Human response to vibration in residential environments (NANR209), technical report 2: measurement of response

Based on a review of the literature and the best practice guidance available, a social survey questionnaire was developed to measure residents’ self-reported annoyance and to provide data suitable for establishing exposure-response relationships between levels of annoyance and levels of vibration. The development of the questionnaire was influenced by a number of previous studies such as: the social survey questionnaire developed for the NANR172 Pilot Study of this research (Defra, 2007); best practice guidelines for the development of socio-acoustic surveys issued by ICBEN and presented in the current International Standard (Fields et al., 2001; ISO/TS 15666:2003); the Nordtest Method (2001) for the development of socio-vibration surveys, and a peer review of the social survey questionnaire by international experts in the field. In order to avoid influencing responses and reasons for participation in the research, the survey was introduced as a survey of neighbourhood satisfaction. The questionnaire design, through the use of sections, enables new sections to be added to the questionnaire so that specific vibration sources can be investigated in more depth. In addressing the ‘response’ component in the ‘exposure-response’ relationship, the questionnaire was designed to yield interval-level measurement data suitable for analysis with vibration measurement data via two response scales: the five-point semantic and the eleven-point numerical scales. This decision was largely founded upon the ability of the two scales to meet the criteria established by ICBEN (Fields et al., 2001) for socio-acoustic survey design. Detailed procedures were documented, following the field trial of the questionnaire, in terms of the role of the interviewer, the recording of information and the transfer of the data to the relevant database for subsequent analysis and to inform the vibration team responsible for the ‘exposure’ component of this research project

LDLR-Gene therapy for familial hypercholesterolaemia: Problems, progress, and perspectives

Coronary artery diseases (CAD) inflict a heavy economical and social burden on most populations and contribute significantly to their morbidity and mortality rates. Low-density lipoprotein receptor (LDLR) associated familial hypercholesterolemia (FH) is the most frequent Mendelian disorder and is a major risk factor for the development of CAD. To date there is no cure for FH. The primary goal of clinical management is to control hypercholesterolaemia in order to decrease the risk of atherosclerosis and to prevent CAD. Permanent phenotypic correction with single administration of a gene therapeutic vector is a goal still needing to be achieved. The first ex vivo clinical trial of gene therapy in FH was conducted nearly 18 years ago. Patients who had inherited LDLR gene mutations were subjected to an aggressive surgical intervention involving partial hepatectomy to obtain the patient's own hepatocytes for ex vivo gene transfer with a replication deficient LDLR-retroviral vector. After successful re-infusion of transduced cells through a catheter placed in the inferior mesenteric vein at the time of liver resection, only low-level expression of the transferred LDLR gene was observed in the five patients enrolled in the trial. In contrast, full reversal of hypercholesterolaemia was later demonstrated in in vivo preclinical studies using LDLR-adenovirus mediated gene transfer. However, the high efficiency of cell division independent gene transfer by adenovirus vectors is limited by their short-term persistence due to episomal maintenance and the cytotoxicity of these highly immunogenic viruses. Novel long-term persisting vectors derived from adeno-associated viruses and lentiviruses, are now available and investigations are underway to determine their safety and efficiency in preparation for clinical application for a variety of diseases. Several novel non-viral based therapies have also been developed recently to lower LDL-C serum levels in FH patients. This article reviews the progress made in the 18 years since the first clinical trial for gene therapy of FH, with emphasis on the development, design, performance and limitations of viral based gene transfer vectors used in studies to ameliorate the effects of LDLR deficiency

Breaking the Silence: The role of gossip in organizational culture

From the early 1980s, the number of studies pertaining to organizational culture expanded considerably to the point where it could reasonably be argued that the field had reached a level of maturity. Perhaps indicative of this maturity was the publication of the first handbook of organizational culture and climate (Ashkanasy et al. 2000). The commencement of academic interest in the topic of organizational culture generally coincided with the publication of two books mainly aimed at practitioners—Peters and Waterman’s, In search of excellence (1982) and Deal and Kennedy’s, Corporate cultures: the rites and rituals of corporate life (1982). This is not to suggest that these books account exclusively for the intellectual curiosity generated in the function and purpose of culture for an organization as there were well-known examples which had earlier sought to address the issue of organizational cultures (e.g. Pettigrew 1979). Nonetheless, these tomes were influential in raising interest in, and scope for, research on organizational culture

Old high-redshift galaxies and primordial density fluctuation spectra

We have discovered a population of extremely red galaxies at $z\simeq 1.5$ which have apparent stellar ages of \gs 3 Gyr, based on detailed spectroscopy in the rest-frame ultraviolet. In order for galaxies to have existed at the high collapse redshifts indicated by these ages, there must be a minimum level of power in the density fluctuation spectrum on galaxy scales. This paper compares the required power with that inferred from other high-redshift populations. If the collapse redshifts for the old red galaxies are in the range $z_c\simeq 6$ -- 8, there is general agreement between the various tracers on the required inhomogeneity on 1-Mpc scales. This level of small-scale power requires the Lyman-limit galaxies to be approximately $\nu\simeq 3.0$ fluctuations, implying a very large bias parameter $b\simeq 6$. The high collapse redshifts of the red galaxies as deduced from gravitational collapse provides independent support for the ages estimated from their stellar populations. Such early-forming galaxies are rare, and their contribution to the cosmological stellar density is consistent with an extrapolation to higher redshifts of the star-formation rate measured at $z<5$; there is no evidence for a general era of spheroid formation at extreme redshifts.Comment: 9 Pages MNRAS in press. Uses MNRAS Plain TeX macro

NICMOS Imaging of the Dusty Microjansky Radio Source VLA J123642+621331 at z = 4.424

We present the discovery of a radio galaxy at a likely redshift of z = 4.424 in one of the flanking fields of the Hubble Deep Field. Radio observations with the VLA and MERLIN centered on the HDF yielded a complete sample of microjansky radio sources, of which about 20% have no optical counterpart to I < 25 mag. In this Letter, we address the possible nature of one of these sources, through deep HST NICMOS images in the F110W (J) and F160W (H) filters. VLA J123642+621331 has a single emission line at 6595-A, which we identify with Lyman-alpha at z = 4.424. We argue that this faint (H = 23.9 mag), compact (r = 0.2 arcsec), red (I - K = 2.0) object is most likely a dusty, star-forming galaxy with an embedded active nucleus.Comment: Accepted for publication in Astrophysical Journal Letters. 11 pages, 4 figures, uses aastex v5.0 and psfi

Intra-amniotic delivery of CFTR-expressing adenovirus does not reverse cystic fibrosis phenotype in inbred CFTR-knockout mice

This article is available open access through the publisher’s website at the link below. Copyright © 2008 The American Society of Gene Therapy.Due to its early onset and severe prognosis, cystic fibrosis (CF) has been suggested as a candidate disease for in utero gene therapy. In 1997, a study was published claiming that to how transient prenatal expression of CF transmembrane conductance regulator (CFTR) from an in utero –injected adenovirus vector could achieve permanent reversal of the CF intestinal pathology in adult CF knockout mice, despite the loss of CFTR transgene expression by birth. This would imply that the underlying cause of CF is a prenatal defect for which lifelong cure can be achieved by transient prenatal expression of CFTR. Despite criticism at the time of publication, no independent verification of this contentious finding has been published so far. This is vital for the development of future therapeutic strategies as it may determine whether CF gene therapy should be performed prenatally or postnatally. We therefore reinvestigated this finding with an identical adenoviral vector and a knockout CF mouse line (CftrtmlCam) with a completely inbred genetic background to eliminate any effects due to genetic variation. After delivery of the CFTR-expressing adenovirus to the fetal mouse, both vector DNA and transgenic CFTR expression were detected in treated animals postpartum but statistically no significant difference in survival was observed between the Cftr–/– mice treated with the CFTR-adenovirus and those treated with the control vector.Sport Aiding Medical Research for Kids, the Cystic Fibrosis Trust, and the Katharine Dormandy Trust

Human response to vibration in residential environments (NANR209), executive summary

The aim of the Defra-funded project NANR209 ‘Human response to vibration in residential environments’ was to develop exposure-response relationships for vibration experienced in residential environments from sources outside of the residents’ control. The project was performed at the University of Salford between January 2008 and March 2011. The final report was published on the Defra website on 6th September 2012. The NANR209 Final Report consists of the following documents: • Executive summary • Final project report • Technical report 1: Measurement of vibration exposure • Technical report 2: Measurement of response • Technical report 3: Calculation of vibration exposure • Technical report 4: Measurement and calculation of noise exposure • Technical report 5: Analysis of the social survey findings • Technical report 6: Determination of exposure-response relationships This document is the Executive summary

A Mesolithic settlement site at Howick, Northumberland: a preliminary report

Excavations at a coastal site at Howick during 2000 and 2002 have revealed evidence for a substantial Mesolithic settlement and a Bronze Age cist cemetery. Twenty one radiocarbon determinations of the earlier eighth millennium BP (Cal.) indicate that the Mesolithic site is one of the earliest known in northern Britain. An 8m core of sediment was recovered from stream deposits adjacent to the archaeological site which provides information on local environmental conditions. Howick offers a unique opportunity to understand aspects of hunter-gatherer colonisation and settlement during a period of rapid palaeogeographical change around the margins of the North Sea basin, at a time when it was being progressively inundated by the final stages of the postglacial marine transgression. The cist cemetery will add to the picture of Bronze Age occupation of the coastal strip and again reveals a correlation between the location of Bronze Age and Mesolithic sites which has been observed elsewhere in the region