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Recurring problems with patient safety have led to a growing interest in helping hospitals' governing bodies provide more effective oversight of the quality and safety of their services. National directives and initiatives emphasize the importance of action by boards, but the empirical basis for informing effective hospital board oversight has yet to receive full and careful review.This article presents a narrative review of empirical research to inform the debate about hospital boards' oversight of quality and patient safety. A systematic and comprehensive search identified 122 papers for detailed review. Much of the empirical work appeared in the last ten years, is from the United States, and employs cross-sectional survey methods.Recent empirical studies linking board composition and processes with patient outcomes have found clear differences between high- and low-performing hospitals, highlighting the importance of strong and committed leadership that prioritizes quality and safety and sets clear and measurable goals for improvement. Effective oversight is also associated with well-informed and skilled board members. External factors (such as regulatory regimes and the publication of performance data) might also have a role in influencing boards, but detailed empirical work on these is scant.Health policy debates recognize the important role of hospital boards in overseeing patient quality and safety, and a growing body of empirical research has sought to elucidate that role. This review finds a number of areas of guidance that have some empirical support, but it also exposes the relatively inchoate nature of the field. Greater theoretical and methodological development is required if we are to secure more evidence-informed governance systems and practices that can contribute to safer care.

Parapneumonic effusion and empyema are still an important medical problem since they remain a significant cause of morbidity and mortality (Davies et al. 1999; Farjah et al. 2007). Risk factors for the development of empyema include alcohol abuse, aspiration and poor dental hygiene, chronic lung disease, diabetes mellitus, gastroesophageal reflux, rheumatoid arthritis, and intravenous drug abuse (Ferguson et al. 1996). About one third of cases occur without any identified risk factors (Ferguson et al. 1996; Davies et al. 2003), suggesting that the host immune defense system or modification in bacterial virulence may also play important roles.

Objectives Tissue interposition is an important part of vesicovaginal fistula (VVF) repair that has been shown to improve success rates. The most common interpositional flap used during a transabdominal VVF repair is the omental flap; however, in some cases, it cannot be used. The urachus is a well-vascularized tissue that is easily mobilized for interposition. We describe our experience using a urachal flap in VVF repair. Methods Patients undergoing VVF repair at our center were identified, and a retrospective chart review was performed. Patients who underwent a transabdominal repair with interposition of a urachal flap were included. Results Thirteen patients were identified between 2005 and 2009. All were evaluated with a history, physical, upper and lower tract imaging, and cystoscopy. Median patient age was 49 years (range, 31-88 years). Fistula etiology was hysterectomy in 11 and prolapse repair in 2. Five patients presented with recurrent fistulas having failed previous repair. Of 13 patients, 12 had successful repairs with our described technique, including 4 patients who failed previous repairs. There was no recurrence of fistula after median follow-up of 6 months (range, 2 weeks to 4 years). Two patients had preoperative and postoperative complaints of stress urinary incontinence that was mild and did not require surgery. Conclusions Vesicovaginal fistulas can be a difficult challenge for the reconstructive surgeon. The urachal flap is a well-vascularized tissue flap that can be easily mobilized and interposed for VVF repair. Of 13 patients in this series, 12 were successfully repaired using this technique. We feel that further evaluation and usage of this tissue flap are indicated.

This article attempts to look forward in the field of aircraft structures, at what is likely to happen, and what current R&D is necessary to achieve this. It becomes clear that structural performance is always improving but that the main drivers are likely to be cost, both capital cost and in-service costs. The capital cost is likely to improve by reducing the design and development time as well as low-cost manufacturing. The use of all components of the synthetic environment are here playing an increasing role. The in-service costs will be reduced by more robust structures and better NDE to automate inspections and lengthen their intervals.

A lack of reliable statistics makes tuberculosis (TB) trends in developing countries difficult to estimate. Nonetheless the World Health Organization and the International Union against Tuberculosis and Lung Disease estimated in 1990 that one-third of the worlds population was infected with the tubercle bacillus and that there were 7-8 million new cases of TB annually. 95% of the new cases occurred in the developing world with more than 5 million in Asia and the Western Pacific and more than 1 million in sub-Saharan Africa. Almost 80% of TB cases in developing countries occur among those under age 50 years. The global annual mortality was estimated at 2.5 million with 98% of deaths occurring in developing countries. Worldwide TB is believed to be responsible for 25% of avoidable deaths in young adults. There has been no significant decline in the average annual risk of infection in most developing countries due to incomplete coverage by control programs and inadequate cure rates. The interaction of HIV infection with TB is another factor which contributes to the deteriorating TB situation in many developing countries. Countries with a high population growth rate and little decline in the annual risk of infection should expect either a static or increasing level of TB disease. Immigration from developing countries HIV infection poverty unemployment homelessness overcrowding and population aging contribute to the spread of TB in developed countries. Drug resistance thwarts the control of TB worldwide.

The severe limitations of conventional sleep staging during sleep apnea are now understood. Microarousals are likely to be the dominant cause of symptoms in sleep apnea, but it has been extremely difficult to quantify them in a way that will predict daytime sleepiness or poor vigilance any better than respiratory indices. It is clear that not all apneas are equal on sleep, differences in the degree of arousal required to end an apnea and open the pharynx may help to explain why some individuals with apnea-plus-hypopnea indices (AHIs) of 15 may be symptomless, whereas others are severely disabled. Use of newer techniques to measure arousals, both cortical and autonomic, may produce a better understanding of how to measure sleep.

We conducted a series of studies investigating the antiinflammatory effects of nedocromil sodium, with particular reference to its effects on human bronchial epithelial cells and eosinophils in vitro and on eosinophils in vivo. Nedocromil sodium produced a dose-related inhibition of ozone-induced IL-8 release from human bronchial epithelial cells and also attenuated the release of granulocyte macrophage colony-stimulating factor, tumor necrosis factor-alpha, and soluble intercellular adhesion molecule 1. The culture medium from human bronchial epithelial cell cultures, containing the proinflammatory cytokines IL-8, granulocyte macrophage colony-stimulating factor, "regulated on activation, normal T expressed and secreted," IL-1 beta, and tumor necrosis factor-alpha, increased eosinophil chemotaxis and eosinophil adhesion to cultured human endothelial cells. The chemotaxis and increased adhesion were blocked in the presence of nedocromil sodium. The drug also abrogated the epithelial cell dysfunction (assessed as ciliary beat frequency) induced by the presence of activated eosinophils and blocked the release of eosinophil cationic protein from the eosinophils. We also conducted a double-blind placebo-controlled study of the effects of regular albuterol 200 micrograms or nedocromil sodium 4 mg, both given four times daily for 16 weeks, on inflammatory cell numbers in bronchial biopsy and bronchoalveolar lavage samples. Assessed in terms of total and activated eosinophils in biopsy samples, inflammation decreased with nedocromil sodium and was significantly different from a deterioration with albuterol, although neither of these changes was significantly different from that with placebo treatment. Levels of eosinophil cationic protein in bronchoalveolar lavage samples showed a similar trend.

This review focuses on bacterial induction and release of inflammatory cytokines and adhesion molecules by human bronchial epithelial cells, with special reference to Haemophilus influenzae, a pathogen commonly associated with chronic bronchitis. Studies investigating the mechanisms underlying bacterial colonization of the airways and bacterial-induced chronic airway inflammation have suggested that these are likely to involve localization of bacteria to the site(s) of infection in the respiratory tract and induction of a local airway inflammation resulting in the initiation of epithelial damage. We have hypothesized that the gross airway epithelial damage observed in chronic infective lung disease is an indirect consequence of proteolytic enzymes and toxic oxygen radicals generated by large numbers of neutrophils infiltrating the airways. Furthermore, the infiltration and activation of the neutrophils is a consequence of increased release of proinflammatory mediators from the host respiratory epithelium, induced by bacterial products, such as endotoxin. This hypothesis is based on studies which have demonstrated that the concentrations of circulating cytokines, such as interleukin (IL)-8 and tumour necrosis factor-alpha (TNF-alpha), which have profound effects on neutrophil activity, are increased in endotoxaemia and that airway epithelial cells are a rich source of these cytokines. Support for this hypothesis is provided by studies of cultured human bronchial epithelial cells incubated either in the absence or presence of purified endotoxin preparations from nontypable and type b H. influenzae strains which have demonstrated that these endotoxins lead to significantly increased expression and/or release of proinflammatory mediators, including IL-6, IL-8, TNF-alpha and intercellular adhesion molecule-1 (ICAM-1). Treatment of the cells with steroids can downregulate the expression and/or release of these inflammatory mediators. Additionally, these studies have demonstrated that culture medium collected from endotoxin-treated cultures, 24 h after treatment, significantly increases neutrophil chemotaxis and adhesion to human endothelial cells in vitro.

The problem with the emergence of HIV-associated tuberculosis (which usually occurs in young adults) is that attention has been diverted away from the fact that, in the developed world, the elderly represent the biggest pool of tubercular disease and therefore the greatest pool of infection within the community. Although the incidence rate of tuberculosis continues to decline in most countries, there is evidence from parts of the developing world that rates may be beginning to increase. The presentation of the disease in the elderly is often uncharacteristic, e.g. disease tending to be more insidious in onset, pyrexia often absent and haemoptysis less common. Chest x-ray changes may also mislead the clinician in that disease is frequently present in the mid or lower zones. The elderly are probably at greater risk of extrapulmonary tuberculosis, which also presents in uncharacteristic ways. The diagnosis remains based on clinical presentation and the presence of smear and culture positivity, although some patients may be treated in the absence of microbiological proof. Standard treatment is with a combination of isoniazid, rifampicin and pyrazinamide, with or without a fourth drug such as ethambutol. The incidence of adverse effects in the elderly is much greater than that in younger patients, often resulting in the need to change the medication to drugs which are better tolerated. This may require changing to regimens which are less effective and therefore have to be taken for a longer period of time. The presence of concomitant disease such as liver or renal failure may also necessitate the administration of a suboptimal regimen. Mortality in elderly patients with tuberculosis is considerably higher than that in younger patients, even when treatment appears to have been started on time; even in the developed world mortality exceeds 30% in those patients over 70 years of age.

Recent studies have demonstrated that RANTES, a member of the CC chemokine family affecting monocytes, T cells, basophils, and eosinophils, is expressed by several cell types. To investigate whether human bronchial epithelial cells can also express this chemokine, we investigated human bronchial epithelial cells for their ability to synthesize RANTES, both in vitro and in vivo. Additionally, we investigated the effect of treatment for 4 mo with inhaled corticosteroids on the expression of RANTES in these cells in vivo. Human bronchial epithelial cells cultured from surgical tissue expressed the mRNA for RANTES and synthesized RANTES, as demonstrated by polymerase chain reaction and immunocytochemical staining and enzyme-linked immunosorbent assay, respectively. Incubation of the cultures with 50 ng/ml of tumor necrosis factor-alpha (TNF-alpha) significantly increased the release of RANTES into culture medium after 18 to 48 h of incubation, an effect that was abolished by treatment of the cultures with anti-TNF-alpha antibody. RANTES was also expressed in the bronchial epithelium in vivo, as indicated by positive immunocytochemical staining of bronchial biopsy tissues obtained from mild asthmatic patients before and after treatment with 500 micrograms of inhaled beclomethasone dipropionate (BDP) twice daily or matched placebo for 4 mo. Quantitation, by color image analysis, of the percentage of epithelium staining for RANTES showed that treatment with BDP decreased the expression of RANTES in the bronchial epithelium from 17.12% to 4.22% (P < 0.05). The numbers of EG2-staining cells in the epithelium were also reduced, from 790.1/mm2 to 203.3/mm2 (geometric mean; P < 0.01), after BDP treatment. These results suggest that human bronchial epithelial cells are capable of synthesizing RANTES and may therefore play an important role in the development of inflammation in allergic airways disease. Furthermore, corticosteroids may prevent airway inflammation by downregulating the expression of proinflammatory cytokines in the bronchial epithelium.

Introduction: Penile fractures have classically been thought to require immediate surgical intervention; however, recent series have described acceptable outcomes with delayed repair. In this systematic review, we compared complication rates between immediate and delayed repair of penile fractures.Methods: A systematic search of MEDLINE, Embase, CENTRAL, and Web of Science was performed with predefined search terms between 1974 and 2015. Titles and abstracts were screened prior to full-text review and quality appraisal by two independent investigators. Abstracted outcomes included postoperative erectile dysfunction (ED), tunical scar formation, and penile curvature. Only studies reporting a direct comparison of complications following immediate (24 hours) repair of penile fractures were included.Results: A total of 12 studies met inclusion criteria. All were retrospective, observational studies of low or moderate methodological quality. Of the reported 502 patients, 391 underwent immediate repair and 111 delayed repair. In the immediate repair group, the percent of patients with postoperative ED, tunical scars, and curvature were 6.6%, 5.4%, and 1.8%, respectively, while in the delayed group, the rates of ED, tunical scars, and curvature were 4.5% across the board. Rates of ED and tunical scar formation following immediate compared to delayed repair trended towards favouring immediate repair, but did not differ significantly, while rates of curvature significantly favoured immediate repair. However, cases of curvature were typically reported as mild and none affected sexual functioning.Conclusions: In this systematic review, we demonstrated that ED and tunical scar formation rates between immediate and delayed repair of penile fractures were statistically similar, while immediate repair had a lower rate of penile curvature. Although this suggests that a brief delay in repair may be acceptable in select patients, the results should be interpreted with caution, as the included studies were of low or moderate methodological quality. Most importantly, this review highlights the deficiencies in the current penile fracture literature, setting the stage to improve the quality of future studies.

LOFAR, the LOw-Frequency ARray, is a new-generation radio interferometer constructed in the north of the Netherlands and across europe. Utilizing a novel phased-array design, LOFAR covers the largely unexplored low-frequency range from 10-240 MHz and provides a number of unique observing capabilities. Spreading out from a core located near the village of Exloo in the northeast of the Netherlands, a total of 40 LOFAR stations are nearing completion. A further five stations have been deployed throughout Germany, and one station has been built in each of France, Sweden, and the UK. Digital beam-forming techniques make the LOFAR system agile and allow for rapid repointing of the telescope as well as the potential for multiple simultaneous observations. With its dense core array and long interferometric baselines, LOFAR achieves unparalleled sensitivity and angular resolution in the low-frequency radio regime. The LOFAR facilities are jointly operated by the International LOFAR Telescope (ILT) foundation, as an observatory open to the global astronomical community. LOFAR is one of the first radio observatories to feature automated processing pipelines to deliver fully calibrated science products to its user community. LOFAR's new capabilities, techniques and modus operandi make it an important pathfinder for the Square Kilometre Array (SKA). We give an overview of the LOFAR instrument, its major hardware and software components, and the core science objectives that have driven its design. In addition, we present a selection of new results from the commissioning phase of this new radio observatory., Comment: 56 pages, 34 figures, accepted for publication by A&A

The upper few millimeters of soil harbour photosynthetic microbial communities that are structurally distinct from those of underlying bulk soil due to the presence of light. Previous studies in arid zones have demonstrated functional importance of these communities in reducing soil erosion, and enhancing carbon and nitrogen fixation. Despite being widely distributed, comparative understanding of the biodiversity of the soil surface and underlying soil is lacking, particularly in temperate zones. We investigated the establishment of soil surface communities on pasture soil in microcosms exposed to light or dark conditions, focusing on changes in phototroph, bacterial and fungal communities at the soil surface (0–3 mm) and bulk soil (3–12 mm) using ribosomal marker gene analyses. Microbial community structure changed with time and structurally similar phototrophic communities were found at the soil surface and in bulk soil in the light exposed microcosms suggesting that light can influence phototroph community structure even in the underlying bulk soil. 454 pyrosequencing showed a significant selection for diazotrophic cyanobacteria such as Nostoc punctiforme and Anabaena spp., in addition to the green alga Scenedesmus obliquus. The soil surface also harboured distinct heterotrophic bacterial and fungal communities in the presence of light, in particular, the selection for the phylum Firmicutes. However, these light driven changes in bacterial community structure did not extend to the underlying soil suggesting a discrete zone of influence, analogous to the rhizosphere.

The complex trans -bis (glycinehydroxamato) platinum (II) hydrate, trans -Pt (GHA) 2 ·H 2 O, in which the ligand is coordinated to the metal through its amino and deprotonated hydroxamate nitrogen atoms, has been synthesised. Reaction of this with HCl in aqueous solution produced crystals of trans -dichlorobis(glycine) platinum(II) dihydrate, trans -PtCl 2 (glyOH) 2 ·2H 2 O, resulting from hydrolysis of the glycinehydroxamate ligand. The crystal and molecular structures show that the complex is square planar with the chloride ligands trans to each other, as are the glycine ligands which are N-coordinated. The PtCl and Pt bond distances are 2.283 and 2.037 a, respectively. Extensive intermolecular hydrogen bonding in the crystal gives rise to a layer structure and each water molecule is involved in three hydrogen bonds. The complex trans -dichlorobis (glycylglycine) platinum(II) dihydrate was also prepared but attempts to oxidise it with H 2 O 2 resulted in hydrolysis of the peptide ligand as well as oxidation, giving trans,trans -dichlorobis(glycinato) platinum(IV), trans,trans -PtCl 2 (glyO) 2 . The crystal and molecular structures of this complex, one of the very few known platinum(IV)-amino acid complexes, have also been determined. The complex is octahedral with both glycinates and chlorides bonded trans to one another. In the crystal there are two chemically identical but crystallographically distinct molecules each of which occupies a special position in the crystallographic inversion centre. The average bond distances in this complex are, PtCl 2.305 A, PtN 2.051 A and PtO 1.987 A. In the crystal there is e extensive intermolecular hydrogen bonding, each complex molecule hydrogen bonded to six others giving a sheet-like structure.

The psychological and physiological effects of acute low-potency benzodiazepine administration on lactate-induced panic were examined in 10 patients with panic disorder (PD). The patients, who had panicked during a standard sodium-lactate infusion, underwent a repeat infusion modified by pretreatment with intravenous diazepam (5 mg). Acute Panic Inventory (API) scores preceding the second lactate infusion, which were associated with diazepam pretreatment, were significantly reduced in compared with those measured before the first lactate infusion. However, the second visit “fear of doom” item of the API was significantly reduced relative to the same time point of the first visit 35 min before lactate infusion, when diazepam had not yet been administered. Thus, the reduction of prelactate anxiety preceding the second infusion appeared to reflect both pharmacological and nonpharmacological contributions. The diazepam pretreatment condition was associated with a significantly increased infusion duration and a significant attenuation of rate of API symptom increase in response to lactate. Despite significant attenuation of lactate infusion effects associated with the diazepam pretreatment condition, 7 of 10 patients experienced a second panic attack. This pilot study suggests that diazepam pretreatment is associated with a marked reduction of symptomatic response during a second lactate infusion, although the magnitude of attenuation observed was insufficient to block lactate-induced panic in a majority of lactate-vulnerable PD patients.

Background Four TNF-inhibiting biologicals (TNFi) have been approved by European regulatory authorities for active non-radiographic (nr) and radiographic (r; also termed ankylosing spondylitis) axial (ax) SpA. 1–4 To be eligible to receive TNFi treatment, nr-axSpA patients (pts) must have either a positive MRI showing inflammation of the sacroiliac joints or a positive CRP assessment (CRP >upper limit of normal [ULN]). CRP is also considered a predictor of treatment response in axSpA. 5 However, many axSpA pts are classed as CRP-negative despite levels close to the ULN. Objectives These analyses investigated the reproducibility of negative CRP test results in pts with active axSpA who were intolerant to or had insufficient response to NSAID treatment. Methods The 204-week (wk) phase 3 RAPID-axSpA trial (NCT01087762) evaluated the efficacy and safety of certolizumab pegol (CZP) in axSpA pts, and was double-blind and placebo (PBO)-controlled for the initial 24 wks. At screening, pts were either MRI or CRP (>ULN [7.9mg/L]) positive. PBO-treated pts continued on stable conventional medication and were re-randomized to CZP at Wk16 (ASAS20 non-responders) or Wk24 (ASAS20 responders). These analyses considered CRP data for all PBO-randomized (n=107) pts up until re-randomization to CZP (Wk16 or Wk24). CRP was assessed at screening, baseline and at 9 time points to Wk24. Descriptive methods and linear mixed models (LMM) were used to investigate time trends and variability of CRP, and empirical best linear unbiased prediction (EBLUP) to estimate prediction limits of CRP. Log(CRP+1) transformation was used for modelling. Results Of 106 pts with baseline CRP assessments, 26 (25%) had negative CRP tests at baseline, of whom 13 (50%) had ≥1 positive CRP test to Wk16 (Table). Of the 80/106 (75%) pts with positive CRP at baseline, 25 (31%) had ≥1 negative CRP test to Wk16. LMM did not reveal statistically significant changes in mean CRP to Wk24 in pts randomized to PBO. EBLUP analysis showed that even for a pt with a CRP score of 2mg/L at a single evaluation, the 80% prediction interval for the next assessment (4 wks apart from the first) included 7.9mg/L, indicating that there was >10% chance of a positive CRP test upon re-evaluation. The 4-wk interval prior to re-evaluation was selected because residual autocorrelation was observed between assessments at shorter intervals. The EBLUP result was supported by descriptive evaluations, with 10.8% of CRP assessments ≤3mg/L testing positive (>7.9mg/L) at their subsequent assessment (4 wks apart from the first). This increased to 53.1% when the original CRP assessment was between ≥6 and ≤7.9mg/L. Conclusions In axSpA pts with a clinical indication to initiate TNFi treatment, but with a negative CRP test ( References EMA. Summary of Product Characteristics [SmPC] (Humira) 2012; EMA. SmPC (Cimzia) 2013; EMA. SmPC (Enbrel) 2014; EMA. SmPC (Simponi) 2015; Sieper J. Nat Rev Rheumatol 2012;8:280–7 Disclosure of Interest R. Landewe Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma and Wyeth, Consultant for: Abbott, Ablynx, Amgen, Astra-Zeneca, Bristol Myers Squibb, Centocor, Glaxo-Smith-Kline, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma and Wyeth, Speakers bureau: Abbott, Amgen, Bristol Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma and Wyeth, T. Nurminen Employee of: UCB Pharma, O. Davies Shareholder of: UCB Pharma, Employee of: UCB Pharma, M. Turina: None declared, D. Baeten Grant/research support from: AbbVie, Pfizer, UCB, MSD, Roche, BMS, Boehringer Ingelheim, Eli Lilly, Novartis and Janssen, Consultant for: AbbVie, Pfizer, UCB, MSD, Roche, BMS, Boehringer Ingelheim, Eli Lilly, Novartis and Janssen

Background The RAPID-axSpA trial (NCT01087762) investigated the efficacy and safety of certolizumab pegol (CZP) for the treatment of patients (pts) with axial spondyloarthritis (axSpA), including ankylosing spondylitis (AS; also termed radiographic-axSpA) and non-radiographic (nr)-axSpA pts. Previous reports have shown CZP to be safe and efficacious over 96 weeks (wks) of treatment. 1 Objectives To report 4-year efficacy and safety data from the RAPID-axSpA trial. Methods RAPID-axSpA was double-blind and placebo (PBO)-controlled to Wk24, dose-blind to Wk48 and open-label (OL) to Wk204. Pts fulfilled ASAS criteria and had active axSpA with positive sacroiliac joint MRI and/or raised CRP (>7.9mg/L). Pts originally randomized to CZP (200mg Q2W or 400mg Q4W) continued on their assigned dose in the OL period. Outcomes assessed included: ASAS responses, ASDAS, BASDAI, BASFI, BASMI-linear and enthesitis. Efficacy data are presented for pts originally randomized to CZP (combined doses) as observed case and with imputation: NRI for categorical and LOCF for continuous measures. The safety set consisted of all pts treated with ≥1 dose of CZP to Wk204. Results 325 pts were randomized, of whom 218 received CZP from Wk0. Of CZP-randomized pts, 93% completed to Wk24, 88% to Wk48 and 65% to Week 204 (AS: 67%; nr-axSpA: 63%). In the OL period, 9.2% of pts withdrew due to an adverse event (AE) and 1.4% due to lack of efficacy. The proportion of pts achieving ASAS20/40 and partial remission (PR) responses at Wk24 was maintained over 4 years (to Wk204) in pts remaining in the study (Table). Efficacy, expressed as ASDAS ID rates (LOCF: Wk24: 30.3%; Wk204: 32.1%), mean ASDAS score (baseline: 3.84; LOCF: Wk24: 2.07; Wk204: 1.98), and all other outcomes reported, was maintained to Wk204. Similar improvements were seen in AS and nr-axSpA pts (Figure/Table) and in both CZP dose regimens (data not shown). Function (BASFI) was also improved in both subpopulations, with nr-axSpA pts having a particularly low mean score by Wk204 (Table). Pts in the safety set (N=315) had a total CZP exposure of 981 patient-years (PY), with an AE rate (ER) per 100 PY of 292.9. No new safety signals were identified from Wk96 to Wk204, and no deaths were reported over 4 years. Conclusions CZP efficacy was maintained in axSpA pts over 4 years with no new safety signals. Treatment responses to CZP were similar in AS and nr-axSpA pts. References Sieper J. Arthritis Rheum 2015;67:668–77 Acknowledgement The authors acknowledge Costello Medical Consulting, funded by UCB Pharma, for writing and editorial assistance. Disclosure of Interest D. van der Heijde Consultant for: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Celgene, Daiichi, Eli-Lilly, Galapagos, Merck, Novartis, Pfizer, Roche, Sanofi-Aventis and UCB Pharma, Employee of: Director of Imaging Rheumatology bv, M. Dougados Grant/research support from: UCB Pharma, Abbvie, Pfizer, Lilly, Merck and Novartis, Consultant for: UCB Pharma, Abbvie, Pfizer, Lilly, Merck and Novartis, R. Landewe Grant/research support from: Abbott, Amgen, Centocor, Novartis, Pfizer, Roche, Schering-Plough, UCB Pharma and Wyeth, Consultant for: Abbott, Ablynx, Amgen, Astra-Zeneca, Bristol Myers Squibb, Centocor, Glaxo-Smith-Kline, Novartis, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma and Wyeth, Speakers bureau: Abbott, Amgen, Bristol Myers Squibb, Centocor, Merck, Pfizer, Roche, Schering-Plough, UCB Pharma and Wyeth, J. Sieper Consultant for: Abbott, Merck, Pfizer, UCB Pharma, Novartis, Lilly and Janssen, Speakers bureau: Abbott, Merck, Pfizer, UCB Pharma, Novartis, Lilly and Janssen, W. Maksymowych Grant/research support from: Abbott, Amgen, Bristol Myers Squibb, Eli-Lilly, Janssen, Merck, Pfizer, Synarc, Sanofi and UCB Pharma, Consultant for: Abbott, Amgen, Bristol Myers Squibb, Eli-Lilly, Janssen, Merck, Pfizer, Synarc, Sanofi and UCB Pharma, Speakers bureau: Abbott, Amgen, Bristol Myers Squibb, Eli-Lilly, Janssen, Merck, Pfizer, Synarc, Sanofi and UCB Pharma, M. Rudwaleit Consultant for: Abbott, BMS, Janssen, MSD, Pfizer, Roche and UCB Pharma, F. van den Bosch Consultant for: Abbvie, Bristol Myers-Squibb, Celgene, Janssen, Merck, Novartis, Pfizer, UCB Pharma, Speakers bureau: Abbvie, Bristol Myers-Squibb, Celgene, Janssen, Merck, Novartis, Pfizer, UCB Pharma, J. Braun Grant/research support from: Abbott, Bristol Myers Squibb, Celgene, Celltrion, Chugai, Johnson & Johnson, MSD, Novartis, Pfizer, Roche and UCB Pharma, Consultant for: Abbott, Bristol Myers Squibb, Celgene, Celltrion, Chugai, Johnson & Johnson, MSD, Novartis, Pfizer, Roche and UCB Pharma, P. Mease Grant/research support from: AbbVie, Amgen, BiogenIdec, BMS, Celgene, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant for: AbbVie, Amgen, BiogenIdec, BMS, Celgene, Covagen, Crescendo, Genentech, Janssen, Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Amgen, BiogenIdec, BMS, Celgene, Crescendo, Genentech, Janssen, Lilly, Pfizer and UCB Pharma, O. Davies Shareholder of: UCB Pharma, Employee of: UCB Pharma, B. Hoepken Employee of: UCB Pharma, L. Peterson Employee of: UCB Pharma, A. Deodhar Grant/research support from: AbbVie, Amgen, Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB Pharma, Consultant for: AbbVie, Amgen, Boehringer Ingelheim, Janssen, Novartis, Pfizer, UCB Pharma

BACKGROUND--The Hayek oscillator is a negative pressure cuirass that can operate at a range of frequencies to provide ventilation, and is a technique which could potentially be used on a general ward. This study examined the effect of different frequencies and different ranges of inspiratory and expiratory pressures on gas exchange, respiratory rate, and blood pressure in normal subjects. METHODS--Eight normal subjects received five minute periods of ventilation using the Hayek oscillator at five different frequencies, and a combination of two spans of inspiratory and expiratory pressures and two mean chamber pressures. A "sham" or control period was also performed at each frequency. Measurements were made of changes in gas exchange, spontaneous respiratory rate, and blood pressure before and after ventilation. RESULTS--There was significant intersubject variation in all results, independent of their height and weight. "Sham" settings acted as true controls in terms of gas exchange, but produced a fall in respiratory rate at 30 oscillations/min. The lower oscillatory frequencies of 30 and 60 oscillations/min produced the greatest increase in oxygenation, decrease in end tidal carbon dioxide pressure, and decrease in spontaneous respiratory rate. These effects were most significant at higher spans of pressure and were different from "sham" settings. No adverse effects were observed on blood pressure. CONCLUSIONS--The Hayek oscillator can provide assisted ventilation for short periods in normal conscious subjects with no adverse side effects on blood pressure. Maximal changes in gas exchange and a significant reduction in the spontaneous respiratory rate are seen when a combination of lower frequencies (30 and 60 oscillations/min) and higher spans of pressure are used.

OBJECTIVE To investigate the efficacy and safety of certolizumab pegol (CZP) in a broad population of patients with active RA. METHODS In this 12-week, double-blind period of the phase IIIb trial, RA patients with inadequate response to at least one DMARD were randomized 4:1 to CZP (400 mg at weeks 0, 2 and 4, followed by 200 mg every 2 weeks) or placebo (every 2 weeks) plus current therapy stratified by previous TNF inhibitor use, concomitant methotrexate use and disease duration (

BACKGROUND: Continuous positive airway pressure (CPAP) for symptomatic obstructive sleep apnoea (OSA) improves sleepiness and reduces vascular risk, but such treatment for the more prevalent, minimally symptomatic disease is contentious. METHODS: This multicentre, randomised controlled, parallel, hospital-based trial across the UK and Canada, recruited 391 patients with confirmed OSA (oxygen desaturation index >7.5/h) but insufficient symptoms to warrant CPAP therapy. Patients were randomised to 6 months of auto-adjusting CPAP therapy, or standard care. Coprimary endpoints were change in Epworth Sleepiness Score (ESS) and predicted 5-year mortality using a cardiovascular risk score (components: age, sex, height, systolic blood pressure, smoking, diabetes, cholesterol, creatinine, left ventricular hypertrophy, previous myocardial infarction or stroke). Secondary endpoints included some of the individual components of the vascular risk score, objectively measured sleepiness and self-assessed health status. RESULTS: Of 391 patients randomised, 14 withdrew, 347 attended for their follow-up visit at 6 months within the predefined time window, of which 341 had complete ESS data (baseline mean 8.0, SD 4.3) and 310 had complete risk score data. 22% of patients in the CPAP group reported stopping treatment and overall median CPAP use was 2 : 39 h per night. CPAP significantly improved subjective daytime sleepiness (adjusted treatment effect on ESS -2.0 (95% CI -2.6 to -1.4), p

Urethral stricture disease and its management are complex. The UREThRAL stricture score (USS) as described by Wiegand and Brandes is a novel method to describe and quantify urethral stricture disease.1 To develop the USS, they chose factors they believed to be important and assigned a point value to each domain. The appealing UREThRAL acronym was used to recall the domains of etiology, number of strictures, luminal obliteration, location and length. Retrospectively they analyzed a group of postoperative urethral reconstructive patients to see if the score correlated with a subjective surgical complexity score. As they point out, there would be some debate as to the value of the surgical complexity score. Excision and primary anastomosis is doubtlessly the simplest of the open urethral reconstructive techniques and most would agree that combined graft and flap tissue transfer is used for the most complex stricture disease. Variability in surgical training and surgeon preference would be a significant confounder to the treatment complexity score. The value of a quantifiable urethral stricture score would be in comparing the scores to patient outcomes. Outcome measures continue to be one of the major hurdles to overcome in providing good quality research in reconstructive urology. Measurement of patient outcomes following urethral reconstructive surgery is not standardized. Many different methods have been used in the past to evaluate “success” following urethroplasty. Cystoscopy, urethral x-ray studies, uroflow and post-void residuals have been used to capture outcomes. Assessing the quality of life – the most important outcome – has yet to be standardized. Investigators have used non-validated questionnaires (like the AUA symptom score). Recently, Jackson and colleagues have taken a first step to develop a stricture specific health related quality of life questionnaire.2 The current challenge facing reconstructive urology is to develop a validated and standardized method of assessing patients pre- and postoperatively. In the development of The UREThRAL stricture score, the authors have delineated the important factors in determining the complexity of a stricture. This is valuable reminder to all urologists. At the initial evaluation of stricture disease, the factors pointed out by the authors (etiology, number of strictures, luminal obliteration, location and length) are the keys to determine the severity of the stricture itself. The length, as the authors point out, is heavily weighted and it is accepted to be the most likely determinant of both outcome and treatment.3,4 Longer and more complex strictures should signal the urologist to consider early open surgical intervention rather than pursuing futile and repeated endoscopic management (urethrotomy/dilatation). The poor outcomes5 and cost ineffectiveness6 of repeated endoscopic treatment of urethral strictures are well-described in the literature. Failed endoscopic treatment may be a useful additional factor in the USS. This may encourage earlier consideration for urethral reconstruction, which would benefit the patient and the health care system.

Procalcitonin has been shown to be useful in separating infection from non-infective disorders. However, infection is often paralleled by tissue inflammation. Most studies supporting the use of procalcitonin were confounded by more significant inflammation in the infection group. Few studies have examined the usefulness of procalcitonin when adjusted for inflammation. Pleural inflammation underlies the development of most exudative effusions including pleural infection and malignancy. Pleurodesis, often used to treat effusions, involves provocation of intense aseptic pleural inflammation. We conducted a two-part proof-of-concept study to test the specificity of procalcitonin in differentiating infection using cohorts of patients with pleural effusions of infective and non-infective etiologies, as well as subjects undergoing pleurodesis. Methods We measured the blood procalcitonin level (i) in 248 patients with pleural infection or with non-infective pleural inflammation, matched for severity of systemic inflammation by C-reactive protein (CRP), age and gender; and (ii) in patients before and 24–48 hours after induction of non-infective pleural inflammation (from talc pleurodesis). Results 1) Procalcitonin was significantly higher in patients with pleural infection compared with controls with non-infective effusions (n=32 each group) that were case-matched for systemic inflammation as measured by CRP [median (25–75%IQR): 0.58 (0.35–1.50) vs 0.34 (0.31–0.42) µg/L respectively, p=0.003]. 2) Talc pleurodesis provoked intense systemic inflammation, and raised serum CRP by 360% over baseline. However procalcitonin remained relatively unaffected (21% rise). 3) Procalcitonin and CRP levels did not correlate. In 214 patients with pleural infection, procalcitonin levels did not predict the survival or need for surgical intervention. Conclusion Using a pleural model, this proof-of-principle study confirmed that procalcitonin is a biomarker specific for infection and is not affected by non-infective inflammation. Procalcitonin is superior to CRP in distinguishing infection from non-infective pleural diseases, even when controlled for the level of systemic inflammation.

Future fossil-fueled power generation systems will require emission control technologies such as carbon capture and sequestration (CCS) to comply with government greenhouse gas regulations. The three prime candidate technologies which permit carbon dioxide (CO2) to be captured and safely stored include pre-combustion, post-combustion capture and oxy-fuel (O-F) combustion. For more than a decade Clean Energy Systems, Inc. (CES) has been designing and demonstrating enabling technologies for oxy-fuel power generation; specifically steam generators, hot gas expanders and reheat combustors. Recently CES has partnered with Florida Turbine Technologies, Inc. (FTT) and Siemens Energy, Inc. to develop and demonstrate turbomachinery systems compatible with the unique characteristics of oxy-fuel working fluids. The team has adopted an aggressive, but economically viable development approach to advance turbine technology towards early product realization. Goals include short-term, incremental advances in power plant efficiency and output while minimizing capital costs and cost of electricity. Phase 2 of this development work has been greatly enhanced by a cooperative agreement with the U.S. Department of Energy (DOE). Under this program the team will design, manufacture and test a commercial-scale intermediate-pressure turbine (IPT) to be used in industrial O-F power plants. These plants will use diverse fuels and be capable of capturing 99% of the produced CO2 at competitive cycle efficiencies and cost of electricity. Initial plants will burn natural gas and generate more than 200MWe with near-zero emissions. To reduce development cost and schedule an existing gas turbine engine will be adapted for use as a high-temperature O-F IPT. The necessary modifications include the replacement of the engine’s air compressor with a thrust balance system and altering the engine’s air-breathing combustion system into a steam reheating system using direct fuel and oxygen injection. Excellent progress has been made to date. FTT has completed the detailed design and issued manufacturing drawings to convert a Siemens SGT-900 to an oxy-fuel turbine (OFT). Siemens has received, disassembled and inspected an SGT-900 B12 and ordered all necessary new components for engine changeover. Meanwhile CES has been working to upgrade an existing test facility to support demonstration of a “simple” oxy-fuel power cycle. Low-power demonstration testing of the newly assembled OFT-900 is expected to commence in late 2012.

CONTEXT: Malignant pleural effusion causes disabling dyspnea in patients with a short life expectancy. Palliation is achieved by fluid drainage, but the most effective first-line method has not been determined. OBJECTIVE: To determine whether indwelling pleural catheters (IPCs) are more effective than chest tube and talc slurry pleurodesis (talc) at relieving dyspnea. DESIGN: Unblinded randomized controlled trial (Second Therapeutic Intervention in Malignant Effusion Trial [TIME2]) comparing IPC and talc (1:1) for which 106 patients with malignant pleural effusion who had not previously undergone pleurodesis were recruited from 143 patients who were treated at 7 UK hospitals. Patients were screened from April 2007-February 2011 and were followed up for a year. INTERVENTION: Indwelling pleural catheters were inserted on an outpatient basis, followed by initial large volume drainage, education, and subsequent home drainage. The talc group were admitted for chest tube insertion and talc for slurry pleurodesis. MAIN OUTCOME MEASURE: Patients completed daily 100-mm line visual analog scale (VAS) of dyspnea over 42 days after undergoing the intervention (0 mm represents no dyspnea and 100 mm represents maximum dyspnea; 10 mm represents minimum clinically significant difference). Mean difference was analyzed using a mixed-effects linear regression model adjusted for minimization variables. RESULTS: Dyspnea improved in both groups, with no significant difference in the first 42 days with a mean VAS dyspnea score of 24.7 in the IPC group (95% CI, 19.3-30.1 mm) and 24.4 mm (95% CI, 19.4-29.4 mm) in the talc group, with a difference of 0.16 mm (95% CI, −6.82 to 7.15; P = .96). There was a statistically significant improvement in dyspnea in the IPC group at 6 months, with a mean difference in VAS score between the IPC group and the talc group of −14.0 mm (95% CI, −25.2 to −2.8 mm; P = .01). Length of initial hospitalization was significantly shorter in the IPC group with a median of 0 days (interquartile range [IQR], 0-1 day) and 4 days (IQR, 2-6 days) for the talc group, with a difference of −3.5 days (95% CI, −4.8 to −1.5 days; P < .001). There was no significant difference in quality of life. Twelve patients (22%) in the talc group required further pleural procedures compared with 3 (6%) in the IPC group (odds ratio [OR], 0.21; 95% CI, 0.04-0.86; P = .03). Twenty-one of the 52 patients in the catheter group experienced adverse events vs 7 of 54 in the talc group (OR, 4.70; 95% CI, 1.75-12.60; P = .002). CONCLUSION: Among patients with malignant pleural effusion and no previous pleurodesis, there was no significant difference between IPCs and talc pleurodesis at relieving patient-reported dyspnea. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN87514420.

Objective.To determine the relationship between timing and magnitude of Disease Activity Score [DAS28(ESR)] nonresponse (DAS28 improvement thresholds not reached) during the first 12 weeks of treatment with certolizumab pegol (CZP) plus methotrexate, and the likelihood of achieving low disease activity (LDA) at 1 year in patients with rheumatoid arthritis.Methods.In a post-hoc analysis of the RAPID 1 study, patients achieving LDA [DAS28(ESR) ≤ 3.2] at Year 1 were assessed according to DAS28 nonresponse at various timepoints within the first 12 weeks.Results.Seven-hundred eighty-three patients were included (CZP 200 mg, n = 393; CZP 400 mg, n = 390). A total of 86.9% of patients in the CZP 200 mg group had a DAS28 improvement of ≥ 1.2 by Week 12. Of the 13.1% of patients with DAS28 improvement < 1.2 by Week 12, only 2.0% had LDA at Year 1. Failure to achieve LDA at Year 1 depended on timing of nonresponse — 22.3%, 8.4%, and 2.0% of patients with DAS28 improvement < 1.2 by Weeks 1, 6, and 12, respectively, had LDA at Year 1 — and magnitude of initial lack of DAS28 improvement; for example, compared with the patients with DAS28 < 1.2 improvement, fewer patients with DAS28 < 0.6 had LDA at Year 1 (17.4%, 2.4%, and 0.0% at Weeks 1, 6, and 12, respectively).Conclusion.Failure to achieve improvement in DAS28 within the first 12 weeks of therapy was predictive of a low probability of achieving LDA at Year 1. Moreover, the accuracy of the prediction was found to be strongly dependent on the magnitude and timing of the lack of the response. (Clinical Trial Registration Nos. NCT00152386 and NCT00175877).

Background: Obstructive sleep apnea (OSA) is associated with glucose intolerance. Both chronic sleep disruption and recurrent blood oxygen desaturations (chronic-intermittent hypoxia – CIH) may cause, or exacerbate, metabolic derangements. Methods: To assess the impact of CIH alone, without accompanying upper airway obstructions, on the counter-regulatory response to glucose load and cardiorespiratory parameters, we exposed adult male Sprague-Dawley rats to CIH or sham room air exchanges for 10 h/day for 7, 21 or 35 days and then, one day after conclusion of CIH exposure, conducted intravenous glucose tolerance tests (ivgtt) under urethane anesthesia. Additional rats underwent 35 days of CIH followed by 35 days of regular housing, or had 35 day-long CIH exposure combined with daily administration of the type 1 angiotensin II receptor antagonist, losartan (15 mg/kg, p.o.), and then were also subjected to ivgtt. Results: Compared with the corresponding control groups, CIH rats had progressively reduced glucose-stimulated insulin release and impaired glucose clearance, only mildly elevated heart rate and/or arterial blood pressure and slightly reduced respiratory rate. The differences in insulin release between the CIH and sham-treated rats disappeared in the rats normally housed for 35 days after 35 days of CIH/sham exposure. The losartan-treated rats had improved insulin sensitivity, with no evidence of suppressed insulin release in the CIH group. Conclusions: In adult rats, the glucose-stimulated insulin release is gradually suppressed with the duration of exposure to CIH, but the effect is reversible. Elimination of the detrimental effect of CIH on insulin release by losartan suggests that CIH disrupts glucoregulation through angiotensin/catecholaminergic pathways. Accordingly, treatment with continuous positive airway pressure may ameliorate pre-diabetic conditions in OSA patients, in part, by reducing sympathoexcitatory effects of recurrent nocturnal hypoxia.

When rapid eye movement (REM) sleep occurs, noradrenergic cells become silent, with the abolition of activity in locus coeruleus (LC) neurons seen as a key event permissive for the occurrence of REM sleep. However, it is not known whether silencing of other than LC noradrenergic neurons contributes to the generation of REM sleep. In urethane-anesthetized rats, stereotyped REM sleep-like episodes can be repeatedly elicited by injections of the cholinergic agonist, carbachol, into a discrete region of the dorsomedial pons. We used this preparation to test whether inhibition of ventrolateral pontine noradrenergic A5 neurons only, or together with LC neurons, also can elicit REM sleep-like effects. To silence noradrenergic cells, we sequentially injected the α(2)-adrenergic agonist clonidine (20-40 nl, 0.75 mM) into both A5 regions and then the LC. In two rats, successful bilateral clonidine injections into the A5 region elicited the characteristic REM sleep-like episodes (hippocampal theta rhythm, suppression of hypoglossal nerve activity, reduced respiratory rate). In five rats, bilateral clonidine injections into the A5 region and then into one LC triggered REM sleep-like episodes, and in two rats injections into both A5 and then both LC were needed to elicit the effect. In contrast, in three rats, uni- or bilateral clonidine injections only into the LC had no effect, and clonidine injections placed in another six rats outside of the A5 and/or LC regions were without effect. The REM sleep-like episodes elicited by clonidine had similar magnitude of suppression of hypoglossal nerve activity (by 75%), similar pattern of hippocampal changes, and similar durations (2.5-5.3 min) to the episodes triggered in the same preparation by carbachol injections into the dorsomedial pontine reticular formation. Thus, silencing of A5 cells may importantly enable the occurrence of REM sleep-like episodes, at least under anesthesia. This is a new role for noradrenergic A5 neurons.

Increasing evidence suggests that cytokines play a role in airway inflammation by attracting and activating inflammatory cells. This may lead to epithelial cell damage and airway hyperresponsiveness. Bronchial provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second was measured in patients with mild asthma, and bronchial biopsy specimens were stained for granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-8, and activated eosinophils (EG2) in the bronchial epithelium. The effect of inhaled beclomethasone dipropionate was also assessed in a placebo-controlled double-blind manner. There was a correlation between GM-CSF expression and EG2-staining cells (r = 0.484 p < 0.05) in the epithelium. Provocative concentration of histamine causing a 20% fall in forced expiratory volume in 1 second was correlated with GM-CSF expression (r = -0.462, p < 0.05). Treatment with inhaled beclomethasone dipropionate 500 micrograms twice a day led to a significant decrease in both the expression of GM-CSF (p < 0.01) and IL-8 (p < 0.02) and the number of EG2-staining cells (p < 0.01) in the epithelium. The changes in GM-CSF (r = 0.798, p < 0.01) and IL-8 (r = 0.653, p < 0.02) expression were correlated with the changes in EG2-staining cells after treatment. These results suggest that GM-CSF may influence eosinophil activation in the epithelium in vivo and participate in the etiology of bronchial hyperresponsiveness in mild asthma. Also, beclomethasone dipropionate may inhibit eosinophil activation partly by downregulating the expression of GM-CSF and IL-8 in the bronchial epithelium.

Expression of intercellular adhesion molecule-1 (ICAM-1) appears to be important to the development of bronchial hyperresponsiveness and eosinophilia in Ascaris sensitized monkeys. Beta 1-integrins are expressed on epithelial cells, and may contribute to adherence of epithelial cells to the basement membrane. The aim of this study was to determine whether adhesion receptor expression was altered in human asthmatic bronchial epithelium. Using monoclonal antibody staining, we have examined the expression of ICAM-1 and the alpha 1-alpha 6-subunits of the beta 1-integrin family in bronchial mucosal biopsies from 33 asthmatic and 13 nonasthmatic subjects. The epithelium was positive for ICAM-1 in 26 out of 33 asthmatics, although negative in all 13 nonasthmatics. ICAM-1 expression was not associated with bronchial responsiveness or with medication requirements. Beta 1-integrin staining showed that alpha 2-, alpha 3- and alpha 6-subunits stained the epithelium in all cases. Alpha 4 staining was weakly positive in the epithelium in five asthmatics. Alpha 5 staining was weak in asthmatics and normals. Alpha 4 and alpha 6-subunits also stained inflammatory cells. Epithelial upregulation of ICAM-1 is present in asthma. Beta 1-integrins with alpha 2-, alpha 3- and alpha 6-subunits appear to be constitutively expressed in bronchial epithelium.

Although the cause of the steady increase in tuberculosis (TB) notifications in England and Wales since 1987 is multifactorial, the elderly have made an appreciable contribution. From 1987-1989 the increase was 6% for all ages combined, but 13% in females and 16% in males over the age of 75. Tuberculosis in the elderly therefore remains an appreciable problem. Although the characteristic presentation of chronic cough, malaise and weight loss, with cavitatory changes in the upper lobes still predominates in the elderly, there has been an increased incidence of cryptic miliary disease in which the onset is insidious and chest X-ray often normal. The diagnosis must often be made on suspicion and treatment started before a positive diagnosis is obtained. The elderly are more likely to suffer adverse effects from the anti-tuberculous chemotherapy than the younger population and greater care must be taken. Drug resistance is uncommon in the elderly in the UK. Isoniazid, rifampicin and pyrazinamide are appropriate for the initial two months of treatment. Rifampicin and isoniazid should be continued for a further four months for disease at virtually any site, with the exception of TB meningitis, when a further 10 months therapy should be given. In the UK, preventative therapy in the form of isoniazid or rifampicin and isoniazid probably has no place in disease control in an elderly population; tuberculin tests are frequently negative, even in the presence of active disease, as elderly patients are often anergic.

Objective: Ataque de nervios ("attack of nerves") is an illness category used frequently by Hispanic individuals to describe one or more particular symptom complexes. A review of the literature on ataque suggested some overlap with panic disorder. This study investigated the overlap with panic disorder as well as other DSM-III-R axis I disorders. Method: Hispanic subjects seeking treatment at an anxiety disorders clinic (N = 156) were assessed with a specially designed questionnaire for self-report of ataque de nervios and panic symptoms and with structured or semistructured psychiatric interviews for axis I disorders. Results: Seventy percent of the subjects reported at least one ataque de nervios; 80% of these were female, whereas 57% of the group without these attacks were female. There were no differences in DSM-III-R diagnoses between the groups with and without ataque de nervios. Ataque was frequently associated with one or more anxiety and affective disorders, including panic disorder, generalized anxiety disorder, recurrent major depression, and anxiety not otherwise specified. Of the 45 subjects with both ataque de nervios and primary panic disorder, 80% appeared to have labeled panic disorder as ataque. Ataque de nervios was associated with panic symptoms even in subjects without panic disorder, but the self-reporting of ataque conveyed additional clinical information about the subjects with panic disorder. Ataque de nervios was similar in frequency and symptoms among subjects of Dominican and Puerto Rican origin. Conclusions: Ataque de nervios overlaps with panic disorder but is a more inclusive construct. Further study of its interrelation with axis I disorders is needed.

Tako-tsubo transient cardiomyopathy (TCM) is a syndrome of specific myocardial wall motion abnormalities that appear in response to extreme physiological or emotional stress. The patients have normal coronary arteries and usually present as new-onset heart failure or acute coronary syndrome. We report on a 48-year-old woman with post-community cardiac arrest presenting as an acute myocardial infarction. An emergency physician–performed echocardiogram showed significant wall motion abnormalities, suggesting myocardial infarction. Cardiac catheterization revealed patent epicoronary circulation, and ventriculography demonstrated a rare and only recently described variant of TCM:“reverse” TCM. The patient subsequently died from a subarachnoid hemorrhage.

Thin films of ceria (CeO(2)) have many applications, and their synthesis by liquid-injection MOCVD (metal-organic chemical vapor deposition) or ALD (atomic layer deposition) requires volatile precursor compounds. Here we report the synthesis of a series of homoleptic and heteroleptic Ce(IV) complexes with donor-functionalized alkoxide ligands mmp (1-methoxy-2-methylpropan-2-olate), dmap (1-(dimethylamino)propan-2-olate), and dmop (2-(4,4-dimethyl-4,5-dihydrooxazol-2-yl)propan-2-olate) and their potential as precursors for MOCVD and ALD of CeO(2). New complexes were synthesized by alcohol exchange reactions with [Ce(OBu(t))(4)]. [Ce(mmp)(4)] and [Ce(dmap)(4)] were both found to be excellent precursors for liquid-injection MOCVD of CeO(2), depositing high purity thin films with very low carbon contamination, and both have a large temperature window for diffusion controlled growth (350-600 °C for [Ce(mmp)(4)]; 300-600 °C for [Ce(dmap)(4)]). [Ce(mmp)(4)] is also an excellent precursor for liquid-injection ALD of CeO(2) using H(2)O as oxygen source and demonstrates self-limiting growth from 150 to 350 °C. [Ce(dmap)(4)] has lower thermal stability than [Ce(mmp)(4)] and does not show self-limiting growth in ALD. Heteroleptic complexes show a tendency to undergo ligand redistribution reactions to form mixtures in solution and are unsuitable as precursors for liquid-injection CVD.

Expanded abstract Citation Rahman NM, Maskell NA, West A, Teoh R, Arnold A, Mackinlay C, Peckham D, Davies CW, Ali N, Kinnear W, Bentley A, Kahan BC, Wrightson JM, Davies HE, Hooper CE, Lee YC, Hedley EL, Crosthwaite N, Choo L, Helm EJ, Gleeson FV, Nunn AJ, Davies RJ: N Engl J Med 2011, 365:518-26. PMID: 21830966, available on www.pubmed. gov Background More than 30% of patients with pleural infection either die or require surgery. Drainage of infected fluid is the key to successful treatment, but intrapleural fibrinolytic therapy did not improve outcomes in an earlier, large, randomized trial therapy (Multicenter Intrapleural Sepsis Trial [MIST1]). Methods Objective: To evaluate the efficacy and safety of intrapleural DNase alone, alteplase alone, or the combination of both, to improve pleural drainage. Design: Multicenter, double-blind, double-dummy, 2 × 2 factorial randomized trial. Setting: Eleven centers in the United Kingdom (UK). Subjects: Adult patients (mean age 59 years, 72% men), who had clinical evidence of infection, and pleural fluid that had macroscopic purulence, a positive culture or Gram stain for bacteria, or a pH < 7.2. Intervention: Patients were assigned to 1 of the 4 study interventions for 3 days: double placebo, intrapleural tissue plasminogen activator (t-PA) and DNase, t-PA and placebo, or DNase and placebo. Outcomes: The primary outcome was the change in pleural opacity, measured as the percentage of the hemithorax occupied by effusion, on chest radiography on day 7 as compared with day 1. Secondary outcomes included referral for surgery, duration of hospital stay, and adverse events. Results The mean (± SD) change in pleural opacity was greater in the t-PA-DNase group than in the placebo group (-29.5 ± 23.3% vs. -17.2 ± 19.6%; difference, -7.9%; 95% confidence interval [CI], -13.4 to -2.4; P = 0.005). The change observed with t-PA alone and with DNase alone (-17.2 ± 24.3 and -14.7 ± 16.4%, respectively) was not significantly different from that observed with placebo. The frequency of surgical referral at 3 months was lower in the t-PA-DNase group than in the placebo group (2 of 48 patients [4%] vs. 8 of 51 patients [16%]; odds ratio for surgical referral, 0.17; 95% CI, 0.03 to 0.87; P = 0.03) but was greater in the DNase group (18 of 46 patients [39%]) than in the placebo group (odds ratio, 3.56; 95% CI, 1.30 to 9.75; P = 0.01). Combined t-PA-DNase therapy was associated with a reduction in the hospital stay, as compared with placebo (difference, -6.7 days; 95% CI, -12.0 to -1.9; P = 0.006). Hospital stay with either agent alone was not significantly different from that with placebo. The frequency of adverse events did not differ significantly among the groups. Conclusions Intrapleural t-PA-DNase therapy improved fluid drainage in patients with pleural infection and reduced the frequency of surgical referral and the duration of hospital stay. Treatment with DNase alone or t-PA alone was ineffective.

To determine the levels of resistance to first-line tuberculosis drugs in three cities in three geopolitical zones in Nigeria.A total of 527 smear-positive sputum samples from Abuja, Ibadan and Nnewi were cultured on BACTEC- MGIT 960. Drug susceptibility tests (DST) for streptomycin, isoniazid, rifampicin and ethambutol were performed on 428 culture-positive samples on BACTEC-MGIT960.Eight per cent of the specimens cultured were multi-drug-resistant Mycobacterium tuberculosis (MDR-TB) with varying levels of resistance to individual and multiple first-line drugs. MDR was strongly associated with previous treatment: 5% of new and 19% of previously treated patients had MDR-TB (OR 4.1 (95% CI 1.9-8.8), P = 0.001) and with young adult age: 63% of patients with and 38% without MDR-TB were 25-34 years old (P = 0.01). HIV status was documented in 71%. There was no association between MDR-TB and HIV coinfection (P = 0.9) and gender (P0.2 for both).MDR-TB is an emerging problem in Nigeria. Developing good quality drug susceptibility test facilities, routine monitoring of drug susceptibility and improved health systems for the delivery of and adherence to first- and second-line treatment are imperative to solve this problem.

Pleural infection is associated with 20% mortality in the 80 000 new cases per year in the UK and USA. Streptococcus species cause ∼50% of community-acquired bacterial pleural infection.1 Staphylococcus aureus and anaerobes are isolated in 8% and 20% of cases, respectively, and 12% of pleural infections yield polymicrobial cultures. However, even using culture and nucleic acid amplification techniques (NAATs), 26% of cases remain microbiologically obscure. The negative microbiology may be due to previous antibiotic treatment, varying pathogen prevalence in different pleural fluid locules (already known to vary biochemically2) or the presence of organisms that are difficult to detect using conventional techniques. One such possible organism is Pneumocystis jirovecii , which requires specialist diagnostic techniques (eg, Grocott–Gomori methenamine silver staining or NAATs). P jirovecii has been identified in sputum and bronchoalveolar lavage (BAL) fluid from both immunocompromised and immunocompetent individuals—it has been isolated from BAL fluid using NAATs …