Report of the committee on the Wills Legacy; with an extract from the will of the late James Wills and the ordinances for the management of the Wills hospital.

Report addressed: To the Select and Common Councils of Philadelphia. - p. 3.

E2F6: a member of the E2F family that does not modulate squamous differentiation

The inhibition of E2F has been demonstrated to be important in the initiation of squamous differentiation by two independent manners: promotion of growth arrest and the relief of the differentiation-suppressive properties of E2Fs. E2F6 is reported to behave as a transcriptional repressor of the E2F family. In this study, we examined the ability of E2F6 to act as the molecular switch required for E2F inhibition in order for keratinocytes to enter a terminal differentiation programme. Results demonstrated that whilst E2F6 was able to suppress E2F activity in proliferating keratinocytes, it did not modulate squamous differentiation in a differentiated keratinocyte. Furthermore, inhibition of E2F, by overexpressing E2F6, was not sufficient to sensitise either proliferating keratinocytes or the squamous cell carcinoma cell line, KJD-1/SV40, to differentiation-inducing agents. Significantly, although E2F6 could suppress E2F activity in proliferating cells, it could not inhibit proliferation of KJD-1/SV40 cells. These results demonstrate that E2F6 does not contain the domains required for modulation of squamous differentiation and imply isoform-specific functions for individual E2F family members. (C) 2004 Elsevier Inc. All rights reserved.

Endometrial and vaginal effects of low-dose estradiol delivered by vaginal ring or vaginal tablet

Aims The major aims of the study were to compare the safety of a continuous low-dose estradiol-releasing vaginal ring (ESTring) to that of a vaginal estradiol tablet (Vagifem®) on the endometrium and the relief of subjective symptoms and signs of urogenital estrogen deficiency. Quality of life and acceptability of treatment delivery were also assessed. Study design A prospective, randomized study in which women were assigned in a 2: 1 ratio to ESTring and Vagifem and followed for 12 months. The primary endpoint was endometrial safety, based on the results of ultrasound measurement of endometrial thickness and a progestogen challenge test at baseline and week 48. Efficacy was determined by subjective assessment of urogenital estrogen deficiency symptoms at baseline and weeks 3, 12, 24, 36 and 48 and assessment of signs of vaginal epithelial atrophy by the clinician at baseline, 12 and 48 weeks. In addition, pelvic floor strength, vaginal cytological evaluation and pH, bacteruria and patient acceptability were assessed. Quality of life was assessed using a menopause-specific quality-of-life questionnire and a 2-day bladder diary at baseline and 12 and 48 weeks. The comparability of the two groups was assessed using ANOVA, χ(2) or Fisher's exact tests. Results A total of 126 women were randomized to ESTring and 59 to Vagifem. There was no statistical difference between the groups in the alleviation of symptoms and signs of urogenital estrogen deficiency. Maturation indices increased in both groups, from generally atrophic at baseline to proliferative or highly proliferative at 48 weeks. After 48 weeks of treatment, there was no statistically significant difference in endometrial thickness between the two groups. A statistically smaller proportion of bleeding/spotting occurred in the ESTring group (n = 0) compared to the Vagifem users (n = 4). Estradiol and total estrone serum levels increased during treatment in both groups but remained within the normal postmenopausal range. General health status in both groups was unchanged but the urogenital component of health burden was significantly improved in both groups. Bladder diary variables showed no differences between treatment groups. Conclusion Equivalent endometrial safety and efficacy in the relief of the symptoms and signs of urogenital estrogen deficiency were demonstrated for the 12 months' use of a low-dose estradiol-releasing vaginal ring and a vaginal estradiol tablet.

Guidelines for the prevention, detection and management of people with chronic heart failure in Australia 2006

* Chronic heart failure (CHF) is found in 1.5%–2.0% of Australians. Considered rare in people aged less than 45 years, its prevalence increases to over 10% in people aged ≥ 65 years. * CHF is one of the most common reasons for hospital admission and general practitioner consultation in the elderly (≥ 70 years). * Common causes of CHF are ischaemic heart disease (present in > 50% of new cases), hypertension (about two-thirds of cases) and idiopathic dilated cardiomyopathy (around 5%–10% of cases). * Diagnosis is based on clinical features, chest x-ray and objective measurement of ventricular function (eg, echocardiography). Plasma levels of B-type natriuretic peptide (BNP) may have a role in diagnosis, primarily as a test for exclusion. Diagnosis may be strengthened by a beneficial clinical response to treatment(s) directed towards amelioration of symptoms. * Management involves prevention, early detection, amelioration of disease progression, relief of symptoms, minimisation of exacerbations, and prolongation of survival.

Transcriptome analysis of a respiratory Saccharomyces cerevisiae strain suggests the expression of its phenotype is glucose insensitive and predominantly controlled by Hap4, Cat8 and Mig1

BACKGROUND: We previously described the first respiratory Saccharomyces cerevisiae strain, KOY.TM6*P, by integrating the gene encoding a chimeric hexose transporter, Tm6*, into the genome of an hxt null yeast. Subsequently we transferred this respiratory phenotype in the presence of up to 50 g/L glucose to a yeast strain, V5 hxt1-7Delta, in which only HXT1-7 had been deleted. In this study, we compared the transcriptome of the resultant strain, V5.TM6*P, with that of its wild-type parent, V5, at different glucose concentrations. RESULTS: cDNA array analyses revealed that alterations in gene expression that occur when transitioning from a respiro-fermentative (V5) to a respiratory (V5.TM6*P) strain, are very similar to those in cells undergoing a diauxic shift. We also undertook an analysis of transcription factor binding sites in our dataset by examining previously-published biological data for Hap4 (in complex with Hap2, 3, 5), Cat8 and Mig1, and used this in combination with verified binding consensus sequences to identify genes likely to be regulated by one or more of these. Of the induced genes in our dataset, 77% had binding sites for the Hap complex, with 72% having at least two. In addition, 13% were found to have a binding site for Cat8 and 21% had a binding site for Mig1. Unexpectedly, both the up- and down-regulation of many of the genes in our dataset had a clear glucose dependence in the parent V5 strain that was not present in V5.TM6*P. This indicates that the relief of glucose repression is already operable at much higher glucose concentrations than is widely accepted and suggests that glucose sensing might occur inside the cell. CONCLUSION: Our dataset gives a remarkably complete view of the involvement of genes in the TCA cycle, glyoxylate cycle and respiratory chain in the expression of the phenotype of V5.TM6*P. Furthermore, 88% of the transcriptional response of the induced genes in our dataset can be related to the potential activities of just three proteins: Hap4, Cat8 and Mig1. Overall, our data support genetic remodelling in V5.TM6*P consistent with a respiratory metabolism which is insensitive to external glucose concentrations.

Application of nanoimprinting technique for fabrication of trifocal diffractive lens with sine-like radial profile

The fabrication of submicron-height sine-like relief of a trifocal diffractive zone plate using a nanoimprinting technique is studied. The zone plate is intended for use in combined trifocal diffractive-refractive lenses and provides the possibility to form trifocal intraocular lenses with predetermined light intensity distribution between foci. The optical properties of the designed zone plate having the optical powers 3 D, 0, -3D in the three main diffraction orders are theoretically and experimentally investigated. The results of the theoretical investigations are in good agreement with experimental measurements. The effects of the pupil size (lens diameter) as well as the wavelength-dependent behavior of the zone plate are also discussed.

Distribution of Diatoms and Development of Diatom-Based Models for Inferring Salinity and Nutrient Concentrations in Florida Bay and Adjacent Coastal Wetlands of South Florida (USA)

The composition and distribution of diatom algae inhabiting estuaries and coasts of the subtropical Americas are poorly documented, especially relative to the central role diatoms play in coastal food webs and to their potential utility as sentinels of environmental change in these threatened ecosystems. Here, we document the distribution of diatoms among the diverse habitat types and long environmental gradients represented by the shallow topographic relief of the South Florida, USA, coastline. A total of 592 species were encountered from 38 freshwater, mangrove, and marine locations in the Everglades wetland and Florida Bay during two seasonal collections, with the highest diversity occurring at sites of high salinity and low water column organic carbon concentration (WTOC). Freshwater, mangrove, and estuarine assemblages were compositionally distinct, but seasonal differences were only detected in mangrove and estuarine sites where solute concentration differed greatly between wet and dry seasons. Epiphytic, planktonic, and sediment assemblages were compositionally similar, implying a high degree of mixing along the shallow, tidal, and storm-prone coast. The relationships between diatom taxa and salinity, water total phosphorus (WTP), water total nitrogen (WTN), and WTOC concentrations were determined and incorporated into weighted averaging partial least squares regression models. Salinity was the most influential variable, resulting in a highly predictive model (r apparent 2  = 0.97, r jackknife 2  = 0.95) that can be used in the future to infer changes in coastal freshwater delivery or sea-level rise in South Florida and compositionally similar environments. Models predicting WTN (r apparent 2  = 0.75, r jackknife 2  = 0.46), WTP (r apparent 2  = 0.75, r jackknife 2  = 0.49), and WTOC (r apparent 2  = 0.79, r jackknife 2  = 0.57) were also strong, suggesting that diatoms can provide reliable inferences of changes in solute delivery to the coastal ecosystem.

Role of membrane lipids in the regulation of erythrocytic oxygen-transport function in cardiovascular diseases

The composition and condition of membrane lipids, the morphology of erythrocytes, and hemoglobin distribution were explored with the help of laser interference microscopy (LIM) and Raman spectroscopy. It is shown that patients with cardiovascular diseases (CVD) have significant changes in the composition of their phospholipids and the fatty acids of membrane lipids. Furthermore, the microviscosity of the membranes and morphology of the erythrocytes are altered causing disordered oxygen transport by hemoglobin. Basic therapy carried out with the use of antiaggregants, statins, antianginals, beta-blockers, and calcium antagonists does not help to recover themorphofunctional properties of erythrocytes. Based on the results the authors assume that, for the relief of the ischemic crisis and further therapeutic treatment, it is necessary to include, in addition to cardiovascular disease medicines, medication that increases the ability of erythrocytes’ hemoglobin to transport oxygen to the tissues. We assume that the use of LIM and Raman spectroscopy is advisable for early diagnosis of changes in the structure and functional state of erythrocytes when cardiovascular diseases develop.

Anti-nociceptive and anti-inflammatory potentials of fractions from the extract of Tetracarpidium conophorum leaf in rats and mice

Tetracarpidium conophorum (TC) (Euphorbiaceae) is a perennial woody climbing shrub in low bush forest of some parts of West Africa and used among the natives for relief of ailments accompanying pain and inflammation. In this study, the analgesic and anti-inflammatory effects of the methanolic extract (METC) and fractions (ethyl acetate, F1 and n-hexane, F2) of Tetracarpidium conophorum leaf were evaluated in rat and mice. The analgesic activity was evaluated using acetic acid-induced writhing, formalin-induced paw licking and hot plate test models. Carrageenan-induced paw oedema was used to assess anti-inflammatory activity in rats. The mechanism of action of (TC) was explored by the use of naloxone, a non-selective opioid receptor blocker. The highest analgesic effect was observed in F2 extract at 57.21% inhibition and was further studied on various analgesic and anti-inflammatory models in graded doses. F2 significantly inhibited the late phase of formalin-induced paw licking and prolong hot plate latency at 55±1°C. The n-hexane fraction also significantly inhibited carrageenan-induced paw oedema in rats at 100 and 200mg/kg doses significantly (p< 0.001) and reduced paw licking response by 85.08% compared with control. Naloxone, an opioid receptor antagonist, did not significantly affect the changes observed with n-hexane fraction, thus ruling out the possibility of the involvement of opioid receptors in the analgesic actions of Tetracarpidium conophorum. Phytochemical screening showed that the leaf extracts contain alkaloids, tannins, saponins and cardenolides. The investigations showed that Tetracarpidium conophorum possesses significant anti-nociceptive and anti-inflammatory activities that should be explored.

Flexible endoscopic treatment of Zenker's diverticulum: thirteen years' experience in Spain

Introduction: Flexible endoscopic treatment is one of the alternative approaches for the management of Zenker's diverticum. The present paper shows our short-term and long-term results with flexible endoscopic cricopharyngeal myotomy/septotomy. Patients and methods: A retrospective analysis of our experience in patients with Zenker's diverticulum treated using a flexible endoscope, assisted by a flexible diverticuloscope, between 2002 and 2015. Myotomy/septotomy was performed with a needle-knife papillotome under deep sedation or general anesthesia. Results: Among the 64 patients treated, two died within 10 days of surgery from causes not directly related to the procedure, and one presented with pharyngo-esophageal perforation, which recovered with conservative management at 47 days after admission. Four additional patients were lost to short-term follow-up. Among the 57 remaining patients, 52 had complete relief of dysphagia after 6 weeks. Eleven of these had recurrent symptoms on the mid and the long term. Eight were retreated with the same flexible endoscopic technique, one with a hybrid endoscopic approach, one with classical open surgery and one refused retreatment. After a mean follow-up of 2 years and a half, 33 of 37 patients reported absent or minimal dysphagia, controllable with punctual dietary restrictions. Conclusions: Flexible endoscopic treatment for Zenker's diverticulum is effective and safe. It represents an option on an equal footing to rigid endoscopy and classical open surgery and may also be used when the latter two are technically impracticable or contraindicated.

Hospital without dyspnea: Rationale and design of a multidisciplinary intervention

Dyspnea is a common and disabling symptom of respiratory and heart diseases, which is growing in incidence. During hospital admission, breathlessness is under-diagnosed and under-treated, although there are treatments available for controlling the symptom. We have developed a tailored implementation strategy directed to medical staff to promote the application of these pharmacological and non-pharmacological tools in dealing with dyspnea. The primary aim is to decrease the rate of patients that do not receive an adequate relief of dyspnea. This is a four-stage quasi-experimental study. The intervention consists in two teaching talks that will be taught in Cardiology and Respiratory Medicine Departments. The contents will be prepared by Palliative Care specialists, based on available tools for management of dyspnea and patients' needs. A cross-sectional study of dyspnea in hospitalized patients will be performed before and after the intervention to ascertain an improvement in dyspnea intensity due to changes in medical practices. The last phase consists in the creation of consensus protocols for dyspnea management based in our experience. The results of this study are expected to be of great value and may change clinical practice in the near future and promote a changing for the better of dyspnea care.

The response to dryness in Australia

The drought Australia now faces is leading to shifts in the perception of the continent, of Australians and the world. The ideals of lush green landscapes are making way for landscape designs in which dryness is a quality of the design. On a map of the world, Australia is enormous, and seems empty because development is concentrated around its edges. Its heart must be red, in the cultural projections of the world from images of Uluru, 'the rock', set in a flat desert with no relief. Of course the country is not really all desert - surely? - with low shrubs pretty much throughout. Inhabitation seems to cling to the edges where teh continent feels microclimatic effects from the adjacent oceans and edging mountain ranges, which screen the population from the real state of the environment - dry, harsh, amazing and unique. Australia is rightly proud of this harsh difference from its edges, but prefers the harshness to be 'out there'. At the moment however, the country is pretty much universally in drought, and the contrast between green and brown, that it has celebrated, even built its identity around, is disappearing to become brown throughout. Without the browning of Australia, some areas, such as tropical Queensland, are having their designed public landscapes and gardens revealed as an elaborate mythology, a landscape fraud.

Pre-eruptive uplift in the Emeishan? [Correspondence]

In their correspondence, He and colleagues question our conclusion of little or no uplift preceding Emeishan volcanism that we reported in our letter1. Debate concerns the nature of the contact between the Maokou limestone and Emeishan volcanics, the depositional environment and volumetric significance of mafic hydromagmatic deposits (MHDs), and evidence for symmetrical domal thinning. MHDs in the Daqiao section are separated from the Maokou limestone by 100 m of subaerial basaltic lavas, but elsewhere MHDs — previously interpreted as basal conglomerates2, 3 — directly overlie the Maokou2, 3. MHDs thus feature strongly in basal sections of the Emeishan lava succession, as also recently shown4 elsewhere in the Emeishan. An irregular surface at the top of the Maokou limestone has been interpreted as an erosional unconformity2, 3, but clastic deposits presented as evidence of this erosion2, 3 are MHDs produced by explosive magma–water interaction1. A clear demonstration that this irregular top surface is an erosional truncation of limestone reef facies (slope/rim, flat, lagoonal) is currently lacking, but is critical because reefs and carbonate platforms show considerable natural relief of tens of metres. The persistent hot, wet climate since the Oligocene has produced well-developed weathering profiles on exposed Palaeozoic marine sedimentary sequences5, but weathering and karst relief of the uppermost Maokou limestone underlying the flood basalts have not been properly documented, nor shown to be of middle Permian age and immediately preceding emplacement of the large igneous province.

Melbourne on film dossier: 'Ghost Rider'

Despite being set in an unnamed Texan city, Ghost Rider (Mark Steven Johnson, 2007) was a landmark film for Melbourne. It was the first international production to be made at the Central City (now Docklands) Studios, much to the relief of the heavily-invested state government. And it demonstrated to the world (or more importantly, to producers resident in a small part of southern California), that the city was willing and available to be made over and made up to fit even (especially!) the most stupid filmmaking fantasies. Announcing the imminent arrival of the production in October 2004, the Herald Sun boldly predicted that '[c]ity lanes, Telstra Dome and the Yarra River will be the stars of the new action film'. In fact Melbourne is, as the filmmakers intended, (virtually) unidentifiable onscreen. For the Victorian State government, Ausfilm, Film Victoria and the Melbourne Film Office, this lack of specificity was something to be celebrated; a few months before Ghost Rider went in to production, the then State Minister for Innovation, John Brumby, declared that 'it's almost inconceivable that [Ghost Rider] won't put Melbourne on the map internationally'.

Israel Museum Jerusalem Coin

Obverse: Silver 5 Lirot coin. Replica of the capital and part of a pillar, of the 7th century BCE found at Ramat Rachel on the outskirts of Jerusalem. Reverse: A stylized relief of the buildings of Israeli Museum in Jerusalem.