Development of a Moderated Online Intervention to Treat Social Anxiety in First-Episode Psychosis.

Background: It is well established that social anxiety disorder (SAD) is a significant clinical problem for individuals with a psychotic disorder. Comorbid social anxiety in individuals with psychosis has been associated with poorer premorbid functioning, increased depression, and a reduced quality of life. Cognitive behavior therapy (CBT) is recommended for people with psychosis as a first-line psychological treatment; however, its focus and evaluation primarily revolves around reducing psychotic symptoms and not necessarily targeting comorbid social anxiety symptoms. We developed a novel online social cognitive behavioral intervention (entitled EMBRACE) specifically designed to treat social anxiety symptoms in first episode psychosis (FEP). Methods: The key clinical and engagement features of the intervention were established through integrating evidence-based material derived from 1) CBT-based treatment models for SAD, 2) relevant literature findings related to psychosis and its clinical correlates (e.g., shame, social rank, and its relationship with social anxiety and paranoia), 3) feedback from youth focus groups in order to inform a user-centered intervention design, and 4) a highly multidisciplinary collaborative development approach to design therapy comics. Results: A detailed description of the final version of the 12-week online social intervention to treat social anxiety in FEP is presented. Conclusion: The EMBRACE intervention was designed to provide young people with the necessary skills and confidence to overcome social anxiety within a supportive, safe online space. By design, it allows young people the opportunity to practice their newly learnt skills to connect with others and in doing so, learn to embrace their true authentic selves

Propolis can potentialise the anti-adhesion activity of proanthocyanidins on uropathogenic Escherichia coli in the prevention of recurrent urinary tract infections

<p>Abstract</p> <p>Background</p> <p><it>Escherichia coli</it>, the main bacteria found in recurrent urinary tract infections (UTI), is now frequently resistant to several currently used antibiotic treatments making new solutions essential. In this study, we evaluated the association propolis and proanthocyanidins type A to reduce bacterial anti-adhesion activity of <it>E. coli </it>on urothelial cells.</p> <p>Results</p> <p>This first double-blind, randomized, cross-over human trial included 5 volunteers that followed 6 different regimens with or without variable doses of cranberry and propolis with a washout period of at least 1 week between each regimen. Urine samples were collected at 0 h, 4-6 h, 12 h and 24 h after cranberry plus propolis or placebo capsule consumption. In vivo urinary bacterial anti-adhesion activity was assessed with a bioassay (a human T24 epithelial cell-line assay) and an in vivo <it>Caenorhabditis elegans </it>model. HPLC-PDA-MS was used to detect propolis and cranberry compounds in urine. Bioassays indicated significant bacterial anti-adhesion activity in urine collected from volunteers who had consumed cranberry plus propolis powder compared to placebo (<it>p </it>< 0.001). This inhibition was clearly dose-dependent, increasing with the amount of PACs and propolis equivalents consumed in each regimen. Results suggested that propolis had an additional effect with PACs and prevent a bacterial anti-adhesion effect over 1 day. An in vivo model showed that the <it>E. coli </it>strain presented a reduced ability to kill <it>C. elegans </it>after their growth in urine samples of patients who took cranberry plus propolis capsules. HPLC confirmed that propolis is excreted in urine.</p> <p>Conclusions</p> <p>This study presents an alternative to prevent recurrent UTI. Administration of PACs plus propolis once daily offers some protection against bacterial adhesion, bacterial multiplication and virulence in the urinary tract, representing an interesting new strategy to prevent recurrent UTI.</p

The morbidity and mortality following a diagnosis of peripheral arterial disease: Long-term follow-up of a large database

BACKGROUND: Awareness of the significance of peripheral arterial disease is increasing, but quantitative estimates of the ensuing burden and the impact of other risk factors remains limited. The objective of this study was to fill this need. METHODS: Morbidity and mortality were examined in 16,440 index patients diagnosed with peripheral arterial disease in Saskatchewan, Canada between 1985 and 1995. Medical history and patient characteristics were available retrospectively to January 1980 and follow-up was complete to March 1998. Crude and adjusted event rates were calculated and Kaplan-Meier survival curves estimated. Cox proportional hazards analyses were conducted to examine the effect of risk factors on these rates. Patients suffering a myocardial infarction or ischemic stroke in Saskatchewan provided two reference populations. RESULTS: Half of the index patients were male; the majority was over age 65; 73% had at least one additional risk factor at index diagnosis; 10% suffered a subsequent stroke, another 10% a myocardial infarction, and 49% died within the mean follow-up of 5.9 years. Annual mortality (8.2%) was higher among patients with PAD than after a myocardial infarction (6.3%) but slightly lower than that in patients suffering a stroke (11.3%). Index patients with comorbid disease (e.g., diabetes) were at highest risk of death and other events. CONCLUSION: A diagnosis of peripheral arterial disease is critical evidence of more widespread atherothrombotic disease, with substantial risks of subsequent cardiovascular events and death. Given that the majority has additional comorbidities, these risks are further increased

Type Ia Supernovae as Stellar Endpoints and Cosmological Tools

Empirically, Type Ia supernovae are the most useful, precise, and mature tools for determining astronomical distances. Acting as calibrated candles they revealed the presence of dark energy and are being used to measure its properties. However, the nature of the SN Ia explosion, and the progenitors involved, have remained elusive, even after seven decades of research. But now new large surveys are bringing about a paradigm shift --- we can finally compare samples of hundreds of supernovae to isolate critical variables. As a result of this, and advances in modeling, breakthroughs in understanding all aspects of SNe Ia are finally starting to happen.Comment: Invited review for Nature Communications. Final published version. Shortened, update

Fulvestrant and the sequential endocrine cascade for advanced breast cancer

Following relapse on endocrine therapy for advanced, hormone receptor-positive breast cancer, it is common for patients to experience responses to alternative endocrine agents. Fulvestrant (‘Faslodex’) is a new type of endocrine treatment – an oestrogen receptor (ER) antagonist with no agonist effects. Fulvestrant downregulates cellular levels of the ER resulting in decreased expression of the progesterone receptor. This unique mode of action means that it is important that fulvestrant is placed optimally within the sequence of endocrine therapies to ensure that patients gain maximum benefit. Fulvestrant has shown efficacy when used after progression on tamoxifen or anastrozole in postmenopausal women with advanced breast cancer. After progression on fulvestrant, subsequent endocrine treatments can produce responses in many patients, demonstrating that fulvestrant does not lead to crossresistance with other endocrine therapies. Responses to fulvestrant have also been observed in patients heavily pretreated with prior endocrine therapy. Fulvestrant is a versatile endocrine agent that may be integrated into the therapeutic sequence prior to, or subsequent to, other hormonal therapies, and represents a valuable additional antioestrogen for the treatment of postmenopausal women with advanced breast cancer

Ovine pedomics : the first study of the ovine foot 16S rRNA-based microbiome

We report the first study of the bacterial microbiome of ovine interdigital skin based on 16S rRNA by pyrosequencing and conventional cloning with Sanger-sequencing. Three flocks were selected, one a flock with no signs of footrot or interdigital dermatitis, a second flock with interdigital dermatitis alone and a third flock with both interdigital dermatitis and footrot. The sheep were classified as having either healthy interdigital skin (H), interdigital dermatitis (ID) or virulent footrot (VFR). The ovine interdigital skin bacterial community varied significantly by flock and clinical condition. The diversity and richness of operational taxonomic units was greater in tissue from sheep with ID than H or VFR affected sheep. Actinobacteria, Bacteriodetes, Firmicutes and Proteobacteria were the most abundant phyla comprising 25 genera. Peptostreptococcus, Corynebacterium and Staphylococcus were associated with H, ID and VFR respectively. Sequences of Dichelobacter nodosus, the causal agent of ovine footrot, were not amplified due to mismatches in the 16S rRNA universal forward primer (27F). A specific real time PCR assay was used to demonstrate the presence of D. nodosus which was detected in all samples including the flock with no signs of ID or VFR. Sheep with ID had significantly higher numbers of D. nodosus (104-109 cells/g tissue) than those with H or VFR feet

Narrowband Biphotons: Generation, Manipulation, and Applications

In this chapter, we review recent advances in generating narrowband biphotons with long coherence time using spontaneous parametric interaction in monolithic cavity with cluster effect as well as in cold atoms with electromagnetically induced transparency. Engineering and manipulating the temporal waveforms of these long biphotons provide efficient means for controlling light-matter quantum interaction at the single-photon level. We also review recent experiments using temporally long biphotons and single photons.Comment: to appear as a book chapter in a compilation "Engineering the Atom-Photon Interaction" published by Springer in 2015, edited by A. Predojevic and M. W. Mitchel

Consensus on circulatory shock and hemodynamic monitoring. Task force of the European Society of Intensive Care Medicine.

OBJECTIVE: Circulatory shock is a life-threatening syndrome resulting in multiorgan failure and a high mortality rate. The aim of this consensus is to provide support to the bedside clinician regarding the diagnosis, management and monitoring of shock. METHODS: The European Society of Intensive Care Medicine invited 12 experts to form a Task Force to update a previous consensus (Antonelli et al.: Intensive Care Med 33:575-590, 2007). The same five questions addressed in the earlier consensus were used as the outline for the literature search and review, with the aim of the Task Force to produce statements based on the available literature and evidence. These questions were: (1) What are the epidemiologic and pathophysiologic features of shock in the intensive care unit ? (2) Should we monitor preload and fluid responsiveness in shock ? (3) How and when should we monitor stroke volume or cardiac output in shock ? (4) What markers of the regional and microcirculation can be monitored, and how can cellular function be assessed in shock ? (5) What is the evidence for using hemodynamic monitoring to direct therapy in shock ? Four types of statements were used: definition, recommendation, best practice and statement of fact. RESULTS: Forty-four statements were made. The main new statements include: (1) statements on individualizing blood pressure targets; (2) statements on the assessment and prediction of fluid responsiveness; (3) statements on the use of echocardiography and hemodynamic monitoring. CONCLUSIONS: This consensus provides 44 statements that can be used at the bedside to diagnose, treat and monitor patients with shock

Mammographic density adds accuracy to both the Tyrer-Cuzick and Gail breast cancer risk models in a prospective UK screening cohort

This work was supported by the National Institute for Health Research (NIHR) and Genesis Breast Cancer Prevention Appeal (references GA10-033 and GA13-006). This article presents independent research funded by the NIHR under its Programme Grants for Applied Research (grant RP-PG-0707-10031). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. The authors also acknowledge the support of Medical Research Council Health eResearch Centre grant MR/K006665/1

Bub1 Is a Fission Yeast Kinetochore Scaffold Protein, and Is Sufficient to Recruit other Spindle Checkpoint Proteins to Ectopic Sites on Chromosomes

The spindle checkpoint delays anaphase onset until all chromosomes have attached in a bi-polar manner to the mitotic spindle. Mad and Bub proteins are recruited to unattached kinetochores, and generate diffusible anaphase inhibitors. Checkpoint models propose that Mad1 and Bub1 act as stable kinetochore-bound scaffolds, to enhance recruitment of Mad2 and Mad3/BubR1, but this remains untested for Bub1. Here, fission yeast FRAP experiments confirm that Bub1 stably binds kinetochores, and by tethering Bub1 to telomeres we demonstrate that it is sufficient to recruit anaphase inhibitors in a kinase-independent manner. We propose that the major checkpoint role for Bub1 is as a signalling scaffold