ABSTRACT
We present updated cosmological constraints from measurements of the gas mass fractions (fgas) of massive, dynamically relaxed galaxy clusters. Our new data set has greater leverage on ...models of dark energy, thanks to the addition of the Perseus cluster at low redshifts, two new clusters at redshifts z ≳ 1, and significantly longer observations of four clusters at 0.6 < z < 0.9. Our low-redshift (z < 0.16) fgas data, combined with the cosmic baryon fraction measured from the cosmic microwave background (CMB), imply a Hubble constant of h = 0.722 ± 0.067. Combining the full fgas data set with priors on the cosmic baryon density and the Hubble constant, we constrain the dark energy density to be ΩΛ = 0.865 ± 0.119 in non-flat Lambda cold dark matter (cosmological constant) models, and its equation of state to be $w=-1.13_{-0.20}^{+0.17}$ in flat, constant-w models, respectively 41 per cent and 29 per cent tighter than our previous work, and comparable to the best constraints available from other probes. Combining fgas, CMB, supernova, and baryon acoustic oscillation data, we also constrain models with global curvature and evolving dark energy. For the massive, relaxed clusters employed here, we find the scaling of fgas with mass to be consistent with a constant, with an intrinsic scatter that corresponds to just ∼3 per cent in distance.
Four benzimidazolium hydroxide compounds, in which the C2‐position is attached to a phenyl group possessing hydrogen, bromine, methyl groups, or phenyl groups at the ortho positions, are prepared and ...investigated for stability in a quantitative alkaline stability test. The differences between the stability of the various protecting groups in caustic solutions are rationalized on the basis of their crystal structures and DFT calculations. The highest stability was observed for the m‐terphenyl‐protected benzimidazolium, showing a half‐life in 3 m NaOD/CD3OD/D2O at 80 °C of 3240 h. A high‐molecular‐weight polymer analogue of this model compound is prepared that exhibits excellent mechanical properties, high ionic conductivity and ion‐exchange capacity, as well as remarkable hydroxide stability in alkaline solutions: only 5 % degradation after 168 h in 2 m KOH at 80 °C. This is the most stable hydroxide‐conducting benzimidazolium polymer to date.
It takes backbone: Through a novel synthetic pathway, pendant benzimidazolium groups attached to a poly(phenylene) backbone, which acts as the sterically protecting group, produces the most alkaline‐stable polybenzimidazolium to date. Crystal structures and DFT calculations of model compounds are used to explain the observed alkaline stability.
In this randomized trial in patients hospitalized with alcoholic hepatitis, pentoxifylline did not improve survival. The 28-day survival advantage in patients treated with prednisolone did not reach ...significance and was not sustained at 90 days or 1 year.
Alcoholic hepatitis is a distinct manifestation of alcoholic liver disease that is characterized by jaundice and liver failure. This condition develops in persons with a history of prolonged and heavy alcohol use.
1
The severity of alcoholic hepatitis is conventionally defined by Maddrey’s discriminant function, which is calculated as 4.6×(patient’s prothrombin time in seconds−control’s prothrombin time in seconds)+patient’s serum bilirubin level in milligrams per deciliter; a value of 32 or higher indicates severe alcoholic hepatitis that carries an adverse prognosis, with mortality of 20 to 30% within 1 month after presentation and 30 to 40% within 6 months after presentation.
2
A . . .
Summary
An analysis of United States (US) Medicare claims data from 2002 to 2015 for women aged ≥ 65 years found that age-adjusted hip fracture rates for 2013, 2014, and 2015 were higher than ...projected, resulting in an estimated increase of more than 11,000 hip fractures.
Introduction
Hip fractures are a major public health concern due to high morbidity, mortality, and healthcare expenses. Previous studies have reported a decrease in the annual incidence of hip fractures in the US beginning in 1995, coincident with the introduction of modern diagnostic tools and therapeutic agents for osteoporosis. In recent years, there has been less bone density testing and fewer prescriptions for osteoporosis treatments. The large osteoporosis treatment gap raises concern of possible adverse effects on hip fracture rates.
Methods
We assessed hip fracture incidence in the US to determine if the previous decline in hip fracture incidence continued. Using 2002 to 2015 Medicare Part A and Part B claims for women ≥ 65 years old, we calculated age-adjusted hip fracture rates, weighting to the 2014 population.
Results
We found that hip fracture rates declined each year from 2002 to 2012 and then plateaued at levels higher than projected for years 2013, 2014, and 2015.
Conclusions
The plateau in age-adjusted hip fracture incidence rate resulted in more than 11,000 additional estimated hip fractures over the time periods 2013, 2014, and 2015. We recommend further study to assess all factors contributing to this remarkable change in hip fracture rate and to develop strategies to reduce the osteoporosis treatment gap.
Despite widespread awareness of risks, significant investments in cybersecurity protection, and substantial economic incentives to avoid security breaches, organizations remain vulnerable to phishing ...attacks. Phishing research has informed effective practical interventions to address phishing susceptibility that emphasize the importance of broadly applicable IT security knowledge. Yet employees still frequently fall victim to phishing attempts. To help understand why, we conceptualize phishing susceptibility as the failure to differentiate between deceptive and legitimate information processing requests that occur within the context of an employee’s typical job responsibilities. We apply this contextual lens to identify characteristics of knowledge workers’ organizational task and social context that may enhance or diminish performance in detecting deception in phishing email attempts. To test our hypotheses, we conducted a study in which employees of the finance division of a large university encountered simulated email-based phishing attempts as part of their normal work routine. We found evidence supporting our hypotheses that an individual’s susceptibility to phishing attacks is influenced by their position in the knowledge flows of the organization and by the impact of workgroup responsibilities on their cognitive processing. We contend that phishing susceptibility is not merely a matter of IT security knowledge but is also influenced by contextualized, multilevel influences on information processing. As phishing attacks are increasingly targeted to specific organizational settings, it is even more important to incorporate this contextualized information processing view of phishing susceptibility.
Summary Background Depression is a common, debilitating, and costly disorder. Many patients request psychological therapy, but the best-evidenced therapy—cognitive behavioural therapy (CBT)—is ...complex and costly. A simpler therapy—behavioural activation (BA)—might be as effective and cheaper than is CBT. We aimed to establish the clinical efficacy and cost-effectiveness of BA compared with CBT for adults with depression. Methods In this randomised, controlled, non-inferiority trial, we recruited adults aged 18 years or older meeting Diagnostic and Statistical Manual of Mental Disorders IV criteria for major depressive disorder from primary care and psychological therapy services in Devon, Durham, and Leeds (UK). We excluded people who were receiving psychological therapy, were alcohol or drug dependent, were acutely suicidal or had attempted suicide in the previous 2 months, or were cognitively impaired, or who had bipolar disorder or psychosis or psychotic symptoms. We randomly assigned participants (1:1) remotely using computer-generated allocation (minimisation used; stratified by depression severity Patient Health Questionnaire 9 (PHQ-9) score of <19 vs ≥19, antidepressant use, and recruitment site) to BA from junior mental health workers or CBT from psychological therapists. Randomisation done at the Peninsula Clinical Trials Unit was concealed from investigators. Treatment was given open label, but outcome assessors were masked. The primary outcome was depression symptoms according to the PHQ-9 at 12 months. We analysed all those who were randomly allocated and had complete data (modified intention to treat mITT) and also all those who were randomly allocated, had complete data, and received at least eight treatment sessions (per protocol PP). We analysed safety in the mITT population. The non-inferiority margin was 1·9 PHQ-9 points. This trial is registered with the ISCRTN registry, number ISRCTN27473954. Findings Between Sept 26, 2012, and April 3, 2014, we randomly allocated 221 (50%) participants to BA and 219 (50%) to CBT. 175 (79%) participants were assessable for the primary outcome in the mITT population in the BA group compared with 189 (86%) in the CBT group, whereas 135 (61%) were assessable in the PP population in the BA group compared with 151 (69%) in the CBT group. BA was non-inferior to CBT (mITT: CBT 8·4 PHQ-9 points SD 7·5, BA 8·4 PHQ-9 points 7·0, mean difference 0·1 PHQ-9 points 95% CI −1·3 to 1·5, p=0·89; PP: CBT 7·9 PHQ-9 points 7·3; BA 7·8 6·5, mean difference 0·0 PHQ-9 points –1·5 to 1·6, p=0·99). Two (1%) non-trial-related deaths (one 1% multidrug toxicity in the BA group and one 1% cancer in the CBT group) and 15 depression-related, but not treatment-related, serious adverse events (three in the BA group and 12 in the CBT group) occurred in three 2% participants in the BA group (two 1% patients who overdosed and one 1% who self-harmed) and eight (4%) participants in the CBT group (seven 4% who overdosed and one 1% who self-harmed). Interpretation We found that BA, a simpler psychological treatment than CBT, can be delivered by junior mental health workers with less intensive and costly training, with no lesser effect than CBT. Effective psychological therapy for depression can be delivered without the need for costly and highly trained professionals. Funding National Institute for Health Research.
Introduction
Controversy and uncertainty exist about the use of benzodiazepine receptor agonists (BZRAs) in pain management. This article curates available research to determine the appropriate role ...of BZRAs in the course of pain management, and how prescribers might address these challenges.
Methods
A narrative review was performed to determine the appropriate role of BZRAs in pain management and to develop practice recommendations. Publications were identified by a search of PubMed, references of retrieved reports, guidelines, and the author’s personal files.
Results
BZRAs were found to have analgesic benefit for two pain conditions: burning mouth syndrome and stiff person syndrome. Absence of research, heterogeneity of trials, and small sample sizes precluded drawing conclusions about efficacy of BZRAs for the other 109 pain conditions explored. Data supports the use of BZRAs to treat co-occurring insomnia and anxiety disorders but only when alternatives are inadequate and only for short periods of time (2–4 weeks). The utility of BZRAs is limited by loss of efficacy that may be seen with continued use and adverse reactions including physiologic dependence which develops in 20–100% of those who take these agents for more than a month.
Conclusions
BZRAs are often used inappropriately in pain management. Their initiation and duration of use should be limited to a narrow range of conditions. When prescribed for 4 weeks or more, patients should be encouraged to discontinue them through a supported, slow tapering process that may take 12–18 months or longer.
A major percentage of fixed nitrogen (N) loss in the oceans occurs within nitrite-rich oxygen minimum zones (OMZs) via denitrification and anammox. It remains unclear to what extent ammonium and ...nitrite oxidation co-occur, either supplying or competing for substrates involved in nitrogen loss in the OMZ core. Assessment of the oxygen (O₂) sensitivity of these processes down to the O₂ concentrations present in the OMZ core (<10 nmol·L−1) is therefore essential for understanding and modeling nitrogen loss in OMZs. We determined rates of ammonium and nitrite oxidation in the seasonal OMZ off Concepcion, Chile at manipulated O₂ levels between 5 nmol·L−1 and 20 μmol·L−1. Rates of both processes were detectable in the low nanomolar range (5–33 nmol·L−1 O₂), but demonstrated a strong dependence on O₂ concentrations with apparent half-saturation constants (Km
s) of 333 ± 130 nmol·L−1 O₂ for ammonium oxidation and 778 ± 168 nmol·L−1 O₂ for nitrite oxidation assuming one-component Michaelis–Menten kinetics. Nitrite oxidation rates, however, were better described with a two-component Michaelis–Menten model, indicating a high-affinity component with a Km
of just a few nanomolar. As the communities of ammonium and nitrite oxidizers were similar to other OMZs, these kinetics should apply across OMZ systems. The high O₂ affinities imply that ammonium and nitrite oxidation can occur within the OMZ core whenever O₂ is supplied, for example, by episodic intrusions. These processes therefore compete with anammox and denitrification for ammonium and nitrite, thereby exerting an important control over nitrogen loss.
Reports on the regulation of neutrophil function by IL-6 are often conflicting. Therapeutic inhibition of IL-6 in RA is associated with occasional neutropenia, but the mechanisms underlying this ...observation are poorly understood. This study investigated interactions between IL-6, the anti-IL-6 receptor agent tocilizumab (TCZ) and neutrophils in vitro and in vivo.
Neutrophils were isolated from healthy controls and incubated in vitro with pharmacologically relevant concentrations of IL-6 or TCZ. Neutrophils were also isolated from RA patients, including a cohort following TCZ therapy. Apoptosis was measured by annexin V/propidium iodide (PI) flow cytometry; phagocytosis was measured by incubating apoptotic neutrophils with THP-1-derived macrophages; chemotaxis was measured using cell migration through hanging-cell inserts towards IL-8 and cell surface proteins, including adhesion molecules CD11b (αMβ2 integrin) and CD62L (L-selectin) were measured by flow cytometry.
IL-6 (10-100 ng/ml) did not affect the rate of neutrophil apoptosis, priming of the respiratory burst or adhesion molecule expression nor act as a neutrophil chemoattractant. However, IL-6 enhanced signal transducer and activator of transcription 3 (STAT3) activation and neutrophil migration towards IL-8. TCZ in vitro did not induce apoptosis or phagocytosis of neutrophils, nor did it have a significant effect upon apoptosis or cell surface molecule expression. Neutrophil functions in ex vivo neutrophils from RA patients receiving TCZ treatment were unaffected.
Therapeutic blockade of IL-6, while inducing a transient neutropenia, does not directly affect neutrophil functions associated with host defence. TCZ-associated neutropenia cannot be explained by direct induction of apoptosis by TCZ, induction of apoptosis following depletion of IL-6, nor increased phagocytosis of neutrophils.
PDF
