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Informative, illuminating, insightful and erudite, Slogan T-Shirts: Cult and Culture is completely unique. Featuring interviews with a wealth of cultural commentators, creative luminaries and credible fashion insiders, from Holly Johnson (of Frankie Goes to Hollywood) to Katharine Hamnett, it offers a multi-faceted approach as to the question of what makes the slogan T-shirt so rich, layered and culturally relevant... because slogans are never simply just words; they are emotive and evocative, suggestive and provocative.

Bisphosphonates are a class of drugs which are strongly attracted to the bone where they influence the calcium metabolism, mainly by inhibition of the osteoclast-mediated bone resorption. This property makes these compounds suited for the treatment of several diseases of the bone. In Paget's disease, several bisphosphonates can reduce bone pain and decrease the bone turnover 60-70%. Cyclical oral etidronate and daily oral alendronate both proved to reduce the vertebral fracture rate for postmenopausal osteoporotic woman, while most investigated bisphosphonates can increase spinal bone mass in osteoporosis. Bisphosphonates can help lowering serum calcium and reverse skeletal complications in malignancy mediated bone diseases. Oral and intravenous administration of therapeutic doses is relatively safe. In general, gastrointestinal disturbances are described most often and the oldest, least potent, bisphosphonate etidronate can induce osteomalacia. The various characteristics of bisphosphonates: physicochemical, biological, therapeutic and toxicological, vary greatly depending on the structure of the individual bisphosphonate. Even small changes in the structure can lead to enormous differences in potency. Overall, this class of drugs offers several prospects for the future.

Respiratory syncytial virus (RSV) can cause severe disease in adults with cardiopulmonary conditions, such as congestive heart failure (CHF). We quantified the rate of RSV-associated hospitalization in adults by CHF status using population-based surveillance in the United States. Population-based surveillance for RSV (RSV-NET) was performed in 35 counties in seven sites during two respiratory seasons (2015-2017) from October 1-April 30. Adults (≥18 years) admitted to a hospital within the surveillance catchment area with laboratory-confirmed RSV identified by clinician-directed testing were included. Presence of underlying CHF was determined by medical chart abstraction. We calculated overall and age-stratified (<65 years and ≥65 years) RSV-associated hospitalization rates by CHF status. Estimates were adjusted for age and the under-detection of RSV. We also report rate differences (RD) and rate ratios (RR) by comparing the rates for those with and without CHF. 2042 hospitalized RSV cases with CHF status recorded were identified. Most (60.2%, n = 1230) were ≥65 years, and 28.3% (n = 577) had CHF. The adjusted RSV hospitalization rate was 26.7 (95% CI: 22.2, 31.8) per 10,000 population in adults with CHF versus 3.3 (95% CI: 3.3, 3.3) per 10,000 in adults without CHF (RR: 8.1, 95% CI: 6.8, 9.7; RD: 23.4, 95% CI: 18.9, 28.5). Adults with CHF had higher rates of RSV-associated hospitalization in both age groups (<65 years and ≥65 years). Adults ≥65 years with CHF had the highest rate (40.5 per 10,000 population, 95% CI: 35.1, 46.6). Adults with CHF had 8 times the rate of RSV-associated hospitalization compared with adults without CHF. Identifying high-risk populations for RSV infection can inform future RSV vaccination policies and recommendations.

Early life stress compromises brain development and can contribute to the development of mental illnesses. A common animal model used to study different facets of psychiatric disorders is social isolation from early life on. In rats, this isolation can induce long-lasting alterations in molecular expression and in behavior. Since social isolation models severe psychiatric symptoms, it is to be expected that it affects the overall wellbeing of the animals. As also promoted by the 3Rs principle, though, it is pivotal to decrease the burden of laboratory animals by limiting the number of subjects (reduce, replace) and by improving the animals' wellbeing (refine). The aim of this study was therefore to test possible refinement strategies such as resocialization and mere adult social isolation. We examined whether the alternatives still triggered the necessary phenotype while minimizing the stress load on the animals. Interestingly, we did not find reduced wellbeing-associated burrowing performance in isolated rats. The hyperactive phenotype seen in socially isolated animals was observed for rats undergoing the adult-only isolation, but resocializing ameliorated the locomotor abnormality. Isolation strongly affected markers of neuroplasticity in the prefrontal cortex independent of timing: mRNA levels of Arc, Bdnf and the pool of Bdnf transcripts with the 3' long UTR were reduced in all groups. Bdnf splice variant IV expression was reduced in lifelong-isolated animals. Some of these deficits normalized after resocialization; likewise, exon VI Bdnf mRNA levels were reduced only in animals persistently isolated. Conversely, social deprivation did not affect the expression of Gad67 and Pvb, two GABAergic markers, whereas changes occurred in the expression of dopamine d1 and d2 receptors. As adult isolation was sufficient to trigger the hyperactive phenotype and impaired neuroplasticity in the prefrontal cortex, it could be a candidate for a refinement strategy for certain research questions. To fully grade the severity of post-weaning social isolation and the alternatives, adult isolation and resocialization, a more profound and multimodal assessment approach is necessary.

The fine-scale grading of the severity experienced by animals used in research constitutes a key element of the 3Rs (replace, reduce, and refine) principles and a legal requirement in the European Union Directive 2010/63/EU. Particularly, the exact assessment of all signs of pain, suffering, and distress experienced by laboratory animals represents a prerequisite to develop refinement strategies. However, minimal and noninvasive methods for an evidence-based severity assessment are scarce. Therefore, we investigated whether voluntary wheel running (VWR) provides an observer-independent behaviour-centred approach to grade severity experienced by C57BL/6J mice undergoing various treatments. In a mouse model of chemically induced acute colitis, VWR behaviour was directly related to colitis severity, whereas clinical scoring did not sensitively reflect severity but rather indicated marginal signs of compromised welfare. Unsupervised k-means algorithm-based cluster analysis of body weight and VWR data enabled the discrimination of cluster borders and distinct levels of severity. The validity of the cluster analysis was affirmed in a mouse model of acute restraint stress. This method was also applicable to uncover and grade the impact of serial blood sampling on the animal's welfare, underlined by increased histological scores in the colitis model. To reflect the entirety of severity in a multidimensional model, the presented approach may have to be calibrated and validated in other animal models requiring the integration of further parameters. In this experimental set up, however, the automated assessment of an emotional/motivational driven behaviour and subsequent integration of the data into a mathematical model enabled unbiased individual severity grading in laboratory mice, thereby providing an essential contribution to the 3Rs principles.

About a third of strokes cause aphasia, or language loss, with profound consequences for the person's social participation and quality of life. These problems may be mitigated by group social support. But this intervention is not available to all individuals. This study investigated whether it is feasible to deliver group social support to people with aphasia via a multi-user, virtual reality platform. It also explored the indicative effects of intervention and the costs. Intervention aimed to promote wellbeing and communicative success. It enabled participants to form new social connections and share experiences of living with aphasia. It comprised 14 sessions delivered over 6 months and was led by community based co-ordinators and volunteers. Feasibility measures comprised: recruitment and retention rates, compliance with intervention and assessment of treatment fidelity. Effects of intervention were explored using a waitlist randomised controlled design, with outcome measures of wellbeing, communication, social connectedness and quality of life. Two intervention groups were randomised to an immediate condition and two were randomised to a delayed condition. The main analysis explored scores on the measures between two time points, between which those in the immediate condition had received intervention, but those in the delayed group had not (yet). A comprehensive approach to economic data collection ensured that all costs of treatment delivery were recorded. Feasibility findings showed that the recruitment target was met (N = 34) and 85.3% (29/34) of participants completed intervention. All groups ran the 14 sessions as planned, and participants attended a mean of 11.4 sessions (s.d. 2.8), which was 81.6% of the intended dose. Fidelity checking showed minimal drift from the manualised intervention. No significant change was observed on any of the outcome measures, although the study was not powered to detect these. Costs varied across the four groups, from £7,483 - £12,562 British Pounds Sterling ( $10,972 - $ 18,419 US dollars), depending on travel costs, the relative contributions of volunteers and the number of hardware loans that were needed. The results suggest that a larger trial of remote group support, using virtual reality, would be merited. However the treatment content and regime, and the selection of outcome measures should be reviewed before conducting the trial.

Activation of nociceptor sensory neurons by noxious stimuli both triggers pain and increases capillary permeability and blood flow to produce neurogenic inflammation 1 , 2 , but whether nociceptors also interact with the immune system remains poorly understood. Here we report a neurotechnology for selective epineural optogenetic neuromodulation of nociceptors and demonstrate that nociceptor activation drives both protective pain behavior and inflammation. The wireless optoelectronic system consists of sub-millimeter-scale light-emitting diodes embedded in a soft, circumneural sciatic nerve implant, powered and driven by a miniaturized head-mounted control unit. Photostimulation of axons in freely moving mice that express channelrhodopsin only in nociceptors resulted in behaviors characteristic of pain, reflecting orthodromic input to the spinal cord. It also led to immune reactions in the skin in the absence of inflammation and potentiation of established inflammation, a consequence of the antidromic activation of nociceptor peripheral terminals. These results reveal a link between nociceptors and immune cells, which might have implications for the treatment of inflammation. An optogenetic study shows that activation of pain-triggering sensory neurons induces an immune response.

This study evaluated an intervention for people with aphasia delivered in a novel virtual reality platform called EVA Park. EVA Park contains a number of functional and fantastic locations and allows for interactive communication between multiple users. Twenty people with aphasia had 5 weeks' intervention, during which they received daily language stimulation sessions in EVA Park from a support worker. The study employed a quasi randomised design, which compared a group that received immediate intervention with a waitlist control group. Outcome measures explored the effects of intervention on communication and language skills, communicative confidence and feelings of social isolation. Compliance with the intervention was also explored through attrition and usage data. There was excellent compliance with the intervention, with no participants lost to follow up and most (18/20) receiving at least 88% of the intended treatment dose. Intervention brought about significant gains on a measure of functional communication. Gains were achieved by both groups of participants, once intervention was received, and were well maintained. Changes on the measures of communicative confidence and feelings of social isolation were not achieved. Results are discussed with reference to previous aphasia therapy findings.

Globally, lake surface water temperatures have warmed rapidly relative to air temperatures, but changes in deepwater temperatures and vertical thermal structure are still largely unknown. We have compiled the most comprehensive data set to date of long-term (1970-2009) summertime vertical temperature profiles in lakes across the world to examine trends and drivers of whole-lake vertical thermal structure. We found significant increases in surface water temperatures across lakes at an average rate of+0.37 degrees C decade(-1), comparable to changes reported previously for other lakes, and similarly consistent trends of increasing water column stability (+0.08 kg m(-3) decade(-1)). In contrast, however, deepwater temperature trends showed little change on average (+0.06 degrees C decade(-1)), but had high variability across lakes, with trends in individual lakes ranging from -0.68 degrees C decade(-1) to+0.65 degrees C decade(-1). The variability in deepwater temperature trends was not explained by trends in either surface water temperatures or thermal stability within lakes, and only 8.4% was explained by lake thermal region or local lake characteristics in a random forest analysis. These findings suggest that external drivers beyond our tested lake characteristics are important in explaining long-term trends in thermal structure, such as local to regional climate patterns or additional external anthropogenic influences.

In the 2015-2016 season, quadrivalent live attenuated influenza vaccine (LAIV) and both trivalent and quadrivalent inactivated influenza vaccine (IIV) were available in the United States. This study, conducted according to a test-negative case-control design, enrolled children aged 2-17 years presenting to outpatient settings with fever and respiratory symptoms for <5 days at 8 sites across the United States between 30 November 2015 and 15 April 2016. A nasal swab was obtained for reverse-transcriptase polymerase chain reaction (RT-PCR) testing for influenza, and influenza vaccination was verified in the medical record or vaccine registry. Influenza vaccine effectiveness (VE) was estimated using a logistic regression model. Of 1012 children retained for analysis, most children (59%) were unvaccinated, 10% received LAIV, and 31% received IIV. Influenza A (predominantly antigenically similar to the A/California/7/2009 strain) was detected in 14% and influenza B (predominantly a B/Victoria lineage) in 10%. For all influenza, VE was 46% (95% confidence interval [CI], 7%-69%) for LAIV and 65% (48%-76%) for IIV. VE against influenza A(H1N1)pdm09 was 50% (95% CI, -2% to 75%) for LAIV and 71% (51%-82%) for IIV. The odds ratio for vaccine failure with RT-PCR-confirmed A(H1N1)pdm09 was 1.71 (95% CI, 0.78-3.73) in LAIV versus IIV recipients. LAIV and IIV demonstrated effectiveness against any influenza among children aged 2-17 years in 2015-2016. When compared to all unvaccinated children, VE against influenza A(H1N1)pdm09 was significant for IIV but not LAIV. NCT01997450.