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Background and study aims The COVID-19 pandemic has had a profound impact on gastroenterology training programs. We aimed to objectively evaluate procedural training volume and impact of COVID-19 on gastroenterology fellowship programs in the United States. Methods This was a retrospective, multicenter study. Procedure volume data on upper and lower endoscopies performed by gastroenterology fellows was abstracted directly from the electronic medical record. The study period was stratified into 2 time periods: Study Period 1, SP1 (03/15/2020 to 06/30/2020) and Study Period 2, SP2 (07/01/2020 to 12/15/2020). Procedure volumes during SP1 and SP2 were compared to Historic Period 1 (HP1) (03/15/2019 to 06/30/2019) and Historic Period 2 (HP2) (07/01/2019 to 12/15/2019) as historical reference. Results Data from 23 gastroenterology fellowship programs (total procedures = 127,958) with a median of 284 fellows (range 273–289; representing 17.8 % of all trainees in the United States) were collected. Compared to HP1, fellows performed 53.6 % less procedures in SP1 (total volume: 28,808 vs 13,378; mean 105.52 ± 71.94 vs 47.61 ± 41.43 per fellow; P

Goals. The goal of this study was to develop an objective and detailed scoring system to assess the quality of bowel preparation. Background. The quality of bowel preparation impacts the success of the colonoscopy. We developed and compared a new bowel preparation scoring system, the New Jersey Bowel Preparation Scale (NJBPS), with existing systems that are limited by a lack of detail and objectivity in the Boston Bowel Preparation Scale (BBPS) and the Ottawa Bowel Preparation Scale (OBPS). Methods. This was a single-center, prospective, dual-observer study performed at Rutgers New Jersey Medical School University Hospital. Patients who were at medium risk for colorectal cancer and undergoing outpatient screening colonoscopy were enrolled in the study, and their bowel preparation was assessed separately by an attending and a fellow using each of the bowel preparation scoring systems. Results. 98 patients were analyzed in the study, of which 59% were female. Most of the patient population was African American (65%) or Hispanic (25%). The average age of the patient was 60 years. Chi-squared analysis using SPSS software revealed intraclass correlation coefficient values between attending and fellow scores for each scale. The NJBPS had the highest value at 0.988, while the BBPS and OBPS had values of 0.883 and 0.894. Limitations. Single-center study. Conclusions. The NJBPS and BBPS scores demonstrated a statistically significant agreement with each other. Overall, there was good interobserver agreement for all three scoring systems when comparing attendings to fellows for the same scoring system. However, the NJBPS possessed a stronger correlation.

The purpose of this study was to examine parent perceptions of professional and community attitudes about autism through the lens of parenting their autistic children from birth through adulthood. Implications of this research may assist with future development and study of professional and community supports of individuals on the autism spectrum and their families. The study participants consisted of 51 parents who had an adult-aged child on the autism spectrum. One-on-one interviews were conducted with parents about their experiences raising a child with autism. Data were double-coded and analyzed using a qualitative, phenomenological approach to explore parents' experiences with and perceptions of society members' attitudes towards autism. Positive and negative themes were identified across parents' perceptions of professionals and of community members. Themes regarding professional attitudes included cooperating with family requests, presuming competence of individuals with autism, complacency towards the needs of families and individuals with autism, and discrimination towards the individual with autism based on age or level of need. Themes regarding community member attitudes included valuing the strengths of individuals with autism, accommodating autistic differences, intolerance of autistic traits, and prejudice towards individuals with autism. Findings indicate that professional and community members presented with both positive and negative attitudes towards autism and individuals on the autism spectrum, with negative attitudes proving more prevalent in parent recollections. Results suggest a need for further research and related training to improve interactions with and support of individuals with autism and their families., (© 2024. The Author(s).)

Objectives: Since 2013 community pharmacies in Wales have been commissioned to provide a common ailments service (CAS), providing pharmacy medicine without charge to patients. In the first review of national pharmacy data, this study aimed to describe the relationship between provision of CAS and deprivation., Methods: A retrospective observational study, using CAS claims data from April 2022 to March 2023 collected as part of routine service delivery. Consultation data were matched to the index of multiple deprivation (IMD) decile of the providing pharmacy. Linear regression was used to describe the correlation between CAS claims data and IMD deciles of the pharmacy postcode., Key Findings: In the study period, 239 028 consultations were recorded. More than twice as many consultations were carried out in pharmacies located in the most deprived decile (33 950) than in pharmacies in the least deprived decile (14 465). Linear regression demonstrated a significant correlation r(10) = -0.927, P < 0.001. There was a strong relationship between greater numbers of consultations and greater deprivation of the pharmacy postcode (R2 = 0.887). This significant correlation with deprivation was also found in the majority of individual conditions. There was no significant correlation between deprivation decile and the number of consultations per patient., Conclusions: Community pharmacies offer a key resource for tackling health inequalities. Patients in those areas with the greatest need are those most likely to use the CAS in pharmacies and receive the care they need. Commissioning services like this naturally supports deprived communities, through a combination of patient behaviours, location, and accessibility., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.)

Genome-wide phenotypic screens in the budding yeast Saccharomyces cerevisiae , enabled by its knockout collection, have produced the largest, richest, and most systematic phenotypic description of any organism. However, integrative analyses of this rich data source have been virtually impossible because of the lack of a central data repository and consistent metadata annotations. Here, we describe the aggregation, harmonization, and analysis of ~14,500 yeast knockout screens, which we call Yeast Phenome. Using this unique dataset, we characterized two unknown genes ( YHR045W and YGL117W ) and showed that tryptophan starvation is a by-product of many chemical treatments. Furthermore, we uncovered an exponential relationship between phenotypic similarity and intergenic distance, which suggests that gene positions in both yeast and human genomes are optimized for function.

Objectives: In England, non-dispensing pharmacy services are commissioned either nationally or locally. For the national service Medicines Use Reviews (MURs), large multiple/chain pharmacies provide more consultations than independents. This study aimed to examine the relationship between community pharmacy organisation type and a local service, Emergency Hormonal Contraception (EHC). It also aimed to explore the influence of deprivation., Methods: Freedom of information requests was sent to all 147 local authorities in England. Data included the number of EHC consultations by individual pharmacies across England (2017/18). Public data were used to identify pharmacies, match with MUR data, and group by organisation type. Bivariate correlations and ANOVA described the relationship between service provision, organisation type and deprivation., Key Findings: Pharmacy data were obtained from 76 (52%) local authorities. Following removal of unidentifiable pharmacies, 3069 were analysed - 56% of the estimated 5461 commissioned pharmacies in England. Bivariate correlations indicated a significant negative correlation between EHC provision and Index of Multiple Deprivation score. Greater deprivation correlated to greater EHC provision. A One-way ANOVA demonstrated significant differences between organisation types for MUR provision (larger organisations providing greater volumes). EHC provision demonstrated significant differences between groups and a U-shaped association; large multiple and independent organisations had higher levels than medium and small chains. A two-way ANOVA showed no significant interaction between deprivation and organisation type., Conclusions: EHC provision does not increase linearly with organisation type. Deprivation appears a more reliable indicator of EHC provision. Provision is likely influenced by local factors but could increase with a nationally commissioned service., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.)

Objectives: In 2014/2015, 46% of community pharmacies were commissioned by local authorities to provide emergency hormonal contraception (EHC) free without prescription in England. Commissioning EHC services influences EHC prescribing from General Practice (GP)-greater community pharmacy provision reduces GP prescribing. This study aimed to examine predictors of GP and pharmacy EHC activity, describing them using path analysis. From this, commissioners and policy-makers may understand ways to influence this., Study Design: Cross-sectional study of routinely recorded data, obtained through freedom of information requests to local authorities., Setting: Community pharmacies and general practices in England, UK., Participants: All local authorities in England were included in the study (147 areas). The study population were all girls, adolescents and women aged 12-55. Of the 147 areas, data from 80 local authorities were obtained covering an eligible female population of 9 380 153., Primary and Secondary Outcome Measures: Correlation between community pharmacy and GP EHC activity., Results: Data from 80 local authorities were analysed, representing 60% of the eligible female population in England. A significant negative correlation was found between rates of community pharmacy provision and GP prescribing (-0.458, p<0.000). Community pharmacy provision and the proportion of pharmacies commissioned were significantly correlated (0.461, p<0.000). A significant correlation was found between increased deprivation and community pharmacy provision (0.287, p=0.010). Standardised total effects on GP prescribing were determined from path analysis including community pharmacy provision (ß=-0.552) and proportion of pharmacies commissioned (ß=-0.299). If all community pharmacies were commissioned to provide EHC, GP EHC prescriptions could decrease by 15%., Conclusion: Community pharmacy EHC provision has a significant influence on GP EHC prescribing. Increasing the proportion of commissioned community pharmacies should have a marked impact on GP workload. The methodology affords the possibility of examining relationships surrounding other commissioned service activity across different settings and their impact on linked care settings., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: A collaborative service initiative involving community pharmacists and a specialist mental health pharmacist was developed to provide pharmacist reviews for care home residents with intellectual disabilities (IDs). This study aimed to characterise the medicines and lifestyle risk outcomes of the service and determine how these align with national priority issues in ID., Design: Descriptive statistical analysis of routinely collected service delivery data., Setting: Residential care homes in the Wirral, England for people with ID., Participants: 160 residents., Interventions: Pharmacist review of residents' medicines and lifestyle risk factors between November 2019 and May 2020., Primary and Secondary Outcome Measures: Numbers of medicines prescribed, the nature of pharmacists' interventions/recommendations and general practitioner (GP)/psychiatrist acceptance., Results: The 160 residents were prescribed 1207 medicines, 74% were prescribed ≥5 medicines and 507 interventions/recommendations were made, averaging 3.3 per resident. The highest proportion (30.4%) were lifestyle risk related, while changing and stopping medicines accounted for 17.9% and 12.8%, respectively. Of the recommendations discussed with GPs/psychiatrists, 86% were accepted. Medicines with anticholinergic properties were prescribed for 115 (72%) residents, of whom 43 (37%) had a high anticholinergic burden score. Pharmacists recommended anticholinergic discontinuation or dose reduction for 28 (24%) residents. The pharmacists made interventions/recommendations about constipation management for 10% of residents and about respiratory medicines for 17 (81%) of the 21 residents with respiratory diagnoses., Conclusions: The findings indicate considerable polypharmacy among the residents and a high level of pharmacists' interventions/recommendations about medicines and lifestyle risk, most of which were accepted by GPs/psychiatrists. This included anticholinergic burden reduction and improving respiratory disease and constipation management, which are national priority issues. Wider adoption of collaborative pharmacist review models could have similar benefits for residential populations with ID and potentially reduce pressure on other health services., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Collagen microfiber-based constructs have garnered considerable attention for ligament, tendon, and other soft tissue repairs, yet with limited clinical translation due to strength, biocompatibility, scalable manufacturing, and other challenges. Crosslinking collagen fibers improves mechanical properties; however, questions remain regarding optimal crosslinking chemistries, biocompatibility, biodegradation, long-term stability, and potential for biotextile assemble at scale, limiting their clinical usefulness. Here, we assessed over 50 different crosslinking chemistries on microfluidic wet-extruded collagen microfibers made with clinically relevant collagen to optimize collagen fibers as a biotextile yarn for suture or other medical device manufacture. The endogenous collagen crosslinker, glyoxal, provides extraordinary fiber ultimate tensile strength near 300MPa, and Young's modulus of over 3GPa while retaining 50% of the initial load-bearing capacity through 6 months as hydrated. Glyoxal crosslinked collagen fibers further proved cytocompatible and biocompatible per ISO 10993-based testing, and further elicits a predominantly M2 macrophage response. Remarkably these strong collagen fibers are amenable to industrial braiding to form strong collagen fiber sutures. Collagen microfluidic wet extrusion with glyoxal crosslinking thus progress bioengineered, strong, and stable collagen microfibers significantly towards clinical use for potentially promoting efficient healing compared to existing suture materials. STATEMENT OF SIGNIFICANCE: Towards improving clinical outcomes for over 1 million ligament and tendon surgeries performed annually, we report an advanced microfluidic extrusion process for type I collagen microfiber manufacturing for biological suture and other biotextile manufacturing. This manuscript reports the most extensive wet-extruded collagen fiber crosslinking compendium published to date, providing a tremendous recourse to the field. Collagen fibers made with clinical-grade collagen and crosslinked with glyoxal, exhibit tensile strength and stability that surpasses all prior reports. This is the first report demonstrating that glyoxal, a native tissue crosslinker, has the extraordinary ability to produce strong, cytocompatible, and biocompatible collagen microfibers. These collagen microfibers are ideal for advanced research and clinical use as surgical suture or other tissue-engineered medical products for sports medicine, orthopedics, and other surgical indications., Competing Interests: Declaration of Competing Interest The authors declare that they are or were employes and/or shareholders of Embody Inc. ., (Copyright © 2021. Published by Elsevier Ltd.)

Approximately 800, 000 surgical repairs are performed annually in the U.S. for debilitating injuries to ligaments and tendons of the foot, ankle, knee, wrist, elbow and shoulder, presenting a significant healthcare burden. To overcome current treatment shortcomings and advance the treatment of tendon and ligament injuries, we have developed a novel electrospun Tissue ENgineered Device (TEND), comprised of type I collagen and poly(D,L-lactide) (PDLLA) solubilized in a benign solvent, dimethyl sulfoxide (DMSO). TEND fiber alignment, diameter and porosity were engineered to enhance cell infiltration leading to promote tissue integration and functional remodeling while providing biomechanical stability. TEND rapidly adsorbs blood and platelet-rich-plasma (PRP), and gradually releases growth factors over two weeks. TEND further supported cellular alignment and upregulation of tenogenic genes from clinically relevant human stem cells within three days of culture. TEND implanted in a rabbit Achilles tendon injury model showed new in situ tissue generation, maturation, and remodeling of dense, regularly oriented connective tissue in vivo. In all, TEND's organized microfibers, biological fluid and cell compatibility, strength and biocompatiblility make significant progress towards clinically translating electrospun collagen-based medical devices for improving the clinical outcomes of tendon injuries.

Introduction: Current collagen fiber manufacturing methods for biomedical applications, such as electrospinning and extrusion, have had limited success in clinical translation, partially due to scalability, cost, and complexity challenges. Here we explore an alternative, simplified and scalable collagen fiber formation method, termed 'pneumatospinning,' to generate submicron collagen fibers from benign solvents., Methods and Results: Clinical grade type I atelocollagen from calf corium was electrospun or pneumatospun as sheets of aligned and isotropic fibrous scaffolds. Following crosslinking with genipin, the collagen scaffolds were stable in media for over a month. Pneumatospun collagen samples were characterized using Fourier-transform infrared spectroscopy, circular dichroism, mechanical testing, and scanning electron microscopy showed consistent fiber size and no deleterious chemical changes to the collagen were detected. Pneumatospun collagen had significantly higher tensile strength relative to electrospun collagen, with both processed from acetic acid. Stem cells cultured on pneumatospun collagen showed robust cell attachment and high cytocompatibility. Using DMSO as a solvent, collagen was further co-pneumatospun with poly(d,l-lactide) to produce a blended microfibrous biomaterial., Conclusions: Collagen microfibers are shown for the first time to be formed using pneumatospinning, which can be collected as anisotropic or isotropic fibrous grafts. Pneumatospun collagen can be made with higher output, lower cost and less complexity relative to electrospinning. As a robust and rapid method of collagen microfiber synthesis, this manufacturing method has many applications in medical device manufacturing, including those benefiting from anisotropic microstructures, such as ligament, tendon and nerve repair, or for applying microfibrous collagen-based coatings to other materials.

Background: A routine 2-dose varicella vaccination program was adopted in 2007 in the US to help further decrease varicella disease and prevent varicella outbreaks. We describe trends and characteristics of varicella outbreaks reported to the Centers for Disease Control and Prevention (CDC) during 2005-2012 from 9 states., Methods: Data on varicella outbreaks collected by 9 state health departments were submitted to CDC using the CDC outbreak reporting worksheet. Information was collected on dates of the outbreak, outbreak setting and number of cases by outbreak; aggregate data were provided on the numbers of outbreak-related cases by age group, vaccination status and laboratory confirmation., Results: Nine hundred and twenty-nine outbreaks were reported from the 6 states, which provided data for each year during 2005-2012. Based on data from these 6 states, the number of outbreaks declined by 78%, decreasing from 147 in 2005 to 33 outbreaks in 2012 (P = 0.0001). There were a total of 1015 varicella outbreaks involving 13,595 cases reported by the 9 states from 2005 to 2012. The size and duration of outbreaks declined significantly over time (P < 0.001). The median size of outbreaks was 12, 9 and 7 cases and median duration of outbreaks was 38, 35 and 26 days during 2005-2006, 2007-2009 and 2010-2012, respectively. Majority of outbreaks (95%) were reported from schools, declining from 97% in 2005-2006 to 89% in 2010-2012. Sixty-five percent of outbreak-related cases occurred among 5-year to 9-year olds, with the proportion declining from 76% in 2005-2006 to 45% during 2010-2012., Conclusions: The routine 2-dose varicella vaccination program appears to have significantly reduced the number, size and duration of varicella outbreaks in the US.

Trichoderma reesei is the main industrial source of cellulases and hemicellulases used to depolymerize biomass to simple sugars that are converted to chemical intermediates and biofuels, such as ethanol. We assembled 89 scaffolds (sets of ordered and oriented contigs) to generate 34 Mbp of nearly contiguous T. reesei genome sequence comprising 9,129 predicted gene models. Unexpectedly, considering the industrial utility and effectiveness of the carbohydrate-active enzymes of T. reesei, its genome encodes fewer cellulases and hemicellulases than any other sequenced fungus able to hydrolyze plant cell wall polysaccharides. Many T. reesei genes encoding carbohydrate-active enzymes are distributed nonrandomly in clusters that lie between regions of synteny with other Sordariomycetes. Numerous genes encoding biosynthetic pathways for secondary metabolites may promote survival of T. reesei in its competitive soil habitat, but genome analysis provided little mechanistic insight into its extraordinary capacity for protein secretion. Our analysis, coupled with the genome sequence data, provides a roadmap for constructing enhanced T. reesei strains for industrial applications such as biofuel production.

Purpose: To present the findings of an outbreak of toxic anterior segment syndrome (TASS)., Setting: Six states, 7 ophthalmology surgical centers, United States., Methods: Cases were identified through electronic communication networks and via reports to a national TASS referral center. Information on the procedure, details of instrument reprocessing, and products used during cataract surgery were also collected. Medications used during the procedures were tested for endotoxin using a kinetic assay., Results: The search identified 112 case patients (median age 74 years) from 7 centers from July 19, 2005, through November 28, 2005. Common presenting clinical features included blurred vision (60%), anterior segment inflammation (49%), and cell deposition (56%). Of the patients, 100 (89%) had been exposed to a single brand of balanced salt solution manufactured by Cytosol Laboratories and distributed by Advanced Medical Optics as AMO Endosol. Two patients continued to have residual symptoms. There were no reports of significant breaches in sterile technique or instrument reprocessing. Of 14 balanced salt solution lots, 5 (35%) had levels exceeding the endotoxin limit (0.5 EU/mL). Based on these findings, the balanced salt solution product was withdrawn, resulting in a termination of the outbreak., Conclusions: This is the first known report of an outbreak of TASS caused by intrinsic contamination of a product with endotoxin. Ophthalmologists and epidemiologists should be aware of TASS and its common causes. To facilitate investigations of adverse outcomes such as TASS, those performing cataract surgeries should document the type and lot numbers of products used intraoperatively.

The complete DNA sequence of the aerobic cellulolytic soil bacterium Cytophaga hutchinsonii, which belongs to the phylum Bacteroidetes, is presented. The genome consists of a single, circular, 4.43-Mb chromosome containing 3,790 open reading frames, 1,986 of which have been assigned a tentative function. Two of the most striking characteristics of C. hutchinsonii are its rapid gliding motility over surfaces and its contact-dependent digestion of crystalline cellulose. The mechanism of C. hutchinsonii motility is not known, but its genome contains homologs for each of the gld genes that are required for gliding of the distantly related bacteroidete Flavobacterium johnsoniae. Cytophaga-Flavobacterium gliding appears to be novel and does not involve well-studied motility organelles such as flagella or type IV pili. Many genes thought to encode proteins involved in cellulose utilization were identified. These include candidate endo-beta-1,4-glucanases and beta-glucosidases. Surprisingly, obvious homologs of known cellobiohydrolases were not detected. Since such enzymes are needed for efficient cellulose digestion by well-studied cellulolytic bacteria, C. hutchinsonii either has novel cellobiohydrolases or has an unusual method of cellulose utilization. Genes encoding proteins with cohesin domains, which are characteristic of cellulosomes, were absent, but many proteins predicted to be involved in polysaccharide utilization had putative D5 domains, which are thought to be involved in anchoring proteins to the cell surface.

Bacillus thuringiensis is an insect pathogen that is widely used as a biopesticide (E. Schnepf, N. Crickmore, J. Van Rie, D. Lereclus, J. Baum, J. Feitelson, D. R. Zeigler, and D. H. Dean, Microbiol. Mol. Biol. Rev. 62:775-806, 1998). Here we report the finished, annotated genome sequence of B. thuringiensis Al Hakam, which was collected in Iraq by the United Nations Special Commission (L. Radnedge, P. Agron, K. Hill, P. Jackson, L. Ticknor, P. Keim, and G. Andersen, Appl. Environ. Microbiol. 69:2755-2764, 2003).

Haemophilus somnus can be either a commensal of bovine mucosal surfaces or an opportunistic pathogen. Pathogenic strains of H. somnus are a significant cause of systemic disease in cattle. We report the genome sequence of H. somnus 129Pt, a nonpathogenic commensal preputial isolate, and the results of a genome-wide comparative analysis of H. somnus 129Pt, Haemophilus influenzae Rd, and Haemophilus ducreyi 35000HP. We found unique genes in H. somnus 129Pt involved in lipooligosaccharide biosynthesis, carbohydrate uptake and metabolism, cation transport, amino acid metabolism, ubiquinone and menaquinone biosynthesis, cell surface adhesion, biosynthesis of cofactors, energy metabolism, and electron transport. There were also many genes in common among the three organisms. Our comparative analyses of H. somnus 129Pt, H. influenzae Rd, and H. ducreyi 35000HP revealed similarities and differences in the numbers and compositions of genes involved in metabolism, host colonization, and persistence. These results lay a foundation for research on the host specificities and niche preferences of these organisms. Future comparisons between H. somnus 129Pt and virulent strains will aid in the development of protective strategies and vaccines to protect cattle against H. somnus disease.

Bacillus anthracis, Bacillus cereus, and Bacillus thuringiensis are closely related gram-positive, spore-forming bacteria of the B. cereus sensu lato group. While independently derived strains of B. anthracis reveal conspicuous sequence homogeneity, environmental isolates of B. cereus and B. thuringiensis exhibit extensive genetic diversity. Here we report the sequencing and comparative analysis of the genomes of two members of the B. cereus group, B. thuringiensis 97-27 subsp. konkukian serotype H34, isolated from a necrotic human wound, and B. cereus E33L, which was isolated from a swab of a zebra carcass in Namibia. These two strains, when analyzed by amplified fragment length polymorphism within a collection of over 300 of B. cereus, B. thuringiensis, and B. anthracis isolates, appear closely related to B. anthracis. The B. cereus E33L isolate appears to be the nearest relative to B. anthracis identified thus far. Whole-genome sequencing of B. thuringiensis 97-27and B. cereus E33L was undertaken to identify shared and unique genes among these isolates in comparison to the genomes of pathogenic strains B. anthracis Ames and B. cereus G9241 and nonpathogenic strains B. cereus ATCC 10987 and B. cereus ATCC 14579. Comparison of these genomes revealed differences in terms of virulence, metabolic competence, structural components, and regulatory mechanisms.

Human chromosome 16 features one of the highest levels of segmentally duplicated sequence among the human autosomes. We report here the 78,884,754 base pairs of finished chromosome 16 sequence, representing over 99.9% of its euchromatin. Manual annotation revealed 880 protein-coding genes confirmed by 1,670 aligned transcripts, 19 transfer RNA genes, 341 pseudogenes and three RNA pseudogenes. These genes include metallothionein, cadherin and iroquois gene families, as well as the disease genes for polycystic kidney disease and acute myelomonocytic leukaemia. Several large-scale structural polymorphisms spanning hundreds of kilobase pairs were identified and result in gene content differences among humans. Whereas the segmental duplications of chromosome 16 are enriched in the relatively gene-poor pericentromere of the p arm, some are involved in recent gene duplication and conversion events that are likely to have had an impact on the evolution of primates and human disease susceptibility.

Chromosome 5 is one of the largest human chromosomes and contains numerous intrachromosomal duplications, yet it has one of the lowest gene densities. This is partially explained by numerous gene-poor regions that display a remarkable degree of noncoding conservation with non-mammalian vertebrates, suggesting that they are functionally constrained. In total, we compiled 177.7 million base pairs of highly accurate finished sequence containing 923 manually curated protein-coding genes including the protocadherin and interleukin gene families. We also completely sequenced versions of the large chromosome-5-specific internal duplications. These duplications are very recent evolutionary events and probably have a mechanistic role in human physiological variation, as deletions in these regions are the cause of debilitating disorders including spinal muscular atrophy.

Chromosome 19 has the highest gene density of all human chromosomes, more than double the genome-wide average. The large clustered gene families, corresponding high G + C content, CpG islands and density of repetitive DNA indicate a chromosome rich in biological and evolutionary significance. Here we describe 55.8 million base pairs of highly accurate finished sequence representing 99.9% of the euchromatin portion of the chromosome. Manual curation of gene loci reveals 1,461 protein-coding genes and 321 pseudogenes. Among these are genes directly implicated in mendelian disorders, including familial hypercholesterolaemia and insulin-resistant diabetes. Nearly one-quarter of these genes belong to tandemly arranged families, encompassing more than 25% of the chromosome. Comparative analyses show a fascinating picture of conservation and divergence, revealing large blocks of gene orthology with rodents, scattered regions with more recent gene family expansions and deletions, and segments of coding and non-coding conservation with the distant fish species Takifugu.

The genome sequence database (GSDB) is a complete, publicly available relational database of DNA sequences and annotation maintained by the National Center for Genome Resources (NCGR) under a Cooperative Agreement with the US Department of Energy (DOE). GSDB provides direct, client- server access to the database for data contributions, community annotation and SQL queries. The GSDB Annotator, a multi-platform graphic user interface, is freely available. Automatically updated relational replicates of GSDB are also freely available.

Contemporary mysticism is in continuity with religious mysticism of all ages. Mysticism, like all religion, has an ideological and an experiential dimension. Traditional Freudian theory is inadequate for understanding either the ideological or the cognitive aspect, because it does not adequately account for either the cognitive process or the self-conscious "I." Categories of both ego psychology and the social scientific approach to religion illuminate contemporary mysticism in ways unavailable to the traditional Freudian psychoanalytic approach. The epistemological implications of the mystical attitude are considered, in both the religious and the scientific enterprises.