Exclusionary Zoning in Southeast Michigan: Community land use as a barrier to regional integration

This project aims to model how regional agencies could review and analyze individual community zoning ordinances on the basis of exclusivity.Ope

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Gastrointestinal parasites in captive olive baboons in a UK safari park

From the safety offered inside vehicles, Knowsley Safari provides its visitors a close-up encounter with a colony of some 240 captive olive baboons. As exiting vehicles may be contaminated with baboon stool and the prevalence of gastrointestinal parasites within the colony is unknown, a comprehensive coprological survey of baboon stool was conducted to address public health concerns. Stools were obtained from vehicles, and sleeping areas, inclusive of video analysis of baboon-vehicle interactions. During the summer of 2021, a purposely selected four-day period of sampling enabled comparative inspections of 2,662 vehicles, with a total of 669 baboon stools examined (371 from vehicles and 298 from sleeping areas). As informed by a pilot study, our frontline diagnostic methods used were: QUIK-CHEK RDT (Giardia and Cryptosporidium), Kato-Katz coproscopy (Trichuris) and charcoal culture (Strongyloides). A total of 13.9% of vehicles were contaminated with baboon stool. Across examined stools, the prevalence of giardiasis was 37.4% whilst cryptosporidiosis was less than 0.01% using RDTs. The absence of faecal cysts by quality control coproscopy, alongside lower than expected levels of Giardia-specific DNA, judged RDT results as misleading, grossly overestimating the prevalence of giardiasis. Prevalence of trichuriasis was 48.0% and strongyloidiasis was 13.7%, with the first report of Strongyloides fuelleborni in the UK. We advise regular blanket administration(s) of anthelminthics to the colony, exploring pour-on formulations, thereafter, smaller-scale indicator surveys could adequately monitor notable gastrointestinal parasites

Gastrointestinal parasites in captive olive baboons in a UK safari park

From the safety inside vehicles, Knowsley Safari offers visitors a close-up encounter with captive olive baboons. As exiting vehicles may be contaminated with baboon stool, a comprehensive coprological inspection was conducted to address public health concerns. Baboon stools were obtained from vehicles, and sleeping areas, inclusive of video analysis of baboon–vehicle interactions. A purposely selected 4-day sampling period enabled comparative inspections of 2662 vehicles, with a total of 669 baboon stools examined (371 from vehicles and 298 from sleeping areas). As informed by our pilot study, front-line diagnostic methods were: QUIK-CHEK rapid diagnostic test (RDT) (Giardia and Cryptosporidium), Kato–Katz coproscopy (Trichuris) and charcoal culture (Strongyloides). Some 13.9% of vehicles were contaminated with baboon stool. Prevalence of giardiasis was 37.4% while cryptosporidiosis was <0.01%, however, an absence of faecal cysts by quality control coproscopy, alongside lower than the expected levels of Giardia-specific DNA, judged RDT results as misleading, grossly overestimating prevalence. Prevalence of trichuriasis was 48.0% and strongyloidiasis was 13.7%, a first report of Strongyloides fuelleborni in UK. We advise regular blanket administration(s) of anthelminthics to the colony, exploring pour-on formulations, thereafter, smaller-scale indicator surveys would be adequate

Structural and biochemical characterisation of the oxidoreductase NmDsbA3 from Neisseria meningitidis

DsbA is an enzyme found in the periplasm of Gram-negative bacteria that catalyses the formation of disulfide bonds in a diverse array of protein substrates, many of which are involved in bacterial pathogenesis. Whilst most bacteria possess only a single essential DsbA, Neisseria meningitidis is unusual in that it possesses three DsbAs, although the reason for this additional redundancy is unclear. Two of these N. meningitidis enzymes (NmDsbA1 and NmDsbA2) play an important role in meningococcal attachment to human epithelial cells, whilst NmDsbA3 is considered to have a narrow substrate repertoire. To begin to address the role of DsbAs in the pathogenesis of N. meningitidis, we have determined the structure of NmDsbA3 to 2.3 &Aring; resolution. Although the sequence identity between NmDsbA3 and other DsbAs is low, the NmDsbA3 structure adopted a DsbA-like fold. Consistent with this finding, we demonstrated that NmDsbA3 acts as a thiol-disulfide oxidoreductase in vitro and is reoxidised by Escherichia coli DsbB (EcDsbB). However, pronounced differences in the structures between DsbA3 and EcDsbA, which are clustered around the active site of the enzyme, suggested a structural basis for the unusual substrate specificity that is observed for NmDsbA3.<br /

Utility of ctDNA to support patient selection for early phase clinical trials: The TARGET Study

Next-generation sequencing (NGS) of circulating tumor DNA (ctDNA) supports blood-based genomic profiling but is not yet routinely implemented in the setting of a phase I trials clinic. TARGET is a molecular profiling program with the primary aim to match patients with a broad range of advanced cancers to early phase clinical trials on the basis of analysis of both somatic mutations and copy number alterations (CNA) across a 641 cancer-associated-gene panel in a single ctDNA assay. For the first 100 TARGET patients, ctDNA data showed good concordance with matched tumor and results were turned round within a clinically acceptable timeframe for Molecular Tumor Board (MTB) review. When a 2.5% variant allele frequency (VAF) threshold was applied, actionable mutations were identified in 41 of 100 patients, and 11 of these patients received a matched therapy. These data support the application of ctDNA in this early phase trial setting where broad genomic profiling of contemporaneous tumor material enhances patient stratification to novel therapies and provides a practical template for bringing routinely applied blood-based analyses to the clinic

New guidelines for the perioperative care of people living with frailty undergoing elective and emergency surgery—a commentary

Frailty is common in the older population and is a predictor of adverse outcomes following emergency and elective surgery. Identification of frailty is key to enable targeted intervention throughout the perioperative pathway from contemplation of surgery to recovery. Despite evidence on how to identify and modify frailty, such interventions are not yet routine perioperative care. To address this implementation gap, a guideline was published in 2021 by the Centre for Perioperative Care and the British Geriatrics Society, working with patient representatives and all stakeholders involved in the perioperative care of patients with frailty undergoing surgery. The guideline covers all aspects of perioperative care relevant to adults living with frailty undergoing elective and emergency surgery. It is written for healthcare professionals, as well as for patients and their carers, managers and commissioners. Implementation of the guideline will require collaboration between all stakeholders, underpinned by an implementation strategy, workforce development with supporting education and training resources, and evaluation through national audit and research. The guideline is an important step in improving perioperative outcomes for people living with frailty and quality of healthcare services. This commentary provides a summary and discussion of the evidence informing the standards and recommendations in the published guideline