Pharmacy Apps: a new frontier on the digital landscape?

BACKGROUND: Over the course of recent years smartphone and tablet technology has evolved rapidly. Similarly, the sphere of healthcare is constantly developing and striving to embrace the newest forms of technology in order to optimise function. Many opportunities for mobile applications (i.e. 'apps') pertinent to the healthcare sector are now emerging. OBJECTIVE: This study will consider whether registered pharmacists within the United Kingdom (UK) believe it appropriate to use mobile apps during the provision of healthcare within the community setting. METHODS: Further to Liverpool John Moores University (LJMU) ethical approval, the 30 item questionnaire was distributed to UK registered pharmacists (n=600) practising within inner city Manchester, Liverpool and Newcastle. The questions were formatted as multiple choice, Likert scales or the open answer type. On questionnaire completion and return, data were analysed using simple frequencies, cross tabulations and non-parametric techniques in the Statistical Package for the Social Sciences (SPSS) (v18). RESULTS: The majority of respondents (78.4% of 211 participants) confirmed that they were confident when using mobile apps on their technology platform. In general, mobile apps were perceived to be useful in facilitating patient consultations (55%) and supporting healthcare education (80%). The main barrier for mobile app use within the workplace was company policy, deemed significant in the case of regional / national chain pharmacies (p<0.001). Pharmacists alluded to the fact that whilst mobile apps demonstrate potential in modern day practise, they will have a greater impact in the future (p<0.001). CONCLUSION: The data indicate that although pharmacists are supportive of mobile apps in healthcare, a number of factors (i.e. risk, company policy and lack of regulation) may preclude their use in modern day pharmacy practise. Clearly, limitations of the technology must be addressed in order to maximise uptake within healthcare systems. Pharmacists suggest that as the younger generation ages, mobile apps will become a more accepted method by which to manage healthcare in the wider population

BAFF and MyD88 signals promote a lupuslike disease independent of T cells

Systemic lupus erythernatosus (SLE) is a systemic autoimmune disease characterized by the production of autoantibodies. However, the underlying cause of disease appears to relate to defects in T cell tolerance or T cell help to 13 cells. Transgenic (Tg) mice over-expressing the cytokine 13 cell-activating factor of the tumor necrosis factor family (BAFF) develop an autoimmune disorder similar to SLE and show impaired B cell tolerance and altered T cell differentiation. We generated BAFF Tg mice that were completely deficient in T cells, and, surprisingly, these mice developed an SLE-like disease indistinguishable from that of BAFF Tg mice. Autoimmunity in BAFF Tg mice did, however, require 13 cell-intrinsic signals through the Toll-like receptor (TLR)-associated signaling adaptor MyD88, which controlled the production of proinflammatory autoantibody isotypes. TLR7/9 activation strongly up-regulated expression of transmembrane activator and calcium modulator and cyclophilin ligand interactor (TACI), which is a receptor for BAFF involved in 13 cell responses to T cell-independent antigens. Moreover, BAFF enhanced TLR7/9 expression on 13 cells and TLR-mediated production of autoantibodies. Therefore, autoirnmunity in BAFF Tg mice results from altered 13 cell tolerance, but requires TLR signaling and is independent of T cell help. It is possible that SLE patients with elevated levels of BAFF show a similar basis for disease

Adaptive Prediction Error Coding in the Human Midbrain and Striatum Facilitates Behavioral Adaptation and Learning Efficiency.

Effective error-driven learning benefits from scaling of prediction errors to reward variability. Such behavioral adaptation may be facilitated by neurons coding prediction errors relative to the standard deviation (SD) of reward distributions. To investigate this hypothesis, we required participants to predict the magnitude of upcoming reward drawn from distributions with different SDs. After each prediction, participants received a reward, yielding trial-by-trial prediction errors. In line with the notion of adaptive coding, BOLD response slopes in the Substantia Nigra/Ventral Tegmental Area (SN/VTA) and ventral striatum were steeper for prediction errors occurring in distributions with smaller SDs. SN/VTA adaptation was not instantaneous but developed across trials. Adaptive prediction error coding was paralleled by behavioral adaptation, as reflected by SD-dependent changes in learning rate. Crucially, increased SN/VTA and ventral striatal adaptation was related to improved task performance. These results suggest that adaptive coding facilitates behavioral adaptation and supports efficient learning.This study was supported by the Wellcome Trust (W.S., P.C.F.), Bernard Wolfe Health Neuroscience Fund (P.C.F.) and the Niels Stensen Foundation (K.M.J.D.). We thank William Stauffer, Armin Lak and Joost Haarsma for useful discussions.This is the final version of the article. It first appeared from Cell Press via http://dx.doi.org/10.1016/j.neuron.2016.04.01

An empirical evaluation of temporal overheating in an assisted living Passivhaus dwelling in the UK

Global concern around energy use and anthropogenic climate change have resulted in an increased effort to reduce the energy demand and CO2 emissions attributable to buildings. This has led to the development of a number of low energy building standards, one of which is the internationally recognised Passivhaus Standard. The Passivhaus Standard aims to reduce the space heating energy demand of a building by adopting a ‘fabric first’ approach, thus ensuring the thermal envelope is highly insulated and airtight whilst also maximising passive solar heat gains. However, adopting such an approach does present a risk of overheating; a situation that is of particular concern when the occupants have additional healthcare requirements. This study uses 21 months of in-use monitored data to consider the overheating risk in a UK Passivhaus dwelling with vulnerable occupants using both static and adaptive thermal comfort assessment methods. The analysis of the data suggests the occurrence of substantial overheating according to PHPP, CIBSE Guide A and CIBSE TM52 criteria. The analysis was then expanded to consider a novel composite method to overcome the limitations of existing approaches, allowing overheating to be assessed during non-typical periods i.e. the heating season. This revealed apparent overheating during colder months, in addition to substantial night-time overheating. This has implications for the thermal comfort assessment of low energy dwellings and the design and operation of Passivhaus buildings, particularly those with vulnerable occupants

Great expectations, inconvenient truths, and the paradoxes of the dog-owner relationship for owners of brachycephalic dogs

Popularity of brachycephalic (flat-faced) dog breeds is increasing internationally despite well-documented intrinsic health and welfare problems associated with their conformation. Given this apparent paradox, greater understanding of the expectations and reality for brachycephalic dog owners and factors driving the dog-owner bond are needed. This study reports a large-scale online survey with valid responses from 2168 owners of brachycephalic dogs (Pugs: n = 789, median age of dogs 2.5 years; French Bulldog: n = 741, median age 2.0 years; Bulldogs: n = 638, median age 2.5 years). The most common owner-reported disorders in their dogs were allergies, corneal ulcers, skin fold infections and Brachycephalic Obstructive Airway Syndrome (BOAS). One-fifth (19.9%) of owners reported that their dog had undergone at least one conformation-related surgery, 36.5% of dogs were reported with a problem with heat regulation, and 17.9% with problems breathing. Despite awareness of their dog’s health issues, 70.9% owners considered their dog to be in very good health or the best health possible. Paradoxically, just 6.8% of owners considered their dog to be less healthy than average for their breed. Dog owner-relationships were extremely strong across all three breeds. Emotional closeness to their dog was highest for owners of Pugs, female owners, and owners with no children in the household. Ownership of brachycephalic dog breeds is a complex phenomenon, characterised by extremely strong dog-owner relationships and unrealistic perceptions of good health set against high levels of disease in relatively young dogs. Perceptual errors in owner beliefs appear to exist between brachycephalic owner perspectives of their own dog’s health versus the health of the rest of their breed, which may be fuelled by cognitive dissonance processes. These novel data improve our understanding of the cognitive processes and relationships that facilitate the rising popularity of breeds that paradoxically are affected by high levels of conformation-related morbidity

Variability in the chemistry of private drinking water supplies and the impact of domestic treatment systems on water quality.

Tap water from 497 properties using private water supplies, in an area of metalliferous and arsenic mineralisation (Cornwall, UK), was measured to assess the extent of compliance with chemical drinking water quality standards, and how this is influenced by householder water treatment decisions. The proportion of analyses exceeding water quality standards were high, with 65 % of tap water samples exceeding one or more chemical standards. The highest exceedances for health-based standards were nitrate (11 %) and arsenic (5 %). Arsenic had a maximum observed concentration of 440 µg/L. Exceedances were also high for pH (47 %), manganese (12 %) and aluminium (7 %), for which standards are set primarily on aesthetic grounds. However, the highest observed concentrations of manganese and aluminium also exceeded relevant health-based guidelines. Significant reductions in concentrations of aluminium, cadmium, copper, lead and/or nickel were found in tap waters where households were successfully treating low-pH groundwaters, and similar adventitious results were found for arsenic and nickel where treatment was installed for iron and/or manganese removal, and successful treatment specifically to decrease tap water arsenic concentrations was observed at two properties where it was installed. However, 31 % of samples where pH treatment was reported had pH < 6.5 (the minimum value in the drinking water regulations), suggesting widespread problems with system maintenance. Other examples of ineffectual treatment are seen in failed responses post-treatment, including for nitrate. This demonstrates that even where the tap waters are considered to be treated, they may still fail one or more drinking water quality standards. We find that the degree of drinking water standard exceedances warrant further work to understand environmental controls and the location of high concentrations. We also found that residents were more willing to accept drinking water with high metal (iron and manganese) concentrations than international guidelines assume. These findings point to the need for regulators to reinforce the guidance on drinking water quality standards to private water supply users, and the benefits to long-term health of complying with these, even in areas where treated mains water is widely available

Type-selective muscular degeneration promotes infiltrative growth of intramuscular lipoma

BACKGROUND: Intramuscular lipoma is a relatively common benign neoplasm that is occasionally described as an infiltrating lipoma. Typical benign tumors show a clear margin, however, the infiltrative growth pattern of this lipoma mimics that of a malignant tumor. Although its growth has an effect on muscle bundles and it is known to never metastasize, the mechanism of infiltrative growth is not well understood. Previously, little attention has been paid to pathogenic features of muscle fibers around an intramuscular lipoma. METHODS: In the present study, we focused on pathologic changes of the surrounding skeletal muscles especially to the degenerative features of involving muscular types, and evaluate the role of type-selective muscular degeneration for the infiltrative growth of intramuscular lipomas. Following a review of the medical records in our institute, 17 lesions containing muscle tissues in their specimens (15 infiltrating lipomas, 2 well-circumscribed lipomas) were analyzed immunohistochemically. The tumor from the most recent case was also subjected to ultrastructural analysis. Two cases of the traumatic muscle damage were also evaluated as the control experiments. RESULTS: These analyses revealed type-selective muscle involution in 11 of 17 intramuscular lipomas and in 10 of 11 of the infiltrative type, with an involving pattern that resembled that of a neurogenic or myogenic disorder. Immunoreactivity to cathepsin-D, a lysosomal catabolic enzyme, was increased in the involved muscle fibers. Subsarcolemmal vacuoles in the muscle fibers of the peripheral areas were also positive for cathepsin-D, while degenerative findings were not visually apparent in these areas. Ultrastructural analysis revealed degenerative changes in those fibers. Neither positive staining for cathepsin-D nor type-selective atrophy was detected in the sections of traumatic muscle damage. CONCLUSIONS: Our findings suggest that type-selective muscular degeneration and endomysial fatty growth as a result of atrophy may modulate the infiltrating growth characteristic of intramuscular lipoma

Evolutionary distances in the twilight zone -- a rational kernel approach

Phylogenetic tree reconstruction is traditionally based on multiple sequence alignments (MSAs) and heavily depends on the validity of this information bottleneck. With increasing sequence divergence, the quality of MSAs decays quickly. Alignment-free methods, on the other hand, are based on abstract string comparisons and avoid potential alignment problems. However, in general they are not biologically motivated and ignore our knowledge about the evolution of sequences. Thus, it is still a major open question how to define an evolutionary distance metric between divergent sequences that makes use of indel information and known substitution models without the need for a multiple alignment. Here we propose a new evolutionary distance metric to close this gap. It uses finite-state transducers to create a biologically motivated similarity score which models substitutions and indels, and does not depend on a multiple sequence alignment. The sequence similarity score is defined in analogy to pairwise alignments and additionally has the positive semi-definite property. We describe its derivation and show in simulation studies and real-world examples that it is more accurate in reconstructing phylogenies than competing methods. The result is a new and accurate way of determining evolutionary distances in and beyond the twilight zone of sequence alignments that is suitable for large datasets.Comment: to appear in PLoS ON

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

Bisphosphonate drugs have actions in the lung and inhibit the mevalonate pathway in alveolar macrophages.

Bisphosphonates drugs target the skeleton and are used globally for the treatment of common bone disorders. Nitrogen-containing bisphosphonates act by inhibiting the mevalonate pathway in bone-resorbing osteoclasts but, surprisingly, also appear to reduce the risk of death from pneumonia. We overturn the long-held belief that these drugs act only in the skeleton and show that a fluorescently labelled bisphosphonate is internalised by alveolar macrophages and large peritoneal macrophages in vivo. Furthermore, a single dose of a nitrogen-containing bisphosphonate (zoledronic acid) in mice was sufficient to inhibit the mevalonate pathway in tissue-resident macrophages, causing the build-up of a mevalonate metabolite and preventing protein prenylation. Importantly, one dose of bisphosphonate enhanced the immune response to bacterial endotoxin in the lung and increased the level of cytokines and chemokines in bronchoalveolar fluid. These studies suggest that bisphosphonates, as well as preventing bone loss, may boost immune responses to infection in the lung and provide a mechanistic basis to fully examine the potential of bisphosphonates to help combat respiratory infections that cause pneumonia