Medium-term prognosis of an incident cohort of parkinsonian patients compared to controls

Funding This work was supported by Parkinson's UK (grant numbers G0502, G0914), BMA Doris Hillier Award, the BUPA Foundation, NHS Grampian Endowments, RS MacDonald Trust.Peer reviewedPublisher PD

Reporting and dealing with missing quality of life data in RCTs : has the picture changed in the last decade?

Peer reviewedPublisher PD

Storage stability of whole and nibbed, conventional and high oleic peanuts (<i>Arachis hypogeae </i>L.)

Peanuts are increasingly being used as nibbed ingredients in cereal bars, confectionery and breakfast cereals. However, studies on their oxidative stability in this format are limited. Storage trials to determine the stability to oxidation were carried out on whole and nibbed kernels of conventional (CP) and high oleic (HOP) peanuts, with respect to temperature and modified atmosphere packaging. HOP exhibited the highest oxidative stability, with a lag phase in whole kernels of 12–15 weeks before significant oxidation occurred. HOP also showed higher levels of intrinsic antioxidants, a trolox equivalent antioxidant capacity (TEAC) of 70 mMol equivalence and radical scavenging percentage (RSP) of 99.8 % at the beginning of storage trials, whereas CP showed values of 40 mMol and 81.2 %, respectively. The intrinsic antioxidants at the beginning of these storage trials were shown to affect the peroxide value (PV), where RSP and TEAC decreased, and PV increased. Therefore, in peanuts the processing format (nibbed or whole) had the highest influence on susceptibility of lipid oxidation, highest to lowest importance: processing format &gt; temperature &gt; atmospheric conditions

Second-line antiretroviral therapy in a workplace and community-based treatment programme in South Africa: determinants of virological outcome.

: Background: As antiretroviral treatment (ART) programmes in resource-limited settings mature, more patients are experiencing virological failure. Without resistance testing, deciding who should switch to second-line ART can be difficult. The consequences for second-line outcomes are unclear. In a workplace- and community-based multi-site programme, with 6-monthly virological monitoring, we describe outcomes and predictors of viral suppression on second-line, protease inhibitor-based ART.Methods: We used prospectively collected clinic data from patients commencing first-line ART between 1/1/03 and 31/12/08 to construct a study cohort of patients switched to second-line ART in the presence of a viral load (VL) ?400 copies/ml. Predictors of VL&lt;400 copies/ml within 15 months of switch were assessed using modified Poisson regression to estimate risk ratios.Results: 205 workplace patients (91.7% male; median age 43 yrs) and 212 community patients (38.7% male; median age 36 yrs) switched regimens. At switch compared to community patients, workplace patients had a longer duration of viraemia, higher VL, lower CD4 count, and higher reported non-adherence on first-line ART. Non-adherence was the reported reason for switching in a higher proportion of workplace patients. Following switch, 48.3% (workplace) and 72.0% (community) achieved VL&lt;400, with non-adherence (17.9% vs. 1.4%) and virological rebound (35.6% vs. 13.2% with available measures) reported more commonly in the workplace programme. In adjusted analysis of the workplace programme, lower switch VL and younger age were associated with VL&lt;400. In the community programme, shorter duration of viraemia, higher CD4 count and transfers into programme on ART were associated with VL&lt;400.Conclusion: High levels of viral suppression on second-line ART can be, but are not always, achieved in multi-site treatment programmes with both individual- and programme-level factors influencing outcomes. Strategies to support both healthcare workers and patients during this switch period need to be evaluated; sub-optimal adherence, particularly in the workplace programme must be addressed

Measles to the Rescue: A Review of Oncolytic Measles Virus

Oncolytic virotherapeutic agents are likely to become serious contenders in cancer treatment. The vaccine strain of measles virus is an agent with an impressive range of oncolytic activity in pre-clinical trials with increasing evidence of safety and efficacy in early clinical trials. This paramyxovirus vaccine has a proven safety record and is amenable to careful genetic modification in the laboratory. Overexpression of the measles virus (MV) receptor CD46 in many tumour cells may direct the virus to preferentially enter transformed cells and there is increasing awareness of the importance of nectin-4 and signaling lymphocytic activation molecule (SLAM) in oncolysis. Successful attempts to retarget MV by inserting genes for tumour-specific ligands to antigens such as carcinoembryonic antigen (CEA), CD20, CD38, and by engineering the virus to express synthetic microRNA targeting sequences, and "blinding" the virus to the natural viral receptors are exciting measures to increase viral specificity and enhance the oncolytic effect. Sodium iodine symporter (NIS) can also be expressed by MV, which enables in vivo tracking of MV infection. Radiovirotherapy using MV-NIS, chemo-virotherapy to convert prodrugs to their toxic metabolites, and immune-virotherapy including incorporating antibodies against immune checkpoint inhibitors can also increase the oncolytic potential. Anti-viral host immune responses are a recognized barrier to the success of MV, and approaches such as transporting MV to the tumour sites by carrier cells, are showing promise. MV Clinical trials are producing encouraging preliminary results in ovarian cancer, myeloma and cutaneous non-Hodgkin lymphoma, and the outcome of currently open trials in glioblastoma multiforme, mesothelioma and squamous cell carcinoma are eagerly anticipated

Modulation of NKG2D expression in human CD8(+) T cells corresponding with tuberculosis drug cure.

BACKGROUND: Biomarkers predicting tuberculosis treatment response and cure would facilitate drug development. This study investigated expression patterns of the co-stimulation molecule NKG2D in human tuberculosis and treatment to determine its potential usefulness as a host biomarker of tuberculosis drug efficacy. METHODS: Tuberculosis patients (n = 26) were recruited in Lahore, Pakistan, at diagnosis and followed up during treatment. Household contacts (n = 24) were also recruited. NKG2D expression was measured by qRT-PCR in RNA samples both ex vivo and following overnight mycobacterial stimulation in vitro. Protein expression of NKG2D and granzyme B was measured by flow cytometry. RESULTS: NKG2D expression in newly diagnosed tuberculosis patients was similar to household contacts in ex vivo RNA, but was higher following in vitro stimulation. The NKG2D expression was dramatically reduced by intensive phase chemotherapy, in both ex vivo blood RNA and CD8(+) T cell protein expression, but then reverted to higher levels after the continuation phase in successfully treated patients. CONCLUSION: The changes in NKG2D expression through successful treatment reflect modulation of the peripheral cytotoxic T cell response. This likely reflects firstly in vivo stimulation by live Mycobacterium tuberculosis, followed by the response to dead bacilli, antigen-release and finally immunopathology resolution. Such changes in host peripheral gene expression, alongside clinical and microbiological indices, could be developed into a biosignature of tuberculosis drug-induced cure to be used in future clinical trials

Disease associated with equine coronavirus infection and high case fatality rate.

BackgroundEquine coronavirus (ECoV) is associated with clinical disease in adult horses. Outbreaks are associated with a low case fatality rate and a small number of animals with signs of encephalopathic disease are described.ObjectivesThe aim of this study is to describe the epidemiological and clinical features of two outbreaks of ECoV infection that were associated with an high case fatality rate.Animals14 miniature horses and 1 miniature donkey testing fecal positive for ECoV from two related disease outbreaks.MethodsRetrospective study describing the epidemiological findings, clinicopathological findings, and fecal viral load from affected horses.ResultsIn EcoV positive horses, 27% (4/15) of the animals died or were euthanized. Severe hyperammonemia (677 μmol/L, reference range ≤ 60 μmol/L) was identified in one animal with signs of encephalopathic disease that subsequently died. Fecal viral load (ECoV genome equivalents per gram of feces) was significantly higher in the nonsurvivors compared to animals that survived (P = .02).Conclusions and clinical importanceEquine coronavirus had a higher case fatality rate in this group of miniature horses than previously reported in other outbreaks of varying breeds. Hyperammonemia could contribute to signs of encephalopathic disease, and the fecal viral load might be of prognostic value in affected horses

How do anticipated worry and regret predict seasonal influenza vaccination uptake among Chinese adults?

Objectives: To test two hypothesized models of how anticipated affect, cognitive risk estimate and vaccination intention might influence vaccination uptake against seasonal influenza. Methods: The study collected baseline and follow-up data during the main influenza seasons (January-March) of 2009 and 2010, respectively, among 507 university students and staff of a university in Hong Kong. Following logistic regression to determine eligible variables, two mediation models of cognitive risk estimate, anticipated affect, vaccination intention and vaccination uptake against seasonal influenza were tested using structural equation modeling. Results: Mediation analyses found that anticipated worry if not vaccinated influenced seasonal influenza vaccination uptake through its effects on either perceived probability of influenza infection (β= 0.45) or intention (.β= 0.45) while anticipated regret if not vaccinated influenced vaccination uptake through its effect on intention (β= 0.45) only; anticipated regret if vaccinated impeded vaccination uptake indirectly through its effect on vaccination intention (β= -0.26) or directly (β= -0.20); perceived probability of influenza infection influenced vaccination uptake through its effect on intention (β= 0.20) or directly (β= 0.22); and finally, intention influenced vaccination uptake directly (β= 0.58). Conclusion: The results suggest that anticipated affect seems to drive risk estimates related to seasonal influenza vaccination rather than vice versa and intention remains an important mediator of the associations of anticipated affect and cognitive risk estimate with vaccination uptake against seasonal influenza. © 2013 Elsevier Ltd.postprin

Inhibition of vicariously learned fear in children using positive modeling and prior exposure

One of the challenges to conditioning models of fear acquisition is to explain how different individuals can experience similar learning events and only some of them subsequently develop fear. Understanding factors moderating the impact of learning events on fear acquisition is key to understanding the etiology and prevention of fear in childhood. This study investigates these moderators in the context of vicarious (observational) learning. Two experiments tested predictions that the acquisition or inhibition of fear via vicarious learning is driven by associative learning mechanisms similar to direct conditioning. In Experiment 1, 3 groups of children aged 7 to 9 years received 1 of 3 inhibitive information interventions psychoeducation, factual information, or no information (control)—prior to taking part in a vicarious fear learning procedure. In Experiment 2, 3 groups of children aged 7 to 10 years received 1 of 3 observational learning interventions—positive modeling (immunization), observational familiarity (latent inhibition), or no prevention (control)— before vicarious fear learning. Results indicated that observationally delivered manipulations inhibited vicarious fear learning, while preventions presented via written information did not. These findings confirm that vicarious learning shares some of the characteristics of direct conditioning and can explain why not all individuals will develop fear following a vicarious learning event. They also suggest that the modality of inhibitive learning is important and should match the fear learning pathway for increased chances of inhibition. Finally, the results demonstrate that positive modeling is likely to be a particularly effective method for preventing fear-related observational learning in children