[Interpretation of the resonance Raman spectrum of cytochrome P-450].
Normal coordinate analysis has been carried out for the Fe(III) protoporphyrin IX dimethyl ester molecule and its vinyl deuterated analogs. All atoms of substituents were included explicitly in the calculations. On the basis of the calculation results the assignment of the resonance Raman active modes of cytochrome P-450 is given. Attention is mainly devoted to the assignment of vinyl and methyl propionate ester modes. It is shown that methyl propionate ester coordinates take part to a certain extent in the number of modes with frequencies below 1300 cm-1. The frequencies have been found which depend on the angle between the vinyl and macrocycle planes. In passing from perpendicular to in-plane conformation the theoretical frequencies of the delta (Cb C alpha C beta and delta (CCb C alpha) modes shift down by 70 and 220 cm-1 and the value of the last one is only about 110 cm-1.


Porto-biliary fistula and portal hypertension due to gallstones. A case report.
This paper reports a patient presenting with obstructive jaundice in whom a percutaneous cholangiogram demonstrated a fistula between the common bile duct and the portal vein, causing portal hypertension. The complications of gallstones are numerous but the formation of a porto-biliary fistula is extremely rare and as a cause of portal hypertension has not been previously reported.


Abortive rabies virus central nervous infection is controlled by T lymphocyte local recruitment and induction of apoptosis.
Nonfatal paralysis, induced by the attenuated Pasteur strain of rabies virus, is characterised by local and irreversible flaccid paralysis of the inoculated limbs. We characterised the spread and localisation of virus in the CNS of infected mice, determined the nature of cell injury and examined the role of the immune response. Data indicate that infection of BALB/c mice induced paralysis in 60% of infected mice, the others recovering without sequelae. In both groups of mice, virus was detected in restricted sub-populations of neurons from the brain and spinal cord, and intensity of the neuropathology correlated with levels of rabies RNA and apoptotic infected neurons. However, apoptosis of neurons and paralysis were not due to a direct deleterious effect of the virus, but induced by a T-dependent immune response, as evidenced by their absence in nude mice. Paralysed and asymptomatic mice developed a similar rabies virus-specific IgG2a antibody response, thus excluding the role of any modification of the humoral immune response. In contrast, three events were critically associated with the development of neurological symptoms: the amount of virus in the CNS, the level of apoptosis in both infected neurons and uninfected surrounding cells and the progressive parenchymal infiltration of CD4+ and CD8+ T cells at the site of infection. These data suggest that during nonfatal rabies infection, the levels of viral replication and primary degeneration of infected neurons by apoptosis could be responsible for the infiltration of T lymphocytes capable of inducing secondary degeneration of neural cells.


Phylogenetic perspectives on the evolution of functional hermaphroditism in teleost fishes.
Hermaphroditism is taxonomically widespread among teleost fishes and takes on many forms including simultaneous, protogynous, and protandrous hermaphroditism, bidirectional sex change, and androdioecy. The proximate mechanisms that influence the timing, incidence, and forms of hermaphroditism in fishes are supported by numerous theoretical and empirical studies on their mating systems and sexual patterns, but few have examined aspects of sex-allocation theory or the evolution of hermaphroditism for this group within a strict phylogenetic context. Fortunately, species-level phylogenetic reconstructions of the evolutionary history of many lineages of fishes have emerged, providing opportunities for understanding fine-scale evolutionary pathways and transformations of sex allocation. Examinations of several families of fishes with adequate data on phylogeny, patterns of sex allocation, mating systems, and with some form of hermaphroditism reveal that the evolution and expression of protogyny and other forms of sex allocation show little evidence of phylogenetic inertia within specific lineages but rather are associated with particular mating systems in accordance with prevalent theories about sex allocation. Transformations from protogyny to gonochorism in groupers (Epinephelidae), seabasses (Serranidae), and wrasses and parrotfishes (Labridae) are associated with equivalent transformations in the structure of mating groups from spawning of pairs to group spawning and related increases in sperm competition. Similarly, patterns of protandry, androdioecy, simultaneous hermaphroditism, and bidirectional sex change in other lineages (Aulopiformes, Gobiidae, and Pomacentridae) match well with particular mating systems in accordance with sex-allocation theory. Unlike other animals and plants, we did not find evidence that transitions between hermaphroditism and gonochorism required functional intermediates. Two instances in which our general conclusions might not hold include the expression of protandry in the Sparidae and the distribution of simultaneous hermaphroditism. In the Sparidae, the association of hypothesized mating systems and patterns of sex allocation were not always consistent with the size-advantage model (SAM), in that certain protandric sparids show evidence of intense sperm competition that should favor the expression of gonochorism. In the other case, simultaneous hermaphroditism does not occur in some groups of monogamous fishes, which are similar in ecology to the hermaphroditic serranines, suggesting that this form of sex allocation may be more limited by phylogenetic inertia. Overall, this work strongly supports sexual lability within teleost fishes and confirms evolutionary theories of sex allocation in this group of vertebrates.


Protective immunity induced by oral immunization with a rotavirus DNA vaccine encapsulated in microparticles.
DNA vaccines are usually given by intramuscular injection or by gene gun delivery of DNA-coated particles into the epidermis. Induction of mucosal immunity by targeting DNA vaccines to mucosal surfaces may offer advantages, and an oral vaccine could be effective for controlling infections of the gut mucosa. In a murine model, we obtained protective immune responses after oral immunization with a rotavirus VP6 DNA vaccine encapsulated in poly(lactide-coglycolide) (PLG) microparticles. One dose of vaccine given to BALB/c mice elicited both rotavirus-specific serum antibodies and intestinal immunoglobulin A (IgA). After challenge at 12 weeks postimmunization with homologous rotavirus, fecal rotavirus antigen was significantly reduced compared with controls. Earlier and higher fecal rotavirus-specific IgA responses were noted during the peak period of viral shedding, suggesting that protection was due to specific mucosal immune responses. The results that we obtained with PLG-encapsulated rotavirus VP6 DNA are the first to demonstrate protection against an infectious agent elicited after oral administration of a DNA vaccine.


Spontaneous germinal activation of quiescent Uq transposable elements in Zea mays L.
The spontaneous germinal activation of quiescent Uq transposable elements is reported. Thirty-nine spotted exceptions were observed at a rate of about 2 x 10(-4) from 687 otherwise colorless ears produced from the cross of a-ruq/a-ruq (colorless or occasionally sectored) X an a-ruq tester (colorless). All exceptions had spotting patterns distinct from the pattern of our original standard Uq (Uq1)-a-ruq spotting. From these spotted exceptions five new Uq elements (Uq2, Uq3, Uq4, Uq5 and Uq6) have been isolated. Genetic evidence for the Uq nature of the five germinal isolates is presented. First, each of the five spotted exceptions was homozygous for the a-ruq reporter allele. Second, four new Uq isolates (Uq2, Uq3, Uq4 and Uq5), after being reconstituted into a alpha degrees sh2/alpha degrees sh2 (no Uq) line, could transactivate the standard a-ruq allele and continue to produce their distinct spotting phenotypes. Third, these five new Uqs are also capable of transactivating the c-ruq65 and c-ruq67 alleles. However, the transactivation of c-ruq is generally weaker than that of a-ruq.


Sunitinib reverse multidrug resistance in gastric cancer cells by modulating Stat3 and inhibiting P-gp function.
Sunitinib, a small-molecule multi-targeted tyrosine kinase inhibitor, has been applied in phase II clinical trial as second-line treatment for advanced gastric cancer. In this study, we determined the effect of Sunitinib on the multidrug resistance in gastric cancer cells selected by vincristine. Our results showed that Sunitinib significantly enhanced the cytotoxicity of adriamycin, vincristine, etoposide, 5-Fluorouracil, and cisplatin in multidrug-resistant gastric cancer cells (SGC7901/VCR). Sunitinib significantly increased the intracellular accumulation and retention of rhodamine 123 in the SGC7901/VCR cells. However, Sunitinib, at a concentration that reverses MDR, had no significant effect on P-gp protein or mRNA expression levels. In addition, the present study revealed that Sunitinib inhibited Stat3 and down-regulated Bcl-2 in SGC7901/VCR cells, which might also contribute to the reversal of MDR. In conclusion, Sunitinib reverses multidrug resistance in gastric cancer cells by inhibiting P-gp transporter function and modulating Stat3 and Bcl-2. Further study with Sunitinib may be helpful for developing combination therapeutic strategy or circumventing gastric cancer MDR to other conventional anti-cancer drugs.


Polyethylene oxide surfaces of variable chain density by chemisorption of PEO-thiol on gold: adsorption of proteins from plasma studied by radiolabelling and immunoblotting.
The mechanisms involved in the inhibition of protein adsorption by polyethylene oxide (PEO) are not completely understood, but it is believed that PEO chain length, chain density and chain conformation all play a role. In this work, surfaces formed by chemisorption of PEO-thiol to gold were investigated: the effects of PEO chain density, chain length (600, 750, 2000 and 5000 MW) and end-group (-OH, -OCH3) on protein adsorption from plasma are reported. Similar to previous single protein adsorption studies (L.D. Unsworth et al., Langmuir 2005;21:1036-41) it was found that, of the different surfaces investigated, PEO layers formed from solutions near the cloud point adsorbed the lowest amount of fibrinogen from plasma. Layers of hydroxyl-terminated PEO of MW 600 formed under these low solubility conditions showed almost complete suppression (versus controls) of the Vroman effect, with 20+/-1 ng/cm2 adsorbed fibrinogen at the Vroman peak and 6.7+/-0.6 ng/cm2 at higher plasma concentration. By comparison, Vroman peak adsorption was 70+/-20 and 50+/-3 ng/cm2, respectively, for 750-OCH3 and 2000-OCH3 layers formed under low solubility conditions; adsorption on these surfaces at higher plasma concentration was 16+/-9 and 12+/-3 ng/cm2. Thus in addition to the effect of solution conditions noted previously, the results of this study also suggest a chain end group effect which inhibits fibrinogen adsorption to, and/or facilitates displacement from, hydroxyl terminated PEO layers. Fibrinogen adsorption from plasma was not significantly different for surfaces prepared with PEO of molecular weight 750 and 2000 when the chain density was the same ( approximately 0.5 chains/nm2) supporting the conclusion that chain density may be the key property for suppression of protein adsorption. The proteins eluted from the surfaces after contact with plasma were investigated by SDS-PAGE and immunoblotting. A number of proteins were detected on the various surfaces including fibrinogen, albumin, C3 and apolipoprotein A-I. The blot responses were zero or weak for all four proteins of the contact system; some complement activation was observed on all of the surfaces studied.


Emerging risk factors for atherosclerotic vascular disease: a critical review of the evidence.
Atherosclerotic vascular disease is an enormous public health problem. A number of emerging risk factors for atherosclerosis have recently been proposed to help identify high-risk individuals. To review the epidemiological, basic science, and clinical trial evidence concerning 4 emerging risk factors: C-reactive protein, lipoprotein(a), fibrinogen, and homocysteine. Using the terms atherosclerosis, cardiovascular disease, risk factors, prevention, screening, C-reactive protein, lipoprotein(a), fibrinogen, and homocysteine, we searched the MEDLINE database from January 1990 to January 2003. Conference proceedings, abstract booklets, bibliographies of pertinent articles and books, and personal files were hand searched to identify additional articles. Original investigations and reviews of the epidemiology of atherosclerosis and the association of conventional and novel risk factors with vascular risk were selected. On the basis of the search strategy, 373 relevant studies were identified. A diverse array of studies were examined, including randomized controlled trials, prospective cohort studies, systematic overviews, case-control, cross-sectional, and mechanistic studies. Data extraction was performed by one of the authors. The available epidemiological and basic science evidence supports, to varying degrees, independent associations between these 4 candidate risk factors and atherosclerotic vascular disease. However, there is relatively little data regarding the additive yield of screening for these factors over that of validated global risk assessment strategies currently in use. Furthermore, controlled intervention studies targeting individuals with these factors for proven risk-reduction therapies, or specifically treating these factors with available therapies, are few. The explanatory power of the major, established cardiovascular risk factors has been systematically underestimated. Although C-reactive protein, lipoprotein(a), fibrinogen, and homocysteine are associated with vascular disease risk, their optimal use in routine screening and risk stratification remains to be determined.


Leflunomide inhibits proliferation and tumorigenesis of oral squamous cell carcinoma.
Oral squamous cell carcinoma (OSCC) is the most prevalent pathological cancer occurring in the head and neck area. Progress has previously been made regarding treatment strategies of OSCC, however the 5‑year survival rate of these patients is only 50%. The present study examined if leflunomide (LEF), a drug primarily used for the treatment of rheumatoid arthritis, exhibited antitumor effects in OSCC. The results demonstrated that LEF inhibited cell proliferation and blocked the cell cycle at the S phase in OSCC cells, with upregulation of cyclin A protein expression. LEF reduced the expression of dihydroorotate dehydrogenase, which is an essential enzyme in the de novo pyrimidine biosynthetic pathway. LEF additionally inhibited colony formation in soft agar and reduced tumor growth in a xenograft model. The results suggested that LEF may act as a potential therapeutic agent in the treatment of OSCC in the future.


Structure of the lc and nmpC outer membrane porin protein genes of lambdoid bacteriophage.
The lc gene of the lambdoid bacteriophage PA-2 and the nmpC gene located on a defective lambdoid prophage in the 12-min region of the Escherichia coli K12 chromosome have been sequenced. The porin proteins encoded by these two genes were almost identical, with only 4 of the 365 residues of the precursor forms of the proteins being different. The Lc and NmpC proteins were strongly homologous to the OmpC, ompF, and PhoE proteins, with greater than 56% of the residues identical in each case. Sequencing of the region flanking the lc gene allowed precise positioning of this gene with respect to the rightward cos site of the phage and to sequences which are homologous between PA-2 and lambda. In wild-type strains of E. coli K12, the nmpC gene is not expressed and contains an IS5 insertion near the 3' end of the coding region. This insertion deletes 18 residues from the COOH terminus of NmpC protein and adds 8 residues from an open reading frame extending into IS5 sequence. Expression of this form of the gene in an expression vector plasmid demonstrated that this altered protein is still capable of being translocated to the outer membrane. Plasmid expression experiments using lc-nmpC hybrid genes show that it is the presence of the IS5 insertion which prevents expression of the porin in wild-type E. coli K12. In the nmpC mutant which expresses the protein, there has been a precise excision of the IS5 which regenerates a COOH terminus of NmpC protein which is identical to that of the Lc protein. Blot hybridization detected no mRNA transcripts from the wild-type nmpC gene, although transcripts were readily detected from the lc gene in PA-2 lysogens and from the nmpC mutant which has excised the IS5. This indicates that IS5 affects the production or stability of transcripts from the adjacent nmpC gene.


The safety of morphine use in acute coronary syndrome: a meta-analysis.
Morphine is widely used for pain control in patients with acute coronary syndrome (ACS). Several studies have questioned the safety of morphine in this setting with a concern of interaction with and reduced efficacy of antiplatelet agents. This study aims to systematically review the safety of morphine use in ACS. MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials were queried from inception through April 2018. Studies comparing morphine to nonmorphine use in ACS were included. Study endpoints included: in-hospital myocardial infarction (MI), all-cause mortality, stroke, major bleeding, minor bleeding and dyspnoea. A total of 64 323 patients with ACS were included from eight studies, seven of which were observational studies and one was a randomised controlled trial. The use of morphine was associated with increased risk of in-hospital recurrent MI (OR 1.30, 95% CI 1.18 to 1.43, p < 0.00001). There was, however, no significant difference in terms of all-cause mortality (OR 0.87, 95% CI 0.62 to 1.22, p = 0.44), stroke (OR 0.81, 95% CI 0.39 to 1.66, p = 0.57), major bleeding (OR 0.49, 95% CI 0.24 to 1.00, p = 0.05), minor bleeding (OR 0.98, 95% CI 0.41 to 2.34, p = 0.97), or dyspnoea (OR 0.55, 95% CI 0.16 to 1.83, p = 0.33). The use of morphine for pain control in ACS was associated with an increased risk of in-hospital recurrent MI. Randomised clinical trials are needed to further investigate the safety of morphine in ACS.


Association between Serum Indoxyl Sulfate Levels and Endothelial Function in Non-Dialysis Chronic Kidney Disease.
Indoxyl sulfate (IS), a product metabolized from tryptophan, is negatively correlated with renal function and cardiovascular diseases in patients with chronic kidney disease (CKD). We investigated the association between serum IS levels and endothelial function in patients with CKD. Fasting blood samples were obtained from 110 patients with stages 3-5 CKD. The endothelial function, represented by vascular reactivity index (VRI), was measured non-invasively using digital thermal monitoring. Serum IS levels were determined using liquid chromatography-mass spectrometry. Twenty-one (19.1%), 36 (32.7%), and 53 (48.2%) patients had poor (VRI < 1.0), intermediate (1.0 ≤ VRI < 2.0), and good (VRI ≥ 2.0) vascular reactivity. By univariate linear regression analysis, a higher prevalence of smoking, advanced age, higher systolic, and diastolic blood pressure (DBP), elevated levels of serum phosphorus, blood urea nitrogen, creatinine, and IS were negatively correlated with VRI values, but estimated glomerular filtration rate negatively associated with VRI values. After being adjusted by using multivariate stepwise linear regression analysis, DBP and IS levels were significantly negatively associated with VRI values in CKD patients. We concluded that IS level associated inversely with VRI values and had a modulating role in endothelial function in patients with stages 3-5 CKD.


Validation of a Pediatric Primary Care Network in a US Metropolitan Region as a Community-Based Infectious Disease Surveillance System.
This cross-sectional study used Geographic Information System methods to compare sociodemographic and clinical characteristics of children enrolled and not enrolled in a primary care network to determine the suitability of the network to estimate population-based disease rates. We validated the network surveillance system by comparing invasive pneumococcal disease rates between network and nonnetwork children using population-based surveillance data. Among the study population of 130300 children, network children were more likely to be female, Black, non-Hispanic, younger, and receive Medicaid. These differences varied across neighborhoods, however, adjusting for neighborhood characteristics did not significantly change observed differences. Rates of invasive pneumococcal disease were not significantly different between network and non-network children. Significant demographic and clinical differences existed between network and non-network children and varied over small areas. Observed population rates of an infectious disease did not significantly differ suggesting that the network can potentially provide valid disease estimates for the community population.


Effect of atriopeptin II on determinants of glomerular filtration rate in the in vitro perfused dog glomerulus.
Atrial natriuretic factor (ANF) is a peptide originally found to be present in extracts of mammalian atria that possess marked natriuretic and diuretic qualities. A number of mechanisms have been suggested to explain these properties. Recently, it has been suggested that ANF may enhance glomerular filtration. In this report, we describe a series of experiments designed to investigate if atriopeptin II, a 23-amino acid synthetic analogue of ANF, increases glomerular filtration rate (GFR) and, if so, the mechanism for this increase. We used the isolated perfused glomerulus technique (n = 6), which allows a single isolated glomerular unit to be perfused and the determinants of single-nephron GFR (SNGFR) to be measured. Two periods were performed in each experiment, the control followed by the experimental. The only difference between the two periods was the addition of atriopeptin II to the experimental perfusate at a final concentration of 5 X 10(-7) M. There was indeed a significant increase in the SNGFR (78 +/- 27 to 108 +/- 29 nl/min, P less than 0.01). This increase was associated with a significant increase in the glomerular capillary hydrostatic pressure (PGC) from 31 +/- 3 to 35 +/- 3 mmHg (P less than 0.05). The filtration fraction also increased in each experiment (from 0.16 +/- 0.3 to 0.25 +/- 0.03, P less than 0.005). Neither the afferent flow nor the efferent arteriolar flow changed, although there was a tendency for both to decrease.(ABSTRACT TRUNCATED AT 250 WORDS)


Fiber-optic multi-sensor array for detection of low concentration volatile organic compounds.
In this paper, we proposed a new type high sensitive volatile organic compounds (VOCs) gas sensor array that is based on the pulse width modulation technique. Four different types of solvatochromic dyes and two different types of polymers, were used to make the five different types of sensing membranes. These were deposited on the five side-polished optical fibers by a spin coater to make the five different sensing elements of the array. In order to ascertain the effectiveness of the sensors, five VOC gases were tested. Finally, principal component analysis (PCA) has been used to discriminates different types of VOCs.


Variability in venous gas emboli following the same dive at 3,658 meters.
Exposure to a reduction in ambient pressure such as in high-altitude climbing, flying in aircrafts, and decompression from underwater diving results in circulating vascular gas bubbles (i.e., venous gas emboli [VGE]). Incidence and severity of VGE, in part, can objectively quantify decompression stress and risk of decompression sickness (DCS) which is typically mitigated by adherence to decompression schedules. However, dives conducted at altitude challenge recommendations for decompression schedules which are limited to exposures of 10,000 feet in the U.S. Navy Diving Manual (Rev. 7). Therefore, in an ancillary analysis within a larger study, we assessed the evolution of VGE for two hours post-dive using echocardiography following simulated altitude dives at 12,000 feet. Ten divers completed two dives to 66 fsw (equivalent to 110 fsw at sea level by the Cross correction method) for 30 minutes in a hyperbaric chamber. All dives were completed following a 60-minute exposure at 12,000 feet. Following the dive, the chamber was decompressed back to altitude for two hours. Echocardiograph measurements were performed every 20 minutes post-dive. Bubbles were counted and graded using the Germonpré and Eftedal and Brubakk method, respectively. No diver presented with symptoms of DCS following the dive or two hours post-dive at altitude. Despite inter- and intra-diver variability of VGE grade following the dives, the majority (11/20 dives) presented a peak VGE Grade 0, three VGE Grade 1, one VGE Grade 2, four VGE Grade 3, and one VGE Grade 4. Using the Cross correction method for a 66-fsw dive at 12,000 feet of altitude resulted in a relatively low decompression stress and no cases of DCS.


[Diagnosis and surgical treatment of reflux esophagitis].
Operations were performed on 192 patients with reflux esophagitis, 23 of them had peptic stricture of the esophagus. Esophago-fundoplication was the main operation. Nissen's (106), Tupe (47), Belsi's (3), Dor's (5), and atypical methods were applied. Whenever indicated it was supplemented by crurorhaphy, SPV, pylorotomy, correction of the duodenal junction, etc. Resection of the esophagus (19) was performed with one-stage esophagoplasty by means of the stomach through a left thoracoabdominal approach (14), the whole stomach passed through the posterior mediastinum from an abdomino-cervical approach (2) and the whole stomach with Lewis' intrathoracic anastomosis (3). Distal gastric resection was carried out in 6 and other operations in 3 patients. The mortality was 1%. Reoperations were performed in 5 patients. The results were good in 81.2% of cases. The tactics is individualized according to the presence or absence of a stricture, its length, and localization of the upper border.


Techniques to improve physicians' use of diagnostic tests: a new conceptual framework.
To review the published literature on interventions aimed at improving physicians' testing practices and propose methodologic standards for these studies and to review selected studies using the PRECEDE framework, a behavioral model that helps categorize interventions based on which behavioral factors are being affected. MEDLINE, EMBASE, and HEALTHStar databases were searched for the years 1966 to January 1, 1998, for English-language articles pertaining to diagnostic testing behavior; bibliographies were scanned to identify articles of potential interest; and researchers in health services, health behavior, and behavior modification were contacted for proprietary and other unpublished articles. A total of 102 articles were identified that described the results of interventions aimed at changing physicians' testing practices. We included the 49 studies that compared diagnostic testing practices in intervention and control groups. Two investigators independently reviewed each article in a blinded fashion using a standard data collection form to obtain a methodologic score and to abstract the key elements of each intervention. On a 38-point methodologic criteria scale, the mean +/- SD score was 13+/-4.4. The desired behavior change was reported in the intervention group in 37 (76%) of 49 studies. Twenty-four (86%) of 28 interventions targeted at many behavioral factors were successful, while 13 (62%) of 21 studies aimed at a single behavioral factor were successful (P=.12). A majority of interventions to improve physicians' testing practices reported in the literature claimed success, with interventions based on multiple behavioral factors trending toward being more successful. While methodologic flaws hamper drawing strong conclusions from this literature, application of a behavioral framework appears to be useful in explaining interventions that are successful and can facilitate interpretation of intervention results.


The current and future uses of machine learning in ecosystem service research.
Machine learning (ML) expands traditional data analysis and presents a range of opportunities in ecosystem service (ES) research, offering rapid processing of 'big data' and enabling significant advances in data description and predictive modelling. Descriptive ML techniques group data with little or no prior domain specific assumptions; they can generate hypotheses and automatically sort data prior to other analyses. Predictive ML techniques allow for the predictive modelling of highly non-linear systems where casual mechanisms are poorly understood, as is often the case for ES. We conducted a review to explore how ML is used in ES research and to identify and quantify trends in the different ML approaches that are used. We reviewed 308 peer-reviewed publications and identified that ES studies implemented machine learning techniques in data description (64%; n = 308) and predictive modelling (44%), with some papers containing both categories. Classification and Regression Trees were the most popular techniques (60%), but unsupervised learning techniques were also used for descriptive tasks such as clustering to group or split data without prior assumptions (19%). Whilst there are examples of ES publications that apply ML with rigour, many studies do not have robust or repeatable methods. Some studies fail to report model settings (43%) or software used (28%), and many studies do not report carrying out any form of model hyperparameter tuning (67%) or test model generalisability (59%). Whilst studies use ML to analyse very large and complex datasets, ES research is generally not taking full advantage of the capacity of ML to model big data (1138 medium number of data points; 13 median quantity of variables). There is great further opportunity to utilise ML in ES research, to make better use of big data and to develop detailed modelling of spatial-temporal dynamics that meet stakeholder demands.


Can growth hormone (GH) accelerate aging? Evidence from GH-transgenic mice.
Overexpression of heterologous growth hormone (GH) in transgenic mice results in numerous phenotypic effects, including a drastically shortened life span. Early onset of pathological changes in the kidneys, glomerulosclerosis and glomerulonephritis, undoubtedly contributes to and perhaps accounts for reduced longevity of these animals. However, GH-transgenic mice exhibit various symptoms of accelerated aging, including increased astrogliosis, shortened reproductive life span, and early onset of age-related changes in cognitive function, hypothalamic neurotransmitter turnover, and plasma corticosterone levels. The hypothesis that supraphysiological levels of GH can accelerate aging derives indirect support from findings in GH-deficient and GH-resistant mutant mice in which aging is delayed and the life-span is increased and from the reciprocal relationship of body size and longevity within species.


Utilizing molecular resonance-localized surface plasmon resonance coupling for copper ion detection in plasma.
The rapid, point-of-care detection of copper in plasma can greatly aid in a large number of diseases where copper has been implicated to be an important factor, such as cancer, Alzheimer's and Diabetes mellitus. Localized surface plasmon resonance (LSPR) technologies show promise in the inexpensive detection of copper, whereas previous platforms are plagued with selectivity and sensitivity issues. Herein, we have created a sensitive and selective on-chip copper sensor which can produce a colorimetric reading in 60 minutes. The selectivity of the assay is based on 'Click' chemistry and is shown to have little interference with other metal ions present in plasma. The sensitivity of the assay is generated from the coupling of the molecular resonance of a dye and the LSPR of the gold nanoparticles. The assay is capable of measuring copper concentrations in human plasma as low as 4 μM and the linear range of sensitivity, 4 to 20 μM, is in the physiologically relevant range. This robust, colorimetric assay should prove useful in a point-of-care setting.


Using Improved Serial Blood Sampling Method of Mice to Study Pharmacokinetics and Drug-Drug Interaction.
In pharmacokinetic evaluation of mice, using serial sampling methods rather than a terminal blood sampling method could reduce the number of animals needed and lead to more reliable data by excluding individual differences. In addition, using serial sampling methods can be valuable for evaluation of the drug-drug interaction (DDI) potential of drug candidates. In this study, we established an improved method for serially sampling the blood from one mouse by only one incision of the lateral tail vein, and investigated whether our method could be adapted to pharmacokinetic and DDI studies. After intravenous and oral administration of ibuprofen and fexofenadine (BCS class II and III), the plasma concentration and pharmacokinetic parameters were evaluated by our method and a terminal blood sampling method, with the result that both methods gave comparable results (ibuprofen: 63.8±4.0% and 64.4%, fexofenadine: 6.5±0.7% and 7.9%, respectively, in bioavailability). In addition, our method could be adapted to DDI study for cytochrome P450 and organic anion transporting polypeptide inhibition. These results demonstrate that our method can be useful for pharmacokinetic evaluation from the perspective of reliable data acquisition as well as easy handling and low stress to mice and improve the quality of pharmacokinetic and DDI studies.


Lupus erythematosus panniculitis in children and adolescents.
Lupus erythematosus panniculitis (LEP) or lupus erythematosus profundus is a rare form of chronic cutaneous manifestation affecting both adults and pediatric patients. The prevalence of this manifestation was seldom reported in juvenile systemic lupus erythematosus (JSLE). From January 1983 to December 2010, 5,506 patients were followed at the Pediatric Rheumatology Unit of our University Hospital and 278 (5%) of them met the American College of Rheumatology classification criteria for JSLE. Two (0.7%) of them had LEP at JSLE onset. These two cases had tender deep inflammatory subcutaneous nodules or plaques at the time of diagnosis, and the histopathologic pattern evidenced lobular or mixed panniculitis with lymphocytic inflammatory cells of the fat lobule. Treatments for LEP included mainly antimalarials, systemic corticosteroids and sunscreen protection. One male patient required thalidomide and immunosuppressive drugs, including mycophenolate mofetil, cyclosporin and intravenous cyclophosphamide. However, skin lesions improved only after rituximab treatment. LEP was rarely observed in our cohort of JSLE patients as the first lupus manifestation. Anti-CD20 monoclonal antibody therapy may be an option for refractory LEP treatment in children.


Feedback GAP: study protocol for a cluster-randomized trial of goal setting and action plans to increase the effectiveness of audit and feedback interventions in primary care.
Audit and feedback to physicians is commonly used alone or as part of multifaceted interventions. While it can play an important role in quality improvement, the optimal design of audit and feedback is unknown. This study explores how feedback can be improved to increase acceptability and usability in primary care. The trial seeks to determine whether a theory-informed worksheet appended to feedback reports can help family physicians improve quality of care for their patients with diabetes and/or ischemic heart disease. Two-arm cluster trial was conducted with participating primary care practices allocated using minimization to simple feedback or enhanced feedback group. The simple feedback group receives performance feedback reports every six months for two years regarding the proportion of their patients with diabetes and/or ischemic heart disease who are meeting quality targets. The enhanced feedback group receives these same reports as well as a theory-informed worksheet designed to facilitate goal setting and action plan development in response to the feedback reports. Participants are family physicians from across Ontario who use electronic medical records; data for rostered patients are used to produce the feedback reports and for analysis. The primary disease outcomes are the blood pressure (BP), and low-density lipoprotein cholesterol (LDL) levels. The primary process measure is a composite score indicating the number of recommended activities (e.g., tests and prescriptions) conducted by the family physicians for their patients with diabetes and/or ischemic heart disease within the appropriate timeframe. Secondary outcomes are the proportion of patients whose results meet targets for glucose, LDL, and BP as well as the percent of patients receiving relevant prescriptions. A qualitative process evaluation using semi-structured interviews will explore perceived barriers to behaviour change in response to feedback reports and preferences with regard to feedback design. Intention-to-treat approach will be used to analyze the trial. Analysis will be performed on patient-level variables using generalized estimating equation models to adjust for covariates and account for the clustered nature of the data. The trial is powered to show small, but clinically important differences of 7 mmHG in systolic BP and 0.32 mmol/L in LDL. ClinicalTrials.gov NCT00996645.


The Role of ATRX in the Alternative Lengthening of Telomeres (ALT) Phenotype.
Telomeres are responsible for protecting chromosome ends in order to prevent the loss of coding DNA. Their maintenance is required for achieving immortality by neoplastic cells and can occur by upregulation of the telomerase enzyme or through a homologous recombination-associated process, the alternative lengthening of telomeres (ALT). The precise mechanisms that govern the activation of ALT or telomerase in tumor cells are not fully understood, although cellular origin may favor one of the other mechanisms that have been found thus far in mutual exclusivity. Specific mutational events influence ALT activation and maintenance: a unifying frequent feature of tumors that acquire this phenotype are the recurrent mutations of the Alpha Thalassemia/Mental Retardation Syndrome X-Linked (ATRX) or Death-Domain Associated Protein (DAXX) genes. This review summarizes the established criteria about this phenotype: its prevalence, theoretical molecular mechanisms and relation with ATRX, DAXX and other proteins (directly or indirectly interacting and resulting in the ALT phenotype).


Establishing clinical severity for PROMIS® measures in adult patients with rheumatic diseases.
Different patient-reported outcome (PRO) measures are used for rheumatic diseases (RD). The aims of this study are-(1) Identify PROMIS® domains most relevant to care of patients with RD, (2) Collect T-Score metrics in patients with RD, and (3) Identify clinically meaningful cut-points for these domains. A convenience sample of RD patients was recruited consecutively during clinic visits, and asked to complete computer-adaptive tests on thirteen Patient-Reported Outcomes Measurement Information System (PROMIS®) instruments. Based on discussion with clinical providers, four measures were chosen to be relevant and actionable (from rheumatologists' perspective) in RD patients. Data from RD patients were used to develop clinical vignettes across a range of symptom severity. Vignettes were created based on most likely item responses at different levels on the T-score metric (mean = 50; SD = 10) and anchored at 5-point intervals (0.5 SDs). Patients with RD (N = 9) and clinical providers (N = 10) participated as expert panelists in separate one-day meetings using a modified educational standard setting method. Four domains (physical function, pain interferences, sleep disturbance, depression) that are actionable at the point-of-care were selected. For all domains, patients endorsed cut-points at lower levels of impairment than providers by 0.5 to 1 SD (e.g., severe impairment in physical function was defined as a T-score of 35 by patients and 25 by providers). We used a modified educational method to estimate clinically relevant cut-points to classify severity for PROMIS measures This allows for meaningful interpretation of PROMIS® measures in a clinical setting of RD population.


FusionScan: accurate prediction of fusion genes from RNA-Seq data.
Identification of fusion gene is of prominent importance in cancer research field because of their potential as carcinogenic drivers. RNA sequencing (RNA-Seq) data have been the most useful source for identification of fusion transcripts. Although a number of algorithms have been developed thus far, most programs produce too many false-positives, thus making experimental confirmation almost impossible. We still lack a reliable program that achieves high precision with reasonable recall rate. Here, we present FusionScan, a highly optimized tool for predicting fusion transcripts from RNA-Seq data. We specifically search for split reads composed of intact exons at the fusion boundaries. Using 269 known fusion cases as the reference, we have implemented various mapping and filtering strategies to remove false-positives without discarding genuine fusions. In the performance test using three cell line datasets with validated fusion cases (NCI-H660, K562, and MCF-7), FusionScan outperformed other existing programs by a considerable margin, achieving the precision and recall rates of 60% and 79%, respectively. Simulation test also demonstrated that FusionScan recovered most of true positives without producing an overwhelming number of false-positives regardless of sequencing depth and read length. The computation time was comparable to other leading tools. We also provide several curative means to help users investigate the details of fusion candidates easily. We believe that FusionScan would be a reliable, efficient and convenient program for detecting fusion transcripts that meet the requirements in the clinical and experimental community. FusionScan is freely available at http://fusionscan.ewha.ac.kr/.


Kin cell lysis is a danger signal that activates antibacterial pathways of Pseudomonas aeruginosa.
The perception and response to cellular death is an important aspect of multicellular eukaryotic life. For example, damage-associated molecular patterns activate an inflammatory cascade that leads to removal of cellular debris and promotion of healing. We demonstrate that lysis of Pseudomonas aeruginosa cells triggers a program in the remaining population that confers fitness in interspecies co-culture. We find that this program, termed P. aeruginosa response to antagonism (PARA), involves rapid deployment of antibacterial factors and is mediated by the Gac/Rsm global regulatory pathway. Type VI secretion, and, unexpectedly, conjugative type IV secretion within competing bacteria, induce P. aeruginosa lysis and activate PARA, thus providing a mechanism for the enhanced capacity of P. aeruginosa to target bacteria that elaborate these factors. Our finding that bacteria sense damaged kin and respond via a widely distributed pathway to mount a complex response raises the possibility that danger sensing is an evolutionarily conserved process.


Do macroeconomic contractions induce or 'harvest' suicides? A test of competing hypotheses.
Researchers often invoke a mortality displacement or 'harvesting' mechanism to explain mortality patterns, such that those with underlying health vulnerabilities die sooner than expected in response to environmental phenomena, such as heat waves, cold spells and air pollution. It is unclear if this displacement mechanism might also explain observed increases in suicide following economic contraction, or if suicides are induced in persons otherwise unlikely to engage in self-destructive behaviour. Here, we test two competing hypotheses explaining an observed increase in suicides following unemployment-induction or displacement. We apply time series methods to monthly suicide and unemployment data from Sweden for the years 2000-2011. Tests are conducted separately for working age (20-64 years old) men and women as well as older (aged 65 years and older) men and women. Displacement appeared among older men and women; an unexpected rise in unemployment predicted an increase in suicides 6 months later, followed by a significant decrease 8 months later. Induction appeared among working age men, but not among working age women; an unexpected rise in unemployment predicted an increase in suicides 4-6 months later. Displacement and induction both appear to have operated following unexpected labour market contractions in Sweden, though with different population segments.


Sparse electromagnetic source imaging using EEG and MEG.
The present study proposed the combined use of EEG and MEG data in a new sparse electromagnetic source imaging (ESI) technique, i.e., variation-based sparse cortical current density (VB-SCCD) method. Monte Carlo simulations were conducted to investigate the performance of the proposed approach in multiple extended brain activations (up to ten) that were randomly generated. Experimental EEG and MEG data from a face recognition task were further used to evaluate the performance of VB-SCCD. The present results indicate that the proposed approach can accurately reconstruct multiple brain activations and their spatial extents. The source imaging results from real data further demonstrate it is capable to recover networked brain activations involving multiple cortical regions, which are consistent with results from functional magnetic resonance imaging in same task paradigm. The present results further indicate the capability of the proposed approach in reconstructing deep brain sources and temporal dynamics of brain sources at millisecond resolutions. It thus suggests that sparse ESI using combined EEG and MEG is a promising technique probing detailed spatiotemporal brain activations.


Antimicrobial sensitivity patterns of Haemophilus pleuropneumoniae isolates from pigs with pneumonia.
Antimicrobial sensitivity patterns were determined for 53 isolates of Haemophilus pleuropneumoniae from pneumonic porcine lung tissue. All strains were sensitive to chloramphenicol, gentamicin, spectinomycin, and sulfachlorpyridazine. Other antimicrobials tested had less efficacy for in vitro inhibition of H pleuropneumoniae.


Molecular changes associated with escitalopram response in a stress-based model of depression.
Converging evidence points at hypothalamus-pituitary-adrenal (HPA) axis hyperactivity and neuroinflammation as important factors involved in the etiopathogenesis of major depressive disorder (MDD) and in therapeutic efficacy of antidepressants. In this study, we examined the molecular effects associated with a response to a week-long treatment with escitalopram in the chronic escape deficit (CED) model, a validated model of depression based on the induction of an escape deficit after exposure of rats to an unavoidable stress. We confirmed our previous result that a treatment with escitalopram (10mg/kg) was effective after 7days in reverting the stress-induced escape deficit in approximately 50% of the animals, separating responders from non-responders. Expression of markers of HPA axis functionality as well as several inflammatory mediators were evaluated in the hypothalamus, a key structure integrating signals from the neuro, immune, endocrine systems. In the hypothalamus of responder animals we observed a decrease in the expression of CRH and its receptors and an increase in GR protein in total and nuclear extracts; this effect was accompanied by a significant decrease in circulating corticosterone in the same cohort. Hypothalamic IL-1β and TNFα expression were increased in stressed animals, while CXCL2, IL-6, and ADAM17 mRNA levels were decreased in escitalopram treated rats regardless of the treatment response. These data suggest that efficacy of a one week treatment with escitalopram may be partially mediated by a decrease HPA axis activity, while in the hypothalamus the drug-induced effects on the expression of immune modulators did not correlate with the behavioural outcome.


Applying the antecedent, behaviour, and consequence taxonomy to unintentional firearm injury as determined by a collaborative firearm injury database.
Unintentional firearm injury (UFI) remains a significant problem in the USA with respect to preventable injury and death. The antecedent, behaviour and consequence (ABC) taxonomy has been used by law enforcement agencies to evaluate unintentional firearm discharge. Using an adapted ABC taxonomy, we sought to categorise civilian UFI in our community to identify modifiable behaviours. Using a collaborative firearm injury database (containing both a university-based level 1 trauma registry and a metropolitan law enforcement database), all UFIs from August 2008 through December 2021 were identified. Perceived threat (antecedent), behaviour and injured party (consequence) were identified for each incident. During the study period, 937 incidents of UFI were identified with 64.2% of incidents occurring during routine firearm tasks. 30.4% of UFI occurred during neglectful firearm behaviour such as inappropriate storage. Most injuries occurred under situations of low perceived threat. UFI involving children was most often due to inappropriate storage of weapons, while cleaning a firearm was the most common behaviour in adults. Overall, 16.5% of UFI involved injury to persons other than the one handling the weapon and approximately 1.3% of UFI resulted in mortality. The majority of UFI occurred during routine and expected firearm tasks such as firearm cleaning. Prevention programmes should not overlook these modifiable behaviours in an effort to reduce UFIs, complications and deaths.


Expansion of the Adherence Club model for stable antiretroviral therapy patients in the Cape Metro, South Africa 2011-2015.
The ambitious '90-90-90' treatment targets require innovative models of care to support quality antiretroviral therapy (ART) delivery. While evidence for differentiated models of ART delivery is growing, there are few data on the feasibility of scale-up. We describe the implementation of the Adherence Club (AC) model across the Cape Metro health district in Cape Town, South Africa, between January 2011 and March 2015. Using data from monthly aggregate AC monitoring reports and electronic monitoring systems for the district cohort, we report on the number of facilities offering ACs and the number of patients receiving ART care in the AC model. Between January 2011 and March 2015, the AC programme expanded to reach 32 425 patients in 1308 ACs at 55 facilities. The proportion of the total ART cohort retained in an AC increased from 7.3% at the end of 2011 to 25.2% by March 2015. The number of facilities offering ACs also increased and by the end of the study period, 92.3% of patients were receiving ART at a facility that offered ACs. During this time, the overall ART cohort doubled from 66 616 to 128 697 patients. The implementation of the AC programme offset this increase by 51%. ACs now provide ART care to more than 30 000 patients. Further expansion of the model will require additional resources and support. More research is necessary to determine the outcomes and quality of care provided in ACs and other differentiated models of ART delivery, especially when implemented at scale.


Forage grasses with lower uptake of caesium and strontium could provide 'safer' crops for radiologically contaminated areas.
Substitution of a species or cultivar with higher uptake of an element by one with lower uptake has been proposed as a remediation strategy following accidental releases of radioactivity. However, despite the importance of pasture systems for radiological dose, species/cultivar substitution has not been thoroughly investigated for forage grasses. 397 cultivars from four forage grass species; hybrid ryegrass (Lolium perenne L. x Lolium multiflorum Lam.), perennial ryegrass (Lolium perenne L.), Italian ryegrass (Lolium multiflorum Lam.) and tall fescue (Festuca arundinacea Shreb.); were sampled from 19 field-based breeding experiments in Aberystwyth and Edinburgh (UK) in spring 2013 and analysed for caesium (Cs) and strontium (Sr) concentrations. In order to calculate concentration ratios (CRs; the concentration of an element in a plant in relation to the concentration in the soil), soils from the experiments were also analysed to calculate extractable concentrations of Cs and Sr. To test if cultivars have consistently low Cs and Sr concentration ratios, 17 hybrid ryegrass cultivars were sampled from both sites again in summer 2013 and spring and summer 2014. Tall fescue cultivars had lower Cs and Sr CRs than the other species. Three of the selected 17 hybrid ryegrass cultivars had consistently low Cs CRs, two had consistently low Sr CRs and one had consistently low Cs and Sr CRs. Cultivar substitution could reduce Cs CRs by up to 14-fold and Sr CRs by 4-fold in hybrid ryegrass. The identification of species and cultivars with consistently low CRs suggests that species or cultivar substitution could be an effective remediation strategy for contaminated areas.


Secret learning for lung cancer diagnosis-a study with homomorphic encryption, texture analysis and deep learning.
Advanced lung cancer diagnoses from radiographic images include automated detection of lung cancer from CT-Scan images of the lungs. Deep learning is a popular method for decision making which can be used to classify cancerous and non-cancerous lungs from CT-Scan images. There are many experiments which show the uses of deep learning for performing such classifications but very few of them have preserved the privacy of users. Among existing methods, federated learning limits data sharing to a central server and differential privacy although increases anonymity the original data is still shared. Homomorphic encryption can resolve the limitations of both of these. Homomorphic encryption is a cryptographic technique that allows computations to be performed on encrypted data. In our experiment, we have proposed a series of textural information extraction with the implementation of homomorphic encryption of the CT-Scan images of normal, adenocarcinoma, large cell carcinoma and squamous cell carcinoma. We have further processed the encrypted data to make it classifiable and later we have classified it with deep learning. The results from the experiments have obtained a classification accuracy of 0.9347.


Derivation of euploid human embryonic stem cells from aneuploid embryos.
Human embryonic stem cells (HESCs) are pluripotent cells derived from the inner cell mass of preimplantation embryos. In this study, to isolate new lines of HESCs, we used blastocyst-stage embryos diagnosed as aneuploid in preimplantation genetic screening (PGS). During in vitro fertilization treatments, PGS is widely applied to identify chromosomal aneuploidies, especially in cases of advanced maternal age. Embryos that are detected as carrying aneuploidies are destined to be discarded unless donated for research. From 74 fresh PGS-defined aneuploid embryos, we derived seven HESC lines. Most of the embryos were left to hatch spontaneously through the hole created for blastomere biopsy and further treated by immunosurgery. The seven HESC lines exhibited morphology and markers typical of HESCs and the capacity for long-term proliferation. The derived HESC lines manifested pluripotent differentiation potential both in vivo and in vitro. Surprisingly, karyotype analysis of the HESC lines that were derived from these aneuploid embryos showed that the cell lines carry a normal euploid karyotype. We show that the euploidy was not achieved through chromosome duplication. Alternatively, we suggest that the euploid HESC lines originated from mosaic embryos consisting of aneuploid and euploid cells, and in vitro selection occurred to favor euploid cells. We assume that aneuploid HESC lines could be isolated mostly from embryos that are uniform for the aneuploidy. These results led us to conclude that the aneuploid mosaic embryos that are destined to be discarded can serve as an alternative source for normal euploid HESC lines.


Age-related pharmacodynamics in a bumblebee-microsporidian system mirror similar patterns in vertebrates.
Immune systems provide a key defence against diseases. However, they are not a panacea and so both vertebrates and invertebrates co-opt naturally occurring bioactive compounds to treat themselves against parasites and pathogens. In vertebrates, this co-option is complex, with pharmacodynamics leading to differential effects of treatment at different life stages, which may reflect age-linked differences in the immune system. However, our understanding of pharmacodynamics in invertebrates is almost non-existent. Critically, this knowledge may elucidate broad parallels across animals in regard to the requirement for the co-option of bioactive compounds to ameliorate disease. Here, we used biochanin A, an isoflavone found in the pollen of red clover (Trifolium pratense), to therapeutically treat Nosema bombi (Microsporidia) infection in bumblebee (Bombus terrestris) larvae and adults, and thus examine age-linked pharmacodynamics in an invertebrate. Therapeutic treatment of larvae with biochanin A did not reduce the infection intensity of N. bombi in adults. In contrast, therapeutic treatment of adults did reduce the infection intensity of N. bombi This transition in parasite resistance to bioactive compounds mirrors the age-linked pharmacodynamics of vertebrates. Understanding how different life-history stages respond to therapeutic compounds will provide novel insights into the evolution of foraging and self-medication behaviour in natural systems more broadly.


Animal exploitation strategies during the South African Middle Stone Age: Howiesons Poort and post-Howiesons Poort fauna from Sibudu Cave.
As one of the few sites that preserve fauna from the Howiesons Poort (HP) and the immediately post-HP Middle Stone Age (MSA), Sibudu Cave provides a unique opportunity to explore the range of variability in subsistence behaviors during this important phase in human behavioral evolution. In addition to providing information on subsistence, the faunal assemblage serves as a means of reconstructing the environmental conditions during these two periods. While the HP fauna is dominated by species that prefer closed (particularly forested) habitats, the fauna from the upper-most layers of the post-HP MSA are largely representative of open conditions. These results largely coincide with macrobotanical analyses and may simply indicate that the extent of the riverine forest near the site was greater during the HP. Alternatively, the pattern could be indicative of a marked intensification in the exploitation of the environment in the immediate vicinity of the shelter during the HP, perhaps resulting from a decline in the productivity of adjacent regions. We also document variation in the frequency of the different bovid size classes over time. The evidence shows a declining focus on the smallest bovids after the HP, with a parallel increase in the frequency of large and very large bovids. Beyond a heavy focus on small bovids, small mammals and suids also occur at higher frequencies during the HP. Although the HP faunal assemblage is largely unique as compared to the bulk of the MSA sequence at Sibudu, the evidence presented here suggests that the transition between the HP and the post-HP MSA may have been more gradual than abrupt. Our results indicate that the HP and post-HP MSA inhabitants of Sibudu Cave were capable hunters; however, hunting strategies appear to show marked variation over time. We propose that the variability in animal procurement strategies reflects a degree of behavioral plasticity beyond that generally attributed to MSA populations.


Placental Location in Maternal-Fetal Surgery for Myelomeningocele.
Uterine incision based on the placental location in open maternal-fetal surgery (OMFS) has never been evaluated in regard to maternal or fetal outcomes. The aim of this study was to investigate whether an anterior placenta was associated with increased rates of intraoperative, perioperative, antepartum, obstetric, or neonatal complications in mothers and babies who underwent OMFS for fetal myelomeningocele (fMMC) closure. Data from the international multicenter prospective registry of patients who underwent OMFS for fMMC closure (fMMC Consortium Registry, December 15, 2010-June 31, 2019) was used to compare fetal and maternal outcomes between anterior and posterior placental locations. The placental location for 623 patients was evenly distributed between anterior (51%) and posterior (49%) locations. Intraoperative fetal bradycardia (8.3% vs. 3.0%, p = 0.005) and performance of fetal resuscitation (3.6% vs. 1.0%, p = 0.034) occurred more frequently in cases with an anterior placenta when compared to those with a posterior placenta. Obstetric outcomes including membrane separation, placental abruption, and spontaneous rupture of membranes were not different among the 2 groups. However, thinning of the hysterotomy site (27.7% vs. 17.7%, p = 0.008) occurred more frequently in cases of an anterior placenta. Gestational age (GA) at delivery (p = 0.583) and length of stay in the neonatal intensive care unit (p = 0.655) were similar between the 2 groups. Fetal incision dehiscence and wound revision were not significantly different between groups. Critical clinical outcomes including fetal demise, perinatal death, and neonatal death were all infrequent occurrences and not associated with the placental location. An anterior placental location is associated with increased risk of intraoperative fetal resuscitation and increased thinning at the hysterotomy closure site. Individual institutional experiences may have varied, but the aggregate data from the fMMC Consortium did not show a significant impact on the GA at delivery or maternal or fetal clinical outcomes.


Activity profile of high-level Australian lacrosse players.
Despite lacrosse being one of the fastest growing team sports in the world, there is a paucity of information detailing the activity profile of high-level players. Microtechnology systems (global positioning systems and accelerometers) provide the opportunity to obtain detailed information on the activity profile in lacrosse. Therefore, this study aimed to analyze the activity profile of lacrosse match-play using microtechnology. Activity profile variables assessed relative to minutes of playing time included relative distance (meter per minute), distance spent standing (0-0.1 m·min), walking (0.2-1.7 m·min), jogging (1.8-3.2 m·min), running (3.3-5.6 m·min), sprinting (≥5.7 m·min), number of high, moderate, low accelerations and decelerations, and player load (PL per minute), calculated as the square root of the sum of the squared instantaneous rate of change in acceleration in 3 vectors (medio-lateral, anterior-posterior, and vertical). Activity was recorded from 14 lacrosse players over 4 matches during a national tournament. Players were separated into positions of attack, midfield, or defense. Differences (effect size [ES] ± 90% confidence interval) between positions and periods of play were considered likely positive when there was ≥75% likelihood of the difference exceeding an ES threshold of 0.2. Midfielders had likely covered higher (mean ± SD) meters per minute (100 ± 11) compared with attackers (87 ± 14; ES = 0.89 ± 1.04) and defenders (79 ± 14; ES = 1.54 ± 0.94) and more moderate and high accelerations and decelerations. Almost all variables across positions were reduced in quarter 4 compared with quarter 1. Coaches should accommodate for positional differences when preparing lacrosse players for competition.


Cooperative spin transition in a lipid layer like system.
A novel iron(II) mononuclear spin transition complex [FeL(py)(2)] displays an abrupt spin transition around 225 K accompanied by a very wide thermal hysteresis loop (∼50 K) that spreads out over 100 K. Crystal structure analysis in both low-spin and high-spin states reveals a lipid layer-like arrangement of the complex molecules and provides insights into the spin switching mechanism.


A theory of taste stimulation.
The treatment in this paper of available quantitative data on the response of taste receptors to sodium salt stimulation clearly indicates that the ions of the chemical stimulus are loosely bound to some substance of the taste receptor. This can be thought of as an initial reaction which ultimately leads to stimulation of the receptor and an eventual depolarization of the associated sensory neuron. The speed of the total reaction suggests that the receptor substance is located on or near the surface of the receptor. The recently proposed (7) enzymatic reactions for chemoreceptors do not appear plausible for sodium salt stimulation of the taste receptors of the rat.


Illicit and nonmedical drug use among Asian Americans, Native Hawaiians/Pacific Islanders, and mixed-race individuals.
The racial/ethnic composition of the United States is shifting rapidly, with non-Hispanic Asian-Americans, Native Hawaiians/Pacific Islanders (NHs/PIs), and mixed-race individuals the fastest growing segments of the population. We determined new drug use estimates for these rising groups. Prevalences among Whites were included as a comparison. Data were from the 2005-2011 National Surveys on Drug Use and Health. Substance use among respondents aged ≥ 12 years was assessed by computer-assisted self-interviewing methods. Respondents' self-reported race/ethnicity, age, gender, household income, government assistance, county type, residential stability, major depressive episode, history of being arrested, tobacco use, and alcohol use were examined as correlates. We stratified the analysis by race/ethnicity and used logistic regression to estimate odds of drug use. Prevalence of past-year marijuana use among Whites increased from 10.7% in 2005 to 11.6-11.8% in 2009-2011 (P<0.05). There were no significant yearly changes in drug use prevalences among Asian-Americans, NHs/PIs, and mixed-race people; but use of any drug, especially marijuana, was prevalent among NHs/PIs and mixed-race people (21.2% and 23.3%, respectively, in 2011). Compared with Asian-Americans, NHs/PIs had higher odds of marijuana use, and mixed-race individuals had higher odds of using marijuana, cocaine, hallucinogens, stimulants, sedatives, and tranquilizers. Compared with Whites, mixed-race individuals had greater odds of any drug use, mainly marijuana, and NHs/PIs resembled Whites in odds of any drug use. Findings reveal alarmingly prevalent drug use among NHs/PIs and mixed-race people. Research on drug use is needed in these rising populations to inform prevention and treatment efforts.


Stability and peptide binding specificity of Btk SH2 domain: molecular basis for X-linked agammaglobulinemia.
X-linked agammaglobulinemia (XLA) is caused by mutations in the Bruton's tyrosine kinase (Btk). The absence of functional Btk leads to failure of B-cell development that incapacitates antibody production in XLA patients leading to recurrent bacterial infections. Btk SH2 domain is essential for phospholipase C-gamma phosphorylation, and mutations in this domain were shown to cause XLA. Recently, the B-cell linker protein (BLNK) was found to interact with the SH2 domain of Btk, and this association is required for the activation of phospholipase C-gamma. However, the molecular basis for the interaction between the Btk SH2 domain and BLNK and the cause of XLA remain unclear. To understand the role of Btk in B-cell development, we have determined the stability and peptide binding affinity of the Btk SH2 domain. Our results indicate that both the structure and stability of Btk SH2 domain closely resemble with other SH2 domains, and it binds with phosphopeptides in the order pYEEI > pYDEP > pYMEM > pYLDL > pYIIP. We expressed the R288Q, R288W, L295P, R307G, R307T, Y334S, Y361C, L369F, and 1370M mutants of the Btk SH2 domain identified from XLA patients and measured their binding affinity with the phosphopeptides. Our studies revealed that mutation of R288 and R307 located in the phosphotyrosine binding site resulted in a more than 200-fold decrease in the peptide binding compared to L295, Y334, Y361, L369, and 1370 mutations in the pY + 3 hydrophobic binding pocket (approximately 3- to 17-folds). Furthermore, mutation of the Tyr residue at the betaD5 position reverses the binding order of Btk SH2 domain to pYIIP > pYLDL > pYDEP > pYMEM > pYEEI. This altered binding behavior of mutant Btk SH2 domain likely leads to XLA.


On the automatic activation of attitudes.
We hypothesized that attitudes characterized by a strong association between the attitude object and an evaluation of that object are capable of being activated from memory automatically upon mere presentation of the attitude object. We used a priming procedure to examine the extent to which the mere presentation of an attitude object would facilitate the latency with which subjects could indicate whether a subsequently presented target adjective had a positive or a negative connotation. Across three experiments, facilitation was observed on trials involving evaluatively congruent primes (attitude objects) and targets, provided that the attitude object possessed a strong evaluative association. In Experiments 1 and 2, preexperimentally strong and weak associations were identified via a measurement procedure. In Experiment 3, the strength of the object-evaluation association was manipulated. The results indicated that attitudes can be automatically activated and that the strength of the object-evaluation association determines the likelihood of such automatic activation. The implications of these findings for a variety of issues regarding attitudes--including their functional value, stability, effects on later behavior, and measurement--are discussed.


Placental Histologic Abnormalities and 2-Year Outcomes in Neonatal Hypoxic-Ischemic Encephalopathy.
We aimed to examine the association between placental abnormalities and neurodevelopmental outcomes in a multicenter cohort of newborn infants with hypoxic-ischemic encephalopathy (HIE) that underwent therapeutic hypothermia. We hypothesized that subjects with acute placental abnormalities would have reduced risk of death or neurodevelopmental impairment (NDI) at 2 years of age after undergoing therapeutic hypothermia compared to subjects without acute placental changes. Among 500 subjects born at ≥36 weeks gestation with moderate or severe HIE enrolled in the High-dose Erythropoietin for Asphyxia and Encephalopathy (HEAL) Trial, a placental pathologist blinded to clinical information reviewed clinical pathology reports to determine the presence of acute only, chronic only, or both acute and chronic histologic abnormalities. We calculated adjusted relative risks (aRRs) for associations between placental pathologic abnormalities and death or NDI at age 2 years, adjusting for HIE severity, treatment assignment, and site. 321/500 subjects (64%) had available placental pathology reports. Placental abnormalities were characterized as acute only (20%), chronic only (21%), both acute and chronic (43%), and none (15%). The risk of death or NDI was not statistically different between subjects with and without an acute placental abnormality (46 vs. 53%, aRR 1.1, 95% confidence interval (CI): 0.9, 1.4). Subjects with two or more chronic lesions were more likely to have an adverse outcome than subjects with no chronic abnormalities, though this did not reach statistical significance (55 vs. 45%, aRR 1.24, 95% CI: 0.99, 1.56). Placental pathologic findings were not independently associated with risk of death or NDI in subjects with HIE. The relationship between multiple chronic placental lesions and HIE outcomes deserves further study.


Pitch-shift responses as an online monitoring mechanism during level tone production.
This paper investigates whether pitch-shift responses can be modulated as a function of level tone height in Taiwanese Southern Min (TSM). Twenty-six native TSM speakers were recruited and asked to produce three TSM words that differed in tone on the first syllable but had the same mid-level tone on the second syllable (hence, HM, MM, and LM). The pitch-shift stimuli appeared at 100 ms after vocalization onset and lasted for 200 ms. The magnitudes of the pitch-shift stimuli were ±250 cents for HM, +250/-150 cents for MM, and ±150 cents for LM, in order to overlap the shifted pitch with another lexical tone. The results show that larger pitch-shift peak amplitudes were elicited when the H level tone of the HM word was downshifted 250 cents to the M level and when the L level tone of the LM word was upshifted 150 cents to the M level tone. However, no significant direction effect was found for the MM word. The M level tone might be perceived non-categorically by native TSM speakers. Overall, the findings suggest that the magnitudes of pitch-shift responses may have to do with the degree of categorical perception.


Baroreflex sensitivity in premature infants - relation to the parameters characterizing intrauterine and postnatal condition.
At present, there are insufficient information about baroreflex sensitivity (BRS) and factors that determine BRS in premature newborns. The objective of this study was to determine the relationship between BRS and the characteristics that reflecting the intrauterine development (gestational age and birth weight), as well as postnatal development (postconception age and the actual weight of the child at the time of measurement). We examined 57 premature infants, who were divided into groups according to gestational age and postconception age as well as birth weight, and weight at the time of measurement. Continuous and noninvasive registration of peripheral blood pressure (BP) was performed in every child within 2-5 min under standard conditions using a Portapres (FMS) device. The results showed a close correlation of baroreflex sensitivity, heart rate and respiratory rate with gestational age, postconception age, birth weight and actual weight at the time of measurement premature newborns. An increase in the characteristics (ages and weights) resulted in increased BRS and diastolic arterial pressure (DAP), and in decreased heart and respiratory rates. Baroreflex sensitivity in the first week was in the group of very premature newborns the lowest (4.11 ms/mmHg) and in the light premature newborns was almost double (8.12 ms/mmHg). BRS increases gradually in relation to postnatal (chronological) and to postconception age as well as to birth and actual weight. The multifactor analysis of BRS identified birth weight and postconception age as the best BRS predictors. The two independent variables together explained 40 % of interindividual BRS variability.


Pyrophosphate-regulated Zn(2+)-dependent DNAzyme activity: an amplified fluorescence sensing strategy for alkaline phosphatase.
In this work, based on the fact that pyrophosphate (PPi) could regulate the activity of Zn(2+)-dependent DNAzyme, we for the first time report a fluorescence turn-on sensing system for alkaline phosphatase (ALP) with improved sensitivity via nonprotein-enzymatic signal amplification. A catalytic and molecular beacon (CAMB) design was employed to further improve its sensitivity. Taking advantage of the strong interactions between PPi and the Zn(2+), the cofactor Zn(2+) was caged, and the DNAzyme activity was effectively inhibited. The introduction of ALP, however, could catalyze the hydrolysis of PPi and release free Zn(2+), resulting in the activation of DNAzyme to catalyze the cleavage of the molecular beacon substrate with a remarkable increase of fluorescent signal. These optimized designs together allow a high sensitivity for ALP, with a detection limit of 20 pM observed, much lower than previously reported methods. It has also been used for detection of ALP in human serum with satisfactory results, demonstrating its potential applications in clinical diagnosis.


[Celiac disease in a group of children and adolescents with type 1 diabetes mellitus].
To know the prevalence of celiac disease (CD) in a group of children and adolescents with type I diabetes mellitus. A cross sectional study was conducted at the Instituto Materno Infantil de Pernambuco (IMIP) in March 2000. The sample consisted of 19 children and adolescents with type I diabetes mellitus that had the human anti-tissue transglutaminase antibodies assessed using kits from the Eurospital Laboratory. In case of positive results it was realized small intestine biopsy to confirm the diagnosis. For the calculation of the prevalence of CD it was considered the number of patients with serum positive histological alterations of the mucous membrane of the small intestine compatible with CD. Four patients presented serum positivity for human anti-tissue transglutaminase antibodies with a serum prevalence of 21% (4/19). Out of these four subjects, three who accomplished small intestine biopsy presented histological alterations compatible with CD. The prevalence of CD in this group was 15.8% (3/19). The prevalence of CD in this study group was high, suggesting that those with type I diabetes mellitus should be led as a group of high risk to develop this disease.


A RAD-sequencing approach to genome-wide marker discovery, genotyping, and phylogenetic inference in a diverse radiation of primates.
Until recently, most phylogenetic and population genetics studies of nonhuman primates have relied on mitochondrial DNA and/or a small number of nuclear DNA markers, which can limit our understanding of primate evolutionary and population history. Here, we describe a cost-effective reduced representation method (ddRAD-seq) for identifying and genotyping large numbers of SNP loci for taxa from across the New World monkeys, a diverse radiation of primates that shared a common ancestor ~20-26 mya. We also estimate, for the first time, the phylogenetic relationships among 15 of the 22 currently-recognized genera of New World monkeys using ddRAD-seq SNP data using both maximum likelihood and quartet-based coalescent methods. Our phylogenetic analyses robustly reconstructed three monophyletic clades corresponding to the three families of extant platyrrhines (Atelidae, Pitheciidae and Cebidae), with Pitheciidae as basal within the radiation. At the genus level, our results conformed well with previous phylogenetic studies and provide additional information relevant to the problematic position of the owl monkey (Aotus) within the family Cebidae, suggesting a need for further exploration of incomplete lineage sorting and other explanations for phylogenetic discordance, including introgression. Our study additionally provides one of the first applications of next-generation sequencing methods to the inference of phylogenetic history across an old, diverse radiation of mammals and highlights the broad promise and utility of ddRAD-seq data for molecular primatology.


Early detection of accelerated aging and cellular decline (AACD): A consensus statement.
The cellular hallmarks of accelerated aging and their clinical expression may be grouped using the terms 'accelerated aging and cellular decline' (AACD) and/or 'age-associated cellular decline'. This construct is designed to capture the biological background predisposing the development of age-related conditions. By classifying risk factors, early indicators, and clinical differentiators of AACD through expert consensus, this study aimed to identify the signs, symptoms, and markers indicative of AACD. In doing so, this work paves the way for future implementation of the AACD concept in the clinical and research settings. An interdisciplinary panel of experts with clinical and research expertise was selected to participate in a virtual workshop to discuss AACD. A modified nominal group technique was used to establish consensus among the group. An extended group of international experts critically reviewed an early draft of the manuscript, and their feedback was then incorporated into the model. Experts identified 13 factors predisposing to or clinically manifesting AACD. Among these, chronic diseases, obesity, and unfavorable genetic background were considered as the most important. There was a consensus that a gradual and nonspecific development often characterizes AACD, making its clinical detection potentially challenging. In addition, signs and symptoms might have multifactorial causes and overlapping origins, such as genetic and epigenetic predispositions. As a result, an initial checklist was outlined, listing clinical factors of special relevance (e.g., fatigue, low quality of sleep, and low mood) to represent early manifestations of the organism's exhaustion, which are also frequently neglected in the clinical setting. Differentiating AACD from other conditions is essential. The use of a combination of biomarkers was proposed as a viable method in a two-step process of differentiation: 1) identification of early AACD clinical indicators, followed by 2) symptom and biomarker confirmation with a focus on system domains (to be potentially targeted by future specific interventions). Although the AACD construct is not yet ready for routine use in clinical practice, its operationalization may support the early identification of age-related conditions (when this might still be amenable to reversion) and also encourage preventative interventions. Further investigation is needed to establish specific biomarkers that confirm independent risk factors for AACD and provide a more definitive structure to the concept of AACD (and age-associated cellular decline).


Numerical investigation of GHz repetition rate fundamentally mode-locked all-fiber lasers.
GHz repetition rate fundamentally mode-locked lasers have attracted great interest for a variety of scientific and practical applications. A passively mode-locked laser in all-fiber format has the advantages of high stability, maintenance-free operation, super compactness, and reliability. In this paper, we present numerical investigation on passive mode-locking of all-fiber lasers operating at repetition rates of 1-20 GHz. Our calculations show that the reflectivity of the output coupler, the small signal gain of the doped fiber, the total net cavity dispersion, and the modulation depth of the saturable absorber are the key parameters for producing stable fundamentally mode-locked pulses at GHz repetition rates in very short all-fiber linear cavities. The instabilities of GHz repetition rate fundamentally mode-locked all-fiber lasers with different parameters were calculated and analyzed. Compared to a regular MHz repetition rate mode-locked all-fiber laser, the pump power range for the mode-locking of a GHz repetition rate all-fiber laser is much larger due to the several orders of magnitude lower accumulated nonlinearity in the fiber cavity. The presented numerical study provides valuable guidance for the design and development of highly stable mode-locked all-fiber lasers operating at GHz repetition rates.


The PRIAMO study: A multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson's disease.
We performed a multicenter survey using a semistructured interview in 1,072 consecutive patients with Parkinson's disease (PD) enrolled during 12 months in 55 Italian centers to assess the prevalence of nonmotor symptoms (NMSs), their association with cognitive impairment, and the impact on patients' quality of life (QoL). We found that 98.6% of patients with PD reported the presence of NMSs. The most common were as follows: fatigue (58%), anxiety (56%), leg pain (38%), insomnia (37%), urgency and nocturia (35%), drooling of saliva and difficulties in maintaining concentration (31%). The mean number of NMS per patient was 7.8 (range, 0-32). NMS in the psychiatric domain were the most frequent (67%). Frequency of NMS increased along with the disease duration and severity. Patients with cognitive impairment reported more frequently apathy, attention/memory deficit, and psychiatric symptoms. Apathy was the symptom associated with worse PDQ-39 score but also presence of fatigue, attention/memory, and psychiatric symptoms had a negative impact on QoL. These findings further support a key role for NMS in the clinical frame of PD and the need to address them specifically in clinical trials using dedicated scales.


Mechanism of cyanamide hydration catalyzed by carbonic anhydrase II suggested by cryogenic X-ray diffraction.
The three-dimensional structure of a possible intermediate in the hydration reaction of cyanamide to urea catalyzed by human carbonic anhydrase II (hCAII) has been determined by cryocrystallographic techniques. The crystal structure shows that two different adducts are formed under the experimental conditions and that they have different occupancy in the crystal. The high occupancy form consists of a binary hCAII-cyanamide complex where the substrate has replaced the zinc-bound hydroxide anion present in the native enzyme, maintaining the tetrahedral geometry around the metal ion. The second, low-occupancy form consists of a hCAII-cyanamide-water ternary complex where the catalytic zinc ion, still being bound to cyanamide, is approached by a water molecule in a five-coordinate adduct. While the first form can be considered a nonproductive complex, the second form may represent an intermediate state of the catalyzed reaction where the water molecule is about to perform a nucleophilic attack on the zinc-activated cyanamide substrate. The structural evidence is consistent with the kinetic data previously reported about this recently described hydrolytic reaction catalyzed by hCAII, and indicates that a different mechanism with respect to that generally accepted for the physiologic carbon dioxide hydration reaction may be adopted by the enzyme, depending on the substrate chemical properties.


Clinical use of sustained-release procainamide in treatment of cardiac arrhythmias.
Although procainamide has been available, and used, in the treatment of atrial and ventricular arrhythmias for approximately thirty years, its short half-life has made it less than optimal for long-term arrhythmia management in ambulatory patients. Currently available sustained-release preparations provide the same therapeutic benefit with a more tolerable dosage schedule. The pharmacology of procainamide and its basic electrophysiologic properties, dosage schedules, and toxicity are discussed. Finally, the current indications for its use are reviewed.


Viscosity of culture medium as a regulator of synthesis and secretion of very low density lipoproteins by cultured hepatocytes.
It has been postulated that hyperlipidemia in the nephrotic syndrome is due to overproduction of lipoproteins and that low colloid osmotic pressure (due to hypoalbuminemia) triggers this. Secretion of very low density lipoproteins (VLDL) by cultured rat hepatocytes has been shown to be inhibited by albumin, globulins, and dextrans, but the effect did not correlate with osmolarity. In the present studies we tested the hypothesis that viscosity rather than osmolarity might be the parameter determining the effectiveness of macromolecules in inhibiting VLDL synthesis and secretion by cultured rat hepatocytes. Synthesis and secretion of VLDL was measured in terms of incorporation of [3H] glycerol into medium triglycerides and also from changes in the mass of secreted VLDL triglycerides and apoproteins. The viscosity of the culture medium was increased by addition of dextran-500, gelatin or methylcellulose MX 880. Synthesis and secretion of VLDL was inhibited in direct proportion to increasing viscosity. At a viscosity of 2, which is about that of normal plasma, VLDL secretion was reduced by 20%. An inhibition of 60-70% in secretion and 30-40% in synthesis of VLDL lipid and protein components was observed at a relative viscosity of approximately 3.7. This viscosity was obtained by addition of any of the following: 3% dextran, 3% gelatin, 0.2% methylcellulose, or a combination of 0.1% methylcellulose plus 2% gelatin. Thus, similar viscosities resulted in similar degrees of inhibition despite differences of up to 16-fold in mass concentration and up to 20-fold in osmolarity.


Mood, Activity Participation, and Leisure Engagement Satisfaction (MAPLES): a randomised controlled pilot feasibility trial for low mood in acquired brain injury.
Acquired brain injury (ABI) affects approximately 79.3 million individuals annually and is linked with elevated rates of depression and low mood. Existing methods for treating depression in ABI have shown mixed efficacy. Behavioural activation (BA) is a potentially promising intervention. Its premise is that individuals with low mood avoid planning and engaging in activities due to low expectations of a positive outcome. Consequently, their exposure to positive reinforcement is reduced, exacerbating low mood. BA aims to break this cycle by encouraging activity planning and engagement. It is unknown whether cognitive demands of traditional BA may undermine efficacy in ABI. Here, we assess the feasibility and acceptability of two groups designed to increase activity engagement. In the activity planning group (traditional BA), the importance of meaningful and positive activity will be discussed and participants encouraged to plan/engage in activities in everyday life. The activity engagement group (experiential BA) instead focuses on engagement in positive experiences (crafts, games, discussion) within the group. The primary aims are to evaluate the feasibility and acceptability of the two groups in ABI. A secondary aim is to explore relative efficacy of the groups compared to an equivalent period of waitlist controls. This study outlines a parallel-arm pilot feasibility trial for individuals with low mood and ABI that compares a traditional vs experiential BA group vs waitlist controls. Adults (≥ 18 years) will be recruited from local ABI services and randomised to condition. Feasibility and acceptability will be assessed via recruitment, retention, attendance and participant feedback. Groups will be compared (pre- and post-intervention and 1 month follow-up) by assessing self-reported activity engagement. Secondary outcomes include self-report measures of depression, anxiety, post-traumatic distress related to the ABI, motivation, participation and sense of control over one's life. The trial has been approved by the Health Research Authority of the NHS in the UK (East of England-Cambridge Central, REF 18/EE/0305). Results will inform future research on interventions for mood in ABI and be disseminated broadly via peer-reviewed journals, conference presentations and social media. ClinicalTrials.gov, NCT03874650 pre-results. Protocol version 2.1, March 5, 2019.


The pituitary response to ovine corticotropin-releasing hormone is enhanced in obese men and correlates with insulin resistance.
Hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis in central obesity has been demonstrated in women. We studied the corticotropin (ACTH) and cortisol response to ovine corticotropin releasing hormone (oCRH) and its association to parameters of adiposity and insulin resistance in a group of 19 healthy obese (BMI > 25 kg/m2) and 9 non-obese men. Relative insulin resistance was assessed by the homeostatic model assessment (HOMA IR). Baseline ACTH was similar, while cortisol was lower in the obese group. The ACTH response to oCRH was significantly higher in the obese group. ACTH incremental area under the curve (iAUC) correlated with age, HOMA IR, and sagittal diameter but not with leptin. In multiple regression analysis, only HOMA IR was an independent predictor of ACTH iAUC. In conclusion, obese men have hyperactivity of the HPA axis at the pituitary level, which appears to be linked to insulin resistance.


Luminescence Enhancement by the Introduction of Disorder into Poly(p-phenylene vinylene).
A method is described for increasing luminescence in poly(p-phenylene vinylene) (PPV) light-emitting diodes. Cis linkages were engineered into the PPV chain. These linkages interrupt conjugation and interfere with the packing of the polymer chains, which results in the formation of amorphous PPV. Large-area electroluminescent devices were prepared from this polymer. Devices made of an aluminum electrode, PPV as the luminescent layer, and an electron-transporting layer have internal quantum efficiencies of 2 percent, a turn-on voltage of 20 volts, and can carry current densities of 2000 milliamperes per square centimeter. The current density is at least an order of magnitude higher than previously obtained.


Jeotgalibacillus soli sp. nov., a Gram-stain-positive bacterium isolated from soil.
A Gram-staining-positive, motile, rod-shaped, spore-forming bacterium, designated P9(T), was isolated from soil in Portugal. This organism was aerobic and catalase- and oxidase-positive. It had an optimum growth temperature of about 35 °C and an optimum growth pH of about 8.0-8.5, and grew in medium with 0-9% (w/v) NaCl. The cell-wall peptidoglycan was of the A1α type, with L-lysine as the diagnostic diamino acid. The major respiratory quinone was menaquinone 7 (MK-7) and the major fatty acids were anteiso-C(15:0) (45.4%), iso-C(15:0) (22.0%) and anteiso-C(17:0) (11.2%). The genomic DNA G+C content was about 39.4 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain P9(T) was most closely related to Jeotgalibacillus campisalis DSM 18983(T) (96.8%) and Jeotgalibacillus marinus DSM 1297(T) (96.5%). These two recognized species formed a coherent cluster with strain P9(T) that was supported by a bootstrap value of 99%. On the basis of the phylogenetic analysis and physiological and biochemical characteristics, strain P9(T) (=DSM 23228(T)=LMG 25523(T)) represents a novel species of the genus Jeotgalibacillus, for which the name Jeotgalibacillus soli sp. nov. is proposed.


Occurrence of biogenic amines in beers produced with malted organic Emmer wheat (Triticum dicoccum).
Because several groups of microorganisms are able to decarboxylate amino acids, the presence of biogenic amines (BA) can be seen as an index of the microbiological quality of the brewing process. BAs were quantified for the first time in the intermediate products and craft beers produced with malted organic Emmer wheat (Triticum dicoccum) in a small size brewery in order to assess the possible presence of critical control points related to biological hazard in the brewing process. BA levels in beers produced exclusively from malted organic Emmer wheat were between 15.4 and 25.2 mg l(-1) in the samples of light beer (Lt) and between 8.9 and 15.3 mg l(-1) in double malt beers (DM) ready for consumption (the beers stored for 90 days at 1-2°C). Cadaverine and tyramine were the main BAs in the Lt and DM beers, respectively. Increased concentrations of BAs seemed to be more related to the heat treatment of the processing product during mashing and wort boiling, rather than to the fermentation process. Much lower concentrations were found in finished beers obtained from 50% malted organic Emmer wheat and 50% malted barley (up to 3.2 mg l(-1)) or from 30% malted Emmer wheat (up to 8.3 mg l(-1)). Thus, Emmer wheat malt can be a useful alternative to wheat and spelt for the production of beer with a limited content of BA, if the processing technology is kept under control.


[Polyvalent diagnostic cholera phage].
A polyvalent diagnostic bacteriophage for rapid identification (in 6-10 hours) of cholera vibrio of both biotypes has been constructed of virulent E1 Tor phages and recommended for laboratory practice. Polyvalent diagnostic bacteriophage is strictly specific, inactive against the nonagglutinating vibrios, microbes of enteric group and those closely affiliated.


Chemical doping of organic semiconductors for thermoelectric applications.
Doping is essential to manipulate the electrical performance of both thermoelectric (TE) materials and organic semiconductors (OSCs). Although organic thermoelectric (OTE) materials have experienced a rapid development over the past decade, the chemical doping of OSCs for TE applications lags behind, which has limited further breakthroughs in this cutting-edge field. Recently, increasing efforts have been devoted to the development of energetically matched host and dopant molecules, exploring novel doping methods and revealing the doping mechanisms. This tutorial review covers the basic mechanisms, fundamental requirements, recent advances and remaining challenges of chemical doping in OSCs for TE applications. We first present the basic knowledge of the trade-off relationship in TE materials and its critical requirements for doped OSCs, followed by a brief introduction of recent advances in the molecular design of OSCs and dopants. Moreover, we provide an overview of the existing categories of doping mechanisms and methods, and more importantly, emphasize the summarized doping strategies for the state-of-the-art OTE materials. Finally, challenges and perspectives on the chemical doping of OSCs are proposed to highlight the research directions that deserve attention towards a bright future of OTE materials.