Environmental and Molecular Mutagenesis Meeting Report Assessing Human Germ-Cell Mutagenesis in the Post-Genome Era: A Celebration of the Legacy of William Lawson (Bill) Russell

ABSTRACT Although numerous germ-cell mutagens have been identified in animal model systems, to date, no human germ-cell mutagens have been confirmed. Because the genomic integrity of our germ cells is essential for the continuation of the human species, a resolution of this enduring conundrum is needed. To facilitate such a resolution, we organized a workshop at The Jackson Laboratory in Bar Harbor, Maine on September [28][29][30] 2004. This interactive workshop brought together scientists from a wide range of disciplines to assess the applicability of emerging molecular methods for genomic analysis to the field of human germ-cell mutagenesis. Participants recommended that focused, coordinated human germ-cell mutation studies be conducted in relation to important societal exposures. Because cancer survivors represent a unique cohort with well-defined exposures, there was a consensus that studies should be designed to assess the mutational impact on children born to parents who had received certain types of mutagenic cancer chemotherapy prior to conceiving their children. Within this high-risk cohort, parents and children could be evaluated for inherited changes in (a) gene sequences and chromosomal structure, (b) repeat sequences and minisatellite regions, and (c) global gene expression and chromatin. Participants also recommended studies to examine trans-generational effects in humans involving mechanisms such as changes in imprinting and methylation patterns, expansion of nucleotide repeats, or induction of mitochondrial DNA mutations. Workshop participants advocated establishment of a bio-bank of human tissue samples that could be used to conduct a multiple-endpoint, comprehensive, and collaborative effort to detect exposure-induced heritable alterations in the human genome. Appropriate animal models of human germ-cell mutagenesis should be used in parallel with human studies to provide insights into the mechanisms of mammalian germ-cell mutagenesis. Finally, participants recommended that 4 scientific specialty groups be convened to address specific questions regarding the potential germ-cell mutagenicity of environmental, occupational, and lifestyle exposures. Strong support from relevant funding agencies and engagement of scientists outside the fields of genomics and germ-cell mutagenesis will be required to launch a full-scale assault on some of the most pressing and enduring questions in environmental mutagenesis: Do human germ-cell mutagens exist, what risk do they pose to future generations, and are some parents at higher risk than others for acquiring and transmitting germ-cell mutations?

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

California State Department of Transportation and Center for Conservation Biology: WRC MSCHP Niche Model Task Order

The goal of this research contract was to provide Caltrans with niche models for the assessment of the conservation potential of lands within the delineated Criteria Areas of the Western Riverside County Multiple Species Habitat Conservation Plan (WRC MSHCP). Caltrans could then use these results to prioritize lands for further evaluation and potential acquisition in order to meet their Implementing Agreement commitments under the WRC MSHCP

California State Department of Transportation and Center for Conservation Biology: WRC MSCHP Niche Model Task Order

The goal of this research contract was to provide Caltrans with niche models for the assessment of the conservation potential of lands within the delineated Criteria Areas of the Western Riverside County Multiple Species Habitat Conservation Plan (WRC MSHCP). Caltrans could then use these results to prioritize lands for further evaluation and potential acquisition in order to meet their Implementing Agreement commitments under the WRC MSHCP

Core 2 Refinement Workshop Report

The County of Riverside and the City of Murrieta requested that the Regional Conservation Authority (RCA) consider a Criteria Refinement for Core 2 in Western Riverside County’s Multiple Species Habitat Conservation Plan (WRC MSHCP). The purpose of this action is to determine if Core 2 can be sustained as a reserve and if WRC MSHCP funds could be more efficiently used in other core areas. The RCA requested a review of the biological research from the Center for Conservation Biology (CCB) that could be brought into their decision-making process. The CCB convened a distinguished group of scientists to review the implications of a Core 2 Criteria Refinement to biological resources. The group evaluated three general topics at a two-day workshop in order to provide this assessment

Supplement 1. SAS code to produce Mahalanobis D2 and its partitions.

<h2>File List</h2><blockquote> <p><a href="SAS_code_for_D2_partition_revised.txt">SAS_code_for_D2_partition_revised.txt</a></p> <p> </p> </blockquote><h2>Description</h2><blockquote> <p>SAS code (SAS Institute 2001) to produce Mahalanobis <i>D</i>² and its partitions (Clark et al. 1993, Dunn and Duncan 2000, Rotenberry et al. 2002). Code modified from Duncan and Dunn (2001). Text may be pasted directly into SAS Editor. User must either ensure appropriately named SAS library and data sets already exist, or modify code to conform to user's existing library and data set names. Further directions appear as comments within body of SAS code. </p> </blockquote

Influence of landscape-scale variables on vegetation conversion to exotic annual grassland in southern California, USA

In California, USA, coastal sage scrub (CSS) vegetation is being converted to exotic annual grassland, and several causes have been suggested. In order to investigate the importance of environmental variables in the conversion and recovery of CSS, particularly nitrogen deposition within the context of historical fire intervals, we employed an information theoretic approach. Prior studies have not assessed both conversion and recovery, and did not analyze nitrogen critical load for vegetation type conversion. We included measures of climate, topography, vegetation, land use, nitrogen deposition, and fire in our analysis, and found that 34% of CSS study sites were converted to exotic grassland between 1930 and 2009. Converted sites had higher nitrogen deposition with a critical load of 11 kg N ha−1 yr −1, also had shallower slopes, and were more west-facing. A smaller number of sites (24%) recovered to CSS, and these sites had about 2.5 times more CSS and 4.5 times less grassland in the surrounding landscape. CSS conservation and restoration efforts are most likely to be successful when focused on sites with <11.0 kg N ha−1 yr −1 and low invasion of exotic grasses. Analyses such as this that identify important threats may be useful in region-wide plans to conserve unique vegetation types. Keywords: Nitrogen deposition, Critical load, Coastal sage scrub, Exotic grass, Invasion, Vegetation type conversio