'The world is full of big bad wolves': investigating the experimental therapeutic spaces of R.D. Laing and Aaron Esterson

In conjunction with the recent critical assessments of the life and work of R.D. Laing, this paper seeks to demonstrate what is revealed when Laing’s work on families and created spaces of mental health care are examined through a geographical lens. The paper begins with an exploration of Laing’s time at the Tavistock Clinic in London during the 1960s, and of the co-authored text with Aaron Esterson entitled, Sanity, Madness and the Family (1964). The study then seeks to demonstrate the importance Laing and his colleague placed on the time-space situatedness of patients and their worlds. Finally, an account is provided of Laing’s and Esterson’s spatial thinking in relation to their creation of both real and imagined spaces of therapeutic care

Fire effects on aquatic ecosystems: an assessment of the current state of science

Fire is a prevalent feature of many landscapes and has numerous and complex effects on geological, hydrological, ecological, and economic systems. In some regions, the frequency and intensity of wildfire have increased in recent years and are projected to escalate with predicted climatic and landuse changes. In addition, prescribed burns continue to be used in many parts of the world to clear vegetation for development projects, encourage desired vegetation, and reduce fuel loads. Given the prevalence of fire on the landscape, authors of papers in this special series examine the complexities of fire as a disturbance shaping freshwater ecosystems and highlight the state of the science. These papers cover key aspects of fire effects that range from vegetation loss and recovery in watersheds to effects on hydrology and water quality with consequences for communities (from algae to fish), food webs, and ecosystem processes (e.g., organic matter subsidies, nutrient cycling) across a range of scales. The results presented in this special series of articles expand our knowledge of fire effects in different biomes, water bodies, and geographic regions, encompassing aquatic population, community, and ecosystem responses. In this overview, we summarize each paper and emphasize its contributions to knowledge on fire ecology and freshwater ecosystems. This overview concludes with a list of 7 research foci that are needed to further our knowledge of fire effects on aquatic ecosystems, including research on: 1) additional biomes and geographic regions; 2) additional habitats, including wetlands and lacustrine ecosystems; 3) different fire severities, sizes, and spatial configurations; and 4) additional response variables (e.g., ecosystem processes) 5) over long (>5 y) time scales 6) with more rigorous study designs and data analyses, and 7) consideration of the effects of fire management practices and policies on aquatic ecosystems

Galectin-3-null mice display defective neutrophil clearance during acute inflammation

Galectin-3 has been associated with a plethora of proinflammatory functions because of its ability, among others, to promote neutrophil activation and because of the reduction in neutrophil recruitment in models of infection in Gal-3-null mice. Conversely, it has also been linked to resolution of inflammation through its actions as an opsonin and its ability to promote efferocytosis of apoptotic neutrophils. Using a self-resolving model of peritonitis, we have addressed the modulation and role of Gal-3 in acute inflammation. We have shown that Gal-3 expression is increased in neutrophils that travel to the inflamed peritoneum and that cellular localization of this lectin is modulated during the course of the inflammatory response. Furthermore, neutrophil recruitment to the inflamed peritoneum is increased in Gal-3–null mice during the course of the response, and that correlates with reduced numbers of monocytes/macrophages in the cavities of those mice, as well as reduced apoptosis and efferocytosis of Gal-3–null neutrophils. These data indicate a role for endogenous Gal-3 in neutrophil clearance during acute inflammation

Increasing the frequency of hand washing by healthcare workers does not lead to commensurate reductions in staphylococcal infection in a hospital ward

Hand hygiene is generally considered to be the most important measure that can be applied to prevent the spread of healthcare-associated infection (HAI). Continuous emphasis on this intervention has lead to the widespread opinion that HAI rates can be greatly reduced by increased hand hygiene compliance alone. However, this assumes that the effectiveness of hand hygiene is not constrained by other factors and that improved compliance in excess of a given level, in itself, will result in a commensurate reduction in the incidence of HAI. However, several researchers have found the law of diminishing returns to apply to hand hygiene, with the greatest benefits occurring in the first 20% or so of compliance, and others have demonstrated that poor cohorting of nursing staff profoundly influences the effectiveness of hand hygiene measures. Collectively, these findings raise intriguing questions about the extent to which increasing compliance alone can further reduce rates of HAI. In order to investigate these issues further, we constructed a deterministic Ross-Macdonald model and applied it to a hypothetical general medical ward. In this model the transmission of staphylococcal infection was assumed to occur after contact with the transiently colonized hands of HCWs, who, in turn, acquire contamination only by touching colonized patients. The aim of the study was to evaluate the impact of imperfect hand cleansing on the transmission of staphylococcal infection and to identify, whether there is a limit, above which further hand hygiene compliance is unlikely to be of benefit. The model demonstrated that if transmission is solely via the hands of HCWs, it should, under most circumstances, be possible to prevent outbreaks of staphylococcal infection from occurring at a hand cleansing frequencies <50%, even with imperfect hand hygiene. The analysis also indicated that the relationship between hand cleansing efficacy and frequency is not linear - as efficacy decreases, so the hand cleansing frequency required to ensure R0<1 increases disproportionately. Although our study confirmed hand hygiene to be an effective control measure, it demonstrated that the law of diminishing returns applies, with the greatest benefit derived from the first 20% or so of compliance. Indeed, our analysis suggests that there is little benefit to be accrued from very high levels of hand cleansing and that in most situations compliance >40% should be enough to prevent outbreaks of staphylococcal infection occurring, if transmission is solely via the hands of HCWs. Furthermore we identified a non-linear relationship between hand cleansing efficacy and frequency, suggesting that it is important to maximise the efficacy of the hand cleansing process

Social networks and labour productivity in Europe: An empirical investigation

This paper uses firm-level data recorded in the AMADEUS database to investigate the distribution of labour productivity in different European countries. We find that the upper tail of the empirical productivity distributions follows a decaying power-law, whose exponent $\alpha$ is obtained by a semi-parametric estimation technique recently developed by Clementi et al. (2006). The emergence of "fat tails" in productivity distribution has already been detected in Di Matteo et al. (2005) and explained by means of a model of social network. Here we show that this model is tested on a broader sample of countries having different patterns of social network structure. These different social attitudes, measured using a social capital indicator, reflect in the power-law exponent estimates, verifying in this way the existence of linkages among firms' productivity performance and social network.Comment: LaTeX2e; 18 pages with 3 figures; Journal of Economic Interaction and Coordination, in pres

Intravitreal administration of recombinant human opticin protects against hyperoxia-induced pre-retinal neovascularization

Opticin is an extracellular glycoprotein present in the vitreous. Its antiangiogenic properties offer the potential for therapeutic intervention in conditions such as proliferative diabetic retinopathy and retinopathy of prematurity. Here, we investigated the hypothesis that intravitreal administration of recombinant human opticin can safely protect against the development of pathological angiogenesis and promote its regression. We generated and purified recombinant human opticin and investigated its impact on the development and regression of pathological retinal neovascularization following intravitreal administration in murine oxygen-induced retinopathy. We also investigated its effect on normal retinal vascular development and function, following intravitreal injection in neonatal mice, by histological examination and electroretinography. In oxygen-induced retinopathy, intravitreal administration of human recombinant opticin protected against the development of retinal neovascularization to similar extent as aflibercept, which targets VEGF. Opticin also accelerated regression of established retinal neovascularization, though the effect at 18 h was less than that of aflibercept. Intravitreal administration of human recombinant opticin in neonatal mice caused no detectable perturbation of subsequent retinal vascular development or function. In summary we found that intraocular administration of recombinant human opticin protects against the development of pathological angiogenesis in mice and promotes its regression

Three-body interactions with cold polar molecules

We show that polar molecules driven by microwave fields give naturally rise to strong three-body interactions, while the two-particle interaction can be independently controlled and even switched off. The derivation of these effective interaction potentials is based on a microscopic understanding of the underlying molecular physics, and follows from a well controlled and systematic expansion into many-body interaction terms. For molecules trapped in an optical lattice, we show that these interaction potentials give rise to Hubbard models with strong nearest-neighbor two-body and three-body interaction. As an illustration, we study the one-dimensional Bose-Hubbard model with dominant three-body interaction and derive its phase diagram.Comment: 8 pages, 4 figure

Drugs Associated with More Suicidal Ideations Are also Associated with More Suicide Attempts

In randomized controlled trials (RCTs), some drugs, including CB1 antagonists for obesity treatment, have been shown to cause increased suicidal ideation. A key question is whether drugs that increase or are associated with increased suicidal ideations are also associated with suicidal behavior, or whether drug-induced suicidal ideations are unlinked epiphenomena that do not presage the more troubling and potentially irrevocable outcome of suicidal behavior. This is difficult to determine in RCTs because of the rarity of suicidal attempts and completions.To determine whether drugs associated with more suicidal ideations are also associated with more suicide attempts in large spontaneous adverse event (AE) report databases.Generalized linear models with negative binomial distribution were fitted to Food and Drug Administration (FDA) Adverse Event (AE) Reporting System (AERS) data from 2004 to 2008. A total of 1,404,470 AEs from 832 drugs were analyzed as a function of reports of suicidal ideations; other non-suicidal adverse reactions; drug class; proportion of reports from males; and average age of subject for which AE was filed. Drug was treated as the unit of analysis, thus the statistical models effectively had 832 observations.Reported suicide attempts and completed suicides per drug.832 drugs, ranging from abacavir to zopiclone, were evaluated. The 832 drugs, as primary suspect drugs in a given adverse event, accounted for over 99.9% of recorded AERS. Suicidal ideations had a significant positive association with suicide attempts (p<.0001) and had an approximately 131-fold stronger magnitude of association than non-suicidal AERs, after adjusting for drug class, gender, and age.In AE reports, drugs that are associated with increased suicidal ideations are also associated with increased suicidal attempts or completions. This association suggests that drug-induced suicidal ideations observed in RCTs plausibly represent harbingers that presage the more serious suicide attempts and completions and should be a cause for concern

52-week efficacy and safety of telbivudine with conditional tenofovir intensification at week 24 in HBeAg-positive chronic Hepatitis B

Background and Aims: The Roadmap concept is a therapeutic framework in chronic hepatitis B for the intensification of nucleoside analogue monotherapy based on early virologic response. The efficacy and safety of this approach applied to telbivudine treatment has not been investigated. Methods: A multinational, phase IV, single-arm open-label study (ClinicalTrials.gov ID NCT00651209) was undertaken in HBeAg-positive, nucleoside-naive adult patients with chronic hepatitis B. Patients received telbivudine (600 mg once-daily) for 24 weeks, after which those with undetectable serum HBV DNA (<300 copies/mL) continued to receive telbivudine alone while those with detectable DNA received telbivudine plus tenofovir (300 mg once-daily). Outcomes were assessed at Week 52. Results: 105 patients commenced telbivudine monotherapy, of whom 100 were included in the efficacy analysis. Fifty-five (55%) had undetectable HBV DNA at Week 24 and continued telbivudine monotherapy; 45 (45%) received tenofovir intensification. At Week 52, the overall proportion of undetectable HBV DNA was 93% (93/100) by last-observation-carried-forward analysis (100% monotherapy group, 84% intensification group) and no virologic breakthroughs had occurred. ALT normalization occurred in 77% (87% monotherapy, 64% intensification), HBeAg clearance in 43% (65% monotherapy, 16% intensification), and HBeAg seroconversion in 39% (62% monotherapy, 11% intensification). Six patients had HBsAg clearance. Myalgia was more common in the monotherapy group (19% versus 7%). No decrease in the mean glomerular filtration rate occurred in either treatment group at Week 52. Conclusions: Telbivudine therapy with tenofovir intensification at Week 24, where indicated by the Roadmap strategy, appears effective and well tolerated for the treatment of chronic hepatitis B. Trial Registration: ClinicalTrials.gov NCT0065120