The environment is increasingly being recognized for the role it might play in the global spread of clinically relevant antibiotic resistance. Environmental regulators monitor and control many of the pathways responsible for the release of resistance-driving chemicals into the environment (e.g., antimicrobials, metals, and biocides). Hence, environmental regulators should be contributing significantly to the development of global and national antimicrobial resistance (AMR) action plans. It is argued that the lack of environment-facing mitigation actions included in existing AMR action plans is likely a function of our poor fundamental understanding of many of the key issues. Here, we aim to present the problem with AMR in the environment through the lens of an environmental regulator, using the Environment Agency (England’s regulator) as an example from which parallels can be drawn globally. The issues that are pertinent to environmental regulators are drawn out to answer: What are the drivers and pathways of AMR? How do these relate to the normal work, powers and duties of environmental regulators? What are the knowledge gaps that hinder the delivery of environmental protection from AMR? We offer several thought experiments for how different mitigation strategies might proceed. We conclude that: (1) AMR Action Plans do not tackle all the potentially relevant pathways and drivers of AMR in the environment; and (2) AMR Action Plans are deficient partly because the science to inform policy is lacking and this needs to be addressed.

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BACKGROUNDThe current study was performed to determine whether tumor mitotic rate (TMR) is a useful, independent prognostic factor in patients with localized cutaneous melanoma.METHODSFrom the Sydney Melanoma Unit database, 3661 patients with complete clinical information and details of primary tumor thickness, ulcerative state, and TMR were studied. TMR was expressed as mitoses per mm2 in the dermal part of the tumor in which most mitoses were seen, as recommended in the 1982 revision of the 1972 Sydney classification of malignant melanoma. To determine which was the more prognostically useful method of grouping TMR, two separate methods (A and B) were used. Factors predicting melanoma‐specific survival were analyzed using the Cox proportional hazards regression model.RESULTSPatients with a TMR of 0 mitoses/mm2 had a significantly better survival than those with 1 mitosis/mm2 (P < 0.0001) but no significant survival differences were recorded for the stepwise increases from 1–2, 2–3, 3–4, and 4–5/mm2. Tumor thickness, ulceration, and TMR were closely correlated, whether TMR was grouped using Method A (0, 1–4, 5–10, and ≥ 11 mitoses/mm2) or Method B (0–1, 2–4, and ≥ 5 mitoses/mm2). However, Cox regression analysis indicated that the TMR was a highly significant independent prognostic factor, particularly when grouped according to Method A, in which it was second only to tumor thickness as the most powerful predictor of survival (P < 0.0001).CONCLUSIONSTMR is an important independent predictor of survival for melanoma patients. If confirmed by studies from other centers, it has the potential to further improve the accuracy of melanoma staging, as well as to define more rigidly the risk categories for patients entering clinical trials. Cancer 2003;97:1488–98. © 2003 American Cancer Society.DOI 10.1002/cncr.11196