EMBASE. Searching identified 9915 articles that measured satisfaction, acceptability or therapeutic rapport, of which 23 met criteria for the review. Three studies were carried out in Australia, 11 in USA, 4 in Canada, 3 in Scotland and 2 in England. Studies overwhelmingly supported the notion that TA can be developed in psychotherapy by videoconference, with clients rating bond and presence at least equally as strongly as in-person settings across a range of diagnostic groups. Therapists also rated high levels of TA, but often not quite as high as that of their clients early in treatment. The evidence was examined in the context of important aspects of TA, including bond, presence, therapist attitudes and abilities, and client attitudes and beliefs. Barriers and facilitators of alliance were identified. Future studies should include observational measures of bond and presence to supplement self-report.


Loving-kindness meditation to enhance recovery from negative symptoms of schizophrenia.
In this article, we describe the clinical applicability of loving-kindness meditation (LKM) to individuals suffering from schizophrenia-spectrum disorders with persistent negative symptoms. LKM may have potential for reducing negative symptoms such as anhedonia, avolition, and asociality while enhancing factors consistent with psychological recovery such as hope and purpose in life. Case studies will illustrate how to conduct this group treatment with clients with negative symptoms, the potential benefits to the client, and difficulties that may arise. Although LKM requires further empirical support, it promises to be an important intervention since there are few treatments for clients afflicted with negative symptoms.


Chronic disease prevention and the politics of scale: lessons from Canadian health reform.
The authors examine the politics of health-promotion dissemination in health policy using provincial cases from the Canadian Heart Health Initiative (CHHI)-Dissemination Phase, a nationwide chronic disease prevention initiative that took place between 1994 and 2005. Drawing on an analysis of health policy documents and key informant interviews from three provincial CHHI projects, the authors highlight the challenges to incorporate health-promotion strategies oriented toward collective approaches to health within variably "individual" oriented policy climates during a time of health reform. In doing this, the authors uncover a "politics of scale" where researchers developed very different strategies to advance chronic disease prevention within a contested political terrain. What emerged were strategies unique to provincial context. Understanding the politics of scale within health policy development provides insight into how health-promotion strategies should be shaped to achieve maximum effect.


Profound duodenogastric reflux causes pancreatic growth in rats.
Although duodenogastric reflux is a physiological event, excessive reflux may be a pathogenetic factor in several diseases of the foregut, including cancer. Long term profound duodenogastric reflux produces pancreatic and gastric tumours in rats. The trophic effect of surgically induced duodenogastric reflux on the pancreas was investigated and the mechanisms involved were examined. Rats with profound reflux from a split gastroenterostomy were compared with sham operated and unoperated controls after two and six weeks. In the six week experiment, one reflux and one sham group were given the cholecystokinin (CCK) receptor antagonist devazepide (25 nmol/kg/h). Duodenogastric reflux caused a significant increase in pancreatic weight, DNA, and plasma CCK and gastrin concentrations at both two and six weeks. Devazepide substantially reduced the pancreatic weight increase after six weeks but did not abolish it completely. CCK and gastrin were not affected by devazepide. These results suggest that CCK is largely responsible for the pancreatic growth induced by reflux but another factor may also be involved. The trophic effect of duodenogastric reflux may contribute to the increased incidence of pancreatic cancer reported after gastric surgery.


The role of memantine in the treatment of major depressive disorder: Clinical efficacy and mechanisms of action.
A developing body of evidence indicates that disturbed glutamate neurotransmission especially through N-methyl-d-aspartate (NMDA) is central to the pathophysiology of major depressive disorder (MDD) and NMDA receptor antagonists have shown therapeutic potential in the MDD treatment. Memantine is an uncompetitive NMDA receptor antagonist, approved for treatment of Alzheimer's disease (AD) that in contrast to other NMDA receptor antagonists at therapeutic doses does not induce highly undesirable side effects. Neuroprotective properties and well tolerability of memantine have been attributed to its unique pharmacological features such as moderate affinity, rapid blocking kinetics and strongly voltage-dependency. In this review we summarized clinical trial evidence of antidepressant effectiveness of memantine and its mechanisms of action. Available data indicate contradictory findings relating to clinical efficacy suggesting further research is necessary in determining as to whether memantine will eventually be an advantageous therapy for MDD. Preclinical data proposed various neurobiological mechanisms underlying antidepressant-like properties of memantine that are responsible for synaptic plasticity and cell survival.


Multi-faceted palliative care intervention: aged care nurses' and care assistants' perceptions and experiences.
This paper is a report of a study to describe residential aged care nurses' and care assistants' perceptions of a multi-faceted palliative care intervention to identify potential areas to be addressed during subsequent action research phases. Action research was used to enhance the delivery of a palliative approach in residential aged care. The chronic care model guided the development of a multi-faceted intervention. This involved the: (1) establishment of a 'link nurse' role; (2) learning and development strategies for nurses, care assistants and general practitioners; (3) use of multi-disciplinary team meetings; and (4) access to specialist consultation. A purposive sample (n = 28) of aged care nurses and care assistants participated in a series of four focus groups conducted in July 2005. Thematic content analysis of the transcripts was performed. Four themes emerged: (1) targeted education can make a difference; (2) a team approach is valued; (3) clinical assessment tools are helpful; and (4) using the right language is essential. Participants described increased understanding of palliative care concepts, enhanced competencies, greater confidence to deliver palliative care and a desire to adopt a multi-disciplinary approach to care planning. Sustaining a culture that is committed to ongoing learning and development interventions and creating multi-disciplinary teams in the aged care setting is critical to embedding a palliative approach. The chronic care model is a useful framework to guide the development of interventions leading to better palliative care outcomes for residents and their families.