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Abstract Rudolf Schuessler has argued that sixteenth-century thinkers developed a concept of equal probability that was virtually absent before 1500 and that may have contributed to the birth of mathematical probability shortly after 1650. This note uses additional textual evidence to argue that the concept of equal probability was in fact generally available to medieval thinkers. It is true that ascriptions of equal probability are comparatively rare in medieval texts, but this can be explained without positing a conceptual blind spot.

Abstract Two recent publications have greatly increased the amount of Wyclif available in translation: the Trialogus, translated by Stephen Lahey, and a thematic anthology translated by Stephen Penn. This review article documents the failings that make these translations worse than useless. A post mortem leads the author to claim that the publication of these volumes, the first of which has already been warmly received, is a sign of a gathering crisis in medieval studies, and one that we should take steps to avert.

AbstractFrancis of Marchia (c. 1290-1344) is said to have challenged Aristotelian orthodoxy by uniting the celestial and terrestrial realms in a way that has important implications for the practice of natural philosophy. But this over-looks Marchia's vital distinction between bare potentiality, which is actualizable only by God, and natural potency, which is the concern of the natural philosopher. If due attention is paid to this distinction and to its implications, Marchia's position no longer seems to be revolutionary.

Only the hardiest of readers will slog through the sections on truth conditions (§4.5) and validity (§4.6) that pave the way for a completeness proof that \"may be skipped without loss of continuity\" (§4.7), and yet the semantic technicalities that they introduce are mercilessly relied upon in chapter 5 (and again in chapters 8-10).The Achilles heel, though, comes in chapter 8, where Parsons expands Linguish to cover the \"relatives\" (anaphoric expressions) that will serve as bound variables.[...]following a suggestion of Reinhard Hülsen's, Parsons takes \"singled supposition\" from the standard theory of reflexive pronouns-or rather, from a version of it that he extracts from Marsilius of Inghen and diagnoses via \"reverse engineering\" in Burley, Ockham, and Buridan (§8.2)-and applies it to relatives in general.

Globally, most patients with hypertension are treated with monotherapy, and control rates are poor because monotherapy only reduces blood pressure by around 9/5 mm Hg on average. There is a pressing need for blood pressure-control strategies with improved efficacy and tolerability. We aimed to assess whether ultra-low-dose combination therapy could meet these needs. We did a randomised, placebo-controlled, double-blind, crossover trial of a quadpill—a single capsule containing four blood pressure-lowering drugs each at quarter-dose (irbesartan 37·5 mg, amlodipine 1·25 mg, hydrochlorothiazide 6·25 mg, and atenolol 12·5 mg). Participants with untreated hypertension were enrolled from four centres in the community of western Sydney, NSW, Australia, mainly by general practitioners. Participants were randomly allocated by computer to either the quadpill or matching placebo for 4 weeks; this treatment was followed by a 2-week washout, then the other study treatment was administered for 4 weeks. Study staff and participants were unaware of treatment allocations, and masking was achieved by use of identical opaque capsules. The primary outcome was placebo-corrected 24-h systolic ambulatory blood pressure reduction after 4 weeks and analysis was by intention to treat. We also did a systematic review of trials evaluating the efficacy and safety of quarter-standard-dose blood pressure-lowering therapy against placebo. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614001057673. The trial ended after 1 year and this report presents the final analysis. Between November, 2014, and December, 2015, 55 patients were screened for our randomised trial, of whom 21 underwent randomisation. Mean age of participants was 58 years (SD 11) and mean baseline office and 24-h systolic and diastolic blood pressure levels were 154 (14)/90 (11) mm Hg and 140 (9)/87 (8) mm Hg, respectively. One individual declined participation after randomisation and two patients dropped out for administrative reasons. The placebo-corrected reduction in systolic 24-h blood pressure with the quadpill was 19 mm Hg (95% CI 14–23), and office blood pressure was reduced by 22/13 mm Hg (p<0·0001). During quadpill treatment, 18 (100%) of 18 participants achieved office blood pressure less than 140/90 mm Hg, compared with six (33%) of 18 during placebo treatment (p=0·0013). There were no serious adverse events and all patients reported that the quadpill was easy to swallow. Our systematic review identified 36 trials (n=4721 participants) of one drug at quarter-dose and six trials (n=312) of two drugs at quarter-dose, against placebo. The pooled placebo-corrected blood pressure-lowering effects were 5/2 mm Hg and 7/5 mm Hg, respectively (both p<0·0001), and there were no side-effects from either regimen. The findings of our small trial in the context of previous randomised evidence suggest that the benefits of quarter-dose therapy could be additive across classes and might confer a clinically important reduction in blood pressure. Further examination of the quadpill concept is needed to investigate effectiveness against usual treatment options and longer term tolerability. National Heart Foundation, Australia; University of Sydney; and National Health and Medical Research Council of Australia.

Thermal injury induces concurrent inflammatory and immune dysfunction, which is associated with adverse clinical outcomes. However, these effects in the pediatric population are less studied and there is no standard method to identify those at risk for developing infections. Our goal was to better understand immune dysfunction and identify soluble protein markers following pediatric thermal injury. Further we wanted to determine which early inflammatory, soluble, or immune function markers are most predictive of the development of nosocomial infections (NI) after burn injury. We performed a prospective observational study at a single American Burn Association-verified Pediatric Burn Center. A total of 94 pediatric burn subjects were enrolled and twenty-three of those subjects developed a NI with a median time to diagnosis of 8 days. Whole blood samples, collected within the first 72 hours after injury, were used to compare various markers of inflammation, immune function, and soluble proteins between those who recovered without developing an infection and those who developed a NI after burn injury. Within the first three days of burn injury, innate and adaptive immune function markers (ex vivo lipopolysaccharide-induced tumor necrosis factor alpha production capacity, and ex vivo phytohemagglutinin-induced interleukin-10 production capacity, respectively) were decreased for those subjects who developed a subsequent NI. Further analysis of soluble protein targets associated with these pathways displayed significant increases in soluble CD27, BTLA, and TIM-3 for those who developed a NI. Our findings indicate that suppression of both the innate and adaptive immune function occurs concurrently within the first 72 hours following pediatric thermal injury. At the same time, subjects who developed NI have increased soluble protein biomarkers. Soluble CD27, BTLA, and TIM-3 were highly predictive of the development of subsequent infectious complications. This study identifies early soluble protein makers that are predictive of infection in pediatric burn subjects. These findings should inform future immunomodulatory therapeutic studies.