Barriers and facilitators to intraorganizational collaboration in public health: Relational coordination across public health services targeting individuals and populations.
Modern public health emphasizes population-focused services, which may require collaborative work both across and within organizations. Studies have explored interorganizational collaborations, but there are little data regarding collaborations within public health organizations. We measured intraorganizational collaboration and identified barriers and facilitators to collaboration within a large public health department through a mixed-methods study. Our study occurred at the Maricopa County (Arizona) Department of Public Health, the third largest local public health jurisdiction in the United States. To measure collaboration, we surveyed staff using the relational coordination tool. To identify barriers and facilitators to collaboration, we performed key informant interviews with department personnel. Relational coordination scores varied according to the focus of the service; clinical services had significantly lower levels of relational coordination than population-focused services (p < .01). We found high levels of mutual respect and lower levels of shared knowledge across services. Facilitators to collaboration included purposive cross-program meetings around specific topics, the organization's structure and culture, and individuals' social identities. Barriers included raised expectations for collaboration, low slack resources, member's self-interest, and trust. The relational coordination of services varied significantly according to the focus of the service. Population-focused public health services had higher levels of relational coordination than individually focused services. Collaboration was facilitated and impeded by both well-known and potentially emergent factors, such as purposive cross-service meetings and organizational culture. Population-focused services possessed higher levels of collaboration than individually focused services. Intraorganizational collaboration for improved population health relies on deliberate support from senior management and structured activities to increase shared knowledge and mutual respect.


Hapten-specific T cell responses to 4-hydroxy-3-nitrophenyl acetyl. XII. Fine specificity of anti-idiotypic suppressor T cells (Ts2).
The fine specificity of anti-idiotypic, effector-phase suppressor T cells (Ts2) induced by the intravenous injection of syngeneic spleen cells covalently coupled with the 4-hydroxy-3-nitrophenyl acetyl (NP) hapten was studied in an in vitro plaque-forming cell system. By comparing the ability of these suppressor cells to bind monoclonal anti-NP antibodies that express different levels of serologically detected NPb idiotypic determinants, it was shown that anti-idiotypic suppressor T cells do not recognize the predominant NPb idiotypic determinants that are defined by serologic analysis. The implications for the possible expression and/or recognition of different sets of idiotypic determinants on T and B cells are discussed.


Profile of H1N1 infection in a tertiary care center.
A novel swine origin influenza virus (H1N1) is spreading worldwide and threatens to become pandemic.H1N1 critical illness mostly affects young patients and is often fatal. The aim of the present study is to evaluate the clinical characteristic of H1N1 infection in a tertiary care hospital. A total of 92 nasal and pharyngeal swabs from suspected cases of swine flu were processed by real time reverse transcriptase polymerase chain reaction (rRT-PCR). Twenty(21.73%) were positive of which two were treating physicians and five (25%) patients expired. The age group of positive cases of H1N1 was between 21 and 30 years and age group of patients who died ranged from 40 to 45 year. This overview indicates that although the majority of hospitalized persons infected with novel influenza A (H1N1) recovered without complications, certain patients had severe and prolonged disease. It was also noted that 2009 influenza A (H1N1) infection - related clinical illness predominantly affects young patients. All hospitalized patients with novel influenza A (H1N1) infection should be monitored carefully and treated with antiviral therapy. Mandatory vaccination of health-care workers is especially important in emerging pandemic.


Enzyme evolution explained (sort of).
Sites in proteins evolve at markedly different rates; some are highly conserved, others change rapidly. We have developed a maximum likelihood method to identify regions of a protein that evolve rapidly or slowly relative to the remaining structure. We also show that solvent accessibility and distance from the catalytic site are major determinants of evolutionary rate in eubacterial isocitrate dehydrogenases. These two variables account for most of the rate heterogeneity not ascribable to stochastic effects.


Public understanding of cigarette smoke constituents: three US surveys.
The Tobacco Control Act requires public disclosure of information about toxic constituents in cigarette smoke. To inform these efforts, we studied public understanding of cigarette smoke constituents. We conducted phone surveys with national probability samples of adolescents (n=1125) and adults (n=5014) and an internet survey with a convenience sample of adults (n=4137), all in the USA. We assessed understanding of cigarette smoke constituents in general and of 24 specific constituents. Respondents commonly and incorrectly believed that harmful chemicals in cigarette smoke mostly originate in additives introduced by cigarette manufacturers (43-72%). Almost all participants had heard that nicotine is in cigarette smoke, and many had also heard about carbon monoxide, ammonia, arsenic and formaldehyde. Less than one-quarter had heard of most other listed constituents being in cigarette smoke. Constituents most likely to discourage respondents from wanting to smoke were ammonia, arsenic, formaldehyde, hydrogen cyanide, lead and uranium. Respondents more often reported being discouraged by constituents that they had heard are in cigarette smoke (all p<0.05). Constituents with names that started with a number or ended in 'ene' or 'ine' were less likely to discourage people from wanting to smoke (all p<0.05). Many people were unaware that burning the cigarette is the primary source of toxic constituents in cigarette smoke. Constituents that may most discourage cigarette smoking have familiar names, like arsenic and formaldehyde and do not start with a number or end in ene/ine. Our findings may help campaign designers develop constituent messages that discourage smoking.


Influence of Nb on the Microstructure and Fracture Toughness of (Zr0.76Fe0.24)100-xNbx Nano-Eutectic Composites.
The present study demonstrates the evolution of eutectic microstructure in arc-melted (Zr0.76Fe0.24)100-xNbx (0 ≤ x ≤ 10 atom %) composites containing α-Zr//FeZr₂ nano-lamellae phases along with pro-eutectic Zr-rich intermetallic phase. The effects of Nb addition on the microstructural evolution and mechanical properties under compression, bulk hardness, elastic modulus, and indentation fracture toughness (IFT) were investigated. The Zr-Fe-(Nb) eutectic composites (ECs) exhibited excellent fracture strength up to ~1800 MPa. Microstructural characterization revealed that the addition of Nb promotes the formation of intermetallic Zr54Fe37Nb₉. The IFT (KIC) increases from 3.0 ± 0.5 MPa√m (x = 0) to 4.7 ± 1.0 MPa√m (x = 2) at 49 N, which even further increases from 5.1 ± 0.5 MPa√m (x = 0) and up to 5.9 ± 1.0 MPa√m (x = 2) at higher loads. The results suggest that mutual interaction between nano-lamellar α-Zr//FeZr₂ phases is responsible for enhanced fracture resistance and high fracture strength.


Pancreatic cancer serum detection using a lectin/glyco-antibody array method.
Pancreatic cancer is a formidable disease and early detection biomarkers are needed to make inroads into improving the outcomes in these patients. In this work, lectin antibody microarrays were utilized to detect unique glycosylation patterns of proteins from serum. Antibodies to four potential glycoprotein markers that were found in previous studies were printed on nitrocellulose coated glass slides and these microarrays were hybridized against patient serum to extract the target glycoproteins. Lectins were then used to detect different glycan structural units on the captured glycoproteins in a sandwich assay format. The biotinylated lectins used to assess differential glycosylation patterns were Aleuria aurentia lectin (AAL), Sambucus nigra bark lectin (SNA), Maackia amurensis lectin II (MAL), Lens culinaris agglutinin (LCA), and Concanavalin A (ConA). Captured glycoproteins were evaluated on the microarray in situ by on-plate digestion and direct analysis using MALDI QIT-TOF mass spectroscopy. Analysis was performed using serum from 89 normal controls, 35 chronic pancreatitis samples, 37 diabetic samples and 22 pancreatic cancer samples. We found that this method had excellent reproducibility as measured by the signal deviation of control blocks as on-slide standard and 41 pairs of pure technical replicates. It was possible to discriminate cancer from the other disease groups and normal samples with high sensitivity and specificity where the response of Alpha-1-beta glycoprotein to lectin SNA increased by 69% in the cancer sample compared to the other noncancer groups (95% confidence interval 53-86%). These data suggest that differential glycosylation patterns detected on high-throughput lectin glyco-antibody microarrays are a promising biomarker approach for the early detection of pancreatic cancer.


Use of Imitation Training for Targeting Grammar: A Narrative Review.
Purpose The purpose of this narrative review was to examine the evidence for imitation training for targeting grammar in children with developmental language disorder. Method Studies investigating imitation training were compiled from two databases-PsycINFO and Linguistics and Language Behavior Abstracts-as well as from reference lists of several books and articles reviewing language therapy. Results Twenty-one studies were reviewed. We summarized the demographic and methodological characteristics of the included studies. We identified substantial differences in the implementation of imitation training across the studies and noted a lack of studies considering how those differences might affect therapy outcome. Studies showed a rapid increase in the production of grammatical targets during imitation training activities, higher performance relative to a control group that did not receive any therapy, and generalization to untrained exemplars. However, the studies did not unequivocally link the increased performance to the imitation training therapy. Studies also showed limited generalization to conversational speech. Conversationally based therapy resulted in faster or higher usage in conversational speech, while imitation training resulted in faster immediate gains in usage during therapy trials. Conclusion We believe that imitation training can continue to be a useful tool in a speech-language pathologist's toolbox, but with suggested modifications. Specifically, we suggest use of imitation training as a means for rapidly achieving production of previously absent grammatical targets. However, we do not recommend sole or long-term use of imitation training for working on grammar. Further research is needed to refine our use of the procedure.


Fluorescence lifetime spectroscopy of tissue autofluorescence in normal and diseased colon measured ex vivo using a fiber-optic probe.
We present an ex vivo study of temporally and spectrally resolved autofluorescence in a total of 47 endoscopic excision biopsy/resection specimens from colon, using pulsed excitation laser sources operating at wavelengths of 375 nm and 435 nm. A paired analysis of normal and neoplastic (adenomatous polyp) tissue specimens obtained from the same patient yielded a significant difference in the mean spectrally averaged autofluorescence lifetime -570 ± 740 ps (p = 0.021, n = 12). We also investigated the fluorescence signature of non-neoplastic polyps (n = 6) and inflammatory bowel disease (n = 4) compared to normal tissue in a small number of specimens.


Narrative in adolescent specific language impairment (SLI): a comparison with peers across two different narrative genres.
Narrative may provide a useful way in which to assess the language ability of adolescents with specific language impairment and may be more ecologically valid than standardized tests. However, the language of this age group is seldom studied and, furthermore, the effect of narrative genre has not been explored in detail. A total of 99 typically developing adolescents and 19 peers with specific language impairment were given two different types of narrative task: a story-telling condition and a conversational condition. Four areas of narrative (productivity, syntactic complexity, syntactic errors and performance) were assessed. The group with specific language impairment was poorer on most aspects of narrative confirming recent research that specific language impairment is a long-term disorder. A number of measures also showed interactions between group and genre, with story-telling proving to be a disproportionately more difficult task for the specific language impairment group. Error analysis also suggested that the specific language impairment group was making qualitatively different errors to the typically developing group, even within a genre. Adolescents with specific language impairment are not only poorer at both types of narrative than peers, but also show different patterns of competence and error, and require more support from the narrative-partner. Assessments of adolescents are less frequent than at younger ages. This is partly because of the sparsity of tests available in this age range. Qualitative analysis of narrative might prove a useful alternative. The findings suggest that in every-day conversation, young people with specific language impairment manage their difficulties more discreetly and this might make them harder to identify in a mainstream setting.


Psychiatric symptoms among postpartum women in an urban hospital setting.
The object of this study was to evaluate postpartum women for psychiatric symptomatology including cognitive disturbances, anxiety, depression, and anger to better meet their needs for support and involve them in the care of their infants. We interviewed 52 postpartum mothers at the Bronx Lebanon Hospital Center within 5 days of delivery and determined the presence of psychiatric symptoms using the 29-item Psychiatric Symptom Index. Despite the fact that adult mothers were happier they were pregnant (71.4% versus 29.4%; P = 0.010) and less likely to be worried about their baby's health (25.7% versus 52.9%; P = 0.003), adult mothers demonstrated higher depressive symptomatology ( P = 0.009), higher amounts of anger ( P = 0.004), and greater overall psychiatric symptomatology ( P = 0.005) than adolescent mothers. Mothers whose infants were in the neonatal intensive care unit did not report significantly higher psychiatric symptomatology than mothers whose infants were healthy. Physicians need to be aware of the high levels of depression and anger present among postpartum women so appropriate support can be given.


Information discriminant analysis: feature extraction with an information-theoretic objective.
Using elementary information-theoretic tools, we develop a novel technique for linear transformation from the space of observations into a low-dimensional (feature) subspace for the purpose of classification. The technique is based on a numerical optimization of an information-theoretic objective function, which can be computed analytically. The advantages of the proposed method over several other techniques are discussed and the conditions under which the method reduces to linear discriminant analysis are given. We show that the novel objective function enjoys many of the properties of the mutual information and the Bayes error and we give sufficient conditions for the method to be Bayes-optimal. Since the objective function is maximized numerically, we show how the calculations can be accelerated to yield feasible solutions. The performance of the method compares favorably to other linear discriminant-based feature extraction methods on a number of simulated and real-world data sets.


How to choose one-dimensional basis functions so that a very efficient multidimensional basis may be extracted from a direct product of the one-dimensional functions: energy levels of coupled systems with as many as 16 coordinates.
In this paper we propose a scheme for choosing basis functions for quantum dynamics calculations. Direct product bases are frequently used. The number of direct product functions required to converge a spectrum, compute a rate constant, etc., is so large that direct product calculations are impossible for molecules or reacting systems with more than four atoms. It is common to extract a smaller working basis from a huge direct product basis by removing some of the product functions. We advocate a build and prune strategy of this type. The one-dimensional (1D) functions from which we build the direct product basis are chosen to satisfy two conditions: (1) they nearly diagonalize the full Hamiltonian matrix; (2) they minimize off-diagonal matrix elements that couple basis functions with diagonal elements close to those of the energy levels we wish to compute. By imposing these conditions we increase the number of product functions that can be removed from the multidimensional basis without degrading the accuracy of computed energy levels. Two basic types of 1D basis functions are in common use: eigenfunctions of 1D Hamiltonians and discrete variable representation (DVR) functions. Both have advantages and disadvantages. The 1D functions we propose are intermediate between the 1D eigenfunction functions and the DVR functions. If the coupling is very weak, they are very nearly 1D eigenfunction functions. As the strength of the coupling is increased they resemble more closely DVR functions. We assess the usefulness of our basis by applying it to model 6D, 8D, and 16D Hamiltonians with various coupling strengths. We find approximately linear scaling.


Effects of extracellular vesicles on placentation and pregnancy disorders.
In humans, pregnancy maintenance depends on normal placental formation following trophoblast invasion into the endometrium and vascular remodeling. In the early stages of pregnancy, immune tolerance, inflammatory response and adaptation to hypoxia need to be precisely regulated in the placental microenvironment. Various types of cells, such as trophoblasts, endothelial cells, immune cells, mesenchymal stem cells (MSCs) and adipocytes, induce normal placental development via intercellular interactions through soluble factors. Extracellular vesicles (EVs) are used to diagnose various diseases because their constituents vary depending on the type of cell of origin and pathological characteristics. EV-derived microRNAs (miRNAs) and proteins in the placenta regulate inflammatory responses and the invasion of trophoblasts through intercellular delivery in the placental microenvironment. If the placenta does not adapt to the changed environment during early pregnancy, pregnancy disorders such as pre-eclampsia, preterm birth and gestational diabetes mellitus can occur. Thus, the important roles of EVs during pregnancy and development is fast emerging. This review describes the physiological role of EVs during placentation and their composition in the human placenta. It also suggests the possibility of finding EV markers that can diagnose pregnancy disorders. Furthermore, it describes the properties of EVs that affect pregnancy in livestock.


Effect of fish oil, olive oil, and vitamin E on liver pathology, cell proliferation, and antioxidant defense system in rats subjected to partial hepatectomy.
The high capacity of liver regeneration after partial hepatectomy (PH) is well known. This study investigated the role of the antioxidant defense system in regeneration among Wistar-albino male rats subjected to 70% partial hepatectomy after a pretreatment period of 2 weeks with eicosapentanoic acid (EPA) rich fish oil (FO), first pressed virgin olive oil (OO), or vitamin E. The control group of 10 rats underwent PH only. On postoperative day 3, all rats were humanely killed. Liver sections of animals treated with FO or vitamin E showed significant increases in regeneration within both liver parenchyma and cut surface compared with the control group (P < .05). Liver sections of OO displayed an insignificant increase in liver regeneration (P > .05), with less increase in parenchyma than of the cut surface. The enhancement of the liver parenchymal regeneration in the FO group was significantly greater than that of the vitamin E group. Concerning liver function tests (LFT), there was no significant difference among the groups. When the treatment groups were compared to the control group glutathione (GSH) levels were increased and content of malondialdehyde (MDA), nitric oxide (NO), and superoxide dismutase (SOD) were decreased. Based on these results, we concluded that after 70% PH in rats, the liver parenchyma and cut surface regeneration were greatest with FO and least with OO treatment. Both FO and vitamin E served to improve the antioxidant defense system more than OO treatment.


Challenges in polyoxometalate-mediated aerobic oxidation catalysis: catalyst development meets reactor design.
Selective catalytic oxidation is one of the most widely used chemical processes. Ideally, highly active and selective catalysts are used in combination with molecular oxygen as oxidant, leading to clean, environmentally friendly process conditions. For homogeneous oxidation catalysis, molecular metal oxide anions, so-called polyoxometalates (POMs) are ideal prototypes which combine high reactivity and stability with chemical tunability on the molecular level. Typically, POM-mediated aerobic oxidations are biphasic, using gaseous O2 and liquid reaction mixtures. Therefore, the overall efficiency of the reaction is not only dependent on the chemical components, but requires chemical engineering insight to design reactors with optimized productivity. This Perspective shows that POM-mediated aerobic liquid-phase oxidations are ideal reactions to be carried out in microstructured flow reactors as they enable facile mass and energy transfer, provide large gas-liquid interfaces and can be easily upscaled. Recent advances in POM-mediated aerobic catalytic oxidations are therefore summarized with a focus on technological importance and mechanistic insight. The principles of reactor design are discussed from a chemical engineering point of view with a focus on homogeneous oxidation catalysis using O2 in microfluidic systems. Further, current limitations to catalytic activity are identified and future directions based on combined chemistry and chemical engineering approaches are discussed to show that this approach could lead to sustainable production methods in industrial chemistry based on alternative energy sources and chemical feedstocks.


Roles of a solo LuxR in the biological control agent Lysobacter enzymogenes strain OH11.
Lysobacter enzymogenes is a ubiquitous plant-associated and environmentally friendly bacterium emerging as a novel biological control agent of plant disease. This bacterium produces diverse antifungal factors, such as lytic enzymes and a secondary metabolite (heat-stable antifungal factor [HSAF]) having antifungal activity with a novel structure and mode of action. The regulatory mechanisms for biosynthesis of antifungal factors is largely unknown in L. enzymogenes. The solo LuxR proteins have been shown to be widespread, playing important roles in plant-associated bacteria. Here, we cloned and studied a solo LuxR protein, LesR, from L. enzymogenes strain OH11. Overexpression but not deletion of lesR significantly impaired HSAF biosynthesis levels and antimicrobial activities but did not show visible effect on production of major lytic enzymes. Overexpression of lesR also led to remarkably accelerated cell aggregation and induced production of a melanin-like pigment in L. enzymogenes; these two phenotypes are mediated by the diffusible factor cell-to-cell signaling system of L. enzymogenes. The C-terminus helix-turn-helix domain was shown to be critical for several lesR-controlled functions. Overall, our study provides the first example of the roles and mechanisms of a solo LuxR protein in a plant-associated L. enzymogenes.


Individual subject meta-analysis of parameters for Giardia duodenalis shedding in animal experimental models.
Giardia duodenalis is a zoonotic protozoan parasite with public health importance worldwide. While articles about animal model infectivity have been published for G. duodenalis, the studies have used diverse protocols and parameters to evaluate the infectivity of this protozoan parasite. Hence, the objectives of this study were to (1) conduct a meta-analysis of published literature for cyst shedding and diarrhea outcomes in animal models and (2) develop recommendations to help standardize experimental dose response studies. Results showed that, for the outcome of cyst shedding in faeces, the covariates of infective stage (cyst versus trophozoite), Giardia dose, and the interactions between doses and infective stage, as well as dose and species of experimental host, were all significant (P value ≤ 0.05). This study suggests inoculation of the experimental host with cysts rather than trophozoites and administration of higher doses of Giardia will most likely result in cyst shedding. Based on the results of this meta-analysis, the infective stage (cyst versus trophozoite), parasite dose, and the interactions between dose and infective stage, as well as dose and species of experimental host, should be considered when designing experimental dose response studies that will assist in the study of zoonotic neglected tropical diseases globally.


The pediatrician and disaster preparedness.
Recent natural disasters and events of terrorism and war have heightened society's recognition of the need for emergency preparedness. In addition to the unique pediatric issues involved in general emergency preparedness, several additional issues related to terrorism preparedness must be considered, including the unique vulnerabilities of children to various agents as well as the limited availability of age- and weight-appropriate antidotes and treatments. Although children may respond more rapidly to therapeutic intervention, they are at the same time more susceptible to various agents and conditions and more likely to deteriorate if not monitored carefully. The challenge of dealing with the threat of terrorism, natural disasters, and public health emergencies in the United States is daunting not only for disaster planners but also for our medical system and health professionals of all types, including pediatricians. As part of the network of health responders, pediatricians need to be able to answer concerns of patients and families, recognize signs of possible exposure to a weapon of terror, understand first-line response to such attacks, and sufficiently participate in disaster planning to ensure that the unique needs of children are addressed satisfactorily in the overall process. Pediatricians play a central role in disaster and terrorism preparedness with families, children, and their communities. This applies not only to the general pediatrician but also to the pediatric medical subspecialist and pediatric surgical specialist. Families view pediatricians as their expert resource, and most of them expect the pediatrician to be knowledgeable in areas of concern. Providing expert guidance entails educating families in anticipation of events and responding to questions during and after actual events. It is essential that pediatricians educate themselves regarding these issues of emergency preparedness. For pediatricians, some information is currently available on virtually all of these issues in recently produced printed materials, at special conferences, in broadcasts of various types, and on the Internet. However, selecting appropriate, accurate sources of information and determining how much information is sufficient remain difficult challenges. Similarly, guidance is needed with respect to developing relevant curricula for medical students and postdoctoral clinical trainees.


Vocal recognition in the spotted hyaena and its possible implications regarding the evolution of intelligence.
Spotted hyaenas, Crocuta crocuta, are gregarious carnivores whose social lives share much in common with those of cercopithecine primates. We conducted playback experiments to determine whether free-living hyaenas are capable of identifying individual conspecifics on the basis of their long-distance vocalization, the 'whoop'. When prerecorded cub whoops were played to mothers and other breeding females (controls), mothers responded significantly more vigorously to whoops of their own cubs than did controls. We also tested the hypothesis that specific vocal recognition abilities are based on kinship in this species. Listeners that were related to the whooping cub responded more vigorously to recorded vocalizations than did unrelated individuals, with response intensity in some cases increasing directly with the size of the coefficient of relatedness (r). Our final goal was to determine whether control animals in these experiments can recognize third-party social relationships among other group members, an ability demonstrated by vervet monkeys, Cercopithecus aethiops, in similar playback experiments conducted by earlier investigators. In contrast to vervets, control females in the present experiments were no more likely to look at the mother of the whooping cub than at other control females after playback. This suggests that hyaenas may accomplish many of the same social feats as do vervets without possessing the ability to recognize third-party relationships. If confirmed in other domains of hyaena social life, our findings have important implications regarding selection pressures favouring the evolution of intelligence. Copyright 1999 The Association for the Study of Animal Behaviour.


Regulation of RUVBL1-RUVBL2 AAA-ATPases by the nonsense-mediated mRNA decay factor DHX34, as evidenced by Cryo-EM.
Nonsense-mediated mRNA decay (NMD) is a surveillance pathway that degrades aberrant mRNAs and also regulates the expression of a wide range of physiological transcripts. RUVBL1 and RUVBL2 AAA-ATPases form an hetero-hexameric ring that is part of several macromolecular complexes such as INO80, SWR1, and R2TP. Interestingly, RUVBL1-RUVBL2 ATPase activity is required for NMD activation by an unknown mechanism. Here, we show that DHX34, an RNA helicase regulating NMD initiation, directly interacts with RUVBL1-RUVBL2 in vitro and in cells. Cryo-EM reveals that DHX34 induces extensive changes in the N-termini of every RUVBL2 subunit in the complex, stabilizing a conformation that does not bind nucleotide and thereby down-regulates ATP hydrolysis of the complex. Using ATPase-deficient mutants, we find that DHX34 acts exclusively on the RUVBL2 subunits. We propose a model, where DHX34 acts to couple RUVBL1-RUVBL2 ATPase activity to the assembly of factors required to initiate the NMD response.


Developing a GIS-based model to quantify spatiotemporal pattern of home appliances and e-waste generation-A case study in Xiamen, China.
The growing amount of electronic waste (e-waste) poses considerable risks to the environment and human health, especially when treated inadequately. However, it is difficult to assess the significance of these issues without quantitative understanding of spatiotemporal patterns of e-waste generation. This paper proposes a new model to estimate in-use stock of electric household appliances (HAs) and e-waste generation at the level of 1 km × 1 km grids by coupling geographic information system (GIS) and material flow analysis (MFA). We took Xiamen, a rapidly urbanized city in China, as a case and the results showed that demands for HAs increased from 1980, peaked in 2016, and then declined. In-use HAs exhibited a logistic growth and significantly increased in both spatial extent and intensity. E-waste generation kept rising until 2019, and its spatial center expanded outward from downtown to suburban areas. Our study highlights that a dynamic and spatial model is useful for designing effective policies for e-waste management by providing spatiotemporal details of e-waste types and generation magnitudes and explicitly recognizing generation hotspots in cities.


Bone mass and turnover in fibromyalgia.
Physical inactivity accelerates bone loss. Since patients with fibromyalgia are relatively physically inactive, bone mass and markers of bone metabolism were determined in 12 premenopausal women with fibromyalgia and in healthy age matched female control subjects. No differences were found in lumbar bone mineral density, femoral neck bone mineral density, serum levels of alkaline phosphatase, osteocalcin, ionized calcium and phosphate. The urinary excretion of both hydroxyproline and calcium relative to urinary creatinine excretion was significantly higher in patients with fibromyalgia, p = 0.01. This was linked to lower urinary creatinine excretion (p = 0.02) probably reflecting lower physical activity in the patients with fibromyalgia. We conclude that bone mass and turnover are generally not affected in premenopausal women with fibromyalgia.


Comparing the genetic changes detected in the primary and secondary tumor sites of ovarian cancer using comparative genomic hybridization.
Our objective was to compare the genetic abnormalities in the primary tumors of epithelial ovarian cancer and their associated secondary peritoneal implants using comparative genomic hybridization (CGH). CGH was performed on seven apparent stage III ovarian serous cancer cases. Dissected tissue samples from the primary tumor and from the metastatic peritoneal implant were obtained at initial surgical staging and analyzed in each case. We used CGH as this technique allows the entire genome of the tumor to be examined simultaneously for chromosomal imbalances without the need for tissue culture or targeting of specific loci. The chromosomal abnormalities detected in the distinct sites were then reviewed and compared. CGH studies were successful in all 14 samples from the seven patients. The analysis revealed chromosomal aberrations in six patients with certain repeated changes as amplification of 1q, 2p, 2q, 3q, 6q, 8q, and 12p and underrepresentation of 18q and X chromosomes. Comparing the genomes of the primary tumors with the metastatic samples showed four cases with a balanced metastatic CGH profile while the primary site was aberrant. Greater chromosomal complexity associated with the primary site was detected in two other patients. In one case, both primary and secondary sites had no detectable chromosomal imbalances. The cytogenetic patterns in six of the seven primary tumors showed complex karyotypic changes, unlike the inconsistent findings that were associated with the secondary sites. The chromosomes of the secondary sites expressed either normal genomes or fewer genetic aberrations. Such genomic heterogeneity between the primary and secondary sites may indicate that the secondary peritoneal implants are de novo carcinogenesis occurrences. The results may support the concept that at least part of advanced ovarian cancer is a multicentric disease in the early stages. Further genetic studies are needed to reassess this assumption.


Mechanistically linked serum miRNAs distinguish between drug induced and fatty liver disease of different grades.
Hepatic steatosis is characterised by excessive triglyceride accumulation in the form of lipid droplets (LD); however, mechanisms differ in drug induced (DIS) and/or non-alcoholic fatty liver disease (NAFLD). Here we hypothesized distinct molecular circuits of microRNA/LD-associated target genes and searched for mechanistically linked serum and tissue biomarkers that would distinguish between DIS and human NAFLD of different grades. We analysed >800 rat hepatic whole genome data for 17 steatotic drugs and identified 157 distinct miRNAs targeting 77 DIS regulated genes. Subsequently, genomic data of N = 105 cases of human NAFLD and N = 32 healthy controls were compared to serum miRNA profiles of N = 167 NAFLD patients. This revealed N = 195 tissue-specific miRNAs being mechanistically linked to LD-coding genes and 24 and 9 miRNAs were commonly regulated in serum and tissue of advanced and mild NAFLD, respectively. The NASH serum regulated miRNAs informed on hepatic inflammation, adipocytokine and insulin signalling, ER-and caveolae associated activities and altered glycerolipid metabolism. Conversely, serum miRNAs associated with blunt steatosis specifically highlighted activity of FOXO1&HNF4α on CPT2, the lipid droplet and ER-lipid-raft associated PLIN3 and Erlin1. Altogether, serum miRNAs informed on the molecular pathophysiology of NAFLD and permitted differentiation between DIS and NAFLD of different grades.


Excess of rare cancers in Werner syndrome (adult progeria).
The association between genetic disorders and diverse cancers has provided clues for laboratory research into carcinogenesis. Such an opportunity now arises from studies of cancer in Werner syndrome (WRN). Soft-tissue sarcoma (STS) and benign meningioma have been associated with WRN, an autosomal recessive disorder characterized by premature aging, more commonly reported in Japan than elsewhere, in part because of inbreeding. In the literature we found 124 case-reports of neoplasia and WRN from Japan and 34 from outside Japan, 1939-August, 1995. They reveal a greater diversity of neoplasia in WRN than was previously known. In Japanese, there were 127 cancers, 14 benign meningioma, and 5 myeloid disorders, as compared with 30, 7 and 2 respectively in non-Japanese. The ratio of epithelial to non-epithelial cancers was about 1:1 for Japanese and for non-Japanese instead of the usual 10:1. Both series had excess of STS, osteosarcoma, myeloid disorders, and benign meningioma. In addition, the Japanese had an excess of thyroid cancer (20 versus 2 cases in non-Japanese) and melanoma (21 versus 3 cases), including 5 intranasal and 13 of the feet. STS, osteosarcoma, melanoma, and thyroid carcinoma accounted for 57% of all cancer in WRN as compared with 2% expected based on the Osaka population at 25-64 years of age. Multiple tumors were reported in 19 Japanese and 5 non-Japanese. In Japan, nine first-degree relatives had WRN and cancer, six of whom were concordant as to site and/or cell type. The WRN gene has been mapped to chromosome 8p. The high frequency of thyroid cancer and melanoma in Japanese, not found in Caucasians, may be related to a report of linkage disequilibrium with the WRN gene in Japanese but not in Caucasians and to haplotype differences within and between the two races, suggesting multiple independent mutations.


KIBRA polymorphism is related to enhanced memory and elevated hippocampal processing.
Several studies have linked the KIBRA rs17070145 T polymorphism to superior episodic memory in healthy humans. One study investigated the effect of KIBRA on brain activation patterns (Papassotiropoulos et al., 2006) and observed increased hippocampal activation in noncarriers of the T allele during retrieval. Noncarriers were interpreted to need more hippocampal activation to reach the same performance level as T carriers. Using large behavioral (N = 2230) and fMRI (N = 83) samples, we replicated the KIBRA effect on episodic memory performance, but found increased hippocampal activation in T carriers during episodic retrieval. There was no evidence of compensatory brain activation in noncarriers within the hippocampal region. In the main fMRI sample, T carriers performed better than noncarriers during scanning but, importantly, the difference in hippocampus activation remained after post hoc matching according to performance, sex, and age (N = 64). These findings link enhanced memory performance in KIBRA T allele carriers to elevated hippocampal functioning, rather than to neural compensation in noncarriers.


12-month efficacy and safety of OROS MPH in children and adolescents with attention-deficit/hyperactivity disorder switched from MPH.
The aim of this study was to evaluate long-term clinical treatment with OROS methylphenidate (MPH) (Concerta) in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) who had been previously treated with immediate release (IR) MPH. Subjects aged 6-16 years (n=105) who were stable on IR MPH (10-60 mg/day) were switched to 18, 36 or 54 mg OROS MPH once daily for 21 days, depending on prestudy MPH dose. Subjects who benefited from OROS MPH could continue in a 12-month extension period. ADHD symptoms and treatment response were assessed by parents/caregivers and investigators. Out of 105 enrolled children, 101 completed the 21-day treatment phase. In all, 89 parents/caregivers (88.1%) wanted their child to continue with the study treatment into the extension phase, and 56 children (63 %) completed the 1-year trial. The parent/caregiver global assessment of satisfaction ranged from 49 to 69% during the extension phase, and 49 to 71% of investigators rated the treatment as adequate. Efficacy and satisfaction were found more commonly in patients in the older age group (10-16 years), those on a higher dose (36 mg or 54 mg) and with the predominantly inattentive ADHD subtype. OROS MPH was well tolerated. Children and adolescents can effectively and safely be switched from IR MPH to OROS MPH with improved symptom control and compliance.


Oral tumours and tumour-like conditions in Kenya: II. Age, sex and site distribution.
This paper presents the age, sex and site distribution of oral tumours and tumour like conditions in Kenya. It confirms some important points. First, there is an overall lower mean age for oral tumours in African series compared to non African series. Secondly, sex bias in the distribution of oral tumours is less marked for most tumours in Africans. Thirdly, there is difference in site distribution and oral tumours between Africans and non-African populations.


Inactivity/sleep in two wild free-roaming African elephant matriarchs - Does large body size make elephants the shortest mammalian sleepers?
The current study provides details of sleep (or inactivity) in two wild, free-roaming African elephant matriarchs studied in their natural habitat with remote monitoring using an actiwatch subcutaneously implanted in the trunk, a standard elephant collar equipped with a GPS system and gyroscope, and a portable weather station. We found that these two elephants were polyphasic sleepers, had an average daily total sleep time of 2 h, mostly between 02:00 and 06:00, and displayed the shortest daily sleep time of any mammal recorded to date. Moreover, these two elephants exhibited both standing and recumbent sleep, but only exhibited recumbent sleep every third or fourth day, potentially limiting their ability to enter REM sleep on a daily basis. In addition, we observed on five occasions that the elephants went without sleep for up to 46 h and traversed around 30 km in 10 h, possibly due to disturbances such as potential predation or poaching events, or a bull elephant in musth. They exhibited no form of sleep rebound following a night without sleep. Environmental conditions, especially ambient air temperature and relative humidity, analysed as wet-bulb globe temperature, reliably predict sleep onset and offset times. The elephants selected novel sleep sites each night and the amount of activity between sleep periods did not affect the amount of sleep. A number of similarities and differences to studies of elephant sleep in captivity are noted, and specific factors shaping sleep architecture in elephants, on various temporal scales, are discussed.


Evaluation of squamous epithelium in adenoacanthoma and adenosquamous carcinoma of the endometrium: immunoperoxidase analysis of involucrin and keratin localization.
A study was undertaken to determine whether immunoperoxidase stains for keratin and involucrin, the latter a protein present in cells of stratified squamous epithelium that have differentiated beyond the basal stage, distinguish any differences in squamous cells present in the adenoacanthoma from those in the adenosquamous carcinoma of the uterine corpus. Forty-eight tumors were studied, of which 33 were adenoacanthomas and 15 adenosquamous carcinomas. The patients with adenoacanthomas were slightly younger (mean 61.5 vs. 64.5 years) and had tumors that were generally better differentiated than the adenosquamous carcinomas. The squamous epithelium in every tumor, regardless of histologic type, stained positively for keratin. There were no obvious differences in staining when tumors were stratified for histologic type, grade, or location within the tumor. The glandular portion of both tumor types stained irregularly, but nonetheless positively, for keratin in 71% of the cases. Involucrin was detected in 57% of adenoacanthomas and 87% of adenosquamous carcinomas. The deeper or more central portion of the squamous morules stained only if the more superficial or peripheral areas were positive. The extent of the involucrin staining was less in the adenosquamous carcinomas than in the adenoacanthomas. The glandular component of the tumors did not stain for involucrin. It is concluded that no qualitative differences in the staining reactions with respect to keratin and involucrin distinguish the adenoacanthomas from the adenoaquamous carcinoma. These findings support the argument that the adenoacanthoma and adenosquamous carcinoma represent a spectrum of squamous differentiation in a single tumor type.


The Recovery Knowledge Inventory for Measurement of Nursing Student Views on Recovery-oriented Mental Health Services.
Recovery-oriented services are a goal for policy and practice in the Australian mental health service system. Evidence-based reform requires an instrument to measure knowledge of recovery concepts. The Recovery Knowledge Inventory (RKI) was designed for this purpose, however, its suitability and validity for student health professionals has not been evaluated. The purpose of the current article is to report the psychometric features of the RKI for measuring nursing students' views on recovery. The RKI, a self-report measure, consists of four scales: (I) Roles and Responsibilities, (II) Non-Linearity of the Recovery Process, (III) Roles of Self-Definition and Peers, and (IV) Expectations Regarding Recovery. Confirmatory and exploratory factor analyses of the baseline data (n = 167) were applied to assess validity and reliability. Exploratory factor analyses generally replicated the item structure suggested by the three main scales, however more stringent analyses (confirmatory factor analysis) did not provide strong support for convergent validity. A refined RKI with 16 items had internal reliabilities of α = .75 for Roles and Responsibilities, α = .49 for Roles of Self-Definition and Peers, and α = .72, for Recovery as Non-Linear Process. If the RKI is to be applied to nursing student populations, the conceptual underpinning of the instrument needs to be reworked, and new items should be generated to evaluate and improve scale validity and reliability.


Sex differences in the medical care of VA patients with chronic non-cancer pain.
Despite a growing number of women seeking medical care in the veterans affairs (VA) system, little is known about the characteristics of their chronic pain or the pain care they receive. This study sought to determine if sex differences are present in the medical care veterans received for chronic pain. Retrospective cohort study using VA administrative data. The subjects were 17,583 veteran patients with moderate to severe chronic non-cancer pain treated in the Pacific Northwest during 2008. Multivariate logistic regression assessed for sex differences in primary care utilization, prescription of chronic opioid therapy, visits to emergency departments for a pain-related diagnosis, and physical therapy referral. Compared with male veterans, female veterans were more often diagnosed with two or more pain conditions, and had more of the following pain-related diagnoses: fibromyalgia, low back pain, inflammatory bowel disease, migraine headache, neck or joint pain, and arthritis. After adjustment for demographic characteristics, pain diagnoses, mental health diagnoses, substance use disorders, and medical comorbidity, women had lower odds of being prescribed chronic opioid therapy (adjusted OR [AOR] 0.67, 95% CI 0.58-0.78), greater odds of visiting an emergency department for a pain-related complaint (AOR 1.40, 95% CI 1.18-1.65), and greater odds of receiving physical therapy (AOR 1.19, 95% CI 1.05-1.33). Primary care utilization was not significantly different between sexes. Sex differences are present in the care female veterans receive for chronic pain. Further research is necessary to understand the etiology of the observed differences and their associations with clinical outcomes.


[Validation of the WHOQOL-BREF quality of life questionnaire among Chilean older people].
The WHOQOL-BREF is a generic questionnaire to measure quality of life created by the Study Group on Quality of Life of the World Health Organization. To adapt and evaluate the psychometric properties of the Spanish version of the WHOQOL-BREF instrument in a group of Chilean older subjects living in Metropolitan Santiago. A linguistic-cultural adaptation of the Spanish version of the WHOQOL-BREF was performed and tested in a pilot study. Subsequently, the modified scale was applied to a group of 1186 older women aged 72 ± 8 years and 334 men aged 72 ± 7 years. The psychometric properties such as internal consistency, item-total correlation of responses, and construct validity were evaluated. A confirmatory factor analysis was done to check if the dimensions described in the original version, were evaluated. Analyses were performed with STA-TA statistical software 10.0 and LISREL 8.50. Confirmatory factor analysis confirmed that the dimensions physical health, psychological, social relationships and environment, described by the authors in their original description, were maintained. The instrument had a good internal consistency with a Cronbach alpha of 0.88 for the total scale and ranging from 0.70 to 0.79 in each of the dimensions. The evaluated version of the WHOQOL-BREF has an acceptable reliability and validity, and suggests that it is suitable for the assessment of Quality of Life in elderly people in Chile.


Functional impact of 10 days of bed rest in healthy older adults.
Many older individuals decline functionally during hospitalization, and the deleterious consequences of bed rest may be one cause. This study reports on the effect of 10 days of bed rest on multiple functional parameters in healthy older adults. Healthy older men and women (n = 11, 67 +/- 5 years old) remained on bed rest for 10 days continuously, and consumed a eucaloric diet providing the Recommended Dietary Allowance for protein. Measures of lower extremity strength and power, aerobic capacity and physical performance, as well as physical activity were performed before and after bed rest. All measures of lower extremity strength were significantly lower after bed rest including isotonic knee extensor strength (-13.2 +/- 4.1%, p =.004) and stair-climbing power (-14 +/- 4.1%, p =.01). Maximal aerobic capacity was 12% lower after bed rest (p =.04), whereas measures of physical performance (Short Physical Performance Battery, and a five-item physical performance test) were not significantly different. Voluntary physical activity decreased after bed rest, and the percentage of time spent inactive increased (7.6 +/- 1.8%, p =.004). There were no medical complications. In healthy older adults, 10 days of bed rest results in a substantial loss of lower extremity strength, power, and aerobic capacity, and a reduction in physical activity, but has no effect on physical performance. Identification of interventions to maintain muscle function during hospitalization or periods of bed rest in older adults should be a high priority.


Thermoregulatory and blood responses during exercise at graded hypohydration levels.
We studied the effects of graded hypohydration levels on thermoregulatory and blood responses during exercise in the heat. Eight heat-acclimated male subjects attempted four heat-stress tests (HSTs). One HST was attempted during euhydration, and three HSTs were attempted while the subjects were hypohydrated by 3, 5, and 7% of their body weight. Hypohydration was achieved by an exercise-heat regimen on the day prior to each HST. After 30 min of rest in a 20 degrees C antechamber the HST consisted of a 140-min exposure (4 repeats of 10 min rest and 25 min treadmill walking) in a hot-dry (49 degrees C, 20% relative humidity) environment. The following observations were made: 1) a low-to-moderate hypohydration level primarily reduced plasma volume with little effect on plasma osmolality, whereas a more severe hypohydration level resulted in no further plasma volume reduction but a large increment in plasma osmolality; 2) core temperature and heart rate responses increased with severity of hypohydration; 3) sweating rate responses for a given rectal temperature were systematically decreased with severity of hypohydration; and 4) the reduction in sweating rate was more strongly associated with plasma hyperosmolality than hypovolemia. In conclusion, an individual's thermal strain increases linearly with the severity of hypohydration during exercise in the heat, and plasma hyperosmolality influences the reduction in sweating more profoundly than hypovolemia.


CLB5 and CLB6, a new pair of B cyclins involved in DNA replication in Saccharomyces cerevisiae.
The functions of the Cdc28 protein kinase in DNA replication and mitosis in Saccharomyces cerevisiae are thought to be determined by the type of cyclin subunit with which it is associated. G1-specific cyclins encoded by CLN1, CLN2, and CLN3 are required for entry into the cell cycle (Start) and thereby for S phase, whereas G2-specific B-type cyclins encoded by CLB1, CLB2, CLB3, and CLB4 are required for mitosis. We describe a new family of B-type cyclin genes, CLB5 and CLB6, whose transcripts appear in late G1 along with those of CLN1, CLN2, and many genes required for DNA replication. Deletion of CLB6 has little or no effect, but deletion of CLB5 greatly extends S phase, and deleting both genes prevents the timely initiation of DNA replication. Transcription of CLB5 and CLB6 is normally dependent on Cln activity, but ectopic CLB5 expression allows cells to proliferate in the absence of Cln cyclins. Thus, the kinase activity associated with Clb5/6 and not with Cln cyclins may be responsible for S-phase entry. Clb5 also has a function, along with Clb3 and Clb4, in the formation of mitotic spindles. Our observation that CLB5 is involved in the initiation of both S phase and mitosis suggests that a single primordial B-type cyclin might have been sufficient for regulating the cell cycle of the common ancestor of many, if not all, eukaryotes.


The prognostic role of KRAS, BRAF, PIK3CA and PTEN in colorectal cancer.
Mutations in KRAS, BRAF, PIK3CA and PTEN expression have been in focus to predict the effect of epidermal growth factor receptor-blocking therapy in colorectal cancer (CRC). Here, information on these four aberrations was collected and combined to a Quadruple index and used to evaluate the prognostic role of these factors in CRC. We analysed the mutation status in KRAS, BRAF and PIK3CA and PTEN expression in two separate CRC cohorts, Northern Sweden Health Disease Study (NSHDS; n=197) and Colorectal Cancer in Umeå Study (CRUMS; n=414). A Quadruple index was created, where Quadruple index positivity specifies cases with any aberration in KRAS, BRAF, PIK3CA or PTEN expression. Quadruple index positive tumours had a worse prognosis, significant in the NSHDS but not in the CRUMS cohort (NSHDS; P=0.003 and CRUMS; P=0.230) in univariate analyses but significance was lost in multivariate analyses. When analysing each gene separately, only BRAF was of prognostic significance in the NSHDS cohort (multivariate HR 2.00, 95% CI: 1.16-3.43) and KRAS was of prognostic significance in the CRUMS cohort (multivariate HR 1.48, 95% CI: 1.02-2.16). Aberrations in PIK3CA and PTEN did not add significant prognostic information. Our results suggest that establishment of molecular subgroups based on KRAS and BRAF mutation status is important and should be considered in future prognostic studies in CRC.


Subacromial decompression surgery for rotator cuff disease.
Surgery for rotator cuff disease is usually used after non-operative interventions have failed, although our Cochrane Review, first published in 2007, found that there was uncertain clinical benefit following subacromial decompression surgery. To synthesise the available evidence of the benefits and harms of subacromial decompression surgery compared with placebo, no intervention or non-surgical interventions in people with rotator cuff disease (excluding full thickness rotator cuff tears). We searched CENTRAL, MEDLINE, Embase, Clinicaltrials.gov and WHO ICRTP registry from 2006 until 22 October 2018, unrestricted by language. We included randomised and quasi-randomised controlled trials (RCTs) of adults with rotator cuff disease (excluding full-thickness tears), that compared subacromial decompression surgery with placebo, no treatment, or any other non-surgical interventions. As it is least prone to bias, subacromial decompression compared with placebo was the primary comparison. Other comparisons were subacromial decompression versus exercises or non-operative treatment. Major outcomes were mean pain scores, shoulder function, quality of life, participant global assessment of success, adverse events and serious adverse events. The primary endpoint for this review was one year. For serious adverse events, we also included data from prospective cohort studies designed to record harms that evaluated subacromial decompression surgery or shoulder arthroscopy. We used standard methodologic procedures expected by Cochrane. We included eight trials, with a total of 1062 randomised participants with rotator cuff disease, all with subacromial impingement. Two trials (506 participants) compared arthroscopic subacromial decompression with arthroscopy only (placebo surgery), with all groups receiving postoperative exercises. These trials included a third treatment group: no treatment (active monitoring) in one and exercises in the other. Six trials (556 participants) compared arthroscopic subacromial decompression followed by exercises with exercises alone. Two of these trials included a third arm: sham laser in one and open subacromial decompression in the other.Trial size varied from 42 to 313 participants. Participant mean age ranged between 42 and 65 years. Only two trials reported mean symptom duration (18 to 22 months in one trial and 30 to 31 months in the other), two did not report duration and four reported it categorically.Both placebo-controlled trials were at low risk of bias for the comparison of surgery versus placebo surgery. The other trials were at high risk of bias for several criteria, most notably at risk of performance or detection bias due to lack of participant and personnel blinding. We have restricted the reporting of results of benefits in the Abstract to the placebo-controlled trials.Compared with placebo, high-certainty evidence indicates that subacromial decompression provides no improvement in pain, shoulder function, or health-related quality of life up to one year, and probably no improvement in global success (moderate-certainty evidence, downgraded due to imprecision).At one year, mean pain (on a scale zero to 10, higher scores indicate more pain), was 2.9 points after placebo surgery and 0.26 better (0.84 better to 0.33 worse), after subacromial decompression (284 participants), an absolute difference of 3% (8% better to 3% worse), and relative difference of 4% (12% better to 5% worse). At one year, mean function (on a scale 0 to 100, higher score indicating better outcome), was 69 points after placebo surgery and 2.8 better (1.4 worse to 6.9 better), after surgery (274 participants), an absolute difference of 3% (7% better to 1% worse), and relative difference of 9% (22% better to 4% worse). Global success rate was 97/148 (or 655 per 1000), after placebo and 101/142 (or 708 per 1000) after surgery corresponding to RR 1.08 (95% CI 0.93 to 1.27). Health-related quality of life was 0.73 units (European Quality of Life EQ-5D, -0.59 to 1, higher score indicating better quality of life), after placebo and 0.03 units worse (0.011 units worse to 0.06 units better), after subacromial decompression (285 participants), an absolute difference of 1.3% (5% worse to 2.5% better), and relative difference of 4% (15% worse to 7% better).Adverse events including frozen shoulder or transient minor complications of surgery were reported in approximately 3% of participants across treatment groups in two randomised controlled trials, but due to low event rates we are uncertain if the risks differ between groups: 5/165 (37 per 1000) reported adverse events with subacromial decompression and 9/241 (34 per 1000) with placebo or non-operative treatment, RR 0.91 (95% CI 0.31 to 2.65) (moderate-certainty evidence, downgraded due to imprecision). The trials did not report serious adverse events.Based upon moderate-certainty evidence from two observational trials from the same prospective surgery registry, which also included other shoulder arthroscopic procedures (downgraded for indirectness), the incidence proportion of serious adverse events within 30 days following surgery was 0.5% (0.4% to 0.7%; data collected 2006 to 2011), or 0.6% (0.5 % to 0.7%; data collected 2011 to 2013). Serious adverse events such as deep infection, pulmonary embolism, nerve injury, and death have been observed in participants following shoulder surgery. The data in this review do not support the use of subacromial decompression in the treatment of rotator cuff disease manifest as painful shoulder impingement. High-certainty evidence shows that subacromial decompression does not provide clinically important benefits over placebo in pain, function or health-related quality of life. Including results from open-label trials (with high risk of bias) did not change the estimates considerably. Due to imprecision, we downgraded the certainty of the evidence to moderate for global assessment of treatment success; there was probably no clinically important benefit in this outcome either compared with placebo, exercises or non-operative treatment.Adverse event rates were low, 3% or less across treatment groups in the trials, which is consistent with adverse event rates reported in the two observational studies. Although precise estimates are unknown, the risk of serious adverse events is likely less than 1%.


The Trajectory of Tolerance for Wandering-related Boundary Transgression: An Exploration of Care Staff and Family Perceptions.
This study aimed to explore the experience of living with and caring for a person with dementia who wanders and transgresses boundaries into out-of-bounds and potentially hazardous areas (wandering-related boundary transgression [BT]), from the perspective of family members and care staff. This descriptive qualitative study utilized four focus groups with care staff (n = 28), one with family members (n = 4), and individual interviews (n = 8) with family members. Content analysis generated key concepts that formed the basis of the development of a theoretical understanding of the experience. Care staff and families described wandering-related BT as a common dementia-related behavior in residential aged care (RAC). Drawing on the generated concepts, a complex theoretical trajectory of tolerance for BT was developed. At one end of the trajectory, BT was perceived as being beyond the control of the individual and when unwitnessed by others, having little or no impact. Tolerance for BT shifted when the BT was witnessed by others, and potentially unsafe consequences for the person who wanders or their coresidents were experienced. Under the latter circumstances, BT was perceived as a troubling behavior that needed more effective management. Underpinning the complexity of this behavior was a constantly shifting perception of how hazardous this behavior might be, a factor that appeared to contribute to the challenges faced by families and care staff.


A novel automated lazy learning QSAR (ALL-QSAR) approach: method development, applications, and virtual screening of chemical databases using validated ALL-QSAR models.
A novel automated lazy learning quantitative structure-activity relationship (ALL-QSAR) modeling approach has been developed on the basis of the lazy learning theory. The activity of a test compound is predicted from a locally weighted linear regression model using chemical descriptors and the biological activity of the training set compounds most chemically similar to this test compound. The weights with which training set compounds are included in the regression depend on the similarity of those compounds to a test compound. We have applied the ALL-QSAR method to several experimental chemical data sets including 48 anticonvulsant agents with known ED50 values, 48 dopamine D1-receptor antagonists with known competitive binding affinities (Ki), and a Tetrahymena pyriformis data set containing 250 phenolic compounds with toxicity IGC50 values. When applied to database screening, models developed for anticonvulsant agents identified several known anticonvulsant compounds that were not only absent in the training set but highly chemically dissimilar to the training set compounds. This initial success indicates that ALL-QSAR can be further exploited as a general tool for accurate bioactivity prediction and database screening in drug design and discovery. Because of its local nature, the ALL-QSAR approach appears to be especially well-suited for the development of highly predictive models for the sparse or unevenly distributed data sets.


Attempted suicide among young adults: progress toward a meaningful estimate of prevalence.
The results of epidemiologic surveys on attempted suicide are often difficult to interpret; they compare and provide varying estimates of the prevalence of attempted suicide. The authors sought to estimate the prevalence of attempted suicide in a young adult population and to define more precisely what respondents mean when they report a suicide attempt. Survey respondents were a representative sample of all 18-24-year-old freshman students at a major public university. The self-administered, anonymous survey included questions about suicidal thoughts and behaviors and about any injury and need for medical care resulting from reported attempts. Of the 694 respondents, 374 (54%) reported having ever considered suicide and 181 (26%) had considered suicide during the preceding 12 months. Thirteen (2%) students reported having attempted suicide during the preceding 12 months, and 72 (10%) reported ever having attempted suicide. The number of students answering affirmatively to questions about injuries sustained, medical care sought, and hospitalization as a result of attempted suicide decreased progressively: only 18 (3%) students reported having ever sought medical care due to a suicide attempt, and seven (1%) were ever hospitalized. The prevalence of self-reported attempted suicide is not representative of the prevalence of self-injury and provides little information concerning the seriousness of the attempt. The use of specific questions similar to those used in this study should be considered in future surveys.


Hamstring Injury Prevention Practices in Elite Sport: Evidence for Eccentric Strength vs. Lumbo-Pelvic Training.
Hamstring strain injuries are endemic in running-based sports. Given the economic and performance implications of these injuries, a significant body of research has emerged in recent years in an attempt to identify risk factors and develop or optimise injury prevention strategies. Surveys of injury prevention practices among medical and conditioning staff in elite sport suggest that many sporting clubs invest significant efforts in eccentric hamstring conditioning and lumbo-pelvic or trunk stability programmes. The purpose of this narrative review was to critically evaluate the evidence underpinning these practices. Single-exercise eccentric training interventions have proven effective in the prevention of primary and recurrent hamstring strains, when compliance is adequate. However, despite its almost universal acceptance, the authors are aware of only one, very recent, prospective risk factor study examining the effect of lumbo-pelvic motion during sprinting on hamstring injury risk. Furthermore, the interventions exploring the effect of lumbo-pelvic training on hamstring injury rates have not measured stability in any way. An improved understanding of the evidence underpinning commonly employed hamstring injury prevention practices may enable clinicians and coaches to better prioritise effective strategies in the increasingly complex environment of elite sport.


Room for (performance) improvement: provider-related factors associated with poor outcomes in massive transfusion.
Massive transfusion (MT) protocols improve survival in patients with exsanguinating hemorrhage. Both the increased plasma to red blood cells (RBC) and platelets to RBC ratios, and the "protocolization" of product delivery seem to be critical components of the reduction in mortality. The purpose of this study was to identify the incidence and impact of MT protocol noncompliance and to intervene in provider-related events associated with poor compliance and outcomes. A MT protocol was initiated in 2006 at a Level I trauma center. All cases of protocol activation were reviewed by a multidisciplinary performance improvement (PI) group for compliance and the need for "real-time" protocol adjustments. Educational conferences, Grand Rounds presentations, and individual provider education were performed on a quarterly basis. Compliance of seven measures were evaluated as follows: type and screen sent from emergency department (ED), activation of protocol in ED, activation by trauma attending, administration of 2:3 plasma to RBC, administration of 1:5 platelets to RBC, protocol discontinuation on leaving operating room, and no products wasted. Univariate, multivariate, and time-series analyses were performed. All 125 MT protocol activations occurring from February 2006 to January 2008 were reviewed. Full compliance for all PI measures during the entire period was 27%. There were no differences in demographics, injury severity, or physiologic scores between patients for whom activations were compliant and those who were noncompliant. Full compliance was an independent predictor of survival (86.7% vs. 45.0%, p < 0.001). Both activation of the protocol in the ED and achievement of prespecified ratios of plasma: RBC (2:3) and platelets: RBC (1:5) were independent predictors of 24-hour and 30-day survivals. All PI measures demonstrated improved compliance during the study period with the exception of ED activation. Failure to send type and screen from the ED is an independent predictor of wasted blood products. Early activation of a MT protocol and achieving predefined ratios was associated with improved survival. ED activation and direct blood bank notification by the trauma attending were associated with a reduction in blood product wastage. A multidisciplinary PI process helps to identify provider/specialty noncompliance and to assess the impact of these factors, and it was associated with improvement in compliance and MT outcomes over time.


Family-based intervention for schizophrenic patients in China. A randomised controlled trial.
We developed and evaluated a comprehensive, ongoing intervention for families of schizophrenic patients appropriate for China's complex family relationships and unique social environment. Sixty-three DSM-III-R schizophrenic patients living with family members were enrolled when admitted to hospital and randomly assigned to receive standard care or a family-based intervention that included monthly 45-minute counselling sessions focused on the management of social and occupational problems, medication management, family education, family group meetings, and crisis intervention. At 6, 12, and 18-month follow-ups by blind evaluators, the proportion of subjects rehospitalised was lower, the duration of rehospitalisation was shorter, and the duration of employment was longer in the experimental group than in the control group; these differences were statistically significant at the 12 and 18-month follow-ups and were not explained by differences in drug compliance. Family intervention was associated with significantly lower levels of family burden. This intervention is less costly than standard treatment, is suitable for urban families of schizophrenic patients in China and feasible given the constraints of the Chinese mental health system.


Discovery of Unusual Biaryl Polyketides by Activation of a Silent Streptomyces venezuelae Biosynthetic Gene Cluster.
Comparative transcriptional profiling of a ΔbldM mutant of Streptomyces venezuelae with its unmodified progenitor revealed that the expression of a cryptic biosynthetic gene cluster containing both type I and type III polyketide synthase genes is activated in the mutant. The 29.5 kb gene cluster, which was predicted to encode an unusual biaryl metabolite, which we named venemycin, and potentially halogenated derivatives, contains 16 genes including one-vemR-that encodes a transcriptional activator of the large ATP-binding LuxR-like (LAL) family. Constitutive expression of vemR in the ΔbldM mutant led to the production of sufficient venemycin for structural characterisation, confirming its unusual biaryl structure. Co-expression of the venemycin biosynthetic gene cluster and vemR in the heterologous host Streptomyces coelicolor also resulted in venemycin production. Although the gene cluster encodes two halogenases and a flavin reductase, constitutive expression of all three genes led to the accumulation only of a monohalogenated venemycin derivative, both in the native producer and the heterologous host. A competition experiment in which equimolar quantities of sodium chloride and sodium bromide were fed to the venemycin-producing strains resulted in the preferential incorporation of bromine, thus suggesting that bromide is the preferred substrate for one or both halogenases.


Risky business: trauma exposure and rate of posttraumatic stress disorder in African American children and adolescents.
Demographics, parental risk factors, and experiencing interpersonal trauma (domestic violence, community violence, and physical and sexual abuse) are related to childhood posttraumatic stress disorder (PTSD). Little is known about these factors and the risk of PTSD in African American children. This study examined associations between PTSD symptoms and gender, age, parent mental illness, parent substance abuse, and interpersonal trauma in African American children. Participants were 257 children and adolescents, ages 8-17 years (M = 11.7, SD = 2.5), who received outpatient mental health treatment. Being female and witnessing domestic violence was associated with more PTSD symptoms. Exposure to community violence and physical abuse increased the odds of clinically significant PTSD symptomatology by more than 2 times. The rate of PTSD (16%) was lower in the current study than in other same-age study populations (25%-40%). Risk factors and identification strategies for PTSD are discussed.


Distribution and diversity of Escherichia coli populations in the South Nation River drainage basin, eastern Ontario, Canada.
We investigated the prevalence and diversity of Escherichia coli strains isolated from surface waters from multiple watersheds within the South Nation River basin in eastern Ontario, Canada. The basin is composed of mixed but primarily agricultural land uses. From March 2004 to November 2007, a total of 2,004 surface water samples were collected from 24 sampling sites. E. coli densities ranged from undetectable to 1.64 x 10(5) CFU 100 ml(-1) and were correlated with stream order and proximity to livestock production systems. The diversity of 21,307 E. coli isolates was characterized using repetitive extragenic palindromic PCR (rep-PCR), allowing for the identification of as many as 7,325 distinct genotypes, without capturing all of the diversity. The community was temporally and spatially dominated by a few dominant genotypes (clusters of more than 500 isolates) and several genotypes of intermediary abundance (clustering between 10 and 499 isolates). Simpson diversity indices, assessed on a normalized number of isolates per sample, ranged from 0.050 to 0.668. Simpson indices could be statistically discriminated on the basis of year and stream order, but land use, discharge, weather, and water physical-chemical properties were not statistically important discriminators. The detection of Campylobacter species was associated with statistically lower Simpson indices (greater diversity; P < 0.05). Waterborne E. coli isolates from genotypes of dominant and intermediary abundance were clustered with isolates obtained from fecal samples collected in the study area over the same period, and 90% of the isolates tested proved to share genotypes with fecal isolates. Overall, our data indicated that the densities and distribution of E. coli in these mixed-use watersheds were linked to stream order and livestock-based land uses. Waterborne E. coli populations that were distinct from fecal isolates were detected and, on this basis, were possibly naturalized E. coli strains.


Suicide risk assessment in the emergency department: Are there any tools in the pipeline?
It is estimated that as many as 1 in 10 individuals who complete suicide had been seen in emergency departments within the prior 2months. However, very little evidence underlies the current recommendations on managing patients with suicidal ideation presenting to the emergency department. The American College of Emergency Physicians (ACEP) and Veterans Affairs/Department of Defense (VA/DoD) have developed clinical practice guidelines for the screening and treatment of patients with suicidal ideation who present to emergency departments. In this study we investigated the extent to which new and ongoing studies are being conducted to address the current limitations in suicide screening in emergency departments. We identified low-level recommendations in clinical practice guidelines that have been set forth by the ACEP and VA/DoD. PICO questions were then created to help identify relevant studies pertaining to screening patients with suicidal ideation in the emergency department. PICO questions were used to develop search strings, which were then used to locate studies from ClinicalTrials.gov and the World Health Organization's International Clinical Trials Registry Platform. Seventeen PICO questions were created for this study. We found 11 studies addressing gaps identified in the clinical practice guidelines. Of the 17 PICO questions created, 10 were being addressed by 11 studies. Little research is being done to improve suicide risk assessment tools in the emergency department. Further research in this area may decrease health care costs, improve patient care, and save the lives of those at risk of dying by suicide.


Mediator subunit 12 coordinates intrinsic and extrinsic control of epithalamic development.
In the developing brain, the production of neurons from multipotent precursors must be carefully regulated in order to generate the appropriate numbers of various differentiated neuronal types. Inductive signals from extrinsic elements such as growth factors need to be integrated with timely expression of intrinsic elements such as transcription factors that define the competence of the cell. The transcriptional Mediator complex offers a mechanism to coordinate the timing and levels of intrinsic and extrinsic influences by acting as a rapid molecular switch for transcription of poised RNA pol II. The epithalamus is a highly conserved region of the vertebrate brain that differentiates early and rapidly in the zebrafish. It includes the pineal and parapineal organs and the habenular nuclei. Mutation of the Mediator complex subunit Med12 impairs the specification of habenular and parapineal neurons and causes a loss of differentiation in pineal neurons and photoreceptors. Although FGF ligands and transcription factors for parapineal and photoreceptor development are still expressed in the pineal complex of med12 mutants, FGF signaling is impaired and transcription factor expression is reduced and/or delayed. We find that the timely expression of one of these transcription factors, tbx2b, is controlled by Med12 and is vital for parapineal specification. We propose that the Mediator complex is responsible for subtle but significant changes in transcriptional timing and amplitude that are essential for coordinating the development of neurons in the epithalamus.


Effects of melatonin and caffeic acid phenethyl ester on testicular injury induced by myocardial ischemia/reperfusion in rats.
Experimental studies indicate that ischemia/reperfusion (I/R) causes remote organ injury although the molecular mechanism has not been clearly defined. In this report, the role of oxidative injury on testicular damage following myocardial I/R injury and the effects of antioxidant agents, melatonin and caffeic acid phenethyl ester (CAPE), on testicular injury were investigated. As far as we know, this is the first report demonstrating that myocardial I/R induces damage to the testes. Thirty-two male Wistar rats were randomly divided into four groups: sham operation (SO), I/R + vehicle, I/R + melatonin, and I/R + caffeic acid phenethyl ester. To produce cardiac damage, the left main coronary artery was occluded for 30 min, followed by 120 min reperfusion, in anesthetized rats. Serum nitric oxide (NO) and malondialdehyde (MDA) levels and morphological changes were examined. I/R was accompanied by a significant increase in serum MDA and NO levels, whereas, melatonin and CAPE administration significantly reduced these values. Melatonin was more efficient in reducing MDA levels than CAPE (P < 0.05). I/R induced myocardial damage, manifested as the histopathological evidence of intracellular vacuolization, interstitial edema, neutrophil infiltration and coagulative necrosis. I/R + vehicle group showed many histological alterations such as focal tubular atrophy, and degeneration and disorganization of the seminiferous epithelium in testes. The number of atrophic tubules and degenerating cells was significantly higher in I/R + vehicle group than that of SO group. Melatonin and CAPE significantly reduced the number of degenerating cells; additionally, melatonin reduced the number of atrophic tubules (P < 0.05). Our results indicate that myocardial I/R induces severe testicular damage and antioxidant agents, especially melatonin, have protective effects on testicular injury after myocardial I/R. Our data emphasize that oxygen-based reactants may play a central role in remote organ injury.


Idelalisib: a rare cause of enterocolitis.
Idelalisib is an oral, phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, approved by FDA since July 2014 for the treatment of relapsed follicular B-cell non-Hodgkin lymphoma. Data from three phases of the study involving idelalisib demonstrate diarrhea (47%) to be the common adverse effect. The other side effects are pyrexia (28%), fatigue (30%), nausea (29%), cough (29%), pneumonia (25%), abdominal pain (26%) and rash (21%). The characteristic histological findings of idelalisib colitis include intraepithelial lymphocytosis, neutrophilic cryptitis and epithelial cell apoptosis within the crypts. Histological findings help differentiate among other causes of diarrhea and entero-colitis. We present a female patient with recurrent follicular lymphoma treated with idelalisib and presented with diarrhea. She was found to have entero-colitis and was treated successfully with drug discontinuation and prednisone.


cGMP modulates basal and activated microvessel permeability independently of [Ca2+]i.
To investigate the mechanisms whereby guanosine 3',5'-cyclic monophosphate (cGMP) modulates microvessel permeability in vivo, we measured changes in microvessel hydraulic conductivity (Lp) and endothelial cytoplasmic Ca2+ concentration ([Ca2+]i) in response to the cGMP analogs 8-bromo-cGMP (8-BrcGMP) and 8-(p-chlorophenylthio)cGMP (8-pCPT-cGMP) in the presence and absence of inflammatory stimuli in intact individually perfused microvessels in frog and rat mesenteries. The cGMP analog caused a transient increase in Lp and potentiated ATP or bradykinin-induced increases in Lp in frog and rat mesenteric microvessels, respectively. The mean peak value of the test Lp/control Lp after exposure to 8-BrcGMP was 5.3 +/- 0.5 in frog microvessels and 2.8 +/- 0.4 in rat microvessels. The ATP-induced increase in Lp in frog microvessels was further raised by 8-BrcGMP from 7.0 +/- 0.9 to 12.4 +/- 1.9 times the control. In rat mesenteric microvessels, the bradykinin-induced increase in Lp was potentiated by 8-BrcGMP from 4.8 +/- 0.4 to 8.3 +/- 1.3 times the control and was suppressed by the guanylate cyclase inhibitor LY-83583 to 2.6 +/- 0.5 times the control. A similar but larger effect was found when using 8-pCPT-cGMP. In contrast to the actions of increased cGMP on microvessel permeability, cGMP analogs had no effect on basal endothelial [Ca2+]i and did not alter the magnitude and time course of ATP or bradykinin-induced increases in endothelial [Ca2+]i. These results suggested that an elevation of cGMP levels in endothelial cells is a necessary step to increase microvessel permeability in intact microvessels, and this regulatory process occurs downstream from Ca2+ influx, which differs from that reported in large-vessel endothelium in culture and in vascular smooth muscle cells. Experiments carried on microvessels in both frog and rat mesenteries provided a direct comparison of the endothelial cell regulatory mechanisms between species.


Low socioeconomic status over 12 years and subclinical cardiovascular disease: the study of women's health across the nation.
The inverse relation between socioeconomic status and cardiovascular disease is well established. However, few studies have investigated socioeconomic status assessed repeatedly during adulthood in relation to subclinical atherosclerosis. We aimed to test whether consistently low socioeconomic status, as indexed by education, income, and financial strain, for 12 years of midlife was related to later carotid intima-media thickness and plaque among women. The Study of Women's Health Across the Nation is a multisite longitudinal study of midlife women. Education was assessed at the study baseline, income and financial strain were obtained yearly for 12 years, and a carotid ultrasound was obtained at study year 12 among 1402 women. Associations were tested in linear and multinomial logistic regression models adjusted for demographic, biological, and behavioral risk factors. A high school education or less (odds ratio [OR] [95% confidence interval {CI}], 1.72 [1.15-2.59]; P<0.01), some college education (OR [95% CI], 1.65 [1.17-2.32]; P<0.01), consistently low income (OR [95% CI], 1.83 [1.15-2.89]; P<0.05), and consistent financial strain (OR [95% CI], 1.78 [1.21-2.61]; P<0.01) for 12 years were associated with higher carotid plaque, and consistent financial strain was associated with elevated maximal intima-media thickness (β [SE]=0.02 [0.01]; P<0.05) controlling for standard cardiovascular disease risk factors. When socioeconomic status indices were considered together, financial strain (β [SE]=0.02 [0.01]; P<0.05) and low education (high school education or less: OR [95% CI], 1.55 [1.01-2.37]; P<0.05; some college: OR [95% CI], 1.56 [1.09-2.21]; P<0.05) were most consistently associated with intima-media thickness and plaque, respectively, controlling for risk factors. The findings indicate the importance of targeting economically disadvantaged women in efforts to prevent cardiovascular disease among women.


Detection and characterisation of Complement protein activity in bovine milk by bactericidal sequestration assay.
While the Complement protein system in human milk is well characterised, there is little information on its presence and activity in bovine milk. Complement forms part of the innate immune system, hence the importance of its contribution during milk ingestion to the overall defences of the neonate. A bactericidal sequestration assay, featuring a Complement sensitive strain, Escherichia coli 0111, originally used to characterise Complement activity in human milk was successfully applied to freshly drawn bovine milk samples, thus, providing an opportunity to compare Complement activities in both human and bovine milks. Although not identical in response, the levels of Complement activity in bovine milk were found to be closely comparable with that of human milk. Differential counts of Esch. coli 0111 after 2 h incubation were 6.20 and 6.06 log CFU/ml, for raw bovine and human milks, respectively - the lower value representing a stronger Complement response. Exposing bovine milk to a range of thermal treatments e.g. 42, 45, 65, 72, 85 or 95 °C for 10 min, progressively inhibited Complement activity by increasing temperature, thus confirming the heat labile nature of this immune protein system. Low level Complement activity was found, however, in 65 and 72 °C heat treated samples and in retailed pasteurised milk which highlights the outer limit to which high temperature, short time (HTST) industrial thermal processes should be applied if retention of activity is a priority. Concentration of Complement in the fat phase was evident following cream separation, and this was also reflected in the further loss of activity recorded in low fat variants of retailed pasteurised milk. Laboratory-based churning of the cream during simulated buttermaking generated an aqueous (buttermilk) phase with higher levels of Complement activity than the fat phase, thus pointing to a likely association with the milk fat globule membrane (MFGM) layer.


Structures of N-termini of helices in proteins.
We have surveyed 393 N-termini of alpha-helices and 156 N-termini of 3(10)-helices in 85 high resolution, non-homologous protein crystal structures for N-cap side-chain rotamer preferences, hydrogen bonding patterns, and solvent accessibilities. We find very strong rotamer preferences that are unique to N-cap sites. The following rules are generally observed for N-capping in alpha-helices: Thr and Ser N-cap side chains adopt the gauche - rotamer, hydrogen bond to the N3 NH and have psi restricted to 164 +/- 8 degrees. Asp and Asn N-cap side chains either adopt the gauche - rotamer and hydrogen bond to the N3 NH with psi = 172 +/- 10 degrees, or adopt the trans rotamer and hydrogen bond to both the N2 and N3 NH groups with psi = 1-7 +/- 19 degrees. With all other N-caps, the side chain is found in the gauche + rotamer so that the side chain does not interact unfavorably with the N-terminus by blocking solvation and psi is unrestricted. An i, i + 3 hydrogen bond from N3 NH to the N-cap backbone C = O in more likely to form at the N-terminus when an unfavorable N-cap is present. In the 3(10)-helix Asn and Asp remain favorable N-caps as they can hydrogen bond to the N2 NH while in the trans rotamer; in contrast, Ser and Thr are disfavored as their preferred hydrogen bonding partner (N3 NH) is inaccessible. This suggests that Ser is the optimum choice of N-cap when alpha-helix formation is to be encouraged while 3(10)-helix formation discouraged. The strong energetic and structural preferences found for N-caps, which differ greatly from positions within helix interiors, suggest that N-caps should be treated explicitly in any consideration of helical structure in peptides or proteins.


Comparative analyses of genetic trends and prospects for selection against hip and elbow dysplasia in 15 UK dog breeds.
Hip dysplasia remains one of the most serious hereditary diseases occurring in dogs despite long-standing evaluation schemes designed to aid selection for healthy joints. Many researchers have recommended the use of estimated breeding values (EBV) to improve the rate of genetic progress from selection against hip and elbow dysplasia (another common developmental orthopaedic disorder), but few have empirically quantified the benefits of their use. This study aimed to both determine recent genetic trends in hip and elbow dysplasia, and evaluate the potential improvements in response to selection that publication of EBV for such diseases would provide, across a wide range of pure-bred dog breeds. The genetic trend with respect to hip and elbow condition due to phenotypic selection had improved in all breeds, except the Siberian Husky. However, derived selection intensities are extremely weak, equivalent to excluding less than a maximum of 18% of the highest risk animals from breeding. EBV for hip and elbow score were predicted to be on average between 1.16 and 1.34 times more accurate than selection on individual or both parental phenotypes. Additionally, compared to the proportion of juvenile animals with both parental phenotypes, the proportion with EBV of a greater accuracy than selection on such phenotypes increased by up to 3-fold for hip score and up to 13-fold for elbow score. EBV are shown to be both more accurate and abundant than phenotype, providing more reliable information on the genetic risk of disease for a greater proportion of the population. Because the accuracy of selection is directly related to genetic progress, use of EBV can be expected to benefit selection for the improvement of canine health and welfare. Public availability of EBV for hip score for the fifteen breeds included in this study will provide information on the genetic risk of disease in nearly a third of all dogs annually registered by the UK Kennel Club, with in excess of a quarter having an EBV for elbow score as well.


Plant nutrient supply determines competition between phytophagous insects.
Indirect competition is often mediated by plant responses to herbivore feeding damage and is common among phytophagous insect species. Plant-mediated responses may be altered by abiotic conditions such as nutrient supply, which can affect plant growth, morphology, and the concentration of primary and secondary metabolites. Nutrient supply can be manipulated by the type and amount of fertilizer applied to a plant. Brassica oleracea plants were grown in several types of fertilizer, including those commonly used in sustainable and conventional agricultural systems. The occurrence of indirect competition between two phytophagous species from different feeding guilds (a phloem-feeder and leaf-chewer) was assessed. The leaf-chewer reduced aphid populations on plants growing in most fertilizer treatments, but not on those in the ammonium nitrate fertilizer treatment, which caused the highest concentration of foliar nitrogen. The potential consequences of our findings are discussed for phytophagous species in conventional and sustainable agricultural systems.


High-latitude dust over the North Atlantic: inputs from Icelandic proglacial dust storms.
Mineral aerosols play an important role in the atmosphere-ocean climate system. Research has focused almost exclusively on sources in low-latitude arid regions, but here we show that there are substantial sources in cold, higher latitudes. A 6-year record of measurements made on Heimaey, an island south of Iceland, reveals frequent dust events with concentrations exceeding 20 micrograms per cubic meter. Much of this potentially iron-rich dust is transported southward and deposited in the North Atlantic. Emissions are highest in spring and spatially and temporally associated with active glacial outwash plains; large dust events appear to be associated with glacial outburst floods. In response to global warming, ice retreat on Iceland and in other glacierized areas is likely to increase dust emissions from these regions.


A High-Throughput Glycosyltransferase Inhibition Assay for Identifying Molecules Targeting Fucosylation in Cancer Cell-Surface Modification.
In cancers, increased fucosylation (attachment of fucose sugar residues) on cell-surface glycans, resulting from the abnormal upregulation of the expression of specific fucosyltransferase enzymes (FUTs), is one of the most important types of glycan modifications associated with malignancy. Fucosylated glycans on cell surfaces are involved in a multitude of cellular interactions and signal regulation in normal biological processes, as well as in disease. For example, sialyl LewisX is a fucosylated cell-surface glycan that is abnormally abundant in some cancers where it has been implicated in facilitating metastasis, allowing circulating tumor cells to bind to the epithelial tissue within blood vessels and invade into secondary sites by taking advantage of glycan-mediated interactions. To identify inhibitors of FUT enzymes as potential cancer therapeutics, we have developed a novel high-throughput assay that makes use of a fluorogenically labeled oligosaccharide as a probe of fucosylation. This probe, which consists of a 4-methylumbelliferyl glycoside, is recognized and hydrolyzed by specific glycoside hydrolase enzymes to release fluorescent 4-methylumbelliferone, yet when the probe is fucosylated prior to treatment with the glycoside hydrolases, hydrolysis does not occur and no fluorescent signal is produced. We have demonstrated that this assay can be used to measure the inhibition of FUT enzymes by small molecules, because blocking fucosylation will allow glycosidase-catalyzed hydrolysis of the labeled oligosaccharide to produce a fluorescent signal. Employing this assay, we have screened a focused library of small molecules for inhibitors of a human FUT enzyme involved in the synthesis of sialyl LewisX and demonstrated that our approach can be used to identify potent FUT inhibitors from compound libraries in microtiter plate format.