Functional intersection of ATM and DNA-dependent protein kinase catalytic subunit in coding end joining during V(D)J recombination.
V(D)J recombination is initiated by the RAG endonuclease, which introduces DNA double-strand breaks (DSBs) at the border between two recombining gene segments, generating two hairpin-sealed coding ends and two blunt signal ends. ATM and DNA-dependent protein kinase catalytic subunit (DNA-PKcs) are serine-threonine kinases that orchestrate the cellular responses to DNA DSBs. During V(D)J recombination, ATM and DNA-PKcs have unique functions in the repair of coding DNA ends. ATM deficiency leads to instability of postcleavage complexes and the loss of coding ends from these complexes. DNA-PKcs deficiency leads to a nearly complete block in coding join formation, as DNA-PKcs is required to activate Artemis, the endonuclease that opens hairpin-sealed coding ends. In contrast to loss of DNA-PKcs protein, here we show that inhibition of DNA-PKcs kinase activity has no effect on coding join formation when ATM is present and its kinase activity is intact. The ability of ATM to compensate for DNA-PKcs kinase activity depends on the integrity of three threonines in DNA-PKcs that are phosphorylation targets of ATM, suggesting that ATM can modulate DNA-PKcs activity through direct phosphorylation of DNA-PKcs. Mutation of these threonine residues to alanine (DNA-PKcs(3A)) renders DNA-PKcs dependent on its intrinsic kinase activity during coding end joining, at a step downstream of opening hairpin-sealed coding ends. Thus, DNA-PKcs has critical functions in coding end joining beyond promoting Artemis endonuclease activity, and these functions can be regulated redundantly by the kinase activity of either ATM or DNA-PKcs.


On universal common ancestry, sequence similarity, and phylogenetic structure: the sins of P-values and the virtues of Bayesian evidence.
The universal common ancestry (UCA) of all known life is a fundamental component of modern evolutionary theory, supported by a wide range of qualitative molecular evidence. Nevertheless, recently both the status and nature of UCA has been questioned. In earlier work I presented a formal, quantitative test of UCA in which model selection criteria overwhelmingly choose common ancestry over independent ancestry, based on a dataset of universally conserved proteins. These model-based tests are founded in likelihoodist and Bayesian probability theory, in opposition to classical frequentist null hypothesis tests such as Karlin-Altschul E-values for sequence similarity. In a recent comment, Koonin and Wolf (K&W) claim that the model preference for UCA is "a trivial consequence of significant sequence similarity". They support this claim with a computational simulation, derived from universally conserved proteins, which produces similar sequences lacking phylogenetic structure. The model selection tests prefer common ancestry for this artificial data set. For the real universal protein sequences, hierarchical phylogenetic structure (induced by genealogical history) is the overriding reason for why the tests choose UCA; sequence similarity is a relatively minor factor. First, for cases of conflicting phylogenetic structure, the tests choose independent ancestry even with highly similar sequences. Second, certain models, like star trees and K&W's profile model (corresponding to their simulation), readily explain sequence similarity yet lack phylogenetic structure. However, these are extremely poor models for the real proteins, even worse than independent ancestry models, though they explain K&W's artificial data well. Finally, K&W's simulation is an implementation of a well-known phylogenetic model, and it produces sequences that mimic homologous proteins. Therefore the model selection tests work appropriately with the artificial data. For K&W's artificial protein data, sequence similarity is the predominant factor influencing the preference for common ancestry. In contrast, for the real proteins, model selection tests show that phylogenetic structure is much more important than sequence similarity. Hence, the model selection tests demonstrate that real universally conserved proteins are homologous, a conclusion based primarily on the specific nested patterns of correlations induced in genetically related protein sequences. This article was reviewed by Rob Knight, Robert Beiko (nominated by Peter Gogarten), and Michael Gilchrist.


Novel insights into the mechanism of SepL-mediated control of effector secretion in enteropathogenic Escherichia coli.
Type three secretion systems (T3SSs) are virulence determinants employed by several pathogenic bacteria as molecular syringes to inject effector proteins into host cells. Diarrhea-producing enteropathogenic Escherichia coli (EPEC) uses a T3SS to colonize the intestinal tract. T3S is a highly coordinated process that ensures hierarchical delivery of three classes of substrates: early (inner rod and needle subunits), middle (translocators), and late (effectors). Translocation of effectors is triggered upon host-cell contact in response to different environmental cues, such as calcium levels. The T3S substrate specificity switch from middle to late substrates in EPEC is regulated by the SepL and SepD proteins, which interact with each other and form a trimeric complex with the chaperone CesL. In this study, we investigated the link between calcium concentration and secretion regulation by the gatekeeper SepL. We found that calcium depletion promotes late substrate secretion in a translocon-independent manner. Furthermore, the stability, formation, and subcellular localization of the SepL/SepD/CesL regulatory complex were not affected by the absence of calcium. In addition, we demonstrate that SepL interacts in a calcium-independent manner with the major export gate component EscV, which in turn interacts with both middle and late secretion substrates, providing a docking site for T3S. These results suggest that EscV serves as a binding platform for both the SepL regulatory protein and secreted substrates during the ordered assembly of the T3SS.


Diagnostic criteria for malnutrition - An ESPEN Consensus Statement.
To provide a consensus-based minimum set of criteria for the diagnosis of malnutrition to be applied independent of clinical setting and aetiology, and to unify international terminology. The European Society of Clinical Nutrition and Metabolism (ESPEN) appointed a group of clinical scientists to perform a modified Delphi process, encompassing e-mail communications, face-to-face meetings, in group questionnaires and ballots, as well as a ballot for the ESPEN membership. First, ESPEN recommends that subjects at risk of malnutrition are identified by validated screening tools, and should be assessed and treated accordingly. Risk of malnutrition should have its own ICD Code. Second, a unanimous consensus was reached to advocate two options for the diagnosis of malnutrition. Option one requires body mass index (BMI, kg/m(2)) <18.5 to define malnutrition. Option two requires the combined finding of unintentional weight loss (mandatory) and at least one of either reduced BMI or a low fat free mass index (FFMI). Weight loss could be either >10% of habitual weight indefinite of time, or >5% over 3 months. Reduced BMI is <20 or <22 kg/m(2) in subjects younger and older than 70 years, respectively. Low FFMI is <15 and <17 kg/m(2) in females and males, respectively. About 12% of ESPEN members participated in a ballot; >75% agreed; i.e. indicated ≥7 on a 10-graded scale of acceptance, to this definition. In individuals identified by screening as at risk of malnutrition, the diagnosis of malnutrition should be based on either a low BMI (<18.5 kg/m(2)), or on the combined finding of weight loss together with either reduced BMI (age-specific) or a low FFMI using sex-specific cut-offs.


Raman measurements of substrate temperature in a molecular beam epitaxy growth chamber.
A method is described for directly measuring the temperature of a substrate in a molecular-beam epitaxy (MBE) growth system. The approach relies on the establishment of the temperature dependence of Raman-active phonons of the substrate material using independently known calibration points across the range of interest. An unknown temperature in this range is then determined based on the Raman peak position with the substrate in situ the MBE chamber. The apparatus relies on conventional optics and Raman components. Shifting and broadening of the Raman spectrum are described based on the effects of thermal expansion and anharmonic decay. The choice of reference temperature is discussed. The method is qualified by examining the substrate temperature dependence, relative to that of a standard thermocouple, during a commonly used ramp procedure. Both temperature difference and time lag are obtained.


GenomeLandscaper: Landscape analysis of genome-fingerprints maps assessing chromosome architecture.
Assessing correctness of an assembled chromosome architecture is a central challenge. We create a geometric analysis method (called GenomeLandscaper) to conduct landscape analysis of genome-fingerprints maps (GFM), trace large-scale repetitive regions, and assess their impacts on the global architectures of assembled chromosomes. We develop an alignment-free method for phylogenetics analysis. The human Y chromosomes (GRCh.chrY, HuRef.chrY and YH.chrY) are analysed as a proof-of-concept study. We construct a galaxy of genome-fingerprints maps (GGFM) for them, and a landscape compatibility among relatives is observed. But a long sharp straight line on the GGFM breaks such a landscape compatibility, distinguishing GRCh38p1.chrY (and throughout GRCh38p7.chrY) from GRCh37p13.chrY, HuRef.chrY and YH.chrY. We delete a 1.30-Mbp target segment to rescue the landscape compatibility, matching the antecedent GRCh37p13.chrY. We re-locate it into the modelled centromeric and pericentromeric region of GRCh38p10.chrY, matching a gap placeholder of GRCh37p13.chrY. We decompose it into sub-constituents (such as BACs, interspersed repeats, and tandem repeats) and trace their homologues by phylogenetics analysis. We elucidate that most examined tandem repeats are of reasonable quality, but the BAC-sized repeats, 173U1020C (176.46 Kbp) and 5U41068C (205.34 Kbp), are likely over-repeated. These results offer unique insights into the centromeric and pericentromeric regions of the human Y chromosomes.


ATP-Mediated Transient Behavior of Stomatocyte Nanosystems.
In nature, dynamic processes are ubiquitous and often characterized by adaptive, transient behavior. Herein, we present the development of a transient bowl-shaped nanoreactor system, or stomatocyte, the properties of which are mediated by molecular interactions. In a stepwise fashion, we couple motility to a dynamic process, which is maintained by transient events; namely, binding and unbinding of adenosine triphosphate (ATP). The surface of the nanosystem is decorated with polylysine (PLL), and regulation is achieved by addition of ATP. The dynamic interaction between PLL and ATP leads to an increase in the hydrophobicity of the PLL-ATP complex and subsequently to a collapse of the polymer; this causes a narrowing of the opening of the stomatocytes. The presence of the apyrase, which hydrolyzes ATP, leads to a decrease of the ATP concentration, decomplexation of PLL, and reopening of the stomatocyte. The competition between ATP input and consumption gives rise to a transient state that is controlled by the out-of-equilibrium process.


Heterosexual behaviours among men who sell sex to men in coastal Kenya.
African men who have sex with men often sell sex to men, and MSM who sell sex (MSM-SW) often also have female partners. We compared sexual risk behaviour of MSM-SW who were sexually active with female partners (bisexual MSW) to MSM-SW with only male partners (exclusive MSW). Descriptive behavioural study : A novel, validated daily event and partner diary self-completed by 82 MSM who sold sex over a follow-up period of 42 days with weekly review. Cumulative individual counts of sex and condomless sex were compiled by partner characteristics. The incidence of specific partnerships and sex acts were compared within and between bisexual and exclusive MSW. Most (59%) MSM-SW reported female partners during follow-up. The majority of both male and female partners were cash-paying clients originating locally. Bisexual MSW reported a similar rate of condomless sex with male and female partners, but significantly fewer male partners than exclusive MSW. Bisexual MSW had lower HIV prevalence, were more likely to only report insertive anal sex roles, and reported lower frequencies of condomless receptive anal sex than exclusive MSW. Bisexually active male sex workers in coastal Kenya create HIV and other sexually transmitted infection transmission pathways to partners and clients in both MSM and heterosexual networks, but differed from exclusive MSW in having lower HIV acquisition and transmission risks. Epidemiological projection methods are liable to overestimate bridging potential of MSM-SW and MSM populations without account for systematic differences in risk within these populations.


Temperature can interact with landscape factors to affect songbird productivity.
Increased temperatures and more extreme weather patterns associated with global climate change can interact with other factors that regulate animal populations, but many climate change studies do not incorporate other threats to wildlife in their analyses. We used 20 years of nest-monitoring data from study sites across a gradient of habitat fragmentation in Missouri, USA, to investigate the relative influence of weather variables (temperature and precipitation) and landscape factors (forest cover and edge density) on the number of young produced per nest attempt (i.e., productivity) for three species of songbirds. We detected a strong forest cover × temperature interaction for the Acadian Flycatcher (Empidonax virescens) on productivity. Greater forest cover resulted in greater productivity because of reduced brood parasitism and increased nest survival, whereas greater temperatures reduced productivity in highly forested landscapes because of increased nest predation but had no effect in less forested landscapes. The Indigo Bunting (Passerina cyanea) exhibited a similar pattern, albeit with a marginal forest cover × temperature interaction. By contrast, productivity of the Northern Cardinal (Cardinalis cardinalis) was not influenced by landscape effects or temperature. Our results highlight a potential difficulty of managing wildlife in response to global change such as habitat fragmentation and climate warming, as the habitat associated with the greatest productivity for flycatchers was also that most negatively influenced by high temperatures. The influence of high temperatures on nest predation (and therefore, nest predators) underscores the need to acknowledge the potential complexity of species' responses to climate change by incorporating a more thorough consideration of community ecology in the development of models of climate impacts on wildlife.


Noncanonical GLI1 signaling promotes stemness features and in vivo growth in lung adenocarcinoma.
Aberrant Hedgehog/GLI signaling has been implicated in a diverse spectrum of human cancers, but its role in lung adenocarcinoma (LAC) is still under debate. We show that the downstream effector of the Hedgehog pathway, GLI1, is expressed in 76% of LACs, but in roughly half of these tumors, the canonical pathway activator, Smoothened, is expressed at low levels, possibly owing to epigenetic silencing. In LAC cells including the cancer stem cell compartment, we show that GLI1 is activated noncanonically by MAPK/ERK signaling. Different mechanisms can trigger the MAPK/ERK/GLI1 cascade including KRAS mutation and stimulation of NRP2 by VEGF produced by the cancer cells themselves in an autocrine loop or by stromal cells as paracrine cross talk. Suppression of GLI1, by silencing or drug-mediated, inhibits LAC cells proliferation, attenuates their stemness and increases their susceptibility to apoptosis in vitro and in vivo. These findings provide insight into the growth of LACs and point to GLI1 as a downstream effector for oncogenic pathways. Thus, strategies involving direct inhibition of GLI1 may be useful in the treatment of LACs.


Facilitating early recovery of bowel motility after colorectal surgery: a systematic review.
To determine how restored gastrointestinal motility can be accelerated after colorectal surgery. Regaining normal bowel functions after surgery is described as unexpectedly problematic. Postoperative ileus is expected after all surgery where the peritoneum is entered, and the length of surgery has little or no impact in terms of the duration of Postoperative ileus. There is some speculation about the best way to facilitate bowel motility after colorectal surgery. A systematic review. The computerised databases Medline, Scopus and CINAHL were searched to locate randomised, controlled trials by using the following keywords: colorectal surgery, postoperative ileus, recovery of function and gastrointestinal motility. The systematic search was limited to studies published between January 2002-January 2012. Reference lists were also searched manually. A total of 34 randomised, controlled trials were included in the review. Recovery of gastrointestinal motility was accelerated when one of the following forms of treatment was administered: probiotics, early feeding in combination with multimodal regimens, pentoxifylline, flurbiprofen, valdecoxib, ketorolac, clonidine, ropivacaine, lidocaine or spinal analgesia. Gum chewing, preoperative carbohydrate loading, bisacodyl and Doppler-guided fluid management have an uncertain effect on bowel motility. The use of nonpharmacological interventions, intrathecal morphine, restricted fluid therapy and choline citrate yielded no significant acceleration in bowel motility. A multimodal treatment, where the use of morphine is restricted, seems to be the best way to accelerate the recovery of gastrointestinal bowel motility. However, more studies are required to optimise the multimodal protocol. The early return of bowel functions leads to quicker overall postoperative recovery, which may ease patient discomfort and decrease hospitalisation costs.


The need for an ethnomedical science.
Ethnomedicine is an intellectual area which embraces theoretical concerns that are relevant to both the social and biological sciences. The relation which exists between disease, social behavior, and human adaptation constitutes the primary subject matter of ethnomedicine. This relation is examined in terms of man's unique capacities for symbolization and culture. Since ethnomedical generalizations explain how social groups deal with a generic disease, they can be used to examine contemporary problems which involve the organization and practice of medicine as well as problems that stem from relations of the medical system with other subsystems in the group. Recasting contemporary social problems in this way may help to clarify their roots and sources (13,28). In focusing on fundamental properties of disease in man, ethnomedicine can also help to clarify the effects and meanings of disease and thereby make its control more rational. A theory of disease, an ultimate aim of ethnomedical inquiry, will serve as an explanatory device with wide-ranging applications.


Airborne particles in Swansea, UK: their collection and characterization.
Urban air particulate matter (PM) has previously been associated with a variety of adverse health effects. It is now believed that the smallest particles, ultrafine or nanoparticles, are linked to the greatest health effects. The physicochemistry of these particles is likely to provide information regarding their toxicity. Therefore, the aim of this study was to further the understanding of the heterogeneous and changing particle concentrations in urban air, in conjunction with gaining an understanding of the physicochemistry of the particles. A Dekati electrical low-pressure impactor was used to collect the particles and real-time data in a busy traffic corridor in Swansea, Wales, over a period of 10 nonconsecutive weeks. Particle concentrations in the street canyon were analyzed and particle physicochemistries investigated using a variety of techniques. Particle number concentrations were found to vary both diurnally and from day to day in the traffic corridor. Of all particles, the nano to fine size fraction was consistently identified in the highest concentrations (maximum: 140,000 particles cm(-3)). Particle physicochemistry was found to vary as a function of size, with larger particles exhibiting a greater variety of morphologies (and consequently particle types) and associated metals.


Minimal clinically important decline in physical function over one year: EPOSA study.
The Australian/Canadian hand Osteoarthritis Index (AUSCAN) and the Western Ontario and McMaster Universities knee and hip Osteoarthritis Index (WOMAC) are the most commonly used clinical tools to manage and monitor osteoarthritis (OA). Few studies have as yet reported longitudinal changes in the AUSCAN index regarding the hand. While there are published data regarding WOMAC assessments of the hip and the knee, the two sites have always evaluated separately. The current study therefore sought to determine the minimal clinically important difference (MCID) in decline in the AUSCAN hand and WOMAC hip/knee physical function scores over 1 year using anchor-based and distribution-based methods. The study analysed data collected by the European Project on Osteoarthritis, a prospective observational study investigating six adult cohorts with and without OA by evaluating changes in the AUSCAN and WOMAC physical function scores at baseline and 12-18 months later. Pain and stiffness scores, the performance-based grip strength and walking speed and health-related quality of life measures were used as the study's anchors. Receiver operating characteristic curves and distribution-based methods were used to estimate the MCID in the AUSCAN and WOMAC physical function scores; only the data of those participants who possessed paired (baseline and follow up-measures) AUSCAN and WOMAC scores were included in the analysis. Out of the 1866 participants who were evaluated, 1842 had paired AUSCAN scores and 1845 had paired WOMAC scores. The changes in the AUSCAN physical function score correlated significantly with those in the AUSCAN pain score (r = 0.31). Anchor- and distribution-based approaches converged identifying 4 as the MCID for decline in the AUSCAN hand physical function. Changes in the WOMAC hip/knee physical function score were significantly correlated with changes in both the WOMAC pain score (r = 0.47) and the WOMAC stiffness score (r = 0.35). The different approaches converged identifying two as the MCID for decline in the WOMAC hip/knee physical function. The most reliable MCID estimates of decline over 1 year in the AUSCAN hand and WOMAC hip/knee physical function scores were 4 and 2 points, respectively.


Cell type-dependent activation of 5-lipoxygenase by arachidonic acid.
5-Lipoxygenase (5-LO) is the key enzyme in the biosynthesis of proinflammatory leukotrienes. We show that stimulation of polymorphonuclear leukocytes (PMNL), rat basophilic leukemia (RBL)-1, or transfected HeLa cells with arachidonic acid (AA) caused prominent 5-LO product formation that coincided with the activity of extracellular signal-regulated kinases (ERKs) and p38 mitogen-activated protein kinase. 5-LO product formation in AA-stimulated PMNL and RBL-1 cells was independent of Ca2+. However, in HeLa cells expressing a 5-LO mutant lacking potential 5-LO phosphorylation sites, removal of Ca2+ caused a prominent loss of 5-LO activity. For Mono Mac 6 (MM6) cells, AA failed to activate ERKs, and AA-induced 5-LO product formation was only minute. Also, activation of ERKs by phorbol esters did not lead to prominent 5-LO product synthesis. Instead, 5-LO activation in MM6 cells required Ca2+ or alternative signaling pathways induced by hyperosmotic stress. In summary, mechanisms for activation of 5-LO differ considerably between cell types.


Discovery of antibiotic (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one.
In the face of the clinical challenge posed by resistant bacteria, the present needs for novel classes of antibiotics are genuine. In silico docking and screening, followed by chemical synthesis of a library of quinazolinones, led to the discovery of (E)-3-(3-carboxyphenyl)-2-(4-cyanostyryl)quinazolin-4(3H)-one (compound 2) as an antibiotic effective in vivo against methicillin-resistant Staphylococcus aureus (MRSA). This antibiotic impairs cell-wall biosynthesis as documented by functional assays, showing binding of 2 to penicillin-binding protein (PBP) 2a. We document that the antibiotic also inhibits PBP1 of S. aureus, indicating a broad targeting of structurally similar PBPs by this antibiotic. This class of antibiotics holds promise in fighting MRSA infections.


Systematic analysis of the achaete-scute complex-like gene signature in clinical cancer patients.
The achaete-scute complex-like (ASCL) family, also referred to as 'achaete-scute complex homolog' or 'achaete-scute family basic helix-loop-helix transcription factor', is critical for proper development of the nervous system and deregulation of ASCL plays a key role in psychiatric and neurological disorders. The ASCL family consists of five members, namely ASCL1, ASCL2, ASCL3, ASCL4 and ASCL5. The ASCL1 gene serves as a potential oncogene during lung cancer development. There is a correlation between increased ASCL2 expression and colon cancer development. Inhibition of ASCL2 reduced cellular proliferation and tumor growth in xenograft tumor experiments. Although previous studies demonstrated involvement of ASCL1 and ASCL2 in tumor development, little is known on the remaining ASCL family members and their potential effect on tumorigenesis. Therefore, a holistic approach to investigating the expression of ASCL family genes in diverse types of cancer may provide new insights in cancer research. In this study, we utilized a web-based microarray database (Oncomine; www.oncomine.org) to analyze the transcriptional expression of the ASCL family in clinical cancer and normal tissues. Our bioinformatics analysis revealed the potential involvement of multiple ASCL family members during tumor onset and progression in multiple types of cancer. Compared to normal tissue, ASCL1 exhibited a higher expression in cancers of the lung, pancreas, kidney, esophagus and head and neck, whereas ASCL2 exhibited a high expression in cancers of the breast, colon, stomach, lung, head and neck, ovary and testis. ASCL3, however, exhibited a high expression only in breast cancer. Interestingly, ASCL1 expression was downregulated in melanoma and in cancers of the bladder, breast, stomach and colon. ASCL2 exhibited low expression levels in sarcoma, melanoma, brain and prostate cancers. Reduction in the expression of ASCL3 was detected in lymphoma, bladder, cervical, kidney and epithelial cancers. Similarly, ASCL5 exhibited low expression in the majority of brain cancer subtypes, such as glioblastoma and oligodendroglioma. This analysis supports the hypothesis that specific ASCL members may play an important role in cancer development. Collectively, our data suggest that alterations in the expression of ASCL gene family members are correlated with cancer development. Furthermore, ASCL family members were categorized according to cancer subtype. The aim of this report was to provide novel insights to the significance of the ASCL family in various cancers and our findings suggested that the ASCL gene family may be an ideal target for future cancer studies.


Brain Injury and Dementia in Pakistan: Current Perspectives.
Alzheimer's disease (AD) is the most common form of dementia, accounting for 50-75% of all cases, with a greater proportion of individuals affected at older age range. A single moderate or severe traumatic brain injury (TBI) is associated with accelerated aging and increased risk for dementia. The fastest growth in the elderly population is taking place in China, Pakistan, and their south Asian neighbors. Current clinical assessments are based on data collected from Caucasian populations from wealthy backgrounds giving rise to a "diversity" crisis in brain research. Pakistan is a lower-middle income country (LMIC) with an estimated one million people living with dementia. Pakistan also has an amalgamation of risk factors that lead to brain injuries such as lack of road legislations, terrorism, political instability, and domestic and sexual violence. Here, we provide an initial and current assessment of the incidence and management of dementia and TBI in Pakistan. Our review demonstrates the lack of resources in terms of speciality trained clinician staff, medical equipment, research capabilities, educational endeavors, and general awareness in the fields of dementia and TBI. Pakistan also lacks state-of-the-art assessment of dementia and its risk factors, such as neuroimaging of brain injury and aging. We provide recommendations for improvement in this arena that include the recent creation of Pakistan Brain Injury Consortium (PBIC). This consortium will enhance international collaborative efforts leading to capacity building for innovative research, clinician and research training and developing databases to bring Pakistan into the international platform for dementia and TBI research.


Ocular angiostrongyliasis--first case report from Jamaica.
A 30-year-old female presented with a one-month history of blurred vision in her left eye. Examination revealed a live motile worm in the anterior chamber of the left eye. She also had retinal pigment epithelial disturbance with focal intraretinal haemorrhage. The 19.9 mm worm was surgically removed and identified as Angiostrongylus cantonesis. She was treated with oral mebendazole. Her vision improved from counting fingers in the left eye to 6/36. This is the first documented case of ocular angiostrongyliasis in Jamaica.


Motivational Interviewing to Address Suicidal Ideation: A Randomized Controlled Trial in Veterans.
Although the months following discharge from psychiatric hospitalization are a period of acute risk for veterans, there is a dearth of empirically supported treatments tailored to veterans in acute psychiatric hospitalization. We conducted a randomized controlled trial to test the efficacy of Motivational Interviewing to Address Suicidal Ideation (MI-SI) that explored and resolved ambivalence, and a revised MI-SI (MI-SI-R) that resolved ambivalence, on suicidal ideation (SI) in hospitalized veterans who scored > 2 on the Scale for Suicidal Ideation. Participants were randomized to receive MI-SI plus treatment as usual (TAU), MI-SI-R+TAU, or TAU alone. MI-SI+TAU and MI-SI-R+TAU included two in-hospital therapy sessions and one telephone booster session. Participants completed follow-up assessments over 6 months. Participants in all groups experienced reductions in the presence and severity of SI, but there were no significant differences among the groups. For the presence of SI, results were in the hypothesized direction for both MI-SI+TAU conditions. Results are nondefinitive, but the effect size of both versions of MI-SI+TAU on the presence of SI was consistent with prior MI findings. Exploratory analyses suggest MI-SI-R may be preferable to MI-SI. More intensive MI-SI-R with a greater number of follow-ups may increase its effectiveness.


Do dietary and supplementary intakes of antioxidants differ with smoking status?
Differences in dietary and supplementary intake of antioxidants were determine between different categories of smokers and never-smokers. Data from a large, cross-sectional, population-based study were used. Subjects (n = 4244) were divided into five smoking categories according to the number of cigarettes smoked per day. Differences in intake of antioxidants or frequency of supplement use were assessed using multiple linear regression analysis and multiple logistic regression analysis, adjusting for potential confounders such as age, body mass index, education level, alcohol intake, and total energy intake. Men who smoked > 20 cigarettes/day had significantly lower intakes of beta-carotene and especially ascorbic acid compared to those who never smoked, resulting from an almost 60% lower fruit intake. Moderate and heavy smoking women also had lower ascorbic acid and fruit intake but differences were not as large as in men. A higher percentage of female heavy smokers compared with never-smokers consumed vitamin C (21.1% versus 14.1%), vitamin E (5.6% versus 1.8%), and multivitamin supplements (18.5% versus 12.2%). Among men only the moderate smokers differed significantly from never-smokers in supplement intake, in the sense that male moderate smokers had a higher percentage of multivitamin use (15.3% versus 12.2%) compared to never-smokers. Male heavy smokers not only have a lower dietary antioxidant intake than never-smokers, but additionally seem to use supplementation relatively infrequently.


Improved Protein Model in SPICA Force Field.
The previous version of the SPICA coarse-grained (CG) force field (FF) protein model focused primarily on membrane proteins and successfully reproduced the dimerization free energies of several transmembrane helices and the stable structures of various membrane protein assemblies. However, that model had limited accuracy when applied to other proteins, such as intrinsically disordered proteins (IDPs) and peripheral proteins, because the dimensions of the IDPs in an aqueous solution were too compact, and protein binding on the lipid membrane surface was overstabilized. To improve the accuracy of the SPICA FF model for the simulation of such systems, in this study, we introduce protein secondary structure-dependent nonbonded interaction parameters to the backbone segments and reoptimize almost all nonbonded parameters for amino acids. The improved FF proposed here successfully reproduces the radii of gyration of various IDPs, the binding sensitivity of several peripheral membrane proteins, and the dimerization free energies of several transmembrane helices. The new model also shows improved agreement with experiments on the free energy of peptide association in water. In addition, an extensive library of nonbonded interactions between proteins and lipids, including various glycerophospholipids, sphingolipids, and cholesterol, allows the study of specific interactions between lipids and peripheral and transmembrane proteins. Hence, the new SPICA FF (version 2) proposed herein is applicable with high accuracy for simulating a wide range of protein systems.


HIV-1 infection-induced apoptotic microparticles inhibit human DCs via CD44.
Acute HIV-1 infection results in dysregulated immunity, which contributes to poor control of viral infection. DCs are key regulators of both adaptive and innate immune responses needed for controlling HIV-1, and we surmised that factors elicited during acute HIV-1 infection might impede DC function. We derived immature DCs from healthy donor peripheral blood monocytes and treated them with plasma from uninfected control donors and donors with acute HIV-1 infections. We found that the plasma from patients with HIV specifically inhibited DC function. This suppression was mediated by elevated apoptotic microparticles derived from dying cells during acute HIV-1 infection. Apoptotic microparticles bound to and inhibited DCs through the hyaluronate receptor CD44. These data suggest that targeting this CD44-mediated inhibition by apoptotic microparticles could be a novel strategy to potentiate DC activation of HIV-specific immunity.


Molecular crystallization controlled by pH regulates mesoscopic membrane morphology.
Coassembled molecular structures are known to exhibit a large variety of geometries and morphologies. A grand challenge of self-assembly design is to find techniques to control the crystal symmetries and overall morphologies of multicomponent systems. By mixing +3 and -1 ionic amphiphiles, we assemble crystalline ionic bilayers in a large variety of geometries that resemble polyhedral cellular crystalline shells and archaea wall envelopes. We combine TEM with SAXS and WAXS to characterize the coassembled structures from the mesoscopic to nanometer scale. The degree of ionization of the amphiphiles and their intermolecular electrostatic interactions are controlled by varying pH. At low and high pH values, we observe closed, faceted vesicles with two-dimensional hexagonal molecular arrangements, and at intermediate pH, we observe ribbons with rectangular-C packing. Furthermore, as pH increases, we observe interdigitation of the bilayer leaflets. Accurate atomistic molecular dynamics simulations explain the pH-dependent bilayer thickness changes and also reveal bilayers of hexagonally packed tails at low pH, where only a small fraction of anionic headgroups is charged. Coarse-grained simulations show that the mesoscale geometries at low pH are faceted vesicles where liquid-like edges separate flat crystalline domains. Our simulations indicate that the curved-to-polyhedral shape transition can be controlled by tuning the tail density in regions where sharp bends can form the polyhedral edges. In particular, the pH acts to control the overall morphology of the ionic bilayers by changing the local crystalline order of the amphiphile tails.


SU-D-218-03: Resonant Frequency of Rotating Anode X-Ray Tubes.
To evaluate a new rotating anode X-ray tube from the resonant frequency point of view for stable and safe operation, and to validate a finite element model for insight into X-ray tube rotor dynamics and vibration. The 3-dimensional FEM model of the X-ray tube motor has been developed using ANSYS and COMSOL. The resultant resonant frequency from the FEM simulation is substantiated by experiments. During deceleration of the X-ray tube, an accelerometer and a corresponding amplifier send the time domain vibration response to a spectrum analyzer which generates the power spectrum. In the frequency domain analysis, a peak signifies large vibrations at that frequency. To corroborate the FEM model, the resonant frequency of the motor assembly without the anode attached was also measured. Lastly, a rough estimate of the resonant frequency can also be observed in angular speed curves which are obtained utilizing a quadrature position sensor. The first mode resonance is expected at 20.3 Hz from the FEM simulation. This result matches closely with the peak at 22.2 Hz in the power spectrum and the location of the abrupt decreasing acceleration (slope) in the speed curve at 22 Hz. Without the anode, the FEM simulation result of 35.1 Hz is equal to the first peak at 35.1 Hz, and the angular acceleration is suddenly reduced at 34.4 Hz. For image-guided interventional procedures using a hybrid system, the X-ray tube should create flux at various times requiring repeatedacceleration and deceleration of the motor. Hence it is ideal that the resonant frequency is higher than operational speed, although alternatively the motor could accelerate through the resonant frequency quickly. Design improvements to modify the location of resonance of our motor assemblyare underway using the verified FEM model. NIH R01 EB007626, Richard M. Lucas Foundation.


Recent advances in the monitoring and management of diabetic ketoacidosis.
Diabetic ketoacidosis (DKA) is still a major contributor to morbidity and mortality in diabetes. The triad of hyperglycaemia, ketosis and acidosis can be diagnosed within a few minutes of the patient presenting, by measuring blood glucose and ketones using a meter, and venous blood pH on a blood gas analyser. Quantifying ketosis allows accurate distinction between simple hyperglycaemia and metabolic decompensation. We review the management of DKA, and the emerging role of near-patient testing in diagnosing ketosis and monitoring its resolution.


Will This Patient Be Difficult to Intubate?: The Rational Clinical Examination Systematic Review.
Recognizing patients in whom endotracheal intubation is likely to be difficult can help alert physicians to the need for assistance from a clinician with airway training and having advanced airway management equipment available. To identify risk factors and physical findings that predict difficult intubation. The databases of MEDLINE and EMBASE were searched from 1946 to June 2018 and from 1947 to June 2018, respectively, and the reference lists from the retrieved articles and previous reviews were searched for additional studies. Sixty-two studies with high (level 1-3) methodological quality that evaluated the accuracy of clinical findings for identifying difficult intubation were reviewed. Two authors independently abstracted data. Bivariate random-effects meta-analyses were used to calculate summary positive likelihood ratios across studies or univariate random-effects models when bivariate models failed to converge. Among the 62 high-quality studies involving 33 559 patients, 10% (95% CI, 8.2%-12%) of patients were difficult to intubate. The physical examination findings that best predicted a difficult intubation included a grade of class 3 on the upper lip bite test (lower incisors cannot extend to reach the upper lip; positive likelihood ratio, 14 [95% CI, 8.9-22]; specificity, 0.96 [95% CI, 0.93-0.97]), shorter hyomental distance (range of <3-5.5 cm; positive likelihood ratio, 6.4 [95% CI, 4.1-10]; specificity, 0.97 [95% CI, 0.94-0.98]), retrognathia (mandible measuring <9 cm from the angle of the jaw to the tip of the chin or subjectively short; positive likelihood ratio, 6.0 [95% CI, 3.1-11]; specificity, 0.98 [95% CI, 0.90-1.0]), and a combination of physical findings based on the Wilson score (positive likelihood ratio, 9.1 [95% CI, 5.1-16]; specificity, 0.95 [95% CI, 0.90-0.98]). The widely used modified Mallampati score (≥3) had a positive likelihood ratio of 4.1 (95% CI, 3.0-5.6; specificity, 0.87 [95% CI, 0.81-0.91]). Although several simple clinical findings are useful for predicting a higher likelihood of difficult endotracheal intubation, no clinical finding reliably excludes a difficult intubation. An abnormal upper lip bite test, which is easily assessed by clinicians, raises the probability of difficult intubation from 10% to greater than 60% for the average-risk patient.


Reporting of occupational cancer in Denmark.
Many patients with occupational diseases fail to obtain compensation because their disease is not recognized as occupational and reported to the authorities. The present study examined the reporting of pleural mesotheliomas and sinonasal adenocarcinomas--cancers with well-known associations with occupational exposures to asbestos and wood dust--in Denmark in 1983-1987. The estimated underreporting was around 50%. Examination of the medical records of patients who had not been reported in 1986-1987 revealed that in most cases the medical records did not contain sufficiently detailed information about occupational exposures. It was recommended that a formal screening interview be carried out whenever a diagnosis is made of a potential occupational cancer. Medical associations may play a major role by issuing guidelines addressing occupational diseases within the fields of their expertise.


Enhanced active motion of Janus colloids at the water surface.
We have investigated the active motion of self-propelled colloids confined at the air-water interface and explored the possibility of enhancing the directional motion of self-propelled Janus colloids by slowing down their rotational diffusion. The two dimensional motion of micron-sized silica-platinum Janus colloids has been experimentally measured by particle tracking video-microscopy at increasing concentrations of the catalytic fuel, i.e. H2O2. Compared to the motion in the bulk, a dramatic enhancement of both the persistence length of trajectories and the speed has been observed. The interplay of colloid self-propulsion, due to an asymmetric catalytic reaction occurring on the colloid, surface properties and interfacial frictions controls the enhancement of the directional movement. The slowing down of the rotational diffusion at the interface, also measured experimentally, plays a pivotal role in the control and enhancement of active motion.


Cyberknife stereotactic radiosurgical rhizotomy for trigeminal neuralgia: anatomic and morphological considerations.
To search for correlations between specific anatomic, geometric, and morphological properties of the trigeminal nerve and the success of radiosurgical treatment and elimination of facial hypesthesia as a complication. Forty-six patients with at least 6 months of follow-up after CyberKnife (Accuray, Inc., Sunnyvale, CA) rhizotomy were retrospectively reviewed. Patients treated after 2004 were entered into the study after congruity in treatment parameters was established. Anatomic variations regarding the length of each nerve segment and angle of trigeminal nerve takeoff from brainstem to Meckel's cave in the axial and sagittal planes were studied. Dose distribution to surrounding critical structures (brainstem and trigeminal ganglion) was measured. After spatial relationships of involved structures and dose distributions were recorded, their relationship to treatment success, failure, or complication (primarily facial numbness) was tabulated. Forty-five patients (97.2%) experienced pain relief immediately or within weeks. Thirty-four patients maintained excellent outcome. Some degree of facial numbness developed in 18 patients (39.1%) and was mild in 11 of them (Grade II on the Barrow Neurological Institute scale). Patients with a sagittal-angle trigeminal nerve takeoff from the brainstem in the range of 150 to 170 degrees measured from the horizontal plane had a more favorable outcome (P = 0.03) than patients with less obtuse relationships to the proximal nerve origin. Patients who received higher doses of radiation to the brainstem/dorsal root entry zone of the trigeminal nerve experienced a higher rate of posttreatment facial anesthesia. There may be important anatomic and geometric relationships between the treated trigeminal nerve and surrounding critical structures that warrant pretreatment target volume placement and dose distribution considerations.


Molecular signatures in Arabidopsis thaliana in response to insect attack and bacterial infection.
Under the threat of global climatic change and food shortages, it is essential to take the initiative to obtain a comprehensive understanding of common and specific defence mechanisms existing in plant systems for protection against different types of biotic invaders. We have implemented an integrated approach to analyse the overall transcriptomic reprogramming and systems-level defence responses in the model plant species Arabidopsis thaliana (A. thaliana henceforth) during insect Brevicoryne brassicae (B. brassicae henceforth) and bacterial Pseudomonas syringae pv. tomato strain DC3000 (P. syringae henceforth) attacks. The main aim of this study was to identify the attacker-specific and general defence response signatures in A. thaliana when attacked by phloem-feeding aphids or pathogenic bacteria. The obtained annotated networks of differentially expressed transcripts indicated that members of transcription factor families, such as WRKY, MYB, ERF, BHLH and bZIP, could be crucial for stress-specific defence regulation in Arabidopsis during aphid and P. syringae attack. The defence response pathways, signalling pathways and metabolic processes associated with aphid attack and P. syringae infection partially overlapped. Components of several important biosynthesis and signalling pathways, such as salicylic acid (SA), jasmonic acid (JA), ethylene (ET) and glucosinolates, were differentially affected during the two the treatments. Several stress-regulated transcription factors were known to be associated with stress-inducible microRNAs. The differentially regulated gene sets included many signature transcription factors, and our co-expression analysis showed that they were also strongly co-expressed during 69 other biotic stress experiments. Defence responses and functional networks that were unique and specific to aphid or P. syringae stresses were identified. Furthermore, our analysis revealed a probable link between biotic stress and microRNAs in Arabidopsis and, thus gives indicates a new direction for conducting large-scale targeted experiments to explore the detailed regulatory links between them. The presented results provide a comparative understanding of Arabidopsis - B. brassicae and Arabidopsis - P. syringae interactions at the transcriptomic level.


The impact of molar pregnancy on the male partner.
Molar pregnancy is a complication of 1 in 200-2000 pregnancies whereby abnormal placental tissue proliferates in the absence of a fetus and may lead to metastases. The disease origin lies in dispermy or dual fertilisation of the egg. The aim of this study was to explore the impact of molar pregnancy upon the male partner. Institutional ethics committee approval and individual consent were obtained. All women listed on the state molar pregnancy database who were receiving active follow-up (n = 102) and a random sample of women who had been registered in the previous 30 years (n = 56) were sent a postal survey outlining the purpose of the study and an invitation for their partner to participate. Sixty-six women gave permission for their partner to participate in the study. Questionnaires included the Hospital Anxiety and Depression Scale, Satisfaction with Life Scale and Sexual History Form 12. Responding partners were also invited to make comments about any aspect of particular concern. A reminder mail out was issued after 6 weeks. The response rate was 62% (N = 41). The key findings were that 32.5% and 12.5% of men met the case criteria for anxiety and depressive disorder, respectively. These figures represent a doubling of usual community rates for anxiety disorder. However, overall quality of life and sexual functioning outcomes were consistent with community samples. The presence of children played a protective role and was associated with significantly better psychological function and quality of life in univariate and multivariate analysis. Qualitative results complemented the quantitative data, with anxiety as the dominant emotional theme. There are high persisting levels of anxiety in male partners of women with molar pregnancy. Partners may benefit from therapy where anxiety disorders are detected.


Metabolism of parathyroid hormone. Degradation of 125I-labelled hormone by a kidney enzyme.
A study was made of the enzymic degradation of (125)I-labelled parathyroid hormone by rat kidney microsomes. Incubation with microsomes resulted in rapid destruction of the labelled hormone. The microsomal factor was not separable by dialysis, and the reaction was favoured by pH values in the physiological range. Velocity of the reaction varied directly as the substrate concentration, and additional crude parathyroid hormone (trichloroacetic acid-precipitated, 3.68mg./ml.) inhibited destruction of labelled hormone. There was much less inhibition with added trichloroacetic acid-precipitated calcitonin (3.92mg./ml.) and virtually none with added pig insulin (3.80mg./ml.). Gel filtration of control medium on P6 (Bio-Gel) yielded one radioactive peak at the void volume. After incubation with microsomes three further peaks were obtained on gel filtration. Only the void-volume peak contained intact (125)I-labelled parathyroid hormone, indicating that the microsomal enzyme degraded labelled hormone to a number of smaller fragments.


Sperm competition and the evolution of precopulatory weapons: Increasing male density promotes sperm competition and reduces selection on arm strength in a chorusing frog.
Sperm competition theory assumes a trade-off between precopulatory traits that increase mating success and postcopulatory traits that increase fertilization success. Predictions for how sperm competition might affect male expenditure on these traits depend on the number of competing males, the advantage gained from expenditure on weapons, and the level of sperm competition. However, empirical tests of sperm competition theory rarely examine precopulatory male expenditure. We investigated how variation in male density affects precopulatory sexual selection on male weaponry and the level of sperm competition in the chorusing frog Crinia georgiana, where males use their arms as weapons in male-male combat. We measured body size and arm girth of 439 males, and recorded their mating success in the field. We found density-dependent selection acting on arm girth. Arm girth was positively associated with mating success, but only at low population densities. Increased male density was associated with higher risk and intensity of sperm competition arising from multimale amplexus, and a reversal in the direction of selection on arm girth. Opposing patterns of pre- and postcopulatory selection may account for the negative covariation between arm girth and testes across populations of this species.


Who Gets a Laboratory Test in Hospital, Why, and How Often? A Retrospective Observational Study of 4 Australian Hospitals.
Laboratory providers are challenged with the need to deliver improvements in the efficiency and effectiveness of laboratory services. Initiatives have been set to reduce the inappropriate use of tests; however, empirical evidence about the rate and frequency of laboratory tests in hospitals has not been widely available. This study used data linkage techniques to investigate laboratory test use among Australian inpatients. A retrospective observational study was conducted across 3 metropolitan and 1 rural hospital, all serviced by a single laboratory provider. Data for all admitted inpatients between January 2008 and December 2013 were extracted and linked to determine the proportion of admissions with a laboratory test, number of tests per admission, and time to first test. This study included 521480 admissions. Of these, 83.7% had a pathology test. Newborns and neonates had the lowest percentage of admissions with tests (35.2%), whereas admissions for diseases and disorders of the hepatobiliary system and pancreas had the highest (97.5%). Patients had a median of 12 tests per admission. Patients 80-84 years of age had the highest rate of tests per admission (median, 19; interquartile range, 9-36). Forty-nine percent of patients' first tests occurred within 2 h of admission, increasing to 69.9% within 4 h. The vast majority of patients admitted to hospital received laboratory tests. Higher laboratory testing rates were observed with increasing age. These findings can be used to define and compare laboratory testing among inpatients and help identify sources of variation in laboratory testing.


Hematopoietic stem cell transplantation for chronic granulomatous disease.
Chronic granulomatous disease (CGD) is a primary immunodeficiency disease that is caused by the lack of 1 of 5 subunits of the superoxide-producing nicotinamide adenine dinucleotide phosphate oxidase of neutrophils, macrophages, and eosinophils. Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only curative treatment for CGD and can be offered to selected patients. Improved outcome with supportive care and high clinical variability in the disease course, however, make selection of eligible patients for HSCT difficult. This article addresses recent progress in HSCT for CGD, delineates present limitations, and points to future developments.


Paintable band-edge liquid crystal lasers.
In this paper we demonstrate photonic band-edge laser emission from emulsion-based polymer dispersed liquid crystals. The lasing medium consists of dye-doped chiral nematic droplets dispersed within a polymer matrix that spontaneously align as the film dries. Such lasers can be easily formed on single substrates with no alignment layers. The system combines the self-organizing periodic structure of chiral nematic liquid crystals with the simplicity of the emulsion procedure so as to produce a material that retains the emission characteristics of band-edge lasers yet can be readily coated. Sequential and stacked layers demonstrate the possibility of achieving simultaneous multi-wavelength laser output from glass, metallic, and flexible substrates.


Critical amino acids in Escherichia coli UmuC responsible for sugar discrimination and base-substitution fidelity.
The active form of Escherichia coli DNA polymerase V responsible for damage-induced mutagenesis is a multiprotein complex (UmuD'(2)C-RecA-ATP), called pol V Mut. Optimal activity of pol V Mut in vitro is observed on an SSB-coated single-stranded circular DNA template in the presence of the β/γ complex and a transactivated RecA nucleoprotein filament, RecA*. Remarkably, under these conditions, wild-type pol V Mut efficiently incorporates ribonucleotides into DNA. A Y11A substitution in the 'steric gate' of UmuC further reduces pol V sugar selectivity and converts pol V Mut into a primer-dependent RNA polymerase that is capable of synthesizing long RNAs with a processivity comparable to that of DNA synthesis. Despite such properties, Y11A only promotes low levels of spontaneous mutagenesis in vivo. While the Y11F substitution has a minimal effect on sugar selectivity, it results in an increase in spontaneous mutagenesis. In comparison, an F10L substitution increases sugar selectivity and the overall fidelity of pol V Mut. Molecular modeling analysis reveals that the branched side-chain of L10 impinges on the benzene ring of Y11 so as to constrict its movement and as a consequence, firmly closes the steric gate, which in wild-type enzyme fails to guard against ribonucleoside triphosphates incorporation with sufficient stringency.


The Women's Leadership Gap in Diabetes: A Call for Equity and Excellence.
Women are broadly underrepresented in scientific leadership positions and their accomplishments are not provided equal recognition compared with those of men, but the imbalance in the field of diabetes is unknown. Hence, we analyzed multiple aspects of historical and present-day female representation in the diabetes field. We quantified gender representation at annual American Diabetes Association (ADA) meetings; editorial board service positions for ADA and the European Association for the Study of Diabetes (EASD) journals; principal investigators for ADA, JDRF, and National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases P30 grant funding; and ADA, JDRF, and EASD award recipients. There are many women in the field of diabetes: registration for the ADA Scientific Sessions has been 43% female since 2016, and for over five decades, women comprised 83% of ADA Presidents of Health Care and Education. Yet, only 9% of ADA Presidents of Medicine and Science have been women. Women were well represented on editorial boards for journals focused on diabetes education (Diabetes Spectrum, 89% female) and primary care (Clinical Diabetes, 49% female) but not for the more academically targeted Diabetes Care (34% female), Diabetes (21% female), and Diabetologia (30% female). Only one-third of ADA Pathway to Stop Diabetes and JDRF grants have been awarded to women, and females only lead 2 of 18 (11%) of the P30-supported Diabetes Research Centers. Finally, only 2-12% of major ADA, JDRF, and EASD awards were given to women, without significant change over time. Despite increasing recognition of gender imbalance in research and medicine, many disparities in the field of diabetes persist. We call for decreasing barriers for advancement of female investigators and creating environments that promote their retention and equitable recognition for their contributions to the field.


Three-point fix tympanoplasty.
The three-point fix tympanoplasty procedure is a stable and effective technique - with a high degree of graft take and satisfactory hearing results - for reconstruction of most tympanic membrane (TM) perforations. It is difficult to repair a TM perforation, including subtotal perforation, involving the anterior part of the annulus. Reperforation can occur when an underlay graft technique is used. An overlay graft technique may result in anterior blunting/lateralization. We introduce a three-point fix tympanoplasty procedure, which can provide additional support to yield a stable graft. The study enrolled a total of 234 patients who underwent a three-point fix tympanoplasty procedure from November 2005 to June 2011. Anatomic success was defined as an intact, repaired TM, while functional success was defined as a significant decrease in the air-bone gap at the end of follow-up compared with preoperative hearing (air-bone gap). The complication rate was also analyzed. The anatomic success rate was 93.2% (218/234 patients). The functional success rate after an average of 1 year was 73.5%. The postoperative average pure-tone air-bone gap (15.4 ± 11.4 dB) decreased successfully in comparison with the preoperative average air-bone gap (20.6 ± 12.1 dB). There were few postoperative complications (7.7%).


Drebrin-like protein DBN-1 is a sarcomere component that stabilizes actin filaments during muscle contraction.
Actin filament organization and stability in the sarcomeres of muscle cells are critical for force generation. Here we identify and functionally characterize a Caenorhabditis elegans drebrin-like protein DBN-1 as a novel constituent of the muscle contraction machinery. In vitro, DBN-1 exhibits actin filament binding and bundling activity. In vivo, DBN-1 is expressed in body wall muscles of C. elegans. During the muscle contraction cycle, DBN-1 alternates location between myosin- and actin-rich regions of the sarcomere. In contracted muscle, DBN-1 is accumulated at I-bands where it likely regulates proper spacing of α-actinin and tropomyosin and protects actin filaments from the interaction with ADF/cofilin. DBN-1 loss of function results in the partial depolymerization of F-actin during muscle contraction. Taken together, our data show that DBN-1 organizes the muscle contractile apparatus maintaining the spatial relationship between actin-binding proteins such as α-actinin, tropomyosin and ADF/cofilin and possibly strengthening actin filaments by bundling.


The changing face of tobacco use among United States youth.
Tobacco use, primarily in the form of cigarettes, is the leading cause of preventable morbidity and mortality in the United States (U.S.). The adverse effects of tobacco use began to be recognized in the 1940's and new hazards of active smoking and secondhand smoke (SHS) exposure from cigarettes continue to be identified to this day. This has led to a sustained and wide-ranging array of highly effective regulatory, public health, and clinical efforts that have been informed by extensive scientific data, resulting in marked decreases in the use of cigarettes. Unfortunately, the dramatic recent decline in cigarette use in the U.S., has been accompanied by an upsurge in adolescent and young adult use of new, non-cigarette tobacco and nicotine-delivery products, commonly referred to as alternative tobacco products (ATPs). Commonly used ATPs include hookah, cigars, smokeless tobacco, and electronic cigarettes. While there have been a number of review articles that focus on adult ATP use, the purpose of this review is to provide an overview of what is, and is not known about emerging ATP use among U.S. adolescents on a national scale; as well as to identify research gaps in knowledge, and discuss future health and policy needs for this growing public health concern. This paper is not meant to systemically review all published survey data, but to present clear depiction of selected ATP usage in youth populations using national survey data.


Workplace bullying and the association with suicidal ideation/thoughts and behaviour: a systematic review.
The established links between workplace bullying and poor mental health provide a prima facie reason to expect that workplace bullying increases the risk of suicidal ideation (thoughts) and behaviours. Until now, there has been no systematic summary of the available evidence. This systematic review summarises published studies reporting data on workplace bullying and suicidal ideation, or behaviour. The review sought to ascertain the nature of this association and highlight future research directions. 5 electronic databases were searched. 2 reviewers independently selected the articles for inclusion, and extracted information about study characteristics (sample, recruitment method, assessment and measures) and data reporting the association of workplace bullying with suicidal ideation and behaviour. 12 studies were included in the final review-8 reported estimates of a positive association between workplace bullying and suicidal ideation, and a further 4 provided descriptive information about the prevalence of suicidal ideation in targets of bullying. Only 1 non-representative cross-sectional study examined the association between workplace bullying and suicidal behaviour. The results show an absence of high-quality epidemiological studies (eg, prospective cohort studies, which controlled for workplace characteristics and baseline psychiatric morbidity). While the available literature (predominantly cross-sectional) suggests that there is a positive association between workplace bullying and suicidal ideation, the low quality of studies prevents ruling out alternative explanations. Further longitudinal, population-based research, adjusting for potential covariates (within and outside the workplace), is needed to determine the level of risk that workplace bullying independently contributes to suicidal ideation and behaviour.


Circular RNA architecture and differentiation during leaf bud to young leaf development in tea (Camellia sinensis).
Circular RNA (circRNA) discovery, expression patterns and experimental validation in developing tea leaves indicates its correlation with circRNA-parental genes and potential roles in ceRNA interaction network. Circular RNAs (circRNAs) have recently emerged as a novel class of abundant endogenous stable RNAs produced by circularization with regulatory potential. However, identification of circRNAs in plants, especially in non-model plants with large genomes, is challenging. In this study, we undertook a systematic identification of circRNAs from different stage tissues of tea plant (Camellia sinensis) leaf development using rRNA-depleted circular RNA-seq. By combining two state-of-the-art detecting tools, we characterized 3174 circRNAs, of which 342 were shared by each approach, and thus considered high-confidence circRNAs. A few predicted circRNAs were randomly chosen, and 20 out of 24 were experimental confirmed by PCR and Sanger sequencing. Similar in other plants, tissue-specific expression was also observed for many C. sinensis circRNAs. In addition, we found that circRNA abundances were positively correlated with the mRNA transcript abundances of their parental genes. qRT-PCR validated the differential expression patterns of circRNAs between leaf bud and young leaf, which also indicated the low expression abundance of circRNAs compared to the standard mRNAs from the parental genes. We predicted the circRNA-microRNA interaction networks, and 54 of the differentially expressed circRNAs were found to have potential tea plant miRNA binding sites. The gene sets encoding circRNAs were significantly enriched in chloroplasts related GO terms and photosynthesis/metabolites biosynthesis related KEGG pathways, suggesting the candidate roles of circRNAs in photosynthetic machinery and metabolites biosynthesis during leaf development.


Correspondence between alternate measures of maladaptive exercise, and their associations with disordered eating symptomatology.
The study sought to contribute to the measurement of maladaptive exercise by examining the psychometric properties of a variety of instruments and classification algorithms. The primary aim was to identify the items or scales necessary and sufficient to quantify the construct. A secondary aim was to comment on the construct validity of these measures by examining their relationships with disordered eating symptomatology. Questionnaire booklets comprising the Exercise Dependence Scale, the Obligatory Exercise Questionnaire, the Frequency, Intensity, Time Index, and the Eating Attitudes Test were distributed to women attending health and fitness centres. Self-reported age, height, current and desired weight, and length of time as a regular exerciser were also sought. Data were obtained from 302 regular exercisers. While there were statistically significant associations among the measures, no two operationalised maladaptive exercise in the same manner. The Frequency-Intensity-Time Index (FIT) was found to be particularly poor. While variation in the size of relationships between maladaptive exercise and disordered eating was noted, all measures were strongly correlated with the exception of FIT, which demonstrated a modest correlation. Different conceptualisations of maladaptive exercise have led to alternative operational definitions, resulting in its classification being instrument dependent. Further exploration using samples with differing characteristics (e.g., high/low probability of dependence) may allow more specific recommendations to be made about the optimal measurement of maladaptive exercise. Further, the question of whether maladaptive exercise is more likely a cause or consequence of eating disorders remains.


Time trend of suicide in Swiss male farmers and comparison with other men: a cohort study.
The ongoing agricultural reforms present serious challenges for Swiss farmers. Pressure is growing with difficult economic situations and the increasing demands for environmental protection, animal welfare and food safety. The aim of this study was to determine whether the strain is associated with higher risk of suicide in farmers than in men in other professions. We also wanted to analyse any changes in trends over time. Using the Swiss National Cohort, a population-based longitudinal study (1991–2014), we investigated suicide rates for Swiss men aged 35 to 74 years who lived in small communities. We calculated crude rates of suicide and standardised mortality ratios (SMRs) for both calendar periods of four years, and overall. We estimated hazard ratios using Cox proportional hazard regression models of increasing complexity to examine associations with profession (farmer, non-farmer), calendar period, marital status, type of household, religion and language region. We identified 9006 suicides among 1,796,379 men in the total study population, of which 447 occurred in 89,303 farmers. Age-standardised rates of suicide per 100,000 person-years were higher (38.1, 95% CI 34.6–41.8) in farmers than in men with other professions (32.6, 95% CI 31.9–33.3). Although the age-standardised rates decreased for the whole study population until 2006, the declining trend continued afterwards only in non-farmers. The widening gap between farmers and non-farmers also showed in the SMR, which increased from 1.06 (95% CI 0.88–1.27) in the period 1991–1994 to 1.37 (95% CI 1.05–1.79) in 2011-2014. The Cox regression model analyses also revealed a higher risk of suicide for farmers, with hazard ratios ranging from 1.10 (95% CI 1.00–1.22) to 1.17 (95% CI 1.07–1.29). Usage of firearms was the most common method in the overall population (36.5%). In farmers, however, almost 60% committed suicide by hanging. The study shows a higher rate of suicide in farmers compared to non-farmers in Switzerland, with the gap widening increasingly after 2006. It underlines the importance of identifying the difficulties and concerns of male farmers at an early stage in order to make appropriate structural adjustments and to offer low-threshold assistance tailored to their needs and preferences.


Integrated function of a kinetic proofreading mechanism: steady-state analysis testing internal consistency of data obtained in vivo and in vitro and predicting parameter values.
Experimental measurements of the kinetic mechanism involving isoleucyl-tRNA synthetase proofreading valyl-tRNAIle in Escherichia coli have been incorporated into the conventional Michaelis-Menten model for this system. The model was subjected to a detailed mathematical analysis in the steady state. The results of this analysis provide an excellent illustration of the value of integrating fragmentary data into a model of the intact system. (1) Such integration provides a rigorous test for consistency of the individual measurements. For the above synthetase system, the published experimental data were found to be internally inconsistent. (2) Such integration predicts which experimental data are most suspect. In this case, one of the three most questionable measurements, the isoleucine pool size in vivo, was found upon reexamination to be in error by 10-15-fold. Correction of this error produced a self-consistent set of parameter values. (3) The integrated analysis provides predictions for various parameter values. In many cases, these predictions provide estimates for parameter values that are difficult to determine directly or that have yet to be measured experimentally. (4) A sensitivity analysis provides an indication of the relative importance of various parameter values and, hence, an indication of where future experimental effort might be focused most profitably.


F3-Isoprostanes as a Measure of in vivo Oxidative Damage in Caenorhabditis elegans.
Oxidative stress has been implicated in the development of a wide variety of disease processes, including cardiovascular disease, cancer, and neurodegenerative diseases, as well as progressive and normal aging processes. Isoprostanes (IsoPs) are prostaglandin-like compounds that are generated in vivo from lipid peroxidation of arachidonic acid (AA, C20:4, ω-6) and other polyunsaturated fatty acids (PUFA). Since the discovery of IsoPs by Morrow and Roberts in 1990, quantification of IsoPs has been shown to be an excellent source of biomarkers of in vivo oxidative damage. Eicosapentaenoic acid (EPA, C20:5, ω-3) is the most abundant PUFA in Caenorhabditis elegans and gives rise to F3-IsoPs upon nonenzymatic free-radical-catalyzed lipid peroxidation. The protocol presented is the current methodology that our laboratory uses to quantify F3-IsoPs in C. elegans using gas chromatography/mass spectrometry (GC/MS). The methods described herein have been optimized and validated to provide the best sensitivity and selectivity for quantification of F3-IsoPs from C. elegans lysates.


Particulate matter disrupts human lung endothelial barrier integrity via ROS- and p38 MAPK-dependent pathways.
Epidemiologic studies have linked exposure to airborne pollutant particulate matter (PM) with increased cardiopulmonary mortality and morbidity. The mechanisms of PM-mediated lung pathophysiology, however, remain unknown. We tested the hypothesis that PM, via enhanced oxidative stress, disrupts lung endothelial cell (EC) barrier integrity, thereby enhancing organ dysfunction. Using PM collected from Ft. McHenry Tunnel (Baltimore, MD), we assessed PM-mediated changes in transendothelial electrical resistance (TER) (a highly sensitive measure of barrier function), reactive oxygen species (ROS) generation, and p38 mitogen-activated protein kinase (MAPK) activation in human pulmonary artery EC. PM induced significant dose (10-100 microg/ml)- and time (0-10 h)-dependent EC barrier disruption reflected by reduced TER values. Exposure of human lung EC to PM resulted in significant ROS generation, which was directly involved in PM-mediated EC barrier dysfunction, as N-acetyl-cysteine (NAC, 5 mM) pretreatment abolished both ROS production and barrier disruption induced by PM. Furthermore, PM induced p38 MAPK activation and HSP27 phosphorylation, events that were both attenuated by NAC. In addition, PM-induced EC barrier disruption was partially prevented by the p38 MAP kinase inhibitor SB203580 (10 microM) as well as by reduced expression of either p38 MAPK beta or HSP27 (siRNA). These results demonstrate that PM induces ROS generation in human lung endothelium, resulting in oxidative stress-mediated EC barrier disruption via p38 MAPK- and HSP27-dependent pathways. These findings support a novel mechanism for PM-induced lung dysfunction and adverse cardiopulmonary outcomes.


Familial resemblance for VO2max in the sedentary state: the HERITAGE family study.
This study investigates the familial resemblance of maximal oxygen uptake (VO2max) based on data from 86 nuclear families of Caucasian descent participating in the HERITAGE Family Study. In the current study, VO2max was measured twice on a cycle ergometer in 429 sedentary individuals (170 parents and 259 of their offspring), aged between 16 and 65 yr. The VO2max was adjusted by regression procedures for the effects of 1) age and sex; 2) age, sex, and body mass; and 3) age, sex, body mass, fat mass, and fat-free mass, as determined by underwater weighing. Evidence for significant familial resemblance was observed for each of the three VO2max phenotypes. Spouse, sibling, and parent-offspring correlations were significant, suggesting that both genetic and environmental factors contribute to the familial resemblance for VO2max. Maximal heritability estimates were at least 50%, a value inflated to an undetermined degree by nongenetic factors. The hypothesis of maternal inheritance, with the father's contribution being environmental, was also found to fit the data with estimates of maternal heritability, potentially associated in part with mitochondrial inheritance, reaching about 30%. These results suggest that genetic and nongenetic factors as well as maternal influences contribute to the familial aggregation of VO2max in sedentary individuals.


Hexokinase 1 is required for glucose-induced repression of bZIP63, At5g22920, and BT2 in Arabidopsis.
Simple sugars, like glucose (Glc) and sucrose (Suc), act as signals to modulate the expression of hundreds of genes in plants. Frequently, however, it remains unclear whether this regulation is induced by the sugars themselves or by their derivatives generated in the course of carbohydrate (CH) metabolism. In the present study, we tested the relevance of different CH metabolism and allocation pathways affecting expression patterns of five selected sugar-responsive genes (bZIP63, At5g22920, BT2, MGD2, and TPS9) in Arabidopsis thaliana. In general, the expression followed diurnal changes in the overall sugar availability. However, under steady growth conditions, this response was hardly impaired in the mutants for CH metabolizing/ transporting proteins (adg1, sex1, sus1-4, sus5/6, and tpt2), including also hexokinase1 (HXK1) loss- and gain-of-function plants-gin2.1 and oe3.2, respectively. In addition, transgenic plants carrying pbZIP63::GUS showed no changes in reporter-gene-expression when grown on sugar under steady-state conditions. In contrast, short-term treatments of agar-grown seedlings with 1% Glc or Suc induced pbZIP63::GUS repression, which became even more apparent in seedlings grown in liquid media. Subsequent analyses of liquid-grown gin2.1 and oe3.2 seedlings revealed that Glc -dependent regulation of the five selected genes was not affected in gin2.1, whereas it was enhanced in oe3.2 plants for bZIP63, At5g22920, and BT2. The sugar treatments had no effect on ATP/ADP ratio, suggesting that changes in gene expression were not linked to cellular energy status. Overall, the data suggest that HXK1 does not act as Glc sensor controlling bZIP63, At5g22920, and BT2 expression, but it is nevertheless required for the production of a downstream metabolic signal regulating their expression.


Spectroscopic and second-order nonlinear optical properties of Ruthenium(ii) complexes: a DFT/MRCI and ADC(2) study.
In this communication we use the density functional theory-based multi-reference configuration interaction (DFT/MRCI) and the second-order algebraic diagrammatic construction (ADC(2)) methods to compute the spectroscopic and second-order nonlinear optical (NLO) properties of Ru(ii)-based NLO-phores. For some of the complexes, an appropriate treatment of doubly excited states is essential to correctly describe their spectroscopic and photochemical properties. Geometrical and solvent relaxation effects are also assessed. An adequate treatment of solvent effects seems critical for an accurate description of the NLO properties of these complexes.


HIV policy implementation in two health and demographic surveillance sites in Uganda: findings from a national policy review, health facility surveys and key informant interviews.
Successful HIV testing, care and treatment policy implementation is essential for realising the reductions in morbidity and mortality those policies are designed to target. While adoption of new HIV policies is rapid, less is known about the facility-level implementation of new policies and the factors influencing this. We assessed implementation of national policies about HIV testing, treatment and retention at health facilities serving two health and demographic surveillance sites (HDSS) (10 in Kyamulibwa, 14 in Rakai). Ugandan Ministry of Health HIV policy documents were reviewed in 2013, and pre-determined indicators were extracted relating to the content and nature of guidance on HIV service provision. Facility-level policy implementation was assessed via a structured questionnaire administered to in-charge staff from each health facility. Implementation of policies was classified as wide (≥75% facilities), partial (26-74% facilities) or minimal (≤25% facilities). Semi-structured interviews were conducted with key informants (policy-makers, implementers, researchers) to identify factors influencing implementation; data were analysed using the Framework Method of thematic analysis. Most policies were widely implemented in both HDSS (free testing, free antiretroviral treatment (ART), WHO first-line regimen as standard, Option B+). Both had notable implementation gaps for policies relating to retention on treatment (availability of nutritional supplements, support groups or isoniazid preventive therapy). Rakai implemented more policies relating to provision of antiretroviral treatment than Kyamulibwa and performed better on quality of care indicators, such as frequency of stock-outs. Factors facilitating implementation were donor investment and support, strong scientific evidence, low policy complexity, phased implementation and effective planning. Limited human resources, infrastructure and health management information systems were perceived as major barriers to effective implementation. Most HIV policies were widely implemented in the two settings; however, gaps in implementation coverage prevail and the value of ensuring complete coverage of existing policies should be considered against the adoption of new policies in regard to resource needs and health benefits.


High Rate of Non-detectable HIV-1 RNA Among Antiretroviral Drug Naive HIV Positive Individuals in Nigeria.
Plasma HIV-1 RNA concentration, or viral load, is an indication of the magnitude of virus replication and largely correlates with disease progression in an infected person. It is a very useful guide for initiation of therapy and monitoring of response to antiretroviral drugs. Although the majority of patients who are not on antiretroviral therapy (ART) have a high viral load, a small proportion of ART naive patients are known to maintain low levels or even undetectable viral load levels. In this study, we determined the rate of undetectable HIV-1 RNA among ART naive HIV positive patients who presented for treatment at the University College Hospital (UCH), Ibadan, Nigeria from 2005 to 2011. Baseline viral load and CD4 lymphocyte cell counts of 14,662 HIV positive drug naive individuals were determined using the Roche Amplicor version 1.5 and Partec easy count kit, respectively. The detection limits of the viral load assay are 400 copies/mL and 750,000 copies/mL for lower and upper levels, respectively. A total of 1,399 of the 14,662 (9.5%) HIV-1 positive drug naive individuals had undetectable viral load during the study period. In addition, the rate of non-detectable viral load increased over the years. The mean CD4 counts among HIV-1 infected individuals with detectable viral load (266 cells/μL; range = 1 to 2,699 cells/μL) was lower than in patients with undetectable viral load (557 cells/μL; range = 1 to 3,102 cells/μL). About 10% of HIV-1 infected persons in our study population had undetectable viral load using the Roche Amplicor version 1.5.


ATPase Activity of Bacillus subtilis RecA Affects the Dynamic Formation of RecA Filaments at DNA Double Strand Breaks.
RecA plays a central role in DNA repair and is a main actor involved in homologous recombination (HR). In vivo, RecA forms filamentous structures termed "threads," which are essential for HR, but whose nature is still ill defined. We show that RecA from Bacillus subtilis having lower ATP binding activity can still form nucleoprotein filaments in vitro, features lower dsDNA binding activity, but still retains most of wild type RecA activity in vivo. Contrarily, loss of ATPase activity strongly reduced formation of nucleoprotein filaments in vitro, and effectivity to repair double strand breaks (DSBs) in vivo. In the presence of wild type RecA protein, additionally expressed RecA with lowered ATPbinding activity only moderately affected RecA dynamics, while loss of ATPase activity leads to a large reduction of the formation of threads, as well as of their dynamic changes observed in a seconds-scale. Single molecule tracking of RecA revealed incorporation of freely diffusing and nonspecifically DNA-bound molecules into threads upon induction of a single DSB. This change of dynamics was highly perturbed in the absence of ATPase activity, revealing that filamentous forms of RecA as well as their dynamics depend on ATPase activity. Based on the idea that ATPase activity of RecA is most important for DNA strand exchange activity, our data suggest that extension and retraction of threads due is to many local strand invasion events during the search for sequences homologous to the induced DNA break site. IMPORTANCE Single-strand (ss) DNA binding ATPase RecA is the central recombinase in homologous recombination, and therefore essential for DNA repair pathways involving DNA strand exchange reactions. In several bacterial, RecA forms filamentous structures along the long axis of cells after induction of double strand breaks (DSBs) in the chromosome. These striking assemblies likely reflect RecA/ssDNA nucleoprotein filaments, which can extend and remodel within a time frame of few minutes. We show that ATPase activity of RecA is pivotal for these dynamic rearrangements, which include recruitment of freely diffusing molecules into low-mobile molecules within filaments. Our data suggest that ssDNA binding- and unbinding reactions are at the heart of RecA dynamics that power the dynamics of subcellular filamentous assemblies, leading to strand exchange reactions over a distance of several micrometers.


Greenhouse gas emissions resulting from conversion of peat swamp forest to oil palm plantation.
Conversion of tropical peat swamp forest to drainage-based agriculture alters greenhouse gas (GHG) production, but the magnitude of these changes remains highly uncertain. Current emissions factors for oil palm grown on drained peat do not account for temporal variation over the plantation cycle and only consider CO2 emissions. Here, we present direct measurements of GHGs emitted during the conversion from peat swamp forest to oil palm plantation, accounting for CH4 and N2O as well as CO2. Our results demonstrate that emissions factors for converted peat swamp forest is in the range 70-117 t CO2 eq ha-1 yr-1 (95% confidence interval, CI), with CO2 and N2O responsible for ca. 60 and ca. 40% of this value, respectively. These GHG emissions suggest that conversion of Southeast Asian peat swamp forest is contributing between 16.6 and 27.9% (95% CI) of combined total national GHG emissions from Malaysia and Indonesia or 0.44 and 0.74% (95% CI) of annual global emissions.


A novel approach to measure brain-to-brain spatial and temporal alignment during positive empathy.
Empathy is defined as the ability to vicariously experience others' suffering (vicarious pain) or feeling their joy (vicarious reward). While most neuroimaging studies have focused on vicarious pain and describe similar neural responses during the observed and the personal negative affective involvement, only initial evidence has been reported for the neural responses to others' rewards and positive empathy. Here, we propose a novel approach, based on the simultaneous recording of multi-subject EEG signals and exploiting the wavelet coherence decomposition to measure the temporal alignment between ERPs in a dyad of interacting subjects. We used the Third-Party Punishment (TPP) paradigm to elicit the personal and vicarious experiences. During a positive experience, we observed the simultaneous presence in both agents of the Late Positive Potential (LPP), an ERP component related to emotion processing, as well as the existence of an inter-subject ERPs synchronization in the related time window. Moreover, the amplitude of the LPP synchronization was modulated by the presence of a human-agent. Finally, the localized brain circuits subtending the ERP-synchronization correspond to key-regions of personal and vicarious reward. Our findings suggest that the temporal and spatial ERPs alignment might be a novel and direct proxy measure of empathy.


Invited article: Digital beam-forming imaging riometer systems.
The design and operation of a new generation of digital imaging riometer systems developed by Lancaster University are presented. In the heart of the digital imaging riometer is a field-programmable gate array (FPGA), which is used for the digital signal processing and digital beam forming, completely replacing the analog Butler matrices which have been used in previous designs. The reconfigurable nature of the FPGA has been exploited to produce tools for remote system testing and diagnosis which have proven extremely useful for operation in remote locations such as the Arctic and Antarctic. Different FPGA programs enable different instrument configurations, including a 4 × 4 antenna filled array (producing 4 × 4 beams), an 8 × 8 antenna filled array (producing 7 × 7 beams), and a Mills cross system utilizing 63 antennas producing 556 usable beams. The concept of using a Mills cross antenna array for riometry has been successfully demonstrated for the first time. The digital beam forming has been validated by comparing the received signal power from cosmic radio sources with results predicted from the theoretical beam radiation pattern. The performances of four digital imaging riometer systems are compared against each other and a traditional imaging riometer utilizing analog Butler matrices. The comparison shows that digital imaging riometer systems, with independent receivers for each antenna, can obtain much better measurement precision for filled arrays or much higher spatial resolution for the Mills cross configuration when compared to existing imaging riometer systems.


A Quintuple [6]Helicene with a Corannulene Core as a C5 -Symmetric Propeller-Shaped π-System.
The synthesis and structural analysis of a quintuple [6]helicene with a corannulene core is reported. The compound was synthesized from corannulene in three steps including a five-fold intramolecular direct arylation. X-ray crystallographic analysis revealed a C5 -symmetric propeller-shaped structure and one-dimensional alignment in the solid state. The enantiomers of the quintuple [6]helicene were successfully separated by HPLC, and the chirality of the two fractions was identified by CD spectroscopy. A kinetic study yielded a racemization barrier of 34.2 kcal mol-1 , which is slightly lower than that of pristine [6]helicene. DFT calculations indicate a rapid bowl-to-bowl inversion of the corannulene moiety and a step-by-step chiral inversion pathway for the five [6]helicene moieties.


Symptoms in hospitalized patients: outcome and satisfaction with care.
Physical symptoms are responsible for substantial morbidity in outpatients. We assessed symptoms in patients admitted to a hospital to determine their frequency, persistence at discharge, and the relation between symptom outcome and satisfaction with care. During a 12-month period, 2,126 hospitalized medical patients completed a study interview within 2 hours of admission. More than half (n = 1,168) of the patients were re-interviewed within 24 hours of discharge. We ascertained the presence and severity of 11 physical symptoms, as well as activities of daily living, mobility, mood, self-rated health, physiologic severity of illness, satisfaction with care, and length of stay. Symptoms were common at the time of hospital admission, particularly fatigue (80% of patients), dyspnea (60%), cough (51%), dizziness (51%), headache (47%), chest pain (46%), and nausea or vomiting (43%). Individual symptoms failed to resolve by hospital discharge approximately 25% to 50% of the time. The three most prominent predictors of persistence of symptoms were shorter length of stay, severity of the symptom on admission, and total symptom count. Patient satisfaction with care was associated with total symptom severity score at discharge and the degree of symptomatic improvement that had occurred during hospitalization. Because symptoms are common at discharge and associated with decreased satisfaction with care, asking about them would be a reasonable way to enhance patient-oriented care.


Economic Reasoning and Interaction in Socially Extended Market Institutions.
An important part of what it means for agents to be situated in the everyday world of human affairs includes their engagement with economic practices. In this paper, we employ the concept of cognitive institutions in order to provide an enactive and interactive interpretation of market and economic reasoning. We challenge traditional views that understand markets in terms of market structures or as processors of distributed information. The alternative conception builds upon the notion of the market as a "scaffolding institution." Introducing the concept of market as a "socially extended" cognitive institution we go beyond the notion of scaffolding to provide an enactive view of economic reasoning that understands the market participant in terms of social interactive processes and relational autonomy. Markets are more than inert devices for information processing; they can be viewed as "highly scaffolded," where strong constraints and incentives predictably direct agents' behavior. Building on this idea we argue that markets emerge from (a) the economic interaction of both supply and demand sides, in continual and mutual interplay, and (b) more basic social interactions. Consumer behavior in the marketplace is complex, not only contributing to determine the market price, but also extending the consumer's cognitive processes to reliably attain a correct evaluation of the good. Moreover, this economic reasoning is socially situated and not something done in isolation from other consumers. From a socially situated, interactive point of view buying or not buying a good is something that enacts the market. This shifts the status of markets from external institutions that merely causally affect participants' cognitive processes to social institutions that constitutively extend these cognitive processes. On this view the constraints imposed by social interactions, as well as the possibilities enabled by such interactions, are such that economic reasoning is never just an individual process carried out by an autonomous individual, classically understood. In this regard, understanding the concept of relational autonomy allows us to see how economic reasoning is always embodied, embedded in, and scaffolded by intersubjective interactions, and how such interactions make the market what it is.


Hospital volume and surgical outcomes after elective hip/knee arthroplasty: a risk-adjusted analysis of a large regional database.
To examine the relationship between hospital procedure volume and surgical outcomes following elective primary total hip arthroplasty/total knee arthroplasty (THA/TKA). Using the Pennsylvania Health Care Cost Containment Council database, we identified all patients who underwent elective primary THA/TKA in Pennsylvania. Hospitals were categorized according to the annual volume of THA/TKA procedures, as follows: ≤25, 26-100, 101-200, and >200. The 30-day complication rate and 30-day and 1-year mortality rates were assessed by logistic regression models, adjusted for age, sex, race, insurance type, hospital region, 3M All Patient Refined Diagnosis Related Group risk of mortality score, hospital teaching status, and bed count. In the THA and TKA cohorts, the mean age of the patients was 69 years, and 42.8% and 35%, respectively, were men. Compared with patients whose surgeries were performed at very-high-volume hospitals (>200 procedures/year), patients who underwent elective primary THA procedures at hospitals with a very low volume (≤25 procedures/year), a low volume (26-100 procedures/year), or a high volume (101-200 procedures/year) had higher multivariable-adjusted odds ratios (ORs) for venous thromboembolism (OR 2.0, 95% confidence interval [95% CI] 0.2-16.0), OR 3.4 [95% CI 1.4-8.0], and OR 1.1 [95% CI 0.3-3.7], respectively) and 1-year mortality (OR 2.1 [95% CI 1.2-3.6], OR 2.0 [95% CI 1.4-2.9], and OR 1.0 [95% CI 0.7-1.5], respectively). Among patients ages ≥65 years who underwent elective primary TKA at very-low-volume, low-volume, and high-volume hospitals, the ORs for 1-year mortality were significantly higher (OR 0.6 [95% CI 0.2-2.1], OR 1.6 [95% CI 1.0-2.4], and OR 0.9 [95% CI 0.6-1.3], respectively), compared with very-high-volume hospitals. Performance of elective primary THA and TKA surgeries in low-volume hospitals was associated with a higher risk of venous thromboembolism and mortality. Confounding due to unmeasured variables is possible. Modifiable system-based factors/processes should be targeted to reduce the number of complications associated with THA/TKA procedures.