Natural history of falls in an incident cohort of Parkinson’s disease: early evolution, risk and protective features

The natural history of falls in early Parkinson’s disease (PD) is poorly understood despite the profound effect of falls on outcome. The primary aim of this study was to describe the natural history of falls, and characterise fallers over 54 months in 99 newly diagnosed people with PD. Seventy-nine (79.7%) participants fell over 54 months and 20 (20.3%) remained falls-naïve. Twenty six (26.2%) reported retrospective falls at baseline. Gait outcomes, disease severity and self-efficacy significantly discriminated across groups. Subjective cognitive complaints emerged as the only significant cognitive predictor. Without exception, outcomes were better for non-fallers compared with fallers at any time point. Between group differences for 54 month fallers and non-fallers were influenced by the inclusion of retrospective fallers and showed a broader range of discriminant characteristics, notably stance time variability and balance self-efficacy. Single fallers (n = 7) were significantly younger than recurrent fallers (n = 58) by almost 15 years (P = 0.013). Baseline performance in early PD discriminates fallers over 54 months, thereby identifying those at risk of falls. Clinical profiles for established and emergent fallers are to some extent distinct. These results reiterate the need for timely interventions to improve postural control and gait

Natural history of falls in an incident cohort of Parkinson’s disease: early evolution, risk and protective features

The natural history of falls in early Parkinson’s disease (PD) is poorly understood despite the profound effect of falls on outcome. The primary aim of this study was to describe the natural history of falls, and characterise fallers over 54 months in 99 newly diagnosed people with PD. Seventy-nine (79.7%) participants fell over 54 months and 20 (20.3%) remained falls-naïve. Twenty six (26.2%) reported retrospective falls at baseline. Gait outcomes, disease severity and self-efficacy significantly discriminated across groups. Subjective cognitive complaints emerged as the only significant cognitive predictor. Without exception, outcomes were better for non-fallers compared with fallers at any time point. Between group differences for 54 month fallers and non-fallers were influenced by the inclusion of retrospective fallers and showed a broader range of discriminant characteristics, notably stance time variability and balance self-efficacy. Single fallers (n = 7) were significantly younger than recurrent fallers (n = 58) by almost 15 years (P = 0.013). Baseline performance in early PD discriminates fallers over 54 months, thereby identifying those at risk of falls. Clinical profiles for established and emergent fallers are to some extent distinct. These results reiterate the need for timely interventions to improve postural control and gait

A short note on Variograms and Correlograms

Hihm notat nr 1, 2011Norsk: engighet for å øke forståelsen av dataemne, men terminologi avviker. Dette skriftet belyser sammenhenger og forskjeller mellom korrelogrammer og variogrammer. De kan begge sees som en dekomposisjon av seriens empiriske varians. Belyst med kursutviklingen på Oslo Børs sin hovedindeks de siste 5 år, vises en innovativ bruk av konturkart.English: Time series data are of great importance especially to economists and geologists. Both communities use a graphical display of time series auto dependence to help them interpret the data but their terminology differs. This short note shows the relationship between correlograms and variograms and describes their differences. They can both be derived from a decomposition of mean square error. Using the Oslo Stock Exchange index for the last five years, the data are illustrated in a novel use of a contour map

Establishing a robust two-step cloning strategy for the generation of cell lines with a high probability of monoclonality

A regulatory requirement for the production of therapeutic proteins from mammalian cells is that the production cell line is clonal, that is, derived from a single progenitor cell. It is therefore standard procedure to include at least one cloning step during the development of a recombinant cell line for therapeutic protein production. Numerous techniques can be employed for cloning cell lines, but regardless of the cloning method used there should be appropriate evidence to support that the method is fit for purpose. A point highlighted by the increasing interest from regulatory bodies regarding the cloning method used and the probability of monoclonality (P(monoclonality)) achieved during cell line development (CLD). FUJIFILM Diosynth Biotechnologies have thoroughly considered the cloning approach used during CLD: A two-step cloning strategy employed which combines the ClonePix™ as a cloning and screening tool followed by a second cloning step using the industrially accepted method of limiting dilution cloning will be discussed. A collaboration with statisticians led to the development of a method to estimate the resulting P(monoclonality) of cell lines generated using the ClonePix™ and experimental data to support this statistical method was generated, thereby ensuring that the ClonePix™ cloning step is robust. We will highlight the challenges of using the ClonePix™ for a single round of cloning and the advantages of combining it with a second cloning step. We will demonstrate how we achieve a minimum probability of monoclonality of ≥99.78% and typically achieve a P(monoclonality) of 99.9% using a two-step cloning strategy

Time-dependent changes in postural control in early Parkinson’s disease: what are we missing?

Impaired postural control (PC) is an important feature of Parkinson’s disease (PD), but optimal testing protocols are yet to be established. Accelerometer-based monitors provide objective measures of PC. We characterised time-dependent changes in PC in people with PD and controls during standing, and identified outcomes most sensitive to pathology. Thirty-one controls and 26 PD patients were recruited: PC was measured with an accelerometer on the lower back for 2 minutes (mins). Preliminary analysis (autocorrelation) that showed 2 seconds (s) was the shortest duration sensitive to changes in the signal; time series analysis of a range of PC outcomes was undertaken using consecutive 2-s windows over the test. Piecewise linear regression was used to fit the time series data during the first 30 s and the subsequent 90 s of the trial. PC outcomes changed over the 2 mins, with the greatest change observed during the first 30 s after which PC stabilised. Changes in PC were reduced in PD compared to controls, and Jerk was found to be discriminative of pathology. Previous studies focusing on average performance over the duration of a test may miss time-dependent differences. Evaluation of time-dependent change may provide useful insights into PC in PD and effectiveness of intervention

The changing role of the local news media in enabling citizens to engage in local democracies

Using Leeds City Council in the United Kingdom as a case study, we analyse comparatively the changing role of local journalism in the public communications and engagement strategies of local government. Drawing on over 20 semi-structured interviews with elected politicians, Council strategists, mainstream journalists, and citizen journalists, the article explores perceptions of the mainstream news media's role versus new modes of communication in engaging and communicating with citizens. We evaluate the Council's perceptions of its online and offline practices of engagement with different publics, and focus in particular on their interactions with journalists, the news media, and citizen journalists. The article considers how moves towards digital modes of engagement are changing perceptions of the professional role orientations of journalists in mediating between the Council and the general public

Antibacterial activities of bacteria isolated from the marine sponges Isodictya compressa and Higginsia bidentifera collected from Algoa Bay, South Africa

Due to the rise inmulti-drug resistant pathogens and other diseases, there is renewed interest in marine sponge endosymbionts as a rich source of natural products (NPs). The South African marine environment is rich in marine biota that remains largely unexplored and may represent an important source for the discovery of novel NPs.We first investigated the bacterial diversity associated with five South African marine sponges, whose microbial populations had not previously been investigated, and select the two sponges (Isodictya compressa and Higginsia bidentifera) with highest species richness to culture bacteria. By employing 33 different growth conditions 415 sponge-associated bacterial isolates were cultured and screened for antibacterial activity. Thirty-five isolates showed antibacterial activity, twelve of which exhibited activity against the multi-drug resistant Escherichia coli 1699, implying that some of the bioactive compounds could be novel. Genome sequencing of two of these isolates confirmed that they harbour uncharacterized biosynthetic pathways that may encode novel chemical structures.IS

Hyphenated LC-ICP-MS/ESI-MS identification of halogenated metabolites in South African marine ascidian extracts

Extracts of 13 species of marine ascidian collected in Algoa Bay were analyzed by LC-ICP-MS/ESI-MS. This technique allows parallel analysis of the molecular species and the presence of certain elements. The LC-ICP-MS/ESI-MS technique was used to target iodinated metabolites in this study. Three ascidian species afforded the known 3,5–diiodo-4-methoxyphenethylamine (12), which was confirmedby the isolation of this metabolite fromAplidium monile.MS also suggested the presence of theknown 3,5–dibromo-4-methoxyphenethylamine (10) and the new 3-bromo-5–iodo-4-methoxyphenethylamine (11) in the A. monile extract. The presence of the known 3,5-dibromotetramethyltyrosine (21) and the new 3-iodotetramethyltyrosine (23) in extracts of an unidentified Didemnum species was similarly proposed from MS evidence. This is the first report of the occurrence of iodinated metabolites in South African marine invertebrates.IS

A quarter century of marine biodiscovery in Algoa bay, South Africa

Algoa Bay, the largest crenulate bay on the south-eastern coast of South Africa, is currently one of the most well-studied marine ecosystems in southern Africa. A plethora of endemic marine invertebrates inhabits the benthic reefs on the western edge of the Bay in close proximity to South Africa’s sixth largest city. Over the past 25 years, South African marine natural products chemists, together with international collaborators from the US National Cancer Institute and other US institutions, have focused their attention on Algoa Bay’s benthic marine invertebrates as a potential source of new anticancer compounds. This review commemorates a quarter of a century of marine biodiscovery in Algoa Bay and presents the structures and bioactivities of 49 new and 36 known specialized metabolites isolated from two molluscs, eight ascidians, and six sponges. Thirty-nine of these compounds were cytotoxic to cancer cells in vitro with 20 exhibiting moderate to potent cytotoxicity. Six other compounds exhibited antimicrobial activity. Foremost among the potential anticancer compounds is mandelalide A (38) from the Algoa Bay ascidian Lissoclinum species