The effect of lifestyle changes on results of 24-h ambulatory oesophageal pH monitoring

Twenty-four-hour pH monitoring is the 'gold standard' investigation of gastro-oesophageal reflux disease. It has been suggested that results may be influenced by lifestyle alteration during the study. The aim of this study was to determine the influence of lifestyle alteration and anxiety on outcome in pH monitoring.

Ages of 24 widespread tephras erupted since 30,000 years ago in New Zealand, with re-evaluation of the timing and palaeoclimatic implications of the Lateglacial cool episode recorded at Kaipo bog

Tephras are important for the NZ-INTIMATE project because they link all three records comprising the composite inter-regional stratotype developed for the New Zealand climate event stratigraphy (NZ-CES). Here we firstly report new calendar ages for 24 widespread marker tephras erupted since 30,000 calendar (cal.) years ago in New Zealand to help facilitate their use as chronostratigraphic dating tools for the NZ-CES and for other palaeoenvironmental and geological applications. The selected tephras comprise 12 rhyolitic tephras from Taupo, nine rhyolitic tephras from Okataina, one peralkaline rhyolitic tephra from Tuhua, and one andesitic tephra each from Tongariro and Egmont/Taranaki volcanic centres. Age models for the tephras were obtained using three methods: (i) C-based wiggle-match dating of wood from trees killed by volcanic eruptions (these dates published previously); (ii) flexible depositional modelling of a high-resolution C-dated age-depth sequence at Kaipo bog using two Bayesian-based modelling programs, Bacon and OxCal's P_Sequence function, and the IntCal09 data set (with SH offset correction-44±17yr); and (iii) calibration of C ages using OxCal's Tau_Boundary function and the SHCal04 and IntCal09 data sets. Our preferred dates or calibrated ages for the 24 tephras are as follows (youngest to oldest, all mid-point or mean ages of 95% probability ranges): Kaharoa AD 1314±12; Taupo (Unit Y) AD 232±10; Mapara (Unit X) 2059±118cal.yrBP; Whakaipo (Unit V) 2800±60cal.yrBP; Waimihia (Unit S) 3401±108cal.yrBP; Stent (Unit Q) 4322±112cal.yrBP; Unit K 5111±210cal.yrBP; Whakatane 5526±145cal.yrBP; Tuhua 6577±547cal.yrBP; Mamaku 7940±257cal.yrBP; Rotoma 9423±120cal.yrBP; Opepe (Unit E) 9991±160cal.yrBP; Poronui (Unit C) 11,170±115cal.yrBP; Karapiti (Unit B) 11,460±172cal.yrBP; Okupata 11,767±192cal.yrBP; Konini (bed b) 11,880±183cal.yrBP; Waiohau 14,009±155cal.yrBP; Rotorua 15,635±412cal.yrBP; Rerewhakaaitu 17,496±462cal.yrBP; Okareka 21,858±290cal.yrBP; Te Rere 25,171±964cal.yrBP; Kawakawa/Oruanui 25,358±162cal.yrBP; Poihipi 28,446±670cal.yrBP; and Okaia 28,621±1428cal.yrBP.Secondly, we have re-dated the start and end of the Lateglacial cool episode (climate event NZce-3 in theNZ-CES), previously referred to as the Lateglacial climate reversal, as defined at Kaipo bog in eastern North Island, New Zealand, using both Bacon and OxCal P_Sequence modelling with the IntCal09 data set. The ca1200-yr-long cool episode, indicated by a lithostratigraphic change in the Kaipo peat sequence to grey mudwith lowered carbon content, and a high-resolution pollen-derived cooling signal, began 13,739±125cal.yrBP and ended 12,550±140cal.yrBP (mid-point ages of the 95% highest posterior density regions, Bacon modelling). The OxCal modelling, generating almost identical ages, confirmed these ages. The Lateglacial cool episode (ca 13.8-12.6cal.kaBP) thus overlaps a large part of the entire Antarctic Cold Reversal chronozone (ca 14.1-12.4cal.kaBP or ca 14.6-12.8cal.kaBP), and an early part of the Greenland Stadial-1 (Younger Dryas) chronozone (ca 12.9-11.7cal.kaBP). The timing of the Lateglacial cool episode at Kaipo is broadly consistent with the latitudinal patterns in the Antarctic Cold Reversal signal suggested for the New Zealand archipelago from marine and terrestrial records, and with records from southern South America. © 2012 Elsevier Ltd.

miR-24 and miR-205 expression is dependent on HPV onco-protein expression in keratinocytes

A screen of microRNA (miRNA) expression following differentiation in human foreskin keratinocytes (HFKs) identified changes in several miRNAs, including miR-24 and miR-205. We investigated how expression of Human Papilloma Virus Type-16 (HPV16) onco-proteins E6 and E7 affected expression of miR-24 and miR-205 during proliferation and differentiation of HFKs. We show that the induction of both miR-24 and miR-205 observed during differentiation of HFKs is lost in HFKs expressing E6 and E7. We demonstrate that the effect on miR-205 is due to E7 activity, as miR-205 expression is dependent on pRb expression. Finally, we provide evidence that miR-24 effects in the cell may be due to targeting of cyclin dependent kinase inhibitor p27. In summary, these results indicate that expression of both miR-24 and miR-205 are impacted by E6 and/or E7 expression, which may be one mechanism by which HPV onco-proteins can disrupt the balance between proliferation and differentiation in keratinocytes.

Latanoprost for open-angle glaucoma (UKGTS): a randomised, multicentre, placebo-controlled trial

Background
Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo.

Methods
In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140.

Findings
We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28–0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug.

Interpretation
This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period

Truth at 24 frames a second? A working dialogue between a film-maker and a historical consultant about the making of The Enigma of Frank Ryan

We employ a practice-based methodology based on a ‘live’ film project to explore the different ways that film-makers and historians narrate the past. Through a case-study of the production and exhibition of a drama-documentary feature-film, The Enigma of Frank Ryan, on which both authors (film-maker Bell and historian McGarry) worked respectively as director and historical consultant, we explore a range of critical issues arising from our collaboration. Through a dialogue between a director and a historian, a model of good practice between historians and film-makers emerges.