Letter to Mr. William Leary, steward of the Long Point Company, from S.D. Woodruff regarding the painting of the new building at Long Point

Letter to Mr. William Leary, steward of the Long Point Company, from S.D. Woodruff regarding the painting of the new building at Long Point (2 ½ pages, handwritten), June 11, 1875.

Letter from the office of Hart, Ball and Hart of Buffalo, New York to William R. Allen of St. Catharines, Ont.

Letter (2 pages, handwritten) from the office of Hart, Ball and Hart of Buffalo, New York to William R. Allen of St. Catharines, Ont. proposing work to be done regarding the hot water heating of the building. The owner of the building is expected to pay the railway fare of the men and to pay their board while they are in St. Catharines, July 8, 1876.

Letter from the office of Hart, Ball and Hart of Buffalo, New York to William R. Allen of St. Catharines

Letter (4 pages, handwritten) from the office of Hart, Ball and Hart of Buffalo, New York to William R. Allen of St. Catharines elaborating on the specifications of the hot water heating for the residence of Mr. Woodruff, July 17, 1876.

Indenture –sheriff’s deed (vellum) between William Kingsmill, sheriff of the Niagara District and Walter H. Dickson

Indenture –sheriff’s deed (vellum) between William Kingsmill, sheriff of the Niagara District and Walter H. Dickson for 23 acres in the Town of Niagara – instrument no. 1158, Oct. 29, 1842

Indenture between the Honourable William Dickson and of Niagara and Commander Thomas Bushby, then Lieutenant in the Royal Navy

Indenture between the Honourable William Dickson and of Niagara and Commander Thomas Bushby, then Lieutenant in the Royal Navy for land in the village plot of Sherbrooke – instrument no. 230. This was recorded on Sept. 15, 1843 in Book A, folio 281-282. April 15, 1843.

How fast and how often: the pharmacokinetics of drug use are decisive in addiction

How much, how often and how fast a drug reaches the brain determine the behavioural and neuroplastic changes associated with the addiction process. Despite the critical nature of these variables, the drug addiction field often ignores pharmacokinetic issues, which we argue can lead to false conclusions. First, we review the clinical data demonstrating the importance of the speed of drug onset and of intermittent patterns of drug intake in psychostimulant drug addiction. This is followed by a review of the preclinical literature demonstrating that pharmacokinetic variables play a decisive role in determining behavioural and neurobiological outcomes in animal models of addiction. This literature includes recent data highlighting the importance of intermittent, ‘spiking’ brain levels of drug in producing an increase in the motivation to take drug over time. Rapid drug onset and intermittent drug exposure both appear to push the addiction process forward most effectively. This has significant implications for refining animal models of addiction and for better understanding the neuroadaptations that are critical for the disorder.

How is the language of medicines use review leaflets symbolising the service?

Introduction The medicines use review (MUR), a new community pharmacy ‘service’, was launched in England and Wales to improve patients’ knowledge and use of medicines through a private, patient–pharmacist appointment. After 18 months, only 30% of pharmacies are providing MURs; at an average of 120 per annum (maximum 400 allowed).1 One reason linked to low delivery is patient recruitment.2 Our aim was to examine how the MUR is symbolised and given meaning via printed patient information, and potential implications. Method The language of 10 MUR patient leaflets, including the NHS booklet,3 and leaflets from multiples and wholesalers was evaluated by discourse analysis. Results and Discussion Before experiencing MURs, patients conceivably ‘categorise’ relationships with pharmacists based on traditional interactions.4 Yet none of the leaflets explicitly describe the MUR as ‘new’ and presuppose patients would become involved in activities outside of their pre-existing relationship with pharmacists such as appointments, self-completion of charts, and pharmacy action plans. The MUR process is described inconsistently, with interchangeable use of formal (‘review meeting‘) and informal (‘friendly’) terminology, the latter presumably to portray an intended ‘negotiation model’ of interaction.5 Assumptions exist about attitudes (‘not understanding’; ‘problems’) that might lead patients to an appointment. However, research has identified a multitude of reasons why patients choose (or not) to consult practitioners,6 and marketing of MURs should also consider other barriers. For example, it may be prudent to remove time limits to avoid implying patients might not be listened to fully, during what is for them an additional practitioner consultation.

How level and type of deafness affects user perception of multimedia video clips

Our research investigates the impact that hearing has on the perception of digital video clips, with and without captions, by discussing how hearing loss, captions and deafness type affects user QoP (Quality of Perception). QoP encompasses not only a user's satisfaction with the quality of a multimedia presentation, but also their ability to analyse, synthesise and assimilate informational content of multimedia . Results show that hearing has a significant effect on participants’ ability to assimilate information, independent of video type and use of captions. It is shown that captions do not necessarily provide deaf users with a ‘greater level of information’ from video, but cause a change in user QoP, depending on deafness type, which provides a ‘greater level of context of the video’. It is also shown that post-lingual mild and moderately deaf participants predict less accurately their level of information assimilation than post-lingual profoundly deaf participants, despite residual hearing. A positive correlation was identified between level of enjoyment (LOE) and self-predicted level of information assimilation (PIA), independent of hearing level or hearing type. When this is considered in a QoP quality framework, it puts into question how the user perceives certain factors, such as ‘informative’ and ‘quality’.

How the double spherules of infectious bronchitis virus impact our understanding of RNA virus replicative organelles

Powered by advances in electron tomography, recent studies have extended our understanding of how viruses construct "replication factories" inside infected cells. Their function, however, remains an area of speculation with important implications for human health. It is clear from these studies that whatever their purpose, organelle structure is dynamic (M. Ulasli, M. H. Verheije, C. A. de Haan, and F. Reggiori, Cell. Microbiol. 12:844-861, 2010) and intricate (K. Knoops, M. Kikkert, S. H. Worm, J. C. Zevenhoven-Dobbe, Y. van der Meer, et al., PLOS Biol. 6:e226, 2008). But by concentrating on medically important viruses, these studies have failed to take advantage of the genetic variation inherent in a family of viruses that is as diverse as the archaea, bacteria, and eukaryotes combined (C. Lauber, J. J. Goeman, M. del Carmen Parquet, P. T. Nga, E. J. Snijder, et al., PLOS Pathog. 9:e1003500, 2013). In this climate, Maier et al. (H. J. Maier, P. C. Hawes, E. M. Cottam, J. Mantell, P. Verkade, et al., mBio 4:e00801-13, 2013) explored the replicative structures formed by an avian coronavirus that appears to have diverged at an early point in coronavirus evolution and shed light on controversial aspects of viral biology.

Rerum cognoscere causas: part I - How do the ideas of system dynamics relate to traditional social theories and the voluntarism/determinism debate?

This is the first half of a two-part paper which deals with the social theoretic assumptions underlying system dynamics. The motivation is that clarification in this area can help mainstream social scientists to understand how our field relates to their literature, methods and concerns. Part I has two main sections. The aim of the first is to answer the question: How do the ideas of system dynamics relate to traditional social theories? The theoretic assumptions of the field are seldom explicit but rather are implicit in its practice. The range of system dynamics practice is therefore considered and related to a framework - widely used in both operational research (OR) and systems science - that organises the assumptions behind traditional social theoretic paradigms. Distinct and surprisingly varied groupings of practice are identified, making it difficult to place system dynamics in any one paradigm with any certainty. The difficulties of establishing a social theoretic home for system dynamics are exemplified in the second main section. This is done by considering the question: Is system dynamics deterministic? An analysis shows that attempts to relate system dynamics to strict notions of voluntarism or determinism quickly indicate that the field does not fit with either pole of this dichotomous, and strictly paradigmatic, view. Part I therefore concludes that definitively placing system dynamics with respect to traditional social theories is highly problematic. The scene is therefore set for Part II of the paper, which proposes an innovative and potentially fruitful resolution to this problem.

How is the balance of a forecast ensemble affected by adaptive and non-adaptive localization schemes?

This paper investigates the effect on balance of a number of Schur product-type localization schemes which have been designed with the primary function of reducing spurious far-field correlations in forecast error statistics. The localization schemes studied comprise a non-adaptive scheme (where the moderation matrix is decomposed in a spectral basis), and two adaptive schemes, namely a simplified version of SENCORP (Smoothed ENsemble COrrelations Raised to a Power) and ECO-RAP (Ensemble COrrelations Raised to A Power). The paper shows, we believe for the first time, how the degree of balance (geostrophic and hydrostatic) implied by the error covariance matrices localized by these schemes can be diagnosed. Here it is considered that an effective localization scheme is one that reduces spurious correlations adequately but also minimizes disruption of balance (where the 'correct' degree of balance or imbalance is assumed to be possessed by the unlocalized ensemble). By varying free parameters that describe each scheme (e.g. the degree of truncation in the schemes that use the spectral basis, the 'order' of each scheme, and the degree of ensemble smoothing), it is found that a particular configuration of the ECO-RAP scheme is best suited to the convective-scale system studied. According to our diagnostics this ECO-RAP configuration still weakens geostrophic and hydrostatic balance, but overall this is less so than for other schemes.