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Older trauma patients present with poor preinjury functional status and more comorbidities. Advances in care have increased the chance of survival from previously fatal injuries with many left debilitated with chronic critical illness and severe disability. Palliative care (PC) is ideally suited to address the goals of care and symptom management in this critically ill population. A retrospective chart review was done to identify the impact of PC consults on hospital length of stay (LOS), ICU LOS, and surgical decisions.A Level 1 Trauma Center Registry was used to identify adult patients who were provided PC consultation in a selected 3-year time period. These PC patients were matched with non-PC trauma patients on the basis of age, sex, race, Glasgow Coma Scale, and Injury Severity Score. Chi-square tests and Student's t-tests were used to analyze categorical and continuous variables, respectively. Any p value0.05 was considered statistically significant.PC patients were less likely to receive a percutaneous endoscopic gastric tube or tracheostomy. PC patients spent less time on ventilator support, spent less time in the ICU, and had a shorter hospital stay. PC consultation was requested 16.48 days into the patient's hospital stay. Approximately 82% of consults were to assist with goals of care.Specialist PC team involvement in the care of the trauma ICU patients may have a beneficial impact on hospital LOS, ICU LOS, and surgical care rendered. Earlier consultation during hospitalization may lead to higher rates of goal-directed care and improved patient satisfaction.

Anti-neutrophil cytoplasmic autoantibody (ANCA) vasculitis is a rare condition in pediatric patients. Little is known about practice patterns and outcomes of pediatric transplant patients. The purpose of our study was to examine differences in patient characteristics, immunosuppression, and long-term graft outcomes between ANCA and non-ANCA vasculitis recipients. We used the Scientific Registry of Transplant Recipients to evaluate pediatric ANCA vasculitis recipients between the ages of 1 and 22 years old from 1991 to 2017 and compared them to non-ANCA vasculitis patients during the same time cohort in the USA. A total of 26,431 transplant recipients were identified, of these, 337 with ANCA vasculitis. Mean 1-year eGFR was 62.46 and 64.92 ml/min/1.73 m2 (p = 0.002), and mean 5-year eGFR was 57.95 and 59.38 ml/min/1.73 m2 (p = 0.18) between the non-ANCA and ANCA groups, respectively. Five-year graft survival was similar in both groups (non-ANCA 75.5 vs. ANCA 78.6%; p = 0.19). Of those with graft loss within the ANCA group, only 0.6% was secondary to disease recurrence (p = 0.14). Kidney transplant is a safe treatment modality for children with ANCA-related kidney failure. ANCA patients have comparable graft survival when compared to the general transplant population with a low risk of recurrence. Thymoglobulin was used in a higher proportion within the ANCA group compared to the non-ANCA group. Tacrolimus, mycophenolate mofetil/mycophenolic acid, and steroids were the predominant maintenance immunosuppression used in both groups. A higher resolution version of the Graphical abstract is available as Supplementary information.

Efforts to promote COVID-19 vaccine acceptance must consider the critical role of the emergency department (ED) in providing health care to underserved patients. Focusing on patients who lacked primary care, we sought to elicit the perspectives of unvaccinated ED patients regarding COVID-19 vaccination concerns and potential approaches that might increase their vaccine acceptance.We conducted this qualitative interview study from August to November 2021 at four urban EDs in San Francisco, California; Seattle, Washington; Durham, North Carolina; and Philadelphia, Pennsylvania. We included ED patients who were ≥18 years old, fluent in English or Spanish, had not received a COVID-19 vaccine, and did not have primary care physicians or clinics. We excluded patients who were unable to complete an interview, in police custody, under suspicion of active COVID-19 illness, or presented with a psychiatric chief complaint. We enrolled until we reached thematic saturation in relevant domains. We analyzed interview transcripts with a content analysis approach focused on identifying concerns about COVID-19 vaccines and ideas regarding the promotion of vaccine acceptance and potential trusted messengers.Of 65 patients enrolled, 28 (43%) identified as female, their median age was 36 years (interquartile range 29-49), and 12 (18%) interviews were conducted in Spanish. Primary concerns about COVID-19 vaccines included risk of complications, known and unknown side effects, and fear of contracting COVID-19 from vaccines. Trust played a major role for patients in deciding which sources to use for vaccine information and in engendering vaccine acceptance. Health care providers and family or friends were commonly cited as trusted messengers of information.We characterized concerns about COVID-19 vaccines, uncovered themes that may promote vaccine acceptance, and identified trusted messengers-primarily health care professionals. These data may inform the development of nuanced COVID-19 vaccine messaging platforms to address COVID-19 vaccine hesitancy among underserved ED populations.

Purpose Pelvic trauma has increased risk of mortality in the elderly. Our study aimed to analyze the impact of the additional burden of pelvic fractures in severely injured elderly. Methods This is a retrospective analysis of a prospectively maintained trauma registry from 2012 to 2018 at an American College of Surgeons (ACS) verified Level I Trauma Center. Trauma patients aged ≥ 65 years with ISS ≥ 16 and AIS severity score ≥ 3 in at least two body regions were divided in two groups: group I, consisted of elderly polytrauma patients without pelvic fractures, and group II elderly who had concomitant pelvic fractures. We used a double-adjustment method using propensity score matching (PSM) with subsequent covariate adjustment to minimize the effect of confounding factors, and give unbiased estimation of the impact of pelvic fractures. Balance assessment was conducted by computing absolute standardized mean differences (ASMDs) and ASMD

Background New York’s statewide “Get Screened, No Excuses” campaign has been one of the nation’s most aggressive actions to improve access to breast cancer screening. Inner city and suburban county medical centers’ initiatives were studied to compare outcomes of breast cancer screening and factors that influence access to care. Methods Women delinquent in breast cancer screening one year or greater were offered patient navigator services to aid in timely breast cancer screening. Time-to-event completion rates among different stages of breast cancer screening stages in City and County women were compared. Time-to-event completion rates among different stages of breast cancer screening stages. Results 2505 women aged ≥40 years accepted PN services. Mean (SD) age of patients was 56.2 (10) years. The mean (SD) age of those who completed breast screening vs. those who did not was 56.8 (10) and 52.5 (.9) years, respectively ( P < .01). The rates of screening completion during physical examination, mammography and biopsy stages were 74%, 78% and 100% in City vs. 98%, 85% and 100% in County, respectively ( P < .001). Screening phase was the significant predictor of time to completion for breast cancer screening in Cox regression analysis. Over 85% of women completed the breast cancer screening, 74% in City and 97.6% in County ( P < .001). Discussion Screening phase is an important predictor of time-to complete breast cancer screening. Center location served as the effect modifier of the relationship. The rate of completing the screening was significantly higher and faster among Suburban County compared to Inner City women.

Background We conducted in-depth interviews to characterize reasons for COVID-19 vaccine hesitancy in emergency department (ED) patients and developed messaging platforms that may address their concerns. In this trial we seek to determine whether provision of these COVID-19 vaccine messaging platforms in EDs will be associated with greater COVID-19 vaccine acceptance and uptake in unvaccinated ED patients. Methods This is a cluster-randomized controlled trial (RCT) evaluating our COVID-19 vaccine messaging platforms in seven hospital EDs (mix of academic, community, and safety-net EDs) in four US cities. Within each study site, we randomized 30 one-week periods to the intervention and 30 one-week periods to the control. Adult patients who have not received a COVID-19 vaccine are eligible with these exclusions: 1) major trauma, intoxication, altered mental status, or critical illness; 2) incarceration; 3) psychiatric chief complaint; and 4) suspicion of acute COVID-19 illness. Participants receive an orally administered Intake survey. During intervention weeks participants then receive three COVID-19 vaccine messaging platforms (4-minute video, one-page informational flyer and a brief, scripted face-to-face message delivered by ED physicians and nurses); patients enrolled during non-intervention weeks do not receive these platforms. Approximately an hour after intake surveys, participants receive a Vaccine Acceptance survey during which the primary outcome of acceptance of the COVID-19 vaccine in the ED is ascertained. The other primary outcome of receipt of a COVID-19 vaccine within 32 days is ascertained by electronic health record review and phone follow-up. To determine whether provision of vaccine messaging platforms is associated with a 7% increase in vaccine acceptance and uptake, we will need to enroll 1290 patients. Discussion Highlighting the difficulties of trial implementation during the COVID-19 pandemic in acute care settings, our novel trial will lay the groundwork for delivery of public health interventions to vulnerable populations whose only health care access occurs in EDs. Trial Status: We began enrollment in December 2021 and expect to continue through 2022. Conclusions Toward addressing vaccine hesitancy in vulnerable populations who seek care in EDs, our cluster-RCT will determine whether implementation of vaccine messaging platforms is associated with greater COVID-19 vaccine acceptance and uptake in unvaccinated ED patients.

Direct-acting antiviral (DAA) therapy has transformed the outcomes of liver transplant (LT) with hepatitis C virus (HCV). This study aimed to analyze the effects of DAA treatment for HCV-associated hepatocellular carcinoma (HCC) in LT.We included patients confirmed with HCC on explant, analyzed data from United Network for Organ Sharing, and defined the pre-DAA era (2012-2013) and DAA era (2014-2016).HCV-associated HCC cases totaled 4778 (62%) during the study period. In the DAA era, the median recipient age was older and the median days on the waiting list were longer. For the donor, median age, body mass index, and the rate of HCV significantly increased in the DAA era. In pathology, the median largest tumor size was significantly higher; however, the rate of completed tumor necrosis was significant higher in the DAA era. The 3-year graft/patient survival had significantly improved in the DAA era. In multivariable analysis, the DAA era (hazard ratio, 0.79; 95% confidence interval, 0.68-0.91) had significantly affected the 3-year graft survival.DAA has a significant beneficial effect on LT. In the DAA era, graft survival for HCV-associated HCC has been significantly improving.

Malcolm Lowry's 1947 novel, Under the Volcano, is a lyrically sublime fictional encapsulation of existential nightmares endured in a critical period of world history. While the existential element of the novel might well be downplayed in the decades following postmodernism's ascendancy in prescribing interpretive paradigms for fiction, this article proposes to explore further the existential model, if not as a wholly defensible interpretive strategy, then at least as a motif worth dwelling on and reading alongside (or against) a metarhetorical model more in keeping with a postmodern sensibility in order to see what insights might be generated to illuminate both the novel and Lowry's notoriously un-sober working life as a writer. The novel is thus read as an exemplary instance of what could be called drunken literary solipsism or, more elegantly, an exemplary instance of alcoholically transfigured “pure persuasion,” to borrow a term from Kenneth Burke.

Background Complex abdominal wall reconstruction (CAWR) has become a common surgical procedure both in non-elderly and elderly patients. Objective The aim of this study is to analyze the outcomes of the elderly compared to nonelderly undergoing CAWR using propensity score matching. Methods All patients who underwent CAWR using porcine-derived, non-crosslinked acellular dermal matrix (ADM) (Strattice™) between January 2014 and July 2017 were studied retrospectively. Propensity matched analysis was performed for risk adjustment in multivariable analysis and for one-to-one matching. The outcomes were analyzed for differences in postoperative complications, reoperations, mortality, hospital length of stay and adverse discharge disposition. Results One hundred-thirty-six patients were identified during the study period. Non-elderly (aged 18–64 years) constituted 70% (n = 95) and elderly (aged ≥ 65 years) comprised 30% of the overall patient population (n = 41). Seventy-three (56.7%) were females. After adjustment through the propensity score, which included 35 pairs, the surgical site infection (p = 1.000), wound necrosis (p = 1.000), the need for mechanical ventilation (p = 0.259), mortality (p = 0.083), reoperation rate (p = 0.141), hospital length of stay (p = 0.206), and discharge disposition (p = 0.795) were similar. Conclusion Elderly patients undergoing CAWR with biological mesh have comparable outcomes with non-elderly patients when using propensity matching score.

Fatty alcohols are important industrial oleochemicals with broad applications and a growing market. Here, we sought to engineer Yarrowia lipolytica to serve as a renewable source of fatty alcohols (specifically hexadecanol, heptadecanol, octadecanol, and oleyl alcohol) directly from glucose. Through screening four fatty acyl-CoA reductase (FAR) enzyme variants across two engineered background strains, we identified that MhFAR enabled the highest production. Further strain engineering, fed-batch flask cultivation, and extractive fermentation improved the fatty alcohol titer to 1.5 g/L. Scale-up of this strain in a 2L bioreactor led to 5.8 g/L total fatty alcohols at an average yield of 36 mg/g glucose with a maximum productivity of 39 mg/L hr. Finally, we utilized this fatty alcohol reductase to generate a customized fatty alcohol, linolenyl alcohol, from α-linolenic acid. Overall, this work demonstrates Y. lipolytica is a robust chassis for diverse fatty alcohol production and highlights the capacity to obtain high titers and yields from a purely minimal media formulation directly from glucose without the need for complex additives., Highlights • Survey of FAR function was assessed in two background strains. • Direct production of fatty alcohols from glucose was enabled in minimal media. • Fatty alcohol was produced at titers of 5.8 g/L in bioreactors with 36 mg/g average yield. • Production of a customized fatty alcohol, linolenyl alcohol, was demonstrated.

Canine impactions are frequently encountered, occurring in 1.7% of the population. The aim of this paper is to provide guidance on the assessment and management of cases which present in general dental practice. Canine position is considered in four categories; canine overlap with adjacent incisor, vertical canine height, angulation to midline and position of canine root apex. Good, average and poor prognostic outcomes are considered for each category and a brief outline of their management is included. Clinical Relevance: Canine impactions frequently present during routine examination. Appropriate recognition, investigation and referral, if necessary, are paramount to successful treatment.

Is Kenneth Burke’s 1932 novel, Towards a Better Life, an example of protopostmodernism? A number of critics in recent years have resurrected from the corpus of Burke’s theoretical work embryonic – in some cases, advanced – models of postmodern theory. What hasn’t been analyzed in commensurate detail for its uncanny prescience is Burke’s early novel, a work, I would argue, ahead of its time in many respects. While already applauded for its verbal energy and lyrical grace, ‘the internal eventfulness of its sentences,’ as Denis Donoghue puts it, the novel’s theoretical implications remain to be fully adumbrated in respect to a profound concern with the manner in which language games, or ‘terministic screens,’ to use Burke’s neologism, can foreclose prospects for communicative engagement. At the heart of Burke’s novel is a complex and ultimately unresolvable tension between the pleasures of ‘pure persuasion’ (metarhetorical motives) and the imperatives of salutary communicative involvement.

Cerebral air embolism associated with central venous catheter insertion and removal is a rare but serious complication. There are many hypotheses on how air bubbles might be transported from the venous system to intracranial vessels. The literature has described how intra-cardiac defects transpulmonary passage and even retrograde flow of gas bubbles can explain this phenomenon. We present a case that illustrates the devastating effects of cerebral air embolism after a patient selfextracted his central venous catheter.

The mitochondrial ATP-dependent K channel (mitoKATP) has been shown to play a role in cellular protection against apoptosis, or programmed cell death. This channel has been identified and characterized in a number of cell and tissue types but to date the possible existence of mitoKATP in osteoblastic cells has not been investigated. The aim of this investigation was to establish whether the mitochondria of human osteosarcoma-derived osteoblasts (SaOS-2 cells) contain the putative mitoKATP subunits Kir6.1 and Kir6.2. Ultrathin sections of SaOS-2 cells were prepared for transmission electron microscopy using an adaptation of the Tokuyasu method, and immunolabelled using goat anti-Kir6.1 or anti-Kir6.2 antisera as the primary label, and a 10nm colloidal gold-conjugated donkey anti-goat secondary antibody. The suitability of the antisera and the immunostaining protocol were confirmed by using a sample of rat cardiac muscle as a positive control. Ultrastructural analysis revealed that SaOS-2 cells contain Kir6.2 but not Kir6.1, and that Kir6.2 is present in the mitochondria, but in extremely low abundance. These findings suggest that human osteoblast-like cells might contain mitoKATP channels in which Kir6.2 is the pore-forming subunit, although it appears that these channels are likely to be present in extremely low abundance.

AS THE WORLD REELS FROM THE MAJOR ECONOMIC CRISIS OF THE PAST TWO YEARS, A GREAT DEAL OF THE POLITICAL AND BUSINESS FOCUS HAS BEEN PLACED ON FINDING THE NEXT-GENERATION OF ECONOMIC GROWTH OPPORTUNITIES, AND THE FURTHER DEVELOPMENT AND COMMERCIALISATION OF CLEAN ENERGY SOURCES IS KEY TO THAT. SO IS THIS THE TIME FOR THE FUEL CELL TO COME IN FROM THE MARGINS AND PLAY A KEY ROLE? DR. JONATHAN BUTLER AND DR. KERRY-ANN ADAMSON OF FUEL CELL TODAY (FCT) THINK THE TIME IS RIGHT.

Recent fuel cell industry attention has been focused on India, a market for which the biggest single industry order to date was announced recently by Acme Tele Power, Ballard and IdaTech. This deal will see around 30 000 fuel cell systems delivered for stationary fuel cell uninterruptible power supply (UPS) systems over the next three years. This article will explore India's pressing need for reliable electrical power for a variety of stationary applications, and the drivers and barriers for stationary fuel cells in India.

New DNA sequencing technologies deliver data at dramatically lower costs but demand new analytical methods to take full advantage of the very short reads that they produce. We provide an initial, theoretical solution to the challenge of de novo assembly from whole-genome shotgun “microreads.” For 11 genomes of sizes up to 39 Mb, we generated high-quality assemblies from 80× coverage by paired 30-base simulated reads modeled after real Illumina-Solexa reads. The bacterial genomes of Campylobacter jejuni and Escherichia coli assemble optimally, yielding single perfect contigs, and larger genomes yield assemblies that are highly connected and accurate. Assemblies are presented in a graph form that retains intrinsic ambiguities such as those arising from polymorphism, thereby providing information that has been absent from previous genome assemblies. For both C. jejuni and E. coli, this assembly graph is a single edge encompassing the entire genome. Larger genomes produce more complicated graphs, but the vast majority of the bases in their assemblies are present in long edges that are nearly always perfect. We describe a general method for genome assembly that can be applied to all types of DNA sequence data, not only short read data, but also conventional sequence reads.

We report a high-quality draft of the genome sequence of the grey, short-tailed opossum (Monodelphis domestica). As the first metatherian ('marsupial') species to be sequenced, the opossum provides a unique perspective on the organization and evolution of mammalian genomes. Distinctive features of the opossum chromosomes provide support for recent theories about genome evolution and function, including a strong influence of biased gene conversion on nucleotide sequence composition, and a relationship between chromosomal characteristics and X chromosome inactivation. Comparison of opossum and eutherian genomes also reveals a sharp difference in evolutionary innovation between protein-coding and non-coding functional elements. True innovation in protein-coding genes seems to be relatively rare, with lineage-specific differences being largely due to diversification and rapid turnover in gene families involved in environmental interactions. In contrast, about 20% of eutherian conserved non-coding elements (CNEs) are recent inventions that postdate the divergence of Eutheria and Metatheria. A substantial proportion of these eutherian-specific CNEs arose from sequence inserted by transposable elements, pointing to transposons as a major creative force in the evolution of mammalian gene regulation.

International audience; The aspergilli comprise a diverse group of filamentous fungi spanning over 200 million years of evolution. Here we report the genome sequence of the model organism Aspergillus nidulans, and a comparative study with Aspergillus fumigatus, a serious human pathogen, and Aspergillus oryzae, used in the production of sake, miso and soy sauce. Our analysis of genome structure provided a quantitative evaluation of forces driving long-term eukaryotic genome evolution. It also led to an experimentally validated model of mating-type locus evolution, suggesting the potential for sexual reproduction in A. fumigatus and A. oryzae. Our analysis of sequence conservation revealed over 5,000 non-coding regions actively conserved across all three species. Within these regions, we identified potential functional elements including a previously uncharacterized TPP riboswitch and motifs suggesting regulation in filamentous fungi by Puf family genes. We further obtained comparative and experimental evidence indicating widespread translational regulation by upstream open reading frames. These results enhance our understanding of these widely studied fungi as well as provide new insight into eukaryotic genome evolution and gene regulation.

Summary Gardner syndrome represents one end of the spectrum of the disorder known as familial adenomatous polyposis (FAP). The syndrome consists of intestinal polyps which are predominantly adenomas, together with extracolonic features including osteomas, epidermoid cysts, desmoid tumours and dental abnormalities. Desmoid tumours, although histologically benign, may behave aggressively and can cause death in some patients. Several other neoplasms are also associated with Gardner syndrome. The inheritance pattern is autosomal dominant, with a locus on chromosome 5. However, 20% of cases may represent new mutations. The intestinal polyps carry a 100% risk of malignant change, and early diagnosis is therefore essential. As the extracolonic manifestations of the disorder often precede the colonic polyps, they may facilitate early identification of affected patients and allow timely intervention. Several of these manifestations occur in the oral and maxillofacial region and may be discovered during routine dental examination. We report a case of a 37-year-old patient with Gardner syndrome, who has previously undergone a pancolectomy with ileo-rectal anastomosis. Extracolonic features include a recurrent abdominal desmoid tumour, multiple epidermoid cysts, osteomas of the mandible and skull, and dental abnormalities.

[reaction: see text] The effectiveness of simple sulfinyl and sulfonyl groups as electron-withdrawing protecting groups for pyrroles has been analyzed using (13)C NMR spectroscopy and confirmed by consideration of X-ray crystal structures. Additionally, the 2,4-dinitrobenzenesulfinyl and sulfonyl groups are shown to be effective electron-withdrawing protecting groups for pyrroles, and they can be removed by treatment with benzene thiol or thiolate under mild and specific conditions.

Chromosome 18 appears to have the lowest gene density of any human chromosome and is one of only three chromosomes for which trisomic individuals survive to term. There are also a number of genetic disorders stemming from chromosome 18 trisomy and aneuploidy. Here we report the finished sequence and gene annotation of human chromosome 18, which will allow a better understanding of the normal and disease biology of this chromosome. Despite the low density of protein-coding genes on chromosome 18, we find that the proportion of non-protein-coding sequences evolutionarily conserved among mammals is close to the genome-wide average. Extending this analysis to the entire human genome, we find that the density of conserved non-protein-coding sequences is largely uncorrelated with gene density. This has important implications for the nature and roles of non-protein-coding sequence elements.

Although often considered “minimal” organisms, mycoplasmas show a wide range of diversity with respect to host environment, phenotypic traits, and pathogenicity. Here we report the complete genomic sequence and proteogenomic map for the piscine mycoplasma Mycoplasma mobile, noted for its robust gliding motility. For the first time, proteomic data are used in the primary annotation of a new genome, providing validation of expression for many of the predicted proteins. Several novel features were discovered including a long repeating unit of DNA of ∼2435 bp present in five complete copies that are shown to code for nearly identical yet uniquely expressed proteins. M. mobile has among the lowest DNA GC contents (24.9%) and most reduced set of tRNAs of any organism yet reported (28). Numerous instances of tandem duplication as well as lateral gene transfer are evident in the genome. The multiple available complete genome sequences for other motile and immotile mycoplasmas enabled us to use comparative genomic and phylogenetic methods to suggest several candidate genes that might be involved in motility. The results of these analyses leave open the possibility that gliding motility might have arisen independently more than once in the mycoplasma lineage.

Neurospora crassa is a central organism in the history of twentieth-century genetics, biochemistry and molecular biology. Here, we report a high-quality draft sequence of the N. crassa genome. The approximately 40-megabase genome encodes about 10,000 protein-coding genes—more than twice as many as in the fission yeast Schizosaccharomyces pombe and only about 25% fewer than in the fruitfly Drosophila melanogaster. Analysis of the gene set yields insights into unexpected aspects of Neurospora biology including the identification of genes potentially associated with red light photobiology, genes implicated in secondary metabolism, and important differences in Ca21 signalling as compared with plants and animals. Neurospora possesses the widest array of genome defence mechanisms known for any eukaryotic organism, including a process unique to fungi called repeat-induced point mutation (RIP). Genome analysis suggests that RIP has had a profound impact on genome evolution, greatly slowing the creation of new genes through genomic duplication and resulting in a genome with an unusually low proportion of closely related genes.

Positional cloning of mutations in model genetic systems is a powerful method for the identification of targets of medical and agricultural importance. To facilitate the high-throughput mapping of mutations in Caenorhabditis elegans, we have identified a further 9602 putative new single nucleotide polymorphisms (SNPs) between two C. elegans strains, Bristol N2 and the Hawaiian mapping strain CB4856, by sequencing inserts from a CB4856 genomic DNA library and using an informatics pipeline to compare sequences with the canonical N2 genomic sequence. When combined with data from other laboratories, our marker set of 17,189 SNPs provides even coverage of the complete worm genome. To date, we have confirmed >1099 evenly spaced SNPs (one every 91 ± 56 kb) across the six chromosomes and validated the utility of our SNP marker set and new fluorescence polarization-based genotyping methods for systematic and high-throughput identification of genes in C. elegans by cloning several proprietary genes. We illustrate our approach by recombination mapping and confirmation of the mutation in the cloned gene, dpy-18.[The sequence data described in this paper have been submitted to the NCBI dbSNP data library under accession nos. 4388625–4389689 and GenBank dbSTS under accession nos. 973810–974874. The following individuals and institutions kindly provided reagents, samples, or unpublished information as indicated in the paper: The C. elegans Sequencing Consortium and TheCaenorhabditis Genetics Center.]

BackgroundThe effects of neuroleptic medication on schizophrenic patients are both positive (reduction in symptoms) and negative (adverse side-effects). Given that altered cognitive functioning may be a feature of schizophrenia, the use of neuroleptics raises important ethical and legal issues.MethodA selective review was carried out of papers addressing ethical arguments for and against obtaining consent from schizophrenic patients, and the ethical and legal requirements which must be met for consent to occur.ResultsAlthough a balance must be met between arguments for and against obtaining consent, clinicians should seek informed consent in all but exceptional circumstances. Obtaining consent depends on the adequate presentation of information, the absence of duress and the patients' capacity to consent. Various tests of capacity to consent have been proposed.ConclusionsIt is proposed that clinicians employ a proforma to record attempts to obtain informed consent during routine clinical practice.

The equilibrium unfolding reaction of the C-terminal 80-amino-acid dimeric DNA-binding domain of human papillomavirus (HPV) strain 16 E2 protein has been investigated using fluorescence, far-UV CD, and equilibrium sedimentation. The stability of the HPV-16 E2 DNA-binding domain is concentration-dependent, and the unfolding reaction is well described as a two-state transition from folded dimer to unfolded monomer. The conformational stability of the protein, delta GH2O, was found to be 9.8 kcal/mol at pH 5.6, with the corresponding equilibrium unfolding/dissociation constant, Ku, being 6.5 x 10(-8) M. Equilibrium sedimentation experiments give a Kd of 3.0 x 10(-8) M, showing an excellent agreement between the two different techniques. Denaturation by temperature followed by the change in ellipticity also shows a concomitant disappearance of secondary and tertiary structures. The Ku changes dramatically at physiologically relevant pH's: with a change in pH from 6.1 to 7.0, it goes from 5.5 x 10(-8) M to 4.4 x 10(10) M. Our results suggest that, at the very low concentration of protein where DNA binding is normally measured (e.g., 10(-11) M), the protein is predominantly monomeric and unfolded. They also stress the importance of the coupling between folding and DNA binding.

In the current study an analysis of the methodology, relevance and potential of a 2nd generation LiDAR is presented along with analysis of a deployment at a UK onshore wind farm. The results demonstrate the potential of the LiDAR to attain details of wind farm flow and structures, along with the potential to corroborate numerical approaches with the measured data. Advances in CFD approaches and techniques along with the availability of significant computational resources, it is possible to conduct detailed numerical analysis for comparison with the measurement approach. A comparative analysis is presented in the results for the conducted studies. The results show that remote sensing devices offer a valuable and accurate resource for wind vector analysis and flow visualisation, along with the flexibility to organise individual measurement campaigns tailored to situation and client. This approach offers a valuable tool for wind turbine developers in performance and site assessment approaches. The study also shows the methods by which the device can be used as a validation tool for CFD along with the comparison between these two analysis methods. (5 pages)

This article is concerned with cloze procedure and its redefinition in terms of pragmatics by Oller. It also considers the drawbacks of the latter and the contribution which a concordance programme might make to generating discourse level tests from authentic material. The specific context is that of post-intermediate to advanced language learners. It concludes by suggesting that there are certain advantages to be gained from concordance-generated tests, particularly for the classroom teacher.

This article is concerned with the application of recent developments in the computerized exploitation of corpora, through software developed for microcomputers and wordprocessors, to classroom language teaching and elementary error analysis. In particular, it seeks to outline the uses of Microconcord (Tim Johns) for analyzing written texts produced by non-native speakers, and to suggest that the management of assembled corpora of the latter texts may be one way out of the blind alley down which some aspects of CALL seem to have led. It concludes by citing some evidence from a small and specialized corpus, and by suggesting that concordancing of errors from both multi and monolingual sources may provide a new way of analyzing errors and of helping language teachers to help students.

Affiliations des auteurs : cf page 216 de l'article; International audience; Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

Ustilago maydis is a ubiquitous pathogen of maize and a well-established model organism for the study of plant-microbe interactions. This basidiomycete fungus does not use aggressive virulence strategies to kill its host. U. maydis belongs to the group of biotrophic parasites (the smuts) that depend on living tissue for proliferation and development. Here we report the genome sequence for a member of this economically important group of biotrophic fungi. The 20.5-million-base U. maydis genome assembly contains 6,902 predicted protein-encoding genes and lacks pathogenicity signatures found in the genomes of aggressive pathogenic fungi, for example a battery of cell-wall-degrading enzymes. However, we detected unexpected genomic features responsible for the pathogenicity of this organism. Specifically, we found 12 clusters of genes encoding small secreted proteins with unknown function. A significant fraction of these genes exists in small gene families. Expression analysis showed that most of the genes contained in these clusters are regulated together and induced in infected tissue. Deletion of individual clusters altered the virulence of U. maydis in five cases, ranging from a complete lack of symptoms to hypervirulence. Despite years of research into the mechanism of pathogenicity in U. maydis, no 'true' virulence factors had been previously identified. Thus, the discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi. Genomic analysis is, similarly, likely to open up new avenues for the discovery of virulence determinants in other pathogens.

Chromosome 17 is unusual among the human chromosomes in many respects. It is the largest human autosome with orthology to only a single mouse chromosome1, mapping entirely to the distal half of mouse chromosome 11. Chromosome 17 is rich in protein-coding genes, having the second highest gene density in the genome2,3. It is also enriched in segmental duplications, ranking third in density among the autosomes4. Here we report a finished sequence for human chromosome 17, as well as a structural comparison with the finished sequence for mouse chromosome 11, the first finished mouse chromosome. Comparison of the orthologous regions reveals striking differences. In contrast to the typical pattern seen in mammalian evolution5,6, the human sequence has undergone extensive intrachromosomal rearrangement, whereas the mouse sequence has been remarkably stable. Moreover, although the human sequence has a high density of segmental duplication, the mouse sequence has a very low density. Notably, these segmental duplications correspond closely to the sites of structural rearrangement, demonstrating a link between duplication and rearrangement. Examination of the main classes of duplicated segments provides insight into the dynamics underlying expansion of chromosome-specific, low-copy repeats in the human genome.

Here we present a finished sequence of human chromosome 15, together with a high-quality gene catalogue. As chromosome 15 is one of seven human chromosomes with a high rate of segmental duplication, we have carried out a detailed analysis of the duplication structure of the chromosome. Segmental duplications in chromosome 15 are largely clustered in two regions, on proximal and distal 15q; the proximal region is notable because recombination among the segmental duplications can result in deletions causing Prader-Willi and Angelman syndromes. Sequence analysis shows that the proximal and distal regions of 15q share extensive ancient similarity. Using a simple approach, we have been able to reconstruct many of the events by which the current duplication structure arose. We find that most of the intrachromosomal duplications seem to share a common ancestry. Finally, we demonstrate that some remaining gaps in the genome sequence are probably due to structural polymorphisms between haplotypes; this may explain a significant fraction of the gaps remaining in the human genome.