An observational prospective study of topical acidified nitrite for killing methicillin-resistant Staphylococcus aureus (MRSA) in contaminated wounds

Background Endogenous nitric oxide (NO) kills bacteria and other organisms as part of the innate immune response. When nitrite is exposed to low pH, NO is generated and has been used as an NO delivery system to treat skin infections. We demonstrated eradication of MRSA carriage from wounds using a topical formulation of citric acid (4.5%) and sodium nitrite (3%) creams co-applied for 5 days to 15 wounds in an observational prospective pilot study of 8 patients. Findings Following treatment with topical citric acid and sodium nitrite, 9 of 15 wounds (60%) and 3 of 8 patients (37%) were cleared of infection. MRSA isolates from these patients were all sensitive to acidified nitrite in vitro compared to methicillin-sensitive S. aureus and a reference strain of MRSA. Conclusions Nitric oxide and acidified nitrite offer a novel therapy for control of MRSA in wounds. Wounds that were not cleared of infection may have been re-contaminated or the bioavailability of acidified nitrite impaired by local factors in the tissue

Comparative functional histopathology of human breast carcinoma xenografts.

A series of xenografts of human breast carcinomas has been established and serially transplanted in immune-suppressed mice. Certain structural and functional features of the original human tumours, including carcinoembryonic antigen and epithelial membrane antigen, continue to be expressed by the resulting xenografts. Stromal responses such as elastosis and oestrogen-receptor activity were lost by the xenografts. No metastases were detected in tumour-bearing mice. This study suggests that xenografts may have some value in experimental pathology as one type of model of human breast carcinoma

The statistical laws of popularity: Universal properties of the box office dynamics of motion pictures

Are there general principles governing the process by which certain products or ideas become popular relative to other (often qualitatively similar) competitors? To investigate this question in detail, we have focused on the popularity of movies as measured by their box-office income. We observe that the log-normal distribution describes well the tail (corresponding to the most successful movies) of the empirical distributions for the total income, the income on the opening week, as well as, the weekly income per theater. This observation suggests that popularity may be the outcome of a linear multiplicative stochastic process. In addition, the distributions of the total income and the opening income show a bimodal form, with the majority of movies either performing very well or very poorly in theaters. We also observe that the gross income per theater for a movie at any point during its lifetime is, on average, inversely proportional to the period that has elapsed after its release. We argue that (i) the log-normal nature of the tail, (ii) the bimodal form of the overall gross income distribution, and (iii) the decay of gross income per theater with time as a power law, constitute the fundamental set of {\em stylized facts} (i.e., empirical "laws") that can be used to explain other observations about movie popularity. We show that, in conjunction with an assumption of a fixed lower cut-off for income per theater below which a movie is withdrawn from a cinema, these laws can be used to derive a Weibull distribution for the survival probability of movies which agrees with empirical data. The connection to extreme-value distributions suggests that popularity can be viewed as a process where a product becomes popular by avoiding failure (i.e., being pulled out from circulation) for many successive time periods. We suggest that these results may apply to popularity in general.Comment: 14 pages, 11 figure

Interventions for hidradenitis suppurativa: a Cochrane systematic review incorporating GRADE assessment of evidence quality

Background More than 50 interventions have been used to treat hidradenitis suppurativa (HS) and so therapy decisions can be challenging. Objectives To summarise and appraise randomised controlled trial (RCT) evidence for HS interventions in adults. Materials and methods Searches were conducted in MEDLINE, EMBASE, CENTRAL, LILACS, five trials registers and abstracts from eight dermatology conferences until 13 August 2015. Two review authors independently assessed study eligibility, extracted data and assessed methodological quality. Primary outcomes were quality of life and adverse effects of the interventions. Results Twelve trials, from 1983 to 2015, investigating 15 different interventions met our inclusion criteria. Median trial duration was 16 weeks and the median number of participants was 27. Adalimumab 40mg weekly improved the Dermatology Life Quality Index by 4.0 points, which equates to the minimal clinically important difference for the scale, compared to placebo (95% confidence interval (CI) -6.5 to -1.5 points). Evidence quality was reduced to ‘moderate’ because results are based on only a single study. Adalimumab 40mg every other week was ineffective in a meta-analysis of two studies comprising 124 participants. Infliximab 5mg/kg improved DLQI score by 8.4 points after eight weeks in a moderate quality study completed by 33 of 38 participants. Etanercept 50mg twice weekly was ineffective. Inclusion of a gentamicin sponge prior to primary closure did not improve outcomes. Other interventions including topical and oral antibiotics, were investigated by relatively small studies, preventing treatment recommendations due to imprecision. Conclusions More, larger RCTs are required to investigate most HS interventions, particularly oral treatments and surgical therapy. Moderate quality evidence suggests that adalimumab given weekly and infliximab are effective whereas adalimumab every other week is ineffective

Gene-specific repair of Pt/DNA lesions and induction of apoptosis by the oral platinum drug JM216 in three human ovarian carcinoma cell lines sensitive and resistant to cisplatin

JM216, an oral platinum drug entering into phase III clinical trial, exhibited comparable cytotoxicity to cisplatin in three human ovarian carcinoma cell lines: the sensitive (CH1), acquired resistant (CH1cisR) and intrinsically resistant (SKOV-3). Platinum accumulation and binding to DNA were similar in each of the three cell lines at equimolar doses, indicating that the resistant cell lines could tolerate higher intracellular platinum levels and platinum bound to DNA at IC50 concentrations of drug. Comparison with cisplatin demonstrated that intracellular platinum levels were marginally higher with JM216, but that platinum binding to DNA was similar for the two drugs in each of the cell lines. Each of the cell lines exhibited an ability to repair JM216 induced platinum/DNA lesions in the N-ras gene (gene-specific repair) at equitoxic concentrations of drug. However, this occurred to a greater extent in the two resistant cell lines such that by 24 h the CH1cisR and SKOV-3 had removed 72% and 67% respectively compared with approximately 32% for the CH1. Reduced gene-specific repair capacity in CH1 cells was also seen following incubation with 25 μM (or 5 μM – 2 × IC50) cisplatin, whereas the CH1cisR and SKOV-3 cell lines were repair proficient. JM216 induced apoptosis in the three cell lines following a 2h incubation with 2 × the IC50 of drug. Fluorescent microscopy of cells stained with propidium iodide showed that the detached cell population displayed typical apoptotic nuclei. Furthermore, field inversion gel electrophoresis demonstrated the presence of DNA fragments approximately 23–50 kb in size, indicative of apoptosis, in the detached cells. JM216 induced an S phase slow down in each of the three cell lines accompanied by a G2 block in the CH1 pair. Incubation with this concentration of JM216 also resulted in the induction of p53 in the CH1 and CH1cisR. These studies suggest that the relative sensitivity of the CH1 cell line to cisplatin and JM216 is at least partly attributable to a deficiency in gene-specific repair. The oral platinum drug, JM216, exerts its cytotoxic effects through the induction of apoptosis following a slow-down in S phase in both the sensitive and resistant lines. © 1999 Cancer Research Campaig

Rapid Molecular Detection of Rifampicin Resistance Facilitates Early Diagnosis and Treatment of Multi-Drug Resistant Tuberculosis: Case Control Study

Multi-drug resistant tuberculosis (MDR-TB) is a major public health concern since diagnosis is often delayed, increasing the risk of spread to the community and health care workers. Treatment is prolonged, and the total cost of treating a single case is high. Diagnosis has traditionally relied upon clinical suspicion, based on risk factors and culture with sensitivity testing, a process that can take weeks or months. Rapid diagnostic molecular techniques have the potential to shorten the time to commencing appropriate therapy, but have not been put to the test under field conditions.This retrospective case-control study aimed to identify risk factors for MDR-TB, and analyse the impact of testing for rifampicin resistance using RNA polymerase B (rpoB) mutations as a surrogate for MDR-TB. Forty two MDR-TB cases and 84 fully sensitive TB controls were matched by date of diagnosis; and factors including demographics, clinical presentation, microbiology findings, management and outcome were analysed using their medical records. Conventionally recognised risk factors for MDR-TB were absent in almost half (43%) of the cases, and 15% of cases were asymptomatic. A significant number of MDR-TB cases were identified in new entrants to the country. Using rpoB mutation testing, the time to diagnosis of MDR-TB was dramatically shortened by a median of 6 weeks, allowing patients to be commenced on appropriate therapy a median of 51days earlier than those diagnosed by conventional culture and sensitivity testing.MDR-TB is frequently an unexpected finding, may be asymptomatic, and is particularly prevalent among TB infected new entrants to the country. Molecular resistance testing of all acid fast bacilli positive specimens has the potential to rapidly identify MDR-TB patients and commence them on appropriate therapy significantly earlier than by conventional methods

Non-Equilibrium Social Science and Policy

Between 2011 and 2014 the European Non-Equilibrium Social Science Project (NESS) investigated the place of equilibrium in the social sciences and policy. Orthodox economics is based on an equilibrium view of how the economy functions and does not offer a complete description of how the world operates. However, mainstream economics is not an empty box. Its fundamental insight, that people respond to incentives, may be the only universal law of behaviour in the social sciences. Only economics has used equilibrium as a primary driver of system behaviour, but economics has become much more empirical at the microlevel over the past two decades. This is due to two factors: advances in statistical theory enabling better estimates of policy consequences at the microlevel, and the rise of behavioural economics which looks at how people, firms and governments really do behave in practice. In this context, this chapter briefly reviews the contributions of this book across the social sciences and ends with a discussion of the research themes that act as a roadmap for further research. These include: realistic models of agent behaviour; multilevel systems; policy informatics; narratives and decision making under uncertainty; and validation of agent-based complex systems models