Partial characterization of retroviruses from boid snakes with inclusion body disease.
To characterize retroviruses isolated from boid snakes with inclusion body disease (IBD). 2 boa constrictors with IBD and 1 boa exposed to an affected snake. Snakes were euthanatized, and tissue specimens and blood samples were submitted for virus isolation. Tissue specimens were cultured with or without commercially available viper heart cells and examined by use of transmission electron microscopy (TEM) for evidence of viral replication. Reverse transcriptase activ ty was determined in sucrose gradient-purified virus. Western blotting was performed, using polyclonal antibodies against 1 of the isolated viruses. Specificity of the rabbit anti-virus antibody was evaluated, using an immunogold-labeling TEM technique. 3 viruses (RV-1, RV-2, and RV-3) were isolated. The isolates were morphologically comparable to members of the Retroviridae family. Reverse transcriptase activity was high in sucrose gradient fractions that were rich in virus. Polyclonal antibody against RV-1 reacted with proteins of similar relative mobility in RV-1 and RV-2. By use of immunogold labeling, this antibody also recognized virions of both RV-1 and RV-2. A retrovirus was isolated from boid snakes with IBD or exposed to IBD. Western blot analysis of viral proteins indicated that viruses isolated from the different snakes were similar. Whether this virus represents the causative agent of IBD is yet to be determined. The isolation of retroviruses from boid snakes with IBD is an important step n the process of identifying the causative agent of this disease.


The Etruscans: a population-genetic study.
The origins of the Etruscans, a non-Indo-European population of preclassical Italy, are unclear. There is broad agreement that their culture developed locally, but the Etruscans' evolutionary and migrational relationships are largely unknown. In this study, we determined mitochondrial DNA sequences in multiple clones derived from bone samples of 80 Etruscans who lived between the 7th and the 3rd centuries b.c. In the first phase of the study, we eliminated all specimens for which any of nine tests for validation of ancient DNA data raised the suspicion that either degradation or contamination by modern DNA might have occurred. On the basis of data from the remaining 30 individuals, the Etruscans appeared as genetically variable as modern populations. No significant heterogeneity emerged among archaeological sites or time periods, suggesting that different Etruscan communities shared not only a culture but also a mitochondrial gene pool. Genetic distances and sequence comparisons show closer evolutionary relationships with the eastern Mediterranean shores for the Etruscans than for modern Italian populations. All mitochondrial lineages observed among the Etruscans appear typically European or West Asian, but only a few haplotypes were found to have an exact match in a modern mitochondrial database, raising new questions about the Etruscans' fate after their assimilation into the Roman state.


Effects of Sulfidation, Magnetization, and Oxygenation on Azo Dye Reduction by Zerovalent Iron.
Applications of zerovalent iron (ZVI) for water treatment under aerobic conditions include sequestration of metals (e.g., in acid mine drainage) and decolorization of dyes (in wastewaters from textile manufacturing). The processes responsible for contaminant removal can be a complex mixture of reduction, oxidation, sorption, and coprecipitation processes, which are further complicated by the dynamics of oxygen intrusion, mixing, and oxide precipitation. To better understand such systems, the removal of an azo dye (Orange I) by micron-sized granular ZVI at neutral pH was studied in open (aerobic) stirred batch reactors, by measuring the kinetics of Orange I decolorization and changes in "geochemical" properties (DO, Fe(II), and Eh), with and without two treatments that might improve the long-term performance of this system: sulfidation by pretreatment with sulfide and magnetization by application of a weak magnetic field (WMF). The results show that the changes in solution chemistry are coupled to the dynamics of oxygen intrusion, which was modeled as analogous to dissolved oxygen sag curves. Both sulfidation and magnetization increased Orange I removal rates 2.4-71.8-fold, but there was little synergistic benefit to applying both enhancements together. Respike experiments showed that the enhancement from magnetization carries over from magnetization to sulfidation, but not the reverse.


[Alfa and beta diversity of reptilian assemblages in Zapatosa wetland complex, Colombia].
Diversity is a property of community that can described, characterized, and understood according to the functioning of ecosystems. To study the richness and local abundance and species replacement between habitats around the Zapatosa's wetland complex (El Cesar Department), I carried out four field trips between November of 2006 and October of 2007. A total of 640 sampling hours/man analyzed five habitat types chasmophyte forest, dry forest, riparian forest, palm-grove and tree-lined savanna; with the exception of the palm-grove sampled at its 75%, the others were sampled up to their 80%. I found 847 reptiles that were distributed in 48 species. The group with the highest number of species was Colubridae with 14, followed by Gekkonidae with five. Five endemic species and eight with some conservation threat grade at a national level are reported. The riparian forest was the richest and most abundant habitat with 34 species and 196 individuals. For each habitat, Colubridae had the highest number of species, followed by the families Polychrotidae, Gekkonidae and Teiidae, in that order. The reptile species composition was not different between the tree-lined savanna and the chasmophyte forest, but differed among the tree-lined savanna and the riparian forest, palm-grove and dry forest habitats. The most important differences in the species composition among almost all the habitats were influenced by the species Anolis tropidogaster and Gonatodes albogularis, and the higher occurrence of Stenocercus erythrogaster in the chasmophyte forest. The species replacement had an average value of 50%; the biggest amounts of shared species were the lizards, while the snake Leptodeira septentrionalis was the only one present in all habitat types. The forest grows-among-rocks showed the biggest complementarity and number of unique species compared to the other habitats. The wetland complex provides two thirds of the reptile's species reported until now for the Caribbean region, and more than 80% of those reported for the El Cesar department. This wetland complex seems to behave as a center for low land species concentration as it hosts a high proportion of species from those places.


Perturbations of BMP/TGF-β and VEGF/VEGFR signalling pathways in non-syndromic sporadic brain arteriovenous malformations (BAVM).
Brain arteriovenous malformations (BAVM) represent a congenital anomaly of the cerebral vessels with a prevalence of 10-18/100 000. BAVM is the leading aetiology of intracranial haemorrhage in children. Our objective was to identify gene variants potentially contributing to disease and to better define the molecular aetiology underlying non-syndromic sporadic BAVM. We performed whole-exome trio sequencing of 100 unrelated families with a clinically uniform BAVM phenotype. Pathogenic variants were then studied in vivo using a transgenic zebrafish model. We identified four pathogenic heterozygous variants in four patients, including one in the established BAVM-related gene, ENG, and three damaging variants in novel candidate genes: PITPNM3, SARS and LEMD3, which we then functionally validated in zebrafish. In addition, eight likely pathogenic heterozygous variants (TIMP3, SCUBE2, MAP4K4, CDH2, IL17RD, PREX2, ZFYVE16 and EGFR) were identified in eight patients, and 16 patients carried one or more variants of uncertain significance. Potential oligogenic inheritance (MAP4K4 with ENG, RASA1 with TIMP3 and SCUBE2 with ENG) was identified in three patients. Regulation of sma- and mad-related proteins (SMADs) (involved in bone morphogenic protein (BMP)/transforming growth factor beta (TGF-β) signalling) and vascular endothelial growth factor (VEGF)/vascular endotheliual growth factor recepter 2 (VEGFR2) binding and activity (affecting the VEGF signalling pathway) were the most significantly affected biological process involved in the pathogenesis of BAVM. Our study highlights the specific role of BMP/TGF-β and VEGF/VEGFR signalling in the aetiology of BAVM and the efficiency of intensive parallel sequencing in the challenging context of genetically heterogeneous paradigm.


Frequent fires in ancient shrub tundra: implications of paleorecords for arctic environmental change.
Understanding feedbacks between terrestrial and atmospheric systems is vital for predicting the consequences of global change, particularly in the rapidly changing Arctic. Fire is a key process in this context, but the consequences of altered fire regimes in tundra ecosystems are rarely considered, largely because tundra fires occur infrequently on the modern landscape. We present paleoecological data that indicate frequent tundra fires in northcentral Alaska between 14,000 and 10,000 years ago. Charcoal and pollen from lake sediments reveal that ancient birch-dominated shrub tundra burned as often as modern boreal forests in the region, every 144 years on average (+/- 90 s.d.; n = 44). Although paleoclimate interpretations and data from modern tundra fires suggest that increased burning was aided by low effective moisture, vegetation cover clearly played a critical role in facilitating the paleofires by creating an abundance of fine fuels. These records suggest that greater fire activity will likely accompany temperature-related increases in shrub-dominated tundra predicted for the 21(st) century and beyond. Increased tundra burning will have broad impacts on physical and biological systems as well as on land-atmosphere interactions in the Arctic, including the potential to release stored organic carbon to the atmosphere.


Roles and programming of Arabidopsis ARGONAUTE proteins during Turnip mosaic virus infection.
In eukaryotes, ARGONAUTE proteins (AGOs) associate with microRNAs (miRNAs), short interfering RNAs (siRNAs), and other classes of small RNAs to regulate target RNA or target loci. Viral infection in plants induces a potent and highly specific antiviral RNA silencing response characterized by the formation of virus-derived siRNAs. Arabidopsis thaliana has ten AGO genes of which AGO1, AGO2, and AGO7 have been shown to play roles in antiviral defense. A genetic analysis was used to identify and characterize the roles of AGO proteins in antiviral defense against Turnip mosaic virus (TuMV) in Arabidopsis. AGO1, AGO2 and AGO10 promoted anti-TuMV defense in a modular way in various organs, with AGO2 providing a prominent antiviral role in leaves. AGO5, AGO7 and AGO10 had minor effects in leaves. AGO1 and AGO10 had overlapping antiviral functions in inflorescence tissues after systemic movement of the virus, although the roles of AGO1 and AGO10 accounted for only a minor amount of the overall antiviral activity. By combining AGO protein immunoprecipitation with high-throughput sequencing of associated small RNAs, AGO2, AGO10, and to a lesser extent AGO1 were shown to associate with siRNAs derived from silencing suppressor (HC-Pro)-deficient TuMV-AS9, but not with siRNAs derived from wild-type TuMV. Co-immunoprecipitation and small RNA sequencing revealed that viral siRNAs broadly associated with wild-type HC-Pro during TuMV infection. These results support the hypothesis that suppression of antiviral silencing during TuMV infection, at least in part, occurs through sequestration of virus-derived siRNAs away from antiviral AGO proteins by HC-Pro. These findings indicate that distinct AGO proteins function as antiviral modules, and provide a molecular explanation for the silencing suppressor activity of HC-Pro.


Strip meniscometry: a new and simple method of tear meniscus evaluation.
To investigate the applicability and efficacy of a new and simple method of quantification of the volume of tear meniscus, termed "strip meniscometry," in the diagnosis of the dry eye syndromes in a prospective controlled study. One hundred eyes of 50 patients with dry eye (19 males; 31 females) aged between 18 and 76 years (mean, 54.3 years), as well as 80 eyes of 40 normal subjects aged from 15 to 70 years (mean, 50.8 years; 12 males, 28 females) were recruited in this study. The patients and the control subjects underwent strip meniscometry for 5 seconds, tear film lipid layer interferometry, tear film break-up time measurement, and ocular surface vital staining with fluorescein and rose bengal dyes and the Schirmer-1 test. Strip meniscometry scores correlated with tear quantity and stability, ocular surface staining scores, and lipid layer interferometry grades and improved after 2 weeks of punctal plug occlusion. Strip meniscometry is a swift, noninvasive, promising new method that is expected to find application in the diagnosis and evaluation of the outcome of treatment of dry eye syndromes.


Neuromuscular performance of elite rugby union players and relationships with salivary hormones.
This study compared the neuromuscular performance (speed, power, strength) of elite rugby union players, by position, and examined the relationship between player performance and salivary hormones, by squad and position. Thirty-four professional male rugby players were assessed for running speed (10-m, 20-m or 30-m sprints), concentric mean (MP) and peak power (PP) during a 70-kg squat jump (SJ) and 50-kg bench press throw (BT), and estimated 1 repetition maximum (1RM) strength for a box squat (BS) and bench press (BP). Tests were performed on separate days with absolute and normalized (power and strength only) values computed. Saliva was collected before each test and assayed for testosterone (Sal-T) and cortisol (Sal-C). In absolute terms, the backs demonstrated greater speed and BT MP, whereas the forwards produced greater SJ PP and MP and BS 1RM (p < 0.01). However, BT, SJ and BS performances were no different when normalized for body mass in kg (p > 0.05). A comparison (absolute and normalized) of BT PP showed no positional differences (p > 0.05), whereas BP 1RM was greater for the forwards (p < 0.05). These results may be attributed to genetic and/or training factors relating to the positional demands of rugby. The Sal-T and/or Sal-C concentrations of players correlated to speed, power, and strength, especially for the backs (p < 0.05), thereby confirming relationships between neuromuscular performance and hormone secretion patterns. Based on these findings, it was suggested that training to increase whole-body and muscle mass might facilitate general performance improvements. Training prescription might also benefit from acute and chronic hormone monitoring to identify those individuals likely to respond more to hormonal change.


Regional properties of calcium entry in barnacle neurons determined with Arsenazo III and a photodiode array.
Calcium changes were simultaneously measured at many positions on individual neurons from the supraesophageal ganglion of the barnacle by detecting absorbance changes of the indicator dye Arsenazo III with a 10 X 10 photodiode array. These changes were correlated with positions on the stimulated cell determined from Lucifer yellow injections. Absorbance signals were found at all locations on the cells, demonstrating that calcium channels were distributed on the somata, axons, and neuropil processes. By comparing the amplitude of the signal with the membrane area in each region, we could measure the calcium entry per impulse per unit of surface in each part of the cell. Assuming that the properties of the calcium channels are the same in all regions, we determined that calcium channels were distributed uniformly along the commissural axon of one cell and were found at higher density in the neuropil. Because significant calcium changes are only detected when cells are depolarized above about -20 mV, the presence of absorbance signals indicates membrane depolarization above this level. We used this fact to show that calcium spikes propagate along the axon and into the neuropil of one cell, along the axon of another, and not at all in a third. Differences in time course of calcium transients were observed in different regions of cells. The recovery time course was faster at the edge of the cell body than in the center and faster in the neuropil than in the axon or soma. During trains of action potentials or during wide action potentials in tetraethylammonium (TEA) saline, the calcium signal reached a plateau in the neuropil while continuing to rise in the axon and soma.


Trichoscopy in trichotillomania: a useful diagnostic tool.
Trichotillomania (TTM) is characterized by patchy alopecia of hair bearing areas. This is because of compulsive urge to pull the hair. Scalp is the most common site for pulling hair. Usually, patients may have only small areas of baldness, in severe forms, tonsure pattern of baldness is observed. Diagnosis is by history and clinical examination. However, it is difficult to differentiate from other causes of noncicatricial alopecia. Here, authors observed trichoscopic patterns and evaluated their importance in the diagnosis of TTM. This study was conducted in S. Nijalingappa Medical College, Bagalkot, from January 2014 to July 2014. Ten patients with clinically suspected TTM were included in the study. Informed consent was taken and ethical clearance was obtained. Dermlite3 dermoscope was used with Sony camera attachment to save the images. Histopathological examination was conducted in all the patients to confirm the diagnosis. Ten patients were included in the study. Mean age of the patients was 34 years. Most common symptom was patchy loss of hair in the frontal area (100%). Common trichoscopic feature was decreased hair density and broken hairs. Trichoptilosis (split ends) and irregular coiled hairs were seen in 80% patients. Novel diagnostic signs like black dots, flame hair, v-sign, follicular hemorrhages, were seen in 30% each. Tulip hair and hair powder were observed in 10% of patients. All patients had the noninflammatory alopecia with distorted and collapsed inner root sheath in histopathology. Trichotillomania is often chronic and difficult to treat. Hence, early diagnosis and treatment is necessary. Authors believe that the trichoscopy plays a vital role in the diagnosis of this condition by demonstrating specific trichoscopic patterns.


Implementing the SCCM Family-Centered Care Guidelines in Critical Care Nursing Practice.
Family-centered care is an important component of holistic nursing practice, particularly in critical care, where the impact on families of admitted patients can be physiologically and psychologically burdensome. Family-centered care guidelines, developed by an international group of nursing, medical, and academic experts for the American College of Critical Care Medicine/Society of Critical Care Medicine, explore the evidence base in 5 key areas of family-centered care. Evidence in each of the guideline areas is outlined and recommendations are made about how critical care nurses can use this information in family-centered care practice.


Race and Mortality in CKD and Dialysis: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study.
Few studies have investigated racial disparities in survival among dialysis patients in a manner that considers risk factors and mortality during the phase of kidney disease before maintenance dialysis. Our objective was to explore racial variations in survival among dialysis patients and relate them to racial differences in comorbid conditions and rates of death in the setting of kidney disease not yet requiring dialysis therapy. Retrospective cohort study. 3,288 black and white participants in the Chronic Renal Insufficiency Cohort (CRIC), none of whom were receiving dialysis at enrollment. Race. Mortality. Cox proportional hazards regression was used to examine the association between race and mortality starting at: (1) time of dialysis initiation and (2) entry into the CRIC. During 7.1 years of median follow-up, 678 CRIC participants started dialysis. Starting from the time of dialysis initiation, blacks had lower risk for death (unadjusted HR, 0.67; 95% CI, 0.51-0.87) compared with whites. Starting from baseline CRIC enrollment, the strength of the association between some risk factors and dialysis was notably stronger for whites than blacks. For example, the HR for dialysis onset in the presence (vs absence) of heart failure at CRIC enrollment was 1.30 (95% CI, 1.01-1.68) for blacks versus 2.78 (95% CI, 1.90-4.50) for whites, suggesting differential severity of these risk factors by race. When we included deaths occurring both before and after dialysis, risk for death was higher among blacks (vs whites) starting from CRIC enrollment (HR, 1.41; 95% CI, 1.22-1.64), but this finding was attenuated in adjusted models (HR, 1.08; 95% CI, 0.91-1.28). Residual confounding. The apparent survival advantage among blacks over whites treated with dialysis may be attributed to selected transition of a subset of whites with more severe comorbid conditions onto dialysis.


'Finding a balance' in involving patients in goal setting early after stroke: a physiotherapy perspective.
Collaborative goal setting (between patient and professional) confers benefits within stroke and neurological rehabilitation, and is recommended in clinical guidelines. However, evidence suggests that patient participation in rehabilitation goal setting is not maximized, particularly within the hospital setting. The purpose of this study was to investigate physiotherapists' perceptions about their experiences of collaborative goal setting with patients in the sub-acute stages after stroke, in the hospital setting. This qualitative study employed constructivist grounded theory methodology. Nine physiotherapists, of varying experience, were selected using purposive then theoretical sampling from three National Health Service hospital stroke units in England. Semi-structured interviews were conducted, audio-recorded and transcribed. Transcripts were coded and analysed using the constant comparative method of grounded theory to find common themes. Three themes emerged from the data: 1) 'coming to terms with stroke' - the individual patient journey; 2) the evolution of goal setting skill - the individual physiotherapist journey; and 3) 'finding a balance' - managing expectations and negotiating interactions. A provisional grounded theory was constructed, which highlighted that, from the physiotherapists' perspective, collaboration with patients within goal setting early after stroke involved finding a balance between numerous different drivers, which have the potential to compete. Patient-directed and therapist-directed goal setting approaches could be viewed as opposite ends of a continuum, along which patient-centred goal setting is possible. Physiotherapists perceived that collaborating with patients in goal setting was important but challenging. Goal setting interactions with other professionals, patients and families were perceived as complex, difficult and requiring significant effort. The importance of individuality and temporality were recognized suggesting that the goal setting approach needs to be adapted to the context and the individuals involved.


Eating and feeding are not the same: caregivers' perceptions of gastrostomy feeding for children with cerebral palsy.
Using a semi-structured questionnaire, this descriptive study examined perceptions of feeding and adherence to feeding recommendations for caregivers (26 females; mean age 32y 7mo [SD 9.4y], range 20-59y) of children with cerebral palsy (CP) and a gastrostomy tube (GT). Children in the study (15 females, 11 males; mean age 4y 8mo [SD 3y 11mo], range 8mo-16y) had had a GT in place for at least 1 month and been assessed at Level II (n=2), Level III (n=2), Level IV (n=5), and Level V (n=17) of the Gross Motor Function Classification System. A negative response was reported by 18 caregivers when the GT was recommended; however, 21 caregivers reported improvement in the children following placement. All children received formula through the GT that was adequate for complete nutrition, yet 14 caregivers gave other foods through the GT (e.g. juice, cereal, soup, or table food). Of the 17 children receiving oral feedings, meals were an unpleasant experience for over half. Of the remaining nine children, in spite of a strict nil by mouth recommendation by physicians, five continued to receive some oral feedings. Generally, caregivers perceived GT feeding as 'unnatural'. Understanding these perceptions will help clinicians to develop effective, family-centered, patient-appropriate intervention and adherence strategies for GT-fed children with CP.


A purview of waste management evolution: special emphasis on USA.
The generation of waste in urban regions over time is seen to impact the balance of anthropogenic and natural resources. Various national and international initiatives to manage urban solid waste are in place and has thus have evolved at present to form an assortment of different subcomponents involving environmental, administrative, regulatory, scientific, market, technology, and socio-economic factors, which has increasing bearing on the US due to its volume and nature of discards. This paper draws together the various aspects of municipal solid waste (MSW) management as it evolved, particularly in the American society through reviewing works and findings. In many parts of the country, waste management at present, primarily involves landfilling, incineration with and without energy recovery, recycling and composting. Legislation, nature of wastes and market trends continue to redefine management operations and its responsibilities and impacts. Complexities are added to it by the nature of urban development as well. New studies and concepts like 3Rs, cradle-to-cradle, industrial ecology, and integrated waste management are adding new dimensions for solving waste problems towards achieving sustainable resource use. Local initiatives, both public and private are in the forefront of adopting alternate waste management procedures. The assistance from various government and private bodies, supporting shifts in waste management approaches, have immense value, as according to the new paradigms, nothing goes to waste.


Systemic treatment of metastatic uveal melanoma: review of literature and future perspectives.
Up to 50% of patients with uveal melanoma develop metastatic disease with poor prognosis. Regional, mainly liver-directed, therapies may induce limited tumor responses but do not improve overall survival. Response rates of metastatic uveal melanoma (MUM) to systemic chemotherapy are poor. Insights into the molecular biology of MUM recently led to investigation of new drugs. In this study, to compare response rates of systemic treatment for MUM we searched Pubmed/Web of Knowledge databases and ASCO website (1980-2013) for "metastatic/uveal/melanoma" and "melanoma/eye." Forty studies (one case series, three phase I, five pilot, 22 nonrandomized, and two randomized phase II, one randomized phase III study, data of three expanded access programs, three retrospective studies) with 841 evaluable patients were included in the numeric outcome analysis. Complete or partial remissions were observed in 39/841 patients (overall response rate [ORR] 4.6%; 95% confidence intervals [CI] 3.3-6.3%), no responses were observed in 22/40 studies. Progression-free survival ranged from 1.8 to 7.2, median overall survival from 5.2 to 19.0 months as reported in 21/40 and 26/40 studies, respectively. Best responses were seen for chemoimmunotherapy (ORR 10.3%; 95% CI 4.8-18.7%) though mainly in first-line patients. Immunotherapy with ipilimumab, antiangiogenetic approaches, and kinase inhibitors have not yet proven to be superior to chemotherapy. MEK inhibitors are currently investigated in a phase II trial with promising preliminary data. Despite new insights into genetic and molecular background of MUM, satisfying systemic treatment approaches are currently lacking. Study results of innovative treatment strategies are urgently awaited.


EGFR molecular testing in African-American non-small cell lung cancer patients - a review of discrepant data.
Substantial discrepancy in the literature has recently emerged regarding epidermal growth factor receptor (EGFR) mutational frequency in African American (AA) NSCLC. The first wave of tissue profiling studies, including by our group in 2009, consistently observed a significantly lower frequency of EGFR mutation in AA vs. White NSCLC, whereas three recent reports appear to directly contradict these findings. Reasons for this discrepancy are unclear, but one plausible explanation arises from Simpson's paradox, the consequence of aggregating heterogeneous study cohorts (in this case, the proportion of never-smokers in the study cohort). Our review of all prior studies (combined total 386 AA NSCLC cases) underscores the wide variation in the proportion of AA never-smokers among various studies (13-57%), calling inter-study comparisons into question. In parallel, we assessed objective response by RECIST to EGFR targeted therapy for AA NSCLC in the community setting, prior to the advent of routine EGFR testing. We observed a trend toward reduced response for community-based treatment of unselected AA NSCLC (5%; 3/57) as compared to overall response rates of 10% reported by large North American trials of primarily White NSCLC patients, but this was not significant (P=0.223).


Training Deep Spiking Neural Networks Using Backpropagation.
Deep spiking neural networks (SNNs) hold the potential for improving the latency and energy efficiency of deep neural networks through data-driven event-based computation. However, training such networks is difficult due to the non-differentiable nature of spike events. In this paper, we introduce a novel technique, which treats the membrane potentials of spiking neurons as differentiable signals, where discontinuities at spike times are considered as noise. This enables an error backpropagation mechanism for deep SNNs that follows the same principles as in conventional deep networks, but works directly on spike signals and membrane potentials. Compared with previous methods relying on indirect training and conversion, our technique has the potential to capture the statistics of spikes more precisely. We evaluate the proposed framework on artificially generated events from the original MNIST handwritten digit benchmark, and also on the N-MNIST benchmark recorded with an event-based dynamic vision sensor, in which the proposed method reduces the error rate by a factor of more than three compared to the best previous SNN, and also achieves a higher accuracy than a conventional convolutional neural network (CNN) trained and tested on the same data. We demonstrate in the context of the MNIST task that thanks to their event-driven operation, deep SNNs (both fully connected and convolutional) trained with our method achieve accuracy equivalent with conventional neural networks. In the N-MNIST example, equivalent accuracy is achieved with about five times fewer computational operations.


Childhood Adversities as Determinants of Cardiovascular Disease Risk and Perceived Illness Burden in Adulthood: Comparing Retrospective and Prospective Self-Report Measures in a Longitudinal Sample of African Americans.
A large body of evidence suggests that exposure to childhood adversities increases risk for poor quality physical health in adulthood. Much of this evidence is based on retrospective measures which are believed to be contaminated by the limitations and biases of autobiographical memory. Using longitudinal data on 454 African Americans (61 percent female) this study examines the corroboration between prospective and retrospective measures of childhood adversities gathered approximately two decades apart, and the relative ability of the measures to predict self-reported illnesses and a biomarker of 30-year cardiovascular disease risk. Comparisons indicated that the retrospective and prospective measures demonstrated weak convergence and did not provide completely equivalent information about self-reported adverse childhood experiences. A series of regression models indicated that the two measures of adversities exhibited similar associations with the cardiovascular disease biomarker but divergent associations with self-reported illnesses. Furthermore, both the prospective and retrospective measures simultaneously predicted cardiovascular disease risk in adulthood. That the prospective measure did not significantly predict perceived illnesses after adjusting for the retrospective measure is evidence that childhood adversities predict self-reported health burden insofar as respondents remember those adversities as adults. The findings provide evidence that retrospective self-report measures of childhood adversities do not closely converge with prospective measures, and that retrospective measures may not provide valid estimates of the association between childhood adversities and perceived illnesses in adulthood.


Social network approaches to leadership: an integrative conceptual review.
Contemporary definitions of leadership advance a view of the phenomenon as relational, situated in specific social contexts, involving patterned emergent processes, and encompassing both formal and informal influence. Paralleling these views is a growing interest in leveraging social network approaches to study leadership. Social network approaches provide a set of theories and methods with which to articulate and investigate, with greater precision and rigor, the wide variety of relational perspectives implied by contemporary leadership theories. Our goal is to advance this domain through an integrative conceptual review. We begin by answering the question of why-Why adopt a network approach to study leadership? Then, we offer a framework for organizing prior research. Our review reveals 3 areas of research, which we term: (a) leadership in networks, (b) leadership as networks, and (c) leadership in and as networks. By clarifying the conceptual underpinnings, key findings, and themes within each area, this review serves as a foundation for future inquiry that capitalizes on, and programmatically builds upon, the insights of prior work. Our final contribution is to advance an agenda for future research that harnesses the confluent ideas at the intersection of leadership in and as networks. Leadership in and as networks represents a paradigm shift in leadership research-from an emphasis on the static traits and behaviors of formal leaders whose actions are contingent upon situational constraints, toward an emphasis on the complex and patterned relational processes that interact with the embedding social context to jointly constitute leadership emergence and effectiveness.


Myocardial sulfhydryl pool alterations occur during reperfusion after brief and prolonged myocardial ischemia in vivo.
Myocardial sulfhydryl (SH)-containing compounds, including reduced glutathione (GSH), are both defenses against and potential markers of reactive oxygen metabolite injury during ischemia and reperfusion. We examined the alterations in GSH and other myocardial SH pools during reperfusion in anesthetized dogs exposed to brief (15 minutes, n = 7) or prolonged (90 minutes, n = 6) regional ischemia caused by occlusion of the left anterior descending artery. Ninety minutes of ischemia followed by 5 hours of reperfusion, which resulted in myocardial necrosis of 43.9 +/- 4.0% of the area at risk, caused a 22% reduction in total myocardial SH groups (p less than 0.01), a 57% decrease in nonprotein myocardial SH groups (p less than 0.01), a 56% decrease in GSH (p less than 0.01), and a 62% decrease in non-GSH, nonprotein SH groups (p less than 0.02). However, protein SH groups were not significantly reduced (12% decrease, p = NS). Also, myocardial release of GSH and oxidized glutathione (GSSG) into the coronary venous effluent occurred during early reperfusion. In contrast, 15 minutes of ischemia, followed by 30 minutes of reperfusion, did not alter myocardial total SH groups, protein SH groups, or GSH (9% decrease, p = NS); nor was there reperfusion release of GSH or GSSG. However, even with brief ischemia, nonprotein SH groups decreased 23% (p less than 0.05), due mainly to a 59% decrease in the non-GSH, nonprotein SH pool (p less than 0.05). These changes after brief ischemia occurred without alterations in myocardial GSSG or the GSH/GSSG ratio.(ABSTRACT TRUNCATED AT 250 WORDS)


Complications on minimally invasive oblique lumbar interbody fusion at L2-L5 levels: a review of the literature and surgical strategies.
Fusion is the cornerstone in the treatment of an unstable degenerative lumbar spinal disease. Various techniques have been developed. Amongst these techniques exists the oblique lumbar interbody fusion (OLIF), which is the ante-psoas approach. Adequate restoration of disc height with large cages placed in the intervertebral space, indirect decompression, and correction of sagittal and coronal alignment can be achieved with OLIF procedure with the advantage of minimal risk for the psoas muscle and lumbar plexus. Nevertheless, this technique entails complications directly associated with the anatomical location where the fusion takes place. This surgical area is a window between the left lateral border of the aorta, or the left common iliac artery, and the anterior belly of the left psoas muscle. Vascular complications associated with the injury of the main vessels, segmental artery or iliolumbar vein of the lumbar spine have been reported, as well as urologic lesions due to ureter transgression, amongst others. Although these complications have been described in the literature, an article that complements this information with technical advice for its avoidance is yet to be published. This article is a review of the most frequent complications associated with the OLIF procedure in L2-L5 lumbar levels, as well as a description of technical strategies for the prevention of such complications.


A plant leucine zipper protein that recognizes an abscisic acid response element.
The mechanism by which phytohormones, like abscisic acid (ABA), regulate gene expression is unknown. An activity in nuclear extracts that interacts with the ABA response element (ABRE) from the 5' regulatory region of the wheat Em gene was identified. A complementary DNA clone was isolated whose product is a DNA binding protein (EmBP-1) that interacts specifically with an 8-base pair (bp) sequence (CACGTGGC) in the ABRE. A 2-bp mutation in this sequence prevented binding of EmBP-1. The same mutation reduced the ability of the ABRE to confer ABA responsiveness on a viral promoter in a transient assay. The 8-bp EmBP-1 target sequence was found to be conserved in several other ABA-responsive promoters and in promoters from plants that respond to signals other than ABA. Similar sequences are found in promoters from mammals, yeast, and in the major late promoter of adenovirus. The deduced amino acid sequence of EmBP-1 contains conserved basic and leucine zipper domains found in transcription factors in plants, yeast, and mammals. EmBP-1 may be a member of a highly conserved family of proteins that recognize a core sequence found in the regulatory regions of various genes that are integrated into a number of different response pathways.


Semi-passive in-situ pilot scale bioreactor successfully removed sulfate and metals from mine impacted water under subarctic climatic conditions.
Mine drainage contaminated with metals is a major environmental threat since it is a source of water pollution with devastating effects on aquatic ecosystems. Conventional active treatment technologies are prohibitively expensive and so there is increasing demand to develop reliable, cost-effective and sustainable passive or semi-passive treatment. These are promising alternatives since they leverage the metabolism of microorganisms native to the disturbed site at in situ or close to in situ conditions. Since this is a biological approach, it is not clear if semi-passive treatment would be effective in remote locations with extremely cold weather such as at mines in the subarctic. In this study we tested the hypothesis that sulfate-reducing bacteria, which are microorganisms that promote metal precipitation, exist in subarctic mine environments and their activity can be stimulated by adding a readily available carbon source. An experiment was setup at a closed mine in the Yukon Territory, Canada, where leaching of Zn and Cd occurs. To test if semi-passive treatment could precipitate these metals and prevent further leaching from waste rock, molasses as a carbon source was added to anaerobic bioreactors mimicking the belowground in-situ conditions. Microbial community analysis confirmed that sulfate-reducing bacteria became enriched in the bioreactors upon addition of molasses. The population composition remained fairly stable over the 14 month operating period despite temperature shifts from 17 to 5 °C. Sulfate reduction functionality was confirmed by quantification of the gene for dissimilatory sulfite reductase. Metals were removed from underground mine drainage fed into the bioreactors with Zn removal efficiency varying between 20.9% in winter and 89.3% in summer, and Cd removal efficiency between 39% in winter and 90.5% in summer. This study demonstrated that stimulation of native SRB in MIW was possible and that in situ semi-passive treatment can be effective in removing metals despite the cold climate.


Cation influence on heterocyclic ammonium ionic liquids: a molecular dynamics study.
Four different ionic liquids (ILs) consisting of the bis(trifluoromethanesulfonyl)imide ([NTf2]-) anion, with structurally similar systematically varying cations, are investigated herein through classical molecular dynamics. The following cations were examined: pyrrolidinium ([pyrHH]+), piperidinium ([pipHH]+), N-butyl-pyrrolidinium ([pyrH4]+) and N-butyl-N-methyl-pyrrolidinium ([pyr14]+). The focus herein is on understanding the effect of increased ring size and alkyl chain addition, resulting in three protic ILs and one aprotic IL ([pyr14][NTf2]), on the physicochemical properties of the liquids studied herein. Addition of alkyl groups to the cation appears to cause a distinct weakening of inter-ionic interactions and ordering in comparison to increasing the ring size. The influence of these structural changes, however, is clearer on the ordering of like ions than oppositely charged ions. The protic ILs exhibit important similarities in the spatial arrangement of ions on account of their strong and directed H-bonding interactions. The cation is seen to influence particular conformations of the anion which further explains the more selective ordering in the protic ILs. However, the aggregation of the butyl side chain is also seen to be an important structural determinant in [pyrH4][NTf2] and [pyr14][NTf2]. We analyze the formation of domains in order to quantitatively evaluate the microheterogeneity arising in these systems from the separation of phases according to polarities. Velocity autocorrelation functions are studied in order to characterize the stronger caging effect in the protic ILs and the weakening of the caging effect upon addition of alkyl groups to the cation, these are consistent with the coordination environment within the respective liquids. In conclusion, significant correlations between the structure and properties of these ILs are observed and quantified within this contribution.


Urinary levoglucosan as a biomarker of wood smoke exposure: observations in a mouse model and in children.
Biomass smoke is an important source of particulate matter (PM), and much remains to be discovered with respect to the human health effects associated with this specific PM source. Exposure to biomass smoke can occur in one of two main categories: short-term exposures consist of periodic, seasonal exposures typified by communities near forest fires or intentional agricultural burning, and long-term exposures are chronic and typified by the use of biomass materials for cooking or heating. Levoglucosan (LG), a sugar anhydride released by combustion of cellulose-containing materials, is an attractive candidate as a biomarker of wood smoke exposure. In the present study, Balb/c mice and children were assessed for LG in urine to determine its feasibility as a biomarker. We performed urinary detection of LG by gas chromatography/mass spectrometry after intranasal instillations of LG or concentrated PM (mice) or biomass exposure (mice or humans). After instillation, we recovered most of the LG within the first 4 hr. Experiments using glucose instillation proved the specificity of our system, and instillation of concentrated PM from wood smoke, ambient air, and diesel exhaust supported a connection between wood smoke and LG. In addition, LG was detected in the urine of mice exposed to wood smoke. Finally, a pilot human study proved our ability to detect LG in urine of children. These results demonstrate that LG in the lungs is detectable in the urine of both mice and humans and that it is a good candidate as a biomarker of exposure to biomass smoke.


Strategies to minimize intraoperative blood loss during major surgery.
Reducing operative blood loss improves patient outcomes and reduces healthcare costs. The aim of this article was to review current surgical, anaesthetic and haemostatic intraoperative blood conservation strategies. This narrative review was based on a literature search of relevant databases up to 31 July 2019 for publications relevant to reducing blood loss in the surgical patient. Interventions can begin early in the preoperative phase through identification of patients at high risk of bleeding. Directly acting anticoagulants can be stopped 48 h before most surgery in the presence of normal renal function. Aspirin can be continued for most procedures. Intraoperative cell salvage is recommended when anticipated blood loss is greater than 500 ml and this can be continued after surgery in certain situations. Tranexamic acid is safe, cheap and effective, and routine administration is recommended when anticipated blood loss is high. However, the optimal dose, timing and route of administration remain unclear. The use of topical agents, tourniquet and drains remains at the discretion of the surgeon. Anaesthetic techniques include correct patient positioning, avoidance of hypothermia and regional anaesthesia. Permissive hypotension may be beneficial in selected patients. Promising haemostatic strategies include use of pharmacological agents such as desmopressin, prothrombin complex concentrate and fibrinogen concentrate, and use of viscoelastic haemostatic assays. Reducing perioperative blood loss requires a multimodal and multidisciplinary approach. Although high-quality evidence exists in certain areas, the overall evidence base for reducing intraoperative blood loss remains limited.


Pristine Basal- and Edge-Plane-Oriented Molybdenite MoS2 Exhibiting Highly Anisotropic Properties.
The layered structure of molybdenum disulfide (MoS2 ) is structurally similar to that of graphite, with individual sheets strongly covalently bonded within but held together through weak van der Waals interactions. This results in two distinct surfaces of MoS2 : basal and edge planes. The edge plane was theoretically predicted to be more electroactive than the basal plane, but evidence from direct experimental comparison is elusive. Herein, the first study comparing the two surfaces of MoS2 by using macroscopic crystals is presented. A careful investigation of the electrochemical properties of macroscopic MoS2 pristine crystals with precise control over the exposure of one plane surface, that is, basal plane or edge plane, was performed. These crystals were characterized thoroughly by AFM, Raman spectroscopy, X-ray photoelectron spectroscopy, voltammetry, digital simulation, and DFT calculations. In the Raman spectra, the basal and edge planes show anisotropy in the preferred excitation of E2g and A1g phonon modes, respectively. The edge plane exhibits a much larger heterogeneous electron transfer rate constant k(0) of 4.96×10(-5) and 1.1×10(-3) cm s(-1) for [Fe(CN)6 ](3-/4-) and [Ru(NH3 )6 ](3+/2+) redox probes, respectively, compared to the basal plane, which yielded k(0) tending towards zero for [Fe(CN)6 ](3-/4-) and about 9.3×10(-4) cm s(-1) for [Ru(NH3 )6 ](3+/2+) . The industrially important hydrogen evolution reaction follows the trend observed for [Fe(CN)6 ](3-/4-) in that the basal plane is basically inactive. The experimental comparison of the edge and basal planes of MoS2 crystals is supported by DFT calculations.


Enterobacter bugandensis: a novel enterobacterial species associated with severe clinical infection.
Nosocomial pathogens can cause life-threatening infections in neonates and immunocompromised patients. E. bugandensis (EB-247) is a recently described species of Enterobacter, associated with neonatal sepsis. Here we demonstrate that the extended spectrum ß-lactam (ESBL) producing isolate EB-247 is highly virulent in both Galleria mellonella and mouse models of infection. Infection studies in a streptomycin-treated mouse model showed that EB-247 is as efficient as Salmonella Typhimurium in inducing systemic infection and release of proinflammatory cytokines. Sequencing and analysis of the complete genome and plasmid revealed that virulence properties are associated with the chromosome, while antibiotic-resistance genes are exclusively present on a 299 kb IncHI plasmid. EB-247 grew in high concentrations of human serum indicating septicemic potential. Using whole genome-based transcriptome analysis we found 7% of the genome was mobilized for growth in serum. Upregulated genes include those involved in the iron uptake and storage as well as metabolism. The lasso peptide microcin J25 (MccJ25), an inhibitor of iron-uptake and RNA polymerase activity, inhibited EB-247 growth. Our studies indicate that Enterobacter bugandensis is a highly pathogenic species of the genus Enterobacter. Further studies on the colonization and virulence potential of E. bugandensis and its association with septicemic infection is now warranted.


Novel corticosteroid-binding globulin variant that lacks steroid binding activity.
Corticosteroid-binding globulin (CBG) is the principal carrier for glucocorticoids in the circulation and a regulator of their bioavailability. Inherited CBG deficiencies are rarely reported, and only three causative mutations in four families have been described. In a 26-yr-old female with hypotension, fatigue, and undetectable total serum cortisol at presentation, we have identified a novel homozygous c.776g>t transversion in exon 3 of the CBG (SERPINA6) gene. This results in a p.Gly237Val substitution that is predicted to influence the positioning of two β-sheets that constitute part of the CBG steroid-binding site. Two siblings were also homozygous for the variant, whereas her mother and an unaffected sibling were heterozygous. No other symptomatic family members were identified apart from the proband. Individuals homozygous for the variant had serum CBG levels below the reference range when measured by RIA, but CBG was unmeasurable in cortisol-binding capacity assays. In the same individuals, we observed very low baseline and stimulated total serum cortisol levels but normal free serum and salivary cortisol and plasma ACTH. In a study of ultradian cortisol pulsatility, increased pulse frequency was only observed in the proband. We describe a novel CBG variant that lacks steroid binding activity. All mutant homozygotes have very low total serum cortisol, but normal free serum cortisol levels. The only biochemical feature to distinguish the symptomatic subject was increased cortisol pulsatility, and we suggest that this may influence glucocorticoid signaling and contribute to symptoms previously associated with CBG deficiency.


Artificial Cell Research as a Field that Connects Chemical, Biological and Philosophical Questions.
This review article discusses the interdisciplinary nature and implications of artificial cell research. It starts from two historical theories: Gánti's chemoton model and the autopoiesis theory by Maturana and Varela. They both explain the transition from chemical molecules to biological cells. These models exemplify two different ways in which disciplines of chemistry, biology and philosophy can profit from each other. In the chemoton model, conclusions from one disciplinary approach are relevant for the other disciplines. In contrast, the autopoiesis model itself (rather than its conclusions) is transferred from one discipline to the other. The article closes by underpinning the relevance of artificial cell research for philosophy with reference to the on-going philosophical debates on emergence, biological functions and biocentrism.


Changes in the Glycosylation of Kininogen and the Development of a Kininogen-Based Algorithm for the Early Detection of HCC.
Background: Hepatocellular carcinoma (HCC) has the greatest increase in mortality among all solids tumors in the United States related to low rates of early tumor detection. Development of noninvasive biomarkers for the early detection of HCC may reduce HCC-related mortality.Methods: We have developed an algorithm that combines routinely observed clinical values into a single equation that in a study of >3,000 patients from 5 independent sites improved detection of HCC as compared with the currently used biomarker, alpha-fetoprotein (AFP), by 4% to 20%. However, this algorithm had limited benefit in those with AFP <20 ng/mL. To that end, we have developed a secondary algorithm that incorporates a marker, fucosylated kininogen, to improve the detection of HCC, especially in those with AFP <20 ng/mL and early-stage disease.Results: The ability to detect early-stage AFP-negative (AFP <20 ng/mL) HCC increased from 0% (AFP alone) to 89% (for the new algorithm). Glycan analysis revealed that kininogen has several glycan modifications that have been associated with HCC, but often not with specific proteins, including increased levels of core and outer-arm fucosylation and increased branching.Conclusions: An algorithm combining fucosylated kininogen, AFP, and clinical characteristics is highly accurate for early HCC detection.Impact: Our biomarker algorithm could significantly improve early HCC detection and curative treatment eligibility in patients with cirrhosis. Cancer Epidemiol Biomarkers Prev; 26(5); 795-803. ©2017 AACR.


Genetic dissection of complex traits with chromosome substitution strains of mice.
Chromosome substitution strains (CSSs) have been proposed as a simple and powerful way to identify quantitative trait loci (QTLs) affecting developmental, physiological, and behavioral processes. Here, we report the construction of a complete CSS panel for a vertebrate species. The CSS panel consists of 22 mouse strains, each of which carries a single chromosome substituted from a donor strain (A/J) onto a common host background (C57BL/6J). A survey of 53 traits revealed evidence for 150 QTLs affecting serum levels of sterols and amino acids, diet-induced obesity, and anxiety. These results demonstrate that CSSs greatly facilitate the detection and identification of genes that control the wide diversity of naturally occurring phenotypic variation in the A/J and C57BL/6J inbred strains.


Allelic variants of cytochrome P450 2C9 modify the interaction between nonsteroidal anti-inflammatory drugs and coumarin anticoagulants.
Cytochrome P450 (CYP) plays a key role in the metabolism of coumarin anticoagulants and nonsteroidal anti-inflammatory drugs (NSAIDs). Because CYP2C9 is a genetically polymorphic enzyme, genetic variability could play an important role in the potential interaction between NSAIDs and coumarins. We investigated whether NSAIDs were associated with overanticoagulation during therapy with coumarins and evaluated the effect of the CYP2C9 polymorphisms on this potential interaction. We conducted a population-based cohort study among patients of an anticoagulation clinic who were treated with acenocoumarol or phenprocoumon between April 1, 1991, and May 31, 2003, and whose CYP2C9 status was known. Patients were followed up until an international normalized ratio (INR) of 6.0 or greater was reached or until the end of treatment, death, or the end of the study. Proportional hazards regression analysis was used to estimate the risk of an INR of 6.0 or greater in relation to concomitant use of a coumarin anticoagulant and NSAIDs after adjustment for several potentially confounding factors. To study effect modification by CYP2C9 genotype, stratified analyses were performed for wild-type patients and patients with a variant genotype. Of the 973 patients in the cohort, 415 had an INR of 6.0 or greater. Several NSAIDs increased the risk of overanticoagulation. The risk of overanticoagulation was 2.98 (95% confidence interval, 1.09-7.02) in coumarin-treated patients taking NSAIDs with a CYP2C9*2 allele and 10.8 (95% confidence interval, 2.57-34.6) in those with a CYP2C9*3 allele. Several NSAIDs were associated with overanticoagulation. For NSAIDs that are known CYP2C9 substrates, this risk was modified by allelic variants of CYP2C9. More frequent INR monitoring of patients taking NSAIDs is warranted.


Effect of a chemical chaperone, tauroursodeoxycholic acid, on HDM-induced allergic airway disease.
Endoplasmic reticulum (ER) stress-induced unfolded protein response plays a critical role in inflammatory diseases, including allergic airway disease. However, the benefits of inhibiting ER stress in the treatment of allergic airway disease are not well known. Herein, we tested the therapeutic potential of a chemical chaperone, tauroursodeoxycholic acid (TUDCA), in combating allergic asthma, using a mouse model of house dust mite (HDM)-induced allergic airway disease. TUDCA was administered during the HDM-challenge phase (preventive regimen), after the HDM-challenge phase (therapeutic regimen), or therapeutically during a subsequent HDM rechallenge (rechallenge regimen). In the preventive regimen, TUDCA significantly decreased HDM-induced inflammation, markers of ER stress, airway hyperresponsiveness (AHR), and fibrosis. Similarly, in the therapeutic regimen, TUDCA administration efficiently decreased HDM-induced airway inflammation, mucus metaplasia, ER stress markers, and AHR, but not airway remodeling. Interestingly, TUDCA administered therapeutically in the HDM rechallenge regimen markedly attenuated HDM-induced airway inflammation, mucus metaplasia, ER stress markers, methacholine-induced AHR, and airway fibrotic remodeling. These results indicate that the inhibition of ER stress in the lungs through the administration of chemical chaperones could be a valuable strategy in the treatment of allergic airway diseases.


Iridium(I) PNP complexes in the sp³ C-H bond activation of methyl propanoate and related esters.
The utilisation of the PNP iridium pincer complex [Ir(PNP)(COE)][BF4] [PNP = 2,6-bis{(di-tert-butylphosphino)methyl}pyridine; COE = cyclooctene] in the sp(3) C-H activation of methyl propanoate and other related esters was explored. In particular, this study provides further insight into the factors that govern the regioselectivity of such reactions. These included factors such as the steric demands of the substrate, the formation of favourable ring systems as well as the electronic effects that may influence the pKa values of protons. In particular, the effects of water on the outcome of these reactions were of great interest, since earlier literature reports have shown the presence of water to promote selective C-H activation in the α-position of ketones.


Pandemic H1N1 in Canada and the use of evidence in developing public health policies--a policy analysis.
When responding to a novel infectious disease outbreak, policies are set under time constraints and uncertainty which can limit the ability to control the outbreak and result in unintended consequences including lack of public confidence. The H1N1 pandemic highlighted challenges in public health decision-making during a public health emergency. Understanding this process to identify barriers and modifiable influences is important to improve the response to future emergencies. The purpose of this study is to examine the H1N1 pandemic decision-making process in Canada with an emphasis on the use of evidence for public health decisions. Using semi-structured key informant interviews conducted after the pandemic (July-November 2010) and a document analysis, we examined four highly debated pandemic policies: use of adjuvanted vaccine by pregnant women, vaccine priority groups and sequencing, school closures and personal protective equipment. Data were analysed for thematic content guided by Lomas' policy decision-making framework as well as indicative coding using iterative methods. We interviewed 40 public health officials and scientific advisors across Canada and reviewed 76 pandemic policy documents. Our analysis revealed that pandemic pre-planning resulted in strong beliefs, which defined the decision-making process. Existing ideological perspectives of evidence strongly influenced how information was used such that the same evidentiary sources were interpreted differently according to the ideological perspective. Participants recognized that current models for public health decision-making failed to make explicit the roles of scientific evidence in relation to contextual factors. Conflict avoidance theory explained policy decisions that went against the prevailing evidence. Clarification of roles and responsibilities within the public health system would reduce duplication and maintain credibility. A more transparent and iterative approach to incorporating evidence into public health decision-making that reflects the realities of the external pressures present during a public health emergency is needed.


Goldsurfer2 (Gs2): a comprehensive tool for the analysis and visualization of genome wide association studies.
Genome wide association (GWA) studies are now being widely undertaken aiming to find the link between genetic variations and common diseases. Ideally, a well-powered GWA study will involve the measurement of hundreds of thousands of single nucleotide polymorphisms (SNPs) in thousands of individuals. The sheer volume of data generated by these experiments creates very high analytical demands. There are a number of important steps during the analysis of such data, many of which may present severe bottlenecks. The data need to be imported and reviewed to perform initial quality control (QC) before proceeding to association testing. Evaluation of results may involve further statistical analysis, such as permutation testing, or further QC of associated markers, for example, reviewing raw genotyping intensities. Finally significant associations need to be prioritised using functional and biological interpretation methods, browsing available biological annotation, pathway information and patterns of linkage disequilibrium (LD). We have developed an interactive and user-friendly graphical application to be used in all steps in GWA projects from initial data QC and analysis to biological evaluation and validation of results. The program is implemented in Java and can be used on all platforms. Very large data sets (e.g. 500 k markers and 5000 samples) can be quality assessed, rapidly analysed and integrated with genomic sequence information. Candidate SNPs can be selected and functionally evaluated.


Genetic differentiation between Príncipe Island and mainland populations of the grey parrot (Psittacus erithacus), and implications for conservation.
The range of the grey parrot (Psittacus erithacus), one of the most heavily harvested bird species for the international pet trade, spans the forest belt of Central and West Africa and includes the oceanic island of Príncipe (Gulf of Guinea). Morphological variation led to the recognition of two mainland subspecies (P. e. erithacus and P. e. timneh). The population from Príncipe was originally described as a separate species (P. princeps) but is currently included in the nominate race. We used 1932 bp of the mitochondrial genome to clarify the genealogical affinities between the two currently-recognized mainland subspecies and the Príncipe population. Sampling included 20 individuals from Príncipe, 17 from P. e. erithacus, and 13 from P. e. timneh. We found that the two mainland subspecies form two independent lineages, having diverged up to 2.4 million years ago (Ma), and that the Príncipe population is composed of two lineages that diverged in allopatry. The most common lineage is descended from the first colonizers and evolved in isolation for up to 1.4 Ma. Contrary to current understanding, this 'Príncipe lineage' is more closely related to the timneh than to the erithacus subspecies. The second lineage consists of P. e. erithacus birds from the nearby mainland that colonized the island in recent times. The evolutionary dynamics of the grey parrot population of Príncipe are primarily characterized by isolation, with new genetic variation being added through rare immigration events. The heavily harvested Príncipe grey parrot population should therefore be treated as an independent conservation unit.


Synergistic effects of GDNF and VEGF on lifespan and disease progression in a familial ALS rat model.
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the brain and spinal cord. We have recently shown that human mesenchymal stem cells (hMSCs) modified to release glial cell line-derived neurotrophic factor (GDNF) decrease disease progression in a rat model of ALS when delivered to skeletal muscle. In the current study, we determined whether or not this effect could be enhanced by delivering GDNF in concert with other trophic factors. hMSC engineered to secrete GDNF (hMSC-GDNF), vascular endothelial growth factor (hMSC-VEGF), insulin-like growth factor-I (hMSC-IGF-I), or brain-derived neurotrophic factor (hMSC-BDNF), were prepared and transplanted bilaterally into three muscle groups. hMSC-GDNF and hMSC-VEGF prolonged survival and slowed the loss of motor function, but hMSC-IGF-I and hMSC-BDNF did not have any effect. We then tested the efficacy of a combined ex vivo delivery of GDNF and VEGF in extending survival and protecting neuromuscular junctions (NMJs) and motor neurons. Interestingly, the combined delivery of these neurotrophic factors showed a strong synergistic effect. These studies further support ex vivo gene therapy approaches for ALS that target skeletal muscle.


Quantitation of somatostatin receptor type 2 gene expression in neuroblastoma cell lines and primary tumors using competitive reverse transcription-polymerase chain reaction.
We previously reported the presence of somatostatin (SS-14)-binding sites in a wide panel of human neuroblastoma (NB) tumor cell lines. Given that the adrenal gland and its relative embryonal and adult tumors express an abundance of mRNA for somatostatin receptor type 2 (sst2) mRNA, we studied the quantitative expression of sst2 in 6 NB cell lines and 15 primary tumors using competitive reverse transcription (RT)-PCR. This method uses an insertion mutant of the target gene as a competitor for the RT-PCR reaction, thus allowing exact quantitation of sst2 mRNA abundance. We found expression of specific transcripts for sst2 in all of the NB cell lines and tumors investigated (range, 9 x 10(5)-4 x 10(9) molecules/microg RNA). In NB cells, the expression of sst2 was highly correlated with SS-14-binding sites (R = 0.93). In primary tumors, sst2 was positively related to the expression of the neuroendocrine marker secretogranin II (P < 0.05) and negatively related to N-myc amplification (a poor prognostic factor, P < 0.005) and metastatic dissemination (P < 0.05). In addition, Kaplan-Meier curves indicate that sst2 expression is positively related to survival (P = 0.01). In a patient with stage IVs disease (a spontaneously regressing form), we found the highest sst2 expression (4 x 10(9) molecules/microgram RNA), a value relatively similar to that of normal adrenal. In conclusion, these data indicate that quantitation of sst2, as assessed with competitive RT-PCR, could represent a new prognostic tool in the neuroendocrine tumor NB. Since sst2 recognizes octreotide with high affinity, these findings could also have both diagnostic and therapeutic value.


Associations of symptoms, neurocognition, and metacognition with insight in schizophrenia spectrum disorders.
Many persons with schizophrenia experience poor insight and, as a result, are at risk for treatment non-adherence and numerous negative outcomes. However, to date, the etiology of poor insight has not yet been fully elucidated. One recent theory concerning the roots of poor insight in schizophrenia has proposed that it may result, in part, from impairments in metacognition, or the capacity to think about thinking. The present study thus aims to examine whether metacognition is associated with insight even after controlling for the effects of psychiatric symptomatology and neurocognition. In this study, 95 adults with a schizophrenia spectrum disorder were assessed on measures of insight (i.e., awareness of symptoms, treatment needs, and illness consequences), psychiatric symptoms (i.e., positive symptoms, negative symptoms, and general psychopathology), neurocognitive functions (i.e., executive function, memory, and attention), and metacognitive capacities (i.e., self-reflectivity and theory of mind). Univariate correlations followed by stepwise multiple regressions, which controlled for symptoms and neurocognition, indicated that both self-reflectivity and theory of mind were significantly linked with awareness of symptoms; theory of mind was linked with awareness of treatment needs; and self-reflectivity was linked with awareness of illness consequences. Importantly, these findings suggest that metacognitive capacities may be related to insight independent of concurrent psychiatric symptoms and neurocognitive deficits. Moreover, awareness of different facets of the illness may require contributions from different components of metacognition. Future research should investigate how existing metacognitive skill training programs could potentially be tailored, or modified, to help persons with schizophrenia to develop and enhance insight.


Drowning Prevention: Assessment of a Classroom-Based Water Safety Education Program in Vietnam.
Youth drowning continues to be a primary public health issue globally with Eurasian countries experiencing some of the highest recorded rates of injury and death in aquatic settings. The country of Vietnam is currently working toward reducing the number of youth drowning fatalities. Part of these efforts is the introduction of an in-school water safety educational program. For this study, pilot pre/post data were acquired and used to assess overall knowledge acquisition and changes in knowledge of youth in grades 1 to 5 in central Vietnam. A total of 229 schools participated, resulting in 40 198 usable surveys. The results indicated that overall there was a significant change in scores with an acceptable effect size between measures. Mean scores for each of the water safety messages were rated as acceptable (above 90%), satisfactory (between 70% and 90%), and areas of concern (under 70%). Recommendations were made to program leaders about identified areas of concern.


Temperature-dependent Sellmeier equations of nonlinear optical crystal La(2)CaB(10)O(19).
The thermal dependence principal refractive indices ofLa(2)CaB(10)O(19) (LCB) crystal at wavelengths of 0.254, 0.365, 0.405, 0.480, 0.546, 0.644, 0.852, 1.014, and 2.325 μm were accurately measured by using the vertical incidence method within the temperature range from 25 to 170 °C. We derived equations of thermal refractive index coefficients as a function of wavelength that could be used to calculate the principal thermal refractive indices at different wavelengths. The temperature-dependent Sellmeier equations were also derived and used to calculate the phase-matching angles for the third-harmonic generation of LCB crystal at different temperatures. Theoretical and experimental phase-matching angles for the type I third-harmonic generation of LCB crystal at different temperatures were in good agreement.


Sequence and phylogenetic analysis of viper venom serine proteases.
Snakebites are a major neglected tropical disease responsible for as many as 95000 deaths every year worldwide. Viper venom serine proteases disrupt haemostasis of prey and victims by affecting various stages of the blood coagulation system. A better understanding of their sequence, structure, function and phylogenetic relationships will improve the knowledge on the pathological conditions and aid in the development of novel therapeutics for treating snakebites. A large dataset for all available viper venom serine proteases was developed and analysed to study various features of these enzymes. Despite the large number of venom serine protease sequences available, only a small proportion of these have been functionally characterised. Although, they share some of the common features such as a C-terminal extension, GWG motif and disulphide linkages, they vary widely between each other in features such as isoelectric points, potential N-glycosylation sites and functional characteristics. Some of the serine proteases contain substitutions for one or more of the critical residues in catalytic triad or primary specificity pockets. Phylogenetic analysis clustered all the sequences in three major groups. The sequences with substitutions in catalytic triad or specificity pocket clustered together in separate groups. Our study provides the most complete information on viper venom serine proteases to date and improves the current knowledge on the sequence, structure, function and phylogenetic relationships of these enzymes. This collective analysis of venom serine proteases will help in understanding the complexity of envenomation and potential therapeutic avenues.


Discontinuities in quinoa biodiversity in the dry Andes: An 18-century perspective based on allelic genotyping.
History and environment shape crop biodiversity, particularly in areas with vulnerable human communities and ecosystems. Tracing crop biodiversity over time helps understand how rural societies cope with anthropogenic or climatic changes. Exceptionally well preserved ancient DNA of quinoa (Chenopodium quinoa Willd.) from the cold and arid Andes of Argentina has allowed us to track changes and continuities in quinoa diversity over 18 centuries, by coupling genotyping of 157 ancient and modern seeds by 24 SSR markers with cluster and coalescence analyses. Cluster analyses revealed clear population patterns separating modern and ancient quinoas. Coalescence-based analyses revealed that genetic drift within a single population cannot explain genetic differentiation among ancient and modern quinoas. The hypothesis of a genetic bottleneck related to the Spanish Conquest also does not seem to apply at a local scale. Instead, the most likely scenario is the replacement of preexisting quinoa gene pools with new ones of lower genetic diversity. This process occurred at least twice in the last 18 centuries: first, between the 6th and 12th centuries-a time of agricultural intensification well before the Inka and Spanish conquests-and then between the 13th century and today-a period marked by farming marginalization in the late 19th century likely due to a severe multidecadal drought. While these processes of local gene pool replacement do not imply losses of genetic diversity at the metapopulation scale, they support the view that gene pool replacement linked to social and environmental changes can result from opposite agricultural trajectories.


Image thresholding techniques for localization of sub-resolution fluorescent biomarkers.
In this article, we explore adaptive global and local segmentation techniques for a lab-on-chip nutrition monitoring system (NutriChip). The experimental setup consists of Caco-2 intestinal cells that can be artificially stimulated to trigger an immune response. The eventual response is optically monitored using immunofluoresence techniques targeting toll-like receptor 2 (TLR2). Two problems of interest need to be addressed by means of image processing. First, a new cell sample must be properly classified as stimulated or not. Second, the location of the stained TLR2 must be recovered in case the sample has been stimulated. The algorithmic approach to solving these problems is based on the ability of a segmentation technique to properly segment fluorescent spots. The sample classification is based on the amount and intensity of the segmented pixels, while the various segmenting blobs provide an approximate localization of TLR2. A novel local thresholding algorithm and three well-known spot segmentation techniques are compared in this study. Quantitative assessment of these techniques based on real and synthesized data demonstrates the improved segmentation capabilities of the proposed algorithm.


AIPL1 implicated in the pathogenesis of two cases of autosomal recessive retinal degeneration.
To localize and identify the gene and mutations causing autosomal recessive retinal dystrophy in two consanguineous Pakistani families. Consanguineous families from Pakistan were ascertained to be affected with autosomal recessive retinal degeneration. All affected individuals underwent thorough ophthalmologic examinations. Blood samples were collected, and genomic DNA was extracted using a salting out procedure. Genotyping was performed using microsatellite markers spaced at approximately 10 cM intervals. Two-point linkage analysis was performed with the lod score method. Direct DNA sequencing of amplified genomic DNA was performed for mutation screening of candidate genes. Genome-wide linkage scans yielded a lod score of 3.05 at θ=0 for D17S1832 and 3.82 at θ=0 for D17S938, localizing the disease gene to a 12.22 cM (6.64 Mb) region flanked by D17S1828 and D17S1852 for family 61032 and family 61227, which contains aryl hydrocarbon receptor interacting protein-like 1 (AIPL1), a gene previously implicated in recessive Leber congenital amaurosis and autosomal dominant cone-rod dystrophy. Sequencing of AIPL1 showed a homozygous c.773G>C (p.Arg258Pro) sequence change in all affected individuals of family 61032 and a homozygous c.465G>T (p.(H93_Q155del)) change in all affected members of family 61227. The results strongly suggest that the c.773G>C (p.R258P) and c.465G>T (p.(H93_Q155del)) mutations in AIPL1 cause autosomal recessive retinal degeneration in these consanguineous Pakistani families.


Aggregation induced enhanced and exclusively highly Stokes shifted emission from an excited state intramolecular proton transfer exhibiting molecule.
The inner filter effect due to self-quenching dominates the normal emission of dyes at higher concentrations, which would limit their applications. Since normal emission was also observed with aggregation induced emission enhancement (AIEE) active excited state intramolecular proton transfer (ESIPT) exhibiting molecules, two new molecules are synthesized and studied to obtain normal emission free AIEE. The molecules are 4-(3-(benzo[d]thiazol-2-yl)-5-tert-butyl-4-hydroxybenzyl)-2-(benzo[d]thiazol-2-yl)-6-tert-butyl phenol (bis-HPBT) and its oxazole analogue (bis-HPBO). Of these molecules, bis-HPBT, which is weakly fluorescent in tetrahydrofuran solution, shows a sudden high enhancement in fluorescence upon addition of 70% water due to the formation of aggregates. Though the normal emission is also observed in tetrahydrofuran, it is completely eliminated in the aggregates, and the aggregates display exclusive tautomer emission. However, bis-HPBO does not emit such an exclusive tautomer emission in the water/tetrahydrofuran mixture. The enhancement in the fluorescence quantum yield of bis-HPBT in 70% water is ∼300 times higher than that in tetrahydrofuran. The modulated molecular structure of bis-HPBT is the cause of this outstanding AIEE. The observation of almost exclusive tautomer emission is a new additional advantage of AIEE from bis-HPBT over other ESIPT molecules. Since the tautomer emission is highly Stokes shifted, no overlap with the absorption spectrum occurs and therefore, the inner filter effect is averted. The aggregated structure acts as a good fluorescence chemosensor for metal ions as well as anions. The aggregated structure is cell permeable and can be used for cell imaging.


Efficacy of fractional microneedle radiofrequency device in the treatment of primary axillary hyperhidrosis: a pilot study.
Fractional microneedle radiofrequency (FMR) devices deliver energy to the deep dermis through insulated microneedles without destroying the epidermis. These FMR devices have been shown to be effective for the treatment of wrinkles, acne scars and large pores. In this study it was postulated that FMR energy could specifically affect the sweat glands, preserving the skin surface even if sweat glands were seated in the deep dermis. To evaluate the efficacy and safety of FMR for primary axillary hyperhidrosis (PAH) treatment and to conduct a histological analysis before and after treatment. Twenty patients with PAH had 2 sessions of bipolar FMR treatment at 4-week intervals. Clinical improvement was evaluated using a Hyperhidrosis Disease Severity Scale (HDSS) and photographs were taken using the starch-iodine test at every visit and 2 months after the last treatment. The amount of sweat reduction was indirectly assessed using a Tewameter™. Skin biopsies were obtained from 3 of the enrolled patients before and after treatment. The satisfaction and adverse reactions of the research participants were recorded at every follow-up visit. HDSS scores decreased significantly from a baseline of 3.3 to 1.5 and 1.8 after the first and second months of posttreatment follow-up sessions, respectively (p < 0.001). In response to a subjective assessment at 1 month after the second treatment, 75% of patients (n = 15) had an HDSS score of 1 or 2, and 70% of patients (n = 14) expressed more than 50% improvement in their sweating. The starch-iodine reaction was also remarkably reduced in 95% of patients (n = 19) after FMR treatment. Histological findings showed a decrease in the number and size of both apocrine and eccrine glands 1 month after the final treatment. Side effects were minimal and included mild discomfort, transient swelling and postinflammatory hyperpigmentation. FMR treatment was effective for the treatment of PAH without significant adverse reactions due to direct volumetric heating of the lower dermis.


Three palonosetron regimens to prevent CINV in myeloma patients receiving multiple-day high-dose melphalan and hematopoietic stem cell transplantation.
Explore safety and efficacy of three palonosetron-containing regimens for emesis prevention over 7 days in multiple myeloma (MM) patients receiving melphalan (100 mg/m(2)) and hematopoietic stem cell transplantation (HSCT). Randomized, double-blind pilot study in MM patients (n=73) receiving 1, 2, or 3 days of 0.25 mg palonosetron (30-s i.v. bolus) 30 min before melphalan (days -2 and -1) and HSCT (day 0). Patients received dexamethasone (20 mg i.v., days -2 and -1) immediately before or after study drug/placebo. Daily diaries recorded emesis, rescue medication, nausea duration, and adverse events (AEs). Seven-day complete protection (no emesis) occurred in 41.7% [95% confidence interval (CI) 22.1% to 63.4%], 41.7% (95% CI 22.1% to 63.4%), and 44.0% (95% CI 24.2% to 65.1%) of patients receiving 1, 2, or 3 days of palonosetron, respectively (P=0.43). Complete response (emesis free without rescue medication) occurred in 8.3%, 20.8%, and 20.0% (P=0.14). Common AEs (≥10%) were mild-to-moderate diarrhea, constipation, headache, insomnia, and flatulence. No serious AEs occurred. Palonosetron with dexamethasone was safe and effective in preventing emesis in MM patients receiving melphalan and HSCT. This pilot study with a limited number of patients suggests that multiple doses of palonosetron could be more effective than a single dose in making patients emesis free without need for rescue medication. However, even multiple doses of palonosetron resulted in only 20% of patients being emesis free without rescue medication, suggesting that further improvement will require development of more effective combination antiemetic therapy.


Tourism partnerships in protected areas: exploring contributions to sustainability.
Partnerships between natural-area managers and the tourism industry have been suggested to contribute to sustainability in protected areas. This article explores how important sustainability outcomes of partnerships are to their members, how well they are realised and the features of partnerships leading to their achievement. In 21 case studies in Australia, interviews (n = 97) and surveys (n = 100) showed that of 14 sustainability outcomes, improved understanding of protected areas values and improved biodiversity conservation were the most important. Other highly ranked outcomes were greater respect for culture, heritage, and/or traditions; improved quality of environmental conditions; social benefits to local communities; and improved economic viability of the protected area. Scores for satisfaction with outcomes were, like those for importance, all high but were less than those for importance for the majority, with improvement in quality of environmental conditions showing the largest gap. The satisfaction score exceeded that for importance only for increased competitiveness of the protected area as a tourist destination. "Brown" aspects of sustainability, i.e., decreased waste or energy use, were among the lowest-scoring outcomes for both importance and satisfaction. The most important factor enabling sustainability outcomes was provision of benefits to partnership members. Others were increased financial support, inclusiveness, supportive organisational and administrative arrangements, direct involvement of decision makers, partnership maturity, creation of new relationships, decreased conflict, and stimulation of innovation. Improving sustainability outcomes, therefore, requires maintaining these partnership attributes and also increasing emphasis on reducing waste and resource use.


Involvement of lactate transport in two object recognition tasks that require either the hippocampus or striatum.
Growing evidence indicates that hippocampal lactate, released from astrocytes, is an important regulator of learning and memory processing. This study evaluated the selective involvement of hippocampal and striatal lactate in two object recognition tasks. The tasks tested recognition memory after a change in location of two target objects (double object location; dOL) or after replacement of familiar targets with two new objects set in the original locations (double object replacement; dOR). Rats received three study sessions across which exploration times decreased. The recognition index was the change in exploration time of both objects on a test trial from the exploration times on the final study trial. We first verified a double dissociation between hippocampus and striatum across these tasks. The sodium channel blocker, lidocaine, was infused into one of the two brain regions after the study sessions and before the test trial. To test the role of neuronal lactate in recognition memory, an inhibitor of the neuronal lactate transporter, α-cyano-4-hydroxycinnamate (4-CIN), was similarly infused. For both drugs, infusions into the hippocampus but not the striatum impaired recognition in the dOL, whereas infusions into the striatum but not hippocampus impaired recognition in the dOR. The findings obtained with 4-CIN demonstrate for the first time the importance of neuronal lactate uptake in the hippocampus and the striatum for object recognition memory processing. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Characterization and drug sensitivity of four newly established colon adenocarcinoma cell lines to antifolate inhibitors of thymidylate synthase.
Four new cell lines were established from the primary tumors of patients with untreated colorectal adenocarcinoma. Drug sensitivity and characterization of these cell lines was performed. Three of the four cell lines formed colonies in soft agar and all were tumorigenic in nude mice. The cell lines were morphologically similar but had differences in growth characteristics. Two of the cell lines, C18 (CCCL-4) and C29 (CCCL-6), had a longer doubling time compared with C85 (CCCL-1) and C86 (CCCL-2). The C18 and C29 cell lines had chromosome 17 abnormalities and evidence by immunohistochemistry of a mutant p53 and had decreased levels of thymidylate synthase and dihydrofolate reductase proteins, associated with decreased thymidylate synthase catalytic activity in C18 and no detectable activity in C29. Raltitrexed and GW1843U89 showed potent cytotoxic activity and all four cell lines displayed similar cytotoxicity to these folate thymidylate synthase inhibitors. The C18 and C29 cell lines were in general resistant to the other agents tested (methotrexate, 5-fluorouracil, nolatrexed) when compared with the C85 and C86 cell lines. These new cell lines may be useful for the study of colorectal adenocarcinoma and for evaluating new drugs or treatment schedules.


Undifferentiated lingual gestures in children with articulation/phonological disorders.
Previous research using electropalatography (EPG) has shown that a distinctive articulatory characteristic of lingual consonants in the speech of school-age children with articulation/phonological disorders (APD) is a high amount of tongue-palate contact. Consonants produced in this way have been referred to as undifferentiated lingual gestures. This article reviews the EPG literature on undifferentiated gestures with 4 overarching goals: (a) to provide a precise articulatory description of undifferentiated gestures, (b) to estimate the rate of occurrence of undifferentiated gestures in children with APD, (c) to propose an original.interpretation of undifferentiated gestures, and (d) to discuss the significance of the gestures in the light of current theories of APD. Undifferentiated gestures typically occur during productions of lingual consonant targets and are characterized by contact that lacks clear differentiation between the tongue apex, tongue body, and lateral margins of the tongue. The EPG literature reports 17 school-age children with APD, of whom 12 (71%) show evidence of undifferentiated gestures. Standard transcriptions do not reliably detect undifferentiated gestures, which are transcribed as speech errors (e.g., phonological substitutions, phonetic distortions) in some contexts, but are transcribed as correct productions in other contexts. Undifferentiated gestures are interpreted as reflecting a speech motor constraint involving either delayed or deviant control of functionally independent regions of the tongue. The limitations of the current EPG literature are stated, and the need for research into undifferentiated gestures in preschool children is discussed.


Aquatic versus terrestrial attachment: Water makes a difference.
Animal attachment to a substrate is very different in terrestrial and aquatic environments. We discuss variations in both the forces acting to detach animals and forces of attachment. While in a terrestrial environment gravity is commonly understood as the most important detachment force, under submerged conditions gravity is nearly balanced out by buoyancy and therefore matters little. In contrast, flow forces such as drag and lift are of higher importance in an aquatic environment. Depending on the flow conditions, flow forces can reach much higher values than gravity and vary in magnitude and direction. For many of the attachment mechanisms (adhesion including glue, friction, suction and mechanical principles such as hook, lock, clamp and spacer) significant differences have to be considered under water. For example, the main principles of dry adhesion, van der Waals forces and chemical bonding, which make a gecko stick to the ceiling, are weak under submerged conditions. Capillary forces are very important for wet adhesion, e.g., in terrestrial beetles or flies, but usually do not occur under water. Viscous forces are likely an important contributor to adhesion under water in some mobile animals such as torrent frogs and mayflies, but there are still many open questions to be answered. Glue is the dominant attachment mechanism of sessile aquatic animals and the aquatic realm presents many challenges to this mode of attachment. Viscous forces and the lack of surface tension under submerged conditions also affect frictional interactions in the aquatic environment. Moreover, the limitation of suction to the pressure difference at vacuum conditions can be ameliorated under water, due to the increasing pressure with water depth.


Functional specialization for auditory-spatial processing in the occipital cortex of congenitally blind humans.
The study of the congenitally blind (CB) represents a unique opportunity to explore experience-dependant plasticity in a sensory region deprived of its natural inputs since birth. Although several studies have shown occipital regions of CB to be involved in nonvisual processing, whether the functional organization of the visual cortex observed in sighted individuals (SI) is maintained in the rewired occipital regions of the blind has only been recently investigated. In the present functional MRI study, we compared the brain activity of CB and SI processing either the spatial or the pitch properties of sounds carrying information in both domains (i.e., the same sounds were used in both tasks), using an adaptive procedure specifically designed to adjust for performance level. In addition to showing a substantial recruitment of the occipital cortex for sound processing in CB, we also demonstrate that auditory-spatial processing mainly recruits the right cuneus and the right middle occipital gyrus, two regions of the dorsal occipital stream known to be involved in visuospatial/motion processing in SI. Moreover, functional connectivity analyses revealed that these reorganized occipital regions are part of an extensive brain network including regions known to underlie audiovisual spatial abilities (i.e., intraparietal sulcus, superior frontal gyrus). We conclude that some regions of the right dorsal occipital stream do not require visual experience to develop a specialization for the processing of spatial information and to be functionally integrated in a preexisting brain network dedicated to this ability.


Technology in the management of type 1 diabetes mellitus - current status and future prospects.
Type 1 diabetes mellitus (T1DM) represents 5-10% of diabetes cases worldwide. The incidence of T1DM is increasing, and there is no immediate prospect of a cure. As such, lifelong management is required, the burden of which is being eased by novel treatment modalities, particularly from the field of diabetes technologies. Continuous glucose monitoring has become the standard of care and includes factory-calibrated subcutaneous glucose monitoring and long-term implantable glucose sensing. In addition, considerable progress has been made in technology-enabled glucose-responsive insulin delivery. The first hybrid insulin-only closed-loop system has been commercialized, and other closed-loop systems are under development, including dual-hormone glucose control systems. This Review focuses on well-established diabetes technologies, including glucose sensing, pen-based insulin delivery, data management and data analytics. We also cover insulin pump therapy, threshold-based suspend, predictive low-glucose suspend and single-hormone and dual-hormone closed-loop systems. Clinical practice recommendations for insulin pump therapy and continuous glucose monitoring are presented, and ongoing research and future prospects are highlighted. We conclude that the management of T1DM is improved by diabetes technology for the benefit of the majority of people with T1DM, their caregivers and guardians and health-care professionals treating patients with T1DM.


Multiplex Fabry-Perot interferometer: II. Laboratory prototype.
The Multiplex Fabry-Perot interferometer (MFPI) consists of a Fabry-Perot interferometer in which the étalon plate separation is changed over a large optical distance. Fourier transformation of the resultant interferogram allows one to treat the multiple reflections within the étalon cavity in a manner analogous to an array of Michelson-type interferometers. However, the scan distance required by the MFPI is much less than for a comparable Michelson. The design and construction of the MFPI are described. Solar absorption spectra measured with this instrument are compared with results from the FASCODE atmospheric model.


Cutaneous and renal glomerular vasculopathy as a cause of acute kidney injury in dogs in the UK.
To describe the signalment, clinicopathological findings and outcome in dogs presenting with acute kidney injury (AKI) and skin lesions between November 2012 and March 2014, in whom cutaneous and renal glomerular vasculopathy (CRGV) was suspected and renal thrombotic microangiopathy (TMA) was histopathologically confirmed. The medical records of dogs with skin lesions and AKI, with histopathologically confirmed renal TMA, were retrospectively reviewed. Thirty dogs from across the UK were identified with clinicopathological findings compatible with CRGV. These findings included the following: skin lesions, predominantly affecting the distal extremities; AKI; and variably, anaemia, thrombocytopaenia and hyperbilirubinaemia. Known causes of AKI were excluded. The major renal histopathological finding was TMA. All thirty dogs died or were euthanised. Shiga toxin was not identified in the kidneys of affected dogs. Escherichia coli genes encoding shiga toxin were not identified in faeces from affected dogs. CRGV has previously been reported in greyhounds in the USA, a greyhound in the UK, without renal involvement, and a Great Dane in Germany. This is the first report of a series of non-greyhound dogs with CRGV and AKI in the UK. CRGV is a disease of unknown aetiology carrying a poor prognosis when azotaemia develops.