An interface fire is a fire that occurs in the wildland/urban interface (WUI), otherwise known as the I-Zone. Here, Todd emphasizes the importance of observing safety at all times in dealing with ...interface fires. To this end, she further elaborates other safety considerations on the way to and at the WUI incident scene, as well as estimating the resource needs, modes of attack, and when to give up on defending a structure.
A development competition is a sale by tender of publicly owned land with development potential where the bidders are asked also to submit design proposals. A competition must provide a market to ...secure best value in the sale of a land asset; this also enables the vendor to select from the design ideas, development expertise and financial resources of a range of bidders. This should help to secure high quality in urban design, environmental and other benefits for the local community. While there is a clear policy overlap with town planning, and in particular with planning agreements, there is a legal requirement to keep the sale separate from formal planning decisions. Development agreements are usually made between the parties to cover the building period after which the site is conveyed. Large numbers of such competitions are held in the UK each year and they thus provide the basis for many residential, commercial development projects and regeneration of urban locales. Disposal of sites in this way has become more significant due to the concentration of activity on brown-field land. In future, the need to assemble and repackage urban land in the sustainable city is likely to make such competitions yet more frequent. While there are clear advantages in theory, in practice competitions are not without problems. There is often conflict between the aims and tension over the evaluation of bids, especially between the different professions and personnel involved. The paper reports on research that combines quantitative and qualitative methodologies. A postal survey was carried out of UK Local Authority Estates Officers covering their use, experience and views on development competitions. A response rate of 40% was achieved from a sample of 225. A case study of development competitions in Tyne and Wear, UK was also carried out, which involved in-depth interviews with 5 Local Authority Estates Officers and 13 developers. Finally an interview survey of property consultants specialising in advising vendors and developers was undertaken.
Mycoplasma genitalium is a cause of non-gonoccocal urethritis (NGU) in men and cervicitis and pelvic inflammatory disease in women. Recent international data also indicated that the first line ...treatment, 1 gram stat azithromycin therapy, for M. genitalium is becoming less effective, with the corresponding emergence of macrolide resistant strains. Increasing failure rates of azithromycin for M. genitalium has significant implications for the presumptive treatment of NGU and international clinical treatment guidelines. Assays able to predict macrolide resistance along with detection of M. genitalium will be useful to enable appropriate selection of antimicrobials to which the organism is susceptible and facilitate high levels of rapid cure. One such assay recently developed is the MG 23S assay, which employs novel PlexZyme™ and PlexPrime™ technology. It is a multiplex assay for detection of M. genitalium and 5 mutations associated with macrolide resistance. The assay was evaluated in 400 samples from 254 (186 males and 68 females) consecutively infected participants, undergoing tests of cure. Using the MG 23S assay, 83% (331/440) of samples were positive, with 56% of positives carrying a macrolide resistance mutation. Comparison of the MG 23S assay to a reference qPCR method for M. genitalium detection and high resolution melt analysis (HRMA) and sequencing for detection of macrolide resistance mutations, resulted in a sensitivity and specificity for M. genitalium detection and for macrolide resistance of 99.1/98.5% and 97.4/100%, respectively. The MG 23S assay provides a considerable advantage in clinical settings through combined diagnosis and detection of macrolide resistance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
This guideline establishes clinical practice recommendations for the use of behavioral and psychological treatments for chronic insomnia disorder in adults.
The American Academy of Sleep Medicine ...(AASM) commissioned a task force of experts in sleep medicine and sleep psychology to develop recommendations and assign strengths based on a systematic review of the literature and an assessment of the evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. The task force evaluated a summary of the relevant literature and the quality of evidence, the balance of clinically relevant benefits and harms, patient values and preferences, and resource use considerations that underpin the recommendations. The AASM Board of Directors approved the final recommendations.
The following recommendations are intended as a guide for clinicians in choosing a specific behavioral and psychological therapy for the treatment of chronic insomnia disorder in adult patients. Each recommendation statement is assigned a strength ("strong" or "conditional"). A "strong" recommendation (ie, "We recommend…") is one that clinicians should follow under most circumstances. A "conditional" recommendation is one that requires that the clinician use clinical knowledge and experience, and to strongly consider the patient's values and preferences to determine the best course of action. 1. We recommend that clinicians use multicomponent cognitive behavioral therapy for insomnia for the treatment of chronic insomnia disorder in adults. (STRONG). 2. We suggest that clinicians use multicomponent brief therapies for insomnia for the treatment of chronic insomnia disorder in adults. (CONDITIONAL). 3. We suggest that clinicians use stimulus control as a single-component therapy for the treatment of chronic insomnia disorder in adults. (CONDITIONAL). 4. We suggest that clinicians use sleep restriction therapy as a single-component therapy for the treatment of chronic insomnia disorder in adults. (CONDITIONAL). 5. We suggest that clinicians use relaxation therapy as a single-component therapy for the treatment of chronic insomnia disorder in adults. (CONDITIONAL). 6. We suggest that clinicians not use sleep hygiene as a single-component therapy for the treatment of chronic insomnia disorder in adults. (CONDITIONAL).
The purpose of this systematic review is to provide supporting evidence for a clinical practice guideline on the use of behavioral and psychological treatments for chronic insomnia disorder in adult ...populations.
The American Academy of Sleep Medicine commissioned a task force of 9 experts in sleep medicine and sleep psychology. A systematic review was conducted to identify randomized controlled trials that addressed behavioral and psychological interventions for the treatment of chronic insomnia disorder in adults. Statistical analyses were performed to determine if the treatments produced clinically significant improvements in a range of critical and important outcomes. Finally, the Grading of Recommendations Assessment, Development, and Evaluation process was used to evaluate the evidence for making specific treatment recommendations.
The literature search identified 1,244 studies; 124 studies met the inclusion criteria, and 89 studies provided data suitable for statistical analyses. Evidence for the following interventions is presented in this review: cognitive-behavioral therapy for insomnia, brief therapies for insomnia, stimulus control, sleep restriction therapy, relaxation training, sleep hygiene, biofeedback, paradoxical intention, intensive sleep retraining, and mindfulness. This review provides a detailed summary of the evidence along with the quality of evidence, the balance of benefits vs harms, patient values and preferences, and resource use considerations.
Progesterone receptors (PR) are emerging as important breast cancer drivers. Phosphorylation events common to breast cancer cells impact PR transcriptional activity, in part by direct ...phosphorylation. PR-B but not PR-A isoforms are phosphorylated on Ser294 by mitogen activated protein kinase (MAPK) and cyclin dependent kinase 2 (CDK2). Phospho-Ser294 PRs are resistant to ligand-dependent Lys388 SUMOylation (that is, a repressive modification). Antagonism of PR small ubiquitin-like modifier (SUMO)ylation by mitogenic protein kinases suggests a mechanism for derepression (that is, transcriptional activation) of target genes. As a broad range of PR protein expression is observed clinically, a PR gene signature would provide a valuable marker of PR contribution to early breast cancer progression.
Global gene expression patterns were measured in T47D and MCF-7 breast cancer cells expressing either wild-type (SUMOylation-capable) or K388R (SUMOylation-deficient) PRs and subjected to pathway analysis. Gene sets were validated by RT-qPCR. Recruitment of coregulators and histone methylation levels were determined by chromatin immunoprecipitation. Changes in cell proliferation and survival were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and western blotting. Finally, human breast tumor cohort datasets were probed to identify PR-associated gene signatures; metagene analysis was employed to define survival rates in patients whose tumors express a PR gene signature.
'SUMO-sensitive' PR target genes primarily include genes required for proliferative and pro-survival signaling. DeSUMOylated K388R receptors are preferentially recruited to enhancer regions of derepressed genes (that is, MSX2, RGS2, MAP1A, and PDK4) with the steroid receptor coactivator, CREB-(cAMP-response element-binding protein)-binding protein (CBP), and mixed lineage leukemia 2 (MLL2), a histone methyltransferase mediator of nucleosome remodeling. PR SUMOylation blocks these events, suggesting that SUMO modification of PR prevents interactions with mediators of early chromatin remodeling at 'closed' enhancer regions. SUMO-deficient (phospho-Ser294) PR gene signatures are significantly associated with human epidermal growth factor 2 (ERBB2)-positive luminal breast tumors and predictive of early metastasis and shortened survival. Treatment with antiprogestin or MEK inhibitor abrogated expression of SUMO-sensitive PR target-genes and inhibited proliferation in BT-474 (estrogen receptor (ER)+/PR+/ERBB2+) breast cancer cells.
We conclude that reversible PR SUMOylation/deSUMOylation profoundly alters target gene selection in breast cancer cells. Phosphorylation-induced PR deSUMOylation favors a permissive chromatin environment via recruitment of CBP and MLL2. Patients whose ER+/PR+ tumors are driven by hyperactive (that is, derepressed) phospho-PRs may benefit from endocrine (antiestrogen) therapies that contain an antiprogestin.
Pancreatic ductal adenocarcinoma (PDA) is characterized by abundant desmoplasia and poor tissue perfusion. These features are proposed to limit the access of therapies to neoplastic cells and blunt ...treatment efficacy. Indeed, several agents that target the PDA tumor microenvironment promote concomitant chemotherapy delivery and increased antineoplastic response in murine models of PDA. Prior studies could not determine whether chemotherapy delivery or microenvironment modulation per se were the dominant features in treatment response, and such information could guide the optimal translation of these preclinical findings to patients. To distinguish between these possibilities, we used a chemical inhibitor of cytidine deaminase to stabilize and thereby artificially elevate gemcitabine levels in murine PDA tumors without disrupting the tumor microenvironment. Additionally, we used the FG-3019 monoclonal antibody (mAb) that is directed against the pleiotropic matricellular signaling protein connective tissue growth factor (CTGF/CCN2). Inhibition of cytidine deaminase raised the levels of activated gemcitabine within PDA tumors without stimulating neoplastic cell killing or decreasing the growth of tumors, whereas FG-3019 increased PDA cell killing and led to a dramatic tumor response without altering gemcitabine delivery. The response to FG-3019 correlated with the decreased expression of a previously described promoter of PDA chemotherapy resistance, the X-linked inhibitor of apoptosis protein. Therefore, alterations in survival cues following targeting of tumor microenvironmental factors may play an important role in treatment responses in animal models, and by extension in PDA patients.
In this study, patients with type 2 diabetes, albuminuria, and mild-to-moderate renal dysfunction received losartan followed by lisinopril or placebo. The study was stopped early because of increased ...risks of hyperkalemia and acute kidney injury with combination therapy.
Diabetic nephropathy is the leading cause of end-stage renal disease (ESRD) in the United States.
1
Persons with diabetes and proteinuria are at high risk for progression to ESRD.
2
Blockade of the renin–angiotensin system decreases the progression of proteinuric kidney disease,
3
–
5
and the degree of reduction in proteinuria correlates with the extent to which the decrease in the glomerular filtration rate (GFR) is slowed.
2
,
6
Given these observations, it has been hypothesized that interventions that further lower proteinuria will further reduce the risk of progression.
6
Combination therapy with an angiotensin-converting–enzyme (ACE) inhibitor and an angiotensin II–receptor blocker (ARB) results in . . .
PDF
