Angiogenic potential of vitreous from proliferative diabetic retinopathy and eales' disease patients

Proliferative Diabetic Retinopathy (PDR) and Eales' Disease (ED) have different aetiologies although they share certain common clinical symptoms including pre-retinal neovascularization. Since there is a need to understand if the shared end-stage angiogenic pathology of PDR and ED is driven by common stimulating factors, we have studied the cytokines contained in vitreous from both patient groups and analyzed the angiogenic potential of these samples in vitro.

Vitreous samples from patients with PDR (n = 13) and ED (n = 5) were quantified for various cytokines using a cytokine biochip array and sandwich ELISA. An additional group of patients (n = 5) with macular hole (MH) was also studied for comparison. To determine the angiogenic potential of these vitreous samples, they were analyzed for their ability to induce tubulogenesis in human microvascular endothelial cells. Further, the effect of anti-VEGF (Ranibizumab) and anti-IL-6 antibodies were studied on vitreous-mediated vascular tube formation.

Elevated levels of IL-6, IL-8, MCP-1 and VEGF were observed in vitreous of both PDR and ED when compared to MH. PDR and ED vitreous induced greater levels of endothelial cell tube formation compared to controls without vitreous (P<0.05). When VEGF in vitreous was neutralized by clinically-relevant concentrations of Ranibizumab, tube length was reduced significantly in 5 of 6 PDR and 3 of 5 ED samples. Moreover, when treated with IL-6 neutralizing antibody, apparent reduction (71.4%) was observed in PDR vitreous samples.

We have demonstrated that vitreous specimens from PDR and ED patients share common elevations of pro-inflammatory and pro-angiogenic cytokines. This suggests that common cytokine profiles link these two conditions.

One size fits all: stability of metabolic scaling under warming and ocean acidification in echinoderms

Responses by marine species to ocean acidification (OA) have recently been shown to be modulated by external factors including temperature, food supply and salinity. However the role of a fundamental biological parameter relevant to all organisms, that of body size, in governing responses to multiple stressors has been almost entirely overlooked. Recent consensus suggests allometric scaling of metabolism with body size differs between species, the commonly cited 'universal' mass scaling exponent (b) of A3/4 representing an average of exponents that naturally vary. One model, the Metabolic-Level Boundaries hypothesis, provides a testable prediction: that b will decrease within species under increasing temperature. However, no previous studies have examined how metabolic scaling may be directly affected by OA. We acclimated a wide body-mass range of three common NE Atlantic echinoderms (the sea star Asterias rubens, the brittlestars Ophiothrix fragilis and Amphiura filiformis) to two levels of pCO(2) and three temperatures, and metabolic rates were determined using closed-chamber respirometry. The results show that contrary to some models these echinoderm species possess a notable degree of stability in metabolic scaling under different abiotic conditions; the mass scaling exponent (b) varied in value between species, but not within species under different conditions. Additionally, we found no effect of OA on metabolic rates in any species. These data suggest responses to abiotic stressors are not modulated by body size in these species, as reflected in the stability of the metabolic scaling relationship. Such equivalence in response across ontogenetic size ranges has important implications for the stability of ecological food webs.

Does childhood bullying lead to the development of psychotic symptoms? A meta-analysis and review of prospective studies

Purpose: Researchers have demonstrated associations between trauma and psychosis. Childhood trauma, in particular, appears to be an important determinant. Recently, bullying has become considered a traumatic experience in its own right. This review aims to analyse research with prospective designs, which will enable conclusions about whether or not bullying causes psychosis.

Methods: A systematic review of the literature was carried out independently by two reviewers. Eligibility and quality assessment criteria were applied. A meta-analysis and narrative synthesis were then completed.

Results: Ten studies met inclusion criteria. Four used data from the same large database, and were combined as one. The majority provided confirmation that bullying appears to cause later development of psychosis. A meta-analysis yielded an unadjusted odds ratio (OR) of 2.148 [95% confidence interval (CI) 1.140–4.044].

Conclusions: The studies reviewed here suggest that bullying does predict the later development of psychotic symptoms. What is lacking from the literature is adequate investigation into other potential mediating factors. The current review highlights the significant role of bullying within this complex interaction. Potential mediating variables are explored, including a dose–response effect for the severity and frequency of victimization. Suggestions for targeting intervention are also suggested alongside clinical implications and recommendations for future research.

Application of the pMHC Array to Characterise Tumour Antigen Specific T Cell Populations in Leukaemia Patients at Disease Diagnosis

Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC) tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV) and influenza (Flu)) and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1), MelanA, Wilms' Tumour (WT1) and tyrosinase). We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8-1.4 x 106). Fourteen of the twenty-six acute myeloid leukaemia (AML) patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3), tyrosinase (n = 3) and WT1126-134 (n = 1). One of the seven acute lymphocytic leukaemia (ALL) patients analysed had T cells that recognised the MUC1950-958 epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients.

A high-value, low-cost bubble continuous positive airway pressure system for low-resource settings:technical assessment and initial case reports

Acute respiratory infections are the leading cause of global child mortality. In the developing world, nasal oxygen therapy is often the only treatment option for babies who are suffering from respiratory distress. Without the added pressure of bubble Continuous Positive Airway Pressure (bCPAP) which helps maintain alveoli open, babies struggle to breathe and can suffer serious complications, and frequently death. A stand-alone bCPAP device can cost $6,000, too expensive for most developing world hospitals. Here, we describe the design and technical evaluation of a new, rugged bCPAP system that can be made in small volume for a cost-of-goods of approximately $350. Moreover, because of its simple design--consumer-grade pumps, medical tubing, and regulators--it requires only the simple replacement of a <$1 diaphragm approximately every 2 years for maintenance. The low-cost bCPAP device delivers pressure and flow equivalent to those of a reference bCPAP system used in the developed world. We describe the initial clinical cases of a child with bronchiolitis and a neonate with respiratory distress who were treated successfully with the new bCPAP device.

Urinary thrombomodulin levels were significantly higher following occupational exposure to chemicals, in the presence of dipstick protein, but not in the presence of dipstick blood

Currently, there are no biomarkers which can identify patients with an increased risk of developing urothelial cancer as a result of occupational chemical exposure. The aim of this study was to evaluate the relationships between final diagnosis and 22 biomarkers measured in urine, serum and plasma collected from 156 hematuric patients. Fourteen of the 80 patients (17.5%) with urothelial cancer and 13/76 (17.1%) of the controls were deemed to have a history of chemical exposure. We applied Fisher's exact tests to explore associations between chemical exposure and final diagnosis, and tumor stage and grade, where applicable; ANOVA and t-test to compare age across patients with and without chemical exposure; and Zelen's exact test to evaluate relationships across final diagnosis, chemical exposure and smoking. Following pre-selection of biomarkers using Lasso, we identified biomarkers with differential levels across patients with and without chemical exposure using Welch's t-test. Using a one-sided t-test and considering multiple testing using FDR, we observed that TM levels in urine were significantly higher in samples from patients with a history of chemical exposure regardless of their diagnosis as control or urothelial cancer (one-sided t-test, p_UC = 0.014 and p_CTL = 0.043); in the presence of dipstick protein and when urinary pH levels ≤ 6 (p = 0.003), but not in the presence of dipstick blood (p = 0.115). Urothelial cancer patients with a history of chemical exposure were significantly younger (64.1 years) than those without chemical exposure (70.2 years) (one-sided t-test p-value = 0.012); and their tumors were higher grade (Fisher's exact test; p = 0.008). There was a strong association between a history of chemical exposure and smoking in urothelial cancer patients (Zelen's exact test; p = 0.025). Elevated urinary thrombomodulin levels could have the potential to identify chemical exposure in hematuric patients at high risk of developing urothelial cancer.

The Buksh Museum of Hobby-Craft

This article describes the last of three architecture projects carried out over two years’ PhD research in the Indian city of Agra, completed in 2014. The projects aimed to expose ways that residents in the city’s historical Tajganj neighbourhoods had, over four centuries, constructed an urban topography that was meaningful to them. The final project the Buksh Museum of Hobby-Craft explored ways in which re-establishing a civic role for one building could enable those involved to reimagine the potential of this neglected urban district. This was done through assembling temporary additions to a ruined building.

The project was carried out with a local non-governmental organisation (NGO) and ran parallel to an urban regeneration scheme for Tajganj with which this NGO was involved. Several groups with different urban specialisms were involved in this scheme and were committed to fielding their own set of objectives within it: often these goals conflicted. The research project, isolated from these objectives, allowed participants to engage with the conflicting value sets in play, and explore ways of mediating between them without compromising any groups’ role in the regeneration scheme itself.

The HARPS-N Rocky Planet Search. I. HD 219134 b: A transiting rocky planet in a multi-planet system at 6.5 pc from the Sun

We know now from radial velocity surveys and transit space missions thatplanets only a few times more massive than our Earth are frequent aroundsolar-type stars. Fundamental questions about their formation history,physical properties, internal structure, and atmosphere composition are,however, still to be solved. We present here the detection of a systemof four low-mass planets around the bright (V = 5.5) and close-by (6.5pc) star HD 219134. This is the first result of the Rocky Planet Searchprogramme with HARPS-N on the Telescopio Nazionale Galileo in La Palma.The inner planet orbits the star in 3.0935 ± 0.0003 days, on aquasi-circular orbit with a semi-major axis of 0.0382 ± 0.0003AU. Spitzer observations allowed us to detect the transit of the planetin front of the star making HD 219134 b the nearest known transitingplanet to date. From the amplitude of the radial velocity variation(2.25 ± 0.22 ms-1) and observed depth of the transit(359 ± 38 ppm), the planet mass and radius are estimated to be4.36 ± 0.44 M⊕ and 1.606 ± 0.086R⊕, leading to a mean density of 5.76 ± 1.09 gcm-3, suggesting a rocky composition. One additional planetwith minimum-mass of 2.78 ± 0.65 M⊕ moves on aclose-in, quasi-circular orbit with a period of 6.767 ± 0.004days. The third planet in the system has a period of 46.66 ± 0.08days and a minimum-mass of 8.94 ± 1.13 M⊕, at0.233 ± 0.002 AU from the star. Its eccentricity is 0.46 ±0.11. The period of this planet is close to the rotational period of thestar estimated from variations of activity indicators (42.3 ± 0.1days). The planetary origin of the signal is, however, thepreferredsolution as no indication of variation at the corresponding frequency isobserved for activity-sensitive parameters. Finally, a fourth additionallonger-period planet of mass of 71 M⊕ orbits the starin 1842 days, on an eccentric orbit (e = 0.34 ± 0.17) at adistance of 2.56 AU.The photometric time series and radial velocities used in this work areavailable in electronic form at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr(ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/584/A72