Prioritising target non-pharmacological interventions for research in Parkinson’s Disease: Achieving consensus from key stakeholders

Background: In 2014 Parkinson’s UK conducted a research prioritisation exercise with stakeholders highlighting important clinical research questions. The exercise highlighted the need for effective interventions to be developed and tested to tackle a range of non-motor symptoms including: sleep quality, stress and anxiety, mild cognitive impairment, dementia and urinary problems. The present work set out to build on this exercise by prioritising types of non-pharmacological interventions to be tested to treat the identified non-motor symptoms. Methods: A Patient and Public Involvement Exercise was used to reach consensus on intervention priorities for the treatment on non-motor symptoms. Some Delphi techniques were also used to support the feedback collected. A first-round prioritisation survey was conducted followed by a panel discussion. Nineteen panellists completed the first-round survey (9 people with Parkinson’s and 10 professionals working in Parkinson’s) and 16 participated in the panel discussion (8 people with Parkinson’s and 8 professionals working in Parkinson’s). A second-round prioritization survey was conducted after the panel discussion with 13 people with Parkinson’s. Results: Physical activity, third wave cognitive therapies and cognitive training were rated as priority interventions for the treatment of a range of non-motor symptoms. There was broad agreement on intervention priorities between health care professionals and people with Parkinson’s. A consensus was reached that research should focus on therapies which could be used to treat several different non-motor symptoms. In the context of increasing digitisation, the need for human interaction as an intervention component was highlighted.3 Conclusion: Bringing together Parkinson’s professionals and people with Parkinson’sresulted in a final treatment priority list which should be both feasible to carry out in routine clinical practice and acceptable to both professionals and people with Parkinson’s. The workshop further specified research priorities in Parkinson’s disease based on the current evidence base, stakeholder preferences, and feasibility. Research should focus on developing and testing non-pharmacological treatments which could be effective across a range of symptoms but specifically focusing on tailored physical activity interventions, cognitive therapies and cognitive training

Wilson ratio in Yb-substituted CeCoIn5

We have investigated the effect of Yb substitution on the Pauli limited, heavy fermion superconductor, CeCoIn$_5$. Yb acts as a non-magnetic divalent substituent for Ce throughout the entire doping range, equivalent to hole doping on the rare earth site. We found that the upper critical field in (Ce,Yb)CoIn$_5$ is Pauli limited, yet the reduced (H,T) phase diagram is insensitive to disorder, as expected in the purely orbitally limited case. We use the Pauli limiting field, the superconducting condensation energy and the electronic specific heat coefficient to determine the Wilson ratio ($R_{W}$), the ratio of the specific heat coefficient to the Pauli susceptibility in CeCoIn$_5$. The method is applicable to any Pauli limited superconductor in the clean limit.Comment: 5 pages, 1 table, 4 figure

Extended Molecular Gas in the Nearby Starburst Galaxy Maffei 2

We present a 9'x9' fully-sampled map of the CO J=1-0 emission in the nearby starburst galaxy Maffei 2 obtained at the Five College Radio Astronomy Observatory. The map reveals previously known strong CO emission in the central starburst region as well as an extended asymmetric distribution with bright CO lines at the ends of the bar and in a feature at the north-east edge of the molecular disk. This northern feature, proposed previously to be an interacting companion galaxy, could be a dwarf irregular galaxy, although the CO data are also consistent with the feature being simply an extension of one of the spiral arms. We estimate the total molecular gas mass of Maffei 2 to be (1.4-1.7)x10^9 Mo or ~3-4% of its dynamical mass. Adopting the recently determined lower value for the CO-to-H2 conversion factor in the central region, our data lead to the surprising result that the largest concentrations of molecular gas in Maffei 2 lie at the bar ends and in the putative dwarf companion rather than in the central starburst. A gravitational stability analysis reveals that the extended disk of Maffei 2 lies above the critical density for star formation; however, whether the central region is also gravitationally unstable depends both on the details of the rotation curve and the precise value of the CO-to-H2 conversion factor in this region.Comment: accepted to ApJ (Sept 10 2004 issue

An exploration of worry content and catastrophic thinking in middle-aged and older-aged adults with and without Parkinson's disease

Objective: Worry is a common and distressing problem in Parkinson’s disease(PD). However, little is known about the nature and content of worry in PD and how it might differ to non-PD populations. The study aimed to explore the content and nature of worry in middle and older aged adults with and without PD. Method: 4 groups of participants: 20 PD patients(10 high worry, 10 low worry) 19 middle and older aged adults(10 high worry, 9 low worry) completed the Catastrophising Interview(CI) for three worry topics. Worriers were classified(high/low) based on Penn State Worry Questionnaire scores. Data were analysed using Framework Analysis. Results: High worriers showed a greater diversity of worry topics than low worriers. Health worries differentiated high and low worriers in the non-PD sample but were common across all PD participants. The CI revealed that the root concern of worry was often different to that initially described. In particular, PD high worriers were more likely to express underlying concerns about negative self-perception and death/severe incapacity. Conclusion: The CI was able to identify the root cause of worry, demonstrating the value of this technique in the exploration and treatment of worry and psychological distress. Exploring worry content may help to distinguish patients with problematic worry, with worries about self-perception and death/severe incapacity characteristic of high worriers. Therapeutic interventions designed to alleviate problematic worry and distress in PD need to take account of the realities of living with PD and the potentially realistic nature of worries which may appear catastrophic in a healthy population

Implementing effective community-based surveillance in research studies of maternal, newborn and infant outcomes in low resource settings

BACKGROUND: Globally adopted health and development milestones have not only encouraged improvements in the health and wellbeing of women and infants worldwide, but also a better understanding of the epidemiology of key outcomes and the development of effective interventions in these vulnerable groups. Monitoring of maternal and child health outcomes for milestone tracking requires the collection of good quality data over the long term, which can be particularly challenging in poorly-resourced settings. Despite the wealth of general advice on conducting field trials, there is a lack of specific guidance on designing and implementing studies on mothers and infants. Additional considerations are required when establishing surveillance systems to capture real-time information at scale on pregnancies, pregnancy outcomes, and maternal and infant health outcomes. MAIN BODY: Based on two decades of collaborative research experience between the Kintampo Health Research Centre in Ghana and the London School of Hygiene and Tropical Medicine, we propose a checklist of key items to consider when designing and implementing systems for pregnancy surveillance and the identification and classification of maternal and infant outcomes in research studies. These are summarised under four key headings: understanding your population; planning data collection cycles; enhancing routine surveillance with additional data collection methods; and designing data collection and management systems that are adaptable in real-time. CONCLUSION: High-quality population-based research studies in low resource communities are essential to ensure continued improvement in health metrics and a reduction in inequalities in maternal and infant outcomes. We hope that the lessons learnt described in this paper will help researchers when planning and implementing their studies

Examining Chemotherapy-Related Cognitive Changes in Colorectal Cancer Patients: A Feasibility Trial

Introduction: Research suggests that chemotherapy may be related to decline in patients’ cognitive functions. Objectives: To assess the feasibility and acceptability of a multi-site study designed to examine the nature and extent of chemotherapy-related cognitive changes in colorectal cancer patients. Method: Data was collected over 8 months using objective and self-reported measures of cognitive functioning and self-reported quality of life, fatigue and mood questionnaires. The assessment battery was administered pre- and mid-chemotherapy treatment to a consecutive sample of colorectal cancer patients across three Londonbased NHS Trusts. Participants included patients who had undergone colorectal surgery and were scheduled to have adjuvant chemotherapy treatment, or no further cancer treatment. Main outcome measures: Recruitment procedures, rate of recruitment, suitability of exclusion/inclusion criteria, acceptability of data collection procedures and the battery, and attrition rates. Results: From 1 April 2014 to 1 December 2014, 42 eligible participants were invited to take part in the trial. Of the 17 that completed pre-chemotherapy assessments, only 1 withdrew at follow-up due to reasons of ill health from disease recurrence. All participants completed the entire battery and indicated that they found the trial acceptable. Conclusions: What went wrong: Strained researcher resources; loss of eligible participants to competing studies, restrictive upper age limit. Possible solutions: Removal of upper age limit, an increased dedicated research team to increase rate of recruitment. The large multi-site study is feasible with suggested amendments and is acceptable to patients and medical teams. Acceptability of trial to medical teams is further evidenced by requests of collaboration from two additional London based NHS Trusts. Lessons learned: This feasibility trial provides evidence to other researchers designing similar studies in this area of an acceptable design and the need for appropriate funding for resources to recruit large enough consecutive samples of patients with solid tumour cancers

A comparison of rapid point-of-care tests for the detection of avian influenza A(H7N9) virus, 2013

Six antigen detection-based rapid influenza point-of-care tests were compared for their ability to detect avian influenza A(H7N9) virus. The sensitivity of at least four tests, standardised by viral infectivity (TCID50) or RNA copy number, was lower for the influenza A(H7N9) virus than for seasonal A(H3N2), A(H1N1)pdm09 or other recent avian A(H7) viruses. Comparing detection limits of A(H7N9) virus with Ct values of A(H7N9) clinical specimens suggests the tests would not have detected most clinical specimens

The antibacterial activity and release of quaternary ammonium compounds in an orthodontic primer

The aim of this study was to evaluate the impact of 10 wt% benzalkonium chloride (TB-BAC) or 10 wt% cetylpyridinium chloride (TB-CPC) on the antimicrobial properties of the orthodontic adhesive primer, Transbond XT™ (TB). Antimicrobial activity was assessed using a zone of inhibition diffusion test and the release of the antimicrobial compounds was monitored by high performance liquid chromatography (HPLC). Shear bond strength (SBS) was tested using bovine enamel. Control, TB, specimens failed to demonstrate intrinsic antibacterial activity at 1, 7 and 14 days; whereas, TB-BAC and TB-CPC showed antibacterial effects at all times. HPLC analysis indicated no significant differences in the release behaviour of TB-BAC and TB-CPC (t-test, p > 0.05), except for the 7-day release which was higher for TB-BAC (p 0.05)

Nuclear Bar Catalyzed Star Formation: 13^CO, C18^O and Molecular Gas Properties in the Nucleus of Maffei 2

(Abridged) We present resolution maps of CO, its isotopologues, and HCN from in the center of Maffei 2. The J=1-0 rotational lines of 12^CO, 13^CO, C18^O and HCN, and the J=2-1 lines of 13^CO and C18^O were observed with the OVRO and BIMA arrays. The 2-1/1-0 line ratios of the isotopologues constrain the bulk of the molecular gas to originate in low excitation, subthermal gas. From LVG modeling, we infer that the central GMCs have n(H_2) ~10^2.75 cm^-3 and T_k ~ 30 K. Continuum emission at 3.4 mm, 2.7 mm and 1.4 mm was mapped to determine the distribution and amount of HII regions and dust. Column densities derived from C18^O and 1.4 mm dust continuum fluxes indicate the CO conversion factor in the center of Maffei 2 is lower than Galactic by factors of ~2-4. Gas morphology and the clear ``parallelogram'' in the Position-Velocity diagram shows that molecular gas orbits within the potential of a nuclear (~220 pc) bar. The nuclear bar is distinct from the bar that governs the large scale morphology of Maffei 2. Giant molecular clouds in the nucleus are nonspherical and have large linewidths. Dense gas and star formation are concentrated at the sites of the x_1-x_2 orbit intersections of the nuclear bar, suggesting that the starburst is dynamically triggered.Comment: 50 pages, 14 figures, accepted for publication in Ap

Biogenesis of mitochondrial porin

We review here the present knowledge about the pathway of import and assembly of porin into mitochondria and compare it to those of other mitochondrial proteins. Porin, like all outer mitochondrial membrane proteins studied so far is made as a precursor without a cleavble lsquosignalrsquo sequence; thus targeting information must reside in the mature sequence. At least part of this information appears to be located at the amino-terminal end of the molecule. Transport into mitochondria can occur post-translationally. In a first step, the porin precursor is specifically recognized on the mitochondrial surface by a protease sensitive receptor. In a second step, porin precursor inserts partially into the outer membrane. This step is mediated by a component of the import machinery common to the import pathways of precursor proteins destined for other mitochondrial subcompartments. Finally, porin is assembled to produce the functional oligomeric form of an integral membrane protein wich is characterized by its extreme protease resistance