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As discussed, the presence of microvascular disease is likely to alter the ability of the arteriole to autoregulate, with the greatest risk being to the kidney and the brain. While the presence of microvascular disease suggests that lower blood pressure targets may be needed to prevent progression of renal disease or stroke, this may also be the reason that the use of vasodilators may result in enhanced perfusion of hyperperfusion syndromes. Evidence that this may be the case can be observed in a study in which l -arginine (a precursor for the synthesis of nitric oxide) was administered either to prevent or to treat hyperuricaemia-associated hypertension ( Figure2 ) [ 39 ]. If l -arginine was administered prophylactically (chronic treatment), it prevented the development of the arteriolopathy, reduced systemic pressure, and maintained glomerular pressure in the normal range. However, if it was administered after the microvascular lesions were induced (acute infusion), it lowered systemic pressure but paradoxically increased glomerular pressure ( Figure2 ).

Fig.2
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l -Arginine was administered either to prevent (chronic L -Arg) or to treat (acute infusion L-Arg) hyperuricaemia-associated hypertension (induced by oxonic acid administration). When l -arginine was administered chronically, it prevented systemic hypertension, the development of the arteriolopathy, shown as a reduced media-to-lumen (M/L) ratio, and prevented the glomerular hypertension induced by hyperuricaemia. Acute infusion of L-Arg was able to reduce systemic hypertension; however, microvascular lesions already present, precluded the benefit of lowering blood pressure to relief glomerular hypertension; on the contrary, increased renal perfusion induced a further increment in glomerular pressure [ 39 ].

Fig.2
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l -Arginine was administered either to prevent (chronic L -Arg) or to treat (acute infusion L-Arg) hyperuricaemia-associated hypertension (induced by oxonic acid administration). When l -arginine was administered chronically, it prevented systemic hypertension, the development of the arteriolopathy, shown as a reduced media-to-lumen (M/L) ratio, and prevented the glomerular hypertension induced by hyperuricaemia. Acute infusion of L-Arg was able to reduce systemic hypertension; however, microvascular lesions already present, precluded the benefit of lowering blood pressure to relief glomerular hypertension; on the contrary, increased renal perfusion induced a further increment in glomerular pressure [ 39 ].

The observation that stimulating nitric oxide paradoxically increased glomerular pressure in the setting of renal microvascular disease could account for some apparently paradoxical findings in the literature, such as studies reporting that the anti-oxidants vitamin E [ 10 ] or β-carotene [ 15 ] can increase the risk for haemorrhagic stroke. In the Women’s Health Initiative, the use of oestrogens (which increase NO) was also reported to increase the risk for stroke, especially in older women [ 73 ]. It is conceivable that this increased risk is due to the presence of underlying microvascular disease.

This view of the immorality but necessity of modern war makes possible the idea of the atomic bomb as simply another military weapon, like incendiary attacks. Since it was simply another weapon, that would negate the need to issue any sort of demonstration. This was clearly the prevailing military point of view.

At the same time, though, it makes it possible to regard the atomic bomb, as a clearly delineated step in an escalating insanity. For the Japanese, offering a demonstration would give them a well-defined opportunity to avoid a new phase in the devastation of their country. For the Americans, offering a demonstration would afford an opportunity to step back from the escalating immorality of war. However, if the Japanese did not respond to the opportunity to surrender, taking that step would not have been morally compromising, because the essential dividing line between morality and immorality in warfare had already been crossed.

I can see how this sort of position could be regarded as a peculiarly “scientists'” position, because they would regard themselves as having a much keener appreciation of just why the atomic bomb could be regarded as a clearly delineated step in warfare, where the military would regard it as a munition that was highly comparable to an incendiary raid—thus justifying the Chicago scientists’ sense of the need for their intervention.

This, of course, is a rather condescending view of military thinking, and I suspect Oppenheimer, who worked closely with Groves and other military personnel, would have regarded it as such. He would have known that they would have already taken into account (and already rejected as insufficiently consequential) the peculiar features of the atomic bomb as a kind of display.

Anyway, that’s my understanding of that question.

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You bring up a point that is often overlooked: the US and Britain had different styles of war in World War II. Particularly in regard to the idea of terror bombing; the British were proponents of what we now call the “shock and awe” concept, of psychological war. Lord Penney served on the targeting committee that selected Hiroshima, and one of its findings was “that psychological factors in the target selection were of great importance”.

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Your final argument in this post (that it was better for posterity to show what the bomb could do to a city) is the same as Philip Morrison made in a guest lecture in my class.

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If the time for such a decision comes again, we can hope that the single individual making the decision chooses to see Hiroshima that way — as a warning rather than a precedent. But who will that person be? And will they? Or not…

Ad hoc PCI is defined as a therapeutic interventional procedure performed immediately (with the patient still on the catheterization table) following the diagnostic procedure as opposed to a staged procedure performed during a different session. Ad hoc PCI is convenient for the patient, associated with fewer access site complications, and often cost-effective. However, in a review of > 38000 patients undergoing ad hoc PCI, 30% of patients were in categories that were regarded as potential candidates for CABG. Ad hoc PCI is therefore reasonable for many patients, but not desirable for all, and should not automatically be applied as a default approach. Institutional protocols designed by the Heart Team should be used to define specific anatomical criteria and clinical subsets that can or cannot be treated ad hoc . Based on resources and settings, geographical differences can be expected. Table 5 lists potential indications for ad hoc PCI. All other pathologies in stable patients, including lesions of the LM or proximal left anterior descending (LAD) artery and MVD involving the LAD artery, should be discussed by a Heart Team before a deferred revascularization procedure (PCI or CABG). Table 6 lists the recommendations for decision making and patient information.

Table 5
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Potential indications for percutaneous coronary intervention vs. revascularization at an interval

Table 5
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Potential indications for percutaneous coronary intervention vs. revascularization at an interval

Table 6
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Recommendations for decision making and patient information

Table 6
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Recommendations for decision making and patient information

Exercise testing and cardiac imaging are used to confirm the diagnosis of CAD, to document ischaemia in patients with stable symptoms, to risk stratify patients with stable angina and an acute coronary syndrome (ACS), and to help choose treatment options and evaluate their efficacy. In practice, diagnostic and prognostic assessments are conducted in tandem rather than separately, and many of the investigations used for diagnosis also offer prognostic information [ 12 ]. In elective cases, the pre-test likelihood of disease is calculated based on symptoms, sex, and risk factors. Patients with an intermediate likelihood of obstructive CAD will undergo exercise testing while patients with a high likelihood undergo direct invasive examination. Boundaries defining intermediate likelihood of CAD are usually set at 10–90% or 20–80%. Because of high availability and low costs, an exercise electrocardiogram (ECG) is the most commonly used test to confirm the anginal nature of the symptoms and to provide objective evidence of inducible ischaemia. Its accuracy is limited however, especially in women [ 12 ]. Many of the patients with an intermediate likelihood of CAD post-exercise ECG are reclassified into higher or lower likelihood groups after non-invasive functional imaging.

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