Cognitive impairment in Parkinson's disease: impact on quality of life of carers.

BACKGROUND: The quality of life (QoL) of informal caregivers of people with Parkinson's disease (PD) (PwP) can be affected by the caring role. Because of cognitive symptoms and diminished activities of daily living, in addition to the management of motor symptoms, carers of PwP and cognitive impairment may experience increased levels of burden and poorer QoL compared with carers of PwP without cognitive impairment. This study aimed to investigate the impact of cognitive impairment in PD upon QoL of carers. METHODS: Approximately 36 months after diagnosis, 66 dyadic couples of PwP and carers completed assessments. PwP completed a schedule of neuropsychological assessments and QoL measures; carers of PwP completed demographic questionnaires and assessments of QoL. Factor scores of attention, memory/executive function and global cognition, as derived by principal component analysis, were used to evaluate cognitive domains. RESULTS: Hierarchical regression analysis found lower Montreal Cognitive Assessment was a significant independent predictor of poorer carer QoL, in addition to number of hours spent caregiving, carer depression and PD motor severity. Attentional deficits accounted for the largest proportion of variance of carer QoL. Carers of PwP and dementia (n = 9) had significantly poorer QoL scores compared with PwP and mild cognitive impairment (n = 18) or normal cognition (n = 39) carers (p < 0.01). CONCLUSIONS: Attentional deficits were the strongest predictor of carer QoL compared with other cognitive predictors. Carers for those with PD dementia reported the poorest QoL. Interventions such as respite or cognitive behavioural therapy to improve mood and self-efficacy in carers may improve carer QoL. © 2016 The Authors. International Journal of Geriatric Psychiatry published by John Wiley & Sons, Ltd

Kerr-Newman Black Hole Thermodynamical State Space: Blockwise Coordinates

A coordinate system that blockwise-simplifies the Kerr-Newman black hole's thermodynamical state space Ruppeiner metric geometry is constructed, with discussion of the limiting cases corresponding to simpler black holes. It is deduced that one of the three conformal Killing vectors of the Reissner-Nordstrom and Kerr cases (whose thermodynamical state space metrics are 2 by 2 and conformally flat) survives generalization to the Kerr-Newman case's 3 by 3 thermodynamical state space metric.Comment: 4 pages incl 2 figs. Accepted by Gen. Rel. Grav. Replaced with Accepted version (minor corrections

Kinematics and Dynamics of the Galactic Stellar Halo

The structure, kinematics and dynamics of the Galactic stellar halo are reviewed including evidence of substructure in the spatial distribution and kinematics of halo stars. Implications for galaxy formation theory are subsequently discussed; in particular it is argued that the observed kinematics of stars in the outer Galactic halo can be used as an important constraint on viable galaxy formation scenarios

The ACUTE (Ambulance CPAP: Use, Treatment effect and economics) feasibility study: a pilot randomised controlled trial of prehospital CPAP for acute respiratory failure

Background: Acute respiratory failure (ARF) is a common and life-threatening medical emergency. Standard prehospital management involves controlled oxygen therapy and disease-specific ancillary treatments. Continuous positive airway pressure (CPAP) is a potentially beneficial alternative treatment that could be delivered by emergency medical services. However, it is uncertain whether this treatment could work effectively in United Kingdom National Health Service (NHS) ambulance services and if it represents value for money. Methods: An individual patient randomised controlled external pilot trial will be conducted comparing prehospital CPAP to standard oxygen therapy for ARF. Adults presenting to ambulance service clinicians will be eligible if they have respiratory distress with peripheral oxygen saturation below British Thoracic Society (BTS) target levels, despite titrated supplemental oxygen. Enrolled patients will be allocated (1:1 simple randomisation) to prehospital CPAP (O_two system) or standard oxygen therapy using identical sealed boxes. Feasibility outcomes will include incidence of recruited eligible patients, number of erroneously recruited patients and proportion of cases adhering to allocation schedule and treatment, followed up at 30 days and with complete data collection. Effectiveness outcomes will comprise survival at 30 days (definitive trial primary end point), endotracheal intubation, admission to critical care, length of hospital stay, visual analogue scale (VAS) dyspnoea score, EQ-5D-5L and health care resource use at 30 days. The cost-effectiveness of CPAP, and of conducting a definitive trial, will be evaluated by updating an existing economic model. The trial aims to recruit 120 patients over 12 months from four regional ambulance hubs within the West Midlands Ambulance Service (WMAS). This sample size will allow estimation of feasibility outcomes with a precision of < 5%. Feasibility and effectiveness outcomes will be reported descriptively for the whole trial population, and each trial arm, together with their 95% confidence intervals. Discussion: This study will determine if it is feasible, acceptable and cost-effective to undertake a full-scale trial comparing CPAP and standard oxygen treatment, delivered by ambulance service clinicians for ARF. This will inform NHS practice and prevent inappropriate prehospital CPAP adoption on the basis of limited evidence and at a potentially substantial cost. Trial registration: ISRCTN12048261. Registered on 30 August 2017. http://www.isrctn.com/ISRCTN1204826

Automated manufacturing of chimeric antigen receptor T cells for adoptive immunotherapy using CliniMACS prodigy

Novel cell therapies derived from human T lymphocytes are exhibiting enormous potential in early-phase clinical trials in patients with hematologic malignancies. Ex vivo modification of T cells is currently limited to a small number of centers with the required infrastructure and expertise. The process requires isolation, activation, transduction, expansion and cryopreservation steps. To simplify procedures and widen applicability for clinical therapies, automation of these procedures is being developed. The CliniMACS Prodigy (Miltenyi Biotec) has recently been adapted for lentiviral transduction of T cells and here we analyse the feasibility of a clinically compliant T-cell engineering process for the manufacture of T cells encoding chimeric antigen receptors (CAR) for CD19 (CAR19), a widely targeted antigen in B-cell malignancies. Using a closed, single-use tubing set we processed mononuclear cells from fresh or frozen leukapheresis harvests collected from healthy volunteer donors. Cells were phenotyped and subjected to automated processing and activation using TransAct, a polymeric nanomatrix activation reagent incorporating CD3/CD28-specific antibodies. Cells were then transduced and expanded in the CentriCult-Unit of the tubing set, under stabilized culture conditions with automated feeding and media exchange. The process was continuously monitored to determine kinetics of expansion, transduction efficiency and phenotype of the engineered cells in comparison with small-scale transductions run in parallel. We found that transduction efficiencies, phenotype and function of CAR19 T cells were comparable with existing procedures and overall T-cell yields sufficient for anticipated therapeutic dosing. The automation of closed-system T-cell engineering should improve dissemination of emerging immunotherapies and greatly widen applicability

Horizontal DNA transfer mechanisms of bacteria as weapons of intragenomic conflict

Horizontal DNA transfer (HDT) is a pervasive mechanism of diversification in many microbial species, but its primary evolutionary role remains controversial. Much recent research has emphasised the adaptive benefit of acquiring novel DNA, but here we argue instead that intragenomic conflict provides a coherent framework for understanding the evolutionary origins of HDT. To test this hypothesis, we developed a mathematical model of a clonally descended bacterial population undergoing HDT through transmission of mobile genetic elements (MGEs) and genetic transformation. Including the known bias of transformation toward the acquisition of shorter alleles into the model suggested it could be an effective means of counteracting the spread of MGEs. Both constitutive and transient competence for transformation were found to provide an effective defence against parasitic MGEs; transient competence could also be effective at permitting the selective spread of MGEs conferring a benefit on their host bacterium. The coordination of transient competence with cell-cell killing, observed in multiple species, was found to result in synergistic blocking of MGE transmission through releasing genomic DNA for homologous recombination while simultaneously reducing horizontal MGE spread by lowering the local cell density. To evaluate the feasibility of the functions suggested by the modelling analysis, we analysed genomic data from longitudinal sampling of individuals carrying Streptococcus pneumoniae. This revealed the frequent within-host coexistence of clonally descended cells that differed in their MGE infection status, a necessary condition for the proposed mechanism to operate. Additionally, we found multiple examples of MGEs inhibiting transformation through integrative disruption of genes encoding the competence machinery across many species, providing evidence of an ongoing "arms race." Reduced rates of transformation have also been observed in cells infected by MGEs that reduce the concentration of extracellular DNA through secretion of DNases. Simulations predicted that either mechanism of limiting transformation would benefit individual MGEs, but also that this tactic's effectiveness was limited by competition with other MGEs coinfecting the same cell. A further observed behaviour we hypothesised to reduce elimination by transformation was MGE activation when cells become competent. Our model predicted that this response was effective at counteracting transformation independently of competing MGEs. Therefore, this framework is able to explain both common properties of MGEs, and the seemingly paradoxical bacterial behaviours of transformation and cell-cell killing within clonally related populations, as the consequences of intragenomic conflict between self-replicating chromosomes and parasitic MGEs. The antagonistic nature of the different mechanisms of HDT over short timescales means their contribution to bacterial evolution is likely to be substantially greater than previously appreciated

Letter processing and font information during reading: beyond distinctiveness, where vision meets design

Letter identification is a critical front end of the reading process. In general, conceptualizations of the identification process have emphasized arbitrary sets of distinctive features. However, a richer view of letter processing incorporates principles from the field of type design, including an emphasis on uniformities across letters within a font. The importance of uniformities is supported by a small body of research indicating that consistency of font increases letter identification efficiency. We review design concepts and the relevant literature, with the goal of stimulating further thinking about letter processing during reading

The stellar halo of the Galaxy

Stellar halos may hold some of the best preserved fossils of the formation history of galaxies. They are a natural product of the merging processes that probably take place during the assembly of a galaxy, and hence may well be the most ubiquitous component of galaxies, independently of their Hubble type. This review focuses on our current understanding of the spatial structure, the kinematics and chemistry of halo stars in the Milky Way. In recent years, we have experienced a change in paradigm thanks to the discovery of large amounts of substructure, especially in the outer halo. I discuss the implications of the currently available observational constraints and fold them into several possible formation scenarios. Unraveling the formation of the Galactic halo will be possible in the near future through a combination of large wide field photometric and spectroscopic surveys, and especially in the era of Gaia.Comment: 46 pages, 16 figures. References updated and some minor changes. Full-resolution version available at http://www.astro.rug.nl/~ahelmi/stellar-halo-review.pd

Factors associated with herbal use among urban multiethnic primary care patients: a cross-sectional survey

BACKGROUND: The use of herbal supplements in the United States has become increasingly popular. The prevalence of herbal use among primary care patients varies in previous studies; the pattern of herbal use among urban racially/ethnically diverse primary care patients has not been widely studied. The primary objectives of this study were to describe the use of herbs by ethnically diverse primary care patients in a large metropolitan area and to examine factors associated with such use. The secondary objective was to investigate perceptions about and patterns of herbal use. METHODS: Data for a cross-sectional survey were collected at primary care practices affiliated with the Southern Primary-care Urban Research Network (SPUR-Net) in Houston, Texas, from September 2002 to March 2003. To participate in the study, patients had to be at least 18 years of age and visiting one of the SPUR-Net clinics for routine, nonacute care. Survey questions were available in both English and Spanish. RESULTS: A total of 322 patients who had complete information on race/ethnicity were included in the analysis. Overall, 36% of the surveyed patients (n = 322) indicated use of herbs, with wide variability among ethnic groups: 50% of Hispanics, 50% of Asians, 41% of Whites, and 22% of African-Americans. Significant factors associated with an individual's herbal use were ethnicity other than African-American, having an immigrant family history, and reporting herbal use by other family members. About 40% of survey respondents believed that taking prescription medications and herbal medicines together was more effective than taking either alone. One-third of herbal users reported using herbs on a daily basis. More Whites (67%) disclosed their herbal use to their health-care providers than did African-Americans (45%), Hispanics (31%), or Asians (31%). CONCLUSIONS: Racial/ethnic differences in herbal use were apparent among this sample of urban multiethnic adult primary care patients. Associated factors of herbal use were non-African-American ethnicity, immigrant family history, and herbal use among family members. Whereas Hispanics and Asians reported the highest rates of herbal use, they were the least likely to disclose their use to health-care professionals. These findings are important for ensuring medication safety in primary care practices