Search

Background: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the reliance on antigen detection rapid diagnostic tests (Ag-RDTs). Their evaluation at point of use is a priority. Methods: Here, we report a multi-centre evaluation of the analytical sensitivity, specificity, and clinical accuracy of the Mologic COVID-19 Ag-RDT by comparing to reverse transcriptase polymerase chain reaction (RT-qPCR) results from individuals with and without COVID-19 symptoms. Participants had attended hospitals in Merseyside, hospital and ambulance services in Yorkshire, and drive-through testing facilities in Northumberland, UK. Results: The limit of detection of the Mologic COVID-19 Ag-RDT was 5.0 x 102 pfu/ml in swab matrix with no cross-reactivity and interference for any other pathogens tested. A total of 347 participants were enrolled from 26th of November 2020 to 15th of February 2021 with 39.2% (CI 34.0-44.6) testing RT-qPCR positive for SARS-CoV-2. The overall sensitivity and specificity of the Mologic Ag-RDT compared to the reference SARS-CoV-2 RT-qPCR were 85.0% (95% CI 78.3-90.2) and 97.8% (95.0-99.3), respectively. Sensitivity was stratified by RT-qPCR cycle threshold (Ct) and 98.4% (91.3-100) of samples with a Ct less than 20 and 93.2% (86.5-97.2) of samples with a Ct less than 25 were detected using the Ag-RDT. Clinical accuracy was stratified by sampling strategy, swab type and clinical presentation. Mologic COVID-19 Ag-RDT demonstrated highest sensitivity with nose/throat swabs compared with throat or nose swabs alone; however, the differences were not statistically significant. Conclusions: Overall, the Mologic test had high diagnostic accuracy across multiple different settings, different demographics, and on self-collected swab specimens. These findings suggest the Mologic rapid antigen test may be deployed effectively across a range of use settings.

Introduction Multiple techniques exist for the management of colorectal polyps. Recent ESGE guidelines1 have defined an evidence based guide to the optimal technique for removing different sizes of polyps. Previously this decision often depended on an individual operator’s experience and training. We sought to examine current polypectomy practice amongst United Kingdom endoscopy trainees with to these guidelines. Methods The ESGE polypectomy guideline1 suggests polyps Results 2 91 778 polypectomies were performed in 1 76 569 trainee-performed procedures by 3395 trainees over the study period. 10 584 polypectomies were missing data. 2 81 194 polypectomies were analysed. Of 2 50 783 polyps Of 219 (0.1%) adverse events reported amongst all polypectomies, 50.8% were amongst HSP, 19.2% EMR, 16.9% CSP and 12.7% after HBF p Conclusions Cold snare polypectomy is under-utilised for diminutive polypectomy, despite its proven safety and efficacy; its use amongst trainees should be promoted in line with ESGE guidance. Trainees are likely to follow the example of their trainers and, as such, this study likely provides an insight into current polypectomy practice in the wider UK endoscopic community. Trainees in the United Kingdom predominantly remove diminutive polyps with extremely low rates of adverse events. Reference . Ferlitsch M, et al. Colorectal polypectomy and endoscopic mucosal resection (EMR): Endoscopy. 2017 Mar 1;49(3):270–97.

Summary Background Antimicrobial stewardship is a key component in the reduction of healthcare-associated infections, particularly Clostridium difficile infection (CDI). We successfully restricted the use of cephalosporins and, subsequently, fluoroquinolones. From an endemically high level of >280 cases per year in 2007–08, the number of CDIs reduced to 72 cases in 2011–12. Aim To describe the implementation and impact of fluoroquinolone restriction on CDI. Methods This was an interrupted time-series analysis pre and post fluoroquinolone restriction for 60 months based on a Poisson distribution model. Findings In June 2008, fluoroquinolone consumption halved to about 5 defined daily doses (DDD) per 100 occupied bed-days (OBD). This was followed by a significant fall in CDI number [rate ratio (RR): 0.332; 95% confidence interval (CI): 0.240–0.460] which remained low over the subsequent months. Subsequently, fluoroquinolone consumption was further reduced to about 2 DDD/100 OBD in June 2010 accompanied by further reduction in CDI rate (RR: 0.394; 95% CI: 0.199–0.781). In a univariate Poisson model the CDI rate was associated with fluoroquinolone usage (RR: 1.086; 95% CI: 1.077–1.094). Conclusion We conclude that in an environment where cephalosporin usage is already low, the reduction in fluoroquinolone usage was associated with an immediate, large, and significant reduction in CDI cases.

Summary Aims Periprosthetic joint infection (PJI) is a catastrophic and potentially life threatening complication following arthroplasty. In addition to the resulting impact on patient morbidity and mortality, PJI is associated with significant financial cost, which is estimated at £21,937 per case. Methicillin sensitive staphylococcus aureus (MSSA) is a common isolate in PJI and colonisation is a proven risk factor for subsequent infection. The aims of this study were: (1) to determine if MSSA screening and decolonisation reduced MSSA PJI rate in primary joint replacement and (2) to determine cost effectiveness of such a screening program. Methods Pre-operative screening for MSSA was introduced in our institution in 2010. All MSSA positive patients attending for elective arthroplasty were prescribed Octenisan body wash and nasal Bactroban for use 5 days prior to procedure, and five days after. Infection data was collected prospectively and compared with a control group from before. Results Between 2007 and 2014, 12,910 primary arthroplasties (5917 hip, 6993 knee) were performed. There were 3593 in the pre-screening group and 9318 in the post-screening group. Pre-screening PJI MSSA rate was 0.75% which reduced to 0.25% post screening introduction ( p p = 0.03). The screening program was most effective in MSSA prevention in total hip arthroplasty (3% to 1.5%, p = 0.002) and significant in the multivariate analysis. Following the introduction of the screening programme 47 PJIs were avoided, with a cost per infection prevented of £1893. Conclusion The MSSA screening and eradication protocol used in our institution was effective at reducing rates of MSSA PJI. Furthermore, it resulted in significant savings when compared to the cost of prevented infections.

Summary Background In hospital, doctors and nurses frequently discuss acutely unwell patients via the telephone. Telephone communication can be challenging, yet medical students receive little training in how to conduct such interactions. We aimed to provide a simple, innovative, simulation session to address this learning need for third-year medical students at Newcastle University. Methods Groups of students were given a pager and a supervising tutor. Students responded to a ‘bleep’ from a nurse practitioner in a different room, who role-played a ward nurse concerned about a patient. Speakerphones were used, allowing the entire conversation to be audible. After the call, a student-led debriefing session took place. After the debriefing another student ‘held’ the bleep and a different scenario ensued. Following a resuscitation scenario, students made telephone contact with the medical registrar to hand over information pertaining to the case. Before and after the session, students rated their confidence in telephone interaction and handover using a 10–point Likert scale. Students also completed a feedback questionnaire. Results Fifty-four students attended the session. A statistically significant improvement in student confidence in telephone communication and handover was seen after the session. Free-text feedback highlighted that students had not received teaching on this previously, and that they welcomed opportunities to practise such skills within a controlled, safe environment. Discussion Simulation training can be costly, but speakerphones are cheap and readily available. Given the frequency of telephone interaction in hospital, we believe all medical students should receive telephone communication training. Locally, our department has now incorporated these teaching methods into simulation sessions elsewhere in the curriculum. Medical students receive little training in how to conduct [telephone] interactions

Cerebral metabolite disturbances occur among human immunodeficiency virus (HIV)-infected people, and are thought to reflect neuropathology, including proinflammatory processes, and neuronal loss. HIV-associated cortical atrophy continues to occur, though its basis is not well understood, and the relationship of cerebral metabolic disturbance to structural brain abnormalities in HIV has not been well delineated. We hypothesized that metabolite disturbances would be associated with reduced cortical and subcortical volumes. Cerebral volumes were measured in 67 HIV-infected people, including 10 people with mild dementia (acquired immunodeficiency syndrome [AIDS] dimentia complex [ADC] stage >1) via automated magnetic resonance imaging (MRI) segmentation. Magnetic resonance spectroscopy (MRS) was used to measure levels of cerebral metabolites N-acetylaspartate (NAA), myo-inositol (MI), choline-containing compounds (Cho), glutamate/glutamine (Glx), and creatine (Cr) from three brain regions (frontal gray matter, frontal white matter, basal ganglia). Analyses were conducted to examine the associations between MRS and cerebral volumetric measures using both absolute and relative metabolite concentrations. NAA in the mid-frontal gray matter was most consistently associated with cortical (global, frontal, and parietal), ventricular, and caudate volumes based on analysis of absolute metabolite levels, whereas temporal lobe volume was associated with basal ganglia NAA and Glx, and Cho concentrations in the frontal cortex and basal ganglia. Hippocampal volume was associated with frontal white matter NAA, whereas thalamic volume was associated with both frontal white matter NAA and basal ganglia Glx. Analyses of relative metabolite concentrations (referenced to Cr) yielded weaker effects, although more metabolites were retained as significant predictors in the models than the analysis of absolute concentrations. These findings demonstrate that reduced cortical and subcortical volumes, which have been previously found to be linked to HIV status and history, are also strongly associated with the degree of cerebral metabolite disturbance observed via MRS. Reduced cortical and hippocampal volumes were most strongly associated with decreased NAA, though reduced Glx also tended to be associated with reduced cortical and subcortical volumes (caudate and thalamus) as well, suggesting both neuronal and glial disturbances. Interestingly, metabolite-volumetric relationships were not limited to the cortical region from which MRS was measured, possibly reflecting shared pathophysiological processes. The relationships between Cho and volumetric measures suggest a complicated relationship possibly related to the effects of inflammatory processes on brain volume. The findings demonstrate the relationship between MRI-derived measures of cerebral metabolite disturbances and structural brain integrity, which has implication in understanding HIV-associated neuropathological mechanisms.

Beginning with the Better Buying Power initiatives, the military components have been required to perform full life-cycle portfolio-level affordability analyses with respect to major defense acquisition programs at key milestones. Prior to this, there was no formal requirement to reconcile program acquisition baselines with resource forecasts beyond the five years of the Future Years Defense Program. This paper discusses the analytical challenges associated with Affordability Analysis and describes methods and tools that the Institute for Defense Analyses is developing to address these challenges.

Nitric oxide (NO) is a key messenger involved in numerous physiological functions including inflammatory and immune responses. The functions of NO and their underlying mechanisms have been elucidated by extensive studies over the past 10 years. However, the complexity of the interactions between different levels of NO and multiple aspects of tumor development/progression as well as bacterial pathogenesis has led to apparently conflicting findings. The precise role of NO in bacterial and tumor pathogenesis involves a multitude of inter- and intracellular signaling pathways in which interferon gamma signaling and L-arginine metabolism are the major pathways involved in NO synthesis and regulation. The availability of the amino acid L-Arg can be a key factor to control the expression of inducible nitric oxide synthase (NOS2) and cellular NO levels. The role played by the NOS2/NO system both in bacterial pathogenesis and in tumor development is complex due to the dual role these molecules can play promoting or inhibiting infections and cancer. This duality brings to the table a double challenge to determine the net impact of NO on cancer or bacterial behavior and to define the therapeutic role of NO-centered anticancer or antibacterial strategies. We believe that a comprehensive and dynamic understanding of the cascade of molecular and cellular events underlying tumor biology and bacterial pathogenesis that are affected by NO will allow researchers to exploit the potential antitumor and antibacterial properties of drugs interfering with NO metabolism. The contrasting roles of NO/NOS2 in these processes are clarified in this chapter.

The International Association of Oil and Gas Producers (OGP) has taken a strong proactive step to reduce the greatest common cause of death and serious injury plaguing our industry—motor-vehicle crashes (Fig. 1). OGP members formed a task force to study the issue and develop a realistic way to address it. The group selected a process that is elegant in its simplicity, yet remarkably thorough. They reasoned that since the industry was already accustomed to following recommended practice (RP) in nearly every facet of its work, why would it not be willing to develop and apply RP in driving? The work was encouraged by sobering statistics amassed by the World Health Organization and the World Bank, which jointly estimated that 1.2 million people are killed annually in road crashes, and another 50 million are injured. Trends show that these numbers could increase by 65% over the next 20 years unless there is some intervention. While rates in developed countries are expected to decline, those of low- to middle-income countries will erase the decline, and the trend is expected to be steeply upward. Task-force members reminded themselves that the oil and gas industry field force is very active in these at-risk countries. The task force took the position that one of the best ways to minimize driving fatalities is to minimize the occurrence of vehicle crashes. The best way to minimize the occurrence of vehicle crashes is to address their causes in a comprehensive way. Accordingly, the RP covers a spectrum of control areas. The team strived to apply experience, common sense, and best practice in determining the content of the document. Measures both proactive and reactive were included—preventative and mitigating, respectively. While the requirement for driver training and skill assessment will help prevent a crash, the requirement for the wearing of seatbelts reduces the potential for injury should a crash happen. Task-force members sought to create a product that, if applied across the industry, should result in a step change in journey management and a substantial reduction in transport-related incidents. What differentiates an RP from a guideline is that an RP should be formally put into the business and operating practices of the company adopting it, requiring the universe of their enterprise—that is, permanent and temporary employees, partners, contractors, and vendors—to be influenced to adopt the practice as well. It is a powerful and effective incentive. An RP also becomes something by which the industry is recognized by the general public, governments, and regulatory agencies.

Many interface devices for virtual reality provide full immersion inside the virtual environment. This is appropriate for numerous applications that emphasize navigating through a virtual space. However, a large class of problems exists for which navigation is not the critical issue. Rather, these applications demand a fine-granularity visualization and interaction with virtual objects and scenes. This applies to a host of other applications typically performed on a desktop, table or workbench. Responsive Workbench technology offers a new way to develop virtual environments for this rather sizable class of applications. The Responsive Workbench operates by projecting a computer-generated, stereoscopic image off a mirror and through a table surface. Using stereoscopic shuttered glasses, users observe a 3D image displayed above the tabletop. By tracking the group leader's head and hand movements, the Responsive Workbench permits changing the view angle and interacting with the 3D scene. Other group members observe the scene as the group leader manipulates it, facilitating communication among observers. Typical methods for interacting with virtual objects on the workbench include speech recognition, gesture recognition and a simulated laser pointer (stylus). This article features Responsive Workbench applications from four institutions that have pioneered this technology. The four applications are: visualization, situational awareness, collaborative production modeling and planning, and a virtual windtunnel.

Using virtual environments for training and mission rehearsal gives US Navy firefighters an edge in fighting real fires. A test run on the ex-USS Shadwell measured the improvement. The results suggest that virtual environments serve effectively for training and mission rehearsal for shipboard firefighting. VE training provides a flexible environment where a firefighter can not only learn an unfamiliar part of the ship, but also practice tactics and procedures for fighting a fire by interacting with simulated smoke and fire without risking lives or property. These tests proved a successful first step in developing a new training technology for shipboard firefighting based on immersive virtual environments. The tests also indicated potential areas for improvement, requiring additional research. User interaction techniques for manipulating objects in VEs need further study, along with usability studies to determine their effectiveness or utility. Other areas that could enhance VE training systems include more natural and intuitive I/O devices such as 3D sound, speech and natural language input, integrated multimedia and hypermedia instruction, and multi user interaction.

Summary Background Antibiotic stewardship is a key component in the effort to reduce healthcare-associated infections. Aim To describe the implementation and analyse the impact of fluoroquinolone restriction on resistance in Enterobacteriaceae, focusing on urinary isolates of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli , which were historically almost universally resistant to fluoroquinolones. Methods ESBL-producing E. coli hospital and community isolates, obtained between April 2009 and March 2012 from consecutive non-duplicate urine samples, were included in an interrupted time-series analysis based on a Poisson distribution model. Periods before and after fluoroquinolone restriction were compared. The trend in fluoroquinolone resistance in all urinary isolates of Enterobacteriaceae ( N ≈ 20,000 per year) and blood culture isolates of E. coli ( N ≈ 350) between 2009 and 2013 were also analysed. Findings A large decline in the percentage of ciprofloxacin-resistant ESBL-producing urinary E. coli isolates was observed in both hospital (risk ratio: 0.473; 95% confidence interval: 0.315–0.712) and community settings (0.098; 0.062–0.157). The decline was also marked in all urinary isolates of Enterobacteriaceae and E. coli isolates from blood cultures. Conclusion We conclude that reducing fluoroquinolone usage to a level of ≤2 defined daily doses per 100 occupied bed-days in hospital sufficiently removed selection pressure to allow resistant Enterobacteriaceae – specifically, the UK endemic strains of ESBL-producing E. coli – to revert back to fluoroquinolone susceptibility within a short span of four months. This was accompanied with a concomitant reduction in overall ESBL burden.

We describe the case of a 24 year old male with severe fistulating Crohn's disease who failed mutliple modalities of medical and surgical therapy. We present objective and subjective evidence of disease remission after induction and maintenance treatment with leukocyte apheresis. This is the first described case of successful maintenance treatment of severe Crohn's disease with leukocyte apheresis in the United Kingdom.

Virtual reality efforts in the Information Technology Division of the Naval Research Laboratory (NRL) span mission planning, rehearsal, and execution; simulation-based design; and medicine. The authors devote much of their work to ship-based applications, presenting two such efforts in the article. One project focuses on experiments in shipboard firefighting to verify the effectiveness of VR as a mission planning tool. The other project involves visualizing a preliminary design of a new Navy ship. Since that work did not extend into the actual design cycle, they can't quantify the results in terms of hours gained or costs saved. However, the design team and the program managers agreed that the VR visualization was worthwhile and provided a better understanding of the design.

We report the case of a 38-year-old man who developed IgA myeloma of donor origin 7 years after allogeneic renal transplant. The diagnosis of multiple myeloma was unequivocal and based on positive results from serum electrophoresis, skeletal survey and bone marrow investigations. The donor origin of the myeloma cells was confirmed by DNA fingerprinting. We believe this is the first reported case of disseminated multiple myeloma of donor origin developing after allogeneic renal transplant and, as such, gives some insight into the natural history and biology of the disease.

Driving maintains its position as the single highest common cause of fatalities in the oil and gas industry. As the industry has experienced a dramatic increase in activity, driving-related fatalities have increased similarly — from 21.9% in 2004 to 35.6% in 2005 (International Association of Oil & Gas Producers [OGP] data). It is expected that the proliferation and implementation of the OGP LTS RP will achieve the necessary step change in the industry to have impact on this manageable, and hence, very unacceptable statistic. (Define "LTS" and "RP"?) For a company already aligned with the fundamentals of the RP elements, and that has experienced success in reducing crashes, other opportunities to continue a downward trend of vehicular crashes must be investigated. With a reduction in crashes, other land-transport related exposures and losses start to stand out. Remote operations and regional instability present a hazard to both personal and asset security; land transport inefficiency increases cost, potential for security events and crashes, and increases carbon emissions. One method to address both a continued focus on improved driving safety while at the same time having an impact on other related exposures is to take advantage of technology. Making use of leading-edge technologies, a 24-hour real-time journey management system has been developed and deployed successfully in Saudi Arabia by a major oilfield service company. The purpose of this paper is to provide industry with an overview of a technological approach to comprehensive journey management. The authors will share the motivations, expectations, and challenges of the endeavor, accompanied by learnings and outcomes

In Western Canada, a significant portion of fatalities in the oil field can be related to driving events. A major service company has implemented a multifaceted approach to addressing the hazards associated with driving in the oilfield. A key component of the driving program is the driving simulator. In 2001, this service company purchased its first mobile computerized driving simulators to complement its driving program in the United States. The service company worked with the simulator manufacturer to develop a custom oilfield-specific driving program. The program evolved to include a multitude of scenarios and hazards that drivers are exposed to in field operations. Implementation of these simulators helped to account for a 50% reduction in automobile incidents and a 70% reduction in high-potential automotive incidents. The operations for this service company in Canada took notice and utilized a driving simulator as part of a pre-winter campaign in the fourth quarter of 2003. During Q1 of 2004, Canadian operations realized the lowest crash rate in its history. In 2007, the next generation of driving simulator was purchased for dedicated use in this region. New features include the ability to link student driver stations to simulate convoys, the ability of the instructor to interact independently with either or both students, and an enhanced scenario tool box to allow the instructor to craft custom scenarios. This paper describes evolution in the use of a simulator for driver training in an oilfield environment.

Operator fatigue is an issue in all 24-hour operations; operator fatigue is a leading cause of vehicle crashes. The oil and gas industry is a 24-hour operation that relies extensively on land transportation. It comes as no surprise then that drowsy driving has been recognized as a cause of many land transportation-related fatalities. Dealing with drowsy driving is a difficult task. Training is a powerful tool; however, drivers trained to recognize and manage fatigue frequently fail to effectively apply this training at critical times because sound judgment is one of the first things affected by fatigue. As part of an ongoing commitment to crash-free driving, a major oilfield service company turned to a leading fatigue research and technology company to assist in eliminating drowsy driving. This paper reports on the experiences of a field trial with a new fatigue warning device for drivers and operators. The device utilizes a camera system installed in the dashboard of the vehicle that monitors the eyes of the driver. In contrast to previously proposed devices, this system does not utilize infra-red (IR) reflections, and as a result, is able to operate during daytime and when eyeglasses are worn. Deployed in four heavy trucks and one light truck, the systems have successfully recorded sequences of the eyes of drivers during potential fatigue events. This paper also reports on staff acceptance of such fatigue management systems. Privacy concerns are an issue when camera-bsaed systems are used to monitor drivers.

Driving-related events continue to be the single largest cause of fatalities in the oil and gas industry. Only by implementing a common set of expectations based on industry best practice and experience can the industry as a whole make any significant headway in addressing this issue. The International Association of Oil and Gas Producers (OGP) formed a Task Force comprised of several leading member organizations with a charter to produce a document that captured established best practices from industry. This document then would be used to provide a benchmark for land transport safety program content. Each member company is expected to implement the document, or Recommended Practice, themselves and to expect implementation by their contractors. The purpose of this paper is to introduce the Recommended Practice to participants at the 2007 E&P Environmental and Safety Conference, provide insight and background for the document, and to discuss implementation of its elements.

Objectives:The purpose of this study is to provide a comparison of the benefits of reduction mammaplasty (RM) for women with heavy breasts often termed macromastia or breast hypertrophy (BH) surgery. The rationale is to provide information to allow decision-makers to make judgments about the cost-effectiveness of this intervention and make comparisons with other interventions which are commonly undertaken within publicly financed health-care systems.Methods:Data from a previous outcomes study in Sweden is re-analyzed to derive quality of life measures, from which a mean level of benefit outcome is derived and a cost per quality-adjusted life year is calculated (cost per QALY).Results:The low Cost per QALY suggests that reduction mammaplasty is cost-effective when compared with other treatments which are commonly undertaken.Conclusions:The authors suggest that the evidence in favor of funding reduction mammaplasty is strong and that decision-makers review their policy in light of this new evidence.

This report describes introduction of researchers in the Information Technology Division of the Naval Research Laboratory (NRL) to the User Action Notation (UAN), a notation developed at Virginia Tech for representing the design of the interaction component of interactive systems. This report also presents use of the UAN in describing a variety of unique, innovative interaction techniques to evaluate the notation for its ability to represent such techniques, and exploration of possibilities for future research and technology transition with the UAN collaboratively between NRL and Virginia Tech. Human-computer interaction, User action notation, User interface design, Methodology.

Although glucocorticoids are known to regulate their own receptor number, the physiologic significance of this process is not known. In order to assess this process in intact animals the effects of adrenalectomy, stress, and exogenous glucocorticoid on the number of hepatic glucocorticoid receptors in Swiss-Webster mice were evaluated. In males 24 hr after adrenalectomy there was a clear 2- to 2.5-fold increase (upregulation) in glucocorticoid receptor number. Conversely, 24 hr after the ip administration of exogenous corticosterone there was a clear downregulation of receptor number. In each case (upregulation and downregulation) female mice were much less responsive than males. Three stressors were used to evaluate the effect of the endogenous secretion of glucocorticoids on downregulation. Male mice were exposed to ether, vibration, and confinement either once or daily for periods up to 3 days. Animals were sacrificed 24 hr after the last stress and hepatic receptor number was compared to an unstressed control. Cytosolic receptor number was not influenced by any of these stimuli. It is concluded that although glucocorticoids clearly regulate glucocorticoid receptor number, as demonstrated by adrenalectomy and the administration of steroids to adrenalectomized animals, the physiologic significance of this process is uncertain as receptor number does not appear to be changed by stimuli of adrenal glucocorticoids in the intact animal.

The ability of nonradioactive progesterone to accelerate the dissociation of tritiated dexamethasone from the agonist-binding site of the glucocorticoid receptor was used as a probe for the existence of a second antagonist steroid site. The goal was to evaluate if this second site was on the glucocorticoid receptor and, if so, on what region of that protein. The magnitude of acceleration of dissociation was assessed during purification of the receptor as well as with the untransformed (multimeric), transformed (monomeric), and mero-receptor. In each preparation progesterone caused a statistically significant increase in the rate of agonist dissociation. The documentation of acceleration of dissociation during purification suggests that progesterone one is interacting with a site on the glucocorticoid receptor and not with another protein. Evidence for the second binding site was found using each form of the receptor, untransformed, transformed, and mero-receptor, suggesting that the second binding site resides on the steroid-binding domain of the receptor which is on the carboxy-terminus, topographically close to the agonist-binding site.

This study analyzes the effect of including molybdate in the elution buffers used in DEAE cellulose chromatography on the fraction of glucocorticoid receptor which elutes as the transformed species. Inclusion of molybdate leads to a significant decrease in the fraction of receptor eluting as transformed; samples which appear to be nearly 50% transformed if eluted in the absence of molybdate were found to be less than 10% transformed when analyzed using a buffer which contained 5 mM molybdate. This decrease was not caused by loss of receptor or a reversion of transformation. DEAE cellulose accelerates receptor transformation. It is concluded that DEAE cellulose should not be used to quantitate transformation unless molybdate is included in all buffers.

Background In November 2004, a national target was set for the English hospital trusts to reduce the Meticillin-Resistant Staphylococcus aureus (MRSA) bacteremia rate by 60% by April 2008 against the number during 2003/04 (baseline year). In our organisation the number of MRSA bacteremias had risen since 2002 and peaked at 75 in 2005/06. A target was set to reduce the number and series of specific and non- specific interventions was introduced including universal MRSA screening. This study analyzes the impact of universal MRSA screening using a quasi-experimental design using routinely gathered data. Methods This study used data gathered routinely for clinical governance, quality control, financial management and outbreak monitoring purposes. Interrupted Time Series (ITS) analysis of 15 pre- and 19 post- universal MRSA screening (and decolonisation) quarterly numbers of bacteremias was carried out where Meticillin-Sensitive Staphylococcus aureus (MSSA) numbers served as non-equivalent dependent variable (control). Results An immediate sharp fall in MRSA bacteremias was observed following the universal MRSA screening (and decolonisation) commenced in Q2, 2007. The number dropped sharply from 23 (Q2, 2007) to 10 (Q3, 2007) for all MRSA bacteremias, and, from 15 (Q2, 2007) to 6 (Q3, 2007) for bacteremias ≥48 hours of hospitalization. The declining trend continued reaching zero in Q2, 2009 and Q4, 2010 for those with ≥48 hours of hospitalization and all bacteremias, respectively. ITS analysis revealed significant impact of universal MRSA screening on all MRSA bacteremias (β2 -0.554, p 0.000) and those with ≥48 of hospitalization (β2 -0.577, p 0.001). Impact estimation predicted 17 and 13 bacteremias for all and those with ≥48 hours hospitalization, respectively in the 19th quarter post-intervention, if the intervention did not occur. The number of MRSA isolates from non-blood culture systemic sources as percentage of admissions also dropped significantly from 3.32% in Q2, 2007 to 1.51% in Q3, 2007 (β2 -0.506, p 0.000) which is still running low at 0.33% at the end of Q1, 2012. On the other hand, there was no statistically significant impact of universal screening on MSSA bacteremias. Conclusions We conclude that of all interventions, the universal MRSA screening (and decolonisation) is the most effective intervention associated with significant and sharp drop in MRSA burden.